Cirrhosis TBL Flashcards
What is cirrhosis?
- a late stage of progressive liver disease in which there is distortion of hepatic architecture
- Diffuse formation of regenerative nodules that lack normal organization
- These nodules are surrounded by fibrous bands
- Leads to inability of the liver to function properly (synthetically, hemodynamically)
- In general, thought to be irreversible
- Rarely, there can be regression of fibrosis- scar tissue can become thinner and eventually fragment
How long does it typically take to develop cirrhosis?
5-50 years
What occurs in cirrhosis?
collagen deposition in space of Disse activation of hepatic stellate cells constriction of sinusoids defenestration of sinusoids Distorted sinusoidal architecture leads to increased resistance
What is portal hypertension?
- A pathologic increase in the pressure of the portal system due to increased resistance to portal blood flow
- Most commonly due to intrinsic liver disease but can be due to other causes
What are some causes of posthepatic portal hypertension?
Budd-Chiari syndrome Constrictive pericarditis Inferior vena caval obstruction Right-sided heart failure Sever tricuspid regurg
What are some causes of intrahepatic portal hypertension?
Primary biliary cirrhosis (intrahepatic) Sarcoidosis (intrahepatic) Schistosomiasis Alcoholic cirrhosis (sinusoidal) Alcoholic hepatitis (sinusoidal) Cryptogenic cirrhosis Postnecrotic cirrhosis Sinusoidal obstruction syndrome (postsinusoidal)
What are some causes of prehaptic portal hypertension?
Portal vein thrombosis
Splenic vein thrombosis
What is the hepatic venous pressure gradient?
• We can measure the degree of portal hypertension by calculating the HVPG
• HVPG= Wedged HV Pressure- Free HV Pressure (mmHg)
– Normal= 3-5mmHg
– 5+ mmHg= Portal Hypertension
– 10+ mmHg= varices form
– 12+ mmHg= varices bleed
What are common complications of cirrhosis and portal hypertension?
Encephalopathy Ascites Synthetic dysfunction (hypoalbuminemia, coagulopathy, hyperbilirubinemia, thrombocytopenia) HCC variceal bleed hepatorenal syndrome HPS
What is ascites?
• Ascites is defined as the pathologic
accumulation of fluid in the peritoneal cavity
• It is the most common complication of
cirrhosis
• Ascites is often the first clinical
decompensation to occur in cirrhotics
• Ascites is he most common complication of cirrhosis that leads to hospitalization
What is the pathophys of Ascites?
- Cirrhosis and Portal HTN
- Splanchnic and systemic vasodilation
- Decreased effective arterial volume
- Activation of neurohumeral systems
- RAAS
- SNS - Sodium and water retention
- ”leaky” capillaries
(alteration in pressures and permeability) - Ascites
Also caused by overwhelmed lymphatic system and altered Starling forces
What is the serum-ascites albumin gradient?
Serum albumin - ascitic albumin
Is considered high if 1.1+ g/dL
If high, then due to portal hypertension (cirrhosis, alcoholic hep, cardiac dz, massive liver mets, hepatic outflow obstruction, portal vein thrombosis)
If low, then NOT due to portal hypertension (peritoneal carcinoma, TB, pancreatic duct leak, biliary leak, nephrotic syndrome, serositis)
What are some complications of ascites?
Umbilical hernia
Tense ascites
Infection
Hepatic hydrothorax
What are the common causes of spontaneous bacteria peritonitis?
E. coli, Klebsiella, S. pneumo
PMN count 250+
How should ascites be managed?
Salt restriction Diuretics Large volume paracentesis Transjugular intrahepatic portosystemic shunt Liver transplantation
What are varices?
Abnormal dilated veins seen in the setting of portal HTN
Prevalence correlates with severity liver disease
Variceal hemorrhage occurs 5- 10% yearly
Predictors of bleeding include size of varices, decompensated cirrhosis, presence of red wale signs
They often progressively increase in size
How do you treat variceal bleeding?
Hemodynamic – Volume resuscitation (PRBCs) – Correct coagulopathy Pharmacologic – Antibiotics • High rate of infection • Reduction in rebleeding • Mortality benefit – Octreotide (somatostatin analogue) • Reduction in portal pressure • Reduction in rebleeding rates Endoscopic – Esophageal band ligation
How can you prevent a variceal rebleed?
– Repeat band ligation until eradication of varices
– Non-selective beta blocker
• i.e. Nadolol or Propanolol
• NSBBs reduce portal pressures through β-1 (decreased CO) and β-2 (splanchnic vasoconstriction) effects
What is a transjugular intrahepatic portosystemic shunt?
like a cardiac stent
divert from high pressure portal vein system
bore hole through liver; portal vein is congested with blood, want blood out of the portal system
What is hepatic encephalopathy?
• A reversible neuropsychiatric syndrome seen in patients with advanced liver disease
• Symptoms range from mild cognitive
impairment to coma
• Excess ammonia- key mediator
Why do you see problems with ammonia in liver failure?
• Liver – Hepatocyte loss and porto-systemic shunting (bypassing liver) – Reduced capacity to detoxify ammonia • Kidney – Reduced ability of kidney to excrete urea – Increased ammonia production in kidney • Skeletal muscle – increased breakdown of muscle and increased production of glutamine – Converted back to ammonia and glutamate • Gut – Increased glutaminase activity (4-fold) which results in shunting of glutamine back to ammonia and glutamate
What is the net effect of liver failure on ammonia metabolism?
– Increased Production in gut from oral intake – Impaired excretion by kidney – Impaired breakdown by skeletal muscle – Impaired breakdown by liver • Excess ammonia taken up by brain astrocytes – NH3+ glutamateàglutamine – Osmotically activeàastrocyte swelling – Alteration in neurotransmitters
What can contribute to the precipitation of hepatic encephalopathy?
Excess protein (?) TIPS Infection GI bleed Sedatives/hypnotics (hold on to them for much longer) Diuretics Zotemia
How do you treat encephalopathy?
Lactulose
Rifaximin (antiboitic that combats bacteria responsible for ammonia production in the gut)
