calcium metabolism

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normal serum calcium

8.4-10.2 mg/dL

three forms of calcium in extracellular compartment

1. ionized Ca2+ - 50% (MET. ACTIVE)
2. bound to albumin - 40%
3. complexed with anions such as citrate and phosphate - 10%

total calcium measurement has to be adjusted ...

for every 1g/dL of serum albumin that deviates from 4mg/dL -> causes a 0.8 mg/dL variation in calcium

two main hormones involved in calcium metabolism

1. PTH
2. 1,25-hyhydroxy vit D

target organs of the hormones that regulate Ca

bone
kidney
intestines

what the most important hormone for Ca regulation

PTH
-changes in serum Ca level will increase or decrease the levels PTH in a matter of minutes

low Ca levels will cause inc or dec secretion of PTH?

increased secretion

how does the parathyroid know what the Ca levels are?

calcium sensing receptors

what is necessary for noraml secretion of PTH?

normal serum Mg

PTH effects on bone

-stimulates bone turnover, activation of osteoclasts ->results in release of Ca into the circulation

effects of PTH on kidneys

1)inc reabsorption in the distal tubules
2)dec phosphate reabsorption in prox tubules
3) stimulation of the renal cortical enzyme 1-ALPHA-HYDROXYLASE which causes:
25-hydroxy vit D ->to active 1,25 dihydroxy vit D
-this leads to inc absorption of Ca and PO in the gut

effects of PTH on intestines

indirect effect by increasing 1,25 dihydroxy vit D
-> inc Ca and PO in gut

how does vit D get into the curculation?

-oral ingestion
-via conversion of
7-dehydrocholestrol -> vit D via UV light

what happens to vit D from sun light?

in the liver it is converted to 25-hydroxy vit D
then in the renal cprtex it is converted to 1,25-dihydroxy vit D

what enzyme? and where?
vit D (cholicalciferol) -> 25-hydroxy vit D

25-hydroxylase (liver)

what enzyme? and where?
25-hydroxy vit D -> 1,25 dihydroxy vit D

1- alpha-hydroxylase (renal cortex)

which form of vit D is active and what does it do?

1,25 dihydroxy vit D

-promotes Ca absorption in the gut
-dec PTH synthesis
-promotes PO absoption from gut

which vit D do we test?

25-hydroxy vit D

what is the difference between PTH and active vit D?

PTH -> inc Ca and dec PO
Vit D-> inc Ca and inc PO

hypercalcemia

more than 10.2mg/dL

most common presentation of hypercalcemia

LAB FINDINGS
most pts don't have syms until total Ca is over 12 md/dL
definitly have syms over 14 mg/dL

hypercalcemia- neuromuscular

1. prox muscle weakness
2. hypotonia -depressed DTRs

hypercalcemia- neurologic

1. lethargy
2.confusion
3. blurred vision
4. coma

hypercalcemia-cardiac

1. shortening PT interval
2. brady
3. arrith

hypercalcemia-GI

1. dry mouth
2. anorexia
3. nausea & vomiting
4. constipation

hypercalcemia-renal

1. polyuria and polydypsia (causes DI)
2. hypercholremic acidosis
3. nephrocalcinosos
4. kidney stones
4. reversible renal failure

physical findings of hypercalcemia

1. often nothing special
2. depressed mental starus
3. decreased DTRs
4. neck masses (rare)
5. muscle weakness (esp. quads)

3 main mechanisms of pathophysiology of hypercalcemia

1. increased bone resorption
2. inc gut absorption of calcium
3. excessive renal reabsorption

most common cause of hypercalcium (with inc. PTH)

primary hyperparathyroidism (outpt)

most common cause of hypercalcemia (w dec. PTH)

malignancy related hypercalcemia (inpt)
-ligh calcium in the urine

uncommon cause of hypercalcemia

Sarcodosis (granulomatous d/o, also TB)

another common cause of hypercalcemia with inc PTH

Familial hypocalciuric hypercalcemia (FHH)

Familial hypocalciuric hypercalcemia (FHH) pathophysiology

decreased perception of calcium by the calcium sensing receptors on the parathyroid gland and in teh kidney

