Liver Fx Test

Question 1

Role of Kupffer cells lining sinusoids

Answer 1

• bind old serum proteins & remove them from circulation
• phagocytosis of circulating damaged cells eg. erythrocytes
• phagocytose aggravated bacterial/Ab complexes

Question 2

Liver as a storage organ

Answer 2

• Glycogen (0.3% to 10% liver mass)
• Protein blood-clotting factor eg. prothrombin
• Vit. A
• Iron bound to ferritin in parenchymal cells

Question 3

Liver is responsbile for the synthesis of the majority of plasma proteins

Answer 3

• Albumin:
  
  • exclusively synthesized in liver
  • Most abundant plasma protein
  • Low plasma conc. during liver dysfunction
• Coagulation factors:
  
  • Factors II, VII, IX, and X (inactive clotting factors)
  • Prothrombin Time (PT): time required for clot formation of extrinsic clotting factors
• Apolipoprotein synthesis: alterations to cholesterol & TAG metabolism (fatty liver). In severe liver cirrhosis, hepatocytes fail to produce VLDL
• any type of liver dysfunction may compromise hepatic protein synthesis. Hypoproteinemia will manifest itself as edema (decreased COP of blood)

Question 4

Hepatocell injury can be caused by:

Answer 4

• viral hepatitis
• drug-induced hepatitis (acute or chronic)
• chronic obstructive jaundice

Question 5

Acute liver disease/hepatitis caused by?

Answer 5

• Infections
• Toxins: carbon tetrachloride, alpha-amantin
• inadequate perfusion
• drug-induced (lasts less than 3 mo) eg. acetaminophen (Tylenol) & aspirin

Question 6

Acute hepatic failure leads to renal failure

Answer 6

• failure to detox metabolites & xenobiotics
• electrolyte imbalance occurs (Na+ & Ca2+ levels fall); severe metabolic acid-base
• hepatic failure preludes renal failure (toxins affect Glomerular fx)

Question 7

Chronic liver disease

Answer 7

3 types of chronic liver disease

• Chronic hepatitis:
  
  • > 6 mo
  • may be caused by
  • Hep B & C
  • chronic alcohol
  • drug abuse
  • auto-immune disorder
• Alcoholic & Non-Alcoholic Fatty Liver Disease (NAFLD): chronic accumulation of TAG may lead to hepatocyte fibrotic changes -> cirrhosis
  
  • NAFLD characterized by fatty infiltration (steatosis) leading to inflammation, non-alcoholic steatohep (NASH)
  • NASH may progress to liver fibrosis (10-20%).
  • NAFLD associated with metabolic syndrome
• Cholestatic (biliary) disease
  
  • Obstructive cholestasis: mechanical blockage in duct system, eg. gallstones & tumour
  • Metabolic cholestatis: metabolic disturbance in bile production
• Chronic drug-induced: persists more than 3 mo, eg. Minocycline is a tetracycline used to Rx acne

Question 8

3 stages of alcohol-induced liver disease

Answer 8

1. Fatty liver: affects nutrient & O2 distribution to hepatocytes (reversible)
2. Fibrosis: caused by excessive production of ECM constituents particularly collagen by stellate cells
3. Cirrhosis (irreversible)

Question 9

Alcoholic fatty liver

Answer 9

• chronic accumulation of TAG may lead to hepatocyte fibrotic changes, possibly developing into cirrhosis
• AST:ALT >2:1
• elevated GGT
• CT scan showing steatosis

DDX: alcoholic fatty liver & NAFLD

• Alcoholic liver:
  
  • AST:ALT>2:1
  • elevated GGT
  • CT scan showing steatosis
• NAFLD:
  
  • CT scan showing steatosis
  • Dx by exclusion

Question 10

Liver cirrhosis

Answer 10

• terminal stage of chronic liver damage
• irreversible
• liver shrinkage & chronic development of fibrosis

Common causes of liver cirrhosis

• alcohol liver disease
• non-alcoholic steatohep (NASH)
• Wilson’s disease
• Primary biliary cirrhosis
• Autoimmune hep

Question 11

Liver cirrhosis complications

Answer 11

• Portal hypertension causing esophageal varices, caput medusa, internal hemmorhoids
• compromised liver fx
• Ascities
• impaired bile excretion leading to poor Vit D absorption, increased risk of osteoporosis, and Vit K absorption (tendency to bleed easily).
• Bleeding into GIT will lead to anemia
• scar tissue replaces parenchyme tissue, blocking portal blood flow through the liver
• damaged parenchyma tissue stimulates stellate cells to become contractile (ie. myofibroblast) leading to a further reduction in hepatic blood flow
• release of TGF-Beta1 stimulates further fibrosis
• Scar tissue can block bile duct leading to jaundice
• Reduced blood flow through hepatic portal vein causes portal hypertension

Question 12

LFT include

Answer 12

• total bilirubin (conjugated/direct and unconjugated/indirect) & albumin
• Serum proteins: albumin & globulins
• Serum enzymes: AST & ALT, ALP, LDH-5 & gamma-glutamyl
  
  • ALP increased in cholestatic jaundice but Ns
• Prothrombin Time (PT)

Question 13

Lab evaluation of liver disease

Answer 13

• Hepatocyte integrity
  
  • AST
  • ALT
  • LDH-5
  • Non-viral disease: ALT:AST<1
  • Viral Hep: ALT:AST>1
• Biliary excretion fx
  
  • Serum & urine bilirubin, serum bile acids
  • membrane bound enzymes (from damage to bile canaliculus) i.e. serum ALP, serum GGT & serum 5’ nucleotidase
• Hepatocyte fx
  
  • decreased proteins secreted into blood from liver
  • Albumin
  • Prothrombin
  • Fibrinogen
  • hepatocyte metabolism can be gauged by measuring serum ammonia (elevated indicates liver dysfunction)

Question 14

Biomarkers for liver necrosis

Answer 14

• AST
• ALT

Question 15

Biomarkers for cholestasis

Answer 15

• ALP
  
  • synthesized in biliary canaliculi, thus obstruction to canaliculi elevates ALP
  • Ns: Paget’s disease (bone)
• GGT
• 5’nucleotidase

Question 16

GGT

Answer 16

• active mainly in liver (pancreas & kidneys to a lesser extent) & involved in glutathione metabolism
• synthesized particularly in cell lining the bile duct. GGT is a cell surface glycoprotein that cleaves gamma-glutamyl amide bonds
• biochem marker for cholestasis (arrest in flow of bile) & alcoholic fatty liver

Question 17

Serum ammonia

Answer 17

• protein catabolism produces ammonia which the liver converts to urea
• muscle tissue also detox ammonia by combining it with glutamic acid to form glutamine
• Pt with advanced liver damage typically have a significant muscle wastage, attenuating hyperammonemia & hepatic encephalopathy