12.11 Calcium Homeostasis Flashcards
Factor affecting total calcium but not ionised calcium
Albumin
Factors affecting ionised calcium but not total calcium
- pH (alkalosis increases binding to albumin which drops ionised portion)
- PO4 levels (increased levels leads to increased binding of Ca with drop in ionised portion)
- Temperature
Main hormone systems involved in calcium regulation
PTH
- by parathyroid glands
- high circulating calcium via interaction with CaSR inhibit PTH release physiologically
- increase calcium via direct or indirect mechanisms
- Impact: ⬆️ Calcium; ⬇️ PO4
Vit D
- D3: Cholecalciferol (animal source; UV; meds)
- D2: Ergocalciferol (plant source; meds)
- activation in liver{25-OH} & kidney
- activation in kidney requires PTH action (activates 1 alpha hydroxylase)
- maintain + increase circulating calcium
- produce 1,25(OH)2VitD
- effects: ⬆️ Ca; ⬆️ PO4
Calcitonin
- may be used pharmacologically in states of hypercalcemia
Hormonal effects favour increase in circulating calcium levels
Hypercalcemia
Clinical presentation
Incidental findings on biochemistry
Stones - Bones - Abdominal Groans - and Psychic Moans
- renal impairment / renal calculi (associated hypercalciuria) / polyuria
- skeletal fragility or low bone mineral density (mobilization from skeleton) / osteitis fibrosa cystica (rare)
- gastritis (calcium stimulate gastrin release and acid production)
- non-specific new onset psychiatric manifestations (associated disturbed hemodynamic, inherent effects)
Hypercalcemia
Causes
- common mineral abnormality
- numerous causes possible
- part of the excess calcium in circulation always mobilised from skeleton
More than 90-95% of cases
➡️primary hyperparathyroidism
➡️malignancy
- granulomatous disease
Primary Hyperparathyroidism
- excess PTH production by autonomous tumor of parathyroids, almost always benign
Causes
- solitary adenoma (~80%)
- multi-gland hyperplasia (12-15%)
- carcinoma (rare 1-2%)
• very high Ca / PTH
• palpable mass
Malignancy
direct skeletal involvement / metastasis
- mobilize calcium and phosphate from skeleton
humoral hypercalcemia PTH-related peptide
- underlying malignancy produces PTH like peptide, almost never complete molecule
- Similar action to PTH with high calcium and low normal to low phosphate
- not picked up in commercial PTH assays
PTH suppressed
Granulomatous disease
PTH suppressed
- In cases where PTH is low and no malignancy is found
- In sarcoidosis, TB
- induce state of excess active Vitamin D with hypercalcemia, hyperphosphatemia and hypercalciuria (granulomas able to express 1α-hydroxylase able to activate Vitamin D)
Hypocalcemia
Clinical presentation
➡️suspect in high-risk situations (NBNB neck surgery)
➡️ clinical picture due to neuromuscular excitation or deposition of calcium in soft tissue
neuromuscular excitation
- latent tetany and paraesthesia
o Chovstek: tap facial nerve with twitching of mouth 2/3 distance between mouth end to zygoma bone in front of ear {chin; sensitive, non-spesific}
o Trousseau: inflate BP cuff 20mm Hg above systolic BP for 3 minutes, cause carpopedal spasm {tourniket; more spesific}
- convulsions
- laryngeal stridor
soft tissue deposition
- Seen with chronic / longstanding hypocalcemia
- ocular lens with subcapsular cataracts
- basal ganglia calcifications with movement disorders
Hypocalcemia
Pathogenesis
Causes
- failure of adaptive responses by either PTH or Vit D
o PTH deficiency (hypoparathyroidism or hypomagnesemia) / PTH resistance
o Vitamin D deficiency (malabsorption, other) or Vit D resistance - acute complexing or deposition of calcium
o may result in very acute fall in calcium levels
Causes
- primary hypoparathyroidism
• post-surgery (NB most common)
• auto-immune
- malabsorption
• calcium per se; often a combination of calcium along with magnesium, vitamin D, phosphate
- hypomagnesemia
Primary hypoparathyroidism biochemistry
- hypocalcaemia
- hyperphosphatemia
- very low /absent PTH
Malabsorption biochemestry
- hypocalcaemia
- hypophosphatemia
- elevated PTH
Hypomagnesemia
General
Biochemistry
General
- reduce PTH secretion
- reduce peripheral effects of PTH
Biochemistry
- hypocalcaemia
- hyperphosphatemia
- varying PTH level
- MIMICS hypoparathyroidism
Hypophosphatemia
- moderate low phosphate seen in states of excess PTH effect in association with hypercalcemia (primary hyperparathyroidism, PTHr peptide effects in malignancies)
- more overt hypophosphatemia and associated excess phosphate loss in urine may be due to renal tubular losses
in setting of overt hypophosphatemia:
- always evaluate renal loss along with serum biochemistry
- enquire regarding known inherited childhood bone disease (deformities may be present – Vitamin D resistant conditions
with rickets / osteomalacia)
- explore possibility of medication induced tubular loss of phosphate
- be aware of rare entity of tumor induced hypophosphatemia
- refer patient for further evaluation
