IT IS MY POWERPOINT PRESENTATION FOR FINAL YEAR MBBS STUDENTS

1. Calcium ,phosphate,Vitamin-D
and parathyroid
DR IRSHAD ALI K.M
Assistant professor
Department of internal medicine
Govt.medical college .Kottayam

2. PHYSIOLOGY
• FOUR parathyroid glands located posterior to
thyroid gland
• They produce PTH-Para Thyroid Hormone

3. CALCIUM PHOSPHATE RATIO
• Calcium : Phosphate ratio normally is 2:1.
• Increase in plasma calcium levels causes
corresponding decrease in absorption of
phosphate.
• This ratio is always constant.

4. • The serum level of calcium is closely regulated
• normal total calcium of 9-10.5 mg/dL
• normal ionized calcium of 4.5-5.6 mg/dL.
Serum Phosphate levels
• Children - 4 to 7 mg/dL
• Adults - 3 to 4.5 mg/dL

5. • 50% of total calcium is ionized
• The rest bound principally to albumin
• So for every decrement of serum albumin by 1
gm below 4.1 gm add 0.8 mg/dl.

6. QUESTION.??
• Patients albumin level-3.1 gm
• Serum calcium-7.5 mg/dl what is the
corrected calcium?

7. • ANSWER-7.5 + (4.1-3.1)0.8 mg/dl=8.3 mg/dl

8. Parathyroid Hormone
(PTH)
Secreted by parathyroid gland
Glands are four in number
Present posterior to the thyroid gland
Formed from third and fourth branchial pouches
Combined weight of 130mg with each gland weighing
between 30-50mg.
Histologically – two types of cells
Chief cells (forming PTH)
Oxyphilic cells (replaces the chief cells
stores hormone)

9. Anatomy & Location of Parathyroid Gland

10. ACTION-keep the ECF CALCIUM level in
normal range
• KIDNEY-
DCT-increased absorption of calcium
PCT- Stimulation Of 1-hydroxylation
of cholecalciferol
• Increases The Phosphate excretion
• BONE-induces calcium release by dissolution of bone
mineral

11. • PTH-84 AMINO ACID single chain peptide
• The amino terminal portion is critical for its
biological action
• Pre pro(25+6+84amino acids) to
pro(6+84aminoacids) ..then to PTH(84 AMINO
ACIDS)
REGULATION OF PTH –ECF calcium controls by
acting on G protein coupled
receptor(parathyroid, c-cells of
thyroid,kidney,brain)

12. • IN CHRONIC KIDNEY DISEASE INTACT –PTH
(7-84) –biologically active PTH is measured.

13. calcitonin
• Hypo calcemic peptide released from C-cells of
thyroid.
• Orgin of c-cells is from neural crest.
• Action-reduce calcium level by-
inhibition of osteoclast mediated bone
resorption
Stimulation of renal calcium excretion
Tumour marker of medullary carcinoma of thyroid

14. Vitamin D(chole calciferol)
• Absorbed from diet
• Synthesized in skin in response to uv radiation
• 7-dehydrocholestrol is converted to chole
calciferol
• It is then transported to liver where it undergoes
25 hydroxylation .this is the major circulating
form of vitamin-D
• The final step in hormone activation-I alpha
hydroxylation occur in PCT of kidney.
• Inactivation by 24 hydroxylase

15. misnomers……..
• Vitamin D2-plant Sources
• Vitamin D3-animal sources
• 25 (OH) Cholecalciferol-calcidiol
• 1,25 (OH)2 Cholecalciferol-calcitriol

16. Action of vitamin D
• It binds to–VDR (vitamin D receptor) a member of
nuclear receptor family.
• Increases absorption of calcium from gut
• Increases renal calcium and phosphate
reabsorption
• Stimulates the mobilisation of calcium from bone
• Antiproliferative action in parathyroid and cancer
cells
• Post natal hair growth
• Immunological actions

17. Disorders of calcium metabolism
mcq-1
• 1.hypercalcemia is not seen in
I. Lithium therapy
II. Chronic renal failure
III. Multiple myeloma
IV. Vitamin A deficiency

18. Causes of hypercalcemia
• Parathyroid related
• Hypercalcemia of malignancy
• Excessive 1,25(OH)2 VITAMIN D production
• Primary increase in bone resorption
• Excessive calcium intake
• others

