31 - Cirrhosis Flashcards
1
Q
Causes in the Western world
A
- Chronic alcohol abuse
- Chronic hepatitis C
- Less common = non-alcoholic steatohepatitis, chronic hepatitis B, medications (isoniazid, amiodarone, methotrexate), etc.
2
Q
Pathophysiology of cirrhosis
A
- Liver receives blood from hepatic artery & portal vein
- Chronic liver disease can lead to liver scarring (hepatic fibrosis)
- Ongoing disease & deterioration of hepatocyte function can progress to cirrhosis
- Portal vein flow to liver is altered
- *Understand that flow is altered going through the liver
3
Q
Complications from cirrhosis
A
- Portal hypertension
- Esophageal & gastric varices w/ risk of variceal bleeding
- Ascites
- Spontaneous bacterial peritonitis (SBP) – when fluid causing ascites becomes infected
- Hepatic encephalopathy – confusion due to poor liver function that causes toxins to build up & flow around the body
4
Q
Describe portal hypertension
A
- Increased BP in portal venous system
- Hepatic venous pressure gradient (HVPG) > 5 mmHg
- Develops b/c:
- Scarring of liver causing mechanical obstruction of blood flow from portal vein to liver
- Splanchnic (GI) arterial vasodilation & decreased response to vasoconstrictors increases blood flow to portal vein
5
Q
Describe varices
A
- Portal hypertension w/ HVPG > 10 mmHg can lead to esophageal & gastric varices
- Small veins in lower esophagus & stomach become distended as blood is redirected
- High mortality rate; high recurrence rate
6
Q
Describe ascites
A
- Portal HTN can lead to cascade of events resulting in ascites (accumulation of fluid in peritoneal cavity)
- Sodium retention, low serum albumin (decreased oncotic pressure – less fluid to hold protein in the vessels, so fluid spills out), fluid leaks into peritoneal cavity
- W/in 10 years, about ½ of all px w/ cirrhosis develop ascites & ½ of those px die w/in 2 years
7
Q
Describe spontaneous bacterial peritonitis (SBP)
A
- Infection of ascitic fluid w/o obvious surgically treatable source
- Bacteria from GI tract end up in ascitic fluid
- Exact mechanism not been definitely elucidated (possibly bacterial translocation or hematogenous transmission)
- E. coli, K. pneumoniae, & pneumococci are most commonly isolated
- High mortality rate (< 50% survival 1 year after 1st episode)
8
Q
Describe hepatic encephalopathy
A
- Decreased liver function causes neurotoxins to accumulate, affects brain function
- Most commonly implicated = ammonia; increased levels in arterial blood due to:
- Decreased liver function
- Shunting of blood around liver
- Ammonia believed to play key role as attempting to lower levels improves encephalopathy, yet blood levels don’t correlate w/ mental status
- Glutamine & endogenous benzodiazepines are among other substances that may play a role
9
Q
Diagnosis of cirrhosis
A
- Biopsy is most accurate way to confirm cirrhosis, but usually not necessary
- Can usually diagnose from signs & sx, lab values/ abnormal endoscopy/ abnormal radiographic tests
10
Q
Sx of cirrhosis
A
- Weight loss
- Fatigue
- Anorexia
- Jaundice
- Men – impotence, decreased libido
- Abdominal distention (ascites)
- Confusion/mental status changes (encephalopathy)
- Pruritus
- GI bleeding, dark coloured urine
11
Q
Signs of cirrhosis on physical exam
A
- Hepatomegaly, splenomegaly
- Spider angiomata
- Caput medusae (distended veins from umbilicus)
- Digital clubbing/ nail clubbing (enlargement of fingernails or distal ends of fingers)
- Gynecomastia & testicular atrophy in men (b/c of circulating levels of estrogen)
- Jaundice
- Asterixis (associated w/ encephalopathy & increased levels of toxins in blood; when you close your eyes & hold your arms up w/ hands pointing up at 90-degree angle, person can’t hold hands still & will flap & try to go straight)
- Ascites
- Fetor hepaticus (breath has strong, musty smell)
12
Q
Lab value abnormalities in cirrhosis
A
- Moderately elevated aminotransferases (AST:ALT ~2:1 (up to 3:1) common in alcoholic liver disease)
- Elevated alkaline phosphatase (2-3x normal) w/ concomitant GGT rise
- Decreased serum albumin (test of liver function)
- Prolonged prothrombin time & elevated INR
- Hyperbilirubinemia
- Thrombocytopenia, leukopenia, anemia (RBCs go into spleen so that’s why splenomegaly can occur)
- Increased serum creatinine (decreased renal function)
- Hyponatremia (would think hyper b/c more sodium is in blood vessels, but more water too so causes hypo)
13
Q
2 tools for grading severity of liver disease
A
- Child-Pugh classification – used for recommending drug dosage adjustments in liver failure
