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Alimentary > S1: The Liver - An Introduction to its Functions > Flashcards

S1: The Liver - An Introduction to its Functions Flashcards

1
Q

What is the largest gland in the body and the 2nd largest organ in the body?

A

Liver

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2
Q

What aspects of the structure of the liver affect its function?

A
  • Its vascular system
  • The biliary tree (system of ducts that transport bile out of liver into the small intestine)
  • 3D arrangement of liver cells within the vascular and biliary system
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3
Q

What divides the liver into the right and left lobe?

A

The falciform ligament

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4
Q

What is the top and bottom lobe of the liver called?

A

Caudate (top) and Quadrate (bottom) lobe.

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5
Q

What is the green sac underneath the liver called?

A

The gall bladder with the common bile duct delivering bile to the duodenum

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6
Q

Describe the blood supply to the liver

A
  • Each lobe receives its own blood supply
  • 75% of the blood supply to the liver is from the portal vein (i.e. blood returning from the GI tract, full of digested products
  • 25% is from the hepatic artery straight from the aorta
  • Venous drainage is through hepatic vein into the vena cava
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7
Q

What are the two primary cells of the liver?

A
  • Hepatocytes (60%) which perform most metabolic functions
  • Kupffer cells (30%) are a type of tissue macrophage (remove aged/damaged RBC, bacteria, viruses)

Other cells are liver endothelial cells and stellate cells

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8
Q

What is the functional unit of the liver?

A

The hepatic lobule

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9
Q

What is the hepatic lobule?

A

They are hexagonal plates of hepatocytes around a central vein (hepatic venule). At each six corners is a triad of branches of the portal vein, hepatic artery and bile duct.

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10
Q

How does blood enter the hepatic lobules?

A

Blood enters the lobules through branches of the portal vein and hepatic artery, it then flows through small channels called sinusoids that are lined with primary liver cells (i.e. hepatocytes).

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11
Q

What do hepatocytes do?

A

The hepatocytes remove toxic substances, including alcohol, from the blood which then exits the lobule through the central vein (hepatic venule).

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12
Q

Compare the direction of blood flow to bile flow at the hepatic lobule

A

Flow of blood (from hepatic artery and portal vein) is in the opposite direction to bile flow.

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13
Q

Where is bile secreted?

A

Bile is secreted by hepatocytes into a series of channels that lie between cells called canaliculi

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14
Q

Describe to biliary system

A

Bile secreted flows into small ducts (dultule) and then into large ducts (2 R + L hepatic ducts) that join to form the common hepatic duct. The cystic duct from the gall bladder then joins to form the common bile duct.
- The bile can flow from the liver to the common bile duct into the duodenal papillae (or flow down cystic duct into the gallbladder)

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15
Q

How does the liver’s microstructure support its role?

A
  • Massive surface area for exchange of molecules
  • Sophisticated separation of blood from bile
  • Specific positioning of pumps to achieve specific localisation of materials (at cellular level)
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16
Q

What is the protective barrier in the liver?

A

Kupffer cells which are phagocytic macrophages.

  • They are found in the sinusoids and filter the portal blood.
  • Very effecting at cleansing the blood

The kupffer cells remove gut bacteria/antigens from the blood so less than 1% of bacteria entering into the portal blood succeeds in passing through the liver into systemic circulation

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17
Q

What is bile?

A
  • Complex fluid consisting of water, electrolytes and organic molecules
  • Greenish-yellow in colour

Organic molecules found in bile include:

  • Bile acids
  • Cholesterol
  • Bilirubin
  • Phospholipids
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18
Q

What are the two stages bile is secreted in?

A
  1. By Hepatocytes into canaliculi which consists of bile salts, cholesterol and other organic
  2. Epithelial cells lining the bile ducts where bile is modified by water and Na+/bicarbonate rich secretion. The second secretion is stimulated by the hormone secretin.
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19
Q

What controls bile entry into the duodenum?

A

Sphincter of Odii

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20
Q

From the common bile duct, what are the 2 routes that bile can take?

A
  1. Diverted via cystic duct to be concentrated and stored in the gall bladder.
  2. Bile enters the major duodenual papilla (opening of bile duct and pancreatic duct into the duodenum)
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21
Q

How do gall stones form?

A

Cholesterol is insoluble in aqueous solution but is made soluble in bile.

In abnormal conditions, the cholesterol precipitates out of solution forming gallstones.

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22
Q

What might cause gall stones?

