Ques. 1 What is Jaundice?
Ans. It is a syndrome characterized by yellowish discolouration of the skin, sclera, and other mucous membrane of body due to hyper bilirubinaemia. Normal blood bilirubin content is 1/400,000 to 1/1000,000, i.e. 0.2-0.5 units, a unit being 1/200,000 or 0.5 mg percent. The renal threshold is 1/50,000 or 4 units or 2 mg percent. Clinically manifestation of the Jaundice occurs when 1/80,000 is exceeded, but when hyper bilirubinaemia is below level there is no yellow staining of the tissues (Latent Jaundice) as is cancer and cirrhosis of liver and pernicious anaemia.
Ques. 2 What are the various types of Jaundice seen in clinics?
Ans. The various types of jaundice seen in clinics are :
- According to Richs Jaundice are of 3 types: (i) Regurgitation Jaundice. (ii) Mixed Jaundice. (iii) Retention Jaundice.
- According to McNee’s – Clinically Jaundice are of 3 types: (i) Obstructive. (ii) Toxic. (iii) Haemolytic.
Haemolytic Jaundice – (Pre-hepatic Jaundice)
This is due to increased bilirubin in plasma with excessive breakdown of R.B.C. due to some toxic effect; resulting in:
- presence of stercobilinogen in faeces.
- presence of urobilinogen in urine.
- excess bilirubin in plasma.
Ques. 3 What are the causes and clinical manifestations of Jaundice?
Ans. Causes : This generally occur in malaria, black water fever, alcoholic family jaundice, incompletible blood transfusion, snake bite, paxorysmal haemoglobinuria & acute streptococcal infections.
The conjunctive being rarely affected, staining colour is lemon yellow, splenomegaly is frequent, liver is enlarged or normal, anaemia profound, the sedimentation rate of the RBC increased, Vanden Bergh’s test is indirect.
Obstructive Jaundice (Post-hepatic Jaundice).
It is due to obstruction of passage of conjucated bilirubin from liver cell to intestine. It is mainly due to obstruction of extrahepatic origin, and some time due to intrahepatic obstruction. It is also known as cholestasis.
Causes: (a) Extra-hepatic :
- Blockage of common bile duct by gallstone, congenital stenosis, growth stricture etc.
- Obstruction of ampula of vater due to carcinoma.
- Obstruction at the pancreas due to origin of cancer at the head of the pancreas by mechanical pressure.
- Formation of lymph node at portahepatic.
- Parasitic obstruction at the common bile duct (Ascaris lumbricoides)
(b) Intra-hepatic :
- Tumour inside the liver cell.
- Carcinoma at the lobule of the liver.
Clinical manifestations :
In obstructive Jaundice, the onset is stormy, the conjunctivae are more pigmented than the skin, colour being dirty yellow, pruritus is severe, the liver is enlarged, stools bulky whitish and Vanden Bergh’s test is direct immediate positive.
In this case –
- Absence of stercobilinogen in stool (so whitish stool).
- Urolibinogen absence in urine.
- Increased amount of bilirubin in plasma:
Toxic Jaundice (Hepatic Jaundice).
It is due to some of the toxins & produced by certain virus or some by injections (chloropromazine).
Main Causes: It is found in catarrhal jaundice, weil’s disease, infective hepatitis, chemical poisonings, bacterial infections (pneumonia, typhoid) & drug toxicity.
Clinical manifestation: The onset is quiet, skin is affected before the conjunctiva, the colour being orange-yellow; pruritus is slight, liver is enlarged or dormal, Vanden Bergh’s test show delayed direct response or biphasic.
Arnold Rich classifies Jaundics as:
- Regurgitative Jaundice , i.e., a jaundice in which the whole bile accumulates and is returned to the circulating blood.
- Mixed jaundice, being a combination of both.
- Retention Jaundice i.e., a form of jaundice due to the inability of the liver to dispose of the bilirubin provided by the circulating blood.
Ques. 4 What is Latent Jaundice?
Ans. It is a condition where increase bilirution in blood without any clinical manifestations of Jaundice. In this case inner cells completely turn into yellowish greenish except cells of brain matter. Generally it is seen in the case of bilirubin content of blood is above 2 to 3 mg/100 ml.
Ques. 5 What is meant by Reaction of Jaundice (Vanden Bergh Reaction)?
Ans. Pathologically reaction of Jaundice classified under following heads:
- Indirect Vanden Bergh Reaction.
- Biphasis Vanden Bergh Reaction.
- Direct Vanden Bergh Reaction.
- In obstructive Jaundice – Vanden Bergh test is direct and prompt.
- In Haemolytic Jaundice – Vanden Bergh test is indirect.
- In Toxic or infective Jaundice – Where there is parenchymatous liver damage – Vanden Bergh test is delayed direct or biphasic.
Ques. 6 What is the test done to determine the type of Jaundice? Or, What is Vanden Bergh test? How it is done?
Ans. This test helps in detection of bile pigment in blood serum. There are three types of reactions.
- Direct, (b) Biphasic, (c) Indirect.
Two solutions are used in this test are: -
- Solution I : Sulphanilic acid 1 gm.
Concentrated HCI 1.5 ml.
Dist. Water 100 ml.
- Solution II : Sodium nitrate 5 gm.
Water 100 ml.
- 25 ml. of No. I solution is mixed with 0.75 ml. of No. II solution : Diazoreagent.
- Then 1 ml. of serum is taken in a small test tube and to it equal amount of Diazo-reagnet is added, any one of the following reactions may be occurred.
