WATER & ELECTROLYTE IMBALANCE

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Learning Outcomes

At the end of the course students should be able to:

1. explain the causes, the pathophysiology, effects and complications of hypernatremia and hyponatremia.

2. define, give causes and describe the characteristics of Inappropriate ADH Syndrome

3. explain the causes, pathophysiology, effects and complications of hyperkalemia and hypokalemia.

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Normal body water and electrolyte distribution

60% body weight in man, 55% in woman66% intracellular, 33% in extracellular ( 8% in plasma)plasma) 4

Normal Homeostasis

H2O freely permeable OSMOLALITY of ECF and ICF, same 280-290,osmol/kg ECF Osmolality dependent on molar concentration of

- mainly Na+ and its anions e.g Cl- HC03- - others : glucose and urea

-protein, contributes 0.5% to plasma osmolality

ICF osmolality dependent on K+ concentration ECF: interstitial fluid and plasma

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Plasma Concentration of Na+ and K+

Na+ conc : ECF > ICF, 140 mM vs 10 mM

Normal Plasma Na+ : 135-145 mmol/l

K+ conc : ECF

Importance of Normal Homeostasis

Changes in ECF Na+ conc leads to water shifting between ICF & ECF

Changes in ECF K+ affects ratio of [K+ in] to [K+ out] and has effects on membrane potential of cells

Changes in ECF Na+ conc and K+ concentration lead to clinical consequences

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Normal Control of Water & Electrolyte Distribution

INTAKE/PRODUCTION LOSS

Water Dietary Intake Oxidative metabolism

Sodium Dietary Intake

Potassium Dietary Intake

Obligatory daily water requirement is 1110 mL

Kidney,Skin, Gut, Lung

Kidney, Skin, Gut

Kidney, Gut Minimum volume of urine

necessary for normal excretion of waste products is 500 ml/24 hrs

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Maintanance of normal ECF and ICF VolumeMechanism Source Stimulus Effect

1. GFR Kidney Na + & water excretion

2. Aldosterone Adrenal reduced renal perfusion

Renal Na+ and water retention

3. ADH Hypothalamus Increased ECF tonicityDecrease blood volume

Pure retention water

4.ANF Cardiac atria Increase blood volume

Renal Na & water retention

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Body Fluid and Electrolyte Imbalance

Can occur as a result of :

Water & electrolyte loss Water & electrolyte overload

lead to clinical effects and complications

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Fluid Loss- water & electrolyte lossCan occur in two situations :

Isotonic fluid loss - water loss accompanied by an equivalent amount of Na+

Hypotonic fluid loss - pure water loss

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Isotonic fluid loss

CAUSES1. Haemorrhage2. Burns3. GIT loss : diarrhoea, vomiting, fistula4. Renal loss : diuretics, Addisons disease

polyuric phase of ARF5. Effusion of ECF into body spaces :

haematoma, ascites, pancreatitis

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Isotonic Fluid Loss

leads to both water and sodium depletion No immediate change to plasma sodium

concentration No fluid movement from ICF to ECF Complication : reduced in plasma volume leading to

circulatory collapse & shock

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Effects and Clinical complications isotonic fluid loss

LOSS OF H2O FROM ECF

ECF Osmolality normal

Stimulate renin-angiotensin

aldosterone release

Na+ & H2O reabsorption

Reduced urine volume

& concentrated

:

Hemoconcentratio n: haematocrit,

blood Hb concentration, Plasma protein

:

Reduced renal blood flow

Reduced GFR

Increased blood urea and creatinine

NO Water movement from ICF

REDUCED ECF/PLASMA VOL.

Circulatory collapse

SHOCK

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Hypotonic fluid loss

Kidney

Skin

Lungs

Reduced water intake

CAUSES Diabetes Insipidus

Osmotic diuresis: e.g diabetes mellitus

Excessive sweating Fever, exercise in hot weather

Hyperventilation

Elderlies, infants, unconscious

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Clinical Effects and complications of hypotonic fluid loss

LOSS OF H2O FROM ECF

ECF Osmolality

Dehydration:Dryness of mouth

Difficulty in swallowing

Stimulate thirst response :

thirst

:

Plasma Na +HYPERNATREMIA

:

Immediate ADH response:

Urinereduced volume &

concentratedReduced urine

output

Water moves out of ICF

CEREBRAL DEHYDRATION

Haemorrhage

Confusion, coma

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Summary of Effects of Fluid loss

Hypotonic Loss Isotonic LossPlasma Na+ Normal tohaematocrit slightlyECF VolumePlasma urea Normal toUrine outputthirst early lateTachycardia & hypotension

Fluid replacement

Late

cautious

Early

rapid

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Hypernatraemia High plasma sodium concentration

Usually caused by hypotonic fluid loss

DIABETES INSIPIDUS -Impt cause of hypotonic loss-Decrease secretion of VASOPRESSIN from posterior pituitary , causes :

i. pituitary /hypoythalamic diseases : tumours

ii. Nephrogenic DI kidney fails to response to vasopressin e.g

chronic renal parenchyma dis.

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Hypernatremia due to Primary Na+ overload. uncommon Causes :

1. Administration of hypertonic NaCl or NaHCO3 to unconscious patients.

2. Infants given feeds containing salt .3. Shipwrecked sailors drinking seawater

high urine Na+ (100-200mmol/l).

