Disorders of Ca2+ metabolism Flashcards
Ca2+ range
8.5 mg/dl - 10.5 mg/dl
Ca2+ regulating hormones
- PTH
- made in parathyroid - 1,25(OH)2D3
- made in kidney - Calcitonin
- made in thyroid
Ca2+ regulating organs
- bone
- kidney
- intestine
PTH effects
↓ Calcium excretion
↑ bone resorption
↑ Ca2+ abs
↑ 1,25 OH2D production
↑ Phosphate excretion
Major storage form of Vit D
25OHVIt D
(it gets converted to active form 1,25 OH2 Vit D by kidney
Effects of 1,25(OH)2VitD
↑ Bone resorption → ↑ serum ca → ↑Ca absorption + ↑ Phosphate absorption
*note that PTH effects is ↑ phosphate excretion
What do these cells regulate?
- Parathyroid cell
- Parafollicular C cell
- Renal tubular cell
- Parathyroid cell
- PTH secretion - Parafollicular C cell
- Calcitonin secretion - Renal tubular cell
- calcium excretion
SOme causes of hypercalcemic disorders
LOTS! (12)
- primary hyperparathyroidism
- Familial hypocalciuric hypercalcemia
- granulomatous disease
- VIt D intox
- Vit A intox
- hyperthyroidism ect
Of the 12 hypercalcemic disorders, when would you expect ↑ PTH levels?
primary hyperparathyroidism
Familial hypocalciuric hypercalcemia
*labs are exactly same. need to differentiate via piss
Classifications of primary hyperparathyroidism
- 85% adenoma
- 15% hyperplasia
- usually familial
3.
Clinical features of primary hyperparathyroidism
> 50% asymptomatic
If severe
Bones, Stones, Groans, Moans syndrome
- Skel disease
- kidney disease
- muscle weakness
- arthritis
- HTN
- Band keratopathy
Band keratopathy
seen in hyperparathyroidism
labs to dx primary hyperparathyroidism
- ↑ serum Ca2+
- ↓ serum phosphate
- ↑ serum PTH
is primary hyperparathyroidism due to sporadic or familial causes?
90% sporadic
10% familial
- familial HPT
- MEN I + IIA
MEN I germline can cause
3 P’s (337)
Pituitary tumors
Parathyroid Hyperplasia
Pancreatic Islet tumors
- MENIN gene mutation
MEN IIA germline can cause
2 P’s
Pheochromocytoma
Parathyroid hyperplasia
Medullary thyroid carcinoma
- RET gene mutation
Secondary hyperparathyroidism
parathyroid glands become active on their own
- Secondary hyperplasia due to ↓ Ca2+ abs and/or ↑ PO43-,
most often due to chronic renal disease!!!!
(↓ 1, 25 Vit D)
or nutritional vit defic.
Labs of secondary hyperparathyroidism
- ↓ Ca2+
- ↑ Phosphorous
- ↓ 1, 25 Vit D (most often due to chronic renal disease)
1 mediator of hypercalcemia of malignancy
what lab values would you expect?
PTH related peptide (PTH-RP)
↓ serum PTH
↑ serum Ca2+
↑ PTH-RP
Familial hypocalciuric hypercalemia
- what lab values will you see?
Have inactivating mutations in Ca2+ sensor receptor
- body will compensate and ↑ PTH secretion +
↓ Ca2+ excretion
labs:
↓ Urinary Ca2+
↑ Serum PTH + Ca2+
All causes of hypocalcemia will have a ↑ serum PTH except which one?
↓ PTH if pt has hypoparathyroidism
Corrected serum total calcium
measure if you see that serum ca2+ is low
Add 0.8 mg/dl to total calcium for every 1 g/L Albumin is
Clinical features of Hypocalcemia
- paresthesias
- muscle cramps
- muscle weakness
- chvostek’s sign
- tap facial nerve, wink on that side of face above lips - Trousseau’s sign
- make duck with hand if you put a bp cuff on
what do you think when both Ca and Phos are low?
VIt D deficiency
- osteomalacia
- changes both in the same direction
Vit D dependent rickets Type 1
Congenital 1 alpha hydroxylase deficiency
- cant make active Vit D (low 1,25, high 25)
Vit D dependent rickets Type 2
congenital vit D receptor deficiency/not working
- have nl levels of Vit D and everything down stream
- give them high enough levels, then they WILL respond
Lab values for nutritional vit D deficiency
Serum:
↓ Ca2+
↓ Phosphate
↓ 25 (OH) VIt D
↑ PTH
↑ Serum alkaline phosphate (suggesting osteomalacia)
lab values for hypoparathyroidism and pseudohypoparathyroidism
hypoparathyroidism
↑ serum phosphate
↓ serum ca
↓ serum PTH
pseudohypoparathyroidism
↑ serum phosphate
↑ serum PTH
↓ serum Ca
- note that pseudohypoparathyroidism can result in short 4th and 5th metacarpals
- *pseudopara: PT receptors in kidney and bones are not responsive to PTH itself. PTH mech doesnt work. Give Vit D.
- give Vit D
PTH endocrine signaling pathway
activate alpha subunit of GPCR → cAMP → PTH action
Albrights hereditary osteodystrophy
Pseudohypoparathyroidism
- can result in short 4th and 5th metacarpals
↑ serum phosphate
↑ serum PTH
↓ serum Ca
- pseudopara: PT receptors in kidney and bones are not responsive to PTH itself. PTH mech doesnt work. Give Vit D.
- give Vit D since they cant make active Vit D