19. Parathyroid related-excessive PTH
production
i. Primary-hyperparathyroidism-
adenoma,hyperplasia,rarely carcinoma
ii. Tertiary-long term stimulation of PTH secretion
in renal insufficiency
iii. Ectopic PTH secretion
iv. Inactivating mutation in the CaSR-calcium
sensor receptor or in G protein-FHH(familial
hypocalciuric hypercalcemia)
v. Alteration in CaSR Function-lithium Therapy

20. Hypercalcemia of malignancy
• Overproduction of PTHrP-many solid tumours
• Lytic skeltal metastases-breast,myeloma

21. Excessive 1,25(OH)2D Production
• Granulomatous disease-
sarcoidosis,tuberculosis,silicosis
Lymphoma
Vitamin D Intoxication

22. Primary increase in bone resorption
• hyperthyroidism
• Immobilization
• Excessive calcium intake-milk alkali
syndrome,TPN
• Other Causes-adrenal
Insufficiency,pheochromocytoma,VIPoma
• Medication-thiazides,Vitamin-A,Antiestrogens

23. ANSWER
1.hypercalcemia is not seen in (AI-95)
• Lithium therapy
• Chronic renal failure
• Multiple myeloma
• Vitamin A deficiency
Seen in vitamin A TOXICITY

24. MCQ-2 (ALL INDIA-2009)
2.HYPERCALCEMIA is associated with all except-
• HYPERPARATHYROIDISM
• SARCOIDOSIS
• MILK ALKALI SYNDROME
• CELIAC DISEASE

25. ANSWER
• CELIAC DISESAE Isnot a cause for
hypercalcemia

26. MCQ-3 (aiims-95,97)
3.All are causes of hypercalcemia except-
• Thyrotoxicosis
• Sarcoidosis
• Viamin A toxicity
• Phenytoin toxicity

27. MCQ-4
• Which of the following is not a feature of
hypercalcemia
a. Diarrhoea
b. Polyuria
c. Depression
d. vomiting

28. Clinical features
• Mild-hypercalcemia-11-11.5 mg/dl-
asymptomatic
• Increased peptic ulcer disease,vague
neuropsychiatric manifestations,personality
changes,depression
• Nephrolithiasis

29. • Severe hypercalcemiea-more than 12-13
mg/dl
• Lethargy,stupor,coma
• Git symptoms-
nausea,anorexia,constipation,pancreatitis
• Polyuria,poly dipsia-hypercalcemia decreases
renal concentrating ability
• Bone pain,fracture risk

30. Ecg
• Bradycardia
• AV BLOCK
• Short QT interval

31. ANSWER
• Which of the following is not a feature of
hypercalcemia
• Diarrhoea
• Polyuria
• Depression
• vomiting

32. • Hypercalcemia associated with constipation
....not diarrhoea

33. MCQ-6 ALL INDIA
• A 55 year old chronic smoker is brought to the
casuality with history of
polyuria,polydipsia,nausea and altered
sensorium for last two days.He has been
diagnosed as having squamous cell
carcinoma.on examination he was
lethargic,and confused.ECG was normal
except for narrow QT interval.which one of the
following is most likely-

34. • Hypernatremia
• Hypercalcemia
• Hypokalemia
• hyponatremia

35. How will u treat this condition
• Hydration-4-6 litres of intra venous saline over
24 hours
• Loop diuretics-it should not be initiated until
the volume status has been restored.
• Drugs that inhibit bone resorption –
bisphosphonates –zoledronic acid-4 mg over
30 minutes,pamidronate-60-90 mg over 2-4
hrs,ibandronate-2 mg ovr 2 hrs
• dialysis

36. • Gallium nitrate-200 mg /m2 iv daily for 5 days
• Iv phosphates-calcium phosphate complexes
deposits over tissue and damages
• 1,25(OH)2D MEDIATED-
glucocorticoids/prednisolone
• Ketoconazole,chloroquine ,hydroxy
chloroquine-decreases its production

37. MCQ-7 ALL INDIA
• Hypercalcemia not seen in
I. Primary hyperparathyroidism
II. Multiple myeloma
III. Tumourlysis syndrome
IV. Sarcoidosis

38. Tumour lysis syndrome
• Hyper uricemia
• Hyperphosphatemia
• Hyperkalemia
• Lactic acidosis
• Increased phosphate drives calcium in to the
bone-
• Calcium phosphate is deposited in renal
tubles---hypocalcemia

