1. Disorder of Ca Metabolism
DR ROHANI
MODERATOR: DR ROZI

2. Calcium
 Present in the body greater amounts than
any other mineral
 Distribution:2 major pools
 Readily exchangable comprising 1 % of total
body ca: act as immediate reserve for sudden
change in plasma ca
 Not readily exchangeable comprising 99 % &
consist of bone
 Normal plasma concentration:
 8-10 mg/dL (2.0-2.5 mmol/L)

3.  Total plasma ca consists :
 Ca bounds to alb (40%)
 Ca complexed with citrate and phosphorus
(10%)
 Freely diffusible ionized ca (50%)
 Ionized conc also depends on arterial pH

4.  Only unbound ca (free/ ionized)
biologically active:
 serum level must be adjusted for abnormal
albumin levels.
 1-g/dL drop in serum alb below 4 g/dL,
measured serum ca decreases by 0.8
mg/dL
 Corrected Ca =total Ca in mmol/L + [0.02
x (40-alb in g/dL)]

5. Biochemical function of Calcium
 Membrane excitation:
 Excitable membrane of nerve and muscle
contain specific Ca ionic channels
 Control membrane excitability
 Influx of ca ion occurs during excitation of
nerves and muscle
 Haemostasis : activation of clotting factors
in plasma
 Muscle contraction

6.  Excitation-secretion process
 Influxof ca req for secretion both endocrine &
exocrine organs
 Ca: necessary for release of neurotransmitter
 Structural support
 Bound cell surfaces, important for membrane
stability & intercellular adhesion
 Important component of bone

7. Ca Metabolism
 Regulate by 3 hormones:
 Parathyroid
 Calcitonin
 Vitamin D
 Act on bone, kidney and intestine

8. Absorption
 Gastrointestinal tract
 Passive:
 Depends plasma calcium concentration
 Active :
 Stimulated by 1:25-dihydroxycalciferol

9.  Kidney
 Influence by PTH
 Filtered at glomerulus (98%)
 Reabsorbed
 Proxtubule(60 %)
 Loop and distal tubule (40%)

10. Parathyroid hormone (PTH)
 Produced by 4 small glands (parathyroid
glands)
 Contain 2 cell types:
 Chiefcells: sectrete PTH
 Oxyphil cell: unknown function

11.  Synthesis PTH controlled by extracellular
ionized ca
 Decreased extracellular ionized ca increases
PTH synthesis
 Action PTH
 Increases plasma ca and lowers plasma
phosphate concentration
 Act on bone, kidney and GIT (indirectly`)

12. PTH
 Increase rate bone resorption
 Stimulate activity of osteocytes and osteoclast
 Raise se ca concentration

13. Calcitonin
 Secreted by parafollicular (C) cell in the
thyroid gland
 Single chain polypeptide
 Secretion calcitonin increased when
extracellular ca rises to 2.4 mmol/L
 Parafollicular C have ca-sensing receptor
 When ca binds to these receptor
stimulates calcitonin secretion

14. Action
Decreases plasma calcium and phosphate
levels :direct inhibition of osteoblasts
 Increases renal excretion of phosphate
and calcium

15. Vitamin D
 Steroid compound derived from
cholecalciferol (D3)
 25-Hydroxycalciferol: circulating form
(inactive)
 1,25-Dihydroxycholecalciferol: active form

16.  Cholecalciferol (D3): produced in the skin
from 7-dehydrocholesterol by UV light
 Liver : D3 hydroxylated to 25-
hydroxycholecalciferol
 Kidney:
 convert 25-hydroxycholecalciferol to 1,25-
dihydroxycholecalciferol
 By action of renal 1-hydroxylase
 Stimulated by PTH

17. Action of Vit D
 1,25-dihydroxycholecalciferol
 Act on small intestine: promote absorption of
calcium and phosphate
 Facilitate bone mineralization by increasing
ECF concentration of ca and phosphate
 Increase synthesis ca-binding protein:
promote ca absorption
 With PTH mobilizes ca and phosphate from
bone
 Important for bone remodelling

21. Disorders of calcium metabolism
 Hypercalcemia
 Hypocalcemia

22. Hypercalcemia
 Serum calcium level greater than 10.5 mg/dL
(>2.5 mmol/L)
 Mild: Total Ca 10.5-11.9 mg/dL (2.5-3 mmol/L)
or Ionized Ca 5.6-8 mg/dL (1.4-2 mmol/L)
 Moderate: Total Ca 12-13.9 mg/dL (3-3.5
mmol/L) or Ionized Ca 5.6-8 mg/dL (2-2.5
mmol/L)
 Hypercalcemic crisis: Total Ca 14-16 mg/dL (3.5-
4 mmol/L) or Ionized Ca 10-12 mg/dL (2.5-3
mmol/L)

23. Hypercalcemia
 Causes:
 Hyperparathyroidism
 Malignancy
 Excessive vit D intake
 Granulomatous d/o (sarcoidosis, tuberculosis)
 Chronic immobilization
 Milk-alkali syndrome: Excess ca intake
 Drug induced:
 Thiazide diuretics
 Lithium

24. Clinical manifestations:
 CVS: hypovolaemia,
 Ecg:
 Shortened QT interval
 CNS: confusion, drowsiness, weakness
 Renal : polyuria d2 nephrogenic diabetes
insipidus
 GIT: epigastric pain, nausea, vomiting,
constipation

