Hepatobilliary system Flashcards
How many liver segments are there and how many are there per lobe
8, 4 each
1?
Right lobe
2?
Diaphragm
3?
Left lobe
4?
Falciform ligament
5?
Ligamentum teres
6?
Gallbladder
Describe the blood inflow and outflow of the liver
Inflow:
75% Hepatic portal vein
25% Hepatic artery
Outflow:
Bile
3x hepatic veins
What is the purpose of blood delivered by the hepatic artery and the hepatic portal vein?
HPV:Deliver digested products to the liver
HA: Deliver oxygenated blood for resp/met
Describe the morphology of a liver lobule, incl what is in every corner and what’s in the center
Hexagonal structural unit of liver tissue
Each corner consists of a portal triad
Links with 3x adjacent lobules
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 are the 3 vessels contained within a portal triad and what are their functions?
Branch of hepatic artery
Brings O2-rich blood into liver to support hepatocytes ↑ energy demands
Branch of portal vein
Mixed venous blood from GIT (nutrients, bacteria & toxins) and spleen (waste products)
Hepatocytes process nutrients, detoxify blood & excrete waste
Bile duct
Bile produced by hepatocytes drains into bile canaliculi
Coalesce with cholangiocyte-lined bile ducts around lobule perimeter
What is a hepatic acinus and what is contained within it
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
Outline the microfunction of a hepatic acinus, including the blood supply and drainage and the zone by zone O2 conc and risk of toxicity.
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)
Acinus split into 3x regions
Zone 1 – O2 ↑, Toxin risk ↑
Zone 2 – O2 →, Toxin risk →
Zone 3 – O2 ↓, Toxin risk ↓
What nerve innervates the gall bladder
The vagus nerve
Give 3 unusual characteristics of a hepatic sinusoid endothelial cell
No basement membrane
Fenestrated (discontinuous endothelium)
Allow lipids & large molecule movement to and from hepatocytes
What is the role of kupffer cells
Hepatic Sinusoidal macrophage cells
Attached to endothelial cells
-Phagocystosis
Eliminate & detoxify substances arriving in liver from portal circulation
What is the role of 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 is the function and shape of a hepatocyte
80% of liver mass
Cubical
Synthesis e.g. albumin, clotting factors & bile salts
Drug metabolism
Receive nutrients & building blocks from sinusoids
What is the role of a hepatic cholangiocyte
Secrete HCO3- & H2O into bile
Give the 3 general 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
Glycolysis def and where is occurs
Anaerobic conversion of glucose → lactate
- (RBCs, renal medulla & skeletal muscle)
Aerobic oxidation of glucose (CNS, heart,
- (Skeletal muscle, most organs)
Glycogenesis def and where it occurs
synthesis of glycogen from glucose
- (liver & muscle)
Glycogenolysis def
Breakdown of glycogen into glucose
Gluconeogenesis def
Production of glucose from non-sugar molecules
-Amino acids (glutamine) in liver & renal cortex
-Lactate (from anaerobic glycolysis in RBCs & muscles)
-Glycerol (from lipolysis)
Lipolysis def
Breakdown of triacylglycerols into FFAs and glycerol
Lipogenesis def
Synthesis of triacylglycerols
Outline the function of hepatocytes within carbohydrate met
Glucose from the liver is released, travels to muscle cell
Undergoes glycolysis, forming pyruvate then lactate
Lactate travels to hepatocyte and is recycled by lactate dehydrogenase into pyruvate
ATP is used to power gluconeogenesis to reproduce glucose and restart the cycle
Outline the function of hepatocytes within protein synthesis
Amino acids (either from muscle cell in fasted state or diet in fed state) travel to hepatocyte
They are turned into secreted proteins
Outline the function on hepatocytes within non-essential amino-acid synthesis
-All occurs in the liver
Dietary alanine is processed into a-ketoglutarate
Reversible reaction then forms glutamate and pyruvate via transamination
Which amino acids can be formed from a-ketoglutarate?
Glutamate, proline, arginine
Which amino acids can be formed from pyruvate?
Alanine, valine, leucine
Which amino acids can be formed from oxaloacetate?
Aspartate, methionine, lysine
What issue does the glucose alanine cycle solve?
For conversion of amino acids into glucose
-Removal of nitrogen as urea
-Conversion of pyruvate into glucose
Outline the glucose alanine cycle?
