Calcium and Phosphorus PDF

Calicum and Posphorous Calcium: Mainly in the ECF, about 99% of Ca in bone and teeth. In serum, as two forms: 1-Diffusible free calcium : 50%ionize ca 10% complex calcium 2- Non-Diffusible 40-50% protein bound Increase pH leads to decrease Cai Decrease pH leads to incr...

Calicum and Posphorous Calcium: Mainly in the ECF, about 99% of Ca in bone and teeth. In serum, as two forms: 1-Diffusible free calcium : 50%ionize ca 10% complex calcium 2- Non-Diffusible 40-50% protein bound Increase pH leads to decrease Cai Decrease pH leads to increase Cai Non diffusible ca is bound to albumin 50 % Recommended dietary allowances of calcium (RDA) 400-500 mg / day Adult 800 mg /day Children 1200 mg /day pregnancy &lactation  Factor Enhancing Ca absorption : 1- 1,25 –dihydroxy cholecalciferol 2-acidity of digestive mass 3- presence of lactose 4-the need for ca. 5- ca : P ratio 1:1 to 1:2 Factors depressing ca absorption 1- Oxalic and phytic acid 2- Increased GIT motility 3- Lack of exercise 4- Emotional Instability 5- Unabsorbed F. A.  Absorption of calcium A- Active transport process B- Simple diffustion Summary of absorption & metabolism of Ca Diet intake 1 gm Bone Formation Resorption GUT Abs. 400 mg Plasma 10 mg /100ml Sec.200 mg 800 Mg/day urine 200/day Tissue  Physiological function of Ca A- Blood clotting Ca injury ------- platelete ------------- thromboplastin Prothrombin ----------------- Thrombin Fibrinogen ------------ Fibrin clot B-Bone & teeth formation CaHPo4 ( 3 Ca3 ( Po4) 2. Ca (oH) 2 ) Hydroxy apatite C- Muscle contraction D- Membrane permeability  Phosphorus 1% of adult body P in ICF is 50X more than ECF Phosphorus in the blood 1-inorganic p 2-organic or ester p : glycerophosphate , nucleotide phosphate. 3- Lipid P : Lecithin, Cephalin Sphingomyclin Recommended dietary allowances 2 X RDA of Ca in adult 2/3 that of Ca for infant before 6 months  Absorption Mainly in the jejunum Excretion : 30-40% of intake in feces or in urine Physiological Function of Phosphorus 1- Regulation of energy release 2- Absorption and transportation of nutrient 3- Part of essential body compounds : DNA,RNA,Enzymes,Vitamines 4- Calcification of bone & teeth : 80 % of P in bone +teeth with Ca. S. Ca X S. P = 40( Normal) 5- Regulation of acid base balance  Phosphorous Turnover ) Day) Factors influencing Ca + P levels: I. Vitamin D 7 dehydrocholesterol cholecalciferol liver 25 Oh-cholecalciferol kidney 1,25 Di-OH- cholecalciferol (D.H.C.C):  Vitamin D Action it increases intestinal absorption of Ca by stimulates synthesis of Ca binding protein stimulates Ca dependant ATPase – Increase intestinal absorption of P increase Ca resorption from bone increase Ca reabsorption by Distal Tubule increase both serum Ca & PO4 II- Parathormone (P.T.H) Polypeptide hormone ,84 aa from C- cells of parathyroid gland. MW 9500 daltons Stimulated by low level of Cai  Action Of PTH on BONE : enhance bone resorption 1. Increase collagenase activity by oseteoclasts 2. Inhibits the activity of osteoblast 3. Promote glycolysis leads to accumulation of lactate, citrate, & organic acids so decrease pH leads to increase bone dissolution. B. On kidneys : stimulate renal dihydroxylation of vit. D 1. Increase Ca rebsorption by renal tubules by the effect of DHCC-DT. 2. Increase PO4 excretion by inhibiting proximal tubule reabsorption of Pi 3. Prevents reabsorption of Na, K ,HCO3 , aa and H2o from PT  C. on GIT : increase intestinal reabsorption of Ca indirectly thru