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GIT physiology > Thyroid gland > Flashcards

Thyroid gland Flashcards

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1
Q

2 types of thyroid hormone

A

Thyroxine - T4

Triiodothyronine - T3

  • Regulate metabolic rate
  • Normal growth and development
  • Cretinism associated with abnormal growth of thyroid gland
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2
Q

Function of calcitonin

A

Control of plasma Ca2+

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3
Q

Structure of thyroid gland

A

weighs 20g

Goiter => enlarged gland

  • Bilobed with thin isthmus
  • Highly vascular - 4-6 ml/min/g
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4
Q

Microscopic structure of thyroid gland

A

Closely packed acini or follicles

WALL

  • Single layer of cells
  • Columnar - active
  • Cuboidal/low columnar - inactive

INTERIOR

  • Clear proteinaceous colloid
  • Basement membrane
  • Mucopolysaccharides

Activity of individual lobules can vary

(photo below - INACTIVE - colloid is large for storage)

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5
Q

I Owe Our Cousin Reimbursement

5 steps in synthesis of thyroid hormones

A
  1. Iodide trapping
  2. Oxidation
  3. Organification
  4. Coupling
  5. Release
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6
Q

Iodide trapping

A
  • Na+ dependent active process
  • DIET - Iodide (I-): eggs, seafood, salt - 1mg/week
  • Plasma I- = 1-1.5 ug/L

TRAPPING

  • Secondary active transport mechanism - Na=/K= ATPase
  • Tissue:Plasma [I-]: 20-30:1 // MAX TSH stimulation 200:1
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7
Q

Oxidation

A
  • Iodide to iodine I- + I- => I2
  • Catalysed by peroxidase enzymes at cell-colloid interface
  • Iodine incorporated into colloid
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8
Q

Thyroglobulin of organification

A
  • Glycoprotein (10% CHO)
  • MW 660,000
  • 2 identical subunits
  • 132 tyrosine residues - 25-30 iodinated
  • 6-8 go to form iodo-thyronine
  • 3-4 molecules T4 per molecule thyroglobulin
  • 1 in 5 thyroglobulin molecules have T3
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9
Q

Organification

A
  • I2 coupled to tyrosine residues of thyroglobulin
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10
Q

Coupling

A
  • Iodinated tyrosine residues
  • Coupling of 2 DITs = T4
  • Coupling of DIT with MIT = T3
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11
Q

Release

A
  • Pinocytosis
  • Exocytosis of colloid via pseudopodia - most recently synthesised first used
  • Fuse with lysosomes
  • Acid proteases break down thyroglobulin
  • Iodide conserved by deiodination of MIT & DIT
  • 80 ug of T4 & 4ug T3 (10x more potent) released per day
  • Release stimulated // TSH
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12
Q

Total T4 in blood

A

1 x 10-7 mol/L

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13
Q

Total T3 in blood

A

2 x 10-9 mol/L

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14
Q

Free circulating T4

A

0.03% - 3 x 10-11 M

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15
Q

Free circulating T3

A

10-12 M

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16
Q
  1. 3 thyroid hormone binding proteins
  2. where are they degraded
  3. When are they cleared
A
  1. Thyroxin-binding globulin (TBG), Thyroxin binding pre-albumin (TBPA), Albumin
  2. Liver
  3. 6-7 days for T4 and 1 day for T3
17
Q

Hypothalamic Pituitary Thyroid Axis

A

TRH = Thyrotropin Releasing Hormone

18
Q

Thyrotropin Releasing Hormone

  1. Released by
  2. What does it use as a 2nd messenger
  3. What does it do
  4. Where is it degraded
A
  1. Tripeptide released by hypothalamus
  2. Acts using Ca2+ as a 2nd messenger
  3. Increases secretion of TSH and stimulates prolactin release
  4. Rapidly degraded in plasma

-ve feedback via T3 & T4

19
Q

TSH

  1. Produced by
  2. Type of protein
  3. normal plasma conc
  4. structure
  5. actions of TSH
A
  1. Anterior pituitary
  2. Glycoprotein - 15% CHO & MW 28000
  3. 1 x 10-12 M
  4. 2 peptide chains: alpha = that of LH, FSH, hCG (pregnancy test); specificity lies in beta chain
    • Increased iodide uptake
  • increased synthesis and secretion of T3 & T4
  • increased vascularity & hypertrophy of thyroid gland
20
Q

Increased basal metabolic rate by thyroid hormone

A

EUTHYROID

30-40 kCal/m2/hour

HYPERTHYROID

60-65 kCal/m2/hour

HYPOTHYROID

20-25 kCal/m2/hour

21
Q

Increased O2 consumption/heat production by tissues (as a result of thyroid hormone)

