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These notes are my own study guide for what I think is important for my mini II material that I have not yet learned. There is a lot that you need to know where the details may be left out or the topic skipped completely.
Inhibin (in the female it’s made in response to progesterone) causes negative feedback at the ant. pituitary only to suppress FSH release.
Testosterone or estrogen causes negative feedback on both the ant pituitary and the hypothalamus to suppress both GnRH and LH release.
Prolactin is regulated by both PRLRH and PRLRIH. PRLRIH is a dopamine agonist which means that you can use bromocriptine to suppress the release of PRL and this can be used as an anti-breast cancer. Dopamine is no good because of it’s lack of ability to cross the blood-brain barrier.
ADH release from the post. pituitary is a result of hyperosmolarity or hypovolemia.
It stimulates a V1 receptor which uses an IP3 pathway to cause constriction of vascular smooth muscle.
It stimulates a V2 receptor which uses cAMP to cause increased reabsorption of water in the distal tubule.
Diabetes insipidus is a disease related to the loss of action of ADH. There are two forms:
1) Nephrogenic which is characterized by the loss of function of the V2 receptors.
2) Neurogenic which is characterized by a shortage of release of ADH from the post. pit.
Both cause excess excretion of body fluids and hypovolemia.
Thiocynate or perchlorate inhibits uptake of I-.
PTU (propylthiouracil) inhibits:
1) Organification (formation of MIT and DIT) in the colloid.
2) Coupling in the colloid.
3) Endocytosis of TIT and thyroxine into the follicular cells.
4) Release of T3, T4.
The thyroid is stimulated by both TSH and TSI. TSI is made in the liver and has no feedback inhibition.
Wolff-Chaikoff effect is when T3, T4 release is decreased in response to I- loading. If you are going to operate on a thyroid tumor it’s best to give extra I- pre-op because it will cause lowering of thyroxine release so when surgery causes a T3/T4 surge you don’t get so much to cause cardiac problems.
T3 stimulates:
1) BMR
2)
O2 uptake
3)
CV rate
4)
Respiratory rate
5)
Bone formation
Hyperthyroidism which is usually due to excessive levels of TSI.
Goiter can appear in either:
1) Hyperthyroidism because of excessive work causes hypertrophy.
2) Hypothyroidism because low T3, T4 leads to extra TSH release which causes accumulation of essential parts but it does not have everything needed to make T3, T4.
It is secreted by chief cells in response to low extracellular Ca2+. (The actual release is mediated by increased intracellular Ca2+.)
PTH acts on a cAMP receptor system to:
1) Stimulate osteoblasts to cause osteoclasts (probably using ILs) to break down bone.
2) Increases Ca2+ reabsorption and PO4- excretion.
3) Activation of 1a-hydroxylase which converts vitamin D to it’s active form.
1o hyperparathyrodisim is a result of a parathyroid tumor and causes:
1) Hypercalcemia
2) Hypophosphatemia
2o hyperparathyrodisim results from excess of PTH secreted in response to hypocalcemia due to a pathology related to something like vit D deficiency. It also causes hypercalcemia and hypophosphatemia.
Hypoparathyrodism is usually are result of surgery and causes hypocalcemia and hyperphosphatemia. The hypocalcemia can be treated by administration of Ca2+ supplements and active vit D.
Pseudohypoparathyrodisim is when there is a lack of response to PTH receptors that causes excessive release of PTH because you get continual hypocalcemia. It presents just like hypoparathyrodism except they have greatly elevated PTH levels.
Thyroid parafollicular cells (c-cells) release calcitonin in response to hypercalcemia. It functions to inhibit osteoclasts.
Vitamin D is the only vitamin that can be synthesized in the body. It causes:
1) Increased intestinal absorption of Ca2+.
2) Increased renal reabsorption of both Ca2+ AND PO4-.
3) It stimulates osteoclast activity.
Vitamin D deficiency (Rickets/Osteomalasia) presents with poor bone mineralization and causes chronic renal failure.
Secreted in b-cells of the islets of Langerhan.
It’s release can be stimulated by either cholinergic or sympathetic systems. It is also stimulated directly by high blood glucose levels. As the blood glucose levels rise more glucose is transported into the b-cells which causes increased ATP production. The higher energy charge then causes the K+ cannels to close that depolarizes the cell. This depolarization brings on the influx of Ca2+ which stimulates the release of glucose.