Glutamate/pyruvate is converted to alanine in muscle cell
Alanine travels to the liver, is deaminated to produce urea as well as converted into pyruvate
The pyruvate is converted into glucose in the liver and then transported to muscle to be respired
Outline hepatocytes role within fat metabolism
Triglycerides are converted to fatty acids
They are transported to the liver
B-oxidation converts them into acetyl CoA which enters the TCA cycle(Conversion to acetoacetate and then release as tissue energy source)
How are lipoproteins synthesised within hepatocytes?
Hepatic glucose is converted into pyruvate and glycerol, then acetyl CoA, then into cholesterol via HMG CoA-reductase
The glycerol is converted into tri-acyl glycerol, apoproteins, phospholipids and cholesterol, which combine to form lipoproteins
What occurs to lipoproteins after synthesis?
HDL-Picks up excess cholesterol
LDL-Transport cholesterol to tissues
VLDL-Transport fatty acids to tissues(incl. muscle)
What do hepatocytes store?
Storage of 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
Vitamin B12
Copper(Excess Cu is Wilsons’)
How do hepatocytes detoxify blood?
P450 enzymes
Phase 1 (modification)
– more hydrophilic
Phase 2 (conjugation)
– attach water soluble side chain
to make less reactive
Outline the gross composition of bile
Give the 3 major functions of bile
Cholesterol homeostasis
Absorption of lipids & lipid soluble vitamins (A, D, E, & K)
Excretion of:
xenobiotics/drugs
cholesterol metabolites
adrenocortical & other steroid hormones
Alkaline phosphatase
What causes biles’ colour?
Yellow-Bilirubin
Green-Biliverdin
How much bile is produced per day and by what?
500mls/day
60% from hepatocytes
40% from cholangiocytes
Outline the primary/secondary secretion stages of bile and what happens in each of them
Primary-secretion
Bile secretions reflect serum concentrations
Secretion of bile salts (acids), lipids & organic ions
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
What are the proteins which are responsible for the biliary excretion of bile salts & toxins
Biliary transporters
What are the main importers(basolateral) in the bile tube?
Organic anion transporting peptide (OATPs) – bile salt uptake
Na+ taurocholate-cotransporting polypeptide (NTCP) - bile salt uptake
What are the main exporters(apical) in the bile tube?
Bile Salt Excretory Pump (BSEP) – active transport of BAs into bile
MDR related proteins (MRP2 & MRP3) –
-vely charged metabolites
Products of multidrug resistance genes
MDR1 → excretion of neutral & +ve xenobiotics & cytotoxins
MDR3 → phospatidylcholine
What is the key component of bile and what is it synthesised from?
Bile salts(acids)
-Synthed from cholesterol
What are Na+ and K+ conjugated into in the liver?
Glycine and taurine
What are the 2 primary bile acids, where are they synthesised and what do they turn into and how?
Cholic acid –> Deoxycholic acid
Chenodeoxycholic acid –> Lithocolic acid
> Both are converted by gut bacteria
What are the 2 surfaces of micelles and give their properties
1x surface hydrophilic domains (hydroxyl & carboxyl) - faces OUT → dissolves in water
2nd surface hydrophobic domains (nucleus & methyl) faces IN → dissolves in fat
Outline the overall function of bile salts and enzymes in the digestion of lipids
- Emulsification
Bile salts and phospholipids form micelles around triglycerides - Enzyme action
Lipase and Colipase break down the triglycerides into glycerol and FFAs
What is the sphincter of Oddi and when does it open/close?
Between meals Sphincter of Oddi closed → bile diverted into gall bladder for storage
Eating → Sphincter of Oddi relaxes
Gastric contents (FFAs, AAs > CHOs) enter duodenum causing release of cholecystokinin (CCK)
CCK causes gall bladder to contract
What happens to bile salts after their role in absorption?
95% bile salts reabsorbed 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
Give 2 functions of the gall bladder in relation to bile
Stores ~50ml of bile
-Concentrates and acidifies bile
How does the gall bladder contract?
CCK(Cholecystokinin) binds to CCKA receptors & neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)
Give the sources of bilirubin
75% BR from Hb (erythrocytes) breakdown
22% from catabolism of other haemoproteins
3% from ineffective BM erythropoiesis
How much bilirubin is excreted into bile daily and what is the percentage breakdown of where it ends up
200-250mg BR excreted into bile/day
85% excreted in faeces
BR→urobilinogen→stercobilinogen→stercobilin(brown)
15% enters enterohepatic circulation
BR→deconjugated→lipophilic form
Urobilinogen
Stercobilinogen
1% enters systemic circulation & excreted by kidneys
Outline some of the causes of jaundice
