Liver and Biliary System Flashcards
What structures does the portal triad encapsulate? PBH
Portal Vein
Bile Duct
Hepatic Artery
What are the functions of the liver? (6)
Metabolism
Bile Production
Cholesterol Metabolism
Glucose storage
Iron Storage
Production of clotting factors, serum proteins, fat soluble vitamins, and proteins
What is the goal of the liver when it encounters drugs?
Elimination of foreign substances
What is the difference between phase 1 and phase 2 metabolism?
Phase 1 is the activation, while phase II is the conjugation, goal is to go from lipophilic to water solube
What is the function of Bile?
Digestion of fats in the duedenum,
What is Bile composed of? (3)
Acids, salts, phospholipids/surfactants (main ones)
How much bile does the liver excrete every day?
500-1000ml
What is the function of the gallbladder?
Used as a storage site for bile in the event the stomach needs more
What are the steps to normal Bilirubin metabolism (9)
- Hemoglobin release and breakdown (spleen, bone marrow)
- Heme enzymatically converted to bilirubin.
- Bilirubin enters the liver through the circulation
- Hepatocytes add additional functional groups to bilirubin to increase its solubility and excretion
- Most of the conjugated bilirubin is then excreted in the bile.
- Bile enters the GI tract
- A small fraction of the bilirubin is
reabsorbed and sent back to the liver - Most of the bilirubin (~90%) is excreted in
the feces after being enzymatically
reduced by colon bacteria. - The break down products contribute to
fecal colour.
Blood –> Heme –> Bilirubin –> Bile –> GI Tract –> limited reabsorption if bilirubin –> Bile is excreeted
What are the risk factors for liver disease?
Obesity/Diabetes
Exposure to chemcials/toxins
Alcohol abuse
Family history
Hep B/C
What are the symptoms of liver disease
Nausea, vomiting or loss of appetite
Abdominal swelling (ascites) or tenderness in the area of the liver
Chronic fatigue
Itchy skin (pruritus) *Dark coloured urine *Pale stool
Dementia-like confusion (if hepatic encephalopathy is present)
Ascites
How does Jaundice occur?
This is due to the livers inability to transform unconjugated bilirubin to the conjugated form, This free bilirubin escapes to the blood causing yellow colour.
What is Cirrhosis?
liver becomes fibrotic after some severe chronic injury, such that the liver becomes nodular with regenerating hepatocytes surrounded by scar tissue
What is NAFLD
Non-alcoholic fatty liver disease, which is associated with hypertension, diabetes, dyslipidemia,
Is NAFLD reversible? How?
Yes, weight loss and exercise
What is the main cause of posthepatic Jaundice Obstruction?
Intrahepatic cholestasis (bile not moving out of the liver through the ducts)
Extrahepatic obstruction of the biliary tract, which prevents bilirubin from moving into the intestines.
What is Intrahepatic cholestasis
bile not moving out of the liver through the ducts
What can Intrahepatic cholestasis caused by?
functional impairment of the hepatocytes in the secretion of bile and/or due to an obstruction at any level of the excretory pathway of bile.
What can Cholestatic jaundice be classified into?
Intrahepatic or extrahepatic cholestasis
What does cholestasis lead to?
Retention of the constituents of bile in the blood
Hepatocellular Causes (With respect to intrahepatic cholestasis)
Viral hepatitis, acute alcoholic hepatitis, parenteral nutrition
Canalicular Membrane Changes (With respect to intrahepatic cholestasis)
Drugs:oral contraceptives, antibiotics, antithyroid drugs, sulphonamides; cholestasis in pregnancy
Canalicular/Ductular Luminal Obstruction: (With respect to intrahepatic cholestasis)
Cholestasis due to sickle cell disease, bacterial infections, sepsis, cystic fibrosis
Ductopenia (With respect to intrahepatic cholestasis)
Familial, drug- induced, chronic allograft rejection, Hodgkin disease, sarcoidosis, primary sclerosing cholangitis, primary biliary cholangitis
How is intrahepatic cholestasis treated?
Surgical, but also symptom based
How is pruritis managed?
Cholestyramine (reduces cholesterol)
ursodeoxycholic acid in some cases, antihistamines (sleep), phenobarbitone or naloxone (investigational)
How are pigmentary stones formed? Cholelithiasis
Solubility of the cholesterol or bile pigments is exceeded in the bile
A nidus of precipitated salts forms
More precipitate is added and the “stone” grows larger
Symptoms only when they cause obstruction, irritation or infection results
What is Ursodiol?
Most common drug used. It solubilizes cholesterol in micelles and acts by dispersing cholesterol in aqueous media.
