The Chemical

Pathology of Fluid and

Electrolyte Balance 1
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
 Fluid & Electrolyte Disorders

Important in: Clinical Examples:

◆ maintenance of cellular ◆ Hemorrhage - accidents, surgery,

homeostasis obstetrics
◆ CVS physiology - BP ◆ Diarrhea & Vomiting

◆ renal physiology - GFR ◆ Poor intake – elderly, unconscious

◆ Electrophysiology: heart, CNS ◆ Increased losses - pyrexia, heat

◆ Diabetes insipidus
◆ Diabetes mellitus
Abnormal electrolytes
◆ primary disease state e.g. ◆ Diuretic therapy

diabetes ketoacidosis, chronic ◆ Endocrine disorders - ADH,

renal failure aldosterone
◆ secondary consequence of many
diseases Commonest Chemical Pathology
◆ iatrogenic Test - - 100,000 per year
 Body Fluid Distribution
Water (L) [Na] mM [K] mM
-------------------------------------------------------------------------------
ECF
Vascular 3.5 140 4.5
Interstitial 10.5 140 4.5
------------------------------------------------------------------------------
ICF
Intracellular 28 10 110
------------------------------------------------------------------------------
TOTAL 42
--------------------------------------------------------------------------------
Osmolality
◆ Measured osmolality:
– Usually measured by freezing point depression
– a measure of the osmotically active particles (ions and
molecules) present in a fluid - in plasma: Na, K, Cl, HCO3,
urea, glucose
◆ Calculated osmolality
– A rough estimate of the plasma osmolality (285-
295mmol/kg)
– Determined by the equation: 2 (Na) + urea + glucose (mM)
◆ Osmolar Gap
– Difference b/w calc & meas osmolality - usually <
10mmol/L
– If plasma contains a large amount of ‘unmeasured’
substances e.g. ethanol, the gap between measured and
calculated osmolality widens = osmolal gap
 Water homeostasis

◆ Distribution: varies with age and sex

◆ Water as % total body weight
 Adults 60%; Infants 75%
 Young: males 60%; females 54%
 Elderly: males 50%; females 45%
 Water Intake/Loss depend on:
 Diet
 Activity & Environment
 Minimum amount to maintain normal body function for:
 Renal elimination of metabolic waste products
 Replacement of losses from skin, lungs, gut
Daily water balance
at least 600mmol solute excreted by kidney daily
insensible loss from skin and lungs: increased in a/c, hot weather
metabolic water obtained from metabolism of CHO, fats, proteins
ICF and ECF water content depend on:
Fluid shifts across cell membranes
Loss of fluid from the body
Fluid intake

Input Output
Oral fluids 600 urine 500
Food 500 Lungs 400
Metabolism 400 Skin + gut 500 + 100 = 600

1500 1500
 Cell membrane shifts
◆ Movement of water across cell membranes is in response to
changes in osmolality
◆ K+ is major ICF cation while Na+ is major ECF cation - both
remain in their compartments by action of SODIUM PUMP
◆ Na+, the major ECF cation – responsible for osmotic pressure
of ECF - changes in its concentration influence osmolality and
thereby fluid movements between ICF and ECF
– ▲ECF Na+ or ▼ECF H20 → ▲ ECF osmolality
→ ▲ water flow from ICF to ECF (cellular dehydration)
– ▼ECF Na+ or ▲ECF H20 → ▼ECF osmolality
→ ▲water flow from ECF to ICF (cellular overhydration)
Loss of body fluid
◆ Mainly controlled by the kidney – collecting duct in medulla
◆ Influenced by ADH – synthesized in hypothalamus/posterior
pituitary – formation and secretion regulated by hypothalamic
osmoreceptors and atrial/carotid sinus baroreceptors
◆ Osmoreceptors respond to change in osmolality (> ~2%):
 ▲ECF osmolality → ▲ADH release →▲renal water
reabsorption to dilute ECF → concentrated urine
 ▼ECF osmolality → ▼ADH release →▼renal water
reabsorption to dilute ECF → dilute urine
◆ Baroreceptors respond to changes in IVV (> ~10%):
 ▼IVV →▲ADH release →▲renal H20 absorption, restore IVV
 ▲IVV →▼ADH release →▼renal H20 absorption, restore IVV
Control of extracellular volume
dependent on extracellular Na content
▲ ECF [Na] → ▲ECF osmolality →
– thirst → ▲oral fluid intake
– ▲ secretion of ADH → ▲renal water retention
– water shift out of cells into the ECF
– ▲ ECF volume

▼ ECF [Na] → ▼ ECF osmolality →

– ▼ secretion of ADH → ▲renal water loss
– water shift from the ECF into cells
– ▼ ECF volume

 In some situations, baroreceptors can override osmoreceptors e.g.

