Approach to a patient with JAUNDICE

Group A9 Cho, Chua Family, Co Family, Cofreros *THIS IS THE LO-FI VERSION. Background omitted for user friendly printing ^_^* ~KC

General Data

Patient
Name: C.T. Age: 45 years old Gender: female Status: married Occupation: bank teller from Las Pias

Chief Complaint

YELLOWISH DISCOLORATION OF SKIN

History of Present Illness

One month PTC Bearable intermittent colicky right upper quadrant pain radiating to the back, not related to food intake No other accompanying symptoms No medication taken

Husband noted yellowish discoloration of skin One week PTC Passage of tea colored urine Passage of light colored stools Intense puritus No fever Persistence of symptoms

Review of Systems
(-) significant change in weight (-) loss of consciousness, (-) headache (-) blurring of vision (-) ear discharge, (-) tinnitus (-) cough, (-) difficulty of breathing (-) chest pain, (-) palpitation

Review of Systems
(-) dysuria, (-) frequency, (-) urgency, (-) pollakiuria (-) hematemesis, (-) melena, (-) hematochezia (-) joint pains (-) polyuria, (-) polydipsia, (-) polyphagia (-) heat or cold intolerance

Personal History
Non smoker Non alcoholic beverage drinker

Usual diet

Past Medical History

No other medical or surgical illness requiring hospitalization No history of blood transfusion

Immunizations

Family History
(-) HPN (-) DM (-) Cancer (-) PUD

Obstetric and Gynecologic History

G2P2 (2002) Menarche: 13 years old LMP: August 20-25, 2007 PMP: July 19-24, 2007 No dysmenorrhea Regular menstruation
Estrogens stimulate hepatic lipoprotein receptors, increase uptake of dietary cholesterol, and increase biliary cholesterol secretion lead to decreased bile salt secretion and decreased conversion of cholesterol to cholesteryl esters
Fauci, Anthony, Et. al., eds. Harrison's Principles of Internal Medicine. 17th ed. US: McGraw-Hill, 2008

Physical Examination

General Survey
Conscious Coherent Obese Oriented as to time, place, and person

Vital Signs
BP 110/80 CR 80 regular PR 80 regular RR 19 Temp 37oC Height 1.5m Weight 70kg BMI 31 (Class I obesity)

Skin
No skin rashes, jaundiced

HEENT
Pink palpebral conjunctivae, icteric sclerae No nasal nor aural discharge, icteric frenulum

Neck
Thyroid gland not enlarged, supple neck, no palpable cervical lymphadenopathy

Respiratory
Symmetrical chest expansion Resonant Unimpaired transmission of vocal and tactile fremiti Clear breath sounds

Cardiovascular
Adynamic precordium Apex beat at 5th LICS, MCL at the apex, loud S1 followed by soft S2 at the base, soft S1 followed by loud S2 No heaves, no lifts, no thrills, no murmurs Pulse +2 on all extremities

Gastrointestinal
Abdomen flabby Tympanitic Normoactive bowel sounds (+) Murphys sign Liver and spleen not palpable
Murphys sign a sign of inflammation of the gallbladder: continuous pressure over the gallbladder while the patient is taking a deep breath will cause a catch in the breath at the point of maximum inhalation [JB Murphy (1857-1916), US surgeon] The Bantam Medical Dictionary. 5th ed. New York, NY: Bantam Dell, 2004.

Rectum
No skin tags No fissures Tight sphincteric tone No pararectal tenderness No pararectal masses Light colored stool on examining finger

*Missing PE Findings
Breast and axillae Genitourinary Musculoskeletal Neurologic

Salient Features

Salient Features
Pertinent Positive
45 years old, female, bank teller Yellowish discoloration of skin Bearable intermittent colicky RUQ pain radiating to the back Passage of tea colored urine, light colored stools Intense pruritus Regular menstruation, G2P2

Salient Features
Pertinent Positive
Obese, BMI 31 Icteric sclerae Icteric frenulum (+) Murphys sign Light colored stool on examining finger

