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M202 > W30 Liver Biology (MAH) > Flashcards

W30 Liver Biology (MAH) Flashcards

1
Q

What are the main functions of the liver?

A
  • Energy metabolism
  • Bile production & bilirubin metabolism
  • Fat-soluble vitamin storage and/or metabolism
  • Detoxification and clearance
    -Drug metabolism (Cyp P450)
    -Urea cycle (aa metabolism)
    -Ethanol
    -RBCs
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2
Q

What are some other functions of the liver?

A
  • Thyroid hormone function - deiodination of T4 to T3
  • Synthesis of nearly every plasma protein in the body, some examples include albumin, binding globulins, protein C, protein S, and all the clotting factors of the intrinsic and extrinsic pathways besides factor VIII.
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3
Q

What is bile made of?
Where is bile made, stored and secreted?

A
  • Made of bile acids, and bilirubin, cholesterol and water
  • Made and secreted from the liver, stored in the gall bladder
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4
Q

Liver anatomy:
How many lobes and ligaments?
What are the names of the:
lobes?
ligaments?

A

4 lobes and 5 ligaments
porta hepatis/ portal triad

Lobes:
Caudate
Left and Right
Quadrate

Ligaments:
Triangular (Left and Right)
Round
Coronary
Falciform

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5
Q

Liver Histology
What is the functional unit of the liver?
structure?

A

=Hepatic lobule
* Each lobule is hexagonal and a portal triad sits at each corner of the hexagon.
* The foundation of the lobule is composed of hepatocytes
* Based on function and perfusion, hepatocytes are divided into 3 zones.

Sinusoids (porous blood vessels) drain into central vein- hepatic veins- inferior vena cava

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6
Q

The liver is a unique organ due to its dual blood supply; which components are involved?

A
  1. Portal vein (approximately 75%)
    - nutrient rich blood from GI tract
  2. Hepatic artery (approximately 25%)
    - O2 rich blood from heart
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7
Q

What functions are Hepatocytes involved in? (7)
What is bile made up of

A

The primary functional cell in the liver

  1. Glucose Homeostasis (Glycogenesis, Glycogenolysis)
  2. Store vitamins A, D, E, K, B12 and minerals,iron & copper
  3. Deamination of aa – remove NH3
  4. Synthesise albumin & clotting factors
  5. Regulation of lipoprotein synthesis (VLDL and HDL)
  6. Regulate lipid metabolism (FA - B oxidation – ATP)
  7. Bile synthesis (digestion, absorption of fats & fat-soluble vitamins)
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8
Q

What metabolism is the liver involved in? (4)

A

Carbohydrate metabolism:
* The liver is involved in glycogenesis, glycogenolysis, and gluconeogenesis.

Fatty acid metabolism:
* The liver can esterify free fatty acids with glycerol-3-phosphate to produce triglycerides.
* The liver also metabolises fatty acids through β–oxidation and makes ketones.
* Cholesterol is synthesised in the liver.

Amino acid metabolism:
* The liver can catabolise amino acids or use them for gluconeogensis.
* The liver synthesises much of the body’s non–essential amino acids.

Proteins:
* Almost all plasma proteins are synthesised in the liver

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9
Q

Lipid metabolism in the liver:

A

The liver is the main site of fatty
acid and cholesterol metabolism.

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10
Q

Alcohol Metabolism

A
  • Alcohol is absorbed from both the stomach and the intestine.
  • It is initially converted by gastric cells and by hepatocytes into acetaldehyde, a toxic substance.
  • In turn, this is metabolized to acetate which is then converted to acetyl–CoA to enter the citric acid cycle.
  • There are two other pathways for the conversion of alcohol to acetaldehyde but these normally make much smaller contributions to alcohol catabolism. However, the brain cells lack ADH (alcohol dehydrogenase) and use catalase to convert the alcohol to acetaldehyde.
  • In the mitochondria, the formation of NADH provides additional electrons to the electron transport chain.
  • The net effect of alcohol metabolism is to provide 29 kJ (7 kcal)/g of energy. This compares with 37kJ/g from fat and 16kJ/g from carbohydrate or protein catabolism.
  • All adults are not equally equipped to catabolize alcohol. Rapid formation of acetaldehyde, which is highly toxic, by a variant of ADH results in facial flushing, nausea, and a rapid heart rate.
  • The fetus lacks ADH and so metabolizes any alcohol entering the fetal circulation from the mother very slowly
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11
Q

Ethanol cycle
The liver metabolizes ethanol through 3 enzymatic pathways:
What are they?

A
  1. Alcohol dehydrogenase (ADH)
  2. Cytochrome p450
  3. Catalase in peroxisomes

Max metabolism 170g/day
Rate limiting steps: ADH (regulated by
availability of NAD)

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12
Q

Amino acid synthesis

A
  • Amino acids are transported to the liver during digestion and most of the body’s protein is synthesised here. If protein is in excess, amino acids can be converted into fat and stored in fat depots, or if required, made into glucose for energy by gluconeogenesis
  • Transamination using transaminase or
    aminotransferase [transfer of amine group]
  • aa Metabolism
  • Oxidative deamination
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13
Q

Protein synthesis:

A
  1. Albumin (50% of all proteins)&raquo_space;transportation of hormones, drugs etc, maintains osmolarity
  2. Immune proteins&raquo_space;c-reactive protein, complement C1-9
  3. Hormones&raquo_space; IGFs, thrombopoietin (platelets), angiotensinogen (RAAS)
  4. Clotting factors&raquo_space; prothrombin & fibrinogen (repair blood vessels)
  5. Anticoagulants&raquo_space;antithrombin & α2 macroglobulin (prevent clotting)
  6. Carrier proteins&raquo_space;transferrin (Fe), IGFBP
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14
Q

What are the Coagulation factors produced by the liver?

A
  • Vit K-dependent factors: II
    (prothrombin), VII, IX, X
  • Fibrinogen
  • Factor V
  • Factor VIII
  • Factor XI, XII, XIII
  • Antithrombin III
  • Plasminogen
  • Protein C , S
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15
Q

Thyroid hormone functions? (6)

A
  1. Conversion of Thyroxine (T4) to Triiodothyronine (T3)
  2. Inactivation of Thyroid Hormones
  3. Thyroid Hormone Metabolism and Excretion
  4. Regulation of Thyroid Hormone Levels
  5. Synthesis of Thyroid Binding Proteins
  6. Impact on Cholesterol Metabolism
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16
Q

The liver as a storage organ:

A
  • Fat–soluble vitamins:
    -Vit A (1–2 years’ supply)
    -Vitamin D is stored mainly in adipocytes - can be several years supply, depending on the amount that has been synthesized in skin and ingested in the diet.
  • several months supply of E and K.
  • The water–soluble vitamins are not stored to any extent. The exception is B12 (3–5 years’ supply)
  • The liver also stores iron and copper.
  • The body regulates iron absorption as iron is only lost from the body to any extent through blood loss.
  • If the control of iron absorption is inadequate, as in the inherited disease, hemochromatosis, then too much iron accumulates in the liver and damages the cells leading to cirrhosis of the liver.
17
Q

Hepatocyte

A

M202 (72 decks)

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