The Chemical

Pathology of Fluid and

Electrolyte Balance -2
Prof. Abayomi O. Akanji
Clinical Chemistry Unit
Department of Pathology
Faculty of Medicine
 Important Concepts & Definitions

◆ Concentrations Measured Parameters (P, Ur)

◆ Compartments ◆ Sodium
◆ Contents ◆ Potassium
◆ Volumes ◆ Chloride
◆ Rates of gain & loss ◆ Bicarbonate
◆ Urea & Creatinine
All five concepts are ◆ Osmolality
interconnected!
Estimated Parameters
In the main the laboratory ◆ Water
measures concentrations. ◆ Osmolality
The other factors are deduced ◆ Osmolar gap, Anion gap
Hyponatraemia due to SIADH
ADH Renal water reabs IVV

Urine volume Urine osmolality

Haemodilution

Renal Na reabs Plasma osmolality

Urine [Na] Plasma [Na]

Plasma [creat] / [urea]

 Polyuria
◆ Urinary volume > 3L/day
◆ Caused by:
◆ Water diuresis
– Decreased ADH secretion
◆ Physiological: compulsive water drinking
◆ Pathological: neurogenic diabetes insipidus
– Defective ADH action on the kidney
» Nephrogenic diabetes insipidus
◆ Congenital
◆ Renal disease (pyelonephritis, analgesic nephropathy)
◆ Hypokalaemia, hypercalcaemia
◆ Drugs e.g. lithium, outdated tetracyclines
◆ Solute diuresis
» Sodium: increased intake, diuretics, renal salt-losing disorders
» Urea: CRF, diuretic phase of ARF, hypercatabolic states
» Glucose: diabetes mellitus
Fluid deprivation test - Interpretation
◆ Patient deprived of
water overnight and Status Posmol ADH Uosmol
through test mmol/kg given (mmol/kg)
◆ 0800h: urine collected Normal ~300 no >800
hrly, Osmol measured -
Terminate test if Uosmol Neurogenic > 300 yes preADH <300
> 800mmol/kg – patient DI post- > 800
normal
◆ Hourly Uosmol until Partial > 300 yes Post > 800
plateau is reached (2 neurogenic
values diff by < DI
30mmol/kg) Nephro- > 300 yes preADH <300
◆ blood sample for Posmol genic DI post- < 300,
No change
◆ Give 5u aq vasopressin
s.c., and measure Partial > 300 yes preADH <300
Uosmol after 1hr nephro- post- < 300,
genic DI No change
Potassium - Major intracellular cation –
high cellular concentration maintained by Na/K pump
◆ Homeostasis: balance between
Major functions: ◆ Adequate intake
◆ normal neuro- ◆ Distribution between ICF and
muscular function ECF: influenced by acid-base
status, aldosterone, insulin,
◆ membrane catecholamines
polarization ◆ Excretion and losses
Balance – Gut: diarrhea, vomiting,
renal failure → ▲ losses
◆ Total body K: 3500 mmol
– Renal: influence of
◆ Intracellular K: 3400 aldosterone, cellular K+
mmol (130-150 mmol/L) concn and rate of luminal
◆ Extracellular K: 75 mmol urine flow
(3.0-5.0 mmol/L)
Potassium Distribution
Total
Na K mmol
Plasma 140 4.5 2% 70
Interstitial fluid 140 4.5
Intracellular fluid 10 110 98% 3400

K concentrations of body fluids (mmol/L):

