Liver, Biliary tract and Pancreas Flashcards
- Liver failure:
PATTERNS OF HEPATIC INJURY
- Degeneration and intracellular accumulation:
- cell swelling + enlargement
- fat, iron, copper etc. accumulate - Necrosis + apoptosis:
- coagulative necrosis - Regeneration:
- mitotic figures - Inflammation:
- hepatitis - Fibrosis:
- in response to inflammation or direct toxic insult
- first around portal tract + central vein + within sinusoids - Cirrhosis:
- progressive parenchymal injury + fibrosis
- end-stage liver disease, increases risk of pregnancy
- Liver failure:
LIVER FAILURE hepatic failure
= total loss (80-90%) of over function as a direct result of injury/disease
- develops due to insidious destruction of hepatocytes or by repetitive discrete waves of parenchymal damage
- can also be due to sudden massive destruction of hepatic tissue
- Liver failure:
LIVER FAILURE etiology
- Acute liver failure with massive hepatic necrosis
- cause: drugs, viral hepatitis, idiopathic
- massive hepatic necrosis ⇒ shrink
- need transplant - Chronic liver disease
- most common route - Hepatic dysfunction without obvious necrosis
- acute fatty liver of pregnancy
- tetracycline toxicity
- Reye syndrome
- Liver failure:
LIVER FAILURE clinical features
- Jaundice
- due to retention of bilirubin + bile stasis - Malabsorption/ weight loss
- due to bile, enzyme, vitamin deficiency - Hypoalbuminemia
- due to impaired synthesis ⇒ edema + muscle wasting - Hyperammonemia
- due to decreased urea-cycle ⇒ hepatic encephalopathy - Hyperestrogenemia
- metabolism impaired ⇒ palmar erythema, spider angiomas, hypogonadism, gynecomastia - Palmar erythema, spider angiomas on skin
- Ascites, splenomegaly, gastroesophageal varices
- Hepatorenal syndrome
- Hepatic cardiomyopathy
- Liver failure:
LIVER FAILURE complications
- Hepatic encephalopathy
- Hepatorenal syndrome
- Coagulopathy
- Hepatopulmonary syndrome
- Liver failure:
HEPATIC ENCEPHALOPATHY
CLINICAL FEATURES:
- behavioral abnormalities
- stupor, deep coma
- death
- rigidity, hypo-reflexia, seizures, asterixis
MORPHOLOGY:
- minor changes in brain - edema, astrocytic reaction
PATHOGENESIS:
- severe loss of hepatocellular function
- shunting of blood from portal to systemic circulation
⇒ exposure of brain to altered metabolic environment
ACUTE: elevated ammonia ⇒ impair neuronal functioning + promote edema
CHRONIC: altered AA metabolism in brain ⇒ deranged neurotransmission
- Liver failure:
HEPATOPULMONARY SYNDROME
- vasodilation in pulmonary vessels in patients with acute or chronic liver failure ⇒ blood runs quick ⇒ no gas exchange
- symptoms: dyspnea, hypoxemia
- if severe: no transplant
- Liver failure:
HEPATORENAL SYNDROME
= development of renal failure without any primary kidney diseases
PATHOGENESIS:
- unknown, but splanchnic vasodilation + systemic vasoconstriction ⇒ stasis in venous circulation ⇒ decreased flow to cortex of kidneys
CLINICAL FEATURES:
- oliguria
- azotemia
- hyperosmolar urine
- Liver failure:
HEMORRHAGIC DIATHESIS
- liver impairment ⇒ synthesis of clotting factors impaired ⇒ increased bleeding tendency + thromocytopenia
- can lead to massive hemorrhage in GI + other places
- Cholestasis, cholelithiasis, jaundice:
CHOLESTASIS etiology
- primary sclerosing cholangitis
- primary biliary cirrhosis
- abdominal mass
- biliary atresia
- biliary trauma
- congenital anomalies of the biliary tract
- gallstones
- drugs
- Cholestasis, cholelithiasis, jaundice:
PRIMARY BILIARY CIRRHOSIS PBS
= chronic progressive (+fatal) cholestatic autoimmune liver disease
AGE: middle-aged women, 40s-50s
MORPHOLOGY:
- destruction of intrahepatic bile ducts
- portal inflammation and scarring ⇒ cirrhosis + liver failure
PATHOGENESIS:
- high titer of antimitochondrial ABs AMA
- onset insidious ⇒ pruritus + jaundice
