Gastro - Hepatobilary tract

Question 1

Describe the anatomical location of the liver

Answer 1

Liver sits at the top of the chest, the nipple being the the point of the dome and the inferior border at the right subcostal margin, protected by ribs sits in thorax.

Question 2

What ligaments exist in the liver

Answer 2

Falciform ligament - anterior fold of peritoneum

Ligamentum teres – umbilical vein foetal remnant

Question 3

How are the lobes of the liver seperarated

Answer 3

Left and right lobes separated by the middle hepatic vein extending from left IVC to the gallbladder

Question 4

Describe the inflow and outlow if hepatic blood

Answer 4

Inflow of blood – 25% arterial blood via hepatic artery – support demands of high metabolic activity of hepatocytes
75% mixed venous by portal vein – contains toxins, waste and nutrients for processing

Outflow via left, middle and right hepatic veins which join into the ICV and go towards heart directly

Question 5

Describe the segmentation of liver components

Answer 5

8 Segments, 1 behind hepatic portal vein but in front of ICV, Left side consists of 234 in a clockwise projection and 5678 on right side

Question 6

Describe the structure of a hepatic lobule

Answer 6

Hepatic lobule
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

Question 7

Describe the structure of a portal triad

Answer 7

Portal triad
Branch of hepatic artery
Brings Oz-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 cholengeocyte-lined bile ducts around
lobule perimeter

Question 8

Describe the structure of a hepatic acinus

Answer 8

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

Question 9

Why is the acinus important? Explain answer

Answer 9

Allows for the 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)
Acinus split into 3x regions
Zone 1 – O2 ↑, Toxin risk ↑
Zone 2 – O2 →, Toxin risk →
Zone 3 – O2 ↓, Toxin risk ↓

Question 10

Sinusoidal endothelial cells

Answer 10

Sinusoidal endothelial cells
No basement membrane
Fenestrated (discontinuous endothelium)
Allow lipids & large molecule movement to and from hepatocytes

Question 11

Kuppfer cells

Answer 11

Kuppfer cells
Sinusoidal macrophage cells
Attached to endothelial cells
Phagocystosis
Eliminate & detoxify substances arriving in liver from portal circulation

Question 12

Hepatic stellate cells

Answer 12

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

Question 13

Hepatocyte

Answer 13

Hepatocyte
80% of liver mass
Cubical
Synthesis e.g. albumin, clotting factors & bile salts
Drug metabolism
Receive nutrients & building blocks from sinusoids

Question 14

Cholangiocyte

Answer 14

Cholangiocyte

Secrete HCO3- & H2O into bile

Question 15

Functions of hepatocytes

Answer 15

Numerous functions including:
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

Question 16

Define :
Glycolysis 
Glycogenesis
Glycogenolysis 
Gluconeogenesis
Lipolysis
Lipogenesis

Answer 16

Glycolysis - anaerobic conversion of glucose → lactate
– (RBCs, renal medulla & skeletal muscle)
- aerobic oxidation of glucose (CNS, heart,
skeletal muscle, most organs)
Glycogenesis – synthesis of glycogen from glucose
- (liver & muscle)
Glycogenolysis – breakdown of glycogen to glucose
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)
Lipolysis – breakdown of triacylglycerols → glycerol & FFAs
Lipogenesis – synthesis of triacylglycerols (storage in fat depots)

Question 17

Describe the Cori cycle

Answer 17

Cori cycle - metabolic pathway in which lactate produced by anaerobic glycolysis in muscles is transported to the liver and converted to glucose, which then returns to the muscles and is cyclically metabolized back to lactate

Question 18

Where do AA come from in different metabolic states

Answer 18

Amino acids in fed state come from diet in fasting state via breakdown of muscles with alanine being the primary breakdown AA

Question 19

Describe some key Transaminiation reactions

Answer 19

Alanine plus alpha keto glutarate -> Glutamate plus pyruvate
Transamination
Different keto-acids can be converted into multiple amino acids depending on the transaminase enzyme (vital for production of non-essential amino acids)

Alpha- keto glutarate → e.g. glutamate, proline, arginine

Pyruvate → e.g. alanine, valine, leucine

Oxaloacetate → e.g. aspartate, methionine, lysine

Question 20

why cant a Muscle can potentially utilise amino acids to produce glucose for energy

