Thyroid Physiology Flashcards
explain the anatomy of the thyroid
- sits below the cricoid cartilage
- composed of Follicles: a layer of folliular cells, surrounding a lumen and then filled in the center with colloid (a storage fluid of thyroid hormones)
Colloid: is predominatly thyroglobulin: which is iodinated at specifical tyrosine residues
parafollicular cells dispursed throughout the thyroid: responsible for releasing calcitonin
The role of Iodine, thyroid and binding to make thyroid hormones
Iodine: is consumed via the diet, and a portion of it is uptaken by the thyroid: the rest is excreted
Iodide (I-) is transported into the follicle cell across the basal membrane by a sodium (NA+, I- symporter)
- Na+ constantly being pumped out and K+ pumped into cells via ATPase cells
- then the Na+ is going to passively diffuse into the cell
- the I- hitches a ride = symporter
- allows iodide to be transporter against its e-chem gradient
Then
- iodide in the follicular cells transits into th elumen (colloid center) of the follicle through an anion exchanger called pendrin (diffusion)
Additionally
- Thyroglobulin and thyroperoxidase are packaged into the secretory vesicles, fused with the membrane of the follicular cells and releasing them into the colloid as well
explain the relationship between TPO, thyroglobulin and the process of iodination
TPO + H2O2 = converts iodidie to iodine (this traps it in here, cant leave because it has no more charge)
- iodionation of tyrosines is catalyzed by TPO
thryglobulin couples with iodide traps it inside the colloid
excess iodine results in decreased activity: shuts down this ability to uptake
So the iodine binds to the tyrosine residuals on the throglobuin moelcules - different locations of the binding of iodine ellicts different structres of the new molecule
DIT, MIT and the formation of T3 and T4 and reverse T3
Iodine binds to tyrosine residuals at the thyroglobuin inside the colloid
- if Two iodines bind = DIT
- if 1 iodine binds = MIT
equal amounts of MIT and DIT will be made; independent to the concentration of iodine within the body
2 DIT form together to created T4 = the partial active (prohormone for T3)
1 DIT and 1 MIT form together to created T3 = the active form of the thyroid hormone
the difference between T3 and reverse T3 is that the Iodine binnds to a different tyrosine residual
Reverse t3 is an inactive waste product
the entire process of converstion from T4 to T3 in the peripheral tissue is mediated by the action of TPO
How do the contents of the colloid fluid (the T3,T4, MIT, DIT) get released
- the colloid fluid is endocytosed into the follicle cell & fused with a lysosome
- then thyroglobulin protein is protolysed and released the T3,T4,MIT and DIT
from there…
- T3 and T4 cross the basal membrane & enter capillaries
- DIT and MIT are Deionated by the thyroid and then degraded (obv. if not used)
- the iodide released from teh DIT and MIT are recycled into the colloid
How is the T4 and T3 carried through the blood
- 70% of the T3 and T4 are carried through the blood on thyroxine-bindng globulin
- other carrier moelcules include: albumin, thransthyretin
remember: only free T3 and T4 are active: but they are degraded qucker if they are free; thus binding to the above proteins, like thyroxine binding glboulin allows T3 and T4 to exisit for longer periods in the serum
(T4 = 8 days, T3 = 1 day)
How is T4 converted to T3
HOw does T3 enter the cells to act
T4: a prohormone
converts to T3 in the peripheral tissues (mainly)
- a deiondinase clips off one of the Iodines, so it goes from T4 to T3 = active!
T4 can also be metabolizes (to T0) through the liver, kidney & muscle
T3 Entering Cells
- T3 (and T4) can center cells either by the process of diffusion across the membrane OR they can use faciliated diffusion through a carrier moelcule to assist
Thyroid molecules: are steroid like! thus they enter into the cell and act on the DNA/RNA of the cell to turn off or turn on protein transcription
bind direclty onto DNA
within the cell, any T4 will most likely be converted to T3
intracellular receptors bind more readily to T3 > than T4 > and the lease able to bind to reverse T3
If a Thyroid receptor within a cell is NOT bound to a thyroid hormone, it is bound to TRE: thyroid regulatory element which prevents the receptor from being able to act on a gene
- when the Thyroid receptor binds to T3, this released the TRE: and allows the complex (a homodimer or heterodimer) to then go and alter gene expression
Explain the mechansim (receptors and hormones) that allow for the thyroid axis
TRH
TSH
T3,T4
TRH: acts at a water-soluable peptide, binds to a receptor on the cell membrane, activates secondary response
TRH travels to the ant. pituitary and triggers the release of TSH
TSH: then goes to general circulation, as a thropic factor in the thyroid, increases vascularity in the thyroid
TSH also stimualtes the uptake of I-, thyroglobulin synthesis, TPO syntehsis, thyroid hormone syntehsis and secretion aka the entire making and relasing of thyroid hormones
then,
when enough T3 and T4 is made, these go and inhibit TRH and TSH secretion (& inhibit the TRh receptors on the pituitary)
What do actve thyroid hormones do in the body
Thyroid hormones: regulate your basal metabolic rate
how?
