ELECTROLYTE IMBALANCE IN HEMATOLOGY
Present by--Dr. Md. Ashiqur Rahman.HMO,Hematology.
Major electrolyte
Cation Anion
1. ECF: Na+
2. ICF: K+ & Mg++
1. ECF: HCO3- & CL-
2. ICF: PO4,SO4,organic acid and proteins.
Electrolyte Imbalance in Hematology ward
Electrolyte imbalance in leukemia related to disease process or drug therapy
1. TLS– hyperkalaemia,hyperphosphatemia,hypoCa++,hyperuraecimia.
2. During relapse-- hypoK+,hypoMg++,hypoPO4
3. SIADH(cyclophosphamaide,vincristine).
4. Hypercalcaemia—due to bone infiltration or PTH-r peptide.
5. Nonspecific—GI loss through vomiting, diarrhea
Electrolyte imbalance in Lymphoma1. TLS
2. Hypercalcaemia
3. SIADH
Electrolyte imbalance in Multiple Myeloma1. Hypercalcaemia.
2. Pseudohyponatraemia.
Assessment of fluid & electrolyte balance in hospitalized pts
Step 1:asses the clinical volume status Examine pts for signs of hypo/hypervolaemia
Check daily wt change
Step 2:review fluid balance chart Check total volume IN and OUT on previous day(IN—OUT=+400ml in normal balance)
Step 3:assess ongoing pathological loss Check loss from GIT and surgical drain
Estimate increased insensible loss(e.g.fever) and internal sequestration(“third space”)
Step 4:check plasma U&Es Check plasma Na as a marker of water balance
Check plasma K as guide to EC K balance
Check HCO3 as a clue to acid-base disorder
Check urea and creatinine to monitor renal function
Step 5:prescribe appropriate i.v. fluid for replacement therapy
Hyponatraemia
Serum Na + : <135 meq/L
Incidence : 1.5-2.5%(Hospitalized)
Hyponatraemic encephalopathy highest in children, menstruating females and hypoxic pts.
Mortality/Morbidity Acute hyponatraemia (developing over 48 h or less) are subject
to more severe degrees of cerebral edema
sodium level is less than 105 mEq/L, the mortality is over 50%
Chronic hyponatraemia (developing over more than 48 h) experience milder degrees of cerebral edema
Brainstem herniation has not been observed in patients with chronic hyponatraemia
Types of Hyponatraemia and causes
Causes of SIADH:
Tumours, especially small-cell lung cancer ,Hodgkin’s disease CNS disorders: stroke, trauma, infection, psychosis Pulmonary disorders: pneumonia, tuberculosis Drugs
Anticonvulsants, e.g. carbamazepine Psychotropics, e.g. haloperidol Antidepressants, e.g. amitriptyline, fluoxetine Cytotoxics, e.g. cyclophosphamide, vincristine Hypoglycaemics, e.g. chlorpropamide Opiates, e.g. morphine
Sustained pain, stress, nausea, e.g. post-operative state, acute porphyria Idiopathic
Diagnosis: Low plasma sodium concentration (typically < 130 mmol/l)
Low plasma osmolality (< 270 mmol/kg)
Urine osmolality not minimally low (> 150 mmol/kg)
Urine sodium concentration not minimally low (> 30 mmol/l)
Low-normal plasma urea, creatinine, uric acid
Exclusion of other causes of hyponatraemia
Pseudohyponatremia
The aqueous phase is diluted by excessive proteins or lipids. The TBW and total body sodium are unchanged.
hypertriglyceridemia
multiple myeloma
Note-
A rise in plasma lipid by 4.6 gm/L or in plasma
protein of 10 gm/dl lowers plasma Na+
by 1mEq/L .
A rise in serum glucose by 5.6meq/l decrease
serum Na+ by 1.6meq/L.
Clinical Manifestations
>125- Asymptomatic
125- Anorexia, Nausea, Vomiting, Malaise.
