Cirrhosis Flashcards
Cirrhosis
Late stage of progressive hepatic fibrosis
Characterized histologically by regenerative nodules surrounded by fibrous tissue
Generally irreversible
two types:
Compensated (no complications)
Decompensated (complications)
ex of complications of cirrhosis
variceal hemorrhage
ascites
encephalopathy
jaundice
suspect cirrhosis in
Any patient with chronic liver disease
Chronic abnormal aminotransferases (ALT) and/or alkaline phosphatase (alk phos)
Liver insufficiency Low albumin ( 1.3) High bilirubin (> 1.5 mg/dL) Portal hypertension Low platelet count (
Etiologies of cirrhosis
Viral:
Hepatitis C*
Hepatitis B
Alcoholic liver disease*
Autoimmune:
Primary biliary cirrhosis
Primary sclerosing cholangitis
Autoimmune hepatitis
Metabolic:
Hemochromatosis (iron)
Wilson Disease (copper)
Alpha-1 Antitrypsin deficiency
Vascular:
Budd-Chiari syndrome
Congestive heart failure
Non-alcoholic fatty liver disease
signs of cirrhosis
scleral icterus jaundice spider angioma pectoral alopecia enlarged left lobe caput medusae umbilical hernia white nails/clubbing femal escutcheon edema muscle wasting gynecomastia splenomegaly ascites testicular atrophy palmar erythema/Dupuytren's contracture purpura/petechiae
prehepatic portal htn
Prehaptic portal htn:
- portal vein thrombosis
- schistosomiasis (eggs get stuck before sinusoids–> portal htn)
- cirrhosis
Post sinusoidal htn
post-sin obstructive syndrome:
obstruce of small veins after sinusoids
Liver biopsy and cirrhosis
not necessary:
Decompensated cirrhosis (variceal hemorrhage, ascites, encephalopathy)
CT scan diagnostic of cirrhosis
not needed for pretransplant eval
Way to assess mortality in cirrhosis
Child-Turcotte-Pugh Score (CTP)
MELD score
Mathematical survival model created from data on patients undergoing TIPS
MELD score estimates risk of 3-month mortality
Uses 3 laboratory values
- Serum total bilirubin
- Serum creatinine
- INR
Calculating MELD score
normal 6
- 4 + 9.8 x log (INR) +
- 2 x log (Cr) +
- 8 x log (Bilirubin)
Organ allocation for liver transplant
Fulminant hepatic failure has highest priority
MELD score determines priority in cirrhosis
Amongst patients with same blood type, highest MELD score determines priority
Waiting time used only to break ties with identical MELD scores
MELD scores are updated at regular intervals
Mech of portal htn
P=RxF (pressure, resistance, flow)
Portal hypertension can result from:
increase in resistance to portal flow and/or
increase in portal venous inflow
mech leading to portal htn in cirrhosis
Increased intrahepatic resistance
is the initial mechanism leading to portal hypertension
-distorted sinusoidal architecture leads to increased resistance in cirrhosis
causes of portal htn
- cirrhosis (sinusoidal site)
- prehepatic :portal or splenic v thrombosis, schistosomiasis
-post sinusoidal: veno-occlusive disease
post hepatic: Budd Chiari syndrome (hepatic v thrombosis
Intrahepatic resistance in cirrhosis
structural (sinusoidal fibrosis and regenerative nodules) but also functional (active vasoconstriction)
- in cirrhosis Nitric oxide activity is reduced and vasoconstrictors are increased
Splanchnic vasodilation in portal htn
results from increase in NO
(shear stress in splanchnic vasculature increases NO, as does bacterial translocation from ascites)–> splnachnic vasodil, increase in portal inflow
MEch of portal htn in sirrhosis
Increased intrahepatic resistance
Structural (fibrosis, regenerative nodules)
Active vasoconstriction (decreased nitric oxide, increased vasoconstrictors)
Increased portal venous inflow
Splanchnic vasodilation (increased nitric oxide)
Safest method for measuring portal pressure
measurement of the hepatic venous pressure gradient (HVPG)
subtracting the free hepatic venous pressure (FHVP) from the wedged hepatic venous pressure (WHVP):
HVPG= WHVP-FHVP
FHVP is “internal zero” (correct for extravascular, intraabdominal pressure increases)
Normal HVPG: 3-5 mmHg
Will be NORMAL in presinusoidal portal htn and post-hepatic portal htn; increased in sinusoidal portal htn, post-sinusoidal.
