Calcium metabolism Flashcards
Review calcium and phosphate homeostasis
Ingest ca and phosphate to which some released in faeces but some absorbed by GIT , where some is filtered into kidney and released in urine and remaining deposited in bone -> bone turnover -> controlled by PTH and calcitriol
Discuss the role of GIT in calcium balance
- Calcium absorption is incomplete due to two factors:
- Activated vitamin D required for intestinal calcium absorption
- Insoluble salts (ca phosphate, ca oxalate) not absorbed.
- Normal adult:
- Ingests 1000 mg of calcium per day
- Absorbs 400 to 500 mg calcium.
- Loses 300 mg of calcium into the stool via digestive secretions.
- Thus, net absorption is only 100 to 200 mg.
- In steady state, this quantity of calcium is excreted in the urine.
Discuss role of bone in calcium balance
- Main calcium reservoir in body (99%)
- Most of the body calcium exists in bone as hydroxyapatite.
- Bone is a calcium reservoir that is involved in maintaining a normal plasma ionized calcium concentration
- This process depends upon the activity of osteoblasts and osteoclasts, which are regulated by many hormones and proteins, including parathyroid hormone (PTH) and calcitriol
Discuss role of renal system in calcium balance
- Only ionized calcium filtered by glomerulus.
- 97 to 99 % of filtered calcium reabsorbed in the nephron.
- 70 % reabsorbed passively in the proximal tubule.
- 20 % reabsorbed passively in the TALH.
- 15 % reabsorbed actively in distal nephron.
- Distal calcium reabsorption is responsible for physiologic calcium regulation as well as the dysregulation observed in many disease states
How does calcium present in plasma?
- 40% bound to albumin
- 15% complexed with citrate, sulfate, or phosphate
- 45% ionized (or free) calcium.
ionised under hormonal control PTH,calcitriol
Formula to deduce total calcium in blood a/w albumin
- Laboratory reports total (free and bound) calcium
- Caution in hypoalbuminemia, acid-base disorders, CKD.
- Ca corr (mmol/L) = (0.02 * (40 - Pt’s Albumin)) + Serum Ca
Define PTH and main features
84 AA polypeptide produced by chief cells
Ionised Ca2+ sensed by CaSR on parathyroid cells
PTH secreted in response to fall in iCa2+
‘Phosphate trashing hormone’
Net effect: ↑ calcium, ↓ phosphate
Role of PTH in regulating calcium conc
Increased GI absorption
•PTH promotes renal formation of calcitriol aka active Vit D aka 1,25 hydroxyvit D via upregulation of 1α hydroxylase enzyme activity.
•Calcitriol enhances intestinal calcium and phosphate absorption
Increased bone resorption
•Activates bone resorption by binding to PTH receptors on osteoblasts.
•Results in increases in osteoclast number and activity
Increased renal resorption
•PTH causes a rapid increase in calcium reabsorption in the distal nephron.
•PTH also promotes renal formation of calcitriol via upregulation of of 1α hydroxylase enzyme activity.
•PTH increases renal excretion of phosphate.
Define calcitriol
Active form of vitamin D.
Enzymatic activation in liver and kidneys.
PTH increases the activity of 1-alpha-hydroxylase, which increases calcitriol production
Net effect: ↑ calcium, ↑ phosphate
Effect of calcitriol on Ca plasma regulation
Increased intestinal absorption
•Calcitriol enhances apical intestinal calcium absorption by increasing the expression of TRPV6 channels.
Increased bone resorption
•Calcitriol increases bone calcium release by binding to osteoblasts and osteocytes and by increasing pyrophosphate levels, a mineralization inhibitor.
Increased renal resorption
•Calcitriol increases reabsorption of calcium in the distal convoluted tubule and the collecting duct by increasing expression of TRPV5 channels and calbindin-D28k.
Clinical manifestations of hypercalcaemia
“Stones, bones, groans and psychiatric overtones”
Stones Nephrolithiasis
Bones Bone pain, weakness
Groans Abdominal pain, constipation
Psychiatric overtones Depression, confusion, lethargy
Lab:Shortened QT interval Additional : •Dehydration •Acute kidney injury •Chronic kidney disease (nephrocalcinosis) •Nephrogenic diabetes insipidus •Type 1 (distal) Renal Tubular Acidosis
Causes of hypercalcaemia
- PTH excess- hyperparathyroidism prim and sec, lithium, PTH related protein secreting neoplasm, familial hypercalcinaemia, hpocalcinuric
- Vitamin D excess- increased intake, ectopic calcitriol production-granulomatous disorders
- Hormone independent bone turnover- bone mets, Paget’s , hyperthyroidism, immobilisation
- Increased calcium intake- Milk-Alkali syndrome
- Thiazide diuretics-increases calcium resorption in DT
Which is the most common causes of hypercalcinaemia
Primary hyperparathyroidism by far the most common cause in ambulant, asymptomatic outpatients.
Malignancy and immobility most common cause in inpatients. Poor prognostic factor, 50% survival at 1 month
Dx of hypercalcaemia
- Step 1: Correct for hypoalbuminaemia
- Cacorr (mmol/L) = (0.02 * (40 - Pt’s Albumin)) + Serum Ca
- Step 2: Physical exam and CXR
- Cancer usually obvious at this stage
- Granulomatous disease
- Step 3: Check PTH level
- PTH high or normal: Primary hyperparathyroidism
- PTH suppressed: Measure PTHrP, Calcidiol and Calcitriol
- PTHrP elevated: Malignancy
- Calcidiol elevated: Vitamin D excess
- Calcitriol but not calcidiol elevated: Ectopic production
- None elevated: Bone mets, rare causes
Compare malignant hyperparathyroidism to primary hyperparathyroidism
Malignant symptoms severity: mild to severe onset: days - weeks exam: abnormal prevalence: commonest in inpatients serum calcium : >3mmol/l
Primary hyperparathyroidism symptoms severity: mild onset: weeks to months exam: normal prevalence: commonest in outpatients serume calcium - <3mmol/L
