This document discusses calcium homeostasis and disorders of calcium metabolism. It begins by describing the functions of calcium in the body and where calcium is stored. It then discusses calcium regulation by parathyroid hormone, vitamin D, and calcitonin. Causes, signs and symptoms, and treatment approaches for hypercalcemia and hypocalcemia are reviewed. The key points are that calcium levels are tightly controlled by hormones to maintain levels between 2.25-2.62 mmol/L and that disorders can result from excess or deficiencies of these regulating hormones.

1. Nassr Saif AL-Barhi
SULTANTE OF OMAN

2.  Function of calcium
 Calcium homeostasis
 Hyper/ hypo calcemia
◦ Causes
◦ Signs and symptoms
◦ Management

3. 1. Neuromuscular excitability.
2. Excitation-contraction coupling (cardiac &
smooth m).
3. Stimulus-secretion coupling
4. Maintenance of tight junctions
5. Clotting of blood (co-factor)
6. Intracellular Ca (2nd messenger, cell motility)
7. Calcification of bones & teeth

4.  Total body : 1 Kg
◦ 99%  bone
◦ 0.9%  intracellular
◦ 0.1%  ECF
 In blood
◦ 45%  mostly albumin
◦ 40%  free or ionized
◦ 15%  small anions : phosphate and citrate
Ionized Ca is Physiologically important.

6.  Normal serum level of Ca in adult bw 2.25 to
2.62 mmol/L.
 Total Ca is usually measured, then corrected
to albumin. Why???
 Corrected Ca:
Corrected Ca (mmol/L) = measured Ca + 0.02 (40 – albumin)

7.  Serum Ca level is determined by net absorption
(GI) & excretion (RENAL).
 Each components is tightly regulated-
hormonally- to keep normal serum level .

8.  Calcium regulation :mainly by 3 common
hormones :
1}Parathyroid hormone .
2}Vitamin D .
3}Calcitonin .

9.  the major hormone for regulation of the
serum Ca2+
 synthesized and secreted by the chief cells of
the parathyroid glands.

10.  controlled by the serum [Ca2+] by negative
feedback.
 Decreased serum [Ca2+] increases PTH
secretion.
 severe decreases in serum [Mg2+] inhibit PTH
secretion and produce symptoms of
hypoparathyroidism.

11.  PTH actions:
 I Ca & PO4 reabsorption in kidney.
◦ renal production of 1,25 dihydroxy
vitD3.
◦ intestinal absorption of Ca.
◦ increase bone resorption.
Overall effect :increase serum Ca & decrease serumPO4

12.  Vitamin D is a steroid hormone that has long
been known for its important role in
regulating body levels of calcium and
phosphorus, and in mineralization of bone.
◦ In children, vitamin D deficiency causes rickets;
◦ In adults, vitamin D deficiency causes osteomalacia.

14. ◦ Vitamin D actions:
◦ increase Ca & PO4 absorption from intestine.
◦ increase renal reabsorption of Ca &PO4.
◦ increase bone resorption from old bone
&mineralize new bone{net resorption} .
Overall effect :increase serum Ca & PO4

15.  is synthesized and secreted by the
parafollicular cells of the thyroid.
 Peptide that inhibit bone osteoclast & so
inhibit bone resorption.
 Increasing renal secretion.
 Used as a treatment for osteoporosis and
hypercalcaemia
Overall effect : decrease serum Ca & PO4.

16. PTH Vitamine D Calcitonin
Stimulation of
secretion
↓ serum [Ca2+] ↓ serum [Ca2+]
↑ PTH
↓ serum
phosphate
↑ serum
[Ca2+]
Bone ↑ resorption ↑ resorption ↓ resorption
Kidney ↓ P
reabsorption
↑ Ca2+
reabsorption
↑ P reabsorption
↑ Ca2+
Reabsorption
Intestine ↑ Ca2+
absorption
(via vitamin D)
↑ Ca2+ absorption
↑ P absorption
Serum calcium ↑ ↑ ↓
Serum phosphate ↓ ↑

18.  A 35 -year –old female reported to
emergency with severe pain in the left flank
region, which was radiating towards lower leg
and back. History revealed that she frequently
suffered from urinary tract infections and had
several such episodes of pain. She further
reported that she constantly felt weakness,
fatigue and bone pains from the previous few
months. There was no history of fever and
there was no personal or family history of
medical problems.

