we started the second week of endocrine with a look at parathryoid and calcium issues. calcium levels are regulated hormonally by 3 main agents: PTH from the parathyroid, activated vitamin D from the kidneys, and calcitonin from the thyroid. PTH has four main actions: increases osteoclastic activity, increases reabsorption of calcium in the kidneys, decreases reabsorption of phosphate in the kidneys, and stimulates activation of vitamin D in the kidneys. whereas PTH has the effect of raising serum calcium levels, calcitonin (secreted from the C cells of the thyroid) lowers them by inhibiting osteoclastic bone resorption.
parathyroid hormone can be secreted in excess in many conditions, categorized by 1º, 2º, 3º. 1º is usually due to a parathyroid adenoma and results in osteoporosis, kidney stones, abdominal symptoms, and fatigue (bones, stones, groans, moans). it may also be asymptomatic and found by elevated serum calcium levels. hypercalcemia can also be caused by other conditions such as multiple sclerosis and sarcoidosis, in which case PTH levels would be low due to negative feedback to the parathyroid. 2º hyperparathyroid is often due to renal failure, which causes chronically low levels of calcium, resulting in compensatory PTH secretion. 3º refers to hypercalcemia from autonomous PTH secretion.
on the other end, hypoparathyroidism is mainly caused by surgical procedures-- such as removing part of the thyroid in grave's disease. signs and symptoms might include neuromuscular instability, parkinsons-like movements, and muscle tetany. the characteristic signs on a PE are chvosek (tapping on the TMJ causes contraction of the periorbital or perioral muscles) or trousseau's sign (carpal pedal spasm from occluding forearm blood supply).
the thyroid gland produces thyroid hormone mostly in the form of T4, most of which is bound to TBG in the blood. hypothyroidism can be due to primary causes (autoimmune dysfunction of the thyroid itself), secondary (dysfunction of anterior pituitary secretion of TSH), or tertiary (dysfunction of hypothalamic secretion of TRH), though the latter two are relatively rare. primary hypothyroidism can affect newborns, and cretinism can develop if thyroid hormones are low during the first few weeks of life, resulting in mental retardation, short stature, puffy facial features, among other symptoms.
for adults, hypothyroidism occurs more frequently in females, and is most commonly due to autoimmune disease, although outside the US can also be attributed to iodine deficiency. besides the signs and symptoms related to slowed metabolism (decreased circulation, energy, hair loss, etc), one might also notice follicular hyperkeratosis-- red bumps over the hair follicles on the outer arms, which is related to a defect in vitamin A synthesis, as well as diminished DTR's. lab values would show decreased levels of T4 but increased levels of TSH. secondary hypothyroidism results from pituitary dysfunction, causing low TSH and T4/T3 levels but high TRH levels. patients might present with signs of general pituitary dysfunction, or an intracranial mass (such as pituitary adenoma symptoms).
hyperthyroidism manifests with signs of metabolic excess such as heat intolerance, weight loss, irritability, warm/moist skin, muscle tremors, high cardiac output, etc. the most common cause is autoimmune via antibodies to the thyroid's TSH receptors as in grave's disease. grave's patients might also present with pretibial myxedema, a skin thickening specific to the legs. hyperthyroid states are diagnosed by testing for antibodies against the thyroid as well as checking radioactive iodine uptake. high uptake plus positive antibodies means primary / autoimmune hyperthyroid. high uptake plus negative antibodies can mean plummer's syndrome, toxic thyroid nodules that can stimulate thyroid hormone production. low uptake plus negative antibodies can indicate thyroiditis.
four types of thyroid cancer have been identified: papillary is the most common and has a relatively good prognosis. follicular is more malignant and makes up 15% of thyroid cancers. medullary involves proliferation of c-cells and subsequent elevation of calcitonin levels. anaplastic / undifferentiated type is the most rare and has the worst prognosis.
questions
physiology...
1. what are the three hormones that are in charge of calcium regulation and where are they secreted from?
2. what steps would be taken in order to make a diagnosis of hyperparathyroid from a patient with high calcium levels?
3. what are the four main actions of PTH?
4. what are the actions of calcitonin and where is it secreted from?
hyperparathyroid states...
5. what is 1º hyperparathyroidism usually due to?
6. what are the signs and symptoms of 1º hyperparathyroidism?
7. besides hyperparathyroidism, what are some other causes of hypercalcemia?
8. in general, how high or low are PTH levels in hypercalcemia that is not of parathyroid origin?
9. what is the most common cause of 2º hyperparathyroidism?
10. what is the mechanism of pathogenesis for 2º hyperparathyroidism?
