Presentation on fluid and electrolyte balance in hematology

1. Fluid and electrolyte imbalance
in hematology
Presenter: Dr Ankit Jitani

2. Basic concepts

3. The Composition of the Human
Body

5. Principal of fluid and electrolyte balance

7. Osmolality Osmolarity
• Osmols of solute per Kg of
solvent
• Does not depend on
temperature and pressure
• Measured using Osmometer
• Calculation (plasma):
2 x (Na+K)+glucose/18+
BUN/2.8 (mg/dl)
• Osmols of solute per litre if
solvent
• Depends on volume which
varies with temp & pressure
• Unreliable in conditions like
pseudohyponatraemia

8. Regulation of osmolality
number of solute particles per litre

9. Regulation of extracellular volume
Regulation of extracellular volume

11. Case based approach to electrolyte abnormalities

12. Case 1
• 4-year old boy, B-ALL, BFM 2002
• On day 17, developed headache, vomiting, became drowsy
followed by GTCS
• There were no localizing neurological signs
• Serum Electrolytes
▫ Sodium: 113 mEq/L
▫ Potassium: 4.2 mEq/L
▫ Serum osmolality: 260 mOsm/L (normal: 280-290 mOsm/L)
▫ Urine osmolality: 625 mOsm/L
▫ Urine sodium 280 mEq/d (normal: 100-260 mEq/d)
• ECG, Chest X-ray, Echocardiography, CT brain and LFT, RFT
were normal

13. Case 2
• 49-year-old male
• Malaise, tiredness, bone pain
• 4-year history of progressive MM (IgG-lambda)
• Recently treated with morphine, bisphosphonate and
radiation
• Lab results
▫ Sodium 124
▫ Potassium 4.4
• On ABG
▫ Sodium 137
▫ Potassium 4.8
• Serum osmolality: 285 mOsm/L

14. Approach to diagnosis
Hyponatremia

15. Probable causes of hyponatremia
• Case 1:
▫ SIADH induced
Hyponatremia
▫ Vincristine induced
• Other causes of SIADH
▫ CNS disorders: infections,
bleeding, trauma
▫ Malignancies: SCLC
▫ Pulmonary disorder
▫ Drugs:
Cyclophosphamide,
Ifosfamide, opiods,
thiazides
• Case 2
▫ Pseudohyponatremia
• Causes:
▫ Hyperproteinemia
▫ Hyperlipidemia

16. Treatment approach
Hyponatremia
Chronic/asymptomatic (>48 hrs)Acute/Symptomatic (<48 hrs)
1. Water restriction
2. Treat underlying cause
3. 3% NaCl correction
i. 1-2 mEq/hr till symptoms abate
ii. 0.5 m/Eq/hr after that
iii. Total (max) 10 mEq/24 hrs
4. Frusemide and salt tablets
5. Resistant cases
i. Tolvaptan: 15mg/24 hrs PO
ii. Conivaptan: 20 mg in 100 ml D5 IV
iii. Demeclocycline: 300-600 mg PO
1. Water restriction
2. Treat underlying cause

17. Adrogue- Madias Equation
• Change in serum sodium per litre of infusate
(Infused Na - S. Na)
(TBW+1)
• Sodium content of infusate (per litre):
▫ 3 % NaCl: 513 meq/L
▫ 0.9% NaCl: 154 meq/L
▫ Ringers Lactate: 130 meq/L
▫ 0.45 % NaCl: 77 meq/L
▫ 5% dextrose: 0 meq/L

18. Adrogue- Madias Example
• 70 kg man
• Serum Na: 110 mEq/dl
• TBW= 70 x 0.6 = 42
• Expected change/litre of 3% NaCl =
(513-110)/(42+1) = 9.37 meq/L
• Desired correction: 8 mEq over 16 hrs (0.5 mEq/hr)
• Amt of fluid required= 8/9.37 = 0.85 L over 16 hrs

19. Central pontine myelinolysis
• Rapid correction of hyponatremia
• Mechanisms:
▫ Disrupted integrity of BBB -> entry of immune
mediator -> demyelination
▫ Delay in re-accumulation of osmotic osmolytes
• Oligodendrocytes

