Disorders of Calcium Metabolism

Июль 24, 2022

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Disorders of Calcium Metabolism

Содержание

2. Calcium An essential intracellular and extracellular cation Extracellular calcium is required to maintain normal biological function
3. calcium 40-45 % ionized 40-45 % albumin bound 10% complexed citrate, sulphate 8.5–10.5 mg/dl ECF Filtration
4. Calcium and Albumin 40-45% of circulating calcium is bound to albumin Change in serum albumin change
5. Calcium and Albumin At pH 7.4 each g/dl of serum albumin binds 0.8 mg/dl of calcium
6. Disorders of Calcium Metabolism Hypercalcemia Serum Calcium >10.4 mg/dl Hypocalcemia Serum Calcium
7. Causes of hypercalcemia PTH-mediated Primary hyperparathyroidism (sporadic) –solitary adenoma or hyperplasia Familial MEN1 and -2a FHH
8. Causes of hypercalcemia Vitamin D intoxication Chronic granulomatous disorders: Activation of extrarenal 1 alpha-hydroxylase (increased calcitriol)
9. Diagnosis of Hypercalcemia Serum Ca ⭡ Measure serum albumin or ionized calcium Albumin corrected calcium normal
10. Manifestations of hypercalcemia
11. Renal manifestations The most important renal manifestations are polyuria, resulting from decreased concentrating ability in the
12. Renal manifestations Nephrolithiasis — When hypercalcemia is due to primary hyperparathyroidism or sarcoidosis, it is often
13. Gastrointestinal manifestations Nausea. Constipation may be related to decreased smooth muscle tone and/or abnormal autonomic function.
14. Cardiovascular symptoms Shortened QT interval Ventricular arrhythmias ST-segment elevation mimicking myocardial Long-standing hypercalcemia, as occurs in
15. Hyperparathyroidism Secondary hyperparatroidism: due to vitamin D deficiency; renal failure Tertiary hyperparathyroidism: in longstanding renal failure
16. Primary Hyperparathyroidism Incidence 1/1000- 42/100 000 Postmenopausal women 1/200; ⭡ X 3.0 in women then in
17. or multiple adenomas, nearly 100% 15-20% up to 60% nearly 100% 30-100% 10-25%
18. Clinical Manifestations of Prim Hyperparathyroidism CNS - Cognitive difficulties, apathy, drowsiness, obtundation or even coma GI
19. Bone and Joint Manifestations in Primary Hyperparathyroidism Osteoporosis Diffuse bone pain Osteitis fibrosa cystica Diffuse demineralization
22. Treatment When is surgery indicated in PHPT patients ?
23. Guidelines for Surgery
24. Other Considerations Neuropsychological disturbances Weakness and easy fatigability Depression Intellectual weariness Increased sleep requirements Improved by
25. US in the diagnosis of PTA
26. 99mTc- sestamibi Parathyroid Scan 20 min 3 hours 90% sensitivity in parathyroid tissue detection
27. What is 4D-CT? 4D-CT includes image sets in three planes (axial, coronal, sagittal) from the angle
28. 4D CT in diagnosis of PHPT Arterial phase images are acquired 25 seconds after the start
29. Patients who weren‘t operated- Monitoring guidelines
30. General Measures Hydration Adequate Mobility Diet neither restrictive nor excessive in calcium Adequate vitamin D status
31. Calcium-sensing Receptor A member of the G protein-coupled receptor family Contains seven hydrophobic helices that anchor
32. Inactivating Mutations in Calcium Sensing Receptor Inactivating mutation Familial hypocalciuric hypercalcemia (FHH) - heterozygous Calcium set
33. Hypercalcemia of Malignancy Lung, breast, and prostate cancer frequently invade skeleton and destroy bone tissue Damage
34. PthrP Induced Hypercalcemia Squamous cell carcinoma Islet cell tumor (pancreas) Adult T cell leukemia Renal cell
35. PTHrP-PTH related peptide Gen located on the chromosome 12 Gen is expressed in the embrional tissues:
36. Treatment Hydration Bisphosphonates IV, Denosumab Calcitonin Glucocorticoids Dialysis
37. Hydration First step in the management of severe hypercalcemia - Isotonic saline Usually ⭣ serum calcium
38. Loop Diuretics In the past intensive administration of furosemide was used (80 to 100 mg every
39. Calcitonin The efficacy of calcitonin (4 IU/kg every 6-12 hours) is limited to the first 48
40. Bisphosphonates Structurally related to pyrophosphate Great affinity for bone and their resistance to degradation Bind to
41. Zoledronic Acid (ZOMERA) Zoledronic acid belongs to a new class of highly potent bisphosphonates Heterocyclic, nitrogen-containing
42. Denosumab Mechanism of Action © 2007 Amgen. All rights reserved. RANKL RANK OPG Denosumab Bone Formation
43. Inhibit the growth of neoplastic lymphoid tissue Counteract the effects of vitamin D Glucocorticoids
44. Low PTH Hypocalcemia
45. Hypocalcemia Low PTH (hypoparathyroidism) Genetic disorders: Abnormal parathyroid gland development Abnormal PTH synthesis; Activating mutations of
46. Hypocalcemia High PTH (secondary hyperparathyroidism in response to hypocalcemia) Vitamin D deficiency or resistance Parathyroid hormone
47. Drugs induced hypocalcemia Inhibitors of bone resorption (bisphosphonates, calcitonin, denosumab), especially in vitamin D deficiency Cinacalcet
48. Trousseau's sign is the induction of carpopedal spasm by inflation of a sphygmomanometer above systolic blood
49. Hypocalcemia: Carpopedal spasm and ECG changes Carpopedal Spasm Sinus rhythm with diffuse T wave inversion QT
50. Treatment of Acute Hypocalcemia Promptly correct symptomatic or severe hypocalcemia with cardiac arrhythmias or tetany with
51. Treatment of Acute Hypocalcemia For those with milder symptoms of neuromuscular irritability (paresthesias) and corrected serum
52. To prevent Hypocalcemia due to Hungry bone syndrome Start oral calcium and vitamin D treatment early.
53. Primary hypoparathyroidism
58. Natpara Natpara- for use in patients who can’t be normalized on regular oral therapy, or have
59. Causes of magnesium depletion Causes of magnesium depletion Renal losses Gasro-intestinal losses
60. Treatment of Hypomagnesemia If the serum magnesium concentration is low, 2 g (16 mEq) of magnesium
61. Treatment of Hypomagnesemia Oral repletion- if available and tolerable. A typical daily dose in a patient
63. Скачать презентацию

