1. Associate Professor of Internal Medicine
D.D OF JAUNDICE BY
DR. Hayam Hebah
Associate Professor of Internal Medicine
AL Maarefa College

2. DEFINITION
Jaundice is a yellowish staining of the skin, sclera, and mucous membranes by ↑ bilirubin.
Clinically detected typically once the serum bilirubin level rises above 3 mg /dl.
Can be caused by a wide variety of benign or life-threatening disorders.
Pseudojaundice - a harmless form of jaundice in which the yellowing of the skin results from an excess of beta-carotene, not from an excess of bilirubin; usually from eating lots of carrots, pumpkin, or melon.
N= mg/dL ( µmol/L),
direct bil. ≤ 0.2 mg/dL (3.4 µmol/L)

5. Pathophysiology
Hepatic form of jaundice includes Dubin Johnson syndrome and Rotor syndrome.

6. Bilirubin handling in Kidney
Conjugated Bilirubin
Unconjugated Bilirubin
Urobilinogen in urine
Bound (20 days)
Bilirubin in urine is conjugated
Not filtered or secreted
Nil in urine
Normally traces
↑ in Cholestaiss

9. DD OF UNCONJUGATED HYPERBILIRUBINEMIA(Prehepatic jaundice)
Increased bilirubin production : -Hemolysis
-Dyserythropoiesis
-Hematoma
Impaired hepatic bilirubin uptake : -Congestive heart failure
- Portosystemic shunts
-Drugs - Rifamycin, rifampin, probenecid
Impaired bilirubin conjugation :-Crigler-Najjar syndrome types I and II
- Gilbert syndrome (decreased uptake and/or conjugation)
-Neonatal physiologic jaundice
-Breast milk jaundice
-Hypothyroidism/hyperthyroidism
-Ethinyl estradiol
-Liver diseases - Chronic hepatitis, cirrhosis, and Wilson disease

10. Gilbert Syndrome
AD, low glucuronyl transferase enzyme, low uptake of bilirubin,
diagnosed by a history and physical examination and confirmed by standard blood tests. Repeated investigations and invasive procedures are not usually justified for establishing a diagnosis.
Hyperbilirubinemia( mild) is the only biochemical serum abnormality in Gilbert syndrome. Serum bilirubin concentrations range from 1-5 mg/dL.
2 provocative tests, energy deprivation and nicotinic acid administration, have been used to diagnose the condition. SO FASTING IS associated with ↑ jaundice.
Does not need ttt

11. Hepatocellular jaundice
Parenchymal liver disease , enables liver to transport bilirubin to bile.
Both conjugated and unconjugated bilirubin increase
Occur in acute or chronic liver disease.
Associated with ↑ transaminases(AST , ALT) ,
GGT, ALP may also ↑

12. POSTHEPATIC(OBSTRUCTIVE ) (CHOLESTATIC) JAUNDICE
Mechanism of jaundice:
Failure of hepatocytes to initiate bile flow
Obstruction of bile ducts or portal tracts.
Obstruction of bile flow in the extrahepatic bile ducts between the porta hepatis and ampulla of Vater.

13. Causes of cholestatic jaundice
Intrahepatic
Primary biliary cirrhosis
Primary sclerosing cholangitis
Alcohol
Drugs as OCP,
hepatic infiltration (lymphoma, granuloma,amyloid,metasta ses)
cystic fibrosis
severe bacterial infections
Pregnancy
Chronic rt heart failure
Inherited cholestatic liver disease
Extrahepatic
Carcinoma
Ampullary
Pancreatic
Bile duct
(cholangiocarcinoma)
Liver metastasis
Choledocholithiasis
Parasitic infection
Traumatic biliary strictures
Chronic pancreatitis.

14. Suggestive clinical features of cholestatic jaundice
Static or increasing jaundice
Fluctuating jaundice
Abdominal pain
Cholangitis
Abdominal scar
Irregular hepatomegaly
Palpable GB
Abdominal mass
Occult blood in stools.

15. Key diagnostic points in history in patients with jaundice
History of itching preceding the jaundice(obstructive d.t bile acids)
Abdominal pain( stones)
Weight loss (CLD or malignancies)
Urine and stool colors
Fever ± rigors (cholangitis)
Drug history
Alcohol intake
Iv drug abuse or blood transfusion
Travel history
Autoimmune diseases or IBD

16. history
Potential toxins (eg, drugs), environmental chemicals (eg, solvents), or wild mushrooms must be carefully excluded(toxic hepatitis).
Risk factors for viral hepatitis should be elicited : Transfusion ,IV drug use ,multiple sexual partners ,exposure to a person who is infected.
Colicky abdominal pain or fever suggests gallstone disease.
Weight loss or constitutional systems suggests malignancy or chronic infection.

