PHM 424 CIRRHOSIS
What are the common causes of liver disease / cirrhosis?
-alcoholism
-chronic hepatitis C
-metabolic liver disease
-immunologic disease
-vascular disease
-drugs
How does the liver filter the blood?
-blood enters via hepatic artery, portal vein, and vile ducts
-blood drains via sinusoidal space of hepatic lobule (lined with hepatocytes)
-filtered blood goes through hepatic venules and empties into larger hepatic veins and
eventually into inferior vena cava
How are hepatocytes arranged in the liver?
-arranged in plates that are one cell thick and organized around central veins
-six or more surfaces of each hepatocyte make contact with other hepatocytes, border bile
canaliculi, or are exposed to sinusoidal space
What are the functions of zone 1 hepatocytes?
-gluconeogenesis
-urea synthesis
-oxidative energy metabolism
What are the functions of zone 2 hepatocytes?
-glycolysis
,-lipogenesis
What is the function of hepatic stellate cells?
-store vitamin A
-help maintain normal matrix in sinusoidal space
-undergo activation in chronic liver disease
What occurs when hepatic stellate cells are activated in chronic liver disease?
-stellate cells lose vitamin A, become highly proliferative, and synthesize fibrotic scar tissue in
sinusoidal space
-sinusoidal endothelial cells become less permeable and macromolecules have lesser ability
to reach hepatocytes
What are the complications of cirrhosis?
-portal HTN
-gastroesophageal varices
-ascites
-spontaneous bacterial perforation (SBP)
-hepatic encephalopathy (HE)
-coagulation defects
-hepatorenal syndrome
-hepatopulmonary syndrome
What are the possible outcomes of abstinence from alcohol in alcohol-induced cirrhosis?
-resolution of ascites
-improved responsiveness of ascites to medical therapy
-(if cause is not alcohol, disease progresses severely by the time ascites is formed to point
where liver transplant is necessary)
How does cirrhosis lead to sinusoidal portal HTN?
- by causing splanchnic vasodilation and forming new blood vessels, which increases
splanchnic blood flow (leading to sinusoidal portal HTN)
, What is considered portal HTN?
- pressure gradient of >5 mmHg between the portal and central venous pressures (hepatic
venous pressure gradient, HVPG)
What happens after an HVPG of >10 mmHg is reached?
- esophageal and gastric varices and variceal bleeding may occur
What is ascites?
-accumulation of fluid in the peritoneal cavity
-severe ascites = positive 'fluid wave'
What is the cause of ascites in cirrhosis?
-fibrosis --> increased intrahepatic vascular resistance --> portal HTN
-portal HTN --> splanchnic vasodilation --> drop in BP --> activation of RAAS by kidneys
-antidiuretic hormone secretion --> increased blood volume that leaks into peritoneal space
through mesenteric artery and damaged liver --> ascites
What should be evaluated in an ascitic fluid analysis?
-cell count with differential: PMN >250 cells/mm3
-ascitic fluid total protein: >4 g/dL indicates SBP
-serum-ascites albumin gradient (SAAG)
-culture if infection is suspected
How is a SAAG calculated and assessed?
-serum albumin - ascites albumin = SAAG
- >1.1 g/dL indicates likely due to portal HTN
What is spontaneous bacterial perforation?
What are the common causes of liver disease / cirrhosis?
-alcoholism
-chronic hepatitis C
-metabolic liver disease
-immunologic disease
-vascular disease
-drugs
How does the liver filter the blood?
-blood enters via hepatic artery, portal vein, and vile ducts
-blood drains via sinusoidal space of hepatic lobule (lined with hepatocytes)
-filtered blood goes through hepatic venules and empties into larger hepatic veins and
eventually into inferior vena cava
How are hepatocytes arranged in the liver?
-arranged in plates that are one cell thick and organized around central veins
-six or more surfaces of each hepatocyte make contact with other hepatocytes, border bile
canaliculi, or are exposed to sinusoidal space
What are the functions of zone 1 hepatocytes?
-gluconeogenesis
-urea synthesis
-oxidative energy metabolism
What are the functions of zone 2 hepatocytes?
-glycolysis
,-lipogenesis
What is the function of hepatic stellate cells?
-store vitamin A
-help maintain normal matrix in sinusoidal space
-undergo activation in chronic liver disease
What occurs when hepatic stellate cells are activated in chronic liver disease?
-stellate cells lose vitamin A, become highly proliferative, and synthesize fibrotic scar tissue in
sinusoidal space
-sinusoidal endothelial cells become less permeable and macromolecules have lesser ability
to reach hepatocytes
What are the complications of cirrhosis?
-portal HTN
-gastroesophageal varices
-ascites
-spontaneous bacterial perforation (SBP)
-hepatic encephalopathy (HE)
-coagulation defects
-hepatorenal syndrome
-hepatopulmonary syndrome
What are the possible outcomes of abstinence from alcohol in alcohol-induced cirrhosis?
-resolution of ascites
-improved responsiveness of ascites to medical therapy
-(if cause is not alcohol, disease progresses severely by the time ascites is formed to point
where liver transplant is necessary)
How does cirrhosis lead to sinusoidal portal HTN?
- by causing splanchnic vasodilation and forming new blood vessels, which increases
splanchnic blood flow (leading to sinusoidal portal HTN)
, What is considered portal HTN?
- pressure gradient of >5 mmHg between the portal and central venous pressures (hepatic
venous pressure gradient, HVPG)
What happens after an HVPG of >10 mmHg is reached?
- esophageal and gastric varices and variceal bleeding may occur
What is ascites?
-accumulation of fluid in the peritoneal cavity
-severe ascites = positive 'fluid wave'
What is the cause of ascites in cirrhosis?
-fibrosis --> increased intrahepatic vascular resistance --> portal HTN
-portal HTN --> splanchnic vasodilation --> drop in BP --> activation of RAAS by kidneys
-antidiuretic hormone secretion --> increased blood volume that leaks into peritoneal space
through mesenteric artery and damaged liver --> ascites
What should be evaluated in an ascitic fluid analysis?
-cell count with differential: PMN >250 cells/mm3
-ascitic fluid total protein: >4 g/dL indicates SBP
-serum-ascites albumin gradient (SAAG)
-culture if infection is suspected
How is a SAAG calculated and assessed?
-serum albumin - ascites albumin = SAAG
- >1.1 g/dL indicates likely due to portal HTN
What is spontaneous bacterial perforation?