Salient Features
Pertinent Negative
No Fever No significant change in weight Liver and spleen not palpable

Definition of Terms
Jaundice Carotenemia / Carotenoderma Murphys Sign

What is Jaundice?
Icterus; a yellowing of the skin or sclerae, indicating excess bilirubin (a bile pigment)
Scleral icterus indicates a serum bilirubin of at least 51 umol/L (3.0 mg/dL) a medical condition in which there is yellowing of the whites of the eyes, skin, and mucous membranes, caused by bile pigments in the blood It is a symptom of liver diseases such as hepatitis and cirrhosis, or of a blocked bile duct
Microsoft Encarta 2007. 1993-2006 Microsoft Corporation. All rights reserved. Fauci, Anthony, Et. al., eds. Harrison's Principles of Internal Medicine. 17th ed. US: McGraw-Hill, 2008
26

What is Carotenoderma?
Carotenosis cutis; harmless reversible yellow coloration of the skin caused by carotenemia (due to increased ingestion of carotene eg. carrots) Concentrated on the palms, soles, forehead and nasolabial folds Occasionally, it can cause a yellowish discoloration of the skin, resembling a mild jaundice True jaundice = icteric sclerae Carotenoderma = anicteric sclerae
The New American Medical Dictionary and Health Manual 7th Edition by Robert E. Anthony, Et. al., eds. Harrison's Principles of Internal Medicine. 17th ed. Rothenberg M.D., F.A.C.S. Fauci, US: McGraw-Hill, 2008
27

What is Murphys Sign?

a sign of inflammation of the gallbladder pain on palpation of the right subcostal area during inspiration, frequently associated with acute cholecystitis or any inflammation of the gallbladder [JB Murphy (1857-1916), US surgeon]
The Bantam Medical Dictionary. 5th ed. New York, NY: Bantam Dell, 2004.
28

Pathophysiology

M E T A B O L I S M O F B I L IR U B I N
hemoglobin of senescent red blood cells
Heme Iron Biliverdin Globin Unconjugated Bilirubin
Conjugates with glucuronic acid in hepatocytes

Conjugated bilirubin (bile)

90% Enterohepatic circulation
Coverted by intestinal flora

Excreted by the kidneys

10%

urobilinogen
oxidation

Stercobilin (feces)

Prehepatic Jaundice

Intrahepatic/Parenchymal Jaundice

Posthepatic/Obstructive Jaundice

 Classification of Jaundice Based on Underlying Derangement of Bilirubin Metabolism

Unconjugated Hyperbilirubinemia Conjugated Hyperbilirubinemia

Unconjugated Hyperbilirubinemia
OVERPRODUCTION Hemolysis Ineffective Erythropoiesis DECREASED HEPATIC UPTAKE Prolonged Fasting Sepsis DECREASED BILIRUBIN CONJUGATION Hereditary Transferase Deficiency Acquired Transferase Deficiency

Conjugated Hyperbilirubinemia
IMPAIRED HEPATIC EXCRETION
Hereditary Disorders Recurrent (benign) Intrahepatic Cholestasis Cholestatic Jaundice of pregnancy Hepatocellular Disorders Drug reactions Alcoholic Hepatitis Viral Hepatitis

EXTRAHEPATIC BILIARY OBSTRUCTION

Intraductal Obstruction Gallstones -Choledocholithiasis -Cholangitis Malignancy of the head of pancreas Compression of Biliary Ducts Pancreatic CA Inflammation -Pancreatitis

Cholelithiasis, Choledocholithiasis 1. Onset Insidious

Gall bladder CA, CholangioCA Chronic

Malignancy of the head of the pancreas Chronic

Viral Hepatitis

Acute / Chronic

2. RUQ pain
3. Jaundice 4. Relation of Pain to Jaundice 5. Fever 6. Presence of Prodrome (Flu-like symptoms) 7. Pruritus 8. Murphys Sign

YES (mild)
YES Pain followed by Jaundice NO / YES NO YES (-)

YES (severe)
YES Pain followed by Jaundice YES NO NO (-)

NO
YES Painless Jaundice YES NO YES (-)

