Aherrera Notes

Dr. Jaime Aherreras Internal Medicine Notes 2009

Aherrera Notes
Dr. Jaime Aherreras Internal Medicine Notes 2009

I. II. III. IV. V. VI. VII. VIII. IX. X.

Aherrera Notes | TAABLE OF CONTENTS

Basic Information Cardiology Endocrinology Gastroenterology Hematology Infectious Disease Nephrology Neurology Pulmonology Rheumatology

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Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

WARD NOTES

1) MUST KNOW FORMULAS

I. DOPAMINE DOSAGE COMPUTATION
Dopamine Drip used primarily for stabilization of the Hypotensive Patient Formulation of Dopamine: o Dilute 200mg (1 Ampule) in 250cc D5W (Factor used: 13.3) o Drip at 2.5 10mcg/kg/min o Maximum Dose of 20mcg/kg/min (Dopa-Max) o If Double Strength: 2 Ampules in 250cc D5W (use 26.6)

Rate (ugtt/min) = . (mcg/kg/min) x body weight . 13.3 Dopamine Doses (from Harrisons p1453) DOSE < 2 mcg/kg per min 2-4 mcg/kg per minute > 5 mcg/kg per minute
o o o

Dose (mcg/kg/min) = .

(ugtt/min) x 13.3 body weight

MECHANISM OF ACTION
Stimulate DA1 and DA2 Receptors Stimulate B1-Receptors Effects on A1-Receptors overwhelm the Dopaminergic Receptors

EFFECT
Vasodilation of Splanchnic and Renal Vasculature Increase in Cardiac Output with little or no change in Heart Rate or SVR Vasoconstricion, leading to Increase in SVE, LV Filling Pressures, and Heart Rate

**NOTE: Dopamine is generally the 1st choice for Tx in situations where Modest Inotropy & Pressor Support are required
It is an Endogenous Catecholamine that stimulates B1, A1 Receptors, and Dopaminergic Receptors (DA1, DA2) in the heart and circulation Dopamine also releases Norepinephrine from nerve terminals, which itself stimulates A1 and B1 Receptors, thus raising Blood Pressure Most useful in treatment of heart failure patients who have Depressed Cardiac Output with Poor Tissue Perfusion

Example) Case on Septic Shock: Patient is a 45kg / F, given 2 amps of Dopamine in 250cc PNSS at a rate of 19uggts/min In 1 Ampule of Dopamine = 200mg/amp Strength Factors: In 1 Ampule of Dobutamine = 250mg/amp NOTE: 19ugtts/min = 19cc/hr

1 amp of Dopamine = 13.3 2 amps of Dopamine = 26.6

QUESTION: What is the Dose of Dopamine being given to the patient at a rate of 19uggts/min?: Dose Given (in mcg/kg/min) = Rate (in ugtt/min) x 26.6 = 19 uggt/min x 26.6 = 45 kg 45 kg 11.23 mcg/kg/min

ANSWER: 11.23mcg/kg/min is the dose given to the Patient at a rate of 19uggts/min (or 19cc/hr) Since we are giving 11.23mcg/kg/min, we have a Vasoconstricting Effect. This is what we want for a patient with Septic Shock. We can increase the ugtts/min if patient is still Hypotensive up to 34ugtt/min (20mcg/kg/min) for a 45kg patient (Dopa Max). If still No Response with Dopa Max, we can give LEVOPHED (Norepinephrine). In the computation, we used 26.6 because 2 ampules of dopamine were used for the patient. Recall the Action of Dopamine at Different Doses (Dr. Magno Notes): 1. At 1-5mcg = RENAL VASODILATOR Exerts selective Renal and Mesenteric Vasodilation Acts on Dopamine Receptors Improve Renal Blood Flow and Urine Output 2. At 6-10mcg = INOTROPIC Positive Inotropic Effect Acts on Beta-1 Adrenergic Receptors Increase Heart Rate 3. At 10-20mcg = VASOCONSTRICTOR Peripheral Vasoconstriction Acts on A-Adrenergic Receptors Increase Systemic Vascular Resistance Deleterious for CHF and Low Cardiac Output

II. DOBUTAMINE DOSAGE COMPUTATION

A. Dobutamine Drip selectively stimulates Beta-1 Adrenergic Receptors o Direct Inotropic Stimulation with Reflex Arterial Vasodilation o Afterload Reduction and Augmented Cardiac Output o BP remains constant, HR increases minimally o For patients with Chronic Refractory Heart Failure o NOT for Heart Failure resulting from Diastolic Dysfunction or High-Output State B. Formulation of Dobutamine o Dilute 250mg (1 amp) in 250cc D5W (use 16.6) o Drip at 2.5 10mcg/kg/min o Maximum Dose of 20mcg/kg/min o If double strength: 2 Ampules in 250cc D5W (use 33.2) Rate (ugtt/min) = mcg/kg/min x body weight 16.6 C. Action of Dobutamine at Different Doses: o 0 10 mcg/kg/min = INOTROPIC EFFECT o 10 20 mcg/kg/min = VASOCONSTRICTION mcg/kg/min = . (ugtt/min) x 16.6 body weight .

Notes from Harrisons: Dobutamine has a Positive Inotropic Action and Minimal Positive Chronotropic Activity at Low Doses (2.5ug/kg/min) but moderate Chronotropic Activity at Higher Doses

III. NORADRENALINE (LEVOPHED) Rounds Each ampule has 2mg Noradrenaline per amp Usual Starting Dose is at 2-4 mcg/min with a maximum of 15 mcg/min
Noradrenaline (LEVOPHED) Drip: 2mg Noradrenaline in 2mL Ampule Usual Preparation: D5W 250mL + 1 Amp (2mg) Levophed to run at 15-60ugtts/min Concentration = 2mg = 2,000mcg = 8mcg Noradrenaline per cc (this is the concentration of 1 Amp + 250cc D5W) 250cc 250cc Drip of 2-8mcg Noradrenaline/min is equivalent to 15-60 ugtts/min Example: We are using 1 Amp (2mg) in 250cc D5W. If we mix 1 Amp with 250cc D5W, the concentration of Levophed will be 8mcg/cc (as computed above) 1) If Our desired dose to give patient is 2mcg/min (usual starting dose), what is the Rate? Step 1: Convert 2mcg/min to mcg/hour 2mcg/min x 60 mins 120mcg/hr Step 2: If we desire a dose of 120mcg/hr given a concentration of 8mcg Levophed per cc, compute the rate: 120mcg/hr = 15 cc/hr or 15 ugtts/min 8mcg/cc 2) If our desired dose is 8mcg/min 480mcg/hr 480mcg/hr = 60 ugtts/min 8mcg/cc Example 2) We are using 4 ampules (8mg) in 250cc of D5W. We want to give the patient a dose of 2mcg/min. What is the rate? Concentration = 8 mg . = 8,000 mcg = 32mcg Noradrenaline per mL (Concentration of 4 Amps + 250cc D5W) 250cc 250cc Since we initially want to give a dose of 2 mcg/min .2 mcg x 60 min = 120 mcg / hr min hr 120 mcg/hr = 4 cc/hr or 4 uggt/min 32 mcg/cc **NOTE: cc/hr is equal to uggts/min

III. COMMON FORMULAS USED A. General Formulas BMI = kg / m2

Underweight Normal Weight Overweight Obese I Obese II < 18.5 18.5 22.9 23 24.9 25 29.9 > 30

Ideal Body Weight: Females: 100 pounds + (5 pounds per inch over 5 feet) Males: 106 pounds + (6 pounds per inch over 5 feet) **NOTE: Divide 2.2 to convert to kilograms

B. Cardiac Output, Mean Arterial Pressure (MAP), Anion Gap, Osmolality, Etc. Cardiac Output Mean Arterial Pressure Heart Rate x Stroke Volume Systolic BP + (2 x Diastolic BP) 3
Normal Value: 70 100 mmHg

Urine Anion Gap Serum Anion Gap Urine Osmolality Plasma Osmolality

( Na + K ) Cl Na ( HCO3 + Cl ) ( SG 1 ) x 40,000 [2 (Na + K)] + RBS (mmol/L) + BUN (mmol/L) or 2 (Na in mmol/L) + (Glucose in mg/dL / 18) + (BUN / 2.8) Normal Value is 280 300 mOsm/L Normal Value (from Harrisons) = 275-290 mosm/kg RBS: 1 mmol/L = 18 mg/dL

Effective Plasma Osmolality

2 Na + RBS in mmol/L or 2 Na + RBS in mg/dL 18

C. Adequacy of Urine Collection o M: 20-23mL/kg o F: 15-20mL/kg D. 24-Hour Urine Collection Adequacy

o o o Creatinine is produced at a constant rate and in an amount directly proportional to skeletal mass Creatinine Coefficient = 23mg/kg of IBW (men) and 18mg/kg of IB (women) If 24 hr urine creatinine is LESS than IBW x Creatinine Coefficient INADEQUATE Collected Specimen Unpredictable when Serum Crea > 530umol/L

IV. BUN / CREATININE RATIO; CREATININE CLEARANCE A. BUN / Crea Ratio (SI Units)

BUN:Crea Ratio = BUN x 247 Crea

Conversion Factor for Serum BUN: 1 mmol/L = 2.8 mg/dL B. Fractionated Urine Na (Best test to Diagnose if Renal or Prerenal)

Interpretation: If < 10: Intrinsic Renal Cause If 10-20: Doubtful Cause If > 20: Pre-Renal Cause

FENa =

[ UNA x PCR ] x 100 [ PNA x UCR ]

Interpretation: <1 Pre-Renal >1 Renal (Oliguric ATN)

C. Creatinine Clearance (mL/min): Cockroft and Gault Equation

CreaClearance = . (140 age) x weight in kg . 72 x Serum Crea in mg/dL

CreaClearance = . (140 age) x weight in kg . 72 x (Serum Crea in umol/L / 88.4)

IMPORTANT Notes: o If Female, multiply everything by 0.85 o If Creatinine is NOT in mg/dL, divide it by 88.4 Normal Creatinine Clearance o 100-125mL/min in Males o 85-105mL/min in Females Staging of Chronic Kidney Disease (CKD) CKD STAGE DESCRIPTION Kidney damage with normal / increased GFT I Kidney damage with mildly decreased GFR II Moderately decreased GFR III Severely decreased GFR IV Renal Failure V GFR mL/min / 1.73m2 90 60 89 30 50 15 29 < 15 (for dialysis)

V. ELECTROLYTES A. Calcium
1. Corrected Calcium (mg/dL)

[ (40 Albumin in g/L) x 0.02 ] + Measured Ca2 in mmol/L OR ( 4 Albumin in g/dL x 0.08 ) + Measured Ca2+ in mg/dL

A Fall in Serum Albumin of 1gm/dL is associated with a Fall of 0.8mg/dL in Total Calcium

LOW in Renal Failure, Hypoparathyroidism, Severe Hypomagnesemia, Hypermagnesemia, Acute Pancreatitis, Rhabdomyolysis, Tumor Lysis Syndrome, Vitamin-D Deficiency, Pseudohypoparathyroidism; Rarely due to Multiple Citrated Blood Transfusions, critically ill patients, Anti-Neoplastic Agents, Antimicrobials, Agents used to Treat Hypercalcemia Use with Hypocalcemia ONLY if Ionized Calcium cannot be measured Make sure that the alteration in Serum Calcium is NOT due to Abnormal Albumin Concentrations About 50% of Total Calcium is Ionized, and the rest is bound principally to Albumin When Serum Albumin Levels are REDUCED, a Corrected Calcium Concentration is calculated by adding 0.2mM (0.8mg/dL) to the Total Calcium Level for every Decrement in Serum Albumin of 1.0g/dL below the reference value of 4.1 for Albumin, and conversely for elevations in Serum Albumin
Example: Present Total Calcium = 8mg/dL Present Serum Albumin = 2.5g/dL (N: 4g/dL) Corrected Ca2+ = (4 2.5) x 0.8 = 1.2 Corrected Total Calcium = 8 + 1.2 = 9.2 mg/dL

2. Hypocalcemia Calcium Gluconate 10% Solution of 10mL/amp: 1-2amp Slow IV Push (10-15mins) with Cardiac Monitoring then incorporate 1amp Calcium Gluconate to present IV Fluids Chronic Treatment: Calcium Carbonate 500mg 1 tab BID-TID Vitamin-D3 Supplements (Calcitriol 0.25mcg/cap OD-BID) Treat Hypomagnesemia 3. Hypercalcemia Hydrate: 0.9%NSS at 150-600cc/hr (up to 1-4 Liters in 24 hours) Furosemide 20-40mg IV q8-12 hours Bisphosphonates (Pamidronate 30-90mg/day as a single 24-hour Infusion for 3 Days)

B. Sodium 1. Corrected Sodium

0.016 (RBS in mg/dL 100) + Measured Na+ in mmol/L Plasma Na+ Concentration FALLS by 1.4 mmol/L for every 100 mg/dL RISE in the Plasma Glucose Concentration

2. Hyponatremia: Sodium Deficit

( Desired Na Actual Na ) x Body Weight in kg x 0.6

Target Na+ = 125 135 mEq/L NOTE: 0.6 is Total Body Water NaCl 1 Tab = 17 mEq NaHCO3 GrX 1 tab = 7 mEq a. Sodium Correction Time needed to Infuse = ( Desired Na Measured Na ) / 0.5 Total # of L needed = Na Deficit / 154 Drip Rate = Total # of L needed / Time needed to Infuse Give Patient 50% of Calculated amount of Na+ in the first 8 hours, and the other 50% in the next 16 hours (correct at a Rate NOT > 0.5meq/L/hr)

b. Sample Case for Hyponatremia A 70-kg male has a Na+ Value of 105 mmol/L We want to raise the plasma Na+ concentration from 105 to 115 mmol/L Formula: Deficit in Plasma Na+ x Total Body Water (TBW) [115 105] x 70 x 0.6 = 420 mmol Plain NSS (PNSS) has 154 Na+ Content per Liter; therefore, we can give 2-3 L of PNSS in one day

3. Hypernatremia
a. Water Deficit

Water Deficit =

Plasma Na+ Concentration - 140 140 OR

x 0.6 x BW (kg)

Water Deficit = [ ( Actual Na Desired Na ) ] x 0.6 x BW (kg) Desired Na

TBW is 0.6 mg/kg for MALES TBW is 0.5 mg/kg for FEMALES

Desired Na+ is 140 Total Body Water (TBW) in Hypernatremia is due to water loss Should be corrected SLOWLY over at least 48-72 hours, ideally with hourly Serum Na+ determination to target 0.5mmol/L/h, but NOT > 12mmol/L over the 1 st 24 hours b. Sample Case on Hypernatremia A 50 kg woman with a Plasma Na+ Concentration of 160 mmol/L Water Deficit = 2.9 L Water deficit should be corrected slowly over at least 48-72

160 140 x 0.4 x 50 kg = 2.9 L 140

hours. Safest route of administration of water is by mouth or via a nasogastric tube. Alternatively, 5% Dextrose in Water of Half-Isotonic Saline can be given IV

4. Water Excess

Water Excess =

Normal Na+ x TBW Actual Na+

- TBW

Hyponatremia Plasma Na+ Concentration < 135 mmol/L Clinical Manifestations: Brain Swelling or Cerebral Edema Stupor, Seizures, and Coma do NOT usually occur unless the Plasma Na+ falls below 120mmol/L of Decreases RAPIDLY Goals of Therapy: 1) To raise plasma Na+ Concentration by restricting water intake and promoting water loss; and 2) To correct the underlying disorder Rx: Plasma Na+ Concentration should be raised by NO more than 0.5-1.0 mmol/L per hour and by LESS than 10-12 mmol/L over the first 24 hours For Severe Symptomatic Hyponatremia: Treated with Hypertonic Saline, and Plasma Na + Concentration should be raised by 1-2 mmol/L per hour for the first 3-4 hours or until seizures subside. It should be raised by no more than 12 mmol/L during the first 24 hours. Osmotic Demyelination Syndrome (ODS): Risk of correcting Hyponatremia too rapidly Flaccid Paralysis, Dysarthria, Dysphagia Hypernatremia Plasma Na+ Concentration > 145 mmol/L Clinical Features: Water shifts OUT of cells, leading to Contracted ICF Volume Decreased Cell Volume is associated with an Increased Risk of Subarachnoid or Intracerebral Hemorrhage Therapeutic Goals: Stop Ongoing Water Loss and to Correct the Water Deficit

C. Potassium o Hypokalemia = Plasma K+ Concentration < 3.5 mmol/L o Hyperkalemia = Plasma K+ Concentration > 5.0 mmol/L 1. Potassium Deficit (Desired K+ - Measured K+) 0.27 x 100
Oral Kcl: 15cc: 10 mEqs 30cc: 20 mEqs Kalium Durule: 1 tab = 10 mEqs

Desired K is 3.5 Target K is 3.5 4.9 mEq/L If K is 2.0 3.5 mEq/L, replace 10-20 mEq KCl for every 0.1 mEq/L Drop in K Maximum Drip: Max 10 mEqs / hr Central Line: Max 20 mEqs / hr Desired K is:

4.0 mEq/L for Cardiac Causes, requiring IV administration of K 3.5 mEq/L for Non-Cardiac Causes, requiring Oral Administration of K

Administer as 10% Solution, 15cc + 20mEqs KCl; 1/2 of the dose given within 24 hours, then the excess within the next 3 days
Sample Orders for Hypokalemia: 1. Oral Route Kalium Durule 0.75gm (10 meq) TID PO x 2-3 days; or Oral KCl Solution 15-30cc TID (1gm KCl = 14meq K+, to be diluted in Oral Feeding or Water **NOTE: Each Oral Dose should NOT exceed 20-40 meq K+ 2. Intravenous Route Usual Concentration is 20-40 meq K+ in 1L Saline or Dextrose Solution Ex) Add 20-60 meq KCl in 1L Plain NSS x 12 hours If K+ Level is <2 and (+) ECG Abnormalities, use Glucose Free Solution

2. Hyperkalemia
Mild (K <5.5) Moderate (K = 5.5-6.5) Restrict Potassium Intake Kayexelate or Sorbisterit 20g; or Kalmiate 1 Sachet in 50-150cc Water TID x 3 Doses (up to 4-5 Doses/day) Furosemide 40-80mg IV Stat or Drip 0.5-20mg/hr Salbutamol Nebulization Calcium Gluconate 10mL 1amp in 10% Solution Slow IV Push Repeat after 10minutes if no improvement Glucose-Insulin D50-50mL + 10 units Humulin R Slow IV stat; then q6 0 x 3 Doses 500mL 10% Dextrose + 10 Units Insulin over 30-60minutes 1L 10% Dextrose + 20 Units Insulin with 1/3 solution given in first 30 minutes and the remainder over the subsequent 2-3 hours Sodium Bicarbonate 1 amp Dilute in 100cc D5W Slow IV Push > 10 minutes Fastest way to decrease Potassium (K+ shift in <15minutes)

Severe (K > 6.5)

D. Bicarbonate ( Desired HCO3 Actual HCO3 ) x (Weight in Kg) x 0.4

For correction of deficit, administer 1/2 of computed value as Bolus, then remaining 1/2 as IV Drip Desired HCO3 of 15 18 if patient has Chronic Renal Disease For Severe Acidosis: < pH 7.20 in Pure HAGMA, Goal is to Increase HCO3 to 10 mEq/L and pH to 7.15

VI. OTHER CONVERSION FACTORS To mg/dL RBS: BUN: Crea: Ca2+: Bilirubin: Multiply by 18 Multiply by 2.8 Divide by 88.4 Divide by 0.25 Divide by 17.10 1.33 mEqs K 20 mEqs K 10 mEqs K 45 mEqs Na 7 mEqs Na

Equivalents

1cc Oral KCl: 15cc Oral KCl: 1 K Durule (750mg): NaHCO3 50mL: NaHCO3 Gr X Tab:

Regular requirement for NaHCO3 is 21mEq/day, so we usually give NaHCO3 GrX TID

VII. TEMPERATURE CONVERSION Degrees Fahrenheit to Degrees Celsius: C = (F 32) x 5/9 Degrees Celsius to Degrees Fahrenheit: F = (C x 9/5) + 32 VIII. INTRAVENOUS FLUIDS
IV SOLUTION D5W D10W 0.9 NSS D5LR NM NR D50.9 NaCl D5NMK GLUCOSE 50 gm/L 100 gm/L 154 130 40 140 154 40

Na+ 154 109 40 98 154 40

Cl-

K+

Ca2+

HCO3

4 13 5 30

28

50 gm/L 50 gm/L

IX. PULMONOLOGY FORMULAS A. Alveolar-Arterial O2 Difference (PAO2 PaO2) or Alveolar-Arterial O2 Gradient (A-a Gradient) A a Gradient PAO2 PaO2
or

( FiO2 x 713) (PCO2 / 0.8) - PaO2

This formula is derived from: Alveolar PO2 (PAO2) = FiO2 x (PB PH2O) PaCO2/R In NORMAL Persons: PAO2 PaO2 < 15 mmHg Four Basic Mechanisms of Hypoxia: o Decrease in Inspired PO2 o Hypoventilation o Shunt o Ventilation/Perfusion (V/Q) Mismatch A-a Gradient: 1. Normal Gradient (both reduce Alveolar Oxygenation): Decrease in Inspired PO2 Hypoventilation 2. Elevated Gradient: Shunting (ie. Intracardiac Shunt): Low PO2 is NOT correctable with Supplemental O2 V/Q Mismatch: Low PO2 is CORRECTED with Supplemental O2 Shunting VS V/Q Mismatch: 1. Shunt: Alveolar Collapse (Atelectasis) Intraalveolar Filling (Pneumonia, Pulmonary Edema) Intracardiac Shunt Vascular Shunt within Lungs 2. V/Q Mismatch: Airway Disease (Asthma, COPD) Interstitial Lung Disease Alveolar Disease Pulmonary Vascular Disease

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B. Desired FiO2 Desired FiO2

[ ( Desired PO2 / PAO2 ) + ( PACO2 / 0.8) ] x 100 713 Where: PAO2 = (FiO2 x 713) (PCO2 / 0.8) Desired PO2 = 80 ( # of yrs > 60 y/o) = If < 60y/o = 104 (0.43 x age)

Simplified Version (ER Rounds):

Step I: Compute for PAO2 PAO2 = (FiO2 x 713) (PCO2 / 0.8) Step II: Compute for AaO2 AaO2 = PaO2 PAO2 Step III: Compute for Desired FiO2 . Desired PO2 . + PCO2 AaO2 0.8 713 . x 100

EXAMPLE: COPD Patient with the following values (ABG): pH = 7.365 PCO2 = 42.4 PO2 = 109 HCO3 = 24.4 FiO2 = 60% O2 Sat = 90% Step I: PAO2 = (0.6 x 713) (42.4 / 0.8) = 374.8 Step II: AaO2 = . 109 . = 0.29 374.8 Step III: FiO2 = . 60 . + 42.4 0.29 0.8 713 . x 100 = 36% - therefore, we can decrease FiO2 to 36%

**NOTE: Instead of 80, we used 60 because patient has (+) COPD

**NOTE: Desired PO2: o Instead of 80 (80 is usually used), we can use 80-100 o In COPD, we can use 60

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2) NUTRITION (DIET)
I. COMPUTATION OF DIET IN NORMAL PATIENTS (Ambulant, etc) Total Caloric Requirement Ideal Body Weight x 35 Kcal (Kcal/day) CHO (g/day) CHON (g/day) Fats . TCR x 0.6 4 1gm / kg The Rest Subtract CHO + CHON from the TCR .

**NOTE: In DM Patients, we give 3 meals + 2 snacks (to avoid Hypoglycemia) o If we want to Up Build Patients (for thin patients), we can give as much as 40 Kcal 60 Kcal per kg
Example: 70kg Patient If we use 30 Kcal/kg Patient will need 2,100 Kcal/day 1. Carbohydrates: 2,100 x 0.6 315g/day 4 2. Proteins: 1gm x 70 = 70g/day If patient has CKD, we may go down to as much as 0.6g/kg If patient has CKD and is on Dialysis, we can use 0.9g/kg 3. Fats REST

II. OSTERIZED FEEDING TCR 1800 Kcal/day (for a 60kg patient) o CHO 270g/day o CHON 60g/day Divided into 6 Equal Feeding o Fats Rest 1:1 Dilution III. DM DIET TCR 1800 Kcal/day (for a 60kg patient) o CHO 270g/day o CHON 60g/day 3 Meals, 2 Snacks o Fats Rest No Simple Sugars Low Salt, Low Fat Diet Na <2g TC < 200mg Saturate Fats < 7% MUFA > PUFA If CBG >180: give HR 4uSC If CBG >250: give HR 6uSC CBG Monitoring pre-meals and at bedtime

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3) NOTES ON INHERITED PATIENTS

I. GBS vs HYPOKALEMIC PERIODIC PARALYSIS In Hypokalemic Periodic Paralysis = INTACT Deep Tendon Reflexes (DTR) In GBS, the DTRs are usually disrupted II. ORGANOPHOSPHATE POISONING A. Signs of GOOD Atropinization Dry Mucosa HR > 60 Hypoactive BS Pupils > 4mm B. Atropine Toxicity T > 390C Flushing (-) Sweating Psychosis, Restlessness

III. ACUTE MYOCARDIAL INFARCTION CKMB should be > 2x elevated (Normal is 16, therefore, 32 is already MI) CKMB / CK Total should be > 5% MI! IV. HEPARIN DRIP COMPUTATION (Unfractionated Heparin) A. Initial Therapy Warfarin = Monitor PT (INR) o Bolus = 60-80 U/kg Heparin = Monitor PTT o Infusion = 14-18 U/kg/hr
aPPT (s) < 40 s 40 49 50 75 76 85 86 100 101 150 > 150 Bolus (H) 3000 0 0 0 0 0 0 Stop (min) 0 0 0 0 30 60 60 Rate Change (cc/hr) 22 1 No Change -1 -2 -3 -4 Rpt aPTT (hrs) 6 6 Next am Next am 6 6 6 aPTT < 1.25 times 1.25 1.5 times 1.5 2.5 times 2.5 3.0 times > 3.0 times CHANGE 80 Units/kg/Bolus; then Increase by 4 units/kg/hr 40 Units/kg/Bolus; then Increase by 2 units/kg/hr NO Change! Decrease by 3 Units/kg/hr STOP for 1 Hour; then Decrease by 3 Units/kg/hr

B. Example Case: 60kg male with Massive MI o Give 80 U/kg = 4,800 u IV Bolus (initial push) o Then, maintain on Drip: Add 10,000 Units Heparin with PNSS to make 100cc o Infusion is at 18 u/kg/hr, therefore, we are giving 1,080 Units per Hour (U/hr) o Give 10.8 cc/hr 10.8 ugtt/min o Monitor PTT and make necessary adjustments C. Example Case 2: PTT: Control is 37.1; then Patient is 33.3 33.3 / 37.1 = 0.9 times Give 80 Units/kg BOLUS Then INCREASE the Dose of heparin being given by 4 Units/kg/hr Computation: 4 x 60kg = 240 Units (therefore, we should ADD 240 units per hour) **NOTE: In 1 cc, there is 100 u Therefore, adjust the Heparin Dose by ADDING 2cc/hr (or 2ugtts/min) to the Baseline Drip D. Deep Vein Thrombosis o DVT Dose = 12 u UFH BID o DVT Prophylaxis Dose = 5 u BID

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ANTICOAGULANT THERAPY WITH LOW-MOLECULAR WEIGHT AND UNFRACTIONATED HEPARIN (from Harrisons)
CLINICAL INDICATION HEPARIN DOSE AND SCHEDULE TARGET PTT 2-2.5x < 1.5x 1.5-2.5x 1.5-2.0x 1.5-2.5x LMWH DOSE AND SCHEDULE 100 U/kg SC BID 100 U/kg SC BID 100 U/kg SC BID 100 U/kg SC BID 100 U/kg SC BID

Venous Thrombosis Pulmonary Embolism Treatment 5000 U IV Bolus; 1000-1500 U/h Prophylaxis 5000 U SC q8-12h Acute Myocardial Infarction With Thrombolytic Tx With Mural Thrombus Unstable Angina Prophylaxis General Surgery Orthopedic Surgery Px with CHF, MI 5000 U IV Bolus; 1000 U/hr 8000 U SC q8 + Warfarin 5000 U IV Bolus; 1000 U/hr 5000 U SC BID 10,000 U SC BID 10,000 U SC BID

< 1.5x 1.5x 1.5x

100 U/kg SC BID before & BID 100 U/kg SC BID before & BID 100 U/kg SC BID

PTT at RECHECK Normal (27-35s) < 50s 50 60s 60 85s 85 100s 100 120s > 120s

INTERVENTION 5000 U Bolus; 1300 U/h Infusion Rebolus with 5000 U and Increase Infusion by 100 U/h Increase Infusion Rate by 100 U/h No Change Decrease Infusion Rate by 100 U/h Stop Infusion for 30 minutes and Decrease Rate by 100 U/h at Restart Stop Infusion for 60 minutes and Decrease Rate by 200 U/h at Restart

**NOTE: LMWH does NOT affect PTT

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V. OTHER DRIPS (A to E from Blue Book) A. Nicardepine Drip 1. D5W 250mL + Nicardepine 20mg Concentration = 0.08mg/mL Drip of 15-67ugtts/min is equivalent to 1-5mg/hr OR 2. D5W 90mL + Nicardepine 10mg in Soluset Concentration = 0.1mg/mL Drip of 10-50ugtts/min is equivalent to 1-5mg/hr Maximum Dose = 15mg/hr NOTE: IV Infusion Site must be changed every 12 hours should a peripheral line be used B. Noradrenaline (LEVOPHED) Drip: 2mg Noradrenaline in 2mL Ampule D5W 250mL + 1 Amp Levophed at 15-60ugtts/min Concentration = 8mcg of Noradrenaline per mL Drip of 2-8mcg Noradrenaline/min is equivalent to 15-60 ugtts/min C. Hydralazine (Apresoline) Drip D5W 250mL + Apresoline 2 Amps (20mg/amp) at 5-30ugtts/min (up to 60 ugtts/min) Maximum Daily Dose = 3.5mg/kg body weight per 24 hours D. Isosorbide Dinitrate (ISOKET) Drip 1. D5W 90mL + Isoket 10mg in a Soluset Drip of 10-50 ugtts/min is equivalent to 1-5 mg/hr 2. If with CHF, may use DOUBLE Dose: D5W 90mL + Isoket 20mg in a Soluset Drip of 5-25 ugtts/min is equivalent to 1-5 mg/hr E. Glyceryl Trinitrate (PERLINGANIT) Drip: 1mg/mL in 10mL Vials 1. D5W 90mL + Perlinganit 10mg (1 vial) in a Soluset Drip of 10-50 ugtts/min is equivalent to 1-5 mg/hr 2. If with CHF, may use DOUBLE Dose: D5W 90mL + Perlinganit 20mg (2 Vials) Drip of 5-25 ugtts/min is equivalent to 1-5 mg/hr F. NTG Drip o 10mg NTG in enough PNSS to make 100cc in Soluset x 10cc/hr o May increase or decrease by 2cc/hr to achieve Chest Pain-Free State G. Omeprazole Drip o 80mg IV Bolus o 40mg + 100cc PNSS to run for 5 Hours (Continuous Drip) H. Somatostatin Drip o 250mg IV Bolus; then 3mg in D5W 250cc x 120 3mg + 500cc PNSS x 42cc/hr (250mg/hr) I. Electrolytes 1. NaHCO3 Drip 150mg NaHCO3 + 250cc D5W x 240 2. MgSO4 Drip 2-4mg in 250cc D5W x 120 3. KCl Drip (Correction) Please incorporate 40 meqs KCl to 1L PNSS to run for 80 x __ Cycles Repeat K+ Post-Correction J. Insulin Drip (Medicine Notes)

15

o o

Formulation: Dilute 20 Units of Insulin in 100cc PNSS to concentration of 0.2 Unit/cc Standard Insulin Concentration is 1 Unit Regular Insulin per 10mL Saline (0.1 unit/cc) 1. For Hyperkalemia (from Blue Book) Glucose-Insulin Drip a. 50mL of 50% Dextrose in Water + 10 Units Insulin in 2-5 Minutes Eg. Mix D50-50 mL + 10 Units Humulin-R Slow IV Stat, then q6 hours x 3 Doses b. 500mL of 10% Dextrose + 10 Units Insulin over 30-60 Minutes If Volume Overload is NOT a problem c. 1000mL of 10% Dextrose + 20 Units Insulin with 1/3 of Solution given in the first 30 Minutes and the remainder over the subsequent 2-3hours 2. For Hyperglycemia a. Loading Dose CBG > 200 = 0.075 0.1 Unit/Kg IV Push CBG > 300 = 0.1 0.125 Unit/Kg IV Push If DKA = 0.2 Unit/Kg IV Push b. Maintenance Dose 0.1 Unit/kg/hr, titrate to desired Blood Glucose 3. Dosing Table a. Intravenous (IV)

CBG
< 70 70 120 121 180 181 240 241 300 > 300

ACTION
Discontinue for 30 minutes, give 15-20mL of D50-50, re-measure in 30 mins If > 100, resume drip at 1 unit/hr. Continue glucose infusion Decrease Rate by 0.3 unit/hr No Change in Rate Increase Rate by 0.3 unit/hr Increase Rate by 0.6 unit/hr Increase Rate by 1.0 unit/hr

b. Subcutaneous (SC)

CBG
< 80 80 180 181 200 201 300 > 300

ACTION
Discontinue for 30 minutes, give 15-20mL of D50-50, re-measure in 30 minutes No Change in Rate Humulin-R 6 Units SC Humulin-R 8 Units SC Humulin-R 10 Units SC

K. Dopamine, Dobutamine, Heparin o See above discussion VI. VIRCHOWS TRIAD: Encompasses the three broad categories of factors that are thought to contribute to thrombosis The triad consists of: o Alterations in normal blood flow (Stasis) o Injuries to the vascular endothelium o Alterations in the constitution of blood (Hypercoaguability) VII. METABOLIC SYNDROME (SYNDROME X, INSULIN RESISTANCE SYNDROME) Consists of a constellation of Metabolic Abnormalities that confer in Risk of Cardiovascular Disease and Diabetes Mellitus Major Features include: NCEP:ATPIII 2001 CRITERIA for Metabolic Syndrome: Three or More of the following: o Central Obesity Central Obesity: Waist Circumference > 102cm (M), > 88cm (F) o Hypertriglyceridemia Hypertryglyceridemia: TG > 150mg/dL or specific medication o Low HDL Cholesterol Low HDL Cholesterol: < 40 mg/dL and 50 mg/dL, respectively, or specific medication o Hyperglycemia Hypertension: BO > 130 systolic or > 85 Diastolic or specific medication o Hypertension
Fasting Glucose > 100 mg/dL or specific medication or previously diagnosed T2DM

16

4) ARTERIAL BLOOD GAS (ABG)

Steps in Interpreting ABGs: 1) Check pH and Primary Disturbance 2) Check the Compensatory Mechanism 3) Check for presence of a Mixed Acid-Base Disturbance 4) For Metabolic Acidosis: Compute for Anion Gap (AG) 5) Note if with Good Oxygenation (should be > 90%)

I. FORMULA A. Metabolic Acidosis Decrease in PCO2 = 40 (HCO3 x 1.25) +/- 2 B. Metabolic Alkalosis Increase in PCO2 = 40 + (HCO3 x 0.75) +/- 2 C. Respiratory Acidosis 1. Acute Respiratory Acidosis HCO3 = 24 + [(PCO2 / 10) x 1] +/- 2 2. Chronic Respiratory Acidosis HCO3 = 24 + [(PCO2 / 10) x 4] +/- 2 D. Respiratory Alkalosis 1. Acute Respiratory Alkalosis HCO3 = 24 [(PCO2 / 10) x 2] +/- 2 2. Chronic Respiratory Alkalosis HCO3 = 24 [(PCO2 / 10) x 4] +/- 2

17

II. COMPENSATORY MECHANISMS

DISORDER Metabolic Acidosis Metabolic Alkalosis Respiratory Acidosis Acute < 2 weeks Subacute 2-6 weeks Chronic > 6 weeks Respiratory Alkalosis Acute Chronic PRIMARY DISTURBANCE Decrease in HCO3 Increase in HCO3 Increase in pCO2 COMPENSATORY RESPONSE 1.2 mmHg DECREASE in pCO2 for every 1 mEq/L FALL in HCI3 0.7 mmHg INCREASE in pCO2 for every 1 mEq/L RISE in HCO3 Acute: 1 mEq/L INCREASE in HCO3 for every 10mmHg RISE in pCO2 Chronic 3-5 mEq/L INCREASE in HCO3 for every 10mmHg RISE in pCO2 Decrease in pCO2 Acute: 2 mEq/L DECREASE in HCO3 for every 10mmHg FALL in pCO2 Chronic: 5 mEq/L DECREASE in HCO3 for every 10mmHg FALL in pCO2

Normal Values: pH pCO2 (mmHg) HCO3 (mEq/L) Anion Gap Cl (mEq/L) 7.4 + 0.3 40 + 4 24 + 2 12 + 2 105

III. CASE: An 50/M, 60kg, intubated patient had the following ABG results, post-intubation pH = 7.2 decreased pCO2 = 18 decreased HCO3 = 7 decreased A. Formula for Metabolic Acidosis: Decrease in pCO2 = 40 (HCO3 x 1.25) = 40 ([24 7] x 1.25) = 18.75

*NOTE: 24 is the desired HCO3; 7 is the actual HCO3

Since the Actual Decrease in PCO2 (18) is within +/- 2 of 18.75 COMPENSATED!!!!! This means that for every decrease in HCO3, there should be a 1.25 Decrease in PCO2
SAMPLE SCENARIO: If the Actual PCO2 is NOT within +/-2: If pCO2 is 10 there may be Overcompensation, or a COMBINED Metabolic Acidosis AND Respiratory Alkalosis If pCO2 is 25 UNCOMPENSATED!

B. Compute for Bicarbonate Deficit: HCO3 Deficit = (Desired HCO3 Actual HCO3) x weight x 0.4 = (18 7) x 60 kg x 0.4 = 264 mEq Deficit = Give half dose as IV Bolus, then the remaining in Drip = Example: Give 100 mEq IV Bolus NOW, then the remaining 150 mEq as Drip IV. OXYGEN SATURATION > 80 Adequate Oxygenation 60 80 Mild Hypoxemia 40 60 Moderate Hypoxemia < 40 Severe Hypoxemia

18

V. METABOLIC ACIDOSIS A. High Anion Gap Metabolic Acidosis

. AG . HCO3 . Cl . HCO3

If:

= 1 Pure HAGMA < 1 HAGMA + NAGMA > 1 HAGMA + Metabolic Alkalosis = 1 NAGMA < 1 NAGMA + HAGMA > 1 NAGMA + Metabolic Alkalosis

B. Normal Anion Gap Metabolic Acidosis

If:

VI. ANION GAP A. High-Anion Gap Metabolic Acidosis (HAGMA) o Methanol o Uremia o DKA MUDPILES o Paraldehyde o Isoniazid o Lactic Acidosis o Ethanol o Salicylates B. Normal-Anion Gap Metabolic Acidosis (NAGMA) o Renal o GI Losses

Diseases with HAGMA: -Lactic Acidosis -Ketoacidosis Diabetic Alcoholic Starvation -Toxins Ethylene Glycol Methanol Salicylates Propylene Glycol Pyroglutamic Acid -Renal Failure (Acute and Chronic) Diseases with NAGMA -Renal HCO3 Loss (Proximal RTA Type 2) -Enhanced NH4 Excretion -Ingestion of HCl, NH, Cl, Lysine, Arginine -GI HCO3 Loss (Diarrhea) or Acid Gain -Impaired NH4 Excretion -Distal RTA (Type 1) -Diarrhea -Urinary Tract Obstruction

VII. SOME EXAMPLES OF MIXED ACID-BASE DISORDERS FROM HARRISONS: A. Mixed Metabolic and Respiratory 1. Mixed Acidosis Respiratory Alkalosis Key: High- or Normal-AG Metabolic Acidosis INTERPRETATION: Prevailing PCO2 BELOW Predicted Value Lactic Acidosis, Sepsis in ICU Example: Na 140, K 4.0, Cl 106, HCO3 14; AG 20 PCO2 24, pH 7.39 2. Metabolic Acidosis Respiratory Acidosis Key: High- or Normal-AG Metabolic Acidosis Prevailing PCO2 is ABOVE Predicted Value Example: Na 14, K 4.0, Cl 102; HCO3 18; AG 20 PCO2 38, pH 7.3 INTERPRETATION: Severe Pneumonia, Pulmonary Edema

3. Metabolic Alkalosis Respiratory Alkalosis Key: PCO2 does NOT Increase as Predicted; pH is HIGHER than Expected Example: Na 140, K 4,0, Cl 91, HCO3 33; AG 16 INTERPRETATION: PCO2 38, pH 7.55 Liver Disease and Diuretics 4. Metabolic Alkalosis Respiratory Acidosis Key: PCO2 is HIGHER than Predicted; pH is NORMAL INTERPRETATION: Example: Na 140, K 3.5, Cl 88, HCO3 42; AG 10 COPD on Diuretics PCO2 67, pH 7.42 B. Mixed Metabolic Disorders 1. Metabolic Acidosis Metabolic Alkalosis Key: Only detectable with High-AG Acidosis; AG >>> HCO3 INTERPRETATION: Example: Na 140, K 3.0, Cl 95, HCO3 25, AG 20 Uremia with Vomiting PCO2 40, pH 7.42 2. Metabolic Acidosis Metabolic Acidosis INTERPRETATION: Key: Mixed High-AG Normal AG Acidosis; HCO3 Diarrhea and Lactic Acidosis accounted for by combined change in AG & Cl Toluene Toxicity Example: Na 135, K 3.0, Cl 110, HCO3 10, AG 15 Tx of DKA PCO2 25, pH 7.20

19

ECG TEACHING NOTES (PGH, 2008)

1) INTRODUCTION
I. NORMAL VALUES < 0.12 sec P-Wave < 0.25 Mv in Limb Leads < 0.1 Mv Terminal Negative Deflection in V1 0.12 0.20 sec (up to 5 small boxes) PR Interval < 0.11 0.12 sec QRS Duration 5 10 mm (0.5 1.0 Mv) T Wave < 0.44 (females) QTc < 0.48 (males)

Formula of Corrected QT-Interval (QTc) Corrected QT Interval = . QT Actual . R-R Interval

Computation of Heart Rate Rate = . 300 . # of Big Sq = . 1500 . # of Small Sq

Important Notes:
o o o

ST Depression: Ischemia Significant Q-Wave: > 25% of QRS ST Elevation: Infarction Significant ST-Segment Depression: > 1mm Significant ST-Segment Elevation: > 1mm Limb Leads; > 2mm Chest Leads

II. AXIS Computation of Frontal Axis: Axis = . 90 x aVF . |I| + |aVF|

Where:
o o

Avf and I are integers derived by subtracting the Positive Deflection from the Negative Deflection The Avf in the numerator is an Integer, while the I and Avf in the Denominator are absolute values of integers If I is a Negative Integer, then adjust the Axis by adding | 90 |

Interpretation: Right Axis Deviation (RAD) Left Axis Deviation (LAD) Normal Axis Extreme Axis Deviation
Read As:

> 1000 < -300 -300 to 1000 -900 to 1800

III. NORMAL ECG

Regular Sinus Rhythm (RSR) Normal Axis (NA) Within Normal Limits

IV. EJECTION FRACTION ON ECG Ejection Fraction = (QRS aVr x 2.64) + (Age x 0.645)

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2) SOME COMMON FINDINGS

I. NON-SPECIFIC ST-T WAVE CHANGES T-Wave Inversion < 5mm (< 0.5Mv) ST Segment Depression < 1mm (< 0.1 Mv) Flattening of ST Segment without the presence of U-Waves **NOTE: Mention leads where ST-Segment changes and T-Wave inversions occur II. ISCHEMIA T-Wave Inversion > 5mm (> 0.5Mv) read as To Consider Ischemia ST-Segment Depression > 1mm (> 1Mv) in 2 or more contiguous leads read as Ischemia **NOTE: Significant ST-Segment Depression > 1mm in at least 2 contiguous leads (Horizontal or Downsloping) III. POOR R-WAVE PROGRESSION In Leads V1-V3 (R-Wave < 3mm or 0.3Mv) AND Normal R-Wave in V4-V6 Do NOT Read as Poor R-Wave Progression in the following conditions: o Left Ventricular Hypertrophy o Left Bundle Branch Block o Wolff-Parkinson-White Rhythm o Anteroseptal Wall MI o Low-Voltage QRS Complexes **NOTE: NO Clinical Relevance: Do NOT Write: o Early transition / counterclockwise rotation o Persistent S V5-V6 or Persistent Posterobasal Forces IV. ATRIAL ENLARGEMENT Right Atrial Enlargement Left Atrial Enlargement P-Wave with 2.5mm Amplitude (0.25Mv) in any of Lead II, III or Avf P-Wave Widened > 3mm (> 0.12sec) especially Lead II; OR Terminal Segment of P-Wave in V1 > 1 small box (>0.04 sec OR 0.1Mv depth) Do NOT include Notching in Lead II as Criterion Bi-Atrial Enlargement RAE (Tall P-Waves > 2.5mm In Leads II, III, Avf) PLUS LAE (Terminal Segment Of P-Wave > 1 Small Box (0.04 Sec) In V1 Or Widened PWave, Especially Lead II > 3mm (>0.12sec)

21

V. VENTRICULAR ENLARGEMENT A. Left Ventricular Hypertrophy 1. Sokolow-Lyon Criteria [S in V1] + [R in V5 or V6] is Greater than 35mm (do NOT use S in V2); OR Avl > 11mm **IMPORTANT Notes: Cut-Off for LVH, regardless of Age > 35mm No need to Indicate By Voltage 2. Cornell Criteria S in V3 + R in AvL Female > 20mm Male > 28mm B. Left Ventricular Strain LVH by Voltage Criteria + Significant Asymmetric ST-Segment Depression with Broad-Inverted T-Wave Read as LVH with Strain, Cannot Rule Out Concomitant Ischemia C. Right Ventricular Hypertrophy RAD + R/S Ratio > 1 in V1 + R/S Ratio < 1 in V6 o o RAD is a Prerequisite Criterion for RVH An Upright V1 or Prominent R in V1 without RAD will NOT be signed out as RVH and need not be described

D. Biventricular Hypertrophy Hypertrophy in presence of BBB: RAD + rsR Pattern in V1 (R-Wave Amplitude > 15mm or 1.5Mv) VI. LOW VOLTAGE COMPLEXES Chest Leads are more significant QRS Complexes < 5mm (0.5Mv) in Limb Leads < 10mm (1.0Mv) in Chest Leads Read as Low Voltage Complexes in Limb OR Chest Leads

22

3) ABNORMAL ECG FINDINGS

I. EARLY REPOLARIZATION CHANGES Embryonic R + ST-Elevation NOT fulfilling criteria for ST-Elevation in MI Check morphology of ST-Segment if more convex rather than concave II. BUNDLE BRANCH BLOCKS AND INTRAVENTRICULAR CONDUCTION DEFECT LBBB RBBB Non-Specific Intraventricular Conduction Delay: Widened QRS without Repolarization changes, NOT meeting the Criteria for LBBB or RBBB LAFB LPFB Bifasicular Block Trifasicular Block III. ELECTROLYTE ABNORMALITIES Low Sensitivity of U Wave U Wave Prominent + Normal T-Wave Read as Prominent U Wave Prominent U Wave + Flattened T-Wave Read as T/C Hypokalemia ST-Segment Depression + U Wave + Normal T-Wave Read as Cannot R/O Ischemia; Prominent U Wave Flattened T-Waves + Normal QRS-Complex Read as Non-Specific ST-T Wave Changes QTc Computed to Adjust for Bradycardia (HR < 60bpm) or Tachycardia (HR > 100bpm) o Normal Value: Female < 0.48 o Normal Value: Male < 0.47 **NOTE: Use the Lead with the longest Absolute QT Interval without Prominent Q-Wave OR Largest Amplitude T-Wave A. Digitalis Effect o Seen in patients without Significant ECG Changes due to Organic Disease o Should describe Drug Effects in leads seen o Read as Scooping of ST-Segment Depression, Non-Specific ST-T Wave Changes, probably Digitalis Effect B. Hyperkalemia o At least > 2 Contiguous Leads with Peaked T-Waves > 10mm (1.0Mv) o Read as Peaked T-Waves, T/C Hyperkalemia IV. MYOCARDIAL INFARCTION A. Timing of MI Acute Significant ST-Elevation + T-Wave Inversion +/- Q-Waves Old Significant Q-Wave + Isoelectric ST Segment + Upright T-Wave Age Undetermined ST-T Wave Change +/- Q-Wave not fulfilled by Criteria for Old and Acute MI B. Definitions Significant ST-Segment Elevation > 1mm Limb Leads > 2mm Chest Leads

23

Significant Q-Wave C. Walls of Involvement LEADS V1 V1-V2 V1-V3 or V1-V4 V3-V4 V5-V6 V3-V6 V1-V6 II, III, Avf

> 25% of the QRS Complex; or > 0.04 sec MYOCARDIAL WALL INVOLVED Posterior Septal Anteroseptal Anterior Lateral Anterolateral Massive Anterolateral Inferior

D. Correspondence of Specific ECG Leads (from Medicine Notes) LEADS CORRESPONDING LV AREAS II, III, Avf Inferior Wall I, Avl High Lateral V1, V2 Septal Wall V3, V4 Anterior Wall V5, V6 Lateral Wall V1 V3 Anteroseptal Wall V3 V6, I, AvL Anterolateral Wall V5, V6, II, III, AvF Inferolateral Wall Almost All Leads Diffuse / Global / Massive Mirror Image V1, V2 Posterior LV Wall V3R, V4R RV Wall V. INTERPRETING ECGs (Rounds) A. AV Block Primary AV Block Prolonged PR interval (More than 5 small squares or more than 0.2msec) Secondary AV Block I: There is prolonging PR-Interval, then Drop Beat II: There is a Regular PR-Interval, then Drop Beat Tertiary AV Block With AV dissociation (look for P-waves, look for Q waves DISSOCIATED!) The PR and QRS Waves are Independent from each other B. Q-Waves o 20% of R; Wide OLD Infarct! o In aVr, there is usually a Q-Wave C. QRS o Normal = 0.08 0.12 o If Wider = Bundle Branch Block D. ST Elevation / Depression o ST Elevation = at least 2 small boxes in contiguous leads o ST Depression = at least 1 small box E. T-Waves o Peaked T-Waves = 10 boxes in chest leads; 5 boxes in limb leads o If Inverted T-Waves = CANNOT rule out ischemia

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VI. VENTRICULAR TACHYCARDIA A. Ventricular Tachycardia can be classified based on its MORPHOLOGY: 1. Monomorphic Ventricular Tachycardia Means that the appearance of all the beats match each other in each lead of a surface electrocardiogram (ECG)
2. Polymorphic Ventricular Tachycardia Has beat-to-beat variations in morphology This most commonly appears as a cyclical progressive change in cardiac axis referred to by its French eponym Torsades de Pointes (literally twisting of the points). B. Classification Based on Duration of the Episodes: o Technically, three or more beats in a row on an ECG that originate from the ventricle at a rate of more than 100 beats per minute constitute a ventricular tachycardia 1. Non-Sustained Ventricular Tachycardia If the fast rhythm self-terminates within 30 seconds, it is considered a non-sustained ventricular tachycardia 2. Sustained Ventricular Tachycardia If the rhythm lasts more than 30 seconds it is known as a sustained ventricular tachycardia (even if it terminates on its own after 30 seconds) C. Classification Based on SYMPTOMS 1. Pulseless VT Associated with NO effective cardiac output, hence, no effective pulse, and is a cause of cardiac arrest In this circumstance it is best treated the same way as ventricular fibrillation (VF) and is recognized as one of the shockable rhythms on the cardiac arrest protocol 2. Some VT is associated with Reasonable Cardiac Output and may even be Asymptomatic The heart usually tolerates this rhythm poorly in the medium to long term, and patients may certainly deteriorate to Pulseless VT or to VF

VII. PACEMAKER A. Indications for Permanent Pacemaker Insertion (Pacing) o Permanent Pacemaker Insertion should be implanted in the following conditions (Class-I Indications)
1. Complete Heart Block with: (+) Symptoms due to the AV Block (eg. Syncope, Heart Failure) Asystole > 3 seconds by Holter Monitoring even if without symptoms HR < 40 bpm even without symptoms (any escape rhythm < 40 bpm) 2. Second Degree AV Block, Permanent or Intermittent, with Symptomatic Bradycadia 3. Sinus Node Dysfunction with Symptomatic Bradycardia. In some patients, this is due to Long-Term Essential Drug Therapy for which there are NO Acceptable Alternatives Eg. Digoxin for Tachycardia-Bradycardia Syndrome 4. Carotid Sinus Stimulation causing Recurrent Syncope or Asystole > 3 seconds in the absence of any medication that depresses the Sinus Node or AV Conduction B. WOF: Pacemaker Syndrome o Neck vein engorgement, Dizziness, Dyspnea, Chest Pain

25

o This occurs when Atrium pumps against a Closed Mitral Valve due to Asynchronization VIII. ECG FINDINGS OF PERICARDITIS Diffuse ST-Segment Elevations = Concave Diffuse ST-Segment Elevation

A. ECG of Pericarditis

B. ST Elevation in Pericarditis is Different from MI: In Myocardial Infarction, it is CONVEX o In MI = ST-Segment Elevation WITH T-Wave Inversion o Difference = In Pericarditis, when T-Wave Inversion appears, ST-Segment Elevation disappears

IX. OTHER NOTES (during rounds): A. ECG Findings of Mitral Stenosis o LA-Enlargement = WIDE P-Wave o RAD o RVH B. Significant Q-Waves o 1) Q-Wave > 25% of R-Wave o 2) Q-Wave is > 0.04 seconds (or 1 small box) duration

26

MECHANICAL VENTILATION

1) BASIC INFORMATION
I. WEANING FROM MECHANICAL VENTILATION Indications for WEANING: Mental Status: Awake, Alert, Cooperative PaCO2 > 60mmHg with FiO2 < 50% PEEP < 5cm PaCO2 and pH Acceptable Spontaneous TV > 5mL VC > 10mL/kg MIP > 25cmH2O RR < 30/min Rapid Shallow Breathing Index (RBI) < 100 Stable Vital Signs following a 1-2 hour Spontaneous Breathing Trial A. Removal of Mechanical Ventilator support requires that a number of criteria be met 1. Upper Airway Function must be Intact for a patient to remain extubated If a patient can breathe on his own through an ET Tube but develops stridor or recurrent aspiration once tube is removed, Upper Airway Dysfunction or an abnormal swallowing mechanism should be suspected 2. Weaning Index Respiratory Drive and chest wall function are assessed by observation of RR, Tidal Volume, Inspiratory Pressure, and Vital Capacity Weaning Index: Ratio of Breathing Frequency to Tidal Volume (breaths per minute per liter), is both sensitive and specific for predicting the likelihood of successful extubation If Ratio < 105 with patient breathing without mechanical assistance through an ET Tube, successful extubation is likely 3. Alveolar Ventilation is deemed adequate when: Elimination of CO2 is sufficient to maintain arterial pH in the range of 7.35 to 7.40, and an SaO 2 > 90% can be achieved with an FiO2 < 0.5 and PEEP < 5cmH2O B. Approaches to Weaning
o o T-Piece and CPAP Weaning are best tolerated by patients who have undergone MV for brief periods and require little respiratory muscle reconditioning SIMV and PSV are best for patients intubated for extended periods likely to require gradual respiratory-muscle reconditioning 1. T-Piece and CPAP Brief spontaneous breathing trials with supplemental O2 Initiated for 5mins/hour followed by a 1-h interval of rest Trials are increased in 5 to 10 minutes/hour increments until patient can remain ventilator independent for periods of several hours Extubation can then be attempted 2. SIMV Involves gradual tapering the mandatory backup rate in increments of 2 to 4 breaths per minute while monitoring blood gas parameters and respiratory rates Rates > 25 / min on withdrawal of mandatory ventilator breaths generally indicate Respiratory Muscle Fatigue and the need to combine periods of exercise with rest Exercise periods are gradually increased until a patient remains stable on SIMV at < 4 breaths per minute A CPAP or T-Piece Trial can then be attempted before extubation 3. PSV Usually initiated at a level adequate for full ventilator support (PSVMax) ie. PSV is set slightly below the peak inspiratory pressures required by the patient during volume-cycled ventilation Level of pressure support is then gradually withdrawn in increments of 3-5cmH2O until a level is reached at which the RR increases to 25 breaths/min At this point, intermittent periods of higher pressure support are alternated with periods of lower-pressure support to provide muscle reconditioning while avoiding diaphragmatic fatigue Gradual withdrawal of PSV continues until the level of support is just adequate to overcome the reistance of the ET Tube (~5 to 10cmH2O)

27

Support can be discontinued and the patient extubated

II. INDICATIONS FOR INTUBATION (Medicine Notes) Impending Respiratory Failure; Apnea RR > 35 PaCO2 > 50 NOTES on FiO2: PaO2 < 60 FiO2 at Room Air = 21% TV < 3.5mL/kg O2 via Nasal Prong = # lpm x 0.4 + 20 VC < 10-15mL/kg Inspiratory Force < 25cmH2O FEV < 10mL/kg The primary indication for initiation of mechanical ventilation is Respiratory Failure, of which there are 2 basic types: VQ/VT > 0.6 Hypoxemic Respiratory Failure To deliver High FiO2 Hypercarbic Respiratory Failure Absent Gag pH < 7.35 III. SPONTANEOUS BREATHING TRIAL (Harrisons) Consists of a Period of breathing through the Endotracheal Tube WITHOUT Ventilator Support (both Continuous Positive Airway Pressure [CPAP] of 5cmH2O & an Open T-Piece Breathing System can be used) for 30-120 mins A. If the Following are Present, Patient has passed the Screening Test and should undergo Spontaneous Breathing Trial o Stable Oxygenation (PaO2/FIO2 > 200) and PEEP < 5cmH2O o Cough and airway reflexes are intact o No Vasopressor Agents or Sedatives are being administered B. Spontaneous Breathing Trial is Declared a FAILURE and STOPPED if any of the following occur: o 1) RR > 35/min for > 5mins o 2) O2 Saturation < 90% o 3) HR > 140/min or a 20% Increase or Decrease from Baseline o 4) Systolic BP < 90mmHg or > 180mmHg o 5) Increased Anxiety ot Diaphoresis If at the end of the Spontaneous Breathing Trial, the ratio of the Respiratory Rate and Tidal Volume in Liters (f/V T) is < 105, the patient can be EXTUBATED