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Calcium
An essential intracellular and extracellular cation
Extracellular calcium is required to maintain

normal biological function of nervous system, the musculoskeletal system, regulation of neuromuscular contractility and blood coagulation
Intracellular calcium is needed for normal activity of many enzymes.
Regulation of endocrine and exocrine secretory activities: insulin, aldosterone
Activation of compliment system
Bone metabolism: calcium salts provide structural integrity of the skeleton ( mineralization)

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calcium
40-45 %
ionized
40-45 %
albumin
bound
10%
complexed
citrate, sulphate
8.5–10.5 mg/dl
ECF
Filtration
5-7gr
Reabsorption
4.9-6.7gr
98%
Diet 0.5-1.5 gr
Absorption
0.25-0.5gr
Secretion
0.1-0.2gr
Feces
0.35-0.6gr
Resorption
0.3-0.5 g
Formation
0.3-0.5 g
Bone
1000

0.15-0.3 g/24h

Total body Ca
1 to 1.5 kg
99%- skeleton
0.1% ECF
rest intracellular

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Calcium and Albumin
40-45% of circulating calcium is bound to albumin
Change

in serum albumin change in measured total serum calcium concentration
Calcium is bound to carboxyl groups in albumin, this binding is highly pH dependent
Acute acidosis binding ionized calcium
Acute alkalosis binding ionized calcium
A shift of 0.1 pH unit produces a change in ionized calcium of 0.04 to 0.05 mmol/L ( 0.16-0.2 mg/dl)
These changes are not reflected at the total calcium