- increases oxygen utalization
- energy expenditure
- heat production
Critically important functions include
- maturateion & differentiaion of bone
- neurological functions (neonates)
- growth
- metabolism
- SNS function
- skeletal muslce function
- CV function
- reproduction
Hyperthyroid State would then..
- increase protein synthesis, increased degradation, increase lipid synthesis, decrease serum cholesterol, increase glycogenolysis, increase thermogenesis, increase beta adrenergic receptor expression
Hypothyroid State would then…
- decrease protein and lipid synthesis, increase cholesterol synthesis, decrease gluconeogensis, decrease glycogenolysis, theormogenesis, etc.
Briefly explain the ideas behind thyroid screening for diseases
screening for congential hypothyroidism is a must in newborns
in older adults, less clear
- there is no benefit to early detection of hyper/hypo diease states that pushes the need to regularly screen
some governing bodies say yes, others say no
Explain the autp-antibody pathology of Hashimotos and Graves Disease
Hashimotos: autoimmune induced hyPOthyroid: thus TPO and anti-thyroglobuin anti-bodies are made which stop the production of T3 and T4: these antibodies are direclty againts the thyroid follicle substances
hashimotos actually destrorys the thyroid, essentailly over time damanging the follicle cells (aka why you might get hyper first as they pop open, then hypo as they are destroyed
Graves: autoimmune induced hYPERthyroid: these are autoantibodies with are targets of teh TSH receptors, binding to the TSH receptor triggering continuous production of the T3 and T4
graves does not destroy the thyroid follicles, instead just binds to TSK receptors mkaing the thyroid work overtime
Hypothyroidism
Primary
- very common
- can be the result of a defect anywehre in teh axis, hypothalmus, pituitary, thyroid
Primary Hypothyroid
- a vast majority of cases
- iodine is sufficient: then its autoimmune usually causing
- can be post surgical
- can be drug induced (methimazole, PTU, lithium, amioderone)
- infliterative (sarcoid, amyaloid)
Secondary Hypothyroidism
- a pituitary tumor (blocking TSH production)
- post0partum pituitary necrosis (sheehans syndrome)
- Trauma of pituitary gland directly
tertiary Hypothyroid
- damange to the hypothalmus
- tumors
- trauma
- radiaion (from brain cancer)
- infilterative disease
in other countires, a lack of iodine in utero can cause this -> leading to hormone issues, decreased receptor action, autoimmune, dysfunction of the thyroid
neonate screening helps with this
Clinical symptoms of hypothyroid
lab tests
Symptoms
- gatigue, apathy
- depression-like
- cold intolerance
- weight gain
- SOB, decreased exercsie
- constipation
- cool,dry skin (no sweating)
Labs
- in primary: TSH increased
- in secondary : TSH usually decreased
- Free T4: decreased
Hashimotos Thyroiditis
most common hypothyroid where iodine def. isnt a problem
T-cells recognize the thyroid antigens of TPO and thyroglobuin as forgein
these stimulate B-cells to created anti-thyroid antibodies
induce formation of CD8 cytotoxic cells
a majority of lymphocytic infiltrative disease
Patient
- middle aged women
- can have painless diffuse goiter
Hyperthyroidsm
Patho and symptoms of thyrotoxicosis
Thyrotoxicosis
- hyper-metabolic state of elevated T3 and T4
Symptoms
- nervousness, palpatations, rapid pulse, weakness, weight loss, dirrhea, heat intolerance, excess weat, tremoor, eye changes