IV. ASSIST CONTROL MODE (Medicine Notes) Each breath is assisted by the vent even if the RR exceeds the BUR Parameters: VT, PEEP, BUR, PFR/IFR, FiO2, Sensitivity Flow Pattern A. Tidal Volume
o o General: 8-10 mL/kg In ARDS: 6 mL/kg B. PEEP: o 5cm H2O C. Back Up Rate o 16-20 D. Peak Flow Rate: o 40-60 mL o Asthma / COPD: Increase to allow more time to exhale o ARDS: Decrease to Prevent further injury E. FiO2 Start at 100% o If lungs are NORMAL (eg. Trauma patient), start at 50% o DECREASED to tolerable % as fast as possible (doesnt have to be decreased by 10%) o Non-Toxic FiO2 = 50% (Golden Time to reach this is 4 hours) F. Sensitivity (Trigger) 2 L o Pressure: (-) 1.5 to 2.0 cmH2O (the more negative, the more work patient does) o Flow: Usually 2L

28

G. Flow Pattern: o Square Wave

2) BASIC MODES OF VENTILATION (Mech-Vent Work Shop: Dr.Divinagracia Lecture)

Indications for Mechanical Ventilation: 1. Clinical Assessment Presence of Apnea, Tachypnea (>40/min) Respiratory Failure that cannot be corrected by any other means 2. Arterial Blood Gases (ABG) Severe Hypoxemia (PO2 < 50) despite High-Flow Oxygen Significant CO2 Retention (PCO2 > 50) 3. Worsening Physiological Parameters Are of limited use since patients with Respiratory Insufficiency are unable to perform PFTs and their Respiratory Failure mandates immediate intervention However in some cases especially in Neuromuscular Diseases, these parameters can be used as warnings that the patient will go into Respiratory Failure sooner rather than later: o 1) Vital Capacity < 15mL/kg o 2) Inspiratory Force < -25cm H2O o 3) FEV1 <10mL/kg TWO Main Modes of Ventilation: Volume Cycled / Controlled: we set the Tidal Volume (ex. AC Mode) Pressure Controlled Ventilation: we set the Peak Airway Pressure (Favorable in ARDS)

I. ASSIST / CONTROL MODE (A/C MODE) The Patient breathes at his OWN Rate and the Ventilator senses the Inspiratory Effort and delivers a Preset Tidal Volume with EACH patient effort If patients Respiratory Rate decreases past a Preset Rate, the Ventilator delivers Tidal Breaths at the Preset Rate EVERY BREATH is assisted A. Advantages and Disadvantages ADVANTAGES Useful in Patients with Neuromuscular Weakness or CNS Disturbances The INITIAL Mode usually set upon advent of Mechanical Ventilation It totally Unloads (rests) the Respiratory Muscles requiring NO Work on the Patients part DISADVANTAGES Tachypnea may result in Significant Hypocapnea and Respiratory Alkalosis Improper setting of Sensitivity to trigger the Ventilator may result in fighting the ventilator when sensitivity is set too low Increases Sensitivity may result in Hyperventilation; Sensitivity is generally set so that an Inspiratory Effort of 2cmH2O will trigger the Ventilation Since there is almost NO work involved by the Respiratory Muscles, Muscle Tone is NOT well Maintained (Atrophy). Muscle Atrophy starts within 6 hours

29

B. Selection of Ventilator Settings for A/C Mode SETTING 1) Tidal Volume (VT)
How much volume will the Machine Deliver?

USUAL VALUE
8-10 mL/kg of Ideal Body Weight 6mL/kg for ALI/ARDS 10-15mL/kg for Neuromuscular Dse 16 - 22

2) Back-Up Rate: Number of Tidal Breaths Delivered per Min

Minimum number of breaths per minute Usually set 2 to 4 below the Spontaneous Rate and then the Effect on the patient of Decreasing Rate is noted (this can be adjusted depending on the desired PaCO2 or pH Ex) If set at 8, patient will NOT breath below RR < 8 Faster RR = Blow of CO2 PaCO2 and pH

3) Oxygen Concentration (FiO2)

Initial FiO2 should be 100% unless it is evident that a Lower FiO2 will provide adequate oxygenation We can start at 50% if Neuromuscular Disease (ex. MG)

100%

4) Inspiratory Flow Rate (IFR)

How fast do we deliver the air? 60L/minute is FASTER than 40L/minute (Higher Flow Rates Higher Peak Pressure) This is the Rate air is delivered to the patient to achieve the Tidal Volume set Rate needs to be HIGHER (80L/min) in COPD & Asthma An IFR LOWER than the patient demand will Increase the work of breathing and is a common cause of Patient-Ventilator Discordance (Fighting or Bucking the Ventilator) In Patients with Hypoxemia, deliver the air SLOWER (so that Inspiration Time is Longer more time to exchange PO2

40-60 L/minute

5) Inspiratory Flow Pattern (IFP)

Square Wave

How do you deliver the Air? This is how flow is distributed throughout the Respiratory Cycle Normal Person: Sine Wave

Wave Forms usually Available: a. Sine Wave: The maximum flow is at Mid Inspiration and resembles a Normal Spontaneous Tidal Breathing b. Square Wave This provides a maximum peak flow throughout the Inspiratory Period Fast Delivery patients prefer it (but has higher pressures) c. Decelerating Wave The flow is maximal at the Start and diminishes as Inspiration ends

6) PEEP
Physiologic PEEP of about 5cm H2O should be added regardless of FiO2 to prevent the Alveolar Injury due to the Shearing Effect of opening and closing the Alveoli Pressure at End Expiration (it is Positive)

5cm H2O

30

Should be Increased in ARDS -2.0cm or 2L Different for PGH Vents

7) Sensitivity
Ranges anywhere from 5 to 0.5cmH2O (Pressure Sensitivity) or 1 to 5 Liters (Flow Sensitivity) The MORE Sensitive (eg. 0.5cm or 1L), the EASIER for the patient to Trigger the Ventilator which may lead to Hyperventilation The LESS Sensitive (eg. 5cm or 5L), the HARDER for the patient to trigger the Ventilator which may lead to Increased Work of breathing and thus can cause Patient-Ventilator Desynchrony

a. Pressure Sensitivity Ex) If set at 1, the patient has to exert a 1cmHg Pressure for the Vent to Deliver the Tidal Volume b. Flow Sensitivity Ex) If set at 1L, patient has to create a negative pressure Advantage: Patients with COPD (difficult to empty lungs) they will have LESS work

Sensitivity in PGH Mechanical Ventilators: o Turn knob Counterclockwise becomes Less Sensitive o Turn know Clockwise becomes More Sensitive I:E Ratio: o Normal is 1:2 o In COPD, adjust to 1:3 o In ARDS, adjust to 1:1 o Ex) In COPD, we Increase the IFR so that the IE Ratio will be 1:3

31

II. SYNCHRONIZED INTERMITTENT MANDATORY VENTILATION (SIMV) There are two separate circuits for contribution of Minute Ventilation o One circuit delivers Ventilator Breaths in a manned identical to A/C, with the Ventilator breath being timed or synchronized to patient effort o The Mechanical Ventilator breaths are limited to a preset number Additional patient effort leads to Spontaneous Breaths made through a separate fresh gas system Allows patient to take as many spontaneous breaths as he chooses around the Intermittent Synchronized Ventilator Breaths The patients contribution to Minute Ventilation depends on the number of Spontaneous Breaths and Inspiratory Effort
Sample Case: SIMV Mode; BUR set at 12; Patients actual RR is 20 ONLY the 12 of 20 Breaths are Assisted in SIMV o 12 will Receive the COMPLETE TV set o 8 will Receive the TV, depending on the Patients efforts In CONTRAST, in AC Mode ALL 20 will be Assisted

A. Advantages and Disadvantages

ADVANTAGES Maintains Respiratory Muscle tone due to the continued use of the Inspiratory Muscles and thus prevents Disuse Atrophy There is Decreased Intrathoracic Pressure as compared to A/C which may lead to improved Hemodynamics Useful for WEANING because as the Back-Up Rate is Decreased, the patient gradually assumes the Bulk of Breathing DISADVANTAGES Even with the same Back-Up Rate as the A/C, there is MORE WORK of Breathing The Increased Work of breathing results in Increased Oxygen Consumption which is deleterious in patients with Myocardial Insufficiency This mode is NOT useful in patients with Depressed Respiratory Drive or Impaired Neurologic Status

B. Selection of Ventilator Settings for the SIMV Mode o Rate: Initial Rate should be Close to the Patients Rate and then the Rate Decreased noting the effect on Patient Acceptance o VT, FiO2, IFR, IFP, PEEP SAME of that in A/C C. A/C Mode VS SIMV: Assist Work of Breathing Can be Used for Weaning A/C MODE Total Almost NONE NO SIMV MODE Partial Variable YES

III. RECENT MODALITIES OF MECHANICAL VENTILATION 1) Pressure Limited Ventilation o Pressure Support Ventilation (PSV) o Pressure Controlled Ventilation (PCV) 2) Combination of Volume-Cycled and Pressure-Limited Ventilation o SIMV with PSV 3) Inverse Ratio Ventilation o PCV with Inverse Ratio o A/C with Very Low Flow Rates

32

3) OTHER NOTES IN MECHANICAL VENTILATION

I. RESPIRATORY MONITORING Gas Exchange o Carbon Dioxide and Ventilation o Oxygen Lung and Chest Wall Mechanics o Pressure-Volume Relationships o Mean Airway Pressure o Auto-PEEP Effort Breathing Effort Ventilatory Drive and Breathing Pattern Strength and Muscle Reserve II. SOME FORMULAS: A. PAO2-PaO2 Gradient PAO2 = FiO2 (Patm PH2O) (PaCO2 / R)
Normal PAO2-PaO2 Gradient = 10 Increases by 5-6 per decade over 50 At Sea Level: FiO2 = 0.21 PH2O = 47 PBREATH = 760 PaCO2 = Measured by Labs R = 0.8

B. Desired FiO2 Desired FiO2 = (PaO2 Desired x FiO2 Known) PaO2 Known C. Minute Ventilation Minute Ventilation = Kg x 100 RR III. WEANING PARAMETERS AND STRATEGIES Weaning: process of abruptly or gradually withdrawing Ventilatory Support when the cause of the Respiratory Failure is under resolution A. When should Weaning be Initiated? o Liberation from MV in the EARLIEST possible time without compromising the patients safety and recovery is of prime importance to minimize the complications associated with MV and Intubation Weaning: Shifting breathing workload from Machine to Patient Spontaneous Breathing Trials: Testing the patients ability to breath independently B. Weaning is NOT Synonymous with Extubation o Need for Mechanical Ventilation is NOT the same as the Need for Artificial Airway o Weaning Failure: inability to maintain adequate Respiration THROUGH an Artificial Airway o Extubation Failure: inability to maintain adequate Respiration AFTER removal of Artificial Airway
Example: Desired FiO2 = 80 x 21% 50

33

C. Conditions which SHOULD be Met for Weaning o Resolution or Improvement of the cause of Respiratory Failure o Cessation of Sedative Drugs o Cessation of Neuromuscular Blocking Agents o Absence of Sepsis or marked Fever o Stable Cardiovascular Status o Correction of Electrolyte Disorders o Correction of Metabolic Disorders o No planned General Anesthesia o Adequate Gas Exchange o Adequate Respiratory Pump Capacity 1. Objective Measurements Adequate Oxygenation Stable Cardiovascular System (HR < 140; Stable BP; No (or Minimal Pressors) Afebrile (T <380C) No significant Respiratory Acidosis Adequate Hemoglobin (Hgb > 8-10g/dL) Adequate Mentation (arousable, GCS > 13, no continuous sedative infusion) Stable Metabolic Status 2. Subjective Clinical Assessment Resolution of Disease Acute Phase M.D. believes Discontinuation possible Adequate Cough 3. Pulmonary Gas Exchange Minimal PO2 > 60mmHg with: FiO2 < 0.4 with a PEEP level < 5cmH2O PaO2/PAO2 > 0.35 PaO2/FiO2 Ratio > 200 Normal PCO2 or back to Baseline for Chronic retainers with Normal pH 4. Rapid Shallow Breathing Index (RSBI) Overall has the BEST Combination of Sensitivity and Specificity among Weaning Indices Threshold Value >105

RSBI = f (per minute) / VT (in Liters)

D. Methods of Weaning: o T-Piece Weaning (abrupt and simple) o SIMV o Pressure Support Ventilation o Noninvasive Ventilation

34

IV. OXYGEN DELIVERY Low Flow: Nasal Cannula, Face Mask, Reservoir Mask Indications: o PaO2 < 60mmHg or SaO2 < 90% o Acute Situation where Hypoxemia is suspected o Severe Trauma o Acute Myocardial Infarction o Short Term, Post Operative A. Nasal Cannula o FiO2 Increases approximately 2-4% / L o Flowrates >6 lpm do NOT augment the inspired gas o High Flows can dry the Nasal Mucosa o Humidification is recommended for Flow Rates > 4 lpm o Provides 23-45% of O2 o Maximum Flow Rates = 6 lpm B. Simple Masks o Provides 31-61% O2 o Flow Rates = between 5-10 lpm o The reservoir is the space between the mask and the patients face o Higher Potential FiO2 o Less than 5 lpm is NOT recommended o 5 lpm is needed to flush exhaled CO2 from the Mask V. OXYGEN TOXICITY Injury to the Lung Parenchyma and Airway epithelium due to Cytotoxic Free Oxygen Radicals Gas exchange abnormalities occur in 24-48 hours with 100% oxygen FiO2 up to 0.5 for 2-7 days usually does NOT result in Toxicity If needed, an FiO2 of 100% can be used for up to 24 hours WITHOUT significant Lung Injury

35

LABORATORY WORK UPS AND ANTIBIOTICS

1) NORMAL LABORATORY VALUES (PGH VALUES)

CBC Values WBC RBC Hgb Hct MCV MCH MCHC RDW-CV Platelets Neut% Lymph% Mono% Eo% Baso% Pro/Mye/Jv Stabs Blasts Reticulocytes 4-11x109/L 4-6 x 1012/L 120-180 g/L 0.370-0.540 % 80-100 fL 27-31 pg 320-360 g/L 11-16% 150-450 x 109/L 0.5-0.7 0.2-0.5 0.02-0.09 0.0-0.06 0.0-0.02 0 0.02-0.04 0 0.005-0.015 4-11 x 103/mm3 4-6 x 106/mm3 12.0-18.0g/dL BLOOD CHEM Glucose BUN Creatinine Sodium Potassium Chloride Calcium Magnesium Phosphates Total protein Albumin Globulin AST (SGOT) ALT (SGPT) Alk phos Total bilirubin Dir bilirubin Ind bilirubin Urate Amylase Lipase LDH ESR CRP Ammonia RF Cardiac Enzymes CK-total CK-MB CK-MM Troponin I Cut Off for MI Lipid Profile HDL LDL Cholesterol Triglycerides

150-450 x 103/mm3

Thyroid Hormones Free T4 0.8-2.0 ng/dL Free T3 2.3-4.2 pg/dL TSH 0.25-4.30 microunits/mL Serum T3 70-200 ng//dL Serum T4 4.0-11.0 ug/dL ABG pH PCO2 PO2 HCO3 Urinalysis Color Transparency SG PH
Sugar, Albumin

7.35-7.45 35-45 mmHg 90-100 mmHg 22-28 mEq/L

3.9-6.1 mmol/L 2.6-6.4 mmol/L 53-115 umol/L 140-148 mmol/L 3.6-5.2 mmol/L 100-108 mmol/L 2.12-2.52 mmol/L 0.70-1.00 mmol/L 0.9-1.55/0.42-1.97 64-83 g/L 34-50 g/L 23-35 g/L 15-37 U/L 30-65 U/L 36-92 umol/L 0-17.1 umol/L 0 - 5.00 umol/L 3.4-13.7 umol/L 0.13-0.44 mmol/L 30-110 U/L 23-300 U/L 100-190 U/L M: 0-15 mm/h 0.2-3.0 mg/L 19-60 ug/dL < 20 IU/mL

75-110 mg/dL 7-20 mg/dL 0.6 1.3 ng/mL 140-148 mEq/L 3.6-5.2 mEq/L 100-108 mEq/L 8.7-10.2 mg/dL 1.5-2.3 mg/dL 6.4-8.3 g/dL 3.4-5.0 g/dL

0.3-1.3 mg/dL 0.1-0.4 mg/dL 0.2-0.9 mg/dL

F: 0-20 mm/h 11-35 umol/L

RBC WBC Casts Crystals Epith cells Bacteria Mucus thr

Yellow Clear/hazy 1.016-1.022 4.6-6.5 (-) 0/0-2/hpf 0-2/0-5/hpf

hyaline, coarse, fine, granular, waxy

55-170 U/L 0-16 U/L 8-97 U/L 0-0.09 ng/mL > 0.4 ng/mL

0-0.09 ug/L > 0.4 ug/L

Small amounts Small amounts (-) Small amounts

0.91-1.56 mmol/L 1.1-3.8 mmol/L 4.2-5.2 mmol/L 0.41-2.37 mmol/L

35-60 mg/dL 40-145 mg/dL 160-200 mg/dL < 180 mg/dL

HDL or LDL divided by 0.0259 to convert to mg/dL TAG divided by 0.0113 to convert to mg/dL

24 Urine Chemistry Total volume Creatinine Total protein Na+ K+ ClUric acid Ca++ 500-2000 cc 0.65-0.70 g/L 0-0.1 g/24hour 80-216 mmol/L 25-100 mmol/L 80-340 mmol/L 4.42-5.9 mmol/24hr 2.5-7.5 mmol/24hr 8.8-14 mmol/d < 100mg/d Varies with intake

Cancer Markers AFP PSA CA 125 CA 19-9 CEA 0-8.5 ng/L 0-4 ng/mL 0-35 U/mL 0-37 U/mL
(-)Smoker: 0-3 ug/L (+)Smoker: 0-5 ug/L

36

Phosphorus Amylase Microalbumin

22.4-33.6 mmol/24hr 64.75-490.25 U/L N: 0.0-0.03 g/d Microalbuminuria: 0.03-0.30 g/d Clinical Albuminuria: >0.3g/d

37

2) CLINICALLY USEFUL ANTIBIOTICS (from the Blue Book)

DRUG Penicillins Penicillin Oxacillin PO/IV Flucloxacillin Amoxicillin PO, Ampicillin IV Co-Amoxiclav Ampi-Sulbactam Piperacillin / Tazobactam Glycopeptide Vancomycin Monobactams Aztreonam Carbapenems Imipenem-Cilastin Meropenem Ertapenem Macrolides Erythromycin Azithromycin Clarithromycin Dirithromycin Tetracycline Doxycycline Tetracycline Aminoglycosides Amikacin Gentamicin Tobramycin Netilmicin First Generation Cephalosporins Cephalexin PO Cefazolin IV Second Generation Cephalosporins Cefuroxime IV Cefuroxime Axetil PO Cefoxitin Third Generation Cephalosporins Ceftriaxone Ceftazidime Cefotaxime Fourth Generation Cephalosporins Cefepime Cefpirome Quinolones GRAM (+) +++ ++ ++ ++ ++ 1/2 ++ ++ +++ GRAM (-) ++ ++ 1/2 ++ ++ 1/2 ANAEROBES

REMARKS Narrow spectrum penicillins Specifically used for Staphylococcus aureus Broad spectrum penicillin Good anaerobic coverage Good anaerobic coverage Use as reserve drug for Pseudomonas Reserve drug & most active for S.aureus and Enterococcus. Give very slowly as IV infusion Alternate to Aminoglycosides in renal failure Use as reserve drug Gm (+) activity as good as Penicillin For Gm (-): may add Amikacin for Synergism Anaerobic activity as good as Metronidazole Very little activity against pseudomonas May cause GI upset

++ + ++ 1/2 ++ 1/2 + +

+++

+++ +++

+++

++ ++ 1/2 ++ 1/2

+++ + 1/2 ++

+ + + 1/2

++

++

For patients > 8 years old Tetracycline is cheaper, but given QID With Anti-Pseudomonas activity Amikacin with Anti-TB action

+++

+++

++ 1/2 ++ 1/2 ++ ++ ++ ++ +++

++ ++ ++ +++ +++ +++ +++

+ + ++ 1/2 ++ ++ ++ ++

IV drug Oral drug Cephalosporin with best Anaerobic coverage For multidrug resistant Typhoid Ceftazidime is best for Pseudomonas Cefotaxime is best for Meningitis These should be reserved for the very resistant strains

38

Ciprofloxacin Norfloxacin Ofloxacin Fleroxacin Levofloxacin Moxifloxacin Others Co-Trimoxazole Co-Trimazine Chloramphenicol Clindamycin Metronidazole Rifampicin

+++

Used for multidrug resistant Typhoid Fever Ciprofloxacin is best for Pseudomonas Norfloxacin is good for Severe UTI Moxifloxacin with better Anaerobic activity

++

+++

++ 1/2 ++ 1/2 ++ ++

++ 1/2 ++ 1/2 ++

++ 1/2 +++ ++ 1/2 + Drug of choice for Uncomplicated Typhoid Above diaphragm Anaerobes Good Gm(+) Activity Below diaphragm Anaerobes Used for pulmonary tuberculosis

ADDITIONAL NOTES: Drugs with Anti-Pseudomonas Properties: o Aminoglycosides (Tobramycin, Netilmicin, Amikacin, Gentamicin) o Ceftazidime, Cefoperazone, Quinolones (Ciprofloxacin), Ticarcillin and Piperacillin o Monobactams (Aztreonam), Carbapenems (Meropenem) o Fourth Generation Cephalosporins (Cefepime and Cefpirome) Drugs with Good Anaerobic Properties: o Clindamycin o Metronidazole o Chloramphenicol Cefoxitin Meropenem Ampicillin-Sulbactam Amoxycillin-Clavulanic Acid High Dose Penicillin

Drugs with Good Central Nervous System (CNS) Penetration in Meningitis: o Ceftriaxone Ampicillin Penicillin-G o Ceftazidime Meropenem Vancomycin o Cefuroxime Ampicillin-Sulbactam o Cefotaxime Ciprofloxacin o Chloramphenicol and Co-Trimoxazole have high diffusion to the CSF even WITHOUT Meningitis Drugs safe for patients with Liver Disease: o Aminoglycosides o Ampicillin o Amoxicillin o Cephalexin o Cefoxitin o Cefuroxime o Ofloxacin o Penicillin-G o Carbapenems

39

On Cephalosporins o 4th Generation Cephalosporins have the same indications as 3rd Generation Cephalosporins and should remain as reserved drugs o The only two Third Generation Cephalosporins active against Pseudomonas are Ceftazidime and Cefoperazone. Cefaperazone may cause bleeding in predisposed patients o Cephalosporins that cross the Blood-Brain Barrier: Ceftriaxone, Ceftazidime, Cefotaxime, Ceftizoxime o Cephalosporins with Best Anaerobic Coverage: CEFOXITIN. Other Cephalosporins also have some Anaerobic properties o Cefuroxime Axetil is given with Meals o Cefazolin is the Drug of Choice ONLY for Surgical Prophylaxis of abdominal operations & implant surgery On Aminoglycosides: o Aminoglycosides are given q 8-12 hours in 30 minutes by Slow IV or IM to avoid possible neuromuscular paralysis. They must have loading doses, and should be given for < 7 days to avoid Nephrotoxicity. Creatinine is measured every 3 days. o Amikacin: Expensive but it is the most potent and least nephrotoxic Loading Dose = 7.5mg/kg Maintenance Dose = 15mg/kg/day in 2 divided doses IM, IV o Gentamicin, Tobramicin, Netilmycin Loading Dose = 2mg/kg Maintenance Dose = 1.5mg/kg/dose q 8hours IM, IV o Gentamicin is the cheapest aminoglycoside. Spectinomycin is used for Gonorrhea. Streptomycin is used for PTB On Macrolides o Erithromycin is given with meals. If with GI upset, lower the dose o Azithromycin is given 1 hour before meals Rifampicin o Aside from Anti-TB properties, Rifampicin may be used synergistically with Oxacillin for S.aureus o Resistance may develop easily when Rifampicin is used alone

NOTES ON ANTIBIOTICS 1. Methicillin Resistant Staphylococcus aureus (MRSA) Give Vancomycin, then shift to Oral Zivox (?) when MGH General Rule: o If (+) with Bacteremia: 14 days o If (+) Solid Organ Abscess: 4-6 weeks 2. Two Organisms NOT Targeted by Cephalosporins Enterococcus Listeria monocytogenes 3. Ceftriaxone Doses (double check): 2g OD = usual dose 2.5g OD = Gonorrhea 3g OD = Typhoid 2g BID = Meningitis 4. Some Antibiotics to Target Pseudomonas Ceftazidime Piperacillin-Tazobactam Carbapenems (Meropenem) EXCEPT Ertapenem 5. Anaerobic Coverage (ex. If Pneumonia has + Aspiration) Clindamycin Metronidazole 6. HLARE High Level Aminoglycoside Resistance Enterococcus Mx: Vancomycin 7. ESBL Extended Spectrum Beta Lactamases Mx: Carbapenems **NOTE: Use Penicillins, Ampicillin

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qwertyuiopasdfghjklzxcvbnmqwertyui opasdfghjklzxcvbnmqwertyuiopasdfgh jklzxcvbnmqwertyuiopasdfghjklzxcvb nmqwertyuiopasdfghjklzxcvbnmqwer CARDIOLOGY tyuiopasdfghjklzxcvbnmqwertyuiopas dfghjklzxcvbnmqwertyuiopasdfghjklzx cvbnmqwertyuiopasdfghjklzxcvbnmq wertyuiopasdfghjklzxcvbnmqwertyuio pasdfghjklzxcvbnmqwertyuiopasdfghj klzxcvbnmqwertyuiopasdfghjklzxcvbn mqwertyuiopasdfghjklzxcvbnmqwerty uiopasdfghjklzxcvbnmqwertyuiopasdf ghjklzxcvbnmqwertyuiopasdfghjklzxc vbnmqwertyuiopasdfghjklzxcvbnmrty uiopasdfghjklzxcvbnmqwertyuiopasdf ghjklzxcvbnmqwertyuiopasdfghjklzxc vbnmqwertyuiopasdfghjklzxcvbnmqw ertyuiopasdfghjklzxcvbnmqwertyuiop
Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

CONGESTIVE HEART FAILURE

CONGESTIVE HEART FAILURE

Heart Failure is a clinical syndrome that occurs in patients who, because of an inherited or acquired abnormality of cardiac structure and/or function, develop a constellation of clinical symptoms (dyspnea & fatigue) and signs (edema and rales) that lead to frequent hospitalizations, a poor quality of life, and a shortened life expectancy

Categorized into TWO Groups: o Systolic Failure: HF with a Depressed Ejection Fraction o Diastolic Failure: HF with a Preserved Ejection Fraction Compensatory Mechanisms Activated in the Presence of Cardiac Injury and/or LV Dysfunction: o 1) Activation of the Renin-Angiotensin-Aldosterone (RAA) and Adrenergic Nervous Systems, which are responsible for maintaining Cardiac Output through increased retention of salt and water o 2) Increased Myocardial Contractility LV Remodeling Changes:
o o o o o Myocyte Hypertrophy Alterations in the Contractile Properties of the Myocyte Progressive Loss of Myocytes through Necrosis, Apoptosis, and Autophagic Cell Death B-Adrenergic Desensitization Abnormal Myocardial Energetics and Metabolism Reorganization of the Extracellular Matrix with dissolution of the organized structural collagen weave and subsequent replacement by an interstitial collagen matrix that does not provide structural support to the myocytes

I. FRAMINGHAM CRITERIA FOR DIAGNOSIS OF CONGESTIVE HEART FAILURE A. Major Criteria o Paroxysmal Nocturnal Dyspnea P-R-I-N-C-E-S-P o Neck Vein Distention o Rales o Cardiomegaly o Acute Pulmonary Edema 1 Major + 2 o S3 Gallop o Increased Venous Pressure (>16cmH2O) o Positive Hepatojugular Reflux

Minor Criteria

B. Minor Criteria o Extremity Edema D-P-V-T-H-E-N (the private hen) o Night Cough o Dyspnea on Exertion o Hepatomegaly o Pleural Effusion o Vital Capacity reduced by 1/3 from Normal o Tachycardia (>120bpm) C. Major or Minor o Weight Loss 4.5kg over 5 days Treatment

II. NYHA CLASSIFICATION OF CHF

FUNCTIONAL CLASS DESCRIPTION Dyspnea occurs with Greater than Ordinary Physical Activity Dyspnea occurs with Ordinary Physical Activity Dyspnea occurs with Less than Ordinary Physical Activity Dyspnea may be present even at Rest GENERAL GUIDE
Climbs > 2 flights of stairs with Ease Can climb 2 flights of stairs but with difficulty Can climb < 1 flight of stairs Dyspnea at rest

I II III IV

III. CANADIAN CARDIOVASCULAR SOCIETY CLASSIFICATION OF ANGINA

FUNCTIONAL CLASS I II III IV DESCRIPTION Angina occurs with Greater than Ordinary Physical Activity Angina occurs with Ordinary Physical Activity Angina occurs with LESS than ordinary Physical Activity Angina may be present even at REST

IV. CLUES SUGGESTING DIGITALIS TOXICITY Digitalis glycosides are given to enhance myocardial performance in situations of chronic heart failure as well as to control many Supraventricular Dysrhythmias NORMAL Serum Levels of Digoxin may produce subtle alterations in ECG called the Digitalis Effect
A. Toxic Levels are associated with: o Potentially Life-Threatening Dysrhythmias o Heart Blocks o Etc
Digitalis preparations have a narrow therapeutic range, so maintaining the desirable serum level of the drug is difficult. HYPOKALEMIA, a common side effect of diuretic therapy, POTENTIATES the Toxic Effects of Digitalis. Antidysrhythmic agents such as Quinidine and Amiodarone, as well

B. Clues PE Suggesting Digitalis Toxicity as Verapamil, are known to Increase Serum Digoxin Level o Change in visualization o Interruption in conduction system (bradycardia, branch blocks) C. ECG Manifestations of the Dig Effect Include:
o o o o o

Depressed ST-Segments in leads where the main QRS Deflection is Positive (eg. In the inferior and lateral leads); the STSegments gradually slope downward and look scooped out Elevated ST-Segments in leads where the main QRS Deflection is Negative (eg. Lead V1) Flattened or Inverted T-Waves Shortened QT Interval Prolongation of the PR-Interval compared with a Pretreatment Baseline; the PR Interval often lengthens by 0.04 to 0.08 seconds (or more)

D. ECG Manifestations of Digitalis Toxicity include: o The same ST-Segment and T-Wave changes noted with the Dig Effect o Significant Prolongation of the PR-Interval o Supraventricular Dysrhythmias
Extreme Sinus Bradycardia Atrial Premature Complexes (APCs) Sinoatrial (SA) Block Junctional Premature Complexes (JPCs) Junctional Escape Rhythm Accelerated Junctional Rhythm Junctional Tachycardia Atrial Tachycardia with AV Block Ventricular Premature Complexes (VPCs) Ventricular Bigeminy Ventricular Tachycardia (VT) Ventricular Fibrillation Atrial Tachycardia with AV Block Second Degree AV Block Type I Third Degree AV Block Bidirectional VT (alternating Polarity of the QRS Complex) is associated with Poor Prognosis

Ventricular Dysrhythmias

Atrioventricular (AV) Block

o o o o

E. Treatment of Digitalis TOXICITY

Withholding further Digoxin Potassium Replacement Therapy (carefully AVOID Hypokalemia) Digoxin Antibody Fragments (Digoxin Immune Fab) Temporary Pacing Diphenylhydantoin (for treatment of Digitalis-Induced Ventricular Dysrhythmias)

V. SOME SIGNS AND SYMPTOMS OF CHF Cardinal Symptoms of HF: Fatigue and Shortness of Breath In early stages, DYSPNEA is observed only during exertion Origin of Dyspnea = Multifactorial (Most Important: Pulmonary Congestion) A. Orthopnea o Dyspnea occurring in the RECUMBENT position (later manifestation of HF than is exertional dyspnea) o Nocturnal Cough: frequent manifestation of this process o Relieved by sitting upright or by sleeping with additional pillows B. Paroxysmal Nocturnal Dyspnea o Acute episodes of severe shortness of breath and coughing that generally occur at night and awaken the patient from sleep, usually 1-3 hours after patient retires o Cardiac Asthma: wheezing secondary to bronchospasm C. Cheyne-Stokes Respiration o Also referred to as Periodic Respiration or Cyclic Respiration o Common in advanced HF and is associated with Low Cardiac Output o Caused by a diminished sensitivity of the respiratory center to Arterial PCO 2 o There is an Apneic Phase, during which the arterial PO2 Falls and PCO2 Rises o These changes in the arterial blood gas content stimulate the depressed respiratory center, resulting in Hyperventilation and Hypocapnia, followed in turn by recurrence of Apnea D. Jugular Venous Pressure (JVP) o Estimation of the Right Atrial Pressure o Two main objectives of the examination of the neck veins are inspection of their waveform and estimation of the central venous pressure (CVP) o Right Internal Jugular Vein is best for this purpose o Vertical distance between the top of the oscillating venous column and the level of the sternal angle is determined generally, it is Less than 3cm (3cm + 5cm = 8cm blood) o Most Common cause of a high venous pressure is an Elevated Right Ventricular Diastolic Pressure **IMPORTANT Notes: CVP = pressure within the right atrium CVP is equal to [JVP + 5] E. Abdominojugular Reflux o Done in patients suspected of having right ventricular failure who have normal CVP at rest o Palm of examiners hand is placed over the abdomen, and firm pressure is applied for 10s or more o Normal Persons: maneuver does NOT alter the JVP significantly o Right Heart Function Impaired: Upper Level of venous pulsation usually INCREASES o Definition of a Positive Abdominojugular Test: An increase in JVP during 10s of firm midabdominal compression followed by a rapid drop in pressure of 4cm blood on release of the compression F. Cardiac Examination o An S3 (Protodiastolic Gallop) is most commonly present in patients with Volume Overload who have Tachycardia and Tachypnea, and often signifies Severe Hemodynamic Compromise o An S4 is NOT a specific indicator for HF, but is usually present in patients with Diastolic Dysfunction Nice to Know: Water-bottle Sign = Pericardial Effusion Electrolytes that can cause arrhythmias = Potassium, Calcium, Magnesium Kussmauls Sign An increase, rather than the normal decrease, in CVP during INSPIRATION Most often caused by Severe Right Sided Heart Failure Frequent finding in patients with Constrictive Pericarditis or Right Ventricular Infarction Mitral Stenosis Normal Mitral Valve Orifice = 4-6cm2 Threshold for Surgical management of Mitral Valve Stenosis < 1.7cm2

VI. TREATMENT FOR HEART FAILURE (Triple Therapy Dr. Abarquez) Diuretics (Spironolactone: Diuretic of choice because it also blocks aldosterone) ACE Inhibitors / ARBS Caution in use of Beta-Blockers = may push patient into further congestion Digoxin Management of HF with DEPRESSED Ejection Fraction (<40%) 1. General Measures / Activity / Diet o Modest exercise o Salt Restriction (2-3g daily) o Fluid restriction (<2L/day) if with (+) Hyponatremia or difficult to control fluid retention despite high doses of diuretics and Na+ Restriction 2. Pharmacologic Management o Diuretics (only agents that can adequately control fluid retention in advanced HF) o Preventing Disease Progression ACE Inhibitors B-blockers Effects of Digitalis (Dr. Abarquez Lecture) o Inotropy o Lusitropy (attenuates Growth and Collagen Factor) o Neurogenic o Preload & Afterload o Vagotonic o Less Apoptosis (has Anti-Apoptotic Events)

VII. OTHER SIDE NOTES: A. Some Trials on Congestive Heart Failure o RALES: Randomized Aldactone Evaluation Study (Benefits of Spironolactone) o VHeFT: Vasodilators in Heart Failure B. Effects of Anti-Hypertensives: o Enalapril = Preload and Afterload o Hydralazine = Afterload o ISDN = Preload C. Note on HDL VS LDL o If Decreased HDL but NORMAL LDL = we may give Fibrates to Increase HDL o If LDL is Increased, we must address the LDL first!
**CONVERSION Factor: HDL or LDL divided by 0.0259 to convert to mg/dL TAG divided by 0.0113 convert to mg/dL

HYPERTENSION (from Harrisons)

CLASSIFICATION Normal Pre-Hypertension Stage 1 Hypertension Stage 2 Hypertension Isolated Systolic Hypertension SYSTOLIC (mmHg) < 120 120 139 140 159 > 160 > 140 DIASTOLIC (mmHg) And < 80 Or 80 89 Or 90 99 Or > 100 And < 90

Clues for Secondary Hypertension: o Age of Onset < 20 or > 50 o (-) Family History o DBP > 110 120 o Sudden Increase in BP in a patient with Stable Stage I HPN o Poor BP Control, despite Good Compliance A. Hypertensive Urgency o Use ORAL Drugs first o ALA Hypertensive Crisis o Uncontrolled HPN with NO End-Organ Damage o Lower BP within 24 hours B. Hypertensive Emergency o Use IV Medications, stat o AKA Malignant Hypertension o WITH End Organ Damage (Papilledema, Encephalopathy, Eclampsia, etc) o Lower BP within 1 Hour

C. Treatment of Hypertensive Urgency / Emergency (Medicine Notes) 1. Oral / Sublingual

Nifedipine Captopril Clonidine 5-10 mg SL q30 mins, then 5-10mg PO or SL q6-8hours; OR 30mg/tab PO OD-BID (max 90mg/day) 25 mg/tab 1/2-1 tab SL q30 mins 75 mcg/tab SL q1 (max 700mcg) Initial 5mg/h; titrate by 2.5 mg/h at 5-15 min intervals Max: 15mg/h 5-10mg IV q3-6 hours (0.1-0.5mg/kg/dose, max 20mg/dose) Duration: 3-6 hours Especially for patients with concomitant CAD 1 amp (150mcg/amp) SC, IM or IV with patient supine Initial 0.3 ug/kg/min; usual 2-4 ug/kg/min; Max 10 ug/kg/min for 10mins

2. IV
Nicardipine IV Hydralazine ISDN IV Clonidine Nitroprusside IV

Stages in the Evolution of Heart Failure (Recommended Therapy by Stage): STAGE A

At risk for heart failure, but without structural heart disease or symptoms of HF Patients with HPN, CAD, DM Or Patients using Cardiotoxins with FHx CM

STAGE B
Structural Heart Disease but without Symptoms of HF Patients with previous MI, LV Systolic Dysfunction, Asymptomatic Valvular Disease

STAGE C
Structural Heart Disease with Prior Current Symptoms of HF Patients with known Structural Heart Disease, Shortness of Breath and Fatigue, Reduced Exercise Tolerance

STAGE D
Refractory HF requiring Specialized Interventions Patients who have marked Symptoms at rest despite maximal therapy (eg. Those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions)

Structural Heart Disease Therapy: Treat HPN Encourage smoking cessation Treat Lipid D/O Encourage regular exercise Discourage Alcohol Intake, Illicit Drug use ACE Inhibition

Symptoms of HF Develop

Refractory Symptoms of HF at Rest Therapy: All measures under Stage A, B, and C Mechanical assist devices Heart Transplant Continuous (not intermittent) IV Inotropic Infusions for Palliation Hospice Care

Therapy: All measures under Stage-A ACE Inhibitors in appropriate patients Beta-Blockers

Therapy: All Measures under Stage-A Drugs (Routine Use): -Diuretics -ACE Inhibitors -Beta-Blockers -Digitalis -Dietary Salt Restriction

ISCHEMIC HEART DISEASE

ISCHEMIC HEART DISEASE

Condition in which there is an Inadequate supply of blood and oxygen to a portion of the Myocardium IMBALANCE between Myocardial Oxygen Supply and Demand Most Common Cause: Atherosclerotic Disease of an Epicardial Coronary Artery sufficient to cause a regional reduction in Myocardial Blood Flow and inadequate perfusion of the Myocardium supplied by involved artery Obesity, Insulin Resistance, and T2DM are increasing and powerful risk factors for IHD

Patients with IHD fall into Two Large Groups: o 1) Patients with Chronic Coronary Disease (CAD) who most commonly present with Stable Angina o 2) Patients with Acute Coronary Syndromes Acute Coronary Syndromes is Composed of: o Unstable Angina and Non-ST-Segment Elevation MI o Acute Myocardial Infarction (MI) with ST-Elevation I. STABLE ANGINA PECTORIS This episodic clinical syndrome is due to TRANSIENT Myocardial Ischemia Males: 70% of all patients with angina pectoris Typical History: Man older than 50y/o or Woman older than 60y/o who complains of chest discomfort usually described as heaviness, pressure, squeezing, smothering, or choking, and only rarely as frank pain Levines Sign: Hand placed over sternum with a clenched fist, to indicate a squeezing, central, substernal discomfort A. Clinical Presentation o Angina is usually crescendo-decresendo in nature, typically lasts 2-5 minutes, and can radiate to either shoulder and to both arms o Does NOT radiate to Trapezius Muscles (such a radiation pattern is more typical of Pericarditis) o Episodes of Angina typically caused by Exertion or Emotion, Relieved by Rest and Sublingual Nitroglycerin B. Electrocardiogram (ECG) o May be NORMAL (at rest) o ST-Segment and T-Wave changes as well as LV hypertrophy and intraventricular conduction disturbances are suggestive of IHD, they are non specific since they can also occur in Pericardial, Myocardial and Valvular Heart Disease C. Stress Testing o Most widely used for both Diagnosis of IHD and estimating prognosis involves recording the 12-Lead ECG before, during and after exercise

II. MANAGEMENT OF STABLE ANGINA PECTORIS 1) Explanation of he Problem and reassurance about the ability to formulate a Treatment Plan 2) Identification & Treatment of aggravating conditions 3) Recommendations for adaptation of Activity as needed 4) Treatment of Risk Factors that will decrease occurrence of Adverse Coronary Outcomes 5) Drug Therapy for Angina 6) Consideration of Revascularization A. Dyslipidemia o Treatment of Dyslipidemia is Central when aiming for Long-Term Relief from Angina, reduced need for Revascularization, and reduction in MI and death o HMG-CoA Reductase Inhibitors (Statins): can lower LDL Cholesterol (25-50%), raise HDL Cholesterol, and Lower Triglycerides B. Pharmacologic Treatment 1. Drug Therapy
Nitrates Systemic Venodilation with concomitant reduction in LV End Diastolic Volume and Pressure, thereby reducing Myocardial Wall Tension and O2 Requirements Dilation of Epicardial Coronary Vessels Increased Blood Flow in Collateral Vessels Long Acting Nitrates B-Adrenergic Blockers Ca+ Channel Blockers None of the Long Acting Nitrates is as effective as Sublingual Nitroglycerin for the Acute Relief of Angina Reduce Myocardial O2 Demand by inhibiting the increases in HR, arterial pressure, and myocardial contractility caused by Adrenergic Activation Coronary Vasodilators that produce variable and dose dependent reductions in Myocardial O2 Demand, Contractility, and Arterial Pressure

**NOTE Beta-Blockers VS Ca2+ Channel Blockers Beta Blockers have been shown to improve Live Expectancy following Acute MI (Ca+ Channel Blockers have not) Ca2+ Channel Blockers are indicated in patients with: Inadequate responsiveness to the combination of B-Blockers & Nitrates Adverse Reactions to B-Blockers (depression, fatigue, sexual) Angina and history of Asthma or COPD Sick Sinus Syndrome or significant AV Conduction Disturbances Prinzmetals Angina Sympomatic Peripheral Arterial Disease 2. Anti-Platelet Drugs
Aspirin Clopidrogel Irreversible Inhibitor of Platelet Cyclo-Oxygenase Activity, therefore interferes with Platelet Activation. Chronic administration of 75 to 325mg PO per day has been shown to reduce coronary events. Oral Agent that blocks ADP Receptor Mediated Platelet Aggregation

3. Other Therapies: ACE-Inhibitors Ranolazine **NOTE: NSAIDS should be AVOIDED! C. Coronary Revascularization
Percutaneous Coronary Intervention (PCI) Coronary Artery Bypass Grafting (CABG) Involves Balloon Dilatation usually accompanied by Coronary Stenting. Most common indication for PCI is Angina Pectoris, despite medical therapy, accompanied by evidence of Ischemia during a Stress Test For those with Three-Vessel IHD, Stenosis of the Left Main Coronary Artery

UNSTABLE ANGINA & NSTEMI

Unstable Angina Angina Pectoris with at least ONE of THREE Features: o 1) Occurs at rest or with Minimal Exertion lasting > 10 minutes o 2) Severe and of New Onset o 3) Occurs with a Crescendo Pattern Non-ST-Elevation Myocardial Infarction (NSTEMI) Clinical Features of Unstable Angina (UA) develops evidence of Myocardial Necrosis as reflected by Elevated Cardiac Enzymes Clinical Features: o Chest Pain radiating to the Neck, Left Shoulder, and Left Arm o Dyspnea o Diaphoresis, Pale Cool Skin, Sinus Tachycardia, S3 or S4, Basilar Rales, Hypotension Criteria to Document AMI 1) Chest Pain 2) ECG Changes 3) Cardiac Enzymes

I. DEFINITION OF TERMS: A. Unstable Angina o STABLE Angina Pectoris is characterized by Chest or Arm Discomfort that may NOT be described as pain, but is reproducibly associated with Physical Exertion or Stress, and is RELIEVED within 5-10 minutes by REST and/or Sublingual Nitroglycerin o UNSTABLE ANGINA is defined as Angina Pectoris or Equivalent Ischemic Discomfort with at least ONE of the Three Features: 1) Occurs at Rest (or with minimal exertion), usually lasting > 10 Minutes 2) It is Severe and of New Onset (ie. Within the prior 4-6 weeks) 3) Occurs with a Crescendo Pattern (ie. Distinctly more Severe, Prolonged, or frequent than previously) B. Non-ST-Elevation Myocardial Infarction (NSTEMI) o Clinical Features of Unstable Angina (UA) + evidence of Myocardial Necrosis as reflected in Elevated Cardiac Biomarkers II. PATHOPHYSIOLOGY (Four Pathophysiologic Processes) 1) Plaque Rupture or Erosion with Superimposed Nonocclusive Thrombus (Most Common Cause) 2) Dynamic Obstruction (eg. Coronary Spasm as in Prinzmetals Variant Angina) 3) Progressive Mechanical Obstruction 4) Secondary UA related to Increased Myocardial O2 Demand and/or Decreased Supply (eg. Tachycardia, Anemia) III. CLINICAL PRESENTATION Clinical Hallmark: CHEST PAIN substernal region or sometimes epigastrium, radiates to neck, left shoulder, and left arm, severe enough to be considered painful Anginal Equivalents: Dyspnea, Epigastric Discomfort PE: Unremarkable, or if (+) Large Area of Myocardial Ischemia or a Large NSTEMI: o Diaphoresis o Pale cool skin o Sinus tachycardia o 3rd & 4th heart sound o Basilar rales o Hypotension

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IV. DIAGNOSIS A. ECG o ST-Segment Depression o Transient ST-Segment Elevation o T-Wave Inversion

In patients with clinical features of UA, the presence of New ST-Segment Deviation, even of only 0.05 mV, is an important predictor of adverse outcome. T-Wave changes are sensitive for Ischemia but less specific, unless they are New, Deep T-Wave Inversions (> 0.3mV)

B. Cardiac Biomarkers o Patients with UA who have elevated Biomarkers of Necrosis such as CKMB and Troponin (a much more specific and sensitive marker of Myocardial Necrosis) are at INCREASED Risk for Death or Recurrent MI o Elevated Levels of these markers distinguish patients with NSTEMI from those with UA
There is a direct relationship between the degree of Troponin Elevation and Mortality. However, in patients WITHOUT a clear clinical history of Myocardial Ischemia, MINOR Troponin Elevations have been reported and can be caused by Congestive Heart Failure, Myocarditis, or Pulmonary Embolism, or they may be False Positive Readings. Thus, in patients with an UNCLEAR History, Small Troponin Elevations may NOT be diagnostic of an ACS

V. DIAGNOSTIC PATHWAYS
Four major diagnostic tools are used in the Diagnosis of UA/NSTEMI in the Emergency Department: History + ECG + Cardiac Markers + Stress Testing. Goals are to: Recognize or exclude MI (using Cardiac Markers) Evaluate for Rest Ischemia (Chest Pain at rest, serial, or continuous ECGs) Evaluate for significant CAD (using provocative stress testing) First step is to assess the likelihood of Coronary Artery Disease. Patients at high or intermediate likelihood are admitted to the hospital. Those with clearly atypical chest pain are sent home. Patients with a Low Likelihood of Ischemia enter the pathway and are observed in a monitored bed in the ED observation unit over a period of 6 hours, and 12-Lead ECGs are performed if the patient has recurrent chest discomfort. A panel of Cardiac Markers (eg, Troponin, CKMB) is drawn at baseline and 6 hours later. If patient develops recurrent pain, has ST-Segment or T-Wave Changes, or has Positive Cardiac Markers, he is admitted to the hospital and treated for UA/NSTEMI. If patient has negative markers and no recurrence of pain, he is sent for exercise treadmill testing, with imaging reserved for patients with abnormal baseline ECG. If positive, patient is admitted.

QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.

DIFFERENTIALS FOR CHEST PAIN:

Could the Chest Pain be due to an Acute, Potentially Life-Threatening Condition that warrants Immediate Hospitalization? o Acute Ischemic Heart Disease o Aortic Dissection o Pulmonary Embolism o Spontaneous Pneumothorax If Not, could it be due to a Chronic condition likely to lead to Serious Complications? o Stable Angina o Aortic Stenosis o Pulmonary Hypertension If Not, could the Discomfort be due to an Acute Condition that Warrants Specific Treatment? o Pericarditis o Pneumonitis / Pleuritis o Herpes Zoster If Not, could the Discomfort be due to another Treatable Chronic Condition? o Esophageal Reflux Esophageal Spasm o Peptic Ulcer Disease Gallbladder Disease o Other GI Conditions Cervical Disk Disease o Arthritis of the Shoulder or Spine Costochondritis o Musculoskeletal Disorders Anxiety State

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VI. MANAGEMENT OF UA/NSTEMI A. Medical Treatment o Bed rest with continuous ECG monitoring for ST-Segment Deviation and cardiac rhythm o Ambulation is permitted if patient shows NO recurrence of ischemia and does NOT develop a biomarker necrosis for 12-24 hours o Medical Therapy: Simultaneous Anti-Ischemic Treatment + Antithrombotic Treatment
DRUG CATEGORY Nitrates CLINICAL CONDITION Administer IV when symptoms are not fully relieved with three sublingual nitroglycerin tablets and initiation of beta blocker therapy Unstable Angina WHEN TO AVOID Hypotension Patient receiving Sildenafil or other PDE 5 Inhibitor PR Interval (ECG) > 0.24s 20 or 30 Atrioventricular Block Heart Rate < 60bpm BP < 90mmHg Shock LV Failure with CHF Severe Reactive Airway Disease Pulmonary Edema Evidence of LV Dysfunction (for Diltiazem or Verapamil) Hypotension Respiratory Depression Confusion Obtundation

Beta Blockers

Ca2+ Channel Blockers

Patients whose symptoms are not relieved by adequate doses of nitrates and Beta Blockers or in patients unable to tolerate adequate doses of one or both of these agents or in patients with variant angina Patients whose symptoms are not relieved after three serial sublingual nitroglycerin tablets or whose symptoms recur with adequate anti ischemic therapy

Morphine Sulfate

B. Anti-Ischemic Treatment o Bed Rest o Nitrates o Beta Blockers

Aspirin Clopidogrel

D. Anticoagulation Therapy Unfractionated Heparin (Mainstay) LMWH Enoxaprin

C. Anti-Thrombotic Therapy E. Invasive VS Conservative Strategy o High Risk Patients (Multiple Risk Factors): ST-Segment Deviation and/or (+) Biomarkers o Class I Recommendations for Use of an Early Invasive Strategy: Recurrent Angina at rest / low level activity despite Rx Elevated TnT or TnI New- ST-Segment Depression Recurrent Angina / Ischemia with CHF symptoms, rales, MR Positive Stress Test In this strategy, following treatment with Anti-Ischemic and Anti-Thrombotic EF < 0.40 Agents, Coronary Arteriography is carried out within ~48 hours of admission, Decreased BP followed by Coronary Revascularization (PCI or Coronary Artery Bypass Sustained VT Grafting), depending on the coronary anatomy) PCI < 6 months, prior CABG VII. LONG TERM MANAGEMENT Risk Factor Modification Long Term Tx with Five Classes of Drugs have been shown beneficial: o Beta Blockers (anti-ischemic tx & reduce triggers for MI) o Statins (long-term plaque stabilization) o ACE Inhibitors (long-term plaque stabilization) o Antiplatelet Therapy (Aspirin + Clopidrogel for at least 9-12 months) VIII. PRINZMETALS VARIANT ANGINA Ischemic Pain that occurs at rest, but NOT usually with exertion, and is associated with Transient ST-Segment Elevation (due to Focal Spasm of an Epicardial Coronary Artery) Diagnostic Hallmark: Transient Coronary Spasm on Coronary Angiography

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ACUTE MYOCARDIAL INFARCTION

I. CLINICAL PICTURE PAIN: Most Common Presenting complaint in patients with STEMI (heavy, squeezing, crushing) Similar to Angina, but occurs at REST, usually more Severe, and Lasts Longer, does NOT subside with cessation of activity (in contrast to angina pectoris) A. Physical Findings: o Anxious, restless, pallor, diaphoresis o Anterior Infarction: Tachycardia + Hypertension o Inferior Infarction: Bradycardia + Hypotension o Precordium is usually quiet, dyskinetic bulging (in anterior infarct), 4th and 3rd Heart Sounds, pericardial friction rub (transmural STEMI) B. Temporal Stages of MI o Acute (first few hours 7 days) o Healing (7 28 days) o Healed (> 29 days) II. LABORATORY TESTS IN CONFIRMING THE DIAGNOSIS: ECG Serum Cardiac Biomarkers Cardiac Imaging Non-Specific Indices of Tissue Necrosis and Inflammation A. Electrocardiogram o Initial Stage: Total Occlusion of an Epicardial Coronary Artery produces ST-Segment Elevation o Most patients initially presenting with ST-Segment Elevation ultimately evolve Q Waves

ECG Findings (from Medicine Notes): INTERPRETATION Hyperacute Acute MI Recent MI Undetermined Old MI Q WAVE (-) (-/+) (++) (++) (++) ST ELEVATION (-/+) (++) (++) (-) (-) T WAVE Peaked (-/+) Inverted Inverted Upright TIMING 0 6 hours 6 24 hours 24 72 hours 72 hrs 6 wks > 6 wks

B. Molecular Markers in the Diagnosis of AMI (Blue Book) TESTS TIME TO PEAK DURATION DETECTION
Troponin-T Troponin-I CK-MB 3-12 hrs 3-12 hrs 3-12 hrs 24 hours 24 hours 24 hours 5-14 days 5-10 days 2-3 days

MOST COMMON SAMPLING SCHEDULE

Once at least 12 hrs after chest pain Once at least 12 hrs after chest pain Every 12 hrs x 3; Start at 6 hrs after chest pain

Cardiac-Specific Troponin T and Troponin I: Have amino acid sequences different from those of the skeletal muscle forms; Highly Specific Increase after STEMI to levels > 20 times higher Preferred Biochemical Markers for MI Remain elevated for 7-10 days after STEMI
QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.

