1. Jaundice
Yellow discoloration of sclera, skin, mucous membranes due to deposition of bile pigment
Clinically detected with serum bilirubin 2-2.5mg/dL or  (2 times normal)

2. What is bilirubin?
The breakdown product of Hemoglobin from injured RBCs and other heme containing proteins.
Produced by reticuloendothelial system
Released to plasma, bound to albumin
Hepatocytes conjugate it and extrete through bile channels into small intestine.

4. What causes  bilirubin?
Prehepatic Unconjugated
Hepatic mixed
Post-hepatic conjugated

5. Causes Hepatocellular disease Viral infections (hepatitis A, B, and C)
Chronic alcohol use
Autoimmune disorders
Drugs
Pregnancy

6. Causes Parenteral nutrition Sarcoidosis Dubin-Johnson syndrome
Rotor's syndrome
Primary biliary cirrhosis
Primary sclerosing cholangitis

7. Drugs that may cause liver damage
Analgesics
Paracetamol
Aspirin
Non-steroidal anti-inflammatory drugs
Cardiac drugs
Methyldopa
Amiodarone
Psychotropic drugs
Monoamine oxidase inhibitors
Phenothiazines (such as chlorpromazine)
Others
Sodium valproate
Oestrogens (oral contraceptives and hormone replacement therapy)

8. Symptoms
Yellow discoloration of the skin, sclerae and mucous membranes
Itching (pruritus) due to deposits of bile salts on the skin
Stool becomes light in color
Urine becomes deep orange and foamy

9. Clinical Features Careful history and examination
Family history (Gilbert, Rotor, Crigler-Najjar, Dubin-Johnson, Sickle Cell)
Healthy young person with fever, malaise, myalgias = viral hepatitis (try to locate source)
Gradually develops symptoms = hepatic/bile duct obstruction (consider liver disease/cirrhosis)
Develops acutely with abdominal pain = acute cholangitis sec to choledocholithiasis

10. Clinical Features
Painless jaundice in older person with epigastric mass & weight loss = biliary obstruction from malignancy
Hepatomegaly with pedal edema, JVP, and gallop = CHF

11. History that should be taken from patients presenting with Jaundice
Duration of jaundice
Previous attacks of jaundice
Pain
Chills, fever, systemic symptoms
Itching
Exposure to drugs (prescribed and illegal)
Biliary surgery
Anorexia, weight loss
Colour of urine and stool
Contact with other jaundiced patients
History of injections or blood transfusions
Occupation

12. Examination of patients with Jaundice
Liver
Size
Shape
Surface
Enlargement of gall bladder
Splenomegaly
Abdominal mass
Colour of urine and stools
Depth of jaundice
Scratch marks
Signs of chronic liver disease
Palmar erythema
Clubbing
White nails
Dupuytren’s contracture
Gynaecomastia

13. Laboratory Tests Pigment studies Alkaline Phosphatase
Serum bilirubin, direct
Serum bilirubin, total
Urine R/E for bilirubin and urobilinogen
Alkaline Phosphatase
Liver aminotransferrase levels
AST
ALT
Elevated levels usually indicate cellular damage to the liver
> 70% of liver cells may be damaged before LFT’s become elevated

14. Blood Studies Serum Ammonia
Liver converts ammonia to urea. Ammonia rises in liver failure
Protein Studies
Serum albumin
Low levels seen with liver disease
Serum Globulin
Elevated levels with advanced cirrhosis and chronic active hepatitis

15. CBC PT
Other labs pertinent to history
Coombs test
Hb electrophoresis
Viral hepatitis screen
ULTRASOUND

16. Tumor Marker
Alpha-fetoprotein (AFP)
Increased levels are seen with hepatic carcinoma
Prothrombin Time (PT)
Time required for a firm fibrin dot to form
In liver dysfunction, increase clotting time with increased risk of bleeding

17. Liver Biopsy Used to obtain a specimen of liver tissue
Done under local anesthesia

18. Autoantibody and immunoglobulin characteristics in liver disease
Auto antibodies
Immunoglobulin
Primary billiary cirrhosis
High titre of antimitochondrial antibody in 95% of patients
Raised IgM
Autoimmune chronic active hepatitis
Smooth muscle antibody in 70%, antinuclear factor in 60%, Low antimitochondrial antibody titre in 20%
Raised IgG in all patients
Primary sclerosing cholangitis
Antinuclear cytoplasmic antibody in 30%