<120- Headache, Lethargy, Disorientation confusion, Depressed reflexes
<110- Seizures, Brain stem herniation, Coma, Resp. arrest, Death
Diagnosis CT head, ECG Repeat Na level Correct hyperglycemia Laboratory tests
1. Plasma osmolality normally ranges from 275 to 290 mosmol/kg If >290 mosmol/kg :
Hyperglycemia or administration of mannitol If 275 – 290 mosmol/kg :
hyperlipidemia or hyperproteinemia If <275 mosmol/kg :
Euvolaemic status(SIADH)
2. Urine osmolality : Normal value is > 100 mosmol/kg
< 100 mosmol/kg hypoosmolar hyponatremia
Excessive sweating Burns Vomiting Diarrhea
3. Urine sodium concentration 4. Uric acid level
Treatmentfour issues must be addressed Asymptomatic vs. symptomatic
acute (within 48 hours)
chronic (>48 hours)
Volume status
1st step is to calculate the total body water Total body water (TBW) = 0.6 × body weight
Calculation of Na+_
Na deficit = TBW ( desired Na- actual Na)
=0.6 x wt(kg) x (desired [Na] - actual [Na])=0.6x60kgx(120-107)=468
Desired range is usually= 120-125 meq/l
Change in Na (meq/L) = (Infusion fluid Na+- pt Na+) / (TBW+1) for 1000ml soln . =(513-107)/(36+1) = 10.9meq/l
Infusion fluid’s content-
IV Fluids One liter of Lactated Ringer's Solution contains:
sodium ion = 130 mmol/L
chloride ion = 109 mmol/L
lactate = 28 mmol/L
potassium ion = 4 mmol/L
calcium ion = 1.5 mmol/L
One liter of Normal Saline contains: 154 mEq/L of Na+ and Cl−
One liter of 3% saline contains: 514 mEq/L of Na+ and Cl−
Treatment Cont.
Symptomatic: relatively rapid correction.
1. acute hyponatremia : more rapid rates of correction may be possible
8 to 10 meq/L in 4 to 8 hours i.e. aim for correction 1-1.5 meq/L/h or until asymptomatic
2. chronic hyponatremia slower rates of correction
12 meq/L in 24 hours i.e. aim for correction 0.5 meq/L/h.
Donot correct by >10mmol/l/24hr
Rx Hyponatremia (Example)
Na deficit (mmol) = 0.6 x wt(kg) x (desired [Na] - actual [Na])
60 kg women, serum Na 107, seizure resistant to benzodiazepines. Na defecit = 0.6 x (60) x (120 – 107) = 468 mEq Want to correct at rate 1.5 mEq/L/h, so target rate of correction per hr. is- 0.6 x
(60) x 1.5= 54 mEq Time required = 468/54 =8.7hr 3% NaCl has 513 mEq/L of Na513mmol NaCl in 1000 c.c sol54mmol NaCl in (1000 x 54)/513=105 c.c
So, rate of 3% NaCl infusion= 105 cc/h for 8.7h to correct serum Na to 120 mEq/l
so The final order will be 105cc/hr (27d/min) for 8.5hr
If fluid overload:Fluid restriction < 1litre(5 cups/day)+/- diureticRx of underlying cause
Rx Hyponatremia cont.
Asymptomatic or Chronic
SIADH Water restriction 0.5-1 liter/day
Salt tablets
Lithium (induces NDI)
Demeclocycline Inhibits the effects of ADH
Onset of action may require up to one week
300-600 mg bid (can be nephrotoxic)
When to stop correction?
Symptoms gone
Na level 125meq/L
Total correction 20meq/L
Note: Calculations are always at best estimates, and anyone getting hyponatremia corrected by IV saline (0.9% or 3%) needs frequent serum electrolyte monitoring (q1h if on 3% NS).
Complication:1. Rapidly develop hyponatraemia leads to CEREBRAL ODEMA.
2. Rapidly correction of hyponatraemia leads to CPM(central pontinemyelinolysis)
CPM:Abrupt increase in ECF osmolarity shifting water out of cerebral neuron,risking
detachment from their myelin sheath is called myelinolysis.This produce permanent structural and functional damage to mid-brain.
Risk factors:
1. Alcoholism
2. Chronically ill pt
3. Liver cirrhosis
4. Malnutrition
5. Hypokalaemia
More common if Na+ correction rate >20meq/l/24h
C/F: Symptoms usually develop 2-6days after elevation of Na+
1. dysarthia 2. dysphagia 3. locked –in syndrom 4. nystigmus 5. seizure 6. ataxia 7. paralysis 8. etc
MRI is preferred investigation.
Hypokalaemia
Persistent reduction of serum potassium
below 3.5mEq/l ECF K+ : 5meq/l
ICF K+ : 140 meq/l
Total body K+ : 3500mmol(ECF K+ is 2% of total K+=70mmol)
Type of hypokalaemia:
1. Spurious Hypokalaemia: Drugs: Insulin/β agonist/ Theophylline e.t.c
Catecholamine excess (Acute stress) e.g. AMI
Periodic Hypokalaemia paralysis.
