Hepatobility System Flashcards
What is the blood supply of liver?
- hepatic artery (25%)
- portal vein (75%)
What is the outflow of the liver?
- Bile
- 3 x hepatic veins
How many segments are in the liver?
8
What is the micromorphoglocial function of the liver?
- Lobules
* Portal triads (tracts
What is the functional?
- Acinus
- Blood flow
- Bile flow
What is the hepatic lobule?
•Hexagonal structural unit of liver tissue
What does each corner condition of in the hepatic lobule?
- Each corner consists of a portal triad
* Links with 3x adjacent lobules
What is in the centre of liver lobule?
- Centre of liver lobule is a central vein
- Collects blood from hepatic sinusoids → hepatic veins → systemic venous system
- Within lobule rows of hepatocytes
- Each has sinusoid-facing side & bile canaliculi-facing side
What is the branch of the hepatic artery in portal triad?
•Brings O2-rich blood into liver to support hepatocytes ↑ energy demands
What is the branch of the portal vein in portal triad?
- Mixed venous blood from GIT (nutrients, bacteria & toxins) and spleen (waste products)
- Hepatocytes process nutrients, detoxify blood & excrete waste
What is the branch of the bile duct in the portal triad?
- Bile produced by hepatocytes drains into bile canaliculi
* Coalesce with cholangiocyte-lined bile ducts around lobule perimeter
What is the hepatic acinus?
- Functional unit of liver
- Hard to define anatomically cf hepatic lobule
- Consists of two adjacent 1/6th hepatic lobules
- Share 2x portal triads
- Extend into hepatic lobules as far as central vein
What is the three zone model?
Three zone model
•Blood into hepatic acinus via Point A (portal triad)
•Blood drains out of hepatic acinus via Point B (central vein)
•Hepatocytes near outer hepatic lobule (zone 1) receive early exposure to blood contents:
•Good components (O2)
•Bad components (toxins)
What are the 3x region of the acinus?
- Zone 1 – O2 ↑, Toxin risk ↑
- Zone 2 – O2 →, Toxin risk →
- Zone 3 – O2 ↓, Toxin risk ↓
What in sinusoidal endothelial cells?
- No basement membrane
- Fenestrated (discontinuous endothelium)
- Allow lipids & large molecule movement to and from hepatocytes
What are kuppfer cells?
- Sinusoidal macrophage cells
- Attached to endothelial cells
- Phagocystosis
- Eliminate & detoxify substances arriving in liver from portal circulation
What are hepatic stellate cells?
(Ito; perisinusoidal)
•Exist in dormant state
•Store vit A in liver cytosolic droplets
•Activated (fibroblasts) in response to liver damage
•Proliferate, chemotactic & deposit collagen in ECM
What are hepatocytes?
- 80% 0f liver mass
- Cubical
- Synthesis e.g. albumin, clotting factors & bile salts
- Drug metabolism
- Receive nutrients & building blocks from sinusoids
What are cholangiocyte?
•Secrete HCO3- & H2O into bile
What are the functions of hepatocytes?
- Metabolic & catabolic functions:synthesis & utilization of carbohydrates, lipids and proteins.
- Secretory& excretory functions:synthesis &secretion of proteins, bile and waste products.
- Detoxification & immunological functions:breakdown of ingested pathogens & processing of drugs
What is glycolysis?
- anaerobic conversion of glucose → lactate
– (RBCs, renal medulla & skeletal muscle) - aerobic oxidation of glucose (CNS, heart, skeletal muscle, most organs)
What is glycogenesis?
– synthesis of glycogen from glucose
- (liver & muscle)
What is Glycogenolysis?
breakdown of glycogen to glucose
What is gluconeogenesis?
-production of glucose from non-sugar molecules:
•amino acids (glutamine) in liver & renal cortex
•Lactate (from anaerobic glycolysis in RBCs & muscles)
•Glycerol (from lipolysis)
What is lipogenesis?
-synthesis of triacylglycerols (storage in fat depots)
What is lipolysis?
– breakdown of triacylglycerols → glycerol & FFAs
Whats happens in muscle cell? Carbohydrate metabolism
- Glucose
- Glycolysis: 2 ATP, Pyruvate, NAD+-> NADH - Pyruvate to oxygen to TCA cycle and acetyl CoA: 1 TAP, 3NADH, 1FADH2 mitochondria
- Pyruvate fermente to lactée
What happens in the liver? What is the Cori Cycle? carbohydrate metabolism
- Lactate with lactate dehydrogenase to pyruvate
- Pyruvate to gluconeogensis to glucose
- Glucose goes back to muscle cell
What is protein synthesis like?
