Blood Gas Analysis

Acids and bases

An acid is defined as any compound, which forms hydrogen ions in solution ("proton donors). An acid that entirely dissociated is said = strong acid i.e. : HCl An acid that partially dissociated is said = weak acid i.e. : phosphoric acid A base is a compound that combines with hydrogen ions in solution ("proton acceptors). A base that entirely dissociated is said = strong base i.e. : NaOH An base that partially dissociated is said = weak base i.e. : bicarbonate (conjugate base)

pH = Log10[H+]
pH : potenz (power) of Hydrogen Peter Sorensen (1909, Denmark) Negative Log Hydrogen ion concentration Wasserstoffionen exponent (Jerman)

[H+] (moles/liter) 0.1 0.01 0.001 0.0001 0.00001 0.000001 0.0000001

[H+] (moles/liter) 10-1 10-2 10-3 10-4 10-5 10-6 10-7

pH 1 2 3 4 5 6 7

0.00000001
0.000000001 0.0000000001 0.00000000001 0.000000000001 0.0000000000001 0.00000000000001

10-8
10-9 10-10 10-11 10-12 10-13 10-14

8
9 10 11 12 13 14

The regulation of the internal environment includes the regulation of the body fluid hydrogen ion concentration, [H+] Although [H+] is very small compared to most solutes, being around 107 equ/liter, it has marked effects on an important part of the body machinery - enzymes.
An introduction to acid-base balance, Watson Philip D., 2004

Neutral pH
7.40 (7.35-7.45) Extracellular fluid: 7.4 Intracellular: 7.0-7.2 Viable range: 6.80 - 7.80

Acid-base balance
Acid-base balance refers to the mechanisms the body uses to keep its fluids close to neutral pH so that the body can function normally

Production of Hydrogen Ions

Two groups of important acids : Carbonic acid (H2CO3) and Non carbonic acid Carbonic acid (volatile acids) from CHO and fat metabolism; 15,000 mmol of CO2/day, mostly handled by respiration. Non carbonic acid (non-volatile acids) from protein metabolism; 1.0-1.5 mmol H+/day/kg; captured in the form of H2SO4, H2PO4, etc., and excreted by the kidneys. Normal [H+] is ~40 nanomol/L (<<< [Na+] and [Cl-] in plasma); if [H+] increase, it binds proteins and changes their function Ingested nonsignificant contribution to the body's hydrogen

Control of [H+] Ion Concentration

Excretion of CO2 by the lungs Blood and tissue buffering

Renal excretion of H+ and regeneration of HCO3-

Excretion of CO2 by the lungs

H+ + HCO3H2CO3 CO2 + H2O LUNGS

In plasma, there is very little CO2 in the form of carbonate (CO3 ) and carbonic acid Nearly all the CO2 is in the bicarbonate form The control of PCO2 level necessitates either excretion or retention of CO2 by the lungs The respiratory system can produce rapid compensation for changes in pH by altering the level of PaCO2

Buffering
The ability to reduce the magnitude of changes in [H+] by binding or releasing [H+]

Blood and tissue buffering

a)Bicarbonate The most important buffer system; CO2 removed by the lungs and bicarbonate regenerated by the kidney b)Proteins Contain weak acidic and basic groups within their structure; plasma proteins form important buffering systems; intracellular proteins limit pH changes within cells; protein matrix of bone buffer hydrogen ions in chronic acidosis c)Haemoglobin Haemoglobin (Hb) carriage of O2 but also transport of CO2 and buffering hydrogen ions

CO2 + H2O H2CO3 H+ + HCO3- H+ + CO3=

Plasma has a [HCO3-] of approximately 24 meq/l and [H2CO3] of 1.2meq/l pH = 6.1 + log 20 = 1

7.4

If 1.2meq HCl is added to 1 litre of a solution of 24meq NaHCO2 in water, 1.2meq HCO3- will be converted to H2CO3

If the H2CO3 is held constant 1.2meq HCl causes the [HCO3- ] to diminish by 1.2meq but the H2CO3 level remains constant at 1.2meq/l

Renal [HCO3-] reabsorption and regeneration

Bicarbonate filtered/day = 4520 mmol Proximal tubule is major site of reabsorption (75-90% of the filtered load); the remaining 10-25% is reabsorbed in distal tubule; generation of new HCO3- : 1.0 - 1.5 mmol/kg/day Principle mechanism of HCO3- reabsorption is with Na+; requires: Na+/K+ ATPase, Na+/H antiport, carbonic anhydrase and glutamine generation and luminal carbonic anhydrase Urine bicarbonate free (if pH is < 5.8, it is free of HCO3-); urine pH is ~5.0 - 5.5 due to acid secreted into urine

