This document discusses calcium disorders including an overview of calcium, hypercalcemia, hypocalcemia, and inherited calcium disorders. It defines calcium and its roles in the body. Hypercalcemia is defined as a serum calcium level >10.5 mg/dL and can be caused by increased bone resorption, gastrointestinal absorption, or decreased renal excretion. It discusses the etiology, clinical exam, differential diagnosis, investigations, management, and complications of hypercalcemia. Hypocalcemia is defined as a total calcium <8.5 mg/dL and discusses its etiology including hypoparathyroidism, renal insufficiency, hypomagnesemia, vitamin D deficiency, and others. It also discusses the

1. Calcium Disorders

2. Objectives
1. Overview of calcium
2. Hypercalcemia
3. Hypocalcemia
4. Inherited Calcium disorders

3. Overview of Calcium
Saleh Hassan Alorainy

4. Definition
• A mineral found mainly in the hard part of bones, where it is stored.
• Calcium is essential for healthy bones and is also important for
muscle contraction, heart action, and normal blood clotting.
• Food sources of calcium include dairy foods; some leafy green
vegetables and seafood.
Calcium (serum) 8.6-10.3 mg/dL
Calcium (ionized) 4.4-5.2 mg/dL

5. Sources

6. Body requirements

7. Role
• Bone strength
• Transmission of Nerve impulses
• Contraction of Smooth, Skeletal and
cardiac muscles
• Blood Clotting

8. Bone strength
• Bone is composed of a tough
organic matrix that is greatly
strengthened by deposits of
calcium salts. Average compact
bone contains by weight about
30 percent matrix and 70 percent
salts.
• Osteoblasts Deposit bone
• Osteoclasts Resorb Bone

9. Nerve Impulse
• Presynaptic Membrane
contains voltage-gated
Ca+2 channels, after an
action potential a surge of
Ca+2 inters the cell
allowing the cytoplasmic
vesicles to release the
neurotransmitters into the
synaptic cleft

10. Muscle Contraction

11. Blood Clotting
• Except for the first two
steps in the intrinsic
pathway, calcium ions
are required for
promotion or
acceleration of all the
blood clotting reactions.
Therefore, in the
absence of calcium ions,
blood clotting by either
pathway does not occur.

12. Homeostasis

13. Regulation
PTH
Vitamin D

14. Regulation
• Calcitonin: increased plasma Ca2+ concentration Inhibition
of osteoclast bone resorption Decrease plasma Ca2+
concentration.
• Calcitonin Role in Calcium regulation is uncertain

15. Hypercalcemia

16. Definition, Etiology, Clinical Exam &
Differential Diagnosis
Khalid Mohammed Alkhalifah

17. Definition
Hypercalcemia is a disorder commonly encountered by primary care physicians. The diagnosis often
is made incidentally in asymptomatic patients.It results when the entry of calcium into the
circulation exceeds the excretion of calcium into the urine or deposition in bone. The serum calcium
in Hypercalcemia varies among laboratories but generally is > 10.5 mg/dL.
This occurs when there is :
1. accelerated bone resorption
2. excessive gastrointestinal absorption
3. decreased renal excretion of calcium.

18. Etiology
The most common causes are the following:
1. Hyperparathyroidism (primary)
2. Malignancy (Multiple myeloma)
Other causes:
• Calcium supplementation
• Iatrogenic (thiazides)
• Immobility (especially in the ICU setting)
• Milk-alkali syndrome
• Paget disease
• Excess vitamin D

19. Clinical Exam
• History:
Usually asymptomatic but can present with:
1. bones (osteopenia, fractures)
2. stones (kidney stones)
3. abdominal groans (anorexia, constipation)
4. psychiatric overtones (weakness, fatigue, irritability, altered mental status).
5. coma in Severe elevations in calcium levels.
• Physical examination:
1. Hypertension and Short QT interval
2. pancreatitis in Abdominal examination
3. proximal muscle weakness
4. Hyperreflexia and tongue fasciculations
5. Polyuria and dehydration

20. Differential Diagnosis
1. Hyperparathyroidism
2. Malignancy
3. Vitamin Toxicity
4. Acute Complications of Sarcoidosis

21. Investigation, Management,
Complications & Prognosis
Fahad Saleh Alkhalaf

22. Investigations
• General investigations:
o Calcium level
o PO level
o Alkaline phosphate
o Parathyroid level
o Vitamin D level

23. 1. Evaluate calcium imbalance
• Initial test: serum calcium concentration
• Confirm true hypercalcemia:
• measure ionized calcium or calculate corrected calcium.
Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 (4.0 - serum albumin
[g/dL]). where 4.0 represents the average albumin level.
• Increased ionized calcium, regardless of total calcium levels → true hypercalcemia
(potentially symptomatic)
• Increased total calcium with normal ionized (active) calcium → factitious
hypercalcemia (asymptomatic finding)

24. Note
The corrected calcium concentration calculated using
serum albumin may not be accurate when major pH changes have
taken place in the body (e.g., following surgery).
In these cases, it is possible to measure the free calcium ion activity
directly (ie, ionized calcium level). directly.

