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Transcript of LIVER DISEASES
Physiology of liverLiver is the largest organ of the body.Sets in the right side of the belly.Weighs between 1.0-2.5 kg.Heavier in males than females.It is reddish in color & feel rubbery to touch.Have two sections-right & left lobe. The right lobe is further divided into the interior and posterior segments
The externally visible falciform ligament divides the left lobe into the medial and lateral segments.Liver is supplied with blood from two sources the hepatic artery & portal vein.Responsible for 25 %of the basal metabolism & intimately concerned with the metabolism of fats,protiens & CHO.
structure of liverComposed of 50,000-100,000 lobules. Each lobule consist of a central vein surrounded by tiny liver cells grouped in the sheet or bundle.Small branch of hepatic vein extends through their centre. .Space b/w these cells contain sinusoids (blood vessels that are irregular in shape, incomplete in size &wider than blood capillaries .)
Blood supplythe liver receives blood containing oxygen from the heart. This blood enters the liver through the hepatic artery. The liver also receives blood filled with nutrients, or digested food particles, from the small intestine. This blood enters the liver through the portal vein. In the liver, the hepatic artery and the portal vein branch into a network of tiny blood vessels that empty into the sinusoids.The liver cells absorb nutrients and oxygen from the blood as it flows through the sinusoids. At the same time, they secrete sugar, vitamins, minerals, and other substances into the blood. The sinusoids drain into the central veins, which join to form the hepatic vein. Blood leaves the liver through the hepatic vein.Each lobule also contains bile capillaries, tiny tubes that carry the bile secreted by the liver cells. The bile capillaries join to form bile ducts, which carry bile out of the liver. Soon after leaving the liver, the bile ducts join together, forming the hepatic duct. Excess bile flows into the gall bladder, where it is stored for later use. Blood supply
Functions of liverSecretion of bile Storage of glycogenMetabolism of fatsDeamination of amino acidsProduction of the plasma protiens.Storage & transport of vitamins & minerals.Storage of iron .Production of clotting factors .Production of heat .Detoxification.Acts as filter
Role of branched chain amino acids & aromatic amino acids in liver disease major hypothesis for the pathogenesis of portal systemic encephalopathy has been termed the altered neurotransmitter Theory. A plasma amino acid imbalance existsin ESLD in which the branched-chain amino acids( BGAAs) valine, leucine, and isoleucine are decreased, and aromatic amino acids (AAAs) tryptophan, phenylalanine, and tryrosine,plus methionine, glutamine, asparagine, and histidine are increased.The BCAAs furnish as much as 30% of energy requirements for skeletal muscle, heart, and brain when gluconeogenesis and ketogenesis are depressed .This causes serum BCAA levels to fall. At the same time, plasma AAAS and methionine are released into circulation by muscle proteolysis, but the synthesis into protein and liver clearance of AAAs is depressed . This changes the plasma molar ratio of BCAAs to AAAS and may contribute to the development of hepatic encephalopathy. AAAs may limit the cerebral uptake of BCAA because they compete for carrier-mediated transport at the blood-brain barrier....Amino Acids Commonly Altered in Liver DiseaseAromatic Amino Acids: serum levels are increased.
Branched hain Amino Acids: levels are decreased.
Valine*Leucine"Isoleucine*Ammonlogenic Amino Acids: levels are increased.
1.Aspartate aminotransferase (AST or SGOT)Located in cytosol and mitochondria of hepatocyte also in cardiac and skeletal muscle, brain, pancreas, kidney and leukocytes.An enzyme similar to ALT but less specific for liver disease.Levels of AST are increased with liver damage or death of hepatocytes.In some cases viz alcoholic hepatitis or shock liv the elevation in serum AST level may be, higher than the elevation in serum ALT level. AST Normal range 2-40 U/L.
2.Alanine aminotransferase (ALT or SGPT)It is located in cytosol of hepatocytes found in several other body tissues.It is highest in liver.ALT level is increased in case of liver cell death, caused due to, Hepatitis, any shock, injury or excess alcohol or drug toxicity.Normal range 2-40 U/L
3.Serum alkaline phosphataseAn enzyme that is widely distributed in liver, bone, placenta, intestine, kidney, leukocytes.It is mainly bound to canalicular membranes of liver produced in the bile ducts.This enzyme activity can be increased with bone disorders, pregnancy , normal growth & some malignancies.40 - 129 U/L
4.bilirubinBilirubin is a yellow breakdown product of the normal heme catabolism .It is excreted in bile & urine and elevated levels may indicate certain diseases.It is responsible for the yellow color of the bruises ,urine & brown color of feces & yellow discoloration of skin.functionsBilirubin is created by the activity ofbiliverdin reductaseonbiliverdin, a green tetrapyrrolic bile pigment that is also a product of heme catabolism. Bilirubin, when oxidized, reverts to become biliverdin once again. This cycle, in addition to the demonstration of the potent antioxidant activity of bilirubin,has led to the hypothesis that bilirubin's main physiologic role is as a cellular antioxidant.