Abnormal acid-base balance

Acidosis is a state of excess H+ Acidemia results when the blood pH<7.35 Alkalosis is a state of excess HCO3Alkalemia results when the blood pH>7.45

The Traditional Approach

The Henderson-Hasselbalch equation A H+ + B[H+] [B-] =Q [A] [H+] [B-] [A] = K [H+] = K [A] [B-] log [H+] [A] = log K + log [B-] pX = - log X = log 1 X - pH = - pK - log [A] [B-] [B-] pH = pK + log [A]

Control of HCO3- is assumed to be a primary parameter

CO2 + H2O H2CO3 H+ + HCO3- H+ + CO3=

[HCO3-] pH = pK + log [H2CO3] [HCO3-] pH = pK + log [0.03 x PCO2] Plasma has a [HCO3-] of approximately 24meq/l and [H2CO3] of 1.2meq/l pH = 6.1 + log 20 1 pH = 7.4

The Anion Gap

The difference between major plasma cations and major plasma anions : [Na+] - [Cl-] - [HCO3] Anion Gap = 140-105-25 = 10 If chloride is reduced to 95 meq/l, bicarbonate would be increased to 35.6; Anion gap = 140-9535.6 = 9.4 If lactic acid is increased from its normal 1 meq/l to 10 meq/l, bicarbonate would fall to 18 meq/l; Anion gap = 140-105-18 = 17 Any strong acid will increase the anion gap by reducing the bicarbonate Some people include potassium in the anion gap : [Na+] + [K+] - [ClG] - [HCO3]; the normal value = 14

Classification of acid-base defect

(Henderson-Hasselbalch)
Plasma pH
Low

Acid-base imbalance Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis

Primary Compensation disturbance

increased pCO2 increased renal net acid excretion with resulting increase in serum bicarbonate decreased renal net acid excretion with resulting decrease in serum bicarbonate hyperventilation with resulting low pCO2 hypoventilation with resulting increase in pCO2

High

decreased pCO2 decreased HCO3increased HCO3-

Low
High

Techniques for measuring pH status

pH electrode, Blood sampling Astrup Method pH and PCO2 Electrode Systems

Acid-Base Diagram

From Goldberg, M., Green, S.B., Moss, M.L., et al.: JAMA 223:269-275, 1973

Arterial Blood Gas (ABG) Interpretation

Does the patient have an acidosis or an alkalosis? What is the primary problem metabolic or respiratory? Is there any compensation? (respiratory compensation is immediate while renal compensation takes time)

Summary of ABG Interpretation

pH
7.35 to 7.45
< 7.35 > 7.45 < 7.35 > 44

paCO2 HCO3 ( mm Hg) (meq/L)

36 to 44 22 to 26 Normal
Acidosis Alkalosis

Interpretation

22 to 26 Respiratory acidosis

< 7.35
< 7.35 > 7.45 > 7.45

36 to 44
> 44 < 36 36 to 44

< 22
< 22 > 26

Metabolic acidosis Mixed acidosis Metabolic alkalosis Mixed alkalosis Compensated respiratory acidosis

22 to 26 Respiratory alkalosis

> 7.45
closer to 7.35 closer to 7.35 closer to 7.45

< 36
> 44 < 36 < 36

> 26
> 26 < 22 < 22

Compensated metabolic acidosis

Compensated respiratory alkalosis Compensated metabolic alkalosis

closer to 7.45

> 44

> 26

Clinical condition of AB disturbances

Acute: airway obstruction, severe pneumonia, chest trauma/ pneumo-thorax; Drug intoxication (narcotics, sedatives); Respiratory NaHCO2 therapy; Neuromuscular blockade; head trauma. Acidosis Chronic: BPD, COPD; Neuromuscular disease; Extreme obesity; Chest wall deformity; Increased production of CO2. Pain; Anxiety; Hysterical hyperventilation; Restrictive lung disease; Severe CHF; Pulmonary emboli; Drugs; Sepsis; Respiratory Fever; Thyrotoxicosis; Induced hyperventilation during Alkalosis anaesthesia; Overaggressive mechanical ventilation; Hepatic failure; Some types of CNS damage. Elevated Anion Gap: Ketoacidosis-diabetic; Alcoholic; Starvation; Lactic acidosis-hypoxia; Shock; Sepsis; Seizures; Toxic ingestion (salicylates, methanol, ethylene glycol, ethanol, isopropyl alcohol, paraldehyde, toluene); Renal failureuremia. Normal Anion Gap: RTA; Hypoaldosteronism; Potassium sparing diuretics; Pancreatic loss of bicarbonate; Diarrhea; Carbonic anhydrase inhibitors; Acid administration (HCl, NH4Cl, arginine HCl); Cholestyramine. Loss of gastric juice; Diuretic alkalosis; Ingestion or injection of excess base; Steroid alkalosis.