11. what is the hallmark of 3º hyperparathyroidism?
hypoparathyroid...
12. what is the most common cause of hypoparathyroidism?
13. what are the signs / symptoms of hypoparathyroidism?
14. what are the classic PE findings for hypoparathyroidism?
15. describe the first sign from question 14.
16. describe the second sign from question 14.
thyroid physiology review...
17. which cells in which gland is TSH made in?
18. TSH levels are mainly regulated by...
19. what are the three proteins that carry thyroid hormones in the blood?
hypothyroidism intro...
20. what is the difference between primary, secondary, and tertiary hypothyroidism?
21. what is peripheral hypothyroidism?
22. what are some etiologies for primary hypothyroidism?
23. hypothyroid is the number one reversible cause of...
24. what is cretinism and what are its manifestations?
primary hypothyroidism...
25. which gender is hypothyroidism more common in?
26. what are the most common causes of adult hypothyroidism in the US and the world?
27. what is follicular hyperkeratosis and what is it due to?
28. what is a common PE finding for hypothyroidism?
29. what are the lab values for the thyroid hormones in hypothyroidism?
secondary hypothyroidism...
30. what is a condition associated with secondary hypothyroidism?
31. what are the signs / symptoms of a patient with secondary hypothyroidism?
32. what åre the typical lab values for a patient with secondary hypothyroidism?
33. what is a contraindication for thyroid hormone replacement therapy?
hyperthyroidism...
34. what are some of the symptoms of hyperthyroidism?
35. what are some PE findings for hyperthyroidism?
36. what is the most common cause of hyperthyroidism?
37. what is the mechanism for the condition in question 36?
38. what is a symptom associated with the condition in question 36 that manifests on the extremities?
39. how is the cause of hyperthyroidism determined diagnostically?
40. according to the method in question 39, primary hyperthyroid would be characterized by...
41. according to the method in question 39, plummer's syndrome would be characterized by...
42. according to the method in question 39, thyroiditis would be characterized by...
other thyroid pathologies...
43. what are the 4 types of thyroid cancer?
44. which thyroid cancer is the most common?
45. which is more malignant, follicular or papillary?
46. the medullary type is characterized by proliferation of which cell?
47. how does anaplastic thyroid cancer present?
answers
1. PTH from parathyroid, calcitonin from thyroid, and activated vitamin D from the kidneys.
2. recheck. check for high ionized calcium levels. check for high PTH levels.
3. stimulates osteoblastic activity
inhibits reabsorption of phosphate in the kidneys
stimulates reabsorption of calcium in the kidneys
stimulates activation of vitamin D in the kidneys
4. secreted from C cells of the thyroid, decreases serum calcium by decreasing bone resorption via osteoclasts.
5. parathyroid adenoma.
6. bones, stones, abdominal moans, groans.
7. multiple sclerosis, paget's disease, vitamin D intoxication, sarcoidosis.
8. low because of negative feedback to the parathyroid.
9. renal disease.
10. depressed serum calcium leads to overcompensation via PTH secretion.
11. development of autonomous hypersecretion of PTH, causing hypercalcemia.
12. surgically induced.
13. neuromuscular instability, parkinsons-like movements, tetany.
14. chvosek and trousseau's sign.
15. tapping around the TMJ causes contraction of muscles around the mouth or eyes.
16. "carpal pedal spasm" resulting from occluding blood supply to forearm for several minutes.
17. thyrotroph cells of the anterior pituitary.
18. T3 levels.
19. TBG, transthyretin, albumin.
20. primary is a dysfunction in secretion of the thyroid gland itself, secondary is dysfunction in secretion of TSH from AP, tertiary is dysfunction in secretion of TRH from hypothalamus.
21. peripheral resistance to thyroid hormones, or reduced T4 to T3 conversion, or excess rT3.
22. congenital
iodine deficiency related (goitrogens)
thyroid ablation
23. depression.
24. primary hypothyroid during the first few weeks of life, resulting in mental retardation, short stature, puffy facial features, dry skin, myxedema.
25. females.
26. autoimmune, and iodine deficiency.
27. red bumps over the hair follicles on the outer arm, due to vitamin A synthesis defect.
28. diminished DTR's
29. high TSH, low T4.
30. sheehan's.
31. symptoms of deficiency of other pituitary hormones, or intracranial mass.
32. high TRH, low TSH, low T4 and T3.
33. adrenal cortisal insufficiency / addison's, MI, thyrotoxicosis
34. heat intolerance
irritability
weight loss
exophthalmos
35. may have goiter
warm, moist skin
conjunctival injection
high cardiac output
tremor
fast DTR's
36. grave's disease.