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Clinical Effects and Complications of Hypernatraemia

Hypernatremia RESULTS Iin ECF HYPEROSMOLALITY

H2O moves out of ICF Leads to cellular dehydration Clinical effects :

i. stimulate thirst centre - thirstyii. Cerebral cells - mental confusion

and comaiii. Cerebral haemorrhage

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HYPONATRAEMIALow measurable plasma sodium concentration

CAUSES OF HYPONATREMIA

Sodium depletion-Excessive LOSS

KIDNEY : diuretic therapy, hypoaldesteronismAcute tubular necrosis

SKIN: excessive sweating, burns,cystic fibrosis

GIT: vomiting, diarhhoea, fistula

SICK Cell Syndrome

Primary water overloadSIADH: Syndrome of Inappropriate ADH secretion

Dilutional Pseudohyponatremia

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Hyponatremia Sick-cell syndrome

very ill patients, failure of the Na/K ATPase to extrude Na+. re-setting of the hypothalamic osmostat ADH secretion at lower plasma osmolality

Dilutionale.g Diabetes mellitus, plasma glucose draws H2O from ICF into ECF, diluting the plasma Na

+ Pseudohyponatremia - gross hyperlipidaemia. in certain disease states, - replacing 5 -10% of plasma volume.

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Syndrome of Inappropriate ADH Secretion ( SIADH )

Excessive secretion of ADH Hormone Retention of H2O in ECF and ICF Expansion of ECF by water leads to

hyponatremia H2O move from ECF to ICF causing

swelling of cells Complication: cerebral edema - mental

confusion

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SIADH

Low plasma osmolality High urine osmolality

- Urine is inappropriately concentrated despite low plasma osmolality

Urine sodium is high in the face of hyponatremia

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Causes of SIADH

Intracranial Pathology Pulmonary Pathology Ectopic production of ADH Drugs

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Clinical effect of Hyponatremia

H2O moving form ECF into ICF Cellular swelling Cerebral edema - drowsiness, coma

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Disturbance of potassium metabolism

Most body K+ in the cells

Plasma K+ is a small fraction of body K+, and hence not always an accurate reflection of whole body K+ status

K+ concentration ICF vs ECF : 150 vs 5 (mmol/l) ( i.e. levels are 30 x higher in the cell)

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The kidney plays a central role in maintaining K+ balance. Filtered K+ is practically all reabsorbed

K+ play a role in generating cell membrane action

potential

Normal function of some intracellular enzymes: e.g pyruvate kinase

i/c K+ depletion may lead to cell injury and dysfunction e.g - rhabdomyolysis

( necrosis) and renal tubular dysfunction

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Hypokalemia - Causes

1. Decreased potassium intake

2. Renal K+ loss diuretic therapy mineralocorticoid excess renal tubular acidosis acute renal failure diuretic phase

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3. Gastrointestinal K+ Loss Diarrhoea Enteric fistulae Vomiting

4. Conditions : movement of K+ from ECF ICF

Acute alkalosis Diabetic acidosis on treatment with insulin -adrenergic drugs

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Clinical effects/complications of Hypokalaemia

Cardiac arrythmias

Muscle weakness

GIT smooth muscle weakness leading to constipation, progressing to paralytic ileus.

Polyuria and dehydration

Glucose intolerance. Hypokalaemia impairs insulin release

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Hyperkalaemia -Causes1. Excessive K+ Intake

- in patients with renal impairment - treatment with K+ sparing diuretics -overenthusiastic intravenous K+ replacement for hypokalaemia, - rapid transfusion of stored blood,

K+ leaked out of the RBCs.

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Hyperkalaemia

2. Decreased Renal Excretion

Acute renal failure Certain drugs Adrenal insufficiency

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Causes of Hyperkalaemia Conditions causing movement of K+

from ICF to ECF Acidosis displace I/C K+

from the plasma.

K+ release from acutely damaged cells crush injury to muscle acute haemolysis Tumor lysis syndrome

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Spurious hyperkalaemiaThe finding of high serum K+ measurement in a patient in whom circulating K+ is, in fact, normal.

- release from red cells during or after venepuncture - drip arm contamination - release of K+ from white cells or platelets

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Effects of hypokalemia

HYPOKALAEMIA enhances K+ efflux from cell

K+ efflux hyperpolarizes excitable cells, making it increasingly difficult to initiate an action potential. This slows or even blocks nerve conduction, resulting in muscle weakness and/or diastolic cardiac arrest.

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Effects of Hyperkalaemia

Hyperkalaemia opposes K+ efflux, reducing membrane potential, and facilitating depolarization. In the heart this hyperexcitable state can lead to ectopic beats and ventricular fibrillation.

Certain drugs, the sulphonylureas, used to treat diabetes, specifically block K+ channels in pancreatic -cells. By inhibiting K+ efflux down its concentration gradient, these drugs decrease cell membrane polarization and facilitate depolarization, which triggers insulin release. The physiological blocker for these K+ channels is ATP, which explains how glucose, by increasing intracellular ATP in the -cell, stimulates insulin release.

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Effects of hyperkalemia Lowers resting mem potential & inc. the rate of repolarization and predisposes to :

ventricular arrythmias. Cardiac arrest due to ventricular fibrillation may be the first sign.

ECG changes are characteristic (early warning) peaked T-waves absent P-waves widening of the QRS complex

Hyperkalaemia can kill without warning. .

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Figure 1. ECG changes typically seen in hypokalaemia (left) and hyperkalaemia (right). Normal ECG at centre.

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