DHCC CALCITONIN (CT) secreted by C-cells of thyroid gland polypeptide 32 aa , MW 3500 D stimulated by High Ca  Calcitonin Action : inhibit bone resporption * increase activity of osteoBlast * incr. excretion of Ca & PO4 KATACALCIN: (KC) * polypeptide 21 aa * stimulated by high Ca Action: same as CT except no effect on plasma PO4  HYPOCALCEMIA serum Ca < 8mg/dl , while normal value Ca = 8.5-10.5 mg/dl Causes : Hypoparathyroidism : deceased PTH level primary : *following neck surgery for GOITER – malignancy or hyperparathyroidism , * post radiation therapy for neck cancer findings : *decreased serum level of PTH\ * decreased serum CA, *increased serum PO4 Pseudo hypoparthyroidism : an inborn error there is a dec. in the responsiveness – of kidney & bone tissue to PTH normal or slight inc. in serum PTH – increased serum PO4 – decreased serum Ca – II Acute Pancreatitis : dec. or normal serum Ca – dec. serum albumin – III. Vit. D deficiency IV. hyperphosphatamia ( inc serum PO4) renal failure – post treatment with cytotoxic drugs – Drugs: esterogen , mithramycin – Decrease formation of DHCC – Promote Ca deposition in soft tissue – Chelating Ca within blood – -Inhibit Ca resorption from bone – V. Calcitonin Excess VI. Hypomagnesemia & hypoproteneimia Clinical Manifestation of hypocalcemia latent tetany skin changes emotional & behavioural changes delay eruption of teeth hypotension & heart failure on ECG : prolonged ST segment Hypercalcemia Total serum Ca > 12mg/dl on repeated occasions  Causes I. hyperparathyroidism primary: Adenoma or hyperplasia of the thyroid gland. nausea and vomiting, abdominal pain and depression renal change (calculi , polyuria , renal failure) secondary: vit D deficiency & Ca Malnutrition dietary , renal disease , liver disease – anticonvulsant therapy – – Findings: increased or normal serum Ca value Increased serum PO4 Decreased urine Ca & increased U. PO4 II. Hypercalcemia of Malignancy : secondary to cancer of the lung , breast, kidney, prostate , leukemia , lymphoma. Demineralization of Bone III.Hyperthyroidism : s. Ca (mild), urine Ca& PO4 , S. alkaline phosphate. IV. Sarcodosis : V : Pagets disease of bone  Clinical manifestation of hypercalcemia 1- polyuria & polydipsia 2-metabolic alkalosis 3- on ECG shortening of ST segment 4- Nausea, Vomiting , constipation, muscular hypotonia , stupor & even coma. Bone changes in Different diseases osteoporoses : Reduction of bone matrix with secondary loss of Ca Inc. bone resorption (osteoclast) Dec. Bone formation (osteoblast) In old female , common in post menopause Secondary to systemic disease OSteomalasia : failure of mineralization of bone Rickets Deficiency of vit D – S. Ca X S. P < 40 – – Biochemical findings: decreased or normal serum calcium – decreased serum PO4 & increased urine PO4 & – citrate Amino aciduria – increase serum PTH – The main causes of rickets 1-lack Ca intake and Vit D intake 2-ineffective conversion of provitD3  vit D3 3-intestinal malabsorption 4-vit. D resistant a. chronic renal failure b. inherited deficiency of 1α-hydroxylase enz 5-excessive renal PO4 loss A-Fanconi syndrome – B-Defect in PO4 renal handling –  Renal Osteodystrophy 1- decrease in bone bc. Of decrease in Ca 2-chronic renal failure 3- s.PO4 increased , while decreased Ca 4-impaired renal 25 OH Vit D result : increase S. PO4 , decreased s. Ca  secondary hyperparathyroidism phosphate binding : Al hydroxide (antacid) to pull all PO4 and decrease it. Renal rickets : in children with chronic renal failure Causes impaired vit. Metabolism PO4 retention ( i.e. increased ) Decreased s Ca A 45-year-old man was in the intensive care unit for multiple trauma following a road traffic accident. Some of his biochemistry results were as follows: Plasma Calcium 1.98 mmol/L (2.15–2.55) Albumin 30 g/L (35–45) Phosphate 0.92 mmol/L (0.80–1.35) What is the albumin-adjusted calcium?.  