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Calcium and Albumin
At pH 7.4 each g/dl of serum albumin binds

0.8 mg/dl of calcium
Serum calcium should be “corrected” according to serum albumin level
Normal level of serum albumin is 4 g/dl
Change of 1 g/dl in serum albumin 0.8 mg/dl in total serum calcium
Example: A patient with total serum calcium 7.5 mg/dl albumin 2 g/dl, has corrected serum calcium of 9.1 mg/dl

Ca = SerumCa + 0.8 * (NormalAlbumin - PatientAlbumin)

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Disorders of Calcium Metabolism
Hypercalcemia Serum Calcium >10.4 mg/dl
Hypocalcemia Serum Calcium <

8.5 mg/dl

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Causes of hypercalcemia
PTH-mediated
Primary hyperparathyroidism (sporadic) –solitary adenoma or hyperplasia
Familial MEN1

and -2a
FHH
Tertiary hyperparathyroidism (renal failure)

PTH-independent
Hypercalcemia of malignancy:
PTHrp
Activation of extrarenal 1 alpha-hydroxylase (increased calcitriol)
Osteolytic bone metastases and local cytokines

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Causes of hypercalcemia
Vitamin D intoxication
Chronic granulomatous disorders: Activation of extrarenal 1

alpha-hydroxylase (increased calcitriol)
Medications :
Thiazide diuretics
Lithium
Teriparatide
Excessive vitamin A
Theophylline toxicity
Associated with high bone turnover
Hyperthyroidism
Immobilization
Acromegaly
Miscellaneous Pheochromocytoma Adrenal insufficiency Parenteral nutrition
Milk alkali syndrome

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Diagnosis of Hypercalcemia
Serum Ca ⭡
Measure serum albumin
or ionized calcium
Albumin corrected

calcium normal

Medical history
and medication use history

Measure PTH

PTH ⭡ or N

Check calciuria

PTH ⭣

Malignancy

Check 1,25(OH)2D3

If high- Primary HPT; if low FHH

Lymphomas

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Manifestations of hypercalcemia

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Renal manifestations
The most important renal manifestations are polyuria, resulting from decreased

concentrating ability in the distal tubule, nephrolithiasis, and acute and chronic renal insufficiency.
Nephrogenic diabetes insipidus — Chronic hypercalcemia leads to a defect in concentrating ability that may induce polyuria and polydipsia in up to 20 percent of patients. The mechanism is incompletely understood, but the downregulation of aquaporin-2 water channels receptors, and calcium deposition in the medulla with secondary tubulointerstitial injury and impaired generation of the interstitial osmotic gradient may play important roles.

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Renal manifestations
Nephrolithiasis — When hypercalcemia is due to primary hyperparathyroidism or

sarcoidosis, it is often longstanding, and the resulting chronic hypercalciuria may cause nephrolithiasis. Increased calcitriol production may also play an important role in both diseases.
Renal tubular acidosis — Chronic hypercalcemia causes type 1 (distal) renal tubular acidosis .The ensuing hypercalciuria and hypocitraturia can contribute to the development of nephrolithiasis.

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Gastrointestinal manifestations
Nausea.
Constipation may be related to decreased smooth muscle tone

and/or abnormal autonomic function.
Peptic ulcer disease has been described in patients with hypercalcemia due to primary hyperparathyroidism and may be caused by calcium-induced increases in gastrin and acid secretion.
Pancreatitis due to deposition of calcium in the pancreatic duct and calcium activation of trypsinogen within the pancreatic parenchyma

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Cardiovascular symptoms
Shortened QT interval
Ventricular arrhythmias
ST-segment elevation mimicking myocardial
Long-standing hypercalcemia,

as occurs in primary hyperparathyroidism, can lead to other cardiac abnormalities, including deposition of calcium in heart valves, coronary arteries, hypertension; and cardiomyopathy.