Cirrhosis and varices
increased resistance to portal flow–> increased portal pressure–> varices, variceal growth
varices increase in diameter progressively (none to small to large at rates of 7-8% per year)
Predictors of variceal HEMORRHAGE
variceal size
red signs
child b/c
2 year probability of first bleed: small 7%, large 30%
major determinant of variceal rupture
variceal wall tension (T)
T=tpx r/w
tp: transmural pressure
r: radius
w: wall thickness
What can decrease risk of variceal bleeding
decrease in HVPG to a level below 12 mmHg essentially eliminates the risk of recurrent variceal hemorrhage, while a reduction of at least 20% from baseline reduces this risk significantly (7-13%)
Endoscopic variceal band ligations
Bleeding controlled in 90% Rebleeding rate 30% Compared with sclerotherapy: Less rebleeding Lower mortality Fewer complications Fewer treatment sessions
Therapy for varices/hem
three types of therapy for varices and variceal hemorrhage (pharmacotherapy, endoscopic therapy, shunt therapy)
Combining a vasoconstrictor with a venodilator will have a combined effect reducing both flow and resistance
Shunt therapy, by bypassing the liver (the site of increased resistance) maximally reduces resistance, leading to normalization of portal pressure. However, by bypassing the liver this therapy can lead to other complications such as encephalopathy and liver failure
Octeotride
vasoconstrictor that decreases splanchnic flow**
Most common complication of cirrhosis for portal htn and vasodilation
development of ascites
(Extreme: hepatorenal syndrome)
SLIDE 71
Most common cause of ascites
cirrhosis 80%
Portal htn progression to hepatorenal syndrome
Portal htn w/o ascites *HVPG 10, mod vasodil) refractory ascites (>10 sever vasodil) hepatorenal syndrome (>10, extreme vasodil)
Work up of ascites
diagnostic paracentesis
routine:
PMN count, culture
Protein, albumin
Optional Glucose LDH amylase cytology RBC count TB smear/culture cytology triglycerides
Indications of paracentesis
New-onset ascites Admission to hospital Symptoms/signs of SBP Renal dysfunction Unexplained encephalopathy
contraindic: none
***serum ascites albumin gradient
SAAG Calculation: serum albumin minus ascites albumin
SAAG 1.1 g/dLcorrelates to pressure of 11 mmHg (HVPG)
The cutoffs for SAAG and ascites protein levels are 1.1 g/dL and 2.5 g/dL respectively. Cirrhotic ascites is typically high SAAG and low protein; cardiac ascites is high SAAG and high protein; and ascites secondary to peritoneal malignancy is typically low SAAG and high protein.
