Pathophysiology Chapter 38 Liver Function and Disorders

Liver anatomy

largest organ, strutural unites liver lobules, contain hepatocytes that are responsible for metabolic functions, radiate outward from central vein

protal triad

contains hepatic artery, hepatic portal vein, bile duct

hepatic artery

supply oxygen rich artieral blood to liver

hepatic portal vein

carry venous blood loaded with nutrients from digestive viscera

bile duct

carry bile

liver sinusoids

blood from hepatic portal vein and hepatic artery infiltrates from the portal triad and empties into central vein

direction of flow liver

portal vein/hepatic artey -> sinusoids -> central vein -> hepatic vein ->IVC

liver function

carb, lipid, protein metabolism, processing of drugs and hormones, bile pigment formation, excretion of bilirubin, storage, Vit D activation

carbhohydrtate metabolism

gylcogen stored in liver is the primary storage polysaccharide, only liver glycogen is availble for maintencne of contant blood glucose

gluconeogenesis

formation of glucose from excess amino acids, fat, and other non carbs

glycogenesis

formation of glycogen

lipgeneesis

formation of fats

Glycogenolysis

conversion of glycogen to glucose

glycolysis

hydrolysis of glucose to pyruvate

lipolysis

catbolic degation of triacycgylcerol

lipid metabolism

hepatocytes store some triglycerides, break fown fatty acids for ATP, synthesize liporpteins and cholesterol, use cholesterol to make bile salts

protein metabolism

hepatocytes deaminate from amino acids, ATP production or conversion to carbs or fats, hepatocytes synthesize most plasma proteins, albumin, alpha and beta globulins, prothrombin

processing of drugs and hormones

detoxify substances like alc, excrete drugs, alter or excrete hromones

mechanisms of detoxifying foreign materials

bind the compound reversibly to a protein so material is inactivation

modify the compound chemically so its readily excreted

bile pigment formation

yellow green alkaline solution containing bile salts, pigments, cholesterol, neutral fats, phosphlipids, electrolytes

bile pigments

primary is bilirubin

bilirubin

waste product of heme of hemoglobin formed during breakdow of senescent erytrhocytes

liver stores

glyocgen, amino acids, lipids, vitamins, iron

liver failure

decrease in detoxzification reactions, gluconeogenesis, protein porduction and failure of liver to secrete conjugated bilirubin to be conjugated

jaundice

yellowing of skin associated with accumulation of bilirubin in the skin caused by liver and gallbladder disorderes, bilirubin>2.5-3

jaundice causes

excess production, reduced hepatic uptake, impaired conjugation, decreased hepatic excretion, decreased bile flow

prehepatic jaundice

results from acute or chronic hemolytic anemia

hepatic jaundice

result from disorders of bilirubin metabolism and transport

post hepatic jaundice

results from comprimised ability of liver to excrete bilirubin

Pruitis

bile salt deposits in the skin

unconjugated bilirubin

not been processed by the liver, insoluble in water, cannot be excreted in urine, may be increased in blood in severe hemolytic disease

conjugated bilirubin

water soluble, nontoxic, normally excreted in feces by excess may be in urine

conjugation

takes place in liver, free bilirubin enters liver with albumin, enzyme glucanoyl transeferase converts unconjugated bilirubin to a water soluble form, conjugated

normal bilirubin

0.3-1.2

crigler najjar syndrome

cannot conjugate bilirubin, patients die early in life from kernicterus, bilirubin in the brain

Gilbert Syndrome

cannot get bilirubin into liver for conjugation, milder disease

Dubin-Johnson syndrome

defective liver excretion of bilirubin to bile, causes black liver

rotor syndrome

similar to dubin johnsom but less severe

AST test

liver enzyme, releases with injury to hepatocytes, associated with brain and heart tissue

ALT test

liver enzyme, released with injury to hepatocytes

alkaline phosphate test

bile ducts released when biliary tree is obstructed, cells of bile ducts release Alk phos

alcoholic liver disease

AST:ALT = 2:1

degenration hepatic injury

ballooning, feathery degeneration, fat, pigment

inflammation hepatic injury

viral or toxic, hepatitis, regeneration fibrosis, cirrhosis

neoplastia hepatic injury

99% metastatic, 1% primary

steatosis

fatty degeneration or fatty change

portal hypertension

varices in lower esophagus, stomach, rectum, splenomegaly, asicites, hepatic encephalopathy

gastroesophageal varices etiology

results from portal hypertension, alcoholic or postepatic cirrhosis, infection from liver flukes, vasoactive hormones, increased splanchnic blood flow, increased vascular resistance in liver

