Disorders of Ca metabolism Flashcards
PTH effects
directly on kidney/bone; indirect on GI via vit D
which form of vitamn D comes from animal vs plants
- D3 from animals/we make in skin
- D2 from plant source (also has molecules inhibiting absorption)
major vitamin D store
25 hydroxyvitamin D– fat soluble— big reservoir
is hydroxylation regulated
No; based on mass effect
what regulates creation of 1, 25 (OH)2 vit D
PTH
parathyroid disorders vs vitamin D disorders
- vitamin D disorders: Ca and phosphate go in same direction since it increases Ca and phosphate absorption
- parathyroid disorders: moves Ca and P in opposite directions
vit D actions
increase Ca and P absorption
- at higher leves, increases bone resorption
Calcitonin
smaller hormone reducing Ca by reducing osteoclastic activity mainly
how do we regulate serum Ca/detect low Ca
Parafollicular C cells/parathyrod cells/renal tubular cells all have Ca sensor receptor– signals to inside of cell what level of Ca is
Hypercalcemia disorders
- primary hyperparathyroidism
- hypercalcemia of malignancy
- granulomatous disorders (express 1alpha hydroxylase enzyme–so high 1, 25 vit D)
- vit D/A intoxication
- hyperthyroid
- thiazide diuretics
- Milk-Alkali syndrome
- immobilization
- adrenal insufficiency
- acute renal failure
- family hypocalciuric hypercalcemia
most common hypercalcium disorder
primary hyperparathyroidism,
hypercalcemia of malignancy
what do you order after see high Ca to help with diagnosis
PTH–
- PTH elevated in hyperparathyroidism and low in all other except familial hypocalciuric hypercalcemia
- low PTH– more likely malignancy
brown tumors
hyperparathyroidism causes
85% due to adenoma and the other 3 are atrophied
- 15% due to hyperplasia–usually familial and 4 glands affected
-
clinical features of primary hyperparathyroidism
- > 50% asymptomatic
- sk disease
- kidney disease
- GI disease
- psych disease
(Bones, Stones, Groans, Moans) - arthritis, muscle weakness, Band Keratopathy, HTN , anemia
most common sxs of primary hyperparathyroidism
NO SXS!!
Osteoclastoma
benign “brown tumor”
- severe hyperparathyroidism–once tumor removed, osteoclast dies and spot filled in
Band keratopathy
band of Ca deposition of cornea medially/laterally– circumferential
Primary hyperparathyroidism
- elevated serum Ca
- low serum Phosphate
- elevated PTH (nl, midnl or elevated)
hos often familial vs sporadic HPT
90% sporadic (can be hyperplastic)
10% familial (can be hyperplastic)
familial cases of HPT
Familial HPT, MEN 1, MEN 2
MEN1-
- pituitary tumors (multiple), pancreatic islet tumors (multiple), parathyroid hyperplasia
- germline mutation in Menin gene
MEN2
medullary thyroid carcinoma (more aggressive)
- pheochromocytoma
- parathyroid hyperplasia
- mutaiton in Ret gene (GDNF receptor)–abnormally expressed
treat HPT
- surgery – adenoma- (1 gland)– minimally invasive
- for hyperplasia remove 3 1/2 and can leave insitu or removed and - reimplanted to be more available if it becomes overactive in future
- Calcimimetic Drug (Cinacalcet): not curative, but f not good surgical candidate
- Anti-resorptive Bone Drug( bisphosphonate, denosumab)
Secondary hyperparathyroidism
elevated PTH in response to stimuli–low Ca orhigh serum P or low vitamin D
- PTH elevated, but Ca low or low nl; phos high or high nl
Hypercalcemia of Malignancy
- Lung Canver (sq cell esp)
- Breat Cancer
- Head and neck
- Kidney
-Bladder - Pancreatic
Ovarian
Multiple Myeloma
Lymphoma–express alpha hydroxylase–convert vit D to active form– hyperabsorb Ca
hypercalcemia mediators
in malignancy due to PTH related Peptide - TGFbeta -TNF Interleukin 1, 6 TANK-L DKK-1 1, 25 (OH)2 vit D
PTHrp
- protein made by gene expressed in placenta, lactating breasts, skin
- possibly role in Ca crossing placenta and transporting Ca from maternal circulation to milk
- first 13 amino acids the same as PTH, this is the part that binds to the receptor
Hypercalcemia of malignancy
high Ca, low PTH, high PTH-RP or other mediators (1, 25, hydroxy vit D)
Familial hypocalciuric hypercalcemia
- inactivating mutations in Ca sensor receptor, so it doesn’t sense Ca levels–PT just continues to make PTH and kidneys continue to hold onto Ca
- elevated Ca (mild)
- mild elevated serum PTH
- decreased Urine Ca and low Ca/Creatinine ratio (
treatment for Familial hypocalciuric hypercalcemia
NOTHING–not harmful
Causes of hypocalcemia
vitamin D deficient, hypoparathyroidism, pseudohypoparathyroidism, hypomagnesemia, renal failure, liver failure, acute pancreatitis, hypoproteinemia
most common hypocalcemia cause
vitamin D deficiency
Labs in hypocalcemia
- elevated PTH, except for hypoparathyroidism(low)
how much Ca bound to Ca
- 50% bound to protein
- 50% free/ionized
- if low Ca in hospital, most likely due to low serum proteins
what to consider on hospitalized pt with low Ca
- most often due to low serum proteins, so do corrected serum total calcium
- add 0.8 mg/dl to total Ca for every 1g/dl Albumin is
sxs of hypocalcemia
paresthesias( lips/fingers), muscle cramps, muscle weakness, Chvostek’s Sign/Trousseau’s sign (both when more recent)
-may have sxs if acute but if chronic may have few sxs
Trousseau’s sign
sign of acute hypocalcemia– when putting on BP cuff, will have carpopedal spasm
Chvostek’s Sign
when tapping facial nerve in someone who has hypocalcemia, corner of lip will twitch
Vit D disorders
- Acquired deficiency (poor intake/inadequate sunlight)
- Acquired 1,25(OH)2 vit D def (renal disease, hypoparathyroidism)
- Congenital 1 alpha hydroxylase deficiency – “Vit D dependent Ricket’s Type 1:
- Congenital Vitamin D receptor Deficiency - Vit D dependent Rickets Type 2 –give enough vit D will responsd
Labs on vit D deficiency
low Ca, Low, P, low 25 OH vit D
elevated PTH
Alk phos up if osteomalacia
Pseudofracture
not actual fracture–demineralizaiton where artery crosses bone
- commonly tibia, femoral neck
“Milkman’s fracture”
treat vit D def
- replete with high doses vitamin D then maintain on 1000 units a day
hypoparathyroidism
low Ca, high P, low PTH
spontaneous hypoparathyroidism in young ppl
- autoimmune, oft associated with adrenal insufficiency and mucocutaneous candidiasis due to T cell immunodeficiency
pseudohypoparathyroidism
- inability to respond to PTH on membrane bound receptor. Have inactivating mutation in alpha Gs subunit–PTH can bind but no signalling
- oft associated with Albright’s Hereditary Osteodystrophy: shortnening 4/5th metacarpals
(but can occur without pseudohypoparathyroidism)
labs on Pseudohypoparathyroidism
- low Ca
- high P
- ## high PTH