YES (severe)
YES Pain followed by Jaundice YES YES NO (-)

Most Probable Clinical Impression

CHOLELITHIASIS

Predisposing Factors
Female Forty Fertile Fat

4Fs

Increased biliary cholesterol

Decreased of bile acid and phospholipids

Supersaturation of bile Gallbladder hypomotility (delayed emptying and stasis) Increased pronucleating factors -mucous glycoprotein -heat labile glycoprotein Nucleation Decreased pronucleating factors -apolipoproteins -Lecithin vesicles

Microstone Formation Mucus hypersecretion Calcium salts, GB hypomotility

Gallstone Formation

Gallstone Formation

Inflammation (+) Murphys sign

Obstruction

Increased in intraluminal pressure

Repetitive biliary contraction

progressive dilatation of the intrahepatic bile duct

Bearable intermittent colicky RUQ pain radiating to back not related to food intake

reabsorption and regurgitation of conjugated bilirubin into the bloodstream

reabsorption and regurgitation of conjugated bilirubin into the bloodstream

Decreased amount of bile (bilirubin) duodenum

hyperbilirubinemia

Decreased stercobilin

Deposition of bilirubin in sclerae, mucous membrane and skin

Renal excretion of bilirubin

Light colored stool on examining finger

Tea colored urine

Jaundice Icteric sclerae Icteric frenulum

Acts as an pruritogenic substance (stimulates opiodergic neurons and helps release serotonin)

COMPLICATIONS
Cholecystitis Biliary tract obstruction (from stones in the bile
ducts or choledocholithiasis)

Cholangitis Gallstone Pancreatitis

Diagnostic Tests

Diagnostic Tests
Gallbladder ultrasound Plain abdominal xray
procedure of choice for detection of stone sensitivity and specificity = 95% may detect gallstones containing sufficient calcium to be radioopaque

Oral cholecystogram Radioisotope scans

can delineate the size and number of gallstones and determine whether they are calcified replaced by gallbladder ultrasound
accurate identification of cystic duct obstruction

Endoscopic retrograde cholangiopancreatography

used primarily to diagnose and treat conditions of the bile ducts, including gallstones
Harrisons 17th edition p.1994 http://www.emedicine.com/med/topic836.htm#Author: Douglas M Heuman, MD, FACP

RADIOLOGY

ULTRASONOGRAPHY

Ultrasound of normal gallbladder

Ultrasound of the gall bladder with Gall stones

ULTRASONOGRAPHY

gallbladder with gallstone & thickened wall

ULTRASONOGRAPHY

(1) Normal bile duct (2) Portal vein (3) Inferior vena cava

Dilated bile duct with stone

COMPUTERIZED TOMOGRAPHY

Bile duct adenoma

Dilated bile ducts w/ debris and stones

Pancreatic tumor

MR CHOLANGIOGRAPHY

Bilateral multiple intrahepatic bile duct stones with irregularly dilated intrahepatic bile duct with stricture

common bile duct calculus

ENDOSCOPIC RETROGRADE CHOLANGIO PANCREATOGRAPHY (ERCP)

Normal bile duct

Bile duct with stricture

Percutaneous Transhepatic Cholangiography (PTC)

Dilated Bile duct with stone

Robbins and Cotran Atlas of Pathology, International Edition

DiFiores Atlas of Histology, 10th Edition

Folds are gone

Muscle hypertrophy Rokistanky-Aschoff sinuses extend deep

Bile granuloma
Fibrosis Wheaters Basic Histopathology, 4th Edition

Robbins and Cotran Atlas of Pathology, International Edition

Yellowish pigmentation

Robbins and Contran Atlas of Pathology, International Edition

Bile lakes

Robbins and Cotran Atlas of Pathology, International Edition

Feathery degeneration

Wheaters Basic Histopathology, 4th Edition

Robbins and Cotran Atlas of Pathology, International Edition

Robbins and Cotran Atlas of Pathology, International Edition

Treatment

Rational Approach to Pharmacotherapy

Basic Problems
Jaundice Right upper quadrant pruritus
Probably due to biliary obsructiont

Therapeutic Goals
To relieve biliary obstruction To relieve pain and pruritus Weight reduction

Treatment
Pharmacologic Non-pharmacologic

Treatment for GALLSTONES

Cholic Acids
Ursodeoxycholic acid (Ursodiol; UDCA)
Specifically for the treatment of cholesterol gallstones

Ursodeoxycholic Acid (Ursodiol)

Naturally occurring bile acid that makes up <5% of the circulating bile salt pool in humans. The only proven agent for dissolving gallstones.

