Thyroid Metabolic Hormones Flashcards

1
Q

What is the ideal shape of the thyroid gland?

A

butterfly shape

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2
Q

What are the two major hormones the thyroid gland produces and secretes?

A

Thyroxine (T4) 93%
Triiodothyronine (T3) 7%

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3
Q

What do the two thyroid hormones help maintain?

A

The basal metabolic rate (BMR)

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4
Q

What does the BMR represent?

A

The chemical reactions in your body that involve consuming nutrients and oxygen to produce energy, heat and carbon dioxide.

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5
Q

What happens if there is a chronic lack of thyroid hormones?

A

Basal metabolic rate decreases by 40%-50% below normal, person feels cold and gains weight possibly

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6
Q

What happens if there is chronic excessive thyroid hormones?

A

Basal metabolic rate increases by 60-100% above normal, person feels hot all the time and loses weight possibly.

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7
Q

What is another hormone that is produced and secreted by the thyroid gland?

A

Calcitonin

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8
Q

What is iodine?

A

chemical element whose solid is a shiny metal

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9
Q

how much iodine is required to maintain thyroid hormone levels?

A

up to 1mg/week

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10
Q

How do we get iodine?

A

Since we don’t eat shiny metals, we have to get it in the form of iodides

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11
Q

What are iodides?

A

chemical complexes that include the I- ion. Ingested orally and absorbed from the gastrointestinal tract into blood circulation

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12
Q

What is iodide trapping?

A

The thyroid gland has an iodide pump to actively transport the iodide from the blood into the thyroid.

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13
Q

Is iodide trapping effective?

A

No only about 20% of iodides actually make it into the thyroid the rest are secreted by the kidneys.

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14
Q

TRUE or FALSE. The concentration of iodide in the thyroid is 30 times greater than in the blood.

A

True

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15
Q

Is there any other body parts that require iodide?

A

No the thyroid is the major one and to date the only one that needs it.

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16
Q

The thyroid gland is composed of what?

A

Many follicles filled with colloid

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17
Q

What is colloid mainly composed of?

A

A glycoprotein called thyroglobulin which contains thyroid hormones

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18
Q

What synthesizes the thyroglobulin?

A

The Golgi apparatus in the thyroid cells

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19
Q

How are Thyroxine (T4) and Triiodothyronine (T3) formed?

A

By combining tyrosine with either 3 or 4 iodide molecules.

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20
Q

What is needed to add iodide to tyrosine?

A

peroxidase

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21
Q

What happens if the peroxidase system is blocked or there is not enough iodide?

A

The formation of TH is stopped

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22
Q

Each thyroglobulin contains how many tyrosine amino acids?

A

70

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23
Q

Where do the thyroglobulin that contain TH secrete the TH into?

A

into the follicular colloid to be stored

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24
Q

Why is it that if the production of TH were to stop it would take months before the effects of deficiency are seen?

A

Because the stored TH is normally sufficient to supply the body for 2 to 3 months.

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25
Q

What is the process of the release of T3 and T4 from the thyroid gland?

A

*The surface of the thyroid cell send out pseudopod extensions that close around small portions of colloid

*Lysosomes in the cell fuse with these vesicles to form digestive enzymes from lysosomes mixed with colloid.

*The proteinases (one of the enzymes) digest the thyroglobulin molecules and release thyroxine and triiodothyronine from thyroglobulin.

*T4 and T3 diffuse through thyroid cell into blood.

*Iodines become available again for recycling in gland cell to produce additional TH. Lack of deiodinase enzyme will cause iodine deficiency because of the failure of this recycling process.

*93% of TH released from gland is thyroxine and 7% of TH is triiodothyronine. In few days most of the thyroxine is slowly deiodinated to become triiodothyronine ( removal of one iodines from T4 ). Therefore, the hormone finally used by the tissues is mainly T3.

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26
Q

Once T3 and T4 enter the blood they immediately combine with several plasma binding proteins, which are they?

