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Physiology II > Thyroid Hormonal System > Flashcards

Thyroid Hormonal System Flashcards

1
Q

Endocrine vs. Exocrine

A

Endocrine - ductless

Exocrine - duct or glands

The objective of both is to secrete a hormone into circulation.

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2
Q

The major systems involved in the maintenance of homeostasis are _____ and _____.

A

Nervous

Endocrine

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3
Q

What are the major endocrine glands?

A

Hypothalamus

Pituitary gland

Parathyroid glands

Adrenal glands

Thyroid gland

Pancreas

Ovaries/Testes

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4
Q

Most animals have two separate glands or lobes on either side of the trachea, some connected by an _______.

A

Isthmus

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5
Q

What species only has one thyroid lobe/gland?

A

Pig

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6
Q

Where is the thyroid gland located?

A

Neck at the proximal tracheal rings. It lies on the lateral aspect of the trachea, below the larynx.

It appears brownish-red in color.

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7
Q

What is the funtional unit of the thyroid? Describe its arrangement and components.

A

The thyroid is arranged in follicles, which consists of a spherical arrangement of epithelial cells that produce thyroid hormone.

Colloid is present within the follicles, which is a fluid rich in thyroglobulin.

The cells between follicles are known as parafollicular cells. These cells produce calcitonin and are therefore known as C cells.

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8
Q

Colloid is rich in ______.

A

Thyroglobulin

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9
Q

C cells of the thyroid secrete ______.

A

Calcitonin

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10
Q

Chief cells are located in the ______ and secrete ______.

A

Parathyroid

Parathyroid hormone (PTH)

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11
Q

What are the precursors to the synthesis of thyroid hormones?

A

Tyrosine amino acids

Iodide (I-)

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12
Q

Describe iodine trapping.

A

Iodide is obtained from the diet and actively taken up from the blood to the thyroid epithelial cells by a sodium-iodide symporter or transporter (iodide trap)

It is then transferred tot he lumen or colloid.

This process concentrates iodine in the colloid several fold higher compared to plasma.

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13
Q

What are tyrosine amino acids?

A

They are provided by thyroglobulin, a tyrosine rich protein synthesized by epithelial cells and secreted into the follicle lumen or colloid.

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14
Q

The enzyme that catalyzes the synthesis of thyroid hormones is ______.

A

Thyroid peroxidase (TPO)

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15
Q

Iodine trap is mediated by _____, while the oxidation of iodide to iodine is mediated by _______.

A

TSH

TPO

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16
Q

Describe the reactions catalyzed by TPO.

A
  1. Oxidation of iodide to iodine
  2. Iodination of tyrosines on thyroglobulin (organification of iodide)
  3. Coupling of MIT and DIT to form T3, rT3, or T4
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17
Q

Tyrosine + I = ?

A

MIT (monoiodothyronin) + DIT (diiodothyronine)

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18
Q

MIT + DIT = ?

DIT + DIT = ?

A

T3 or rT3

T4

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19
Q

Storage of thyroid hormone as colloid unti need is mediated by ______.

A

TSH

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20
Q

Which one is more abundant? T3 or T4? Which was is more biologically active? Inactive?

A

T4 is more abundant

T3 is most bioactive

rT3 is an impotent molecule

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21
Q

TRUE/FALSE.

T3 and rT3 can only be produced by the coupling of MIT and DIT.

A

FALSE.

They may also be produced through the deiodination of T4, catalyzed by various deiodinases in target tissues.

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22
Q

Describe the secretion of thyroid hormone.

A
  1. Thyroglobulin with thyroid hormones is endocytosed
  2. Endosomes fuse with lysosomes
  3. Enzymes digest thyroglobulin and release thyroid hormones and thyroglobulin
  4. Free thyroid hormones diffuse out of lysosomes and into interstitilal space to blood.
  5. Thyroglobulin and I- are recycled
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23
Q

TRUE/FALSE.

T3 and T4 act has negative feedback control on the hypothalamus and pituitary gland.

A

TRUE.

They inhibit both TSH and TRH production. Once concentrations of T3 and T4 decrease, the negative feedback signal is reduced and TRH and TSH stimulation can begin again.