 MOA/PD:
Decreases cholesterol content of bile by reducing hepatic cholesterol secretion Retards cholesterol crystal nucleation Inhibits intestinal absorption of cholesterol

Stabilizes the hepatocyte canalicular

membranes reduction in the concentration of other

endogenous bile acids

Inhibition of immune-mediated hepatocyte destruction

 PK:
Taken orally (usually at a dose of 8-10

mg/kg/day)
Conjugated in the liver with glycine or taurine and excreted in the bile Undergoes extensive first-pass effect Absorption: 90% Serum half-life: ~100 hours Site of action: liver, bile and gut lumen

 Clinical Use:
Dissolution of small cholesterol gallstones in patients who refuse to undergo surgery or who are poor candidates for surgery

Effective for obese patients who undergo rapid weight loss therapy
Used in the treatment of primary biliary cirrhosis and primary sclerosing cholangitis

 Drug Interactions:
Estrogens, oral contraceptives and clofibrate :: increases hepatic cholesterol secretion promoting cholesterol gallstone formation

Adverse Effect:
no known adverse effect

Treatment for CHOLELITHIASIS-INDUCED

PRURITUS

 Cholestyramine
bile-acid binding resin they bind bile acids in the intestinal lumen and prevent their reabsorption useful for patients with hypertriglyceridemia helps relieve pruritus in patients with cholelithiasis and bile acid accumulation

enhances the conversion of cholesterol to bile

acids in liver via 7a-hydroxylation

 Dosage:
total dosage of 30-32 g/d may be needed for maximum effect mixed with juice or water and allowed to hydrate for 1 minute. should be taken in two to three doses with meals (they lack effect when taken between meals)

Side effects:
constipation
fat malabsorption steatorrhea

 Drug Interaction: - absorption of drugs are decreased or impaired

by resins:

digitalis thiazides warfarin tetracycline thyroxine iron salts

pravastatin fluvastatin folic acid phenylbutazone aspirin ascorbic acid

- prothrombin time should be measured frequently in patients who are taking resins and anticoagulants

Treatment for PAIN

 Ketorolac (Acular, Toradol)

NSAID promoted for systemic use mainly as an
analgesic, and not as anti-inflammatory drug
used successfully to replace morphine that involves mild to moderate postsurgical pain.

Given intravenously or intramuscularly

should not be used for patients who are likely to need surgery

Alternative Medicine
Gallbladder Flush

Gallbladder Flush"
1) Patient drinks four glasses of pure apple juice (not cider) and eats five apples (or applesauce) per day for five days 2) Fasts briefly 3) Takes magnesium 4) Drinks large quantities of lemon juice mixed with olive oil before bed 5) The next morning, they painlessly pass a number of green and brown pebbles purported to be stones flushed from the Adjuvant biliary herbal treatment system for gallstones.

Savage AP, O'Brien T, Lamont PM. Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, UK. PMID: 1555068 [PubMed - indexed for MEDLINE]

The gallstone cure that wasn't

Experimentation revealed that mixing equal volumes of oleic acid (the main component of olive oil) and lemon juice produced semi-solid white balls after the addition of a small amount of potassium hydroxide. The green "stones" passed by patients resulted from the action of gastric lipases on the triglycerides that make up olive oil, yielding long-chain carboxylic acids (mainly oleic acid). This process was followed by saponification into large insoluble micelles of potassium carboxylates (lemon juice contains a high concentration of potassium) or "soap stones.
Sies CW, Brooker J. Could these be gallstones? Lancet 2005;365:1388. Alan R. Gaby "The gallstone cure that wasn't". Townsend Letter for Doctors and Patients. FindArticles.com. 26 Oct. 2008. http://findarticles.com/p/articles/mi_m0ISW/is_268/ai_n15795429

