Hepatobiliary System Flashcards
1
Q
What is the inflow of the liver?
A
- hepatic artery (25%)
- portal vein (75%)
2
Q
What is the outflow of the liver?
A
- bile
- 3x hepatic veins
3
Q
What is the purpose of blood delivered to the liver by:
- portal vein?
- hepatic artery?
A
Portal vein:
- mixed venous blood from GIT (nutrients, bacteria & toxins) and spleen (waste products)
- hepatocytes process nutrients, detoxify blood & excrete waste
Hepatic artery:
-brings oxygen rich blood into liver to support hepatocytes increased energy demands
4
Q
What is a hepatic lobule?
A
- hexagonal structural unit
- each corner has portal triad which links with 3x adjacent lobules
- central vein in the centre of liver lobule which collects blood from hepatic sinusoids, goes to hepatic veins, then to systemic venous system
- rows of hepatocytes; each has sinus-facing side & bile canaliculi-facing side
5
Q
What are the functions of hepatocytes?
A
-hepatocytes process nutrients, detoxify blood & excrete waste
6
Q
What happens to the bile produced by the hepatocytes?
A
-drains into oil canaliculi and combine with bile ducts on the lobule perimeter
7
Q
What is the portal triad?
A
- branch of hepatic artery
- branch of portal vein
- bile duct
8
Q
What is the hepatic acinus?
A
- functional unit of liver
- consist of 2 adjacent 1/6th hepatic lobules
- share 2x portal triads
- extend into hepatic lobules as far as central vein
9
Q
What are sinusoidal endothelial cells in the liver?
A
- no basement membrane
- fenestrated (gaps-discontinuous endothelium)
- allows lipids and large molecule movement to and from hepatocytes
10
Q
What are kupffer cells in the liver?
A
- sinusoidal macrophage cells
- attached to endothelial cells
Phagocytosis
-eliminate & detoxify substances arriving in liver from portal circulation
11
Q
What are hepatic stellate cells?
A
- exist in dormant state in the space disc
- store vitA in liver cytosolic droplets
- activated (act as fibroblasts) in response to liver damage- cause scarring
- proliferate, chemotactic deposit collagen in ECM
12
Q
What are hepatocytes?
A
- 80% of liver mass
- cubical
- synthesis e.g albumin, clotting factors, bile salts
- drug metabolism
- receive nutrients & building blocks from sinusoids
13
Q
What do cholangiocytes do?
A
-secrete HCO3- & H2O into bile
14
Q
What are the numerous functions of hepatocytes? (3 groups)
A
- Metabolic & catabolic functions:
- synthesis & utilisation 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
15
Q
What is glycolysis?
A
- anaerobic conversion of glucose to lactate in RBC, renal medulla & skeletal muscle
- aerobic oxidation of glucose in CNS, heart, skeletal muscle, most organs
16
Q
What is gluconeogenesis and where does this occur?
A
Glucose production from non-sugar molecules:
- AA (glutamine) in liver & renal cortex
- lactate (from anaerobic glycolysis in RBCs and muscles)
- glycerol (from lipolysis)
17
Q
How does carbohydrate metabolism occur in the liver?
A
Cori Cycle:
- Glucose enters muscle cells and pyruvate made (in anaerobic conditions)
- lactate made via fermentation
- lactate shuttled to liver and pyruvate made via lactate dehydrogenase
- glucose made via gluconeogenesis (6ATP required)
- glucose back to muscle cells
18
Q
How does protein synthesis occur in the liver?
A
- AA from diet or from muscle cells (fasted state) go into liver
- AA become secreted proteins such as plasma proteins, clotting factors, lipoproteins
19
Q
Which protein should be looked at to determine how well the liver is working?
A
-albumin
20
Q
How many non-essentail AA are there?
A
- 11
- the ones that the liver can manufacture
21
Q
How does the liver synthesise ‘non-essential’ AA?
A
- alanine from diet into liver
- transamination to a-keto glutarate, producing pyruvate and glutamate
- via transamination and transaminases
22
Q
Which non-essential AA do the following produce?
- a-keto glutarate
- pyruvate
- oxaloacetate
A
a-keto glutarate:
-glutamate, prolin
pyruvate:
-alanine
oxaloacetate:
aspartate
23
Q
What is the importance of the glucose-alanine cycle?
A
- deamination
- muscles can use AA to make glucose for ATP but:
- to convert pyruvate to glucose and to remove nitrogen as urea requires energy
-therefore, transferred to liver via glucose-alanine cycle
24
Q
Which AA have the highest concentrations in the blood?
A
- alanine
- aspartate
- glutamine
- glutamate
25
How does the glucose-alanine cycle occur?
- pyruvate (from glycolysis) and glutamate (from AA breakdown) make alanine in muscle cells
- alanine shuttled with a-ketoglutarate in the liver to make pyruvate and glutamate
- glutamate converted to urea into blood
- pyruvate converted to glucose (deamination) into glycolysis in muscle cells
26
How does triglyceride metabolism occur in the liver?
- fat stored in adipose tissue and liver
- when glycogen stores full, liver converts excess glucose and AA to fat
- in muscle cells, triglycerides broken down into FAs, shuttled to liver
- FAs undergo B-oxidation to acetyl CoA, enters TCA cycle
OR
- FA undergo B-oxidation to make acetyl CoA,
- 2 acetyl CoA combine to make acetoacetate, transported out as tissue energy source
27
How does lipoprotein synthesis occur in the liver?