Creatine Phosphokinase (CK) Rises within 4-8 hours and returns to normal by 48-72 h An important drawback of Total CK measurement is its lack of Specificity for STEMI May be elevated with Skeletal Muscle Disease or Trauma, including IM Injection MB Isoenzyme of CK has advantage over Total CK that is not present in significant concentration in extracardiac tissue & therefore is more specific CKMB Mass: CK Activity > 2.5 suggests, but is NOT diagnostic of a Myocardial rather than a Skeletal Muscle Source for the CKMB Elevation

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III. CASE: 57/M CC: Chest Heaviness HPI: Chest heaviness, 5/10, squeezing, diffuse, midsternum, sudden, with exertion, relieved by rest, radiating Persistence of chest heaviness, 10/10, diaphoresis, shortness of breath PMHx: PTB (1998), treated; (-) HPN, DM Social: Smoker, occasional alcoholic Pertinents in the History: o Duration of his initial chest pain = 10 minutes (relieved by rest) o Duration of his second chest pain = 10 minutes (not relieved by rest) Pertinents in the Physical Exam: o Crackles, bilateral to mid o Apex beat at the 6th ICS MCL; (-) S3/S4 Initial Management and Labs o ECG revealed ST Elevation on Leads II, III, AvF (Inferior Wall Infarct) o Aspirin, Streptokinase o Initial Assessment: Acute Coronary Syndrome **QUESTION: Why are patients with Inferior Wall MI prone to Hypotension? o In 90% of patients, the Inferior Wall is supplied by the Right Coronary Artery, which also supplies the SA-Node Hypotension IV. KILLIPs CLASSIFICATION OF AMI CLASS Class I DESCRIPTION RISK OF MORTALITY (Blue Book) 0-5% Risk Mortality

No Signs of Pulmonary or Venous Congestion (0-5% Mortality Rate) No Rales Normal Blood Pressure Moderate Heart Failure (+) Rales at the Lung Bases Normal Blood Pressure with Basal Congestion S3-Gallop Tachypnea or Signs of Right-Sided Heart Failure (Venous & Hepatic Congestion) Severe Heart Failure (+) Midbasal Rales (+) S3 and S4 Normal Blood Pressure Pulmonary Edema Shock with Systolic Pressure < 90mmHg & evidence of Peripheral Vasoconstriction Peripheral Cyanosis Mental Confusion and Oliguria Pulmonary Congestion Hypotension; Cardiogenic Shock

Class II

10-20% Mortality Rate

Class III

35-45% Mortality Rate

Class IV

85-95% Mortality Rate

V. CONTRAINDICATIONS TO GIVING BETA-BLOCKERS (METOPROLOL) Low Cardiac Output State Evidence of CHF Hypotension AV Conduction Block (Relative Contraindication) Asthma, etc **NOTE: In Patients with 1st-Degree AV-Blocks (Relative Contraindication): o Look at PR Interval (Cut-Off is > 0.20s) o We can give Metoprolol if PR < 0.24s o We CANNOT give Metoprolol if PR > 0.24s

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VI. INITIAL MANAGEMENT A. PreHospital Care: 1. Prognosis in STEMI is largely related to the occurrence of general classes of complications:

Electrical Complications (Arrhythmias) Mechanical Complications (Pump Failure)

**NOTE: Most Out-of-Hospital Deaths from STEMI = due to Sudden Ventricular Fibrillation Vast majority of deaths due to V-Fib occur within 24 hours of the onset of symptoms (over half occur in the 1st hour) 2. Major Elements of Prehospital Care:
Recognition of symptoms Rapid deployment of an emergency medical team capable of performing resuscitative maneuvers Expeditious transportation Expeditious implementation of reperfusion therapy

B. Management in the Emergency Department o ASPIRIN: rapid action is achieved by chewing 160-325mg tablet, then followed by daily administration of Aspirin in a dose of 75-162mg o Supplemental O2 (Nasal Prongs or Face Mask 2-4 L/min) o Goals in the ER:
Control of Cardiac Discomfort Rapid identification of patients who are Candidates for Urgent Reperfusion Therapy Triage of Lower-Risk Patients to appropriate location in the hospital Avoidance of inappropriate discharge of patients with STEMI

VII. GOALS FOR MANAGEMENT OF ACUTE ST-ELEVATION MI (STEMI) Reperfusion When ST-Segment Elevation of at least 2mm in 2 Relief of Chest Pain contiguous precordial leads and 1 mm in two adjacent Anti-Platelets / Anti-Coagulants limb leads is present, a patient should be considered a
candidate for reperfusion therapy A. Primary Goal in Management in STEMI = REPERFUSION o Ideally, we do Thrombolysis (Streptokinase) o Other modes of Reperfusion: Primary Percutaneous Coronary Intervention (PCI), Bypass (CABG) o Golden Period for Thrombolysis: < 6 hours Ideally initiated within 30 minutes of presentation (Door to Needle Time < 30 mins) Although the reduction of mortality rate is more modest, therapy remains of benefit for many patients seen 3-6 hours after onset of infarction 1. Absolute CONTRAINDICATIONS to Thrombolysis History of Cerebrovascular Hemorrhage at ANYTIME History of a Non-Hemorrhagic Stroke or other Cerebrovascular Event within the PAST YEAR Marked hypertension (a reliably detected SBP > 180mmHg and/or DBP > 110mmHg Suspicion of Aortic Dissection Active Internal Bleeding (excluding menses) 2. Relative CONTRAINDICATIONS to Thrombolysis (requires assessment of the Risk:Benefit Ratio) Current use of Anticoagulants (International Normalized Ratio > 2) Recent (< 2 weeks) Invasive or Surgical Procedure or Prolonged (>10min) Cardiopulmonary Resuscitation Known bleeding diathesis Pregnancy Hemorrhagic Ophthalmic Condition (eg Hemorrhagic Diabetic Retinopathy) Active Peptic Ulcer Disease History of Severe Hypertension that is currently adequately controlled 3. Primary Percutaneous Coronary Intervention Usually Angioplasty and/or Stenting Effective in restoring perfusion in STEMI when carried out on an emergency basis in the first few hours of MI Indications For Percutaneous Coronary Intervention (PCI) Percutaneous Transluminal Coronary Angioplasty (PTCA) alternative to Bypass Surgery Fundamental Indication for PCI: o Presence of one or more Coronary Stenoses thought to be responsible for a Clinical Syndrome that warrant Revascularization o Approachable by Catheter-Based Techniques o With Risks and Benefits that compare favorably with those of Bypass Surgery

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B. Relief of Chest Pain o Nitrates o Morphine o B-Blockers

Sublingual Nitroglycerin

Avoid giving NSAIDS in the ACUTE Setting of Myocardial Infarction (AMI)

Can be given up to 3 doses of 0.4mg at 5 min intervals. In addition to diminishing or abolishing chest pain, nitroglycerin can be capable of both decreasing Myocardial O2 Demand (by lowering Preload) and increasing Myocardial Oxygen Supply (by dilating infarct-related coronary vessels). IV Nitroglycerin should be considered if there is return of chest pain + ST segment or T wave shifts Very effective analgesic for the pain Control pain by diminishing O2 demand. Reduce the risks of reinfarction & ventricular fibrillation

Morphine IV Beta Blockers

C. Anti-Platelets and Anti-Coagulation o Aspirin 80mg o Clopidrogel o Heparin 1. We give Anti-Coagulants and Anti-Platelets for Secondary Prevention It has no use in the Acute Ischemic Event Secondary Prevention = Preventing complications or recurrence 2. Heparin: Anticoagulant Binds Anti-Thrombin III and activates it (Antithrombotic) Standard Antithrombin agent used in clinical practice is Unfractionated Heparin or UFH (an alternative to UFH is Low-Molecular-Weight Heparin / LMWH) Heparin (Unfractionated Heparin or UFH): Initial Bolus 60-70 U/kg (maximum 5000 U) IV, followed by infusion of 12-15 U/kg per hour (initial maximum 1000 U/h) titrated to a PTT 1.5-2.5 times control When UFH is added to a regimen of Aspirin and a non-fibrin-specific thrombolytic (Streptokinase), additional mortality benefit occurs **NOTE: Risks of Heparin Heparin Induced Thrombocytopenia (HIP) Bleeding (if there is bleeding, we can give Protamine Sulfate) VIII. HOSPITAL PHASE MANAGEMENT
Activity Patients should be kept at bed rest for the first 12 hours. In the absence of complications, patients should be encouraged to resume an upright posture by dangling their feet over the side of the bed & sitting in a chair within the first 24 hours, By the 2nd and 3rd day, patients are ambulating in their room with increasing duration and frequency. By day 3, patients should be increasing ambulation progressively to a goal of 185 m (600ft) at least 3x a day Nothing or only clear fluids (due to risk of emesis and aspiration) for the first 4-12 hours Use of stool softener. Many patients require sedation during hospitalization to withstand period of enforced inactivity

Diet Bowels Sedation

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IX. ACC / AHA GUIDELINES FOR MANAGEMENT OF AMI (Medicine Notes)

Initial Recognition and Management in the ER Initial evaluation of the patient ideally should be accomplished within 10 minutes of his / her arrival at the ER NO more than 20 minutes should elapse before an assessment is made At the ER, patient with Suspected MI should immediately Receive: O2 Support SL Nitrates (Defer if BP < 90 or HR < 50) Adequate Analgesia (Morphine or Mependine) ASA 160-325mg orally 12 L ECG must be done: o ST Segment Elevation (> 1mV in contiguous leads) o Presence makes patient a Candidate for Immediate Reperfusion Therapy by Fibrinolysis, PTCA **IMPORTANT Notes: Acute MI, LBBB = Manage like ST-Segment Elevation MI NSTEMI = should NOT receive Thrombolytic Therapy 1) Thrombolysis Greatest benefit initiated within 6 hours from the onset of symptoms Benefit also observed when begun 12 hours Associated with High Risk for ICH, which occurs within 1st day of Therapy Factors that Increase Risk for ICH: o Age > 65 y/o o BW < 70kg o Systemic HPN o Administration of Tissue Plasminogen Activator 2) Primary PTCA May be performed as alternative to Thrombolytics Provided that it can be accomplished promptly with prompt access to E CABG HOSPITAL MANAGEMENT 1. First 24 Hours Confirm MI by Serial ECG and measurement of Cardiac Enzymes Reinfarction and Death frequently occurs within the 1st 24 hours Limit Physical Activities for at least 12 hours Anxiety and Pain appropriate Analgesics Prophylactic Antiarrhythmias NOT recommended in the 1st 24 hours of Hospitalization a. Increased Risk for Embolic Stroke: o Large Anterior Wall MI **Risk is reduced by Early Administration of Heparin o LV Mural Thrombus b. Thrombolytics o Streptokinase o Anisoylated Plasminogen Streptokinase Activator Complex (APSAC) o Urokinase c. Heparin Administration AFTER Thrombolysis shows: o Limited evidence of Benefit for Streptokinase, APSAC, Urokinase o Improved Clinical Outcome with ALTEPLASE IV at least 48 hours after administration of Alteplase **NOTE: High Dose IV Heparin Recommended when PTCA was done d. Medications: o Aspirin o IV Nitrates for 24-48 hours after hospitalization o ACE Inhibitors should be continued in patients with impaired LV systolic function (EF < 40%) or CHF o On Admission: Lipid Profile, Serum Electrolytes including Mg 2. After 1st 24 Hours Continue ASA, B-Blocker, ACE-Inhibitor Patients with MI that is spontaneous or provoked in the days to weeks after AMI should undergo: o Elective Coronary Angio o Consider PTCA or CABG However, this does NOT salvage myocardium nor reduce Reinfarction or Death Thus, reserve the said procedures for survivors who have preserved LV systolic function and spontaneous or provoke Ischemia

17

Temporary Pacemaker Insertion (TPI) Patients with: o Sinus Bradycardia, unresponsive to meds o Mobitz Type II 20 AV Block o 30 Heart Block o BBB o Newly Acquired BBB o R or LBBB in Conjunction with 10 AV Block Immediate Surgical Intervention: Failed PTCA with Persistent Chest Pains or Hemodynamic Instability Persistent or recurrent ischemia refractory to meds and NOT candidate for catheter intervention Cardiogenic Shock and Coronary Artery, NOT amendable to PTCA Mechanical Abnormality, leading to severe Pulmonary Congestion and Hypotension (eg. Papillary Muscle Rupture, MR, VSD)

X. COMPLICATIONS (Medicine Notes)

A. Pericarditis o Patients with Recurrent Chest Pain o Should receive High Dose ASA (650mg q4 to 6 hrs) o If caused by MI, should be treated with: IV Nitrates Analgesics Antithrombotics B. CHF o Should receive Diuretics and an Afterload Reducing Agent C. Cardiogenic Shock o Intra-Aortic Balloon Pump o E Coronary Angio PTCA CABG D. RV Infarction and Dysfunction o Intravascular Volume Expansion and Inotropic Agent E. Atrial Fibrillation o Manifestation of extensive LV systolic dysfunction o Hemodynamic Compromise o Direct Cardioversion o DIGITALIS to Slow the Ventricular Response F. Ventricular Fibrillation o Direct Current Countershock G. Monomorphic Ventricular Tachycardia o Direct Current Countershock if with associated angina and congestion o If NOT, should be treated with: Lidocaine Procainamide Amiodarone H. Symptomatic Bradycardia o Atropine XI. PREPARATION FOR DISCHARGE A. Should undergo Stress-Testing Exercise o Submaximal at 4-7 day; or symptom limited at 10-14 days o This is done to: Assess patients functional capacity and ability to perform test at home or work Evaluate efficacy of patients current medical regimen Stratify risk for subsequent cardiac event B. Long Term Management o Meds: ASA, Beta-Blocker, Selected Dose of ACE-Inhibitors o Weight reduction o Diet Low Fat and Cholesterol (Target LDL < 100mg/dL) o Smoking cessation

Formal Cardiac Rehab Program or engage in 20 minutes of exercise at least at level of brisk walking at least 3x per week

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RHEUMATIC HEART DISEASE

RHEUMATIC HEART DISEASE

I. RHEUMATIC FEVER (JONES CRITERIA) Acute Rheumatic Fever (ARF) is a multisystem disease resulting from Autoimmune Reaction to infection with Group-A Streptococci (cardiac valvular damage may persist after other features have disappeared) RF is a Hypersensitivity Reaction induced by Group-A B-Hemolytic Streptococcus In RF, Antibodies against M-Proteins of certain strains of Streptococcus Cross-React with Tissue Glycoproteins in the Heart, Joints, and other tissues A. Major Manifestations Carditis (40-60%) Migratory Polyarthritis (75%) Syndenhams Chorea (<10%) Erythema Marginatum Subcutaneous Nodules Pancarditis involving the pericardium, myocardium, and endocardium Most often affecting the ankles, wrists, knees, elbows Involuntary jerking movements Evanescent macular eruption w/ round borders, usually concentrated on trunk Found over extensor surfaces of joints

B. Minor Manifestations 1. Clinical: Arthralgia (joint pains) Fever 2. Laboratory Findings of: Elevated Acute Phase Reactants (ESR / CRP) Prolonged PR interval PLUS Supporting Evidence of Antecedent Group-A Strep Infection o (+) Throat Culture or Rapid Strep-Antigen Test o And/or Elevated or Rising Strep-Antibody Test

2 Major Criteria OR 1 Major and 2 Minor Criteria PLUS Evidence of Preceding Infection

Management of Rheumatic Fever Diagnostics: include ASO Titer, ESR, CRP, Throat Swab CS, ECG, 2D Echo Treatment For Infection: Pen-G or Ampicillin IV x 10 days For Arthritis alone: ASA 75mg/kg/day x 2 weeks (when 1/2 dose for 2-3 weeks) For Mild Carditis: ASA 75mg/kg/day x 6-8 weeks, then taper For Mod to Severe Carditis: Add Prednisone 1-2mg/kg/day x 2-3 weeks; continue both ASA and Prednisone until Normal ESR is reached For Chorea: Dizepam tab PO Prophylaxis: Penicillin-G 1.2 M u q 3-4 weeks RF without Carditis: 5 years until 30 y/o Penicillin-V 250mg/cap BID RF with Mild Carditis: until 45 y/o Erythromycin 250mg/cap BID RF with Mod-Sev Carditis: Lifetime

III. PE OF A PATIENT WITH MITRAL STENOSIS (MS) A. Inspection / Palpation

Malar flush with pinched and blue facies In patients with sinus rhythm and severe pulmonary hypertension or associated tricuspid stenosis, the JVP reveals prominent a waves due to vigorous right atrial systole NOTE: JVP vs CVP o RV Tap (due to enlarged RV) JVP is measured from Sternal Angle B. Auscultation CVP is measured from Midclavicular Line o S1 is usually accentuated and slightly delayed Difference of CVP from JVP is 5 (therefore, 3 + 5 = 8) o Splitting of S2 (there is Delayed Closure of Pulmonic Valve) Normal JVP = 3cm o Opening Snap Normal CVP = 8cm o Low pitched rumbling Diastolic Murmur o o IV. PERCUTANEOUS TRANSLUMINAL MITRAL VALVE COMISSUROTOMY (PTMC) Right Atrium Transluminal approach to Left Atrium Mitral Valve (Creates a whole in the septum between the LA and RA)

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INFECTIVE ENDOCARDITIS

INFECTIVE ENDOCARDITIS
I. CLASSIFICATION OF INFECTIVE ENDOCARDITIS (IE) ACUTE BACTERIAL IE Pathogenic Organism Staph. Aureus (Virulent) Clinical Presentation High Fever, Acute Course Cardiac Pathology Normal cardiac valves, No Murmurs Prognosis Fatal in 6 weeks if Untreated SUBACUTE BACTERIAL IE Strep. Viridans, Enterococci (Less Virulent) Low Grade Fever, Subacute Course Damaged Valves, (+) Murmurs Better Prognosis

II. DUKES CRITERIA FOR INFECTIVE ENDOCARDITIS (IE) A. Criteria for Infective Endocarditis o Two Major Criteria, or o One Major and Three Minor, or o Five Minor Criteria using definitions for these criteria as listed below o Possible Infective Endocarditis: findings consistent with Infective Endocarditis that fall short of the criteria listed above B. MAJOR Criteria o 1) Positive Blood Culture Results for Infective Endocarditis Typical Organisms for Infective Endocarditis: Streptococci viridans, HACEK Group, Strep bovis, Staph aureus, or Enterococci recovered from Two or More Blood Cultures o 2) Either Positive Echocardiography Study result for Infective Endocarditis: Oscillating Intracardiac Mass, Abscess or New Dehiscence of Prosthetic Valve or New Valvular Regurgitation Or Persistently Positive Blood Culture Results: Microorganism consistent with IE recovered from One or more Blood Cultures drawn more than 12 Hours Apart C. MINOR Criteria (Mnemonic: PF-VIME) o 1) Predisposing Heart Condition or Injected Drug User o 2) Febrile Syndrome o o o o 3) Vascular Phenomena: Arterial embolism, CNS hemorrhage, conjunctival hemorrhage, Janeway lesions 4) Immunologic Phenomena: Immune-complex Glomerulonephritis, rheumatoid factor, false-positive VDRL test, Oslers nodes, or Roth spots 5) Microbiologic Evidence: Positive Blood Culture results, but NOT Positive for Major Criterion 6) Echocardiogram: Suggestive of Infective Endocarditis, but NOT Positive for Major Criterion

III. MANAGEMENT A. Diagnostic o Blood CS x 3 Sites; CBC, Crea, U/A, RF o 2D Echo with Doppler, TEE B. Treatment:
Acute IE Subacute IE 1) NAFCILLIN or OXACILLIN 2g IV q4 or VANCOMYCIN 500mg IV q6 or 1g IV q12 x 4weeks 2) GENTAMYCIN 100-200mg IV, then 80mg IV q8 x 3-5 days 1) PEN-G 2-4 M u IV q4 x 4 weeks or AMPICILLIN 2g IV q4 2) GENTAMYCIN 80mg IV q8 x 2 weeks

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OTHER CARDIOVASCULAR DISEASES

CARDIAC TAMPONADE
Life Threatening Condition wherein Pericardial Effusion has compressed the Heart, impairing its Pumping Most Common Causes: Neoplasm, Idopathic Pericarditis, Uremia Other Causes: TB, Bacterial, Post-Pericardiostomy Syndrome, Acute MI, Trauma, Iatrogenic

I. CLINICAL FEATURES A. Three Principal Features o Increased Intracardiac Pressure o Limited Ventricular Filling o Decreased Cardiac Output B. Symptoms o Dyspnea, Orthopnea, Fatigue o Hepatic Engorgement C. Physical Examination o Hypotension o Elevated JVP (Neck Vein Engorgement) o Pulsus Paradoxus ( > 10mmHg decrease in SBP during Inspiration) o RR > 20, HR > 100 o Muffled Heart Sounds II. MANAGEMENT A. Diagnostics
12-L ECG CXR 2D Echo (Diagnostic) Low Voltage QRS Complexes Electrical Alterans Cardiomegaly No Pulmonary Venous Congestion RV Collapse with significant Pericardial Effusion BECKS TRIAD: Hypotension Engorgement of Neck Veins Muffled Heart Sounds

B. Treatment o Emergency Pericardiocentesis o Emergency Tube Pericardiostomy w/ Creation of Pericardial Window (recurrent cases / chronic cases / infectious cases)

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PERICARDITIS
Acute Pericarditis most common pathologic process involving the Pericardium Cardinal Manifestations: Pain, Pericardial Friction Rub, ECG changes, Pericardial Effusion with Cardiac Tamponade and Paradoxical Pulse (Chest Pain is an important, but not invariable symptom)

I. CLINICAL PRESENTATION Chest Pain: Severe, Retrosternal, Left Precordial, referred to neck, arms or left shoulder, pleuritic (consequent to accompanying pleural inflammation) Pleuritic Chest Pain: Sharp and aggravated by inspiration, coughing, changes in body position Pain resembles an Acute MI HOWEVER, Pericardial Pain may be relieved by Sitting Up and Leaning Forward and is intensified by lying supine Pericardial Friction Rub (85%): may have up to 3 components per cardiac cycle, high pitched, and is described as rasping, scratching or grating (heard more frequently at end-expiration with patient upright & leaning forward) Etiologic Classification of Pericarditis: Infectious (Viral, Pyogenic, TB, Fungal, other infections) Non-Infectious (AMI, Uremia, Neoplasia, Myxedema, Cholesterol, Chylopericardium, Trauma, Aortic Dissection, etc) Pericarditis related to Hypersensitivity or Autoimmunity II. LABORATORY A. Cardiac Biomarkers o May have MODEST Increases in Serum Biomarkers of Myocardial Damage (CK and Troponin) B. ECG o ECG without Massive Effusion usually displays changes secondary to Acute Subepicardial Inflammation o Evolves through 4 stages: Stage 1 Widespread Elevation of ST Segments, with Upward Concavity, involving two or three standard limb leads and V2 to V6; with reciprocal depressions only in aVR & sometimes V1, as well as PR segment depression Stage 2 After several days, ST Segments return to normal, & only then, or later, do the T waves become inverted (Stage 3) Stage 3 T Waves become inverted Stage 4 ECG returns to Normal in Stage 4 (weeks or months after the acute onset) **NOTE: In contrast, findings in Acute Myocardial Infarction: ST Elevations CONVEX, and reciprocal depressions are usually more prominent QRS changes occur, particularly development of Q waves, and notching & loss of R-Wave amplitude T-Wave are Inversions usually seen within hours BEFORE the ST-Segments have become Isoelectric Sequential ECGs are useful in distinguishing Acute Pericarditis from AMI (in AMI, Elevated ST-Segments return to NORMAL within hours) C. Echocardiography o Most Effective Imaging Technique o Can identify accompanying Cardiac Tamponade D. CT / MRI o Diagnosis of Pericardial Fluid or Thickening may be confirmed by CT or MRI III. PERICARDIAL EFFUSION Effusion is usually associated w/ Pain and/or the above mentioned ECG changes, as well as with an enlargement of the Cardiac Silhouette Can lead to Cardiac Tamponade Ewarts Sign: a Patch of Dullness and Increased Fremitus (and Egophony) beneath the angle of the Left Scapula (caused by compression of the base of the left lung by the pericardial fluid

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SUPERIOR VENA CAVA SYNDROME

Clinical Manifestation of SVC obstruction causing severe decrease in venous return from head & neck & upper extremities 90% is secondary to malignancy (lung ca 85%)

I. CLINICAL PRESENATION Neck and Facial Swelling (Periorbital) Dyspnea, Cough, Hoarseness, Nasal Congestion, Tongue Swelling, Epistaxis, Headaches, Hemoptysis Dysphagia, Pain, Dizziness, Lethargy, Syncope Symptoms are aggravated by bending forward or lying down II. PHYSICAL EXAMINATION Diagnosis of SVC Syndrome is CLINICAL. Tracheal Obstruction Neck Vein Engorgement is the one potentially Life-Threatening Complication Visible collateral veins on chest wall Cyanosis, Edema on Face, Arms, Chest Distant or Unilaterally Absent Breath Sounds (sometimes normal breath sounds) If Severe: Proprosis, Glossal and Laryngeal Edema, Obtundation III. MANAGEMENT A. Diagnostics: Imaging Studies
CXR CT Scan Widening of the Superior Mediastinum Pleural Effusion in 25% of cases Diminished or Absent Opacification of the Central Venous Structures Prominent Collateral Venous Circulation Most Reliable View of Mediastinal Anatomy NO Advantage over CT Scan

MRI

B. Treatment o Relieve Symptoms: Decreasing Cardiac Output, Decrease Venous Pressure (Diuretics, Low Salt Diet, Head Elevation, Oxygen) o Obtain Histologic Diagnosis o Other Modalities: Radiation, Chemotherapy, Surgery

CARDIOMYOPATHIES
Dilated Restrictive Hypertrophic Left and/or Right Ventricular Enlargement, impaired systolic function, CHF, Arrhythmias, Emboli Endomyocardial scarring or myocardial infiltration resulting in restriction to Left and/or Right Ventricular Filling Disproportionate LV Hypertrophy, typically involving Septum more than free wall, with or without an Intraventricular Systolic Pressure gradient; usually of a Non-Dilated LV Cavity

23

PHYSIOLOGY OF THE CARDIOVASCULAR SYSTEM

I. CONTROL OF CARDIAC PERFORMANCE AND OUTPUT Extent of shortening of heart muscle, and therefore, the stroke volume of the ventricle in the intact heart depend on three major influences: o The Length of the Muscle at Onset of Contractions (Preload) o The Tension that the Muscle is called upon to Develop during Contraction (Afterload) o The Contractility of the Muscle (extent and velocity of shortening at any given preload and afterload) Laplaces Law: When Myocardial Contractility becomes impaired and the ventricle Dilates, Afterload RISES and limits Cardiac Output

II. ASSESSMENT OF CARDIAC FUNCTION Cardiac Output and Stroke Volume may be depressed in Heart Failure Ejection Fraction = ratio of Stroke Volume to End-Diastolic Volume (Normal is 67 + 8%) Ejection Fraction is frequently depressed in Systolic Heart Failure, even when the stroke volume itself is normal III. CARDIAC DIAGNOSIS: 1) Underlying Etiology 2) Anatomic Abnormalities 3) Physiologic Disturbances 4) Functional Disability Is the disease congenital, hypertensive, ischemic, or inflammatory in origin? Which chambers are involved? Are they hypertrophied, dilated, or both? Which valves are affected? Are they regurgitant and/or stenotic? Is there Pericardial involvement? Has there been a Myocardial Infarction? Is an arrhythmia present? Is there evidence of congestive heart failure or of myocardial ischemia? How strenuous is the physical activity require to elicit symptoms?

IV. HEART SOUNDS A. First Heart Sound (S1) o Coincides with the Closure of the Mitral Valve and Tricuspid Valve (Systolic Phase) o Best heard at the APEX o Start of Systole B. Second Heart Sound o Caused by the Closure of the Aortic and Pulmonic Valves (Diastole) o Indicates End of Systole (or beginning of Diastole) o Best heard at the BASE o SPLITTING is normally heard C. Third Heart Sound (S3) o Coincides with EARLY DIASTOLE or RAPID VENTRICULAR FILLING o It is caused by the Flow of Blood during Rapid Ventricular Filling o Best Heard after S2 o Suggestive of Heart Failure / Left Ventricular Failure D. Fourth Heart Sound (S4) o Coincides with LATE DIASTOLE or ATRIAL SYSTOLE (Atrial Contraction / Slow Ventricular Filling) o Best Heard before S1 o Occurs when diminished Ventricular Compliance Increases the Resistance to Ventricular Filling o Most Patients with an Acute MI and Sinus Rhythm have an audible S4

V. RENIN-ANGIOTENSIN-ALDOSTERONE AXIS

VI. ACTIVATION OF NEUROHORMONAL SYSTEMS

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In Heart Failure

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Typical Clinical Features of Major Causes of Acute Chest Discomfort

CONDITION
Angina

The CO in HF results in an unloading of high pressure baroreceptors (circles) in the LV, carotid sinus, and aortic arch. This unloading leads to generation of afferent signals to CNS that stimulate cardioregulatory centers in brain which release AVP from posterior pituitary. AVP (ADH) is a powerful vasoconstrictor that increases permeability of renal collecting ducts, leading to reabsorption of free H2O. These afferent signals to CNS also activate efferent SNS pathways that innervate the heart, kidney, peripheral vasculature, and skeletal muscles ASSOCIATED FEATURES
Precipitated by exertion, exposure to cold, psychologic stress S4 Gallop or MR murmur during pain Similar to angina but occurs with low levels of exertion or even at rest Unrelieved by nitroglycerin May be associated with evidence of heart failure or arrhythmia Late-Peaking Systolic Murmur radiating to Carotids May be relieved by sitting up and leaning forward (+) Pericardial Friction Rub Associated with HPN and/or underlying CT D/O (eg. Marfan Syndrome) Murmur of Aortic Insufficiency, Pericardial Rub, Pericardial Tamponade, or Loss of Peripheral Pulses Dyspnea, Tachypnea, Tachycardia, Hypotension Dyspnea, signs of increased venous pressure including edema and JVP distention Dyspnea, cough, fever, rales, occasional rub Dyspnea, Decreased Breath Sounds on side of Pneumothorax Worsened by Postprandial Recumbency Relieved with food or antacids May follow meal Aggravated by movement May be reproduced by localized pressure on exam Vesicular Rash Situational factors may precipitate symptoms Often with anxiety / depression in Hx

DURATION
More than 2 and less than 10 mins 10-20 mins Variable (often > 30mins) Recurrent episodes as described for angina Hours to Days; may be episodic Abrupt Onset of unrelenting pain

QUALITY
Pressure, tightness, squeezing, heaviness, burning Similar to angina but often more severe Similar to angina but often more severe As described for angina Sharp Tearing or Ripping Sensation; Knifelike Pleuritc Pressure Pleuritic Pleuritic Burning Burning Burning, Pressure Aching Sharp or Burning Variable

LOCATION
Retrosternal, often with radiation to or isolated discomfort in neck, jaw, shoulders, or arms frequently on left Similar to angina Similar to angina

Unstable Angina Acute MI

Aortic Stenosis Pericarditis Aortic Dissection

As described for angina Retrosternal or toward Apex May radiate to left shoulder Anterior Chest, often radiating to the back, between shoulder blades

Pulmonary Embolism Pulmonary Hypertension Pneumonia or Pleuritis Spontaneous Pneumothorax Esophageal Reflux Peptic Ulcer Gallbladder Disease Musculoskeletal Disease Herpes Zoster Emotional / Psychiatric

Abrupt Onset; Several Minutes to a Few Hrs Variable Variable Sudden Onset; Several Hours 10-60 mins Prolonged Prolonged Variable Variable Variable, may be fleeting

Often lateral, on the side of Embolism Substernal Unilateral, often localized Lateral to Side of Pneumothorax Substernal, Epigastric Epigastric, Substernal Epigastric, RUQ, Substernal Variable Dermatomal Distribution Variable; may be retrosternal

25

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Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

ENDOCRINE DISORDERS

1) THYROID STORM
Clinical presentation of Uncomplicated Thyrotoxicosis are generally present and accentuated in Thyroid Storm Known Precipitants of Thyroid Storm (associated with Rapid Rise in Thyroid Hormone Levels)
o o o o o o o o o o o Thyroid Surgery Withdrawal to Therapy, Radioiodine Therapy Iodinated Contrast Dye Condition associated with an Acute or Subacute Nonthyroidal Illness Nonthyroidal Surgery Infection, CVA Pulmonary Embolism Parturition DKA Emotional Stress Trauma

I. BURCH AND WARTOFSKYS DIAGNOSTIC CRITERIA FOR THYROID STORM

A. Thermoregulatory Dysfunction (Temperature) 37.2 37.7 0C 37.8 38.2 0C 38.3 38.8 0C 38.9 39.3 0C 39.4 39.9 0C > 40.0 0C B. Central Nervous System Effects Absent Mild (Agitation) Moderate (Delirium, Psychosis, Extreme Lethargy) Severe (Seizure, Coma) C. Gastrointestinal-Hepatic Dysfunction Absent Moderate (Diarrhea, Nausea/Vomiting, Abdominal Pain) Severe (Unexplained Jaundice) D. Cardiovascular Dysfunction 1. Tachycardia (Beats Per Minute) 99 109 110 119 120 129 130 139 > 140 2. Congestive Heart Failure Absent Mild (Pedal Edema) Moderate (Bibasilar Rales) Severe (Pulmonary Edema) Atrial Fibrillation 3. Precipitant History Negative Positive 5 10 15 20 25 30 0 10 20 30 0 10 20 Scoring: < 25 Unlikely Storm 25 44 Impending Storm > 45 Highly Suggestive of Thyroid Storm

5 10 15 20 25 0 5 10 15 10 0 10

II. NOTES FROM LECTURE ON THYROID STORM A. Thyrotoxicosis VS Hyperthyroid o Thyrotoxicosis: Clinical Syndrome resulting from Cellular Responses to Excessive Thyroid Hormone (may be EXOGENOUS or ENDOGENOUS) o Hyperthyroid: Thyrotoxicosis that results from Increased Production of Thyroid Hormones from the Thyroid Gland itself (ENDOGENOUS) B. Causes of Thyrotoxicosis:
PRIMARY THYROTOXICOSIS Graves Disease Toxic Multinodular Goiter Toxic Adenoma Thyroid CA / Mets Struma Ovarii SECONDARY THYROTOXICOSIS TSH Secreting Pituitary Adenoma Thyroid Hormone Resistance Syndrome H-Mole THYROTOXICOSIS WITHOUT HYPERTHYROIDISM Leakage Subacute Thyroiditis Painless Thyroiditis Suppurative Thyroiditis Thyrotoxicosis Factitia Exogenous Thyroid Hormone Diet Pills Other Causes of Thyroid Gland Destruction: Amiodarone Radiation Infarction of Adenoma Ectopic Thyroid Gland Struma Ovarii (Thyroid Tissue in ovary)

C. Thyroid Storm o Extreme Accentuation of Hyperthyroidism, usually with Graves Disease of Toxic Multinodular Goiter o < 10% of Hospital Admissions for Thyrotoxicosis o Mortality Rate = 20-30% o Point of which Thyrotoxicosis transforms to Storm is controversial 1. Precipitants of Thyroid Storm Pre-Existing Thyrotoxicosis, Untreated or Partially Treated Infection, Trauma, Surgery Due to poorly prepared Thyroidectomy in Graves Disease patient Other conditions associated with a Rapid Rise in Hormone Levels: Withdrawal of Antithyroid Drug Therapy Radioiodine Therapy Vigorous Thyroid Palpation Iodinated Contrast Dyes Salicylates (competes with Albumin Binding Increase in Free Thyroid Hormone Levels) Conditions associated with an Acute or Subacute Non-Thyroidal Illness Infection CVA Trauma DKA 2. Pathophysiology No evidence that there is an Increased Production of T3 or T4 causing the Storm Magnitude of Increase in Thyroid Hormones does NOT appear to be Critical Increased Catecholamine Receptors (Key Role) Decreased Binding to TBG (Increased Free T3/T4) 3. Atypical Presentation Suspect Hyperthyroid in patients with Fever and Atrial Fibrillation NOT controlled with appropriate Cardiac Management Apathy and Coma RARE Manifestation of storm

 Key to Management = EARLY Recognition Graves Ophthalmopathy 4. Some Laboratory Findings: 90% will NOT go back to Normal Increased FT4, Increased FT3 RAI can Worsen Ophthalmopathy if still in Decreased TSH the Active Phase (wait until Ophthalmopathy is 12 L ECG more stable before giving RAI) Leukocytosis, shift to the Left if (+) Infection Mild Hypercalcemia Liver Function Test Abnormalities Hyperglycemia (Mild to Moderate)

III. MANAGEMENT OF STORM

Goals in Management: 1) Stop Synthesis of New Hormones within the Thyroid 2) Halt release of stored Thyroid Hormone from Thyroid Gland 3) Prevent conversion of T4 to T3 4) Control Adrenergic Symptoms associated with Thyrotoxicosis 5) control systemic Decompensation with Treatment 6) Treat Underlying cause Key Notes: Thyroid Hormone Levels will Normalize after 4-Weeks (TSH longer time to Normalize) Some Tests done in the PGH Lab: o Total T4/T3 o Free T4/T3 o Tsh o Thyroglobulin Assay o Anti-TPO o TgAb Liver Function Tests: In Thyroid Storm, we give High Doses of PTU Monitor Liver Function Tests, Agranulocytosis If Storm is resolving, Liver Function Tests should have a Decreasing Trend If LFTs are still increasing, DECREASE the Dose of PTU

A. Inhibit New Hormone Production 1. Propylthiouracil (PTU) Inhibits Thyroid Peroxidase (which is involved in organification and coupling) Drug of choice because it inhibits Peripheral Conversion of T4T3 (in HIGH doses) Given in Large Doses: 600-1000mg Loading Dose and 200-300mg every 6 hours given orally or by nasogastric tube or per rectum Mechanism Of Action Inhibit synthesis of thyroid hormones by inhibiting organification of iodine and coupling of the iodotyrosinases Inhibit Peripheral Conversion of T4 to T3 Proposed to have direct effects on the immune system producing a decrease in circulating thyroid-stimulating antibodies and restoration of normal suppressor cell activity 2. Methimazole 20-25mg PO q6 Inhibit Hormone Synthesis

B. Inhibit Hormone Release 1. Stable Iodide (SSKI) Given 1 hour after PTU it blocks the release of hormone from the gland (block the synthesis first before giving Iodine) Wolff-Chaikoff Effect: One hour after the first dose of PTU, Stable Iodide is given to BLOCK Thyroid Hormone Synthesis via the Wolff-Chaikoff Effect (the DELAY allows the Antithyroid Drug to prevent the excess Iodine from being incorporated into new hormone) Administration: A saturated solution of Potassium Iodide (5 drops SSKI every 6 hours), or Ipodate or Iopanoic Acid (0.5mg every 12h), may be given orally **NOTE: Opposite of Wolff-Chaikoff = Jod Basedow (worsens) 2. Others: Lugols Solution 4-8 Drops PO q6-8 Sodium Ipodate 1-3g PO QID Iopanoic Acid 1g PO q8
Mechanism of Iodine: Decreases Fractional Turnover of Thyroid Iodine and T4 Secretion Rate Blocks Thyroid Hormone release

C. Beta-Blockers: 1. Propranolol To reduce tachycardia and other adrenergic manifestations 60-80mg PO q4 or 80-120mg q6 High doses or Propranolol decrease T4T3 conversion CAUTION is needed to avoid Acute Negative Inotropic Effects, but controlling the heart rate is important, as some patients develop a form of High-Output Heart Failure 2. Cardioselective Agents (for patients with Pulmonary Diseases) Atenolol 500-200mg PO QID Metoprolol 100-200mg Nadolol 3. Esmolol (IV) 50-100 ug/kg/min D. Supportive o Acetaminophen 325-650mg PO/PRN q4-q6 o Hydrocortisone 100mg IV q8 (decreases T4 to T3 conversion; Vasomotor Stability) o Volume Depletion and Poor Nutrition: IV Fluids / Electrolytes Glucose 5-10% Vitamins Oxygen Vasopressors Treatment of CHF (Digoxin, Diuretics) Glucocorticoids to correct Relative Adrenal Insufficiency E. Alternative Treatment Lithium Carbonate: o Lithium Carbonate 300mg PO q8 (mimics iodine) Inhibits Coupling of Iodotyrosines Inhibits release of Thyroid Hormones o Potassium Perchlorate 1g PO QID Inhibit conversion of T4 to T3 by decreasing Type-1 o Cholestyramine 4g PO QID F. Removal of T4 and T3 from the Serum: o Cholestyramine o Plasmapheresis o Hemodialysis o Hemoperfusion
Deiodinase Activity

2) HYPERTHYROIDISM / HYPOTHYROIDISM
I. HYPERTHYROIDISM Consequence of Excessive Thyroid Hormone Action Thyrotoxicosis is defined as a state of Thyroid Hormone Excess and is NOT synonymous with Hyperthyroidism (which is the result of excessive thyroid function) however, the major etiologies of Thyrotoxicosis are Hyperthyroidism caused by Graves Disease, Toxic MNG, and Toxic Adenomas Causes:
o o o o o o o o Toxic Diffuse Goiter (Graves Disease) Toxic Adenoma Toxic Multinodular Goiter (Plummers Disease) Painful Subacute Thyroiditis Silent Thyroiditis, including Lymphocytic and Postpartum variations Iodine Induced Hyperthyroidism Excessive Pituitary TSH or Trophoblastic Disease Excessive Ingestion of Thyroid Hormone
SIGNS Tachycardia; Atrial Fibrillation in the elderly Tremor Goiter Warm, Moist Skin Muscle Weakness, Proximal Myopathy Lid Retraction or Lag Gynecomastia

A. Clinical Manifestations (Attributable to the effects of EXCESS Thyroid Hormones in the circulation)
SYMPTOMS Hyperactivity, Irritability, Dysphoria Heat Intolerance and Sweating Palpitations Fatigue and Weakness Weight Loss with Increased Appetite Diarrhea Polyuria Oligomenorrhea, Loss of Libido

B. Laboratory Examinations
o o o o o Sensitive TSH Analysis: single best screening test for Hyperthyroidism T4 or Free T4 Triiodothyronine T3 Radioimmunoassay (RIA) or Free T3 Thyroid Autoantibodies not routinely necessary Radioactive Iodine Uptake Thyroid Scan done to help determine the cause of Hyperthyroidism

TSH level is suppressed and total and unbound Thyroid Hormone Levels are increased. In 2-5% of patients, only T3 is increased (T3 Toxicosis). The converse state of T4 Toxicosis, with elevated Total and Unbound T4 and Normal T3 Levels, is occasionally seen when Hyperthyroidism is induced by Excess Iodine, providing surplus substrate for Thyroid Hormone Synthesis.

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C. Treatment (Surgical + Antithyroid Drugs + Radioactive Iodine) 1. Surgical Intervention No uncommonly performed, unless Coexistent Thyroid Cancer Common candidates include pregnant patients who are intolerant to medications or non-pregnant during definitive therapy, but refuses Radioactive Iodine Those with very large goiters Pediatric patient Complications: Hypoparathyroidism, Vocal Cord Paralysis 2. Anti-Thyroid Drugs a. Methimazole 5mg/tab Dose: 10-20mg PO q8 Maximum Dose: 80mg/d b. PTU 50mg/tab Dose: 50-150mg/tab PO q8 starting dose Maximum Dose: 1200mg/day Adverse Reactions: Rash, Agranulocytosis Indicated in patients with Graves Disease, elderly patients who require post treatment prior to radioactive iodine therapy C. Radioactive Iodine Therapy Yields quickest resolution of the Hyperthyroidism Leads to Hypothyroidism and require lifelong Thyroid Replacement Therapy
Pharmacology Notes (Med School) 1. Prophylthiouracil (PTU) Inhibits Organification and Coupling Inhibits Peripheral Conversion of T4 to T3 2. Methimazole Inhibits Organification and Coupling (only) 3. Iodide Inhibits Hormone Release Decrease Vascularity of Thyroid Gland 4. Anion Inhibitors Competitive Inhibitor of Iodide Transport Mechanism Ex) Perchlorate; Thiocyanate 5. B-Adrenergic Antagonists Reduces Activity of Thyroid Hormone on Target Tissues Ex) Propranolol 6. Radioactive Iodine Damages the Gland thru Cytotoxic Effects It is ONLY used for Hyperthyroid!!! NOT Hypothyroid!!!

II. HYPOTHYROIDISM Results from Undersecretion of Thyroid Hormone Iodine Deficiency remains the Most Common Cause of Hypothyroidism worldwide In areas of Iodine Sufficiency, Autoimmune Disease (Hashimotos Thyroiditis) and Iatrogenic Causes are most common (treatment of Hyperthyroidism) Secondary Causes: Pituitary Disease, Hypothalamic Disease A. Clinical Features (Descending Order of Frequency)
SYMPTOMS Tiredness, Weakness Dry Skin Feeling Cold Hair Loss Difficulty Concentrating and Poor Memory Constipation Weight Gain with Poor Appetite Dyspnea Hoarse Voice Menorrhagia (later Oligomenorrhagia or Amenorrhea) Paresthesia Impaired Hearing SIGNS Dry coarse skin; Cool Peripheral Extremities Puffy Face, hands, and feet (Myxedema) Diffuse Alopecia Bradycardia Peripheral Edema Delayed Tendon Reflex Relaxation Carpal Tunnel Syndrome Serous Cavity Effusions

B. Laboratory Examinations o TSH immunoassay o Free T4 o Thyroid Autoantibodies o Thyroid Scan o UTZ

In Hypothyroid: Increased TSH IRMA; Decreased FT4 A normal TSH Level Excludes Primary (but NOT Secondary) Hypothyroidism. If the TSH is elevated, an Unbound T4 level is needed to confirm the presence of Clinical Hypothyroidism, but T4 is Inferior to TSH when used as a screening test, because it will not detect Subclinical Hypothyroidism. Circulating Unbound T3 Levels are NORMAL in 25% of patients. T3 measurements are therefore, NOT indicated

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C. Treatment 1. Primary Hypothyroidism a. Levothyroxine Na 25mcg, 50mcg, and 100mcg Start usually with 25-50mcg/d use Lower Dosages 12.5-25mcg for patients > 60y/o and those with cardiac disease Treatment for Life WOF Adrenal Failure, Hypotension, nausea and vomiting b. Course: Symptoms improve in weeks WOF for heart failure from too aggressive therapy c. Plan Increase Dose by 25-50mcg every 4 weeks until patient is Euthyroid d. Goal of Treatment: Maintain Plasma TSH in the Normal Range. Monitor Plasma TSH q3-4 months 2. Secondary Hypothyroidism Monitor Serum T4 and other Pituitary Hormones Give steroid replacement first prior to L-Thyroxine Treatment III. GOITER AND NODULAR THYROID DISEASE GOITER: Enlarged Thyroid Gland Biosynthetic Defects, Iodine Deficiency, Autoimmune Disease, and Nodular Diseases can each lead to Goiter A. Diffuse Non-Toxic (Simple) Goiter o When Diffuse Enlargement of the Thyroid occurs in the absence of Nodules and Hyperthyroidism, it is referred to as Diffuse Non Toxic Goiter (Simple Goiter or Colloid Goiter) o Thyroid Function is preserved, most Goiters are Asymptomatic o Pembertons Sign: refers to symptoms of faintness with evidence of facial congestion and external jugular venous obstruction when arms are raised above the head o Tx: Iodine or Thyroid Hormone Replacement induces variable regression of goiter in iodine deficiency o Levothyroxine can be started to suppress the TSH into Low-Normal, but detectable range B. Non-Toxic Multinodular Goiter o Most are Asymptomatic EUTHYROID o Thyroid Architecture is distorted, and multiple nodules can be appreciated C. Toxic Multinodular Goiter o Presence of Functional Autonomy in Toxic MNG (in contrast to Non Toxic MNG) o Clinical Presentation: Subclinical Hyperthyroidism or Mild Thyrotoxicosis o Tx: Antithyroid Drugs often with B-Blockers can normalize Thyroid Function o Laboratory: TSH is Low T4 Level is normal or minimally increased T3 is often elevated to a greater degree than T4

3) DIABETES MELLITUS
I. CLINICAL FEATURES (Notes from Rounds) A. Symptoms of DM o Polyuria o Polydypsia o Unexplained Weight Loss

**NOTE: Polyphagia was removed Target BP if (+) DM: < 130/80

B. Note that Patients with DM are on the following drugs o Aspirin o Statins o Anti-Hypertensives **NOTE: Studies have shown benefits in using these drugs C. Nice To Knows: o Metformin = CONTRAINDICATED in patients with Renal Insufficiency o Target Glucose in patients with Infection = 110-130 (?) o Human Biphasic Insulin 30% SHORT Acting + 70% INTERMEDIATE Acting Short Acting = Onset of Action is after 30 minutes therefore, give it 30 minutes before meals Intermediate Acting = Onset is after 2 hours therefore, give it 2 hours before meals **NOTE: Lispro / Aspart (Analogs) = when given SC, it acts IMMEDIATELY Therefore, give it IMMEDIATELY before meals, to AVOID Hypoglycemia Ex) Lispro 30u immediately before meals

II. DIAGNOSIS OF DM A. Diagnostic Criteria for DM is Based on the following Premises: o 1) Spectrum of Fasting Plasma Glucose (FPG) and the Response to an Oral Glucose Load (OGTT) o 2) DM is Defined as the Level of Glycemia at which Diabetes-Specific Complications occur, rather than on the deviations from a Population-Based Mean 1. Glucose Tolerance is Classified into THREE Categories Based on FPG: Normal FPG < 5.6 mmol/L (100 mg/dL) Impaired Fasting Glucose FPG = 5.66.9 mmol/L (100-125 mg/dL) Diabetes Mellitus FPG > 7.0 mmol/L (126 mg/dL) 2. Based on Response to Oral Glucose Tolerance Test (OGTT) Impaired Glucose Tolerance 7.8 to 11.1 mmol/L (140 to 199 mg/dL) Diabetes Mellitus Glucose > 11.1 mmol/L (200 mg/dL) **NOTE: This is 2 hours after a 75-g Oral Glucose Load B. Criteria for the Diagnosis of Diabetes Mellitus: Symptoms of Diabetes PLUS Random Blood Glucose Concentration > 11.1 mmol/L (200 mg/dL); or Fasting Plasma Glucose > 7.0 mmol/L (126 mg/dL); or Two Hour Plasma Glucose > 11.1 mmol/L (200 mg/dL) during an Oral Glucose Tolerance Test
Random is defined as without regard to time since the last meal Fasting is defined as No Caloric Intake for at least 8 hours Current Criteria for Diagnosis of DM emphasize that the FPG is the MOST reliable and convenient test for identifying DM in asymptomatic individuals

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III. OVERVIEW OF SOME DRUGS USED: A. Insulin

INSULIN PREPARATION Lispro (Rapid) Aspart (Rapid) Regular (Short) Isophane (Intermediate) Glargine (Long) Detemir (Long) ONSET OF ACTION 5-15 mins 5-15 mins 30-60 mins 2-4 hours 2-4 hours 3-8 hours PEAK 30-90 mins 30-90 mins 2-3 hours 4-10 hours Peakless Peakless DURATION 4-6 hours 4-6 hours 6-10 hours 10-20 hours 24 hours

1. Intermediate Acting Humulin-N (Brand Name) = NPH or Humulin Isophane (Generic) Given at a dose of 0.3 0.5 units/kg SC (2/3 given am; 1/3 given pm) Ex) In a 60 kg patient at a dose of 0.4 units/kg, we can give HN 20 0 4 2. Short Acting Humulin-R (Brand Name) = Regular Insulin Usually given 30 minutes before meals Ex) 4 u Pre-Breakfast 3. Rapid Acting Usually given 5 minutes before meals B. Insulin Secretagogues 1. Sulfonylureas Gliclazide Glibenclamide 2. Non-Sulfonylureas Repaglinide Nateglinide C. Insulin Sensitizers (Enhance Insulin Sensitivity) 1. Biguanide Metformin 2. Thiazolidinedione Rosiglitazone Pioglitazone D. Intestinal Absorption Inhibitors 1. Carbohydrase Inhibitor Acarbose Miglitol 2. Lipase Inhibitor Orlistat

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IV. LECTURE ON DIABETES MELLITUS A. Type 1 VS Type 2 CM o T1DM: Absolute Insulin Deficiency o T2DM: Relative Insulin Deficiency with Insulin Resistance o In T2DM, the Insulin Dose is usually higher because of Insulin Resistance B. Diagnosis of DM: o Recent Studies suggest that HbA1c > 6.5: usually Diabetic already (not yet a recommendation) C. Complications of DM: o Acute: DKA, HHS, Hypoglycemia o Chronic: Microvascular: Neuropathy, Retinopathy, Nephropathy Macrovascular: MI, Stroke, PAOD D. Treatment Goals (according to ADA 2009) HbAIc Fasting / Preprandial Plasma Glucose Postprandial Plasma Glucose Bedtime Plasma Glucose <7 70-130mg/dL (3.9-7.2mmol/L) <180mg/dL (<10mmol/L) 110-150mg/dL (6-8.3mmol/L)

**IMPORTANT NOTES: According to AACE: HbA1c should be <6.5 When monitoring Glucose, include FBS, HbA1c, and Postprandial Glucose (PPG) E. Management of Diabetes 1. Consider the Mechanism of Action of the Drug: PATHOPHYSIOLOGY OF DM
Islet Cell Dysfunction (A and B) A: Increased Glucagon B: Decreased Insulin Non-Suppressable Hepatic Glucose Output (responsible for Fasting Hyperglycemia) Insulin Resistance High Carbohydrate Diet Decreased Incretin Levels / Activity GLT GIP

DRUGS USED
Sulfonylureas Meglitinides Insulin DPP-IV Inhibitors GLP-1 Analogues Metformin Thiazolidinediones Incretin Agents Metformin Thiazolidinediones A-Glucosidase Inhibitors DDP-IV Inhibitor GLP-1 Analogues Metformin

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2. Consider Side Effects (Two Most Common Side Effects = Hypoglycemia and Weight Gain)
a. Common Side Effects Insulin Sulfonylureas Metiglinides Thiazolidinediones Hypoglycemia Weight Gain Hypoglycemia Weight Gain Few Hypoglycemia Weight Gain No Hypoglycemia if MonoTx Weight Gain Edema, CHF, Osteoporosis, Anemia No Hypoglycemia if MonoTx Weight Loss Lactic Acidosis (especially if with CKD, Heart Problem, Hypoxia) No Hypoglycemia if MonoTx Weight Loss Diarrhea, Flatulence, Abdominal Pain No Hypoglycemia if MonoTx Weight Loss No Hypoglycemia if MonoTx Headache, Nasopharyngitis

Metformin

Acarbose

GLP-1 Agonist DP-IV Inhibitors

**IMPORTANT Notes: -Reason for Weight Loss in DM (symptom of DM) due to Lipolytic Actions in DM -Hypoglycemia in SU: o Glyburide > Glibenclamide > Glimepiride > Gliclazide > Glipizide o Glyburide is not available in the Philippines o Glibenclamide: used in the Philippines, but NOT advisable for elderly it is prone to Hypoglycemia due to its Long Action b. Some Contraindications: Metformin: Hypoxia, Renal Dysfunction, Liver Disease, CHF Glibenclamide: CKD Some Drugs that can be used in CKD: Meglitinides, Acarbose, etc

3. Consider MonoTx or Combination Tx or Insulin Recent Studies show: Do Combination Therapy Earlier to achieve Goals earlier Current Suggestions:
HbA1c LEVELS 6 7% 7 10% MANAGEMENT Oral Monotherapy Combination Therapy Oral + Oral Oral + Basal Insulin Biphasic Insulin Insulin

> 10%

The following REQUIRE Replacement Therapy (Institute Insulin Therapy) Type 1 DM History of Pancreatectomy or Pancreatic Dysfunction Wide fluctuations in Glucose (Brittle Diabetes) History of DKA Insulin use > 5 years Diabetes > 10 years (because of Progressive B-Cell Destruction)

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4. Consider Primary Effect of Drug (either Preprandial or Postprandial)

a. Monotherapy DRUG GROUP Sulfonylureas Meglitinides Metformin Thiazolidinediones Incretin Acarbose DDP-IV Inhibitor b. Combination Therapy Sulfonylureas + Metformin Sulfonylureas + Rosiglitazone Sulfonylureas + Acarbose Repaglinide + Metformin PRIMARY CONTROL Fasting Plasma Glucose Postprandial Plasma Glucose Fasting Plasma Glucose Fasting Plasma Glucose Postprandial Plasma Glucose Postprandial Plasma Glucose Postprandial Plasma Glucose Fasting Plasma Glucose Fasting Plasma Glucose Fasting Plasma Glucose, Postprandial Plasma Glucose Fasting Plasma Glucose, Postprandial Plasma Glucose

c. Suggested Regimen based on HbA1c If HbA1c is <7% Control Postprandial first 7-9% Control either Preprandial and Postprandial >9% Control Preprandial (fasting) first d. Insulin INSULIN PREPARATION Lispro (Rapid) Aspart (Rapid) Regular (Short) Isophane (Intermediate) Glargine (Long) Detemir (Long) PRIMARY CONTROL Postprandial Plasma Glucose Postprandial Plasma Glucose Postprandial Plasma Glucose Fasting Plasma Glucose Fasting Plasma Glucose Fasting Plasma Glucose

5. Evaluate at the Appropriate Time (based on Peak Effect)

DRUG STARTED Sulfonylureas Meglitinide WHEN WILL DRUG TAKE EFFECT? 1-2 Weeks 1-2 Weeks WHEN TO MONITOR RESPONSE? (Clinical Monitoring) FPG at 2 Weeks HbA1c at 3 Months FPG at 2 Weeks HbA1c at 3 Months PPG at Initiation FPG at 2 Weeks HbA1c at 3 Months HbA1c at 3 Months PPG at Initiation FPG at 4 Weeks HbA1c at 3-6 Months FPG at 2 Weeks HbA1c at 3 Months PPG at Initiation

Metformin Acarbose Thiazolidinediones DPPV-IV Inhibitors

2-3 Weeks 2-4 Weeks 1-2 Months 2 Weeks (?)