Answer 20

To convert pyruvate to glucose requires energy

To remove nitrogen as urea requires energy

Question 21

Glucose-alanine cycle

Answer 21

Glucose-alanine cycle:
The glucose-alanine cycle transports nitrogen
to the liver from the muscle. Pyruvate produced
from anaerobic glycolysis in muscle cells is
transported to liver under the action of
aminotransferase can be converted into alanine
through transfer of from glutarate
amino group ( + Alpha-keto glutarate).
Alanine Pyruvate Glucose through
Gluconeogenesis (Alanine is a
Glucogenic amino acid,
undergoing transamination reactions). Amino
acid from alanine is transferred to alpha-keto
glutarate Pyruvate + Glutamate (Reversible
reaction).
Amino groups destined to ammonia or aspartate
for urea biosynthesis.
Nitrogen is also transported to the liver in form of
glutamine, synthesised from glutamate and
glutamine ammonia in reaction catalysed by
Ammonia released through action
synthetase
of glutaminase.

Question 22

Triglyceride metabolism

Answer 22

Triglycerides are stored within
adipocytes, and are hydrolysed by
hormone sensitive lipases into
fatty acids -5 Shuttled into the liver
by the carnitine shuttle -5
Undergo beta-oxidation
into acetyl-CoA Enters into T CA
cycle or substrate for ketogenesis.
Glycogen is the main energy
reserve stored within liver &
muscle -5 Glycogen storage at
maximum capacity results
in glucose & amino acid conversion
into triglycerides as storage within
liver & adipose tissue.
2 acetyl CoA Acetoacetate

Question 23

Lipoprotein, structur, types

Answer 23

Lipids, triacylglycerols & cholesterol are transported in circulation as
components of lipoproteins, globular micelle like particles that consist of nonpolar
core of triacylglycerols. and cholesteryl-esters surrounded by an amphpathic coating
Of protein. phospholipid & cholesterol.
Chylomicrons: Transport triacylglycerols and cholesterol from
VLDL IDL & LDL: Transport endogenous triacylglycerol’ and cholesterol from
liver to tissues (liver synthesises triacyclglycerols from excess glucose).
+ HDLs: Transport endogenous cholesterol from
Lipoprotein synthesis:
Glucose Pyruvate -+ Acetyl — CoA Fatty acids & Cholesterol
Glucose Glycerol
Glucose + 3 Fatty acids
Triacylglycerol + Apoprotein phospholipids + cholesterol
Cholesterol functions:
Ill.
Stabilisation and membrane integrity through fluid dynamics within the
phospholipid bilayer
Steroidogenesis (Mineralcorticoids, cortisol, aldosterone)
Vitamin K (Essential 6r clotting factors II,VII, IX & X)

Question 24

Pyruvate glutamate ATP production

Answer 24

Pyruvate = 6ATP glutamate = 4 ATP

Question 25

Describe Fat as a fuel

Answer 25

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

Question 26

Storage of which molecules occurs in the liver

Answer 26

``` Storage 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 copper Storage of iron as ferritin. Available for erythropoiesis ```

Question 27

Describe the Biliary system

Answer 27

``` Biliary system: Bile ductules from hepatic lobules converge into respective right and left hepatic ducts. Right & left hepatic ducts confluence at the hepatic hilum (porta hepatitis) Common hepatic duct Cystic duct arising from the gallbladder converges with common hepatic duct the Common bile duct. Common bile duct converges with main pancreatic duct at the Ampulla Of Vater (hepato-pancreatic ampulla), entry of bile and pancreatic secretions into the duodenum is regulated by the Sphincter Of Oddi. ```

Question 28

Process of Detoxification

Answer 28

``` Detoxification (xenobiotics) Occurs via P450 enzymes in two phases: Phase 1 (modification) – more hydrophilic ``` Phase 2 (conjugation) – attach water soluble side chain to make less reactive

Question 29

Bile composition

Answer 29

``` Bile composition: Water 97% Bile salts 0.7% Inorganic salts 0.7% Bile pigments (bilirubin,bilivirden) 0.2% Fatty acids 0.15% Lecithin 0.1% Fat 0.1% Cholesterol 0.06% Alkaline phosphatase … Drug metabolites Higher mw > urine Trace metals Fe, Zn, Mn, Pb, Cu ```

Question 30

Bile uses

Answer 30

Cholesterol homeostasis Absorption of lipids & lipid soluble vitamins (A, D, E, & K) ``` Excretion of: xenobiotics/drugs cholesterol metabolites adrenocortical & other steroid hormones Alkaline phosphatase ```