Medical Treatment
Extracorporeal Shock Wave Lithotripsy (ESWL)

Extracorporeal Shock Wave Lithotripsy (ESWL)

Principle:
shatter stones to smaller pieces in order to pass them out into the stool (only for patients with small number of stones)

Surgical Treatment
1) Cholecystectomy / Gallbladder Removal 2) Endoscopic Retrograde Sphincterotomy (ERS)

Cholecystectomy or Gallbladder Removal

Has a 99% chance of eliminating the recurrence of cholelithiasis Only symptomatic patients must be indicated to surgery
Glasgow RE, Mulvihill SJ (2006). Treatment of gallstone disease. In M Feldman et al., eds., Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 8th ed., vol. 1, pp. 14191442. Philadelphia: Saunders Elsevier.

Cholecystectomy or Gallbladder Removal

There is a significant proportion of the population, between 5-40%, who develop a condition called postcholecystectomy syndrome:
gastrointestinal distress persistent pain in the upper right abdomen chronic diarrhea
Glasgow RE, Mulvihill SJ (2006). Treatment of gallstone disease. In M Feldman et al., eds., Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 8th ed., vol. 1, pp. 14191442. Philadelphia: Saunders Elsevier.

Two Cholecystectomy Options

1) Open 2) Laparoscopic

Open Cholecystectomy
Traditional open cholecystectomy Major abdominal surgery in which the surgeon removes the gallbladder through a 4- to 7-inch (10 to 18 cm) incision below the right lower ribs Patients usually remain in the hospital over night and may require several additional weeks to recover at home.
Management of Gallstones Charles F. Bellows , M.D., and David H. Berge r, M.D., Baylor College of Medicine, Houston, Texas Richard A. Crass , M.D., University of Florida Health Science Center, Jacksonville, Florida August 15, 2005 Volume 72, Number 4 www.aafp.org/afp American Family Physician

Laparoscopic Cholecystectomy
replaced open cholecystectomy as the first-choice of treatment for gallstones unless there are contraindications to the laparoscopic approach requires several small incisions in the abdomen to allow the insertion of surgical instruments and a small video camera
*new* Single Port Access Surgery
performed through a single incision on the patient's belly-button

60-second VIDEO CLIP Laparoscopic Cholecystectomy

Will add in the final powerpoint

Laparoscopic Cholecystectomy Procedure

1) The gallbladder is identified and carefully Calot's Triangle (the area bound by the cystic artery, cystic duct, and common hepatic duct) is cleared. 2) The cystic duct and the cystic artery are identified, clipped with tiny titanium clips and cut. 3) The gallbladder is separated from the liver bed and removed through one of the small incisions.
Management of Gallstones Charles F. Bellows , M.D., and David H. Berge r, M.D., Baylor College of Medicine, Houston, Texas Richard A. Crass , M.D., University of Florida Health Science Center, Jacksonville, Florida August 15, 2005 Volume 72, Number 4 www.aafp.org/afp American Family Physician

Advantages of Laparoscopic Cholecystectomy

Does not require the abdominal muscles to be cut Less pain Quicker healing Improved cosmetic results Fewer complications such as infection Most patients can be discharged on the same or following day as the surgery most patients can return to any type of occupation in about a week

Endoscopic Retrograde Sphincterotomy (ERS)

relatively new endoscopic technique developed to examine and treat abnormalities of the bile ducts, pancreas and gallbladder cutting of the sphincter or muscle that lies at the juncture of the intestine with both the bile and pancreatic ducts Single-operator duodenoscope-assisted cholangioscopy is an effective alternative in the management of choledocholithiasis not
removed by conventional methods, including mechanical lithotripsy. Farrell JJ, Bounds BC, Al-Shalabi S, Jacobson BC, Brugge WR, Schapiro RH, Kelsey PB. Division of Digestive Diseases, UCLA School of Medicine, University of California at Los Angeles Center for the Health Sciences, Los Angeles, California 90095, USA. jfarrell@mednet.ucla.edu

