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Physiology III > Metabolism 10 (Exam 4) > Flashcards

Metabolism 10 (Exam 4) Flashcards

1
Q

Where is the thyroid located?

A

Immediately below the larynx and anterior to the trachea

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2
Q

What are the two hormones we think about when we think of the thyroid?

A

Thyroxine (T4) and Triiodothyronine (T3) (these are tyrosine based hormones)

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3
Q

How do T4 and T3 profoundly affect the metabolic rate of the body?

A

In the absence, basal metabolic rate drops 40-50%

In excess, basal metabolic rate increases 60-100%

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4
Q

What is the thyroid predominantly controlled by?

A

Thyroid-stimulating Hormone (TSH)

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5
Q

Of the two hormones secreted by the thyroid gland, which of the two predominates?

A

Thyroxine (T4) - 93%

Triiodothyronine is only about 7%

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6
Q

How do T3 and T4 differ in rapidity and intensity of action?

A

T3 is 4 times more potent, but is present in much less quantities in the blood and persists for a much shorter amount of time

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7
Q

Thyroid glands have a lot of closed follicles. What are they filled with? What are they lined with?

A

Filled with colloid

Line with cuboidal epithelial cells

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8
Q

What makes up colloid?

A

Thyroglobulin (a large glycoprotein)

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9
Q

What does thyroglobulin contain?

A

the two thyroid hormones - Thyroxine (T4) and Triiodothyronine (T3)

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10
Q

Once a secretion has entered the closed follicle of the thyroid gland, what happens?

A

It has to be re-absorbed into the follicular epithelium and into the blood

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11
Q

How much blood per minute does the thyroid gland receive?

A

5 times its weight

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12
Q

How much iodine is required to form thyroxine?

A

50 mg/year (1 mg/wk)

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13
Q

Where does iodine need to be absorbed?

A

On the basolateral side of the cell from the blood

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14
Q

How does iodide enter the cell?

A

Uses secondary active transport via a sodium-iodide symport (2 Na/1 I) (called NIS)

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15
Q

What happens to iodide once in the cell?

A

It is concentrated in the cell with iodide trapping (30x concentration compared to blood concentration)
It can be concentrated up to 250x if it is maximally active

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16
Q

What greatly stimulates the activity of the iodide pump?

A

TSH

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17
Q

After iodide has been concentrated in the cell, what happens?

A

Iodide is pumped into the colloid space via a chloride-iodide ion counter-transporter
Thyroglobulin is secreted into the colloid space by epithelial cells

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18
Q

After Iodide and thyroglobulin have made it into the colloid space, what takes place?

A

Iodide is oxidized by peroxidase and now has the ability to bind tyrosine (which comes from the thyroglobulin)

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19
Q

What does the enzyme peroxidase do? What will happen in the absence of peroxidase?

A

Peroxidase oxidizes iodide so it can bind to tyrosine

Blocking peroxidase drops thyroid hormone production to 0

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20
Q

Where are thyroid hormones made?

A

They are made within the thyroglobulin molecule in the colloid space

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21
Q

The binding of iodine to thyroglobulin is termed ___.

A

Organification. It’s the process by which tyrosine is iodized

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22
Q

What is T4 (think tyrosine)?

A

two diiodotyrosine coupled together

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23
Q

What is T3 (think tyrosine)?

A

A monoiodotyrosine and diiodotyrosine coupled together

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24
Q

What happens to thyroid hormone after it has been made in the thyroglobulin molecule?

A

They are stored in the molecule until needed

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25
Q

What is a unique feature of the thyroid gland?

A

It can store large amounts of its hormones (2-3 months worth)
Most of the time animals don’t make hormones to store them, they make them as they need them

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26
Q

If an animal comes in with a thyroid problem, we can assume the problem has likely existed for how long? (specifically thinking about hypothyroid)

A

At least 2-3 months

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27
Q

Once the animal needs thyroid hormones T3 and T4 to be released, what happens on the apical side (colloid side) of the cell?