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Hyperparathyroidism
Secondary hyperparatroidism: due to vitamin D deficiency; renal failure Tertiary hyperparathyroidism:

in longstanding renal failure

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Primary Hyperparathyroidism
Incidence 1/1000- 42/100 000
Postmenopausal women 1/200;
⭡ X 3.0 in

women then in men;
At age 70-79 21:1000
80% single gland involvement – adenoma
20% multiple gland involvement – hyperplasia
<2% carcinoma
MEN

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or multiple adenomas, nearly 100%
15-20%
up to 60%
nearly 100%
30-100%
10-25%

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Clinical Manifestations of Prim Hyperparathyroidism
CNS - Cognitive difficulties, apathy, drowsiness, obtundation

or even coma
GI - Anorexia, nausea, vomiting, constipation and rarely acute pancreatitis
CVS - Hypertension, A-V nodal delay, shortened QT interval, enhanced sensitivity to digitalis, compete heart block, ventricular arrhythmias
RENAL- Loss of concentrating ability, polyuria, polydipsia, nephrolithiasis and occasionally nephrocalcinosis, nocturia

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Bone and Joint Manifestations in Primary Hyperparathyroidism
Osteoporosis
Diffuse bone pain
Osteitis fibrosa cystica
Diffuse

demineralization
Subperiostal bone resorption
Phalanges
Lamina dura
Distal clavicles

Cystic lesions
Brown tumors
Cysts
Deformities, Fractures, Pain
Arthritic symptoms
Resorption of articular bone
Periarticular metastatic calcification
Pseudogout
Gout

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Treatment
When is surgery indicated in PHPT patients
?

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Guidelines for Surgery

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Other Considerations
Neuropsychological disturbances
Weakness and easy fatigability
Depression
Intellectual weariness
Increased sleep requirements
Improved by surgery
Onset

of Menopause
Increased bone loss

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US in the diagnosis of PTA

Слайд 26

99mTc- sestamibi Parathyroid Scan
20 min
3 hours
90% sensitivity in parathyroid
tissue detection

Слайд 27

What is 4D-CT?
4D-CT includes image sets in three planes (axial, coronal,

sagittal) from the angle of mandible to the mediastinum.The “fourth” dimension of 4D-CT is the perfusion information derived from multiple contrast phases.
It is most commonly performed with three phases: non-contrast, arterial, and delayed phase imaging .

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4D CT in diagnosis of PHPT
Arterial phase images are acquired 25

seconds after the start of the injection and the delayed (venous) phase are acquired 80 seconds from the start of the injection.

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Patients who weren‘t operated- Monitoring guidelines

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General Measures
Hydration
Adequate Mobility
Diet neither restrictive nor excessive in calcium
Adequate vitamin D

status
Prompt medical attention for the possibility of worsening of hypercalcemia (intercurrent illness accompanied by risk of dehydration)

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Calcium-sensing Receptor
A member of the G protein-coupled receptor family
Contains seven

hydrophobic helices that anchor it in the plasma membrane. The large (~600 amino acids) extracellular domain - critical to interactions with extracellular calcium
Large (~200 amino acids) cytosolic tail.

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Inactivating Mutations in Calcium Sensing Receptor
Inactivating mutation
Familial hypocalciuric hypercalcemia (FHH) -

heterozygous
Calcium set point serum calcium
Urinary calcium reabsorption urinary
calcium
Neonatal severe hyperparathyroidism (NSHPT) – homozygous
parathyroid
Familial hypocalciuric hypercalcemia (FHH) - heterozygous
Calcium set point serum calcium
Urinary calcium reabsorption urinary
calcium
Neonatal severe hyperparathyroidism (NSHPT) – homozygous-incompatible with life if not resect the parathyroid

No need for parathyroid surgery in FHH!!

