What are the causes of prolonged jaundice?

Jaundice present tor more than 6 months may be arbitrarily called as prolonged Jaundice'. The common causes are given below.

• Cholestatic viral hepatitis.
• Chronic hepatitis.
• Cirrhosis of liver.
• Carcinoma of liver (secondary).
• Thalassaemia.
• Drug-induced hepatitis (eg. rifampicin. INH. chlorpromazine).
• Extrahepatic biliary obstruction (eg. stone, stricture, carcinoma of the head of pancreas).
• Alcoholic hepatitis.
• Wilson's disease.
• Other causes like Gilbert's syndrome primary biliary cirrhosis, hereditary spherocytosis, sickle cell anaemia, autoimmune haemolytic anaemia, sclerosing cholangitis etc.

Clinical assessment of jaundice

What is Jaundice?

Difference between conjugated and unconjugated hyperbilirubinemia

What are the clinical features of haemolytic jaundice?

Features of hepatocellular jaundice

What are the clinical fatures of of obstructive jaundice ?

What is polycythemia?

Polycythemia is the excessive amount of RBC mass that leads to redness of conjunctiva, mucous membrane, skin and nailbed .

Polycythemia may be primary or secondary

Primary polycythemia 

Primary polycythemia  is a proliferative polycythemia is the malignant counterpart.

Secondary polycythemia 

Is a condition where you get it secondary to some systemic cause

This may be often accompanied by central cyanosis and clubbing as seen in congenital cyanotic heart disease and interstitial lung disease .This is called as secondary polycythemia

Laboratory criteria for polycythemia

In males

• RBC mass is > 36 ml/kg
• PCV > 55 %

In females

• RBC mass > 32 ml/kg
• PCV > 47 %

How to detect polycythemia?

Polycythemia is examined in the same manner as anemia.Examine the lower palpebral conjunctiva, longue, soft palate, nail beds, palms and soles, and general skin surface.The colour of the mucous membrane turns dusky-red. Patients with  polycythemia usually have facial plethora  and suffused conjunctiva, increased redness of lower palpebral conjunctiva and palmar erythema.

What are the common causes of polycythemia? 

• COPD.
• Congenital cyanotic heart diseases e.g. Fallot's tetralogy.
• Right-to-lcft shunt in the heart.
• Polycythemia rubra vera.
• High altitude and severe dehydration  can produce relative polycythemia

Thrombosis and peptic ulceration (often with bleeding) are noted complications of polycythemia.

What is normal reticulocyte count. reticulocyte index and red cell mass 

Reticulocyte count- 0.2-2% of RBCs (increased in haemolyttc anaemia).

Reticulocyte Index— Reticulocyte % X Patient's PCV/Normal PCV

Red cell mass-in males Male is 30ml/kg of body weight.

Female - 25 ml/kg of body weight.

It is increased in polycythemia rubra vera

Difference between conjugated and unconjugated hyperbilirubinemia

Following are the difference between conjugated and unconjugated hyperbilirubinemia

                                               Unconjugated                                  conjugated                 

Water solubility                      0                                                        +

Affinity for lipids                      +                                                       0               

Renal excretion                         0                                                       +

Van den Bergh reaction     Indirect                                              Direct

Fractions of normal bilirubin

Normal serum bilirubin level is 0.3-1.0 mg/dl.

Conjugated fraction is 0.1-0.3 mg/dl and

Unconjugated fraction is 0.2-0.7 mg/dl.

What are the conditions which produce predominantly conjugated and unconjugated hyperbilirubinemia?

Conjugated hyperbilirubinaemia is said to occur with > 50% conjugated fraction of bilirubin is conjugated

Causes of conjugated hyperbilirubinemia

• Viral or drug-induced hepatitis.
• Drug-induced cholestasis.
• Cholestatic jaundice of pregnancy.
• Cirrhosis of liver.
• Dubin-Johnson syndrome.
• Rotor syndrome.
• Secondary carcinoma of liver.

Causes of unconjugated hyperbilirubinemia

Unconjugated hyperbitirubinaemia is said to occur when the unconjugated fraction is > 80%

Causes of conjugated hyperbilirubinemia

• Haemolysis.
• Ineffective erythropoiesis.
• Prolonged fasting (<300 cal/day).
• Gilbert's syndrome and rarely Crigler-NaJ|ar syndrome
• Neonatal jaundice.

What is Jaundice?

Jaundice is defined as yellowish discoloration of sclera, mucous membrane, nailbed of skin due to excess amount of serum bilirubin of > 2 mg/dl. 

Subclinical jaundice -Serum bilirubin 1-2 mg/dl 

Normal -  serum bilirubin  < 1 mg/dl

What is latent jaundice?

The normal serum bilirubin level is 0.3-1.0 mg/dl. Clinical jaundice is evident only when scrum bilirubin exeeds  2.5 mg/d .Jaundice is said to be latent, i.e. when it is clinically non-evident and detected only by serum analysis.This is seen when the serum bilirubin level is in between l-2.5mg/dl.

What are the sites you should examine for jaundice ?

Upper bulbar conjunctiva is examined after retract the uppereyelid and ask the patient to look downwards both eye should be examined at a time 

• Undersurface of tongue.
• Soft palate.
• Palms and soles.
• General skin surface.

How to examine for jaundice ?

While examining for jaundice first elevate the upper eyelid, Then ask the patient to look down and then look at the periphery of the sclera in bright natural day light

As in the artificial light you cannot detect the light yellow discolouration of sclera always examine the patient in the natural light.You should take the patient in front of an open window for examination of jaundice.

Why the upper bulbar conjunctiva is selected for examination of jaundice?