A
  • Thyroxine-binding globulin ( mainly )
  • Thyroxine-binding prealbumin ( less so )
  • Albumin ( less so )
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27
Q

How long does it take for half of T3 to be released into tissues?

A

a day

28
Q

How long does it take for half of T4 to be released into tissues and why?

A

6 days because the plasma-binding proteins have a higher affinity for T4

29
Q

What do T3 and T4 do when they enter a cell?

A

Bind with intracellular proteins (T4 binds more strongly)

30
Q

TRUE or FALSE. After injection of a large quantity of thyroxine into a human being, there is a long latent period of 2 - 3 days (no effect on metabolic rate) before the T4 activity is observed.

A

True

31
Q

How long does it take for the T4 activity to reach a maximum?

A

10-12 days

32
Q

What is the half life of T4?

A

15 days (can go up to 2 months)

33
Q

What is the latent period of T3?

A

6-12 hours

34
Q

How long does it take for T3 to reach maximal cellular activity?

A

2-3 days

35
Q

Why is the release of T4 slower than that of T3?

A

Because the plasma-binding proteins have a higher affinity to thyroxine

36
Q

What is the general effect of TH?

A

To cause nuclear transcription of genes for synthesizing large numbers of substances in the cells.

37
Q

What are the substances that TH has an effect on?

A

enzymes
Structural proteins
transport proteins
Other substances

38
Q

What happens before TH acts on the genes?

A

Almost all thyroxine is deiodinated to triiodothyronine, then T3 binds with the intracellular thyroid receptors in the nucleus.

39
Q

True or False. More than 90% of the thyroid hormone that binds to receptors is T3 , less than 10% of thyroid hormone that binds to receptors is T4.

A

true

40
Q

What is the cascade of events once the thyroid hormone attaches to the thyroid hormone receptors and the complex is then attached to the DNA genetic strands.

A

Once attached, the receptors become activated and initiate the transcription process ==> Different types of messenger RNA are formed ==> Many new types of proteins are formed by RNA translation on cytoplasmic ribosomes.

Most of actions of thyroid hormone result from the enzymatic and other functions of these new proteins.

41
Q

What is the effect of thyroid hormones on the mitochondria?

A
  • Increase the number mitochondria.
  • Increase the total membrane surface area (size) of mitochondria ==> increase the formation rate of ATP to energize cellular function.
42
Q

What is the effect of TH on carbohydrate metabolism?

A

Stimulates all aspects of carbohydrate metabolism because of the increase of metabolic enzymes. The effects include as follows.
* Increase absorption rate of glucose from gastrointestinal tract.
* Increase uptake rate of glucose by cells (independent of insulin)
* Enhance glycolysis (use of glucose for energy through anaerobic conversion of glucose to lactic acid).
* Enhance gluconeogenesis ( formation of glycogen from protein or fat ).
* Increase insulin secretion, which also promotes glucose uptake.
* TH decreases glycogen stores in the liver and skeletal muscle, this is called glycogenolysis, it allows more glucose to enter the circulation.

43
Q

Effect of TH on fat metabolism

A
  • In adipose tissue, TH will increase fat catabolism, this is called lipolysis, defined as a breakdown of triglycerides into free fatty acids.
  • When this happens, TH mobilizes fatty acids from fat tissues, which increases free fatty acids concentration in the plasma.
  • Accelerate oxidation of free fatty acids by cells.
  • TH decrease the quantity of cholesterol, phospholipids and triglyceride in plasma even though it increases the free fatty acids. (because TH increases the secretion rate of cholesterol in the bile and consequent loss of cholesterol in the feces).
  • In the hepatic cells (in the liver), TH can promote fat anabolism, this is called de novo lipogenesis, defined as the creation of new triglycerides from glucose, glycerol and free fatty acids.
    o “Thyroid hormones are a well-known inducer of hepatic de novo
    lipogenesis”
  • “Although thyroid hormones stimulate lipogenesis, there is a net reduction in total hepatic triglycerides during hyperthyroidism due to fatty acid metabolism occurring at a higher rate than fatty acid synthesis.”
  • If there is a lack of TH (hypothyroidism) it causes excessive deposition of fat in liver. This is due to the lower amount of catabolism in the liver.
  • Prolonged hypothyroidism cause severe arteriosclerosis (hardening of arteries) due to accumulation of cholesterol.
44
Q

