03b: Calcium Flashcards
Calcium in the plasma is in which forms? Star the form that’s utilized by the body to maintain cellular functions and neuromuscular activity.
- Free ions* (50%)
- Bound to plasma proteins (40%)
- Diffusible complexes (10%)
List the calcium-regulating hormones (calciotropic hormones) that are responsible for maintaining the serum calcium within the normal range
- PTH
- Calcitonin
- Vit D
When the pH is below 7.4, (more/less) calcium is bound to albumin, thus a (higher/lower) fraction is in the ionized form.
Less
Higher
Equation for total serum calcium corrected for albumin
(4.0-albumin)(0.8) + total Ca
The concentrate of calcium ions in the extracellular fluid is kept constant by the regulation of:
- Intestinal absorption
- Bone mobilization
- Tubular reabsorption
T/F: In adults, less than half of the calcium in the diet is absorbed.
True - usually between 20 and 30% (may be higher in increased demand states like pregnancy/lactation, growing kids)
The hormone that is most responsible for regulating intestinal calcium absorption
1,25-dihydroxy vit D
The amount of phosphorus in the normal adult is about (X) kg, of which (Y)% is in the skeleton.
X = 1 Y = 85
When determining serum P levels, it is important that a level be obtained under which condition? Why?
Fasting
There are decreases in plasma P with the ingestion of CHO (due to increase insulin secretion) and P levels can rapidly rise after a meal.
T/F: only 10% of dietary phosphorus is absorbed
False - Dietary phosphorus is efficiently absorbed (60%) by the small intestine in a passive manner
1,25(OH)2D (increases/decreases) phosphorus absorption in the which part of GI tract?
Increases
Small intestine (ileum, jejunum)
The major control of phosphorus economy is exerted by which organ system?
Kidneys
During exposure to sunlight, (X) undergoes a photochemical reaction to form (Y).
X = 7-dehydroxycholesterol (provitamin D3; cholesterol precursor) Y = previtamin D3
Once formed, previtamin D3 undergoes either (X) or (Y) process
X = isomerization to vitamin D3 Y = photoisomerization (via absorbing solar radiation) into biologically inert compounds (lumisterol and tachysterol )
T/F: increased pigmentation will increase the capacity of the skin to produce vitamin D3
False - melanin competes w provitamin D3 for solar radiation
(X) is the major circulating form of vitamin D. Where is it made?
X = 25-hydroxyvitamin D
Liver
Obese patients are often vitamin D deficient because:
sequestration of vitamin D in their body fat
T/F: 1,25(OH)2D is the vitamin D metabolite that is measured to determine the vitamin D status of a patient.
False - 25(OH)D
(X) form of vit D interacts with (specific/nonspecific) receptor known as (Y). What kind of receptor is it?
X = 1,25(OH)2D
Specific
Y = the vitamin D receptor (VDR)
Nuclear
1,25(OH)2D interacts with (X) receptor; and the complex interacts with (Y).
X = VDR Y = Retinoid-X R (RXR)
PTH has which actions on kidney?
- Increase Ca reabs; increase P clearance
2. Increase 1,25(OH)2D synthesis (to increase Ca absorption from gut)
1,25(OH)2D increases Ca absorption in the which part of GI tract?
Mainly duodenum (lesser extent in jejunum and ileum)
T/F: The biologically active
portion of the PTH molecule resides in the last 34 amino acids.
False - first 34 AA
The action of PTH at a cellular level involves which signaling pathway?
Adenylate cyclase/cAMP pathway
PTH increases Ca mobilization from bone by directly (inducing/inhibiting) (X) on (Y) cells.
Inducing
X = RANKL
Y = osteoblasts
(interacts with RANK and stimulates preosteoclasts to become active mature osteoclasts)
T/F: Calcitonin is produced by the parathyroid gland.
False - by C cells in thyroid
(X) cells have calcitonin receptor. The activity of these cells is (increased/decreased) upon the hormone’s binding.
X = mature, active osteoclasts
Decreased
(X) is a factor made by (osteoclasts/osteoblasts/osteocytes). Its major function is to (increase/decrease) P excretion in kidney by internalization of (Y) transporter.