37. antibody against TSH receptor causes constant stimulation of thyroid gland.
38. skin thickening on the legs: pretibial myxedema.
39. testing for antibodies to thyroid plus radioactive iodine uptake.
40. high uptake and positive antibodies.
41. high uptake and negative antibodies.
42. low uptake and negative antibodies.
43. papillary, follicular, medullary, anaplastic.
44. papillary.
45. follicular.
46. c cells that produce calcitonin.
47. rapid and painful enlargement of the thyroid, poor prognosis.
Showing posts with label parathyroid. Show all posts
Showing posts with label parathyroid. Show all posts
Monday, May 10, 2010
Monday, February 2, 2009
organ systems: calcium and phosphate
this is the 5th lecture in the series on the kidney and talks about the kidneys' role in the regulation of calcium and phosphate levels. the kidney is one of three regulatory sites for calcium blood levels, the other two being the intestine and the bone. falling blood calcium levels trigger the release of parathyroid hormone from the parathyroid glands, which has a multifaceted effect that ultimately raises blood calcium levels.
in the kidney, the 60% of calcium that is filtered (meaning not bound to blood proteins) is mainly reabsorbed in the proximal convoluted tubule in a fashion similar to the reabsorption of sodium. PTH regulation plays a role in the reabsorption of calcium in the thick ascending limb and distal convoluted tubule; by upregulating calcium channels and pumps in the tubular epithelium. it also downregulates phosphate transporters, leading to the simultaneous decreasing of phosphate reabsorption. the rationale behind this is that high phosphate levels and calcium levels would lead to mineralization in non-bone tissues.
in the intestines, PTH stimulates calcium absorption from the gut by way of regulating the synthesis of vitamin D into its active form. vitamin D then activates calcium channels and calbindin, which transports calcium across the cells.
in the bones, PTH regulates blood calcium levels by maintaining the balance between calcium being deposited onto new bone surfaces by osteoblasts (deposition) vs. calcium being released into the bloodstream by the breakdown of bone by osteoclasts (resorption). in general, PTH stimulates osteoclast activity by signalling apoptosis in osteoblasts, thereby raising calcium levels. if PTH is pulsed, however, osteoblast apoptosis is inhibited and deposition by osteoblasts can actually be stimulated.
a few pathologies related to calcium regulation: hyperparathyroidism results in the excess secretion of PTH and thus excessively high blood Ca2+ levels, as well as a loss of calcium levels in the bone. hypoparathyroidism is the opposite condition which results in low blood calcium levels. osteomalacia is a demineralization of the bone which results from a deficiency of calcium or vitamin D. osteoporosis is also a demineralization of the bone which results in the loss of bone matrix, not just calcium.
questions
1. what are calcium and phosphate used for in the body?
2. how closely regulated are calcium levels in the body?
3. where are the main sites for homeostatic control of calcium levels?
4. what are the primary hormones that provide homeostatic maintenance of calcium and phosphate levels?
5. what form is calcium found in the body? how much is filtered in the kidney?
6. how does acidosis relate to Ca2+ in the blood? what does it result in?
7. how does alkalosis relate to Ca2+ in the blood? what does it result in?
8. PTH is secreted in response to...
9. describe the reabsorption of Ca2+ in the kidney.
10. describe PTH's control over phosphate reabsorption.
11. why does PTH stimulate reabsorption of Ca2+ and simultaneous excretion of PO4-?
12. describe vitamin D's role in intestinal calcium absorption.
13. describe PTH's role in vitamin D synthesis.
14. describe vitamin D's role in intestinal phosphate absorption.
15. what are the two factors that regulate bone formation and remodeling?
16. describe how stress regulates remodeling of bone.
17. calcium and phosphate are stored in bone in the form of...
18. how is hydroxyapetite formation inhibited in non bone tissues?
19. how do osteoblasts overcome the solubilizing of calcium and phosphate by pyrophosphate in bone?
20. what is calcitonin and where is it released from?
21. how does calcitonin lower blood Ca+ levels?
22. how does PTH stimulate deposition of bone?
23. how does PTH stimulate resorption of bone?
24. how is PTH used to control the balance between deposition/resorption of bone?
25. what effect does hyperparathyroidism have on Ca2+ levels?
26. what effect does hypoparathyroidism have on Ca2+ levels?
27. osteomalacia is...
28. osteoporosis is...
answers
1. muscle contraction, secretion of neurotransmitters, hormones, enzymes, etc.
