HYPERCALCEMIA - PowerPoint PPT Presentation

1 / 33
About This Presentation
Title:

HYPERCALCEMIA

Description:

Dialysis. Others. Syed Nasrat Imam, MD. Hydration. Furosemide. ... Contraindication-liver, kidney dysfunction, thrombocytopenia, or any coagulopathy. ... – PowerPoint PPT presentation

Number of Views:1584
Avg rating:3.0/5.0
Slides: 34
Provided by: syednasr
Category:

less

Transcript and Presenter's Notes

Title: HYPERCALCEMIA


1
HYPERCALCEMIA
  • SYED NASRAT IMAM, MD
  • The Chicago Medical School
  • Chicago, IL

Syed Nasrat Imam, MD
2
CALCIUM
  • An essential intracellular and extracellular
    cation
  • Extracellular calcium is required to maintain
    normal biological function of nervous system, the
    musculoskeletal system, and blood coagulation
  • Intracellular calcium is needed for normal
    activity of many enzymes
  • Preservation of the integrity of cellular
    membrane
  • Regulation of endocrine and exocrine secretory
    activities
  • Activation of compliment system
  • Bone metabolism

Syed Nasrat Imam, MD
3
CALCIUM
  • Respiratory alkalosis and elevated pH cause
    increase in the binding of calcium and lowers
    ionized calcium. Decrease in pH has the opposite
    effect. As a general rule a shift of 0.1 pH unit
    produces a change in ionized calcium of 0.04 to
    0.05 mmol/L
  • Chelators such as citrate may transiently
    decrease ionized calcium
  • Total body Ca -1 to 1.5 kg, 99- skeleton, 0.1
    ECF , rest intracellular.
  • One gram per deciliter of albumin binds
    approximately 0.8 mg/dl of calcium

Syed Nasrat Imam, MD
4
FORMULA
  • 0.8 for each gm of Albumin
  • 0.16mg/dl for each gm of globulin.
  • (Uca/Pca) (Ucr/Pcr) FEca
    lt1 - Familial hypocalciuric hypercalcemia, FEca
    gt2 - primary hyperparathyroidism
  • ?? in pH will ?? protein bound Ca by 0.12mg/dl
  • 80-90 of protein bound Ca is bound to Albumin.
  • Increase in serum pH of 0.1 may cause decrease in
    ionized Ca of 0.16mg/dl
  • Calcium Protein bound - 40 Complexed - 13
    Ionized fraction - 47

FEca
Uca/Pca x Pcr/Ucr
Syed Nasrat Imam, MD
5
CLINICAL MANIFESTATIONS
  • GI- Anorexia, Nausea, Vomiting, Constipation and
    rarely acute Pancreatitis.
  • CVS- Hypertension, shortened QT interval, and
    enhanced sensitivity to digitalis.
  • RENAL- Polyuria, Polydipsia, and occasionally
    Nephrocalcinosis.
  • CNS- Cognitive difficulties, Apathy, Drowsiness,
    Obtundation, or even Coma.

Most common symptom is probably nocturia
Syed Nasrat Imam, MD
6
SYMPTONS
  • More than 50 of all patients with primary
    hyperparathyroidism are asymptomatic when
    hypercalcemia is first discovered.
  • Diagnostic Finding Frequency ()
    Likelihood Ratio
    In Primary HPT
    In Malignancy Finding nt Finding
    -nt Renal Calculi 29 4
    7.3 0.74 Peptic Ulcer 13
    10 1.3
    0.97 Hypertension 49 25 2
    0.68 Polyuria 22 29 0.76
    1.1 Mental status change 23 33 0.7
    1.1 GI Distress 25 34 0.74
    1.1 Muscular weakness 32 36 0.89
    1.1 Bone Pain 28 58 0.48
    1.7 Constipation 19 58 0.33
    1.9 Weight Loss 19 64 0.30
    2.3 Anorexia 19 64 0.30
    2.3 Fatigue 31 73 0.42 2.6

