Liver 1 Flashcards
(23 cards)
What are 3 mechanisms of liver injury and repair?
- Hepatocyte and parenchymal responses
- Scar formation and regression
- Inflammation and immunity
In hepatocyte and parenchymal responses, what degenerative but potentially reversible changes are seen?
- Ballooning Degeneration
- Steatosis
- Cholestasis
In hepatocyte and parenchymal responses, what is seen in irreversible injury and cell death?
Necrosis
- cell swelling and rupture
Apoptosis
- activation of caspase cascades
- cellular shrinkage and eosinophilia
- spotty necrosis –> confluent necrosis (zonal –> bridging –> submassive –> massive hepatic necrosis)
In hepatocyte and parenchymal responses, what is seen in regeneration?
Mitotic replication of hepatocytes
2. Activation of primary stem cell niche (canals of Hering)
3. Ductular Reaction – Stem Cell Activation and hepatocytes reach replicative senescence
How does scar formation occur in liver injury?
- collapse of underlying reticulin
- hepatic stellate cells activated and converted into highly fibrogenic myofibroblasts
– activated by cytokines and chemokines from inflammatory cells, endothelial cells, hepatocytes, bile duct epithelial cells, in response to ECM disruption or direct stimulation from toxins
- portal fibroblasts and ductular reaction (during this there is a epithelial mesenchymal transition which results in more ECM components, myofibroblasts and inflammation produced) also contribute
- Portal/periportal fibrosis –> portal central and portal portal bridging fibrosis –> cirrhosis
- Pericellular/perisinusoidal fibrosis
- Reversal of fibrosis/cirrhosis regression
What can be seen in inflammation of liver
Lymphocytes, plasma cells, neutrophils, eosinophils, histiocytes/macrophages
Granulomas
Microabscesses
What are the 5 consequences of liver failure?
- Coagulopathy
- Hepatic Encephalopathy
- Cholestasis
- Hepatorenal, Hepatopulmonary Syndrome
- Portal HTN
What are 3 causes of acute liver failure
Drugs/Toxins
Acute Hep A/B/E
Autoimmune Hepatitis
Histologic features of acute liver failure
- Massive Hepatic Necrosis
- loss of hepatocytes
- red blood cell extravasation
- florid ductular reaction - Diffuse injury without obvious cell death (diffuse microvesicular steatosis)
What are 3 leading causes of chronic liver failure?
- Chronic Hep B and C
- NAFLD
- Alcoholic Liver Disease
Histologic features of chronic liver failure?
Cirrhosis
Do all cirrhosis lead to chronic liver failure? Is all end stage chronic liver disease cirrhotic? Is regeneration of cirrhotic liver possible?
No. No. Yes
What is liver cirrhosis?
Diffuse transformation of liver into a regenerative parenchymal nodules surrounded by fibrous bands
Accompanied by disturbed vascular architecture (due to variable degrees of vascular (often portosystemic) shunting
Mechanisms of scar formation in liver?
- Dense fibrous tissue forming from a) collapse of underlying reticulin and b) activation of HSCs into highly fibrogenic myofibroblasts
What maintains the balance in matrix remodelling?
Progression of established to regression of cirrhosis?
- Broad Septa
- Large region of extinction containing few small buds of parenchyma
- Nodules expand against their neighbours
- Septa are compressed and reabsorbed
- Large regions of extinction are filled in by expansion of adjacent nodules and new micronodules from buds
What are clinical features of cirrhosis? Complication? Common terminal events?
- 40% asymptomatic until advanced stages
- Non-specific manifestations: anorexia, weight loss, weakness
- Advanced Disease: Symptoms and Signs of liver Failure
Hepatocellular Carcinoma
- Hepatic Encephalopathy
- Bleeding fro esophageal varices
- Bacterial infections/sepsis
What encompasses the stigmata of chronic liver disease?
- Cholestasis
- Jaundice –> Pruritus (due to bile salt deposition), Scleral Icterus - Hyperestrogenemia (liver usually inactivates estrogen)
- Palmar Erythema
- Spider Angiomas
- Hypogonadism
- Gynaecomastia - Coagulopathy
- Portal HTN
- Ascites
- Portosystemic Venous Shunts, caput medusae, Anorectal varices
- Splenomegaly
- Hepatic Encephalopathy: Asterixis
Causes of portal hypertension?
Consequences of portal hypertension>
- Portosystemic shunting of blood = collateral channels = caput medusae, esophageal varices, hemorrhoids OR portosystemic shunting of blood = shunting of ammonia from GIT into general circulation (ammonia not cleared by liver) = hepatic encephalopathy
- Splenomegaly (can lead to anemia, leukopenia, thrombocytopenia and bleeding as spleen is overactive and sequestes all the blood cells)
- Ascites
- Hepatorenal Syndrome
Common sites of porto-systemic shunts?
What are causes of ascites?
Cirrhosis, CCF, Hypoalbuminaemia, Malignancies
What can be found in an ascitic tap if
a) normal
b) infection
c) cancer
a) few mesothelial cells, mononuclear inflammatory cells
b) neutrophils
c) malignant cells (via transdiaphragmatic lymphatics [hydrothorax, R>L]
