Cirrhosis and Chronic Liver disease

Question 1

Natural history of chronic liver disease

Answer 1

chronic liver disease –> compensated cirrhosis –> decompensated cirrhosis (variceal hemorrhage, ascites, encephalopathy, jaundice) –> death or liver transplant

Question 2

Causes of complications from cirrhosis

Answer 2

portal hypertension –> variceal hemorrhage, ascites, encephalopathy

liver insufficiency –> encephalopathy, jaundice

Question 3

in whom should we suspect cirrhosis?

Answer 3

any patient with chronic abnormal ALT and/or alk phos

Question 4

lab signs of liver insufficiency

Answer 4

low albumin, prolonged PT/INR, high bilirubin

Question 5

lab signs of portal hypertension

Answer 5

low platelets (less than 150,000)

Question 6

cirrhosis findings on imaging

Answer 6

nodular liver, caudate hypertrophy, ascites, splenomegaly, venous collaterals, HCC

Question 7

liver biopsy is NOT necessary in the presence of

Answer 7

decompensated cirrhosis, CT scan diagnostic of cirrhosis (nodular liver surface)

Question 8

When should you do a liver biopsy?

Answer 8

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

Question 9

Purpose of the MELD score

Answer 9

estimates risk of 3-month mortality

Question 10

Components of MELD score

Answer 10

serum total bilirubin, serum creatinine, INR

Question 11

Computing the MELD score

Answer 11

6.4 + 9.8 x log (INR) + 11.2 x log (Cr) + 3.8 x log (bilirubin)

Question 12

Who has the highest priority in organ allocation for liver transplant

Answer 12

person with the highest MELD score among those with identical blood types

Question 13

Two mechanisms of portal hypertension

Answer 13

increased resistance to portal flow

increase in portal venous inflow

Question 14

initial mechanism of portal hypertension in cirrhosis

Answer 14

increased intrahepatic resistance in the sinusoids (sinusoidal fibrosis + active vasoconstriction)

Question 15

mechanism of vasoconstriction in cirrhosis

Answer 15

cirrhosis –> reduced endothelial NO –> vasoconstriction and increased resistance

Question 16

mechanism of increased portal venous inflow

Answer 16

cirrhosis –> increased resistance to portal flow –> increased portal pressure –> decreased splanchnic arteriolar resistance (NO release) –> increased portal blood inflow

Question 17

safest and most reproducible method to measure portal pressure

Answer 17

measure the hepatic venous pressure gradient

HVPG = WHVP (wedged hepatic venous pressure) - FHVP (free hepatic venous pressure)

Question 18

normal values in HVPG equation

Answer 18

HVPG = WHVP (5) - FHVP (2) = 3 mm Hg

Question 19

HVPG in presinusoidal portal hypertension

Answer 19

normal (3 mmHg)

Question 20

HVPG in sinusoidal portal hypertension

Answer 20

elevated (~18 mmHg)

WHVP ~20 mmHg

Question 21

HVPG in post-sinusoidal portal hypertension

Answer 21

elevated (~18 mmHg)

WHVP = ~20 mmHg

Question 22

HVPG in post-hepatic (heart failure) portal hypertension

Answer 22

normal

WHVP = 20
FHVP = 18

Question 23

portal hypertension with normal HVPG

Answer 23

pre-hepatic, pre-sinusoidal, post-hepatic

Question 24

major determinent of variceal rupture

Answer 24

variceal wall tension

= transmural pressure x (radius/wall thickness)

Question 25

management of increased resistance to portal flow

Answer 25

TIPS (transjugular intrahepatic portosystemic shunt)

Question 26

management of increased portal blood inflow

Answer 26

vasoconstrictors (octreotide) --> increased splanschnic arteriolar resistance

Question 27

management of varices/variceal hemorrhage

Answer 27

beta blockers | variceal ligation, if contraindicated for beta blockers

Question 28

most common cause of ascites

Answer 28

cirrhosis (80%)

