Jaundice

Definitions

1. Hyperbilirubinemia 1-1.5 mg/dl < Serum bilirubin level < 2.5-3 mg/dl Normal serum bilirubin level = 1 – 1.5 mg/dl
2. Jaundice Yellowish discoloration of skin, sclera and mucous membranes due to ↑ serum bilirubin > 2.5-3 mg/dl Every 500 mg of blood → 7.5 g hemoglobin → 250 mg bilirubin
and its deposition in these tissues. Daily production of bilirubin = 250 mg
3. Cholestasis Disorder of either bile secretion or functional or mechanical stoppage of bile flow Normal level of Unconjugated bilirubin = 75 – 80% of total bilirubin
(On the level of IHBDs or EHBDs) leading to passage of bile components of bile into blood. Normal level of conjugated bilirubin < 20% of total bilirubin
Unconjugated hyperbilirubinemia → Direct bilirubin < 20% of total bilirubin
Conjugated hyperbilirubinemia → Direct bilirubin >/= 20% of total bilirubin

Heme degradation pathway

Forms of bilirubin:

1. Unconjugated = Indirect (Bilirubin + Plasma protein "Albumin" )

a. Hemobilirubin
2. Conjugated = Direct (Bilirubin + Glucuronic acid )
a. Cholebilirubin
b. Stercobilinogen
c. Urobilinogen
Approach to a case of jaundice

Approach to a case of jaundice

1. History

2. Physical examinations

3. Lab workup

4. Imaging
 History

1. Chronic illnesses as hepatic, cardiac, autoimmune, malignancies, genetic, etc. 1. Antibiotics

2. Alcohol intake a. Amoxicillin / clavulanate
3. Drug history especially hepatotoxic drugs b. Trimethoprim / salfamethoxazole
4. Clinical picture 2. Antiepileptics
a. Fever + localization → sepsis a. Phenytoin
b. Fever + prodromal symptoms → viral hepatitis b. Carbamazepine
c. Fever + Rt. Hypochondrial abdominal pain, itching, dark urine + pale stool → obstructive jaundice + cholangitis. 3. Anti-TB
d. Significant weight loss + anorexia → malignancy. a. Riampicin
b. Isoniazid
4. NSAIDs
a. Acetamenophen
b. Diclofenac
5. Hypolipidemics
a. Statins
b. Niacin
6. Anaesthetic
a. Halothan
b. Chloroform
7. Anti-rheumatics
a. Sulphasalazine
b. Azathioprine
c. Methotrexate
8. Antiretroviral drugs
a. Retonavir
b. Indinavir
c. Lamividin
d. Tenofovir

Physical examinations

1. General
a. Stigmata of chronic liver disease (gynecomastia, spider naevi, caput medusa, palmar erythema)
b. Signs of hepatic encephalopathy (Disturbed level of consciousness, Astrexesis = Flapping tremors)
2. Local
a. Abdominal examination for hepatosplenomegaly, ascites, positive murphy sign.
 Investigations

Lab Imaging
1. Serum bilirubin. 1. Ultrasonography → (biliary tract disorders – liver cirrhosis – vascular patency)
2. CBC. 2. CT
3. Liver enzymes ( ALT, AST) → indicators of hepatocellular necrosis. 3. MRCP
4. Serum albumin. 4. ERCP
5. PT and INR. 5. EUS
6. Alkaline phosphatase.
7. GGT. If still unknown diagnosis, move on to the last step → liver biopsy.
Special testing
1. Autoimmune panel (ANA, ASMA, Anti LKM)
2. Markers of viral hepatitis:
• HAV IgM → Acute A.
▪ HCV Ab, HCV RNA PCR → chronic c.
▪ HbsAg, HBV DNA PCR → chronic B.
▪ HbcIgM → Acute B.

Causes of jaundice

Unconjugated hyperbilirubinemia Conjugated hyperbilirubinemia

1. ↑ production → ↑ hemolysis Intrahepatic cholestasis Extrahepatic cholestasis
▪ hemolytic anemia 1. Viral hepatitis 1. Choledocholithiasis
▪ RBC enzyme disorder → G6PD def. 2. Alcoholic liver dis 2. Biliary stricture
▪ RBC membrane disorder → spherocytosis – elliptocytosis ▪ Alcoholic steatosis 3. Biliary – vascular fistula
▪ Hb dis → thalassemia – sickle cell anemia ▪ Alcoholic hepatitis 4. Biliary atresia
▪ Malignancy → polycythemia vera ▪ cirrhosis 5. Cholangitis
2. Defective transport 3. Non alcoholic steatohepatitis ▪ Bacterial
▪ ↓ albumin 4. Drug induced liver dis ▪ 1ry sclerosing
▪ Displacement of bilirubin from protein binding sites 5. Sepsis ▪ 2ry sclerosing
3. Defective uptake 6. Autoimmune disorders 6. Chronic pancreatitis
▪ ↓ Z & Y proteins (Gilbert syndrome) ▪ Primary biliary cirrhosis 7. Pancreatic tumors
4. Defective conjugation ▪ Autoimmune hepatitis ▪ Pancreatic adenocarcinoma
Glucoronyl transferase enzyme 7. Ischemic hepatitis 8. Gallbladder carcinoma
Absent Deficient 8. Genetic hepatic dis 9. Cholangiocarcinoma
Criggler Najjar type Ⅰ Criggler Najjar type Ⅱ ▪ Wilson dis 10.Choledochal cysts
Severity More severe - Poor prognosis Less severe ▪ Hemochromatosis 11. Infections
9. Malignancy ▪ HIV
C/P Encephalopathy (cause of death) Neurological manifestations ▪ HCC ▪ AIDS
▪ Metastatic dis ▪ CMV
1. Phototherapy
TTT 2. Liver transplantation Phenobarbital
3. Exchange transfusion
 Post operative jaundice

Pre-hepatic Hepatic Post-hepatic

(Bilirubin overload) (Hepatocellular insufficiency) (Obstruction to bile flow)
1. Hemolysis 1. Viral hepatitis 1. Retained stones
▪ Drugs 2. Drug induced (anesthesia) 2. Injury to ducts
▪ Transfusion 3. Ischemic hepatitis (shock, hypoxemia, low output states) 3. Tumor
▪ Sickle cell crisis 4. Sepsis 4. Cholecystitis
2. Reabsorption of hematomas 5. Liver resection (loss of parenchyma) 5. Pancreatitis

Ischemic hepatitis

Definition Diagnosis
1. Marked shooting in liver enzymes (ALT, AST) → Markers of hepatocellular necrosis.
▪ Massive necrosis of liver cells
▪ Normal levels of ALT, AST → 25 – 45
▪ Ischemia of the liver cells, massively affect the liver mass in short time causing functional 2. Acute phase reactants → LDH mg/dl
disturbance and jaundice ▪ In ischemic hepatitis → 3000 – 5000
mg/dl