R AMZI S HAWAHNA LIVER FUNCTION TEST. Liver: Is the largest solid organ Has large reserve capacity...
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Transcript of R AMZI S HAWAHNA LIVER FUNCTION TEST. Liver: Is the largest solid organ Has large reserve capacity...
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RAMZI SHAWAHNA
LIVER FUNCTION TEST
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Liver: Is the largest solid organ Has large reserve capacity Is capable of regeneration
Function:
Metabolism: fat, protein, drugs, hormones Filtration: bacteria, endotoxins, viruses, antigens, byproducts of coagulation Storage: fluids, vitamins, minerals
LIVER
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LIVER DYSFUNCTION DIAGNOSIS
The diagnosis of liver disease depends on a combination of patient history, physical examination, laboratory testing, biopsy and sometimes imaging studies such as ultrasound scans.
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LIVER FUNCTION TESTS A misnomer
elevated aminotransferases/alkaline phosphatase are only markers of liver injury, not liver dysfunction
These can be affected by extrahepatic factors nutritional state hemolysis antibiotic use
Poor sensitivity and specificity for liver disease
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HISTORY Systemic symptoms Family Hx
Hemochromatosis, Wilson’s Disease, alpha1 antitrypsin deficiency
Gilbert’s syndrome, Dubin-Johnson Syndrome, Rotor’s syndrome
Alcoholism Drug abuse
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HISTORY
Occupational exposuresChemicals (vinyl choloride,
dimethylformamide, 2-Nitropropane, Trichloroethylene)
Other co-morbid illnessesAutoimmune diseases, IBD, Diabetes Mellitus
MedicationsPrescriptionHerbals, Vitamins
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MEDICATIONS CAUSING ELEVATION OF AMINOTRANSFERASES
Acetaminophen
Amoxicillin-clavulanic acid
NSAIDS
Phenytoin
Valproate
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GENERAL CATEGORIES OF TESTS
variety of tasks, no single testnot very sensitive (cirrhosis)or specific (non-hepatic factors)
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THREE CATEGORIES Markers of Liver Injury/Necrosis Markers of Cholestatic Liver Disease Markers of Liver Function
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COMMON SERUM LIVER CHEMISTRY TESTS
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Normal values
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ALT (SGPT) AND AST (SGOT) LEVELS
AST and ALT are markers of hepatocellular injury
Participate in gluconeogenesis, transfer of amino groups from aspartate or alanine to ketoglutaric acid to form oxaloacetete or pyruvate.
AST present in cytosol and mitochondria in liver, cardiac muscle, skeletal muscle, kidney, brain, pancreas, lungs, WBC and RBC.
ALT a cytosolic enzyme, highest concentration in the liver
ALT considered a “liver specific” enzyme
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THREE CATEGORIES Markers of Liver Injury/Necrosis Markers of Cholestatic Liver Disease Markers of Liver Function
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ALKALINE PHOSPHATASE
•Present in nearly all tissues - isoenzymes
•Localised in the microvilli of the bile canalicus in the liver
•Also present in bone, intestine, placenta, kidney and WBCs
•Elevation may be physiological or pathological
•Normal adult serum AP is from liver and boneIntestine contributes about 15%
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ALKALINE PHOSPHATASE Catalyze the hydrolysis of a large number
of organic phosphate esters, optimally at an alkaline pH.
Liver - synthesized in the bile duct epithelial cells
Bone - osteoblastic activity Kidneys Intestine Placenta- levels may double late in
pregnancy
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ELEVATION OF SERUM ALKALINE PHOSPHATASE Isolated Associated with hyperbilirubinemia
(cholestatic disorders) May be sole abnormality in many cholestatic
or infiltrative diseases To be interpreted in the clinical setting of
history and physical examination if sole abnormality
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GGT Catalyzes the transfer of the γ-
glutamyl group from γ-glutamyl peptides (glutathione) to other peptides and L-amino acids.
Elevated in liver, biliary, or pancreatic disease.
Very sensitive for detecting hepatobiliary disease, but poor specificity
Used primarily to confirm hepatic origin of elevated ALP
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BILIRUBIN
Product of hemoglobin breakdown 2 Forms
Unconjugated (indirect)- insoluble↑ in hemolysis, Gilbert syndrome, meds
Conjugated (direct)- soluble↑ in obstruction, cholestasis, cirrhosis, hepatitis, primary biliary cirrhosis, etc.
