YOUNG BOYS Flashcards

1
Q

(1) Where is thyroid gland

A

2 x lobes and an isthmus ( large organ/tissue connecting 2 separate organs/tissue)
In front of trachea
-Blood supply, surrounding tissue, embryological origin SDL.

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2
Q

(1) Type of gland is thyroid? and 3 main hormones from it

A
  • Its an endocrine gland

- T3 (Triiodothyronine), T4 (Thyroxine) and Calcitonin (Ca2+ homeostasis)

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3
Q

(1) 2 cell types in the thyroid and their function

A

Follicle cells: Absorb Iodide from blood and make T4 and T3

C-Cells: Produce calcitonin

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4
Q

(1) 6 stages of T3 and T4 synthesis

A

1) Thyroglobulin synthesis
2) Uptake and concentration of Iodide (I-)
3) Oxidation of Iodide to iodine
4) Iodination of thyroglobulin
5) Couping of 2 iodinated tyrosine molecules for T3/T4
6) Secretion

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5
Q

(1) Role of Thyroglobulin

A

1) TG translated in ER of Foicle cells
2) Secreted into folicular lumen (colloid)
3) Acts as carrier molecule for T3 and T4
4) Endocytosis back into Follicle cell
5) T3/T4 cleaved from carrier and secreted

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6
Q

(1) Stages of thyroid hormone synthesis

A

1) Thyroglobulin with tyrosine residues present
2) Iodine added to Tyr to form iodinated thyroglobulin
3) The iodinated tyrosines are cleaved out to form T3

Thyroglobulin/Tyrosine + Iodine = Monoiodotyrosine (MIT)
MIT + Iodine = Diiodotyrosine (DIT)
MIT + DIT = T3
DIT + DIT = T4

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7
Q

(1) Iodide abosorption through MA/I symporter

A
  • Iodide actively transported into Folicle cell (from blood) by Na/I symporter
  • 1 to 1 Na+/I- maintains membrane potential
  • Not concentration dependent (allows increased cellular storage)
  • Iodine is rare thus must be actively transported as it must be concentrated.
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8
Q

(1) Why T3 and T4?

A

T4 is mainly secreted as this is the inactive form.

-T4 can be transported to target cells and these cells convert T4 into active T3

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9
Q

(1) How is the HPT (Hypothalamus-pituitary thyroid axis) used?

A

Hypothalamus: Thyrotrophin-releasing hormone
Pituitary: Thyroid-stimulating hormone
Thyroid: T3 and T4

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10
Q

(1) Properties of Thyrotrophin-releasing hormone

A
  • Polypeptide produced in hypothalamus
    (pyro) (Gln-His-Pro-NH2)
  • Medial neurons of PVN
  • 242aa precursor containing 6 copies of inactive TRH (Gln-His-Pro-Gly) flanked by Arg-dipeptides

1) Produced in PVN
2) Travel to A lobe
3) Stim production and release TSH (by triggering cAMP mediated signal transduction)

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11
Q

(1) How are T3 and T4 carried through the blood

A

T3/T4 are lipophilic (insoluble in blood)
30% bound to Albumin
70% bound to Thyroxin binding globulin (TBG)
-TBG has higher affinity to T4 due extra iodine present in T4 (improves base interactions)

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12
Q

(1) 3 types of Deiodinase isotypes

A

Type 1

  • Cell surface
  • Convert T4 to T3/rT3

Type 2

  • Intracellular (cytoplasm)
  • Converts T4 to T3

Type 3

  • Main deactivation deioninase
  • Converts T4 to rT3
  • Converts T3 to T2
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13
Q

(1) Effect of T3

A

T3 modifies basal metabolic rate to increase ATP production and O2 consumption
HOW?
-Increases O2 intake (ventilation)
-Increases substrate availability (glucose)

ALSO
1) Increases Pol I/III
(Increased transcription of ATP pump and receptors)
2) Increases production of Na/K ATPase pumps
(Increase speed of neuronal repolarisation)
3) Increases B-agrenergic receptors expression
(Enhances effects of adrenaline)
(Increased B1: Cardiac output, B2-ventilation, A1: Glucose uptake)