X = FGF-23
Osteoclasts and osteocytes;
Increase
Y = Na-P
Preferred range of 25-(OH) vit D blood level is (X) ng/mL
X = 40-60
Circulating concentrations of 1,25(OH)2D3 are useful for which purpose?
To determine disorders in metabolism of 25(OH)D to 1,25(OH)2D
T/F: The serum assay for calcitonin is especially valuable for evaluating disorders in Ca, P, and bone metabolism.
False - only really valuable for determining presence of C-cell (medullary) tumor in thyroid
64 y.o. F with mild renal failure has very low 1,25(OH)2D levels. Assuming she is otherwise healthy and renal function is only mildly impaired, what could be causing the low vit D level?
Hyperphosphatemia (serum P directly inhibits 1-hydroxylase even if kidney’s capacity to produce 1,25(OH)2D is adequate)
List some hypercalcemic disorders that are associated with an acquired disorder in the
metabolism of 25(OH)D to 1,25(OH)2D.
- Hyper-PTH
- Chronic granulomatous disorders (sarcoid, TB, silicosis; granulomatous tissue has capacity to produce 1,25(OH)2D in unregulated manner)
List two causes of acquired hypo-PTH. Star the more common one.
- Surg removal/damage after thyroid surg*
2. SEVERE hypo-Mg (chronic alcoholics with poor nutrition)
List the classification of causes for hypercalcemia
- PTH-related (hyper-PTH)
- Malignancy-related (PTHrP secretion)
- Vit D-related (excess ingestion)
- Disorders w high bone turnover (ex: hyperthyroid)
- Chronic renal failure (chronic 2o hyper-PTH)
Major cause of hyper-PTH:
Solitary adenoma (85%)
FHH (Familiar Hypocalciuric Hypercalcemia) is due to (X) mutation in (Y). What’s the mechanism behind the hypercalcemia?
X = point Y = Ca sensor in parathyroid chief cells
Inhibition of PTH release occurs at higher serum Ca levels (new equilibrium)
Gold standard sites for DEXA (bone densitometry).
- Lumbar spine (90% trabecular/metabolically active bone)
2. Proximal femur
DEXA: T-score is useful in estimating (X). For each T-score decrease by one, (X) (increases/decreases) by (Y).
X = fracture risk
Increases
Y = factor of 2 (doubled)
WHO definition of Normal Bone Density:
T-score above -1
WHO definition of Osteopenia (low bone mass):
T-score between -1 and -2.5
WHO definition of Ostoporosis:
T-score of -2.5 or below
WHO definition of severe Ostoporosis:
T-score of -2.5 or below PLUS presence of fragility fracture
The Z-score is useful in
comparing:
Patient’s bone density with the average expected density for a given age
Estrogen and selective estrogen receptor modulators (i.e. raloxifene) (increase/decrease) (X) bone process by which mechanism?
Decrease
X = resorption
Bind estrogen Rs in osteoblasts and decreasing RANKL
Denosumab is a monoclonal antibody which (increases/decreases) (X) bone process by which mechanism?
Decreases
X = resorption
Preventing the interaction between RANK and RANKL by binding RANKL (mimicks osteoprotegerin)
Bisphosphonates (ex: alendronate, risedronate,
ibandronate and zoledronic acid) (increase/decrease) (X) bone process by which mechanism?
Decrease
X = resorption
Directly impairing osteoclast function (bind Ca hydroxyapatite, taken up by osteoclasts, and inhibit Farnesyl pyrophosphate synthase)
How do thiazide diuretics impact bone formation/resorption?
Decrease resorption by decreasing PTH (via increasing renal Ca reabsorption)
Proton pump inhibitors, such as omeprazole, (increase/decrease) (X) bone process by which mechanism?
Increase
X = resorption
decrease gastric acid and may decrease absorption of calcium carbonate (thus increasing PTH)
List some drugs that may increase bone resorption by altering vit D metabolism or Ca absorption/excretion.
- Anticonvulsants (phenytoin, phenobarbital)
- Glucocorticoids
- PPIs
- Loop diuretics
Currently, the only FDA-approved osteoporosis therapy that is anabolic to bone is:
Teriparatide (synthetic PTH analog - given in pulses)
Second most common metabolic bone disease in older adults is (X). It’s characterized by (high/low) production of (Y).