25.  Treatment
 Symptomatic: req rapid treatment
 Initial rx: rehydration f/b brisk diuresis (U/O:
200-300 ml/h)
 Hydration: IV infusion D5%, o.45 % NaCl or
NS > 3L at 250- 500ml/h to correct hypovol
 Frusemide : to induce diuresis and reduce ca
reabsorption
 Hydration and diuresis may remove potential
risk of CVS and neurological cx , usua se ca
remains elevated

26.  Additional therapy with bisphosphonate /
calcitonin may be req esp severe hyperca (ca
> 15 mg/dL)
 Bisphosphonates
 Binds hydroxylapatite in bone matrix and inhibit
osteoclastic act
 Iv pamidronate 60mg in 50-500 ml NS over 4-24H
 Onset effect in 24H , peak effect 5-6 days
 Mg –checked: avoid hypomagnesaemia
 Clodronate
 Iv 300 mg in 500 ml NS at least 2h for 7-10 days/ PO
1.6 -3.2 g/d in 1-2 devided doses
 Calcitonin
 IV 5-10 U/ kg in 100 ml NS over 6-24h/ IM/SC/
intranasal 200-400 U/d in 2-4 devided doses

27.  Corticosteroids
 Useful in hypervitaminosis D, bone mets and
sarcoidosis
 Ineffective with hyperparathyroidism
 Onset within hours but efficacy min
 Mithamycin (plicamycin)
 Insevere hyperca, unresponsive to above
measures
 Severe adverse effect:
 Bone marrow suppresion, hepatic and renal toxic
effect
 Rapidly reduces osteoclastic activity

28.  Additional treatment depends on underlying
cause
 90% of hypercalcemia d2 malignancy/
hyperPTH
 Lab test: double anti body PTH assay
 Se PTH concentration:
 SUPRESSED: MALIGNANCY STATE
 ELEVATED: HYPERPARATHYROIDISM

29. ANAESTHETIC CONSIDERATION
 Ionized ca monitored closely
 Saline diuresis should be cont intraop with
great care to avoid hypovolemia
 Central venous and pulm artery pressure
monitoring advisable –pts with decreased
cardiac reserve
 Avoid acidosis

30. HYPERPARATHYROIDISM
 PTH : principal regulator of ca
homeostasis
 Increase se ca:
 Promoting bone resorption
 Limiting renal excretion
 Indirectly enhancing GI absorption (effect on vit D
met)

31.  Causes
 Primary hyperparathyroidism:
 Adenoma, carcinoma and hyperplasia of
parathyroid gland
 secondary hyperparathyroidism
 Adaptive response to hypocalcemia
 Renal failure/ intestinal malabsorption syndrome
 Ectopic hyperparathyroidism
 Production of PTH by tumour outside parathyroid
gland
 Mostclinical manifestations d2
hypercalcaemia

32. Effects of hyperparathyroidism
 CVS: HPT, ventricular arrythmias, ECG
changes (shortened QT interval)
 Renal :
 Hyperchloremic met acidosis
 Poluria, dehydration, polydipsia, renal stone
 GIT:
 Ileus, N & V, PUD, Panvreatitis
 Musculoskletal : muscle weakness,
osteoporosis
 Neurologic : mental status change (e.g:
delirium, psychosis, coma)

33. Hypocalcemia
 Hypoparathyroidism
 Pseudohypoparathyroidism
 Vit D Def
 Nutritional
 Malabsorption
 Hyperphosphatemia
 Precipitation of calcium
 Pancreatitis
 Rhabdomyolysis
 Fat embolism
 Chelation of calcium
 Multiple rapid red blood transfusion or rapid infusion of
large amounts of albumin

34.  Clinical manifestations
 CNS:
 Muscle spasm
 Carpopedal spasm, laryngeal spasm
 Trosseau’s sign: inflate BP cuff 10 mmHg above
SBP for 3 min: postive if flexion
metocarpophalangeal jt & extension
interphalangeal jt
 Chovstek’s sign: tap facial nerve at ant border
masseter ms, 2 cm in front of ear lobe
 Positive : twitching of upper lip

35.  Circumoral numbness
 Convulsions, depression and dementia
 CVS:
 Prolonged QT and non-spesific t-wave
changes
 Hypotension d2 decrease cardiac contractility

36.  Treatment
 Medical emergency
 Treated with:
 Calcium chloride 3-5 ml of 10% solution
 Calcium gluconate 10-20 ml 10 % solution
 10 ml 10% CaCl = 272 mg of ca
 10 ml calcium gluconate =93 mg of ca
 To avoid precipitation: should not be given
with bicarbonate / phosphate containing
solutions

37.  Severe sx:
 IV 20-40 ml Ca gluconate or 10 ml CaCL in
100 ml infused over 2-5 min
 f/up with 20-60 ml Ca gluconate / 20-40 ml
CaCl in 500 ml infusedd over 6 H
 SX mild
 -oral elemental Ca 1-3 gm /d in 3 devided
dose

38.  Anaesthetic considerations
 Should be corrected preoperatively
 Serial ionized ca level should be monitored
intraoperatively in pt’s with hx hypoca
 Avoid alkalosis: prevent further decrease in ca
 IV ca may necessary following rapid
transfusions of citrated blood products/ large
vol of albumin
 Responses to NMBAs are inconsistent and req
close monitoring with nerve stimulator

39. REFERENCES
 emedicine.medscape.com
 PRINCIPLES OF PHYSIOLOGY FOR
ANAESTHETIST: IAN POWER & PETER
KAM
 Bedside ICU Handbook : Tan Tock Seng
Hospital