B6-050 CBCL Hyperparathyroidism Flashcards
parathyroid glands are located
on the back of thyroid
cells that produce PTH
chief cells
chief cells are stimulated to produce PTH by [3]
low calcium
high phosphate
low vitamin D
PTH stimulates osteoblasts to secrete
RANKL
RANKL binds to RANK on osteoclasts stimulating them to
resorb bone
bone resorption releases [2] ions into blood
Ca++
PO43-
decreased calcium levels stimulates PTH to activate […] to increase calcium levels in the blood
osteoclasts
PTH stimulates […] in the PCT to activate vitamin D
a-1-hydroxylase
PTH stimulates a-1-hydroxylase in the […] to activate vitamin D
PCT
once activated in the kidney, […] stimulates GIT to absorb calcium in the gut
vitamin D
once activated in the kidney, vitamin D stimulates GI tract to absorb […] in the gut
calcium
phosphate is excreted from what part of the kidney?
PCT
how does PTH decrease phosphate ions in blood?
inhibits transporter for reabsorption of Na+ and phosphate in PCT
decreases the phosphate concentration in blood
PTH
**phosphate trashing hormone
calcium is reabsorbed from what part of the kidney?
DCT
PTH can directly stimulate the transporter for reabsorption of […] in the DCT
Ca++
summarize the effects of PTH on the kidney [4]
increase a-1-hydroxylase
increase PO4 excretion in urine
decrease PO4 in serum
increase calcium in serum
overall effects of hypersecretion of PTH [2]
hypercalcemia
hypophosphatemia
primary causes of high PTH [3]
adenomas
hyperplasia
carcinoma
MEN1 and 2 mutations cause […] hyperparathyroidism
primary
most common cause of secondary hyperparathyroidism
chronic kidney disease
causes of secondary hyperparathyroidism [3]
CKD
vitamin D deficiency
low calcium diet
what stimulates PTH production in CKD? [2]
low calcium
high phosphate
hyperparathyroidism due to chronic hypocalcemia
secondary
phosphate binds
free calcium
how does CKD cause hyperparathyroidism?
reduced GFR causes hyperphosphatemia –> hypocalcemia
reduced function of PCT causes hyperphosphatemia and hypocalcemia
reduced function of DCT causes
hyperphosphatemia and hypocalcemia
malabsorptive syndromes like Crohns or celiac can cause
decreased absorption of vitamin D –> secondary hyperparathyroidism
How does pancreatic insufficiency cause secondary hyperparathyroidism?
pancreatic lipase is important for fat absorption, and vitamin D is absorbed with fat –> decreased absorption of vitamin D
how do gallstones cause secondary hyperparathyroidism?
bile is important for fat absorption
vitamin D needs fat to be absorbed
no bile —> decreased absorption of vitamin D
decreased sun exposure can cause
secondary hyperparathyroidism
**less formation of active vitamin D
chronic hypocalcemic state that progresses over time, past secondary
tertiary hyperparathyroidism
consistent, constant stimulation of the parathyroid leads to
hyperplasia
uncontrolled release of PTH independent of any signaling from feedback regulation
tertiary hyperparathyroidism
mneumonic for primary hyperparathyroidism
bones
stones
groans
thrones
psychiatric overtones
PTH liberates [3] things from bones
Ca++
PO43-
hydroxyapatites
excessive PTH causes […] of bone
demineralization
**increased risk of fracture
bone density decreases due to constant demineralization
osteoporosis
**increased risk of fracture
condition occurring due to increased bone resorption
osteoclasts and connective tissues form cavities that look like cyst
osteitis cystica fibrosis
**occurs due to primary hyperparathyroidism –> increased osteoclast activity
nephrocalcinosis
calcium and phosphate stones deposit in small parts of kidney tubules or smaller calyxes
nephrolithiasis
calcium and phosphate stones form in ureter/renal calyx
[…]calemia decreases smooth muscle activity
hypercalcemia
how does hypercalcemia decrease smooth muscle activity
increased Ca++ blocks Na+ channels in smooth muscle
**results in reduced GI motility
GI symptoms of primary hyperparathyroidism
constipation
abdominal pain
nausea
vomiting
how can primary hyperparathyroidism cause ulcers?
