9 - Cirrhosis and Portal Hypertension Flashcards
What is cirrhosis?
End stage of chronic liver disease
Regenerative nodules surrounded by fibrous septa
Disruption of architecture of liver
Common etiologies of Cirrhosis
Alcohol
Viral Hepatitis
NAFLD
Genetic/Metabolic Diseases
Pathway to Cirrhosis
Injury
Inflammation –> Fibrosis
Resolution OR Cirrhosis —> HCC
Forms of Injury Leading to Cirrhosis
Viral Hepatitis Alcohol Steatohepatitis PBC ???????
Cirrhosis Pathogenesis
Stellate cells sit in space of disse and store Vita A
During cirrhosis, they transform into myofibroblasts and make and deposit collagen
Stimulated by inflammation, cytokines and toxins
Collagen I & III are deposited in all portions of the lobule
Ultimately architecture and vasculature of hepatocytes are disrupted.
Complications of Cirrhosis
Portal Hypertension
Varices Ascites Hepatohydrothorax Spontaneous Bacterial Peritonitis Hepato-Renal Syndrome
Anatomy - 2 sources of blood flow to liver
Hepatic Artery
Portal Vein
Pre-Hepatic Hyptertension
Portal Vein Thrombosis
Splenic Vein Thrombosis
Intra-Hepatic Portal Hypertension
Pre-Sinusoidal (Schistosomiasis)
Sinusoidal (Cirrhosis)
Post-Sinusoidal (Veno-occlusive disease) - Bush Tea or medications
Post-Hepatic Portal Hypertension
Budd - Chiari:
Obstruction of vena cava or hepatic vein
Liver Blood Flow - High Flow
Mesenteric Vessels feeding the portal vein
Liver Blood Flow - Low Pressure
Sinusoidal network
Effects of Cirrhosis
Fixed scarring of liver
Sinusoidal blood vessels - Increased resistance
This causes increased pressure in portal vein
However, portal vein FLOW actually increases as well
Why does portal vein flow increase in response to cirrhosis, even though the pressure is increased due to resistance?
Cytokines (like TNF) are released in response to the increased sinusoidal resistance and mildly increased portal vein pressure.
This leads to nitrous oxide release
NO release leads to splanchnic bed dilatation
This leads to increased splanchnic flow
Systemic effects of cirrhosis
High cardiac output
Low SVR
Catheter in Hepatic Vein - Deflated Ballooon
Measures what?
Free HV Pressure
Catheter in Hepatic Vein - Inflated Ballooon
Measures what?
Portal Vein Pressure
Normal PV - HV pressure gradient
Less than 7
Significant PV - HV pressure gradient for Portal Hypertension
Greater than 10
Cirrhosis - Effects on Blood Flow - Portal Hypertension
Fibrosis restricts blood flow, increases portal vein pressure
Collaterals acquire increased pressure, affecting spleen, esophagus, stomach (varices), gastropathy
Ascites due to fluid shift into the peritoneum
Shunting of blood from liver decreases metabolism of “toxins”
Portal bacteremia not cleared induces peritonitis
Physical Exam Findings of Cirrhosis
Telangiectasias
Varices
Esophageal Varices
Sequellae of Portal Hypertension
Risk of bleeding proportional to size and degree of portal hypertension
Graded in increasing size I, II or III
Even with optimal therapy, risk of death from an esophageal bleed is greater than 20%
Gastric Varices
Also from portal hypertension
Near Gastro-Esophageal Junctures
Portal Gastropathy
Gastropathy from portal hypertension
Oozing capillaries
Leads to anemia in some cirrhotic patients
Esophageal Varices - Emergency
Hypotensive
Tachycardic
Esophageal Varices - Acute Treatment
Stabilize Hemodynamics (Give Volume)
Decrease Portal Pressure (Octreotide Acutely - IV, Somatostatin)
Locally stop bleeding (Banding)
Prophylactic Antibiotics
Esophageal Varices - Chronic Treatment
Non-Selective Beta Blockers (Propanolol, Nadolol, Carvedilol) Banding Ablation TIPS Surgical Shunt Transplantation
TIPS
Transjugular Intrahepatic Porto-Systemic Shunt
From Portal Vein to IVC
A good portion of the portal venous flow bypasses liver entirely!