- hepatic decompensation with portal HT, variceal bleeding, hepatic encephalopathy
- elevated APP + cholesterol
- Cholestasis, cholelithiasis, jaundice:
PRIMARY SCLEROSING CHOLANGITIS PSC
MORPHOLOGY:
- progressive fibrosis + destruction of extra hepatic + large intrahepatic bile ducts
- segmental changes
- associated with IBD (UC)
PATHOGENESIS:
- linkage with certain HLA alleles
- ANCA ⇒ immunologically mediated disease
CLINICAL FETURES:
- progressive fatigue, pruritus, jaundice
- weight loss, ascites, variceal bleeding, encephalopathy
TREATMENT: transplant
- Cholestasis, cholelithiasis, jaundice:
CHOLELITHIASIS pathogenesis
- Cholesterol stones (80%):
- cholesterol exceeds solubilizing capacity in bile⇒ cholesterol precipitates into cholesterol monohydrate crystals
⇒ supersaturation of bile with cholesterol
⇒ establishment of nucleation sites by calcium salts
⇒ stasis in gallbladder ⇒ precipitation
⇒ mucous hypersecretion to trap crystals - Pigment stones (20%):
- presence of unconjugated bilirubin ⇒ insoluble calcium bilirubinate salt
- risk factors:
⇒ age (forty)
⇒ gender (female)
⇒ hereditary (familial)
⇒ obesity (fat)
⇒ environment
⇒ acquired disorders
- Cholestasis, cholelithiasis, jaundice:
CHOLELITHIASIS morphology
- Cholesterol stones:
- in gallbladder
- 50-100% cholesterol
- pale yellow ⇒ grey-white
- ovoid, firm
- radiolucent 80% - Pigment stones:
- anywhere in biliary tree
- black: gallbladder, small, large quantity, crumble easily, 50-75% radiopaque
- brown: heptic ducts, big, small quantity, soft, greasy, radiolucent
- Cholestasis, cholelithiasis, jaundice:
CHOLELITHIASIS clinical features
- asymptomatic
- excruciating pain
- empyema
- perforation
- fistulae
- inflammation of biliary tree
- obstructive cholestasis or pancreatitis
- Cholestasis, cholelithiasis, jaundice:
JAUNDICE definition
= yellow discoloration of skin, mucosa and sclera as a result of hyperbilirubinemia and deposition of bilirubin in tissues
- common sign of liver disease
- systemic retention of bilirubin ⇒ elevated serum levels
- Cholestasis, cholelithiasis, jaundice:
JAUNDICE pathogenesis + clinical features
TYPES: - prehepatic (hemolytic anemia) - hepatic (liver disease) - posthepatic (gallstone, tumor) MECHANISM: - excessive production of bilirubin - reduced hepatic uptake - impaired conjugation - decreased hepatocellular excretion - impaired bile flow INBORN ERRORS CAUSING JAUNDICE: - Gilbert syndrome - Criggler-Najjar - Dublin-Johnson syndrome
- Circulatory disorders of liver:
HEPATIC ARTERY INFLOW IMPAIREMENT
- interruption does not always cause ischemia due to dual blood supply
- hepatic artery thrombosis in transplanted liver ⇒ ischemia
- thombosis / compression of intrahepatic branch of hepatic artery due to:
- polyarteritis nodosa
- embolism
- neoplasia
- sepsis
⇒ local parenchymal infarct
- Circulatory disorders of liver:
PORTAL VEIN OBSTRUCTION AND THROMBOSIS
SYMPTOMS:
- abdominal pain
- ascites
- portal HT
- congestion + bowel infarction
CAUSE OF EXTRAHEPATIC PORTAL VEIN OBSTRUCTION:
- peritoneal sepsis
- pancreatitis ⇒ splenic vein thrombosis
- thromobgenic diseases + post surgical thrombosis
- vascular invasion by cancer
- Circulatory disorders of liver:
HEPATOPORTAL SCLEROSIS
- result of myeloproliferative disorder + hyper coagulability, peritonitis
- Circulatory disorders of liver:
IMPAIRED BLOOD FLOW THROUGH THE LIVER
CAUSES:
- cirrhosis
- sickle cell disease ⇒ sinusoids packed with sickled RBCs
- DIC
- RS-HF
MORPHOLOGY OF LIVER IN HF:
- RS-HF: enlarged, tense and cyanotic liver, congestion of centrilobular sinusoids ⇒ atrophies
- LS-HF: hepatic hypoperfusion ⇒ ischemic necrosis of hepatocytes
- combined: nutmeg liver
- Circulatory disorders of liver:
PELIOSIS HEPATIS
- sinusoidal dilation when efflux of hepatic blood is obstructed