Question 31

Bile production, composition, synthesis

Answer 31

``` 500 mls produced each day Bile is yellow/green due to pigments such as bilirubin & biliverdin Hepatocytes Cholangiocvtes Secrete 60% of total bile Secrete 40% of total bile Primary secretion Bile secretions reflect serum concentrations • Secretion of bile salts (acids), lipids & organic ions Secondary modification Alteration of pH (alkaline electrolyte solution) H20 drawn into bile by osmosis via paracellular junctions Luminal glucose & organic acids reabsorbed HC03- & Cl- actively secreted into bile by CFTR (Cystic Fibrosis Transmembrane Regulator) • IgA exocytosed ```

Question 32

Biliary transporters

Answer 32

Biliary excretion of bile salts & toxins performed by biliary transporters on apical surface & basolateral membranes of hepatocytes + 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 → excretion of xenobiotics & cytotoxins MDR3 → phospatidylcholine.

Question 33

Key components of bile, Na and K salt conjugation, primary and secondary synthesised bile acids:

Answer 33

``` Key components of bile. (Acids = Salts) Bile acids synthesised from cholesterol Na+ & K+ salts of bile acids conjugated in liver to glycine & taurine 2x primary bile acids synthesised in liver Cholic acid Chenodeoxycholic acid 2x secondary bile acids produced from primary acids by gut bacteria Deoxycholic acid Lithocolic acid ```

Question 34

Function of bile salts

Answer 34

Function of bile salts: Reduce surface tension of fats Emulsify fat prior to its digestion & absorption Bile salts form Micelles 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

Question 35

Regulation of Bile flow

Answer 35

Regulation of Bile flow: 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

Question 36

Enterohepatic circulation

Answer 36

Enterohepatic circulation: 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

Question 37

Functions of gallbladder

Answer 37

Functions of gallbladder: 1. Stores bile (50 mls) - concentrates bile - acidifies bile 2. GB contraction triggered by CCK - Binds to CCKA receptors & neuronal plexus of GB wall (innervated by preganglionic parasympathetic fibres of vagus nerve)

Question 38

Bilirubin

Answer 38

Bilirubin: Free BR (indirect/unconjugated) = H2O-INSOLUBLE, yellow pigment Source 75% BR from Hb (erythrocytes) breakdown 22% from catabolism of other haemoproteins 3% from ineffective BM erythropoiesis 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

Question 39

Bilirubin excretion

Answer 39

``` 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 ```

Question 40

what are Gall stones

Answer 40

Gall stones are crystalline masses formed abnormally within the gall bladder or bile ducts from bilirubin, cholesterol and calcium salt. Cholecystitis: Inflammation of the gall bladder Cholelithiasis: The formation Of gall stones resulting in obstruction Within the bile ducts. Gallstone obstruction within the cystic duct causes Mirizzrs syndrome. Obstructions can occur Within Cystic duct. common bile duct. hepat0Dancreatic duct. and -5 Pancreatitis (Obstruction to outflow Of pancreatic secretions). cholaringitis: associated With the the common bile duct.

Question 41

Endoscopic retrograde cholangopancrætography

Answer 41

Endoscopic retrograde cholangopancrætography (ERCP): A procedure used to diagnose diseases Of the gallbladder, biliary system, pancreas & liver. The procedure identifies upstream through the main pancreatic duct, common bile duct towards the biliary system in comparison to entrance through the ampulla Of Vater Within the Wires can be inserted into the common bile duct to assist With the removal Of Obstructive bile stones within the common bile ducts, this can be identified using contrast dyes (cholangiogram) (Obstruction black).

Question 42

Sphincterotomy

Answer 42

Sphincterotomy: Small incision in the Sphincter Of Oddi within the Ampulla Of Vater, can help remove small gallstones. Stent placement Stent is a drainage tube that is placed in the bile duct or the pancreatic duct to hold the duct open, allowing it to drain Gallstone removal: ERCP remove gall stones from bile duct not gallbladder itself

Question 43

PCT

Answer 43

PCT: The point of entry of the needle is usually planned by using ultrasound guidance (increasingly used worldwide). A direct fluoroscopic approach was described initially and is still used commonly. A long two-part needle (approximately 15 cm) 22 G is inserted under ultrasound guidance into one of the peripheral ducts; after removing the needle stylet one can observe bile reflux at the needle hub or inject a small amount of contrast to confirm duct puncture on fluoroscopy. Once a satisfactory position of the needle is confirmed, an adequate amount of contrast material is injected and various projections of the biliary tree are obtained to evaluate the obstructive pathology. Images are taken in PA, RAO and LAO views,