20. Central pontine myelinolysis
• One or more days after overcorrection
• Manifestations:
▫ Para/quadriparasis
▫ Dysphagia/dysarthria/diplopia
▫ Locked in syndrome
• Re-lowering of plasma Na+ can attenuate the
condition

21. Case 3
• A 15 year old girl with B-ALL
• On BFM-2002 induction
• Developed septicemia with fungal pneumonia on
day 29 of chemotherapy
• Transferred to ICU and was put on mechanical
ventilation
• Decreased urine output, diminished DTR
• Lab
▫ Serum Na+: 160 mEq/L
▫ Urine osmolality: 900 mOsm/L

22. Hypernatremia
• Contributing Factors
▫ Decreased water intake: sedated, intubated
▫ Corticosteroids
▫ Na containing IV fluids
▫ Insensible water loss
▫ Diabetes insipidus
▫ Hyperaldosteronism
▫ Uncontrolled diabetes: osmotic diuresis
▫ Increase in oral Na intake

23. Hypernatremia approach
Hypercalcemia
Hypokalemia
Drugs:
Ifosfamide
Anti-viral

24. Adrogue Madias equation
• 70 kg man with Na: 160 mEq/L
• Ongoing loss: 2 L diarrhoea + 1 L urine
• Correction with D5: expected change/L of D5
(0- 160)/(42+1) = -3.75meq/l
• Correction @ 0.5 mEq/l (3.75/0.5= 7.44)
• 1000ml over 7-8 hrs = 125ml/hr
• Ongoing loss= 3 L/day
• 125+125 = 250ml/hr

25. Case 4
• 20 yr male with B-ALL under UKALL XII
• Developed febrile neutropenia, treated with IV antibiotics- no
response
• Amphotericin B added
• Serum K+- 2.1mEq/L
• Treated and discharged
• Readmitted after one month: Weakness, lethargy, irritability
and decreased intestinal motility
▫ Serum creatinine: 0.45 mg/dl
▫ serum potassium: 2.1 mEq/L
▫ 24 hour urinary volume: 1.5 liter
▫ Urine k: 20 mEq/L
▫ Serum osmolality: 287 mosm/L
▫ Urine osmolality: 400 mEq/L
▫ TTKG: 13
Urine K/Urine Osm
TTKG:
Serum K/Serum Osm

26. Case 4

27. Hypokalemia workup

28. Treatment algorithm

29. Treatment
• Stop diuretics
• Correct Magnesium
• K+ replacement (IV or PO)
• (Body wt x Deficit x 0.4 [correction factor]) + body wt
• IV: ECG monitoring
• Encourage potassium-rich foods
▫ Normotensive: oral KCl
▫ Hypertensive: K+ sparing diuretics
• Treat underlying cause

30. Case 5
• A 78 year old lady, diagnosed with ET presented with
knee injury
• Platelet count: 2200 x 103
• Serum K+: 7.2 mEq/L
• Normal renal function
• Normal ECG
• Treated with insulin-dextrose, K+ binding resins,
diuretics
• Operated & then referred to hematology
• Apheresis done: Plt: 1300 x 103 and Serum K+: 5.5
• Plasma K+ (heparin): 3.84 mEq/L

32. Approach to hyperkalemia
Hyperkalemia
Spurious Transcellular shift
Leucocytosis
Thrombocytosis
ECF-ICF Exchange
Insulin Deficiency
Hypertoicity
Β2 blockade
Acidosis
Cellular release
TLS
Hemolysis
Rhabdomyolysis
Impaired renal excretion
Decreased GFR (<20ml/min)
Endogenous production
Retention of metabolic waste
Exogenous administration
Potassium supplements
Blood products
Decreased aldosterone effect
ACE inhibitors/ARBs
Potassium sparing diuretics
Cyclosporine
NSAIDs
Heparin
Trimethoprim
Papillary necrosis (SCD)

