liver 4 + SG

what is cirrhosis

the result of liver injury characterized by development of regenerative nodules surrounded by fibrous bands of connective tissue

what are the normal liver functions that are disordered in cirrhosis

decreased:

• synthesis

• detoxification

• excretion

• extractioni

• storage

• removal

what are some signs of cirrhosis

• confusion

• pruritis

• palmar erythema and spider angiomata

• asterixis

• gastrointestinal bleeding

• spontaneous bacterial peritonitis

• thrombocytopenia

• anemia

why is this a sign of cirrhosis: confusion

inc ammonia in the blood → toxic

why is this a sign of cirrhosis: pruritis

bile salt accumulation

why is this a sign of cirrhosis:gastrointestinal bleeding

portal hypertension → varices rupture, especially in esophagus

why is this a sign of cirrhosis: spontaneous bacterial peritonitis

ascites can become infected from transmigration of gut bacteria

why is this a sign of cirrhosis: thrombocytopenia

low platelets due to portal hypertension causing congestion of the spleen → platelets sequester in spleen → drops in blood

why is this a sign of cirrhosis: anemia

low iron (multifactorial) → cause abnormally small RBC and low B12 and folate cause abnormally large RBC

what are the complications of cirrhosis

• hepatic encephalopathy

• coagulopathy

• hepatocellular carcinoma

• portal hypertension

  • esophageal varices

  • ascites

  • hepatorenal syndrome

how does cirrhosis disrupt the blood flow in the liver

• decreased flow of nutrients and oxygen to hepatocytes

• compression of larger vessels by nodules and firbous septae

• sinusoids are narrowed w a thicked basement membrane → less permeable to proteins → insiffienct delivery

• portosystemic shunts occur in liver within the scar and extrahepatic- varices

in cirrhosis, how do the hepatic fibrosis-stellate cells activations change the blood flow of the liver

increased resistance → dec flow

how do liver endothelial cells respond when sensing the inc resistance/dec flow from the stellate cells

• they will become less sensitive to vasodilators: NO

• and become more sensitive to vasoconstrictors

what is the net effect from activated hepatic fibrosis-stellate cells and endothelial cells

blood cannot get thru the liver as well

what is the splanchnic circulation

circulation that goes from the systemic circulation to the bowel

how will the splanchnic circulation respond to cirrhosis happening in the liver and how this will affect the portal system

will inc secretion of NO in the splanchinic side → vasodilation → inc flow going into the bowel → vessels from portal system cannot dilate to compensate → portal hypertension

how will the systemic circulation respond to cirrhosis happening in the liver and how this will affect the kidneys

sense the inc of resistance/dec flow → inc NO secretion → dec BP → inc CO → effective circulatory volume will go down bc BP dec → kidneys not being effectively perfused

how will the kidneys respond to the dec perfusion

dec perfusion → inc secretion of renin → inc vasoconstriction → further dec kidney perfusion → hepatorenal syndrome

what are the consequences of portal hypertension

• portosystemic collaterals

• splenomegaly, pancytopenia

• inc pressure in varices → bleeding

• ascites

• hepatic encephalopathy

• spontaneous bacterial peritonitis

what are varices

veins that are portal connections to the systemic circulation, so if portal tension is high → blood will back up and cause the dilation of these veins; these are also very thin and pose risk for rupture, will bleed v badly

where can varices be found

• esophagus

• rectum → hemorrhoids

• caput medusae

what are the 3 main components that are contributing to ascites in cirrhotic pts

• dec oncotic pressure from dec albumin

• inc sinusoidal and portal pressure

• inc in aldosterone and ADH

why does a dec oncotic pressure from dec albumin contribute to ascites in cirrhotic pts

less albumin being made by the liver → this will dec the oncotic pressure in the capillaries → fluid will not want to come back into the venous side of the capillaries

why does an inc sinusoidal and portal pressure contribute to ascites in cirrhotic pts

there is an inc in hydrostatic pressure due to fibrosis/inc resistance in vessels → push all the fluid out into tissues

why does an inc in aldosterone and ADH contribute to ascites in cirrhotic pts

the kidneys are not getting perfused efficiently → will inc aldosterone and ADH secretion → will inc retention of Na and H2O → fluid overload

why are NSAIDs contraindicated in hepatorenal syndrome

will dec prostaglandin production → this is essential for hepatic artery vasodilation → so NSAIDs will cause further constriction of artery → dec perfusion to kidney even more

in a healthy person, how does ammonia metabolism work

protein broken down by bacteria → ammonia is made → will go to liver and be converted to urea → go through systemic circulation → get filtered out and excreted by the kidney

what happens in w ammonia metabolism in liver disease

less ammonia is converted to urea → less urea is excreted due to hepatic renal syndrome → the rest of urea goes back to colon → get broken down by bacteria back ammonia → start this cycle all over again → increasing levels of ammonia in the body

how do shunts inc ammonia blood levels

there are shunts that can bypass the liver → inc amounts of ammonia that do not go to the liver at all to be converted to urea → inc ammonia blood level even more → will lead to hepatic encephalopathy

what is asterixis

flapping or dorsiflexed hands in outstretched position, sign of central neurological dysfunction → seen in hepatic encephalopathy

what is the second highest cause of hepatic encephalopathy

drugs

what are the most common causes of cirrhosis

• chronic hepatitis- HBV, HCV

• metabolic dysfunction associated liver disease

• alcohol associated liver disease

what are the principal cell drivers of fibrosis

stellate cells

in what stages of cirrhosis are reversible vs irreversible

• stage I and II, sometime even III

• IV is NOT reversible

what is the most common type of liver neoplasm

a BENIGN cavernous hemangioma

what are common liver malignant neoplasms

• metastatic carcinoma

• hepatocellular carcinoma

• cholangiocarcinoma

• angiosarcoma

histologically, what are the key findings in hepatocellular carcinoma

• absence of lobular architecture → no normal portal tracts seen

• thickened trabeculae composed of pleomorphic, atypical cells that vaguely resemble hepatocytes

what is hepatic adenoma

benign neoplasm → mass arises in a non-cirrhotic liver

what is associated w hepatic adenoma

oral contraceptives, anabolic steroids

where does cholangiocarcinoma arise from

arises from cholangiocytes that line the biliary tract → NOT the gallbladder

how can cholangiocarcinoma be classified as

• intrahepatic

• extrahepatic

risk factors for intrahepatic cholangiocarcinoma

exposure to Thorotrast, infection by liver flukes, primary sclerosing cholangitis, cirrhosis

where does angiosarcoma arise from

malignant tumor of endothelial cells

what is angiosarcoma associated w

previous exposure to arsenic, vinyl chloride

what is cavernous hemangioma

benign neoplasm of endothelial cells → most common liver tumor

in a lab test, what does an elevated alpha fetoprotein (AFP) tell you

is a marker used to water for hepatocellular carcinoma in people at risk

what people are at risk for hepatocellular carcinoma

people w:

• chronic hep B

• chronic hep C

• people w family history

• people w porphyria