24
Q

Briefly describe the Hypothalamic - Pituitary - Thyroid Axis.

A

Stimuli (such as cold exposure) stimulate the

Hypothalmus to secrete TRH, which travels to the

Anterior Pituitary (Adenohypophysis) to release TSH, which travels to the

Thyroid Gland to release Thyroid hormones (T3 and T4)

T3 and T4 act on cells throughout the body but also negatively inhibit TSH and TRH release.

25
Q

What are some external factors that influence T3 levels?

A

Cold - Increase

Diet - High carbohydrate diet - increases T3

Low Carbohydrate - Decrease T3

26
Q

TRUE/FALSE.

T3 and T4 are hydrophilic.

A

FALSE.

There are Lipophilic.

27
Q

What is the function of thyroid binding proteins?

Where are they produced?

What is the main one?

A

Thyoid binding proteins require transport proteins to circulate outside and within cells. <1% is free.

They are produced in the liver.

Thyroid binding globulin (TBG) binds about 70-80%. Other proteins include transthyrein and albumin.

28
Q

Which thyroid hormone has a higher affinity to protein? What implications does this have?

A

T3 has a lower affinity for binding proteins, meaning it has a shorter half-life than T4 (hours vs. days).

29
Q

Describe the activity of T3 and T4 once it has entered the cell.

A
  1. Free T3 and T4 are taken up by passive and active diffusion/transport.
  2. T3 and T4 bind to cytosolic transport proteins
  3. T4 is deiodinated to T3 by deiodinase (DI, DII, DIII)
  4. T3 binds to mitochondrial and nuclear receptors (thyroid receptor α or β)

Binding to mitochondria - activates oxidative phosphrylation and ATP
Binding to nucleus increases mRNA transcription –> translation –> protein synthesis

30
Q

What are the major excretory organs for thyroid hormones?

A

Liver and Kidney

31
Q

How does the liver alter thyroid hormones?

A

T4 undergoes glucuronidation by the enzyme T4 UDP - glucuronyl transferase

T3 undergoes sulphation

They are then put into bile for excretion/reabsorption.

32
Q

How do some pharmaceutical drugs cause acute hypothyroidism? List some examples.

A

By increasing liver UDP-glucuronyl transferase activity. This increases the clearance of T4, which means loss of T3.

Phenobarbital and environmental toxins (perchlorates) can do this.

33
Q

_____ is produced by the thyroid C cells.

What is its major stimulus and primary action?

A

Calcitonin.

High extracellular/blood calcium levels. It wants to decrease calcium levels by:

  1. Decreasing osteoclast activity (deposition of bone increases)
  2. Inhibits tubular reabsorption of calcium (increases excretion)
  3. Inhibits intestinal uptake of calcium and increases its excretion in the digestive tract.

**Calcitonin also has negative feedback on C cells once levels of calcium decrease.

34
Q

Describe the stimulus and action of parathyroid hormone.

A

Stimulus: low Calcium blood levels

Action: Raise calcium levels

  1. Bone: stimulate osteoclast activity and inhibit deposition of osteoblasts
  2. Kidney: increase tubular reabsorption and inhibit the excretion of calcium
  3. Digestive tract: stimulate intestinal uptake and inhibit excretion of calcium. PTH stimulates production of Vitamin D by kidney (stimulates production of calcium-binding protein that faciliates absorption of calcium from GI tract).
35
Q

What is the molecular structure of thyroid hormones?

A

Small peptide of two tyrosines linked together with iodine at three or four positions on the aromatic rings.

36
Q

Where are DI expressed?

A

Liver

Kidney

Lung

Eyes

Thyroid gland (Cats, goats, sheep, cattle express little or no D1 at the thyroid gland level)

37
Q

Where is DII expressed?

A

Brain

Myocardium

Skeletal muscle

Brown fat tissue

38
Q

Where is DIII expressed?

A

Liver

Skin

Brain

Placenta

39
Q

What is hypothyroidism?

A

Associated with decreased synthesis, secretion and storage of thyroid hormones, which is assocaited with a decreased metabolic rate.

Most common in dogs. Commonly seen in cats following bilateral thyroidectomy as a result of hyperthyroidism.

40
Q

What are the main types of thyrid hormone disorders?

