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Outline Function of calcium
Calcium homeostasis
Hyper/ hypo calcemia
◦ Causes ◦ Signs and symptoms◦ Management
Calcium function
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
Calcium homeostasis 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.
Normal serum level of Ca in adult b\w 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)
Serum Ca level is determined by net
absorption (GI) & excretion (RENAL).
Each components is tightly regulated-
hormonally- to keep normal serum level .
Calcium regulation :mainly by 3 common hormones :
1}Parathyroid hormone .
2}Vitamin D .
3}Calcitonin .
Calcium metabolism
Parathyroid hormone the major hormone for regulation of the
serum Ca2+
synthesized and secreted by the chief cells of the parathyroid glands.
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.
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
Calcium metabolism
Vitamin D 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.
◦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
Calcium metabolism
Calcitonin 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.
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 ↓ ↑
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.
Case
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
Defination 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 )
Defination
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)
Hypercalcemia: causes 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
Hypercalcaemia 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.
Hypercalcaemia Malignancy:
◦ Secretion peptide with PTH-like activity .◦ Direct invasion of bone and production of local
factors that mobilize ca.
Evaluation 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
Hypercalcaemia 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
Bones, Stones, Psychotic, CNS, Abdominal
CardiovascularHypertensionArrhythmiasShort QTCa. deposition on valves,coronary arteries and myocardial fibers
GIT ConstipationAnorexiaNausea & VomitingPUDPancreatitis
Renal PolyuriaPolydipsiaNephrogenic DINephrolithiasisRenal Faliure
RheumatologicalPseudogoutChondrocalcinosisWeakenessBone pains
PsychiatricAnxietyDepressionCognitive dysfuctionPsychosis ( > 4 mmol/l)
confusion
NeurologicalHypotoniaHyporeflexiaMyopathyParesis
Hypercalcaemia 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
Investigation
PTH
IF IT IS normal or high
24-hour urinary calcium
IF lowFamilial
hypocalciuric hypercalcemia
If normal or highPrimary
hyperparathyroidism
or normal phosphate
low PTH
solid tumors(humoral hypercalcemia)
• Immobilization
Milk alkali syndrome ( hypercalcemiawith 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)
Hypercalcaemia Cardiac findings:
◦ Arrhythmias◦ Hypotension◦ Shortened QT interval, in severe cases:Osborn
waves (J waves)
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).
Management:
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),
Management:
case
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
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)
Causes
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 .
Hypocalcaemiaclinical manifestation
Increased neuromuscular irritability Parasthesia, muscle cramps. Tetany Seizures Laryngospasm, bronchospasm Chvostek’s sign, Trousseau’s sign. Prolonged QT on ECG.
Hypocalcaemiaclinical manifestation
Chvostek sign: Spasm of facial muscles induced by tapping over the facial
nerve in the region of zygomatic arch.
measurement of the serum albumin concentration.
measurement of serum intact parathyroid hormone .
serum magnesium, Creatinine. Phosphate. vitamin D metabolites. alkaline phosphatase
INTERPRETATION OF SERUM CALCIUM
Management Mild symptoms:
◦ Oral calcium In chronic kidney disease
◦ Alfacalcidol ( vit D analogue) Severe symptoms
◦ Calcium gluconate (IV)
http://www.uptodate.com/contents/treatment-of-hypercalcemia#H18.
http://ezproxy.squ.edu.om:2265/contents/etiology-of-hypocalcemia-in-adults?source=search_result&search=calcium+homeostasis&selectedTitle=14%7E89.
Toronto note ,27th Edition, 2011. Kumar & Clark .Clinical medicine 5th
edition.
References