Annual Laboratories: o Lipid Profile o Liver Function Tests o Urine Albumin:Creatinine Ratio o Serum Creatinine / GFR o TSH in T1DM, Dysplipidemia, and women > 50 o Dilated Eye Exam

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6. Other Notes on Management Approved Drugs for Management of Pre-Diabetes (Impaired Glucose Tolerance) Acarbose Metformin TZD If (+) Hypoglycemia Stop SU: Glucose levels will normalize after 3-5 days If (+) Renal Disease, Glucose will normalize after 1 wk V. DIABETIC FOOT (NEUROISCHEMIC FOOT ULCER / NIFU) A. University of Texas Grading:
0
Stage A Stage B Pre or Postulcerative Lesion, completely epithelialized Pre or Postulcerative Lesion, completely epithelialized with Infection Pre or Postulcerative Lesion, completely epithelialized with Ischemia Pre or Postulcerative Lesion, completely epithelialized with Infection and Ischemia

I
Superficial Wound, not involving Tendon Capsule or Bone Superficial Wound, not involving Tendon Capsule or Bone with Infection Superficial Wound, not involving Tendon Capsule or Bone with Ischemia Superficial Wound, not involving Tendon Capsule or Bone with Infection and Ischemia

II
Wound Penetrating to Tendon or Capsule Wound Penetrating to Tendon or Capsule with Infection Wound Penetrating to Tendon or Capsule with Ischemia Wound Penetrating to Tendon or Capsule with Infection and Ischemia A: Non-infected; Non-ischemic B: Infected; Non-ischemic C: Non-infected; Ischemic D: Infected; Ischemic

III
Wound Penetrating to Bone or Joint Wound Penetrating to Bone or Joint with Infection Wound Penetrating to Bone or Joint with Ischemia Wound Penetrating to Bone or Joint with Infection and Ischemia

Stage C

Stage D

I: Change in color; Pre-ulcerative; Post-ulcer II: Dermal involvement III: Deep tissues (Muscle and bone)

B. Wagner
0 I II III IV V No Open Lesion but may have deformity or cellulites Superficial Ulcer, partial or full thickness Dermis only (Gram Positive: Cloxacillin, Ampi-Sul, 1st Gen Cephalosporins Ulcer extends to ligament, tendon, joint capsule or deep fascia without abscess / osteomyelitis Tendon, Joint Capsule (Gram Negative: Aminoglycosides Deep Ulcer with abscess, osteomyelitis, or joint sepsis Bone (Anaerobic Coverage) Localized Gangrene (localized to forefoot or heel) Advanced Gangrene

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4) DIABETIC EMERGENCIES
I. DIABETIC KETOACIDOSIS DKA and Hyperglycemic Hyperosmolar State (HHS) are ACUTE Complications of Diabetes DKA was formerly considered a Hallmark of DM Type 1 HHS is primarily seen in individuals with DM Type 2 BOTH disorders are associated with Absolute or Relative Insulin Deficiency, Volume Depletion, and Acid-Base Abnormalities A. DKA vs HHS
Glucose mmol/L (mg/dL) Na+ mEq/L K+ Mg2+ ClP Creatinine Osmolality (mOsm/mL) Plasma Ketones Serum Bicarbonate mEq/L Arterial pH Arterial PCO2 mmHg Anion Gap [Na-(Cl+HCO3)] DKA 13.9 33.3 (250 600) 125 135 Normal to Increased Normal Normal Decreased Slightly Increased 300 320 ++++ < 15 mEq/L 6.8 7.3 20 30 High HHS 33.3 66.6 (600 1200) 135 145 Normal Normal Normal Normal Moderately Increased 330 380 +/Normal to Slightly Decreased > 7.3 Normal Normal to Slightly High

B. Clinical Features of DKA

SYMPTOMS Nausea / Vomiting Thirst / Polyuria Abdominal Pain Shortness of Breath PRECIPITATING EVENTS Inadequate Insulin Administration Infection (PNA / UTI / Gastroenteritis / Sepsis) Infarction (Cerebral, Coronary, Mesenteric, Peripheral) Drugs (Cocaine) Pregnancy PHYSICAL FINDINGS Tachycardia Dehydration / Hypotension Tachypnea / Kussmaul Respirations Respiratory Distress Abdominal Tenderness (may resemble Acute Pancreatitis / Surgical Abdomen) Lethargy / Obtundation / Cerebral Edema Possibly Coma

Symptoms / Signs of DKA usually develop over 24 hours Hyperglycemia Glucosuria, Volume Depletion, Tachycardia Classic Signs: Kussmaul Respiration and a Fruity Odor of patients breath (secondary to Metabolic Acidosis and Increased Acetone) C. Pathophysiology o Results from RELATIVE or ABSOLUTE Insulin Deficiency combined with counterregulatory hormone excess (Glucagon, Catecholamines, Cortisol and Growth Hormone) o BOTH Insulin Deficiency and Glucagon Excess are necessary for DKA to develop o Decreased Ratio of Insulin to Glucagon promotes Gluconeogenesis, Glycogenolysis, Ketone Body Laboratory evaluation of DKA shows an Increased Ion Gap Metabolic formation in the Liver Acidosis and Positive Serum Ketones. Plasma Glucose is usually elevated, D. Differential Diagnosis: but the degree of Hyperglycemia may be moderate (~300mg/dL or lower). o Starvation Ketosis Urine Ketone reaction correlates poorly with Ketonemia, but is usually o Alcoholic ketoacidosis Positive in DKA o Other Increased Anion Gap Acidosis o o o E. Complications of DKA o Lactic Acidosis o Arterial Thrombosis o Cerebral Edema
Hyponatremia, Hyperkalemia, Azotemia, and Hyperosmolality are other findings. Serum Amylase and Transaminases may be elevated, again raising suspicion for Intra-Abdominal Pathology.

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F. Management of DKA
o o o 1) Confirm diagnosis (High Plasma Glucose, (+) Serum Ketones, Metabolic Acidosis) 2) Admit to Hospital; Intensive Care Setting may be necessary for frequent monitoring or if pH < 7.00 or Unconscious 3) Assess: Serum Electrolytes (K, Na, Mg, Cl, Bicarbonate, Phosphate) Acid-Base Status pH, HCO3, pCO2, B-Hydroxybutyrate Renal Function (Creatinine, Urine Output)
Notes on Potassium: If < 3.3: Hold Insulin; Add 40meq K/L If 3.3 5: 20-30 meq K/L If >5: Re-check Potassium q20 Potassium Drips: Peripheral Line: Maximum Rate is 10 meq/hr (Maximum of 60meq/L) Central Line: Maximum Rate is 20 meq/hr

o o o o o

4) Replace Fluids: 2-3 L of 0.9% Saline over first 1-3 hours (10-15mL/kg per hour); subsequently, 0.45% Saline at 150-300mL/h; change to 5% Glucose and 0.45% Saline at 100-200mL/h when Plasma Glucose reaches 250mg/dL (14mmol/L) 5) Administer Short-Acting Insulin: IV (0.1 units/kg) or IM (0.3units/kg), then 0.1 units/kg per hour by continuous IV infusion; Increase 2 to 3 fold if NO response by 2-4 hours. If initial Serum K + is < 3.3mmol/L (3.3mEq/L), do NOT administer Insulin until the K+ is corrected to > 3.3mmol/L (3.3mEq/L) 6) Assess patient: What precipitated episode (noncompliance, infection, trauma, infarction, cocaine)? Initiate appropriate workup for precipitating event (cultures, CXR, ECG) 7) Measure capillary glucose every 1-2 h; measure electrolytes (especially K+, bicarbonate, phosphate) and Anion Gap every 4 h for first 24 hours 8) Monitor BP, pulse, respirations, mental status, fluid intake and output every 1-4 hours 9) Replace K+: 10 mEq/h when Plasma K+ < 5.5mEq/L, ECG normal, urine flow and normal creatinine documented; Administer 40-80 mEq/h when Plasma K+ <3.5mEq/L or if Bicarbonate is given 10) Continue above until patient is stable, glucose goal is 150 250 mg/dL, and acidosis is resolved, Insulin Infusion may be decreased to 0.05 0.1 units/kg/hour 11) Administer Intermediate or Long-Acting Insulin as soon as patient is eating. Allow for overlap in Insulin Infusion and Subcutaneous Insulin Injection

G. Criteria For Resolving DKA o Normalization of Serum Anion Gap o Normalization of Acidosis o (-) Ketones **IMPORTANT Notes: Serum Ketones: B Hydroxybutyrate (which is converted to Acetoacetate) Urine Ketones: Acetoacetate

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MANAGEMENT OF DIABETIC KETOACIDOSIS (Dr. Gatchalian) CASE: 60kg Patient comes in with a CBG of 500 1st thing to do is HYDRATE (up to 3 L can be given) however, if there is NO Improvement, start Insulin 1. Hydration Monitor CBG every 1 hour We can give as much as 3 L, before giving Insulin 2. Insulin Regimen Give a Bolus Dose of 0.15 U/kg Maintain on a Drip at 0.10 U/kg range of 0.1 to 0.6 (Ex. Mix 20 U Insulin in 100cc PNSS) Ex) In a 60 kg patient, we give 9 Units/Hour . 20 U . = . 9 U . 100cc X X = 45 cc / hour or 45 ugtts/min (which is equivalent to 9 U/hour)

3. Adjusting Insulin Monitor CBG every hour and get the difference Ex) If CBG is 500, then decreases to 300 after one hour, the difference is 200
If Difference is: > 75 50-75 < 50 Decrease by HALF MAINTAIN Dose Double Insulin Dose Ex) If we are giving 9 U/hr, give 4.5 U/hr

4. RULE (Subjective for PGH) If you get a CBG Value of LESS than 250 for 2-3 Consecutive Times, we may: o 1) Start D5NR + 20 mEqs KCl x 10 Hours o 2) Start Fixed Dose of Insulin at HN 0.4-0.6 u / kg / hr
II. HYPERGLYCEMIC HYPEROSMOLAR STATE (HHS) A. Clinical Presentation: o Prototype patient: Elderly with Type 2 DM, with a several weeks history of Polyuria, Weight Loss, and diminished Oral Intake that culminates in Mental Confusion, Lethargy, or Coma o PE: reflects profound Dehydration and Hyperosmolality and reveals Hypotension, Tachycardia, and an altered mental status o Notable ABSENT are symptoms of Nausea, Vomiting, and abdominal pain, and the Kussmaul Respirations characteristic of DKA o Often precipitated by a serious, concurrent illness such as MI or stroke, sepsis, pneumonia & other serious infections o Results from Severe Dehydration and Hyperglycemia clinical evidence of Severe Dehydration is the rule o Ketoacidosis is ABSENT because Residual Insulin Secretion, though inadequate for Glycemic Control, effectively inhibits Lipolysis and Ketogenesis B. Pathophysiology o Relative Insulin Deficiency and Inadequate Fluid Intake are the underlying causes of HHS o Hyperglycemia Osmotic Diuresis Volume Depletion, exacerbated by inadequate fluid intake o Insulin Deficiency is only RELATIVE (probably) and less severe than in DKA C. Management o 1) Fluid Replacement o 2) Insulin Therapy o 3) Collection of Electrolyte Deficits

18

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Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

COMMON GASTROINTESTINAL DISEASES

1) UPPER GASTROINTESTINAL BLEEDING (UGIB)

Hemorrhage may develop from any gut organ Upper GI Bleeding presents with MELENA or HEMATEMESIS Lower GI Bleeding produces passage of Bright Red or Maroon Stools
The Most Common Upper GI Causes of Bleeding are Ulcer Disease, Gastroduodenitis, and Esophagitis. Other etiologies include Portal HPN, Malignancy, Tears across the Gastroesophageal Junction, and Vascular Lesions

I. TERMINOLOGIES Hematemesis Melena Hematochezia Occult GI Bleeding Symptoms of Blood Loss or Anemia II. SOURCES OF BLEEDING PUD (Duodenal and Gastric) Gastritis (Stress, Alcohol, Drugs) Esophagitis, Duodenitis Esophageal Varices, Gastroduodenal Varices Mallory-Weiss Tears Angiodysplasia or Telengiectasia Gastro-Esophageal Carcinoma Hemophilia Gastroduodenal Fistula Bleeding Disorders (Leukemia, Aplastic Anemia)

III. MANAGEMENT Antacids H2 Blockers / PPI AntBx: Metronidazole, Amoxicillin, Tetracycline, Clarithromycin Anticholinergics Sucralfate Bismuth PGE2

IV. CLINICAL PRESENTATION Overt GI Bleeding: presents with passage of fresh or altered blood through the mouth or in the stool Occult Bleeding: refers to (+) Fecal Occult Blood Test or Iron-Deficiency Anemia without visible blood in stool Obscure Bleeding: refers to GI blood loss of unknown origin that persists or recurs after negative initial endoscopic evaluation (obscure bleeding can either be Overt or Occult) V. GENERAL CONSIDERATIONS IN OVERT BLEEDING A. Initial Evaluation o Intravascular Volume and Hemodynamic Status o Laboratory Evaluation (CBC, PT/PTT, Blood Type, Liver & Renal Function Tests B. Initial Resuscitation 1. Restoration of Intravascular Volume: Isotonic Saline, LR, or Hetastarch can be used Blood should be used for volume replacement whenever possible and should be initiated as soon as it is evident that patients bleeding is massive, ongoing, or severe enough that Colloid Infusion alone is NOT adequate for Tissue Oxygenation Packed RBC Transfusion: should be continued until patients condition is hemodynamically stable and hematocrit reaches 25% or greater 2. Correction of Coagulopathy Discontinuation of offending anti-coagulants followed by infusion of FFP can be used to correct prolonged coagulation parameters Protamine Infusion: 1mg antagonizes 100 units of heparin Parenteral Vitamin-K (10mg SC or IM) for prolonged PT from Warfarin Tx or Hepatobiliary Disease Platelet Infusion if Platelet Count < 50,000mm3 3. Airway Protection Intubation to prevent aspiration should be considered in diminished mental status (shock, hepatic encephalopathy), massive hematemesis, or active variceal hemorrhage

VI. APPROACH TO PATIENT A. History & PE

Degree of Volume Loss Level of Bleeding Etiology of Bleeding Patients with Lower GI Bleed have less hemodynamic compromise than those with Upper GI Bleed Hematemesis or Coffee-Ground Emesis, Melena, Hematochezia Important points in history include prior bleeding episodes, alcohol use, liver disease, coagulation disorders, and bleeding tendencies: History of emesis prior to GI bleed = suggest Mallory-Weiss Tear NSAIDs and Aspirin Hypotension and Hypovolemic Shock preceding bleed suggests Ischemic Injury to the gut Radiation Therapy to prostate or pelvis suggests radiation proctitis Prior Aortic Graft Surgery possibility of Aortoenteric or Aortocolonic Fistula Precipitating Factors Abnormalities in coagulation (liver disease, von-willebrands disease, vitamin-K deficiency, DIC) Medications (warfarin, heparin, aspirin, NSAIDs, thromboytics), Color of Stool Can provide important clues NG Aspiration Useful in diagnosing Upper GI Bleeding Anoscopy/Sigmoidosocpy DRE may identify potential source of bleeding in anorectum

B. Further Evaluation and Therapy

Esophagogastroduodenoscopy (EGD) Colonoscopy Tagged RBC Scanning Arteriography Surgery Preferred method of investigation and therapy of upper GI bleed All patients with acute Lower GI bleed from unknown source should undergo endoscopic evaluation of colon RBCs labeled with technetium 99m remain in circulation for as long as 48 hours and extravasate into the bowel lumen with active bleeding Allows rapid localization and potential therapy of GI bleeding when bleeding rates exceed 0.5mL/min Emergent total colectomy may be a lifesaving maneuver for massive, unlocalized lower GI bleed; this should be preceded by EGD to rule out rapidly bleeding upper source

VII. THERAPY FOR SPECIFIC LESIONS

Peptic Ulcer Disease (PUD) High Dose-Proton Pump Inhibitors (Omeprazole 40mg PO BID) reduces rate of recurrent bleeding & need for surgery. Use of High Dose PPIs has documented utility in patients who are awaiting endoscopic treatment or in those whom endoscopy is contraindicated or postponed Therapeutic Endoscopy: advantage of immediate treatment & should be implemented in all patients early in the hospital course (within 24 hours). Fluid resuscitation & hemodynamic stability are essential prior to endoscopy. Surgery for intractable or recurrent bleeding Risk Factors for increased morbidity & mortality: Age > 60 y/o More than one comorbid illness Blood Loss > 5 units Shock on Admission Bright-Red Hematemesis with Hypotension Variceal Hemorrhage Coagulopathy Large (>2cm) Ulcers Recurrent Hemorrhage (within 72 hours) Requirement for Emergency Surgery

ICU admission and Intubation for airway protection in patients who are actively bleeding from varices. Octreotide Infusion to reduce Portal Pressures acutely. Esophageal Varices Variceal Ligation of Banding = Endoscopic Therapy of Choice (controls active hemorrhage) Sclerotherapy (used less frequently because of complications) TIPS / Transjugular Intrahepatic Portosystemic Shunt to decompress the portal pressure Shunt Surgery Balloon Tamponade Gastric Varices Octreotide Infusion or other pharmacologic therapy should be initiated early (as for Esophageal Varices) Variceal Ligation or Banding usually NOT successful Sclerotherapy can be attempted, TIPS, Balloon Tamponade Pharmacologic Prophylaxis with B-Adrenergic Antagonists Shown to REDUCE Portal Pressure & lower risk of recurrent bleeding Propranolol and Nadolol reduce resting heart rate by 25% Hepatic Transplantation

Stress Ulcer

Encountered in ICU setting, especially those who require mechanical ventilation > 48 hours, with coagulopathy, sepsis, burns, or CNS processes Prophylactic Therapy: Histamine-Receptor Antagonists and Sucralfate, PPIs

2) PANCREATITIS
Pathologic Spectrum varies from Edematous Pancreatitis (Mild & Self-Limited) to Necrotizing Pancreatitis (correlates with the Severity of the attack)

I. RANSONS CRITERIA IN PANCREATITIS POOR Predictive Power! > 3 Factors at time of Admission (1) or during initial 48 hours (2) indicates an Increased Mortality Rate These patients need closer monitoring in an ICU stting FIRST 24 HOURS Patients age > 55 y/o Leukocytosis or WBC > 16,000 mm3 Hyperglycemia or FBS > 200 mg/dL Serum LDH > 400 units/mL Serum AST or SGOT > 250 units/mL AFTER 48 HOURS OF ADMISSION Fall in Hematocrit by > 10% Fluid Deficit of > 4000 mL Hypocalcemia (<8mg/dL) Hypoxemia (PO2 < 60mmHg) Increase in BUN to > 1.8 mmol/L after IV-Administration Hypoalbuminemia

Severe Acute Pancreatitis: Risk Factors that Adversely Affect Survival in Acute Pancreatitis:
o o 1) Associated with Organ Failure and/or Local Complications such as Necrosis 2) Clinical Manifestations Obesity BMI > 30 Hemoconcentration (Hct > 44%) Age > 70 3) Organ Failure Shock Pulmonary Insufficiecny (PO2 < 60) Renal Failure (CR > 2.0mg%) GI Bleeding 4) > 3 Ransom Criteria (not fully utilizable until 48 hours) 5) Apache II Score > 8 (Cumbersome)

o o

II. ACUTE PANCREATITIS AUTODIGESTION: One of the pathogenic theories of pancreatitis wherein pancreatitis results when Proteolytic Enzymes (Trypsinogen, Chymotrypsinogen, Proelastase, and Phospholipase-A) are activated IN the Pancreas, rather than in the Intestinal Lumen A. Common Causes of Acute Pancreatitis o Gallstones, Alcohol = MOST COMMON o HyperTriglyceridemia, Hypercalcemia o ERCP, Trauma, Post-Op, Sphincter of Oddi Obstruction o Drugs (MEAT-V) Mercaptopurine, Estrogen, Azathioprine, Tetracycline, Valproic Acid B. Clinical Features o Steady and Boring Abdominal Pain, Epigastric or Periumbilical in location, radiating to the BACK o Pain is more intense when SUPINE o Relieved by sitting with the Trunk Flexed and Knees drawn up (Fetal Position / Prostration) o Associated with nausea, vomiting, and abdominal distention
Abdominal Pain (Major Symptom) BORING and Steady in Character (in Epigastrium & Periumbilical Region) Radiates to the Back (in 50% of Cases) or other Parts of the Abdomen (Chest, Flanks) ACUTE in Onset (Sudden) Lasts for Several Hours Moderate to Severe

**NOTE: It is Frequently more Intense when patient is SUPINE, and relieved by Sitting

C. Physical Examinations o Distressed & anxious patient, Low Grade Fever, Tachycardia o Hypotension: which may be due to: Hypovolemia 20 to exudation of Blood and Plasma CHON into retroperitoneal space Increased formation and release of Kinin Peptides which cause Vasodilation and Increased Vascular Permeability Systemic Effects of Proteolytic and Lipolytic Enzymes o Obstructive Jaundice due to Edema of the Head of the Pancreas o Erythematous Skin Nodules 2 0 to Subcutaneous Fat Necrosis o Bibasilar Rales, Atelectasis, Pleural Effusion o Hypoactive Bowel Sounds o Findings in Severe Necrotizing Pancreatitis: Cullens Sign = Faint blue discoloration around umbilicus which occurs as the result of Hemoperitoneum Turners Sign = blue-red-purple / green-brown discoloration of flanks due to tissue catabolism of Hemoglobin D. Diagnosis of Acute Pancreatitis o Any severe acute pain in abdomen or back should suggest Acute Pancreatitis o Diagnosis confirmed by a Threefold or Greater Elevated Level of Serum Amylase and/or Lipase o Strong Indicators include: Hemoconcentration (Hct > 44%), Signs of Organ Failure E. Differential Diagnosis = Any Disease with (+) Abdominal Pain
Perforated Viscus (especially Peptic Ulcer) Acute Cholecystitis and Biliary Colic Acute Intestinal Obstruction Mesenteric Vascular Occlusion Connective Tissue Disorders with Vasculitis Pneumonia Diabetic Ketoacidosis Other Differentials Can usually identified by imaging studies or endoscopy Readily diagnosed by the presence of Free Intraperitoneal Air Pain of Biliary Tract in Origin is usually right-sided or epigastric than periumbilical, and is gradual in onset; Ileus is usually absent; UTZ is helpful in diagnosing Cholelithiasis and Cholecystitis Both Pancreatitis and Acute Cholecystitis can have elevated serum amylase Should be colicky pain, xrays showing mechanical obstruction Evident in elderly debilitated patients with brisk leukocytosis, abdominal distention, and bloody diarrheal; Angiography shows vascular occlusion SLE, Polyarteritis Nodosa Pain referred in Upper Abdomen Serum Lipase Level is NOT Elevated in DKA (however, Amylase is elevated) Renal Colic, Myocardial Infarction, Dissecting Aortic Aneurysm

Serum Amylase & Lipase levels are widely used as Screening Tests for Acute Pancreatitis in patients with Abdominal Pain or Back Pain. Values greater than THREE TIMES the upper limit of Normal virtually clinch the Diagnosis if Gut Perforation or Infarction is excluded. In the absence of objective evidence of pancreatitis by abdominal UTZ, CT, ERCP, or EUS, mild to moderate elevations of Amylase and/or Lipase are problematic in making a diagnosis of Pancreatitis. In Acute Pancreatitis, Serum Amylase is usually elevated within 24 hours of onset and remains so for 1-3 days. Levels return to normal within 3-5 days unless there is extensive pancreatic necrosis, incomplete ductal obstruction, or pseudocyts formation. Approximately 85% of patients with acute pancreatitis have an elevated serum amylase level. Serum Amylase is often elevated in other conditions (because enzyme is found in many organs pancreas, salivary glands, liver, small intestine, kidney, fallopian tube and can be produced by various tumors carcinomas of the lung, esophagus, breast, ovary. Renal Insufficiency Salivary Gland Lesions: Mumps, Calculus, Irraiation Sialadenitis, Maxilofacial Surgery Tumor Hyperamylasemia: CA of Lung, Esophagus, Breast, Ovarian Macroamylasemia, Burns, DKA, Pregnancy, Renal Transplantation, Cerebral Trauma, Drugs (Morphine) Cholecystitis, Choledocholithiasis, Perforated / Penetrating Peptic Ulcer, Intestinal Obstruction / Infarction, Ruptured Ectopic Pregnancy, Peritonitis, Aortic Aneurysm, Chronic Liver Disease, Postoperative Hyperamylasemia Serum LIPASE may now be the Single Best Enzyme to measure for the diagnosis of Acute Pancreatitis. An Assay for Trypsinogen has a theoretical advantage over Amylase and Lipase determinations in that the pancreas is the ONLY organ that contains this enzyme. No single blood test is reliable for the diagnosis of Acute Pancreatitis in patients with Renal Failure.

F. Diagnostics: 1. Amylase
Diagnosis of Pancreatitis is usually established by detection of an INCREASED Level of Serum Amylase (Salivary Gland Disease and Gut Perforation or Infarction should be EXCLUDED!) There is NO Definite Correlation between the Severity of Pancreatitis & Degree of Elevation After 48 to 72 hours, Amylase tend to RETURN to NORMAL (even with continuing evidence of pancreatitis) Elevated Levels may remain for 7 to 14 days Three Fold Elevation of Serum Lipase is usually Diagnostic of Acute Pancreatitis Markedly Increased Levels of Peritoneal or Pleural Fluid Amylase (>1500nmol/L or > 5000U/dL) Leukocytosis (15,000 20,000 per uL) Hemoconcentration in more severe disease (Hematocrit > 44%) Hyperglycemia, Hypocalcemia, Hyperbilirubinemia Elevated Serum Lactate Dehydrogenase (LDL) Levels > 8.5umol or > 500 U/dL POOR Prognosis Hypertriglyceridemia in 15-20% (Amylase and Lipase are normal in these patients) Hypoxemia ECG: ST-Segment and T-Wave Abnormalities, simulating Myocardial Ischemia 1) Localized Ileus, usually involving the jejunum (Sentinel Loop) 2) Generalized Ileus with Air-Fluid Levels 3) Colon Cut-Off Sign, which results from isolated distention of Transverse Colon 4) Duodenal Distention with Air-Fluid Levels 5) A Mass, which is frequently a Pseudocyst Can confirm clinical impression of Acute Pancreatitis, even if Amylase is NORMAL Can indicate severity Useful in Acute Pancreatitis to evaluate the gallbladder Pancreas is enlarged in Acute Pancreatitis High resolution imaging of the Pancreatic Parenchyma and Pancreatic Duct with a trasducer fixed to an endoscope that can be directed onto the surface of the pancreas through stomach or duodenum May provide useful information on the status of pancreatic ductal system Necrosis, Abscess, Pseudocyst, Ascites, Obstructive Jaundice Pleural Effusion, ARDS, Hypotension, DIC, GI Hemorrhage, Oliguria, Hyperglycemia, Fat Necrosis, Encephalopathy

2. Lipase

3. Other Findings:

4. Plain Films of the Abdomen in Acute Pancreatitis

5. CT-Scan 6. Sonography 7. Endoscopic Ultrasonography (EUS) 8. Endoscopic Retrograde Cholangiopancreatography (ERCP)

Local Systemic

G. Complications:

1. Necrotizing Pancreatitis Represents a severe form of Acute Pancreatitis, usually identified on Dynamic Dual-Phase CT Scanning with Contrast Infected Pancreatic Necrosis: (+) Increasing Abdominal Pain, marked Leukocytosis, Bacteremia Mx for Infected Necrosis: CT-Guided Percutaneous Aspiration for GS/CS to Confirm 2. Pseudocysts Suggested by persistent pain or hyperamylasemia Complications: Infection, Hemorrhage, Rupture (Pancreatic Ascites), Obstruction of adjacent structures Asymptomatic Non-Enlarging Pseudocyts < 6cm: followed clinically with serial imaging studies Symptomatic / Complicated Pseudocysts: decompression by Percutaneous, Endoscopic, Surgical Technique 3. Infection Sources of Fever: Pancreatic Necrosis, Abscess, Infected Pseudocyst, Cholangitis, Aspiration Pneumonia Cultures should be obtained and Broad-Spectrum Antibiotics should be administered 4. Pulmonary Complications Atelectasis, Pleural Effusion, Pneumonia, ARDS Cellular Injury & death result in liberation of bradykinin peptides, vasoactive substances, & histamine that can produce vasodilation, increased vascular permeability, and edema with profound effects on many organs, most notably: LUNG 5. Renal Failure Due to Severe Intravascular Volume Depletion or Acute Tubular Necrosis

H. Indicators of Organ Failure

Cardiovascular Pulmonary Renal GIT Hypotension (BP < 90mmHg) or Tachycardia ( > 130 beats/min) PO2 < 60mmHg Oliguria (<50ml/h) or Increasing BUN, Creatinine Gastrointestinal Bleeding

I. Treatment = Supportive (Disease is Self-Limited & subsides spontaneously, usually 3-7 days after treatment is instituted) 1. Aggressive Volume Repletion with IV Fluids Serum Electrolytes, Ca2+, Glucose levels should be monitored and supplemented 2. Narcotic Analgesics: For PAIN Relief Most Commonly used agent because it has the least effect on the Sphincter of Oddi Meperidine Morphine & Pantazocine
It is the DOC because it does NOT cause Spasm of the Sphincter of Oddi) However, it is Contraindicated in Renal Failure. Should be avoided if possible

3. Nothing Per Orem (NPO) NPO until they are free of pain and nausea NG Suction is reserved for patients with Ileus or Protracted Nausea & Vomiting and is not routine (Nasogastric Suction to Decrease Gastrin Release from the Stomach and Prevent Gastric Contents from Entering the Duodenum) When can we Start giving Food (Med School Notes)? When patient is Stable already (+) Abdominal Sounds, etc Start with CARBOHYDRATES 4. Urgent ERCP and Biliary Sphincterotomy Within 72 Hours of presentation can improve the outcome of Severe Gallstone Pancreatitis Thought to result from reduced biliary sepsis, rather than being a true improvement of pancreatic inflammation 5. Acid Suppression May be necessary in severely ill patients with risk factors for Stress Ulcer Bleeding 6. Prophylactic Antibiotics For SEVERE Pancreatitis (Nectrotizing Acute Pancreatitis)

III. CHRONIC PANCREATITIS Chronic Inflammatory Disease of the Pancreas commonly seen with Chronic Alcohol Abuse Characterized by Irreversible Damage to the Pancreas, as distinct from the Reversible Changes noted in Acute Pancreatitis Presence of histologic abnormalities, including chronic inflammation, fibrosis and progressive destruction in both Exocrine and eventually Endocrine Tissue A. Clinical Features (Symptoms are IDENTICAL to Acute Pancreatitis) o PAIN = may be Continuous, Intermittent or Absent o WEIGHT LOSS o Abnormal Stools, MALABSORPTION Signs of Malabsorption are Common in Chronic Pancreatitis

B. Diagnosis 1. Amylase and Lipase They are NOT Elevated (in contrast to Relapsing Acute Pancreatitis) 2. Classic Triad (seen in < 1/3 or Patients) Pancreatic Calcification Steatorrhea Diabetes Mellitus 3. Intubation Test Secretin Stimulation Test Usually gives Abnormal Results when 60% or More of Pancreatic Exocrine Function has been lost 4. Cobalamin Malabsorption Corrected by the Administration of Oral Pancreatic Enzymes 40% of Patients have Cobalamin (Vitamin B12) Malabsorption 5. Marked Excretion of Fecal Fat Corrected by Administration of Oral Pancreatic Enzymes 6. Serum Trypsinogen Level DECREASED In the presence of Steatorrhea, a Serum Trypsinogen Level < 10ng/mL = Diagnostic of Chronic Pancreatitis 7. Radiographic Hallmark = (+) CALCIFICATION throughout the Pancreas Ultrasound CT-Scan ERCP C. Treatment (Directed to TWO MAJOR Problems = Pain + Malabsorption) 1. Management of Pain (Critical in Chronic Pancreatitis) ABSTINENCE from Alcohol and Fatty meals Use of Narcotics Pancreatic Enzymes Surgery ERCP and Sphincterotomy if (+) Pancreatic Duct Obstruction from stones, structures, papillary stenosis 2. Management of Malabsorption (Exocrine Insufficiency) Pancreatic Enzyme Replacement Supportive Measures Diet should be Moderate in Fat (30%), High in protein (24%), and Low in CHO (40%) Restriction of Long-Chain Triglyceride Intake can help Patients who DONT respond satisfactorily to Pancreatic Enzyme

3) PEPTIC ULCER DISEASE

Most Common Cause of UGIB Ulcer: Break in the Mucosal Surface > 5mm, with Depth into the Mucosa Burning Epigastric Pain exacerbated by Fasting and improved with Meals

I. FEATURES Epigastric Burning Pain Bloatedness, Nausea, Vomiting, Insomnia UGIB II. DIAGNOSIS
X Ray Double contrast upper GI series.

Alarming Symptoms: Weight Loss, Early Satiety, Bleeding, Anemia, and lack of appropriate response to Acid Suppression

Benign: Smooth, regular, round ulcer, ulcer crater beyond gastric wall, gastric folds into the base, collar of edema / Hamptons line around the base, distensible gastric wall in the ulcer area Endoscopy Gastric Acid Analysis Primary Diagnostic Maneuver (usually with biopsy of the ulcer) Achlorydia usually in malignant

III. COMPLICATIONS Hemorrhage: Most Serious Perforation (intense pain, rigid abdomen, decreased BS, direct & rebound tenderness Gastric Outlet Obstruction: early satiety, epigastric fullness, nausea and vomiting of undigested food, weight loss Penetration (into adjacent organ): sudden onset of pain radiating to the back, High Amylase and Lipase (treatment is surgical) IV. TREATMENT PROTOCOLS FOR H. pylori NO Single Agent is effective in eradicating the Organism Combination Therapy for 14 days provides the GREATEST Efficacy Goals in Treating PUD: o 1) Relief of Symptoms (Pain or Dyspepsia) o 2) Promote Ulcer Healing o 3) Prevent Ulcer Recurrence & Complications DRUG Triple Therapy 1. Bismuth Subsalicylate PLUS Metronidazole PLUS Tetracycline 2. Ranitidine Bismuth Citrate PLUS Tetracycline PLUS Clarithromycin or Metronidazole 3. Omeprazole (Lansoprazole) PLUS Clarithromycin PLUS Metronidazole OR Amoxicillin Quadruple Therapy Omeprazole (Lansoprazole) Bismuth Subsalicylate Metronidazole Tetracycline DOSE 2 tablets QID 250mg QID 500mg QID 400mg BID 500mg BID 500mg BID 20mg BID (30mg BID) 250 or 500mg BID 500mg BID 1g BID 20mg (30mg) daily 2 tablets QID 250mg QID 500mg QID

4) ACUTE CHOLANGITIS
I. CHARCOTS TRIAD AND REYNOLDS PENTAD A. Charcots Triad o Right Upper Quadrant Pain o Jaundice o Fever **NOTE: Seen in 70% of patients with Bacterial Cholangitis B. Reynolds Pentad o Right Upper Quadrant Pain o Jaundice o Fever o Altered Mental Status o Shock II. TREATMENT OF ACUTE CHOLANGITIS Mild (Grade I) Moderate (Grade II) Non responsive to medical management Severe (Grade III) Patients with acute cholangitis and organ failure

Observation (Antibiotic, Analgesia, prevention of organ damage) Early Biliary Drainage Urgent Biliary Drainage

**NOTE: Treatment for all = Treatment of ETIOLOGY

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5) COMMON CAUSES OF GI SYMPTOMS

ABDOMINAL PAIN Appendicitis Gallstone Disease Pancreatitis Diverticulitis Ulcer Disease Esophagitis GI Obstruction Inflammatory Bowel Dse Functional Bowel D/O Vascular Disease Gynecologic Renal Stone NAUSEA & VOMITING Medications GI Obstruction Motor Disorders Functional Bowel D/O Enteric Infection Pregnancy Endocrine Disease Motion Sickness CNS Disease DIARRHEA Infection Poorly Absorbed Sugars Inflammatory Bowel Dse Microscopic Colitis Functional Bowel D/O Celiac Disease Pancreatic Insufficiency Hyperthyroidism Ischemia Endocrine Tumor GI-BLEEDING Ulcer Disease Esophagitis Varices Vascular Lesions Neoplasm Diverticula Hemorrhoids Fissures Inflammatory Bowel Dse Infectious Colitis OBSTRUCTIVE JAUNDICE Bile Duct Stones Cholangiocarcinoma Cholangitis Sclerosing Cholangitis Ampullary Stenosis Ampullary Carcinoma Pancreatitis Pancreatic Tumor

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6) OTHER GI DISEASES
I. ACHALASIA Motor disorder of the Esophageal Smooth Muscle in which the LES does NOT relax normally with swallowing, and the Esophageal Body undergoes Non-Peristaltic Contractions Underlying Abnormality = Loss of Intramural Neurons (Inhibitory Neurons containing VIP and Nitric Oxide Synthase are predominantly involved, but Cholinergic Neurons are also affected in Advanced Disease) A. Primary VS Secondary o Primary Idiopathic Achalasia: Most of the patients (in the US) o Secondary Achalsia: May be caused by: Gastric Carcinoma that infiltrates Esophagus Lymphoma Chagas Disease Certain Viral Infections Eosinophilic Gastroenteritis Neurodegenerative Disorders B. Clinical Features o Main Symptoms: Dysphagia, Chest Pain, Regurgitation o Dysphagia: Appears early Occurs with BOTH Liquids and Solids Worsened by Emotional Stress and Hurried Eating **NOTE: The presence of Gastroesophageal Reflux argues AGAINST Achalasia In patients with Long-Standing Heartburn, cessation of Heartburn and appearance of Dysphagia suggest development of Achalasia on top of Reflux Esophagitis C. Diagnosis
Chest X-Ray Absence of Gastric Air Bubble Tubular Mediastinal Mass beside the Aorta (sometimes) Air-Fluid Level in Mediastinum in Upright Position represents Retained Food in Esophagus Esophageal Dilatation Sigmoid Esophagus (in advanced cases) Normal Peristalsis is LOST in the Lower 2/3 of Esophagus Terminal Part shows a Persistent Beaklike Narrowing (represents Non-Relaxing LES) Basal LES Pressure NORMAL or ELEVATED Swallow-Induced Relaxation either does NOT occur or is Reduced in Degree, Duration, Consistency Esophageal Body shows an Elevated Resting Pressure In Response to Swallows, Primary Peristaltic Waves are Replaced by Simultaneous-Onset Contractions These contractions may be of Poor Amplitude (Classic Achalasia) or of Large Amplitude and Long Duration (Vigorous Achalasia) CCK Test Cholecystokinin (CCK), which normally causes a Fall in the Sphincter Pressure, Paradoxically causes Contraction of the LES This paradoxical response occurs because, in Achalasia, the Neurally Transmitted Inhibitory Effect of CCK is Absent, owing to the loss of Inhibitory Neurons Endoscopy To exclude Secondary Causes of Achalasia, particularly Gastric Carcinoma

Barium Swallow Fluoroscopy Manometry

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II. DIFFUSE ESOPHAGEAL SPASMS and RELATED MOTOR DISORDERS Symptoms: Chest Pain and Dysphagia Recognized by Manometric Features DES: Characterized by Non-Peristaltic Contractions, usually of Large Amplitude and Long Duration An Esophageal Motility Pattern showing Hypertensive but Peristaltic Contractions has been called Nutcracker Esophagus A. Clinical Features o Non-Peristaltic Patterns are dye to Dysfunction of Inhibitory Nerves o Histopathology: Patchy Neural Degeneration localized to Nerve Processes, rather than the Prominent Degeneration of Nerve Cell Bodies seen in Achalasia (Diffuse Esophageal Spasm may progress to Achalasia) B. Diagnosis of Diffuse Esophageal Spasm Barium Swallow The Normal Sequential Peristalsis below the Aortic Arch is REPLACED by Uncoordinated Simultaneous Contractions that produce the appearance of Curling or Multiple Ripples in the Wall, Sacculations, and Pseudodiverticula the Corkscrew Wsophagus Barium Swallow is frequently Normal in DES and Mostly Normal in Related Disorders Manometry DES and other related disorders are Manometric Diagnoses

Several Techniques to Provoke Esophageal Spasms: Cold Swallows (produce Chest Pain but do NOT produce Spasm on Manometry) Solid Boluses Pharmacologic Agents (Edrophonium) induce both Chest Pain and Motor Abnormalities C. Treatment = Agents that Relax Smooth Muscle o Sublingual Nitroglycerin (0.3 to 0.6mg) o Long-Acting Agents: Isosorbide Dinitrate (10-30mg PO before meals), Nifedipine (10-20mg PO before meals) III. DIARRHEA Loosely defined as Passage of Abnormally Liquid or Unformed Stools at an Increased Frequency For adults: Stool Weight > 200g/d can be generally considered Diarrheal A. Acute VS Chronic o Acute: < 2 Weeks o Persistent: 2-4 Weeks o Chronic: > 4 Weeks B. Pathology of Causative Agents 1) Toxin-Producers Pre-Formed Toxins: Bacillus cereus, Staphylococcus aureus, Clostridium perfringens Enterotoxin: Vibrio cholerae, Enterotoxigenic E.coli, Klebsiella pneumoniae, Aeromonas 2) Enteroadherent Enteropathogenic and Enteroadherent E.coli Giardia organisms Cryptosporidiosis Helminths 3) Cytotoxin-Producers Clostridium difficile Hemorrhagic E.coli 4) Invasive Organisms Minimal Inflammation: Rotavirus and Norwalk Variable Inflammation: Salmonella, Campylobacter and Aeronomas Species, Vibrio parahaemolyticus, Yersinia Severe Inflammation: Shigella Species, Enteroinvasive E.coli, Entamoeba histolytica **REITERs SYNDROME = Arthritis, Urethritis, Conjunctivitis Salmonella Campylobacter Reiters Syndrome may accompany or follow infections by Shigella the following Yersinia **NOTE: More than 90% of Acute Diarrhea are caused by INFECTIOUS AGENTS Remaining 10% are caused by Medications, Toxic Ingestions, Ischemia, etc

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LIVER DISEASES

1) VIRAL HEPATITIS
I. CLINICAL & EPIDEMIOLOGIC FEATURES OF VIRAL HEPATITIS A. Hepatitis-A Virus
Antigen (s) Antibodies Features Diagnosis Age Preference Transmission Fecal-Oral Percutaneous Perinatal Sexual Clinical Severity Fulminant Progress to Chronicity Carrier Cancer Prognosis Prophylaxis Therapy HAV Anti-HAV Early Fecal Shedding Acute Infection = IgM and Anti-HAV Previous Infection = IgG Anti-HAV Children, Young Adults +++ Unusual +/Mild 0.1% None None None Excellent Immunoglobulin Inactivated Vaccine NONE (No Specific Treatment it is just Supportive) Blood-Borne Virus, Carrier State Young Adults (Sexual and Percutaneous) Babies, Toddlers +++ +++ ++ Occasionally Severe 0.1-1% Occasional (1-10%) 90% of Neonates 0.1 30% (+) Neonatal Infection Worse with Age, Debility Recombinant Vaccine Interferon (Immunomodulator); Lamivudine (Antiviral) HCV, C100-3, C33c, C22-3, NS5 Anti-HCV Blood-Borne Agent (formerly labeled as Non-A, Non-B Hepatitis) Acute Diagnosis = Anti-HCV Chronic Diagnosis = Anti-HCV and HCV RNA Any Age, but More Common in Adults +++ +/+/Moderate 0.1% Common: 50-70% chronic hepatitis; 80-90% chronic infection 1.5-3.2% + Moderate NONE Interferon + Ribavirin

Some Points: There is NO Progression to Chronicity! No Carrier State! No Predisposition to Development of Hepatocellular Cancer

B. Hepatitis-B Virus
Features Age Preference Transmission Fecal-Oral Percutaneous Perinatal Sexual Clinical Severity Fulminant Progress to Chronicity Carrier Cancer Prognosis Prophylaxis Therapy

Some Points: It CAN Progress to CHRONICITY (especially if it is Transmitted Perinatally from mother to neonate) There is a Recombinant Vaccine! Prognosis is WORSE with Age It is a DNA Virus (unlike Hepatitis-A) If we are Vaccinated = we will be (+) Anti-HBs

C. Hepatitis-C Virus
Antigen (s) Antibodies Features Diagnosis Age Preference Transmission Fecal-Oral Percutaneous Perinatal Sexual Clinical Severity Fulminant Progress to Chronicity Carrier Cancer Prognosis Prophylaxis Therapy

Some Points: NO Vaccine Yet (because of the Several Subtypes!) Formerly labeled as Non-A NonB Hepatitis Most Common: Blood Transfusion Infection Complications and Sequalae RARELY = Fulminant Hepatitis-C Chronic Hepatitis-C

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D. Hepatitis-D Virus
Antigen (s) Antibodies Features HBsAg, HDV Antigen Anti-HBs, Anti-HDV Defective RNA-Virus requires Helper Function of HBV (Hepadnaviruses) HDV Antigen present in Hepatocyte Nucleus Anti-HDV, HDV-RNA HBV/HDV Coinfection: -IgM Anti-HBc and Anti-HDV HDV Superinfection: -IgG Anti-HBc and Anti-HDV Any Age (Similar to HBV) +++ + ++ Occasionally Severe 5-20% Common Variable +/Acute = Good Chronic = Poor HBV-Vaccine (None for HBV Carriers) Interferon +/-

Complications and Sequelae Fulminant Hepatitis Mild Disease Asymptomatic Carriers

Diagnosis

Age Preference Transmission Fecal-Oral Percutaneous Perinatal Sexual Clinical Severity Fulminant Progress to Chronicity Carrier Cancer Prognosis Prophylaxis Therapy

E. Hepatitis-E Virus
Antigen (s) Antibodies Features Diagnosis Age Preference Transmission Fecal-Oral Percutaneous Perinatal Sexual Clinical Severity Fulminant Progress to Chronicity Carrier Cancer Prognosis Prophylaxis Therapy HEV Antigen Anti-HEV Agent of Enterically Transmitted Hepatitis IgM/IgG Anti-HEV (assays being developed) Virus in Stool, Hepatocyte, Cytoplasm, Bile Young Adults (20-40 years) +++ Mild 1-2% None None None Good Unknown None

Summary of Some Differences:

Incubation Onset Vaccination Transmission Therapy A 15-45 Acute IG, Inactivated Feco-Oral None B 30-180 Insidious or Acute Recombinant Percutaneous (+++) Perinatal (+++) Sexual (++) Interferon Lamivudine C 15-160 Insidious NONE Percutaneous (+++) Sexual (+/-) Interferon Ribavirin D 30-180 Insidious or Acute HBV Vaccine Percutaneous (+++) Perinatal (+) Sexual (++) Interferon E 14-16 Acute Unknown Feco-Oral None

15

II. SIMPLIFIED DIAGNOSTIC APPROACH IN PATIENTS PRESENTING WITH ACUTE HEPATITIS (Medicine Notes) INTERPRETATION HBsAg IgM Anti HAV IgM Anti HBC Anti HCV Acute Hepa B + + Chronic Hepa B + Acute Hepa A + + Superimposed on Chronic Hepa B Acute Hepa A & B + + + Acute Hepa B + Acute Hepa A & B + (HBsAg below detection threshold) Acute Hepa B + (HBsAg below detection threshold) Acute Hepa C + III. COMMONLY ENCOUNTERED SEROLOGIC PATTERNS OF HEPATITIS-B INFECTION
INTERPRETATION Acute HBV Infection (High Infectivity) Chronic HBV Infection (High Infectivity) 1) Late-Acute or Chronic HBV Infection (Low Infectivity) 2) HBeAg-Negative (Precore-Mutant) Hepatitis B (Chronic or, rarely, Acute) 1) HBsAg of one Subtype and Heterotypic Anti-HBs (Common) 2) Process of Seroconversion from HBsAg to AntiHBs (RARE) 1) Acute HBV Infection 2) Anti-HBc Window 1) Low Level Hepatitis B Carrier 2) Hep B in Remote Past Infection Recovery from HBV Infection 1) Immunization w/ HBsAg (Vaccination) 2) Remote Past Infection (?) 3) False Positive HBsAg Anti-HBs Anti-HBc HBeAg Anti-HBe

+ + +

IgM IgG IgG

+ + -

+ -

+ + +

+ IgM IgG IgG -

+/+/-

+/+/+/+/-

**NOTE: Anti-HBc Window = period wherein only the IgM Anti-HBc (Core Antigen) is POSITIVE!

16

A. Genomic Structure of HBV o HBs = Surface Antigen o HBV-DNA = DNA Polymerase o HBc = Core Antigen o HBe = Envelope a. Antigen = HBsAg HBsAg is detectable in > 95% of Patients with Acute Hepatitis-B It is found in Serum, Body Fluids, Hepatocyte Cytoplasm b. Antibody = Anti-HBs Appears following Infection Protective Antibody! B. Scheme of TYPICAL Clinical and Laboratory for Hepatitis-B o Jaundice will come LATER than the Increase in ALT (unlike in Hepatitis-A) o (+) HBsAg IMPORTANT Notes:
When patient presents with Jaundice, look out for HBeAg, IgM Anti-HBc and HBeAg If after 6 months, the HBsAg is still present, then the Patient already has CHRONIC Hepatitis-B ALT Increase PRECEDES Jaundice

QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.

1. Antigens and Antibodies HBs Anti-HBs HBc Anti-HBc (IgM; IgG) HBe Anti-HBe 2. Golden Period = 24-WEEKS ALL the ANTIGENS must DECREASE in 24-Weeks otherwise, it progresses to Chronicity! Chronic Hepatitis = Persistence of Antigen (HBsAg) BEYOND 6-Months or 24 Weeks **Window Period = BOTH HBs and HBe Antigens are NEGATIVE The only marker which is positive would be IgM Anti-HBc

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C. Complications and Sequelae 1. Serum-Sickness Like Syndrome During the PRODROMAL PHASE Signs and Symptoms: Arthralgia / Arthritis Rash Angioedema Hematuria, Proteinuria (5-10%) 2. Fulminant Hepatitis (90% will die) Massive Hepatic Necrosis It is a RARE Event Signs and Symptoms = ENCEPHALOPATHY Coma Small Liver Excessively Prolonged Prothrombin Time (PT) **Hepatic Failure with Encephalopathy: SMALL Liver = Rapidly SHRINKING Liver Size Rapidly Rising Bilirubin Level Markedly Prolonged PT even as Transaminases FALL Clinical Signs: o Confusion o Disorientation o Somnolence o Ascites & Edema **Terminal Events for Fulminant Hepatic Failure (Causes of Death) Cerebral Edema (Most Common) Brainstem Compression GIT-Bleeding Sepsis Respiratory Failure Cardiovascular Collapse Renal Failure **NOTE: Mortality Rate > 80% 3. Chronic Hepatitis There is an INCREASED Risk to develop Hepatocellular Carcinoma 95% of Patients with Hepatocellular Carcinoma will be Positive for Hepatitis-B **NOTE: Chronic if (+) HBsAg Persisting > 6 MONTHS 4. Increased Risk for Hepatocellular Carcinoma Hepatitis-B = Most Common Cause of Hepatocellular Carcinoma

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D. Chronic Hepatitis-B (Antigens PERSIST > 6 Months) o Clinical and Laboratory Features, suggesting Progression from ACUTE to CHRONIC Hepatitis-B: 1) Lack and Complete Resolution of Clinical Symptoms of Anorexia, Weight Loss, Fatigue and Persistence of Hepatomegaly 2) Presence of Bridging or Multilobular Hepatic Necrosis on Liver Biopsy during Protracted, Severe Acute Viral Hepatitis 3) Failure of Serum Transaminase, Bilirubin and Globulin Levels to return to Normal within 6-12 months after Acute illness 4) Persistence of HBeAg beyond 3 months or HBsAg beyond 6 Months after Acute Hepatitis IMPORTANT Notes:
In Chronic Hepatitis B, HBsAg does NOT down (Anti-HBC may go down & be replaced by IgG)
QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.

ALT may be Fluctuating if it is Elevated, it may signify Activity

**NOTE: Chronic Hepatitis-B is (+) HBsAg Persisting > 6-MONTHS: 1. Active Chronic Hepatitis = TREAT! (+) HBs Antigen (+) HBeAg ALT is Abnormal (Increased) **IMPORTANT Notes: o HBeAg = Marker for Infectivity! o Anti-HBe = Marker of Recovery! 2. Inactive Chronic Hepatitis (+) HBs Antigen (-) HBe Antigen (+) Anti-HBe (Marker of Recovery) ALT is NORMAL We DONT have to Treat just Observe 3. Precore Type (Mutant Strain) (+) HBs Antigen (-) HBe Antigen (+) Anti-HBe (Antibody) ALT is ABNORMAL We have to Treat!

19

2) CASE ON LIVER MASS

50/M with a chief complaint of Right Lower Lobe Liver Mass Dx: T/C Hepatocellular Carcinoma (HCCA)

I. NOTES ON LIVER DISEASES Fatigue: Common symptom of liver pathologies Jaundice: Common feature in Severe / Advanced cases Importance of Digital Rectal Examination (DRE) in Liver Diseases: o Hemorrhoids would indicate portal hypertension o Melena would come from bleeding varices, due to portal hypertension II. ALCOHOLIC LIVER DISEASE Pathology of Alcoholic Liver Disease comprises THREE Major Lesions o Fatty Liver o Alcoholic Hepatitis o Cirrhosis The following contain ~12 g of Alcohol: o One Beer o Four Ounces of Wine o One Ounce of 80% Spirits Threshold for Developing Alcoholic Liver Disease: o MEN: > 60-80 g/day for 10 YEARS (approximately 4 beers; because in 1 beer = 12g) o WOMEN: 20-40 g/day for 10 YEARS III. HEPATOCELLULAR CARCINOMA Most metastatic CA to the liver would come from the GI tract because of Hematogenous spread Signs of Cirrhosis (CLD) = Palmar Erythema, Gynecomastia in males, Testicular Atrophy Signs of Portal HPN = Caput medusae, Telangiectasia, Spider angiomata IV. DIFFERENTIALS A. Focal Nodular Hyperplasia o Considered because of the mass o However, rule out a more serious pathology, before considering a benign one o Size of the mass would point to a malignancy B. Renal Cell Carcinoma o TRIAD: Hematuria + Flank Mass + Flank Pain o Not considered because these are absent in the patient

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V. DIAGNOSTICS A. Triphasic CT-Scan (for Liver Masses) o Three Phases = Arterial + Venous + Plain o Done to see the vascularity of the mass, because it would light up in the arterial phase Highly Vascular Masses would suggest a Malignancy B. Dynamic Ultrasound C. AFP Levels o Before doing a biopsy, get AFP levels first o If AFP is > 200, the mass is most probably MALIGNANT **NOTE: If the following are present, there is NO need for a BIOPSY 1) Mass > 2cm detected by any imaging modality 2) Elevated AFP > 200 3) Features of Malignancy in Dynamic Scan (Triphasic CT, Dynamic UTZ) **NOTE: If the following are present, treat as HEPATOCELLULAR CA!!!! Read algorithm in harrisons D. Biopsy o Biopsy is NOT done in all cases of Hepatic Masses to avoid Invasive Procedure and its complications o If we do a biopsy, check PT/PTT E. Chest X-Ray o To check for any masses, pathologies, etc o Pleural Effusion: On CXR, we would see Blunting of Costophrenic Angles, Meniscus Sign On CXR, for pleural effusion to blunt the Costophrenic Sulci, there must be 175cc of Fluid Reactive Pleural Effusion: Pleural effusion on the right in cases of liver abscess, liver mass, etc VI. EXAMS TO EVALUATE LIVER FUNCTION Albumin Bleeding Parameters Bilirubin **NOTE: ALT / AST are NOT markers of Liver Function! o They are Functions of HEPATOCELLULAR DAMAGE

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VII. DIAGNOSTICS TO EVALUATE LIVER DISEASES A. Tests Based on Detoxification and Excretory Functions o Serum Bilirubin o Urine Bilirubin o Blood Ammonia o Serum Enzymes
SERUM ENZYMES 1. Enzymes the Reflect DAMAGE to Hepatocytes Aminotransferases (Transaminases) are sensitive indicators of Liver Cell Injury and are most helpful in recognizing Acute Hepatocellular Diseases such as Hepatitis Includes: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) o AST = found in the liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, and erythrocytes (in decreasing order of concentration) o ALT = found primarily in the LIVER Any type of Liver Cell Injury can cause modest elevations in the Serum Aminotransferases Aminotransferases > 1000 U/L occur almost exclusively in disorders associated with Extensive Hepatocellular Injury (Viral Hepatitis, Ischemic Liver Injury, Toxin/Drug Induced Liver Injury) Important Notes: o In most Acute Hepatocellular Disorders: ALT > AST o AST:ALT Ratio > 2:1 is suggestive, while a Ratio of > 3:1 is Highly Suggestive of Alcoholic Liver Disease o The AST in Alcoholic Liver Disease is rarely > 300U/L and the ALT is often normal (a low level of ALT in serum is due to Alcohol Induced Deficiency of Pyridoxal Phosphate) 2. Enzymes that Reflect Cholestasis Alkaline Phosphatase, 5Nucleotidase, and -Glutamyl Transpeptidase are usually elevated in Cholestasis

B. Tests that Measure Biosynthetic Function of the Liver

1. Serum Albumin Frequently decreased in Chronic Liver Disease Half Life is relatively long (~20 days) therefore, Serum Levels may be NORMAL in Acute Liver Disease 2. Serum Globulins

C. Coagulation Factors
o o o With the EXCEPTION of Factor-VIII, the blood clotting factors are made exclusively in HEPATOCYTES Useful for this purpose is the Serum Prothrombin Time (Factors II, V, VII, X) Biosynthesis of Factors II, VII, IX, X depends on Vitamin-K
Used to screen for dilation of Biliary Tree and to detect Gallstones & Cholecystitis in patients with right sided abdominal pain associated with Abnormal Liver Blood Tests Can detect and characterize Liver Masses, Abscesses, and Cysts Diagnostic Modality of Choice for Hepatocellular Carcinoma SCREENING Helical CT Scan with Contrast Useful in evaluation of Parenchymal Liver Disease Has the added feature of Contrast Enhancement to define space-occupying lesions (Abscess and Tumor) MRI Allows calculation of Liver Volume Similar information as the CT Scan, but visualizes vessels without use of IV contrast Helpful in diagnosis of Benign Masses such as Focal Nodular Hyperplasia & Hamngioma

VIII. RADIOGRAPHIC EVALUATION

Ultrasoonography

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3) LIVER ABSCESS
Liver is the organ most subject to the development of abscesses FEVER: Most Common presenting sign of Liver Abscess I. CLINICAL PRESENTATION Right Upper Quadrant signs / symptoms: Pain, guarding, punch tenderness, rebound tenderness Chills, anorexia, weight loss, nausea, vomiting; 50% of patients have Hepatomegaly, Right Upper Quadrant Pain, Jaundice II. PYOGENIC VS AMEBIC A. Pyogenic Abscess o Result from hematogenous infection, spread from intra-abdominal infection or ascending infection from biliary tract o Clinical Features: Fever, chills, weight loss, abdominal pain from tender hepatomegaly o 50% of patients are jaundiced o Laboratory Studies: Leukocytosis, Elevated AP In Pyogenic Abscesses, UTZ examination will demonstrate a cystic o Diagnosis: Confirmed by CT or UTZ mass in the liver, often with multiple complex septations or B. Amebic Liver Abscess o Should be considered in patients from endemic areas o Diagnosis requires high index of clinical suspicion o Tx: Metronidazole, Chloroquine
inhomogenous fluid characteristics. CT findings will include a complex hypodense mass with peripheral enhancement. In patients with a solitary dominant abscess, percutaneous aspiration with evaluation by GS/CS is essential to direct further antimicrobial & drainage therapy

III. DIAGNOSIS Single Most Reliable Laboratory Finding: Elevated Serum Alkaline Phosphatase 50% have elevated Bilirubin, and 48% have elevated Aspartate Aminotransferase Other Labs: Leukocytosis, Anemia (Normo-Normo), Hypoalbuminemia, concomitant Bacteremia On Radiography: (+) Elevation of the Right Hemidaphragm, right basilar infiltrate, right pleural effusion Imaging Methods (CT, MRI, UTZ): most reliable methods
IV. PYOGENIC LIVER ABSCESS 70% MIXED Flora Pyogenic Liver Abscess is MORE Toxic than an Amoebic Mass Commonly caused by: Anaerobes, E. coli, Klebsiella, Enterococcus, Bacteroides, Staphylococcus aureus, Streptococcus A. Etiology o Biliary Tract Disease (Acute Cholecystitis; Cholangitis) o Appendicitis o Diverticulitis o Intrinsic Hepatic Lesion General Management o Undetermined (10%) Drainage (Percutaneous or Surgical) = Mainstay of Therapy B. Clinical features o Fever, Chills, RUQ Pain, Anorexia, Nausea Several Factors predicting Failure of Percutaneous Drainage o Tender Hepatomegaly (50%) (favors Surgical Intervention): C. Diagnosis Presence of Multiple, Sizable Abscesses 1. Laboratory Viscous Abscess contents that tend to plug the catheter 80% Elevated Alkaline Phosphatase Associated Disease requiring surgery 33% Jaundice = Increased Bilirubin Lack of a clinical response to percutaneous drainage in 4-7 days 40% = (+) Blood Culture 2. Diagnostic Procedures: Ultrasound: Cystic mass, multiple complex septations, hypoechogenic, inhomogenous fluid characteristics CT-Scan: Complex hypodense mass with peripheral enhancement Ultrasound Guided Aspiration D. Treatment o Broad Spectrum Antibiotics = for Gram (-) Anaerobes o Aspiration = Percutaneous or Surgical Drainage o Drugs used for Empirical Therapy include the same ones used in Intraabdominal Sepsis and 2 0 Bacterial Peritonitis o Aerobic Gram (-) Bacilli and Anaerobes: Broad Spectrum Penicillin: Ticarcillin / Clav 3.1g q4-6 Cefoxitin 2g q4-6 IV Imipenem 500mg q6 IV Meropenem 1g q8 IV Combination: Ampicillin + Metronidazole + Ciprofloxacin

Empirical Therapy

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V. AMOEBIC LIVER ABSCESS Etiology: Entamoeba histolytica there is local proteolytic destruction of the liver parenchyma with focal infarction (invasion of the colonic mucosa into the portal system) Clinical Features: RUQ Pain, Fever, Chills, Pleuritic Pain, Night Sweats, Intestinal Amoebiasis (50%), Hx of Diarrhea Jaundice is not common in Ameobic Liver Disease, in contrast to Pyogenic Liver Abscess (Med Notes) Laboratory: Leukocytosis (50%), Increased Transaminases, Increased Serum Bilirubin, Increased Alkaline Phosphatase (80%) A. Diagnosis 1. Ultrasound = COMPLEX MASS (Most Commonly seen) Usually Solitary RIGHT Lobe (90%) 2. CT-Scan Complex Hypodense Mass with Peripheral Enhancement 3. Gallium Scan (+) Filling Defect 4. Aspiration Biopsy ANCHOVY PASTE Fluid with TROPHOZOITES (when we Aspirate) 5. Serologic Test (+) in 95% of Case Indirect Hemagglutination Gel Diffusion B. Therapy = AMOEBICIDES: o METRONIDAZOLE 750mg PO or IV 5-10 days o Choloroquine C. Complications = CYST RUPTURE into the following: o Pleural Space o Lungs o Bowel o Retroperitoneum

Aspiration & Drainage is rarely indicated. It is indicated only if there is (+) Secondary Pyogenic Infection More than 90% respond to Metronidazole Tx, with Decrease in Pain and Fever within 72 hours Indications for Aspiration of Liver Abscess: Need to rule out Pyogenic Abscess No Clinical Response in 3-5 days Threat of Imminent Rupture Need to prevent Rupture of Left Lobe Abscess into Pericardium

VI. HEPATOBILIARY TUBERCULOSIS

A. Presentation o 1) Miliary Hepatic Tuberculosis (Disseminated) o 2) Focal or Nodular Tuberculosis = Single or Multiple Conglomerate Tubercles o 3) Tuberculosis of Bile Ducts (or Tubular Tuberculosis) B. Presenting Complaints o JAUNDICE (Most Common Complaint) o Abdominal Pain, Abdominal Mass, Fever, Abdominal Enlargement, Weight Loss C. Clinical & Laboratory Features: A. Physical Examination Findings Jaundice = ALL Patients Abdominal Tenderness (RUQ, Epigastric, RLQ) Cervical Lymphadenopathy, Scrofuloderma, Fluid Wave, Abdominal Distention, Normal Physical Examination, Hepatosplenomegaly B. Chest X-Ray Findings Pulmonary TB Normal Pneumonia, Pulmonary Congestion, Elevated Right-Hemidiaphragm **NOTE: We do NOT need a Pulmonary Tuberculosis to have a Diagnosis of Liver Tuberculosis! C. Sonographic Findings o Biliary Obstruction: Intrahepatic Duct, Common Bile Duct, Common Hepatic Duct, Unspecified o Hepatomegaly: With Calcification (Liver Calcifications = MOST Common) or Without Calcification o Others: Contracted Gallbladder, Cholecystitis, Cholelithiasis, Choledocholithiasis, TB-Liver, Pancreatic Head Mass, Pancreatitis, Portal Hypertension, Splenomegaly D. Treatment of Hepatobiliary Tuberculosis o Anti-TB Therapy (12-18 Months Triple / Quadruple Treatment) o Surgery

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4) TUMORS OF THE LIVER

Hepatocellular Carcinoma (HCC) is one of the most common malignancies worldwide I. CLINICAL FEATURES Abdominal Pain, Weight Loss, Weakness, Abdominal Fullness & Swelling, Jaundice & Nausea Most Common Symptom = Abdominal Pain Jaundice is usually due to obstruction of Intrahepatic Ducts by the underlying liver disease Hepatomegaly = Most Common Physical Sign (50-90%) Abdominal Bruits, Ascites (should be examined by cytology), Splenomegaly, Weight Loss, Wasting Signs of Chronic Liver Disease: Jaundice, Dilated Abdominal Veins, Palmar Erythema, Gynecomastia, Testicular Atrophy, Peripheral Edema II. APPROACH TO THE PATIENT A. Serologic Assays o A-Fetoprotein (AFP): Serum Tumor Marker in HCC o In a patient presenting with either a new hepatic mass or other indications of recent hepatic decompensation, CEA, Vitamin B12, AFP, Ferritin, PIVKA-2 and Antimitochondrial Ab should be measured, and Standard Liver Function Tests should be performed (including PT, PTT, Albumin, Transaminases, Alk Phos, G-Glutamyl Transpeptidase) B. Radiology o UTZ Examination of liver is an excellent screening tool o Two Characteristic Vascular Abnormalities are: 1) Hypervascularity of the Tumor Mass (Neovascularization or Abnormal Tumor-Feeding Arteries) 2) Thrombosis by Tumor invasion of otherwise normal portal veins
To determine Tumor Size and Extent, and the presence of Portal Vein Invasion accurately, a Helical / Triphasic CT Scan of the Abdomen and Pelvis with Fast Contrast Bolus Technique should be performed to detect the vascular lesions typical of HCC.