Types of bilirubinUnconjugated bilirubin (indirect)Erythrocytes(red blood cells) generated in thebone marroware disposed of in the spleenwhen they get old or damaged. This releaseshemoglobin, which is broken down tohemeas the globin parts are turned intoamino acids. The heme is then turned into unconjugated bilirubin in the reticuloendothelial cells of the spleen. This unconjugated bilirubin is not soluble in water, due to intramolecular hydrogen bonding. It is then bound toalbuminand sent to theliverConjugated bilirubin(direct)In the liver it is conjugated withglucuronic acidby the enzymeglucuronyltransferase, making it soluble in water. Much of it goes into the bile and thus out into the small intestine. However 95% of the secreted bile is reabsorbed by the small intestine. This bile is then resecreted by the liver into the small intestine. This process is known asenterohepatic circulation. About half of the conjugated bilirubin remaining in the large intestine(about 5% of what was originally secreted) is metabolized by colonic bacteria to urobilinogen, which can be further metabolized tostercobilinogen, and finally oxidized tostercobilin. Stercobilin gives feces its brown colorBlood testsBilirubin is broken down by light. Tubes containing blood or (especially) serum to be used in bilirubin assays should be protected from illumination. Total bilirubin ("TBIL") measures both BU and BC. Total and direct bilirubin levels can be measured from the blood, but indirect bilirubin is calculated from the total and direct bilirubin.Indirect bilirubin is fat-soluble and direct bilirubin is water-soluble.Bilirubin (in blood) is in two forms.
Blood testsAbb.Name(s)Water-soluble?Reaction"BC""Conjugated" or"Direct bilirubin"Yes (bound toglucuronic acid)Reacts quickly when dyes (diazo reagent) are added to the blood specimen to produceazobilirubin"Direct bilirubin""BU""Unconjugated" or "Indirect bilirubin"NoReacts more slowly. Still produces azobilirubin. Ethanol makes all bilirubin react promptly then calc: Indirect bilirubin = Total bilirubin - Direct bilirubinNormal Ranges of Bilirubin in Blood -mol/Lmg/dL0.2-1.9,[Total bilirubin5.117.00.31.00.1-1.2Direct bilirubin1.05.10-0.30.10.30.1-0.4Hyperbilirubinemia
Hyperbilirubinemia results from a higher than normal level of bilirubin in the blood. Mild rises in bilirubin may be caused by:Hemolysis or increased breakdown of red blood cellsGilbert's syndrome - a genetic disorder of bilirubin metabolism that can result in mild jaundice, found in about 5% of the populationRotor syndrome: non-itching jaundice, with rise of bilirubin in the patient's serum, mainly of the conjugated type. Moderate rise in bilirubin may be caused by:Pharmaceutical drugs (especially antipsychotic, some sex hormones, and a wide range of other drugs)Sulfonamides are contraindicated in infants less than 2 months old as they increase unconjugated bilirubin leading to kernicterus.Hepatitis (levels may be moderate or high)ChemotherapyBiliary stricture (benign or malignant)Very levels of bilirubin may be caused by:Neonatal hyperbilirubinaemia, where the newborn's liver is not able to properly process the bilirubin causing jaundiceUnusually large bile duct obstruction, e.g. stone in common bile duct, tumour obstructing common bile duct etc.Severe liver failure with cirrhosis (e.g. primary biliary cirrhosisCholedocholithiasis (chronic or acute)presence of gallstone in the common bile duct
5.Gamma-glutamyl transpeptidase (GGT)An enzyme associated with microsomes and plasma membranes in hepatocytes also present in kidney, pancreas, heart , brain.An enzyme produced in the bile ducts that like alkaline phosphatase, may be elevated in the serum of patients with bile duct disease.It is increased with liver disease, pulmonary disease, diabetes mellitus and during alcohol ingestion by many drugs.
Serum albuminMain export protein synthesized in the liver and most imp. factor in plasma osmotic pressure maintenance, secreted in the blood.Major protein circulating in blood stream.Low serum albumin levels indicate poor liver function.Serum albumin concentration is usually normal in chronic liver diseases until cirrhosis and liver damage is present. Albumin 3.4 - 4.8 g