33. Treatment strategy
• Cell membrane stabilisation:
▫ Calcium gluconate 1 gm of 10% IV over 2-3 mins
• Movement of extracellular K into intracellular compartment
Treatment Dosing Onset/Duration Decline
Insulin Dextrose 10U with D5 Onset 15 mins
Lasts 6-8 hrs
1 mEq/L
β2-adrenergic
agonists
Albuterol: 10-20 mg
nebulised/ inhaled
Onset 10-30 mins
Lasts 3-6 hrs
1 -1.5
mEq/L
Resin: Sodium
polystryrene
sulphonate
25-50mg 100ml 20% sorbitol
PO / 50gm in 200ml 30%
sorbitol PR
Onset 1-2 hrs
Lasts 4-6 hrs
0.5-1
mEq/L
Sodium bicarbonate 2-4 mEq/min until
bicarbonate normalize
(150 mEq in 1 L D5)
Onset 4 hrs
Lasts >6 hrs
0.5-0.75
mEq/L
Diuretics Variable Onset 30-60 min
Lasts 3-4 hrs
Variable
Hemodialysis Immediate Variable

34. Calcium Homeostasis Phosphorus Homeostasis
• Bones: 99 %
• ECF: 1%
• Active ionised Calcium: 45%
(4.6 to 5.1 mg/dl)
• Albumin bound Calcium: 40 %
• 15 % calcium bound to organic
& inorganic anions (sulfate,
phosphate, citrate, lactate)
• 85% in bone
• 1% in ECF
• Rest in ICF

35. Regulation of Calcium & Phosphorus
balance
PTH
1, 25 OH
Vitamin D
BoneKidney
Calcium reabsorption
Phosphorus excretion
Calcium release
Phosphorus release
Calcium absorption
Phosphorus absorption
Parathyroid gland 25 OH Vitamin D
Vitamin D
UV Light
DietSerum ionised
calcium
Serum
Phosphorus
Intestine

36. • 72-year-old gentleman
• One-month history of progressive confusion, recurrent falls,
abdominal pain, anorexia, constipation, weight loss, pain in
coccyx
• Initial workup:
▫ Pancytopenia
▫ Serum creatinine: 2.44 mg/dl
▫ Serum calcium: 15.9 mg/dl
▫ Serum albumin: 2.5 mg/dl
▫ Serum PTH: 25 pg/mL (10-65 pg/mL)
▫ Serum Vitamin D: 35 ng/mL
• Treated with IV hydration and Zolendronate
▫ Serum creatinine: 1.4 mg/dl
▫ Serum calcium: 11 mg/dl
Case 6

37. Approach to hypercalcemia
Hypercalcemia
PTH-independent mechanism
Check Vitamin D
Bone Resorption
•Osteolytic malignancy
•Immobilisation
•Hyperthyroidsm
PTH related peptide
•Humoral hypercalcemia of
malignancy
Decreased Ca excretion
•Volume depletion
•Thiazide diuretic
Excess 1,25-OH
•Granulomatous
disease (sarcoidosis)
•Lymphoma
•Calcitriol overdose
Excess 25-OH
•Vitamin D
intoxication
Hyperparathyroid state

38. Treatment
Treatment Dosing Onset Comments
Isotonic saline Bolus (3-4L), then
adjust to output of
100-150 mL/hr
2-4 hrs Watch for volume
overload
Careful use of diuretics
Calcitonin 4-8 IU/Kg IM or SC
q6-12
4- 6hrs Lowers Ca 1-2 mg/dl
Bisphosphonates Zolendronate 4mg IV
over 15 mins
Onset 2 days, peak at 4-
6 days and lasts 2-4 wk
Renal insufficiency
Denosumab 60-120 mg SC Onset 3 days, ½ life 25
days
Watch for
hypocalcemia and
infection
Glucocorticoids Prednisolone 20-60
mg or equivalent
5-10 days Effective in
hemtological
malignancy and
granulomatous disease
Hemodialysis Low calcium dialysate IMMEDIATE Severe hypercalcemia,
volume overload

