Introduction to the Liver Flashcards

1
Q

Describe the anatomy and structure of the liver

Describe the blood supply and drainage of the liver

A
  • The largest gland in the body. Its major aspects are the vascular system, biliary tree, and 3d arrangement of Hepatocytes with the vascular and biliary systems.

The biliary system is the system of ducts to transport the bile out of the liver and into the small intestine.

  • 75% comes from the HPV and the remaining 25% is from the Proper hepatic artery. Blood is drained by hepatic vein, before going into the IVC.
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2
Q

What are the cells of the liver?

Describe the structure of the Hepatic Lobule

Describe where the bile comes from and goes

LOOK AT DIAGRAMS!

A
  • The 2 main cells in the liver are the Hepatocytes and Kupffer cells (type of macrophage that carries out phagocytic activity). Other cells present are liver endothelial and stellate cells.
  • At each corner of the hexagon is a ‘3 lane structure’, which consists of a branch of the HPV, Hepatic artery and Bile duct. Blood enters the lobules through the branches of the HPV and Hepatic artery, flowing through channels called Sinusoids. As blood passes, the hepatocytes remove toxic substances like alcohol, from the blood, before it goes into the central vein.
  • Bile flows in the opposite direction (away from central vein) into the bile duct.
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3
Q

How does the liver’s microstructure support its role?

What is the role of the Kupffer cells? Where are they found?

A
  • Large surface area - efficient exchange
    Distinct separation of blood from bile
  • Found in sinusoids - Work as the liver’s protective barrier. As blood flows through the sinusoids, these cells remove the gut bacteria and antigens. So, a very small number of bacteria from the HPV can survive past the liver.
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4
Q

What is Bile?

How is Bile secreted?

A
  • Complex fluid of water, electrolytes and organic molecules. The organic molecules include bile acids, cholesterol, bilirubin, phospholipids.
  • Secreted in 2 stages:
    1. By Hepatocytes - bile salts, cholesterol, lechthin etc.
  1. By Epithelial cells of the bile duct - large watery solution of Na+ and HCO3- - its stimulated by Secretin in response to ACID in the duodenum; will neutralise acid.
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5
Q

Describe the pathways that the bile can take after its production

What sphincter controls the entry of the common bile duct into the duodenum?

What stimulates the release of bile from the gallbladder?

LOOK AT DIAGRAM!

A
  • Bile is secreted by the hepatocytes, travelling down the Canaliculi in the hepatic lobule before draining into the hepatic ducts. The hepatic ducts go into the common bile duct.

The common bile duct can go directly into the duodenum OR can be diverted into the cystic duct to reach the gallbladder, where its concentrated and stored.

  • Sphincter of Oddi
  • Cholecystokinin (CCK) - in response to FAT in the duodenum.
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6
Q

What are Gallstones?

What are the 2 types of gallstones?

What causes this condition?

What are the risk factors?

Why can they lead to many other conditions?

A
  • Abnormal condition caused by chemical imbalance in the gallbladder
  • Cholesterol (80%) and Pigment (20%) stones
  • • High fat diet - ↑Synthesis of Cholesterol
    • Inflammation of gallbladder epithelium - changes absorptive characteristics of mucosal layer - Excessive water and bile salts absorption = cholesterol concentrates.
  • More common in women than men due to obesity, excess oestrogen, HRT
  • Can form anywhere along the biliary tree = obstruction
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7
Q

How are Bile acids formed?

LOOK AT DIAGRAM!

A

From Cholesterol in Hepatocytes:

  1. Cholesterol → Cholic and Chenodeoxycholic Acids
  2. These bile acids are then conjugated with Glycine/Taurine to form more soluble bile acids.
  3. The conjugated forms are then secreted into the Canaliculi
  4. Exist as Bile SALTS in the intestine, where bacterial metabolism converts them into Secondary Bile acids.
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8
Q

What occurs in the enterohepatic circulation of bile acids?

LOOK AT DIAGRAM!

A

Bile acids play a role in FAT ABSORPTION.

95% of bile is reabsorbed back into the veins at the TERMINAL ILEUM (enterohepatic circulation), where it’s taken back to the liver and taken up by hepatocytes for re-secretion.

The remaining 5% of bile is lost in the faeces.

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9
Q

What is the physiological significance of Bile?

A
  • Essential for fat digestion and absorption via emulsification
  • Bile and pancreatic secretions neutralises gastric fluids as it enters the duodenum - helps digestive enzymes
  • Role in elimination of waste products from blood e.g. Bilirubin and Cholesterol
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10
Q

What is Bilirubin?

A
  • Yellow pigment formed from the breakdown of haemoglobin - has no use and is very TOXIC
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11
Q

Explain the process in the the formation and elimination of Bilirubin

What will be increased in the urine in hepatitis or damage to hepatopcytes?

LOOK AT DIAGRAM!

A
  • • In phagocytes, RBCs are broken down into globin, iron, and Haem
    • Haem is converted into free Bilirubin
    • Bilirubin is released into plasma, bound to Albumin.
    • The free Bilirubin then taken up by Hepatocytes and are conjugated with Glucuronic acid.
    • The Conjugated bilirubin is secreted into bile and eliminated in faeces/urine.

In faeces, its excreted as Stercobilin - brown colour
In urine, its excreted as Urobilin and Urobilinogen - yellow colour

  • Urobilin and Stercobilinogen
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12
Q

What is Jaundice?