- Fasted state from muscle and fed state from diet to from amino acids
1. Amino acids go into liver
2. Amino acids form proteins
3. Secreted proteins e.g. plasma porteins, clouting factor, lipoproteins
Give example of synthesis of non essential amino acids?
- Diet
- Alanine - Transamination of alanine, to form alpha keto glutarate
- To produce glutamate and pyruvate
- Reaction can go back and froward
- alanine transaminase (ALT in blood transfer)
What is the synthesis of non-essential amino acids like?
- Different keto-acids can be converted into multiple amino acids depending on the transaminase enzyme (vital for production of non-essential amino acids)
- a-keto glutarate → e.g. glutamate, proline, arginine
- Pyruvate → e.g. alanine, valine, leucine
- Oxaloacetate → e.g. aspartate, methionine, lysine
Describe the hepatocyte function for protein metabolism?
-Glucose-alanine cycle – Deamination
-Problem: Muscle can potentially utilise amino acids to produce glucose for energy;
BUT
1.To convert pyruvate to glucose requires energy
2.To remove nitrogen as urea requires energy
-Solution: transfer problem to the liver (glucose-alanine cycle)
What is the glucose alanine cycle?
-alanine, aspartate, glutamine, glutamate
In Muscle CELL:
1. Pyruvate from glycolysis and glutamate from amino acid breakdown
2. To Alananine transaminase
3. This is shuttled along to the liver with alpha ketogenic glucatamte
4. Produce energy and then go to urea cycle.
What happened in urea cycle?
- In liver
1. Glutamate to urea (+4ATP)
2. Pyruvate to glucose (+6ATP) - Deamination?
- Glucose goes to glycolysis in muscle cell
- Urea goes to blood
Why is fat important?
Fat
•main energy store in body (100x glycogen).
•Stored in adipose & liver.
•When glycogen stores full, liver converts excess glucose & amino acids to fat for storage
What happens in triglyceride metabolism?
- Adipose tissue cell:
1. Triglyceride
2. to Fatty acids - In liver
3. To fatty acids in liver
4. To acetyl CoA by Beta oxidation
5. Then to TCA cycle
What do you do if want to export energy from liver?
- Adipose tissue cell:
1. Triglyceride
2. to Fatty acids - In liver
3. To fatty acids in liver
4. To acetyl CoA by Beta oxidation: two of these combined
5. To form acetoacetate
5. This is transported out as tissue energy source
How does lipoprotein synthesis happen?
- IN LIVER:
1. Glucose goes into liver
2. transferred to glycerol or pyruvate which then goes to acetyl CoA
3. Acetyl CoA goes to fatty acids and cholesterol
4. Glycerol and fatty acids combined form triacylglycerol
5. Add apoproteins phospholipids and cholesterol too triacyglycerol to form lipoproteins
What are different types of lipoproteins?
- VLDL (transports fatty acids to tissues)
- Goes to triglycerides in adipose tissue cell to be stored - Or VLDL goes to LDL (transport cholesterol to tissue
- HDL from lipoproteins (empty and picks up excess cholesterol)
What is the function of the liver?
•fat soluble vitamins (A,D,E,K). -Stores sufficient 6-12 month (except Vit K where store is small) -Vit K essential blood clotting •Storage of iron as ferritin. -Available for erythropoeisis -Copper
How does the liver carry out detoxification (xenobiotics)?
P450 enzymes •Phase 1 (modification) – more hydrophilic •Phase 2 (conjugation) – attach water soluble side chain to make less reactive
What are the uses of bile?
•Cholesterol homeostasis
•Absorption of lipids & lipid soluble vitamins (A, D, E, & K)
-Excretion of things
What does bile excrete?
- xenobiotics/drugs
- cholesterol metabolites
- adrenocortical & other steroid hormones
- Alkaline phosphatase
What happens in primary secretion?
- Bile secretions reflect serum concentrations
* Secretion of bile salts (acids), lipids & organic ions
What happens in secondary modification?
