Calcium metabolism

Question 1

Ca distribution in blood

Answer 1

45% albumin bound
15% bound to anions - phosphate, citrate
40% free calcium (ionized)

Question 2

Sources of calcium regulation

Answer 2

diet
bone - 99.9% calcium stored
kidney - excretion

Question 3

Ca hormones

Answer 3

PTH - increase Ca
Calcitriol - increase Ca
calcitonin - decrease Ca

Question 4

Drop in Ca - homeostatic pathway

Answer 4

1) sensed by parathyroid glans
2) secrete PTH from parathyroid chief cells
3) in kidney:
- increase calcitriol formation
- decrease Ca excretion
- increase phosphorus excretion
4) PTH effects on bone - increase calcium and phosphorus release
5) calcitriol effects on intestines
- increase Ca and phosphorus absorption

Question 5

PTH effects - prolonged/sustained

Answer 5

bone resorption increased

stimulates osteoblasts to produce RANKL, resulting in increased osteoclast activity

Question 6

PTH effects - episodic, normal

Answer 6

promotes bone growth and mineralization

Question 7

Calcitonin production

Answer 7

parafollictular/C cells of thyroid

Question 8

Calcitonin action

Answer 8

antagonizes PTH

fine control of Ca homeostasis - not essential for maintaining serum Ca

Question 9

Hypercalcemia causes

Answer 9

90%: primary hyperparathyroidism/malignancy
measure iPTH to narrow cause
(high: primary hyperPTism/familial hypercalcemic hypocalciuria
normal/decreased: usually malignancy)

Question 10

Hyperparathyroidism features

Answer 10

Longstanding, asymptomatic hypercalcemia/mild hypercalcemia
Seen in postmenopausal females
normal PE

FHx of hyperPTIism, multiple endocrine dysplasia

Question 11

DDx of hyperparathyroidism

Answer 11

Primary hyperparathyroidism
Hyperparathyroidism related to familial syndromes
familial hypocalciuric hypercalcemia
Secondary and tertiary hyperPTism (CKD leading to metabolic bone disease)

Question 12

Malignancy (hypercalcemia) features

Answer 12

rapid increase in serum Ca
more symptomatic
presents in advanced disease, poorer diagnosis

Question 13

DDx of hypercalcemia due to malignancy

Answer 13

Humoral hypercalcemia of malignancy - 80% (PTH-related peptide, common in squamous cell carcinomas)
Osteolytic bone metastases - 20%
Vitamin D intoxication
Chronic granulomatous disorders - sarcoidosis, TB
Meds

Question 14

Clinical presentations of hypercalcemia

Answer 14

neuropsychiatric: anxiety, depression, cognitive dysfunction
GI: constipation, anorexia, nausea
Renal: polyuria, nephrolithiasis
Muscle weakness, bone pain, osteoporosis

Question 15

Tx of mild hypercalcemia

Answer 15

<3 mmol/L
avoid aggravating factors - thiazide diuretics, lithium
bed rest
adequate hydration
treat underlying cause

Question 16

Tx of moderate hypercalcemia

Answer 16

3-3.5 mmol/L
depends on symptoms
if acute rise, treat as severe

Question 17

Tx of severe hypercalcemia

Answer 17

>3.5 mmol/L
3-pronged treatment:
IV saline
calcitonin
biphosphonates (zolendronate)

Question 18

Hypocalcemia approach

Answer 18

differentiate based on PTH levels

Question 19

Hypocalcemia with low PTH DDx

Answer 19

Surgical: thyroidectomy
AI: rare, usually with polygrandular autoimmune syndrome
Congenital: hypoplasia of PT gland (DiGeorge syndrome), mutations
Destruction/infiltration: Wilson’s disease, hemochromatosis, HIV

Question 20

Hypocalcemia with high PTH DDx

Answer 20

Vitamin D deficiency
CKD - usually early
Sepsis/severe illness: pancreatitis
Postsurgical hemorrhage: due to citrate in blood products (chelates calcium)
Osteoblastic metastases
Premature infants

Question 21

Clinical presentations of acute hypocalcemia

Answer 21

tetany, seizures
CV dysfunction, prolonged QT interval, ventricular dysrhythmia
Papilledemia - with severe hypocalcemia

Question 22

Clinical presentations of chronic hypocalcemia

Answer 22

dental changes
cataracts
extrapyramidal disorders

Question 23

Tx of hypocalcemia

Answer 23

treat underlying cause

supplement vit D, magnesium, parathyroidectomy

Question 24

Role of magnesium in hypocalcemia

Answer 24

Hypomagnesemia can decrease PTH secretion/cause PTH resistance
Can occur due to malabsorption, diarrhea, alcoholism, malnutrition
Need to check/treat hypomagnesemia

Question 25

Bone resorption time period

Answer 25

rapid, ~ 3 weeks

Question 26

Bone formation time period

Answer 26

Slow, 3-4 months | mineralization occurs over years

Question 27

Bone resorption mechanism

Answer 27

1) Osteocytes signals denuded bone surface with elderly/damaged bone to be removed 2) attracts osteoclasts 3) osteoclasts dissolve material by attaching themselves to bone surface and secreting acid

Question 28

Bone formation mechanism

Answer 28

1) signalling through Wnt pathway - sclerostin: secreted by osteocytes to inhibit Wnt when there is lack of mechanical stress 2) Osteoblasts increase in number, activity and maturity 3) Lay down osteoid, then mineralized

Question 29

Hormones affecting osteoblast

Answer 29

Progesterone, PTH, testosterone - increase | GCs - inhibit

Question 30

Local regulators of bone resorption/formation

Answer 30

Osteoblasts and osteoblast-derived lining cells (LCs) secrete RANK-ligand osteoprotegrin - help stimulate new resorption - RANKL interacts with RANK receptor on osteoclast precursors leads to osteoclast maturation Osteoclasts signalling --> osteoblast maturation mediated through Wnt pathway

Question 31

Systemic regulators of bone resorption/formation

Answer 31

PTH, calcitriol, GH, GCs, thyroid hormones, sex hormones

Question 32

estrogen effects on bone density

Answer 32

decrease resorption in both genders

Question 33

testosterone effects on bone density

Answer 33

decrease resorption | increase formation

Question 34

Cortisol effects on bone density

Answer 34

increase resorption at higher than physiological doses (also suppresses estrogen) decreased formation

Question 35

Resorption markers of bone remodelling

Answer 35

C-terminal telopeptide (CTX) - most specific/sensitive NTX pyridinoline Deoxypyridinoline

Question 36

Bone formation markers

Answer 36

Alkaline phosphatase - total and bone-specific Procollagen-1-N peptide - most sensitive and specific Osteocalcin

Question 37

Vitamin D formation

Answer 37

1) cholesterol + acetate --> 7-dehydrocholesterol 2) +UV --> cholecalciferol (D3) (same as ingested form) 3) Liver: converted to 25(OH)D3 4) Kidney: converted to 1,25(OH2)D3 - active form

Question 38

Vitamin D dose in Ca absorption

Answer 38

<80 nmol/L, Ca absorption rises with increasing vitamin D | above 80 nmol/L, no effect