Effect of TH on protein metabolism

A
  • TH will increase protein synthesis in many tissues to help them maintain or increase their chemical reactions. That is an anabolic effect TH has at normal levels.
  • If TH is in excess, it will also increase proteolysis, since the tissues are active they need protein turnover to increase. This is a catabolic effect, but it helps with growth to occur properly. Over time though, it can weaken the muscle in a hyperthyroid patient.
45
Q

Effect of TH on vitamin metabolism

A
  • Vitamins are essential parts of enzymes or coenzymes. TH increases quantities of enzymes, in turn, increase the need for vitamins.
  • Increase of TH can cause a relative vitamin deficiency unless the increased quantities of vitamins are available.
46
Q

Effect of TH on increasing active transport of ion through cell membranes

A
  • TH can activate enzymes: Na-ATPase and K-ATPase, ==> increase the transport rate of Na and K ions through cell membrane of tissues.
    *Increase heat production in the body because active transport uses energy from ATP.
    *TH also causes most cell membrane to become leaky to Na ions, which activates the Na pump.
47
Q

The effect of TH on growth

A

*Lack of TH ( hypothyroid ) causes growth rate retarded for growing children.
*Excessive TH ( hyperthyroid ) causes rapid skeletal growth, early bone mature for children.

48
Q

Effect of TH on cardiovascular system

A

*Increase blood flow and cardiac output because of the rapid utilization of oxygen for increased metabolism.
*Increase heart rate because of the increase of cardiac output.
*Increase the strength of the heart beat (because of increased enzymatic activity ).
*Increase slightly blood volume because of vasodilation which allows increased quantities of blood to collect in the circulatory system.
*Increase arterial pressure because of the increased blood flow.

49
Q

Effect of TH on respiration

A

Increase rate and depth of respiration because of increased rate of metabolism ==> increased use of oxygen.

50
Q

Effect of TH on gastrointestinal tract

A

Increase secretion rate of digestive juice and motility of gastrointestinal tract.
Excessive TH causes diarrhea and lack of TH causes constipation.

51
Q

Effect of TH on Central nervous system

A

Increase brain activity ( cerebration ).
Excessive TH ( hyperthyroid ) cause anxiety, extreme worry and paranoia.

52
Q

Effect of TH on muscle function

A

*Muscle becomes weakened with excessive TH, because of excessive protein catabolism.
*Lack of TH causes muscle to become sluggish and slow relaxation after a contraction.
*Hyperthyroid causes muscle tremor because of increased reactivity of neuronal synapses in the areas of the spinal cord that control muscle tone.

53
Q

What is the regulatory mechanism for controlling TH secretion?

A

TRH is transported to anterior pituitary through the hypothalamic-hypophysial portal vessel,
TRH bind with TRH receptors on the pituitary cell membrane,
Activates phospholipase second messenger system to produce phospholipase C and other second messenger products
Cause thyrotropin secreting cell in the anterior pituitary to produce and release thyroid-stimulating hormone (TSH/thyrotropin ),
TSH bind with TSH receptor on basal membrane surface of thyroid cell,

54
Q

Thyrotropin-releasing hormone is secreted by what?

A

nerve endings in the median eminence of the hypothalamus.

55
Q

TSH causes increased release of T3 and T4 into the blood by increasing what?

