Calcium And Vit D Deficiencies

Question 0

Bone and calcium

Answer 0

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

Question 1

Calcium measurements

Answer 1

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

Question 2

Vitamin D and calcium

Answer 2

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

Question 3

PTH

Answer 3

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

Question 4

1,25(OH)2D3

Answer 4

Calcitriol-> calcaemic hormone

Renal production is increased by-> increased PTH, hypocalcaemia and hypophosphatemia

Question 5

Calcitriol effects on gut

Answer 5

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

Question 6

Calitriol effects on bone

Answer 6

Increase bone resorption
Increase proliferation and differentiation of osteoclast precursors
Osteoblasts also as have R’s so probably increase too-> mediate osteoclast function

Question 7

Calcitriol effects on parathyroid

Answer 7

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

Question 8

Other hormones that effect Ca and bone

Answer 8

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

Question 9

Hypercalcaemia causes

Answer 9

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

Question 10

Differential diagnosis between HPTH and cancer

Answer 10

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

Question 11

Signs and symptoms of hypercalcaemia

Answer 11

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

Question 12

Investigations of hypercalcaemia

Answer 12

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

Question 13

Confirming HTPH

Answer 13

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

Question 14

Hypercalcaemia treatment

Answer 14

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

Question 15

Hypercalcaemia and dehydration

Answer 15

Increased Ca -> dehydration-> increased proximal tubule Na reabsorption-> consequent Ca reabsorption

Question 16

Renal pathophysiology

Answer 16

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

Question 17

Primary hyperparathyroidsim

Answer 17

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

Question 18

Calcium sensing receptor

Answer 18

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

Question 19

Hypocalcaemia common causes

Answer 19

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

Question 20

Rare causes of hypoparathyroidsim

Answer 20

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+

Question 21

Investigations of hypocalcaemia

Answer 21

Urea and creatinine 
Serum PTH levels
Parathyroid antibodies
Serum Mg levels
Phosphate level
1,5(OH)D3 
X-ray metacarpals

Question 22

Clinical features of hypocalcaemia

Answer 22

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

Question 23

Treatment of hypocalcaemia

Answer 23

Acute-> with tetany-> IV 10mls 10% Ca gluconate in fusion over 30 mins to 4 hours
Maintenance-> oral aufacalcitriol and calcium

Question 24

Vit D deficiency causes

Answer 24

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

Question 25

Clinical features of vit D deficiency

Answer 25

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

Question 26

Diagnosis of vit d deficiency

Answer 26

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

Question 27

Treatment of vit D deficiency

Answer 27

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