Liver Flashcards
What is the largest parenchymal organ?
the liver
Where is the liver located?
below the diaphragm
Which lobe of the liver is larger?
the right lobe
Where is the hepatic portal vein bringing blood from?
the GI tract
What is the basic functional unit of the liver?
liver lobule
-hexagonal with central vein, corners contain portal triads
What makes up a portal triad?
portal vein
bile duct
hepatic artery
What are the functions of the liver?
metabolism of food substances and drugs
production of bile
cholesterol metabolism & lipoproteins; production of steroid hormones from cholesterol
glucose storage (glycogen) and release
iron storage
production of various other substances
-clotting factors, serum proteins, fat-soluble vitamins
What is the goal when a drug enters the liver?
elimination of foreign (ex: drug) substances
How does the liver metabolize drugs?
active drug to inactive drug
prodrug to active drug
increased solubility
increased lipophilicity
pathway depends on chemical structure, influence of pharmacogenomics in some cases (CYP450s)
What is the function of bile?
aid in digestion of fats in the duodenum
What is the composition of bile?
bile acid
salts
phospholipids
cholesterol
pigments
water
electrolytes that keep the total solution slightly alkaline
-pH of 7-8
How much bile is excreted each day?
500-1000ml
most (95%) of the bile that has entered the intestines is reabsorbed in the terminal ileum, and returned to the liver for reuse
Which organ secretes bile?
gallbladder
Describe normal bilirubin metabolism.
- Hb release and breakdown (spleen, bone marrow)
- heme enzymatically converted to bilirubin
- bilirubin enters the liver through the circulation
(unconjugated) - hepatocytes add additional functional groups to bilirubin to
increase its solubility and excretion (conjugated) - most of the conjugated bilirubin then is excreted in bile
- bile enters the GI tract
- a small fraction of the bilirubin is reabsorbed and sent back
to the liver (enterohepatic circulation) - most of the bilirubin (~90%) is excreted in feces after being
enzymatically reduced by colon bacteria - the breakdown products contribute to fecal colour
Describe the epidemiology of liver disease in Canada.
approximately 1/10 have liver disease (>3M people)
over 100 forms of liver disease affecting all age groups
95% of deaths from chronic liver disease are due to:
-chronic hepatitis B or C
-alcoholic liver disease
-NAFLD
-liver cancer
What are the risk factors for liver disease?
obesity/diabetes
chemicals or toxins (drugs, herbals, illegal drugs)
alcohol abuse
family history
hepatitis B or C
How does early-stage liver disease present itself?
asymptomatic
What are the symptoms that are experienced in advancer liver disease?
jaundice (yellowing of skin and eyes)
nausea, vomiting, loss of appetite
abdominal swelling (ascites) or tenderness in liver area
fatigue
pruritis
dark urine
pale stool
dementia-like confusion
What causes jaundice?
elevation of serum bilirubin
What does jaundice indicate?
problem with the livers processing of bile
What are the different causes of jaundice?
prehepatic: hemolysis
hepatic: cirrhosis, tumors, drugs, viral, hepatitis
posthepatic: carcinoma, gallstones
What is the only indicator of jaundice?
yellow colour to skin, nails, and sclera
What is hepatic jaundice?
the liver is unable to transform unconjugated bilirubin to the conjugated form or conditions in which the liver cannot transfer the conjugated bilirubin into bile ducts
-free bilirubin then escapes into blood
What are some disorders that cause hepatic jaundice?
hepatitis A, B, C
alcoholic liver disease
drug-induced liver disease
chronic hepatitis due to various causes
cirrhosis
liver metastases
What is cirrhosis?
liver becomes fibrotic after chronic injury such that the liver becomes nodular with regenerating hepatocytes surrounded by scar tissue
What is NAFLD associated with?
obesity
Type II diabetes
hypertension
dyslipidemia
excess caloric intake with macronutrient imbalance
What do 10% of cases of NAFLD progress to?
steatosis and cirrhosis
What are the symptoms of NAFLD?
may be silent or patients may have abdominal pain, fatigue, jaundice at more advanced stages
Is NAFLD reversible?
reversible with:
-weight loss
-exercise
-dietary changes such as Mediterranean diet (limits red meat,
sweets, and baked goods)
What are the main causes of posthepatic jaundice?
intrahepatic cholestasis (bile not moving out)
extrahepatic obstruction of the biliary tract (prevents bilirubin from moving into the intestines)
What is cholestasis?
stagnation or a marked reduction in bile secretion and flow
What are examples of disorders that cause posthepatic jaundice?
inflammation, scar tissue, tumor, gallstones
pancreatic or biliary disorders involving inflammation and obstruction
carcinoma of pancreas head or common bile duct of gallbladder
What causes cholestasis?
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
-intrahepatic or extrahepatic
-leads to retention of constituents of bile in blood
What are the prominent features of cholestasis?
pruritis
malabsorption of fat and fat-soluble vitamins