- rare condition
- associated with exposure to anabolic steroids + oral contraceptives
- complication: intra-abdominal hemorrhage
- Circulatory disorders of liver:
BUDD-CHIARI SYNDROME
= thrombosis of 2+ major hepatic veins CAUSES: - myeloproliferative disease - pregnancy - postpartum state - oral contraceptives - paroxysmal nocturnal hemoglobinuria - intra-abdominal cancers SYMPTOMS: - hepatomegaly - weight-gain - ascites - abdominal pain MORPHOLOGY: - swollen, red-purple liver - tense capsule - congestion + necrosis
- Circulatory disorders of liver:
SINUSOIDAL OBSTRUCTION SYNDROME
PATHOGENESIS:
- toxic injury to sinusoidal endothelium ⇒ damaged cells slough off ⇒ create emboli
- damage accompanied by passage of RBCs into space of Disse, proliferation of stellate cells, fibrosis of hepatic vein
- 20-30 days after bone marrow transplant
- caused by: drugs, total body radiation
- Acute and chronic hepatitis:
ACUTE HEPATITIS etiology
- viral hepatitis
- yellow fever
- non-viral infection
- alcohol
- toxins
- drugs
- autoimmune diseases
- metabolic diseases
- Acute and chronic hepatitis:
HEPATITIS A
PATHOGENESIS:
- virus invades hepatocytes ⇒ replicates ⇒ apoptosis
- feco-oral transmission
- short incubation (15-50d)
- sporadic / endemic
- clinically mild disease + full recovery
- no carrier state or chronicity
- vaccine available
- diagnosis: anti HAV ABs
- Acute and chronic hepatitis:
HEPATITIS B
PATHOGENESIS:
- virus incorporate viral genome into host genome ⇒ replicate ⇒ produce viral antigens ⇒ immune response ⇒ apoptosis
- transmission by blood and body fluids
- long incubation (60-90d)
- vaccine available
CLINICAL COURSES:
1. acute hepatitis with recovery and clearance of virus
2. non-progressive chronic hepatitis
3. progressive hepatitis ending with cirrhosis
4. fulminant hepatitis with massive liver necrosis
5. asymptomatic carrier state
- Acute and chronic hepatitis:
HEPATITIS C
PATHOGENESIS:
- virus encorporate viral genome to host genome ⇒ replicate ⇒ produce antigens ⇒ immune response ⇒ apoptosis
- transmission by blood
- long incubation (7-8w)
- asymptomatic
- persistent infection
- cirrhosis ⇒ liver cancer
- no vaccine
- Acute and chronic hepatitis:
HEPATITIS D
- replication of hepatitis D needs co-infection of hepatitis B
- mild / fulminant
- incubation: 60-90d
- composed of Dane particle with HBV envelope
- IgM anti HDV AB
- hepatitis B vaccine
- Acute and chronic hepatitis:
HEPATITIS E
- water borne endemic hepatitis
- feco-oral transmission
- incubation: 4-5w
- mortalility in pregancy
- self-limiting
- Acute and chronic hepatitis:
CLINICAL FEATURES OF ACUTE HEPATITIS
PHASES: 1. incubation period 2. symptomatic preicteric period 3. symptomatic icteric period 4. covalescence SYMPTOMS: - malaise, fever, weight loss, nausea, headache, muscle + joint pain, vomiting, diarrhea, enlarged tender liver, jaundice
- Acute and chronic hepatitis:
CHRONIC HEPATITIS general + pathogenesis
GENERAL: - inflammation of liver that lasts more than 6 months ⇒ inflammation + necrosis - may progress to cirrhosis CAUSES: - hepatitis virus - Wilson disease - alpha-1 antitrypsin deficiency - chronic alcoholism - drugs - autoimmunity
- Acute and chronic hepatitis:
CHRONIC HEPATITIS morphology + clinical features
MORPHOLOGY: - periportal inflammation - periportal + bridging necrosis ⇒ fibrosis ⇒ macronodular cirrhosis CLINICAL FEATURES: - mild symptoms/ asymptomatic - spider angiomas - palmar erythema - hepatomegaly - hepatic tenderness
- Alcohol- and drug-induced liver disease:
ALCOHOLIC LIVER DISEASE forms
- Hepatic steatosis ⇒ large, soft, yellow greasy liver
- Alcoholic hepatitis ⇒ hepatocytes swell, necrosis, Mallory bodies, neutrophilic infiltrate, fibrosis
- Cirrhosis ⇒ nodular, yellow, fatty and enlarged liver