25. 2. Differentiate between low PTH and high PTH:
To determine the underlying cause of hypercalcemia
PTH: the most important test for patients with disorders of calcium balance
3. Further tests
• ECG:
oQT interval shortening
oIn severe hypercalcemia: J wave

27. Copyrights apply

28. Management
• Treatment approach:
o treatment depends on the Ca2+ level and the symptoms
o treat the underlying cause of the hypercalcemia
o treat acute, symptomatic hypercalcemia aggressively
o bed rest

29. Mild or moderate asymptomatic
hypercalcemia
• Encourage adequate oral hydration
• Reduce dietary intake of calcium
• Avoid thiazide diuretics, lithium, high-calcium diet
• Monitor

30. Increase Urinary Ca2+ Excretion IV hydration with isotonic saline
Calcitonin
Loop diuritics
Diminish Bone Resorption Bisphosphonates
Calcitonin
Decrease intestinal Ca2+ Absorption Glucocoticoids
Dialysis very severe cases (total calcium > 18 mg/dL; ionized
calcium > 4.5 mmol/L)
or concomitant renal failure
1st step in management is FLUID!! (fill the tank to the maximum)
Patients with calcium levels greater than 14ml/dl
Or symptomatic patients with calcium levels greater than 12 must be treated immediately and aggressively

31. Copyrights apply

32. Complications
• Osteoporosis
• Nephrolithiasis
• Arrythmias
• Altered mental status

33. Prognosis
Prognosis of hypercalcemia depends upon the underlying etiology
• Very poor if underlying cause is malignancy
• Excellent if underlying cause is treated properly

34. Hypocalcemia

35. Definition, Etiology, Clinical Exam &
Differential Diagnosis
Abdulmlk Abdullah AlMadhi

36. Definition
• Hypocalcemia Total calcium <8.5 mg/dL, if serum protein is normal
OR Ionized calcium < 4.5mg/dL.
• Because a significant portion of calcium is bound to albumin, any
alteration in the level of albumin will affect the measured level of
calcium.

38. Etiology
1. Hypoparathyroidism is a common cause of hypocalcemia. Calcium is
tightly regulated by the parathyroid hormone (PTH). in the setting of
absent, decreased, or ineffective PTH hormone, the body loses this
regulatory function, and cause hypocalcemia.
• Hypoparathyroidism is commonly due to surgical destruction of the
parathyroid glands ; Hypoparathyroidism may also be due to autoimmune
problem.
2. Renal insufficiency : decreased Ca reabsorption , or mainly due to
decreased production of 1,25-dihydroxy Vitamin D.

39. Etiology
3. Hypomagnesemia:
Always measure serum magnesium in a hypocalcemic patient.
Hypomagnesemia impairs PTH secretion
Magnesium plays a central role in adenylate cyclase activity and
subsequently in the production of cyclic adenosine monophosphate
(cAMP) .
Since PTH secretion is mediated by cAMP, altered adenylate cyclase
function in magnesium deficiency causes impairment in PTH levels.
4. Vitamin D deficiency .

40. Etiology
5. Pseudohypoparathyroidism:
autosomal recessive disease, causing congenital end-organ resistance to PTH
(so PTH levels are actually high); also characterized by mental retardation
and short metacarpal bones.
6. Hyperphosphatemia:
PO4 binds with Ca2+ resulting in calcium phosphate deposition.
7. DiGeorge syndrome
• Deletion on chromosome 22 .

41. Clinical Exam
• Asymptomatic
• Rickets and osteomalacia
• Increased neuromuscular irritability
The neuromuscular symptoms of hypocalcemia due to the decreased interaction of calcium
with sodium channels. Since calcium blocks sodium channels and inhibits depolarization of
nerve and muscle fibers, reduced calcium lowers the threshold for depolarization.
A. Numbness/tingling around the mouth and lips in fingers, and toes. This is often the
earliest symptom of hypocalcemia.
B. Tetany
• Hyperactive deep tendon reflexes
• Chvostek sign :tapping a facial nerve leads to a contraction (twitching) of facial muscles
• Trousseau sign: Inflate BP cuff to a pressure higher than the patient’s systolic BP for 3
minutes. This elicits carpal spasms

43. Clinical Exam

44. Investigation, Management,
Complications & Prognosis
Meshal Abdulrahman Almuhaidib

45. Investigation
• Confirm true hypocalcemia
o Measure total and ionized calcium
o AND/OR check serum albumin and calculate corrected calcium
• Evaluate for other electrolyte abnormalities
o BMP
o Serum phosphate and magnesium
• Serum intact PTH: Indication: best initial study for confirmed hypocalcemia with
no clear etiology
• Interpretation
o Low (or normal) PTH suggests hypoparathyroidism
o High PTH suggests parathyroid gland function is preserved
• ECG: Prolonged QT interval
QRS complex and ST-segment changes (may mimic myocardial infarction)

