Endocrine Physiology II Flashcards
HPA Regulation of Thyroid Hormones, Adrenocortical Hormones, Parathyroid Gland: Ca2+ and PO4-Regulation
What does the thyroid gland do?
- Increases the rates of chemical reactions in most cells, increasing metabolic rate
- Promotes desposition of calcium in the bones and decreases extracellular fluid calcium ion concentration
Hormones: Thyroxine (T4), triodothyronine (T3), and calcitonin
What percentage of metabolically active hormones (thyroxine, triiodothyronine) are secreted by the thyroid? Which is more potent?
93% thyroxine (T4)
7% triiodothyronine (T3)
Triiodothyronine is about 4X as potent as thyroxine, but persists in the blood in small quantitites and is only available a short amount of time
Anatomically, what makes up the thyroid gland and thier function?
The thyroid gland is composed of a large number of follicles that are filled with a secretory substance called colloid that are lined with cuboidal epithelial cells (polar) that secrete into the interior of the follicles.
Colloid is mostly made up of a large glycoprotein called thyroglobulin, which contains the thyroid hormones.
It also contains c cells that secrete calcitonin, a hormone that contributes to regulation of plasma calcium ion concentration
How is the Hypothalamus, Pituitary, and thyroid axis regulated?
What stimulates the HPT Axis?
What inhibits the HPT Axis?
How are T4 and T3 made?
- Thyroglobulin is synthesized from tyrosine in the follicular lumen
- Iodides are transported from the blood into the thyroid glandular cells and follicles through a Na+-Iodide symporter creating iodide trapping
3-5. Peroxidase converts iodide through a organification and coupling reaction to MIT and DIT into T3 and T4
- Endocytosis of TG bound to MIT, DIT and T3, T4
- Proteases in lysosomes hydrolyze T3 and T4 off of the TG and they enter into circulation
- While the rest of the molecule is recycled through deiodination
What can inhibit the Na+I symporter?
What can inhibit the peroxidase enzyme?
Wait – how do MIT & DIT help make T3 and T4?
Tyrosine residues on thryroglobulin are oxidized to MIT and DIT and eventually these molecules couple with each other and form thyroxine (T4). Thyroxine (T4) is two DIT molecules and biologically active. Thriiodothyronine (T3) is MIT + DIT and biologically active, although only 1/15th of the final hormones.
What is Hashimoto’s Thyroiditis?
(Chronic lymphocytic thyroiditis, Primary Hypothyroidism)
It is an autoimmune disorder against the thyroid gland, where the thyroid gland is destroyed and levels of T3, T4 are diminished
What is Pituitary Hypothyroidism?
It is a “secondary” disorder of the pituitary or hypothalamus where there is low levels TSH, T3 and T4 hormones.
What is Graves Disease?
(TSI - autoimmune primary hyperthyroidism)
Most common form of hyperthyroidism where the thyroid gland is increased 2-3X normal and inreased secretion up to 15X normal. Caused by thyroid stimulating immunoglobins (TSIs) that bind to the same location of TSH and stimulate T3, T4 release. Ultimately, this results in low levels of TSH because of negative feedback.
What percentage of total thyroid hormones are in free form?
What are the cellular effects of thyroid hormones?
Normal, healthy T3 functions—4 B’s:
Basal metabolic rate
β-adrenergic effects
Brainmaturation
Bone“turnover” and Bone growth
(Hypo & hyper = increased fracture)
What are normal/abnormal levels of TSH and T4?
What are the causes, symptoms and treatments for hypothyroidism?
What are the causes, symptoms and treatments for hyperthyroidism?
What are clinical manifestations of thyroid storm? What is it?
Most typical in patients with:
•Graves Disease (Thyroid stimulating immunoglobulins)
•Thyroid Neoplasms
•High-dose of Thyroid meds
•Subclinical hyperthyroidism
Precipitated by:
•Surgical Injury to Thyroid
•Anesthesia induction
How is thyroid storm treated? Rationale for each medical intervention?
What is cretinism?
Cretinism is caused by extreme hypothyroidism during fetal life, infancy, or childhood resulting in failure of growth and mental retardation within a few weeks after birth
The thyroid gland produces thyroid hormones by a process of:
Thyroid hormones undergo metabolism in peripheral tissues, leading to the production of the more active __ and deactivation of thyroid hormones.
T3
Anatomically, the two adrenal glands that lie at the superior poles of the two kidneys are composed of two major parts, what are they? What hormones do they secrete?
Adrenal medulla - central 20% of the gland, and is involved in secretion of epinephrine and norepinephrine in response to sympathetic stimulation
Adrenal cortex - secretes corticosteroids, that are all synthesized from the steroid cholesterol. There are two major types, the mineralocorticoids and the glucocorticoids. The adrenal cortex can also secrete small amounts of sex hormones such as androgens (exhibiting similar effects as testosterone in the body)
The adrenal cortex functionally is two glands, what are the major differences between the medulla and cortex?
Mineralocorticoids mostly affect electrolytes of extracellular fluids, especially ________ and __________. The principle mineralocorticoid is __________
Mineralocorticoids mostly affect electrolytes of extracellular fluids, especially sodium and potassium. The principle mineralocorticoid is aldosterone
Glucocorticoids mainly exhibit effects that increase blood glucose concentration, and the principal glucocorticoid is _________
Glucocorticoids mainly exhibit effects that increase blood glucose concentration, and the principal glucocorticoid is cortisol
The adrenal cortex has three distinct layers, what are they? Name the principle regulators for each layer, and the main hormones each layer secretes.