39. ANSWER
• Hypercalcemia not seen in
I. Primary hyperparathyroidism
II. Multiple myeloma
III. Tumourlysis syndrome
IV. Sarcoidosis

40. • Thiazide diuretics causes hypercalcemia by
decresing its excretion ...so shouldnot be used
in hypercalcemia

41. Hypocalcemia
• Low para thyroid hormone level-
hypoparathyroidism
• High parathyroid hormone level-secondary
hyperparathyroidism

42. Low para thyroid hormone level-
hypoparathyroidism
• Parathyroid agenesis -
isolated,
Di george syndrome
Parathyroid destruction
surgical
radiation
infiltration by mets or systemic disease
auto immune
Reduced parathyroid function
hypomagnesiemia
activating CaSR or G protein mutation

43. High parathyroid hormone level-
secondary hyperparathyroidism
• Vitamin D defeciency-
impaired production
nutritional
renal insufficiency,
vitamin D RESISTANCE
PTH resistance syndrome-
PTH RECEPTOR MUTATION
PSEUDO HYPOPARATHYROIDISM

44. • DRUGS-calcium chelators,
Inhibitors of bone resorption-
bisphosphonates,plicamycin
Altered VITAMIN D metabolism-
phenytoin,ketoconazole
Miscellaneous-acute pancreatitis,acute
rhabdomyolysis,hungry bone syndrome after
parathyroidectomy,osteoblastic metastases with
marked stimulation of bone formation –
carcinoma prostate

45. MCQ-8
8.Hypocalcemia seen in
I. Acute pancreatitis
II. Parathyroid adenoma
III. Breast cancer
IV. Hodgkins lymphoma

46. • Hypercalcemia causes acute pancreatitis and
acute pancreatitis causes hypocalcemia

47. ANSWER
• Hypocalcemia seen in
• Acute pancreatitis
• Parathyroid adenoma
• Breast cancer
• Hodgkins lymphoma

48. Symptoms:
Irritability,
muscle cramps,
depression,
bronchospasm, and seizures.
Signs:
Increased reflexes, prolonged QT interval on ECG (the only
cause of a prolonged QT with a normal duration of the T wave
itself)

49. Tetany (Carpopedal spasm)
Basic feature of tetany is uncontrolled,
painful, prolonged contraction (spasm)
of the voluntary muscles.
Chvostek’s sign
Contraction of ipsilateral facial muscles
when tapping facial nerve over the
angle of the mandible.
Erbs sign
◦ Hyperexitability of muscles to electrical stimulation

50. • CARPAL SPASM INDUCED BY inflation of a
blood pressure cuff to 20 mm of Hg above the
patient ‘s systolic BP for three minutes-
TROUSSEAU’S SIGN

51. Approach to hypocalcemia
• Measure serum
calcium,albumin,phosphorus,magnesium
levels
• PTH LEVEL
• Serum 25 hydroxy vitamin D LEVEL

52. • LOW PTH WITH LOW CALCIUM-
HYPOPARATHYROIDISM
• ELEVATED PTH LEVEL- WITH HYPOCALCEMIA
CHECK VITAMIN D AXIS-Secondary
hyperparathyroidism

53. treatment
Acute symptomatic hypocalcemia-10 ml 10%
wt/vol diluted in 50 ml NS or 5%D
Continuing hypocalcemia to be treated with IV
infusion of 10 ampules of calcium gluconate in
1 litres of 5D or 0.9%NS Over 24 Hours
Chronic Hypocalcemia
Calcium Suppliments-elemental Calcium 1000-
1500 Mg/Day
Vitamin D-supplimentation

54. PHOSPHATE METABOLISM
• 85 % Present In Bone
• ABSORBED BY Small Intestine And Proximal Renal
Tubule.
• Absorption Stimulated By Vit D
• Absorption Inhibited By Large Dose Of Calcium
And Sevelamer Hydrochloride
• Low Serum Phosphate Level Stimulates Renal
Proximal Tubular Synthesis Of 1,25 (OH)2D
• Serum Phosphate Levels Vary By As Much As 50%
On Normal Day.