A
  • High fat diet (leading to increased synthesis of cholesterol)
  • Inflammation of the gallbladder epithelium which changes the absorptive characteristics of the mucosa (excessive absorption of H2O and bile salts leads to cholesterol concentrating)
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23
Q

Which gender is gall stones more common with?

A

It is more common in women than men (risk factors include obesity, excess oestrogen e.g. From pregnancy)

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24
Q

Where do gall stones form?

A

Gallstones can form anywhere along the biliary tract.

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25
Q

What are bile acids derivative of and where do they form?

A

Bile acids are derivatives of cholesterol and made in hepatocytes

26
Q

Describe the formation of bile acids

A

Cholesterol is converted into bile acids cholic acid and chenodeoxycholic acid.

These are conjugated with amino acids (either glycine/taurine) to make it more soluble.

This conjugated form is secreted into cannaliculi.

The intestinal bacteria convert it to secondary bile acids.

27
Q

Explain the enterohepatic circulation of bile acids

A

Bile acids from the liver/gallbladder are secreted into the small intestine where they play a role in fat absorption.

  • Most of the bile acids are reabsorbed back into the blood at the terminal ileum
  • They are then taken back up to the liver in the heptatic portal vein where they are taken up into hepatocytes
  • They are then resecreted in new bile

Bile acids are therefore recirculated 6-8 times a day. Only about 5 % is lost in faeces.

28
Q

What is the function of bile?

A
  • It is essential for fat digestion and absorption via emulsification
  • Bile and pancreatic juice neutralises gastric juice as it enters the small intestine which hence aids digestive enzymes
  • It eliminates waste products in the blood in particular bilirubin and cholesterol
29
Q

The liver metabolises and excretes many compounds into bile.

Which of these is most important?

A

Bilirubin

  • it is a yellow pigment formed from the breakdown of haemoglobin
  • It is useless and toxic
  • Made in large quantities so must be eliminated
30
Q

What are aged/damaged RBC destroyed?

A

Dead/damaged RBC are digested by macrophages throughout the body (e.g. kupffer cells) and predominantly in the spleen.

  • The Fe2+ is recucles and globin chains are catabolised into various amino acids and then reused.
  • The haem cannot be recycled so it converted into bilirubin.
31
Q

Describe the formation and elimination of bilirubin

A
  • Haem is converted into free bilirubin and released into plasma
  • It is carried bound to albumin
  • The bilibrubin is then stripped of albumin and absorbed into hepatocytes
  • They are then conjugated with glucoronic acid
  • The conjugated bilirubin is secreted into bile and metabolised by bacteria in the intestinal lumen and subsequently eliminated into faeces/urine

The major metabolite in faeces is stercobilin giving it a brown colour and in urine it is yellow urobilin and urobilinogen.

32
Q

What causes jaundice?

A

Excessive quantities of free or conjugated bilirubin accumulate in ECF

This causes yellow discolouration of the skin, sclera (white part of eye) and mucous membranes.

33
Q

What are the three types of jaundice?

A
  1. Pre-hepatic
  2. Heptatic
  3. Post-hepatic
34
Q

What is pre-hepatic jaundice?

A

Increased haemolysis can cause excess free bilirubin and the liver doesn’t have the capacity to process/conjugate it. Unconjugated bilirubin cannot be excreted in urine and remains in circulation. e.g. neonatal jaundice

35
Q

What is hepatic jaundice?

A

Problems with hepatocytes cause an increase in uncongugated and conjugated serum bilirubin

36
Q

What is post-hepatic jaundice?

A

Passage of conjugated bilirubin into the duodenum is blocked (e.g. gallstones, carcinoma of pancreas/bile ducts) and it leaks into circulation and urine making it very dark.

37
Q

What can damage hepatocytes and cause hepatic jaundice?

A

Damage to hepatocytes and biliary tree from cirrhosis, drugs, viral infections – hepatitis A,B,C,E; Gilberts syndrome

38
Q

What is glucose buffer function?

A

Carbohydrate metabolism is critical for all animals to maintain glucose in blood within a narrow range.

39
Q

How does liver maintain the glucose buffer function?

A

Glycogenesis
Glycogenolysis
Gluconeogenesis
Glycolysis

40
Q

What is glycogenesis?

A

Excess glucose entering blood after meal rapidly removed and stored as glycogen (stimulated by insulin). Liver stores large amounts of glycogen.

41
Q

What is glycogenolysis?

A

When blood glucose falls, the liver activates other pathways to break glycogen and return glucose to blood (stimulated by glucagon and adrenaline)

42
Q

What is gluconeogenesis?