39. Case 7
• A 64-year-old male with a history of CLL, under BR
• On day 3: vomiting, diarrhea, muscle cramp,
anorexia, weakness, shortness of breath
• Urine output: 1000 ml
• Investigations:
▫ Urea: 150 mg/dL
▫ Serum creatinine: 4.9 mg/dL
▫ Uric acid: 19 mg/dL
▫ Potassium: 6.0 mEq/L
▫ Phosphate: 10.9 mg/dL
▫ Calcium: 6.9 mg/dL

40. Case 7
Management
• IV fluid NS to maintain urine output
>100ml/m2/hr
• Allopurinol kept on hold
• Rasburicase: 8 mg IV over 15 mins
• Sodium bicarbonate was avoided: alkalisation
increase uric acid excretion but cause calcium
precipitate
Jones GL et al. British Journal of Haematology, 2015, 169, 661–671

41. Case 7
Management
• Hyperkalemia: insulin-dextrose, cardiac monitoring
• Hyperphosphatemia: hydration & diuresis
• Hypocalcemia: no cardiac symptoms, so avoided
(Ca2+ combine with PO4
3- & worsen precipitation in
soft tissues)
• Renal function improved, with increased urine
output, normalization of electrolytes, and return of
his appetite
Jones GL et al. British Journal of Haematology, 2015, 169, 661–671

42. TLS
Cairo-Bishop definition Howard Definition
• Lab TLS: two or more of the
following,
▫ Uric acid > 8 mg/dL or 25%
increase
▫ potassium > 6 meq/L or 25%
increase
▫ phosphate > 4.5 mg/dL or 25%
increase
▫ calcium < 7 mg/dL or 25%
decrease
• Clinical TLS:
▫ increased serum creatinine (1.5
times upper limit of normal)
▫ cardiac arrhythmia or sudden
death
▫ seizure
• > 2 electrolyte laboratory
abnormalities must be present
simultaneously
• 25% increase with value
already outside baseline
Cairo MS, Bishop M. Br. J. Haematol. 2004
Howard, SC; Jones DP et al. New England Journal of Medicine. 2011

43. Hypocalcemia approach
Hypocalcemia
PTH-present but ineffective Hypoparathyroid state
1. Hypo-hyper
Magnesium
2. Infiltration- malignant
replacement
3. Radiation induced
destruction
PTH resistance
•Bisphosphonates
Chelation
•TLS, hemolysis
•Pancreatitis
•Citrate containing
infusion: blood products,
plasmapheresis
Vitamin D
deficiency
•Gram negative sepsis
•Low dietary intake
•Liver disease
•Advanced renal
disease
•P450 enzyme

44. Chvostek and Trousseau sign

45. Treatment
1. ECG changes present
i. Early hemodialysis
ii. MgSO4 bolus: 2g IV over 15 mins (empirically,
normal renal function)
iii. Calcium gluconate:
a. Load: 2g 10% Calcium Gluconate, 50-100ml in D5/NS
in 10-15 mins
b. Maintain: 6g in 500ml D5/NS @ 0.5-
1.5mg(elemental)/kg/hr
2. Oral: 1-2g elemental Ca, separate from meals
3. Calcitirol: 0.25-4 mcg/d

46. Elemental calcium content
• IV:
▫ Calcium gluconate: 1gm= 93mg elemental
▫ Calcium chloride: 1gm= 272 mg elemental
• Oral:
▫ Calcium carbonate: 40%
▫ Calcium gluconate: 9%
▫ Calcium lactate: 23%
▫ Calcium citrate: 20%
▫ Calcium acetate: 25%

47. Hyperphosphatemia
• Features of associated hypocalcemia: secondary
to phosphate binding with calcium

48. Treatment of hyperphosphatemia
• Treatment of the underlying cause
• Forced saline resuscitation & acetazolamide
(15mg/kg 4 hrly)
• Hemodialysis in severe cases and renal insufficiency
• Treatment of symptomatic hypocalcemia
• Phosphate binders

49. Hypophosphatemia

50. Management
Close monitoring of Ca level

51. Magnesium homeostasis
• Bone: 60%
• ECF: 1%
• ICF: rest
• Serum Mg is poor predictor of intracellular and total
body store
• Not easily exchanged across cell membrane
• No hormone involved in Mg regulation
• Balance maintained by renal tubular resorption