A
  • Proteolysis of thyroglobulin
  • Activity of iodide pump
  • Iodination of tyrosine for forming TH
  • Size and number of thyroid cells
56
Q

How is the secretion of TSH from anterior pituitary controlled by feedback regulation mechanism ?

A
  • The concentration level of TH in the body fluid will feedback directly to anterior pituitary.
  • Increased TH will directly affect anterior pituitary to cause decrease of secretion of TSH ==> decrease the release of TH ==> eventually to maintain a constant concentration of free TH in the circulatory body fluids.
57
Q

What is another regulatory mechanism of TSH secretion? (indirect)

A

Increased TH ==> increased metabolic function ==> increased heat production ==> increased body temperature ==> affect on hypothalamus, which is the body temperature controlling centre ==> cause decreased release of TRH from hypothalamus ==> decreased release of TSH from anterior pituitary ==> decreased release of TH from thyroid cells.

58
Q

What is hyperthyroidism?

A

increase in TH secretion thyroid gland increases in size, more thyroid cells

59
Q

What are the causes of hyperthyroidism?

A

Caused by autoimmunity.
The antibody is called thyroid-stimulating immunoglobulin. It can bind with the same membrane receptors for binding TSH ==> activate cAMP second messenger system.
thyroid-stimulating immunoglobulin has much prolonged stimulating effect on the thyroid gland (12 hours for TSI in contrast to 1 hour for TSH ).
The high level of TH secretion caused by thyroid-stimulating immunoglobulin will suppress the production of TSH in anterior pituitary.

60
Q

What can also cause the over-secretion of TH

A

Thyroid adenoma developed in the thyroid tissues. (production of TSH will be depressed)

61
Q

Symptoms and consequences of hyperthyroidism.

A
  • High state of excitability
  • Intolerance to heat
  • Increased sweating
  • Mild to extreme weight loss
  • Different degrees of diarrhea
  • Muscle weakness
  • Nervousness
  • Exophthalmos ( protrusion of eyeballs )
  • Extreme fatigue
  • Inability to sleep
  • Tremor of hands
  • Other psychiatric disorders
62
Q

How does autoimmunity links to hypothyroidism?

A

Patient first has thyroid inflammation (thyroiditis), ==> progressive deterioration ==> finally, cause fibrosis of gland ==> secretion of TH is diminished or stopped.

63
Q

How does insufficient intake of iodine link to hypothyroidism?

A

Lack of iodine prevents production of T4 and T3 , but does not stop the production of thyroglobulin ==> less or no TH is available to inhibit the production of TSH by the anterior pituitary ==> cause pituitary releasing excessive TSH ==> thyroid cells secrete large amounts of thyroglobulin into the follicles ==> glands grow larger and larger ==> but the thyroglobulin still contains less or no T4 and T3 ==> TSH production cannot be suppressed ==> cause worse process.

64
Q

What is the possible cause as to why an enlarged thyroid (without iodine deficiency) causes hypothyroidism?

A

Mild thyroiditis ( inflamed ) causes slight hypothyroidism ==> increase secretion of TSH ==> progressive growth of non-inflamed part of gland.

65
Q

What are some other genetic abnormalities that can cause hypothyroidism?

A

Deficient iodide-trapping mechanism ( not enough iodines pumped in),
*Deficient peroxidase system ==> iodides are not oxidized to iodine,
Deficient coupling of iodinated tyrosine in thyroglobulin ==> TH cannot be formed,
*Deficiency of deiodinase enzyme ==> iodine cannot be recovered from iodinated tyrosines ==> deficiency of iodine.

66
Q

What are the S&S of hypothyroidism?

A

*Fatigue
*Extreme somnolence (feeling sleepy)
*Extreme muscular sluggishness (slow to respond)
*Slow heart rate
*Decreased blood volume and cardiac output
*Increased weight
*Constipation
*Mental sluggishness
*Depressed growth of hair
*Scaling of skin
*Edematous appearance ( myxedema )
*Increase of blood cholesterol ==> arteriosclerosis