A

When hepatic glycogen reserves become exhausted, blood glucose concentrations are still maintained, glucose is synthesised from lactate, amino acids and glycerol (from triglycerides)

43
Q

What is glycolysis?

A

Process by which glucose is converted into pyruvate releasing energy

44
Q

What are the three sources of fatty acids for metabolism?

A
  1. Dietary source of triglycerides
  2. Triglycerides stored in adipocytes
  3. Triglycerides synthesised in the liver
45
Q

Explain the ways that fat is metabolised in the liver

A
  1. Triglycerides are oxidized in hepatocytes to produce energy.
    1. Lipoproteins are synthesised in the liver
    2. Excess carbohydrates and proteins are converted into fatty acids and triglycerides and hence stored in adipose tissue
  2. There is synthesis of large quantities of cholesterol and phospholipids, some packaged as lipoproteins.
46
Q

Explain protein metabolism in the liver

A
  • Deamination and transamination of amino acids
  • Convertion of non-nitrogenous part of the amino acid to glucose and lipids
  • Remaining nitrogen pool can be built into tissue protein or put into the urea cycle
  • Synthesis of nearly all plasma proteins
47
Q

Why is the synthesis of urea important?

A

It removed ammonia from the body

Ammonia is very dangerous and can interfere with GABA and dopamine - can depress cerebral flood flow and cerebral o2 consumption leading to hepatic encephalopathy

48
Q

List various toxic substances metabolised and excreted by the liver

A

Bilirubin
Ammonia
Hormones e.g. all steroid hormones (androgens, oestrogens, cortisol, aldosterone) and thyroxine are inactivated by conjugation in the liver and then excreted
Drugs and exogenous toxins e.g. aspirin, paracetamol and ethanol.

49
Q

What are the two phases where the liver metabolises drugs and hormones?

A

Phase 1
Oxidation/reduction reactions occur in the smooth ER and catalysed by a family of cytochrome p450 enzymes –> common feature of reactions is to make substrate more polar

Phase 2
Conjugation in order to make the drug water soluble to be eliminated- conjugation with glucuronyl most important

50
Q

What is ‘phase 3’? (not always referred to as a phase)?

A

Elimination of conjugated substance into blood or bile using ATPase pumps

51
Q

What is paracetomol also called?

A

Acetaminophen

52
Q

What are the 3 pathways that paracetomol is metabolised in?

A

Glucoronidation
Sulfation
N-hydroxylation and dehydration,

53
Q

What does paracetamol having a narrow therapeutic index mean?

A

Accidental overdose is common due to liver only having a limited capacity of enzymes to break down paracetamol.

54
Q

What are the two types of gallstones?

A

Cholesterol (80%)

Pigment (20%)

55
Q

How is alcohol metabolised?

A

Alcohol cannot be stored so must be oxidised in the liver.

Ethanol -*—> Acetylaldehyde –**–> Acetate

  • = Alcohol dehydrogenase
  • *= Acetaldehyde dehydrogenase (ALDH2)
56
Q

List some liver diseases caused by prolonged heavy drinking

A

Fatty liver – Alcohol abuse can lead to the accumulation of fat within liver cells (reversible)
Alcoholic hepatitis – Excessive use of alcohol can cause acute and chronic hepatitis (inflammation of liver, recovery possible)
Alcoholic cirrhosis – Liver cells damaged and replaced by scar formation (irreversible)

57
Q

Explain liver regeneration

A
  • Adult hepatocytes are long lived and normally do not undergo cell division ie they are in G0 phase of cell cycle
  • After partial hepatectomy (removal of 70% of liver) or in response to toxic injury, they rapidly re-enter cell cycle and proliferate
  • This regeneration is rapid and proliferation stops once the original mass of the liver is established
58
Q

Name some blood clotting factors synthesised in the liver

A

Blood clotting factors are synthesised in the liver, these include:
-Fibrinogen
-Prothrombin
-Nearly all the other factors e.g. V, VI, IX, X, XII

59
Q

What vitamin is essential for the formation of pro-thrombin and factors?

A

Vitamin K

60
Q

What cells are important for storage of fat soluble vitamins A D E K in the liver?

A

Stellate cells (type of hepatocytes)

61
Q

What does the liver store?

A

Vitamin B12

Folate

62
Q

What do liver function tests do?

A

They check certain enzymes and proteins in the blood and can be used to indicate various conditions e.g. Hepatitis

Alimentary (18 decks)

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