A
  1. Primary - thyroid gland dysfunction is most common
  2. Secondary - pituitiary gland dysfunction (i.e. TSH deficiency) is rare
  3. Tertiary - hypothalamic dysfuntion (i.e. TRH deficiency) is rare or not described
  4. Congenital - thyroid gland hyperplasia reported in foals as a result of mares diet (e.g. low I-) during pregnancy.
41
Q

What are some clinical signs associated with canine hypothyroidism?

A

Metabolic: Lethargy, obesity/weight gain, exercise intolerance, cold intolerance

Dermatologic: hair thinning/alopecia, dry/poor coat, skin hyperpigmentation

42
Q

At what age are dogs most commonly diagnosed?

A

Middle-aged (4-10 years). Diagnostic ranges between 0.5 and 15 years.

43
Q

TRUE/FALSE.

Male dogs are more susceptible to hypothyroidism than female dogs.

A

FALSE.

There is no clear difference.

44
Q

Describe the etiology of canine hypothyroidism.

A

>95% of clinical cases result form destruction of thyroid gland (i.e. primary hypothyroidism).

Lymphocytic tthyroiditis (autoimmune disease)

Idiopathic (unknown atrophy of thyroid gland)

45
Q

Lymphocytic Inflammation of thyroid gland (thyroiditis)

A

T-lymphocytes and other immune responders infiltrate the thyroid gland due to antibody production against thyroglobulin, T3 or T4

Thyroid follicles collapse and replace with fibrotic or CT

46
Q

Describe idiopathic atrophy of thyroid gland.

A

Thyroid follicles collapse and replaced with adipose or fatty tissue.

47
Q

How do you diagnosis hypothyroidism in dogs?

A

Screening: test for tT4 (total thyroxine = protein bound plus free)

Limitation: Serum tT4 may be influenced directly by the connection to binding proteins to non-thyroidal diseases, pharmaceuticacls, environmental toxins

Alternative: serum free fT4 concentration are less subject to fluctiations and nonthyroidal repsonses (i.g. binding proteins) and typically analyzed to corroborate or negate tT4 results.

Limitation: low blood concentrations and requires test to measure free T4 which are more complex, less readily available and costly.

48
Q

What test was once used as the gold standard to test TSH?

A

TSH stimulation test. It is still used for corroboration of low T4 results.

TSH is administered. A blood sample is taken before and after. You expect to see an increase in serum concentrations of T4 after TSH is administered.

No increase is indicative of primary hypothyroidism.

49
Q

What are some more reliable tests for diagnosing hypothyroidism?

A

Equilibrium dialysis and radioimmunoassay or enzyme immunoassay

50
Q

TRUE/FALSE.

A relatively large percentage of hypothyroid dogs have “normal” TSH, thus TSH alone cannot be used for diagnosis but may be used to confirm low serum concentrations.

A

TRUE.

It may also be associated with a compensatory increase in putitary output.

51
Q

The most common feline endocrine disorder is ______.

A

hyperthyroidism (thyrotoxicosis).

52
Q

What are some common clinical signs or symptoms of hyperthyroidism in cats? What are some risk factors?

A

Loss of weight, heart races, tremors, vomitting, weak, eating and drinking excessively.

95% of cases occur in cats older than 10 years old. There does not appear to be a sex predilection.

53
Q

How does the TSH stimulation test performed in cats differ than that of dogs?

A

It is used to corroborate high T4 results and interpretation of results is different - if no increase is seen that is indicative of hyperthyroidism (T4 is being produced at maximal rate and it is an over functional thyroid).

54
Q

Describe thyroid parafollicular cell dysfunction.

A

Rare disorder in dogs and cats where C cell production of calcitonin may be impaired, leading to high blood calcium concentrations.

55
Q

Describe hyperparathyroidism.

A

Uncommon

Parathyroid glands overproduce PTH → high calcium levels

Parathyroid may become enlarged due to hyperplasia of parathyroid or chief cells.

More common in cats.

56
Q

Describe hypoparathyroidism.

A

↓ PTH → Low blood calcium concentration

Occurs spontaneously

Uncommon in dogs, rarely seen in cats.

Physiology II (8 decks)

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