2. very closely, varying only 1-2% daily or weekly
3. kidney, bone, intestines
4. parathyroid hormone, vitamin D, calcitonin
5. 40% protein bound (and thus not filterable by the kidney), 10% in Ca2+ form, 50% bound to anions. 60% filtered in the kidney.
6. H+ compete with Ca2+ for sites on albumin, which transports the ions in the blood. if the pH is low, then there is less protein bound calcium and thus more free ionized form. this causes decreased neural activity and muscle weakness.
7. if there are less H+ in the blood, then Ca2+ binds to proteins in the blood and reduces the free ionized form. this causes neuromuscular irritability and CNS problems.
8. a fall in blood Ca2+ level.
9. 2/3 of the Ca2+ is reabsorbed in the proximal convoluted tubule, and 1/3 is reabsorbed in the thick ascending loop and distal convoluted tubule. PTH provides fine control over Ca2+ reabsorption in the ascending loop and distal convoluted tubule.
10. PTH inhibits reabsorption of phosphate in the proximal convoluted tubule, where most phosphate reabsorption takes place.
11. because raising both phosphate and calcium levels could create calcium phosphate in soft tissues.
12. vitamin D upregulates of calcium membrane transporters as well as calbindin, which carries calcium across the cell.
13. PTH, secreted in response to falling Ca2+ levels, regulates the synthesis of 1,25 hydroxylated vitamin D- the active form.
14. vitamin D upregulates Na-PO4 cotransporter in intestinal cells.
15. hormones and physical stress.
16. stress creates a piezoelectric effect that initiates osteoblast (bone building) and osteoclast (bone destroying) activity on opposing surfaces which remodels bone.
17. hydroxyapetite: Ca10(PO4)6OH2
18. it remains in soluble form by pyrophosphate.
19. osteoblasts contain alkaline phosphatases that cleave pyrophosphates, freeing calcium and phosphate to form bone.
20. a hormone that is released in response to rising Ca2+ levels that counters the effects of PTH. released from parafollicular cells of the thyroid.
21. by inhibiting osteoclast activity; free Ca2+ is then used to deposit bone by osteoblasts.
22. PTH stimulates osteoclast activity, which can induce release of growth factors from bone matrix which can in turn stimulate osteoblast deposition of bone.
23. PTH stimulates osteoblast to initiate RANK/RANKL paracrines which activates osteoclasts and thus stimulates bone resorption.
24. if PTH is secreted intermittently, osteoblast apoptosis is inhibited and deposition occurs. if PTH is secreted continuously, osteoblasts continue to undergo apoptosis and osteoclast activity resorbs bone.
25. excess secretion of PTH causes blood Ca2+ levels to rise and bone density to fall.
26. reduction in osteoclastic activity reduces resorption of calcium and lowers blood calcium levels.
27. demineralization of bone resulting from deficiency in calcium or vitamin D.
28. loss of bone matrix
in the kidney, the 60% of calcium that is filtered (meaning not bound to blood proteins) is mainly reabsorbed in the proximal convoluted tubule in a fashion similar to the reabsorption of sodium. PTH regulation plays a role in the reabsorption of calcium in the thick ascending limb and distal convoluted tubule; by upregulating calcium channels and pumps in the tubular epithelium. it also downregulates phosphate transporters, leading to the simultaneous decreasing of phosphate reabsorption. the rationale behind this is that high phosphate levels and calcium levels would lead to mineralization in non-bone tissues.
in the intestines, PTH stimulates calcium absorption from the gut by way of regulating the synthesis of vitamin D into its active form. vitamin D then activates calcium channels and calbindin, which transports calcium across the cells.
in the bones, PTH regulates blood calcium levels by maintaining the balance between calcium being deposited onto new bone surfaces by osteoblasts (deposition) vs. calcium being released into the bloodstream by the breakdown of bone by osteoclasts (resorption). in general, PTH stimulates osteoclast activity by signalling apoptosis in osteoblasts, thereby raising calcium levels. if PTH is pulsed, however, osteoblast apoptosis is inhibited and deposition by osteoblasts can actually be stimulated.
a few pathologies related to calcium regulation: hyperparathyroidism results in the excess secretion of PTH and thus excessively high blood Ca2+ levels, as well as a loss of calcium levels in the bone. hypoparathyroidism is the opposite condition which results in low blood calcium levels. osteomalacia is a demineralization of the bone which results from a deficiency of calcium or vitamin D. osteoporosis is also a demineralization of the bone which results in the loss of bone matrix, not just calcium.
questions
1. what are calcium and phosphate used for in the body?
