Liver Pathophysiology in General Flashcards
2 Cirrhosis Staging Methods
- 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
Steatosis (2 types)
- 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
Mallory Hyaline
eosinophilic cytoplasmic inclusions; aggregates of denatured keratin filaments
How do you detect alpha-1-anti-trypsin?
PAS stain
Hepatocyte Apoptosis v Necrosis
- 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
5 Inflammatory Cells Liver Makes In Response (by etiology)
- 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)
Liver Regeneration
- 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)
How does cirrhosis develop?
- 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
Portal HTN (definition, cause, sources)
- 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)
Hepatic Encephalopathy (mechanism, phases, tx)
- 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
Ascites ( 3 theories)
- 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)
HCC (who is at highest risk + how to screen)
- highest risk in hemochromatosis, NASH and Hep B, Hep C
- AFP and US screening every 6 mo if cirrhosis of any cause
