YOUNG BOYS Flashcards
(1) Where is thyroid gland
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.
(1) Type of gland is thyroid? and 3 main hormones from it
- Its an endocrine gland
- T3 (Triiodothyronine), T4 (Thyroxine) and Calcitonin (Ca2+ homeostasis)
(1) 2 cell types in the thyroid and their function
Follicle cells: Absorb Iodide from blood and make T4 and T3
C-Cells: Produce calcitonin
(1) 6 stages of T3 and T4 synthesis
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
(1) Role of Thyroglobulin
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
(1) Stages of thyroid hormone synthesis
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
(1) Iodide abosorption through MA/I symporter
- 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.
(1) Why T3 and T4?
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
(1) How is the HPT (Hypothalamus-pituitary thyroid axis) used?
Hypothalamus: Thyrotrophin-releasing hormone
Pituitary: Thyroid-stimulating hormone
Thyroid: T3 and T4
(1) Properties of Thyrotrophin-releasing hormone
- 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)
(1) How are T3 and T4 carried through the blood
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)
(1) 3 types of Deiodinase isotypes
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
(1) Effect of T3
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)
(1) WAT is Cretinism
T3 associated disorder
- Caused by iodine deficiency during fetal deveopment.
- Imparied physical growth + neurological development
(1) WAT is Hyperthyroidism
T3 associated disorder (too much)
-Sweating, weight and muscle loss, increased appetite, goitre
(1) WAT is hypothyroidism
T3 associated disorder (too little)
-Slow/lethargic, overweight, goitre
(1) WAT is Goitre
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
(2) Regulation of Calcium levels
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)
(2) 3 Main areas of calcium reaborption
1) Kidneys (uses 1,25(OH)2D3 from vit D)
2) Bone ca2+ reabsorption
3) GUT Ca2+ reabsorption
(2) Where are the parathyroid glands
4 parathyroid glands situated in the posterior surfaces of the thyroid gland
(2) 2 cell types in parathyroid glands
Oxyphil cells: (function unknown)
Chief cells: Make and secrete PTH
(2) Function of Parathyroid hormone
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
(2) Role of parathyroid hormone related peptide (PTHrP)
-Regulates chondrocyte proliferation and mineralisation
-Key in placental calcium transport
(Same effect of PTH, BUT DOESN’T cause increased calcitriol (1,25D3) levels)
(2) Role of vitamin D
- Ca2+ upake from gut
- Cartilage production (mineralisation: ca2+ and PO4 reaborption/excretion)
- Required for osteoblast and osteoclast differentiation