- Indirect reaction : At first 1 ml. of serum is treated with 2 ml. of 9% alcohol. It is shaken and centrifuged. 1 ml. of supernatant fluid is taken and to it 0.25 ml. of Diazoreagent is added. A reddish-violet colour appears immediately.
- Direct reactions :
- Immediate or Prompt- A bluish violet colour immediately appears (with in 10-30 seconds).
- Delayed-Reddish colour appears which gradually becomes violet & this takes from 5-15 minutes or even half an hour.
- Biphasic reaction : A reddish colour appears promptly and after much longer time becomes of violet colour.
- Vanden Bergh test indirect – Haenmolytic Jaundice.
- Vanden Bergh test is delayed direct or biphasic – Toxic or infective Jaundice where there is parenchyatous liver damage.
- Vanden Bergh test is direct and prompt – Obstractive Jaundice.
Ques. 7 How will you investigate a case of Jaundice in the laboratory?
Ans : The differences between Obstructive, Toxic and Haemolytic Jaundice:-
Toxic or defective
Colour of skin
Irritation of skin
Colour of stool
Albumin and globulin
Yellow, orange or greenish
Seen in conjunctiva
Bile pigments present.
Large or very large
May be palpable
May or may not present
Normal Until later
Steadly raising serum
bilirubin and direct
Yellow, orange of greenish.
Seen in skin before
May be present
Normal of pale
Often no bile pigments
Large, normal of small
Usually not serere
Normal or increased
Low albumin, raised
Moderate serum billirubin
Light yellow, ‘lemon yellow’
No bile pigments
A little large or round
Normal, fragility of
Red cells may be increased.
High serum bilirubin
and no direct reaction.
Ques. 8 What are the Physio-pathogenesis of Jaundice?
Ans. The bile pigments involved are bilirubin, biliverdin, the urobilinogens, and the urobilinoid pigments. These natural bile pigments derived from the catabolism of heme; sources include Hb and non-Hb heme of degener ating RBCs, RBC precursors in marrow, and heme proteins of liver and other tissues. There is no evidence for direct synthesis of bilirubin from heme precursors.
Bilirubin is a pigmented organic anion closely related to porphyrins and other tetrapyrroles. As an insoluble waste prouduct of heme catabolism, it must be converted to the water soluble products products for excretion. This transformation is over all purpose of bilirubin metabolism takes place in five major steps. Abnormalities at any of following steps can result in Jaundice.
Formation : About 250 to 350 mg of bilirubin are formed daily, and 80 to 85 percent is derived from breakdown of senescent RBCs. The remaining 15 to 20 percent of the pigment arises from other heme proteins primarily located in the bone marrow and liver. The hene moiety of Hb is degraded to iron and the intermediate product, biliverdin by microsomal enzyme heme oxygenase.
The biliverdin product in converted to bilirubin available supernatant enzyme, biliverdin reductage.
Little information is available concerning specific reactions leading from non-Hlb heme to bilirubin. One of the major areas of interest, however, involves the early labeled bilirubin that bilirubin which is synthesized from heme other than that of the circulating RBCs, early labeled bilirubin comprises 10 to 20 percent of bilirubin secreted under normal circum stances, but upto 80 percent of that secreted by patients with pernicious anaemia, thalacemia, & erythropoitic porphyria. Early labeled bilirubin is heterogeneous; the first major component arises from noneryth ropoietic heme, has its origin primarily in liver, and is related in part of the turnover of heme-containing enzymes in liver. The second major component is crythropoietic in origin & includes both Hb and non-Hb heme.
Plasma transport :
Bilirubin, which is insoluble in water, is transported in plasma bound to albumin. Although the binding is light, it is weakend under certain conditions, such as acidosis, and there is competition for binding sites. For example, by certain antibiotiotics, thyroxine & free fatty acids. This circulating unconjugated (in direct-reacting) bilirubin cannot difuse across cell membranes other than those in the liver & therefore, does not appear in the urine.
The details of bilirubin uptake by liver have not been worked out, the process is rapid, does not involve the uptake of serum albumin & probably involves active transport. The role of ligandin (Y protein) & other intracellular binding proteins remains to be defined.
Free bilirubin is concentrated in liver and then conjugated with glucuronic acid to from bilirubin diglucuronide, or conjugated (“direct-reacting”) bilirubin. This reaction, catalyzed by microsomal enzyme glocoronyl transferase, renders to pigment water soluble. Bilirubin conjugates other than diglucuronide are also formed but their significance is uncertain.
Biliary excretion :
Conjugated bilirubin is secreted into bile canaliculus alongwith the other constituents of bile. This process is complex and can be affected by the presence of other organic anions or drugs. In gut, the pigment is deconjugated and reduced by bacterial flora to various compounds collectively called stercobilinogens. Most of these are excreted in the faeces, but substantial amounts are absorbed & re-excreted in bile; small amounts reach the urine as urobilinogen. The Kidney can also excrete bilirubin diglucuronide, but not unconjugated bilirubin. Renal excretion of bile pigments is not important normally but may become so with deep Jaundice.
So from above discussion it is seen that-increased formation, impaired hepatic uptake, or decreased conjugation cause unconjugated hyperbilirubinemia. Impaired biliary excretion also they produce conjugated byperbilinemia. In practice, however, hepatic diseases & biliary obstruction usually create multiple defects, resulting in a mixed hyperbilirubinemia. In most patients with obvious hepatobiliary disease, bilirubin fractionation is, therefore, of little diagnostic value.
Haemolysis & several uncommon disorders of bilirubin metarbolism produce jaundice in the absence of demonstrable liver disease.