What are some complications of gallstones
Obstruction at the biliary cirrhosis or obstruction near the pancreas head
What are the main causes of Cirrhosis of the liver?
Hep B C D, NAFLD, Alcohol
Describe the things that can lead to liver failure? (5)
Liver cellular damage, Fibrosis, nodule formation, impaired blood flow, bile obstruction
What is the leading cause of non-alcoholic fatty liver disease?
Obesity, Diabetes
What is the treatment that is involved in treating cirrhosis?
Weight reduction, blood lipid management
What are the stages of alcoholic liver disease?
Fatty Liver
Alcoholic hepatitis
Alcoholic Cirrhosis
Disease progression of alcoholic hepatitis can be attributed?
- lipid peroxidation
- dysregulated lipid metabolism
- acetaldehyde protein adduct formation
- disruption of cytoskeletal and membrane function
What occurs due to the inability of lipoprotein transport to occur?
Lipid Vacuoles form and develop
How does liver dysfunction disrupt other parts of the body?
Edema, Muscle wasting, collateral veins, jaundice, hair thinning
What are some systemic complications due to cirrhosis? (5)
Reduced clotting factor formation
Hematemesis and
Hepatic Encephalopathy
Hepatorenal syndrome
Steroid hormones deficiencies
Hematemesis and exsanguination
What is Hematemesis?
Internal bleeding
what is exsanguination?
Process of draining
What are the liver function tests we focused on?
AST and ALT
What are some other Liver function tests other then AST/ALT we test for? (3)
Albumin, Bilirubin, and prothrombin time
What factors cause elevated AST or ALT values?
Autoimmune hepaptitis
Hep B/C
Drugs
Ethanol
Fatty liver
Growths
Hemodynamic disorders
Iron deficiency
Muscle injury
Hepatocellular carcinoma is what?
tumor that is relatively uncommon in North America, although its incidence is rising, principally in relation to the spread of hepatitis C infection.
What are the two types of benign liver tumors discussed?
- Hemangioma
- Hepatocellular adenoma
What is intrahepatic Cholestasis?
Inability of the hepatic cells to not excrete bile. Can happen within the liver or biliary pathway
What is the treatment for non-alcholic fatty liver disease?
Weight reduciton/Dietary improvement, blood lipid management
What do reactive oxygen species do?
They can generate free radicals that react with membranes and proteins in the liver
What does alcohol interfere with?
It is a hepatotoxin that interferes with mitochondrial and microsomal function in hepatocytes, leading to an accumulation of lipids in the liver
What is ALT?
alanine aminotransferase, can be indicative of acute injury to the liver
What is AST?
Aspartate aminotransferase, high value could mean acute liver injury
What is the biggest risk factor of hepatocellular carcinoma?
Hep B/Hep C
What is the definition of drug-induced liver injury?
Hepatic inflammation, necrosis or jaundice due to exposures to a medication or toxin
Medications can cause DILI at what types of doses?
Therapeutic doses and overdose
What is idiosyncratic drug metabolism/
Where normal therapeutic doses cause liver damage
What are the 3 major drug classes that cause liver disease?
Antimicrobials,
Herbal and dietary supplements
Cardiovascular agents
What is the #1 cause of acute liver failure?
Drugs
What is the signs of DILI?
Wide range
Asymptomatic to liver enzymes elevation to liver failure
What is Zonal hepatocellular necrosis?
This could be indicative of a DILI because the drug has caused necrosis around the central vein located near the middle of the liver lobule
What is macro/microsteatosis?
Accumulation of fat droplets in the liver
Micro is most serious as it is associated with Reyes syndrome in children!
What is the normal range of ALT?
12-37U/L
What are ALT?
Found mainly in hepatocyte cytosol, and is more liver specific
What is the normal range of AST
15-65
What are AST?
Found in hepatocyte mitochondria, and will be more elevated then ALT during chronic alcohol use and cirrohisis
What is total protein and albumin?
Major proteins produced by the liver
What is the significance on Oncotic pressure?
Oncotic pressure draws fluids into the blood stream
What is globulin?
Help with immune response
What is direct bilirubin?
This is conjugated and water-soluble, a sign of normal funciton
What is indirect bilirubin
This is an indirect measurement taken from total-direct and it can indicate whether hepatic function has decreased
Is increased or decreased bilirubin an indicator for liver injury?
increased
What does a prothrombin time tell us?
How long it takes the blood to clot
GGT can also be elevated with
Alcohol toxicity
Which zone does acetaminophen affect first?
closest to the central vein, Zone 3 or pericentral cells
What is cholestasis?
marked reduction bile flow and secretion
What is Cholelithiasis?
Gallstones
What is cholecystitis?
Infection of ulcers