Syed Nasrat Imam, MD
7
SIGNS
Band keratopathy The deposition of Ca as
corneal opacities is usually sign of long
standing hypercalcemia -most commonly associated
with primary hyperparathyroidism. Calcium
deposition begins near the limbus at the 3 9
oclock position, presumbly because there is less
friction from the lids near the limbus because
the tear film is most alkaline in the most
exposed area, band running across the cornea from
the 3 to 9 oclock position
Syed Nasrat Imam, MD
8
SIGNS
Bony tenderness Hyperactive tendon reflexes
Tongue fasciculations Hypercalcemia in pregnant
female may cause hypocalcemia in her neonates by
suppressing the fetal parathyroid. Hypercalcemia
- small dec. in GFR - due to hemodynamic effects
hyposthenuria (a loss of renal concentrating
abilities)
Syed Nasrat Imam, MD
9
COMPLICATIONS Sinus bradycardia Increase in
the degree of a heart block Cardiac
arrhythmia HTN Pancreatitis PUD
Nephrolithiasis Accelerated vascular
calcification
Syed Nasrat Imam, MD
10
CALCIUM HOMEOSTASIS
THREE HORMONE AND THREE ORGAN
  • PTH
  • ACTIVATED VITAMIN D
  • CALCITONIN
  • BONE
  • KIDNEY
  • SMALL INTESTINE

Syed Nasrat Imam, MD
11
THREE HORMONES
  • PTH (84 amino acid)
  • Actions on Bone Actions on Kidney
    Actions on GI
  • Parathyroid cells are unusual in the respect
    that hormone degradation rather than synthesis is
    adjusted according to physiological demand. As
    much as 90 can be destroyed within the chief
    cells.
  • If blood levels of ionized calcium drop by as
    little as 0.1 mg/dl, secretion of PTH is
    stimulated
  • Half-life of PTH is minutesKidney reacts
    quickly to changes in PTH and is responsible for
    minute to minute adjustments of blood calcium.
  • PTH acts directly on distal portion of the
    nephron to decrease urinary excretion of calcium
    mediated by cAMP.
  • PTH powerfully inhibits tubular reabsorption of
    phosphate and thus increases the amount excreted
    in the urine, mainly in proximal tubules
  • PTH stimulates the renal enzyme that converts vit
    D to its active form but has no direct effects on
    intestinal transport of calcium or phosphate.
  • Action of PTH to increase 1,25(OH)2D is blunted
    in hyperphosphatemia

Syed Nasrat Imam, MD
12
  • ACTIONS OF PARATHYROID HORMONE
  • The principal regulator of calcium concentration
    in extracellular fluid
  • Increases the calcium concentration and
    decreases the phosphate concentration in the
    blood.
  • Bone responds in 2-3 hours 1st phase to small
    increases of PTH. PTH?Receptors on surface
    osteocytes? intervention of GTP binding
    protein?activates adenylate cyclase?Increases
    permeability to of osteocytes to calcium in
    surrounding bone fluid compartment?Calcium enters
    cytosol and then extruded to ECF compartment on
    other side of bone membrane and shifts
    equilibrium to solubilization
  • 2nd phase- becomes evident about 12 hours later
    characterized by widespread resorbtion of both
    mineral and organic components of matrix.
    Osteoclastic activity predominates
  • Activity of all bone cell types is increased by
    PTH but only osteocytes and osteoblasts have
    receptors for PTH. Activation of and
    recruitment of osteoclasts must be accomplished
    indirectly by some paracrine or endocrine signal
    produced by osteocytes and osteoblasts

Syed Nasrat Imam, MD
13
VITAMIN D
  • Activated Vit D
  • GI - increase Ca absorption.
  • Bone - increase Ca mobilization.
  • Kidney - increase reabsorption within the distal
    tubule.
  • Deficiency of vitamin D severely impairs
    intestinal transport of both calcium and
    phosphorous
  • Mineralization of osteoid occurs spontaneously
    when adequate amounts of calcium and phosphorous
    are available
  • 1,25(OH)2D3 increases the number and activity of
    osteoclasts but osteoblasts have the receptors
  • Effect on calcium absorption in the distal
    nephron Regulation- Hydroxylation of carbon 1
    by cells in the proximal tubules of the kidney
    which converts a nearly inactive precursor to a
    highly active hormone is stimulated primarily by
    PTH and by low phosphate concentrations.
    1,25(OH)2D3 inhibits hydroxylation of carbon in
    the kidney and carbon 25 in the liver and
    stimulates hydroxylation of carbon 24 which
    diverts precursor to a degradative pathway.