Non- pharmacologic treatment

Lifestyle Modification
Increase physical activity Balanced diet with avoidance of fatty foods Weight reduction

Adjuvant herbal treatment for gallstones. Savage AP, O'Brien T, Lamont PM. Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, UK. PMID: 1555068 [PubMed - indexed for MEDLINE]

THANK YOU :-)

MPPRC Group A9 Cho, Chua Family, Co Family, Cofreros

EXTRA SLIDES
Slides that MAY be omitted and Slides na wala lang

Prehepatic jaundice In prehepatic jaundice, excess unconjugated bilirubin is produced faster than the liver is able to conjugate it for excretion. The liver can excrete six times the normal daily load before bilirubin concentrations in the plasma rise. Unconjugated bilirubin is insoluble and is not excreted in the urine. It is most commonly due to increased haemolysis for example, in spherocytosis, homozygous sickle cell disease, or thalassaemia major and patients are often anaemic with splenomegaly. The cause can usually be determined by further haematological tests (red cell film for reticulocytes and abnormal red cell shapes, haemoglobin electrophoresis, red cell antibodies, and osmotic fragility). Hepatic and posthepatic jaundice Most patients with jaundice have hepatic (parenchymal) or posthepatic (obstructive) jaundice. Several clinical features may help distinguish these two important groups but cannot be relied on, and patients should have ultrasonography to look for evidence of biliary obstruction. The most common intrahepatic causes are viral hepatitis, alcoholic cirrhosis, primary biliary cirrhosis, drug induced jaundice, and alcoholic hepatitis. Posthepatic jaundice is most often due to biliary obstruction by a stone in the common bile duct or by carcinoma of the pancreas. Pancreatic pseudocyst, chronic pancreatitis, sclerosing cholangitis, a bile duct stricture, or parasites in the bile duct are less common causes. In obstructive jaundice (both intrahepatic cholestasis and extrahepatic obstruction) the serum bilirubin is principally conjugated. Conjugated bilirubin is water soluble and is excreted in the urine, giving it a dark colour (bilirubinuria). At the same time, lack of bilirubin entering the gut results in pale, "putty" coloured stools and an absence of urobilinogen in the urine when measured by dipstick testing. Jaundice due to hepatic parenchymal disease is characterised by raised concentrations of both conjugated and unconjugated serum bilirubin, and typically stools and urine are of normal colour. However, although pale stools and dark urine are a feature of biliary obstruction, they can occur transiently in many acute hepatic illnesses and are therefore not a reliable clinical feature to distinguish obstruction from hepatic causes of jaundice.

http://www.aafp.org/afp/20030915/1135.html

Carson, K., Hunt, C.(1999) Management of pruritus. Medical Management of Liver Disease. Edited by Edward L. Krawitt. 636 pp., illustrated. New York, Marcel Dekker

 Pathophysiology
Pruritus originates within the skin's free nerve endings, which are most heavily concentrated in the wrists and ankles. The sensation of pruritus is transmitted through C fibers to the dorsal horn of the spinal cord and then to the cerebral cortex via the spinothalamic tract. Pruritus generates a spinal reflex response, the scratch, which is as innate as a deep tendon reflex. Regardless of the cause, pruritus often is exacerbated by skin inflammation, dry or hot ambient conditions, skin vasodilation, and psychologic stressors.
http://www.aafp.org/afp/20030915/1135.html

Serotonin appears to be a key component of the pruritus that occurs with several diseases, including polycythemia vera, uremia, cholestasis and lymphoma, and of morphine-associated pruritus. Serotonin inhibitors such as cyproheptadine (Periactin), pizotifen, paroxetine (Paxil), and ondansetron (Zofran) have proved effective in treating several of these pruritic conditions. Cholestasis-related pruritus is most severe at night, with a predilection for the hands and feet. Hyperpigmentation may result in areas of heavy scratching. In patients with hyperpigmentation, the middle of the back is spared, resulting in a classic butterfly-shaped dermatitis

http://www.aafp.org/afp/20030915/1135.html Krajnik M, Zylicz Z. Understanding pruritus in systemic disease. J Pain Symptom Manage 2001;21:151-68.