III. BENIGN TUMORS (found predominantly in women) Hemangiomas Considerable effort has gone into differentiating these three entities radiologically. The most Adenomas useful diagnostic differentiating tool is a Triphasic CT-Scan performed with HCC fast Bolus Focal Nodular Hyperplasia (FNH) Protocol for Arterial-Phase Imaging, together with subsequent delayed venous-phase imaging.
A. Hemangioma o Most Common BENIGN Liver Tumor (5-7% Autopsy; Women > Men) o Treatment is unnecessary unless their expansion causes symptoms B. Hepatic Adenoma o Usually in Women (Childbearing Age) Common in Contraceptive Pill Use o They can cause pain and can bleed or rupture, causing acute problems. Low potential for Malignant Change and a 30% risk of Bleeding. o Symptoms: RUQ Fullness, Intraabdominal Hemorrhage (25%) Biopsy is not Suggested due to Hypervascularity o Treatment: STOP Pill; Surgery o Diagnosis: CT Scan = Hepatic Mass; Cold Spot Abnormal Liver Function Test, Abnormal Alpha Fetoprotein C. Hepatic Cyst (Can be Multiple or Solitary): Problems = Bleeding and Infection Solitary Cyst RIGHT Liver Lobe Asymptomatic; Occasionally = PAIN & FEVER (Secondary Bleeding, Infection or Rupture) Polycystic Liver Multiple Cysts (Several mm to 10-15cm); ASYMPTOMATIC Disease Complications: Hemorrhage, Infection, Rupture (+) Cyst: Pancreas, Spleen, Lungs Laboratory Findings: Liver Function Tests are NORMAL, Mild in Alkaline Phosphatase Treatment: Surgical Aspiration / Decompression D. Focal Nodular Hyperplasia o Typically benign, and usually no treatment is needed

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IV. PRIMARY HEPATOCELLULAR CARCINOMA 80-90% of all Primary Liver Carcinoma Most Commonly due to Cirrhosis prior to a Chronic Hepatitis-B Incidence: 4x Men > Women A. Etiologic Factors o Chronic Liver Disease: Alpha-1 Antitrypsin Deficiency, Tyrosinosis (40% Risk), Hemochromatosis, Primary Biliary Cirrhosis o Previous Hepatitis-B Infection 90-95% of Hepatocellular Carcinoma = (+) HBV Infection 60-70% of Hepatocellular Carcinoma = Chronic Hepatitis / Cirrhosis o Others: Mycotoxins, Humoral Factors (Increased Androgen), Schistosomiasis (?), Clonorchiasis (?) B. Clinical Features o Hepatomegaly o Hepatic Bruit or Fruction Rub o Ascites (Bloody in 50%) o Non-Specific Symptoms (Malaise, Weight Loss, Anorexia, Abdominal Pain) o Clinical Deterioration or SUDDEN Increase in Transaminases in a STABLE Cirrhotic Patient C. Diagnosis o Laboratory: Alkaline Phosphatase, Transaminases o Gallium Scan: Focal Filling Defects o Alpha Fetoprotein Elevation: 85-90% o Angiography: Hypervascularity, Tumor Blush o Liver Biopsy D. Treatment o NO Effective Treatment (Survival Rate < 6 months) o Surgery = 5-year Survival Rate < 10% o Radiotherapy & Chemotherapy = RARE Response V. METASTATIC HEPATIC MALIGNANCY It is MORE COMMON Than Primary Hepatocellular Carcinoma (MOST COMMON MALIGNANT Neoplasm) Primary Source = Gastrointestinal Carcinoma (Colon, Stomach, etc) A. Tumors Metastatic to the Liver: o Colon These three are predominantly the primary sites, however, metastatic tumors to the liver o Pancreas can originate from any organ primary. o Breast **Other Sources may be from: GIT Carcinoma Malignant Melanoma Carcinoma of the Pancreas, Lungs, Breast, Kidney, Ovary Lymphoma B. Clinical Features o Fever, RUQ Pain o Hepatomegaly, Friction Rub, Jaundice C. Diagnosis o Liver Biopsy o CT or Ultrasound Guided Aspiration Biopsy D. TREATMENT (Depends on the Underlying Primary Source) o Radiotherapy, Chemotherapy o Hepatic Artery Infusion o Surgery

VI. APPROACH TO PATIENTS WITH JAUNDICE Yellowish discoloration of tissue resulting from the Deposition of Bilirubin

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Hepatocellular Conditions producing Jaundice: Viral Hepatitis Hepatitis A, B, C, D, E Epstein-Barr Virus Cytomegalovirus Herpes Simplex Alcohol Drug Toxicity Predictable Dose Dependent: Acetaminophen Unpredictable, Idosyncratic: Isoniazid Environmental Toxins (Vinyl Chloride) Wilsons Disease Autoimmune Hepatitis
QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.

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LECTURE ON LIVER CIRRHOSIS Additional Notes from Harrisons

LIVER CIRRHOSIS
Characterized pathologically as IRREVERSIBLE Chronic Injury of the Hepatic Parenchyma Include extensive fibrosis in association with the formation of Regenerative Nodules Central Event leading to Hepatic Fibrosis: Cytokine-Mediated (tgf-B) Activation of the Hepatic Stellate Cells producing Fibrin Forming Type-1 Collagen Results from: o Hepatocyte Necrosis o Collapse of the supporting network with subsequent connective tissue deposition o Distortion of Vascular Bed, and Nodular Regeneration of remaining Liver Parenchyma

I. ALCOHOLIC CIRRHOSIS Excessive chronic alcohol use can cause different types of Chronic Liver Disease: Alcoholic Fatty Liver, Alcoholic Hepatitis, and Alcoholic Cirrhosis Diagnosis requires an accurate history regarding amount and duration of alcohol consumption Laboratory Tests can be completely normal in patients with Early Compensated Alcoholic Cirrhosis In Advanced Liver Disease, patient may be: LIVER ENZYMES: o Anemic from either Chronic GI Blood Loss AST / ALT >2 Alcoholic Liver Disease o Nutritional Deficiencies AST / ALT <1 Viral o Hypersplenism related to Portal Hypertension Alk Phos > Liver Enzymes Cholestatic o Direct Suppressive Effect of Alcohol on the Bone Marrow II. CAUSES AND COMPLICATIONS OF CIRRHOSIS
COMPLICATIONS OF CIRRHOSIS:
Portal Hypertension (Gastroesophageal Varices, Portal Hypertensive Gastropathy, Splenomegaly, Hypersplenism, Ascites / SBP Hepatorenal Syndrome (Type 1, Type 2) Hepatic Encephalopathy Portopulmonary Hypertension CAUSES OF CIRRHOSIS Alcoholism Chronic Viral Hepatitis (Hep-B, Hep-C) Autoimmune Hepatitis Non-Alcoholic Steatohepatitis Biliary Cirrhosis Primary Biliary Cirrhosis Primary Sclerosing Cholangitis Autoimmune Cholangiopathy Coagulopathy (Factor Deficiency, Fibrinoysis, Thrombocytopenia) Bone Disease (Osteopenia, Osteoporosis, Osteomalacia) Hematologic Abnormalities (Anemia, Hemolysis, Neutropenia, Thrombocytopenia) Malnutrition Hepatopulmonary Syndrome Cardiac Cirrhosis Inherited metabolic Liver Disease - Hemochromatosis - Wilsons Disease - A1-Antitrypsin Deficiency - Cystic Fibrosis Cryptogenic Cirrhosis

III. LABORATORY FINDINGS IN CIRRHOSIS (from the Lecture) Liver Insufficiency: o Decreased Albumin: < 3.8 g/dL o Prolonged PT (INR > 1.3) o Increased Bilirubin: > 1.5 mg/dL Portal Hypertension o Decreased Platelet Count: < 175,000 AST / ALT Ratio > 1 Imaging (CT or UTZ) o Nodular Liver o Splenomegaly o Venocollaterals Liver Biopsy: NOT always necessary if: o 1) Decompensated Cirrhosis (Variceal Hemorrhage, Ascites, etc) o 2) Liver/Spleen imaging diagnostic of Cirrhosis

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IV. SEVERITY OF LIVER DISEASE: Child Turcotte Pugh MELD Score A. Child Pugh Criteria for Hepatic Functional Reserve A Serum Bilirubin Serum Albumin Prothrombin Time Ascites Neurologic Disorder (mg/dL) (umol/L) (g/dL) (g/L) Seconds Prolonged INR < 2.0 < 34 > 3.5 > 35 0-4 < 1.7 None None B 2.0-3.0 34-51 3.0-3.5 30-35 4-6 1.7 2.3 Easily controlled Minimal C > 3.0 > 51 < 3.0 < 30 >6 > 2.3 Poorly controlled Advanced Coma

B. MELD Score o Estimates the Risk of 3 month Mortality (higher the MELD score likely to die in three months) o Three Laboratory Values used: Serum Total Bilirubin Serum Creatinine INR 6.4 + 9.8 x log(INR) + 11.2 x log(Cr) + 3.8 x log(Bilirubin)

V. HISTORY OF CHRONIC LIVER DISEASE Chronic Liver Disease Compensated Cirrhosis Decompensated Cirrhosis Death

Compensated VS Decompensated: Presence of Complications! Variceal Hemorrhage Ascites Encephalopathy Jaundice

VI. COMPLICATIONS OF CIRRHOSIS Portal Hypertension Variceal Hemorrhage SBP Ascites Hepatorenal Syndrome Encephalopathy Jaundice Liver Insufficiency Encephalopathy

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VII. INVESTIGATING ASCITES

CONDITION Cirrhosis Neoplasm TB Peritonitis Pyogenic Peritonitis CHF GROSS APPEARANCE Straw colored or bile stained Straw colored, hemorrhagic, mucinous, or chylous Clear, Turbid, Hemorrhagic, Chylous Turbid or purulent Straw-colored PROTEIN (g/L) < 25 (95%) > 25 (75%) > 25 (50%) If purulent, > 25 Variable (15-53) < 25 (100%) SAAG (g/dL) > 1.1 < 1.1 < 1.1 < 1.1 > 1.1 CELL COUNT RBC, WBC, per uL >10,000u/L 1% < 250 (90%) Predominantly Mesothelial 20% > 1000 (50%) Variable Cell types 7% > 1000 (70%) Usually > 70% L Unusual Predominantly PMN Leukocytes 10% < 1000 (90%) Usually Mesothelial, Mononuclear < 250 Mesothelial, Mononuclear Variable If chylous, ether extraction, sudan staining Amylase in Ascitic Fluid & Serum OTHER TESTS

Cytology, cell block, peritoneal biopsy Peritoneal Biopsy, Stain and Culture for AFB Positive Gram Stain, Culture

Nephrosis

Straw-colored or chylous

< 1.1

Unusual

Pancreatic Ascites

Turbid, Hemorrhagic, or Chylous

Variable, often >25

Variable, may be blood stained

A. SAAG: Serum to Ascites Albumin Gradient o Serum Albumin [minus] Albumin in Ascitic Fluid (Gradient) o The gradient correlates DIRECTLY with Portal Pressure 1. If SAAG is > 1.1g/dL (or 11 g/L) Cause of Ascites is PORTAL HYPERTENSION with (97% Specificity): Cirrhosis Cardiac Ascites Budd Chiari Syndrome Management of Ascites: Portal Vein Thrombosis Dietary Salt Restriction (2g Salt/day) Veno-Occlusive Disease Diuretic Therapy Fatty Liver of Pregnancy Paracntesis 2. If SAAG is < 1.1g/dL (or 11 g/L) TIPS Peritoneal Carcinomatosis Spontaneous Bacterial Peritonitis: Infection (Peritonitis, TB) Infectious complication of Portal HPN-Related Nephrotic Syndrome Ascites Pancreatic or Biliary Ascites B. Absolute WBC Count (PMN) > 250/mm3 o Infection o When Mononuclear Cells are predominant: TB, Fungal C. RBC Count > 50,000/mm = Hemorrhagic Ascites o Malignancy o TB o Trauma D. Others: Amylase TAG Cytology Gram Stain or Culture pH < 7
Increased in Pancreatic Ascites Increased in Chylous Ascites Positive in Malignancy Bacterial Infections Bacterial Infection
3

Abdominal Pain & Distention, Fever, Decreased Bowel Sounds, Worsening of Hepatic Encephalopathy Diagnosis is likely when Ascitic Fluid has > 250 neutrophils/u/L

E. Management of Ascites o Removal of > 1 L at a time (Paracentesis) may lead to Hypovolemia, Shock o Unless 10grams Albumin is replaced IV for each 1 L Ascitic Fluid removed

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VIII. HEPATIC ENCEPHALOPATHY: Grading System for Hepatic Encephalopathy:

GRADE 0 1 2 LEVEL OF CONSCIOUSNESS Normal Inverted Sleep Pattern, Restless Lethargic, Slow Responses Somnolent but can be aroused, confused Coma PERSONALITY AND INTELLECT Normal Forgetful, Mild Confusion, Agitation, Irritable Disorientation from time, amnesia, decreased inhibitions, inappropriate behavior Disorientation for place, aggressive Nil NEUROLOGIC ABNORMALITIES Normal Tremor, Apraxia, Incoordination, Impaired handwriting Asterixis, Dysarthria, Hypoactive Reflexes Asterixis, Hyperactive Reflexes, Babinskis Sign. Muscle Rigidity Decrebrate EEG ABNORMALITIES Normal Slowing Triphasic Waves Slowing Triphasic Waves

3 4

Slowing Triphasic Waves Slowing Delta Waves

**NOTE: Asterixis is POSITIVE in Stage I, II, and III but Negative on IV! o There will be NO Asterixis when patients is already in COMA o First Manifestation is the Reversal of the Sleep-Wake Pattern Treatment is multifactorial and includes management of the precipitating factors. Sometimes hydration & correction of electrolyte imbalance is all that is necessary. Mainstay of Treatment (in addition to correction of precipitating factors) is to use Lactulose, which result in Colonic Acidification. Catharsis ensues, contributing to the elimination of waste products in the gut. Goal: 2-3 Stools per day. Treatment of Hepatic Encephalopathy (Washington) Treat Precipitating Factors Dietary Protein Restriction (Controversial) Non-Absorbable Disaccharide (Lactulose, Lactitol) Neomycin Metronidazole (250mg PO q8h)

Portosystemic Encephalopathy is a serious complication of chronic liver disease and is broadly defined as an alteration in mental status & cognitive function occurring in the presence of liver failure. Encephalopathy is more commonly seen in patients with chronic liver disease. Gut-derived neurotoxins are not removed by the liver because of vascular shunting and decreased hepatic mass get to the brain & cause symptoms. Ammonia levels are typically elevated in patients with hepatic encephalopathy.

A. Pathogenesis (Most Important): o SEVERE Hepatocellular Dysfunction and/or Intrahepatic & Extrahepatic Shunting of Portal Venous Blood into the Systemic Circulation BYPASSING the Liver (There is FAILURE to DETOXIFY the substances) B. Common Precipitants of Hepatic Encephalopathy: o Increased Nitrogen Load: Gastrointestinal Bleeding, Excess Dietary Protein, Azotemia, Constipation o Electrolyte and Metabolic Imbalance: Hypokalemia, Alkalosis, Hypoxia, Hyponatremia, Hypovolemia o Drugs: Narcotics, Tranquilizers, Sedatives, Diuretics o Miscellaneous: Infection, Surgery, Superimposed Acute Liver Disease, Progressive Liver Disease, Portal-Systemic Shunts C. Aims of Treatment: o 1) Eliminate or Treat the Precipitating Factors o 2) Lower Blood Ammonia (and other Toxins): Decreases Absorption of Proteins and Nitrogenous Products from the Intestine D. Approach to the Patient with Hepatic Encephalopathy, BUN (Blood Urea Nitrogen) Initial Evaluation: Exclude other Causes of Disordered Mentation, Identify Precipitants and Correct Determine Electrolytes, BUN, Creatinine, NH3 (Optional), Glucose

Protein Restriction Inadequate Response (?)

Laxative (eg. LACTULOSE 30-120mL, 1 to 4x daily until 4 stools/day)

Broad-Spectrum Antibiotics (eg. Neomycin 500-1000mg qid; or Metronidazole 250mg tid)

Inadequate Response (?)

Consider Liver Transplantation

31

MANAGEMENT OF COMPLICATIONS (Lecture)

I. VARICES Gastroesophageal Varices: Most important complication of cirrhosis Dilation of Coronary and Gastric Veins Can lead to bleeding A. Pathophysiology Resistance to Portal Flow Increased Resistance to Portal Pressure Decreased Splanchnic Arteriolar Resistance Increased Splanchnic Flow (Increased Portal Blood Inflow)

VARICES! o o o o Varices increase progressively by 7-8% per year Determinant of Severity of Varices = Severity of Liver Disease Everyone with Cirrhosis should be Endoscoped! Two Year probability of FIRST Bleed: 7% in Small Varices 30% in Large Varices

B. Principles in Treatment of Varices: 1. Vasoconstrictors Examples: Non-Selective B-Blockers, Terlipressin, Vasopressin, Octreotide Mechanism: Increases Splanchinc Arteriolar Resistance Note on Beta-Blockers: Selective B-Blockers (B1): Metoprolol, Atenolol Non-Selective B-Blockers (B1 + B2): Propranolol, Nadolol, Esmolol Rationale for Use of Non-Selective B-Blockers: If you Block the B2-Receptors in Vessels Unopposed A1-Receptor Action Constriction of Splanchnic Vessels Increased Resistance Terlipressin: Dose: 2mg q40 (very expensive) BUT, there is increased survival 2. Venodilators ISMN (NOT used alone usually combined with B-Blockers) Mechanism: Decreases Intrahepatic Resistance to Decrease Portal Pressure AND Decreases Systemic Pressure to Decrease Portal Blood Inflow 3. Shunt TIPS, Surgical Shunts Mechanism: Decreases resistance to Portal Flow Decrease Portal Pressure 4. Endoscopic Therapy Sclerotherapy Band Ligation

32

C. Management of the Different Stages of Cirrhosis: STAGE MANAGEMENT No Varices Pre-Primary Prophylaxis: Prevention of Variceal Development There is NO Specific Treatment Recommendation: Repeat Endoscopy in 2-3 years (sooner if with Decompensated Liver Disease) In studies, B-Blockers did NOT prevent the development of Varices (Timolol actually increases adverse effects) Varices, but NO Hemorrhage Primary Prophylaxis: Prevention of First Variceal Hemorrhage 1) Small Varices Recommendation: Repeat Endoscopy in 1-2 years B-Blockers (?) data are not clear 2) Medium to Large Varices Recommendation: Beta-Blockers + Endoscopic Variceal Ligation Variceal Hemorrhage Treatment of Acute Variceal Hemorrhage: 1) General Management: IV Fluids Do NOT overtransfuse (this can actually increase Portal Volume Increase bleeding) Antibiotic Prophylaxis 2) Specific Treatment: Pharmacologic: Terlipressin, Somatostatin, Vasopressin + Nitroglycerin Endoscopic: Ligation, Sclerotherapy Shunt: TIPS, Surgical Shunts 3) TIPS (Transjugular Intrahepatic Portal Shunt) Rescue treatment for recurrent Variceal Hemorrhage Indicated in patients who re-bleed on Combination Endoscopic Management and Pharmacologic Treatment Problem: Hepatic Encephalopathy (may be decreased by giving Lactulose) Recurrent Hemorrhage Secondary Prophylaxis: Prevent Recurrent Hemorrhage 1) B-Blockers Plus Endoscopic Variceal Ligation (BEST) 2) B-Blockers + ISMN or Endoscopic Variceal Ligation 3) TIPS / Shunt

33

II. ASCITES Cirrhosis: Most Common Cause of Ascites Other Causes: Peritoneal Malignancy, Heart Failure, Peritoneal TB A. Diagnostic Tap = 30-60cc o PMN Count, Culture (SBP) o Albumin, Protein (Cirrhotic Ascites) o Glucose or LDH (Secondary Infection) o Amylase (Pancreatic Ascites) o Cytology (Malignant Ascites) B. Indication for Diagnostic Paracentesis o New Onset Ascites o Admission to Hospital o S/Sx of SBP o Renal Dysfunction o Unexplained Encephalopathi **NOTE: Contraindications: NONE! Do we give FFP before Paracentesis? There are NO Recommendations! Avoid the RIGHT side in Paracentesis (because these patients are usually maintained on Lactulose which causes Dilation of the Cecum) LLQ is the better site (Lateral to the Inferior Epigastric Vessels) C. Differential Diagnoses: Hepatic Sinusoids SAAG > 1.1 Capillarized Sinusoid Ascites Protein < 2.5
Sinusoidal HPN: -Cirrhosis -Late Budd-Chiari

Peritoneum SAAG < 1.1 Peritoneal Lymph Ascites Protein > 2.5
Malignancy TB

Normal Leaky Sinusoid Ascites Protein > 2.5

Post-Sinusoidal HPN -Cardiac Ascites -Early Budd-Chiari -Venoocclusive

34

D. Management of the Different Stages of Ascites: STAGE MANAGEMENT Portal Hypertension No Specific Therapy! Salt Restriction without Ascites Uncomplicated Ascites Definition: Ascites responsive to Diuretics in the absence of Infection & Renal Dysfunction Goal: to achieve Negative Sodium Balance 1) Salt Restriction Effective in 10-20% of cases 2g salt/day (or 5.2g of Dietary Salt) Fluid Restriction NOT necessary, unless there is Hyponatremia (Na <125) 2) Diuretics Should be Spironolactone-Based (Furosemide should NOT be used alone!) Dose: Spironolactone 100-400mg/day Furosemide 40-160mg/day for Inadequate Weight Loss or if (+) HyperK + Note: Diuretics if Weight Loss < 1kg in the 1st week and < 2kg thereafter Diuretics if Weight Loss > 0.5kg/day in patient without edema; or > 1kg/day in those with edema

Side Effects: Renal Dysfunction, Hyponatremia, Hyperkalemia, Encephalopathy, Gynecomastia

3) Large Volume Paracentesis (LVP) VS Diuretics in Uncomplicated Ascites LVP: Faster resolution and Fewer Complications! Refractory Ascites LVP + Albumin (Mainstay) TIPS PVS Definition of Terms: Diuretic-Intractable Ascites: Maximum doses of Diuretics could NOT be reached because of Side-Effects Diuretic-Resistant Ascites: No response to Maximum Doses of Diuretics Volume Expanders: Albumin Dextran-70 Polygeline Albumin: Decreases the Incidence of Post-Paracentesis Circulatory Dysfunction Use Albumin if > 5L of Ascites is removed (if < 5 L, may use Synthetic Expanders) Dose: 6-8 g per Liter of Ascitic Fluid Removed Hepatorenal Syndrome Discussed in Another Lecture

35

III. SPONTANEOUS BACTERIAL PERITONITIS (SBP) Most Common Infection in Cirrhotic Patients S/Sx: Fever, Jaundice, Abdominal Pain A. Early Diagnosis: Diagnostic Paracentesis o PMN Count > 250/mm3 o Done if Sx of SBP occur B. Pharmacologic Management o Antibiotics: 3rd Generation Cephalosporins, Quinolone (Ciprofloxacin) or B-Lactams (Co-Amoxiclav) o Usually Cefotaxime 2g q120 2g q60 o Duration: 5-10 days o Repeat Paracentesis in 48 hours if NO clinical Improvement with Antibiotics (no need to repeat if with Clinical Improvement in repeat paracentesis, there should be a 25% decrease in the PMN count) C. Albumin (Plus Antibiotics) Indicated if: o BUN > 30 mg/dL o Creatinine > 1.0 o Bilirubin > 4 g/dL **NOTE; Albumin is NOT indicated if (+) 100% Predicted Cure and Survival! D. Prophylaxis for SBP: o Indicated for these Patients: 1) Cirrhotic with Active Variceal Hemorrhage 2) Patient Recovered from SBP (Long-Term) o Tx: Norfloxacin 400mg PO BID x 7 days IV. HEPATIC ENCEPHALOPATHY Ammonia Levels are NOT reliable NOT necessary! Clinical Diagnosis Ammonia has good correlation with Severity, but is NOT good in Diagnosis A. Precipitants of Hepatic Encephalopathy o Excess Protein, Infection, Constipation o TIPS o GI Bleeding o Sedation o Diuretics ( Serum K+, Plasma Volume Azotemia) B. Mechanisms of Action of Lactulose o Colonic Acidification o Catharsis C. Protein Restriction (?) o NOT necessary in Hepatic Encephalopathy o Do NOT restrict protein, unless patient is in Stage IV

36

qwertyuiopasdfghjklzxcvbnmqwertyui opasdfghjklzxcvbnmqwertyuiopasdfgh jklzxcvbnmqwertyuiopasdfghjklzxcvb nmqwertyuiopasdfghjklzxcvbnmqwer HEMATOLOGY tyuiopasdfghjklzxcvbnmqwertyuiopas dfghjklzxcvbnmqwertyuiopasdfghjklzx cvbnmqwertyuiopasdfghjklzxcvbnmq wertyuiopasdfghjklzxcvbnmqwertyuio pasdfghjklzxcvbnmqwertyuiopasdfghj klzxcvbnmqwertyuiopasdfghjklzxcvbn mqwertyuiopasdfghjklzxcvbnmqwerty uiopasdfghjklzxcvbnmqwertyuiopasdf ghjklzxcvbnmqwertyuiopasdfghjklzxc vbnmqwertyuiopasdfghjklzxcvbnmrty uiopasdfghjklzxcvbnmqwertyuiopasdf ghjklzxcvbnmqwertyuiopasdfghjklzxc vbnmqwertyuiopasdfghjklzxcvbnmqw ertyuiopasdfghjklzxcvbnmqwertyuiop
Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

LECTURE ON RATIONAL BLOOD USE

INTRODUCTION
Whole Blood Red Cells Platelets Cryoprecipitate
I. ADVANTAGES OF COMPONENT THERAPY Less volume transfused Correct dose Lower risk for immunologic transfusion reactions (Plasma = responsible for reactions) Coagulation Factors are preserved Decreased disease transmission Unwanted Leukocyte and Platelet Aggregates eliminated More patients can benefit II. AVAILABILITY Red Cell Products (Whole Blood, PRBC, Washed RBC, Leukocyte Depleted Red Cells) FFP Cryosupernate Cryoprecipitate Platelets (Random Donor Platelets or Apheresed) III. KEY NOTES There are only TWO Indications for Whole Blood Transfusion: o Massive Hemorrhage / Bleeding o Exchange Transfusion Whole Blood: o No more Viable Platelets, Fibrinogen if stored for several days o Massive Blood Loss means Loss of >30% acutely Most Common Fatal Hemolytic Transfusion Reaction: Clerical Error! o Donor should have Hgb > 125 o Risks: Early ( < 5 days) or Late ( > 7 days) In Transfusion Reactions, there are only TWO Conditions when we can Continue Transfusion: o Mild Allergic Reaction o Febrile Non-Hemolytic Reaction (continue when Fever subsides) All Blood Units should be Infused within 4 Hours o If (+) Risks (such as Congestion), we can divide the units into Aliquots Each unit should be tested for ABO and Rh Group o Tested in the Philippines: HIV 1 & 2, HBV, HCV, Syphilis, Malaria o Others: HTLV 1 & 2, CMV, etc (Plasma can transmit most infections)

Platelet-Rich Plasma Plasma Derivatives

BLOOD PRODUCTS
I. PACKED RED BLOOD CELL (PRBC) A. Humans have Profound Capacity to Tolerate Anemia o Increase CO o Decrease Blood Viscosity o Redistribution o 2,3-DPG (change in affinity of Hgb to O2) B. Current Standards (NIH Consensus Conference Report, 1988) HEMOGLOBIN < 7 g/dL PRBC is Justified 6 10 g/dL > 10 g/dL MANAGEMENT

Individualized signs and symptoms of O2 Deprivation, Risks vs Benefits If (-) Cardiac / Neuro / Pulmo patient can tolerate this level without transfusion Almost Never (more Harmful to transfuse)

Sample Case: 32 year old female for Elective Cholecystectomy. Hgb: 84, Hct: 0.23, MCV: 65, MCH: 23. Do you transfuse? Blood Loss in Elective Cholecystectomy: ~300-500cc Most would opt to Type and Screen (if Blood Loss is < 500cc) this means that there is no need for crossmatching yet, no need for transfusion **NOTE: In Cancer Patients: Quality of Life is improved at Hemoglobin Level of 11 12 g/dL C. Revised (Local) Guidelines for Adult BT of PRBC (~250cc): NVBSP Guidelines o 1) Hgb < 7 g/dL or Hct < 21% (If not due to a treatable cause, such as Fe deficiency) o 2) Symptomatic Anemia, regardless of Hemoglobin Level (usually < 10g/dL) Dyspnea Syncope Postural Hypotension Tachycardia Chest Pain TIA 3) Hgb < 7 g/dL or <21% with concomitant hemorrhage, COPD, CAD, Hemoglobinopathy, Sepsis 4) Patients receiving General Anesthesia, if: a) Pre-Op Hemoglobin < 7 g/dL or Hct < 21% b) Major Blood Letting Operation and Hemoglobin < 10 g/dL or Hct < 30% (Open Heart, Laminectomy) c) Signs of Hemodynamic Instability or Inadequate O2 Carrying Capacity (Symptomatic Anemia)
CLASS I Up to 750 mL Up to 15 % < 100 Normal Normal or Decreased 14 20 > 30 Slightly anxious CLASS II 750 1500 mL 15 30 % > 100 Normal Decreased 20 30 20 30 Mildly anxious CLASS III 1500 2000 mL 30 40 % > 120 Decreased Decreased 30 40 5 15 Anxious and confused CLASS IV > 2000 mL > 40 % > 140 Normal Decreased > 35 Negligible Confused, Lethargic

o o

D. Classification of Hypovolemic Shock according to Blood Loss

Blood Loss (mL) Blood Loss (% BV) Pulse Rate Blood Pressure Pulse Pressure Respiratory Rate Urine Output (cc/h) CNS / Mental Status

E. CONTRAINDICATIONS to Red Cell Transfusion: o Volume Expansion when O2 Carrying Capacity is adequate o Prophylaxis: No signs/symptoms of Anemia o Enhance General Sense of Well-Being o Promote Wound Healing F. Indications of Prophylactic Paracetamol / Anti-Histamines o Paracetamol: give only if (+) Febrile o Anti-Histamine: give only if (+) previous history of Allergy o Tx; Give Leukocyte Depleted Products G. Transfusion of PRBC: o Give Blood Transfusion over 4 Hours after proper Blood Typing and Crossmatching o 1 Unit raises Hemoglobin by 1g/dL or Hematocrit by 3% II. PLATELET TRANSFUSION Indications: Therapeutic and Prophylactic o Therapeutic: ex) Bleeding o Prophylactic: ex) Patient undergoing surgery (indications are controversial) In Patients with Decreased Platelet Production: o At > 100,000: Bleeding Time is NOT affected o At 10,000: Bleeding Time is Prolonged o At < 10,000: Bleeding Time is > 30 minutes and NOT related to Platelet Count o At < 5,000: Spontaneous Bleeding Example: Case on ITP o Tx is Steroids o If Platelet Count is 12,000 do NOT Transfuse yet Platelet Count will Increase in response to the Steroids Dose and Response: POOLED / RANDOM DONOR PLATELETS 1 Unit / 10kg BW Dose SINGLE DONOR / APHERESIS PLATELETS 1 Pack (equivalent to 4-8 Units of RDP) Advantage: may reduce Infectious Disease Transmission by reducing the number of Donor Exposures Corrected Count Increment (CCI) > 10,000 within 1 Hour and > 7,500 within 24 Hours Post-Transfusion

Response

1 Unit increases PC by 5,000 10,000 cells/uL

Platelets are NOT useful in the following (these are due to Increased Platelet Destruction): o Drug Induced Thrombocytopenia o TTP, HUS, ITP o Heparin Induced Thrombocytopenia Note on Dengue Hemorrhagic Fever: o If (-) Bleeding, NO Transfusion! A. Random Donor Platelets (RDP) o Volume: 50 cc o Dose: 1 Unit / 10 kg Body Weight (ex: if 60kg, give 6 units) o Content: > 5.5 x 1010 Platelets/bag o Can carry Organisms (bacteria from the environment can go into the blood induce Sepsis) B. Single Donor Platelets (SDP) / Apheresed Platelets o Volume: 200 600 cc o Dose: 1 Apheresis Product / Transfusion Episode

 Some Generalizations: o If Platelet Count < 10,000 give Prophylaxis (EXCEPT in Immune Mediated Diseases) o If Major Surgeries maintain > 50,000 o In Minor Surgeries maintain > 30,000 o Cross Matching is NOT required prior to Platelet Transfusion, but should be ABO Type-Specific o Pre-Medications NOT necessary CCI = Posttransfusion Count Pretransfusion Count . x Body Surface Area Number of Platelets Transfused x 10

III. FRESH FROZEN PLASMA (FFP) TRANSFUSION Indication: Control or Prevention of Bleeding in Multiple Coagulation Defects o Liver Disease with Coagulopathy o Hemophilia o DIC o Reversal of Warfarin Effect Dose: 4-7 Units for an Average Adult (15-20 mL/kg) o Response: Increase Coagulation Factors by about 2% Shelf Life: 1 year when frozen at 300C

IV. CRYOPRECIPITATE TRANSFUSION Indications: o Hemophilia-A with Bleeding or Anticipated o VonWB Disease o Fibrinogen Deficiency in DIC o Factor XIII Deficiency Shelf Life: 1 year when Frozen at 300C Dose: In Pools of 6 Units each o Response: Increase Fibrinogen by 30-60 mg/dL V. CRYOSUPERNATE TRANSFUSION Indications: o Hemophilia-B o Factor II, VII. . . . . VII. GRANULOCYTE CONCENTRATE TRANSFUSION Indications: o Gram (-) Sepsis with ANC at < 500, NOT responding to Antibiotics

BASIC HEMATOLOGY NOTES

INTRODUCTION
I. SOME FORMULAS Hemoglobin: Hematocrit: Serum Fe: TIBC: Serum Ferritin M: 16 + 2 F: 13 + 2 M: 47 + 6 F: 40 + 6 50 150 mg/dL 54 64 mmol/dL M: 100 F: 30

A. Reticulocyte Count (0.005 0.015) o To know if with Marrow Problem or Anemia secondary to Hemodialysis or Blood Loss o Reticulocyte Count % = PGH Value x 100% o Corrected Reticulocyte Count: Patients Reticulocyte Count x Patients Hct / Normal Hct x 1000 Normal Hct Values = 0.4-0.5 for Males; 0.38-0.48 for Females (usually 0.45) **NOTE: Reticulocyte Index: Corrected Reticulocyte Count / 2
Interpretation: LOW Retic Count = Marrow problem because of decreased production HIGH Retic Count = Compensatory or Destruction or Blood Loss

Absolute Reticulocyte Count = Patients Reticulocyte x Patients Reticulocyte 45 Corrected Reticulocyte Count = Absolute Reticulocyte Count Maturation Time (MT) MT is 1 1.5 2.0 2.5 when Hct is 45% 35% 25% 15%
Interpretation: CRC < 1% > 2% Hypoproliferative BM Hemolysis or 100,000mm2 Blood Loss

B. Hematology Formulas o MCH = Hgb/RBC o MCV = Hct (100)/RBC o MCHC = Hgb/Hct MCH = Hypo / Hyperchromic MCV = Micro / Macrocytic

N: 27 31 N: 76 100 N: 330 390

Chromic Cytic

IMPORTANT Notes: Microcytic, Hypochromic = Iron Deficiency, Thalassemia, Chronic Inflammatory Disease, Myelodysplastic Macrocytic = Megaloblastic Anemia, Hemolysis, Liver Disease, Alcoholism, Hypothyroidism, Aplastic Anemia Normocytic, Normochromic = Anemia of Chronic Disease o Anemia of Endocrine Failure = Mild Normocytic Normochromic Anemia o Anemia of Chronic Renal Failure = Normocytic, Normochromic Anemia (Reticulocytes are DECREASED) Aplastic Anemia, Pure Red Cell Aplasia, Myelophthisic Anemia, Myelodysplastic Syndromes These are the Hypoproliferative Anemias associated with Marrow Damage The have the following Characteristics: o Normochromic, Normocytic or Macrocytic o Characterized by LOW Reticulocyte Count

Microcytic Anemia
Iron Deficiency Anemia Thalassemia Lead Poisoning Chronic Infection

Macrocytic Anemia
(Macrocytosis: MCV > 100Fl) Macrocytosis Reticulocytosis Liver Disease Downs Syndrome Megaloblastic Folic Acid Deficiency B12 Deficiency

C. Absolute Neutrophil Count (ANC) (Neutrophils + Stabs) x WBC x 1,000 < 500 = NEUTROPENIC!

II. TRANSFUSION THERAPY (Medicine Notes) A. Packed RBC (pRBC) o Indications: 1) Hgb < 7g/Dl or Hct < 21% in Hemodynamically STABLE Patients or without CVD 2) Hgb < 8g/Dl or Hct < 24% in UNSTABLE and CVD Patients % Increase: 1 Unit Prbc x 4 hours increases Hemoglobin by 10 B. Fresh Frozen Plasma (FFP) o Volume = 200Ml o Content: Normal Levels of all Coagulating Factors o Dose: 15mL/kg (each unit will raise factors by 3-5% or 10-15u/kg) o Indications: PT INR > 1.5x Normal PTT > 5 sec of Upper Limit of Control Active Bleeding Coagulation Deficit of Factor II, V, VII, X, XII Reversal of Warfarin TTP C. Platelet o Volume: 50cc o Dose: 1 unit / 10 kg o Indication: PC < 10-20,000 (Prophylaxis) If PC < 50,000 in Bleeding Patients or undergoing Procedure Massive Bleeding **NOTE: Given over 30 minutes; NO Pre-BT Meds D. Cryoprecipitate o Volume: 15-20mL o Dose: Pool of 2 or 6 u (each unit Increase by 5-10%) 1 bag/10kg BW o Pre-Med Tx: Paracetamol 500mg; Diphenhydramine 25-50mg PO/IV o In Non-Hemolytic Febrile Transfusion: Meperidine 25-50mg IV to prevent chills E. Whole Blood o Volume: 500Ml o Dose: 20mL/kg x 4 hours o Contains 1/2g of Fe per mL o Therefore, 500mL = 250g Iron III. HEMA CLEARANCE
A. Transfusion Threshold o NO Cardiac Disease: Hgb 70 o With Cardiac Disease: Hgb 80 100 **NOTE: How do you know if enough was transfused? Check Symptoms B. Platelet (50cc) Fast Drip o With Bleeding: < 100 T (NOT Purpura nor Petechiae) o W/O Bleeding: < 20 T C. RBC: Run x 4 hours D. FFP FD 15cc/kg 2 Units q 12 (if you expect bleeding) 4 units FD

IV. SCREENING ASSAYS (from Harrisons)

Commonly used Screening Tests are: o PT o aPTT o Platelet Count

A. Prothrombin Time (PT) o PT assesses Factor I (Fibrinogen), II (Prothrombin), V, VII, and X o Measures the time for clot formation of the citrated plasma after recalcification and addition of Thromboplastin o International Normalized Ratio (INR) is determined by: (PTPATIENT / PTNormal.Mean)ISI o INR was developed to assess Anticoagulation due to reduction of Vitamin-K Dependent Coagulation Factors, it is commonly used in the evaluation of patients with Liver Disease B. Activated Partial Thromboplastin Time (aPTT) o Assesses the Intrinsic and Common Coagulation Pathways: Factors XI, IX, VIII, X, V, II, Fibrinogen, and also Prekallikrein, High Molecular Weight Kininogen and Factor XII Prolonged PT: Factor VII Deficiency Vitamin-K Deficiency Early Warfarin Anticoagulation Prolonged aPTT and PT Factor II, V, or X Deficiency Vitamin-K Deficiency Late Direct Thrombin Inhibitors Prolonged aPTT: 1. No Clinical Bleeding Factors XII, High Molecular Weight Kininogen, Protein Kinase 2. Variable, but usually Mild Bleeding Factor XI Mild in Factor VIII & IX 3. Frequent Severe Bleeding Severe Deficiencies of Factor VIII and IX 4. Heparin

Interpreting PT 1. INR If > 1: means that blood is LESS Coaguable, prone to bleeding, ideal for ACS px If < 1: coaguable blood 2. Activity > 70% = needed if you will do Invasive Procedures / Surgeries

COMMON HEMATOLOGIC CASES

I. PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) Main Defect = MUTATION in Pig-A Gene (in the X-Chromosome), which is necessary for GPI Anchor Without this Anchor, Cell Membranes are Easily Destroyed (there are proteins which attach to this glycoprotein) It is a DISTINCTIVE Disorder because it is an Intracorpuscular Defect acquired at the Stem Cell Level A. Characterized by Three Common Manifestations: o Hemolytic Anemia o Venous Thrombosis o Deficient Hematopoiesis B. Diagnosis o Clinical Symptoms = Ictericia, Pallor, Thrombosis o PERIPHERAL CYTOPENIAS **NOTE: Other Findings (from the book) Anemia is highly Variable Hematocrit from < 20% to Normal NORMOCHROMIC and NORMOCYTIC Bone Marrow appears NORMOCELLULAR C. Treatment Washed Packed-RBC Transfusion Corticosteroids 15-30mg EOD Iron Replacement for IDA Heparin / Warfarin ATG 150mg/kg (Total) over 4-10 days Hematopoietic Stem Cell Transplant (HSCT) To Avoid further HEMOLYSIS To Control the Hemolysis Questionable because if we give more Iron, we can promote Hemolysis If with History of Thrombosis For Marrow Hypoplasia Transplant

II. APLASTIC ANEMIA PANCYTOPENIA with Bone Marrow HYPOCELLULARITY (Fats > Cellular Elements) Acquired Aplastic Anemia = Abrupt Onset of Low Blood Counts in a previously Well Young Adult Pancytopenia = it means DIMINISHED Amounts of RBC, WBC, Platelets (all the blood elements) A. Clinical Course & Signs/Symptoms = Depends on SEVERITY o Anemia = Pallor, EF, Weakness o Bleeding = Most Common EARLY Symptom o Thrombocytopenia = Bleeding Diathesis o Leukopenia = Fever, Signs of Infections o (-) Organomegaly (in General) B. Pathogenesis of Aplastic Anemia o Bone Marrow results from SEVERE Damage to the Hematopoietic Cell Compartment o In Aplastic Anemia = there is Replacement of the Bone Marrow by Fat (HYPOCELLULAR Marrow) C. Laboratory Diagnosis o NORMOCYTIC, NORMOCHROMIC or MACROCYTIC RBC o Reticulocytopenia o Pancytopenia D. Treatment of Aplastic Anemia o HSCT (Hematopoietic Stem Cell Transplant) o Horse ATG 40mg/kg/d x 4 days or Rabbit ALG 3.5mg/kg/d x 5 days o Cyclosporin 12mg/kg/d Orally o Androgens / Steroids / Growth Factors o Transfusions o Avoidance / Treatment of Infections o Removal of Suspected Etiologic Agent o Treatment for Severe & Very Severe = BONE MARROW Transplant

10

III. ANEMIA (from Medicine Notes) A. Three Major Classes of Anemia o Marrow Production Defects (Hypoproliferative) o Red Cell Maturation Defects (Ineffective Erythropoiesis) o Decreased Red Cell Survival (Blood Loss / Hemolysis) Anemia CBC; Reticulocyte Count

Reticulocyte Index < 2.5 Red Cell Morphology Normocytic Normochromic Hypoproliferative
Marrow Damage *Infiltration / Fibrosis *Aplasia Iron Deficiency Decreased Stimulation *Inflammation *Metabolic Defect *Renal Disease Nuclear Defects *Folate Deficiency *Vitamin B12 Deficiency *Drug Toxicity *Refractory Anemia

Reticulocyte Index > 2.5 Hemolysis / Hemorrhage

Blood Loss Intravascular Hemolysis Metabolic Defect Membrane Abnormality

Micro or Macrocytic

Maturation Disorder
Cytoplasmic Defects *Iron Deficiency *Thalassemia *Sideroblastic Anemia

Hemoglobinopathy Immune Destruction Fragmentation Hemolysis

B. Signs and Symptoms o Most often recognized by Abnormal Screening Lab Tests o Acute Leukemia: Always due to Blood Loss o 30% Loss of Blood Volume: Unable to compensate w/ Vascular Contractions and changes in Regional Blood Flow o 40% Blood Loss: will manifest signs and symptoms of Hypovolemic Shock o Hgb of 7-8 mg/Dl = Signs and Symptoms of Anemia will develop: Bleeding Easy Fatigability Malaise Fever Weight Loss Night Sweats C. Physical Examination o Findings of infection, blood in stool, lymphadenopathy, petechiae, splenomegaly o Forceful heartbeat, strong peripheral pulses, systolic flow murmur (Hemic) o Pale skin and mucous membranes

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D. Laboratory Examinations: 1. CBC Hemoglobin, Hematocrit Red Cell Indices MCV (N: 90 + 8) MCH (N: 30 + 3)

Microcytosis: MCV < 80 Macrocytosis: MCV > 100 MCV and MCH reflect defects in Hemoglobin Synthesis

2. Peripheral Blood Smear Anisocytosis = change in Cell Size Poikilocytosis = changes in Cell Shape (suggests defect in maturation of RBC precursors in BM or fragmentation of circulating RBCs) Polychromasia = Reticulocytes which are released Prematurely from the BM (slightly larger than normal and grayish blue), seen in Fibrosis, Infiltration of BM by Malignant Cells 3. Reticulocyte Count Key to the initial classification of Anemia < 2-3x the normal = Inadequate Marrow Response
An accurate Reticulocyte Count is key to the initial classification of Anemia. Normally, Reticulocyte Count ranges from 1-2% and reflects the daily replacement of 0.8-1.0% of the circuloating red cell population. A reticulocyte count provides a reliable measure of red cell production In order to use the Reticulocyte Count to estimate marrow response, two corrections are necessary. The first correction adjusts the reticulocyte count based on the reduced number of circuloating red cells. With anemia, the % of reticulocytes may be increased while the absolute number is unchanged. To correct for this effect, the reticulocyte percentage (%) is multiplied by the ratio of the patients hemoglobin or hematocrit to the expected hemoglobin/hematocrit for age and gender of the patient. This provides an estimate of reticulocyte count corrected for anemia. In order to convert the corrected reticulocyte count to an index of marrow production, a further correction is required, depending on whether some of the reticulocytes in circulation have been released from the marrow prematurely. For this second correction, the peripheral blood smear is examined to see if there are polychromatophilic macrocytes present. These cells, representing prematurely released reticulocytes, are referred to as shift cells, and the relationship between the degree of shift. The correction is necessary because these prematurely released cells survive as reticulocytes in circulation for > 1 day, thereby providing a falsely high estimate of daily red cell production. If the Reticulocyte Production Index is < 2 in the face of established Anemia, a Defect in Erythroid Marrow Proliferation or Maturation must be present

E. Calculation of Reticulocyte Production Index (Medicine Notes) 1. Correction #1 for Anemia (Produces the Absolute Reticulocyte Count) Abs. Ret Ct = Ret Count x . Hemoglobin of Patient . Expected Hgb for the Age and Gender

Example: Person whose reticulocyte count is 9%; Hgb 7.5g/Dl, Hct 23% Absolute Reticulocyte Count = 9 x (7.5/15) OR 9 x (23/45) = 4.5% 2. Correction #2 for Anemia (Produces the Reticulocyte Index) Reticulocyte Production Index = Retic Count x . Hemoglobin of Patient / Expected Hemoglobin . Maturation Time Correction **NOTE: Maturation Time Correction varies from 1-3, but 2 is usually used Example: IN a person whose Reticulocyte Count is 9%, Hgb 7.5gm/Dl, Hct 23% Reticulocyte Production Index = 9 x 7.5 / 15 = 2.25 2

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F. Bone Marrow Examination Hypoproliferative Anemia Hemolytic Disease Maturation Disorder RETICULOCYTE PRODUCTION INDEX <2 >3 Decreased E/G RATIO 1:2 or 1:3 At least 1:1 Increased

**NOTE: E/G Ratio or Erythroid / Granulocytic Ratio 1. Hypoproliferative Anemia Reticulocyte Production Index with little or no change in RBC morphology (Normocytic, Normochromic) At least 75% of all cases of Anemia Majority due to Mild to Moderate Deficiency or Inflammation Other Causes: Marrow damage, inadequate EPO stimulation in Renal Failure Key Labs: Serum Iron, TIBC, Evaluation of Renal and Thyroid Function, Marrow Biopsy Serum Ferritin
Acute or Chronic Inflammation In Mild to Moderate Deficiency Serum Iron Serum Iron % Transferrin Saturation % Transferrin Saturation N or TIBC TIBC Ferritin Ferritin

**NOTE: Anemia of Chronic Disease Cytokines causes ANEMIA This is in contrast to Anemia of Iron Deficiency

2. Red Cell Maturation Defects / Ineffective Erythropoiesis

Slight to Moderately Elevated Reticulocyte Production Index that is accompanied by either Macrocytic or Microcytic Red Cell Indices Marrow Morphology: E/G Ratio > 1:1 (Erythroid Hyperplasia) Has TWO Types: Nuclear Maturation Defects (From Vitamin B12, Folic Acid Deficiency, Drug Damage, Myelodysplasia) Cytoplasmic Maturation Defects (Defects from Severe Iron Deficiency) RBC Production Indices > 2.5x the Normal There is INCREASED Erythropoiesis: presence of Polychromatophilic Macrocytes in PBS

3. Blood Loss / Hemolytic Anemia

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HEMATOLOGIC MALIGNANCIES
I. ACUTE LEUKEMIA Present with manifestations of CYTOPENIAS Anemia: Fatigue and Dyspnea Thrombocytopenia: Cutaneous or Mucosal Hemorrhages Neutropenia: Fever and Infection Leukemic Infiltration of organs: Lymphadenopathies, Splenomegaly (common in ALL), Gingival Hyperplasia and Skin Nodules (common in AML)
A. Acute Myeloid Leukemia (AML) o 80% of adult Acute Leukemia o Characterized by predominance of Blasts (Myeloblasts and Early Promyelocyte) in the BM and PBS
o o Etiology: Hereditary, radiation, chemical and other occupational exposures, drugs Classifications: WHO Classification + FAB Classification (see harrisons) 1. Clinical Presentation Non-Specific Symptoms that begin gradually or abruptly and are the consequence of Anemia, Leuokcytosis, Leukopenia, or Leukocyte Dysfunction, or Thrombocytopenia Fatigue, weakness, anorexia, weight loss, fever, abnormal hemostasis, bone pain, lymphadenopathy, nonspecific cough, headache, or diaphoresis 2. On Physical Examination Fever, Splenomegaly, Hepatomegaly, Lymphadenopathy, Sternal Tenderness, evidence of Infection & Hemorrhage 3. Hematologic Findings Anemia (can be severe) Normocytic Normochromic Decreased Erythropoiesis often results in a Reduced Reticulocyte Count Decreased RBC survival by accelerated destruction Active Blood Loss Median Presenting Leukocyte Count is ~15,000u/L Auer Rods: if present, the Myeloid Lineage is virtually certain Platelet Counts < 100,000/uL Elevation of Serum Uric Acid (50%) 4. Treatment: Induction + Postremission Management Goal: to quickly induce Complete Remission (CR) Once CR is obtained, further therapy must be used to prolong survival and achieve cure