- Alteration of pH (alkaline electrolyte solution)
- H2O drawn into bile by osmosis via paracellular junctions
- Luminal glucose & organic acids reabsorbed
- HCO3- & Cl- actively secreted into bile by CFTR (Cystic Fibrosis Transmembrane Regulator)
- IgA exocytosed
How much bile is sued in every day?
500mL
What colour is bile?
Green (biliverdin) / yellow (bilirubin) due to pigments
How much bile do hepatocytes secrete?
Secrete 60% of total bile
How much bile do cholanglocytes secrete?
Secrete 40% of total bile
What are biliary transporters?
•Biliary excretion of bile salts & toxins performed by biliary transporters on apical surface of hepatocytes + cholangiocytes
What are the main biliary transporters?
- Bile Salt Excretory Pump (BSEP) – active transport of BAs into bile
- MDR related proteins (MRP1 & MRP3)
- Products of the familial intrahepatic cholestasis gene (FIC1)
- Products of multidrug resistance genes:
- MDR1 → excretion of xenobiotics & cytotoxins
- MDR3 → phospatidylcholine.
What is the key component of bile?
Bile acids/salts (SAME THING(
Where are bile acids synthesised from?
Cholesterol
Where are the Na+ and K+ salts of bile acids conjugated?
Na+ and K+ salts of bile acids are conjugated in liver to glucose and taurine
What are the 2 primary acids synetshsied in liver?
- Cholic acid
2. Chenodoxycholic acid
What are the 2 secondary bile acids produced from primary acids by gut bacteria?
- Deoxycholic acid
2. Lithocolic acid
What is the function of bile salts?
- Reduce surface tension of fats
* Emulsify fat prior to its digestion & absorption
What do bile salts form?
Micelles
Describe bile salts
- Steroid nucleus planar- has 2x faces (Amphipathic)
- 1x surface hydrophilic domains (hydroxyl & carboxyl) - faces OUT → dissolves in water
- 2nd surface hydrophobic domains (nucleus & methyl) faces IN → dissolves in fat
- FFAs & cholesterol INSIDE
What happens between meals?
Sphincter of Oddi closed → bile diverted into gall bladder for storage
What happens when you are eating?
Sphincter of Oddi relaxes
What is the gastric contents causing?
Gastric contents (FFAs, AAs > CHOs) enter duodenum causing release of cholecystikinin (CCK)
What causes the gallbladder to contract?
CCK
What is the enterohepatic circulation?
•95% bile salts absorbed from terminal ileum
•By Na+/bile salt co-transport Na+-K+ ATPase system
• 5% converted to 2o bile acids in colon:
•Deoxycholic acid absorbed
•99% Lithocolic acid excreted in stool
• absorbed B.salts back to liver & re-excreted in bile
-(enterocyte to hepatocyte)
What is the function of gallbladder?
- Stores bile (50ml)
- Concentrates bile
- Acidifies bile
1. fat to CCK to CCK RECEPTORS and chases contract and hit from vagus nerve
How does the gallbladder contract?
- GB contraction triggered by CCK
- Binds to CCKA receptors & neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
What is bilirubin (BR)?
Free BR (indirect/unconjugated) = H2O-INSOLUBLE, yellow pigment
What is the source of bilirubin (BR)?
- 75% BR from Hb (erythrocytes) breakdown
- 22% from catabolism of other haemoproteins
- 3% from ineffective BM erythropoiesis
What happens to free BR?
- Free BR bound to albumin in blood
- Most dissociates in liver & enters hepatocytes
- BR conjugated with 2x molecules of UDP-glucuronate → bilirubin diglucuronide (direct bilirubin)
- Secreted ACROSS concentration gradient into biliary canaliculi → GIT
How much bilirubin is excreted?
-200-250mg BR excreted into bile/day •85% excreted in faeces -BR → urobilinogen → stercobilinogen → stercobilin (brown compound) •15% enters enterohepatic circulation -BR → deconjugated → lipophilic form -Urobilinogen -Stercobilinogen •1% enters systemic circulation & excreted by kidneys
What are the different types of audience?
- Prehepatic: too much bilirubin produced e.g. anemia so more haemoglobin
- Intrahepatic; probs with live, not taken up much BR or decrease section or conjuction, or decrease outflow (choleilathisis)
- Posthepatic: decrease extra hepatic outflow
What are different solutions?
- ERCP
- PTC
