L8 thyroid parathyroid Flashcards
anatomy of thyroid gland
- butterfly shaped, two lobes joined at the front by an isthmus
- located in the front of neck, around larynx cartilage
- each lobe 5x3x2cm
- one of the largest endocrine glands, 20-60g
microscopic anatomy of thyroid gland
- a follicle is the functioning unit
- follicular cells: secrete thick colloid that fills lumen and iodine
- colloid made of thyroglobulin (Tg) (high molecular weight protein)
- Tg facilitates assembly of thyroxine (T4) and triiodothyronine (T3) in lumen
- colloid: gelatinous protein
- c cells: secrete calcitonin
TSH
thyroid stimulating hormone,
- prod by anterior pituitary to stimulate thyroid gland to secrete T3, T4 into bloodstream
- done by follicular cells reabsorbing iodinated Tg and degrading it.
T3 T4 uses
homeostasis of all cells
influences cell differentiation, growth, metabolism
major metabolic hormone as it targets almost all cells
iodide trapping
- follicular cells have sodium-iodide symporter (NIS) on their cell membrane
- NIS transport iodide along with sodium, using the sodium’s concentration gradient (maintained by NaK pump)
- inside cell, iodide ions are transported across the cell towards the apical membrane, where pendrin facilitates the efflux of iodide into the lumen
- the iodide ions are oxidized and incorporated into Tg, leading to the formation of thyroid hormones T3 and T4
sources of iodine
food - seafood, kelp, eggs, bread, dairy, salt
supplements
recommended daily intake of iodine
~150ug
TPO
thyroperoxidase
- exists on lumen-facing membrane of follicular cells
- catalyses oxidation of iodide ions in the presence of H2O2, converting iodide into its more reactive form, iodine, which is essential for the iodination process.
- iodine undergoes a reaction with tyrosine which results in the formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT). MIT and DIT serve as precursors for the formation of the thyroid hormones T3 and T4.
proteolysis of Tg
Tg is phagocytoses into follicular cell, fuses with lysosome to form phagolysosome. Tg is them hydrolyses to T3 and T4, which are them secreted into circulation
T4
primary secretory product of thyroid gland, 70-90ug produced per day
T3
15-30ug produced per day, from two sources
1) 80% from de-iodination of T4 in peripheral tissue
2) 20% from thyroid secretion
enzymes that deiodinate T4
monodeiodinase
type I: in liver, kidney, thyroid, pituitary, 80% of the process
type II: in CNS, pituitary, brown adipose tissue, heart
type III: in placenta and CNS, converts to rT3 which is inactive
what is 5’ deiodination
the iodine atom is removed from the 5’ position of the outer ring of T4.
why does T4 need to be converted to T3
more biologically active and has a higher affinity to bind to nuclear receptors, regulating gene expression and metabolic processes in target cells
T4 and T3 roles in growth and development
- increase formation of protein
- increase utilization of O2 and ATP synthesis
- increase heat production
- increase fat metabolism
- decrease fat store
-essential for normal brain development
metabolic effects of T3
- stimulates lipolysis and release of free fatty acids and glycerol
- stimulates cholesterol metabolism into bile acids
- facilitate rapid removal of LDL from plasma
- stimulates carbohydrate metabolism and protein degradation
types pf hypothyroidism
1) primary: from thyroid destruction
2) secondary: deficient TSH secretion due to lesions in pituitary eg tumour
3) tertiary/ central: deficit in stimulation of TSH release
primary hypothyroidism
Hashimoto’s thyroiditis, autoimmune antibodies against TPO. inflamed gland, fatigue, muscle weakness, weight gain, high TSH, low T3/4
secondary hypothyroidism
low TSH, due to compressing lesions, surgery/ radiation to pituitary, iron overload due to thalassemia
tertiary/ central hypothyroidism
congenital due to deficit iodine during pregnancy. require daily dose of thyroxine
hyperthyroidism
graves disease