A

EXCEPT

  • Brain
  • Spleen
  • Testes
  • Ovary

Thermogenic effect moderated by:

  1. Increased blood flow to skin
  2. Increased sweating
  3. Increased ventilation

CAUSE

  • Increased Na+/K+ dependent ATPase
  • Futile metabolic cycles
22
Q

What are the 3 metabolic effects of thyroid hormones

A
  1. Increase muscle protein and fat breakdown
  2. Increase all aspects of CHO metabolism
  3. Increase GI motility
23
Q

Other metabolic effects of thyroid hormones

A
  • Increased HR and contractility
  • Increased myosin Ca2+ ATPase gene transcription
  • Increased numbers of beta-adrenergic receptors
  • Heart
  • Skeletal muscle
  • Adipose tissue
  • Increased sensitivity to catecholamines
  • Necessary for normal menstrual cycles
24
Q

Growth and development - pre-natal effects of thyroid hormones

A
  • Not essential for growth
  • Required for reproductive, skeletal and CNS system
  • Must be of foetal origin
25
Q

Growth & development - post-natal actions of thyroid hormones

A
  • Required for normal growth and development
  • Acts synergistically with GH on bone growth
26
Q

What happens in primary hypothyroidism

A
  • LACK OF IODIDE
  • Decreased T3
  • Decreased negative feedback
  • Increased TSH and Increased TRH
  • Increased growth of thyroid
  • GOITRE
27
Q

Manifestation of primary hypothyroidism in infancy

A
  • Cretinism
  • non-reversible
  • dwarfed stature
  • poor bone development
  • muscle weakness
  • mental deficiency
  • slow pulse
  • GI disturbances
28
Q

Manifestation of primary hypothyroidism - juvenile or adult

A

Chronic thyroiditis - Hashimotos

Autoimmune destruction of thyroid gland

29
Q

Sub-acute thyroiditis

A
  • Thyroid inflammation
  • Initial hyperthyroidism followed by hypothyroidism
  • transient, reversible
  • can lead to permanent hypothyroidism
30
Q

Secondary hypothyroidism

A

Pituitary disease

  • TSH not biologically active
  • Selective TSH deficiency - rare genetic disease
  • Autoimmune destruction of TSH secreting cells
31
Q

Tertiary hypothyroidism

A

Hypothalamic disease

  • Tumour
  • Radiation

(common causes)

32
Q

Resistance to thyroid hormones - hypothyroidism

A
  • Resistance at tissue level - rare
  • Genetic defect in thyroid nuclear receptor
33
Q

What are the clinical findings of hypothyroidism

A
  • Dry rough epidermal layer of skin
  • Non-pitting puffiness
  • Mucopolysaccharides, Hyaluronic acid, chondroitin sulphate
  • Hydrophilic and accumulate water - Myxedema
  • Course dry hair and hair loss
  • Decreased sebaceous gland activity - contributes to dry skin
  • decreased CO => bradycardia
  • Slow reflexes, decreased mental function - memory, alertness
  • Partial deafness - mucopolysaccharides accumulate in middle ear
  • Decreased appetite
  • Weight gain
  • Cold intolerance
  • fatigue
34
Q

Hyperthyroidism - thyrotoxicosis

A
  • Excessive ingestion of thyroid hormones
  • Graves disease is most common (>60% of cases)
  • Autimmune LATS, TSH receptor, no feedback
  • exophthalmus
  • Toxic multinodular goiter - follicles “autonomy” growth, caused by a benign adenoma
  • Hyperthyroid phase of thyroiditis - toxic adenoma
  • Ectopic production site - pituitary tumour producing TSH
  • Exophthalmus
35
Q

Clinical findings of thyrotoxicosis

A
  • Diffuse goitre
  • Exophthalamus - oedema ocular muscles - graves
  • Increased basal metabolic rate
  • Increased appetite
  • Weight loss
  • Heat intolerance
  • Sweating
  • Increased HR
  • Increased contractility - palpatations
  • Increased systolic BP, decreased diastolic BP
  • Tremor
  • Increased nervous alertness and excitability
  • Irregular menses
  • Infertility
  • Increased GI movements
  • Increased bowel movements
  • Proximal muscle weakness
  • Hypokalemic periodic paralysis
36
Q

Treatment of hyperthyroidism

A

BETA BLOCKERS

THIONAMIDES

  • inhibit thyroid hormone synthesis

RADIOACTIVE IODINE

  • ablation (I131/I125)

PERCHLORATE

  • inhibits iodine trapping

NATURAL GOITROGENS

  • Progoitrin
  • Cabbages, kale, kohlrabi

LITHIUM

  • Inhibits thyroid hormone release

GIT physiology (11 decks)

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