47. Management
• Severe and/or symptomatic
hypocalcemia: e.g., tetany, seizures, prolonged QT interval, serum
calcium ≤ 7.5 mg/dL (< 1.9 mmol/L)
oIV calcium supplementation: calcium gluconate or calcium chloride
oContinuous telemetry
oConsider transfer to critical care unit
• Mild and/or chronic hypocalcemia: no symptoms or only mild
neuromuscular irritability (e.g., paresthesias), serum calcium 7.6–8.4
mg/dL (1.9–2.12 mmol/L)
• Oral calcium supplementation: calcium citrate, calcium carbonate
• Loop diuretics Lose calcium. Discontinue them in hypocalcemia.

48. Complications
• Nail and skin symptoms( eczema)
• Osteopenia and osteoporosis
• Painful premenstrual syndrome (PMS)
• Depression
• Dental Problems

49. Prognosis
• The prognosis of hypoglycemia depends on the cause of this condition, severity, and duration
• If the cause of fasting hypoglycemia is identified and treated early, the prognosis is excellent. If
the problem is not curable, such as a malignant tumor, the long-term prognosis is poor
• Severe and prolonged hypoglycemia can be life threatening and may be associated with increased
mortality in patients with diabetes.
• If the patient has reactive hypoglycemia, symptoms often spontaneously improve over time, and
the long-term prognosis is very good.
• Reactive hypoglycemia is often treated successfully with dietary changes and is associated with
minimal morbidity. Mortality is not observed

50. inherited Calcium Disorders
Saleh Alorainy

51. Inherited Diseases that present with Hypercalcemia
• Familial benign hypocalciuric hypercalcemia (FHH)
• Autosomal Dominant
• Asymptomatic Hypercalcemia
• Low urinary calcium excretion
• Normal PTH in 80% of patients
• Neonatal severe primary hyperparathyroidism
• symptomatic hypercalcemia, skeletal manifestations
of hyperparathyroidism, in the first 6 months of life.
• failure to thrive, dehydration, hypotonia, constipation,
rib cage deformities, and multiple fractures due to
bony undermineralization.
• require urgent parathyroidectomy
• Jansen’s disease
• Autosomal Dominant
• short-limbed dwarfism, severe hypercalcemia and
hypophosphatemia
• normal or undetectable serum levels of PTH.
• Williams syndrome
• Autosomal Dominant
• supravalvular aortic stenosis, elfin-like facies,
psychomotor retardation, and infantile
hypercalcemia.
• Infantile hypercalcemia
• Autosomal Recessive
• failure to thrive, severe hypercalcemia, hypercalciuria,
and nephrocalcinosis
• elevated circulating 1,25(OH)2D concentrations.

52. Inherited Diseases that present with Hypocalcemia
• Inherited hypoparathyroidism:
• may develop hypocalcemic seizures in the neonatal or infantile periods and require lifelong treatment
with oral vitamin D.
• Autosomal dominant, autosomal recessive, and X-linked recessive inheritances.
• Mutations of one or more PTH related genes
• DiGeorge Syndrome:
• Neonatal hypoparathyroidism, T-cell immunodeficiency, congenital heart defects, and deformities of
the ear, nose, and mouth.
• Failure of 3rd and 4th pharyngeal pouch derivatives to develop.
• Often die from infections related to the immunodeficiency.
• Autosomal dominant hypocalcemia type 1 and 2:
• characterized by life- long mild or severe hypocalcemia
• normal to low serum PTH concentrations,
• ADH 1 (CaSR), ADH2 (Gα11).

53. References
• Guyton and Hall Textbook of Medical Physiology 13TH EDITION
• Linda S. Costanzo - Physiology (2017)
• Goldman-Cecil Medicine 25th Edition
• Step-Up to Medicine 4th Edition
• Clinical medicine
• Osmosis
• National Institute of Health WebMed
• https://www.medicinenet.com/script/main/art.asp?articlekey=2575
• https://www.researchgate.net/figure/Calcium-recommendations-for-Americans-mg-d-12_tbl1_331976843
• https://www.researchgate.net/figure/Cont_tbl3_331976843
• https://www.researchgate.net/figure/Non-dairy-sources-of-calcium-in-the-diet-18_tbl4_331976843
• https://www.ncbi.nlm.nih.gov/books/NBK430714/
• UpToDate
• AMBOSS
• Medscape

54. Questions?

55. This Seminar Was Done By:-
• Saleh Hassan Alorainy
• Khalid Mohammed Alkhalifah
• Fahad Saleh Alkhalaf
• Abdulmlk Abdullah AlMadhi
• Meshal Abdulrahman Almuhaidib

56. Thank You!