Metabolic Acidosis

Metabolic Alkalosis

Effectiveness of Oxygenation
Further evaluation of the arterial blood gas requires assessment of the effectiveness of oxygenation of the blood Hypoxemia decreased oxygen content of blood - paO2 less than 60 mm Hg and the saturation is less than 90% Hypoxia inadequate amount of oxygen available to or used by tissues for metabolic needs

Mechanisms of Hypoxemia
Inadequate inspiratory partial pressure of oxygen Hypoventilation Right to left shunt Ventilation-perfusion mismatch Incomplete diffusion equilibrium

Assessment of Gas Exchange

Alveolar-arterial O2 tension difference A-a gradient PAO2-PaO2 PAO2 = FIO2(PB - PH2O) - PaCO2/RQ* Arterial-Alveolar O2 tension ratio PaO2/PAO2 Arterial-inspired O2 ratio PaO2/FIO2 P/F ratio
*RQ=respiratory quotient= 0.8

Assessment of Gas Exchange

ABG A-a grad

PaO2
Low FIO2 Alveolar hypoventilation Altered gas exchange Regional V/Q mismatch Intrapulmonary R to L shunt Impaired diffusion Anatomical R to L shunt (intrapulmonary or intracardiac)
N=normal

PaCO2
/N/ N/ N/ N/

RA
N N

100%
N N N/ N

Stewart Approach

How to understand acid-base

A quantitative Acid-Base Primer for Biology and Medicine Peter A. Stewart, Edward Arnold, London 1981

The independent and dependent factors or variables

Independent Variables
Strong Ion Difference

Dependent Variables Chemistry

Law of Mass Action Charge Balance etc.

PCO2

pH [HCO3-] Etc.

Protein Concentration

Ions
Strong ions (entirely dissociated)
Kation : Na+,K+,Mg+,Ca++ Anion : Cl-,SO4-,PO4=, laktat-, keto-

Weak ions (partially dissociated)

Albumin-, Posfat-, HCO3-

Independent variables
Strong ion difference
pCO2
(Na+ + K+ + Mg2+ + Ca2+) (Cl + lactate)
H2O + CO2 H2CO3 H+ + HCO3

Weak acids/ ATOT A + AH proteins

Ion

Concentration (meq/L) Sodium 140 Potassium 4 Calcium 3 Magnesium 1 Total strong Cations 148 Chloride 104 Lactate 8 Total strong anions 112 Difference (Cations - Anions) 36
Concentration (meq/L) 36 6.6 x 10-10 12.2 36

Concentration (meq/L) SID 36 pCO2 (mmHg) 40 ] [HCO3 35.8 +] [H 27 x 10-6 pH 7.6 [OH] microEq/L <1

Concentration (meq/L) SID 36 pCO2 (mmHg) 40 Protein 11.4 ] [HCO3 26 [H+] 40 x 10-9 pH 7.4

SID [H+] pH [OH-]

Effects of strong ions alone

Strong ions and CO2

Independent and dependent variables in normal plasma

Computer program, Watson (AcidBasics II)

Classification of Primary Acid-Base Disturbances

Acidosis Alkalosis

I. Respiratory
II. Nonrespiratory (metabolic) 1. Abnormal SID a. Water excess/deficit*

PCO2

PCO2

SID, [Na+] SID, [Na+] SID, [Cl-] SID, [Cl-] [Alb] [Pi]

b. Imbalance of strong anions

i. Chloride excess/ deficit 2. Nonvolatile weak acids a. Serum albumin b. Inorganic phosphate [Alb] [Pi] ii. Unidentified anion excess SID, [XA-]

Fencl, Jabor, Kazda, et al.: Metabolic Acid-Base Disturbances, American Journal Of Respiratory and Critical Care Medicine Vol 162 2000

Disturbances
Lactic acidosis Keto acidosis Vomiting Diarrhea Renal failure

Strong Ion Difference

Heart failure Lung disease Hyperventilation Hypoventilation

PCO2

Chemistry
Law of Mass Action Charge Balance etc.

pH [HCO3-] Etc.

Protein Concentration
Malnutrition Dehydration Nephrotic syndrome

Clinical condition and independent variables

Vomiting Vomiting deplete Cl faster than the cations; SID increases = metabolic alkalosis; Kidney compensate by a decreased excretion of Cl, returns plasma SID towards normal The electrolytes lost and the subsequent acidbase disturbance depends upon the site and nature of the disease, SID can move in either direction Direct effects on PCO2 Effects PCO2 and SID (poor tissue perfusion can cause lactate production) Increases plasma protein concentration Cause significant decreases in serum albumin concentration

Diarrhea Lung disease and ventilation rate Heart failure Dehydration Malnutrition and nephrotic syndrome