Week 4: Hypocalcemia Flashcards
1
Q
Causes of hypocalcemia
A
Low serum albumin-most common Chronic renal failure Magnesium deficiency Hypoparathyroidism Pseudohypoparathyroidism Osteomalacia due to Vitamin D deficiency Hungry bone syndrome Acute hemorrhagic/edematous pancreatitis Hyperphosphatemia
2
Q
Low serum albumin causing hypocalcemia
A
- Must correct the serum Ca: (4-measured albumin) x0.8 +serumCa=corrected
- if corrected serum calcium is normal, evaluation is over
- Causes of low serum albumin: malnutrition, liver cirrhosis, nephrotic syndrome
- level of ionized Ca is normal but total Ca is low
3
Q
Hypocalcemia due to chronic renal failure
A
- reduction of phosphate clearance->hyperphosphatemia
- decreased production of 1,25(OH)2VitD leads to decreased Ca absorption in the gut
- skeletal resistance to PTH
- elevated serum BUN and Cr
- with decreasing GFR, PTH levels rise due to decreased levels of activated Vit D, hyperphophatemia and hypocalcemia
- high phosphorus stimulates PTH
- phophorus also complexes with Ca–>decreases Ca levels–>doesn’t bind to CaSR and releases inhibition on PTH release
- P also stimulates FGF 23 (normally inhibits PTH) but in hyperparathyroidism, this function is not effective
4
Q
Magnesium Metabolism
A
- normal distribution: extracellular Mg is only 1% of total body. Rest is in skeleton and soft tissue
- Need optimally 400 mg/day, 30-50% absorbed in gut
- kidneys: mostly reabsorbed in PCT (15-20%) and TALH (65-75%)
- problems with magnesium deficiency usually due to gut or kidney issues
5
Q
physiological role of magnesium deficiency
A
- enzyme substrate formation (e.g. kinases, ATPase, GTPMg)
- direct enzyme activation
- influence membrane properties: nerve conduction, calcium channel activity, potassium transport
6
Q
Causes of Magnesium deficiency: GI
A
- low dietary intake
- malabsorption syndromes (celiacs)
- extensive bowel resection
- bariatric surgery
- acute and chronic diarrhea
- Intestinal and biliary fistulas
- Protein calorie malnutrition
- Acute hemorrhagic/edematous pancreatitis
- Primary intestinal Mg malabsorption (mutation in TRPM6, a magnesium channel)
7
Q
Causes of magnesium deficiency: Renal
A
- alcohol
- osmotic diuresis: diabetes
- diuretics
- hypercalcemia: nephrogenic Di
- chronic IV therapy (Na)
- metabolic acidosis
- drugs for transplant patients
- PPIs
- chronic renal disease
- cardiac glycosides
- genetic defects such as gitleman’s
8
Q
Mechanism of magnesium deficiency as cause of hypocalcemia
A
- Impaired PTH secretion
- PTH is inappropriately normal or low in Mg deficiency
- In normal individuals, high serum Mg will inhibit PTH secretion
- in Mg deficiency: Mg is important part of GTP part of G protein receptors. Without Mg, Ca sensing receptor doesn’t work and can’t detect low Ca levels. That’s why there are low/normal PTH even with low Mg. - there is skeletal and renal PTH resistance
- Impaired formation of 1,25(OH)2 VitD
- Resistance to Vitamin D
9
Q
Hypoparathyroidism as cause of hypocalcemia
A
- post surgical: 90%
- idiopathic (autoimmune): 10%
- congenital
- infiltrative disease
- radiation therapy
- activating mutation of the Ca sensing receptor: decreased set point and increased sensitivity to Ca
10
Q
Pseudohypoparathyroidism
A
- similar to hypoPTH with hypocalcemia and hyperphosphatemia. But has elevated PTH and end organ resistance to PTH
1. Type 1a (alb rights hereditary osteodystrophy) - inactivating mutation of GNAS1 gene with reduction of Gsa protein. hormones bind but don’t act. blunted response
- resistance to PTH, TSH, LH, FSH, glucagon
- short, mental retardation, shorted 4th metacarpal
2. Type Ib: hormone resistance to PTH only
3. Type Ic: resistance to multiple hormones, unknown mechanism
4. Type II: renal resistance, no phosphaturic response to PTH
11
Q
Hypocalcemia: osteomalacia and rickets
A
- Vitamin D deficiency
- decreased Ca absorption through gut
- skeletal PTH resistance
- secondary hyperPTH
12
Q
Hungry Bone syndrome
A
- healing phase of hyperPTH. Bone trying to heal itself and can happen after parathyroid surgery
- prolonged drops in Ca levels
- Ca goes from serum to bone rapidly and there is rapid remineralization of bone
- also can occur in healing phase of hyperthyroidism, bone marrow neoplasia, Rx of Vit D deficiency, or in osteoclastic bone metastasis
13
Q
Hypocalcemia due to acute hemorrhagic and edematous pancreatitis
A
Multifactorial causes
- pancreatic lipase liberates FFA, and FFA chelate calcium (saponification)
- magnesium deficiency from alcohol
- excessive calcitonin secretion due to excessive glucagon secretion
- systemic protease inhibits PTH secretion or degrades circulating PTH
14
Q
Hyperphosphatemia as cause of hypocalcemia
A
- calcium and phosphate bind together in plasma
- high phosphate inhibits synthesis of 1,25(OH)2VitD
- high phosphate may be due to renal failure, cell lysis (rhabdomyolysis, admin of chemoRx agents), excessive PO4 administration, hypoPTH, pseudohypoPTH
15
Q
Symptoms and signs of hypocalcemia
A
- Neuromuscular hyperexcitability
- paresthesias, hyperreflexia
- Trousseau’s sign and Chvostek’s sign
- tetany - Neurological
- seizures, depression, anxiety, irritability
- papilledema
- increased CSF pressure - Dermatologic
- dry, scaly skin, brittle nails, monilia of nails - Opthalmologic
- cataracts - Prolonged QT: can lead to arrhythmias
- calcification of basal ganglia