Ca++ activates gastrin and stimulates parietal cells to increase HCl in stomach
how can primary hyperparathyroidism cause pancreatitis?
Ca++ activates pancreatic enzymes in pancreatic ducts –> autodigestion causing significant abdominal pain
how does primary hyperparathyroidism causes nephrogenic diabetes insipidus?
Ca++ inhibits ADH –> less water is reabsorbed
symptoms of nephrogenic DI caused by primary hyperparathyroidism
polyuria: increased urine output
polydipsia: to compensate for water lost in bloodstream there is excessive thirst
how does primary hyperparathyroidism cause decreased mental function?
Ca++ can bind to Na+ channels in brain and block electrical activity
neurological manifestations of primary hyperparathyroidism
lethargy
depression
AMS: can progress to coma due to severe hypercalcemia
reduction of deep tendon reflexes
Ca++ in the channel will hinder […] from entering cells of smooth muscles or neurons
Na+
**causes slow activity and neurological symptoms
Ca++ in the channel will hinder Na+ from entering cells of […] and […]
smooth muscle
neurons
**causes slow activity and neurological symptoms
how does secondary hyperparathyroidism caused by CKD effect the kidneys?
kidney is damaged and unable to resorb calcium
how does secondary hyperparathyroidism caused by CKD effect the GI tract?
kidney damage prevents activation of vitamin D
without activated vitamin D, GI tract cannot absorb calcium
how does secondary hyperparathyroidism caused by CKD effect the bones?
increase bone demineralization due to hypocalcemia
group of conditions caused by CKD leading to secondary hyperparathyroidism that damages bone
renal osteodystrophy
since PTH cannot get Ca++ from kidneys or GI, it causes massive demineralization of bone
demineralization causing cystic cavities in bone
osteitis cystica fibrosa
[…]calcemia shortens the QT interval
hypercalcemia
seen in secondary and tertiary hyperparathyroidism when there is too much Ca++ and it deposits around the vessels
calciphylaxis
Ca++ deposition around vessels causing ischemia/necrosis of skin lesions
calciphylaxis
calcium in the serum may appear low if […] is also low
albumin
equation for correction of calcium
serum Ca + 0.8 x (4-albumin)
medications that can cause hypercalcemia
thiazides
lithium
calcium supplements
vitamin D supplements
typically, if calcium is elevated, PTH is
decreased
elevated calcium with normal/high PTH
PTH mediated hypercalcemia
first step in diagnosing hypercalcemia
recheck serum calcium
check PTH levels
85% of primary hyperparathyroidism occurs due to
solitary parathyroid adenoma
expected labs for primary hyperparathyroidism
elevated PTH
elevated serum calcium
elevated urine calcium
low phosphate
should you biopsy parathyroid carcinoma?
no, risk for seeding
hypercalcemia caused by a parathyroid carcinoma can be treated with
cinacalcet
primary treatment of parathyroid carcinoma
surgical resection
excessive PTH secretion as a secondary response to hypocalcemia
secondary hyperparathyroidism
chronic hypocalcemia causes parathyroid […]
hyperplasia
results from progression of secondary hyperparathyroidism
tertiary hyperparathyroidism
prolonged hypocalcemia causes development of autonomous parathyroid function and hypercalcemia
tertiary hyperparathyroidism
in tertiary hyperparathyroidism, […] remains despite discontinuation of vitamin D and calcium supplements
hypercalcemia
most commonly occurs in CKD or post kidney transplant
tertiary hyperparathyroidism
in tertiary hyperparathyroidism, […] remains high despite vitamin D therapy and correction of hyperphosphatemia
PTH
inheritance pattern of FHH
autosomal dominant
parathyroid glands and kidney detect serum calcium concentrations via
calcium sensing receptor
FHH is an [….] mutation of CaSR
inactivating
parathyroid gland perceives serum calcium is low due to decreased sensitivity, leading to increased PTH secretion and serum calcium
FHH
paradoxical hypocalciuria in the setting of hypercalcemia
FHH
does FHH resolve with surgery?
no