2. how closely regulated are calcium levels in the body?
3. where are the main sites for homeostatic control of calcium levels?
4. what are the primary hormones that provide homeostatic maintenance of calcium and phosphate levels?
5. what form is calcium found in the body? how much is filtered in the kidney?
6. how does acidosis relate to Ca2+ in the blood? what does it result in?
7. how does alkalosis relate to Ca2+ in the blood? what does it result in?
8. PTH is secreted in response to...
9. describe the reabsorption of Ca2+ in the kidney.
10. describe PTH's control over phosphate reabsorption.
11. why does PTH stimulate reabsorption of Ca2+ and simultaneous excretion of PO4-?
12. describe vitamin D's role in intestinal calcium absorption.
13. describe PTH's role in vitamin D synthesis.
14. describe vitamin D's role in intestinal phosphate absorption.
15. what are the two factors that regulate bone formation and remodeling?
16. describe how stress regulates remodeling of bone.
17. calcium and phosphate are stored in bone in the form of...
18. how is hydroxyapetite formation inhibited in non bone tissues?
19. how do osteoblasts overcome the solubilizing of calcium and phosphate by pyrophosphate in bone?
20. what is calcitonin and where is it released from?
21. how does calcitonin lower blood Ca+ levels?
22. how does PTH stimulate deposition of bone?
23. how does PTH stimulate resorption of bone?
24. how is PTH used to control the balance between deposition/resorption of bone?
25. what effect does hyperparathyroidism have on Ca2+ levels?
26. what effect does hypoparathyroidism have on Ca2+ levels?
27. osteomalacia is...
28. osteoporosis is...
answers
1. muscle contraction, secretion of neurotransmitters, hormones, enzymes, etc.
2. very closely, varying only 1-2% daily or weekly
3. kidney, bone, intestines
4. parathyroid hormone, vitamin D, calcitonin
5. 40% protein bound (and thus not filterable by the kidney), 10% in Ca2+ form, 50% bound to anions. 60% filtered in the kidney.
6. H+ compete with Ca2+ for sites on albumin, which transports the ions in the blood. if the pH is low, then there is less protein bound calcium and thus more free ionized form. this causes decreased neural activity and muscle weakness.
7. if there are less H+ in the blood, then Ca2+ binds to proteins in the blood and reduces the free ionized form. this causes neuromuscular irritability and CNS problems.
8. a fall in blood Ca2+ level.
9. 2/3 of the Ca2+ is reabsorbed in the proximal convoluted tubule, and 1/3 is reabsorbed in the thick ascending loop and distal convoluted tubule. PTH provides fine control over Ca2+ reabsorption in the ascending loop and distal convoluted tubule.
10. PTH inhibits reabsorption of phosphate in the proximal convoluted tubule, where most phosphate reabsorption takes place.
11. because raising both phosphate and calcium levels could create calcium phosphate in soft tissues.
12. vitamin D upregulates of calcium membrane transporters as well as calbindin, which carries calcium across the cell.
13. PTH, secreted in response to falling Ca2+ levels, regulates the synthesis of 1,25 hydroxylated vitamin D- the active form.
14. vitamin D upregulates Na-PO4 cotransporter in intestinal cells.
15. hormones and physical stress.
16. stress creates a piezoelectric effect that initiates osteoblast (bone building) and osteoclast (bone destroying) activity on opposing surfaces which remodels bone.
17. hydroxyapetite: Ca10(PO4)6OH2
18. it remains in soluble form by pyrophosphate.
19. osteoblasts contain alkaline phosphatases that cleave pyrophosphates, freeing calcium and phosphate to form bone.
20. a hormone that is released in response to rising Ca2+ levels that counters the effects of PTH. released from parafollicular cells of the thyroid.
21. by inhibiting osteoclast activity; free Ca2+ is then used to deposit bone by osteoblasts.
22. PTH stimulates osteoclast activity, which can induce release of growth factors from bone matrix which can in turn stimulate osteoblast deposition of bone.
23. PTH stimulates osteoblast to initiate RANK/RANKL paracrines which activates osteoclasts and thus stimulates bone resorption.
24. if PTH is secreted intermittently, osteoblast apoptosis is inhibited and deposition occurs. if PTH is secreted continuously, osteoblasts continue to undergo apoptosis and osteoclast activity resorbs bone.
25. excess secretion of PTH causes blood Ca2+ levels to rise and bone density to fall.
26. reduction in osteoclastic activity reduces resorption of calcium and lowers blood calcium levels.
27. demineralization of bone resulting from deficiency in calcium or vitamin D.
28. loss of bone matrix
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