Approach to patient with hypo/hyper

calcaemia

Nassr Saif AL-Barhi

SULTANTE OF OMAN

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

◦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 ↓ ↑

Hypercalcaemia

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

WHAT IS THE NEXT??

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

Causes:◦ > 90% of cases:

Primary hyperparathyroidism Malignancy

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:

Hypocalcaemia

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

case

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

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

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

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 .

Medication:

◦ Anticonvulsant

◦ Some Cemotherapeutic drugs e.g cisplatin

Causes

Hypocalcaemiaclinical manifestation

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

Hypocalcaemiaclinical manifestation

Trousseau’s sign

ousseau’s signs

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

Thank you