Cirrhosis Flashcards
What is the histology of cirrhosis
parenchymal nodules surrounded by dense bands of fibrosis in liver- it converts smooth liver into bumpy surface with depressed areas of scarring and buldging regenerative areas
What tests used to diagnose cirhhosis
if AST:ALT= >2 this indicates excess alcohol intake due to increase mitochondrial function. If ALT is low shows that liver damaged and leaking enzymes into bloodstream
Alkaline phosphatase elecated in cirrhosis
GGT elevates in alcoholic liver disease
serum albumin reduced in cirrhosis
Decrease INR, as decrease rate to form clot, as less coagulant production from vit K due to cirrhosis
How does cirrhosis affect blow flow and vol reg
increased fibrosis and collagion deposits will compress blood vessels, which reduce blood flow, due to increased resistance. Contraction of vasular SMC, myofibroblasts and disruption of blood flow due to scarring and parenchymal nodules. Also alteration to sinusoidal epithelial cells cause decrease NO protuction and increase endothelin-1, Angiotensinogen and eicosonoids causing vasoconstriction. This remodelling intefere with metobolic exchange between blood and hepatocytes. As a result of the portal hypertension there is increa portal venous blood flow causing arteriole vasodialation in splanchnic circulation due to increased splanchnic arterial blood flow, so more venous efflux into portal system, causing hepatic encephalopathy, ascites, portosystemic venous shunts and congestive spelomegaly
How does cirrhosis cause ascites
sinusoidal hypertension and hypoalbunameia. The hyper tension provides the fluid with more hydrostatic pressure to be pushed out of capillaries into peritoneal cavity and decreased allbumin in blood lowers the oncotic pressure intravacularly and further fasicliates movement into peritoneal space as well as causing pitting oedema and swelling of legs and feet
How does cirrhosis cause bruising
due to portal hypertension there is increase chance of bledding from GI varisces.
Liver makes less TPO, meaning less platelets production
splenomegaly causes increase pooling of platelets in spleen
How does cirrhosis cause jaundice
due to the high amount of albumin in the liver, it produces a very high level of unconj billirubing some of this can be converted to conj billirubin, hwoever as the uradine glucoronyl transferase are in klimited amounts not as much can be giving the darker colour of urine, however the unconj billirubin will leak out of the liver due to damage and it has a high affinity for collagen, which is why it deposits into the skin and sclera of eyes giving the yellow hue colour
MOA lactulose
It is broken down by GI flora to organic acids such as lactic acid, which can react with high amounts of nitrogenous waste such as ammonia due to liver insufficiency to make ammonium, which can diffuse into the blood plasma, thus excreted out, which prevents hepatic encephalopathy
What is pathophysiology of cirrhosis
liver injury causes necrosis and apoptosis reulting in leakage of cell contents and ROS, which activate macrophages (Kupuffer cells) and stellate cells to release pro-inflam cytokines and TGF-β, which causes transdiffrentiation of stellate cells to myofibroblasts and PDGF, which causes myofibroblast prolif. The macrophages will release MMPs and myofibroblasts and concurrent macrophages release TIMPs, causing matrix deposition and scar formation overtime
MOA Spirolactone
aldosterone anatgonist
they competively bind at sodium-potassium exchange site in DCT to aldosterone-dependent receptors blocking aldosterone, meaning that less Na+ is reabsorbed, so less water is reabsorbed, causing increase exretion (urine output), which lowers blood vol
