The Liver Flashcards
(24 cards)
AST and ALT are found in?
Level of enzymes to achieve hepatospecificity
Variation in levels
Ratios of AST to ALT
- AST: cardiac muscle, liver, skeletal muscle, kidney, brain, lung, and pancreas (in decreasing order of concentration)
- ALT: liver and kidney
- >3x ULN indicates hepatic disease (excluding rhabdomyolysis)
- Diurnal variation (highest in the afternoon)
- AST:ALT is usually <1 and may be >1 in alcohol abuse and cirrhosis
Lactate dehydrogenase
Isoenzymes
- LD1 and LD2: heart, RBCs, and kidney
- LD4 and LD5: liver, skeletal muscle
- LD3: lung, spleen, lymphocytes, and pancreas
- In normal serum: LD2>LD1>LD3>LD4>LD5
Flipped LD ratio (LD1>LD2):
- acute MI
- Hemolysis
- Renal infarction
Elevated LD4 and LD5: liver damage, skeletal muscle insults
LD isoenzymes are rarely measured; total LD elevation is nonspecific marker of tissue injury or proliferation
Elevations in alk phos may be caused by
- Bone growth in childhood
- Pregnancy (placental alk phose)
- Postprandially (intestinal alk phos), especially in Lewis+ group B or O secretors
- oral contraceptives
- NSAIDs
- Malignancy results in regan isoenzyme (reexpression of placental alkaline phosphatase gene in tumor cells)
Decreased alk phos is seen in
- Hypophosphatasia (an inborn deficiency)
- Malnutrition
- Hemolysis
- Wilson disease
- Theophylline therapy
- Estrogen therapy in postmenopausal women
Alkaline phosphatase is a sensitive marker of
hepatic metastases
Alk phos isoenzymes
Heat/urea inhibition
Biliary: +
Bone: +++
Placenta: -
Intestinal: +
Alk phos isoenzymes
Anodal mobility
Biliary: 1
Bone: 2
Placenta: 3
Intestinal: 4
Gamma glutamyl transferase (GGT)
- used to confirm an elevated alk phos is from the biliary tree
- increased in patients exposed to
- warfarin
- barbiturates
- dilantin
- valproate
- methotrexate
- alcohol
- May be increased in renal failure and pancreatic disease
Source of 5’ nucleotidase
Biliary epithelium
Ammonia
- sources
- metabolism
- elevated in
- measurement is very sensitive to
- Sources:
- skeletal muscle (urea cycle)
- gut (from enteric bacteria that break down protein)
- Normally removed by liver
- May be elevated in
- Liver failure
- In bypass of liver due to collateral circulation
- Excess protein in the gut (variceal bleed)
-
Inborn error of metabolism affecting
- Urea cycle: ornithine transcarbamoylase
- Fatty acid oxidation: carnitine deficiency
- Organic acidemias: carboxylase deficiency
- Total parenteral nutrition
- Atonic bladder with superimposed UTI with urease producing bacteria
- Ureterosigmoidostomy
- Valproic acid therapy
- Cigarette smoking
- Measurement very sensitive to preanalytic conditions
Characteristics of unconjugated and conjugated bilirubin
- Unconjugated (indirect) bilirubin
- water insoluble
- bound to albumin in the blood
- does not appear in urine (bilirubinuria indicates conjugated hyperbilirubinemia)
- Conjugated (direct) bilirubin:
- water soluble
- excreted in bile into intestine where bacteria convert some of it to urobilinogen
- Some urobilinogen is reabsorbed and excreted in urine
What is delta bilirubin
Bilirubin covalently bound to albumin, forming after prolonged hyperbilirubinemia; very slowly excreted
Measurement of bilirubin
- Without an accelerator (alcohol), mainly conjugated bilirubin is measured (direct reaction)