17. Recent anesthesia with halothane suggests halothane hepatitis.
A history of intense pruritus suggests cholestatic disease .
A family history of jaundice suggests inborn errors of bilirubin metabolism.
In patients with severe intercurrent illnesses, consider sepsis, hepatic ischemia, and opportunistic infections.
Severe right heart failure or tricuspid insufficiency with hepatomegaly suggests hepatic congestion.

18. Patients on parenteral nutrition may experience cholestasis that sometimes improves with the addition of lipid infusions.
Patients with AIDS may experience biliary obstruction from opportunistic infections (e g, AIDS cholangiopathy).
Patients with chronic liver disease may experience transient elevation of their bilirubin levels following blood transfusion, which results due to a more rapid turnover of the infused cells.
In patients younger than years, a history of a recent flulike syndrome treated with aspirin raises the possibility of Reye syndrome.
Pregnancy suggests benign recurrent cholestasis or, in late pregnancy, acute fatty liver of pregnancy.

19. Examination:
Depending on the underlying illness, stigmata of chronic liver disease may or may not be present.
Palpation of the abdomen may reveal the following:
A mass (eg, a distended gallbladder, abdominal tumors)
Tenderness over the liver (eg, as in cases of hepatitis or hepatic distention resulting from congestion or infiltrative disease)

20. Tenderness over the gallbladder fossa (as occurs in cases of biliary disease or infection)
Unexplained darkening of the skin, diabetes, or heart failure suggests hemochromatosis.
Kaiser-Fleisher rings suggests Wilson disease.
Cutaneous or neurologic findings of chronic alcoholism may be helpful diagnostic findings.
In addition to color of sclera it self .

21. Differential Diagnosis of Conjugated Hyperbilirubinemia
I. Acute or Chronic Hepatocellular Dysfunction
A. Infection
Viral hepatitis A-E 
Cytomegalovirus (CMV) hepatitis
Epstein-Barr virus hepatitis
Sepsis

22. B. Inflammation Without Infection
Toxic liver injury 
Drug toxicity (eg, acetaminophen)
Halothane hepatitis
Alcoholic hepatitis
Iron overload (hemochromatosis)
Copper overload (Wilson disease)
Autoimmune hepatitis

23. C. Metabolic Dysfunction
Ischemia ("shock liver")
 Acute fatty liver of pregnancy
Alpha-1 antitrypsin deficiency
Preeclampsia
Reye syndrome
Total parenteral nutrition
D. Inborn Errors of Metabolism
Dubin-Johnson syndrome 
Rotor syndrome
Benign recurrent cholestasis

24. II. Diseases That Prevent Flow of Bile into the Intestine
A. Damage to Intrahepatic Bile Ducts or Portal Tracts
Primary biliary cirrhosis
Graft versus host disease
Sclerosing cholangitis. 
Veno-occlusive disease

25. B. Damage to or Obstruction of Larger Bile Ducts
Choledocholithiasis
Sclerosing cholangitis
AIDS cholangiopathy
Hepatic arterial chemotherapy
Postsurgical strictures
Bile duct cancers
Developmental disorders of the bile ducts (eg, Caroli)
Extrinsic compression of the bile duct
Tumors
Acute pancreatitis

26. c. Diffuse Infiltrative Diseases
Granulomatous diseases 
Sarcoidosis
Disseminated mycobacterial infections
Lymphoma
Wegener granulomatosis
Amyloidosis
Diffuse malignancy

27. D. Diseases That Interfere with Biliary Secretion of Bilirubin
Anabolic steroids (testosterone, norethandrolone)
Antithyroid agents (methimazole)
Azathioprine (Immunosuppressive drug)
Chlorpromazine HCI (Largactil)
Clofibrate, Erythromycin estolate
Oral contraceptives (containing estrogens)
Oral hypoglycemics (especially chlorpropamide)

28. Algorithmic approach for Jaundice

29. First Step : estimate serum bilirubin
if> 1 mg /dl so it is elevated.
Second Step : is the hyperbilirubinemia conjugated (>20%) or unconjugated or both?
Third Step : If CSB is increased , do AST, ALT, serum alkaline phosphatase & GGT.
Fourth Step : If hepatocellular:
hepatitis markers, EBV, CMV
toxic hepatitis : drugs & alcohol
Malignancy: alpha fetoprotein
Cirrhosis: ALD-NAFLD

