Bile pigments and Jaundice
Bile pigments
The bile pigments are the waste products of the hemoglobin (Hb) breakdown give yellow/green colour to bile. Bilirubin, the brownish yellow pigment is readily oxidized into biliverdin which gives green colour to the bile of the herbivores.
Bilirubin is produced from Hb with destruction of RBC in the reticuloendothelial system (RES) of the body (eg. spleen, liver and bone marrow).
It is normally present in the blood in low concentration. Bilirubin is highly soluble in all the cell membranes. But high concertration of bilirubin is very toxic, needs excretion through bile,one of the very important functions of the liver.
When the RBC have lived out their life span of 120 days they have become too fragile to exist longer in the circulatory system, their cell membrane rupture and release Hb.
Released Hb undergo phagocytosis by tissue macrophages (RES). Haemoglobin is split into haem and globin of which globin is readily transported to protein pool of the body for reutilization.
Haem ring gives (a) free iron that is transported in the blood by transferrin and (b) 4 pyrol nuclei , the substrate for bile pigments. The first pigment formed is biliverdin and is rapidly reduced to free bilirubin , which is gradually released into the plasma.
Free billirubin immediately and strongly combine with the plasm albumin and transported through the blood and the interstitial fluid. Bilirubin bound with plasma protein called as “Free bilirubin” is insoluble that can’t pass through kidney.
Within hours, this free billirubin pass through the hepatic cell membrane, where it is released from the plasma albumin, but instantaneously combines with one of the 2 protein (Y and Z proteins) inside the liver cell which traps the bilirubin.
Soon after bilirubin is released from these proteins it conjugated with glucuronic acid, phosphate and sulphate to form bilirubin glucuronide and 10% as bilirubin phosphate and rest as billirubin sulphate respectiely.
These conjugated forms are excreted by active transport into the bile canaliculi.
Formation and fate of urobilinogen
In the intestine, ½ the conjugated bilirubin is converted into highly soluble urobilinogen and stercobilinogen by bacterial action. Some of the urobilinogen gets absorbed from intestinal mucosa into the blood. Most of them re-excreted into the gut by the liver.
After exposure to air the urobilinogen is oxidized to urobilin and excreted through urine, giving yellow colur to urine. Stercobilinogen is converted into stercobilin and excreted through the feces.
Jaundice
Jaundice is much a symptom than a disease. It gives a yellowish tint to the body tissues, including the skin and deep tissues.
Usual cause of jaundice is the presence of large quantities of bilirubin in the ECF, either free or conjugated form.
Normal plasma concentration of bilirubin (both free and conjugated) is about 0.5 mg/100 ml of plasma.
In abnormal conditions, it can rise up to 40mg/100 ml. Skin may appear yellow when the concentration of bilirubin rises to about 1.5 mg/100 ml.
- Physiological classification of jaundice:
- Hemolytic jaundice
- Obstructive jaundice
Hemolytic jaundice
Hemolytic jaundice is due to excessive destruction of RBC with rapid release of bilirubin in to the blood. In this condition excretory function of the liver is not impaired. Plasma concentration of both free and conjugated form of bilirubin are elevated much above the normal level. The rate of formation of urobilinogen in the intestine is also increased.
Obstructive jaundice
Obstruction in the bile ducts or damage to the liver cells leads to improper excretion of the usual amounts of bilirubin in to the G.I tract. In this condition the rate of bilirubin formation is normal.
The free bilirubin gets into the liver cell for conjugation. Rupture of the bile canaliculi directly empties conjugated bilirubin into the lymph, hence most of the plasma bilirubin are of conjugated type rather than free bilirubin.
Differential diagnosis of hemolytic and obstructive jaundice
Vanden Berg test is the specific test to differentiate free and conjugated bilirubin in the plasma. In the case of direct Vandenberg reaction Vandenberg reagent shows immediate reaction with conjugated bilirubin.
Free bilirubin in the presence of alcohol precipitates the protein and releases the bilirubin, which reacts with Vandenberg reagent. Hence it is called as indirect Vandenberg test.
Indirect Vandenberg reaction is the confirmatory test of hemolytic jaundice due to high content of free bilirubin in the plasma, whereas obstructive jaundice can be confirmed by direct Vandeberg reaction due to increased content of conjugated bilirubin.
In the case of total obstruction of bile flow, lack of bilirubin in the intestine prevents the conversion of bilirubin in to urobilinogen by bacterial action. Urobilinogen is not available for reabsorption through portal blood and the excretion of urobilin through urine, henc test for urobilinogen in urine is completely negative .
The stools become clay coloured due to lack of stercobilin and other bile pigments. Kidney can excrete only highly soluble conjugated bilirubin but not the albumin bound “free bilirubin”.
In severe case of obstructive jaundice large quantities of conjugated bilirubin froms foam and becomes intense yellow colour while shaking the urine.