19.  Her physical examination was normal except
for tenderness in the left renal region.
 The attending physician ordered for complete
blood count, electrolytes and a complete
urine analysis.
 The laboratory investigation report revealed a
normal complete blood count (CBC), and
significantly elevatedcalcium level and low
phosphorus level. Urine was cloudy and had
plenty of puscells. The patient was admitted
and treated for renal colic

21.  Normal serum calcium levels are (2.25 to
2.62 mmol/L)
 Normal ionized calcium levels are (1.15 to
1.31 mmol per L)

 Hypercalcemia: is defined as total serum
calcium (>2.62 m mol/L ) or ionized
serum calcium ( >1.31 m mol/L )

22.  Severe hypercalemia is defined as total serum
calcium (> 3.5 mmol/L)
 Hypercalcemic crises is present when severe
neurological symptoms or cardiac arrhythmias are
present in a patient with a serum calcium (> 3.5
mmol/L) or when the serum calcium is (> 4 mmol/L)

24.  With normal or elevated PTH
◦ Primary or tertiary hyperparathyroidism
◦ Lithium induced hyperparathyroidism
◦ Familial hypocalciuric hypercalcemia
 With low PTH
◦ Malignancy ( lung, breast)
◦ Elevated vitamin D3
◦ Thyrotoxicosis
◦ Pagets disease
◦ Thiazide diuritics
◦ Glucocorticoid defeciency

25.  Causes:
◦ > 90% of cases:
 Primary hyperparathyroidism
 Malignancy

26.  Hyperparathyroidism:
◦ Primary:
 Caused by single parathyroid gland adenoma
,occasionally hyperplasia , rarely carcinoma
◦ Secondary:
 Physiological response to hypocalcemia.
◦ Tertiary:
 Parathyroid hyperplasia after long standing secondary
Hyperparathyroidism.

27.  Malignancy:
◦ Secretion peptide with PTH-like activity .
◦ Direct invasion of bone and production of local
factors that mobilize ca.

28.  Evaluation of a patient with hypercalcemia
should include:
◦ a careful history
◦ physical examination focusing on
 clinical manifestations of hypercalcemia,
 risk factors for malignancy
 causative medications
 a family history of hypercalcemia-associated
conditions

29.  Almost 80% : asymptomatic.
 Mild : often asymptomatic.
 More sever :
◦ General malaise
◦ Depression
◦ Bone pain
◦ Abdominal pain
◦ Nausea
◦ Constipation
◦ Polyurea & nocturia
◦ Calculi
◦ Renal failure
 Very high:
 Dehydration
 Confusion
 Clouding of
consciosness
 Risk of cardiac arrest

30. Bones, Stones, Psychotic, CNS, Abdominal
Cardiovascular
Hypertension
Arrhythmias
Short QT
Ca. deposition on valves,
coronary arteries and
myocardial fibers
GIT
Constipation
Anorexia
Nausea & Vomiting
PUD
Pancreatitis
Renal
Polyuria
Polydipsia
Nephrogenic DI
Nephrolithiasis
Renal Faliure
Rheumatological
Pseudogout
Chondrocalcinosis
Weakeness
Bone pains
Psychiatric
Anxiety
Depression
Cognitive dysfuction
Psychosis ( > 4 mmol/l)
confusion
Neurological
Hypotonia
Hyporeflexia
Myopathy
Paresis

31.  Physical Examination:
◦ No specific physical findings
◦ Some related to an underlying disease e.g:
malignancy and nonspecific findings related to
dehydration.
◦ general ex: Band keratopathy
Corneal disease .. Ca in central cornea

32. PTH
IF IT IS normal or high
24-hour urinary calcium
IF low
Familial hypocalciuric
hypercalcemia
If normal or high
Primary
hyperparathyroidism

