Jaundice

 

Jaundice

P.K.Ghatak, MD

Jaundice is a yellowish discoloration of the body, easily noticeable in the white of the eyes, under the surface of the tongue and skin. It is a symptom and not a disease. It is the job of a physician to find the case of jaundice.

The immediate cause of jaundice is presence of excess amount of a pigment - Bilirubin in the blood. Bilirubin is a waste product, appear in the blood from breakdown of the hemoglobin. A small amount of bilirubin is also obtained from muscles and liver and from enzyme system containing iron molecule as in Cytochrome. Bilirubin gives straw color to the urine and yellow-brawn color to stool. A normal bilirubin level in the serum is less than 1 mg/dL, and when jaundice is detected the bilirubin level reaches 2.5 mg/dL or higher.

The liver cells filter bilirubin out of the blood and excrete bilirubin in the bile. Bile reaches the small intestine intermittently from the gallbladder. The bilirubin is partly absorbed from the intestine and returned to the blood. In the kidneys the bilirubin is filtered out and excreted in the urine, the part not absorbed in the gut, is eliminated in the stool.

The possible ways excess bilirubin can accumulate in blood when an excess of Red Blood Cells are destroyed, in diseases of the liver cells, obstruction of the common bile duct and gallbladder diseases.

Physiological Jaundice in all Newborn.

A fetus draws oxygen and nutrients from mother's blood through the placenta. The oxygen level of the placental blood is lower than the oxygen in the lungs. To circumvent this problem, the fetus is provided with a special hemoglobin - Fetal hemoglobin, which is capable of drawing adequate amount of oxygen in low oxygen environment. The fetal hemoglobin is not needed as soon as the newborn child takes the first breath in the form of a cry. This acts fills up child's lungs with air. A mechanism is in place in switching production of adult type of hemoglobin and stop fetal hemoglobin production immediately after the first breath of the newborn. The fetal hemoglobin of the newborn begins to breakdown. As a result, the bilirubin in the blood of the newborns are higher than adults. The normal range of bilirubin in the newborn is about 10 mg/dL on the 1^st day and 15.18 and 20 mg on successive 2nd,3rd and 4^th day. Then the bilirubin level declines rapidly.

Congenital enzyme deficiency diseases, namely Gilbert syndrome and Dubin- Johnson syndrome. Both are inherited as autosomal recessive pattern. Both are benign causes of jaundice, and produce no ill effects. In Gilbert syndrome, the Gluconosyltrasferase enzyme is deficient due to mutation of UGT1A1 gene. In Dubin-Johnson dyndrome a transport protein is deficient which produces accumulation of bilirubin in blood and in the liver.

Bilirubin in the blood.

In normal adults, the bilirubin is present in two forms - conjugated bilirubin and unconjugated bilirubin.

The conjugated bilirubin is formed by the liver cells by reacting it with Glucoronic acid. In the laboratory, it is detected by a test called Direct Acting Bilirubin. The most of the bilirubin in the blood under normal condition is conjugated direct acting bilirubin. A small amount of bilirubin in the blood is unconjugated and is detected in the lab by adding alcohol, and the test for this reason is called indirect acting bilirubin.

Breakdown of hemoglobin produces bilirubin but not in every instance jaundice happens – development of jaundice depends on degree and duration of hemolysis and functional status of the liver and Kidneys.

Cause of jaundice:

A. RBC destruction.

1. Congenital causes

a. abnormal shape and size of RBC.

RBCs travel through capillaries, the diameter of the capillaries are just large enough for normal size RBCs to pass through. In congenital abnormal RBC, as in Hereditary Spherocytosis and Hereditary Elliptocytes, in the attempts to negotiate through the narrow capillaries, the RBC membrane breaks down, releasing hemoglobin.

b. Congenital absence of RBC enzymes. In G6PD (glucose 6 phosphate deficiency) and Pyruvate kinase deficiency, the RBCs are fragile and breaks down easily. In G6PD deficiency the cell membrane fails to maintain integrity and spleen breaks down damaged RBC, in Pyruvate-kinase deficiency, ATP level falls leading to dehydration of RBC and deformed RBCs are similarly broken down.

c.  Abnormal hemoglobin. In Sickle Cell Anemia, the sickle shaped RBCs unable to negotiate through capillaries and breaks down. Similarly, in beta Thalassemia the RBCs break down.