Refeeding
Treatment of megaloblastic Anaemia
2.True hypokalaemia:
Inadequate K+ intake
Extrarenal K+ loss
Renal K+ loss
Clinical Feature
S. K+ meq/l
Category of Symptoms Signs Rx plan
3—3.5 meq/l
Mild hypokalaemia
May be asymptomatic A
2—3 meq/l
Moderate hypokalaemia
Tingling, numbness around lip, muscle weakness,fatigue,abdominal discomfort, constipation
Reduced reflex, abdominaldistention, absent bowel sound
B
<2 meq/l Severe hypokalaemia
Polyuria,nocturia,polydypsia,severe weakness,rhabdomyolysis,missed heart beat
Unable to stand up from sitting position and climbing stairs due to PM,resp. paralysis,SVT,asystole
C
Mild hypokalaemia(3-3.5):Plan A
No specific treatment .
Increase oral intake of banana, dub water, milk chocolate, other K containing food.
Daily 60-80meq /d(20meq/3tsf,3-4 times )
Treatment of underlying disorder (such as vomiting or diarrhoea)
Moderate Hypokalaemia( serum K+ 2-3 meq/L.):Plan B
DRUG:Tab.ElectroK(600mg/8mEq),
Syp.ElectroK(500mg/5ml;6.66mEq/tsf),
Syp. KT (540mg/5ml;7.2mEq/tsf)
Tab. Urokit (potassium citrate1080mg) : ideal in
renal stone disease.(75mg=1mEq)
Advice :take the drug with 1 or 2 glass of water, after meal then take sitting or standing posture for 15 min to avoid gastric irritation by K+ .
Specific treatment of cause of hypokalemia.
Severe Hypokalaemia(<2meq/l):Plan C
Oral:40 meq 6 hourly under close ECG monitoring
I.V.potassium therapy (for severe symptomatic):
1. Avoid i.v till urine output established,
2. Don’t give >10-20meq/hr,
3. Don’t give >40meq/L,
4. Don’t give >240meq/day,
5. Never give directly,
6. Mix KCl with isotonic saline not with D-5% (20meqK+/Lof D-5% will reduce potassium by 0.2-1.4 meq/
7. Alkalosis: K+ with chloride
8. Acidosis: K+ with acetate
9. Lack of response: Mg def.a) Mg >1meq/l: oral Mg++ 30-50meq in ¾ divided dose
b) Mg <1meq/l: I/V mixed with 50ml of N/S or D/W(1st 24hrs 1meq/kg then,0.5meq/kg/day) 2ml vial=1gm/8.1meq 50%Mgso4
Hyperkalaemia Serum K+ : >5.5meq/l
Clinical Features
Often asymptomatic till K+ >6.5meq/l
Vague mascular weakness– 1st symptom
Tingling around lip and finger
Slow or irregular pulse rate
Fatal cardiac arrhythmias– silent killer
Hyporeflexia,gradual paralysis initialylegs>trunk>arms>face>resp. muscles
Pts remains alert and apprehensive
Treatment of Hyperkalaemia:
Mechanism Therapy
Stabilize cell membrane potential*
I.V. calcium gluconate(10ml of 10% sol.)
Shift K+ into cells Inhaled B2 agonistI.V. glucose and insulin(5 U)I.V. NaHOC3**
Remove K from body I.V. frusemide and N/S***Ion exchange resin(e.g.Resonium) orally or rectallyDialysis
*If ECG change suggestive of hyperkalaemia(K typically >7mmol/l).**If acidosis present.***If adequate residual renal function.
Hypercalcemia of malignancy
Relatively common: 20 to 30%
Most common cancers associated with hypercalcemia: breast cancer, lung cancer, multiple myeloma, squamous cell carcinomas
Poor prognosis
Important considerations
Calcium in serum is bound to proteins,
principally albumin
Corrected calcium (mmol/L) = Measured
calcium (mmol/L) + [0.02 x (4 –
measured albumin g/dl)].
OR,
Corrected calcium(mg/dl)=measured calcium(mg/dl)+[0.8 x (4– measured albumin g/dl)].
Mechanisms of cancer-inducedhypercalcemia
Symptoms
Depends on degree of hypercalcemia and the rate of rise.
