Liver Pathophysiology in General

Question 1

2 Cirrhosis Staging Methods

Answer 1

• Old method = CTP score
  
  • Components - encephalopathy, ascites, serum albumin, INR, serum bilirubin
  • Classified as Child’s A B and C
  • First 2 are subjective
• New method = MELD score
  
  • 1- total bilirubin
  • 2- INR
  • 3- serum sodium
  • 4- serum creatinine
  • **Automatic inc in score if hepatocellular carcinoma

Question 2

Steatosis (2 types)

Answer 2

• Steatosis - unusual accumulation of fat in cytoplasm
• Macro - large fat droplet in cytoplasm that pushes nucleus to side of cell
• Micro - cytoplasm intact but small fat droplet; nucleus still in middle of cell

Question 3

Mallory Hyaline

Answer 3

eosinophilic cytoplasmic inclusions; aggregates of denatured keratin filaments

Question 4

How do you detect alpha-1-anti-trypsin?

Answer 4

PAS stain

Question 5

Hepatocyte Apoptosis v Necrosis

Answer 5

• Hepatocyte apoptosis - shrinks, nucleus condenses/fragments, very pink/eosinophilic cytoplasm
• Confluent Necrosis - (when damage is widespread and many hepatocytes undergo necrosis) lose lobule shape as many hepatocytes collapse

Question 6

5 Inflammatory Cells Liver Makes In Response (by etiology)

Answer 6

• Lymphocytes - viral antigens
• Plasma cells - autoimmune hepatitis
• Neutrophils - alcoholic hepatitis (often Mallory hyaline inclusions are surrounded by neutrophils)
• Eosinophils - acute T cell-mediated rejection
• Granuloma - drugs, toxins, fungal infection (more chronic process)

Question 7

Liver Regeneration

Answer 7

• Mitotic replication of hepatocytes adjacent to those that died (don’t need stem cells even after yrs damage)
• BUT if very severe necrosis/ acute liver failure… differentiation of hepatobilliary stem cells (canal of Hering)
• Eventually in chronic diseases the hepatocytes become senescent and must use stem cells (ductular reactions -
  clusters transitioning from hepatobiliary stem cells —> hepatocytes)

Question 8

How does cirrhosis develop?

Answer 8

• Kupffer cells and lymphocytes release cytokines (TNF-alpha and IL-1) AND ROS –> activate Stellate cell genes involved in fibrogenesis
• Dense fibrous septa –> later encircle regenerating hepatocytes (cirrhosis)
• Scar formation can be reversed - if injury interrupted then stellate activation stops, scars condense, MMPs can break scar apart

Question 9

Portal HTN (definition, cause, sources)

Answer 9

• Clinically sig if portal P grad > 12 mmHg (normal < 5); b/n portal vein- hep vein
• P = QR (so inc resistance or inc flow will inc press)
  
  • Cirrhosis causes resistance to portal flow
• Pre-hepatic (portal or splenic vein thrombosis OR acute pancreatitis)
• Intrahepatic (same causes as cirrhosis)
  
  • Pre-sinusoidal - schisto, PBC
  • Sinusoidal - alcoholic cirrhosis, Hep C, NAFLD
  • Post-sinusoidal - venous occlusion, alcoholic hepatitis
• Post-hepatic (block outflow by hepatic vein thrombosis - aka Budd Chiari syndrome OR heart disease)

Question 10

Hepatic Encephalopathy (mechanism, phases, tx)

Answer 10

• State of dec arousal
• Due to brain exposure to ammonia so dx is ammonia serum level; ammonia crosses BBB but no urea cycle in brain so converted to glutamine –> suppresses PSPs
• 4 Stages
  I - altered sleep, affect and orientation; mild confusion
  II- drowsy, accentuated stage I, inappropriate behavior
  III- arousable; marked confusion; speech incoherent; now worried about airway
  IV - coma (not arousable)
• See asterixis, constructional apraxia, abnormal EEG
• Tx - ammonia lowering agents (ammonia mainly from bacteria in GI); lactulose

Question 11

Ascites ( 3 theories)

Answer 11

• Portal HTN / dec albumin–> inc hydrostatic P in sinusoids –> pours out into peritoneal cavity

1- Overflow theory: renal abnormalities –> sodium and water retention

2- Underfilling Theory: peripheral arterial vasodilation via NO in splanchnic –> underfiling –> RAAS

3- Forward Theory: (combo) splanchnic vasodilation –> RAAS –> water and sodium retention + impaired water clearance (impaired water clearance leads to dilution so hyponatremia)

Question 12

HCC (who is at highest risk + how to screen)

Answer 12

• highest risk in hemochromatosis, NASH and Hep B, Hep C

- AFP and US screening every 6 mo if cirrhosis of any cause