-
NO SURGERY!
low calcium in the urine

milk-alkali syndrome

there is almost always underlying renal dz
MORE INFO

causes of primary hyperparathyroidism (HPT)

70-80% of ppl are asymp
3: women:men

80% single parathyroid adenoma
15% have 4-gland hyperplasia
0.5% parathyroid carcinoma

tx for primary HPT

surgery is the only definitive treatment
95% sucess rate

indication for surgery for HPT

1. serum Ca >1mg/dL above upper limit of normal
2.presence of sign or symptoms of hypercalcemia
3. urine calcium >400 mg/24hrs
4. creatine clearance reduced below #0% of age0matched normal
5. decreased bone mineral density
6. pt under 50
7.vit D deficncy (not part of the national recommendations)

**8only one indication needed

general management issues with HPT

-avoid dehydrations
-avoid HCTZ (worsens hypercalcemia)
-keep active
-keep dietary intake modest

-check creatine clearance yearlly
check BMD yearly

MAH pathophysio mech:

1. direct bony met
2. elaboration of PTHrP
3. cytokine production associated with osteoclast activation: lymphotoxin, transforming growth factors, interlukins, TNF,
4. in creased active vit D production (lymphoma)

PTHrP

peptide responsible for the syndrome HHM (humoral hypercalcemia of malignancy)
-frequenctly with squamous cell cancers, renal cell and breast cancers
-PTH level suppressed for degree of hyper-Ca
-PTHrP mimics many of the bio actions of PTH
but does NOT stimulate renal hydroxylase therfore NO increase in vit D

lab eval for hypercalcemia

1. serum calcium (correct for albumin)
2. intact PTH level
3. 24 hr urine calcium normal: <250-300 mg/24hrs (4mg/kg/day)

dd of hypercalcemia:

intact PTH: high
1,25 vit D level: high
phosphorus: normal or low
PHTrP: low

primary hyperparathyroidism

dd of hypercalcemia:

intact PTH: low
1,25 vit D level: normal or low
phosphorus: normal or low
PHTrP: high

cancer (PTHrP)

dd of hypercalcemia:

intact PTH: normal or low
1,25 vit D level: high
phosphorus: high
PHTrP: low

granulomas (sarcodosis)

tx of hypercalcemia

1st: enhance renal Ca excretion-> lasix and IV fluid
2nd: inhibit bone resorption (inhibit oseoclasts)
->calcitonin
->mithramycin-a cytotoxic ABX that inhibits RNA syn thereby inhibiting osteoclasts (not used very often b/c of toxicity)
->bisphosphonates
3rd: inhibit gut absorption -> glucocorticoids
other: oral phosphate therapy

most common outpt cause of hypercalcemia

primary hypercalcemia

most common inpt cause of hypercalcemia

malignancy

serum PTH is low or high in malig-assoc hypercalcemia

low

what is usally underlying in Milk-Alkali syndrome

renal disease

what is the first tx for hypercalcemia

rehydrate pt

hypocalcemia

serum calcium less than 7.6mg/dL or sym pt

symptoms of hypocalcemia

1. paresthesias
2. muscle cramps
3. neuromuscular excitation: tetany
4. bronchospasm
5. laryngeal stridor
6. seizures
7. basal ganglia calcifications -> parkinson's

signs of hypocalcemia

1. cataracts
2. chvostek's sign (tap on facial nerve)
3. trousseau's sign (hold BP cuff 20mg aboce systolic BP for 3min)
4. hyperreflexia
5. prolonged QT interval

causes of hypocalcemia:
low Ca and low PTH

HYPOPARATHYRIODISM:
-surgical
-auto-immune
-infiltrative
-DiGeorge Syndrom (congenital aplasia)
-functional: severe hypomagnesium
Hungry bone syndrome
-idiopathic

causes of hypocalcemia:
low Ca and high PTH

LACK OF VIT D
-lack of sunshine
-dietary
-malabsorption
-liver disease
-anv renal failure
-anticonvulsants- Phenytoin
-VIT D dept Rickets (type 1)
-VIT D resistance ?????

pseudohypoparathyroidism

PTH resistance syndromes

tx of hypocalcemia
-goal
-what else to check

-goal:keep serum CA at the lower range of normal
-always check serum Mg

tx of hypoclacemia if pt is symptomatic:

???

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