 The sensation of pruritus is transmitted through slowconducting unmyelinated C-polymodal and possibly type A delta nociceptive neurons with free nerve endings located near the dermoepidermal junction or in the epidermis. These neurons appear to be located more superficially and are more sensitive to pruritogenic substances than pain receptors. Activators of these nerves include histamine, neuropeptide substance P, serotonin, bradykinin, proteases (eg, mast cell tryptase), and endothelin (which stimulates the release of nitric oxide). Impulses are transmitted from the dorsal root ganglion to the spinothalamic tract. Opioids are known to modulate the sensation of pruritus, both peripherally and centrally. Cholestasis, or a decrease or arrest in the flow of bile, is associated with pruritus. The deposition of bile salts in the skin was thought to directly cause a pruritogenic effect, but this theory has been proven incorrect. In addition, indirect hyperbilirubinemia does not induce pruritus.
http://www.emedicine.com/derm/byname/Pruritus-and-Systemic-Disease.htm
Author: David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic
David F Butler is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa Coauthor(s): Jared J Lund, MD, Staff Physician, Department of Dermatology, Marshfield Clinic, St Joseph's Hospital Editors: Franklin Flowers, MD, Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, University of Florida College of Medicine; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center

 Other theories implicate elevated venous histamine levels, retention of pruritogenic intermediates in bile salt synthesis, and high hepatic concentrations of bile salts resulting in hepatic injury and release of a pruritogenic substance. In support of the last point, rifampin and ursodeoxycholic acid decrease intrahepatic concentrations of bile salts and provide some relief of cholestatic pruritus. The accumulation of endogenous opioids, which modulate pruritus and increase opioidergic tone in the brain, is of recent interest because opioid antagonists have been shown to partially relieve cholestatic pruritus. In support of this theory, treatment with opioid antagonists may induce an opioid withdrawallike syndrome. Perhaps some combination of the pruritogenic substances mentioned above (ie, bile salts, histamine, opioids) induces cholestatic pruritus.
http://www.emedicine.com/derm/byname/Pruritus-and-Systemic-Disease.htm
Author: David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic David F Butler is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa Coauthor(s): Jared J Lund, MD, Staff Physician, Department of Dermatology, Marshfield Clinic, St Joseph's Hospital Editors: Franklin Flowers, MD, Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, University of Florida College of Medicine; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center

Opiate antagonist therapy for the pruritus of cholestasis: the avoidance of opioid withdrawal-like reactions E.A. JONES,1, J. NEUBERGER2 and N.V. BERGASA3 From the 1 Academic Medical Center, Amsterdam, The Netherlands, 2 Queen Elizabeth Hospital, Birmingham, UK, and 3 College of Physicians and Surgeons, Columbia University, New York, NY, USA Increased opioidergic neurotransmission in the brain appears to contribute to the pruritus that complicates cholestasis and certain non-cholestatic chronic liver diseases. Opiate antagonists have been shown to decrease scratching activity in patients with the pruritus of cholestasis. Initiation of oral administration of an orally bioavailable opiate antagonist may precipitate a florid opioid-withdrawal-like reaction in patients with pruritus complicating cholestasis. Such reactions can be minimized, or avoided completely, by cautiously infusing naloxone before giving small oral doses of an orally bioavailable opiate antagonist. The infusion rate of naloxone should initially be very low; it should be increased gradually and stopped when a rate known to be associated with opioid antagonist effects has been attained. Oral therapy with an opiate antagonist can then be initiated. http://qjmed.oxfordjournals.org/cgi/content/abstract/95/8/547

Oral Bile Acid Treatment

Principles:
dissolution of gallstones by the oral administration of bile-acid mixtures enrich the bile with these bile acids and thereby decrease cholesterol supersaturation (dec. crystal formation) and dissolve the stones