The insulin receptor has four subunits, 2 a-subunits outside where the insulin binds, and two b-subunits inside. When insulin binds to the a-subunits it causes the b-subunits to go into the cells and stimulate the glucose transporters to go to the PM and causes the down regulation of the transcription of the genes for the b-subunits.
Insulin mediated glucose uptake also brings K+ into the cells which can cause decrease in extracellular K+. If you administer insulin to a diabetic patient you must also administer K+ to prevent hypokalemia.
IDDM has a high blood glucose level, metabolic acidosis, hyperosmolarity and hyperkalemia. Treat by the administration of insulin or biguamides which cause insulin like effects by an unknown mechanism.
NIDDM involves high blood sugar and high insulin levels but cellular resistance to insulin. Treat with sulfonylurea which:
1) Blocks b-cell K+ channels which causes increased insulin release.
2) Proposed to also increase the number of insulin receptors.
Sulfonylurea will only cause increased insulin secretion if the patient still has functioning b-cells.
Glucagon is released from the a-cells by:
1) Arginine ingestion.
2) Low blood glucose levels
3) CCK
It functions via a cAMP system to cause:
1) Lowering of glucose usage.
2) Higher usages of and levels of FA and ketoacids.
3) Increase in gluconeogenesis.
Somatostatin is released from the d-cells and functions to inhibit the release of both insulin and glucagon.
The adrenal medulla is made of postganglionic sympathetic neurons that make and release catacholamines, primarily Epi. These hormones are degraded by COMT and MAO. The usually pathway is to first go through COMT and then MAO but if COMT is deficient then it can go directly to MAO and later if COMP becomes available it can then be processed by COMT. Normal breakdown will make mandelic acid. If COMT is present but MAO missing then you will end up with metanephrine or normetanephrine. If COMT blocked it will form 3,4-dihydroxy mandelic acid.
It is stimulated by ACTH and the negative feedback is based on cortisol’s negative feedback on both the hypothalamus and ant. pituitary. It causes secretion at three layers with three different products:
1) Glucocorticoids have two classes of effects:
a. Immunosuppression
b. Diabetogenic
i. Increased gluconeogenesis
ii. Increased lipolysis and AA metabolism
iii. Decreased glucose use
iv. Decreased bone formation
2) Mineralocorticoids (aldesterone) is synthesized under stimulation of ACTH but is released under stimulation of angiotensin II.
3) Androgens
Addison’s disease (1o adrenal insufficiency) usually involves damage to all three sections of the adrenal cortex. Since cortisol will be low there will be elevated ACTH levels which will lead to increased MSH since ACTH and MSH are cleaved from the same propeptide. Treat patients with synthetic glucocorticoids, mineralocorticoids and androgens. Patients will present with:
1) Hyperpigmentation
2) Hypotension
3) Anorexia
4) Decreased pubic hair in women (men have testicular produced androgens)
2o adrenal insufficiency results from decreased ACTH or CRH release and has the same symptoms as Addison’s disease. It is treated with synthetic ACTH.
Cushing’s Syndrome involves hyper-glucocorticoid production and can be treated with ketoconazol which is an ACTH antagonist. Patients present with:
1) Buffalo hump
2) Central obesity
3) Hyperglycemia
4) Osteoporosis
Cushing’s Disease is from over production of ACTH by the pituitary. It’s symptoms are the same as, and the disease is a subset of, Cushing’s syndrome.
The dextramethisome suppression test is used to diagnose Cushing’s disease. Dextramethisome is a synthetic glucocorticoid which is administered to see if it will exert feedback on and lower the circulating levels of ACTH and thereby lowering levels of cortisol. If it does then the patient has Cushing’s disease and the tumor must be removed. If it does not lower cortisol level then the problem is at the level of the adrenal and is Cushing’s syndrome.
Conn’s Syndrome (1o hyperaldesteroneism) results from a tumor of the glomerulosa leading to excessive aldesterone release. It is treated with surgery or an aldesterone antagonist. Patients present with:
1) Hypokalemia
2) Hypertension
3) Metabolic acidosis
4) Decreased renin levels
21b-hydroxylase (or 11b-hydroxylase) deficiency results decreased production of mineralocorticoids and glucocorticoids and an increase in androgen production. Patient presents with symptoms of the associated deficiencies of the given hormones. Treat with hormone replacement.
17a-hydroxylase deficiency will result in low androgen and glucocorticoid production and increased mineralocorticoids production. It is treated with hormone replacement. The immediate precursor or cortisol, corticosterone, does have some glucocorticoid activity that will help symptoms be less severe in this case.
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