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14
Q

(1) WAT is Cretinism

A

T3 associated disorder

  • Caused by iodine deficiency during fetal deveopment.
  • Imparied physical growth + neurological development
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15
Q

(1) WAT is Hyperthyroidism

A

T3 associated disorder (too much)

-Sweating, weight and muscle loss, increased appetite, goitre

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16
Q

(1) WAT is hypothyroidism

A

T3 associated disorder (too little)

-Slow/lethargic, overweight, goitre

17
Q

(1) WAT is Goitre

A

T3 associated disorder (enlarged thyroid gland)
Caused by High or low T4 expresion due to:
-Iodine deficiency (induces TSH secretion)
-Graves disease, acts as TSH (IgG)
-Tumours

18
Q

(2) Regulation of Calcium levels

A

1) Regulated by kidney, bone and GIT
2) Ca2+ levels detected by calcium sensing receptors (CaSR)
3) CaSR found in parathyroid gland
4) Stimulate (low)/ suppress (high) release of parathyroid hormone (PTH)

19
Q

(2) 3 Main areas of calcium reaborption

A

1) Kidneys (uses 1,25(OH)2D3 from vit D)
2) Bone ca2+ reabsorption
3) GUT Ca2+ reabsorption

20
Q

(2) Where are the parathyroid glands

A

4 parathyroid glands situated in the posterior surfaces of the thyroid gland

21
Q

(2) 2 cell types in parathyroid glands

A

Oxyphil cells: (function unknown)

Chief cells: Make and secrete PTH

22
Q

(2) Function of Parathyroid hormone

A

Primary effects:

1) Kidney: Increase Ca2+ reaborption
- Promotes PO4 excretion
- Increase production of active vitamin D
2) Bone: Mobilise calcium

Secondary effects:
1) All due to increased vitamin D production

23
Q

(2) Role of parathyroid hormone related peptide (PTHrP)

A

-Regulates chondrocyte proliferation and mineralisation
-Key in placental calcium transport
(Same effect of PTH, BUT DOESN’T cause increased calcitriol (1,25D3) levels)

24
Q

(2) Role of vitamin D

A
  • Ca2+ upake from gut
  • Cartilage production (mineralisation: ca2+ and PO4 reaborption/excretion)
  • Required for osteoblast and osteoclast differentiation
25
Q

(2) WAT is active form of vit D

A

1,25(OH)2D3 = Calcitriol

26
Q

(2) How phosphate is regulated

A

REQUIRED FOR: Metabolism, phosphorylation, phospholipids

Balance depends on:

  • Diet and uptake via gut
  • Intracelular/extracellular movement
  • Urinary excretion (actively reabsorbed by PCT in kidney)

LOW PO4 causes activates calcitriol (from calcidiol)

27
Q

(2) Function of Fibroblast growth factor (FGF-23)

A

Phosphaturic hormone (increase PO4 in urine and decrease PO4 in blood)

  • Counteracts actions of vit D induced PO4 changes
  • Made by osteoblasts

Uses Klotho to inhibit 1A-hydroxylase (prevents vit D activation)
-ALSO inhibits type II sodium-phosphate co-transporters

28
Q

(2) Role of Calcitonin (CT)

A

Made by C cells in thyroid gland

ACTIONS
Bone: Prevents osteoclast action, inhibits bone rebasoprtion
Kidney: Decreases reabsorption of PO4 and Ca2+ in PT

Regulated by circulating Ca (CaR)

29
Q

(2) WAT is hypocalcaemia

A

Low Ca2+

-muscle cramps and seizures

30
Q

(2) WAT is hypercalcaemia

A

High Ca2+

  • Muscle weakness
  • Loss of bone
  • Shortened QT interval on ECG
  • Tiredness
31
Q

(2) Hyperparathyroidism

A

High PTH in blood, weaking of bones through loss of Ca2+.

PRIMARY: Increased PTH secretion by parathyroids (by a tumour)
SECONDARY: Low serum Ca2+ stim PTH ecretion and production, associated is kidney disease and loss of nephrons.

32
Q

(2) How disruption of calcium balance causes disruption in normal bone structure

A

1) Deterioration in microarchitecture (osteoporosis)

2) Defect in mineralisation (rickets/osteomalacia)