2. Other causes of Intravascular hemolysis and its mechanism.

1	ABO blood group mismatch	Presence of antibodies in recipient attacking donor RBCs, on repeated transfusion development of antibodies attacking recipient's own RBCS
2	Mycoplasma infection and cold agglutinins	i-antigen initiates antibody production, which mistakenly attack RBCs, reaction takes place in cold. HIV, E-B virus and other virus also produce cold agglutinins and complement is required for hemolysis.
3	Streptococcus infection	Hemolysin is generated by growing streptococcus in the infected tissue, produces 3 types of hemolysis -alpha, beta and gamma
4	Staphylococcus infection	Alpha, beta, gamma, delta, omega hemolysis generated by staph colonies. In addition, PLV toxin drill holes in the RBC membrane and hemoglobin leaks out in the serum.
5	Enterococcus	Most virulent of all coccal infections, generates alpha and beta hemolysins.
6	Clostridia perfringens	Produces gas gangrene. It produces Alpha toxin which liquefies RBCs, muscles and soft tissues.
7	Autoimmune hemolytic anemia	Misdirected antibodies causes hemolysis, generally follows drug therapy. The common drugs are Cephalosporins, Penicillin, Levodopa, Levofloxacin, Nitrofurantoine, NASDs, Dapsone, Methyldopa, Quinidine and Pyridium.
8	Warm agglutinins	warm antibodies are present in congenital syphilis, SLE and Scleroderma and bacterial infections
9	Malaria and Babesosis	Different morphological shapes and sizes of the stages of developing young forms and parasite load rupture RBC membrane.
10	Complications of pregnancy	Toxemia of pregnancy called Eclampsia and HELP syndrome
11	Non-immune hemolytic anemia	In paroxysmal cold agglutinins hemolysis, antibodies develop following viral or bacterial infection and unknown causes, hemolysis takes place at body temperature. Paroxysmal Nocturnal Hemoglobinemia develop due to an acquired mutation of PIGA gene, the main features and hemolysis, thrombosis and smooth muscle dystonia. Death occurs from the bone marrow failure,
12	Poison and Toxins	RBCs are destroyed by enzymatic action of snake poison and similarly by poison of other animals and plants.
13	Artificial mechanical heart valves and other medical devices	The plastic or metal surface of these devices, including the heart-lung machine, are noncompliant and as RBCs are thrown against them, The RBCs rupture.
14	Other illnesses including hematological and solid organ malignancies.	Some hematological conditions produce abnormal shape and sizes of RBCs, others produces hemolytic cytokines, still other changes coagulation factors and platelet function which causes capillary thrombosis, intramuscular hemolysis.
16	Cirrhosis of liver	Usually chronic addiction to alcohol and also in non-alcoholic steatosis.

3. Obstructive Jaundice.

Obstruction of free flow of bile from the liver to the duodenum can happen in various medical conditions, the chief among them are Gall stones, Cholangiohepatitis, Liver flukes in East Asia countries. Cancer of the head of the pancreas, Metastatic cancer of lymph nodes of portahepatis and lymphoma, and Hepatocellular carcinoma

The main features of obstructive jaundice are progressive deepening of jaundice. Dark urine and light color stool. Intense skin itching due to deposition of bile salt in the skin. Enlarged liver.

4. Viral Hepatitis.

Virus infection disrupts cellular function of the liver cells and bilirubin is not extracted, also inflammatory edema of the liver blocks narrow intra lobular bile canniculi, preventing the forward flow of bile through the duct system

Many viruses infect the liver. The virus that cause the most serious form of hepatitis is Hepatitis B, followed by Hepatitis D and Hepatitis C. Hepatitis A virus and Hepatitis E virus infections break out in South Asian countries following monsoon rain and floods, contaminating drinking water sources with human feces. The hepatitis produced by these two viruses are generally milder and self limited. To name few other important hepatitis viruses are Yellow Fever virus, Adenovirus – Lassa fever is a serious infection. Filovirus – Ebola and Marburg fever viruses. Herpes virus- Cytomegalovirus infection, Epstein-Barr virus and Human Herpes virus 6 are important in this group.

In day to day practice, jaundice is not a rare finding. Off the causes mentioned above, these medical conditions are likely to be encountered.

1. Viral hepatitis. 2. Acute and chronic cholecystitis and gall stone obstruction of bile duct. 3. Bacterial infections. 4.  Cirrhosis of the liver 5. Sickle cell anemia and Thalassemia. 6. Mismatched blood transfusion. 7. Cancer of the head of pancreas and Hepatocellular carcinoma of the liver. 8. Lymphoma. 9. Therapeutic use of certain drugs. 10.Cholangiohepatitis. 11. Liver fluke infestation of biliary system in certain South Asian countries. 12. Gilbert syndrome and Dubin-Johnson syndrome.

 An attempt is made to point out jaundice develops not only from hepatitis but a host of other medical conditions. The obstructive jaundice requires urgent surgical consultation. To relieve intense itching and painful enlarged liver, a transcutaneous bile duct stent can be placed to drain the bile in the small intestine, bypassing the obstruction.

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