Hepatobiliary - liver injury and repair Flashcards
metabolic liver disease
- P: Nonalcoholic fatty liver disease (NAFLD)
- S: Amyloidosis
P=primary (in), S=secondary (out)
toxic liver disease
- P: Alcoholic liver disease (ALD)
- S: Drug-induced liver injury (DILI)
infectious liver disease
- P: Viral hepatitis
- S: Extrahepatic/systemic infections (viruses, bacteria, fungi)
immune-mediated liver disease
- P: Autoimmune hepatitis (AIH)
- P: Primary biliary cholangitis (PBC)
- P: Primary sclerosing cholangitis (PSC)
- S: Systemic lupus erythematosus (SLE)
obstructive liver disease
- P: Small intrahepatic biliary disorders (congenital/ acquired)
- S: Extrahepatic obstructive lesions
vascular liver disease
- P: Veno-occlusive disease (VOD)/ sinusoidal obstruction syndrome (SOS)
- S: Heart failure
neoplasms
- P: Hepatocellular carcinoma (HCC)
- S: Metastatic cancer
investigative tests to test hepatocyte function (3)
Serum aspartate aminotransferase (AST)
Serum alanine aminotransferase (ALT)
Serum lactate dehydrogenase (LDH)
investigative tests to test biliary excretory function (2 ways - 5 tests)
- level of substances normally secreted in bile:
- Serum bilirubin – Total, unconjugated (indirect) and conjugated (direct)
- Urine bilirubin
- Serum bile acids - Plasma membrane enzyme (produced when there is damage to bile canaliculus - high levels = bad)
- Serum alkaline phosphatase (ALP)
- Serum γ-glutamyl transpeptidase (GGT)
investigative tests to test hepatocytes synthetic function - based on serum protein levels
- Serum albumin
+ve = good - Coagulation factors: prothrombin (PT) and partial thromboplastin (PTT) times (fibrinogen, prothrombin, factors V, VII, IX, X)
investigative tests to test hepatocyte metab
- Serum ammonia
- Aminopyrine breath test (test for hepatic demethylation)
+ve = good
investigative tests to test for infections (3)
- Serology: IgM/IgG to HAV, anti-HBs
- Microbiology: CMV/EBV PCR, cultures
- Radiology (for suspected abscess): ultrasound HBS, CT abdomen, MRI liver
investigative tests to test for autoimmune diseases
- Serology: anti-nuclear antibodies (ANA), smooth muscle antibodies (SMA)
investigative tests to test for bile duct obstruction (2)
- Endoscopy: Endoscopic retrograde cholangiopancreatography
(ERCP)/
brushing cytology/
biopsy - Radiology:
Magnetic resonance cholangiopancreatography (MRCP)
CT abdomen
mechanisms of liver injury and repair (3 steps)
- hepatocyte and parenchymal response
- scar formation and regression
- inflammation/ immunity
- hepatocyte and parenchymal response
- 3 possible types of responses
- regeneration:
Mitotic replication of hepatocytes/
Activation of primary stem cell niche (canals of Hering)
-> hepatocytes reach replicative senescence and there is stem cell activation (seen as ‘ductular reaction’) - Irreversible injury and cell death
cell necrosis and apoptosis - Degenerative but potentially reversible changes
Cellular swelling (ballooning degeneration)
Steatosis (accumulation of fat)
Cholestasis (accumulation of bilirubin)
- scar formation and regression
- parenchymal transforming into dense fibrous tissue
• Hepatic stellate cells activated and converted into highly fibrogenic myofibroblasts - cirrhosis
PORTAL/ periportal fibrosis
-> portal-central and portal-portal bridging fibrosis / septa
-> cirrhosis - CELLULAR: Pericellular / perisinusoidal fibrosis
- Reversal of fibrosis / cirrhosis regression
- inflammation/ immunity
- histo features
esp for hepatitis - eliminate infected hepatocytes
- Lymphocytes, plasma cells, neutrophils, eosinophils, histiocytes / macrophages
- Lymphoid aggregates
- Granulomas