Complication: 20% develop hepatic encephalopathy
Surgical Shunts
Don’t get used
Ascites DDX
Portal Hypertentsion Peritoneal Inflammation Ovarian Cancer Nephrogenic Ascites (Nephrotic Syndrome) Pancreatic Ascites Other
“Other” Ascites Etiologies
Schistosomiasis
Non-Cirrhotic Portal Hypertension
Polycystic Liver Disease
Portal Hypertension to Ascites - Pathway
Cirrhosis Splanchnic Arterial Vasodilation Arterial Underfilling Systemic Vasoconstriction Renal Vasoconstriction
Also decreased blood albumin.
This leads to increased hydrostatic pressure and decreased oncotic pressure (all in vessels)
Increases lymph pressure
Lymph and the rest spills out into peritoneum
Initially resorbed by peritoneal surface of diaphragm (communicates with supradiaphragmatic lymphatics
Ascites formation exceeds reabsorption when HVPG > 10 mm HG
Ascites DUE TO PORTAL HTN - Characteristics
Serum - Ascites Gradient (SAG) > 1.1 g/dL
Transudate (Protein
Cirrhotic who develops ovarian cancer
SAG is STILL greater than 1.1!!
Ascites - Treatment
Treat underlying condition
Bedrest
Sodium & Fluid Restriction
Diuretics (Spironolactone, Furosemide, Amiloride, HCTZ, Metolazone, Zaroxyln)
Large-Volume Paracentesis
TIPS
Surgery (Leveen or Denver Shunt, Liver Transplantation)
Hepatohydrothorax
Almost always on the R side
Ascites in the chest
Maybe because IVC perforates diaphragm?
Ascites leaks through rents (
Hepatohydrothorax - Treatment
TIPS - for diuretic-refractory cases
Liver Transplantation
AVOID CHEST TUBES. Surgical repair usually not effective.
Spontaneous Bacterial Peritonitis
Infection of ascitic fluid
Independent of another intra-abdominal source
Monomicrobial
Enteric flora enters portal circulation, not cleared
OR
Translocation of bacteria from the gut
Spontaneous Bacterial Peritonitis - WBC
Ascites WBC > 500 or 250 with greater than 50% PMNs
Spontaneous Bacterial Peritonitis - Risk Factors
GI Bleeding/Hypotension
Advanced Liver Disease
Previous History
Spontaneous Bacterial Peritonitis - Organisms
E. Coli
Klebsiella
Pneumococcus
Enterococcus
Spontaneous Bacterial Peritonitis - Treatment
Broad Spectrum Antibiotics
Then narrow if culture results are known
Re-tap after 48 hours to confirm response to therapy
Volume expand (albumin)
Spontaneous Bacterial Peritonitis - Prevention
Early treatment of other infections
Prophylactic Antibiotics to GI bleeders
Oral Quinolones, TMP-Sulfa can prevent recurrence when given chronically
Spontaneous Bacterial Peritonitis - Presentation
Not typical! Not usually abdominal pain. They come in with something else!
If a cirrhotic is admitted to the hospital, you should perform a paracentesis, or you might miss it!!
If you’ve had Spontaneous Bacterial Peritonitis Once
You have to be on prophylaxis for the rest of your life!!
HepatoRenal Syndrome
Late stage cirrhosis
The compensatory local vasodilators protecting your kidneys in the early stages are starting to not work as well!
Decreased vasodilators
Increased vasoconstrictors
Early Cirrhosis
Decrease in SVR is compensated by Increased HR, CO, Stimulation of RAAS, ADH
Late Cirrhosis
Splanchnic circulation is resistant to Angiotensin II & ADH
Pressure must be maintained by local vasoconstriction
Leads to HepatoRenal Syndrome
HepatoRenal Syndrome
Etiology is an exaggeration of mechanisms involved in ascites formation.
Can happen in perfectly healthy kidneys!!
HepatoRenal Syndrome - Precipitants
GI Bleed
Nephrotoxins (NSAIDS, Aminoglycosides, Sepsis)
Iatrogenic (Diuresis, Paracentesis)
HepatoRenal Syndrome - Diagnosis
Euvolemic patient
But look like a pre-renal patient
Give fluid, but they STAY “pre-renal” appearing
Urine Output
HepatoRenal Syndrome - Treatment
TIPS Glypressin Terlipressin Transplantation Midodrine (increasing vascular resistance) Octreotide (decreasing portal HTN)