Zona glomerulosa - thin layer of cells that lies underneath the capsule, constitutes 15% of the adrenal cortex. Only cells that are capable of secreting aldosterone because they contain aldosterone synthase. Control of aldosterone secretion is mainly from angiotensin II and potassium, both of which stimulate aldosterone secretion
Zona fasciculata - middle and widest zone, constitutes about 75% of the adrenal cortex and secretes glucocorticoids cortisol and corticosterone, as well as many androgens and estrogens. Control is mainly by the hypothalamic-pituitary axis via adrenocorticotropic homone (ACTH).
Zona reticularis - inner zone, secretes adrenal androgens dehydroepiandrosterone and androstenedione, as well as small amounts of estrogen and some glucocorticoids. Control is also from ACTH but also cortical androgen-stimulating hormone, released from the pituitary.
How are adrenocortical hormones synthesized?
What stimulates and inhibits aldosterone secretion from the adrenal cortex?
- Increased K+ in extracellular fluid increases aldosterone secretion
- Increased angiotensin II in extracellular fluid increases aldosterone secretion
- Increased Na+ in extracellular fluid slightly decreases aldosterone secretion
- ACTH from anterior pituitary is necessary for secretion of aldosterone but has little effect in controlling the rate of secretion in most conditions
What is this graph telling us?
High levels of ACTH can also increase aldosterone secretion.
What is this graph telling us?
The major control of aldosterone secretion is RAAS, specifically increases in angiotensin II.
What is the major contributor to Na+ reabsorption and K+ excretion into the urine as a result of aldosterone injection?
What does aldosterone do?
Predict the changes to the following disorders
Predict the changes in the following disorders
Board review question:
D. Hypothyroidism of thyroid origin
Board review question:
How is cortisol regulated?
How does cortisol levels very throughout the day?
What are the major clinical effects of cortisol?
How does cortisol aid in reducing inflammation acutely? What can happen with chronic cortisol release?
- Decreases permeability of the capillaries
- Stabilizes lysosomal membranes
- Decreases the migration of WBCs into the inflammed area and phagocytosis of the damaged cells
- Suppresses the immune system, causing the lymphocyte reproduction to decrease markedly
- Attenuates fever mainly because it reduces release of interleukin-1 from WBC
Metabolic effects of cortisol during a fast and acute stress?
Metabolic effects of cortisol during a overfed and chronically stressed?
What can cause excess cortisol, and the physiological effects of such?
What is cushings syndrome?
Excessive amounts of cortisol are secreted due to adenomas of the anterior pituitary or abnormal function of the hypothalamus that causes high levels of CRH and ACTH, or ectopic secretion of ACTH by a tumor. Lastly, it could be caused by adenomas of the adrenal cortex.
Symptoms: “moon face”, hypertension, increased blood glucose, decreased tissue proteins everywhere except liver, severe weakness, supressed immume system, purplish striae, and severe osteoporosis
Treatment: Removing the adrenal tumor, or drugs that block steroidogenesis or block ACTH secretion
How do the “-corticoid” receptors function?
What is Addison’s disease?
Usually atrophy of the adrenal cortices is autoimmune in nature resulting in an inability of the adrenal cortices to produce sufficient adrenocortical hormones.
Symptoms: hyponatremia, hyperkalemia, mild acidosis, sluggishness of energy mobilization, highly susceptible to deteriorating effects of different types of stress, melanin pigmentation of mucous membranes and skin, round face
Treatment: a person can live for years if small quantities of mineralocorticoids and glucocorticoids are administered daily
Explain short and long term responses to stress
AA Concerns for post-surgical
HPA dysfunction
What is the major storage site for calcium and phosphate?
How much calcium is ingested/excreted per day? How much of the plasma calcium is free or protein bound?
How much phosphate is ingested/excreted per day? How much of the plasma phosphate is free or protein bound?
What happens to calcium and phosphate binding to proteins during an acidotic state?
What is the function of the Parafollicular Cells (C cells) of the thyroid?
What is the function of chief cells of the parathyroid?
How does the Skin, Liver, & Kidney help to regulate hormonal control of Calcium and phosphate?
How does the bone help to regulate the hormonal control of phosphate in our body?
How does Calcitonin and PTH regulation plasma [Ca2+]?
What increases/suppresses PTH secretion?
How does calcium ultimately inhibit PTH release?
The Ca2+ receptor 2nd messenger system works via receptor simulation induced IP3 causes the release of Ca2+ from internal stores (which paradoxically shuts down PTH synthesis), whereas the DAG stimulates PKC to inhibit exocytosis.
How does vitamin D raise calcium levels?
What effect does a negative calcium balance have on calcitriol?
Negative Ca2+ balance (i.e.: lack of dietary Ca2+): increases both calcitriol & PTH levels. Calcitriol (activated Vit. D3) increase renal Ca2+ reabsorption. PTH increases calcitriol expression and increases bone resorption
What effect does a positive calcium balance have on calcitriol?
Positive Ca2+ balance: allows for normal calcitonin and calcitriol levels. Calcitriol promotes intestinal absorption & renal reabsorption of Ca2+. Calcitonin and calcitriol tends to inhibit osteoclasts and net bone mineralization.
How does PTH & Vit.D regulate plasma Ca2+
What does FGF23 do?
How do PTH, Vit. D & FGF23 regulate plasma Pi?
What happens with uncontrolled hyperphosphotemia?
What hormone changes would you expect with kidney failure?
How are calcitonin, phosphate, calcium, PTH, and FGF23 related?
Summary of Ca2+ & Pi regulating hormones!