Syed Nasrat Imam, MD
14
  • CALCITONIN ( 32 amino acid )
  • Parafollicular cells of the Thyroid gland in
    response of hypercalcemia
  • Decrease osteoclast activity.
  • Stimulating a distal tubular - mediated
    calciuresis.
  • Other hormones affecting calcium balance - many
    including prostaglandins that mobilize calcium,
    various growth factors, growth hormone,
    somatomedins, thyroid hormones(decrease skeletal
    mass), gonadal hormones which help maintain bone
    mass, adrenal cortical hormones

Syed Nasrat Imam, MD
15
TARGET ORGAN
  • Small intestine approx. 40 absorbed, 50 of
    that - excreted into bile and other intestinal
    secretions. So only 20 of the total amount of Ca
    ingested daily is available to circulate between
    bone and extracellular fluid.
  • Kidney Glumerulus filters out the Ca that is
    not bound to protein.
  • Proximal tubule - approx. 50 to 70 is
    reabsorbed, Ca reabsorption mirrors Na
    reabsorption.
  • Ascending limb of the loop of henle - approx.
    30 to 40 reabsorbed
  • Distal nephron - about 10 reabsorbed. PTH and
    activated Vit D increases Ca absorption during
    Ca deficient states.
  • Normally kidney excretes approx. 200 mg /day of
    Ca to maintain homeostasis. During states of
    severe Ca depletion, the Kidney can decrease
    urinary excretion to 50mg /day or less.

Syed Nasrat Imam, MD
16
CALCIUM REGULATION
_
PTH

_

1,25(OH)2 D3


CALCITONIN

_
ECF Pool of Calcium
GI Tract
BONE
URINE
Syed Nasrat Imam, MD
17
ETIOLOGY
Approx. 80 of all cases are caused by
Malignancy or Primary Hyperpathyroidism
  • T Thiazide, other drugs - Lithium
  • R Rabdomyolysis
  • A AIDS
  • P Pagets disease, Parental nutrition,
    Pheochromocytoma, Parathyroid disease
  • V Vitamins
  • I Immobilization
  • T Thyrotoxicosis
  • A Addisons disease
  • M Milk-alkali syndrome
  • I Inflammatory disorders
  • N Neoplastic related disease
  • S Sarcoidosis

Syed Nasrat Imam, MD
18
HYPERPARATHYROIDISM
Syed Nasrat Imam, MD
19
HYPERPARATHYROIDISM
  • STONES,
  • BONES,
  • GROANS, AND
  • MOANS

Syed Nasrat Imam, MD
20
Syed Nasrat Imam, MD
21
Syed Nasrat Imam, MD
22
PARATHYROIDECTOMY
  • A serum calcium gt 12mg/dl
  • Hypercalciuria gt 400mg/d
  • Presence of sign and symptoms--S,B,G,M
  • Markedly reduced cortical bone density
  • Hypercalcemia causing decreased GFR
  • Patient age under 50 years?
  • NIH consensus development conference
    recommendation

Syed Nasrat Imam, MD
23
TREATMENT OPTION
  • Gallium nitrate.
  • Steroids.
  • IV Phosphate.
  • Dialysis.
  • Others.
  • Hydration.
  • Furosemide.
  • Bisphosphanate.
  • Calcitonin.
  • Mithramycin.

Syed Nasrat Imam, MD
24
HYDRATION
  • First step in the management of severe
    hypercalcemia. --isotonic saline.
  • Usually reduces - 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.

Syed Nasrat Imam, MD
25
LOOP DIURETICS
  • Facilitate urinary excretion of calcium
  • By inhibiting calcium reabsorption in the thick
    ascending limb of the loop of Henle.
  • Guard against volume overload
  • Volume expansion must precede the administration
    of furosemide, because the drugs effect depends
    on delivery of calcium to the ascending limb.
    Needs frequent measurement of lytes and water

Syed Nasrat Imam, MD
26
  • CALCITONIN Not as effective as
    bisphosphonate, tachyphylaxis quickly occurs and
    limits therapeutic efficacy
  • MITHRAMYCIN Toxic effect limits its use,
    reserved for difficult cases of hypercalcemia
    that are related to malignancy
  • GALLIUM NITRATE Need to infuse it over 5
    days, nephrotoxity limits its use, not used
    frequently
  • CORTICOSTEROIDS For myeloma, lymphoma,
    Sarcoidosis, or vit D toxicity decrease GI
    absorption, 200-300mg hydrocort for upto 5 days,
    slow response limits its use
  • HEMODIALYSIS Zero or low calcium bath, In
    selected condition, eg-hypercalcemia complicated
    by renal failure

