The Liver Flashcards by Alexandra Chan

How many people does liver disease affect

2 million

1/50 of all deaths

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Where is the liver

Sits in the top of the abdomen with a large proportion behind the ribcage
Predominantly in the upper right quadrant and extends in the upper left quadrants

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What are the 4 lobes of the liver

Right lobe
Left lobe
Caudate lobe
Quadrate lobe

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How many units can the liver be split into

4 or 8

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Why is it possible to damage/remove one of the 8 liver units and not damage the others

Each segment contains its own blood supply and venous drainage
Own portal vein, hepatic vein and bile duct

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What proportion of the cardiac output is delivered to the liver

25%

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Describe the dual blood supply of the liver

Liver gains substances from both artery and vein
20% is from the left and right branches of the hepatic artery
80% is from the hepatic portal vein (allows absorbed products from the gut to travel to the liver so nothing from the systemic circulation has not been passed through the liver)

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Where does the blood from the liver drain from

Drains into the inferior vena cava via the hepatic vein

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Why is the blood passing through the liver poorly oxygenated

Mixed of arterial blood and venous blood

Predominantly poorly oxygenated venous blood from the portal vein

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Describe the micro-anatomy of the liver

Morphological hexagonal lobule the size of a sesame seed

Divided into concentric centrilobular, midzonal and periportal parts

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What is the portal triad

Hepatic portal vein
Hepatic artery
Bile duct

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What are the cells of the liver

Kupffer cell
Hepatic stellate cell
Endothelial cell
Cholangiocyte
Hepatocyte

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What are the roles of the liver

Digestion
Biosynthesis
Energy metabolism
Degradation
Detoxification

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Describe hepatocytes of the liver

Makes up 80% of mass
Large cubical cells with pale and rounded nuclei
Radiates from a central vein
Receives nutrients from the sinusoids
Forms cords/sheets
Produces bile, albumin, clotting factors
Flows along canaliculus to the bile duct

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Describe the endothelial cells of the liver

Lines blood vessels and sinusoids
No basement membrane, many fenestrations, discontinuous epithelium
Very leaky to allow lipids and large molecules into hepatocytes

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Describe the cholangiocytes of the liver

Lines biliary structures

Bile duct epithelial cells

Describe the kupffer cells of the liver

Fixed phagocytes/ resident macrophages
Secretion of cytokines that promote HSC activation (proliferation, contraction and fibrogenesis)
Cytokines can promote fibrosis

Describe the Hepatic stellate cells

Vitamin A storage cells (Ito cells)
May be activated to a fibrogenic myofibroblastic phenotype, ECM production and fibrogenesis
Responds to pro-inflammatory environments to lay down excessive ECM and promote fibrosis (associated with liver cirrhosis)

What is the acinus of the liver

Cluster of cells that form a functional unit (less clearly identified)
Unit of hepatocytes divided into zones dependent on proximity to arterial blood supply:
Periportal (1)
Transition zone (2)
Pericentral (3)

Which acinus zone is most susceptible to viral hepatitis

Periportal zone 1

Which acinus zone is most susceptibility to ischaemic injury

Zone 3

What are the acini zones involved in

zone 1 - gluconeogenesis, beta oxidation, cholesterol synthesis
zone 3 - glycolysis, lipogenesis and P450 based drug detoxification

Describe glucose metabolism in the liver and what happens when during fasting

Glucose taken from the blood and stored as glycogen in the muscle and liver
When required it is broken down (muscle cannot release glucose into the blood)
fasting causes the glycogen supply to be exhausted

Explain the process of glucose metabolism in the liver

Glucose is metabolised in the muscle (glycolysis, TCA, fermentation, lactate etc.) to generate ATP
In low oxygen environments, the muscle starts producing lactate form the pyruvate formed in glycolysis
The lactate is passed to the liver and converted back into pyruvate by lactate dehydrogenase (highly energy dependent)
Gluconeogenesis converts pyruvate to glucose (uses 6 ATP)
The glucose is released from the liver for transport to the muscle

What causes the a "burnout" after exercise

Switching from glucose metabolism to other forms that do not produce as much energy for the oxygen supplied

Describe protein metabolism in the liver

1. Amino acids are released into the blood via muscle breakdown or from diet 2. Amino acids are used to make proteins in the liver e.g. plasma proteins, clotting factors, lipoproteins

What happens when certain amino acids cannot be supplied from diet

They are generated in the liver, often by transamination 1. Alanine from the diet 2. Transamination occurs to convert alanine (and alpha ketoglutarate) to glutamate and pyruvate by alanine aminotransferase (reversible reaction) AKG - glutamate, proline, arginine Pyruvate - alanine, valine, leucine Oxaloacetate - Aspartate, methionine, lysine

Describe deamination

Utilisation of amino acids by muscle is highly energy intensive (conversion of pyruvate to glucose and removal of nitrogen as urea) 1. Alanine from glutamate and pyruvate is transferred to the liver 2. Deamination with alpha keto glutarate 3. Pyruvate and glutamate production 4. Pyruvate then generates glucose and transported to muscle cells 5. Glutamate is converted to urea (4 ATP) to remove the NH2 group

Describe fat metabolism in the liver

The main fat energy store is in the adipose and liver When glycogen stores are full, the liver can convert excess glucose and AA to fat for storage 1. Triglycerides are broken down into fatty acids 2. Fatty acids transported to the liver 3. Beta oxidation to generate acetyl coA 4. TCA in the liver

Describe ketone body formation in the liver

1. Triglyceride is broken down into fatty acids 2. Fatty acids transported to the liver 3. Beta oxidation to generate acetyl coA 4. Acetoacetate formation (ketones) 5. Transport to the blood

Describe the formation of a chylomicron in the liver

1. Glucose from the blood conversion to pyruvate and glycerol in the liver 2. Pyruvate converted to acetyl coA 3. Acetyl coA used for fatty acid and cholesterol synthesis 4. Combination of glycerol and the fatty acids to produce TAGs 5. Additions of apoproteins, phospholipids and cholesterol to form lipoproteins

What are the functions of HDL, LDL and VLDL

HDL - takes cholesterol to the liver LDL - takes cholesterol to the peripheral tissue (not produced in the liver) VLDL - transports fatty acids to tissues and is converted to LDL

What are some other functions of the liver

Storage of fat soluble vitamins (ADEK) for 6-12 months Vitamin K storage (clotting) Storage of iron as ferritin for erythropoiesis Detoxification

Describe detoxification in the liver

Phase 1 - P450 enzymes make more hydrophilic for excretion (+ more reactive) Phase 2 - attach large water soluble side chain to make it less reactive