Cirrhosis and Chronic Liver disease Flashcards
Natural history of chronic liver disease
chronic liver disease –> compensated cirrhosis –> decompensated cirrhosis (variceal hemorrhage, ascites, encephalopathy, jaundice) –> death or liver transplant
Causes of complications from cirrhosis
portal hypertension –> variceal hemorrhage, ascites, encephalopathy
liver insufficiency –> encephalopathy, jaundice
in whom should we suspect cirrhosis?
any patient with chronic abnormal ALT and/or alk phos
lab signs of liver insufficiency
low albumin, prolonged PT/INR, high bilirubin
lab signs of portal hypertension
low platelets (less than 150,000)
cirrhosis findings on imaging
nodular liver, caudate hypertrophy, ascites, splenomegaly, venous collaterals, HCC
liver biopsy is NOT necessary in the presence of
decompensated cirrhosis, CT scan diagnostic of cirrhosis (nodular liver surface)
When should you do a liver biopsy?
chronic liver disease without:
variceal hemorrhage/ascites/hepatic encephalopathy + no physical findings of enlarged L hepatic lobe, splenomegaly, or stigmata of CLD + no labs showing thrombocytopenia or impaired hepatic synthetic dysfunction (albumin, PT) + no radiological findings
Purpose of the MELD score
estimates risk of 3-month mortality
Components of MELD score
serum total bilirubin, serum creatinine, INR
Computing the MELD score
6.4 + 9.8 x log (INR) + 11.2 x log (Cr) + 3.8 x log (bilirubin)
Who has the highest priority in organ allocation for liver transplant
person with the highest MELD score among those with identical blood types
Two mechanisms of portal hypertension
increased resistance to portal flow
increase in portal venous inflow
initial mechanism of portal hypertension in cirrhosis
increased intrahepatic resistance in the sinusoids (sinusoidal fibrosis + active vasoconstriction)
mechanism of vasoconstriction in cirrhosis
cirrhosis –> reduced endothelial NO –> vasoconstriction and increased resistance
mechanism of increased portal venous inflow
cirrhosis –> increased resistance to portal flow –> increased portal pressure –> decreased splanchnic arteriolar resistance (NO release) –> increased portal blood inflow
safest and most reproducible method to measure portal pressure
measure the hepatic venous pressure gradient
HVPG = WHVP (wedged hepatic venous pressure) - FHVP (free hepatic venous pressure)
normal values in HVPG equation
HVPG = WHVP (5) - FHVP (2) = 3 mm Hg
HVPG in presinusoidal portal hypertension
normal (3 mmHg)
HVPG in sinusoidal portal hypertension
elevated (~18 mmHg)
WHVP ~20 mmHg
HVPG in post-sinusoidal portal hypertension
elevated (~18 mmHg)
WHVP = ~20 mmHg
HVPG in post-hepatic (heart failure) portal hypertension
normal
WHVP = 20 FHVP = 18
portal hypertension with normal HVPG
pre-hepatic, pre-sinusoidal, post-hepatic
major determinent of variceal rupture
variceal wall tension
= transmural pressure x (radius/wall thickness)
management of increased resistance to portal flow
TIPS (transjugular intrahepatic portosystemic shunt)
management of increased portal blood inflow
vasoconstrictors (octreotide) –> increased splanschnic arteriolar resistance
management of varices/variceal hemorrhage
beta blockers
variceal ligation, if contraindicated for beta blockers
most common cause of ascites
cirrhosis (80%)
mechanism of ascites development
portal hypertension –> shear stress –> NO increase –> vasodilation –> activation of RAAS –> Na and water retention –> ascites
most sensitive method for detection of ascites
abd US
routine ascites fluid analysis
albumin, protein, PMN cell count, cultures
indications for diagnostic paracentesis
new-onset ascites, admission to hospital, s/sx of SBP, renal dysfunction, unexplained encephalopathy
mechanism of refractory ascites caused by cirrhosis
cirrhosis –> increased intrahepatic resistance –> increased sinusoidal pressure –> refractory ascites
cirrhosis –> decreased systemic arteriolar resistance –> decreased effective arterial blood volume –> increased activation of RAAS –> Na and water retention –> refractory ascites
treatment of uncomplicated ascites
salt restriction + diuretics
large volume paracentesis with tense ascites
treatment of refractory ascites
LVP + albumin
TIPS (decrease sinusoidal pressure, increase effective arterial blood volume)
characteristics of hepatorenal syndrome
functional renal failure in patients with cirrhosis
marked arteriolar vasodilation in extra-renal circulation
renal vasoconstriction –> reduced GFR
Type 1 hepatorenal syndrome
rapidly progressive renal failure, creatinine > 2.5 or CrCl less than 20 ml/min
Type 2 hepatorenal syndrome
more slowly progressive, creatinine > 1.5 or CrCl lower than 40 ml/min
which type of hepatorenal syndrome is associated with refractory ascites?
Type 2
pathogenesis of hepatorenal syndrome
cirrhosis –> decreased arteriolar resistance –> decreased effective arterial blood volume –> increased activation of RAAS –> increased renal vasoconstriction –> hepatorenal syndrome
natural history of hepatorenal syndrome
type 2 –> spontaneous bacterial peritonitis –> type 1
Major criteria for dx of hepatorenal syndrome
advanced hepatic failure and portal HTN
Creatinine > 1.5 or CrCl lower than 40
Absence of shock, bacterial infection or nephrotoxic drugs
Absence of excessive GI or renal fluid loss
No improvement in renal function after 1.5L of isotonic saline
Urinary protein less than 500 and normal renal US
Always present in HRS
ascites and hyponatremia
Management of HRS
liver transplant
Most common infection in cirrhotic patients
spontaneous bacterial peritonitis
Mechanism of SBP
bacterial translocation: intestinal dysmotility –> bacterial overgrowth –> increased intestinal permeability –> impaired immunity –> transient bacteremia –> prolonged bacteremia –> ascites colonization –> SBP
paracentesis –> PMN count > 250
SBP
Which organisms are most often isolated in SBP
G- bacilli (E coli, Klebsiella), G+ cocci (Strep)
Initial empiric therapy of SBP
IV cefotaxime, augmentin oral ofloxacin (uncomplicated SBP)
When is SBP more likely to occur?
in patients with low-protein ascites
Characteristics of hepatic encephalopathy
failure to metabolize neurotoxic substances (increased ammonia –> glutamine accumulation) + altered astrocyte morphology and function (astrocytes are the only brain cells that can metabolize ammonia) (Alzheimer’s Type 2 astrocytosis)
Pathophys of hepatic encephalopathy
increased ammonia –> cross BBB –> upregulation of astrocytic peripheral benzodiazepine receptors (PBR) –> neurosteroid production –> modulation of GABA-a receptor –> cortical depression –> hepatic encephalopathy
Diagnosis of hepatic encephalopathy
Clinical findings and history
ammonia levels are unreliable and poorly correlate with diagnosis
Hepatic encephalopathy precipitants
excess protein, GI bleeding, sedatives/hypnotics, diuretics, TIPS, sepsis, azotemia caused by hypokalemia
treatment of hepatic encephalopathy
identify and treat precipitating factor, lactulose, short-term protein restriction
mechanism of lactulose
lowers colon pH –> converts ammonia to ammonium –> ammonium excreted in feces, increased cathartic effect
