Title: Calcium accordion

Distribution

plasma distribution: (2.2 – 2.6 mmol/l)

- 50% ionic (1.25 mmol/l)
- 40% protein bound
- 10% complexed

cellular distribution (1 µmol/l):

- cytoplasm free Ca2+ : 100 nmol/l
- bound to proteins (calbindin)
- in mitochondria
- in endosplasmatic reticulum (sarcoplasmatic reticulum)

Sources

- Milk, dairy products
  - parmesan 1225 mg/100g
  - camembert 380 mg/100g
  - milk 160 mg/100g
- Egg 125 mg/100g
- Brown alge 1000 mg/100g
- Sesame 783 mg/100g
- Hazelnuts 225 mg/100g
- Most vegetables 50-100 mg/100g

Intestinal Absorption

- duodenum, jejunum, ileum, colon
- paracellular
- transcellular (active):
  - Ca-channel TRPV5 and TRPV6 (bbm)
  - intracellular bound to calbindin 9kDa, in vesicles
  - Na-Ca-exchanger, Ca-ATPase (blm)
  - stimulated by Vit D and estrogen

Renal Excretion

ultrafiltration: 50% of serum Ca2+ , 270 mmol/d

reabsorption (98%):

- 70% prox. tubulus (solvent drag)
- 20% loop of Henle, mainly TALH, paracellular,
driven by Na+/K+/2Cl--cotransporter
- 8% distal convoluted tubulus: Ca-channel TRPV5, calbindin, basolateral Na/Ca-exchanger, Ca-ATPase

regulation:

- plasma Ca2+
- PTH (reabsorption↑)
- PTHrP (reabsorption↑ )
- dietary PO4 (PO4 ↑ → reabsorption↑, PO4↓ → reabsorption↓)
- blood pH (alkalosis → reabsorption↑, acidosis → reabsorption↓)
- thiazide diuretics (reabsorption↑), loop diuretics (reabsorption ↓)

Homeostasis

Plasma Ca2+ : 1.25 mmol/l

Hormones:

- Parathyroid hormone (PTH) /PTH related protein (PTHrP)
- Vit D- Hormone
- Calcitonin

Affected processes:

- intestinal absorption
- renal excretion
- bone remodeling

Hypocalcaemia

Symptoms

- serum calcium < 2.2 mmol/l (8.8 mg/dl)
- asymptomatic – severe, life threatening
- neuromuscular irritability, parestehsia
- tetany, spasms, muscle cramps, seizures
- prolonged QT-interval
- laryngospasm, bronchospasm
- ectopic calcification (basal ganglia)
- subcapsular cataracts
- abnormal dentition
- rickets / osteomalacia

Etiology

- low PTH levels
  - parathyroid agenesis
  - parathyroid destruction (surgery, radiation, autoimmune)
- high PTH levels
  - Vit D deficiency (nutritional, sunlight, malabsorption, renal failure)
  - low Calcium intake (lactose intolerance
  - Vit D resistance (rickets)
  - PTH resistance
  - drugs (calcium chelators, phosphate, inhibitors of bone resorption (bisphosphonates), phenytoin, ketoconazole)
- miscellaneous
  - acute pancreatitis
  - massive tumor lysis
  - osteoblastic metastases
  - toxic shock syndrome
  - hyperventilation
  - acute severe illness

Treatment

- calcium infusion
- PTH
- Vit D
- treatment of primary disorder

Hypercalcaemia

- Serum Ca > 10.5 mg/dl (2.5 mmol/l)
- correct for albumin!

Symptoms

- cardiovascular
  - shortened QT interval, arrhythmia, AV blocks, bradycardia (slow heartbeat)
  - hypertension
  - cardiac arrest (when severe)
- neuromuscular
  - emotional instability, psychosis, stupor
  - confusion, delirium
  - headache
  - muscle weakness
  - seizures (rare)
- renal
  - polyury/polydipsia/nocturia
  - hypercalciuria
  - nephrolithiasis, nephrocalcinosis
  - renal failure
- gastrointestinal
  - nausea/vomiting
  - anorexia
  - constipation
  - abdominal pain
  - peptic ulcers
  - pancreatitis
- skeletal
  - bone pain/athralgia
  - osteopenia/osteoporosis in cortical bone
- other
  - shock
  - death

Etiology

- elevated PTH
  - primary hyperparathyroidism
  - tumors producing PTHrP (carcinoma of lung, esophagus, head and neck, renal cell, breast, ovary, bladder)
- elevated Vit D
  - Vitamin D supplementation
  - ectopic production of 1,25(OH)2Vit D in granuloma forming disorders
    - sarcoidosis
    - silicone/paraffine induced granulomatosis
    - Crohn‘s disease
    - tuberculosis, candidiasis, leprosy, coccidiomycosis
    - lymphoma/Hodgkin’s disease
  - increased bone resorption
    - lytic bone metastases (multiple myeloma, hematologic malignancies, breast carcinoma)
    - immobilization
  - miscellaneous
    - pseudo-hypercalcaemia
    - thyrotoxicosis, phaechromozytoma
    - adrenal insufficiency
    - drugs: Vit D, PTH, Vit A, estrogens/anti-estrogens, diuretics, growth hormone,…
    - diseases: inflammations, AIDS, renal failure,…

Treatment

- treatment of primary cause!
- saline infusion, diuretics (Furosemide), (dialysis)
- calcitonin
- bisphosphonates
- glucocortiocids