Calcium disorders

Calcium disorders Seminar
IMAMU medical College

1. Calcium Disorders

2. Objectives Overview of calcium Hypercalcemia Hypocalcemia 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 Ca 2+ concentration Inhibition of osteoclast bone resorption Decrease plasma Ca 2+ 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 : accelerated bone resorptio n excessive gastrointestinal absorption decreased renal excretion of calcium.  

18. Etiology The most common causes are the following: Hyperparathyroidism (primary) 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: bones (osteopenia, fractures) stones (kidney stones) abdominal groans (anorexia, constipation) psychiatric overtones (weakness, fatigue, irritability, altered mental status). coma in Severe elevations in calcium levels. Physical examination: Hypertension and Short QT interval pancreatitis in Abdominal examination proximal muscle weakness Hyperreflexia and tongue fasciculations Polyuria and dehydration

20. Differential Diagnosis Hyperparathyroidism Malignancy Vitamin Toxicity Acute Complications of Sarcoidosis    

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

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

23. 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. 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 Further tests ECG: QT interval shortening In severe hypercalcemia: J wave

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

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

29. Severe/Symptomatic hypercalcemia Treatment for severe/symptomatic hypercalcemia 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 1 st 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

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31. Complications Osteoporosis Nephrolithiasis Arrythmias Altered mental status

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

33. Hypocalcemia

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

35. 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.

36. Etiology 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. Renal insufficiency : decreased Ca reabsorption , or mainly due to decreased production of 1,25-dihydroxy Vitamin D.

37. Etiology 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. Vitamin D deficiency .

38. Etiology 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. Hyperphosphatemia: PO4 binds with Ca2+ resulting in calcium phosphate deposition. DiGeorge syndrome Deletion on chromosome 22 .

39. 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

40. Clinical Exam

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

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

43. Management Severe and/or symptomatic hypocalcemia : e.g.,  tetany ,  seizures ,  prolonged QT interval , serum calcium ≤ 7.5 mg/dL (< 1.9 mmol/L)  IV calcium supplementation: calcium gluconate or calcium chloride Continuous telemetry  Consider 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 Lo op diuretics  Lo se calcium. Discontinue them in hyp o calcemia.

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

45. 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

46. inherited Calcium Disorders Saleh Alorainy

47. 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) 2 D concentrations.

48. 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 3 rd and 4 th 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 (G α11 ).

49. References Guyton and Hall Textbook of Medical Physiology 13TH EDITION Linda S. Costanzo - Physiology (2017) Goldman-Cecil Medicine 25 th 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

50. Questions?

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

52. Thank You!