33. or normal phosphate
low PTH
solid tumors(humoral
hypercalcemia)
• Immobilization
Milk alkali syndrome ( hypercalcemia
with alkalosis and renal failure)
• Drugs: thiazide diuretics .
• Metastatic bone disease
• thyrotoxicosis, Paget’s disease
phosphate with PTHrP↑
Low Vit D metabolites
Calcitriol high
Granulomatous disease
e.g. TB, sarcoid,
lymphoma (esp.
Hodgkins)

35.  Cardiac findings:
◦ Arrhythmias
◦ Hypotension
◦ Shortened QT interval, in severe cases:Osborn
waves (J waves)

36.  Mild hypercalcemia: (calcium <3 mmol/L)
 Moderate hypercalcemia: (calcium between 3 to 3.5
mmol/L)
◦ Do not require immediate treatment.
◦ Avoid factors that can aggravate hypercalcemia,
including:
 Thiazide diuretics and lithium carbonate therapy.
 prolonged bed rest or inactivity.
 a high calcium diet (>1000 mg/day).

37.  Severe hypercalcemia: calcium > 3.5 mmol/L
◦ The acute therapy of such patients consists of a
three-pronged approach
◦ Volume expansion with isotonic saline.
◦ Administration of salmon calcitonin (4 international
units/kg).
◦ The concurrent administration of zoledronic acid (4
mg IV over 15 minutes) or pamidronate (60 to 90
mg over two hours),

38. Total corrected serum Ca <2.25 mmol/L (9.0
mg/dL)

39.  14 years old girl complains of
weakness and difficulty in climbing up
stairs

40. Diagnosis ……..?
Result Ref. range
PTH 53.8 pmol/l 1.6-9.3
Corrected
Calcium
1.9 mmol/l 2.1-2.6
Phosphate 0.75 mmol/l 0.9-1.5
ALP 1008 iu/l 90-270

41.  Vitamin-D level < 10 (NR= 75-200)

42.  HYPOCALCEMIA WITH LOW PTH
(HYPOPARATHYROIDISM) :
◦ Hereditary
 abnormal parathyroid gland development
◦ Acquired:
 destruction of the parathyroid glands (autoimmune,
post-surgical).
◦ functional hypoparathyroidism :
 hypomagnesemia
 acute severe hypermagnesemia
◦ Otheres:
◦ hemochromatosis, Wilson's disease, granulomas, or
metastatic cancer)

43.  HYPOCALCEMIA WITH HIGH PTH:
◦ PTH resistance (impaired PTH action)
 Pseudohypoparathyroidism.
◦ Vitamin D deficiency or resistance
 poor intake or malabsorption coupled with reduced
exposure to ultraviolet light.
◦ Hyperphosphatemia
◦ Acute pancreatitis .

44.  Medication:
◦ Anticonvulsant
◦ Some Cemotherapeutic drugs e.g cisplatin

45.  Increased neuromuscular irritability
 Parasthesia, muscle cramps.
 Tetany
 Seizures
 Laryngospasm, bronchospasm
 Chvostek’s sign, Trousseau’s sign.
 Prolonged QT on ECG.

46.  Trousseau’s sign
ousseau’s signs

47.  Chvostek sign:
 Spasm of facial muscles induced by tapping over the facial
nerve in the region of zygomatic arch.

48.  measurement of the serum albumin
concentration.
 measurement of serum intact parathyroid
hormone .
 serum magnesium,
 Creatinine.
 Phosphate.
 vitamin D metabolites.
 alkaline phosphatase

50.  Mild symptoms:
◦ Oral calcium
 In chronic kidney disease
◦ Alfacalcidol ( vit D analogue)
 Severe symptoms
◦ Calcium gluconate (IV)

51.  http://www.uptodate.com/contents/treatmen
t-of-hypercalcemia#H18.
 http://ezproxy.squ.edu.om:2265/contents/et
iology-of-hypocalcemia-in-
adults?source=search_result&search=calcium
+homeostasis&selectedTitle=14%7E89.
 Toronto note ,27th Edition, 2011.
 Kumar & Clark .Clinical medicine 5th edition.