Liver Flashcards
Explain hepatic portal circulation
A ___ is located b/w two ___ beds. The hepatic portal vein collects __ from ___ in visceral structures located in the ___ and empties into the ___. Hepatic veins __ blood to the __ __ __.
A vein is located b/w two capillary beds. The hepatic portal vein collects blood from capillaries in visceral structures located in the abdomen and empties into the liver. Hepatic veins return blood to the inferior vena cava.
What makes up the portal triad?
hepatic portal vein (80%)
hepatic artery (20%)
bile duct
lymphatic vessel
Describe the role of hepatocyte function (bile)
Liver - hepatocytes synthesize cholesterol to form primary bile acids –> Bile acid pool –> AA (glycine and taurine) conjugate to form bile salts in bile –> Gallbladder: some bile is stored for release during eating and Duodenum and jejunum (bile salts emulsify fats and form micelles to transport fats through the unstirred layer, Micelles release fats at the brush border, Free bile salts proceed through the intestinal lumen –>Rectum: 15%-35% of bile salts are excreted in feces, Ileum and Colon: bile salts are actively transported across the intestinal lumen or are de- conjugated by bacteria into secondary bile acids that diffuse passively across the lumen –> Hepatic portal vein: 65-85% of bile salts and secondary bile acids enter the circulation with protein binding and are transported to the liver
Name 5 hepatic injuries and findings
fibrosis and cirrhosis lab evaluation of liver disease jaundice cholestasis portal hypertension
Fibrous tissues in formed in response to
inflammation
What is bridging fibrosis
with time, fibrous stands link regions of the liver
With continuing fibrosis and parenchymal injury, the liver is subdivided into
nodules of regenerating hepatocytes surrounded by scar tissue
Fibrosis is considered a _____ consequence of _______ damage and has lasting consequences on patterns of _____ _____ and ______ ___ _______
irreversible
hepatic
blood flow and perfusion of hepatocytes
Lab eval of liver disease: hepatocyte integrity
serum aspartate aminotransferase (AST, SGOT)
serum alanine aminotransferase (ALT, SGPT)
Lab eval of biliary tract integrity
serum alkaline phosphatase (AP, ALP, ALKP, etc)
serum y-glutamyltransferase (GGT)
Lab eval of bilirubin
direct (conjugated)
indirect (unconjugated)
Lab eval of hepatocyte function
serum albumin
prothrombin time
serum ammonia
Consequences of liver disease
4H, JF, GP, SWM
hyPO -albuminemia, ammonemia, glycemia, gonadism
Jaundice and cholestasis
gynecomastia and palmar erythemia
spider angiomas, weight loss, muscle wasting
Consequences of liver disease: Hepatic portal HTN
SEA HC
Splenomegaly Esophageal varices Ascites Hemorrhoids Caput medusae
Consequences of liver disease: Life Threatening Complications (HHH MEC)
Hepatic encephalopathy Hepatorenal syndrome Hepatocellular carcinoma Multiple organ failure Esophageal varices rupture Coagulopathy
Explain bilirubin metabolism and elimination
- Normal bilirubin production (.2-.3g/day) is derived primarily from the breakdown of senescent circulating erythrocytes, with a minor contribution from degradation of tissue heme containing proteins
- Extrahepatic bilirubin is bound to serum albumin and delivered to the liver
- Hepatocellular uptake
- Glucuronidation by glucuronosyltransferase in the hepatocytes generates bilirubin monoglucuronides and diglucuronides which are water soluble and readily excreted into bile.
- Gut bacteria deconjugate the bilirubin and degrade it to colorless urobilinogens. The urobilinogens and the residue of intact pigments are excreted in the feces with some reabsorption and re-excretion into bile
Jaundice: accumulation of excess ___ in ____
bilirubin in blood
Jaundice: Causes
excess bilirubin production reduced hepatic uptake impaired conjugation decreased heptocellular excretion impaired bile flow
Jaudice:
excess bilirubin production, reduced hepatic uptake,
impaired conjugation result in ___ ___ ___
increased unconjugated bilirubin
Jaudice:
excess bilirubin production, reduced hepatic uptake,
impaired conjugation result in increased unconjugated bilirubin:
____ to water, tight bound to ___, NOT excreted by ___
insoluble in water, tightly bound to albumin, not excreted by kidney
Jaudice:
excess bilirubin production, reduced hepatic uptake,
impaired conjugation result in increased unconjugated bilirubin:
Unbound plasma fraction
diffused in tissue
produces toxic injury
increases in hemolytic disease of the newborn
may lead to severe neurological damage
Jaundice: decreased heptocellular excretion, impaired bile flow result in ___ ____ ____
increased conjugated bilirubin
Jaundice: decreased heptocellular excretion, impaired bile flow result in increased conjugated bilirubin: ___ in water, ___ bound to albumin, excreted by ____
soluble in water, weakly bound to albumin, excreted by kidney
Cholestasis: in the parenchyma, cholestatic heptocytes are ___ with dilated canalicular spaces, ___ cells may be seen, and ___ cells frequently contain regurgitated ___ ___.