- Accelerators permit unconjugated bilirubin to react as well, providing total bilirubin
General causes of hyperbilirubinemia
- Conjugated hyperbilirubinemia (>30% of serum bilirubin conjugated) is caused primarily by an excretory defect
- Unconjugated hyperbilirubinemia caused by increased production (hemolysis) or a hepatic defect that prevents uptake or conjugation
Pathophysiologic differential diagnosis of unconjugated hyperbilirubinemia
UNCONJUGATED HYPERBILIRUBINEMIA
- Excess conversion of heme to unconjugated bili
- Hemolysis (extravascular)
- Ineffective hematopoiesis (intramedullary hemolysis)
- Large hematoma (resorbed heme)
- Excess delivery of unconjugated bilirubin to liver
- Blood shunting (cirrhosis)
- Right heart failure
- Poor uptake of unconjugated bilirubin into hepatocyte
- Gilbert syndrome
- Drugs (rifampin, probenecid)
- Impaired conjugation of bilirubin in hepatocyte
- Crigler-Najjar syndrome
- Hypothyroidism
Pathophysiologic differential diagnosis of conjugated hyperbilirubinemia
CONJUGATED HYPERBILIRUBINEMIA
- Impaired transmembrane secretion of conjugated bilirubin into canaliculus (hepatocellular jaundice)
- Hepatitis/hepatic injury
- Endotoxin (sepsis)
- Pregnancy (estrogen)
- Drugs: estrogen, cyclosporine
- Dubin-Johnson syndrome
- Rotor syndrome
- Impaired flow of conjugated bilirubin through canaliculi and bile ducts (cholestatic jaundice)
- Intrahepatic:
- primary biliary cirrhosis
- medication
- alcohol
- pregnancy
- sepsis
- Extrahepatic
- primary sclerosing cholangitis
- tumor
- stricture
- stone
- AIDS
- choledochopathy
- Intrahepatic:
Hepatocellular jaundice and Cholestatic jaundice
Levels of:
Alk phos
Transaminases
Serum cholesterol
Pruritis
Prothrombin time and albumin and the liver
Used as a marker of hepatic synthetic function
Liver disease must be very severe to cause prolonged PT
Gamma globulins in the liver
- Autoimmune hepatitis associated with marked polyclonal increase in IgG
- PBC associated with polyclonal increase in IgM
- Decrease albumin:globulin (A/G) ratio (<1.0) usually the result of liver disease
Benign neonatal jaundice (physiologic)
- Noted between 2-3 days of life
- Rarely rises at a rate > 5 mg/dl/day
- Usually peaks by day 4-5
- Rarely exceeds 20 mg/dl
Pathologic neonatal jaundice
- May appear within first 24 hours of life
- May continue to rise beyond 1 week of age
- May persist past 10 days
- Total bilirubin exceeds 12 mg/dl
- Rises quickly, with single day increase >5 mg/dl
- Conjugated bilirubin exceeds 2 mg/dl
Most common causes of neonatal jaundice
Hemolytic disease of the fetus and newborn
Sepsis
Causes of neonatal unconjugated hyperbilirubinemia
- Physiologic jaundice
- Breast milk jaundice
- Polycythemia
- Hemolysis
- HDFN
- Hemoglobinopathies
- Inherited membrane or enzyme defects
- Increased enterohepatic circulation
- Hirschsprung disease
- CF
- Ileal atresia
- Inherited disorders of bilirubin metabolism
- Gilbert syndrome
- Crigler-Najjer syndrome
Causes of neonatal conjugated hyperbilirubinemia
- Biliary obstruction (extrahepatic biliary atresia)
- Sepsis or TORCH infection
- Neonatal hepatitis
- Idiopathic
- Wilson disease
- Alpha 1 antitrypsin deficiency
- Metabolic disorders
- Galactosemia
- Hereditary fructose intolerance
- Glycogen storage disease
- Inherited disorders of bilirubin transport
- Dubin-Johnson syndrome
- Rotor syndrome
- Parenteral alimentation