- glucose into liver, either converted to glycerol and pyruvate
- pyruvate to acetyl CoA, to FA and cholesterol
- glycerol and FA combine to make tri-acyl glycerol
- tri-acyl glycerol + apoproteins phospholipids + cholesterol = lipoproteins
- lipoproteins form VLDL (transport FA to tissue) stored as triglycerides
- VLDL form LDL once deposited FA (transport cholesterol to tissue)
- lipoproteins form HDL (empty- pick up excess cholesterol)
28
What are the major roles of cholesterol?
- membrane integrity
| - hormone & vit D synthesis
29
What is stored in the liver?
- vitamins B12, A, D, E, K (for 6-12 months)
- iron as ferritin for erthyropoeisis
- copper
30
How does detoxification occur in the liver?
P450 enzymes:
```
Phase 1 (modification):
-more hydrophilic
```
```
Phase 2 (conjugation):
-attach water soluble side chain to make less reactive
```
31
What is the major component of bile?
-water
32
What colour is bilirubin?
-yellow
33
What colour is bilivirden?
-green
34
What are the uses of bile?
- cholesterol homeostasis
- absorption of lipids & lipid soluble vitamins (A,D,E,K)
Excretion of :
- xenobiotics(anything foreign)/drugs
- cholesterol/metabolites
- adrenocortical & other steroid hormones
- alkaline phosphatase
35
Compare and contrast hepatocytes and cholangiocytes?
Hepatocytes:
-60% of total bile secretion
Primary secretion:
-bile secretions reflect serum concentrations
-secretion of bile salts (acids), lipids & organic ions
Cholangiocytes:
-40% of total bile secretion
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
36
How much bile produced every day?
-500ml
37
What do the biliary transporters do?
-perform biliary excretion of bile salts and toxins on apical surfaces of hepatocytes and cholangiocytes
Main transporters include:
-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 for excretion of xenobiotics & cytotoxins
MDR3 for phosphatidylcholine
38
What are bile salts made from?
-cholesterol
39
What are the Na+ & K+ salts of bile acids conjugated in the liver to?
-glycine and taurine
40
What are the 2 primary bile acids synthesised in liver?
- cholic acid
- chendeoxycholic acid
-converted into secondary bile acids by GUT BACTERIA
41
What are the 2 secondary bile acids produced from primary acids by gut bacteria?
- deoxycholic acid
| - lithocolic acid
42
What are the functions of bile salts and how do they do this?
- reduce surface tension of fats
- emuslify fat prior to its digestion & absorption
- form micelles
- amphipathic
- hydrophilic side faces out containing hydroxyl & carboxyl
- hydrophobic side contains nucleus and methyl
- FFA and cholesterol on inside
43
Which enzymes hydrolyse the triglycerides?
-lipase and colipase
44
What do the sphincters control?
-output from the hepatic duct and pancreatic duct
45
How is bile secretion regulated?
- between meals, Sphincter of Oddi is closed so bile is diverted into gall bladder for storage
- eating- Sphincter of Oddis relaxes
- gastric contents (FFA, AA, CHOs) enter duodenum causing release of cholecystokinin (CCK)
- CCK causes gall bladder to contract
46
What causes the gall bladder to contract?
-cholecystokinin
47
What is the enterohepatic circulation of bile?
-95% of bile salts absorbed from terminal ileum
by Na+/bile salt co-transport Na/K ATPase system
-5% converted to secondary bile acids in colon:
-deoxycholic acid absorbed
-99% of lithocolic acid excreted in stool
-absorbed bile salts back to liver and re-excrteted in bile.
48
What are the functions of the gallbladder?
Stores bile- 50ml:
- concentrates bile
- acidifies bile
GB contraction triggered by CCK:
-binds to CCKA receptors and neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
49
Where is bilirubin sourced from?
-free bilirubin (indirect/unconjugated) is water insoluble, yellow pigment
- 75% from Hb breakdown
- 22% from catabolism of other haemoproteins
- 3% from ineffective bone marrow erythropoiesis
50
How much bilirubin excited into bile/day?
-200-250mg
85% excreted in faces:
BR to urobilinogen to stercobilinogen to stercobilin (brown compound)
15% enters enterohepatic circulation:
- BR is deconjugated to lipophilic form
- urobilinogen
- stercobilinogen
1% enters systemic circulation and excreted by kidneys
51
What are the causes of jaundice?
1. Pre-hepatic jaundice:
- producing more bilirubin than normal e.g in sickle cell anaemia where RBC being broken down more
- indirect bilirubin as not reached liver so not conjugated
2. Intrahepatic jaundice:
- decreased BR uptake
- decreased BR conjugation
- decreased BR secretion
- decreased outflow= cholestasis
3. Post hepatic jaundice:
- mechanical blockage so decreased extrahepatic outflow
- gall stones, tumours
52
What are the types and causes of jaundice?
1. Pre-hepatic jaundice:
- producing more bilirubin than normal e.g in sickle cell anaemia where RBC being broken down more
- indirect bilirubin as not reached liver so not conjugated
2. Intrahepatic jaundice:
- decreased BR uptake
- decreased BR conjugation
- decreased BR secretion
- decreased outflow= cholestasis
3. Post hepatic jaundice:
- mechanical blockage so decreased extrahepatic outflow
- gall stones, tumours
53
What are gall stones?
Cholelithiasis- stones in GB
Cholecystitis- stones stuck in cystic duct
Cholangitis- stone stuck in common bile duct, infection
Pancreatitis- stone stuck in pancreatic duct
54
How are gall stones treated?
- ERCP - endoscopic retrograde cholangiopancreatography (from below, from stomach)
- PTC - percutaneous trans hepatic cholangiography (from above through liver)