enlarged with dilated canclicular spaces, apoptic cells may be seen and Kupffer cells frequently contain regurgitated bile pigment
Cholestasis: in the portal tract of obstructed livers, there is also bile ___ ____, ___, bile pigment ___, and eventually ____ ____
bile ductular proliferation, edema, bile pigment retention, eventually neutrophilic inflammation
____ immediately adjacent to portal trans are ___ and undergoing __ ___
hepatocytes
swollen
toxic degeneration
Hepatic failure is __ and __ hepatic destruction
sudden and massive
Hepatic failure is the often end point of
progressive liver damage
Hepatic failure means that ___% of liver function must be lost
80-90%
Hepatic failure is __ ___
life threatening (multiple organ failure)
What are the special problems in hepatic failure?
hepatic encepalopathy
hepatorenal syndrome
Cirrhosis impairs __ __ through the liver and causes __ __ __.
blood flow
hepatic portal hypertension
Cirrhosis impairs blood flow through the liver and causes hepatic portal hypertension which causes what 3 problems?
ascites - edema of the abdomen portosystemic shunts (eso varices, hemorrhoids, caput medusae) splenomegaly
What are the three different types of portosystemic shunts in cirrhosis?
esophageal varices, hemorrhoids, caput medusae
Clinical manifestations of liver inflammation
pain, fever, N/V, anorexia, fatigue
Clinical manifestations of Liver necrosis
1.) decreased bilirubin metabolism (hyperbilirubinemia, jaundice)
decreased bile in GI tract (light colored stools)
Decreased vitamin K absorption (bleeding tendency)
Increased urobilinogen (dark urine)
2.) decreased metabolism of proteins, carbs and fats (hypoglycemia)
Decreased plasma proteins (ascites and edema)
3.) Decreased hormone metabolism
Increased androgens and estrogens
(gynecomastia, loss of body hair, menstrual dysfunction, spider angiomas, palmar erythema)
Increased ADH and aldosterone (edema)
4.) Biochemical alterations
Elevated AST, ALT levels
Elevated bilirubin
low serum albumin
prolonged prothrombin time
elevated alkaline phosphatase
5.) liver failure –> hepatorenal failure
6.)hepatic encephalopathy
7.)hepatic coma
8,)Death
What are 7 liver and gallbladder diseases?
viral hepatitis alcoholic liver disease hemochromatosis obstructive biliary tract disease circulatory disorders primary carcinoma of the liver cholelitiasis and choledocholithiasis
Viral hepatitis: Causative Agents (6)
hepatitis A,B,C,D,E,G virus
Viral Hepatitis: clinical syndromes
carrier state/asymptomatic infection
Acute viral hepatitis
Chronic viral hepatitis
Hep A & E both are: self- \_\_\_ \_\_\_ wk incubation do not cause \_\_\_ state do not cause \_\_\_\_ \_\_\_\_ do not cause \_\_\_\_ \_\_ transmission - poor hygiene not usually present in \_\_
self-limiting 2-8 week incubaton do not cause carrier state do not cause chronic hepatitis do not cause cancer oral transmission not usually present in USA
who is winning
I am
HAV: common ___ disease in ___ countries
adult infection is more ___
___ infections - associated with ___
common childhood disease in developing countries
adult infection is more dangerous
sporadic infections - associated with oysters
HEV: ___ infections are ___
typically endemic and seen in ____
high (20%) mortality rate in __ ___
sporadic infections are rare
typically endemic and seen in travelers
high mortality rate in prego women
HEP B,C,D: cause \_\_\_ state cause \_\_ \_\_ cause \_\_ (\_\_ NO increase over \_\_) \_\_\_ transmission - close personal contact present in \_\_
cause carrier state cause chronic hepatits cause cancer (HDV no increase over HBV) parental transmission - close personal contact present in USA
Hepatic steatosis aka ____ ____
fatty liver
Hepatic steatosis is __ damaged liver cells can take up __ __ normally but cannot incorporate them into ___ for ___
alcohol damaged liver cells can take up fatty acids normally but cant incorporate them into lipoproteins for export.