A

The apical side sends out extensions and T3/4 will undergo pinocytosis

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28
Q

Define pinocytosis

A

the ingestion of liquid into a cell by the budding of small vesicles from the cell membrane.

29
Q

After the thyroid hormones T3/4 are inside the cell and are on their way out, what happens?

A

Lysosomes fuse with the vesicles and multiple proteases will cleave the thyroglobulin molecules in order to release T3 and T4 in their free form.
They will then diffuse through the cell wall and into the capillary (out the basolateral side)

30
Q

Only about 3/4 of iodated tyrosine in thyroglobin molecules will become hormones. What happens to the rest?

A

The remainder have iodine cleaved off by deiodinase enzyme and is recycled

31
Q

What would happen if an animal lacked deiodinase enzyme?

A

Many animals would become iodine deficient

32
Q

How much T4 gets deiodinated to T3 once it has left the cell?

A

50%

33
Q

Once in the plasma, do T3 and T4 stay as free hormones?

A

No, 99% are bound to proteins (synthesized by the liver)

34
Q

What proteins bind to T3 and T4?

A

Thyroxine-binding globulin
Thyroxine-binding prealbumin
Albumin

35
Q

Why do proteins need to bind to T3 and T4 once they’ve entered the plasma?

A

We can’t release them to the cells too quickly
1/2 of T4 is released every 6 days
1/2 of T3 is released every day

36
Q

Compare the onset and duration of T3 and T4

A

T4 has a slow onset (2-3 days) and a long duration (Hits its max around day 10 and can take up to 40 days to be cleared from the system)
T3 has about 4 times faster action than T4 (6-12 hours)
- it’s max cellular activity is obtained with 2-3 days

37
Q

What is the general physiological function of T3 and T4?

A

General effect is to activate nuclear transcription of large numbers of genes

38
Q

Why is 90% of the thyroid hormone that binds to receptors T3?

A

Intracellular receptors have a high affinity for T3 and intracellularly, removal of an iodine from T4 continues

39
Q

What happens when T3 binds to an intracellular receptor?

A

Retinoid X receptor will form a heterodimer with Thyroid hormone receptor and this causes huge numbers of mRNA to be formed

40
Q

In addition to transcription upregulation by thyroid hormones, there are some nongenomic cellular effects. Where do they seem to occur?

A

Heart, pituitary, and maybe in the mitochondria

41
Q

How is thyroid hormone secretion regulated?

A

Thyroid stimulating hormone released form the anterior pituitary

42
Q

What is the most important effect that TSH has on the thyroid gland that will stimulate T3/4 secretion?

A

Increased proteolysis of the thyroglobulin - releasing T3/4 (releases within 30 minutes)

43
Q

Besides the most important effect, what other effects does TSH have on the thyroid gland to increase T3/4 secretion?

A

Increased activity of the iodide pump, increasing rate of iodide trapping
Increased iodination of tyrosine to form TH
Increased size and increased secretory activity of the thyroid cells
Increased number of thyroid cells

44
Q

What is one of the most consistent ways of stimulating TSH?

A

constant exposure to cold - indeed animals in arctic regions have basal metabolic rates 15-20% above normal

45
Q

How is TSH negatively regulated?

A

plasma TH concentration

At 1.75 times the concentration, secretion basically goes to zero

46
Q

What are TH’s effect on cellular metabolic activity? (long list)

A
  1. Increase basal metabolic rate (60-100%)
  2. Rate of utilization of foods increases
  3. Increased rate of synthesis of proteins as well as catabolism
  4. Accelerated growth rate
  5. Mental processes excited
  6. Increased endocrine gland activity
  7. Mitochondria increase in size and number
  8. Increase Na/K ATP pump as well as cell membrane leakiness
47
Q

What does increasing mitochondria size and number do?

