3 B: Physiology of Liver Flashcards

1
Q

What are functions of the liver?

A

1) Glycogenolysis & Glycogenesis
2) Protein metabolism/urea synthesis
3) lipid metabolism
4) hormone metabolism
5) iron metabolism and storage
6) vitamin storage
7) drug detoxification
8) Vit D activation pathway
9) plasma protein syntheis
10) synthesis of blood clotting factors
11) bile synthesis

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2
Q

What does storage of glycogen allow?

A

Allows the liver to remove excess glucose from the blood, store it, and then return it to the blood when the blood glucose concentration falls

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3
Q

How much glycogen can the liver store?

A

8% of their weight (100-120 g in an adult)

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4
Q

How much is found in the muscles?

A

1-3% of muscle mass; but total amount exceeds that in liver!

More muscles

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5
Q

Where does amino acid degradation occur?

A

Mostly in the LIVER, and begins with deamination.

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6
Q

What is deamination?

A

The removal of amine (NH2) groups from the amino acids

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7
Q

What do deamination reactions require?

A

Set of enzymes; aminotransferases or transaminases

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8
Q

What is AST ?

A

SGOT (serum glutamate-oxaloacetate transaminase) also called aspartate transaminase

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9
Q

What is ALT?

A

SGPT( serum glutamate-pyruvate transaminase) also called alaine transaminase

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10
Q

What other purpose do AST & ALT have?

A

They are also used to synthesize non-essential amino acids within liver hepatocytes

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11
Q

What are high levels of ALT and AST indicative of?

A

Liver disease

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12
Q

What happens to the amine groups cleaves form the amino acids ?

A

They are converted into ammonia (NH3) or ammonium ions (NH4+), which are then converted into urea

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13
Q

Where is al urea synthesized?

A

The liver

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14
Q

What is hepatic coma or hepatic encephalopathy?

A

In serious liver disease, ammonia that accumulates in the blood and lead to this state

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15
Q

How is urea excreted by the kidneys?

A

Urea diffuses from liver hepatocytes into the body fluids

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16
Q

What is azotemia or uremia?

A

A build-up of urea in the blood which high levels of urea become toxic to a variety of tissues

**Note: This is often a symptom of renal disease or failure!!

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17
Q

What is the normal range of BUN in an adult?

A

5-26 mg/dL

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18
Q

Elevated Blood Urea Nitrogen (BUN) can occur with?

A

1) **impaired renal function
2) increased protein intake or catabolism
3) GI bleeding (due to intestinal flora creating nitrogenous waste)
4) dehydration

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19
Q

What is HMG-COA reductase required for?

A

An important enzyme in liver hepatocytes required for endogenous cholesterol synthesis

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20
Q

What is the only way the body can eliminate excess cholesterol ?

A

Via bile

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21
Q

Why does Ketogenesis occur?

A

Occurs in fasting states or poorly controlled type I diabetes mellitus

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22
Q

The steroid hormones, as well as T3 and T4 are degraded by what?

A

The liver

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23
Q

What form is iron stored as in the liver?

A

Ferritin

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24
Q

Describe iron metabolism and storage

A

1) Mixture of Fe2+ and Fe3+ are ingested
2) Stomach acid converts Fe3+–>Fe2+
3) Fe2+ binds to gastroferritin
4) Gastroferritin transports Fe2+ to s. intestines & releases it for absorption
5) In blood plasma Fe2+ binds to transferrin
6) In liver, some transferrin releases Fe2+ for storage
7) Fe2+ binds to apoferritin to be stored as ferritin
8) Remaining transferrin is distributed to other organs where Fe2+ is used to make hemoglobin, myoglobin, etc

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25
Q

Large quantities of vit A, B12, and D are stored where?

A

Liver

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26
Q

What is the most important organ involved in drug metabolism? Why?

A

The LIVER;
Because it has many enzymes systems
( The MOST important = Cytochrome P450 System)

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27
Q

What is the basic purpose of drug metabolisms in the body ?

A

To make drugs less active and more water soluble and thus more readily excreted in the urine or bile

28
Q

Where can Cytochrome P450 Enzymes be most predominantly found?

A

Predominantly in the LIVER but also in the intestines, lungs and other organs!

29
Q

How are the cytochrome P450 enzymes designated by?

A

By the letter “CYP” followed by a Arabic numeral, a letter and another Arabic numeral (e.g, CYP2D6).

**EACH enzyme is termed an isoform since each derives form a different gene

30
Q

What does phase I and phase 2 enzymes consist of?

A

Phase I= Cytochrome P450 enzymes

Phase 2= Conjugative enzymes

31
Q

What are conjugation reactions designed to do?

A

To make metabolites more polar or hydrophilic, sometimes after they’ve been created by P450 enzymes

32
Q

What do conjugation reactions involve?

A

Endogenous substrate (Glucuronic acid, glutathione, acetyl-CoA or an amino acid), being added to a metabolite)

33
Q

What is Glucuronidation?

