Basic Science applied to medicine

1. Distribution of calcium in the human
body
Hydroxyapatite
98.9%
= 31 mol
= 1250g
1% of which is
available as an
exchangeable pool
0.1% of total body calcium is in the extracellular fluid:
Ionised Calcium: Ca++
50%
1.2 mmol/L
1% of total body calcium is present in the cells
Protein-bound Calcium:
41%
1.2 mmol/L
Anion-bound calcium:
9 %, 0.2 mmol/L
• Present as free, active cation
•Diffuses easily across capillary
membranes
• Bound mainly to albumin
•Cannot diffuse across capillary
membranes
• Bound to small anionic
molecules, eg. phosphate and
citrate
• diffuses easily across capillary
membranes

3. CALCIUM HOMEOSTASIS
Hormone Effect Bone Gut Kidney
PTH ↑ Ca ↓ Po4 Increases
Osteoclasts
Indirect via
Vit. D
Ca reab
Po4 exr.
Vitamin D3 ↑ Ca ↑ Po4 No direct
action
↑ Ca ↑ Po4
absorption
No direct
effect
Calcitonin ↓ Ca ↓ Po4 Inhibits
Osteoclasts
No direct
effect
Ca & Po4
excretion
3

4. ▶Mild: Total Ca 10.5-11.9 mg/dL or Ionized Ca 1.4-2 mmol/L
▶Moderate: Ca 12-13.9 mg/dL or Ionized Ca 2-2.5 mmol/L
▶Hypercalcemic crisis: Ca 14-16 mg/dL or Ionized Ca 2.5-3
mmol/L
HYPERCALCEMIA

5. Hypercalcemia - Clinical
STONES
BONES
GROANSMOANS
5
RENAL
stones
Polyuria ,
Nocturia
failure
Bone pain
Fracture
risk
GIT
Constipatio
n, Nausea
Anorexia,
Pancreatitis
Gastric
ulcer
CNS
Lethargy,
Weakness
Deppression
Confusion,
Coma

6. CAUSES and Diagnostic Approach
✓PTH
↑
PRIMARY HYPERPARATHYROIDISM
TERTIARY HYPERPARATHYROIDISM
FHH
✓urine
Ca
↑
(>200mg/day)
1° ↑PTH
↓
(<100mg/day)
FHH
↓
Non-PTHmediated
✓ PTHrp & Vitamin D
↑ PTHrp
Look for cancer
BREAST
LUNG
MYELOMQA
↑ 1,25D
(Lymphoma
,
Granulomat
ous
disease)
EXCESS
INTAKE
NormalVIT
Dand
PTHrp
THYROTOXICOSIS
ADRENAL INSUF
RENAL FAILURE
IMMOBILISATION
DRUGS

7. ECG

8. ▶Mild, asymptomatic hypercalcemia do not require immediate
therapy, and manage underlying cause.
▶ Symptomatic hypercalcemia requires therapeutic intervention
▶ Initial therapy - volume expansion because hypercalcemia
invariably leads to dehydration
▶ 4–6 L of i/v saline may be required over the first 24 h
▶ Loop diuretics - enhance sodium and calcium excretion.
.
Treatment

9. In hypercalcemia of malignancy
drugs that inhibit bone resorption should be considered.
▶Zoledronic acid (e.g., 4 mg I/V over 30 min)
▶Pamidronate ,Etidronate
▶Onset of action is within 1–3 days.
Because of their effectiveness, bisphosphonates have replaced
calcitonin widely
▶In rare instances, dialysis may be necessary.