19. Summary
An isolated raised serum bilirubin concentration is usually due to Gilbert’s syndrome, which is confirmed by normal liver enzyme activities and full blood count
Jaundice with dark urine, pale stools, and raised alkaline phosphatase and gamma-glutamyl transferase activity suggests an obstructive cause, which is confirmed by presence of dilated bile ducts on ultrasonography
Jaundice in patients with low serum albumin concentration suggests chronic liver disease
Patients with high concentrations of bilirubin (>100 micro mol/l) or signs of sepsis require emergency specialist referral
Imaging of the bile ducts for obstructive jaundice is increasingly performed by magnetic resonance cholangiopancreatography, with endoscopy becoming reserved for the therapeutic interventions

20. Pre-Hepatic Disorders

21. Haemolysis Gilberts Excess bilirubin production Failure to conjugate
Unconjugated Bil ++
Normal ALP/ALT
Low Hb/retics++
Splenomegaly
Pigmented gallstones
Gilberts
Failure to conjugate
2-5%
Autosomal recessive
Asymptomatic
Bilirubin Unconjugated
Normal ALT/ALP
Worse if infection, miss a meal

22. Hepatic Disorders & Hepatic Failure

23. Acute & Chronic Liver Disease
Drugs
Viral
Alcohol
Autoimmune
Chronic
Biliary
Primary biliary cirrhosis
Primary sclerosing cholangitis
Liver cell damage (cirrhotic)
Alcohol
Autoimmune
Viral*
Haemochromatosis*
Wilsons*
A1AT*

24. Physical Findings Acute Chronic
Moderate liver enlargement, tenderness, +/- jaundice
Chronic
Sallow complexion, extremity muscle atrophy, palmar erythema, spider nevi, testicular atrophy, gynecomastia, splenomegaly, ascites

25. Investigations CHRONIC LIVER DISEASE ACUTE LIVER INJURY LFTs LFTs
Hepatitic ALT/AST +++
Cholestatic ALP/GGT+++
Albumin
Low
FBC
Pancytopaenia
Elevated wcc PT
Elevated
ACUTE LIVER INJURY
LFTs
Hepatitic ALT/AST +++
Albumin
Normal
FBC PT
Mild elevation
Exception- paracetomol

26. Blood tests for liver disease
Liver autoantibodies
Anti-mitochondrial
Anti-Smooth muscle
Immunoglobulins
IgM
IgG
IgA
Ferritin/TIBC
PBC
AICAH
Alcohol
Haemochromatosis

27. Gross specimen of cirrhosis of the liver

28. Post-Hepatic
Disorders

29. Intrinsic to the ductal system
Gallstones
Surgical strictures
Infection (cytomegalovirus, Cryptosporidium
infection in patients with acquired
immunodeficiency syndrome)
Intrahepatic malignancy
Cholangiocarcinoma
Extrinsic to the ductal system
Extrahepatic malignancy (pancreas, lymphoma)
Pancreatitis

30. CASE SCENARIO
A 54 years old female is presented in emergency department with complaints of low grade fever, nausea and loss of appetite for last 10 days. now she is worried because of yellow discoloration of sclera and dark colored urine for one day.
What physical signs you can suspect in this case?

31. , CASE SCENARIO
On examination, she has fever of 100-F.she is jaundiced and having tender hepatomegaly.
How will you investigate this case ?

32. CASE SCENARIO Bilirubin 10mg/dl ALT 1593IU Alkaline phosphatase 840IU
Hb 12.3
TLC 8900
Platelets
PT 3 seconds prolong
Serum albumin 3.6mg/dl
What is your likely diagnosis ?

33. CASE SCENARIO
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D

34. CASE SCENARIO
How will you differentiate hepatitis A and hepatitis E infection ?
How will you manage this case ?

35. CASE SCENARIO
Bed rest
Increase oral juices intake in anorexic patients
Anti emetics
Parenteral feeding if severe anorexia and vomiting
Vitamin and liver supportive agents