A

The most common and the most important conjugation reaction

34
Q

What does CP450 Inhibition involve?

A

In the decreed metabolic activity of CP450 enzymes leading to decreased metabolism of drugs

35
Q

What does CP450 Induction involve?

A

Results in increased activity of CP450 enzymes leading to increased metabolism of drugs

36
Q

What are the major types of plasma proteins?

A

1) Albumin
2) Globulin
3) Fibrinogen

37
Q

Where is the albumin, fibrinogen, and 50-80% of the globulin formed?

A

In the LIVER

38
Q

Where are the remainder of the globulins formed?

A

OIn the lymphoid tissues

39
Q

What constitutes the antibodies used in the immune system?

A

Gamma globulins

40
Q

What represents a smaller fraction of proteins found in the blood?

A

Hormones (e.g insulin, GH, ADH, PTH, etc.), angiotensinogen, etc.

41
Q

What are the function of the major classes of plans proteins ?

A

1) excretion of obconic pressure across capillary walls, which prevents EDEMA (albumin)
2) supplying approx. 15% of the buffering capacity of the blood (albumin)
3) transport of thyroid, adrenocortical, gonadal, and other hormones (albumin & globulin)
4) acting as carriers for metals, ions, fatty acids, amino acids, bilirubin, enzymes and drugs (albumin & globulin)
5) Participating in blood clotting (fibrinogen)
6) Participating in immune responses (gamma-globulin)

42
Q

Which Blood Clotting Factors are synthesized by the liver?

A

1, 2, 5, 7, 8, 9, 10, 11 and 12

43
Q

What are the organic constituents of bile?

A

Bile salts (50%), phospholipids (40%), cholesterol (4%), and bile pigments such as bilirubin (2%)

44
Q

What is secreted by cells lining the bile ducts?

A

Bile containing electrolytes and water

45
Q

What are the 2 primarily bile acids synthesized by the Hepatocytes?

A

1) cholic acid

2) chenodeoxycholic acid

46
Q

A portion of the primary bile acids is converted by intestinal bacteria into what 2 secondary bile acids?

A

1) deoxycholic acid

2) lithocholic acid

47
Q

What helps make the bile acids AMPHIPATHIC at duodenal pH?

A

The liver conjugates the bile acids w/ amino acid glycine or taurine to form bile salts–>making them amphipathic

48
Q

What is the most common variety of phospholipids found in bile?

A

LECITHIN

49
Q

Phospholipids are ___________

A

Amphipathic

50
Q

What accounts for most of the cholesterol breakdown in the body?

A

Hepatic synthesis of bile acids

51
Q

In humans how much of cholesterol is converted to bile acids and eliminated in bile everyday?

A

500 mg

***Some cholesterol is also eliminated in the bile as a WASTE PRODUCT

52
Q

What is Bilirubin?

A

A waste product of hemoglobin degradation

53
Q

What are the types of bilirubin?

A

Free bilirubin OR unconjugated bilirubin OR Indirect bilirubin. Conjugated bilirubin OR direct bilirubin

54
Q

How is free bilirubin transported into the blood?

A

By attaching to albumin

55
Q

As free bilirubin passes thru the liver, it is release from?
Where is it moved?

A

Release from albumin & moved into hepatocytes

56
Q

What functions do free bilirubin passing thru liver in hepatocytes preform?

A
  1. Uptake of bilirubin from the circulation
  2. Conjugation of bilirubin
  3. Excretion of bilirubin into the bile
57
Q

What does conjugation involve?

A

The attaching of glucuronic acid to bilirubin in a reaction catalyzed by the enzyme glucuronyl transferase

58
Q

Which type of bilirubin iix more water soluble?

A

Conjugated is more then free or unconjugated bilirubin

59
Q

What are other bile constituents?

A

Ions ( Na+, K+, Cl-, HCO3-) and water are secreted into bile by epithelial cells lining the bile ducts

60
Q

What are other waste products with bile?

A

lipophilic drugs and metabolites, antigen-antibody complexes, etc.

61
Q

Describe the 3 steps of bile formation

A

1) Hepatocytes actively secrete bile into bile canals (canaliculi)
2) Intrahepatic and extra hepatic ducts not only transport this bile, but the cells that line these duct (cholangiocytes) also secrete a watery, HCO3- rich fluid
3) Between meals approx. 1/2 the hepatic bile is diverted to the gallbladder, stores and removes salts & water.

62
Q

What is hepatic bile?

A

The first 2 steps producing 900 ml/day

63
Q

What is the result of removing salts and water?

A

The gall bladder concentrates the key remaining solutes-bile salts, bilirubin, cholesterol and lecithin by 10-20 fold

64
Q

During meals, bile that reaches the duodenum is what?

A

A mixture of relatively DILUTE hepatic bile & CONCENTRATED gall bladder bile.

65
Q

What are the 2 important functions of Bile?

A

1) Provides the sole excretory rout for many solutes that are not excreted by the kidneys.
2) Secreted bile salts and lecithin are required for normal lipid digestion & absorption in the s. intestine