1. Electrolyte Disturbances
Hypercalcemia, Hyponatremia, Hypernatremia, Hyperkalemia

2. Hypercalcemia

3. Etiology
Hypercalcemia results when the entry of calcium into the circulation exceeds the excretion of calcium into the urine or deposition in bone.
Sources of calcium are most commonly the bone or the gastrointestinal tract

4. Etiology Hypercalcemia is a relatively common clinical problem.
Elevation in the physiologically important ionized (or free) calcium concentration.
However, 40 to 45 percent of the calcium in serum is bound to protein, principally albumin; , increased protein binding causes elevation in the serum total calcium.

5. Increased bone resorption
Primary and secondary hyperparathyroidism
Malignancy
Hyperthyroidism
Other - Paget's disease, estrogens or antiestrogens in metastatic breast cancer, hypervitaminosis A, retinoic acid

6. Increased intestinal calcium absorption
Increased calcium intake
Renal failure (often with vitamin D supplementation)
Milk-alkali syndrome
Hypervitaminosis D
Enhanced intake of vitamin D or metabolites
Chronic granulomatous diseases (eg, sarcoidosis)
Malignant lymphoma
Acromegaly

7. Etiology Hyperalbuminemia 1) severe dehydration
2) multiple myeloma who have a calcium-binding paraprotein.
This phenomenon is called pseudohypercalcemia (or factitious hypercalcemia)

8. Other causes Chronic lithium intake Thiazide diuretics
Pheochromocytoma
Adrenal insufficiency
Rhabdomyolysis and acute renal failure
Theophylline toxicity
Familial hypocalciuric hypercalcemia
Immobilization
Total parenteral nutrition

10. Primary hyperparathyroidism
Activation of osteoclasts leading to increased bone resorption in primary hyperparathyroidism (also cancer).
Adenoma (80%)
Hyperplasia (15-20%)
Carcinoma (<1%)

11. Secondary hyperparathyroidism
Due to increased PTH in response to decreased calcium
ESRD

12. Tertiary hyperparathyroidism
An autonomous nodule develops after longstanding secondary hyperparathyroidism

13. Familial hypocalciuric hypercalcemia (FHH)
Mutation in the Ca-sensing receptor in parathyroid and kidney which increases the Ca set point
May also increase the PTH ( parathyroid isn’t sensing Calcium)

14. Malignancy
PTHrP- PTH related peptide (squamous cell lung cancer, renal, breast, bladder)
Cytokines (TNF, INTERLEUKIN-1)
OAF: Local osteolysis (breast cancer, multiple myeloma)
Tumoral effect (Hogkins / NHL)

15. Vitamin D Excess Granulomas (sarcoid, TB, histo)
Vitamin D Intoxication

16. Increased bone turnover
Hyperthyroidism
Immobilization
Paget’s disease
Vitamin A

17. Miscellaneous Thiazides (increase resorption in kidney)
Ca-based antacids (Milk-Alkali Syndrome)
Adrenal insufficiency

18. Clinical Manifestations
Bones
stones
abdominal groans
psychic moans

19. Bones
Osteopenia
Osteitis fibrosa cystica (seen in severe hyperparathyroidism only)

20. Osteitis Fibrosa Cystica
Cysts, fibrous nodules, salt and pepper appearance on X-ray

21. Stones
Nephrolithiasis
Nephrocalcinosis
Nephrogenic Diabetes Insipidus

22. Abdominal Groans Anorexia Nausea Vomiting Constipation Pancreatitis
Peptic ulcer disease

23. Psychic Moans
Fatigue
Depression
Confusion

25. Labs Free Calcium Measured or
Calculated( Measured Ca+(0.8x(4.0-alb) or use med-math?
PTH (irma assay)
PTH rp
VIT D , VIT A
PO4
URINE CALCIUM- 24 HRS

26. Short QT and widened T-wave

28. Treatment Normal Saline (4-6L per day) FILL THE TANK
Furosemide-CALCIURESIS
Start after patient is intravascularly repleted
Bisphosphonates- Inhibits osteoclast activity(reducing bone resorption and turnover) malignancy and ?Immobilization
28 hrs half-life( zolendronate, pamidronate)

29. Treatment SQ/IM( not nasal spray)Calcitonin 4 u/kg q12 hrs
increase to 8 units q 12 hrs
Onset 6-8 hours,duration 2-3 days
Steroids( targets OAF, 5-A Hydroxylase)
Onset hrs days

30. Primary Hyperparathyroid
Surgery (JCEM 2009)
Age <50 yrs, GFR <60ml/min, Cal 1 mg/dl above normal, DEXA <-2.5
Medical
Bisphonates,Calcitonin,estrogen,serm
Early DEXA scans