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Hypercalcemia of Malignancy
Lung, breast, and prostate cancer frequently invade skeleton and

destroy bone tissue
Damage to skeleton usually late in course of disease
Bone damage associated with considerable worsening in patient’s quality of life
Multiple myeloma has skeletal complications in virtually 100% of cases
Breast and lung cancer also cause hypercalcemia of malignancy, without invading skeleton

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PthrP Induced Hypercalcemia
Squamous cell carcinoma
Islet cell tumor (pancreas)
Adult T cell leukemia
Renal

cell carcinoma
Breast carcinoma

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PTHrP-PTH related peptide
Gen located on the chromosome 12
Gen is expressed in

the embrional tissues: cartilage, heart, epithelium, hear bulbs
Expression of the PTHrP gen in adult: plays role in breast development; presents in breast milk in high concentration
Mutation in embryo:
Heterozygous are normal
Homozygous –lethal mutation with major bone and cartilage abnormalities

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Treatment
Hydration
Bisphosphonates IV, Denosumab
Calcitonin
Glucocorticoids
Dialysis

Слайд 37

Hydration
First step in the management of severe hypercalcemia - Isotonic saline
Usually

⭣ serum calcium by 1.6-2.4mg/dl
Hydration alone rarely leads to normalization in severe hypercalcemia
Rate of IV saline based on severity of hypercalcemia and tolerance of CVS for volume expansion, if possible achieve urine output of 300 ml/hr, that is then adjusted to maintain the urine output at 100 to 150 mL/hour.

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Loop Diuretics
In the past intensive administration of furosemide was used (80

to 100 mg every one to two hours).
It needs aggressive fluid hydration (10 liters daily), saline therapy beyond that necessary to restore euvolemia.
Now use of calcitonin and bisphosphonates is more effective.

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Calcitonin
The efficacy of calcitonin (4 IU/kg every 6-12 hours) is limited

to the first 48 hours, due to development of tachyphylaxis, perhaps due to receptor downregulation .
Calcitonin and hydration provide a rapid reduction in serum calcium concentration, while a bisphosphonate provides a more sustained effect.

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Bisphosphonates
Structurally related to pyrophosphate
Great affinity for bone and their resistance to

degradation
Bind to hydroxyapatite in bone and inhibit the dissolution of crystals
Extremely long half life in bone
Poor GI absorption < 1%

Слайд 41

Zoledronic Acid (ZOMERA)
Zoledronic acid belongs to a new class of highly

potent bisphosphonates
Heterocyclic, nitrogen-containing bisphosphonate composed of:
A core bisphosphonate moiety
An imidazole-ring side chain containing 2 critically positioned nitrogen atoms

Слайд 42

Denosumab Mechanism of Action
© 2007 Amgen. All rights reserved.
RANKL
RANK
OPG Denosumab
Bone Formation
Hormones Growth factors
Cytokines
Bone

Resorption Inhibited

Osteoclast Formation, Function, and Survival Inhibited

CFU-GM

Pre-Fusion Osteoclast

CFU-GM=colony forming unit granulocyte macrophage

Provided as an educational resource. Do not copy or distribute.

Osteoblasts

Calcium nadir 8-11 days after injection

Слайд 43

Inhibit the growth of neoplastic lymphoid tissue
Counteract the effects of vitamin

Glucocorticoids

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Low PTH Hypocalcemia

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Hypocalcemia
Low PTH (hypoparathyroidism)
Genetic disorders: Abnormal parathyroid gland development
Abnormal PTH

synthesis; Activating mutations of calcium-sensing receptor (autosomal dominant hypocalcemia)
Post-surgical
Autoimmune: Autoimmune polyglandular syndrome (associated with chronic mucocutaneous candidiasis and primary adrenal insufficiency)
Hypoparathyroidism due to activating antibodies to calcium-sensing receptor
Infiltration of the parathyroid gland (granulomatous, iron overload, metastases)
Radiation-induced destruction parathyroid glands
Hungry bone syndrome (post parathyroidectomy)

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Hypocalcemia
High PTH (secondary hyperparathyroidism in response to hypocalcemia)
Vitamin D deficiency

or resistance
Parathyroid hormone resistance: Pseudohypoparathyroidism
Hypomagnesemia
Renal disease
Loss of calcium from the circulation:
Hyperphosphatemia ; Tumor lysis ; Acute pancreatitis (the mechanism unknown)
Osteoblastic metastases; Acute respiratory alkalosis
Sepsis or severe burns- the cause appears to be a combination of impaired secretion of PTH coupled with reduced calcitriol production