B. Acute Lymphoblastic Leukemia o Characterized by predominance of Lymphoblasts o Occurs most often in children o Form of Acute Leukemia that is MOST Responsive to Therapy
o o o Common in children ALL is NOT a common Leukemia in Adults ALL cell origin is in the Lymphoid Line Most Common ALL Variant (75%) = B-Cell Lineage

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II. CHRONIC LEUKEMIA Characterized by Proliferation of Lymphoid or Hematopoietic Cells that are more mature than those of Acute Leukemia Have a longer, less devastating Clinical Course than acute leukemia A. Chronic Lymphocytic Leukemia (CLL) o Proliferation of neoplastic lymphoid cells (almost always B-Cells) with widespread infiltrations of BM, PBS, Lymph Node, Spleen and Liver o Incapable of producing into Antibody-Producing Plasma Cells o Often occurs in persons > 60 y/o o Presence of Smudge Cells in PBS o Leukemic Cells resemble Normal Mature, Peripheral Blood Lymphocytes o Increased Number of MATURE Lymphocytes (CD-5 B-Cells 95%) in Peripheral Blood & Bone Marrow o Males > Females 1. Complications: Warm Antibody Autoimmune Hemolytic Anemia (AIHA) Hypoagammaglobulinemia and Increased Susceptibility to Bacterial Infection 2. Clinical Features Indolent Clinical Course Generalized Lymphadenopathy and Moderate Hepatosplenomegaly
Asymptomatic or +/- Lymphadenopathy Pallor, Signs of Bleeding, Infections

3. Treatment of Chronic Lymphocytic Leukemia Indications for Treatment: Hemolytic Anemia, Important Cytopenias, Disfiguring Lymphadenopathy, Symptomatic Organomegalies, Marked Systemic Symptoms Treatment / Management: Chlorambucil + Prednisone COP or CHOP Mainstay of Treatment = Fludarabine +/- Chemotherapeutic Agents HSCT (for younger patients) IVIG

B. Chronic Myeloid Leukemia (CML) o Neoplastic Clonal Proliferation of Myeloid Stem Cells o Characterized by reciprocal chromosomal translocation between chromosomes 1 and 2 Philadelphia Chromosome o Marked Leukocytosis (50,000 to 200,000) o Reduction in Leukocyte Alkaline Phosphatase activity in the Leukemic Leukocytes o Clinical Features: Prominent Splenomegaly Modestly Enlarged Liver and Lymph Nodes Terminates in Accelerated Phase (BLASTIC CRISIS) with Increasing number of Blast Cells and Promyelocytes
o o Diagnosis is established by identifying a Clonal Expansion of a Hematopoietic Stem Cell possessing a reciprocal translocation between Chromosomes 9 and 22 Untreated, the disease is characterized by the inevitable transition from a Chronic Phase to an Accelerated Phase and on to Blast Crisis in a Median Time of 4 years 1. Clinical Presentation Clinical Onset of the Chronic Phase is generally insidious Fatigue, malaise, and weight loss, splenic enlargement (early satiety, left upper quadrant mass) 2. Physical Examination Minimal to Moderate Splenomegaly = Most Common Mild Hepatomegaly

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3. Laboratory Hematologic Findings Elevated WBC, with increases in both immature and mature granulocytes Platelet Counts are almost always elevated at diagnosis Mild Normocytic Normochromic Anemia Bone Marrow Cellularity is Increased (at diagnosis) Increased Myeloid to Erythroid Ratio Disease Acceleration: defined by development of increasing degrees of anemia unaccounted for by the bleeding or therapy; cytogenetic clonal evolution; or blood marrow blasts between 10-20%, blood or marrow basophils >20%, or platelet count < 100,000/uL Blast Crisis: defined as Acute Leukemia, with Blood or Marrow Blasts > 20% **NOTE: Cytogenic Hallmark of CML (90-95%) = t(9;22)(q34;q11.2) Originally, this was recognized by the presence of a shortened chromosome 22 (22q-), designated as the Philadelphia Chromosome 4. Treatment Goal of Tx: To achieve prolonged, durable, nonneoplastic, nonclonal hematopoiesis, which entails the eradication of any residual cells containing the BCR/ABL Transcript Hence, goal is complete molecular remission and cure
If Blasts > 20% Blastic Crisis 10-20% Accelerated Phase < 10% Chronic Phase Hydroxyurea o Given as management action of Leukocytes Rupture o Problem: Ruptured WBCs may cause an Increase in Uric Acid Levels therefore, we give Allopurinol AND we give NaHCO3 to Alkalinize the Urine

III. LYMPHOMAS Incidence: Males > Females (3:2) Etiology: Viral (EBV), Chemicals (Benzene Herbicides), Hereditary, Immunodeficiency A. Signs / Symptoms o Painless Enlarged Lymphadenopathy o With or Without Fever, Night Sweats, Weight Loss B. Hodgkins VS Non-Hodgkins Lymphoma:
Spread Extranodal Site Involvement Systemic Symptoms Involvement Cure HODGKINS LYMPHOMA Orderly Spread by Contiguity RARE Of Prognostic Importance Axial and Central Lymph Nodes POSSIBLE for All Types NON-HODGKINS LYMPHOMA Random, Hematogenous Spread In UNFAVORABLE Types Less Common Peripheral, Mesenteric Lymph Nodes Blood; Waldermyers Ring RARE in Low Grade Tumors

C. Diagnosis o Lymph Node or Extra-Nodal Mass BIOPSY o FNAB (+) Limitations (very painful) o Histopathology = (+) REEDSTERNBERG CELL in Hodgkins Lymphoma o Immunohistochemistry D. Differential Diagnosis o Reactive Lymph Node Hyperplasia (as in INFECTIONS) o Undifferentiated Carcinoma E. Prognosis o Hodgkins Lymphoma is BETTER than Non-Hodgkins Lymphoma o International Prognostic Index (IPI) for Non-Hodgkins Lymphoma (FIVE Clinical Factors): Age 60 or Above Serum LDH Levels ELEVATED Performance Status Ann-Arbor Stage III or IV Extranodal Site Involvement

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qwertyuiopasdfghjklzxcvbnmqwertyui opasdfghjklzxcvbnmqwertyuiopasdfgh jklzxcvbnmqwertyuiopasdfghjklzxcvb nmqwertyuiopasdfghjklzxcvbnmqwer INFECTIOUS DISEASE tyuiopasdfghjklzxcvbnmqwertyuiopas dfghjklzxcvbnmqwertyuiopasdfghjklzx cvbnmqwertyuiopasdfghjklzxcvbnmq wertyuiopasdfghjklzxcvbnmqwertyuio pasdfghjklzxcvbnmqwertyuiopasdfghj klzxcvbnmqwertyuiopasdfghjklzxcvbn mqwertyuiopasdfghjklzxcvbnmqwerty uiopasdfghjklzxcvbnmqwertyuiopasdf ghjklzxcvbnmqwertyuiopasdfghjklzxc vbnmqwertyuiopasdfghjklzxcvbnmrty uiopasdfghjklzxcvbnmqwertyuiopasdf ghjklzxcvbnmqwertyuiopasdfghjklzxc vbnmqwertyuiopasdfghjklzxcvbnmqw ertyuiopasdfghjklzxcvbnmqwertyuiop
Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

COMMON INFECTIOUS DISEASES

1) DENGUE INFECTION
I. DENGUE FEVER Acute febrile illness with NO Identifiable Focus of Infection of 2-7 days Duration (sometimes Biphasic) With Two or More of the following: o Headache Tourniquet Test: Inflate cuff midway between Systolic and o Retro-Orbital Pain Diastolic for 5 minutes o Myalgia / Arthralgia (+) If > 20 Petechiae in a 1 square inch area o Rash (Petechial) 1.5 inches from Volar Aspect of Antecubital o Hemorrhagic Manifestations (Petechiae + Tourniquet Test) Fossa o Leukopenia A. Microbiology o Aedes Aegypti = Principal Vector (All four distinct dengue viruses Dengue 1-4 have Aedes Aegypti as their principal vector, and all cause a similar clinical syndrome o Breeds near human habitation relatively fresh water source such as water jars, discarded containers o In rare cases, SECOND infection with a Serotype of Dengue Virus different from that involved in the Primary Infection leads to Dengue Hemorrhagic Fever (HF) with Severe Shock o Incubation Period 2-7 Days B. Clinical Presentation o Sudden Onset of Fever, headache, retroorbital pain, and back pain along with the severe myalgia that gave rise to the colloquial desegnation Break Bone Fever o D1: Macular rash, adenopathy, palatal vesicles and sclerae injection o Others: Anorexia, nausea, vomiting, cutaneous hypersensitivity, maculopapular rash beginning on the trunk and spreading to extremities and face o Epistaxis and scaterred petechiae are often noted in uncomplicated dengue, and preexisting gastrointestinal lesions may bleed during the Acute Illness C. Laboratory Findings o Leukopenia, Thrombocytopenia, Serum Aminotransferase Elevation o Dx: IgM ELISA or Paired Serology during Recovery or by Antigen-Detection ELISA or RT-PCR during the Acute Phase II. DENGUE HEMORRHAGIC FEVER / DENGUE SHOCK SYNDROME Usually with a background of Previous Exposure to another Serotype the transient protection after Dengue Virus Infection is replaced within several weeks by the potential for Heterotypic Infection resulting in Typical Dengue Fever or uncommonly for ENHANCED Disease (Secondary DHF / DSS) Macrophage Infection is CENTRAL to the pathogenesis of Dengue Fever and to the Origin of DHF / DSS A. Pathogenesis Previous Infection with a Heterologous Dengue Virus Serotype Production of Nonprotective Antiviral Antibodies Bind to Virions Surface and through interaction with the Fc Receptor focus Secondary Dengue Viruses on the Target Cell Enhanced Infection B. Induction of Vascular Permeability and Shock depends on Multiple Factors: o 1) Presence of Enhancing and Non-Neutralizing Antibodies o 2) Age (susceptibility to DHF/DSS drops after 12y/o) o 3) Sex (F > M) o 4) Race o 5) Nutritional Status (Malnutrition is Protective) o 6) Sequence of Infection (Serotype 1 followed by Serotype 2 is More DANGEROUS than Serotype 4 followed by Serotype 2) o 7) Infecting Serotype (Serotype 2 is MORE DANGEROUS)

C. Clinical Presentation of DHF

o o Identified by detection of Bleeding Tendencies (Torniquet Test, Petechiae) or Overt Bleeding in Absence of underlying causes Dengue Shock Syndrome: accompanied by Hemorrhagic Signs & results from Increased Vascular Permeability leading to shock Mild DHF / DSS More Severe Cases Restlessness, Letharghy, Thrombocytopenia < 100,000/uL, Hemoconcentration are detected 2 to 5 days after onset of Typical Dengue Fever, usually at the time of Defervescence Frank Shock is apparent, with Low Pulse Pressure, Cyanosis, Hepatomegaly, Pleural Effusions, Ascites, and in some cases Severe Ecchymoses and GI-Bleeding Period of Shock lasts only 1 or 2 days, and most patients respond promptly to close monitoring, oxygen administration, and infusion of Crystalloid or in severe cases Colloid 1. Dengue Hemorrhagic Fever (DHF) Fever or Hx of Fever lasting for 2-7 days Hemorrhagic Manifestations such as: (+) Tourniquet Test Petechiae, Ecchymosis, Purpura Bleeding from Mucosa, GI Tract, IV Sites or other sites, Hematemesis or Melena Thrombocytopenia (100,000 or 1-2 Platelets / OIF) Evidence of Plasma Leakage due to Increased Capillary Permeability Any Hematocrit > 40% of Rise of > 20% in Hematocrit for age and sex A Drop in 20% Hematocrit following volume replacement treatment as compared to baseline Signs of Plasma Leakage (Pleural Effusion, Ascites) 2. Dengue Shock Syndrome (DSS): All the criteria of DHF, PLUS Signs of Circulatory Failure Rapid and Weak Pulses Narrow Pulse Pressure (< 20mmHg) Hypotension for Age (< 60mmHg Systolic for < 5y/o and < 90mmHg Systolic for > 50 y/o) Cold Clammy Extremities D. Diagnosis o Virologic Diagnosis can be made by the usual means, although Multiple Flavivirus Infections lead to a broad immune response to several members of the group, and this situation may result in a lack of Virus Specificity of the IgM and IgG Immune Responses o A secondary Antibody Response can be sought with tests against several Flavivirus Antigens to deminstrate the characteristic Wide Spectrum of Reactivity

III. GRADING OF DENGUE (Medicine Notes)

GRADE 1 Fever with Non-Specific Sx GRADE 2 Grade 1 PLUS: Hemorrhagic Manifestations: (+) Torniquet Test Easy Bruisability Gum Bleeding Epistaxis, Rashes Petechiae on Palate Petechiae on Axillae GRADE 3 Grade 1 + 2 PLUS: Circulatory Failure Rapid Weak Pulse Narrowing Pulse Pressure Hypotension Cold, Clammy Skin Restlessness GRADE 4 Grade 1 + 2 + 3 PLUS Profound SHOCK Undetectable BP or Pulse

IV. MANAGEMENT OF DENGUE HEMORRHAGIC FEVER

A. Diagnostics o CBC with PC, PT, PTT; Torniquet Test o Dengue Serology if Illness LONGER Than 4 days o Others: AST/ALT, urinalysis, CXR Monitor Platelet Count + Hematocrit Levels q12-24 hours

B. Therapeutics o Supportive Hydration o Optional Medications: H2-Blockers if with Abdominal Pain or GI Bleeding o Watch out for Complications: If there is Frank, Uncontrollable Bleeding Fresh Whole Blood is indicated If PT, PTT are prolonged and with Thrombocytopenia, Fresh Frozen Plasma Transfusion is indicated If there is DIC, Platelet Transfusion is indicated **NOTE: In the Absence of Bleeding, there is NO need to administer Platelet Transfusion, even if PC is LOW C. Prevention

2) TYPHOID FEVER

Gram (-) S. typhi and S. paratyphi 3 Major Antigenic Determinants: Somatic-O Antigen, Surface V1 Antigen, Flagellar H-Antigen Incubation Period: varies with the size of infecting dose and averages 10-20 days (range 3-55 days) I. PATHOGENESIS Hallmark: Invasion and Multiplication within the Mononuclear Phagocytic Cells in the liver, spleen, lymph nodes and Peyer Patches of the Ileum Transmitted to humans orally by contaminated food or water II. CLINICAL MANIFESTATION NON-SPECIFIC SYMPTOMS PHYSICAL FINDINGS
Chills Diaphoresis Anorexia Myalgia Cough Weakness / Malaise Sore Throat Dizziness Constipation / Diarrhea Abdominal Pain Abdominal Distention Persistent High Fever Relative Bradycardia Rose Spots (Rashes primarily trunk area) Abdominal Tenderness Hepatomegaly Splenomegaly Thyroid Psychosis / Encephalitis Epistaxis

III. CRITERIA FOR ADMISSION (Medicine Notes) All Patients Suspected of Having Typhoid Fever with ONE or More of the Following: Persistent Vomiting or Unable to take Oral Fluids Severe Dehydration Spontaneous Bleeding Persistent Abdominal Pain Listlessness Changes in Mental Status Weak, Rapid Pulse Cold, Clammy Skin Circumoral Cyanosis Seizures Hypotension or Narrowing Pulses

All Patients suspected of having Complicated Typhoid Fever Intestinal Perforation GI Hemorrhages Peritonitis Pericarditis Hepatic and Splenic Abscesses DIC Myocarditis Meningitis

III. LABORATORY WORK-UP A. Complete Blood Count (CBC) o Leukopenia / Leukocytosis o Thrombocytopenia o Normochromic Anemia; Hypochromia with Blood Loss o Neutropenia B. Culture of Appropriate Specimen 1. Blood Culture Gold Standard Should be taken anytime during the illness, but yield is HIGHERST during the first 2 Weeks Should be taken at least from different sites 2. Stool Culture (+) 2nd 4th Week of Illness 3. Bone Marrow Culture NOT likely done, but indicated in high suspicious cases with (-) Blood or Stool Culture Can be done anytime during t he illness Isolation Rate is around 90%

IV. LABORATORY FINDINGS (from Blue Book) IgM IgG (+) (-) Acute Infection (+) (+) Recent Infection (-) (+) Equivocal: Past Infection or Acute Infection V. TREATMENT A. UNCOMPLICATED Typhoid Fever: Conventional Therapy o Chloramphenicol 3-4g in 4 divided doses x 14 days; Or o Co-Trimoxazole Forte 1-1.5 tabs BID x 14 days; Or o Amoxicillin 4-5g/day in 3 divided doses x 14 days B. For COMPLICATED Cases, Presence of Severe Symptoms, Clinical Deterioration despite Conventional Therapy: (Empiric Therapy for Suspected Resistant Typhoid Fever) o Ceftriaxone (Rocephin) 3gm IV Infusion OD x 5-7 days; or Ceftriaxone may be used for Pregnant o Fluoroquinolones: Women and Children Ciprofloxacin (Cibprobay) 500mg tab PO BID x 7-10 days Ofloxacin (Inoflox) 400mg tab PO BID x 7-10 days Pefloxacin (Floxin) 400mg tab PO BID x 7-10 days VI. PREVENTION Whole Cell Vaccine (Heat Killed) = 2 parenteral doses Purified Vi Polysaccharide fro Capsule = 1 parenteral dise (ViCPS) Attenuated S. typhi = 4 oral doses (Ty21a) VII. COMPLICATIONS: Intestinal Perforation GI Hemorrhage and Peritonitis may occur in the 3 rd to 4th Week of Illness Pancreatitis, Hepatic & Splenic Abscess, Disseminated Intravascular Coagulation, Myocarditis, Meningitis, Encephalitis

3) LEPTOSPIROSIS
MILD FORM = Leptospirosis may present as an Influenza-Like Illness with Headache and Myalgia SEVERE FORM (Weils Syndrome) = characterized by Jaundice, Renal Dysfunction, & Hemorrhagic Diathesis

I. EPIDEMIOLOGY A ZOONOSIS with a worldwide distribution Rodents (especially Rats) = Most Important reservoir, although other Wild Mammals, Dogs, Fish and Birds may also harbor these Microorganisms Transmission of Leptospires: o Direct Contact with Urine, Blood or Tissue from an Infected Animal o Exposure to a Contaminated Environment o Human-to-Human Transmission is RARE! o Since Leptospires are Excreted in the Urine and can survive in water for many months, WATER is an Important Vehicle in their Transmission II. CLINICAL MANIFESTATIONS A. Anicteric Leptospirosis o Leptospirosis may present as an Acute Influenza-Like Illness with Fever, Chills, Severe Headache, etc o Muscle Pain (Calves, Back, Abdomen) = IMPORTANT Feature of Leptospiral Infection 1. Leptospiremic Phase Acute Influenza-Like Illness = Fever, Chills, Severe Headache, Nausea, Vomiting, Myalgias IMPORTANT Feature of Leptospiral Infection = MUSCLE PAIN, which especially affects the Calves, Back and Abdomen Mental Confusion may be Evident Pulmonary Involvement (is not Uncommon) = Manifested in most cases by COUGH and Chest Pain and in a few cases by Hemoptysis MOST COMMON Finding on Physical Examination = FEVER with Conjunctival Suffusion Mild Jaundice may be Present 2. Immune Phase Most Patients become ASYMPTOMATIC within 1-week After an Interval of 1 to 3 days, the Illness recurs in a number of cases The Start of this Second (Immune) Phase COINCIDES with the Development of Antibodies Symptoms are more VARIABLE than during the First (Leptospiremic) Phase Fever is LESS Pronounced and Myalgias are LESS Severe than in the Leptospiremic Phase NOTE: This is where we see the Inflammation Stages **An Important Event during the Immune Phase is the Development of Aseptic Meningitis: Meningeal Symptoms usually DISAPPEAR within a few days, but may persist for weeks Iritis, Iridocyclitis and Chorioretinitis = Late Complications that may persist for years (can become apparent as early as the third week, but often present several months after the initial illness)

B. Severe Leptospirosis (WEILS SYNDROME = Most Severe Form) o Characterized by Jaundice, Renal Dysfunction, Hemorrhagic Diathesis, and HIGH MORTALITY o Mortality = usually due to HEMORRHAGE! o Frequently (but NOT exclusively) associated with Serovar Icterohaemorrhagiae / Copenhageni o Serovar Icterohaemorrhagiae / Copenhageni = Causes the INFECTION (from RATS) o The onset of Illness is NO Different from that of Less Severe Leptospirosis; however, after 4-9 days, Jaundice as well as Renal & Vascular Dysfunction generally develop o NOTE: It has NO Biphasic Disease Pattern like that seen in Anicteric Leptospirosis! **Physical Examination and Other Findings: The Jaundice of Weils Syndrome, which can be profound and give an Orange Cast to the Skin, is usually NOT Associated with Severe Hepatic Necrosis (+) Hepatomegaly & Tenderness in the Right Upper Quadrant (usually detected) (+) Splenomegaly (in 20% of cases) **Findings in Weils Syndrome: 1. Renal Failure Develop during 2nd week of illness (respond to treatment if there is NO Hemorrhage) Hypovolemia and Decreased Renal Perfusion = contribute to the Development of Acute Tubular Necrosis with Oliguria or Anuria Dialysis is sometimes required, although a Fair Number of cases can be managed without Dialysis (Renal Function may be completely regained) 2. Pulmonary Involvement Occurs frequently Presents with Cough, Dyspnea, Chest Pain, and Blood-Stained Sputum Sometimes = Hemoptysis or even Respiratory Failure 3. Hemorrhagic Manifestations (seen in Weils Syndrome) Common Manifestations = Epistaxis, Petechiae, Purpura, Ecchymoses RARE Manifestations = Severe GI-Bleeding, Adrenal or Subarachnoid Hemorrhage 4. Other Manifestations described in SEVERE Leptospirosis: Rhabdomyolysis, Hemolysis, Myocarditis, Pericarditis Congestive Heart Failure, Cardiogenic Shock Adult Respiratory Distress Syndrome Multi-Organ Failure

III. LABORATORY DIAGNOSIS OF LEPTOSPIROSIS

Isolation of Leptospires in Culture (+) Serology: Endemic Single (+), Low Titer Single (+), High Titer Paired Sera, Rising Titer (+) Serology, NOT Endemic Single (+), Low Titer Single (+), High Titer Paired Sera, Rising Titer CERTAIN 2 10 25 5 15 25 Scoring System: (+) = Isolation of Leptospires from Culture Presumptive: o A or A + B = 26 o A + B + C = 25 Suggestive o A or A + B = 20 25 o A + B + C = 20 25

A. Culture Isolation o GOLD Standard o Isolated from Blood / CSF = during the First 10 days o Isolated from Urine = several weeks (beginning around the 1 st week) o Ellinghausen-McCullough-Johnson-Harris (EMJH) Medium, Fletcher Medium, Korthof Medium B. Others o Direct Darkfield Microscopy (Blood or Urine) Usually results in Misdiagnosis and should NOT be used o Serology = Antibody Detection: Microagglutination Test (MAT), Complement Fixation, ELISA, IFA, Microcapsule Agglutination Test (MCAT) o DNA Technology (eg. PCR) C. Renal Changes o Kidneys are Invariably Involved in Leptospirosis o Related Findings Range from: Urinary Sediment Changes (Leukocytes, Erythrocytes, Hyaline or Granular Casts) Anicteric Leprospirosis = Mild Proteinuria Severe Leptospirosis = Renal Failure and Azotemia IV. TREATMENT The Effectiveness of Antimicrobial Therapy for the Mild Febrile form of Leptospirosis is CONTROVERSIAL, but such Treatment is INDICATED for MORE SEVERE FORMS Treatment should be initiated as EARLY as possible; nevertheless, contrary to previous reports, treatment started after the first 4 days of illness is effective. A. In Milder Cases: Oral Treatment with Tetracycline, Doxycycline, Ampicillin, or Amoxicillin should be considered o Amoxicillin 500mg QID PO o Ampicillin 500-750mg IV q6 B. For Severe Cases: IV Administration of Penicillin G, Amoxicillin, Ampicillin, or Erythromycin is recommended o Pen G 1.5 M q6 1 week Jarisch-Herxheimer Reaction o After the start of Antimicrobial Treatment for Leptospirosis, a Jarisch-Herxheimer Reaction similar to that seen in other Spirochetal Diseases may develop o It is a Dramatic, though usually Mild Reaction, consisting of Fever, Chills, Myalgias, Headache, Tachycardia, Increased Respiratory Rate, Increased Circulating Neutrophil Count, and Vasodilation with Mild Hypotension

3) MALARIA
Protozoan Disease transmitted by the Bite of Infected Anopheles Mosquitoes It is a Parasitic Infection caused by a Protozoan Plasmodium spp It is presented with CYCLIC FEVER and CHILLS with SPLENOMEGALY leading to serious illness

I. EPIDEMIOLOGY OF MALARIA MOST IMPORTANT Parasitic Disease in Humans Four Species of Malaria: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae Of the 4 Species of Human Malaria, Plasmodium falciparum causes nearly ALL DEATHS and NEUROLOGICAL COMPLICATION Transmission of P. falciparum = Transmitted by the BITE of an Infected Anopheline mosquito (Anopheles flavirostris in the Philippines) II. LIFE CYCLE OF MALARIA In Humans, although Parasite undergoes development in the Liver, it is the Erythrocytic Cycle thats responsible for disease! o Erythrocytic Cycle = Responsible for the Development of the Disease o Schizonts Rupture & Merozoites are Released = causes PAROXYSM of Malaria

Erythrocyte Changes in Malaria

After INVADING an Erythrocyte, the growing Malarial Parasite progressively consumes and degrades Intracellular Proteins, principally HEMOGLOBIN Potentially Toxic Heme Biologically Inert HEMOZOIN or Malarial Pigment Parasite also alters RBC membrane Irregular Shape More Antigenic & Less Deformable Result: Shortened RBC survival

III. CLINICAL MANIFESTATIONS Initial Symptoms: NON-SPECIFIC and NOT Reliable (Incubation Period = 8-40 days) Headache may be SEVERE, there is NO Neck Stiffness or Photophobia resembling Meningitis A. High Index of Suspicion o Travel to and Overnight Stay in Malarious Area (palawan) o Blood Transfusion in the past 6 months o Intravenous Drug Use **NOTE: Significant Travel History Significant Exposure = at most, 1 Month (Incubation Period = as long as 30-45 days) Ex) If patient had a History of Travel to Palawan 2 years ago, it is NOT Significant B. Other Features:
o o o o o o Nausea, Vomiting, and Orthostatic Hypotension Classic Malarial Paroxysms Anemia Splenic Enlargement Slight Enlargement of the Liver Mild Jaundice

1. Classical Malaria Paroxysm: Cold Stage (Chills) Hot Stage (Fever Spikes) Sweating Stage **IMPORTANT Notes: The CLASSIC Malarial Paroxysms (Fever Spikes, Chills and Rigors) occur at REGULAR Intervals are relatively Unusual and suggest Infection with P. vivax & ovale Fever is IRREGULAR at First (P. falciparum may NEVER become Regular) 2. Periodicity of Attacks ONLY if the Patient is UNTREATED Periodicity = every 3 days, 4 days, etc (it does NOT occur if patient is Treated) Eg. Every 48-Hours for Plasmodium falciparum 3. Periodicity of Malaria:
Tertian Periodicity Cyclic Fever occurring every 48 Hours Includes Plasmodium falciparum, vivax, ovale MALIGNANT VS BENIGN TERTIAN Malignant Tertian Malaria = severe w/ complications (Plasmodium falciparum) Benign Tertian Malaria = mild (Plasmodium ovale, vivax) Cyclic Fever occurring every 72 Hours Includes Plasmodium malariae

Quartan Periodicity

C. Severe FALCIPARUM MALARIA 1. CEREBRAL MALARIA (MOST Life-Threatening) COMA is a characteristic and ominous feature of Falciparum Malaria Death Rate = 20% among adults; 15% in children Diffuse Symmetric Encephalopathy (Focal Neurologic Signs are UNUSUAL 2. Others:
Severe Normocytic Anemia Hypoglycemia, Metabolic Acidosis with Respiratory Distress, Fluid and Electrolyte Disturbance, Acute Renal Failure Acute Pulmonary Edema and Adult Respiratory Distress Syndrome (ARDS)

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IV. DIAGNOSIS A. Thick and Thin Smears o GOLD STANDARD Actual Demonstration of the Parasite in the Blood Smear o Thick Smear = for Quantification of Parasitemia o Thin Smear = for Species Identification B. Others o Rapid Diagnostic Tests o Serology (IFAT, ELISA, IHA) C. Other Findings (Medicine Notes) o Normochromic, Normocytic Anemia o ESR, Plasma Viscosity, CRP o Prolonged PT/PTT, Severe Thrombocytopenia, Metabolic Acidosis o Plasma Glucose, Na, HCO3, Ca2+, Phosphate, Albumin o Lactate, BUN, Crea, Urate, Muscle & Liver Enzymes, Bilirubin (DB & IB) D. For Cerebral Malaria o Mean Opening Pressure at Lumbar Puncture is ~180mmHg of CSF o Normal or has slightly Total Protein and Cell Count V. TREATMENT
We Treat Malaria with COMBINATION Drugs this is because of Chloroquine-Resistance Severe Malaria = DOC is QUININE (for Severe Malaria: Cerebral Malaria, etc) A. First Line of Treatment = Chloroquine + Sulfadoxine / Pyrimethamine (CQ + SP) o First Line in the Drug Treatment of PROBABLE Malaria and CONFIRMED P. falciparum provided that the Disease is NOT Severe B. Artemether-Lumefantrin (Co-ArtemTM) o SECOND Line Drug o Given ONLY to Microscopically CONFIRMED P. falciparum which did NOT respond to Adequate CQ + SP Treatment o It is NOT recommended for PREGNANT Women and children < 8y/o C. Quinine + Tetracycline / Doxycycline o THIRD Line Drug o Should be given to those who did NOT Respond to Co-ArtemTM o DRUG of CHOICE in the Treatment of SEVERE MALARIA! **IMPORTANT Notes: Tetracycline and Doxycycline are CONTRAINDICATED for Pregnant Women and children < 8y/o Instead, give Quinine + Clindamycin D. Primaquine o Given in single dose to CONFIRMED P. falciparum cases to PREVENT Transmission o Given for 14 days to CONFIRMED P. vivax to PREVENT RELAPSE E. Chloroquine o Drug to be used in the Treatment of CONFIRMED P. vivax

Circulatory Collapse, Shock, Septicemia, Abnormal Bleeding Jaundice, Haemoglobinuria High Fever, Hyperparasitaemia (>100,000 Ring Stage/uL)

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4) SCHISTOSOMIASIS
Endemic in 24-Provinces in the Philippines HIGHEST Prevalence of Infection in children 5-15 years of age

I. EPIDEMIOLOGY Schistosoma japonicum = MAJOR Species involved in Schistosomiasis (in the Philippines) Snail Vector = Oncomelania quadrasi (Skin Penetration) Transmission = requires CONTACT between Humans and other Animal Hosts with the Breeding Sites for Snails (there should be SKIN PENETRATION of the Cercaria!) II. CLINICAL ASPECTS Main Pathology and Manifestations = due to Granulomatous Reaction to Eggs deposited in the Liver and other organs Most Serious Consequence in the Liver is OBSTRUCTION of Intrahepatic Portal Branches leading to: o Portal Hypertension with Splenomegaly o Collateral Circulation o Ascites **IMPORTANT Notes: o End of Infection = LIVER CIRRHOSIS o Usually, patients would come for consult due to Signs of Liver Failure (Ascites, Hepatomegaly, etc)

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Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

COMMON RENAL (NEPHROLOGY) DISEASES

1) RENAL TUBULAR ACIDOSIS

Disorder of Renal Acidification out of proportion to the Reduction in GFR Characterized by Hyperchloremic Metabolic Acidosis with Normal Anion Gap

I. TYPE-1 RTA (DISTAL) Distal Nephron does NOT lower Urine pH normally due to excessive back diffusion of H + Ions from the Lumen to the Blood Chronic Acidosis: o Decreased Tissue Reabsorption of Ca2+ o Renal Calciuria (Increasing Osteoclast Activity) Alkaline Urine o Decreased Urine Citrate Excretion A. Diagnosis: o Suggested by Normal Anion Gap Metabolic Acidosis with Urine pH > 5.5 o (-) Bicarbonaturia B. Treatment o NaHCO3 100mEq + 400cc H2O II. TYPE-II RTA (PROXIMAL) Hyperchloremic Acidosis Bicarbonate Reabsorption in the Promximal Tubule is defective leading to Bicarbonaturia Distinguished from Type-I by the ability to Normally Acidify Urine during Spontaneous or Induced Ammonium Acidosis Treatment: NaHCO3 5-15 mmol/kg/day III. TYPE-IV RTA Distal Tubule Secretion of K+ and H+ ions are Abnormal, resulting in Hyperchloremic Acidosis with Hyperkalemia Hyponatremic Hypoaldosteronism = MOST COMMON Cause of Type IV RTA Treatment: Fludrocortisone 0.1-0.2mg/kg/day

2) URINARY TRACT INFECTIONS

Acute Infections of the Urinary Tract can be subdivided into TWO Categories: o Lower Tract Infections = Urethritis and Cystitis o Upper Tract Infection = Acute Pyelonephritis, Prostatitis, and Intrarenal & Perinephric Abscesses

I. CLINICAL FEATURES OF URINARY TRACT INFECTIONS: UTIs exist when Pathogenic Microorganisms are detected in Urine, Uretha, Bladder, Kidney or Prostate Growth of > 105 Organisms/mL of Urine = signifies INFECTION III. URINALYSIS NOT Recommended for Young Females presenting with Typical Symptoms of LOWER Urinary Tract Infection 5 WBC / hpf Routine Screening is NOT recommended for Diabetics, Indwelling Foley Catheters, Cancer Patients (taking Chemotherapy) III. EIGHT CLINICAL SYNDROMES OF UTI Acute Uncomplicated Cystitis in Women Acute Uncomplicated Pyelonephritis Asymptomatic Bacteriuria UTI in Pregnancy Recurrent UTI (recurred > 2x Annually) Complicated UTI (patients with Anatomic, Structural or Functional Abnormality) UTI in Men (almost ALWAYS Complicated) Catheter-Associated UTI

3) ACUTE RENAL FAILURE

Syndrome characterized by Rapid Decline in GFR (hours to days) Diagnosed when Biochemical Screening of Hospitalized Patients reveals a Recent INCREASE in Plasma Urea and Creatinine Concentrations Frequent Clinical Features: Retention of Nitrogenous Waste Products, Oliguria (UO < 400mL/d contributing to extracellular fluid overload), and electrolyte and acid-base abnormalities
First step in evaluating a patient with renal failure is to determine if the disease is Acute or Chronic Findings Suggestive of Chronic Renal Failure: o Anemia o Neuropathy o Renal Osteodystrophy o Small, Scarred Kidneys ARF is often considered to be reversible, although a return to baseline serum creatinine concentrations postinjury might not be sufficiently sensitive to detect clinically significant irreversible damage that may ultimately contribute to CKD. Kidney Size may be Normal or Increased in some CKD: Diabetic Nephropathy Amyloidosis Polycystic Kidney Disease HIV Associated Nephropathy ACUTE KIDNEY DISEASE Normal Normal Absent Absent Often Present Usually Complete CHRONIC KIDNEY DISEASE Small High Present Present Usually Present Sometimes Partial

I. ACUTE VS CHRONIC RENAL FAILURE

Kidney Size Carbamylated Hemoglobin Broad Casts on Urinalysis History of Kidney Disease, HPN, Abnormal Urinalysis Anemia, Metabolic Acidosis, Hyperkalemia, Hyperphosphatemia Reversibility with Time

II. TYPES OF RENAL FAILURE Pre-Renal ARF: Diseases that cause Renal Hypoperfusion Intrinsic ARF: Diseases that directly involve the Renal Parenchyma Post-Renal ARF: Diseases associated with urinary tract obstruction
TYPE Pre-Renal DESCRIPTION Most Common Form, which occurs in the setting of Renal Hypoperfusion Prolonged Hypoperfusion leads to Acute Tubular Necrosis (Ischemic) Clinical Features: thirst, orthostatic dizziness, orthostatic hypotension, tachycardia, reduced jugular venous pressure, decreased skin turgor, dry mucous membranes Intrinsic Can be conceptually divided based on the Predominant Compartment: 1) Ischemic or Nephrotoxic Tubular Injury 2) Tubulointerstitial Diseases 3) Diseases of the Renal Microcirculation & Glomeruli 4) Diseases of Larger Renal Vessels Urinary Tract Obstruction accounts for < 5% of hospital acquired ARF Because one kidney has sufficient reserve to handle generated nitrogenous waste products, ARF from obstruction requires: Obstruction to Urine Flow between external urethral meatus and bladder neck Bilateral Ureteric Obstruction Unilateral Unreteric Obstruction with one functioning kidney SOME EXAMPLES Hypovolemia (GI losses, decreased intake, etc) Low Cardiac Output Systemic Vasodilation Selective Intrarenal Vasoconstriction Hepatorenal Syndrome Ischemic Acute Tubular Necrosis Nephrotoxic ARF

Post-Renal

Bladder Neck Obstruction (Most Common) Prostatic Disease Neurogenic Bladder Therapy with Anticholinergics

Hepatorenal Syndrome (HRS) o Unique form of Prerenal ARF that frequently complicates Advanced Cirrhosis as well as Acute Liver Failure o Kidneys are structurally normal but fail due to splanchnic vasodilation and arteriovenous shunting, resulting in provound renal vasoconstriction

III. URINALYSIS Anuria suggests complete urinary tract obstruction but may complicate severe cases of Prerenal or Intrinsic Renal ARF Findings in Urinalysis (from Med-School Notes) Prerenal ARF
Low Volume Concentrated Urine (High Specific Gravity) No RBC, No WBC (ACELLULAR) (+) Hyaline Casts (Fine Granular Casts) = Tamm Horsfall Protein Usually due to Obstructions, Stones, Prostatic Enlargement, etc NORMAL RBC (this means that the RBC does NOT come from the Glomerulus) Muddy Brown Granular Cast = PATHOGNOMONIC Microscopic Hematuria Mild Tubular Proteinuria (protein is < 1 gram/day) Dysmorphic RBC (the RBC has to pass thru the Glomerulus Distortion of Shape) (+) RBC Casts > 1g Proteinuria (Glomerular Proteinuria) WBC Casts; Granular Cast Eosinophiluria (+) Broad Cast Broad Casts reflect Total Fibrosis and Dilatation of Tubules

Post Renal ARF Acute Tubular Necrosis (ATN) Glomerulnephritis (GN) Allergic Interstitial Nephritis Chronic Kidney Disease (CKD)

IV. DIAGNOSTICS A. Serial Serum Creatinine Measurements o Prerenal ARF: Fluctuating Creatinine Levels that parallel changes in Hemodynamic Status o Renal Ischemia, Atheroembolization, Radiocontrast Exposure: Creatinine rises rapidly (within 24-48 hours) Contrast Nephropathy: Peaks in 3-5 days ATN, Atheroembolic: Peaks later 7-10 days B. Approach to Patients with Azotemia

Radiologic Findings: UTZ: Useful to exclude Post-Renal CT, MRI: Alternative Retrograte / Anterograde Pyelography Plain Film of Abdomen Renal Biopsy: Reserved for patients in whom prerenal and postrenal ARF have been excluded, and the cause of Intrinsic ARF is unclear Complications: ARF impairs renal excretion of Na, K. and H2O and perturbs divalent cation homeostasis and urinary acidification mechanisms As a result, complications include: Intravascular Volume Overload Hyponatremia Hyperkalemia Hyperphosphatemia Hypocalcemia Hypermagnesemia Metabolic Acidosis Uremic Syndrome: Develops because patients are unable to excrete nitrogenous waster products

QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.

V. MANAGEMENT
MANAGEMENT ISSUE Reversal of Renal Insult Ischemic ATN Nephrotoxic ATN THERAPY Restore systemic hemodynamics and renal perfusion through volume resuscitation and use of vasopressors Eliminate Nephrotoxic agents Consider toxin-specific measures (eg. Forced alkaline diuresis for rhabdomyolysis, allopurinol for tumor lysis sx)

Prevention and Treatment of Complications Intravascular Volume Salt and H2O Restriction Overload Diuretics, Ultrafiltration Hyponatremia Hyperkalemia Restruction of Enteral Free Water Intake Avoidance of Hypotonic IV solutions, including dextrose-containing solutions Restriction of Dietary K+ Intake Eliminate K+ supplements and K+-Sparing diuretics Loop Diuretics to promote K+ Excretion Potassium Binding Ion-Exchange Resins (eg. Sodium Polystyrene Sulfonate or Kayexelate) Insulin (10 units regular) and Glucose (50mL of 50% Dextrose) to promote Intracellular Mobilization Inhaled B-Agonist Therapy to promote intracellular mobilization Calcium Gluconate or Calcium Chloride (1g) to stabilize the Myocardium Dialysis Sodium Bicarbonate (maintain Serum HCO3 > 15mmol/L or Arterial pH > 7.2) Administration of other bases (eg. THAM) Dialysis Restriction of dietary phosphate intake Phosphate-Binding Agents (Calcium Carbonate, Calcium Acetate, Sevelamer Hydrochloride, Aluminum OH) Calcium Carbonate or Gluconate (if symptomatic) Discontinue Mg++ Containing Antacids Treatment usually not necessary if < 890umol/L or < 15mg/dL

Metabolic Acidosis

Hyperphosphatemia Hypocalcemia Hypermagnesemia Hyperuricemia

Allopurinol, forced Alkaline Diuresis, Rasburicase Nutrition Dialysis Choice of Agents Drug Dosing Protein and Calorie intake to avoid net negative nitrogen balance To prevent complications of ARF Avoid other Nephrotoxins: ACE Inhibitors / ARBs, Aminoglycosides, NSAIDs, Radiocontrast Adjust doses and frequency of administration for degree of renal impairment

VI. ABSOLUTE INDICATIONS FOR DIALYSIS: Symptoms or Signs of the Uremic Syndrome Management of Refractory Hypervolemia, Hyperkalemia, or Acidosis VII. BUN / Crea Ratio (SI Units)

BUN:Crea Ratio = BUN x 247 Crea

Conversion Factor for Serum BUN: 1 mmol/L = 2.8 mg/dL VIII. CREATININE CLEARANCE (mL/min): Cockroft and Gault Equation

Interpretation: If < 10: Intrinsic Renal Cause If 10-20: Doubtful Cause If > 20: Pre-Renal Cause

CreaClearance = . (140 age) x weight in kg . 72 x Serum Crea in mg/dL

CreaClearance = . (140 age) x weight in kg . 72 x (Serum Crea in umol/L / 88.4)

IMPORTANT Notes: o If Female, multiply everything by 0.85 o If Crea is NOT in mg/dL, divide it by 88.4

4) CHRONIC RENAL DISEASE

CKD Encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function, and a progressive decline in GFR I. DEFINITION OF TERMS A. Chronic Renal Disease o Pathophysiologic Process resulting to IRREVERSIBLE Reduction in Renal Mass and Function occurring MORE than 3 MONTHS o Pathophysiologic Process with Multiple Etiologies, resulting in the Inexorable Attrition of Nephron Number and Function, and frequently leading to End-Stage Renal Disease (ESRD) B. End-Stage Renal Disease (ESRD) or Stage 5 CKD o Irreversible Loss of Renal Function rendering an Individual PERMANENTLY dependent upon RRT o Represents a Clinical State or Condition in which there has been an Irreversible Loss of Endogenous Renal Function, of a Degree Sufficient to render the patient permanently dependent upon Renal Replacement Therapy / RRT (Dialysis or Transplantation) in order to avoid Life-Threatening Uremia Staging of Chronic Kidney Disease (CKD)
STAGE I DESCRIPTION Kidney damage with normal / increased GFT GFR mL/min / 1.73m2 90 ACTION Diagnosis and Treatment, Tx of comorbid conditions, slowing progression, CVD risk reduction Estimating progression Evaluating and Treating complications Preparation for kidney replacement therapy Kidney Replacement (if uremia is present)

II III IV V

Kidney damage with mildly decreased GFR Moderately decreased GFR Severely decreased GFR Renal Failure

60 89 30 50 15 29 < 15 (for dialysis)

 NOTES from Harrisons:

o o o

o C. Azotemia o LABORATORY Finding of an Elevated BUN and Creatinine o May or May NOT have Symptoms o Retention of Nitrogenous Waste as Renal Insufficiency develops D. Uremia o Syndrome Reflecting DYSFUNCTION of all Organ Systems as a result of Untreated or Undertreated ARF or CRF o It is the Clinical and Laboratory Syndrome, reflecting Dysfunction of all Organ Systems as a result of Untreated or Undertreated Acute or Chronic Renal Failure o Refers to more Advanced Stages of Progressive Renal Insufficiency when the Complex, Multiorgan System derangements become CLINICALLY MANIFEST II. ETIOLOGY & EPIDEMIOLOGY
Most Frequent cause of CKD = Diabetic Nephropathy Hypertensive Nephropathy Progressive Nephrosclerosis

The normal annual mean decline in GFR with age from the peak GFR (~120mL/min per 1.73m2) attained during the third decade of life is ~1mL/min per year per 1.73m2, reaching a mean value of 70mL/min per 1.73m2 at 70y/o Measurement of Albuminuria is also helpful for monitoring nephron injury and the response to therapy in many forms of CKD, especially chronic glomerular diseases An Accurate 24-Hour Urine Collection is the Gold Standard for measurement of Albuminuria Microalbuminuria refers to the excretion of amounts of Albumin too small to detect by urinary dipstick

The uremic syndrome and the disease state associated with advanced renal impairment involve more than renal excretory failure. A host of metabolic and endocrine functions normally undertaken by the kidneys are also impaired, and this results in Anemia, Malnutrition, and Abnormal Metabolism of carbohydrates, fats, and proteins. In summary, the pathophysiology of the Uremic Syndrome can be divided into manifestations in three spheres of dysfunction: 1) Those consequent to the accumulation of toxins normally undergoing renal excretion, including products of protein metabolism 2) Those consequent to the loss of other renal functions, such as fluid and electrolyte homeostasis and hormone regulation 3) Progressive systemic inflammation and its vascular and nutritional consequences

II. CLINICAL ABNORMALITIES IN UREMIA

Fluid and Electrolyte Endocrine-Metabolic Neuromuscular Cardiovascular and Pulmonary Dermatologic Gastrointestinal Hematologic and Immunologic

Chronic Renal Failure applies to the process of continuing significant irreversible reduction in nephron number, and typically corresponds to CKD Stages 3-5. Pathophysiology of CKD involves 2 Broad Sets of Mechanisms of Damage: 1) Initiating mechanisms specific to underlying etiology 2) Set of progressive mechanisms, involving hyperfiltration and hypertrophy of the remaining viable nephrons

A. Fluid and Electrolyte, Acid-Base Balance o Sodium and Water Homeostasis o Potassium Homeostasis o Metabolic Acidosis B. Bone Disease and Disorders of Calcium & Phosphate (PO4 Metabolism)
Those Associated with: HIGH Bone Turnover HIGH PTH Levels Those Associated with: LOW Bone Turnover NORMAL PTH Levels Osteitis Fibrosa (classic lesion of secondary hyperparathyroidism)

Osteomalacia Adynamic Bone Disease

C. Cardiovascular Abnormalities (leading cause of Morbidity and Mortality) o Ischemic Heart Disease o Congestive Heart Failure o Hypertension and LVH o Pericarditis (Pericardial Pain with respiratory accentuation, fruction rub)

D. Hematologic Abnormalities o Anemia = Normocytic, Normochromic Type (Cause = Insufficient EPO-Production) o Abnormal Hemostasis Prolonged BT Decreased Activity of Platelet Factor-III Abnormal Platelet Aggregation and Adhesiveness Impaired Prothrombin Consumption E. Neuromuscular Abnormalities o Central, Peripheral and Autonomic Neuropathy starting at STAGE-III CRD o Mild Disturbance in Memory and Concentration and Sleep Disturbances o Indication to Start RRT F. Gastrointestinal and Nutritional Abnormalities o Uremic Fetor: Urineferous Odor of the Breath due to breakdown of UREA to NH 3 in Saliva associated with a Metallic Taste o Gastritis, PUD, Diverticulosis, Pancreatitis G. Endocrine-Metabolic Abnormalities o Glucose Metabolism: Plasma-Insulin is ELEVATED o Low Estrogen Level (Amenorrhea, Inability to carry Pregnancy to Term o In Males: Oligospermia, Germinal Cell Dysplasia, Reduced Testosterone Level H. Dermatologic Abnormalities o Pallor o Ecchymosis and Hematoma (defective Hemostasis) o Pruritus, Excoriations (Calcium Deposition and Secondary Hyperparathyroidism) o Uremic Frost (White Sediments on the Skin) III. EVALUATION OF CKD A. Initial Approach o Symptoms and overt signs of kidney disease are often absent until renal failure supervenes o Particular aspects in the history include: HPN, DM, abnormal urinalysis, problems with pregnancy o PE should focus on BP and target organ damage from HPN, fundoscopy, precordial examination, edema, sensory polyneuropathy, asterixis, pericardial friction rub o The finding of Asterixis or a Pericardial Friction Rub not attributable to other causes usually signifies the presence of the Uremic Syndrome B. Laboratory Studies o Underlying cause / aggravating disease process and degree of renal damage and its consequences o A 24 hour urine collection may be helpful, as protein Excretion > 300mg may be an indication for therapy with ACE Inhibitors or ARBS C. Imaging Studies o Renal Ultrasound: the finding of Bilaterally SMALL Kidneys supports the diagnosis of CKD of long-standing duration, with an Irreversible component of Scarring o Doppler Sonography, Nuclear Medicine Studies, CT or MRI Studies o Voiding Cystogram (for Reflux Nephropathy) D. Renal Biopsy o In a patient with Bilaterally Small kidneys, Renal Biopsy is NOT advised because: 1) It is technically difficult and has a greater likelihood of causing bleeding and other adverse consequences 2) There is usually so much scarring that the underlying disease may not be apparent 3) The window of opportunity to render disease-specific therapy has passed

Other Contraindications to Renal Biopsy: o Uncontrolled Hypertension o Active Urinary Tract Infection o Bleeding Diathesis o Morbid Obesity

**NOTE: Ultrasound-Guided Percutaneous Biopsy is favored

IV. ESTABLISHING THE DIAGNOSIS & ETIOLOGY OF CKD Most Important Initial Step in evaluation of Elevated Serum Creatinine = to distinguish newly diagnosed CKD from Acute or Subacute Renal Failure (because the latter two conditions may respond to therapy specific to the disease) Evidence of Metabolic Bone disease with Hyperphosphatemia, Hypocalcemia, and elevated PTH and bone Alkaline Phosphatase levels suggests chronicity Normochromic, Normocytic Anemia suggests that the process has been ongoing for some time The finding of bilaterally reduced kidney size (<8.5cm in all but the smallest adults) favors CKD V. MANAGEMENT OF CKD A. Slowing the Progression of CKD o Protein Restriction (intake of 0.60 to 0.75g/kg/day) o Reducing Intraglomerular Hyperension and Proteinuria B. Slowing Progression of Diabetic Renal Disease o Control of Blood Glucose (Preprandial Glucose = 90-130mg/dL and HgbA1c < 7%) o Control of Blood Pressure and Proteinuria C. Managing Other Complications of Chronic Kidney Disease (CKD) o Medication Dose Adjustment o Preparation for Renal Replacement Therapy VI. COMPLICATIONS OF HEMODIALYSIS Hypotension = Most Common Acute Complication of Hemodialysis High Output Cardiac Failure Muscle Cramps Anaphylactoid Reactions, etc

5) NEPHRITIC / NEPHROTIC SYNDROME

I. NEPHRITIC SYNDROME Hematuria RBC Casts Proteinuria Hypertension Edema Deteriorating Renal Function II. NEPHROTIC SYNDROME Proteinuria > 3.5 g/m+/24h Hypoalbuminemia Hyperlipidemia Hypercoaguability Edema
Nephrotic Syndrome classically presents with Heavy Proteinuria, Minimal Hematuria, Hypoalbuminemia, Hypercholesterolemia, Edema, and Hypertension

Most Common Cause in Adults = Membranous Glomerulonephritis Most Common in Chilren = Minimal Change Disease

Diabetic Nephropathy o Single Most Common Cause of Chronic Renal Failure in the US o Majority of patients with Diabetic Nephropathy have Type 2 DM

III. APPROACH TO PATIENTS WITH PROTEINURIA > 3 g per day = NEPHROTIC SYNDROME (Non-Selective Proteinuria) In Early DM Patients = (+) Microalbuminuria

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FLUID & ELECTROLYTE / METABOLIC DERANGEMENTS CAUSES OF HYPONATREMIA vs HYPERNATREMIA

HYPONATREMIA
I. Pseudohyponatremia A. Normal Plasma Osmolality Hyperlipidemia Hyperproteinemia Post-TURP B. Increased Plasma Osmolality Hyperglycemia Mannitol II. Hypoosmolal Hyponatremia A. Primary Na+ Loss (20 H2O Gain) Integumentary Loss: sweating, burns GI Loss: vomiting, tube drainage, fistula, obstruction, diarrhea Renal Loss: diuretics, osmotic diuresis, hypoaldosteronism, salt-wasting nephropathy, postobstructive diuresis, nonoliguric acute tubular necrosis B. Primary H2O Gain (20 Na+ Loss) Primary Polydipsia Decreased Solute Intake (eg. Beer Protomania) AVP release due to pain, nausea, drugs Syndrome of Inappropriate AVP Secretion Glucocortidoid Deficiency Hypothyroidism Chronic Renal Insufficiency C. Primary Na+ Gain (Exceeded by 20 Water Gain) Heart Failure Hepatic Cirrhosis Nephrotic Syndrome

HYPERNATREMIA
I. Nonrenal Water Loss Evaporation from the skin and respiratory tract (insensible losses) GI Losses: diarrhea (most common) Increased Insensible Loss due to fever, exercise, heat exposure, severe burns, mechanically ventilated patients Na+ concentration of sweat decreases with profuse perspiration, thereby increasing solute-free water loss II. Renal Water Loss (Most Common Cause of Hypernatremia) Drug Induced Diuresis Osmotic Diuresis (Hyperglycemia, Glucosuria, IV Mannitol) Diabetes Insipidus III. Primary Na+ Gain

CAUSES OF HYPOKALEMIA VS. HYPERKALEMIA

HYPOKALEMIA I. Decreased Intake A. Starvation B. Clay Ingestion II. Redistribution into Cells A. Acid-Base: Metabolic Alkalosis B. Hormonal Insulin B2-Adrenergic Agonists (Endogenous or Exogenous) A-Adrenergic Antagonists C. Anabolic State Vitamin B12 or Folic Acid (RBC production) Granulocyte-Macrophage Colony Stimulating Factor (WBC production) Total Parenteral Nutrition D. Other Pseudohypokalemia Hypothermia Hypokalemic Periodic Paralysis Barium Toxicity II. Increased Loss A. Non-Renal GI Loss (Diarrhea) Integumentary Loss (Sweat) B. Renal
Increased Distal Flow: Diuretics, Osmotic Diuresis, Salt Wasting Nephropathies Increased Secretion of K+ - Mineralocorticoid Excess: 10 Hyperaldosteronism, 20 Hyperaldosteronism (Malignant HPN, Renin-Secreting Tumors, Renal Artery Stenosis, Hypovolemia), apparent Mineralocorticoid Excess (Licorice, chewing tobacco, carbenoxolone), Congenital Adrenal Hyperplasia, Cushing Syndrome, Bartters Syndrome) - Distal Delivery of Non-Reabsorbed Anions: Vomiting, Nasogastric Suction, Proximal (Type 2) Renal Tubular Acidosis, DKA, Glue-Sniffing (Toluene Abuse), Penicillin Derivatives - Other: Amphotericin-B, Liddles Syndrome, Hypomagnesemia

HYPERKALEMIA I. Renal Failure II. Decreased Distal Flow (ie. Decreased Effective Circularing Arterial Volume) III. Decreased K+ Secretion A. Impaired Na+ Reabsorption Primary Hypoaldosteronism: Adrenal insufficiency, Adrenal enzyme deficiency (21-Hydroxylase, 3BHydroxysteroid Dehydrogenase, Corticosterone Methyl Oxidase) Secondary Hypoaldosteronism: Hyporeninemia, Drugs (ACE inhibitors, NSAIDs, Heparin) Resistance to Aldosterone: Pseudohypoaldosteronism, Tubulo-Interstitial Disease, Drugs (K+ Sparing Diuretics, Trimethroprim, Pentamidine) B. Enhanced Cl- Reabsorption (Chloride Shunt) Gordons Syndrome Cyclosporine

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1) SODIUM & WATER

Water is the Most Abundant Constituent of the body, comprising approximately 50% in Women and 60% in Men Total Body Water = 55-75% Intracellular Fluid + 25-45% Extracellular Fluid Osmolality: Solute or Particle Concentration of a fluid

I. EXTRACELLULAR FLUID Extracellular Fluid = Intravascular (Plasma Water) + Extravascular (Interstitial) Spaces Major ECF Particles = Na+ and Anions (Cl- and HCO3) Major ICF Particles = K+ and Organic Phosphate Esters (ATP, Creatine Phosphate, and Phospholipids)
Solutes that are restricted to the ECF or the ICF determine the Effective Osmolality (or Tonicity) of that compartment. Since Na+ is largely restricted to the ECF, Total Body Na+ Content is a reflection of ECF Volume. Likewise, K+ and its attendant anions are predominantly limited to the ICF and are necessary for Normal Cell Function

II. WATER BALANCE Normal Plasma Osmolality is 275 290 mosmol/kg Disorders of water homeostasis result in Hypo- or Hypernatremia Normally, about 600 mosmols must be Excreted per day, and since the maximal urine osmolality is 1200 mosmol/kg, a Minimum Urine Output of 500 mL/d is required for neutral solute balance **NOTE: Arginine Vasopressin (AVP, ADH) o Synthesized in the Supraoptic and Paraventricular Nuclei of Hypothalamus; Secreted by Posterior Pituitary o Net Effect: Passive Water Reabsorption along an Osmotic Gradient o Major Stimulus for AVP Secretion: HYPERTONICITY III. SODIUM BALANCE Sodium is actively pumped out of cells by the Na-K-ATPase Pump Result = 85-95% of Na+ is EXTRACELLULAR

2) HYPOVOLEMIA
True Volume Depletion refers to a state of combined Salt and Water Loss exceeding intake, leading to ECF Volume Contraction (loss of Na+ may be Renal or Extrarenal)

Causes of HYPOVOLEMIA 1. ECF Volume Contracted: Extrarenal Na+ Loss: GI (vomiting, diarrhea, etc), Skin/Respiratory (insensible losses, sweat, burns), Hemorrhage Renal Na+ and Water Loss: Diuretics, Osmotic Diuresis, Hypoaldosteronism, Salt-Wasting Nephropathies Renal Water Loss: Diabetes Insipidus (Central or Nephrogenic) 2. ECF Volume NORMAL or Expanded: Decreased Cardiac Output: Muyocardial, Valvular or Pericardial Disease Redistribution: Hypoalbuminemia (Hepatic Cirrhosis, Nephrotic Syndrome), Capillary Leak (Acute Pancreatitis, Ischemic Bowel, Rhabdomyolysis) Increased Venous Capacitance: Sepsis

A. Pathophysiology o ECF Volume Contraction is manifest by a decreased plasma volume and HYPOTENSION o Hypotension: due to Decreased Venous Return (Preload) and diminished Cardiac Output B. Clinical Features o Most Symptoms: non specific and secondary to electrolyte imbalances and tissue hypoperfusion o More Severe Volume Contraction: End Organ Ischemia (Oliguria, Abdominal and Chest Pain, Confusion)

12

3) HYPONATREMIA / HYPERNATREMIA
I. HYPONATREMIA: Plasma Na+ < 135 mmol/L Clinical Features: related to Osmotic Water Shift, leading to Increased ICF Volume, specifically Brain Cell Swelling or Cerebral Edema (symptoms are primarily neurologic) Stupor, Seizures & Coma do NOT usually occur unless the Plasma Na + concentration falls < 120mmol/L or decreases rapidly II. HYPERNATREMIA: Plasma Na+ > 145 mmol/L Hypernatremia is a state of HYPEROSMOLALITY Majority of cases result from the LOSS of WATER Clinical Features: As a consequence of Hypertonicity, water shifts OUT of cells, leading to a Contracted ICF Volume a decrease in Brain Cell Volume is associated with an Increased Risk of Subarachnoid or Intracerebral Hemorrhage

4) HYPOKALEMIA / HYPERKALEMIA
I. HYPOKALEMIA: Plasma K+ Concentration < 3.5 mmol/L May result from: Decreased Net Intake, Shift into Cells, Increased Net Loss Clinical Features: Symptoms seldom occur unless the Plasma K+ Concentration is < 3 mmol/L A. ECG Changes: o Due to Delayed Ventricular Repolarization and do NOT correlate well with Plasma K + Concentration o Severe K+ Depletion: Increased Risk of Ventricular Arrhythmias o Hypokalemia also predispose to Digitalis Toxicity 1. Early Changes:
Flattening or Inversion of T-Wave Prominent U Wave ST-Segment Depression Prolonged QU Interval Prolonged PR Interval Decreased Voltage Widening of QRS Complex

2. Severe K+ Depletion

B. Management o Correct K+ Deficit and Minimize ongoing losses II. HYPERKALEMIA: Plasma K+ Concentration > 5.0 mmol/L Occurs as a result of either K+ Release from Cells or Decreased Renal Loss Most Serious Effect: Cardiac Toxicity Potentially Fatal Hyperkalemia RARELY occurs unless the Plasma K + is > 7.5 mmol/L and is usually associated with:
o o o Profound Weakness Absent P-Waves QRS Widening Ventricular Arrhythmias

A. ECG Changes o Earliest Finding: Increased T-Wave Amplitude (Peaked T-Waves) o More Severe Degrees of Hyperkalemia:

Prolonged PR Interval & QRS duration AV Conduction Delay Loss of P-Waves

**NOTE: Progressive Widening of QRS Complex & merging with the T-Wave produces a Sine Wave Pattern Terminal Event is usually Ventricular Fibrillation or Aystole B. Treatment o Calcium Gluconate: decreases membrane excitability o Insulin: causes K+ to shift into cells o IV NaHCO3: can also shift K+ into cells o B2-Adrenergic Agonists: promote cellular uptake of K o Loop and Thiazide Diuretics o Sodium Polystyrene Sulfonate (Cation-Exchange Resin) o Hemodialysis

13

5) HYPOCALCEMIA / HYPERCALCEMIA

Calcium Ion plays a critical role in normal cellular function and signaling, regulating diverse physiologic processes such as neuromuscular signaling, cardiac contractility, hormone secretion, and blood coagulation Extracellular Ca2+ Concentrations are maintained w/in exquisitely narrow range thru a series of feedback mechanisms that involve:
o o Parathyroid Hormone (PTH) Active Vitamin-D Metabolite 1,25-Dihydroxyvitmin-D (1,25(OH)2D) A decrease in ECF Ca2+ triggers an Increase in Parathyroid Hormone Secretion (1) via Activation of the Calcium Sensor Receptor on Parathyroid Cells. PTH, in turn, results in Increased Tubular Reabsorption of Ca2+ by the Kidney (2) and Resorption of Calcium from Bone (2) and also stimulates Renal 1,25(OH)2D Production (3). 1,25(OH)2D, in turn, acts principally on the Intestine to Increase Calcium Absorption (4). Collectively, these homeostatic mechanisms serve to restore Serum Ca2+ Levels to Normal.

QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.

I. HYPOCALCEMIA May be asymptomatic if the decreases in Serum Ca2+ are relatively Mild and Chronic, or they may present with LifeThreatening Complications Moderate to Severe Hypocalcemia: Paresthesias, usually of the fingers, toes, and circumoral regions, and is caused by Increased Neuromuscular Irritability Chvosteks Sign: Twitching of the Circumoral Muscles in response to gentle tapping of the facial nerve just anterior to the ear may be elicited Trousseaus Sign: Carpal Spasm may be induced by inflation of a BP cuff to 20mmHg above patients systolic BP for 3mins Severe Hypocalcemia can induce Seizures, Carpopedal Spasm, Bronchospasm, Laryngospasm, and Prolongation of QT-Interval II. HYPERCALCEMIA A. Clinical Manifesations
Mild Hypercalcemia (up to 11 11.5 mg/dL Usually Asymptomatic and recognized only on routine Calcium Measurements Some may complain of vague Neuropsychiatric Symptoms Trouble concentrating, personality changes, or depression Peptic Ulcer Disease or Nephrolithiasis, Increased Fracture Risk Lethargy, Stupor, Coma GI Symptoms: nausea, anorexia, constipation, pancreatitis Decreased Renal Concentrating Ability Polyuria and Polydipsia

More Severe Hypercalcemia (>12-13 mg/dL)

B. Hypercalcemia can present with ECG Changes:

o o

o C. Management (from Endorsements)

1. IV-Hydration Patients presenting with Hypercalcemia are volume-depleted already by ~2L If we hydrate, we improve perfusion to kidneys, we Increase Calcium Excretion 2. Bisphosphanates Inhibits activity of Osteoclasts, thereby inhibiting RESORPTION 3. Diuretics Give Loop Diuretics This will enhance excretion of Ca2+ -- when you give Diuretics, make sure to hydrate the patient 4. Dialysis (In Severe Hypercalcemia, refractory to the usual therapy)

Bradycardia AV Block Short QT Interval

C. Complications of Hypercalcemia
o

Arrhythmias Deposition of Calcium in Vessels, Nephrocalcinosis, etc

14

6) HYPOGLYCEMIA
Most commonly caused by drugs used to treat DM or by exposure to other drugs, including alcohol The lower limit of the Fasting Plasma Glucose in NORMALLY 70mg/dL (3.9mmol/L) Glucose Levels < 55mg/dL (3.0mmol/L) with symptoms that are relieved promptly after the glucose level is raised document Hypoglycemia

I. WHIPPLES TRIAD 1) Symptoms consistent with Hypoglycemia 2) Low Plasma Glucose concentration measured with a precise method (Not a Glucose Monitor) 3) Relief of those symptoms after the Plasma Glucose Level is raised II. ENDORSEMENT NOTES: If there is Hypoglycemia, catecholamines will ELEVATE (ex. jittery, tachycardia, palpitations, sweating, tremors) Late Phase: Patient is already Obtunded III. CLINICAL MANIFESTATIONS Neuroglycopenic Symptoms of hypoglycemia are the direct result of CNS Glucose Deprivation Symptoms: Behavioral changes, confusion, fatigue, seizure, loss of consciousness, and if severe death Neurogenic (or Autonomic) Symptoms of Hypoglycemia are the result of the perception of physiologic changes caused by the CNS-Mediated Sympathoadrenal Discharge triggered by Hypoglycemia IV. TREATMENT OF HYPOGLYCEMIA Readily absorbable Carbohydrates (eg. Glucose and Sugar-Containing Beverages) IV Dextrose Initial Bolus of 20-50mL 50% Dextrose should be given immediately, followed by Infusion of D5W (or D10W) to maintain Blood Glucose above 100mg/dL Glucagon 1mg IM (or SC)

NOTES ON RENAL ABNORMALITIES

I. REMEMBER: 2-3-4-5 > 2x a night is Nocturia > 3 L/day is Polyuria < 400 mL is Oliguria < 50 mL is Anuria
Furosemide = Binds to ALBUMIN Therefore, do NOT give Furosemide in patients with Hypoalbuminemia Instead, we can give Bumetamide In Harrisons: Oliguria refers to a 24 hours urine output of < 500mL, and Anuria is the complete absence of urine formation (< 50mL)

II. IN CKD, WE GIVE BLOCKING THERAPY 1) CaCO3 **NOTE: If Calcium x Phosphate x 12 is < 70 we can give CaCO3 If > 70, we DONT given CaCO3, because we run the risk of Metastatic Calcification 2) NaHCO3 3) FeSO4 III. ACE INHIBITORS AND CKD For Diabetic Patients and those with Chronic Kidney Disease = choice of HPN is ACE Inhibitors or Angiotensin-II Antagonists to delay Diabetic Nephropathy For End-Stage Renal Disease Patients: CAUTION on ACE-Inhibitors use Calcium-Antagonists, Diureticsm and Centrally Acting Agents In giving ACE Inhibitors, watch out for HYPERKALEMIA (especially in End Stage Renal Disease Patients)
Potassium Homeostasis in CKD In CKD, the decline in GFR is NOT necessarily accompanied by a parallel decline in urinary K + Excretion, which is predominantly mediated by aldosterone-dependent secretory events in the distal nephron segments. Some medications can inhibit potassium entry into cells and renal K+ excretion. The most important medications in this respect in clued ACE-Inhibitors, ARBs, Spironolactone and other K+-sparing diuretics such as amiloride, eplerone, triamterene.

15

IV. CRITERIA FOR INITIATING PATIENTS ON MAINTENANCE DIALYSIS Presence of Uremic Symptoms Presence of Hyperkalemia unresponsive to Conservative Measures Persistent Extracellular Volume Expansion despite Diuretic Therapy Acidosis Refractory to Medical Therapy Bleeding Diathesis Creatinine Clearance or Estimated GFR below 10 mL/min per 1.73m2 Clinical Abnormalities in UREMIA (page 1763 for complete list)
o o o o o o o Fluid and Electrolyte Disturbance Endocrine Metabolic Disturbances (Hyperuricemia, 2 0 Hyperparathyroidism, Osteomalacia) Neuromuscular Disturbances (fatigue, headache, sleep disorders, lethargy, etc) Cardiovascular & Pulmonary Disturbances (Pericarditis, CHF, Pulmonary Edema, etc) Dermatologic Disturbances (pallor, pruritus, ecchymoses, hyperpigmentation, uremic frost) Gastrointestinal Disturbances (anorexia, nausea, vomiting, uremic fetor, GI bleeding) Hematologic and Immunologic Disturbances (anemia, lymphocytopenia) VI. SUGAR (IN URINALYSIS) Trace = 5mmol/L +1 = 15 +2 = 30 +3 = 60 +4 = 120
Polyuria > 3L/d. A 24 hour urine collection is needed for this evaluation. Results from either: 1) Excretion of nonabsorbable solutes (eg. Glucose); or 2) Excretion of water (usually from a defect in ADH production or renal responsiveness)

V. ALBUMIN (IN URINALYSIS) Trace = 0.05 0.2 g/L +1 = 0.3 g/L +2 = 1.0 g/L +3 = 3.0 g/L +4 = > 20 g/L

16

qwertyuiopasdfghjklzxcvbnmqwertyui opasdfghjklzxcvbnmqwertyuiopasdfgh jklzxcvbnmqwertyuiopasdfghjklzxcvb nmqwertyuiopasdfghjklzxcvbnmqwer NEUROLOGY tyuiopasdfghjklzxcvbnmqwertyuiopas dfghjklzxcvbnmqwertyuiopasdfghjklzx cvbnmqwertyuiopasdfghjklzxcvbnmq wertyuiopasdfghjklzxcvbnmqwertyuio pasdfghjklzxcvbnmqwertyuiopasdfghj klzxcvbnmqwertyuiopasdfghjklzxcvbn mqwertyuiopasdfghjklzxcvbnmqwerty uiopasdfghjklzxcvbnmqwertyuiopasdf ghjklzxcvbnmqwertyuiopasdfghjklzxc vbnmqwertyuiopasdfghjklzxcvbnmrty uiopasdfghjklzxcvbnmqwertyuiopasdf ghjklzxcvbnmqwertyuiopasdfghjklzxc vbnmqwertyuiopasdfghjklzxcvbnmqw ertyuiopasdfghjklzxcvbnmqwertyuiop
Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

NEUROLOGIC SYMPTOMS

1) NERVOUS SYSTEM DYSFUNCTION

I. SYNCOPE Transient loss of consciousness & postural tone due to reduced Cerebral Blood Flow (associated with spontaneous recovery) Causes of Syncope: o Disorders of Vascular Tone or Blood Volume o Cardiovascular Disorders (Obstructive Lesions, Cardiac Arrhythmias) o Cerebrovascular Disease II. CONFUSION AND DELIRIUM Confusion: Mental and behavioral state of reduced comprehension, coherence, and capacity to reason Delirium: Acute confusional state A. Common Etiologies of Delirium (page 160):
o o o o o o o o o Toxins Metabolic Conditions Infections Endocrinologic Conditions Cerebrovascular Disorders Autoimmune Disorders Seizure-Related Disorders Neoplastic Disorders Hospitalization Terminal End of Life Delirium

B. Step-Wise Evaluation of a Patient with Delirium:

1. Initial Evaluation History, PE CBC, Electrolytes (including Ca2+, Mg2+, P) Liver Function Tests including Albumin Renal Function Tests 2. First Tier Further Evaluation Guided by Initial Evaluation Systemic Infection Screen: U/A and Culture, CXR, Blood Culture ECG, ABG, Toxcology Screen Brain Imaging If suspecting a CNS Infection: Lumbar Puncture following Brain Imaging If suspecting Seizure-Related Etiology: EEG 3. Second Tier Further Evaluation Vitamin levels: B12, Folate, Thiamine Endocrinologic: TSH, FT4, Cortisol Serum Ammonia Sedimentation Rate ANA, Complement Levels, p-ANCA, c-ANCA Infectious Serologies: RPR, Fungal & Viral, HIV Lumbar Puncture Brain MRI

III. UPPER MOTOR NUERON LESION VS LOWER MOTOR NEURON LESIONS SIGN UPPER MOTOR NEURON LOWER MOTOR NEURON Atrophy None Severe Fasciculations None Common Tone Spastic Decreased Distribution of Weakness Pyramidal / Regional Distal / Segmental Tendon Reflexes Hyperactive Hypoactive / Absent Babinskis Sign Present Absent

MYOPATHIC Mild None Normal / Decreased Proximal Normal / Hypoactive Absent

2) SEIZURES
I. SYNCOPE VS SEIZURES The diagnostic dilemma encountered most often is the distinction between a Generalized Seizure and Syncope Features that distinguish Generalized Tonic Clonic Seizure from Syncope include: FEATURES SEIZURE SYNCOPE Immediate Precipitating Factors Usually none Emotional stress, Valsalva, Orthostatic Hypotension, Cardiac Etiologies Premonitory Symptoms None or Aura (eg. Odd Odor) Tiredness, nausea, diaphoresis, tunneling of vision Posture at Onset Variable Usually erect Transition to Unconsciousness Often Immediate Gradual over seconds Duration of Unconsciousness Minutes Seconds Duration of Tonic or Clonic Movements 30 60 s Never more than 15 s Facial Appearance during event Cyanosis, Frothing of Mouth Pallor Disorientation & Sleepiness after event Many minutes to hours < 5 minutes Aching of Muscles after event Often Sometimes Biting of Tongue Sometimes Rarely Incontinence Sometimes Sometimes Headache Sometimes Rarely II. CLASSIFICATION OF SEIZURES A. Partial Seizures o Seizures occur within Discrete Regions of the brain o Divided into: Simple Partial Seizures + Complex Partial Seizures Simple Partial Seizures If Consciousness is FULLY PRESERVED during the seizure, the clinical manifestations are considered relatively SIMPLE and the seizure is termed Simple Partial Seizures Complex Partial Seizures If Consciousness is IMPAIRED, the symptomatology is more complex and the seizure is termed Complex Partial Seizure

B. Generalized Seizures o Arise from BOTH Cerebral Hemispheres simultaneously o Defined as bilateral clinical and electrographic events without any detectable focal onset Absence Seizures Sudden, brief, lapses of consciousness without loss of postural control. (Petit Mal) Lasts for only a few seconds, consciousness returns as suddenly as it was lost, and there is NO postictal confusion Atypical Absence Have features that deviate both clinically and electrophysiologicaly from typical absence seizures (ex. Seizures Lapse of consciousness is usually of longer duration & less abrupt in onset and cessation, and the seizure is accompanied by more obvious motor signs that may include focal or lateralizing features) Generalized Tonic Clonic Seizures (Grand Mal) Primary generalized, tonic-clonic seizures are the main seizure type in ~10% of all persons with Epilepsy. Most common seizure type resulting from metabolic derangements. Begins abruptly without warning, although some with vague premonitory symptoms in the hours leading up to the seizure. Initial Phase (Tonic Phase): Tonic contraction of muscles throughout the body. Respiration impaired, secretions pool in oropharynx, cyanosis develops. Marked enhancement of sympathetics leads to increased HR, BP and papillary size. Clonic Phase: After 10-20 sec, Tonic phase evolves into the Clonic Phase. Produced by superimposition of periods of muscle relaxation on the tonic muscle contraction. The periods of relaxation progressively increase until the end of the Ictal Phase, which lasts no more than 1 minute. Post Ictal Phase: unresposinveness, muscular flaccidity, excessive salivation, bladder / bowel incontinence. Patients gradually regain consciousness over minutes to hours (there is a period of postictal confusion) Atonic Seizures Myoclonic Seizures Sudden loss of postural muscle tone lasting 1 to 2 seconds. Consciousness is briefly impaired, but there is usually no post ictal confusion Sudden and brief muscle contraction that may involve one part of the body or the entire body.

qwertyuiopasdfghjklzxcvbnmqwertyui opasdfghjklzxcvbnmqwertyuiopasdfgh jklzxcvbnmqwertyuiopasdfghjklzxcvb nmqwertyuiopasdfghjklzxcvbnmqwer PULMONOLOGY tyuiopasdfghjklzxcvbnmqwertyuiopas dfghjklzxcvbnmqwertyuiopasdfghjklzx cvbnmqwertyuiopasdfghjklzxcvbnmq wertyuiopasdfghjklzxcvbnmqwertyuio pasdfghjklzxcvbnmqwertyuiopasdfghj klzxcvbnmqwertyuiopasdfghjklzxcvbn mqwertyuiopasdfghjklzxcvbnmqwerty uiopasdfghjklzxcvbnmqwertyuiopasdf ghjklzxcvbnmqwertyuiopasdfghjklzxc vbnmqwertyuiopasdfghjklzxcvbnmrty uiopasdfghjklzxcvbnmqwertyuiopasdf ghjklzxcvbnmqwertyuiopasdfghjklzxc vbnmqwertyuiopasdfghjklzxcvbnmqw ertyuiopasdfghjklzxcvbnmqwertyuiop
Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

PULMONARY DISEASES

1) PULMONARY TUBERCULOSIS
I. CLASSIFICATION OF TB (ATS) CLASS DESCRIPTION ATS Class 0 No Exposure (-) PPD ATS Class 1 (+) Exposure (-) PPD TREATMENT BCG in high prevalence area If with recent exposure: Give Primary Prophylaxis: HR for 4 months or HE for 6 months Repeat PPD in 2 Months -if (+): Treat as Class 2 -if (-): Stop Primary Prophylaxis 70% of adult Filipinos are (+) for PPD, and are therefore naturally infected If with recent PPD Conversion, give Primary Prophylaxis HR for 4 months or HE for 6 months If NOT a recent PPD converter, but currently exposed to a TB Case, give primarily Prophylaxis as above If NOT a recent PPD converter and NO Family member has Active TB, may NOT give Primary Prophylaxis See Table Below

ATS Class 2: TB Infection

(+) Exposure (+) PPD (-) Target Organ TB Lesion

ATS Class 3: PTB Active

See Table Below

ATS Class 4: Previous PTB Disease

ATS Class 5: PTB Suspect

ATC Class 3 patients are further subdivided into WHO Category I, II, III Eg. CXR with Minimal Infiltrates, but NO Symptoms of Active Disease or Previously treated PTB Check previous CXR Reclassify patient into Class III or Class IV in 2-3 Months using Sputum Bacteriology or Serial X-Ray Changes

II. TREATMENT REGIMEN FOR ATS CLASS 3 PATIENTS (TB ACTIVE) WHO TB PATIENTS ALTERNATIVE TB TREATMENT REGIMEN CATEGORY Initial Phase Continuation Phase I* New Smear-Positive PTB New Smear-Negative PTB w/ extended parenchymal involvement New cases of Severe Forms of Extra-Pulmonary TB II Sputum Smear-Positive: Relapse Treatment Failure Treatment after Interruption III ** New Smear-Negative PTB (other than in Category I) New Less Severe Forms of Extra-Pulmonary TB 2 HRZE 4 HR 2 HRZES and 1 HRZE 5 HRE 2 HRZE 4 HR

* Give this regimen if with High Bacterial Load, Cavitary Lesions, AFB + 4 Smears, or High Community Resistance (eg NCR, Davao, Zamboanga, Cavite, Pampanga) If with Cavitary Disease, give Streptomycin IM Alternate Days (60 Doses) instead of Ethambutol ** May give this cheaper regimen for Newly Diagnosed TB and those cases found in Low Community Resistance

III. NOTES FROM BLUE BOOK A. Indications of Active Disease o (+) AFB Sputum Smear (at least 2+) or (+) TB Culture o (+) Symptoms: Constitutional symptoms are more reliable than local symptoms o Increase in CXR Infiltrates (usually apical) B. Indications of Inactive Disease o Six Months interval with NO change in CXR infiltrates and NO constitutional symptoms o Preferable with History of Completed TB Therapy C. Indications of Favorable Disease Response o Completion of prescribed treatment o Conversion of Sputum Smear and Culture to Negative o Resolution of Constitutional Symptoms o Resolution or Improvement of Local Symptoms D. Multiple Drug Resistant TB (MDRTB) and Extremely Drug Resistant Tuberculosis (XDRTB) 1. Multiple Drug Resistant Tuberculosis (MDRTB) Infection with strain of M. tuberculosis which shows in-vitro resistance to at least Isoniazid ad Rifampicin Suspect in TB patients who are still Sputum Smear or Culture Positive despite 3 months of adequate Tx 2. Extremely Drug Resistant Tuberculosis (XDRTB) MDRTB Plus Resistance to Fluoroquinolones and an IV Aminoglycoside NOTE: NO Effective Treatment regimen avilable IV. DOSAGE OF DRUGS
DRUG H: Isoniazid (INH) R: Rifampicin (R) Z: Pyrazinamide (Z) E: Ethambutol (E) S: Streptomycin (S) CHILDREN 5 mg/kg/day 10-20 mg/kg/day 20-30 mg/kg/day 15-20 mg/kg/day 10-18 mg/kg/day ADULTS 300-400mg PO 450-600mg PO 1500mg/day PO 800-1000mg/day PO 1gram IM

V. ALGORITHM FOR DIAGNOSIS OF PTB: CPM GUIDELINES (2008)

TB SYMPTOMATIC (COUGH for 2 weeks of more) Three (3) Sputum Collection 2 or 3 Smear (+) Classify as SMEAR POSITIVE TB Only ONE (1) Smear Positive Collect another 3 Sputum Specimens Immediately At least ONE Smear Positive? Abnormal Findings on CXR Yes No Request for CXR Consistent with Active TB? Yes No Observation / Further Exam, If necessary Yes Classify as SMEAR NEGATIVE TB No Not Consistent with Active TB Consistent with Active TB Yes TB Diagnostic Committee No No Abnormal Findings on CXR All THREE (3) Smear Negative Refer to Physician (Symptomatic Tx for 2-3 wks) If Symptoms Persist, request for CXR

Collection of Sputum Specimens o First Specimen (Spot Specimen): collected at time of consultation, or as soon as the TB symptomatic is identified o Second Specimen: very first sputum produced early in the morning immediately after waking up. It is collected by the patient according to instructions given by the DOTS facility staff o Third Specimen (Second Spot Specimen): collected when TB symptomatic comes back to the DOTS facility to submit the second specimen
**NOTE: Pulmonary Nodule VS Mass: o Pulmonary Nodule is < 3 cm on CXR

VI. NATIONAL TB CONTROL PROGRAM MANUAL OF PROCEDURES, 2005 A. Definition of Terms

TB Symptomatic Any person with cough for two or more weeks with or without the following symptoms: Chest and/or back pains not referable to any other musculo-skeletal disorders Hemoptysis or recurrent blood streaked sputum Significant weight loss Other symptoms: Sweating, fatigue, body malaise, shortness of breath A health workers purposive effort to find TB cases who do not consult with personnel in a DOTS Facility Finding TB cases among TB symptomatics who present themselves in a DOTS facility

Active Case Finding Passive Case Finding

B. Formulation of Anti-TB Drugs o Fixed Dose Combination (FDCs) two or more first line drugs are combined in one tablet o Single Drug Formulation (SDF) each drug is prepared individually C. Classification of TB Cases LOCATION OF SPUTUM SMEAR LESION EXAMINATION Pulmonary TB (PTB) Smear Positive DEFINITION OF TERMS 1. A patient with at least 2 Sputum Specimens Positive for AFB, with or without Radiographic Abnormalities consistent with Active TB; or 2. A patient with 1 Sputum Specimen Positive for AFB and with Radiographic Abnormalities consistent with Active TB as determined by a Clinician; or 3. A Patient with one Sputum Specimen positive for AFB with Sodium Culture Positive for M. tuberculosis A Patient with at least 3 Sputum Specimens Negative for AFB with Radiographic Abnormalities consistent with Active TB, AND There has been no Response to a Course of Antibiotics and/or Symptomatic Medications, AND There is a Decision by a Medical Officer to Treat the Patient with Anti-TB Drugs Extrapulmonary TB 1. A patient with at least one Mycobacterial Smear / Culture Positive from an Extra-Pulmonary Site (organs other than the Lungs = Pleura, Lymph Nodes, Genitourinary Tract, Skin, Joints & Bones, Meninges, Intestines, Peritoneum and Pericardium, among others); or A patient with Histological and / or Clinical Evidence consistent with Active TB and there is a Decision by a Medical Officer to Treat Patient with Anti-TB Drugs

Smear Negative

2.

D. Types of TB Cases o TB Cases shall be Categorized based on the History of Anti-TB Treatment o A thorough understanding on the Types of TB Cases is necessary in determining the correct Treatment Regimen TYPE New Relapse Failure Return after Default (RAD) Transfer-In Other DEFINITION OF TERMS A patient who has NEVER had Treatment for TB or who has taken Anti-TB Drugs for LESS than One Month A patient previously treated for Tuberculosis, who has been declared Cured or Treatment Completed, and is Diagnosed with Bacteriologically Positive (Smear or Culture) Tuberculosis A patient who, while on Treatment, is Sputum Smear Positive at 5 Months or Later during the Course of Tx A patient who returns to Treatment with Positive Bacteriology (Smear or Culture), following Interruption of Treatment for Two Months or More A Patient who has been Transferred from another Facility with proper Referral Slip to continue Treatment All Cases who do NOT fit into any of the above definitions This Group includes: 1) Patient who is Starting Treatment again after Interrupting Treatment for more than 2 Months and has remained or became Smear-Negative 2) A Patient, who was initially Registered as New Smear-Negative Case, turned out to be Smear Positive during Treatment, (The Treatment Outcome of this case is Treatment Failure. ReRegister as Other for the next treatment 3) Chronic Case: a Patient who is Sputum Positive at the End of a Re-Treatment Regimen

VII. SUMMARY OF TREATMENT MODIFICATION BASED ON T HE SPUTUM FOLLOW-UP RESULTS A. Category-I First 2 Months: HRZE If (-) 4 Months of HR o o If (+) Another 1 Month of HRZE

If after 2 Months of HRZE you have Sputum Smear Negative, go directly to 4 Months of HR BUT, if you still have Sputum Smear Positive, take HRZE for another month, then go to HR for 4 Months. This makes the Intensive Phase 3 Months and a Total of 7 Months of Treatment

B. Category-II First 2 Months: HRZES 1 Month of HRZE If (-) 5 Months of HRE C. Category-III First 2 Months: HRZ 4 Months of HR Sputum Smear is done at the end of 2nd Month WHAT TO DO? If (+) Another 1 Month of HRZE

VIII. GUIDE IN MANAGING SCC DRUGS SIDE EFFECTS SIDE EFFECTS DRUGS RESPONSIBLE

Minor Side Effects Patient should be Encouraged to CONTINUE taking Medications Gastro-Intestinal Intolerance Rifampicin Give medication at bedtime Mild Skin Reactions Any kind of Drugs Give Anti-Histamines Orange / Red Colored Urine Rifampicin Reassure the patient Pain at Injection Site Streptomycin Apply Warm Compress Burning Sensation in Feet due to Isoniazid Give Pyridoxine (Vitamin B6) Peripheral Neuropathy 100-200mg daily for Treatment; 10mg daily for prevention Arthralgia due to Hyperuricemia Pyrazinamide Give Aspirin or NSAID If symptoms persist, consider Gout & give Allopurinol Flu-Like Symptoms (Fever, Muscle Pain) Rifampicin Give Anti-Pyretics Major Side Effects Discontinue Taking the Medicines and refer to MHO / CHO immediately Severe Skin Rash (Hypersensitivity) Any Drug (especially Streptomycin) Discontinue Anti-TB Drugs and refer to MHO / CHO Jaundice due to Hepatitis Any Drug (especially Isoniazid, Discontinue Anti-TB Drugs and refer to MHO / CHO. If Rifampicin. Pyrazinamide) symptoms subside, resume treatment & monitor clinically Impairment of Visual Acuity and Color Vision due to Optic Neuritis Hearing Impairment, Ringing of Ear and Dizziness due to Damage of CN-VIII Oliguria or Albuminuria due to Renal Disorder Psychosis and Convulsion Thrombocytopenia, Anemia, Shock Ethambutol Streptomycin Streptomycin Rifampicin Isoniazid Rifampicin Discontinue Ethambutol and refer to Ophthalmologist Discontinue Streptomycin and refer to MHO / CHO Discontinue Anti-TB Drugs and refer to MHO / CHO Discontinue Isoniazid and refer to MHO / CHO Discontinue Anti-TB Drugs and refer to MHO / CHO

IX. OUTCOME OF TREATMENT Cured A Sputum Smear Positive Patient has COMPLETED Treatment and is Sputum Smear NEGATIVE in the Last Month of Treatment and on at least ONE Previous occasion Treatment Completed Died Treatment Failure Defaulter Transfer Out A Patient who has Completed the Treatment, but does NOT meet the Criteria to be Classified as Cured of Failure Patient who DIES for any Reason during the Course of the Treatment Patient who is Sputum Smear POSITIVE at Five Months or LATER during the Treatment. A Sputum Smear Negative Patient initially who turned out to be Positive during Treatment Patient whose Treatment was Interrupted for Two Consecutive Months or More Patient who has been Transferred to another Facility with Proper Referral / Transfer Slip for continuation of Treatment

2) BRONCHIAL ASTHMA
Chronic inflammatory Disorder of the Airways; cells play a role: Mat Cells, Eosinophils, T-Lymphocytes, and Neutrophils Monitoring Severity of Asthma: Peak Expiratory Flow Meter is practical and is recommended for use in both initial assessment and in monitoring severity of asthma

I. CLASSIFICATION OF ASTHMA (ACCORDING TO SEVERITY) Mild Intermittent Mild Moderate Persistent Severe Persistent PARAMETERS Mild Intermittent Daytime Symptoms Night Awakening Rescue B2-Agonist Use PEF or FEV1 Treatment needed to control
Monthly Less than Monthly Less than Weekly > 80% of Predicted Occasional use of B2 Agonists

CHRONIC ASTHMA SEVERITY Mild-Moderate Persistent

Weekly Monthly to Weekly Weekly to Daily 60-80% of Predicted Regular use of Inhaled Corticosteroid and Long-Acting B2 Agonists Daily

Severe Persistent
Nightly Several Daily < 60% of Predicted Use of Combination of Inhaled Corticosteroids, Long-Acting B2 Agonist Plus Oral Steroids

II. TREATMENT Control of Triggers Goals of Pharmacologic Treatment: Achieve CONTROL of Asthma o 1) Minimal (ideally none) chronic symptoms, including nocturnal symptoms o 2) Minimal (Infrequent) Exacerbations o 3) Minimal need for PRN B2-Agonists, ideally none o 4) No Limitations on activities, including exercise o 5) Near Normal PEFR o 6) PEF Variability < 20% o 7) Minimal (or no) adverse effects from treatment III. GINA CLASSIFICATION (Levels of Asthma Control) CONTROLLED Daytime Symptoms None (twice or less/week) Limitation of Activities None Nocturnal Symptoms (Awakening) None Need for Reliever None (twice or less/week) Lung Function Normal Exacerbation None PARTLY CONTROLLED > 2x / week Any Any More than twice/week < 80% Predicted > 1x / year UNCONTROLLED Three or more symptoms of Partly Controlled Asthma in any week

One in any week

IV. DRUGS USED TO TREAT ASTHMA A. Controllers: o Useful in achieving and keeping Persistent Asthma under control o They are also called Preventers o Include the following: Anti-Inflammatory Agents (Corticosteroids) Anti-Allergic Medications Long Acting Bronchodilators Anti Inflammatory Agents (Corticosteroids) Inhaled: Beclomethasone Dipropionate (Qvar Metered Dose Inhaler) Budesonide (Budecort Turbuhaler / Primavent Metered Dose Inhaler) Oral / Systemic: Prednisone (Orasone) Methylprednisolone (Medrol) Long Acting Bronchodilators Long Acting B2 Agonist Formoterol Fumarate (Inhaled) Salbutamol (Oral / Systemic) Bambuterol (Oral / Systemic) Long Acting Theophylline (Sustained Release Formulation) Nuelin SR Formoterol and Budenoside (Symbicort Turbuhaler) Salmeterol and Fluticasone Montelukast Na (Kastair, Singulair) Zafirlukast (Accolate)

Combined Corticosteroids and Long Acting Bronchidilators Leukotriene Receptor Antagonists

B. Relievers o Reverse Airflow Obstruction and QUICKLY relieve its accompanying symptoms such as cough, dyspnea, wheezing and chest tightness o Consists mainly of Short Acting Bronchodilators Short-Acting Bronchodilators Short Acting B2-Agonists 1. Inhaled: Salbutamol (Ventolin / Asmalin / Librentin Metered Dose Inhaler) Procaterol (Meptin Air MDI) Terbutaline Sulfate (Bricanyl Turbuhaler) Terbutaline Sulfate (Bricanyl Metered Dose Inhaler) 2. Oral / Systemic Salbutamol (Ventolin) Procaterol (Meptin) Terbutaline Sulfate (Bricanyl) Terbutaline Sulfate, Guiafenesin (Bricanyl Expectorant Syrup) Short Acting Theophylline (Regular Formulations) Neulin Tab Brondil Tab Anti-Cholinergic Agents Combined Anti-Cholinergics and Short Acting B2 Agonists Ipratropuim Bromide (Atrovent) Ipratropium Bromide + Salbutamol (Combivent Metered Dose Inhaler)

IV. MANAGEMENT OF CHRONIC ASTHMA: HOME TREATMENT CLASSIFICATION CONTROLLER USED Step 1: Mild Intermittent NONE Step 2: Mild-Moderate Persistent Daily Medication: Inhaled Corticosteroids PLUS Long Acting B2 Agonists Daily Medication: Inhaled Corticosteroids PLUS Long Acting B2 Agonists (eg. Seretide or Symbicort Inhaler) Oral Steroid > 7.5mg daily or alternate days

RELIEVER USED Inhaled Short Acting B2 Agonist PRN Only, NOT > 3x/week Inhaled Short Acting B2 Agonist, NOT to exceed 3-4x/day Consider Inhaled Ipratropium Bromide (Seretide or Symbicort Inhaler) Inhaled Short-Acting B2 Agonist, NOT to exceed 3-4x/day Add inhaled Ipratropium Bromide

Step 3: Severe, Persistent

Guide to Treatment Plan: Patients should start treatment at the step most appropriate to the initial severity of the condition. A Rescue Course of prednisone may be needed at any time and any step When to Step Up: If control is not achieved, consider step up. But first review patient medication technique, compliance and environmental control When to Step Down: Review treatment every 3-6 months. If control is sustained for at least 3 months, a gradual stepwise reduction in treatment may be started

V. CLASSIFICATION OF ANTI-ASTHMA DRUGS A. Sympathetic Agonists: 1. A1, B1, B2 Agonists Epinephrine Ephedrine 2. B1, B2 Agonists Isoproterenol 3. Selective B2-Agonists SHORT ACTING Terbutaline Albuterol Levalbuterol Mataproterenol Pirbuterol B. Methylxanthines o Theophylline o Aminophylline o Anhydrous Theophylline o Theobromine o Caffeine C. Anticholinergics o Ipatropium Bromide o Atropine Methylnitrate D. Leukotriene Modifying Drugs o Zafirlukast o Montelukast o

**NOTE: Epinephrine & Isoproterenol are not commonly used because of their effect on the Heart (B1 Receptors)

LONG ACTING Salmeterol Bitolterol Formeterol

Zileuton

E. Glucocorticoids INHALED CORTICOSTEROIDS Beclomethasone Dipropionate Triamcinolone Acetonide Flunisolide Budesonide Fluticasone propionate F. Cromolyn Sodium

SYSTEMIC CORTICOSTEROIDS Prednisone Hydrocortisone Sodium Succinate

VI. BASIC MECHANISMS OF SOME DRUGS IN ASTHMA

ATP Adenylyl Cyclase Bronchodilation (+) cAMP BRONCHIAL TONE Antimuscarinics Acetylcholine Adenosine Theophylline Bronchoconstriction A. Beta Agonists o Stimulates the enzyme Adenylyl Cyclase to enhance cAMP o Increased cAMP causes BRONCHODILATION B. Theophylline o Inhibits Phosphodiesterase so that there is an accumulation of cAMP BRONCHODILATION o Inhibits Adenosine from causing Bronchoconstriction o Disadvantage = lots of side effects C. Antimuscarinics (Muscarinic Antagonists) o Block the effects of Acetylcholine from causing Bronchoconstriction o Includes: Ipratropium and Atropine (+) (+) AMP Theophylline Phosphodiesterase Beta Agonists

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VII. MANAGEMENT OF ACUTE EXCACERBATIONS OF ASTHMA: HOME TREATMENT

Assess SEVERITY: Clinical Features: Cough, Breathlessness, Wheeze, Chest Tightness, Use of Accessory Muscles and Suprasternal Retractions PEF < 80% Personal Best or Predicted (if available) INITIAL TREATMENT: Inhaled Short-Acting Beta-2 Agonist up to 3 Treatments in 1 Hour Alternative: Oral Short-Acting Beta-2 Agonist and/or Theophylline

GOOD RESPONSE (Mild Exacerbation) No symptoms within 1 hr PEF > 80% predicted Sustained response for 4 hrs

INCOMPLETE RESPONSE (Moderate Exacerbation) PEF 60-80% Predicted

POOR RESPONSE (Severe Exacerbation) PEF < 60% Predicted

Continue regular bronchodilator for 24-48 hrs Inhaled Short Acting B2-Agonist 2 puffs q3-4hr Alternative: Oral Short-Acting B2Agonist or Theophylline TID

Add Oral Steroid (1mg/kg/day) Continue Beta-2 Agonist and/or Theophylline regularly

Add Oral Steroid (1mg/kg/day) Repeat inhaled Beta-2 Agonist if available

Consult Clinician Urgently for Instructions Contact clinician within 48hrs for follow up Immediate Transport to Hospital (ER)

VIII. MANAGEMENT OF ACUTE EXACERBATION OF ASTHMA: HOSPITAL CARE Oxygen at 2-6 lpm via Nasal Canula Avoid or Control Trigger Factors Mneumonic: N-A-S-A A. Nebulization o Salbutamol (Ventolin) Neb/Inhaler q3-6 hours (1 Nebule / 2-4 puffs); or o Ipratropium Bromide + Salbutamol (Combuvent) Nebulization 1 vial q6 hours; or o Ipratropium Bromide (Atrovent) 1 Unit Dose vial TID-QID (less tachycardia); or o MDI plus Large Volume Spacer at 2-4 puffs q 20 minutes (cheaper and faster) B. Antibiotics o ONLY if with probable bacterial infection (fever, persistent purulence, crackles) C. Steroids o Acute Attack: Hydrocortisone (Solucortef) 250mg IV stat, then 100mg IV q4-6h x 4 doses or continuous if the condition warrants o More Stable: Start on Oral Steroids as soon as patients can safely swallow and taper off in 10-14 days D. Aminophyline o Only as Add-On Medication (if asthma still not controlled) o Acute Attack: Not controlled by N, A and S, give Aminophylline Bolus at 5-6 mg/kg BW (if not maintained on Theophyllines) then Aminophylline Drip o More Stable: Shift to Long-Acting Theophylline If NOT controlled by N-A-S-A, consider INTUBATION before Respiratory Fatigue sets in

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3) CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Syndrome of Chronic Dyspnea with Expiratory Airflow Limitation that, unlike asthma, does NOT fluctuate markedly

COPD includes Chronic Bronchitis and Emphysema I. CLINICAL PRESENTATION

Chronic productive cough for many years, followed by slowly progressive Breathlessness brought on with Decreasing amounts of Exertion Unusual in the absence of smoking Nocturnal Symptoms are UNUSUAL in COPD unless associated with comorbidities (cardiac disease, obstructive sleep apnea, gastroesophageal reflux, or marked reactive airway component) Tachypnea, pursed-lip breathing, and use of accessory muscles On PE: Hyperresonant chest, decreased breath sounds, adventitious sounds Signs of Cor Pulmonale may be seen in severe or long-standing disease

II. SOME DIAGNOSTICS: A. Chest Radiographs

o o

o B. Pulmonary Function Testing

o o

Low, Flattened Diaphragms Hyperlucent Lungfields with Bullae and diminished Vascular Markings (in Severe Emphysema) Often, disease is prominent in Upper Long Zones (except in A1-Antitrypsin Deficiency: basilar predominance) FEV1 and all other measurements of Expiratory airflow are Reduced FEV1 = Standard Way of objectively assessing the clinical course and response to therapy Total Lung Capacity, Functional Residual Capacity, & Residual Volume may be Increased, indicating Air-Trapping Perfusion of Poorly Ventilated Areas of the Lungs (ie. Areas with Low V/Q) results in an Increased Alveolar-Arterial Oxygen Tension (P(A-a)O2) Gradient and Hypoxemia A subpopulation of patients with Severe Airway Obstruction have chronically Increased Arterial PaCO 2, but Metabolic Compensation (increased HCO3) maintains Arterial pH near normal During Acute Exacerbation of COPD Worsening Airway Obstruction Increased Dead Space Ventilation & Respiratory Fatigue Rapid Rise in PaCO2 Acute Respiratory Acidosis

o C. Arterial Blood Gases

o

III. CLINICAL SYNDROMES: Two Classic Types of COPD (from NMS) Pink Puffers: Patients with EMPHYSEMATOUS, Dyspneic, or Type-A COPD Blue Bloaters: Patients with BRONCHITIC, Tussive, or Type-B COPD
TYPE Pink Puffers PREDOMINANCE Emphysema AGE OF (+) SYMPTOMS Advanced Age (>60) SYMPTOMS Progressive exertional dyspnea Weight Loss Little / No Cough & Expectoration PULMONARY FUNCTION TESTING Mild Hypoxia, Hypocapnia Decreased DLCO Mild Increase in Raw Little Improvement in Airflow after Treatment with Bronchodilators Blue Bloaters Chronic Bronchitis Young Age Chronic Cough & Expectoration Episodic Dyspnea Weight Gain Wheezing, Rhonchi Cor Pulmonale often develops (Edema, Cyanosis) Severe Hypoxia, Hypercapnia Polycythemia Increased Raw Improved Airflow after treatment with Bronchodilators Relatively preserved Lung Volumes and DLCO

Emphysema: Proportional and Matched Losses of Ventilation and Perfusion hence, they are Spared Severe Hypoxemia Chronic Bronchitis: Marked V/Q Mismatch, resulting in Severe Hypoxemia (which is worsened by Hypercapnia)

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IV. CLASSIFICATION AND TREATMENT OF COPD (from Blue Book)

STAGE / SYMPTOMS & SIGNS 0: At Risk
Cough Sputum

FEV1 as % PREDICTED NORMAL

TREATMENT
Smoking Cessation for everyone Reduce indoor pollution Reduce occupational exposure Flu vaccinations yearly As needed B2-Agonists Eg. Terbutaline Sulfate (Bricanyl Turbuhaler) 250mcg/dose: 1 inh prn q2-6h Pulmonary Rehabilitation

I: Mild COPD
Cough, Sputum Little or NO Dyspnea Mild Symptoms NO Abnormal Signs

> 80%

II: Moderate COPD

50 79%

Cough, Sputum Dyspnea on moderate exertion Continuous or intermittent Sx

For intermittent Sx: As needed B2 Agonists For Continuous Symptoms: Maintain on Tiotropium (Spiriva HandiHaler) inhalation of 1 Cap daily If response is Unsatisfactory, add Long-Acting B2 Agonist or Oral Theophylline Consider Mycokinetic Agent Pulmonary Rehabilitation

III: Severe COPD

Cough, Sputum Dyspnea on Mild Exertion Lung Hyperinflation Wheezing

30 49%

As needed B2 Agonists For Continuous Symptoms: Maintain on Tiotropium (Spiriva HandiHaler) Inhalation of 1 capsule daily For frequent exacerbations (>4x/yr): Add inhaled Steroids of Long Acting B-Agonists Eg. Formoterol & Budesonide (Symbicort Turbuhaler) 1-2 inhalations BID Pulmonary Rehabilitation

IV: Very Severe COPD

< 30%

Dyspnea even at rest Chronic Respiratory Failure

In addition to the above treatments: Add long-term O2 Therapy at home Consider surgical treatments like Lung Reduction Surgery and Bullectomy (removal of Bulla)

V. COPD VS ASTHMA (Med School Notes)

Smoker or Ex-Smoker Symptoms under age 35 Chronic Productive Cough Breathlessness Night Time Awakening Significant Diurnal or Day to Day Variability COPD Nearly All Rare Common Persistent and Progressive Uncommon Uncommon ASTHMA Possible Often Uncommon Variable Common Common

VI. THERAPY:
A. Pharmacotherapy o Smoking Cessation: Bupropion, Nicotine Replacement Therapy o Bronchodilators (Symptomatic Benefit) o Anticholinergic Agens o Beta Agonists (Symptomatic Benefit) o Inhaled Glucocorticoids o Oral Glucocorticoids o Theophylline o Oxygen B. Non-Pharmacologic Therapies o Pulmonary Rehabilitation o Lung Volume Reduction Surgery (LVRS) o Lung Transplantation (COPD is the single leading indication for lung transplantation)

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Only 3 Interventions have been demonstrated to influence natural hx of COPD:

1) Smoking Cessation 2) Oxygen Therapy in Chronically Hypoxemic Patients 3) Lung Volume Reduction Surgery

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VII. MANAGEMENT OF ACUTE EXACERBATIONS A. Maintenance of Adequate Gas Exchange: o Oxygen to achieve & maintain PaO2 55-60mmHg (88-90% Oxyhemoglobin Saturation) o Mechanical Ventilation in patients with Acute Ventilatory Failure B. Inhaled B2-Adrenergic Agonists o First Line Therapy for Rapid Symptomatic Improvement in patients with Acute Bronchoconstriction o Inhaled = most effective and safe o Ex) Metaproterenol, Terbutaline, Albuterol (q30-60 min, as tolerated) C. Anticholinergic Agents (Ipratropium Bromide) o Have equivalent efficacy to B2-Adrenergic Agonists in treatment of Acute Exacerbations of COPD, but NO consistent Synergistic Bronchodilation is obtained with combination therapy o Combination of B2-Adrenergic Agonist and Anticholinergic Agent = provides Rapid Onset of the former PLUS the more prolonged Action of the latter D. Glucocorticoids (Methylprednisolone 125mg IV q6h for 3 days) o Moderate improvement in clinical outcomes have been demonstrated o Use in hospitalized patients (role of glucocorticoids for Acute Exacerbations in outpatients is controversial) E. Theophylline o Controversial F. Antimicrobial Therapy o Benefit of Antibiotic Therapy is seen in patients who have more severe underlying lung disease and in those who experience more severe exacerbations G. Chest Physiotherapy o May improve clearance of secretions (>50mL/day) VIII. LONG TERM MANAGEMENT 1) Relief of Symptoms and Managing Acute Exacerbations 2) SLOWING Progression of Airflow Obstruction and Loss of Vital Capacity Includes the Following:
o o o o o o o o Smoking Cessation Optimal Bronchodilator Regimen (not established) Glucocorticoids Oxygen Therapy Pulmonary Hypertension and Cor Pulmonale Comprehensive Pulmonary Rehabilitation Program Influenza Vaccine and Pneumococcal Vaccine Psychoactive Drugs A1-Protease Inhibitor Augmentation Therapy

o IX. SURGICAL CONSIDERATIONS

Non-Thoracic Surgery Lung Resection, Lung Volume Reduction Surgery Lung Transplantation
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X. NOTES FOR COPD (GOLD)

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XI. MECHANICAL VENTILATION FOR OBSTRUCTUVE AIRWAY DISEASES (ASTHMA & COPD) Lecture A. Non-Invasive Positive Pressure Ventilation (NIPPV) for ARF due to COPD o Patient receives air or air-O2 from a Flow Generator through a Full Facial or Nasal Mask o Enhance Ventilation by Unloading the Fatigued Ventilatory Muscles o Improve Gas Exchange by Increasing Alveolar Ventilation 1. At Least TWO of: General Criteria for Acute Ventilatory Failure: Moderate to Severe Dyspnea Patient is Acutely Dyspneic, Altered Mental Status pH < 7.35 or PaCO2 > 45 PaO2 < 50mmHg at Room Air RR > 25

PaCO2 > 50mmHg 2. Best Modes: Arterial pH: significant Respiratory Acidemia PSV BiPAP CPAP 3. Contraindications to NIPPV in COPD Frank Respiratory Arrest Hemodynamic Instability Inability to clear secretions or protect airways Agitation or Uncooperativeness Conditions that preclude placement of a Mask or achievement of a Proper Fit B. Potential Deleterious Consequences of Severe OAD + MV: o Post-Hypercapnic Metabolic Alkalosis o Hypotension Secondary to Acute Hyperinflation o Alveolar Overdistention o Oxygen Toxicity Acute Lung Injury o Cardiovascular o Ventilator Associated Pneumonia (VAP) C. Goals of MV in Severe OAD o Restore Gas Exchange to stable baseline o Rest Ventilator Muscles / Reduce Work of Breathing until Primary Disease Process reverses or improves D. Monitoring Patients with Severe OAD on Mechanical Ventilation: 1. Peak Airway Pressure PAP > 50cmH2O associated with Barotrauma If HIGH, suspect: AF Obstruction (PEEPi, Bronchospasm, Secretions, Mucus Plug) Concomitant problems (Pneumonia, CHF, Pulmonary Embolism) Complications (Pneumothorax, Atelectasis) Patient-Ventilator Dyssynchrony High Inspiratory Flow Rates Small Size of ET Kinks / Blocks along tubings, Right Mainstem Intubation 2. Plateau or Static Pressure PPLAT > 30cmH2O predicted of Barotrauma Estimate of average End-Inspiratory Alveolar Pressure 3. Auto-PEEP (PEEPi) / Dynamic Hyperinflation Airflow obstruction prevents Complete Emptying of Alveolar Gas End Expiratory PALV remains Positive Consequences: Decreased Venous Return Promotes Barotrauma Increased Work of Breathing 4. PaO2, SaO2 Lowest possible FiO2 to maintain SaO2 > 92% or PaO2 > 60mmHg Any further Increase in FiO2 will have little effect on SaO2 and Increases Risk of O2 Toxicity 5. pH, PaCO2 COPD patients are Chronically Hypercapneic Maneuvers that attempt to PaCO2 also Worsen Dynamic Hyperinflation & promote Barotrauma & Hypotension Permissive Hypercapnea: Ignore PaCO2 as long as pH is acceptable

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E. Modes of MV of Patients with Severe OAD: 1. Assist Control Ventilation Deliver breath with Preset Volume and Flow, either when Trigerred by patients Inspiratory Effort or to a Preset Backup Respiratory Rate Excessive Patient Work occurs if Peak Flow Insufficient to meet Patients Ventilatory Demands, especially if Respiratory Drive is heightened or when Trigger Setting is NOT sufficiently sensitive Risk for Hyperinflation 2. Synchronized Intermittent Mandatory Ventilation (SIMV) Deliver Periodic Positive Pressure Breaths from the Ventilator at Preset Volume and Rate and also allow Spontaneous Breathing As Ventilator Rate is Decreased, Inspiratory Work and the Pressure-Time Product INCREASE progressively, NOT only for the Spontaneous Breaths but also for the Assisted breaths largely due to Inability of the Respiratory Centers to adapt to Intermittent Unloading 3. Pressure Support Ventilation Set a Level of Pressure (rather than Volume) to Augment each Spontaneous breath Each breath is Patient-Triggered, Inspiratory Assistance continues until Inspiratory Flow Decreases Tidal Volume is determined by Set Pressure Level, Patients Effort, and pulmonary mechanics F. Ventilator Setting Strategies and Targets in Patients with Severe OAD: 1. FiO2 Achieve PaO2 > 60mmHg, SpO2 > 92% Lowest possible FiO2 to keep SpO2 > 92% 2. Trigger Sensitivity Set the Level of Sensitivity (usually 1 to 2) which will keep patients Inspiratory Effort to a Minimum, but NOT too sensitive that the MV Cycles inappropriately and results in Severe Respiratory Alkalosis Consider the Effect of Auto-PEEP on Triggering: patients need to generate a negative pressure equal in magnitude to the Level of Intrinsic PEEP (Auto-PEEP) in addition to the Sensitivity Setting Flow Triggering (instead of Airway Pressure Change Triggering), is available on Newer Ventilators, can Decrease Inspiratory Effort by 30-40% during Triggering 3. Inspiratory Flow Rate (IFR) Should be HIGH (60-100 L/min) however High IFR can cause Peak Airway Pressure Barotrauma If on A/C Mode at Low Flow Rates = the patient will NEED to Generate Inspiratory Effort against his own Pulmonary Impedance + that of the Ventilator, resulting in Increased Work of Breathing High Inspiratory Flow Rate: Helps satisfy the demands of Most Patients Decreases the likelihood of DHI by Increasing Expiratory Time allow more complete emptying of regions with Gas Trapping 4. Tidal Volume Avoid Alveolar Overdistention Set at 5-7 cc/kg Provide enough pressure to ensure Inhaled Medication Delivery NOT set in PSV 5. Ventilator Rate A/C Mode Back up Rate of 4 Breaths per minute LESS than the Patients Spontaneous Rate to ensure that the MV will continue to supply adequate Volume in case of Sudden Decrease in Respiratory Center Output If with High Spontaneous RR, Expiratory Time will Decrease and can become Shorter than T1 and can result in Inverse Ratio Ventilation Titrating the Level of Mandatory Breaths: consider NOT only the ABG but also the Patients work of breathing and comfort NOT set

IMV PSV

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4) PULMONARY EDEMA
I. CARDIOGENIC PULMONARY EDEMA A. Pathophysiology Increased Pulmonary Venous Pressure Engorgement of Pulmonary Vasculature CHF Lungs become Less Compliant Increased Resistance in Small Airways Increased Lymphatic Flow and Intravascular Pressure Interstitial Edema (net gain of fluid in the Extravascular Space) Alveolar Edema (Outpouring of liquid that contracts both RBC and Macromolecules) Progressive Acidemia, Hypercapnea Respiratory Arrest o Manifested by Bilateral Wet Rales and Rhonchi o CXR: Diffuse Haziness of the lung fields with greater density in the Proximal Hilar Regions B. Treatment 1. Supportive: O2 Support Raise the Arterial O2 Tension > 60mmHg 2. Pharmacologic Morphine Sulfate Furosemide Nitroglycerin Inotropes Dilates pulmonary and systemic veins 2-5mg IV can be repeated 10-25min until effect is seen Potent Venodilators Initial Dose of 20-40mg IV, Max dose of 200mg Venodilator Can potentiate the effect of Furosemide Dobutamine or Phosphatiesterase Inhibitors In patients with concomitant hypotension and shock

3. Acute Hemodialysis and Ultrafiltration 4. Right Heart Catheterization Differentiates between Cardiogenic and Noncardiogenic causes of Pulmonary Edema 5. Precipitating Factors should be corrected II. NON-CARDIOGENIC PULMONARY EDEMA Severe Liver Disease Nephritic Syndrome Other Forms of Pulmonary Edema: Narcotic Overdose parenteral Heroin, Morphine, Methadone, Dextropropoxyphene Protein Losing Enteropathy Exposure to high altitudes due to pulmonary venous constriction or pulmonary Lymphatic Carcinomatosis arteriolar construction Diffuse Pulmonary Infections Neurogenic Pulmonary Edema in patients with CNS disorders without preexisting LV Aspiration dysfunction Shock

18

5) INVESTIGATING AN SPN
SPN: Solitary Pulmonary Nodule

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CAUSES OF CHRONIC COUGH: Intrathoracic: COPD, Bronchial Asthma, Central Bronchial Carcinoma, Endobronchial TB, Bronchiectasis, Left Heart Failure, Interstitial Lung Disease, Cystic Fibrosis Extrathoracic: Postnasal Drip, Gastroesophageal Reflux, Drug Therapy (eg. ACE Inhibitors)

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6) CASE ON PULMONARY DISEASE

I. CASE: 71/F With Chief Complaint of DOB Hypertensive, Dyslipidemia, Congestive Heart Failure FC II, history of PTB Admitted due to Pleural Effusion prob 20 to Left Pleural Mass S/P Thoracentesis (no malignant cells) Symptoms: Dyspnea, back pain, undocumented fever, weight loss, anorexia, easy fatigability, no cough II. OTHER SYMPTOMS (ROS): A. Blurring of Vision o Flame Shaped Hemorrhages = consistent with HYPERTENSION o Diplopia = nagdadalawa ang paningin B. Polyuria o In patients presenting with Pulmonary Mass, significance of Polyuria = Paraneoplastic Syndrome o Patient may also be diabetic, as a part of the Metabolic Syndrome C. Screen for other Organ Systems, as a site of Possible Metastasis o Breasts (Most Common CA for age group) o GI System (changes in stools, abdominal pain) o Liver (history of jaundice) 1. Colon Carcinoma (2nd most common CA): Right Side = sometimes ASYMPTOMATIC Left Side = decreased caliber of stools 2. Gynecologic Carcinomas (3rd most common CA) Ask for gynecologic complaints III. PHYSICAL EXAMINATION Decreased breath sounds, increased tactile fremitus on Left Crackles, wheezes on Right A. Shifting Dullness o Can also be done in the chest / lungs o To differentiate fluid from solid B. No Clubbing in Extremities o Elicit because Pulmonary Mass IV. DIAGNOSTICS A. Chest X-Ray (AP/L) o Findings: the mass is causing an Obstructive Atelectasis to the LEFT, there is shifting of trachea to right o On Lateral: there is NO effusion in the POSTERIOR GUTTER (most dependent portion) B. Bronchoscopy C. Notes on PT / PTT 1. Prothrombin Time (PT) Tests the Extrinsic and Common Coagulation Pathways Prolonged Time = deficiency / dysfunction in Factor V, VII, X, Prothrombin, Fibrinogen 2. Partial Thromboplastin Time (PTT) Tests the Intrinsic and Common Coagulation Pathways Prolongation = deficiency / dysfunction of factor V. VIII. IX. X. XI. XII. Prothrombin, Fibrinogen

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7) COMMUNITY ACQUIRED PNEUMONIA

Pneumonia is an infection of the Pulmonary Parenchuma Results from the Proliferation of microbial pathogens at the alveolar level & hosts response to those pathogens

I. CLASSIFICATION (2004): Management-Oriented Risk Stratification of CAP in Immunocompetent Adults

CAP

Any of the following: 1. RR > 30 / min 2. PR > 125 / min 3. Temp > 400C or < 350C 4. Extrapulmonary evidence of sepsis 5. Suspected aspiration 6. Unstable comorbid conditions* 7. CXR: Multilobar, pleural effusion, abscess, progression of lesion to > 50% of initial within 24 hours

YES

Any of the following: 1. Shock or signs of Hypoperfusion -Hypotension -Altered mental status -Urine output < 30mL/hr

YES

HIGH RISK CAP

2.