- affects more female than male
- autoimmune disorder, antibodies bind to and activate TSH receptor
- exophthalmos – inflammation of the periorybital connective tissue and extraocular muscle
- radioiodine, surgery, antithyroid drug
thyroid hormone carriers
> 99% of T3/4 is bound to plasma carrier proteins
- TBG (thyroxine-binding globulin) binds 75%
- TTR/TBPA (transthyretin/ thyroxine-binding prealbumin) binds 10-15% T4
- Albumin binds 7%
- HDL (high-density lipoproteins bind 6% t3 and 3% T4
free hormone hypothesis
only free/unbound hormones has metabolic activity – around 0.3% of T3 and 0.03% of T4
HOWEVER, the concept is only partially correct
total hormone concentration
- normally kept proportional to the concentration of carrier proteins
- kept appropriate to maintain constant red hormone level
- metabolic state correlates more to concentration of free hormone rather than the total hormone in circulation
drugs that increase T3/4 by increasing TBG
oral contraceptives, methadone, clofibrate, heroin
conditions that increase T3/4 by increasing TBG
pregnancy, chronic active hepatitis, HIV, biliary cirrhosis
drugs that decrease T3/4 by decreasing TBG
glucocorticoids, androgens, salicylates, antiseizure drugs
conditions that decrease T3/4 by decreasing TBG
genetic factors, acute or chronic illness
parathyroid glands
usually 4 small glands on posterior surface of the thyroid
- upper pair are superior parathyroid glands
- lower pair are inferior parathyroid gland
microscopic anatomy of the parathyroid
chief cells and oxyphil cells
- oxyphil cells are derived from the chief cells and it increases in number with age
- adipose cells may appear with age
- many blood capillaries
parathyroid hormone
- secreted by chief cells
- regulates blood calcium levels
- synthesized as preparathyroid hormone in the gland
- cleaved to form proparathyroid, then again to the 84-AA-PTH
- half life = 2-4 min
regulation of plasma calcium levels
PTH and calcitonin regulate by controlling GI absorption, renal excretion and bone calcium flux
- CaSR (calcium sensing receptor) is a GPCR that is expressed on the surface of the parathyroid cells which senses fluctuations int he concentration of extracellular Ca
- binding of Ca to the receptor inhibits secretion of PTH
calcium homeostasis (Ca levels too low)
- PTH secretion increase
- stimulates increased Ca absorption in intestine
- inhibits Ca excretion at kidneys
- increases osteoclasts (bone cell) activity releases calcium from bones
- increases rate of release of phosphate by kidneys
calcium homeostasis (Ca too high)
- calcitonin secretion increase from c cells –– stimulates uptake of calcium by bone and reduces Ca uptake in kidneys
- gastrin is released when Ca is ingested, gastrin then stimulates release of calcitonin, and calcitonin stops gastrin release (neg feedback)
vitamin D in Ca homeostasis
(formed in skin when cholesterol precursor is in contact with UV light)
- liver converts vit D into 25-hydroxyvitamin D
- PTH converts that into 1,25-dihydroxyvitamin D3 (most active form) via 1-hydroxylase in the proximal tubes of the kidney
- this form of vitamin D promotes absorption of Ca from gut by intestinal epithelial cells
hyperparathyroidism
too much PTH secreted due to cancer
- bones are weak and deforms/ break easily
- excessive calcium levels in blood
- calcium phosphate – kidney stones
- painful bones
- depression, anxiety, fatigue
treatment by surgery of gland
hypoparathyroidism
too little PTH due to surgical trauma, magnesium deficit, autoimmune, CaSR deficit
- impaired nerve and muscle function
- muscle spasm and tetany (cramp, numbness, twitching, tingling)
- can be fatal
treated by calcium injection and hormone replacement
history that suggests hypocalcemia (newborn and adult)
Newborns
- may be asymptomatic
- lethargy
- poor feeding
- vomiting
- abdominal distention
Children/adult
- seizure
- twitch
- cramping
- laryngospasm (vocal cord spasm, breathing impaired)