Agents:
Chenodeoxycholic Acid (CDCA) Ursodeoxycholic Acid (UDCA)
Management of Gallstones Charles F. Bellows , M.D., and David H. Berge r, M.D., Baylor College of Medicine, Houston, Texas Richard A. Crass , M.D., University of Florida Health Science Center, Jacksonville, Florida August 15, 2005 Volume 72, Number 4 www.aafp.org/afp American Family Physician

Chenodeoxycholic Acid (CDCA)

This treatment raised concerns due to:
dose-dependent increase in aminotransferases an increase in serum LDL development of bile salt-induced diarrhea
[Innovations in the medical treatment of gallstones and fatty liver: FABACs (Fatty Acid Bile Acid Conjugates)] Keizman D, Goldiner I, Leikin-Frenkel A, Konikoff FM. Department of Gastroenterology, the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Ursodeoxycholic acid (UDCA)

more hydrophilic practically devoid of side effects Disadvantages:
low efficacy slow action stone recurrence
[Innovations in the medical treatment of gallstones and fatty liver: FABACs (Fatty Acid Bile Acid Conjugates)] Keizman D, Goldiner I, Leikin-Frenkel A, Konikoff FM. Department of Gastroenterology, the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

PLEASE CHANGE GALLSTONES TO PRESENCE OF STONE I THE stones sign GALLBLADDER 1. Cholelithiasis YES YES ? ? ? CHANGE THE ORDER TO THIS ONE: ONSET- RUQ pain - JAUNDICE- RELATION OF PAIN TO JAUNDICE- FEVERPRESENCE OF PRODOMEPRURITUS - MURPHYS SIGN- PRESENCE OF 2. Choledocholithiasis YES (10-15%) YES NO YES YES STONES IN THE GALL BLADDER 3. Ascending YES AND (assoc. YES YES (occasional) YES YES PUT CHOLELITHIASIS CHOLEDOCHO UNDER ONE CATEGORY Cholangitis with #2) DELETE ASCENDING CHOLANGITIS 4. Acute Cholecystitis YES (Primary YES YES YES/NO YES compication) GROUP GALLBLADDER CA AND CHOLANGIO CA UNDER ONE CATEGORY 5. Pancreatic CA ADD HEPATITIS NO YES NO YES YES

Gall

Jaundice (+) Murphys Fever Pruritus

EMPHASIS ON HEPATITIS- FEVER, PRODOME (FLU LIKE SYMPTOMS 6. Gall Bladder CA YES (60-90%) YES NO YES NO PANCREATIC CA- CHANGE TO MALIGNANCY OF THE HEAD OF THE PANCREAS 7. CholangioCA NO YES NO YES YES DIFFERENTIATING OBSTRUCTIVE JAUNDICE TO MALIGNANCY IS PRESENCE OF PAIN - PAINFUL JAUNDICE VS PAINLESS JAUNDICE

Differential Diagnosis

Choledocholithiasis

Cholecystitis

CA, CholangioCA

the head of the pancreas

1. Onset
2. RUQ pain 3. Jaundice 4. Relation of pain to jaundice 5. Fever 6. Presence of Prodrome

Chronic
YES (mild) YES NO NO / YES NO

Acute
YES (severe) Unusual in early stage NO YES NO

Chronic
YES (severe) YES NO YES NO

Chronic
YES (dull ache) YES NO (pain in body or tail) YES NO

Acute / Chronic
YES (severe) YES NO OCC. YES

7. Pruritus
8. Murphys Sign 9. Presence of Stones in GB

YES
(-) YES

YES
(+) YES - primary complication

NO
(-) YES / NO

YES
(-) NO

NO
(-) OCC.

http://www.med-online.ro/eng/clinical/eng_057/eng_057_a.php

Extra lang.
Alkaline phosphatase
41-133units/liter

Serum bilirubin
O.3 1.3 mg/dl

 Morphine
prototype opioid agonist

known to relieve severe pain with remarkable

efficacy full agonist at the mu-opioid receptor (major analgesic opioid receptor) produce analgesia through actions at regions in the CNS