10. ▶I/V phosphate may be used, it can be toxic , ca-po4 complexes
cause extensive organ damage.
▶In 1,25(OH) D-mediated hypercalcemia- oral or i/v steroids
preffered ,decrease 1,25(OH) D production.
▶Recently, US FDA approved denosumab (RANKL inhibitor)
for treatment of hypercalcemia of malignancy refractory to
bisphosphonate therapy in December 2014

11. ▶Serum ca < 8.5 mg/dL or an ionized ca <1.0 mmol/L
▶ Ionized ca is the definitive method for diagnosis
▶ Corrected ca(mg%) = serum ca + (4.0 - albumin g%) x 0.8
Hypocalcemia

12. Cardiovascular effects :
▶acute hypocalcemia - syncope, CHF, and angina
Neuromuscular symptoms :
▶Numbness and tingling sensations - perioral area or in the
fingers and toes
▶Muscle cramps, in the back and lower extremities; may
progress to carpopedal spasm (ie, tetany)
▶Wheezing ,Dysphagia,Voice changes
History

13. Neurologic symptoms :
▶Irritability, impaired intellectual capacity, depression, and
personality changes
▶Fatigue,Seizures
Chronic hypocalcemia - dermatologic manifestations:
▶Coarse hair,Brittle nails
▶Psoriasis,Dry skin
▶Chronic pruritus
▶Poor dentition

14. ▶ Hair may appear coarse, and alopecia may be present.
▶ In chronic hypocalcemia - dental caries,enamel hypoplasia.
▶ Eye examination-subcapsular cataract or papilledema
▶ Patient may appear confused, disoriented, Irritabile
▶ Hallucinations, dementia, and seizures may occur.
▶On R/S-wheezes , laryngeal stridor
▶ On CVS- bradycardia, tachycardia, S3
, signs of HF.
PHYSICAL EXAMINATION

15. ▶Chvostek sign - tapping the skin over the facial nerve about 2 cm
anterior to the external auditory meatus.
▶Ipsilateral contraction of the facial muscles is a positive sign.
▶Depending on the ca level, a graded response will occur:
twitching first at the angle of the mouth, then by nose, eye and
the facial muscles.
▶ 10% of the population will have a positive Chvostek sign in the
absence of hypocalcemia so test is not diagnostic

16. ▶ Trousseau sign- placing a blood pressure cuff on the patient’s
arm and inflating to 20 mm Hg above SBP for 3-5 minutes.
▶flexion of wrist and MCP joints ,extension of IP joints and
adduction of the thumb (carpal spasm).
▶The Trousseau sign is more specific than the Chvostek sign
Extra pyramidal symptom :
▶Choreoathetosis ,Parkinsonism,Hemiballism

17. ECG in hypocalcaemia

18. CAUSES and Diagnostic Approach
LOW PARATHYROID
HORMONE LEVEL
HIGH PARATHYROID HORMONE
LEVEL
PARATHYROID
• AGENESIS-digeorge
•DESTRUCTION
surgical
radiation
infiltration
autoimmune
•HYPOFUNCTION-mg,CaSR
•VIT D related
Deficiency
Renal insufficiency
Resistance
•PTH horm resistance syndromes
•DRUGS
Chelators,biphosphanates
Miscellaneous
Acute pancreatitis
Acute rhabdomyolisis
Hungry bone
Osteoblastic metastasis

19. ▶On X-RAY, rickets or osteomalacia may present with the
pathognomonic Looser zones, better observed in the pubic
ramus, upper femoral bone, and ribs.
▶CT scans of head may show basal ganglia calcification
(extrapyramidal neurologic symptoms )

20. ▶Mild to Moderate Hypocalcemia,asymptomatic needs only ca
supplement
▶IV replacement is recommended in symptomatic or severe
hypocalcemia.
▶Doses of 100-300 mg of elemental ca in 50-100 mL of 5% D
should be given over 5-10 minutes.
▶10 mL of calcium gluconate contains 90 mg elemental ca
▶10 mL of calcium chloride contains 272 mg elemental ca
Treatment

21. ▶Measure serum calcium every 4-6 hours to maintain at levels of
8-9 mg/dL.
▶Start oral calcium and vitamin D treatment early
▶oral calcium supplements must be given between meals
otherwise, they will act as phosphate binders
▶ Vit D deficiency - vitamin D supplementation (50,000 U, 2–3
times per week for several months)
▶ Vit D deficiency due to malabsorption- higher doses (100,000
U/d or more).