Gastric Pancreatic/ Small bowel Diarrhea

Plasma Sweat Cells
juice bile fluid fluid fluid

5 10 10 5 5 40 130
Relationship of K+
to H+
• K+ and H+ exchange across
cell membranes
• Both bind to negatively
charged proteins (e.g. Hb)
• Changes in pH cause shifts in
the equilibrium
• acidosis (pH < 7.35) –
K+ moves out of cells
while H+ moves into cells
► Hyperkalaemia
• alkalosis (pH > 7.45) –
K+ moves into cells and
H+ moves out of cells
► Hypokalaemia
** K+ depletion/ excess can
affect acid-base status
Disorders of Potassium - In clinical situations we
measure plasma potassium concentrations
◆ Plasma K range : 3.6 to 5.0
mM
◆ K+ < 3.0 or > 6.0: dangerous
◆ Cardiac conduction defects
◆ Abnormal neuromuscular
excitability
◆ Clinical Problems are common
but typically iatrogenic and
avoidable
Plasma K+ not reflect body K+
◆ Small proportion of total K in
plasma
◆ Total body K determined by
total cell mass
Exchange ICF - ECF affects
Plasma K+
◆ Acidosis/alkalosis
◆ Insulin/glucose therapy:
– cellular uptake of K+ is
promoted by insulin
– insulin secretion ▲by
hyperkalaemia
◆ Adrenaline: infusions result
in a sustained fall in plasma
K+ due to K+ entry into cells
especially muscle
◆ Rapid cellular incorporation
- TPN, leukemia
◆ Haemolysis → leakage of K+
from cells
 Causes of Hyperkalaemia
◆ Artefactual
– Delay in sample analysis,
improper collection
– Haemolysis, leucocytosis,
thrombocytosis
– Drug therapy – (K+
sparing diuretics, ACE
inhibitors)
◆ Renal
– Acute & Chronic Renal
Failure
◆ Acidosis e.g.
– Diabetic ketoacidosis
◆ Mineralocorticoid
Dysfunction
– Adrenocortical failure
– Mineralocorticoid
resistance (antagonism)
– e.g. spironolactone
◆ Cell Death
– Cytotoxic drug therapy
◆ Increased input:
– oral/IV therapy +
decreased renal
function
 Causes of Hypokalaemia
◆ Low intake: ◆ GIT losses
– poor IV therapy – vomiting
– chronic alcoholism – diarrhea / laxatives
– anorexia – fistulae
◆ Increased urine loss ◆ Disturbed distribution
– diuretics / osmotic between ICF and ECF:
diuresis – alkalosis
– tubular dysfunction – insulin/glucose therapy
– mineralocorticoid – Hypokalaemic periodic
excess paralysis
◆ Dialysis: peritoneal and
haemo-dialysis
 Clinical implications K+ abnormalities
◆ Consequences of K+
depletion (< 2.5 mM)
◆ Neuromuscular:
lethargy, muscle
weakness, heart
arrhythmias &
conduction defects
• Kidney: Polyuria,
Reduced concn ability,
alkalosis ► increase
renal HCO3 production
• Gut: paralytic ileus
 Chloride
◆ Homeostasis closely related to that of sodium
◆ Homeostasis: balance between

– Intake: 100-200mmol/day (mainly as NaCl) –

absorption mainly in the small intestine
– Excretion and losses
» Extrarenal:
◆minimal – sweat 5mmol/day

faeces <5mmol/day
» Renal: 99% of filtered load reabsorbed
 Plasma chloride
◆ varies directly with the Na concentration and indirectly with
the HCO3 concentration
– Hyponatraemia – assoc with hypochloraemia
– Hypernatraemia – assoc with hyperchloraemia
– High bicarbonate – assoc with hypochloraemia
– Low bicarbonate – assoc with hyperchloraemia
 Plasma chloride useful in:
- Calculation of anion gap: [(Na + K) – (Cl + HCO3)]
- Spot urinary chloride useful in evaluation of:
- Metabolic acidosis
- Volume depletion
 Disorders of chloride metabolism
◆ Hyperchloraemia - causes Hypochloraemia – causes

◆ Artefactual: Sample from an IV ◆ Hyponatraemia

infusion arm
◆ Association with Hypernatraemia
◆ Metabolic alkalosis
– primary
◆ Metabolic acidosis (normal anion gap)
– secondary to respiratory
– Diarrhea
acidosis
– Renal tubular acidosis
– Ureterosigmoidostomy
– Use of carbonic anhydrase
inhibitors
◆ Respiratory alkalosis (chloride shift)
 Anion gap - measure of anions (other than Cl-
and HCO3-), which balance cations (Na+ and K+)
◆ ‘Unmeasured anions’ = (Na+ + K+) – (Cl- + HCO3-) mmol/L
◆ Increased anion gap will occur if there is:
– ▲ protein, PO42-, SO42-, or Organic acids
– Presence of abnormal anions e.g. drugs (ethanol, ethylene glycol)
◆ Clinically most important cause of high anion gap
– increased plasma organic acids – lactate, ketones

Major cations Concn mM/L Major anions Concn mM/L

Na+ 140 Cl- 100
K+ 4 HCO3- 27
Ca 2+ 4.5 Protein 15
Mg 2+ 1.5 PO42- + SO42- 3
Organic acids 5
Total 150 150
 Summary
◆ Water & electrolyte metabolism central to much acute
clinical care
◆ Multitude of causes of disturbances & many
important effects
◆ Most clinical problems can be solved using a common
sense approach to the concepts of
– volumes
– compartments
– contents
– concentrations
– input /output