Intro to functions of the liver Flashcards
What divides the liver into 2 lobes?
→ Falciform ligament
Where is the blood supply of the liver from?
→ Portal vein - Blood returning from the GI tract
- 75%
→ 25% - hepatic artery
Where do the central veins of the liver lobules drain?
→ Into the hepatic vein
→ Back into the vena cava
What do hepatocytes do?
→ 60% perform most metabolic functions
What do Kupffer cells do?
→ 30% types of tissue macrophages
What cells other than hepatocytes and kupffer cells does the liver have?
→ Stellate
→ Endothelial
What is the functional unit of the liver?
→ Hepatic lobule
What is around the central hepatic vein?
→ Hexagonal plates of hepatocytes
→ At each of the 6 corners is a triad of branches of the portal vein, hepatic artery and bile duct
Where does blood enter the lobules from and flow to?
→ Branches of the portal vein and hepatic artery
→Flows through small channels called sinusoids that are lined with hepatocytes
→ Hepatocytes remove toxic substances from the blood
→ Blood exits the lobule through the central vein
What is the oxygenation like at the hepatic artery?
→ Oxygen rich
Why does blood leaving the lobule have low levels of O2?
→ Hepatocytes near the sinusoids have used up the O2
Describe the flow of bile
→ Bile is secreted by hepatocytes → Series of channels between cells (canaliculi) →Small ducts → Large ducts → Anastomose onto common bile duct
How does the livers microstructure support its role?
→ Large SA - exchange of molecules
→ Sophisticated separation of blood from bile
→ Specific positioning of pumps to achieve localization of materials
How is portal blood filtered?
→ Through the sinusoid - removal of gut bacteria
What is bile?
→ Complex fluid : Water, electrolytes + mix of organic molecules
→ Organic molecules : bile acids, cholesterol, bilirubin + phospholipids
What are the functions of bile?
→ Essential for fat digestion + absorption via emulsification
→ Bile and pancreatic juice neutralize gastric acid as it enters the small intestine
→ Elimination of waste products from blood - bilirubin + cholesterol
→ 500mg of cholesterol converted to bile acids per day
Describe how bile gets to the gall bladder
→ Bile from hepatic ducts → Common bile duct → Duodenum or diverted via cystic duct → Gall bladder → Concentrated and stored (30-50ml)
How is entry of bile into the duodenum controlled?
→ Opening of the sphincter of Oddi
What is bilirubin?
→ Yellow pigment formed from the breakdown of Hb
→ Useless and toxic but made in large quantities so must be eliminated
How are aged RBCs destroyed?
→ Dead/ damaged RBCs are digested by macrophages throughout the body
→ Fe is recycled
→ Globin chains are catabolized
→ Hb cannot be recycled so it is eliminated into bilirubin
How is bilirubin formed?
→ Heme is converted into free bilirubin in a series of steps
→ Released into the plasma and it is carried around bound to albumin
→ Free bilirubin is absorbed by hepatocytes and conjugated with glucuronic acid
→ Conjugated bilirubin is secreted into bile and metabolized by bacteria in the intestinal lumen
→ Eliminated in feces + urine
What is the major metabolite in feces?
→ Stercobilin
What is the major metabolite in urine?
→ Urobilin and urobilinogen
How is jaundice caused?
→ Excessive quantities of free or conjugated bilirubin accumulate in ECF
What are the symptoms of jaundice?
→ Yellow discolouration of the skin, sclera and mucous membranes
What is green jaundice caused by?
→ mutation of biliverdin reductase
What is pre hepatic jaundice?
→ excessive RBC breakdown
→ Excess unconjugated bilirubin is not excreted & remains in circulation
What is hepatic jaundice?
→ Hepatocyte damage
→Excess conjugated &/ unconjugated bilirubin
What is post hepatic jaundice?
→ excess conjugated bilirubin
→ Obstruction into passage of duodenum
→ Enters circulation & into urine
→ pruritus
What is used for neonatal jaundice in low resource countries?
→ Sunlight canopies
What toxic substances does the liver metabolize?
→ bilirubin
→ ammonia
→ hormones
→ Drugs & exogenous toxins
How are steroid hormones inactivated?
→ By conjugation & excretion
Describe phase 1 of the liver metabolizing drugs
Oxidation & Reduction
→ occurs in smooth ER
→ Catalyzed by cytochrome P450
→ Makes substrate into a polar compound
Describe phase 2 of the liver metabolizing drugs
Conjugation
→ Makes the drug more water soluble
→ Glucuronyl is the most prevalent conjugation group
→ Not all drugs use both phases
→ Elimination via ATPase pumps into blood or bile
Why is accidental overdose common with paracetamol?
→ Narrow therapeutic index
When should paracetamol not be taken?
→ After alcohol consumption
What are the 3 pathways that paracetamol is metabolized by?
→ Glucuronidation - 45-55%
→ Sulfation - 20-30%
→ N-hydroxylation & dehydration - < 15% (intermediate NAPQI is toxic)
What happens to paracetamol metabolism if you overdose?
→ Liver enzymes become saturated and glutathione stores are depleted
What is the treatment for paracetamol overdose?
→ N-acetyl cysteine is given which is a precursor to glutathione
Why does the body have to oxidize alcohol?
→ To remove it
→ It cannot be stored
What happens after alcohol is metabolized by liver enzymes?
→ It enters normal metabolic pathways and is metabolized as fat
What are the steps to metabolize alcohol?
→Ethanol → Acetaldehyde by alcohol dehydrogenase
→Excess NADH produced by oxidation must be removed
→Pyruvic acid → Lactic acid - requires NADH
→ Pyruvic acid + NADH + H+ → Lactic acid + NAD+
What can excess NADH be used as?
→ A reducing agent in pathways involved in lipogenesis
→ Synthesize glycerol
→ Synthesize fatty acids
What can NADH directly be used in?
→ The electron transport chain to synthesize ATP
What does NADH inhibit?
→ Normal oxidation of fats and fats may accumulate
How can accumulation of fats in the liver be alleviated?
→ By secreting lipids into the blood
What does excess acetaldehyde lead to and why?
→ Acetaldehyde is toxic
→ Hepatitis and cirrhosis occur
What are three problems associated with drinking?
→ Fatty liver
→ Alcoholic hepatitis
→ Alcoholic cirrhosis
How does fatty liver arise?
→ Alcohol abuse can lead to the accumulation of fat within liver cells
What is cirrhosis?
→ A degenerative disease where liver cells are damaged and replaced by scar formation
What can be an effect of impaired detoxification?
→ Gynecomastia
What blood clotting factors are made in the liver?
→ Fibrinogen
→ Prothrombin
→ V, VI, IX, X, XII
What is needed to make all the clotting factors?
→ Vitamin K
What do stellate cells act as?
→ Important deports for storage of fat soluble vitamins (A,D,E,K)
What does liver dysfunction lead to?
→ Fat malabsorption
→ Vitamin deficiency
What vitamin does the liver store?
→ Vitamin B12
→ Folate
What happens with a vitamin B12 deficiency?
→ Pernicious anaemia
How is iron stored in the liver?
→ As ferritin
