•Jaundice appeared due to mainly liver disease because of increased bilirubin level in the blood. jaundice also develops due to drugs vascular and mass lesion. the diagnosis of jaundice made by patients history, physical examination, and laboratory tests.
Liver function and structure of jaundice
•Liver receives 20% of the blood flow is oxygen-rich blood flow from the hepatic artery, and 80% nutrition-rich blood from portal vein arising from the stomach, intestine, pancreas, and spleen.
•Hepatocytes are the major cells in the liver, remaining cells are kuffer cell (reticuloendothelial system), stellate (fat cell), endothelial and blood vessels cell, bile ductular cell.
•Portal area consists of small arteries, bile ducts, and lymphatics organized in the loose connecting stroma of matrix and collagen. Blood flowing into the portal area is distributed through the sinusoids, passing from zone 1 to zone 3 of the acinus and drain into the hepatic vein(central vein). •Bile flows in the opposite direction. Further, read on united kingdom jaundice
•Hepatocyte’s basolateral sideline the space of Disse and richly lined with microvilli, and exhibit endocytotic and pinocytotic activity with passive and active uptake of nutrients.
•Hepatocytes synthesize essential serum protein, bile, and its carrier regulation of nutrients and metabolism and conjugation of lipophilic compounds for excretion in the bile or urine.
Evaluation of liver function of jaundice
•Biochemical test used for
•1. detect the presence of liver disease
•2.distinguish types of liver disorders
•3. gauge the extent of liver disease
•4. follow response to treatment
•Liver test rarely suggests a specific diagnosis, to increase the sensitivity and specificity of laboratory tests use them as in combination include bilirubin, aminotransferase, alkaline phosphatase, albumin, and prothrombin time. Further, read united states on jaundice
•bilirubin is a breakdown product of the porphyrin ring of heme-containing protein s is found in two fractions conjugated and unconjugated.
•Elevated Unconjugated bilirubin also term indirect bilirubin is water-insoluble and is bound to albumin in the blood.
• direct or Conjugated bilirubin is water-soluble therefore excreted by the kidney.
•Normal value of total bilirubin between 1 and 1.5 mg/dl •If the direct-acting fraction is < 15% of the total, the bilirubin can be considered indirect.
•Isolated elevation of unconjugated bilirubin is seen in hemolytic anemia such ass Crigler-Najjar and gilbert’s syndrome.
• absence of hemolysis and isolated elevation of unconjugated bilirubin is an otherwise healthy patient can attribute to gilbert’s syndrome.
•in contrast, conjugated hyperbilirubinemia almost implies liver or biliary disease the rate-limiting steps in bilirubin metabolism. It is not the conjugation of bilirubin but rather the transport of conjugated bilirubin into the bile canaliculi.
• viral hepatitis, the higher the serum bilirubin, the grater is the hepatocellular damage. •Bilirubin found in urine is Conjugated bilirubin.
Serum enzyme of a jaundice patient
•Elevation of given enzyme activity is thought to primarily reflect its increased rate of entrance into serum from the damaged liver cells.
•1.Elevation of enzymes due to damaged hepatocytes.
•2. Elevation of the enzyme due to cholestasis.
Enzymes that reflect damage to hepatocytes produce jaundice
•The aminotransferase are sensitive indicators of liver cell injury.
•Aspartate aminotransferase (AST) and alanine aminotransferase(ALT).
•ALT primarily found in the liver and more specific for liver injury.
•Normal ranges from 10 to 40 IU /L •Striking elevation >1000 IU/L suggestive of hepatocellular injury 1.viral hepatitis 2. ischemic liver injury 3. toxin or drug-induced liver injury
•Pattern of aminotransferase elevation can be helpful diagnostically. •Acute hepatocellular disorder ALT>or equal to AST
•AST:ALT <1 with chronic viral hepatitis and nonalcoholic fatty liver disease •AST:ALT >1 cirrhosis
•>3:1 highly suggestive of alcoholic liver disease
Enzyme that reflect cholestasis and develop jaundice
•Alkaline phosphatase, 5’ nucleotidase, and y-glutamyl transpeptidase are usually elevated in cholestasis.