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Drugs induced hypocalcemia
Inhibitors of bone resorption (bisphosphonates, calcitonin, denosumab), especially in

vitamin D deficiency
Cinacalcet –calcimimetic
Calcium chelators (EDTA, citrate, phosphate) Foscarnet (due to intravascular complexing with calcium)
Phenytoin (due to conversion of vitamin D to inactive metabolites)
Fluoride poisoning

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Trousseau's sign is the induction of carpopedal spasm by inflation of

a sphygmomanometer above systolic blood pressure for three minutes.
Chvostek's sign is contraction of the ipsilateral facial muscles elicited by tapping the facial nerve just anterior to the ear

Hypocalcemia

Слайд 49

Hypocalcemia: Carpopedal spasm and ECG changes
Carpopedal Spasm
Sinus rhythm with diffuse T

wave inversion
QT prolongation (The corrected qtc is 560 ms )
Prolongation is in the ST segment rather than the T waves

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Treatment of Acute Hypocalcemia
Promptly correct symptomatic or severe hypocalcemia with cardiac

arrhythmias or tetany with parenteral administration of calcium salts with IV calcium therapy.
IV calcium therapy is suggested in asymptomatic patients with an acute decrease in serum corrected calcium to ≤7.5 mg/dL
(1 to 2 g of calcium gluconate, equivalent to 90 to 180 mg elemental calcium, in 50 mL of 5 percent dextrose) can be infused over 10 to 20 minutes. Is effective for 2-3 hours

Слайд 51

Treatment of Acute Hypocalcemia
For those with milder symptoms of neuromuscular irritability

(paresthesias) and corrected serum calcium concentrations greater than 7.5 mg/dL initial treatment with oral calcium supplementation is sufficient. If symptoms do not improve with oral supplementation, intravenous calcium infusion is required.
To effectively treat hypocalcemia in patients with concurrent magnesium deficiency,hypomagnesemia should be corrected first.

Identify and treat the cause of hypocalcemia and taper the infusion.

Слайд 52

To prevent Hypocalcemia due to Hungry bone syndrome
Start oral calcium and

vitamin D treatment early. Patients with postparathyroidectomy hungry bone disease, especially those with osteitis fibrosa cystica, can present with a dramatic picture of hypocalcemia.

Слайд 53

Primary hypoparathyroidism

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Natpara
Natpara- for use in patients who
can’t be normalized on regular

oral therapy, or have complication
s due to it (nephrolithiasis, hyper
Calciuria)

Слайд 59

Causes of magnesium depletion
Causes of magnesium depletion
Renal losses
Gasro-intestinal losses

Слайд 60

Treatment of Hypomagnesemia
If the serum magnesium concentration is low, 2 g

(16 mEq) of magnesium sulfate should be infused as a 10 percent solution over 10 to 20 minutes, followed by 1 gram (8 mEq) in 100 mL of fluid per hour.
Magnesium repletion should be continued as long as the serum magnesium concentration is less than 0.8 mEq/L (1 mg/dL or 0.4 mmol/L).
Persistent hypomagnesemia, as occurs in some patients with ongoing gastrointestinal (malabsorption) or renal losses, requires supplementation with oral magnesium, typically 300 to 400 mg daily divided into three doses.

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Treatment of Hypomagnesemia
Oral repletion- if available and tolerable.
A typical daily

dose in a patient with normal renal function is 240 to 1000 mg (20 to 80 meq [10 to 40 mmol]) of elemental magnesium in divided doses.
If a sustained-release preparation is not available, magnesium oxide 800 to 1600 mg (20 to 40 mmol [40 to 80 meq]) daily in divided doses may be used for moderate to severe hypomagnesemia.
Diarrhea frequently occurs with magnesium oxide therapy.