SLIDE 81
Diuretics
tell kidneys to get rid of salt, water follows, and will get rid of fluid out of body
Portal htn,no ascites
no specific therapy ?salt restriction
uncomplicated ascites tx
1) Salt restriction + diuretics
2) Large volume paracentesis (LVP) with tense ascites
refractory ascites tx
1) LVP + albumin
2) TIPS (only if they have LOW MELD score)
refractory ascites
Occurs in ~10% of cirrhotic patients
-worse survival than diuretic responsive
Diuretic-intractable ascites (80%)
Therapeutic doses of diuretics cannot be achieved because of diuretic-induced complications
Diuretic-resistant ascites (20%)
No response to maximal diuretic therapy (400 mg spironolactone + 160 mg furosemide/day)
LVP vs TIPS and ascites recurrence
TIPS assoc with less ascites recurrence, but more encephalopathy
-no difference in survival
Hepatorenal failure
Renal failure in patients with cirrhosis, advanced liver failure and severe sinusoidal portal hypertension
Absence of significant histological changes in the kidney (“functional” renal failure)
Marked arteriolar vasodilation in the extra-renal circulation
Marked renal vasoconstriction leading to reduced glomerular filtration rate
Acitivty in renin/ald in HRS
markedly increased
Types of hepatorenal syndrome
Type 1
Rapidly progressive renal failure (2 weeks)
Doubling of creatinine to >2.5 or halving of creatinine clearance (CrCl) to 1.5 mg/dL or CrCl
renal failure in cirrhosis
not HRS
vasodilation:
vasodilators
LVP w/o albumin
infection
decreased effective arterial blood vol:
diuretics
diarrhea
hemorrhage
increased renal vasoconstriction:
NSAIDs
Major criteria in dx of HRS
Advanced hepatic failure and portal hypertension
Creatinine > 1.5 mg/dL or creatinine clearance plasma osmolality
Serum sodium
What are always present in HRS?
Ascites
Hyponatremia
Mgmt of HRS
Proven efficacy
Liver transplantation
Under investigation Vasoconstrictor + albumin Transjugular intrahepatic portosystemic shunt (TIPS) Vasoconstrictor (Terlipressin-- IV) Extracorporeal albumin dialysis (ECAD)
Ineffective
Renal vasodilators (prostaglandin, dopamine)
Hemodialysis
What complicates ascites and can lead ot renal dysfunc
spontaneous bacterial peritonitis (SBP):
bacterial transloaction is mech: microorg from intestine to mesenteric lymph nodes and other extraintestinal organs/sites
BT doesn’t increase in prehepatic portal htn
mostly gram-negative enteric organisms
Mech of bacterial translocation
- intestinal bacterial overgrowth
- intestinal permeability
- impaired immunity
Dx of SBP
diagnostic paracentesis
PMN count >250/mm^3
Tx of SBP
Recommended antibiotics for initial empiric therapy
i.v. cefotaxime, amoxicillin-clavulanic acid
oral ofloxacin (uncomplicated SBP)
avoid aminoglycosides
Minimum duration: 5 days
Re-evaluation if ascitic fluid PMN count has not decreased by at least 25% after 2 days of treatment
Consider adding albumin: decreases renal dysfun and short term mortality in SBP
Hepatic Encephalopathy
Neuropsychiatric complication of cirrhosis
Results of both:
Portosystemic shunt (spontaneous, surgical or radiographic)
and
Chronic liver failure
Failure to metabolize neurotoxic substances:
Hyperammonemia results in glutamine accumulation
Alterations of astrocyte morphology and function (Alzheimer type II astrocytosis):
Astrocytes only cells in brain that can metabolize ammonia
***ammonia is thought to be a culprit, poss GABA-R involvement, but ammonia measurement NOT necessary for dx
Dx: Clinical findings/hx (ammonia unreliable) number connection test slow dominant rhythm on EEG
Stages 1 (mild confusion) to 4 (coma)
Tx of minimal hepatic encephalopathy
lactulose or synbiotics may improve condition
Minimal hepatic enceph abnormalities: Attention and cognitive deficits Visual-spacial perception impaired Defects in visual constructive ability Impaired driving ability Evoked potentials and spectral electro-encephalography abnormal
Hepatic Encephalopathy Precipitants
high protein load GI bleeding or constipation infection overdiuresis Narcotics and sedatives TIPS procedure
Tx of hepatic encephalopathy
Identify and treat precipitating factor Infection GI hemorrhage Prerenal azotemia Sedatives Constipation
Lactulose (adjust to 2-3 bowel movements/day) (decreases ammonia production in gut, as do abx)
Protein restriction, short-term (if at all– usually not necessary)
Also: ornithine aspartate, benzoate may increase ammonia fixation in liver