X = Paget’s disease
High
Y = thick, more fragile and vascular bone (deformities, pain, neuro issues)
Most frequent genetic mutation linked to Paget’s disease is in (X) gene, found in (Y)% of patients with familial Paget’s.
X = sequestosome 1 Y = 30
T/F: Most common clinical picture of Paget’s is patient with focal bone pain and neuro symptoms (ex: radiculopathy).
False - most commonly asymptomatic; but most common Sx is bone pain
T/F: In Paget’s, the affected area often shows signs of inflammation.
True (dolor, calor, rubor, tumor)
Pt with high serum level of (X) is confirmed to be muscle (not liver) in origin. What step is taken next to rule out/in Paget’s disease?
X = alk phos
Nuclear medicine bone scan (identify “hot spots”); further evaluation via plain x-rays
List some meds that have been approved for Paget’s disease treatment.
Anti-resorptives - Calcitonin and bisphosphonates (etidronate, tiludronate)
The most dreaded complication of Paget’s disease is:
osteosarcoma
T/F: Osteoporosis does not cause bone pain.
True
T/F: Osteomalacia does not cause bone pain.
False - throbbing, aching pain (check by pressing on sternum)
Trousseau’s sign used to assess (X). Explain the procedure to elicit the sign.
X = latent tetany (ex: carpo-pedal spasm)
Inflate BP cuff to between P systole and diastole - elicits tetany (locally causing alkalosis, causing ionized Ca to decrease)
Chvostek sign used to assess (X). Explain the procedure to elicit the sign.
X = latent tetany (hypocalcemia)
tap facial nerve - twitching of mouth
55 yo F with hypercalcemia. What are the two most likely etiologies?
- 1o Hyper-PTH
2. Malignancy (breast esp)
(X) levels can be used to distinguish hyper-PTH from malignancy (PTHrP). (Y) levels can also be telling.
X = PTH Y = P (will be normal/high in malignancy due to down-regulation of PTH)
PTHrP secreted by (X) cells
X = squamous (carcinoma)
Pt with sarcoid or other granulomatous disease may have (hyper/hypo)-calcemia. Why?
Hypercalcemia
Activated macrophages in granulomas cause unregulated conversion of 25-hydroxy vit D to 1,25-dihydroxy vit D
Young patient presenting with bowed legs and normal Ca/vit D levels. What would you check next? What’s at the top of your DDx?
Phosphate
If low, hypophosphatemic rickets
Hypophosphatemic rickets: (X) inheritance pattern of point mutation in (Y).
X = AD or X-linked Y = FGF-23
Adult patient with unrelenting, throbbing bone pain has normal Ca levels but very low P levels. What’s at the top of the differential?
Oncogenic osteomalacia (a benign or malignant tumor that makes FGF 23)
Point mutation of alpha-1 hydroxylase results in which disorder?
Vit D-dependent Rickets Type I
Mutation/dysfunction of VDR results in which disorder?
Vit D-dependent Rickets Type II (aka vit D-resistant Rickets)
Global alopecia is a classic sign of which (inherited/acquired) cause of (hyper/hypo)-calcemia?
Inherited; hypocalcemia
Vit D-dependent Rickets Type II
Vit D-dependent Rickets Type II: (hyper/hypo)-calcemia, (high/low) levels of 25-hydroxy vit D, (high/low) levels of 1,25 vit D, (high/low) levels of PTH, and (hyper/hypo)-phosphatemia.
Hypocalcemia
High; high; high
Hypophosphatemia
Major cause of hypocalcemia in hospital setting
Low albumin
Abnormal soft tissue calcification (esp of basal ganglia) is seen in which disorder?
Pseudohypoparathyroidism
Pt with unexplained (hyper/hypo)-calcemia can be almost definitively diagnosed with (X) if you notice “dip” of 4th and 5th metacarpals.
Hypocalcemia
X = Pseudohypoparathyroidism
Pt with Pseudo-pseudo-hypoparathyroidism differs from one with Pseudohypoparathyroidism in that:
- PO4, Ca, PTH all normal (PTH still working), despite remaining skeletal deformities/mental retardation
- Gene came from dad, instead of mom