What plasma [Bilirubin] will cause jaundice?

What are the 3 causes of Jaundice?

A
  • Excessive quantities of free/conjugated Bilirubin, which accumulates in the ECF = yellow discolouration of skin, sclera, and mucosal membranes.
  • Plasma [Bilirubin] > 1.5mg/dL
    1. Pre-hepatic:
      • Excessive RBC breakdown
      • Excess Free Bilirubin
  1. Hepatic:
    • Hepatocyte damage e.g. cirrhosis
    • Excess conjugated/free Bilirubin
  2. Post-hepatic:
    • Excess conjugated Bilrubin
    • Obstruction to passage into duodenum
    • It enters the circulation and into urine - dark
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13
Q

CARBOHYDRATE METABOLISM:
Why is it important?

What occurs in it?

A
  • Important in maintaining blood glucose concentration - Known as the Glucose Buffer Function
  • • Glycogenesis - stimulated by Insulin
    • Glycogenolysis - stimulated by Glucagon
    • Gluconeogenesis
    • Glycolysis - ATP formation
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14
Q

FAT METABOLISM:

What occurs during it in the liver?

A
  1. TG’s oxidised in hepatocytes = produce energy
  2. Lipoproteins made in liver
  3. Excess carbohydrates and proteins are converted into FA and TG’s - stored in adipose
  4. Synthesis of lots of cholesterol and phospholipids - some packaged as lipoproteins.
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15
Q

PROTEIN METABOLISM:

What occurs in it?

A
  • Deamination & Transamination of AAs, where they’re converted into glucose and lipids
  • Synthesis of non-essential AAs
  • Synthesis of most plasma proteins
  • Synthesis of urea - removes toxic ammonia from body
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16
Q

What is Biotransformation?

What is Detoxification?

A
  • The alteration of a substance in the body

- The removal of toxic substances from the body

17
Q

What toxic substances does the liver metabolise and excrete?

What can occur in women due to excess oestrogen?

A
  • • Bilirubin
    • Ammonia
    • Drugs e.g. paracetamol
    • Hormones - all steroid hormones are inactivated by conjugation and excretion
  • Spider Angioma
18
Q

How does the liver metabolise drugs and hormones?

A

In 2 phases:
Phase 1: mainly oxidation/reduction via cytochrome P450 - occurs in smooth ER.

Phase 2: Conjugation - makes it more water soluble

The substance is then eliminated into the blood or bile using ATPase pumps.

*Not all drugs use these phases

19
Q

What are the 3 metabolic pathways that occur in the detoxification of Paracetamol?

Why can Paracetamol overdose lead to liver necrosis and kidney damage?

A
    1. Glucuronidation - addition of glucuronic acid
      1. Sulfation
      2. N-hydroxylation and dehydration - produces a toxic intermediate compound, which is then detoxified by conjugating it with glutathione.
  • Liver has a limited supply of enzymes and glutathione - overdose of paracetamol causes the enzymes to be maximised and depleted - leads to liver necrosis and kidney damage due to the toxic metabolites.
20
Q

Why does ethanol have to be metabolised to get rid of it?

What occurs in ethanol metabolism?

Why can ethanol metabolism lead to hypoglycaemia and acidosis?

A
  • It’s easily absorbed in the gut but can’t be stored, so it has to be oxidised in the liver.
  • Step 1: Ethanol → Acetaldehyde, producing NADH - uses Alcohol Dehydrogenase
    Step 2: Acetaldehyde → Acetate, which goes into the blood - uses Acetaldehyde dehydrogenase

Those with deficiency of the step 2 enzyme will have an accumulation of acetaldehyde = Alcohol Flush Reaction

  • During step 1 of ethanol metabolism, lots of NADH is produced, which is then used to convert pyruvate → lactic acid.

The lactic acid building up will cause Acidosis. Since pyruvate is used up, it can no longer be used to make glucose, therefore causing Hypoglycaemia.

21
Q

What causes Alcoholic Liver Disease?

What are the types of liver problems that can occur?

A
  • Prolonged heavy drinking
  • • Fatty liver - fat accumulates in hepatocytes
    • Alcoholic Hepatitis - lots of fibrosis due to inflammation
    • Alcoholic Cirrhosis - hepatocytes destroyed due to connective tissue forming
22
Q

Outline Liver regeneration

Why is the damage in alcoholic liver’s irreversible?

A
  • Adult hepatocytes don’t divide anymore (G0 phase of cell cycle). After a partial hepatectomy or in response to toxic injury, they quickly re-enter the cell cycle and proliferate. Proliferation will stop once the original liver mass is established.
  • Prolonged alcohol abuse reduces its regenerative ability
23
Q

What is the role of the liver in coagulation?

What can occur if the liver is damaged as a result?

What does the liver store?

A
  • It produces many of the Coagulation factors e.g. Fibrinogen, Prothrombin
  • Excessive bleeding - due to lack of clotting factors
  • • Fat-soluble vitamins (A,D,E,K) - in hepatocytes
    • Vitamin B12 and Folate
    • Iron stored as Ferritin (Blood-Fe buffer)
24
Q

Outline LFTs (Liver Function Tests)

A

Check for the levels of certain enzymes and proteins in the blood.

It can screen for infections, monitor progression of a disease to see effectiveness of treatment, measure the severity of a disease, and monitor possible side effects of medications.