55. • Carbohydrate administration can cause
decrease in serum phosphate level by rapid
uptake into the cells and utilization by the
cells
• Metabolic and respiratory alkalosis-
hypophosphatemiea due to intra cellular shift
of phosphate into the cells

56. hypophosphatemia
• Excessive renal excretion/reduced absorption
• Due to inadequate intestinal phosphate
absorption
• Rapid redistribution in to bone or soft tissue

57. Excessive renal excretion/reduced
absorption
PTH /PTHr dependent
1. Primary hyperparathyroidism
2. Secondary hyperparathyroidism-vit.D
Defeciency,bartter’s syndrome
PTH /PTHr independent
Excess FGF23 OR Other phosphatoins
a. X –LINKED HYPOPHOSPHATEMIC RICKETS
b. Autosomal recessive hypophosphatemia
c. Autosomal dominant hypophosphatemic rickets
d. McCune –Albright syndrome

58. e.Intrinsic renal disease-WILSON’S,cystinosis
f.Other systemic disease-
alcoholism,hyperaldosteronism,hypomagnesie
mia,amyloidosis,HUS
g.Drugs-ethanol,acetazolamide,heavy
metals,high dose steroids
h.TIO-Tumour Induced Osteomalacia Syndrome

59. Due to inadequate intestinal
phosphate absorption
• Aluminium containing antacids
• sevelamer

60. Rapid redistribution in to bone or soft
tissue
• Iv glucose
• Insulin therapy
• Gram negative sepsis
• Catecholamines
• Recovery from starvation or acidosis
• Respiratory alkalosis
• Rapid cellular proliferation
• Accelerated net bone formation-after
parathyroidectomy,treatment of vit.D
defeciency,pagets disease,

61. MCQ-9 all india-2007
• HYPOPHOSPHATEMIA SEEN IN
I. Acute renal failure
II. Resolving phase of DKA
III. Respiratory alkalosis
IV. Chronic alcoholism

62. ANSWER
• Renal failure associated with
hyperphosphatemia

63. • HYPOPHOSPHATEMIA SEEN IN(ALL INDIA-
2007)
• Acute renal failure
• Resolving phase of dka
• Respiratory alkalosis
• Chronic alcoholism

64. Clinical features
• Neuro muscular –
lethargy,confusion,disorientation,hallucination,dysarthria,o
culomotor pasy,anisocoria,ataxia,cerebellar
tremor,ballismus,hyporeflexia,impaired sphincter
control,gullaine barre like ascending paralysis,seizures
...death
• Rhabdomyolysis
• Respiratory failure and cardiac dysfunction
• Renal tubular defects-tubular acidosis,glycosuria,impaired
absorption of sodium and calcium
• Erythrocyte microspherocytosis and hemolysis
• Defective leukocyte chemotaxis,platelet dysfunction

65. Acute hypophosphatemia treatment
• Serum calcium should be measured before
correction
• Hypocalcemia should be corrected before
administering iv phosphate
• Serum phosphate level less than 2 mg/dl-iv
neutral mixtures of sodium and potassium
phosphate salts ovr 6 hrs
• Less severe hypophosphatemia can be corrected
by oral phosphate in divided dose 750-2000 mg
/day

66. Chronic hypophosphatemia
TREATMENT
• Vitamin D and CALCIUM
• XLH-ADHR,TIO and tubular disorders-oral
doses of phosphates,calcium ,1,25(OH)2
vitamin D
• TIO-Tumour Removal,octerotide

67. HYPERPHOSPHATEMIA
• Fasting phosphate level more than 5.5 mg/dl

68. Clinical features
• Due to formation of calcium phosphate
precipitates and resulting hypocalcemia
• Thus-tetany,seizures,accelerated
nephrocalcinosis,pulmonary or cardiac
calcifications

69. causes
• Impaired renal phosphate excretion
a. Renal failure
b. Hypoparathyroidism
c. Parathyroid suppression
d. Pseudo hypoparathyroidism
e. Acromegaly
f. Heparin therapy
g. Tumoral calcinosis

70. • Massive extra cellular fluid phosphate load
a. Rapid administration of exogenous
phosphates
b. Extensive cellular injury
c. Transcellular phosphate shifts-
Metabolic/respiratory acidosis

71. treatment
• Volume expansion
• Aluminium hydroxide
• Sevelamer
• Hemodialysis-in setttings of renal failure and
symptomatic hypocalcemia

72. • Thank u