Calcium And Vit D Deficiencies Flashcards
Bone and calcium
25% of weight of normal adult
70% mineral 30% organic matrix (collagen)
Mineral-> calcium and phosphate-> hydroyaporite Ca complex crystalline salt
Bone remodelling is continuous -> 4 month process -> 20% of bone Ca is exchanged per year -> minor imbalances cause substantial bone problems
Calcium measurements
Total plasma Ca 2.2-2.6 mmol/l
40% is ionised-> physiologically relevant part
60% bound to albumin -> must therefore correct for serum albumin -> add /subtract 0.02 mmol/l for every g/l difference of albumin from 40g/l
Vitamin D and calcium
UV light causes vit D2 production in skin via 7-dehydrocholesterol
Also vit D2 dietary intake
Converted in liver by 25-hydroxylase to 25(OH)D2
Converted in kidney by 1a hydroxylase to 1,25(OH)D2, increased by PTH
Either directly to bone or to parathyroid glands
Serum Ca is absorbed from the gut and exchanged with bone
PTH acts on bone to activate osteoclasts and accelerate bone remodelling
PTH
84 amino acid peptide produced by chief cells of the parathyroid gland
Intracellular pre cursors-> pre pro PTH-> pro PTH -> PTH
Highly sensitive to ionised Ca plasma conc-> increased when low-> acts to increase blood and ECF Ca
Bone-> increased recruitment and activation of osteoclasts to accelerate bone resorption
Kidney-> increased kidney production of 1,25(OH2)D3 -> increased intestinal Ca absorption
Increased renal tubular reabsorption of Ca
Deceased resorption of inorganic phosphate-> phosphaturia
1,25(OH)2D3
Calcitriol-> calcaemic hormone
Renal production is increased by-> increased PTH, hypocalcaemia and hypophosphatemia
Calcitriol effects on gut
Increase Ca absorption
Increase permeability of brush border to Ca
Increased synthesis of high affinity Ca binding proteins in cells
Increased extrusion of Ca across basolateral membrane
Calitriol effects on bone
Increase bone resorption
Increase proliferation and differentiation of osteoclast precursors
Osteoblasts also as have R’s so probably increase too-> mediate osteoclast function
Calcitriol effects on parathyroid
Decrease PTH release
1) attaches to intracellular receptor protein
2) complex transported into nucleus where it interacts with DNA to affect synthesis of RNA coding proteins
3) regulated by interferons, interleukin, C-MYC down regularly
Skin and cancer cells also respond suggesting wider role in immunoregulation and cellular differentiation
Other hormones that effect Ca and bone
Calcitonin-> 32aa secreted by thyroid cells-> binds to osteoclasts-> decreases resorption-> minimal role in adults -> more important in high bone turnover rates
Sex steroids-> oestrogens-> decrease bone resorption and increase formation-> receptors on osteoblasts. Androgens convert to oestrogens and increase bone mass
Glucocorticoids-> affect bone forming and resorting cells
Thyroxine-> can cause osteoporosis, mild hypercalcaemia and hypercalciuria
Growth hormone-> acts via IGR-1 or somatomedin C-> stimulates cartilage growth
Hypercalcaemia causes
90% hyperparathyroidsim, primary or tertiary and malignancies or bone, PTHrP, osteoclastic activating factors, myeloma Thyrotoxocisis Addison's Iatrogenic-> vit d excess, milk alkali syndrome, drugs Familial hypocalciuric hypercalcaemia Ectopic PTH Satcoid lymphoma TB granulomas Immobili-> Padget's
Differential diagnosis between HPTH and cancer
History-> long in HTPH, short in cancer Examination-> normal, wt loss Serum Ca-> Stable, unstable Phosphate-> low, low or high Albumin-> normal, low Alkphesis-> normal, high Hb-> normal, low ESR-> normal, high
Signs and symptoms of hypercalcaemia
Nausea, vomiting, anorexia Constipation Abdo pain Peptic ulcer, pancreatitis Polyuria, polydipsia Tiredness Lethargy, muscle weakness Wt loss Arterial goals, bone pain-> pathological fracture Confusion, depression Psychosis Stuper, coma Nephrocalcinosis-> renal stones Renal failure Hypertension Arrhythmia's
Investigations of hypercalcaemia
PTH->increased or upper normal in HPTH, decreased in other causes
Myeloma screen
Plasma phosphate decrease in primary
U+E -> creatine increased in tertiary, chloride upper normal, bicarbonate low normal
24 hr urine Ca -> decreased in HTPH
TFTs to exclude thyrotoxocisis
ESR -> increased in malignancy
Radiology-> look for tumours and renal stones, subperiosteal erosion in hands suggests primary HPTH, isotope bone scan for metastatic hot spots
Steroid suppression test-> HTPH never suppresses
Confirming HTPH
Find adenoma -> ultra sound neck Radioisotope-> parathyroid differentiated from thyroid by thyroid uptake of technetium AA SPECT CT-> anatomical localisation Barium swallow Venous catheter to measure PTH
Hypercalcaemia treatment
Rehydration with 0.9% IV saline -> 4-6l over 24 hours then 3-4l per day
Can also use frusemide but only if fluid levels repleted
Bisphosphanate infusion -> after rehydration-> 15-90 Mg in 0.5l saline IV pamidronate over 2 hours. Can take 2-3 days to come down after
Other treatment not usually necessary
Prednisolone in myeloma
Calcitonin for life threatening
Treat underlying cause
Stop thiazides, calcium, vit D, calcitriol therapy
Hypercalcaemia and dehydration
Increased Ca -> dehydration-> increased proximal tubule Na reabsorption-> consequent Ca reabsorption
Renal pathophysiology
Tumour products-> PTHrP-> active Ca reabsorption in distal tubule
N+V-> decreased GFR-> increased Na/Ca reabsorption in proximal tubule.