52. Hypomagnesemia

53. Manifestations
• Lathergy, confusion
• Ataxia, nystagmus
• Hyperreflexia, seizure
• Arrythemia
• Concomitant K+ & Ca2+ deficiency

54. Treatment
• ECG changes or symptomatic patients
▫ IV: 1-2 gm MgSO4 (1g=96 mg elemental Mg) over
15 mins
▫ 6gm MgSO4 in 1L IVF over 24 hrs
▫ May be needed for 3-7 days to replenish body
store
▫ Monitor DTR to detect hypermagnesemia
Magnesium sulfate solution 50% = 500 mg/ml (2 ml= 1 g= 96 mg elemental)

55. • Asymptomatic or no ECG changes
▫ Mild: 240mg elemental Mg2+/day in divided dose
▫ Severe: 720 mg elemental Mg2+
▫ Diarrhoea: 2-6gm IV @ 1g/hr
• Chronic hypomagnesemia from renal wasting:
amiloride
• Oral preparations:
▫ Milk of magnesia: 400mg/5ml
▫ Calcium/magnesium tabs: 75 mg
▫ Protein/ magnesium complex tabs: 133 mg
Treatment cont..

56. Hypermagnesemia
Uncommon due to remarkable excretory capacity of
kidney

57. Manifestations (>4 mEq/L)
Hyporeflexia: reduced or weak DTR
Weak voluntary muscle contractions
Drowsy, lethargy
Bradycardia
Peripheral vasodilatation
Hypotension
Respiratory failure

58. Management
• Eliminate contributing drugs
• Administer diuretic
• Calcium gluconate: cardiac stabilisation
• Diet restrictions

59. Hypovolemia
• Common Causes
▫ Hemorrhage
▫ Vomiting
▫ Diarrhea
▫ Burns
▫ Diuretic therapy
▫ Fever
▫ Impaired thirst

60. Grades of Dehydration
• Mild (loss: 4% of body weight): decreased skin
turgor, sunken eyes, dry mucous membranes
• Moderate (loss: 5-8 % of body weight): + oliguria,
orthostatic hypotension, tachycardia
• Severe (loss: 8-10 % of body weight): + hypotension,
decreased level of consciousness, stupor
Clinical Fluid & electrolyte balance: Dr Symons, Rev,4/05

61. Treatment
Fluid Management
• Diet therapy– Mild to moderate dehydration. Correct
with oral fluid replacement
• IV therapy– Type of fluid ordered depends on the
type of dehydration and the clients cardiovascular
status
▫ Normo or hyponatremic: 0.9% NaCl
▫ Hypernatremic: D5 or hypotonic saline

62. Fluid replacement
• 0-10 kg: 100 ml/kg/d
• 11-20 kg: 50 ml/kg/d
• > 20 kg: 20 ml/kg/d
• 25 kg : 1000 + 500 + 100 = 1600 ml/d
Example:
• Patient (25 kg) (4-2-1)
• 1-10 kg 4 ml/kg/h 40 ml/h
• 11-20 kg 2 ml/kg/h 20 ml/h
• >20 kg 1 ml/kg/h 5 ml/h
Together: 65 ml/h 1560ml/d
Clinical fluid & electrolyte balance, Dr Symons, Rev,4/05

63. Fluid Volume Excess
▫ Congestive Heart Failure
▫ Early renal failure
▫ IV therapy
▫ Excessive sodium ingestion
▫ SIADH
▫ Corticosteroid

64. Clinical Manifestations
▫ Increased BP
▫ Bounding pulse
▫ Raised JVP
▫ Tender hepatomegaly
▫ Pulmonary edema
 Dyspnea
 Orthopnea
 Crackles

65. Treatment
• Drug therapy
▫ Diuretics
• Restriction of sodium and saline intake
• Intake/output
• Weight monitoring

66. Take home message
• Change in water is the major phenomena in
electrolyte disturbances
• Some electrolyte imbalance occurs
concomitantly
• Aggressive management & monitoring required
in critical care