- Microabscesses
causes of ACUTE liver failure
caused by sudden massive injury
- Drugs/ toxins
- Acute Hepatitis A/B/E (autoimmune hepatitis)
[chronic liver failure: B/C - chronic and persistent]
acute liver failure
gross + histo appearance
shrunken liver with wrinkled liver capsule
- Massive necrosis - RBC extravasation
- death of hepatocytes
- Diffuse injury without obvious cell death - diffuse microvesicular steatosis (in fatty liver of pregnancy/ drug reaction)
acute liver failure
complications
high mortality rate (80%) w/o transplant (cause of major loss in hepatic fn)
impact on liver:
- coagulopathy: impaired hepatic synthetic fn
- hepatic encephalopathy: impaired hepatic metabolism - liver cannot remove toxins -> brain damage
- cholestasis: impaired bile excretion
impact on renal:
- Hepatorenal, hepatopulmonary syndrome
cause of vasodilation of vessels in the lungs -> shortness of breath
portal system:
- Ascites
- Portosystemic venous shunts
- Congestive splenomegaly
- hepatic encephalopathy
causes of chronic liver failure (4)
- Hep B/C infection
- NAFLD (non-alcoholic fatty liver disease)
- alcoholic liver disease, (cryptogenic)
- liver cirrhosis
liver cirrhosis**
transformation of liver into regenerative parenchymal nodules
- fibrous bands - from scarring of liver
- disturbed vascular architecture: vascular shunting
liver cirrhosis **
- clinical features
- complications
- anorexia, weight loss, weakness
- Hepatic encephalopathy
- Bleeding from oesophageal varices
- Bacterial infections / sepsis
chronic liver disease
- clinical presentation (4)
- Cholestasis: buildup of bilirubin
Jaundice -> pruritus (itch)
Scleral icterus
- Hyperoestrogenemia Palmar erythema Spider angiomas Hypogonadism Gynaecomastia
- Coagulopathy - easy bruising
- Portal hypertension Ascites Portosystemic venous shunts: Splenomegaly Hepatic encephalopathy: asterixis ‘hepatic flap’
portal hypertension
causes
- increased flow
- increased resistance
- prehepatic:
Obstructive thrombosis or narrowing
Massive splenomegaly with increased splenic vein blood flow - intrahepatic
Cirrhosis
Diffuse infiltrative processes (granulomatous inflammation, amyloid, malignancy)
non-cirrhotic (Nodular regenerative hyperplasia) - post-hepatic
Hepatic vein outflow obstruction
Heart problems: right heart failure, constrictive pericarditis
ascites definition
ascites = Accumulation of excess fluid in the peritoneal cavity
hepatic encephalopathy pathogenesis from liver failure
liver failure:
increased ammonia
increase metabolism of ammonia -> glutamine in CNS
splenomegaly pathogenesis from liver failure
LF: increase venous pressure -> congestion
-> Retention of leukocytes, erythrocytes and platelets in the spleen
main consequences of liver failure
ABCDE
- ammonia -> hepatic encephalopathy
- bile retention
- coagulopathy
- distension (ascites)
- esophageal varices
chronic ingestion of alcohol pathogenesis (3)**
alcohol forms acetaldehyde
- hepatic steatosis: alcohol increase NADH/NAD+ ratio -> inhibit gluconeogenesis -> promotes lipogenesis causes intracellular lipid accumulation
- alcoholic hepatitis:
acetaldehyde can cause liver cell oxidative injury - alcoholic cirrhosis
liver cirrhosis **
- gross and histo features
gross: Enlarged early, shrunken late stage Nodular surface colour base on what causes it: yellow = fatty change grey = viral hep green = jaundice brown = Fe
histo:
- Bridging fibrous septa
- Regenerative liver nodules
- Inflammatory infiltrate
- Ductular proliferation in septa
- Cholestasis fibrous
- hepatocytes undergoing apoptosis
- chronic: groundglass appearance (flat hazy and uniformly dull cytoplasm)
