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Lily BRS Gastro > Hepatobiliary System > Flashcards

Hepatobiliary System Flashcards

1
Q

Where is the liver?

A

Mostly in URQ just below the nipple and inside the rib cage

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2
Q

What is the morphological anatomy of the liver?

A

Sits under the diaphragm

Small gall bladder underneath right side

Falciform ligament down middle

Ligamentum teres under falciform

Two lobes; right and left, separated by the middle hepatic vein

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3
Q

What is the blood supply to the liver?

A

Inflow:

Hepatic artery 25% (oxygen rich blood to support active hepatocytes)

Portal vein 75% (mixed venous blood from GIT (nutrients,bacteria,toxins) and spleen (waste))

Outflow:

Bile

3 hepatic veins (these drain into the inferior vena cava)

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4
Q

What are the sections of the liver?

A

8segments

1: small and right next to IVC

2-8: start in top left (anatomical) and continue clockwise round

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5
Q

What is the micro morphology of the liver and the functions of the liver?

A

Morphological: lobules, portal triads

Functional: acinus, blood flow, bile flow

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6
Q

What is the structure of a hepatic lobule?

A

Hexagonal structural unit of liver tissue

Each corner consists of a portal triad (these link 3 adjacent lobules)

In the centre is a central vein: collects blood from hepatic sinusoids -> hepatic veins -> systemic venous system

Within the lobule are rows of hepatocytes: each had a sinusoid facing side and a bile cannuliculi facing side

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7
Q

What is the structure of a portal triad?

A

Branch of hepatic artery:

Brings oxygen rich blood into liver to support hepatocytes high energy demands

Branch of portal vein:

Mixed venous blood from GIT (nutrients, bacteria, toxins) and spleen (waste products)

Hepatocytes process nutrients, detoxify blood and excrete waste

Bile duct:

Bile produced by hepatocytes drains into bile cannuliculi

Coalesce with cholangiocyte lined bile ducts around lobule perimeter

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8
Q

What is a hepatic acinus?

A

Functional unit of liver

Consists of two adjacent sixths (triangles) of hepatic lobules

These share 2 portal triads

And extend into lobules as far as a central vein

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9
Q

What is the three zone model? (Hepatic acinus)

A

Acinus is split into three zones. 1 in the middle, 2 further out on either side, 3 furthest out and next to the central vein

Blood enters zone 1 through the portal triad

Drains out of zone 3 Via the central vein

Hepatocytes bear outer hepatic lobule (zone 1) recieve early exposure to blood contents (good Oxygen) (lots of bad too (toxins))

1: high o2, high toxin risk
2: middle o2, middle toxin risk
3: low o2, low toxin risk

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10
Q

What are all the liver cell types?

A

Sinusoidal endothelial cells

Kuppfer cells

Hepatic Stellate cells

Hepatocytes

Cholangiocyte

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11
Q

What at sinusoidal endothelial cells?

A

No basement membrane

Fenestrated

Allow lipids and large molecule movement to and from hepatocytes

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12
Q

What are kuppfer cells?

A

Sinusoidal macrophage cells

Attached to endothelial cells

Phagocytosis: eliminate and detoxify substances arriving in liver from portal circulation

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13
Q

What are hepatic stellate cells?

A

Aka ito cells or perisinusoidal

Exist in dormant state

Store vitamin A in liver cytosolic droplets

Activated in response to liver damage -> proliferate, chemo tactic and deposit collagen in ECM

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14
Q

What are hepatocytes?

A

80% of liver mass

Cubical

Synthesis (albumin, clotting factors, bile salts)

Drug metabolism

Recieve nutrients and building blocks from sinusoids

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15
Q

What are cholangiocytes?

A

Secrete HCO3- and H2O into bile

Found at the end of bile cannuliculi

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16
Q

What is the function of hepatocytes?

A

Metabolic and catabolic:

Synthesis and utilisation of carbohydrates, lipids and proteins

Secretory and excretory:

Synthesis and secretion of proteins, bile and waste products

Detoxification and immunological functions:

Breakdown of ingested pathogens and processing of drugs

17
Q

What is the role of the liver in carbohydrate metabolism?

A

Glycolysis in muscle cells can produce pyruvate

This can either be used aerobicay in the TCA cycle and oxidative phosphorylation, or anaerobically in fermentation to make lactate

The liver can then make this lactate back into pyruvate in the cori cycle using lactate dehydrogenase

This pyruvate can then take part in gluconeogenesis to make glucose

18
Q

What is the role of the liver in protein synthesis?

A

Amino acids travel to the liver (in the fed state from diet and in the fasted state from muscle breakdown)

In the liver amino acids are made into proteins which are then secreted

Eg. Plasma proteins, clotting factors, lipoproteins

19
Q

What is the role of the liver in synthesis of non essential amino acids?

A

Amino acids form the diet such as alanine are carried to the liver

Here they can be combined with keto acids such as alpha keto glutamate

This reversibly makes pyrivate and glutamate (of another aa)

This is transamination

Dofferent keto acids can be converted into multiple amino acids depending on the transaminase enzyme

a-keto glutarate -> glutamate, proline, arginine

Pyruvate -> alanine, valine, leucine

Oxaloacetate -> aspartame, methionine, lysine

20
Q

What is the problem solved by the glucose-alanine cycle?

A

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 liver (glucose-alanine cycle)

21
Q

What is the glucose-alanine cycle?

A

Glutamate (from aa breakdown) and pyruvate (from glycolysis) can undergo deamination to form alanine

Alanine can then be used in the liver to combine with alpha keto glutarate to make pyruvate (which can be used to make glucose)
And glutamate

The pyruvate is used to make glucose which can be used in glycolysis in muscle

The glutamate can be turned into urea, then into the blood where it is excreted

22
Q

What is the role of the liver in triglyceride metabolism?