Nausea,vomiting,anorexia,fatigue,polyuria,dyspepsia,renal colic,muscular weakness, abdominal pain, constipation are common
Others: depression, anxiety, cognitive dysfunction, cardiac arrhythmia
Treatment considerations
Mild hypercalcemia1. Asymptomatic or mildly symptomatic (Ca <12mg/dL or
3mmol/L): do not require immediate treatment.
2. Avoid: thiazide diuretics, lithium carbonate, dehydration, prolonged inactivity, and high calcium diet (>1000 mg/day)
3. Adequate hydration (at least six to eight glasses of water per day) minimizes the risk of nephrolithiasis
Moderate hypercalcemia:
1. Ca 12 -14mg/dL (3 - 3.5 mmol/L): may be well tolerated chronically, and may not require immediate treatment
2. Same recommendations
Treatment considerations
Severe hypercalcemia
1. Symptomatic Ca >14 mg/dL (3.5 mmol/L):require
treatment.
2. Triple therapy (IV hydration + bisphosphonate + calcitonin).
3. Others: loop diuretics, glucocorticoids,phosphates,dialysis
Treatment:
Calcitonin:1. Inhibits bone resorption via interference with osteoclast function; also
promotes urinary calcium excretion
2. Onset of action: 4-6h (works rapidly)
3. Duration of action: 48h
4. Dose: 4 IU/kg IM or SC q12 hours
Efficacy: limited to the first 48h, even with repeated doses, indicating the development of tachyphylaxis, perhaps due to receptor down regulation
Bisphosphonates1. Inhibit bone resorption via interference with osteoclast recruitment and
function
2. Onset of action: 24-72h
3. Duration of action: 2-4 weeks
4. 1st choice: Zoledronic acid 4mg IV over 15 min
Commonly used to prevent adverse skeletal events in pts with metastatic cancer to the bones
Generally well tolerated
Side effects: include: flu-like symptoms(fever, arthralgias, myalgia, fatigue,bone pain), ocular inflammation(uveitis),↓Ca, ↓ P, impaired renal function, nephrotic syndrome, and osteonecrosis of the jaw.
N.B: Caution when impaired renal function, Adequate hydration with saline and treatment with a reduced dose and/or slower infusion rate (4 mg ZA over 30 to 60 minutes) may minimize risk.
HypocalcaemiaTotal serum Ca++: 8.5-10.5 mg/dl (2.12-2.62 mmol/l)
Ionized Ca++: 4.5-5.5 mg/dl (1.12-1.38 mmol/l)
Conversion: mg/dl x 0.25 = mmol/l
Ionized calcium is affected by: Albumin
Blood pH
Serum phosphate
Serum Mg++
Serum HCO3
Relation of albumin with calcium
A. Normal individual.B. Hypoalbuminemia.C. Alkalosis.
A.Primary Hypoparathyroidism.
B.Hypoalbuminemia.C.Secondary
HyperPTH(CRF)D.Alkalosis.E. Primary HyperPTH.F. Malignancy .
Causes of Hypocalcaemia:
Symptoms and signs of hypocalcemia Neuromuscular irritability
Paresthesias
Laryngospasm / Bronchospasm
Tetany
Seizures
Chvostek sign
Trousseau sign
Prolonged QTc time on ECG
1. Tetany is not caused by increased excitability of the muscles.
2. Muscle excitability is depressed hypocalcemia impedes ACh release at NM junctions
3. However, the increase in neuronal excitability.
Trousseau’s sign more sensitive and specific than Chvostek’s sign
Trousseau sign:(very uncomfortable and painful)
A blood pressure cuff is inflated to a pressure above the patients systolic level.Pressure is continued for several minutes.Carpopedal spasm: * flexion at the wrist
* flexion at the MP joints * extension of the IP joints * adduction thumbs/fingers
Investigations:
1. Total calcium.
2. Ionized calcium.
3. Albumin.
4. S. PTH.
5. Phosphate.
6. Magnesium.
7. Blood PH.
8. ECG.
Management:
1. Mild asymptomatic: Often adequate to increase dietary calcium by 1000 mg/day.
2. Symptomatic : 10-20 ml 10% calcium gluconate i.v. over 10-20 mins given with close cardiac
monitoring . Mix with NaCl or 5 % D/W .
Risks:1. Tissue necrosis/calcification if extravasates2. Calcium can inhibit sinus node bradycardia + arrest
(Stop infusion if bradycardia develops)3. Avoid complete correction of hypocalcaemia 4. If Mg – treat and correct hypomagnesaemia by 50mmol MgCl i.v. in 1L N/S
over 12-24 hrs.
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