Disorders of Calcium Metabolism

Содержание

CalciumAn essential intracellular and extracellular cationExtracellular calcium is required to maintain

calcium40-45 % ionized40-45 %albuminbound10% complexedcitrate, sulphate8.5–10.5 mg/dlECFFiltration5-7grReabsorption4.9-6.7gr98%Diet 0.5-1.5 grAbsorption0.25-0.5grSecretion0.1-0.2grFeces0.35-0.6grResorption0.3-0.5 gFormation0.3-0.5 gBone1000

Calcium and Albumin 40-45% of circulating calcium is bound to albuminChange

Calcium and AlbuminAt pH 7.4 each g/dl of serum albumin binds

Disorders of Calcium MetabolismHypercalcemia Serum Calcium >10.4 mg/dlHypocalcemia Serum Calcium <

Causes of hypercalcemia PTH-mediated Primary hyperparathyroidism (sporadic) –solitary adenoma or hyperplasiaFamilial MEN1

Causes of hypercalcemia Vitamin D intoxicationChronic granulomatous disorders: Activation of extrarenal 1

Diagnosis of HypercalcemiaSerum Ca ⭡Measure serum albumin or ionized calciumAlbumin corrected

Manifestations of hypercalcemia

Renal manifestationsThe most important renal manifestations are polyuria, resulting from decreased

Renal manifestationsNephrolithiasis — When hypercalcemia is due to primary hyperparathyroidism or

Gastrointestinal manifestations Nausea. Constipation may be related to decreased smooth muscle tone

Cardiovascular symptomsShortened QT interval Ventricular arrhythmias ST-segment elevation mimicking myocardialLong-standing hypercalcemia,

HyperparathyroidismSecondary hyperparatroidism: due to vitamin D deficiency; renal failure Tertiary hyperparathyroidism:

Primary HyperparathyroidismIncidence 1/1000- 42/100 000Postmenopausal women 1/200; ⭡ X 3.0 in

or multiple adenomas, nearly 100%15-20%up to 60%nearly 100%30-100%10-25%

Clinical Manifestations of Prim HyperparathyroidismCNS - Cognitive difficulties, apathy, drowsiness, obtundation

Bone and Joint Manifestations in Primary HyperparathyroidismOsteoporosisDiffuse bone painOsteitis fibrosa cysticaDiffuse

Treatment When is surgery indicated in PHPT patients ?

Guidelines for Surgery

Other ConsiderationsNeuropsychological disturbancesWeakness and easy fatigabilityDepressionIntellectual wearinessIncreased sleep requirementsImproved by surgeryOnset

US in the diagnosis of PTA

99mTc- sestamibi Parathyroid Scan20 min3 hours90% sensitivity in parathyroid tissue detection

What is 4D-CT? 4D-CT includes image sets in three planes (axial, coronal,

4D CT in diagnosis of PHPTArterial phase images are acquired 25

Patients who weren‘t operated- Monitoring guidelines

General MeasuresHydrationAdequate MobilityDiet neither restrictive nor excessive in calciumAdequate vitamin D

Calcium-sensing ReceptorA member of the G protein-coupled receptor family Contains seven

Inactivating Mutations in Calcium Sensing ReceptorInactivating mutationFamilial hypocalciuric hypercalcemia (FHH) -

Hypercalcemia of MalignancyLung, breast, and prostate cancer frequently invade skeleton and

PthrP Induced HypercalcemiaSquamous cell carcinomaIslet cell tumor (pancreas)Adult T cell leukemiaRenal

PTHrP-PTH related peptideGen located on the chromosome 12Gen is expressed in

TreatmentHydrationBisphosphonates IV, DenosumabCalcitoninGlucocorticoidsDialysis

HydrationFirst step in the management of severe hypercalcemia - Isotonic salineUsually

Loop DiureticsIn the past intensive administration of furosemide was used (80

CalcitoninThe efficacy of calcitonin (4 IU/kg every 6-12 hours) is limited

BisphosphonatesStructurally related to pyrophosphateGreat affinity for bone and their resistance to

Zoledronic Acid (ZOMERA)Zoledronic acid belongs to a new class of highly

Denosumab Mechanism of Action© 2007 Amgen. All rights reserved.RANKLRANKOPG DenosumabBone FormationHormones Growth factorsCytokinesBone

Inhibit the growth of neoplastic lymphoid tissueCounteract the effects of vitamin