3/28 Cirrhosis - Wondisford Flashcards
cirrhosis
definition
defined histopathologically
- development of liver fibrosis
- distorts architecture
- decreased liver fx & regenerative nodules
- death of hepatocytes
- deposition of ECM (fibrosis)
- vascular reorganization
heaptic steatosis
macrovesicular steatosis (more comon form of fatty degen)
- causes: oversupply of lipids due to obesity (NAFL), insulin resistance, alcoholism
- BIG fat droplets
- likely reversible
- early lesion →→→ cirrhosis
microvesicular steatosis
- small intracytoplasmic fat vacuoles (liposomes) that accumulate in cell → foamy pattern in cytoplasm
- causes: acute fatty liver of preg, Reye’s syndrome, hep C
sinusoid in health and disease
Kupffer cells mediate stellate cell activation and liver fibrosis
-
stellate cell activation
- PDGF (platelet derived growth factor) and TNF (tumor necrosis factor) activate stellate cells
- ET1 (endothelin 1) stimulates contraction of activated stellate cells
- PDGF and MCP1 (monocyte chemotactic protein 1) stimulate chemotaxis of activated stellate cells to injured areas
-
fibrosis
- TGFbeta (transforming growth factor beta) stimulates fibrosi
macroscopic cirrhosis
macronodular vs micronodular vs mixed
1. macronodular (> 3mm postnecrotic cirrhosis)
- most common: viral hep B, C
- Wilson’s disease
- alpha1AT def
- more scattered damage
2. micronodular (< 3mm; Laennec’s cirrhosis)
- usually alcohol
- also primary biliary cirrhosis, hemochromatosis
- more uniform damage
3. mixed cirrhosis
regenerative nodule
- surrounded by fibrous connective tissue that bridges between portal tracts
- scattered lymphocytes
- proliferation of bile ducts
symptoms
signs
lab findings
nonspecific sx
- anorexia, fatigue, weakness, fever, jaundice
- n/v, diarrhea
- vague RUQ pain
- amenorrhea, impotence, infertility
signs
- spider telangiectases
- palmar erythema
- jaundice
- scleral icterus
- parotid/lacrimal gland enlargement
- clubbing
- Dupuytren’s contracture
- gynecomastia
- testicular atrophy
- hepatosplenomeg
- ascites
- GI bleed
- hepatic encephalopathy
lab findings
- anemia
- microcytic due to blood loss
- macrocytic due to folate def
- hemolytic - Zieve’s syndrome
- pancytopenia
- prolonged PT
- hypoNa, hypoK, alkalosis (due to RAAS activation)
- glucose disturbances
- hypoalb
ascites
decreased effective blood volume activating RAAS
*need to calculate serum albumin:ascitic gradient (SAAG)
- SAAG > 1.1 → portal HTN
- fluid pushed out of portal circ into peritoneal cavity → incr serum, decr ascitic protein conc
- SAAG < 1.1 → protein leak onto peritoneal cavity
in both cases, you have fluid moving into peritoneum (either being pushed out of circ, or pulled into peritoneum)
ascites tx
- sodium restriction
- aldosterone antagonists
- repeated paracentesis
- consider TIPS (transjug portosystemic shunt)
cirrhotic ascites?
- fever, worsening ascites, jaundice, hypoTN, encephalopathy → need to suspect spontaneous bacteria peritonitis
- see ascitic fluid PMN cell count > 250
- confirmed by culture (usually E. coli, gut bacteria)
hepatic encephalopathy
sx
cause
triggers
tx
confusion, memory loss, inability to concentrate, asterixis (liver flap), obtundation, stupor, coma
cause: portosystemic shunts from cirrhosis → decr ammonia metabolism in liver (along with other substances) → encephalopathy
triggers
- higher NH3 prod: high protein intake, GI bleeding, constipation
- decr NH3 clearance: renal failure, TIPS (liver bypassed), diuretics (incr renal abs)
tx:
- laculose : incr bacteria acid production → incr NH4, trapping ammonia in gut
- neomycin → kills NHS-producing bacteria
abnormal lab values
1. abnormal AST, ALT
- AST > ALT w alcohol and NASH
2. abnormal alk phos
- especially in PBC, PSC
- confirm with GGT
3. high bilirubin and prothrombin time (INR), low albumin are measures of poor hepatic synthetic fx
- indicative of significant loss of hepatocyte mass
hemachromotosis
recessive mutations in HFE gene → decr hepcidin → incr intestinal abs
- incr ferritin, Fe, decr TIBC → incr transferrin saturation
- Fe accumulates esp in liver, pancreas, skin, heart, pit, joints
iron overload can be secondary to chronic transfusion tx
classic triad
- cirrhosis
- DM
- skin pigmentation (“bronze diabetes”)
also: dilated cardiomyopathy (reversible), hypogonadism, arthropathy (Ca pyrophosphate deposition)
tx: repeat phlebotomy, chelation with deferoxamine
alpha1 antitrypsin deficiency
European ancestry (uncommon in Asian descent)
cause: misfolded gene product protein (S or Z) aggregating in hepatocellular ER → cirrhosis with PAS+ globules in liver
in lungs, decreased A1AT → uninhibited elastase in alveoli → decreased elastic tissue → panacinar emphysema
different levels of protease inhibitor based on combo of M, S, Z alleles
Child Pugh score
calculated by adding scores of five factors
hepatorenal disorders/conditions
ascites coincides with portal HTN
- reduces blood flow to liver and intestines → release of vasoactive substances form the liver (PG and NO)
- causes splanchnic arterial beds to dilate → worsens ascites!
- reduced intravascular volume → activation of RAAS → hepatorenal syndrome
- high mortality
tx:
- midodrine (alpha agonist), octreotide (SST analogue) → promote splanchnic vasoconstriction
- albumin
hepatopulmonary syndrome
cause: vasodilators in pulmo circ (similar to how vasodil in splanchnic circ → hepatorenal syndrome) → formation of shunts, especially in lung apical regions → V/Q defect
- pts with cirrhosis and portal HTN experience dyspnea and hypoxemia
- platypnea: SOB standing, relieved by lying down → more uniform perfusion of lung lying down
- marker of poor prognosis in cirrhosis
hepatocellular carcinoma
most common pirmary malignant tumor of liver in adults
assoc: HBV, other causes of cirrhosis, specific carcinogens (aflatoxin from Aspergillus)
findings: jaundice, tender hepatomegaly, ascites, polycythemia, anorexia
hematogenous spread
can lead to BuddChiari
dx: incr alpha-fetoprotein, U/S or contrast CT/MRI, biopsy
other liver tumors