No elevation until loss of > 50% capacity
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UNCONJUGATED HYPERBILIRUBINEMIA >80% of total bilirubin is indirect Liver function is otherwise normal Increased bilirubin production
hemolysis - seldom > 5 mg/dL ineffective erythropoeisis blood transfusion resorption of hematomas
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UNCONJUGATED HYPERBILIRUBINEMIA Decreased hepatocellular uptake
drugs (e.g., rifampin) Gilbert's syndrome?
Decreased conjugationGilbert's syndrome Crigler-Najjar syndromePhysiologic jaundice of the newborn
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CONJUGATED HYPERBILIRUBINEMIA Hepatocellular dysfunction Biliary obstruction + Urobilinogen
unconjugated bilirubin is tightly bound to albumin and not excreted renally
marker of hepatobiliary disease
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ALBUMIN
Synthesized exclusively by the liver 20 day half life - levels usually preserved
acutely Synthesis regulated by nutritional
states, osmotic pressure, systemic inflammation, and hormones
Hypoalbuminemia most common in patients with chronic liver disorders (ie cirrhosis) due to decreased synthesis
Not specific for liver disease
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PROTHROMBIN TIME Factor 1 - fibrinogen Factor II- prothrombin Factor V - proaccelerin; labile factor Factor VII - stable factor Factor IX - Christmas factor Factor X - Stuart Prower factor Factor XII and XIII - prekallikrein and high
molecular weight kinogen
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PROTHROMBIN TIME Parenchymal liver disease
Poor utilization of vitamin K Hypovitaminosis K
Prolonged obstructive JaundiceSteatorrheaDietary DeficiencyAntibiotics (alter gut flora)
Differentiate by giving IV Vitamin Knormalization or 30% improvement within 24
hrs surmises good parenchymal function
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BILIRUBIN METABOLISM
Pre-hepatic Hepatic Post-hepatic
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BILIRUBIN METABOLISM: PRE-HEPATIC
Bilirubin is formed in macrophages of the reticuloendothelial system. The initial substrate is predominantly hemaglobin.
Heme group biliverdin bilirubin Bilirubin is insoluble in water and so must be carried
by albumin within plasma. Bilirubin circulates in the blood before uptake by the
liver. Pre-hepatic jaundice = if bilirubin is not taken up by
the liver or if it is produced in excess, unconjugated bilirubin is deposited in extra-hepatic tissues.
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BILIRUBIN METABOLISM: HEPATIC
Bilirubin is taken up into hepatocytes and bound to intracellular proteins.
Bilirubin + UDP glucuronic acid = bilirubin diglucuronide > bilirubin monoglucuronide > UDP
The glucuronide conjugated form of bilirubin is water soluble and is excreted into bile. Excretion occurs into the bile canaliculus by carrier-mediated transport.
Hepatic jaundice = disorders of bilirubin uptake or conjugation
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BILIRUBIN METABOLISM: POST-HEPATIC
Glucuronide-conjugated bilirubin in bile may be degraded to urobilinogen or partially reabsorbed into plasma.
Urobilinogen pathway: may be reabsorbed by the gut and returned to the
liver converted to urobilin reabsorbed into plasma for excretion by kidneys
Conjugated bilirubin pathway: May be acted upon by bacterial enzymes within the
gut to form the bile pigment stercobilinogen. Stercobilinogen may be reabsorbed into plasma for recycling to the liver or for excretion by the kidney, or, it may be oxidized to stercobilin.
Obstructive jaundice = failure of bilirubin to reach the gut, resulting in a reduction in pigment within the stool
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UNCONJUGATED HYPERBILIRUBINEMIA
Increased Bilirubin Production Extravascular hemolysis Extravasation of blood into tissues Intravascular hemolysis Errors in production of red blood cells
Impaired Hepatic Bilirubin Uptake CHF Portosystemic shunts Drug inhibition: rifampin, probenecid
Impaired Bilirubin Conjugation Gilbert’s disease Crigler-Najarr syndrome Neonatal jaundice (this is physiologic) Hyperthyroidism Estrogens Liver diseases (chronic hepatitis, cirrhosis, Wilson’s)
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CONJUGATED HYPERBILIRUBINEMIA
Intrahepatic Cholestasis (impaired excretion) Hepatitis (viral, alcoholic, and non-alcoholic) Primary biliary cirrhosis or end-stage liver dz Sepsis and hypoperfusion states Pregnancy Infiltrative disease: TB, amyloid, sarcoid,
lymphoma Drugs/toxins i.e. chlorpromazine, arsenic Post-op patient or post-organ transplantation Hepatic crisis in sickle cell disease
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