30. ↑ in Unconjugated Bilirubin
Hemolytic Jaundice - Uncommon
1. Hemolytic Disorders + Anemia
Inherited – Sphero, SS, G6PD, PK
Acquired – MAHA, PNH
2. Ineffective Erythropoesis –B12, Fe, F
3. Drugs – Rifampicin, Probenecid
4. Inherited –Crigler Najjar, Gilberts

31. Other helpful tests:
Complete blood cell (CBC) count to screen for hemolysis
Serologic screen for viral hepatitis, including hepatitis C virus (HCV) antibody and hepatitis B surface antigen (HBsAg) or antihepatitis B core antibody (anti-HBcAb)
Alkaline phosphatase (ALP): If elevated or if an obstruction is suspected, images of the bile ducts should be obtained. Gamma- glutamyl transpeptidase (GGTP) results may help differentiate a hepatic source of the elevated ALP from bone or other causes.
Blood alcohol or acetaminophen levels upon admission (may be useful in certain cases).
Antimitochondrial antibody (AMA)when considering primary biliary cirrhosis
Antinuclear antibodies (ANAs), smooth-muscle antibodies, and when considering autoimmune hepatitis
Iron and genetic studies when considering hemochromatosis
Copper and ceruloplasmin when considering Wilson disease
Alpha-1 antitrypsin fractionation and other studies when considering hereditary liver diseases
AND ABDOMINAL U/S

34. AUTOIMMUNE HEPATITIS
More in females 2nd &3rd decades but may occur in any age or sex.
Clinical presentation:
acute or chronic hepatitis
well-established cirrhosis
rarely fulminant hepatic failure marked bycoagulopathy and jaundice
1/3 of patients present with symptoms of acute hepatitis marked by fever, hepatic tenderness, and jaundice.
Chronic liver disease .

36. CONDITIONS ASSOCIATED WITH AUTOIMMUNE HEPATITIS:
Hashimoto thyroiditis
Thyrotoxicosis
Myxedema
Pleurisy
Coombs positive hemolytic anemia
Ulcerative colitis
SLE
Rheumatoid arthritis
Sjogren ‘s syndrome
Diabetes
Membranoproliferative GN
Celiac disease.

37. Common findings on physical examination are as follows:
Hepatomegaly (83%)
Jaundice (69%)
Splenomegaly (32%)
Spider angiomata (58%)
Ascites (20%)
Encephalopathy (14%)

38. Lab diagnosis:
Elevated aminotransferase levels ( times reference values)
Elevated serum immunoglobulin G (IgG)
Mild to moderately elevated serum bilirubin and alkaline phosphatase – In 80-90% of patients; a sharp increase in the values during the course of autoimmune disease may reflect the development of primary sclerosing cholangitis (PSC) or the onset of hepatocellular carcinoma as a complication of cirrhosis
Seropositive results for antinuclear antibodies (ANAs), smooth-muscle antibodies (SMAs), or liver-kidney microsomal type 1 (LKM-1) or anti–liver cytosol 1 (anti-LC1) antibodies
Hypoalbuminemia and prolongation of prothrombin time – Markers of severe hepatic synthetic dysfunction, which may be observed in active disease or decompensated cirrhosis

39. the hematologic abnormalities may include the following:
Mild leukopenia
Normochromic anemia
Coombs-positive hemolytic anemia
Thrombocytopenia
Elevated erythrocyte sedimentation rate
Eosinophilia (uncommon)

40. Management:
Corticosteroids, alone or in combination with azathioprine, have been the mainstays of drug therapy for patients with autoimmune .
Relapse occurs in 50% of patients within 6 months of treatment withdrawal and in 80% of patients within 3 years of treatment. Reinstitution of the original treatment regimen usually induces another remission; however, relapse commonly recurs after a second attempt at terminating therapy. Patients who relapse twice require indefinite therapy with either prednisone or azathioprine.
Liver transplantation
for patients in whom medical therapy has failed
or for those with decompensated cirrhosis caused by autoimmune hepatitis.
FOR patients who present with fulminant hepatic failure secondary to autoimmune hepatitis.

42. Primary Sclerosing Cholangitis
Narrowed abnormal intra-heptic bile ducts.
Normal Extra hepatic BD

51. Thank you