Syed Nasrat Imam, MD
27
BISPHOSPHONATE
  • Structurally related to pyrophosphate. P-C-P
    bound is a back bone that renders them resistant
    to phosphates. They bind to hydroxyapatite in
    bone and inhibit the dessolution of crystals.
    Their great affinity for bone and their
    resistance to degradation account for their
    extremely long half life in bone.
  • Poor GI absorption- lt10
  • ETIDRONATE PAMIDRONATE CLODRONATE
  • Etidronate- 7.5mg/kg iv over 4 hr for 3-7 days,
    S. ca begins to decrease within 2 days after
    first dose. Response better if pt well hydrated
    before t/t. Oral to prevent recurrent
    hypercalcemia.. Adverse effect-increase s. cr,
    phosphate, long term use-impair bone formation,
    osteomalacia,

Syed Nasrat Imam, MD
28
PAMIDRONATE
  • Inhibits osteoclast function
  • The most potent bisphosphonate.
  • 60mg to 90 mg IV over 24hr.
  • 70 to 100 of patients had decreased s. calcium
    within 24 hr of t/t, 2/3rd of this group had
    normal s cal within 7 days.
  • Adverse effect- mild transient increase in
    temp(lt2deg C), transient leukopenia, small
    reduction in s phosphate level.
  • Excreted by kidney- dose adjustment.

Syed Nasrat Imam, MD
29
MITHRAMYCIN
  • An inhibitor of RNA synthesis in osteoclasts
  • IV 25 microgram/kg over 4-6 hr.
  • Begins to decrease in 12hr, maxm in 48-72 hr.
  • Duration of normocalcemia ranges from a few days
    to several wks. Depending on the extent of
    ongoing bone resorption.
  • Adverse effect- Nausea- can be mini- by slow iv.
    Avoid extravasation-cellulitis.Hepatotoxic- in
    20 pt. Nephrotoxic- increase s. cr, proteinuria.
    Thrombocytopenia.
  • Contraindication-liver, kidney dysfunction,
    thrombocytopenia, or any coagulopathy.

Syed Nasrat Imam, MD
30
GALLIUM NITRATE
  • Inhibit bone resorption by adsorbing to and
    reducing the solubility of hydroxyapatite
    crystals.
  • Adverse effect- Nephrotoxity, hypophosphatemia,
    small reduction in Hb concentration.
  • Clinical experience limited.

Syed Nasrat Imam, MD
31
OTHERS
  • GLUCOCORTICOIDS- inhibiting the growth of
    neoplastic lymphoid tissue, counteracting the
    effects of vitamin D.
  • PHOSPHATE- Can lower rapidly and profoundly, but
    very dangerous. Restricted to pt with extreme,
    life threatening hypercalcemia in whom all other
    measure failed. Hyperphosphatemia and azotemia
    are contraindications.
  • AMIFOSTINE(WR-2721) PG

Syed Nasrat Imam, MD
32
CHOICE OF AGENT
  • Mild (lt3 mmol/l)-Hydration with saline.
  • Moderate(gt3.5mmol/l) with moderate symptoms-
    Bisphosphonate.
  • Severe life threatening( gt4mmol/l) - Saline
    Calcitonin mithramycin,alternatively
    bisphosphonate, if steroids sensitive
    steroids. Hypercalcemia secondary to
    malignancy- survival after the appearance of
    hypercalcemia is very poor - median of 3 months.

Syed Nasrat Imam, MD
33
REFERENCES
  • Recognizing hypercalcemia The 3-hormone,
    3-organ rule-Gregory W. Rutecki, MD and
    Frederick C. Whittier, MD, The journal Of
    Critical Illness. Vol 13, no. 1.Jan 1998
  • Management Of Acute Hypercalcemia, John P.
    Bilezikian, MD, The New England Journal Of
    Medicine,vol 326, No 18, April 30, 1992.
  • Cecils Text Book Of Internal Medicine
  • Harrisons Principle Of Internal Medicine.
  • Renal and Electrolyte Disorders, Vth edition,
    Robert W. Schrier.
  • Potts Jt, ed. 1991 NIH Consensus Development
    Conference Statement on Primary
    Hyperparathyroidism. J Bone Miner Res.
    19916s9-s13
  • Mallette LE. The Hypercalcemia. Semin Nephro.
    199212159-190.
  • Edelson GW, Kleenehoper M. Hypercalcemic crisis.
    Med Clin North Am. 19957979-92

Syed Nasrat Imam, MD
Write a Comment
User Comments (0)
About PowerShow.com