A

Fat is the main energy store in the body. It is stored in adipose and liver. When glycogenstores are full, the liver converts excess glucose and amino acids into fat for storage

In adipose, triglycerides are broken down into fatty acids

In the liver the fatty acids undergo beta oxidation to form acetyl CoA

This then entered the TCA cycle

Or 2 acetyl CoA can be used to make acetoacetate, this can be used as an energy source in tissues

23
Q

What is the role of the liver in lipoprotein synthesis?

A

Glucose in the liver can be made into glycerol. Or pyruvate, which can be used to make Acetyl CoA, which can make cholesterol and fatty acids

The glycerol can be used to make tri acyl glyceride

This can be combined with apoproteins and phospholipids and cholesterol to make lipoproteins

24
Q

What are lipoproteins?

A

VLDL - transports fatty acids to tissues

LDL- bad cholesterol - transports cholesterol to tissues

HDL - empty, picks up excess cholesterol

The role of cholesterol: making steroid hormones, cell membrane integrity

25
Q

What is the storage function of the liver?

A

Storage of:

Fat soluble vitamins - A,D,E,K

Storage lasts around 6-12 months (except vitamin K which is essential for blood clotting)

Storage of iron as ferritin

Available for erythropoiesis

26
Q

What is the role of the liver in detoxification?

A

Detoxification of xenobiotics

P450 enzymes

Phase 1- modification - more hydrophilic

Phase 2 - conjugation - attach a water soluble side chain to make less reactive

27
Q

What is the morphological anatomy of the biliary system?

A

Right and left hepatic ducts of liver

Gall bladder (bile stored)

Bile duct and sphincter

Ampulla and sphincter

28
Q

What is the composition of bile?

A

97% water

  1. 7% bile salts
  2. 7% inorganic salts
  3. 2% bile pigments (bilirubin/bilivirden)
  4. 15% fatty acids
  5. 1% lecithin

Fat, cholesterol, alkaline phosphatase, drug metabolites, trace metals

29
Q

What are the uses of bile?

A

Cholesterol homeostasis

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

Excretion of: xenobiotics, cholesterol metabolites, adrenocortical and other steroid hormones, alkaline phosphatase

30
Q

What is the production of bile like?

A

500 mls per day

Yellow/green due to bilirubin/biliverdin

Hepatocytes: 60% of total bile

Primary secretion - bile secretions reflect serum concentrations, secretion of bile salts, lipids and inorganic ions

Cholangiocytes: 40% of total bile

Secondary modification - alteration of pH. H2O drawn in by osmosis via para cellular junctions. Luminal glucose and organic acids reabsorbed. HCO3- (bicarbonate) and Cl- actively secreted into bile by CFTR (cystic fibrosis transmembrane regulator). IgA exocytosed

31
Q

What are biliary transporters?

A

Biliary excretions of bile salts and toxins performed by biliary transporters on apical surface and basolateral membranes of hepatocytes and cholangiocytes

Look at pp for examples but let’s be honest I’m never gonna remember them

32
Q

What are bile salts?

A

Synthesised from cholesterol

Sodium and potassium of bile salts conjugated in the liver to glycine and taurine

2 primary bile acids synthesised in liver: cholic acid and chenodroxycholicacid

2 secondary bile acids produced from primary acids by gut bacteria: deoxycholic acid and lithocolic acid

(Cholic -> deoxycholic. Chenodeoxycholic -> lithocolic)

33
Q

What is the function of bile salts?

A

Reduce surface renationalise of fats

Emulsify fat prior to digestion and absorption

Bile salts for Micelles:

Steroid nucleus planar- amphipathic (two faces)

1 is hydrophilic, faces outwards and dissolves in water

1 is hydrophobic , faces in and dissolves in fat

FFS and cholesterol inside

34
Q

How is bile flow and secretion regulated?

A

Between meals sphincter of oddi closed -> bile diverted into gall bladder for storage

Eating -> sphincter of oddi relaxes

Gastric contents enter duodenum causing release of cholecystokinin (CCK)

CCK causes gall bladder to contract

35
Q

What is interohepatic circulation?

A

95% of bile salts reabsorbed from terminal ileum

By Na+/bile salt cotransporter sodium potassium ATPase system

5% converted into secondary bile acids in colon: - deoxycholic acid absorbed. - 99% lithocolic acid excreted in stool

Absorbed bile salts back to liver (via portal vein) and re excreted in bile

36
Q

What are the functions of the gall bladder?

A
  1. Store 50 mls of bile. Concentrates and acidifies bile
  2. Gall bladder contraction triggered by CCK

Binds to CCKa receptors and neuronal plexus of GB wall

37
Q

What is bilirubin?

A

Free BR is H2O insoluble, yellow pigment

75% from haemoglobin breakdown

22% from catabolism of other haemoproteins

3% from immefective BM erythropoiesis

Free BR is bound to albumin in blood, most dissociates in the liver and enters hepatocytes

BR conjugated with 2 molecules of UDP-glucuronate -> bilirubin diglucuronide

This is secreted across concentration gradient into biliary canaliculi -> GIT

38
Q

What happens to bilirubin?

A

200-250 mg excreted into bile/day

85% excreted in faeces:

BR -> urobilinogen -> stercobilinogen -> stercobilin (brown compound)

15% enters enterohepatic circulation

BR -> deconjugated -> lipophilic form

1% enters systemic circulation and is excreted by kidneys

Lily BRS Gastro (10 decks)

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