Physiology: Thyroid and Parathyroid Flashcards
(46 cards)
What transporter brings iodide into thyroid follicular cells, and what regulates it?
Iodide (I⁻) is pumped into thyroid follicular cells via the Na⁺/I⁻ symporter, which relies on the Na⁺ gradient maintained by Na⁺/K⁺-ATPase
- TSH loss ↓ symporter activity
What are the inhibitors of the Na⁺/I⁻ symporter and what can inhibition lead to?
thiocyanate (SCN⁻) and perchlorate (ClO₄⁻) block the Na⁺/I⁻ symporter → risk of hypothyroidism and goiter
What is Thyroglobulin and what are its functions?
large glycoprotein responsible for
- carrying tyrosine residues
- transporting and storing T4/T3
What is Organification?
the process where Iodine (I⁰) binds to tyrosine residues on thyroglobulin (TG) to create
- 1 iodine = MIT (monoiodotyrosine) first
- 2 iodines = DIT (diiodotyrosine) second
What is the Coupling Reaction of Thyroid Hormone synthesis?
Two iodinated tyrosines are joined together by peroxidase to make thyroid hormones:
- MIT + DIT → T₃ (active hormone)
- DIT + DIT → T₄ (inactive prohormone)
- DIT + MIT → rT₃ (reverse T₃, inactive)
What is the Wolff-Chaikoff Effect?
Very high iodide levels can shut down organification and block thyroid hormone synthesis temporarily.
- is a protective response to prevent thyrotoxicosis
Where are thyroid hormones stored?
colloid of the follicle which can store large amounts
How are T₃ and T₄ released from the Thyroid Gland?
- the colloid is endocytosed into the thyroid cell after binding to megalin
- TG-megalin complex is carried through the cell by transcytosis
- lysosomes digest TG –> T3 and T4 and unused MIT/DIT
- Free T₃ and T₄ diffuse
- MIT and DIT undergo de-iodination
What is pendrin?
an iodide-chloride antiporter located on the apical membrane used for transport and recycling of Iodine
What occurs once T3 and T4 are transported into the blood?
more than 99% of T3/T4 binds to thyroxine-binding globulin (TBG) and a much smaller amount to albumin
* T4 has higher binding to these plasma proteins compared to T3
How can liver failure effect the transport of T3 and T4 throughout the blood?
TBG is made in the liver so if it can not be made, then this will increase the free concentration of T3/T4 which would inhibit thyroid hormone production
How is T4 made into the more active form T3?
de-ionization through peripheral deiodinases (aka 5’-iodinase)
What are the stimulatory and inhibitory factors of thyroid Hormone secretion?
Stimulatory factors
* TSH
* Thyroid-stimulating immunoglobulins (TSIs)
* Increased TBG levels (e.g. pregnancy)
Inhibitory factors
* Iodide deficiency
* Deiodinase deficiency
* Excessive iodide intake (Wolff-Chaikoff effect)
* Perchlorate, thiocyanate
* Propylthiouracil (PTU)
* Decreased TBG levels (e.g. liver disease)
What happens when TSH binds to its receptor?
activation of adenylyl cyclase pathway to
increase cAMP which will cause every step of thyroid hormone biosynthesis to increase
Thyroid hormone will increase the basal metabolic rate through an increase in?
- O2 consumption and activity of Na+/K+ ATPase
- size and number of mitochondria
- heat production
In the presence of thyroid hormone, increased metabolism will cause a net result of?
catabolism
What is the result of an increase in BMR and O2 consumption by Thyroid Hormone and what drug is given to suppress the effects?
increased cardiac output due to
- increase in beta,1-adrenergic receptors that will increase heart rate and ventricular cardiomyocyte contractility (↑stroke volume)
- drug = metoprolol
What is congenital hypothyroidism or
cretinism and what can this lead to if not treated?
born with a non-functional thyroid gland
- If hypothyroidism is not treated right away, it will lead to irreversible mental retardation due to thyroid hormone being essential for normal maturation of the CNS
What effect does Thyroid hormone have on bones?
help to promote bone formation, ossification and fusion of bone plates and bone maturation
What are the symptoms of HYPO vs HYPER thyroidism?
HYPO: weight gain, cold sensitivity, lethargy, hypoventilation
HYPER: weight loss, increased heat production and intolerance, dyspnea (shortness of breath), and restlessness
What is Myxedema?
a severe form of chronic hypothyroidism seen in adults that refers to swelling and thickening of skin and tissues
What are causes of chronic hypothyroidism?
- Autoimmune thyroiditis (most common)
- Surgical removal or radioactive ablation
- Hypothalamic or pituitary failure
- Iodine deficiency
What is Graves’ Disease?
an auto-immune disease causing excessive production of thyroid hormone (hyperthyroidism)
What are causes of Hyperthyroidism?
- Tumor within the hypothalamus to increase the release of TRH
- Increase production of thyroid hormone due to neoplasm in thyroid gland (thyroid cancer)
- Auto-antibodies that bind to TSH receptor and induce
hypersecretion of thyroid hormone (Graves’ disease) - Too much exogenous thyroid hormone given to a patient with hypothyroidism