Alcoholic liver disease consists of: (3)
hepatic steatosis (fatty liver) (90-100%) alcoholic hepatitis (10-35%) cirrhosis (8-20%)
Hemochromatosis aka
hereditary iron overload
Hemochromatosis: uncontrolled uptake of \_\_\_ , ~1g/year \_\_\_ predominance 5-7:1 (menustration) autosomal \_\_\_ ~0.5% \_\_\_\_ carriers ~10% problems appear \_\_\_ (\_\_ years old)
uncontrolled uptake of iron male predominance autosomal recessive heterozygous carriers problems appear late (50+ years old)
Hemochromatosis: Problems with fully developed disease:
cirrhosis (~100%)
DM (80%)
Skin pigmentation (80%)
Another primary iron overload disease is
bantu siderosis
Secondary iron overload diseases:
Transfusion : 1 transfusion=0.25g of iron
Ineffective erythripoiesis: B-Thakassemia, Sideroblastic anemia
Obstructive biliary tract disease: secondary biliary cirrhosis is the
obstruction of extra hepatic biliary tract
Obstructive biliary tract disease: secondary biliary cirrhosis : common causes
gallstones, biliary atresia, malignancies of biliary tree or pancreas, strictures resulting from surgery
Obstructive biliary tract disease: primary biliary cirrhosis: destruction of \_\_\_ \_\_\_ \_\_\_ elevated \_\_\_ and \_\_\_ \_\_\_\_ late in disease \_\_\_\_\_ antibodies often \_\_\_
destruction of intrahepatic bile ducts elevated alkaline phosphatase and cholesterol hyperbilirubinemia late in disease antimitochondrial antibodies often fatal
Obstructive biliary tract disease: primary sclerosing cholangitis: \_\_\_\_ + \_\_\_\_ bile ducts associated with \_\_\_ \_\_\_ (70%) develops after \_\_ \_\_\_ elevated \_\_ \_\_\_ generally without \_\_ \_\_\_
intrahepatic and extrahepatic bile ducts associated with ulcerative colitis develops after UC elevated alkaline phosphatase generally without antimicrobial antibodies
What are the 4 circulatory disorders of the liver?
hepatic vein outflow obstructon
impaired intrahepatic blood flow
impaired portal vein inflow
impaired hepatic artery inflow
Circulatory disorders of the liver: Hepatic vein outflow obstruction causes
hepatic vein thrombosis (Budd-Chiari syndrome)
veno-occlusive disease
Circulatory disorders of the liver: Hepatic vein outflow obstruction manifestations (HAA EJ)
hepatomegaly, ascites, abdominal pain
Elevated transaminases, jaundice
Circulatory disorders of the liver: Impaired intrahepatic blood flow causes
Cirrhosis, sinusoid occlusion, systemic circulatory compromise
Circulatory disorders of the liver: Impaired intrahepatic blood flow manifestations (AEE)
Ascites (cirrhosis)
esophageal varices (cirrhosis)
elevated transaminases
Circulatory disorders of the liver: Impaired portal vein inflow causes
portal vein obstruction by thrombosis or tumor
Circulatory disorders of the liver: Impaired portal vein inflow manifestations (I SEA)
Intestional congestion
splenomegaly
esophageal varices
ascites
Circulatory disorders of the liver: Impaired hepatic artery inflow causes
complications of liver transplantation
Circulatory disorders of the liver: Impaired hepatic artery inflow manifestations
ischemia to bile ducts and parenchyma
potential loss of graft
Primary carcinoma of the liver aka
hepatocellular carcinoma (HCC)
Hepatocellular carcinoma:
arise from ___
hepatocytes
Hepatocellular carcinoma: caused by
HBV Chronic liver disease (HCV and alcohol) aflatoxin tyrosinemia (40%) cirrhosis (90%)
Hepatocellular carcinoma:
early ___ gives great __ rate
rate of ___ varies with __ rate worldwide
mean survival ~ ___ ___
early HBC gives great rate to HCC
rate of HCC varies with HBV rate worldwide
mean survival ~7 months
Cholelithiasis aka
gallstones
Cholelithiasis: \_\_\_ million Americans (~10% adults) \_\_\_ variability (4% Asia, 40% South America) \_\_\_\_ new cases/year (\_\_\_ surgery) \_\_\_ deaths/year usually \_\_\_ (70-80%)
>20 million americans worldwide variability ~1 million new cases/year (~2/3 surgery) ~1000 deaths/year usually asymptomatic
Risk factors for cholesterol stones (80%) (5F GH)
Fair Fat Fertile Forty Female Gallbladder stasis Hyperlipidemia
Risk factors for pigment stones (20%)
Chronic hemolytic syndromes
Biliary infection
GI disorder (Crohn disorder)
Asian>Western
What is Choledocholithiasis?
presence of stones in the biliary tree
Choledocholithiasis: problems
biliary obstruction pancreatitis cholangitis hepatic abscess chronic liver disease with biliary cirrhosis acute calculous cholecystitis
Acute pancreatiitis: causes “I GET SMASHED”
Idiopathic
Gallstone
Ethanol
Trauma
Steriods
Mumps (Paramyxovirus, E-Barr, Cytomegalovirus)
Autoimmune disease (Lupus, polyarteritis nodosa)
Scorpion sting (Tityus Trinitatis, snake bites)
Hyper-calcemia, lipidemia, triglyceridemia HYPOthermia
ERCP (Endoscopic retrograde cholangio pancreatography
Drugs
Who knows this material?
I DO :)
Who is going to get an A+?
I AM :)