31. Hypercalcemia Quiz PTH Increased Cal Increased PO4 decreased
What do I have?
PRIMARY HYPERPARATHYROIDISM

32. quiz PTH DECREASED CAL INCREASED PO4 DECREASED/ INCREASED- EITHER
WHAT IS IT?
MALIGNANCY

33. QUIZ PTH DECREASED CAL INCREASED PO4 INCREASED WHAT IS IT?
VIT D EXCESS/ BONE TURNOVER

34. QUIZ
PTH NORMAL
CAL INCREASED
PO4 DECREASED
FHH

35. QUIZ PTH INCREASED CAL DECREASED PO4 INCREASED
CKD / PSEUDOHYPOPARATHYROIDISM

36. QUIZ
PTH INCREASED
CAL DECREASED
PO4 DECREASED
VIT D DEF

37. Hyponatremia
Santosh Reddy MD

38. DEFINITION Defined as Serum Sodium less than 136 meq/lt
4 % of hospitalized patients
NEJM 2000:342:1581-9( Adrogue,Madias)

39. Hyponatremia
Disorders of sodium are generally due to changes in total body water, not sodium
Hyper- or Hypo- osmolality
watershifts
changes in brain cell volume
changes in mental status, seizures

40. Hyponatremia: pathophysiology
Excess water compared to sodium, almost always due to increased ADH
The increased ADH may be:
Appropriate (e.g. hypovolemia or hypervolemia with too little effective arterial volume)EAV.
Inappropriate (e.g. SIADH)

41. Workup
Measure plasma osmolality to determine if hypo, hyper, or isotonic hyponatremia
Urine Osmolality
Serum NA
Urine NA

42. Hypertonic Hyponatremia
Excess of another effective osmoles, such as mannitol, glucose
Each 100mg/dL of glucose above 100 causes a decrease in Na by 1.8 mEq/L

43. Isotonic Hyponatremia
Lab artifact from
hyperlipidemia
or hyperproteinemia

44. Hypotonic Hyponatremia
Most common scenario
True excess of water compared to Na

45. Hypotonic Hyponatremia hypovolemic euvolemic hypervolemic
UNa< UNa>20
FeNa<1% FeNa>1%
UNa> UNa<10
FeNa>1% FeNa<1%
CHF, cirrhosis, nephrosis
Renal failure
Renal losses
Extrarenal losses
Pt’s clinical history
Uosm>100 Uosm<100 Uosm var.
SIADH,
adrenal insuff,
hypothyroidism
Primary polydipsia,
low solute
Reset osmostat

46. Hypovolemic Hypotonic Hyponatremia
Renal losses: Thiazides or other diuretics, salt-wasting nephropathy, adrenal insufficiency
Extra-renal losses: GI losses (diarrhea), third-spacing (pancreatitis), inadequate intake, insensible losses

47. Euvolemic Hypotonic Hyponatremia
SIADH
pulmonary-pneumonia, asthma, COPD, PTX, +pressure ventilation, small cell lung cancer
intracranial-trauma, stroke, hemorrhage, tumors, infection, hydrocephalus
drugs-antipsychotics, antidepressants, thaizides
misc-pain, nausea, post-op state
Endocrinopathies (adrenal insuff, hypothyroidism)
Reset osmostat ( exercise, seizures)

48. Low solute
“tea & toast”, “beer potomania” – increased free water intake with greatly decreased solute load
Maximum rate of water excretion on a normal diet is L per day – more than this you overwhelm the excretory capacity of the kidney

49. Hypervolemic Hypotonic Hyponatremia
CHF: low effective arterial volume (EAV)  ADH
Cirrhosis: ascites causes low EAV ADH
Nephrotic syndrome: hypoalbuminemia causes low EAV  ADH
Advanced renal failure

51. Methods to increase Na Restrict free water range 800-1.2 lt per day
Remove stimulus for ADH (volume replete, increase EAV, treat pulmonary pathology, etc)
Demeclocycline (ADH antagonist) 300MG BID TO QID
Normal saline after NA deficit is calculated

52. Treatment NA deficit: HYPOTONIC EUVOLEMIA
TBW ( 60 % MEN : 50% WOMEN) x
(DESIRED NA----MEASURED NA )
Ex: 100 kg Man, MEASURED NA 120
TBW 60 MEQ x 12( D--- M sodium)
720 MEQ PER 24 HOURS

53. Treatment 0.9 % : 154 meq/ LT 3% : 514 meq / LT
GIVE : 4. 6 LT OF 0.9 % NACL
1.4 LT OF 3 % NACL

54. Treatment of Euvolemic Hyponatremia
Asymptomatic: correct at rate of < 0.5 mEq/L/hr
Symptomatic: initital rapid correction of Na (2 mEq/L/hr) until symptoms resolve
Rate of correction should NOT exceed 12mEq in a 24 hour period, or 18mEq in a 48 hour period to avoid Central pontine myelinosis (CNS demyelination  changes in mental status, paralysis, pseudobulbar palsy)
NEPHROLOGY 1994;4:

56. Treatment
Conivaptan( vaprisol): Aquaresis:blocks the activity of AVP ,free water excretion,without losses of NA/K
EVEREST trial for CHF
Tolvaptan( Salt 1 and 2 trials) V2 receptor antagonist( hypervolemic or Euvolemic)

57. Hypernatremia
Santosh Reddy

58. Definition
Increase in the serum sodium concentration greater than 145 meq /L

59. Hypernatremia
Usually loss of hypotonic fluid, can also be infusion of too much hypertonic fluid
Hypernatremia is a strong thirst stimulus, so usually only affects pts w/o access to water (intubated, altered mental status,insensible losses nursing home patient)

60. Hypernatremia By definition, all pts are hypertonic Can be Hypovolemic
Hypervolemic
Euvolemic

61. Workup: Hypernatremia
Check volume status (vitals, orthostatics, JVP, skin turgor, mucous membranes, BUN, Cr)
If hypovolemic, check Uosm and UNa to determine whether free water loss is renal or extra-renal
If euvolemic, check Uosm to evaluate for complete or partial DI

62. Hypernatremia hypovolemic euvolemic hypervolemic
UOsm UOsm>600
UNa> UNa<20
Exogenous hypertonic saline, Mineralocorticoid excess
Renal losses
Extrarenal losses
Uosm<300 Uosm Uosm >600
Complete DI
Partial DI, reset osmostat
Intracellular osmole generation

63. Hypovolemic Hypernatremia
Renal water losses: osmotic diuresis from glucose/mannitol
Extra-renal water losses: diarrhea, insensible (fever, exercise)

64. Euvolemic Hypernatremia
Diabetes Insipidus: central or nephrogenic
Seizures, exercise: intracellular osmole generation  water shifts  transient increase in Na
Reset osmostat( I,I,I)

65. Hypervolemic hypernatremia
Hypertonic saline administration
Mineralocorticoid excess: causes ADH suppression

66. Free water deficit = TBW x (SerumNa-140)
Treatment
Replete free water deficit
Free water deficit = TBW x (SerumNa-140)
140
D5 W replacement
Restore access to water
Correct volume status

67. Treatment Must replete free water deficit via IVF or enteral feeds
Correct at rate < 0.5 mEq/L/hr to avoid cerebral edema
Must consume > 1L H2O/day

68. Treatment For hypovolemia hypernatremia For Hypervolemic hypernatremia
Correct with ¼ or ½ NS
For Hypervolemic hypernatremia
Correct with D5W and a loop diuretic

69. Treatment DI: Central: desmopressin
Nephrogenic : Salt restriction + Thiazides Amiloride, Nsaids.
V 1 A AND V2 receptor blockage trials

70. Hyperkalemia

71. Hyperkalemia Transcellular shifts Decreased excretion by kidneys
Normal GFR
a)Normal aldosterone (CHF,Cirrhosis)
b)Hypoaldosterone(Diabetes etc)

72. Hyperkalemia: Transcellular shifts
Acidosis,
Beta-blockers
insulin deficiency
dig intoxication
massive cellular necrosis
hyperkalemic periodic paralysis

73. Hyperkalemia: decreased excretion
Decreased GFR (AKI)
Hypoaldosteronism with a normal GFR (due to low renin, low aldosterone, or decreased response to aldosterone)

74. Hyperkalemia: symptoms
Weakness
Paresthesias
Palpitations
Peaked T waves on EKG (look like they might hurt to sit on)
Other EKG findings: increased PR interval, widened QRS, sine wave pattern, PEA

75. Peaked T waves

76. Sine wave

77. Workup
Rule out pseudohyperkalemia (IVF + KCl, hemolysis due to venipuncture, increased plt or WBC)
Rule out transcellular shift
Assess GFR
If normal GFR, calculate TTKG

78. TTKG: Trans-Tubular Potassium Gradient
(UrineK/PlasmaK)/(UrineOsm/PlasmaOsm)
TTKG tells you how well aldosterone is working
TTKG<7  decreased effective aldosterone function
TTKG>7  normal aldosterone function

79. Treatment
Calcium Gluconate/Calcium Chloride: stabilizes cell membranes
1-2 amps I.V
1-3 mins onset lasts 20-30mins
Insulin:drives K into cells
regular Insulin 10 units IV with 1-2 amps of D50
Beta-2 agonists: drives K into cells;
Albuterol 10-20mcg inh or IV 0.5mg
Onset mins

80. Treatment Bicarbonate: drives K into cells in exchange for H
1-3 amps
Onset mins last 60 mins
Kayexalate: exchanges Na for K in gut
30-90 mg PO/PR
Onset 1-2 hrs
Diuretics;decreases total body K; IV lasix
hemodialysis: decreases total body K