• A white background is formed by sclera.
• Sclera of eye is rich in elastic fibers.Serum bilirubin has affinity to elastic fibers. Periphery of the sclera is  thick  with more elastic fiber so  early staining by bilirubin will occur at the periphery. In case of marked hyperbilirubinemia, all tissues except the brain is stained by bilirubin, the brain is not stained due the blood-brain barrier block the bilirubin staining of the brain.

What are the three types of jaundice?

Hemolytic anemia —This is a lemon yellow jaundice, Urine colour is normal no yellowish discolouration of urine hence called acholuric jaundice.

Hepatocellular jaundice jaundice- Hyper bilirubinuria with other stigmas of hepatocellular damage and other features of primary liver disease may be seen.

Obstructive jaundice –is characterised by greenish dark yellow jaundice, pruritus, pale stool, palpable gallbladder. 

This is seen in either intra-or extra- hepatic cholestasis.

Differential diagnosis of jaundice

Carotinemia is a condition characterized by yellowish discoloration of skin (carotenoderma) that spare the sclera and mucous membrane.

What are the diseases commonly present as latent jaundice?

• Mitral stenosis (passive venous congestion of liver).
• Myocardial infarction.
• Cirrhosis of liver.
• Pernicious anaemia.
• Acute pancreatitis.
• Pulmonary infarction (acute pulmonary thromboembolism).
• Congestive cardiac failure.

What are the causes of familial non-haemolytic hyperbilirubinaemias?

Gilbert's syndrome.

Crigler-Najjar syndrome.

Dubin-Johnson syndrome.

Rotor syndrome.

What are the clinical fatures of of obstructive jaundice ?

Following are the features of obstructive jaundice

Urine colour is yellow or mustard oil-like colour (due to conjugated bilirubin).

Stool is clay coloyred coloured (china-clay) with steatorrhoea (steatorrhoea means frothy bulky soft ,greasy  and offensive .This is due to absence of bile pigment in the stool.

Jaundice is greenish yellow due to due to oxidation of bilirubin to biliverdin

Generalised pruritus with scratch marks and shiny nails are seen in obstructive jaundice because the bile acids irritate the free nerve endings.

Sinus bradycardia occurs as bile salts directly inhibit the sinoatrial node.

Xanthelasma near eye and xanthoma in knees, buttocks may be seen due to hypercholestrolemia.

Deficiency of fat soluble vitamin produce 

• Petechiae, purpura or ecchymosis are seen due to vitamin K deficiency as lack of bile salts produces malabsorption produces
• Prolonged obstructive jaundice can produce osteomalacia- bonePain. bone fracture due to vitamin D deficiency this is due to malabsorption or steatorrhea and it is called as hepaticosteodystrophy

Gall bladder may be palapable. If it is palpable it indicate that the site of obstruction is bile dut and it is due to carcinoma head of pancreas and not due to choledocholithiasis according to Courvoisiers law

What are the causes of obstructive jaundice?

Obstructive jaundice can be intrahepatic or extrahepatic

Intrahepatic (medical) causes of jaundice are 

• Cholestatic viral hepatitis.
• Chronic active hepatitis.
• Cirrhosis of liver (specially primary biliary cirrhosis).
• Lymphoma.
• Drugs azole. methyl testosterone, anabolic steroids.
• Secondary carcinoma of liver (jaundice is rarely seen in hepatoma).

Extrahepatic /surgical causes of jaundice

• Gall stone impaction in CBD.
• Carcinoma of the head of pancreas.
• Carcinoma of gall bladder.
• Stricture of CBD.
• Enlarged glands at porta hepatis
• Sclerosing cholangitis from inflammatory bowel disease.

What are the medical causes of extrahepat1c obstruction

• Sclerosing cholangitis in ulcerative colitis.
• Obstruction by round worm in CBD.
• Enlarged Iymph nodes at porta hepatis in lymphoma.

Features of hepatocellular jaundice

Features of hepato cellular jaundice  are given below

• There is yellowish discolouration of urine.
• Stool is high coloured and become pale if there is obstruction due to cellular odema
• Orange yellow tinge of bulbar conjunctiva
• Anorexia ,nausea and vomiting is present before the appearance of jaundice
• Tender hepatomegaly is frequent.

Causes of Hepatocellular jaundice

• Viral hepatitis (type A and E commonly).
• Drugs — Rifampicin. INH, after halothane anaesthesia.
• Poisons - Copper sulphate.
• Pregnancy — Acute fatty liver of pregnancy.
• Alcoholic hepatitis.
• Weil s disease.

What are the clinical features of haemolytic jaundice?

Following are the clinical feaatures of hemolytic jaundice

• Acholuric  urine means freshly passed urine is of normal colour as there is no bilirubin in urine but if the urine sample is kept for sometime, this will turn dark yellow due to conversion of urobilinogen to urobilin by oxidation.
• Stool is high-coloured due to excess amount of stercobilinogen and stercobilin.
• Jaundice is usually mild and there is lemon-yellow tinge of bulbarconjunctlva. 
• Serum bilirubin is usually less than 6 mg/dl and this is predominantly of unconjugaled variety.
• Anaemia is present .It can be mild, moderate or severe, according to the degree of haemolytic process.
• Splenomegaly, is very characteristic of haemolytic anemia

What are the causes of  Haemolytic jaundice?

Following are the common causes of haemolytic jaundice

• Thalassaemia.
• Mismatched blood transfusion.
• Snake bite (Viperidae group).
• Malaria (specially falciparum malaria).
• Rh incompatibility.
• Primaquine or sulphonamide-induced (in GePD deficiency).