PaO2 < 60mmHg or Acute hypercapnea (PaCO2 > 50mmHg)

NO

NO

LOW RISK CAP

MODERATE RISK CAP

Outpatient
LOW RISK CAP Stable Vital Signs RR < 30/min PR < 125bpm SBP > 90mmHg DBP > 60mmHg No or Stable Comorbid Conditions No evidence of Extrapulmonary Sepsis No evidence of Aspiration Chest X-Ray: Localized infiltrates No evidence of Pleural Effusion nor abscess NOT progressive within 24 hours

In Patient
MODERATE RISK CAP Unstable Vital Signs: RR > 30/min PR > 125bpm Temp > 400C or < 350C Unstable Comorbid Condition
Uncontrolled DM, Active Malignancies, Progressing Neurologic Disease, CHF Class II-IV, Unstable CAD, Renal Failure on Dialysis, Uncompensated COPD, Decompensated Liver Disease

Intensive Care
HIGH RISK CAP Any of the clinical features of Moderate Risk CAP plus any of the following: 1) Shock or Signs of Hypoperfusion Hypotension Altered Mental State Urine Output < 30mL/hr 2) Hypoxia (PaO2 < 60mmHg) or Acute Hypercapnea (PaCO2 > 50mmHg) Chest X-Ray: * As in Moderate Risk CAP

Evidence of Extrapulmonary Sepsis Hepatic, Hematologic, GI, Endocrine Suspected Aspiration Chest X-Ray: Multilobar Infiltrates Pleural Effusion or Abscess Progression of findings to >50% in 24h

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II. MANAGEMENT OF CAP (from 2004 guidelines) see updated 2010 guidelines when available POTENTIAL PATHOGENS EMPIRIC THERAPY Low Risk CAP S. pneumoniae Previously Healthy: H. influenzae Amoxicillin C. pneumoniae OR M. pneumoniae Extended Macrolides M. catarrhalis Alternative: CoTrimoxazole Gram (-) Enteric Bacilli With Stable Comorbid Illness: Co-Amoxiclav or Sultamicillin OR 2nd Generation Cephalosporins OR Extended Macrolides Moderate Risk CAP S. pneumoniae H. influenzae C. pneumoniae M. pneumoniae M. catarrhalis Gram (-) Enteric Bacilli Legionella pneumophilia Anaerobes (with risk of aspiration) S. pneumoniae H. influenzae C. pneumoniae M. pneumoniae M. catarrhalis Gram (-) Enteric Bacilli Legionella pneumophilia Anaerobes (with risk of aspiration) S. aureus P. aeruginosa IV Non-Pseudomonal B-Lactam With or Without B-Lactamase Inhibitor PLUS Macrolide OR Antipneumococcal Fluoroquinolones (FQ) No Risk for P. aeruginosa: a. IV Non-Pseudomonal B-Lactam with or without BLactamase Inhibitor + IV Macrolide b. IV Antipneumonococcal FQ With Risk for P. aeruginosa IV Pseudomonal B-Lactam with or without B-Lactamase Inhibitor PLUS IV Macrolide or IV Antipneumococcal FQ With or Without Aminoglycoside or IV Ciprofloxacin

High Risk CAP

**NOTE: Respiratory Quinolones (because they cover Pneumococcus) o Levofloxacin o Gatifloxacin o Moxifloxacin

III. DIAGNOSIS A. Differential Diagnosis of Pneumonia o Infectious o Non-Infectious (Acute Bronchitis, Acute Exacerbations of Chronic Bronchitis, Heart Failure, Pulmonary Embolism, Radiation Pneumonitis) B. Diagnostics o Gram Stain and Culture of Sputum o Blood Cultures o Antigen Tests, PCR, Serology IV. CRITERIA IN HARRISONS 17TH EDITION: CURB-65 CRITERIA C: Confusion Scoring System: U: Urea >7mmol/L 0: Outpatient R: Respiratory Rate >30/min 2: In-Patient B: Blood Pressure (Systolic <90 or Diastolic <60) >3: In-Patient ICU 65: Age >65years old

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8) HOSPITAL ACQUIRED PNEUMONIA

I. EARLY VS LATE ONSET HAP EARLY ONSET ( 5 days in Hospital)
S. pneumoniae H. influenzae M. catarrhalis S. aureus Enteric Gram (-) Bacteria

LATE-ONSET (> 5 days)

P. aeruginosa Enterobacter spp Acinetobacter spp K. pneumoniae S. marcescens E. coli Other Enteric Gram (-) Bacteria S. aureus

OTHERS
Anaerobic Bacteria Legionella Candida spp Influenza A and B RSV

**NOTE: Organisms we deal with in Asia are DIFFERENT from the US / Europe II. EMPIRICAL ANTIBIOTIC TREATMENT OF HEALTH CARE ASSOCIATED PNEUMONIA (Harrisons) A. Patients without Risk Factors for MDR Pathogens: o Ceftriaxone (2g IV q24h); or o Moxifloxacin (400mg IV q24h), Ciprofloxacin (400mg IV q8h), or Levofloxacin (750mg IV q24h); or o Ampicillin / Sulbactam (3g IV q6h); or o Ertapenem (1g IV q24h) B. Patients with Risk Factors for MDR Pathogens 1. A Beta-Lactam: Ceftazidime (2g IV q8h) or Cefepime (2g IV q8-12h); or Piperacillin / Tazobactam (4.5g IV q6h), Imipenem (500mg IV q6h or 1g IV q8h), or Meropenem (1g IV q8h); PLUS 2. A Second Agent Active Against Gram-Negative Bacterial Pathogens: Gentamicin or Tobramycin (7mg/kg IV q24h) or Amikacin (20mg/kg IV q24h); or Ciprofloxacin (400mg IV q8h) or Levofloxacin (750mg IV q24h); PLUS 3. An Agent Active Against Gram-Positive Bacterial Pathogens: Linezolid (600mg IV q12h) or Vancomycin (15mg/kg, up to 1g IV q12h)

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9) PLEURAL EFFUSION AND PNEUMOTHORAX

I. PLEURAL EFFUSION Excess quantity of fluid in the pleural space Decreased pleural fluid removal by the lymphatics Excess pleural formation from the interstitial spaces of the lung, parietal pleura, or peritoneal cavity A. Transudative and Exudative Pleural Effusion 1. Transudative VS Exudative a. Transudative Systemic factors that influence the formation and absorption of pleural fluid is altered Ex) LV Failure, Pulmonary Embolus, Cirrhosis b. Exudative Local factors are altered Ex) Bacterial Pneumonia, Malignancy, Viral Infection, Pulmonary Embolus 2. Lights Criteria (Exudative Effusions meet at least ONE, Transudative Effusions meet NONE) Pleural Fluid Protein / Serum Protein > 0.5 Pleural Fluid LDH / Serum LDH > 0.6 Pleural Fluid LDH > 2/3 Normal upper limit for Serum LDH
If one or more of the Exudative Criteria are met and the patient is clinically thought to have a condition producing a Transudative Effusion, the difference between the Albumin Levels in the Serum and the Pleural Fluid should be measured If > 12g/L (1.2g/dL) = TRANSUDATIVE!

3. Symptoms / Signs of Pleural Effusion

Intercostal Pain (Inflammation of Parietal Pleura) Cough, Dyspnea Dullness on Percussion Decreased or Absent Tactile Fremitus Decreased Breath Sounds Tracheal Deviation Pleural Rub

B. Parapneumonic Effusion o Associated with bacterial pneumonia, lung abscess, bronchiectasis o Empyema = Grossly purulent effusion o If free fluid separates the lung from the chest wall by > 10mm THORACENTESIS! o Factors indicating need for procedure more invasive than Thoracentesis (increasing order of importance)
Loculated Pleural Fluid Pleural Fluid pH < 7.2 Pleural Fluid Glucose < 3.3mmol/L (<60mg/dL) Positive Gram Stain or Culture of Pleural Fluid Presence of Gross Pus in the pleural space

C. Thoracentesis
o o o

Usual Site: 8th ICS L PAL Maximum Drainage = 1.5 L every 24 hours Send Specimen: Bottle 1: Cell Count, Differential Count, Total Protein, LDH (5-10mL EDTA) Bottle 2: AFB, Gram Stain, C&S Bottle 3: Cytology and Cell Block (obtain 200cc of Fluid or more to increase yield)

D. Indications for Chest Tube Insertion

o o o 1) Gross Pus on Thoracentesis 2) Presence of Organisms on Gram Stain of the Pleural Fluid 3) Pleural Fluid Glucose < 50mg/dL 4) Pleural Fluid pH below 7.00 and 0.15 units lower than Arterial pH

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E. Indications for Chemical Pleurodesis: Talc or Tetracycline Pleurodesis

o o o 1) Recurrent Pleural Effusion 2) Malignant Pleural Effusions 3) Secondary Pneumothorax including Iatrogenic Pneumothoraces 4) Patients with Poor Surgical Risk Differential Diagnoses of Pleural Effusions: 1. Transudative Pleural Effusion Congestive Heart Failure Cirrhosis Pulmonary Embolization Nephrotic Syndrome Peritoneal Dialysis Superior Vena Cava Obstruction Myxedema Urinothorax 2. Exudative Pleural Effusions Neoplastic Diseases Infectious Diseases (Bacterial, TB, Fungal, Viral) Pulmonary Embolization GI Diseases (Esophageal Perforation, Pancreatic, etc) Collagen Vascular Diseases (SLE, Rheumatoid Pleuritis, etc) Post-Coronary Artery Bypass Surgery Asbestos Exposure Sarcoidosis Uremia Meigs Syndrome Yellow Nail Syndrome Drug-Induced Pleural Disease Trapped Lung Radiation Therapy Post-Cardiac Injury Syndrome Hemothorax Iatrogenic Injury Ovarian Hyperstimulation Syndrome Pericardial Disease Chylothorax

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II. PNEUMOTHORAX
Presence of Gas in the Pleural Space Spontaneous Pneumothorax: Occurs WITHOUT antecedent Trauma to the Thorax A. Primary Spontaneous Pneumothorax o Occurs in the absence of Underlying Lung Disease o Usually due to Rupture of Apical Pleural Blebs, Small Cystic Spaces that lie within or immediately under the visceral pleura o Occur almost exclusively in Smokers, which suggests that these patients have subclinical lung disease o Initial Recommended Treatment: Simple Aspiration o Thoracoscopy and Thoracotomy with Pleural Abrasion is almost 100% successful in preventing recurrences B. Secondary Pneumothorax o Most are due to Chronic Obstructive Pulmonary Disease, but Pneumothoraces have been reported with every lung disease (pneumothorax with lung disease is more life-threatening) o Nearly all should be treated with Tube Thoracostomy o Most should also be treated with Thoracoscopy or Thoracotomy with Stapling of Blebs & Pleural Abrasion C. Traumatic Pneumothorax o Can result from both Penetrating and Non-Penetrating Chest Trauma o Should be treated with Tube Thoracostomy, unless they are very small o Iatrogenic Pneumothorax: due to Transthoracic Needle Aspiration, Thoracentesis, Insertion of Central IV Catheters D. Tension Pneumothorax o Occurs during Mechanical Ventilation or Resuscative Efforts o The positive Pleural Pressure is life-threatening both because Ventilation is severely compromised and because the Positive Pressure is transmitted to the Mediastinum, which results in Decreased Venous Return to the heart and reduced Cardiac Output o Diagnosis is made by Physical Examination: Enlarged Hemithorax with NO Breath Sounds Hyperresonance to Percussion Shift of Mediastinum to the Contralateral Side o Must be treated as a Medical Emergency o A large bore needle should be inserted into the Pleural Space through the 2 nd Anterior Intercostal Space if large amounts of gas escape from the needle after insertion, the diagnosis is confirmed

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10) PULMONARY EMBOLISM

When Venous Thrombi dislodge, they embolize to the Pulmonary Arterial Circulation or, paradoxically, to the Arterial Circulation through a patent foramen ovale or ASD Most Common Gas Exchange Abnormalities: o Hypoxemia (Decreased Arterial PO2) o Increased Alveolar-Arterial O2 Tension Gradient (represents inefficiency of O2 Transfer across lungs)

I. PATHOPHYSIOLOGY: Anatomic Dead Space INCREASES because breather gas does NOT enter gas exchange units of the lung Physiologic Dead Space INCREASES because ventilation to gas exchange units exceeds Venous Blood Flow through the pulmonary capillaries Other Pathophysiological Abnormalities: o Increased Pulmonary Vascular Resistance (due to vascular obstruction) o Impaired Gas Exchange o Alveolar Hyperventilation o Increased Airway Resistance o Decreased Pulmonary Compliance II. CLINICAL PRESENTATION A. High Index of Suspicion o Presence of DVT o Hypercoaguable State o Pathologic Fractures o Long Bone Fractures o Post-Partum Period B. Symptoms: o Unexplained Breathlessness o Cough, Dyspnea o Pleuritic Chest Pain, Syncope C. Physical Examination o Tachypnea, Tachycardia o Increased P2 o Inspiratory Crackles / Rales
NOTES from BLUE BOOK: 1. Diagnosis of Pulmonary Embolism: Clinical setting & high index of suspicion On PE: Increase JVP but Clear Lungs, Load P 2 ABG may show Respiratory Alkalosis, Hypoxemia ECG: Transient RAD, RBBB, S-Waves at precordial leads V/Q Scan: Interpreted as Normal, Low, Intermediate or High Probability of PE Pulmonary Angiography: Gold Standard for Diagnosis 2. Diagnosis of Deep Vein Thrombosis (as source of Emboli) Duplex Ultrasound of the Lower Extremities (Non-Invasive) Ascending Venography: Gold Standard

Differentials: Dissecting Aortic Aneurysm Acute Bronchitis Bronchogenic CA Pericarditis, Pericardial or Pleural Disease Acute Coronary Syndrome / Myocardial Ischemia Congestive Heart Failure Axiety Pneumonia, Asthma, COPD Pleurisy: Viral Syndrome, Costochondritis, Musculoskeletal Rib Fracture, Pneumothorax

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III. DIAGNOSTICS
A. Non-Imaging Diagnostic Modalities: 1. Expected ABG Mild Respiratory Alkalosis Hypoxemia
The most common gas exchange abnormalities are Hypoxemia (Decreased Arterial PO2) and an Increased AlveolarArterial O2 Tension Gradient, which represents the inefficiency of O2 Transfer across the lung. Anatomic dead space increases because breathed gas does not enter gas exchange units of the lung. Physiologic dead space increases because ventilation to gas exchange units exceeds venous blood flow through the pulmonary capillaries. Arterial Blood Gases LACK diagnostic utility for Pulmonary Embolism, even though both the PO 2 and PCO2 often decrease. Among patients suspected of PE, neither the room air Arterial PO2 nor calculation of the Alveolar-Arterial O2 Gradient can reliably differentiate or triage patients who actually have PE at angiography.

2. Plasma D-Dimer (ELISA) Normal Value: < 500ng/mL Useful RULE-OUT Test; It is NORMAL in > 95% of patients WITHOUT Pulmonary Embolism (PE) In patients with low clinical suspicion of DVT, it is NORMAL in > 90% WITHOUT DVT

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QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture.

The quantitative plasma D-Dimer Enzyme-linked Immunosorbent Assay (ELISA) rises in the presence of DVT or PE because of plasmins breakdown of fibrin. Elevation of D-Dimer indicates endogenous although often clinically ineffective thrombolysis. The sensitivity of D-Dimer is > 80% for DVT and > 95% for PE. D-Dimer is NOT Specific. Levels increase in patients with: Myocardial Infarction Pneumonia Sepsis Cancer Postoperative State Second o Third Trimester Pregnancy Troponin Levels increase in RV Microinfarction. Elevated Cardiac Biomarkers predict increase in major complications and mortality from PE

3. ECG in Pulmonary Embolism Most Cited Abnormality (in addition to Sinus Tachycardia) = S1-Q3-T3 S-Wave in Lead I Q-Wave in Lead III This finding is relatively SPECIFIC, but INSENSITIVE Inverted T-Wave in Lead III Most Frequent Abnormality: T-Wave Inversion in Leads V1 to V4

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B. Non-Invasive Imaging Modalities 1. Venous Ultrasonography UTZ of DVT: relies upon loss of vein compressibility A Normal Venous UTZ does NOT exclude Pulmonary Embolus (PE) 2. Chest X-Ray (Multidetector-Row Spiral CT) May be NORMAL or Near Normal Some Signs: Westermarks Sign: Decreased Vascularity Hamptons Hump: Wedge-Shaped Density above Diaphragm in outer 2/3 lung field Pallas Sign: Enlarged Right Descending Pulmonary Artery Knuckles Sign: Abrupt tapering / termination of Vessels 3. Chest CT Scan: 60% Sensitivity; 97% Specificity Principal imaging Test for the Diagnosis of PE CT Scanners can image small peripheral emboli RV Enlargement on chest CT indicates a fivefold likelihood of death within the next 30 days compared with PE patients with Normal RV size on chest CT 4. V/Q Lung Scan (Lung Scanning) Segmental Perfusion defect with Normal Ventilation Key Diagnostic Test second-line diagnostic test for PE High Probability of PE: defined as 2 or more segmental perfusion defects in presence of Normal Ventilation 5. Magnetic Resonance (MR) Contrast Enhanced MR Venography is an excellent imaging modality to diagnose DVT 6. Echocardiography NOT a reliable diagnostic imaging tool for acute PE because most patients w/ PE have normal echocardiograms McConnells Sign: Hypokinesis of the RV Free Wall with Normal Motion of the RV Apex (which is the BestKnown Indirect Sign of PE) C. Invasive Diagnostic Modalities 1. Pulmonary Angiography: GOLD STANDARD Can detect as small as 1-2mm Embolus (+) Intraluminal Filling Defect in Pulmonary Circulation 2. Contrast Phelbography Venous Ultrasonography has virtually replaced contrast phlebography as the Diagnostic Test for suspected DVT IV. TREATMENT Give O2 at 2-4 lpm via NC; consider Intubation Embolectomy Thrombolytics A. Primary Therapy VS Secondary Prevention o Primary Therapy: consists of Clot Dissolution with Thrombolysis or removal of PE by Embolectomy o Secondary Prevention: Anticoagulation with Heparin & Warfarin or placement of an Inferior Vena Cava Filter B. Risk Stratification
ANTICOAGULATION OF VTE: 1. Immediate Parenteral Anticoagulation Unfractionated Heparin, Bolus and continuous infusion, to achieve aPTT 2-3 times the upper limit of the laboratory normal, or Enoxaparin 1mg/kg BID with normal renal function 2. Warfarin Anticoagulation Usual Start Dose is 5-10mg Titrate to INR, target 2.0 3.0 Continue parenteral anticoagulation for a minimum of 5 days and until 2 sequential INR values, at least 1 day apart, return in the target range

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C. Anticoagulation (Medicine Notes) o Foundation for successful treatment of DVT and PE o Immediately effective anticoagulation is initiated with a parenteral drug: UFH, LMWH, Fondaparinux o Parenteral drugs are continued as a transition or bridge to stable, long term anticoagulation with Warfarin (Vitamin-K Antagonist) Warfarin requires 5-7 days to achieve a therapeutic effect
Unfractionated Hepatin (UFH) Anticoagulates by binding to and accelerating the activity of Antithrombin III, thus preventing additional thrombus formation and permitting endogenous fibrinolytic mechanisms to lyse clots Achieve a Target aPTT 2-3 times the upper limit (~aPTT 60-80s)

5000-10,000 u IV bolus, then infusion of 1000-1500 u/h (maintain PTT 1.5-2.5x)

Low Molecular Weight Heparin (LMWH) Warfarin Ex) Initial Bolus of 80 units/kg, followed by initial infusion rate of 18 units/kg per hour Exhibit less binding to plasma proteins and endothelial cells No monitoring or dose adjustment needed Enoxaparin 1mg/kg BID and Tinzaparin 175 unigs/kg OD Vitamin-K Antagonist prevents carboxylation activation of Factors II, VII, IX, X Full effect requires 5 days, even if the Prothrombin Time becomes elevated more rapidly Overlapping UFH, LMWH, or Fondaparinus with Warfarin for at least 5 days can counteract the early procoagulant effect of unopposed warfarin Initiated at a dose of 5mg. Prothrombin is standardized with INR. Target INR = 2.5 (2.0 3.0) Warfarin 5-10mg PO 3 days before stopping heparin (maintain PT INR 2.0-3.0) continue for 3 months

**NOTE: Protamine Sulfate = Administer if there is Life-Threatening or Intracranial Hemorrhage due to UFH / LMWH
Duration of Hospital Stay: Acute PE Patients, who traditionally have required 5-7 day hospital stays for IV heparin as a bridge to warfarin, can be considered for abbreviated hospitalization if (+) excellent prognosis Duration of Anticoagulation: Patients with PE following surgery or trauma ordinarily have a low rate of recurrence after 3-6 months of anticoagulation.

D. Fibrinolysis o Successful fibrinolytic therapy rapidly reverses right heart failure o Thrombosis usually: Dissolves much of the anatomically obstructing pulmonary artery thrombus Prevents continued release of serotonin and other neurohormonal factors that exacerbate pulmonary hypertension Dissolves much of the source of thrombus in the pelvic or deep leg veins, thereby decreasing the likelihood of recurrent PE **IMPORTANT Notes: Preferred Fibrinolytic Regimen is 100mg of Recombinant Tissue Plasminogen Factor (tPA) on IV infusion over 2 hours E. Other Management: o Inferior Vena Caval (IVC) Filters Indications:
1) Active Bleeding that precludes anticoagulation 2) Recurrent Venous Thrombosis despite Intensive Anticoagulation

o o o o

Maintaining Adequate Circulation (for patients with Massive PE and Hypotension = 500-1,000mL normal saline) Pulmonary Embolectomy Pulmonary Thromboendarterectomy Emotional Support Prevention of Posphlebitic Synrdome (compression stockings)

V. PREVENTION (Medicine Notes)

Coumadine x 6 months IVC Filter (for patients with Absolute Contraindications to Anticoagulants) DVT Prophylaxis Compression Stockings and Pneumatic Compression Devices may complement mini-dose UFH, LMWH, a Pentasaccharide, or Warfarin Administration

VI. PREVENTION OF VENOUS THROMBOEMBOLISM

Prophylaxis for Medically Ill Patients: Mini-UFH or LMWH o Mini-UFH: 5000 units SC twice or three times a day o LMWH: Enoxaparin 40mg OD

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11) ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

I. DEFINITION A. Clinical Syndrome of: o Severe Dyspnea of rapid onset o Hypoxemia o Diffuse Pulmonary Infiltrates B. Definition: o Acute Onset o Bilateral infiltrates on CXR o PCWP < 18mmHf or Absence of LAH II. CAUSES OF ARDS
DIRECT LUNG INJURY Pneumonia Aspiration of Gastric Contents Pulmonary Contusion Near-Drowning Toxic Inhalation Injury INDIRECT LUNG INJURY Sepsis Severe Trauma Multiple Bone Fractures Flail Chest Head Trauma Burns Multiple Transfusions Drug Overdose Pancreatitis Post-Cardiopulmonary Bypass

III. ACUTE LUNG INJURY (ALI) VS ACUTE RESPIRATORY DISTRESS SYNDROME

OXYGENATION ALI ARDS PaO2 / FiO2 < 300mmHg PaO2 / FiO2 < 200mmHg ONSET Acute Acute CHEST XRAY Bilateral alveolar or interstitial infiltrates ABSENCE OF LEFT ATRIAL PRESURE PCWP < 18mmHg or No clinical evidence of Increased Left Atrial Pressure

IV. THREE PHASES OF ARDS Exudative (Day 0-7) Proliferative (Day 7-21) Fibrotic
Three Compartments in ARDS Lung: 1) Normally Aerated / Hyperaerated 2) Poorly Aerated (Ground Glass) 3) Non-Aerated (+) Shunting

Pathology: Severe Injury to the Alveolocapillary Unit: Alveolocapillary Leak Permeability Pulmonary Edema (Protein Rich Edema Fluid) Surfactant Disruption Hyaline Membrane Formation Alveolar Collapse, Consolidation Cellular Necrosis, Epithelial Hyperplasia, Inflammation Fibrosis

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V. MANAGEMENT OF ARDS
Some Notes: Mortality: mostly due to Sepsis or Multiple Organ Failure Primary Pulmonary cause / AHRF Causes < 20% of ARDS Mortality Impaired Lung Compliance = Hallmark of ARDS
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Goals in ARDS: Protective Mechanical Ventilation: To accomplish Effective Gas Exchange To minimize further Lung Damage & facilitate Healing Aim to PROTECT the Lung: Decrease Tidal Volume Give PEEP

A. Lung Protective Ventilation (LPV) 1. Avoid Alveolar Overdistention Low Tidal Volume (6-8mL/kg) Control Plateau Pressure to be below UIP 2. Use Sufficient PEEP To prevent significant Shearing or Cyclic Atelectasis to be above LIP 3. Permissive Hypercapnea This is a consequence of Low Tidal Volume (but we allow this) Beneficial effect of Permissive Hypercapnea is still controversial Safety of a very High PaCO2 is NOT proven Usually well-tolerated the ARDSNet used NaHCO3 when pH<7.3 aside from Increasing the Respiratory Rate Contraindications to Permissive Hypercapnea: Increased ICP Active Myocardial Ischemia Hypotension and/or Severe LV Failure with Catecholamine Dependence Pulmonary Hypertension with Acute RV Failure Severe Metabolic Acidosis B. Other Ventilatory Strategies: o Prone Positioning o Recruitment Maneuvers o Pressure VS Volume Limited Mode o High Frequency Ventilation o Inverse Ratio Ventilation o ECMO, Partial Liquid Ventilation o Spontaneous Breathing Trial

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12) RESPIRATORY FAILURE

A Condition in which the Respiratory System FAILS in one or both of its Gas Exchanging Functions Ie. Oxygenation of, and CO2 Elimination from Mixed Venous (Pulmonary Arterial) Blood Findings in Respiratory Failure: o HYPOXEMIA = PO2 < 60mmHg at Sea Level (inadequate blood oxygenation) o HYPERCARBIA = PCO2 > 45 mmHg (excess of circulating CO2)

I. ACUTE VS CHRONIC RESPIRATORY FAILURE A. Acute Respiratory Failure o SUDDEN o Leads to Life-Threatening Respiratory Insufficiency B. Chronic Respiratory Failure o Gradual WORSENING of Respiratory Function leads to Progressive Impairment of Gas Exchange o Metabolic Effects are PARTIALLY Compensated by Adaptations of other Systems II. CLASSIFICATION BASED ON ONSET AND CATEGORY A. Acute VS Chronic: 1. Hypercapneic Respiratory Failure = PaCO2 > 45mmHg (due to HYPOVENTILATION) a. Acute Develops in Minutes to Hours with ACIDEMIA (Ph < 7.3) There is Acute Respiratory Acidosis (Ph is LOW, and PCO2 is HIGH!) b. Chronic Develops over Several Days or Longer However, there may be Compensation in Chronic Respiratory Failure (Ph may even normalize) 2. Hypoxemia Respiratory Failure = PaO2 < 60mmHg when FiO2 > 0.60 a. Acute Develops in Minutes to Hours Ex) Severe Pneumonia **NOTE: FiO2 = Fraction of Inspired Oxygen (Oxygen delivered to the Patient) b. Chronic Develops over Several Days or Longer Ex) Milder Pneumonia
The Central & Peripheral Nervous Systems, Respiratory Muscles & Chest Wall and Airways constitute the RESPIRATORY PUMP: HYPERCAPNEA = Hallmark of Respiratory Pump Failure Hypoventilation Decreased VA Accumulation of CO2 & Respiratory Acidosis Just in comparison, we see Respiratory Alkalosis in people who Hyperventilate HYPOXEMIA constitutes the Primary Disturbances in ALVEOLAR Disturbances, producing Respiratory Failure Pulmonary Edema Pneumonia, etc

III. GENERAL CRITERIA FOR ACUTE RESPIRATORY FAILURE Patient is Acutely Dyspneic PaO2 < 60mmHg (Breathing Room Air) PaCO2 > 45mmHg Arterial Ph shows Significant Respiratory Acidemia (Acute) **NOTE: Many Patients with ARF do NOT Fulfill all FOUR Components of this Definition o MUST SHOW AT LEAST TWO OF THE FOUR CRITERIA o ABG is very Important in the Diagnosis

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IV. TYPES OF RESPIRATORY FAILURE A. TYPE 1: Acute Hypoxemic Respiratory Failure o Occurs when alveolar flooding and subsequent intrapulmonary shunt physiology occurs o Hypoxemia = PO2 < 60mmHg o Mechanism = Problem is in the Lungs itself o Etiology = Air Space Flooding (consequence of Pulmonary Edema, Pneumonia, Alveolar Hemorrhage) 1. Pulmonary Edema Cardiogenic (Increased Hydrostatic Pressure) Non-Cardiogenic (ARDS Secondary to an Acute Lung Injury) 2. Pneumonia In Pneumonia, there is Accumulation of Secretions in the Alveoli This leads to V/Q Abnormalities (Ventilation-Perfusion Mismatch) Decrease in Ventilation, therefore, there will be Hypoxemia 3. Lung Hemorrhage Ex) In a Vehicular Accident, there may be Pulmonary Contusion & Decreased Perfusion This leads to Hypoxemia and V/Q Mismatch 4. ARDS Defined by Diffuse Bilateral Airspace Edema seen by CXR, the absence of Left Atrial HPN, and profound shunt physiology Occurs in sepsis, gastric aspiration, pneumonia, near drowning, multiple BT, pancreatitis B. TYPE 2: Acute Hypoventilatory Respiratory Failure o Due to alveolar hypoventilation and results in the inability to eliminate CO 2 effectively o PCO2 > 45mmHg o Hypoventilation leads to a Problem in CO2 Elimination (Hypercarbia and Respiratory Acidosis) 1. Mechanism = Decreased Alveolar Ventilation (VA) there is Hypoventilation (RR < 10/min) Decrease in CNS Drive = Central Lesion Decrease Neuromuscular Coupling: Ex) Respiratory Muscle Fatigue Increased Load in Respiratory System: Ex) Bronchospasm in Asthma, COPD, Emphysema 2. Clinical Description a. Diminished CNS Drive: Drug Overdose, Brain Stem Injury Sleep disordered breathing Hypothyroidism b. Reduced Strength Impaired Neuromuscular Transmission (Myasthenia Gravis, GB Syndrome, Amyotrophic Lateral Sclerosis, Phrenic Nerve Injury) Respiratory Muscle Weakness (Myopathy, Electrolyte Derangements, Fatigue) c. Increased Overall Load in the Respiratory System: Increase in Resistive Loads Loads due to Reduced Lung Compliance Bronchospasm Alveolar Edema Atelectasis Intrinsic Positive and Expiratory Pressure Pneumothorax Pleural Effusion Abdominal Distention Pulmonary Embolus with Increased Dead Space Fraction, Sepsis

Loads due to Reduced Chest Wall Compliance

Loads due to Increased Minute Ventilation Requirements

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C. TYPE 3: Perioperative Respiratory Failure o Occurs as a result of Lung Atelectasis (occurs so commonly in the Perioperative Period) o Mechanism = ATELECTASIS o Etiology = Decreased Functional Residual Capacity (FRC) w/c lead to Collapse of Dependent Lung Units o Clinical Description (they cause a Decreased FRC) Supine Position / Obese Ascites (Difficulty in Lung Expansion) Upper Abdominal Incision General Anesthesia Airway Secretions D. TYPE 4: Shock o Mechanism = HYPOPERFUSION o Etiology: Cardiogenic, Hypovolemic, Septic o Clinical Description Myocardial Infarction (Cardiogenic Shock) Hemorrhage (Hypovolemic Shock) Dehydration (Hypovolemic Shock) Endotoxemia (Septic Shock)

12) COR PULMONALE

RV Enlargement 20 to a Disease process which Primarily involves the LUNGS, Pulmonary Vasculature, or Respiratory Gas Exchange o Acute: Pulmonary Thromboembolism o Chronic: Severe COPD o Acute on Chronic: COPD + Infection & Worsening Hypoxemia

I. SYMPTOMS / SIGNS A. Clinical Manifestations: o Acute (see Pulmonary Embolism) o Chronic: Productive Cough, Exertional Dyspnea, Easy Fatigability, Weakness B. Physical Examination: RV-Failure Signs o Neck Vein Engorgement o RV Heave o Increased O2 o Systolic Murmur (TR) o Hepatomegaly o Dependent Edema II. MANAGEMENT A. Diagnostics
12-L ECG CXR 2D Echo Tall, Peaked P Waves RAD with RVH Cardiomegaly, RV Form Enlarged Pulmonary Conus Diagnostic Allows measurement of RV Thickness VS LV

B. Management o Oxygen (Vasodilates Pulmonary Arteries, decreasing Resistance and Pulmonary Pressure) o Treat Infection, remove secretions o Diuretics (Caution in Loop Diuretics it causes Metabolic Alkalosis and Decreases Pulmonary Drive) o Bronchodilators (Theophylline)

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13) TYPICAL CHEST EXAMINATION FINDINGS:

CONDITION Normal Consolidation or Atelectasis (with Patent Airway) Consolidation or Atelectasis (with Blocked Airway) Asthma Interstitial Lung Disease Emphysema Pneumothorax Pleural Effusion PERCUSSION Resonant Dull Dull Resonant Resonant Hyperresonant Hyperresonant Dull FREMITUS Normal Increased Decreased Normal Normal Decreased Decreased Decreased BREATH SOUNDS Vesicular (at lung bases) Bronchial Decreased Vesicular Vesicular Decreased Decreased Decreased VOICE TRANSMISSION Normal Bronchophony, Whisphered Pectoriloquy, Egophony Decreased Normal Normal Decreased Decreased Decreased ADVENTITIOUS SOUNDS Absent Crackles Absent Wheezing Crackles Absent or Wheezing Absent Absent of Pleural Friction Rub

36

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Jaime Alfonso Manalo Aherrera, M.D.
Internal Medicine Notes 2009

COMMON RHEUMATOLOGIC CASES

1) SYSTEMIC LUPUS ERYTHEMATOSUS

Autoimmune Disease in which organs and cells undergo damage mediated by Tissue-Binding Autoantibodies and Immune Complexes

I. ACR CRITERIA FOR SLE Discoid Rash We ONLY need FOUR out of the ELEVEN to make a Oral Ulcers Diagnosis of SLE Photosensitivity Arthritis Malar Rash Immunologic Disorder Neurologic Disorder (Seizures, Headaches, Stroke, etc) Renal Disorder (Albuminuria, Hematuria, Pyuria, etc) Antinuclear Antibody Serositis Hematologic Disorder

CLASSIFICATION CRITERIA FOR THE DIAGNOSIS OF SLE (Harrisons):

CRITERIA Malar Rash Discoid Rash Photosensitivity Oral Ulcers Arthritis Serositis Renal Disorder Neurologic Disorder Hematologic Disorder Immunologic Disorder Antinuclear Antibodies REMARKS Fixed Erythema, Flat or Raised, over the Malar Eminences Erythematous Circular Raised Patches with Adherent Keratotic Scaling and Follicular Plugging; Atrophic Scarring may occur Exposure to Ultraviolet Light causes Rash Includes Oral and Nasopharyngeal Ulcers; observed by Physician Non-Erosive Arthritis of 2 or more Peripheral Joints, with Tenderness, Swelling or Effusion Pleuritis or Pericarditis documented by ECG or Rub or Evidence of Effusion Proteinuria > 0.5g/d or 3+, or Cellular Casts Seizures or Psychosis without other causes Hemolytic Anemia or Leukopenia; or Lymphopenia; or Thrombocytopenia in the absence of offending drugs Anti-ds DNA, Anti-Sm, and/or Anti-Phospholipid An Abnormal Titer of ANA by Immunofluorescence at any point in time in the absence of drugs known to induce ANAs

If > 4 of these Criteria, well documented, are present at any time in a patients history, the diagnosis is likely to be SLE (Specificity is ~95%; Sensitivity is ~75%)

II. CLINICAL FEATURES OF SLE Constitutional Fever, Fatigue, Weight Loss Mucocutaneous Musculoskeletal Gastrointestinal CNS Cardiovascular Discoid LE, Subacute Cutaneous LE, Panniculitis, Alopecia, Vasculitis Arthritis, Osteonecrosis, Inflammatory Myositis Pancreatitis, Bowel Vasculitis, Hepatitis Seizures, Psychosis Stroke Most Common Manifestations of Diffuse CNS Lupus = Cognitive Dysfunction Inflammation of all the Linings of the Heart: Pericarditis, Myocardial, Endocardial (Libman-Sacks Endocarditis), Accelerated Atherosclerosis, Raynauds Phenomenon Most Frequent Cardiac Manifestation = PERICARDITIS Pulmonary Pleuritis, Pneumonitis, Pulmonary Hemorrhage, Pulmonary Embolism, Pulmonary Hypertension Most Common Pulmonary Manifestation = PLEURITIS with or without Pleural Effusion May respond to NSAIDs if MILD Glucocorticoid Therapy if Severe Hemolytic Anemia, Leukopenia, Lymphopenia, Thrombocytopenia, Prolonged PTT Most Frequent Hematologic Manifestation = ANEMIA (Normochromic, Normocytic) Conjunctivitis, Uveitis, Scleritis, Retinitis Hypocomplementemia (Low C3 and C4 Levels), Elevated ESR and CRP Azotemia, Renal Failure, Hematuria, Albuminuria, Persistent Pyuria (not infection related) Nephritis = the Most SERIOUS manifestation of SLE Nephritis is usually ASYMPTOMATIC in Most Lupus Patients

Hematologic Eyes Laboratory Abnormalities Renal

III. METHYLPREDNISOLONE (rounds) MPPT: Methylprednisolone Pulse Therapy Drip Usually, dose is 500-1000mg 4-6 hours given 1 dose/day for 3 days (check harrisons) This therapy is given in patients with SLE in Activity: o Carditis o Nephritis o Anemia, Etc FROM HARRISONS: Methylprednisolone Sodium Succinate IV (approved for Lupus Nephritis): Used for SEVERE Disease at a Dose of 1g IV qd for 3 days

IV. MANAGEMENT OF SLE (Harrisons) A. Conservative Therapies for Management of Non-Life Threatening Disease o Sx: Fatigue, Pain, (+) Autoantibodies of SLE, but WITHOUT Major Organ Involvement o Management is directed to suppression of symptoms o Mainstay: Analgesics and Antimalarials 1. NSAIDs Useful analgesics / anti-inflammatories, particularly for arthritis / arthralgias TWO Major Issues CAUTION with NSAIDS SLE patients are at increased risk for NSAID-Induced Aseptic Meningitis, elevated serum transaminases, HPN, and renal dysfunction All NSAIDS (particularly COX-2 Inhibitors) may increase risk for MI 2. Antimalarials (Hydroxychloroquine, Chloroquine, Quinacrine) Reduce dermatitis, arthritis, fatigue Potential Retinal Toxicity B. Life Threatening SLE: Proliferative Forms of Lupus Nephritis o Mainstay for any Inflammatory Life-Threatening or Organ-Threatening Manifestations of SLE = SYSTEMIC GLUCOCORTICOIDS (0.5-2mg/kg per day PO or 1000mg of Methylprednisolone Sodium Succinate IV Daily for 3 days, followed by 0.5-1mg/kg of daily Prednisolone or equivalent o Evidence that glucocorticoid therapy is life-saving comes from studies survival is better in people with DPGN treated with high dose daily glucocorticoids (40-60mg Prednisone daily for 4-6 months) o Currently, high doses are recommended for much shorter periods (recent trials of interventions for severe SLE employ 4-6 weeks of these doses). Thereafter, doses are tapered as rapidly as the clinical situation permits (usually to a maintenance dose of 5-10 mg Prednisone V. MANAGEMENT OF SLE (from Medicine Notes)
For Arthritis For Active SLE (CNS, Renal, Hema) Diclofenac Na 50mg/tab BID Prednisone 5mg/tab PO 40-60mg/day, maintained on dose of 10-20mg MPPT 500-1000mg/am in D5W 50cc x 6h X 3 doses in 3 days (Severe SLE with Organ Damage) Cyclophosphamide 2-3mg/kg/day Cyclophosphamide IV Pulse Therapy 500-1000mg in D5W 500cc x 6h (give Metoclopromide 2 tabs before the drip) for life threatening SLE Sunscreens Hydrocortisone 200mg BID + Betamethasone 0.05% Ointment Coumadine PO

For Photosensitivity For Skin Lesions For Thrombosis

2) RHEUMATOID ARTHRITIS
Chronic multisystem disease of unknown cause systemic disease of unknown etiology Characteristic Features: Persistent Inflammatory Synovitis, usually involving Peripheral Joints in a Symmetric Distribution

I. CLINICAL MANIFESTATIONS Onset: RA is a chronic polyarthritis which begins insidiously with fatigue, anorexia, generalized weakness, and vague musculoskeletal symptoms until the appearance of Synovitis becomes apparent Specific symptoms usually appear gradually as several joints, especially those of hands, wrists, knees, and feet, become affected in a Symmetric Fashion Signs and Symptoms: Pain, Swelling, and Tenderness PAIN in affected joint, aggravated by movement, is the Most Common Manifestation of established RA Generalized Stiffness, usually greatest after periods of Inactivity, Morning Stiffness of > 1 hour duration II. LABORATORY FINDINGS Rheumatoid Factors (RF): Autoantibodies Reactive with the Fc Portion of IgG found in more than 2/3 of adults with the disease and have classically been used to evaluate patients with RA Normochromic, Normocytic Anemia is frequently present in Active RA ESR is increased in nearly all patients with Active RA Synovial Fluid Analysis: presence of Inflammatory Arthritis
Labs Requested for RA: ERC / CRP RF CBC Renal ALT (for MTX Therapy) Urinalysis Synovial Fluid Analysis

III. CRITERIA FOR THE DIAGNOSIS A. Guidelines for Classification: o Four of Seven Criteria are required to classify a patient as having Rheumatoid Arthritis (RA) o Patients with Two or More Clinical Diagnoses are NOT Excluded

B. Criteria o a) Morning Stiffness: Stiffness in and around the joints lasting 1 hour before Maximal Improvement o b) Arthritis of Three or More Joint Areas: At least 3 Joint Areas, observed by a physician simultaneously, have Soft Tissue Swelling or Joint Effusions, not just bony overgrowth. The 14 possible joint areas involved are right or left proximal interphalangeal, metacarpophalangeal, wrist, elbow, knee, ankle, and metatarsophalangeal joints o c) Arthritis of Hand Joints: Arthritis of Wrist, Metacarpophalangeal Joint, or Proximal Interphalangeal Joint o d) Symmetric Arthritis: Simultaneous involvement of the same joint areas on BOTH sides of the body o e) Rheumatoid Nodules: Subcutaneous Nodules over bony prominences, extensor surfaces, or juxtaarticular regions observed by a physician o f) Serum Rheumatoid Factor: Demonstration of abnormal amounts of Serum Rheumatoid Factor by any method for which the result has been positive in less than 5% of normal control subjects o g) Radiographic changes: Typical changes of RA on Posteroanterior Hand and Wrist radiographs that must include erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints
Criteria a-d must be present for at least 6 weeks. Criteria b-e must be observed by a physician

IV. THERAPY GOALS 1) Relief of Pain 2) Reduction of Inflammation 3) Protection of Articular Structures 4) Maintenance of Function 5) Control of Systemic Involvement

Medical Management: NSAIDs or Selective COX-2 Inhibitors Glucocorticoids for: o 1) Symptomatic relief while waiting for a response to a slow-acting immunosuppressive or immunomodulatory agent o 2) Persistent Synovitis despite adequate trials of NSAIDs and immunosuppressive or immunomodulatory agents o 3) Severe constitutional symptoms (fever, weight loss) or extraarticular disease (vasculitis, episcleritis, pleurisy) Immunomodulatory and Immunosuppressive Agents o Methotrexate (initial choice for moderate to severe RA) o Hydroxychloroquine or Sulfasalazine

3) INFECTIOUS ARTHRITIS
Staphylococcus aureus, Neisseria gonorrhoeae, and other bacteria are the MOST COMMON Causes of Infectious Arthritis (various Mycobacteria, Spirochetes, Fungi, and Viruses also infect joints) Acute Bacterial Infection typically involves a Single Joint or a Few Joints Subacute or Chronic Monoarthritis or Oligoarthritis suggests Mycobacterial or Fungal Infection Approach to Patients with Infectious Arthritis: o ASPIRATION of SYNOVIAL FLUID an essential element in the evaluation of potentially infected joints o Ultrasonography or Fluoroscopy may be used to guide aspiration of difficult to localize effusions
Normal Synovial Fluid Acute Bacterial Infections Crystal Induced, Rheumatoid, and other Non Infectious Inflammatory Arthritides Mycobacterial and Fungal Contains < 180 Cells (predominantly Mononuclear Cells) Cell Counts averaging 100,000/uL (25,000-250,000/uL) with > 90% Neutrophils < 30,000-50,000 cells/uL 10,000-30,000/uL with 50-70% Neutrophils & the remainder Lymphocytes

**NOTE: Definitive Diagnosis of Infectious Process: o Identification of Pathogen in Stained Smears of Synovial Fluid o Isolation of Pathogen from Cultures of Synovial Fluid and Blood o Detection of Microbial Nucleic Acids and Proteins by PCR-Based Assays and Immunologic Techniques I. ACUTE BACTERIAL ARTHRITIS A. Pathogenesis o Bacteria enter the joint from the bloodstream; from a contiguous site of infection in bone or soft tissue; or by direct inoculation during surgery, injection, animal or human bite, or trauma o Hematogenous Route: Most Common Route in all age groups B. Microbiology o Infants: Group-B Strep, Gram (-) Enteric Bacilli, and S. aureus o Young Adults & Adolescents: N. gonorrhea (most commonly implicated organism) o S.aureus accounts for most Non-Gonococcal Isolates in Adults of all ages
Infectious Arthritis is generally categorized into Gonogoccal and Nongonococcal Disease. Usual presentation is with fever and an acute monoarticular arthritis, although multiple joints may be affected by hematogenous spread of pathogens Nongonococcal Infectious Arthritis in adults tends to occur in patients with previous joint damage or compromised host defenses. In contrast, Gonococcal Arthritis causes one-half of all septic arthritis in otherwise healthy, sexually active young adults General Principles of Treatment: 1. Joint Fluid Examination Includes Gram Stain and Culture mandatory to make a diagnosis and to guide management Joint Fluid Leukocyte Count: useful diagnostically and as a baseline Cultures of Blood and other extra-articular sites of infection also should be obtained 2. Hospitalization Indicated to ensure drug compliance and careful monitoring 3. IV Antimicrobials Provide good serum and synovial fluid drug concentrations Oral or Intra-Articular Antimicrobials are NOT appropriate as initial therapy 4. Repeated Arthrocenteses Should be performed daily or as often as necessary to prevent reaccumulation of fluid Arthrocentesis is indicated to: o 1) Remove destructive inflammatory mediators o 2) Reduce intra-articular pressure and promote antimicrobial penetration into the joint o 3) Monitor response to therapy by documenting sterility of synovial fluid cultures & decreasing Leukocyte Count 5. Surgical Drainage or Arthroscopic Lavage & Drainage Indications: 1) Septic Hip 2) Joints in which either the anatomy, large amounts of tissue debris, or loculation of pus prevent adequate needle drainage 3) Septic Arthritis with coexistent Osteomyelitis 4) Joints that do not respond in 4-6 days to appropriate Tx and repeated arthrocenteses 5) Prosthetic joint infection

II. NON-GONOCOCCAL BACTERIAL ARTHRITIS 90% present with involvement of a Single Joint most commonly the KNEES (less frequently the hip) (+) Moderate to Severe Pain that is uniform around the joint, effusion, muscle spasm, and decreased range of motion (+) Fever 38.3 38.90C Inflamed, Swollen Joint Cellulitis, Bursitis, and Acute Osteomyelitis, which may produce a similar clinical picture, should be distinguished from Septic Arthritis by their greater range of motion and less-than-circumferential swelling Labs: (+) Blood Cultures in 50-70% of S.aureus infections, Synovial Fluid is turbid, serosanguinous, or frankly purulent, Gram smears confirm presence of large numbers of Neutrophils Total Protein and Lactate Dehydrogenase in synovial fluid are elevated; Glucose Level is Depressed
Synovial Fluid Turbid WBC Count > 100,000 1. On Gram Stain: Gram (+) = we will see 65-75% Staph / Strep In 30-50%, we will have NOTHING on Gram Stain (dont automatically rule this out) Gram (-) Bacilli = 30-50% 2. Culture of Synovial Fluuid: > 90% Culture (+) for Staphylococcus aureus Blood CS will be (+) 50% for Staph Elevated with a Leftward Shift ESR / CRP = HIGH 1. Early Infection Soft Tissue Swelling Joint Space Widening 2. Late Infection Bone Erosions Joint Space Narrowing

Culture other Fluids Peripheral WBC Acute Phase Reactants X-Ray of the Joint

III. GONOCOCCAL ARTHRITIS Accounted for up to 70% of Infectious Arthritis Consequence of Bacteremia arising from Gonococcal Infection or, more frequently, from asymptomatic gonococcal mucosal colonization of the Urethra, Cervix, or Pharynx A. Diffuse Gonococcal Infection (DGI) o Most Common Manifestation: Fever, Chills, Rash, and Articular Symptoms. Small numbers of papules that progress to hemorrhagic pustules develop on the trunk and the extensor surfaces of the distal extremities o Migratory Arthritis and Tenosynovitis of the knees, hands, wrists, feet, and ankles are prominent o Cutaneous Lesions and Articular Findings = due to immune reaction to circulating gonococci and immune complex deposition in tissues o Cultures of Synovial Fluid are consistently NEGATIVE, and Blood Cultures are Positive in < 45% o Synovial Fluid may be difficult to obtain from inflamed joints, and usually contains only 10,000-20,000 leukocytes/uL B. True Gonococcal Septic Arthritis o True Gonococcal Septic Arthritis is LESS Common than the Diffuse Gonococcal Infection (DGI) Syndrome and always follows DGI, which is unrecognized in 1/3 of patients o A single joint (hip, knee, ankle, or wrist) is usually involved o Synovial Fluid has > 50,000 leukocytes/uL and can be obtained with ease o Gonococcus is only occasionally evident in Gram-Stained Smears o Cultures of Synovial Fluid are Positive in < 40% of cases o Blood Cultures are almost always Negative

IV. DIAGNOSIS Difficulty in isolation of Gonococci from Synovial Fluid and Blood Specimens for culture should be obtained from potentially infected mucosal sites Cultures and Gram-Stained Smears of Skin Lesions are occasionally Positive All specimens for culture should be plated onto Thayer-Martin Agar directly or in special transport media at the bedside and transferred promptly to the microbiology laboratory in an atmosphere of 5% CO 2, as generated in a candle jar V. TREATMENT A. Non-Gonococcal Septic Arthritis

EMPIRICAL
1. Gram (+) in Smear Oxacillin or Nafcillin 2g q4h 2. Gram (-) in Smear Cefotaxime 1g q 8h Ceftriaxine 1-2g q 24h 3. Suspect Pseudomonas Add Aminoglycoside; or 3rd Generation Cephalosporin 1. Staphylococcus: 4 Weeks

DURATION
2. Penicillin Sensitive Pneumo / Strep: 2 Weeks on Penicillin-G 2m u q4h 3. Penicillin-Resistant Cefotaxime / Ceftriaxone for 2 Weeks 4. Enteric Gram (-) 3-4 Weeks 2nd /3rd Generation Cephalosporin IV; or Quinolone IV/PO 5. Pseudomonas At Least 2 Weeks

B. Gonococcal Septic Arthritis o CEFTRIAXONE 1g IV or IM q 24 h: 7 days If with Resolution and if Isolate Sensitive 7 day additional Ciprofloxacin 500mg bid po
Ceftriaxone (1g IV or IM every 24 hours) to cover possible Penicillin-Resistant Organisms. Once local and systemic signs are resolving, the 7-day course of Tx can be completed with an oral agent such as Ciprofloxacin (500mg BID)

4) OSTEOARTHRITIS
OA or Degenerative Joint Disease characterized by deterioration of articular cartilage, with subsequent formation of reactive new bone at the articular surface

I. MEDICAL MANAGEMENT: Objectives = Relief of Pain + Prevention of Disability Acetaminophen (dose up to 1000mg up to QID) initial pharmacologic treatment Low-Dose NSAIDs or Selective COX-2 Inhibitors Glucosamine Sulfate 1500mg/day Intra-Articular Glucocorticoid Injections Tramadol Topical Capsaicin II. ADJUNCTIVE MEASURES: Non-Pharmacological Measures Brief periods of rest for the involved joint relieve pain

5) GOUTY ARTHRITIS
90% due to Uric Acid UNDER Excretion 10% due to Uric Acid OVER Production Ex) Beer BOTH Under and Over!

More on Rheumatologic Diseases: Algorithm for the Diagnosis of Musculoskeletal Complaints: Sites of Hand or Wrist Involvement & Diseases

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Definition of Terms: A Palpable (less commonly audible) vibratory or Crepitus crackling sensation elicited with joint motion Alteration of joint alignment such that articulating Subluxation surfaces incompletely approximate each other Abnormal displacement of articulating surfaces such that Dislocation the surfaces are not in contact For diarthrodial joints, the arc of measurable movement Range of through which the joint moves in a single plane Motion Loss of full movement, resulting from a fixed resistance Contracture caused either by tonic spasm of muscle (reversible) or to fibrosis of periarticular structures (permanent) Abnormal shape or size of a structure; may result from Deformity bony hypertrophy, malalignment of articulating structures, or damage to periarticular supportive structures Inflammation of the entheses (tendinous or ligamentous Enthesitis insertions on bone) Epicondilytis Infection or Inflammation involving an Epicondyle

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