Impaired water reabsorption in collecting duct-> nephrogenic DI serum Ca>3 mmol -> decreased GFR
Primary hyperparathyroidsim
1:500 to 1:1000
Most frequent 6th decade of life onwards
75% due to single adenoma
Rest >1 adenoma or 4 gland hyperplasia or ectopic PTH
May be part of multiple endocrine neoplasia
1% parathyroid carcinoma
Often asymptomatic for long periods
Renal complications and bone disease-> osteoporosis and rarely osteitisis fibrosa cystics
Treat if complications of Ca >3.0 mmol
Parathyroid surgery remove adenoma/all 4 glands and treat with calcitriol
Development of calcimimetic drugs alter function of Ca sensing R-> deceased PTH
Calcium sensing receptor
G protein coupled R
Senses extra cellular levels of Ca2+
Regulates PTH release from parathyroid hormones-> controls calcium homeostasis
Mutations inactivating CaSR-> familial hypocalciuric hypercalcaemia
Mutations activating CaSR -> autosomal dominate hypocalcaemia
Chalcalcett is a modifier of CaSR-> may be used as treatment
Hypocalcaemia common causes
Increased serum phosphate-> chronic renal failure, phosphate therapy
Hypoparathryoidism -> decreased PTH,increased phosphate -> post ectomy, severe hypomagnoaemia which inhibits PTH release
Vit d deficiency-> osteomalacia, vit D resistance
Drugs-> calcitonin, bisphosphates
Acute pancreatitis
Blood in massive transfusion
Over heating-> ovidity of Ca to albumin in resp acidosis
Rare causes of hypoparathyroidsim
Idiopathic hypoparathyroidism -> autoimmune-> decreased PTH, increased phosphate-> vitiligo, cutaneous memisiasis,
Di George syndrome-> familial-> 3rd and 4th pharyngeal pouches done develope-> intellectual impairments cataracts, calcified basal ganglia.
Pseudohypoparathyroidsim-> increased PTH, increased phosphate-) end organ resistance-> short stature! short metacarpals, intellectual impairment-> failure of response to PTH
-> increased urinary cAMP-> type 1
-> phosphaturia-> type 2
Pseudopseudohypoparathyroidism-> somatic features without low Ca2+
Investigations of hypocalcaemia
Urea and creatinine Serum PTH levels Parathyroid antibodies Serum Mg levels Phosphate level 1,5(OH)D3 X-ray metacarpals
Clinical features of hypocalcaemia
Irritability Fatigue Anxiety Paraesthesisa Cramps Tetany Laryngeal spasm Convulsions Death Positive chvostechs sign-> taping facial nerve causes twitiching Positive trousseaus sign-> BP cuff-> carpopedal spasm ECG-> increased QT interval Prolonged-> Cataracts Papilloedema Depression/mental changes Heart failure Chorea
Treatment of hypocalcaemia
Acute-> with tetany-> IV 10mls 10% Ca gluconate in fusion over 30 mins to 4 hours
Maintenance-> oral aufacalcitriol and calcium
Vit D deficiency causes
Dietary and poor sunlight
Malabsorption
Renal disease-> impaired hydroxylation
Rarely-> hepatic failure, phenytoin/barbituates,
fanconis syndrome-> hereditary tubular renal tubular defect -> reduced renal absorption of phosphates, amino acids and glucose.
Vit D resistant rickets-> familial hypophosphstemia, x linked hypophosphatemia, phosphaturic, rickets
Renal tubule acidosis
Oncogenic osteomalacia-> non metastatic, sarcomas of ct tumours
Clinical features of vit D deficiency
Children-> rickets
Adults->
-> ostomalacia->bone and muscle pain and tenderness, sub clinical fractures, proximal myopathy, waddling gait
-> vit D deficiency-> secondary hypoparathyroidism and increased bone turnover, osteoporosis and fracture
Diagnosis of vit d deficiency
Low serum phosphate
Increased serum alkaline phosphate
Low or low normal corrected serum Ca
Increased PTH
Decreased 25(OH)D3
Increased bone turnover markers
X-rays-> defective mineralisation, pseudofractures, looser zone (linear area of low density), bicomcave deformities in vertebrae
Bone biopsy -> definitive but rarely necessary
X linked hypophosphatemia-> normal Ca, low phosphate, normal alkaline phosphate, paradoxical increase in bone density
Treatment of vit D deficiency
Sunlight exposure
Oral D2 and D3 supplements
IM cholecsliterol every 6-12 months
Usually need Ca supplements as well
Renal disease-> alphacalcidiol or calitriol
X linked hypophosphatemia-> difficult-> oral phosphate has GI side effects