- Considers bilirubin, albumin, degree of ascites, degree of encephalopathy, & degree of prolongation of PT
- Model for end-stage liver disease score (MELD score) – used in allocation of liver transplants
- Considers creatinine, bilirubin, & INR (more objective info than Child-Pugh)
- Predicts 3-month mortality
14
Q
Tx goals of cirrhosis
A
- Slow rate of progression, modify causative factors (EtOH)
- Treat complications that develop (varices, ascites, SBP, hepatic encephalopathy)
15
Q
Varices tx
A
- 3 aspects to treating varices caused by portal hypertension
1) Primary prophylaxis of varices
2) Tx of acute variceal bleeding
3) Secondary prophylaxis of varices
16
Q
Primary prophylaxis of varices
A
- No varices = no tx
- Small varices w/ no risk factors = no tx
- Small varices w/ risk factors for variceal hemorrhage (red wales, Child-Ugh score C) = treat pt w/ nonselective beta-blocker
- Medium to large varices w/ no bleeding = treat pt w/ nonselective beta blocker or endoscopic variceal ligation (EVL aka banding)
- EVL = tying off vessels so that they fall off & supposed to reduce risk of bleeding; preferred in cases of beta-blocker intolerance
- Non-selective beta blockers = propranolol or nadolol; titrate as tolerated (~ q3days) to HR 55-60 bpm, continue indefinitely except in end stage liver disease (no benefit & may actually cause harm)
- Mechanism = decrease portal venous inflow by decreasing cardiac output (beta-1) & by decreasing splanchnic blood flow (beta-2)
17
Q
Tx of acute variceal bleeding
A
- Medical emergency
- Need to maintain BP w/ fluids, control/correct bleeding (RBCs, platelets as needed)
- Octreotide ASAP 50 mcg IV x1, then 50 mcg/h IV continuous infusion x3-5 days (inhibits vasodilatory glucagon & has local splanchnic vasoconstrictive effect)
- EVL in conjunction
- Prophylaxis for SBP = ciprofloxacin or ceftriaxone up to 7 days
- If still bleeding w/ octreotide & EVL, transjugular intrahepatic portosystemic shunt (TIPS) – shunt bypasses the liver, but can cause encephalopathy b/c toxins aren’t being broken down by liver)
18
Q
Secondary prophylaxis of varices
A
- More than ½ of px re-bleed
- Tx = nonselective beta-blocker (propranolol or nadolol) + chronic EVL
- If pt previously had TIPS, then possible liver transplant candidate
19
Q
Ascites tx
A
- W/ new onset ascites, need a diagnosis
- Medication tx = diuresis & sodium restriction to 2 g daily (fluid restriction usually not necessary unless sodium < 120 mmol/L)
- Diuresis = furosemide (loop diuretic) + spironolactone (K+ sparing diuretic) in a 40 mg:100 mg ratio (to maintain normokalemia)
- Titrate diuretics up every 3-5 days for goal of 0.5 kg weight loss daily (max dose 160 mg furosemide to 400 mg spironolactone)
- Monitor electrolytes (K+ and Na+) and sCr
- For ascites refractory to diuretics – therapeutic paracentesis (can sometimes drain well over 5 L)
- Avoid NSAIDs, generally avoid ACEi/ARB
- Beta-blockers for varices – weigh risk vs. benefit in refractory ascites
20
Q
SBP tx
A
- May be asymptomatic, but often presents w/ one of more of – fever, abdominal pain, encephalopathy, confusion, renal failure
- Diagnosis if PMN (polymorphonuclear leukocyte) > 250 cells/mm3 and positive ascitic fluid bacterial cultures
- Treat empirically if PMNs > 250 or if signs/sx of infection
- Use broad spectrum antibiotics to cover E. coli, K. pneumoniae, & pneumococci = 3rd gen cephalosporins preferred (cefotaxime) over ciprofloxacin
- 5-day tx course (10 days usually not necessary)
- Following episode of SBP, give long-term prophylaxis w/ quinolone or TMP-SMX (lower dosing than standard tx dose – once daily, 5 days/week, weekly dosing)
21
Q
Hepatic encephalopathy tx
A
- Can present acutely (episodic), continually (persistent), or recurring (more than 1 episode < 6 months apart)
- Precipitating factors = electrolyte abnormalities (dehydration, diuretic overuse), infection, GI bleeding, constipation
- Mainstay of therapy = reduce ammonia levels
- Lactulose (non-absorbable disaccharide)
- Can give orally (30 mL/dose), NG, or PR – PO/NG preferred b/c dose for rectal administration is 1 L
- Lowers ammonia by – laxative effect (less time for systemic ammonia absorption from gut); decreased pH leaves NH4+ cations “trapped” in acidified colon
- Acutely can give q1h to initiate laxative effect, then titrate for ~ 3 soft stools daily; monitor for improved mental status
- Rifaximin – poorly absorbed synthetic antibiotic, believed to reduce ammonia-producing bacteria in gut
- Neomycin/metronidazole – not commonly used anymore b/c higher risk of side effects