A

Increases ATP formation rate

48
Q

What does increasing Na/K ATP pumps as well as cell membrane leakiness do?

A

Drives overall heat production up

49
Q

What are TH’s effect on growth?

A

It’s essential for metamorphosis of a tadpole into the frog (endocrine disrupting hormones (EDH))
It is typically manifested in younger animals
- promotes growth and development in the brain

50
Q

What will happen in a younger animal without thyroid hormone?

A

Their brain will literally be smaller and cause decreased mental state, seizures, constipation, lack of growth resulting in dwarfism, retention of baby teeth

51
Q

What does a fetus require if they don’t have a thyroid?

A

They require thyroid therapy within days or permanent damage will occur

52
Q

What specific body functions does TH effect? (long list)

A
  1. Stimulates carb metabolism
  2. Stimulates fat metabolism
  3. increase in TH will decrease plasma cholesterol, phospholipids, and triglycerides even through free fatty acid increase
  4. increases the need for vitamins as enzyme activity is enhanced
  5. increase basal metabolic rate
  6. decrease body weight
  7. increase blood flow and cardiac output due to a greater need for oxygen
  8. increase HR
  9. MAP remains the same but pulse pressure can increase
  10. Increase the rate and depth of respiration
  11. Excitatory effect on CNS and muscles
  12. Negative effect on sleep due to excitability of synapses
  13. Temporary increase in heart strength
53
Q

What are two diseases of thyroid hormone?

A

Hyperthyroidism and hypothyroidism

54
Q

What are the symptoms of hyperthyroidism?

A 
High excitability
Heat intolerance
Sweating
Mild to extreme weight loss
Varying degrees of diarrhea
Muscle weakness
Nervousness
Extreme fatigue but can't sleep
Tremor of the hands
Exophthalmos (eyeball protrusion)
55
Q

What causes hyperthyroidism?

A

Graves’ disease is an autoimmune disease in which TSI’s antibodies bind to the TSH receptor
Thyroid adenoma is a tumor that secretes TH

56
Q

How do you diagnose hyperthyroidism?

A

Measure plasma T3 or T4

Or measure TSH (goes down)

57
Q

How do you treat hyperthyroidism?

A

Remove thyroid or destroy it with radioactive iodine

58
Q

How does hyperthyroidism relate to cats and dogs?

A

Common in cats around age 12-13

Rare in dogs

59
Q

What are the symptoms of hypothyroidism?

A 
Generally opposite of hyper
Extreme fatigue and somnolence (drowsiness) 
Muscle sluggishness (extreme)
Slow HR
Decreased CO
Increased BW
Constipation
Mental Sluggishness
Myxedema (swelling under skin, gives a waxy consistency of the skin)
60
Q

What are the causes of hypothyroidism?

A

Typically a result of an autoimmune attack that destroys the thyroid gland
Diminished iodine consumption causes a goiter (large thyroid)
- due to no suppression of TSH, which causes huge amounts of thyroglobulin colloid into the follicles
Other types of goiter

61
Q

How do you diagnose Hypothyroid?

A

increased blood cholesterol (and thus atherosclerosis)

low plasma T3 and T4

62
Q

How do you treat hypothyroidism?

A

oral ingestion of T4 monthly

63
Q

What are the TH? which is more prevalent/potent?

A

T3 and T4
T3 is most potent
T4 is most prevalent

64
Q

What is the element and enzyme required for T3/4 formation in the thyroid?

A

Iodine and peroxidase

65
Q

What occurs during organification?

A

Iodine is added to thyroglobulin

66
Q

How is TH delivered from the follicle to the blood?

A

Pinocytosis of Tg across apical side, followed by degradation with lysosomes, then diffusion across basolateral side into the capillary

67
Q

Once in the bloodstream, T3 and T4 are free to exert their actions on cells immediately. T or F?

A

False, they are bound to proteins in the plasma and in cells

68
Q

What regulates TH production?

A

TSH

Physiology III (4 decks)

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