Gastro - Hepatobilary tract Flashcards

1
Q

Describe the anatomical location of the liver

A

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.

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2
Q

What ligaments exist in the liver

A

Falciform ligament - anterior fold of peritoneum

Ligamentum teres – umbilical vein foetal remnant

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3
Q

How are the lobes of the liver seperarated

A

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

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4
Q

Describe the inflow and outlow if hepatic blood

A

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

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5
Q

Describe the segmentation of liver components

A

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

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6
Q

Describe the structure of a hepatic lobule

A
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
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7
Q

Describe the structure of a portal triad

A

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

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8
Q

Describe the structure of a hepatic acinus

A

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

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9
Q

Why is the acinus important? Explain answer

A

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 ↓

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10
Q

Sinusoidal endothelial cells

A

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

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11
Q

Kuppfer cells

A
Kuppfer cells
Sinusoidal macrophage cells
Attached to endothelial cells
Phagocystosis
Eliminate & detoxify substances arriving in liver from portal circulation
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12
Q

Hepatic stellate cells

A

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

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13
Q

Hepatocyte

A

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

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14
Q

Cholangiocyte

A

Cholangiocyte

Secrete HCO3- & H2O into bile

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15
Q

Functions of hepatocytes

A

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

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16
Q
Define :
Glycolysis 
Glycogenesis
Glycogenolysis 
Gluconeogenesis
Lipolysis
Lipogenesis
A

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)

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17
Q

Describe the Cori cycle

A

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

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18
Q

Where do AA come from in different metabolic states

A

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

19
Q

Describe some key Transaminiation reactions

A

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

20
Q

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

A

To convert pyruvate to glucose requires energy

To remove nitrogen as urea requires energy

21
Q

Glucose-alanine cycle

A

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.

22
Q

Triglyceride metabolism

A
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
23
Q

Lipoprotein, structur, types

A

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)

24
Q

Pyruvate glutamate ATP production

A

Pyruvate = 6ATP glutamate = 4 ATP

25
Q

Describe Fat as a fuel

A

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

26
Q

Storage of which molecules occurs in the liver

A
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
27
Q

Describe the Biliary system

A
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.
28
Q

Process of Detoxification

A
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

29
Q

Bile composition

A
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
30
Q

Bile uses

A

Cholesterol homeostasis

Absorption of lipids & lipid soluble vitamins (A, D, E, & K)

Excretion of:
xenobiotics/drugs
cholesterol metabolites
adrenocortical & other steroid hormones
Alkaline phosphatase
31
Q

Bile production, composition, synthesis

A
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
32
Q

Biliary transporters

A

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.

33
Q

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

A
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
34
Q

Function of bile salts

A

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

35
Q

Regulation of Bile flow

A

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

36
Q

Enterohepatic circulation

A

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

37
Q

Functions of gallbladder

A

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)
38
Q

Bilirubin

A

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

39
Q

Bilirubin excretion

A
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
40
Q

what are Gall stones

A

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.

41
Q

Endoscopic retrograde cholangopancrætography

A

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).

42
Q

Sphincterotomy

A

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

43
Q

PCT

A

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,