Exam 3- Ch 38 Hepatobiliary and Exocrine Pancreatic Disorders

portal triad

terminal ducts, branches of the portal vein, and branches of the hepatic artery located at each of the six corners of a liver lobule

capillary endothelial cells

exchange substances between blood and hepatocytes

kupffer cells

remove senescent blood cells, microbes, and other foreign materials

liver functions

carbohydrate metabolism, fat metabolism, protein metabolism, bile production and secretion

carbohydrate metabolism

synthesizes glucose from amino acids during periods of fasting or increased demand, stores glucose as glycogen, converts excess glucose to triglycerides for storage in adipose tissues

fat metabolism

synthesizes lipids such as cholesterol needed for cell membrane formation and steroid hormone synthesis, oxidizes fatty acids into acetyl CoA which is channeled into the citric acid cycle to generate ATP

protein metabolism

synthesizes plasma proteins and clotting factors from amino acids, degrades excess amino acids into ammonia and combines ammonia with carbon dioxide to form urea for excretion by kidneys

bile production and secretion

bile is composed of predominantly water (98%), along with bile salts, bilirubin, lipids, and some inorganic salts

enterohepatic circulation

majority of the bile salts are returned from the small intestine to the liver through the hepatic portal vein

bilirubin

yellowish-green pigment that gives bile its color, derived from the breakdown of heme units of the hemoglobin from senescent RBCs

unconjugated bilirubin

bilirubin that is insoluble in blood and circulates attached to plasma proteins

conjugated bilirubin

gets converted to water-soluble form by joining with glucuronic acid & is removed from blood by liver

liver enzymes measured to assess liver function

alanine aminotransferase (ALT), aspartate aminotransferase (AST)

jaundice (icterus)

yellow discoloration of the skin and sclerae due to elevated levels of bilirubin in the blood

pre-hepatic jaundice

caused by excessive RBC production; results in sickle cell disease or hemolytic drug transfusion reaction; labs show increased unconjugated bilirubin

intra-hepatic jaundice

caused by hepatocyte injury; viral hepatitis, alcohol or drug induced liver damage, liver cancers; increased conjugated and unconjugated bilirubin

post-hepatic jaundice

caused by bile flow obstruction; gallstones, bile duct strictures; increased conjugated bilirubin

neonatal jaundice (physiologic jaundice of the newborn)

yellow discoloration of the skin and sclerae usually appears within 2-4 days after birth and resolves on its own within 3 weeks; phototherapy treatment

kernicterus

elevated bilirubin levels for a prolonged period that can result in permanent brain damage

cholestasis

impaired bile flow from the liver to the duodenum, excess bile accumulates in the liver and constituents start accumulating in the blood and body tissues

intra-hepatic cholestasis

bile caniculi or terminal bile duct damage; viral hepatitis, alcohol or drug-induced liver damage, liver cancers

extra-hepatic cholestasis

hepatobiliary tree obstruction; gallstones, bile duct strictures

cholestasis clinical manifestations

itching due to excessive accumulation of bile salts in blood (pruritis), jaundice, localized deposits of fat under the skin (xanthomas, xanthelasmas)

cholestasis treatment

drugs, surgery

hepatitis

inflammation of the liver

hepatitis causes

viruses, excessive and prolonged alcohol consumption, drug toxicities

pre-icterus phase

myalgia, arthralgia, fatigue, loss of appetite, nausea, vomiting, abdominal pain, elevated ALT and AST

icterus phase

abdominal pain, increased serum bilirubin

convalescent phase

increased sense of well-being, return of appetite, disappearance of jaundice

hepatitis prevention

vaccines to prevent hepatitis A, B, and D

hepatitis treatment

HAV, HEV: short-term, resolve on their own, recommended to rest, consume a nutritious diet, abstain from alcohol
HBV, HCV: antiviral drug combinations
HDV: no specific drugs available

heavy drinking

consuming 8 or more drinks per week for women, and 15 or more drinks per week for men

binge drinking

consuming 4 or more drinks on a single occasion for women, and 5 or more drinks on a single occasion for men

alcohol-induced liver damage

excessive and prolonged alcohol consumption that leads to progressive liver damage

stage 1: steatosis

abnormal accumulation of triglycerides in the cytoplasm of hepatocytes due to disturbance in intra-hepatic lipid metabolism; usually no signs or symptoms

signet ring

abnormal intracellular accumulation of triglycerides in the hepatocytes pushes their nuclei to the periphery

stage 2: steatohepatitis

characterized by necrosis of hepatocytes and neutrophilic invasion to remove cellular debris; jaundice, loss of appetite, nausea, vomiting, liver tenderness

cirrhosis

fibrosis and formation of liver nodules as the liver attempts to repair and replace damaged hepatocytes; develops slowly over months or years and can affect many organ systems of body

micronodular cirrhosis

most nodules are

macronodular cirrhosis

most nodules are >3 mm in diameter and vary in shape and size; most common in virus-induced liver damage

mixed cirrhosis

has features of both micronodular and macronodular cirrhosis

alcohol-induced liver damage prevention

avoid or limit alcohol consumption

alcohol-induced liver damage treatment

eliminate alcohol consumption, support nutritional needs, corticosteroids, liver transplantation

drug-induced liver damage phase I reactions

oxidation, reduction, hydrolysis, break down drugs and completely inactivate them or generate less active metabolites

drug-induced liver damage phase II reactions

conjugation, methylation, sulfation, bind molecules to drugs or their metabolites and convert them to water-soluble substances for excretion