gastroesophageal varices pathogenesis

complex venous network that surround the proximal part of stomach and esophagus, can rupture with critcally high portal pressure, leads to massive upper GI bleed

gastroesophageal varices response

collateral venous pathways dilated in response to elevated portal pressure in attempt to transport blood from splanchinic bed around cirrhotic liver and back to heart

gastroesophageal varices clinical features

affects about half of cirrhotic paitents, size is main risk for bleeding, variceal bleeding mortality 50%

gastroesophageal varices hemorrhage

period of 6-8 weeks following initial bleed, great risk of rebleed within first 72 hours

gastroesophageal varices symptoms

hematemesis, melena, bright red rectal bleeding, anemia, shock

gastroesophageal varices treatment

fluid, IV saline, correction coagulopathy and stopping further bleeding with blood components and clotting factors, parenteral vit K, fresh frozen plasma, paltelets, factor VIIa, h2 blocker, proton pump inhibitor, beta blocker, antibiootics

hepatic encephalopathy pathogenesis

complex neuropysichiatric syndrome from too much ammonia associated with hepatic failure or severe chronic liver disease

hepatic encephalopathy cause

unkown, precipitated by conditons that increase protein metabolism(GI hemorrhage, increased protein consumption) and by conditiong that impair hepatocyte function

hepatic encephalopathy clinical manifestations

dementia, psychotic symptoms, spastic myelopahty, cerebella/extrapyrmaidal signs, asterizis liver flap, spastic jerking of hands, amonia lecels, mild confusion and lethargy to stupor and coma

Hepatic encephalopathy treatment

correcting precipitating factors, restricting portein to <60g, >400 g carbs daily, IV vit infusions, high fiber diet, amoxicilin, lactulose

ascites

cirrhosis induced portal hypertension, low concentration of albumin in fluid

ascites pathogenesis

accumulation of fluid in peritoneal cavity, occurs with portal hypertension and hypoalbuminemia

ascites diagnosis

fluid examinantion from abdominal paracentesis, total protein and albumin

ascites treatment

sodium less than 88 per day, bed rest, diretics, paracentesis, laveen or denver shunt, transjugular intrahepatic portsystemic stenting, liver transplant

hepatitis

liver inflammation

hepatitis etiologic agents

viral infections, toxic agents, drugs, autoimmune response, wilsons disease, hemochromatosis

HAV (Hep A)

fecal oral spread, hyegine, drug use, travel, day care, food, vaccine preventable

HBV (Hep B)

sexually transmitted, 100x more infections than HIV< blood borne(sex, drug use, mother child), vaccine preventable, predispose to hepatocellular carcinoma

HCV (Hep C)

blood borne, injection drug use mainly, 4-5 times more common than HIV, not vaccine preventable, chronic infections , cirrhosis, carcinoma, carriers , leading cause of end stage liver disease

hepatitis D(Delta agent)

depends on Hep B for replication, defective virus depends on HBsAg as its envelope

Hepatitis E

fecal oral transmission, water borne epidemics, devveloping countries, high mortality rate in expectant mothers

hepatitis G

recently discovered, parentally and sexually transmitted

hepaitits sequence

incubation phase

prodomal phase, preicteric

icteric phase, jaundice

recovery phase

testing for acute hepatitis

increased AST and ALT, typically higher AST, increase phophatase, increased GGT

testing for chronic hepatitis

increased bilirubin, increased AST and ALT, typically higher ALT, incraesed alkaline phosphatase

hepatitis A testing

serologic testing, anti HAV IgG(previous infection), IgM(acute infection

hepatitis A treatment

rest, nutrition, avoid ETOH, acetaminophen and other hepatoxins

hepatitis a prevention

hand washing, degradation, cleaning laundry and personal items, immunizations

hepatits B risk factors

health care settings 3%, transfusions and dialysis 1%, acupuncture, tattoos, overseas travel

hepatitis B treatment

may resolve spontaneously, 5% lead to chronic infection, liver transplant

hepatits b prevention

vaccine at 0, 1, 6 months, 95% response rate

administration of HBIG postinculation within 7 days of exposure(neonates to postive mothers, after needle or sexual exposure as nonimmune)

hepatitis C treatment

supportive and expectant, liver biposy

hepatitis d diagnosis

anti HSV IgM

cirrhosis

end stage irreversible disease of anything tthat chronically damages the liver, increases risk of heptoma

liver

most regenrative of all organs