Question 29

mechanism of ascites development

Answer 29

portal hypertension --> shear stress --> NO increase --> vasodilation --> activation of RAAS --> Na and water retention --> ascites

Question 30

most sensitive method for detection of ascites

Answer 30

abd US

Question 31

routine ascites fluid analysis

Answer 31

albumin, protein, PMN cell count, cultures

Question 32

indications for diagnostic paracentesis

Answer 32

new-onset ascites, admission to hospital, s/sx of SBP, renal dysfunction, unexplained encephalopathy

Question 33

mechanism of refractory ascites caused by cirrhosis

Answer 33

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

Question 34

treatment of uncomplicated ascites

Answer 34

salt restriction + diuretics large volume paracentesis with tense ascites

Question 35

treatment of refractory ascites

Answer 35

LVP + albumin | TIPS (decrease sinusoidal pressure, increase effective arterial blood volume)

Question 36

characteristics of hepatorenal syndrome

Answer 36

functional renal failure in patients with cirrhosis marked arteriolar vasodilation in extra-renal circulation renal vasoconstriction --> reduced GFR

Question 37

Type 1 hepatorenal syndrome

Answer 37

rapidly progressive renal failure, creatinine > 2.5 or CrCl less than 20 ml/min

Question 38

Type 2 hepatorenal syndrome

Answer 38

more slowly progressive, creatinine > 1.5 or CrCl lower than 40 ml/min

Question 39

which type of hepatorenal syndrome is associated with refractory ascites?

Answer 39

Type 2

Question 40

pathogenesis of hepatorenal syndrome

Answer 40

cirrhosis --> decreased arteriolar resistance --> decreased effective arterial blood volume --> increased activation of RAAS --> increased renal vasoconstriction --> hepatorenal syndrome

Question 41

natural history of hepatorenal syndrome

Answer 41

type 2 --> spontaneous bacterial peritonitis --> type 1

Question 42

Major criteria for dx of hepatorenal syndrome

Answer 42

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

Question 43

Always present in HRS

Answer 43

ascites and hyponatremia

Question 44

Management of HRS

Answer 44

liver transplant

Question 45

Most common infection in cirrhotic patients

Answer 45

spontaneous bacterial peritonitis

Question 46

Mechanism of SBP

Answer 46

bacterial translocation: intestinal dysmotility --> bacterial overgrowth --> increased intestinal permeability --> impaired immunity --> transient bacteremia --> prolonged bacteremia --> ascites colonization --> SBP

Question 47

paracentesis --> PMN count > 250

Answer 47

SBP

Question 48

Which organisms are most often isolated in SBP

Answer 48

G- bacilli (E coli, Klebsiella), G+ cocci (Strep)

Question 49

Initial empiric therapy of SBP

Answer 49

``` IV cefotaxime, augmentin oral ofloxacin (uncomplicated SBP) ```

Question 50

When is SBP more likely to occur?

Answer 50

in patients with low-protein ascites

Question 51

Characteristics of hepatic encephalopathy

Answer 51

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)

Question 52

Pathophys of hepatic encephalopathy

Answer 52

increased ammonia --> cross BBB --> upregulation of astrocytic peripheral benzodiazepine receptors (PBR) --> neurosteroid production --> modulation of GABA-a receptor --> cortical depression --> hepatic encephalopathy

Question 53

Diagnosis of hepatic encephalopathy

Answer 53

Clinical findings and history ammonia levels are unreliable and poorly correlate with diagnosis

Question 54

Hepatic encephalopathy precipitants

Answer 54

excess protein, GI bleeding, sedatives/hypnotics, diuretics, TIPS, sepsis, azotemia caused by hypokalemia

Question 55

treatment of hepatic encephalopathy

Answer 55

identify and treat precipitating factor, lactulose, short-term protein restriction

Question 56

mechanism of lactulose

Answer 56

lowers colon pH --> converts ammonia to ammonium --> ammonium excreted in feces, increased cathartic effect