DISCUSSION Adjusted calcium = 1.98 + (40 – 30) ¥ 0.02 = 1.98 + 0.20 = 2.18 mmol/L Note that the plasma calcium now adjusted falls within the reference range and does not require specific treatment. Remember this if the patient has hypoalbuminaemia A 53-year-old man saw his general practitioner because of bone pain and constipation. A number of laboratory tests were requested, the results for the most relevant of which were as follows: Plasma Albumin-adjusted calcium 2.96 mmol/L (2.15–2.55) Phosphate 0.62 mmol/L (0.80– 1.35) Parathyroid hormone 157 ng/L (20–65)  Discussion The patient has hypercalcaemia. Note also the hypophosphataemia and inappropriately raised PTH concentration. The diagnosis was subsequently found to be primary hyperparathyroidism due to a parathyroid adenoma associated with multiple endocrine neoplasia (MEN) type I. His symptoms are typical of chronic hypercalcaemia A 76-year-old woman with known breast carcinoma was admitted to hospital drowsy, with weight loss and backache. The following results were returned. Plasma Albumin- adjusted calcium 3.96 mmol/L (2.15–2.55) Phosphate 1.12 mmol/L (0.80–1.35) Parathyroid hormone less than 10 ng/L (20–65)  DISCUSSION A bone scan subsequently showed the patient to have widespread bone metastases. Note the severe hypercalcaemia and the appropriately suppressed plasma PTH, suggesting a non-parathyroid source of the hypercalcaemia. Various tumours are associated with bone metastases, including breast tumours. A 72-year-old woman presented to her general practitioner with tiredness, muscle aches and difficulty in standing up. The following test results were found. Plasma Albumin-adjusted calcium 1.76 mmol/L (2.15–2.55) Phosphate 0.52 mmol/L (0.80–1.35) Parathyroid hormone 138 ng/L (20–65) Alkaline phosphatase 763 U/L (< 250) 25-hydroxyvitamin D 5 µg/L (> 75)  DISCUSSION The patient has osteomalacia, as evidenced by the low plasma 25-hydroxyvitamin D concentration. Note also the hypocalcaemia with hypophosphataemia and raised alkaline phosphatase and secondary appropriate elevation of PTH. The symptoms are typical of osteomalacia, which can lead to proximal myopathy and bone pain. The elderly are particularly prone to osteomalacia, in part related to poor dietary vitamin D intake. Calcium, phosphate and magnesium metabolism are closely related and abnormalities are clinically relatively common. Plasma calcium levels are controlled by PTH (raises plasma calcium), vitamin D activity and optimal renal and intestinal function. Hypercalcaemia can result in various symptoms: ‘bones, stones, moans and groans’. The causes include malignant disease, primary or tertiary hyperparathyroidism, certain drugs such as thiazides, granulomatous disease such as sarcoidaosis, milk– alkali syndrome, thyrotoxicosis, Addison’s disease, hypocalciuric hypercalcaemia and acromegaly. Hypocalcaemia can present with paraesthesiae, tetany, osteomalacia and seizures. The causes may be due to poor diet, including vitamin D deficiency, chronic kidney disease, malabsorption, certain drugs, such as loop diuretics, and hypoparathyroidism.