•Alkaline phosphatase consists of many isoenzymes found in bone, placenta, liver, and small intestine. •Elevation of four-time of enzymes considers for cholestasis.
•If elevated enzymes in a healthy person, evaluation is done by electrophoresis and GGT, serum 5’ nucleotidase.
•Absence of jaundice and elevation of enzymes rule out Hodgkin’s disease, diabetes, hyperthyroidism, congestive heart failure, amyloidosis, and inflammatory bowel disease.
Elevation of alkaline phosphatase elevation is not helpful in distinguishing between intrahepatic and extrahepatic cholestasis.
Liver function test for jaundice
•Serum albumin synthesized by hepatocytes and has a long half-life of 18-20 days, levels < 3 g/dl should raise the possibility of chronic liver disease.
•Hypoalbuminemia caused by chronic disease and nephrotic syndrome. That associated with increase interleukin 1 which inhibits albumin synthesis.
•Serum globulin is a group of protein alpha beta and gamma, alpha and beta synthesized by hepatocytes, and gamma by b lymphocytes.
• As a result of liver failure in jaundice patient has increased gammaglobulin
•Diffuse polyclonal increase IgG common in autoimmune hepatitis, IgM in primary biliary cirrhosis, IgA in alcoholic liver disease.
Coagulation factor of a jaundice patient
•Prothrombin time measures factor 2,5,7,10. and biosynthesis of factor 2 7 9 10 depends on vitamin k.
•PT elevated in hepatitis, cirrhosis, and vitamin k deficiency. •INR, total serum bilirubin and creatinine are the component of the MELD score which measures hepatic decompensation.
AMMONIA in jaundice
•AMMONIA is a product of protein metabolism and intestinal bacteria. • liver detoxicate ammonia into urea which is secreted by the kidney.
•Strated mascle plays a role in the detoxification of ammonia. It converts glutamic acid to form glutamine.
•Increased Serum ammonia level in hepatic encephalopathy may not give a proper measurement.
Liver biopsy in jaundice patient
•It is safe procedure and has proven value
•Hepatocellular carcinoma, prolonged hepatitis, unexplained hepatitis, unexplained splenomegaly, hepatic lesions uncharacterized by radiological imaging, fever of unknown origin, staging of malignant melanoma,
•Significant ascites and prolong INR
Non-invasive tests for jaundice patient
•Liver biopsy is a standard test for hepatic fibrosis.
•Multiparameter tests aimed at detecting and staging the degree of hepatic fibrosis and imaging.
•Fibro tests (fibrosure in the united states) include haptoglobin, bilirubin, GGT, apolipoprotein A-1, a2 macroglobulin.
•Transient elastography (fibroscan) and magnetic resonant elastography (MRE) both have gained which is approved by the US food drug administration.
ultrasonography of jaundice patient
•First diagnostic test whose liver test suggests cholestasis, to look for dilated intrahepatic or extrahepatic biliary tree or gall stone.
•Also distinguish between a cystic and solid mass and helps direct percutaneous biopsy.
•Doppler imaging can detect the flow of the hepatic artery and vein.
Use of liver test
|disorder||bilirubin||aminotransferase||Alkaline phosphatase||albumin||Prothombin time|
|Acute hepatocellular necrosis||Both elevated||>500iu ALT>AST||<3x||N||N|
|Chronic hepatocellular necrosis||May elevated||<300||<3X||decrease||prolong|
|Alcoholic hepatitis||May elevated||AST:ALT >2||<3x||decrease||prolong|
|Inta-extra hepatic cholestasis||May elevated||normal||>4x||N||N|
|Obstuctive jaundice||bilirubiuria||Rarely >500||>4x||N||N|
THANK YOU FOR RADING
DR MANISH KHOKHAR MD MEDICINE