intrinsic mechanism of liver damage

predictable and occurs in a dose-dependent manner

idiosyncratic mechanism of liver damage

unpredictable course and is independent of drug dose

risk factors of drug-induced liver damage

age >55 years, female sex, genetic predisposition, excessive and prolonged alcohol consumption, use of multiple interacting drugs

prevention of drug-induced liver damage

patient education on OTC and prescription drugs

treatment of drug-induced liver damage

discontinuation of the offending drug

fulminant hepatitis

rapid and severe impairment of liver function due to massive necrosis of hepatocytes in someone who does not have pre-existing liver disease

fulminant hepatitis causes

overdose of acetaminophen, infection with HBV, ingestion of poisonous mushroom amanita phalloides

fulminant hepatitis treatment

antidotes to counteract effects of poisoning, antiviral drug combinations, liver transplant

portal hypertension

hypertension in the hepatic portal system

portal hypertension cause

increased resistance to venous blood flow in hepatic portal system

pre-hepatic portal hypertension

due to an obstruction of the hepatic portal vein or its tributaries by thrombi in hypercoagulability states

intra-hepatic hypertension

due to compression of the central veins by fibrous bands and nodules in a cirrhotic liver

post-hepatic hypertension

due to obstruction of the major hepatic veins by thrombi, or right-sided heart failure which increases inferior vena cava pressure

ascites

accumulation of serous fluid in peritoneal cavity; characterized by abdominal distention, weight gain, and SOB

ascites pathophysiology

increased pressure in the peritoneal capillaries results in leakage of serous fluid into the peritoneal cavity

caput medusae

a network of distended and engorged veins that radiate from the umbilicus across the abdomen

caput medusae pathophysiology

development of collateral channels via the dilation of pre-existing anastomoses between the hepatic portal vein and the systemic veins in the lower abdominal wall results in appearance of caput medusae

hemorrhoids

distended and engorged veins either inside the rectum or around the anus; characterized by anal itching, pain or discomfort, and bleeding or spotting

portal hypertension pathophysiology

development of collateral channels via the dilation of pre-existing anastomoses between hepatic portal vein and systemic veins in the lower rectum

esophageal varices

distended and engorged veins in the submucosa of the lower third of the esophagus, can lead to internal bleeding and hematemsis

esophageal varices pathophysiology

development of collateral channels via the dilation of pre-existing anastomoses between the hepatic portal vein and the systemic veins in the lower esophagus

hepatic encephalopathy

spectrum of sensory, motor, and cognitive disturbances associated with liver dysfunction

hepatic encephalopathy pathophysiology

shunting of ammonia and other toxins from the intestines to the brain

asterixis

extending of the wrist results in "flapping tremor" of hand, loss of motor control, early sign of hepatic encephalopathy

hypersplenism

a syndrome characterized by rapid destruction of blood cells leading to anemia, leukopenia, and thrombocytopenia

hypersplenism pathophysiology

increased resistance to venous blood flow in the hepatic portal system result in congestion of blood in the spleen, followed by its progressive enlargement

liver failure

loss of 80-90% of liver function as a consequence of any liver disease

liver failure clinical manifestations

reflect alterations in the synthesis, storage, metabolic, and excretory functions of the liver; strong, musty odor of the breath (fetor hepaticus)

liver failure treatment

eliminate/treat underlying cause, support nutritional needs, liver transplant

primary tumors of liver cancer

hepatocellular carcinoma (arises from hepatocytes), cholangiocarcinoma (arises from cells lining the bile ducts)

metastatic tumors of liver cancer

20 timers more common than primary tumors because of liver's rich, dual blood supply

hepatocellular carcinoma risk factors

chronic hepatitis, excessive and prolonged alcohol consumption, exposure to aflatoxins (produced by moulds that grow on agricultural crops)

hepatocellular carcinoma clinical manifestations

loss of appetite, unintentional weight loss, weakness, fatigue, dull abdominal pain, jaundice

hepatocellular carcinoma treatment

surgery, liver transplant

cholangiocarcinoma risk factors

primary sclerosing cholangitis (chronic inflammation of bile ducts leading to formation of scar tissue), liver fluke infections (after eating raw or partly cooked fish infected with parasites)

cholangiocarcinoma clinical manifestations

loss of appetite, unintentional weight loss, weakness, fatigue, dull abdominal pain, jaundice

cholangiocarcinoma treatment

surgery liver transplant

cholelithiasis

presence of stone in the gallbladder (gallstones)

cholelithiasis cause

imbalance in the chemical composition of bile

cholelithiasis clinical manifestations

asymptomatic in 80% of cases; migration of stones to cystic duct results in abrupt RUQ pain (biliary colic)

cholelithiasis treatment

drugs, surgery

cholecystitis

inflammation of the gallbladder

acute cholecystitis

obstruction of the cystic duct by gallstones or a bacterial infection/mechanical trauma to the bladder

chronic cholecystitis

results from repeated episodes of acute cholecystitis

cholecystitis clinical manifestations

RUQ pain, fever, loss of appetite, nausea, vomiting

cholecystitis treatment

antibiotics, cholecystectomy

choledocholithiasis

the presence of gallstones in the common bile duct

choledocholithiasis clinical manifestations

biliary colic, nausea, vomiting

choledocholithiasis treatment

surgery to remove stones

cholangitis

inflammation of common bile duct

acute cholangitis

bacterial infection following an obstruction of the common bile duct by a stone or tumor

chronic cholangitis

may be an autoimmune disorder characterized by a progressive destruction of common bile duct

cholangitis clinical manifestations

RUQ pain, fever, loss of appetite, nausea, vomiting

cholangitis treatment

antibiotics, other drugs

gallbladder cancer risk factors

obesity, recurrent cholelithiasis, chronic cholecystitis