▼ IVV with ▼osmolality → ADH secretion and water retention

◆ The control mechanism acts to maintain IVV and blood flow

ADH (arginine vasopressin – AVP)
◆ Produced by median eminence of hypothalamus, passes into
post pituitary and release increases when osmolality rises
◆ Functions:
– Decreases renal water loss
– Increases thirst
◆ Other factors stimulating ADH secretion:
– stress e.g. trauma, surgery
– Drugs e.g. opiates, barbiturates
◆ Other factors suppressing ADH secretion:
– drugs e.g. alcohol, phenytoin, atropine

Simple tests to ascertain ADH status :

– measure plasma & urine osmolality: urine > plasma suggests ADH is active
– measure plasma & urine urea: urine >> plasma suggests water retention
 Renin - angiotensin system
◆ Renin -> angiotensin -> aldosterone
◆ Activated by reduced IVV
– Na depletion
– hemorrhage
◆ Causes renal Na retention

◆ Simple test to ascertain R/A/A status :

– measure plasma & urine Na
– if urine Na < 10 mmol /L suggests R/A/A active
Regulation of sodium balance
Balance: input = output Renal handling of Na
◆ Intake: mainly Diet (100- ◆ Daily – 25000mM filtered, less
200mmol/day or 6-12g) than 1% appears in urine
◆ Losses: ◆ PCT: 75% reabsorption –

◆ sweat: < 10mM/day

energy dependent process
◆ Ascending loop of Henle: 20-
depends on weather
◆ faeces <10mM/day
30% reabsorption
◆ DCT: 5-10% reabsorp + K
◆ Kidneys: major route -
secretion, under aldosterone
– ▼IVV → ▲ renal Na ◆ Collecting ducts: fine
retention regulation, under aldosterone
– ▲IVV → ▲renal Na (± natriuretic peptides – ANP,
loss BNP)
Control of renal sodium excretion
GFR and renal blood flow
◆ ▼ GFR → ▼ tubular flow → ▲ renal Na conservation
◆ ▲ GFR → ▲tubular flow → ▲ renal Na loss

Renin-angiotensin-aldosterone system
Natriuretic peptides – ANP, BNP: associated with
– Increased GFR + filtration fraction
– Natriuresis, diuresis and kaliuresis
– Decreased renin and aldosterone secretion
– Decreased BP
 Clinical Problems
Problems with urinary
Hyponatraemia: dilution: renal tubular
◆ Too little Na in ECF dysfunction
◆ ▼Fluid delivery to tubules:
◆ Excess water in ECF shock, hypovolaemia
◆ ▼ dilution at tubules: thiazide
Hypernatraemia: & loop diuretics, osmotic
diuresis
◆ Too little water in ECF
◆ ▲ ADH activity in collecting
◆ Too much Na in ECF ducts:
» volume depletion
Dehydration » severe stress
◆ Water deficiency » drugs with ADH-like
activity e.g.
◆ Na and water depletion chlorpropamide
» syndrome of inappropriate
ADH secretion (SIADH)
 Dehydration
Definition: Water loss with or without sodium loss.
May be:
◆ Isotonic (normonatraemic) dehydration:
– Na and H2O loss in ratio of ~140mmol Na / liter of pure water;
– normal plasma [Na] – 135-145mM
◆ Hypertonic (hypernatraemic) dehydration:
– H2O lost in excess of Na: per liter H2O lost, < 135mmol Na lost
– plasma [Na] > 145mM
◆ Hypotonic (hyponatraemic) dehydration:
– Na in excess of H2O : per liter H2O lost, >145mmol Na lost
– plasma [Na] < 135mM
Laboratory Investigation of Disorders
of Plasma Na Concentration
Plasma Urine Posmol:
Plasma Status
osmol osmol Uosmol
– electrolytes
▲fluid dilute
– Na, K Euhydration N ↓
intake urine
– Cl, HCO3:
for acid-base ▼fluid concn
N ↑
balance intake urine
– urea, hypotonic Maximal
creatinine: Over-
fluid ↓ ↓↓ urine
reduced hydration infusion dilution
GFR, renal
failure, Maximal
Reduced
Dehydration ↑ ↑↑ urine
◆ Osmolality fluid intake concn
◆ Urine ↓ concn &
Renal failure var var 1.0
electrolytes dilution
Urine electrolytes:
24hr urine sodium depends on intake so Spot urine &
plasma Na more useful
Spot urine Na
Disorder Etiology Pathophysiology
mmol/L

Volume depletion Extrarenal salt loss Renal stimulation to

Low < 10
± Hyponatraemia e.g. diarrhea conserve Na

Renal salt loss

e.g. diuretics, High > 20
nephritis, SIADH

Oliguria: urine vol Pre-renal e.g. blood Aldosterone acts to Low < 10
< 400ml/day loss, dehydration increase Na retention

Renal e.g. acute ▼Na reabsorption by High > 20

tubular necrosis damaged tubules
Clinical Demonstration of Hydration Disorders
Classification of hyponatraemia:
Plasma Na relatively less than normal equiv water content
1. ▼body Na & H2O:
hypotonic dehydration –
H2O & Na loss replaced
by salt poor fluids e.g.
water, 5% dextrose
◆ Extrarenal Na loss:
– Skin: excessive sweating,
burns
– Gut: vomiting, diarrhea
◆ Renal Na loss:
– Osmotic diuresis e.g.
severe diabetes
– Diuretic therapy
– Mineralocorticoid
deficiency – Addison’s
disease
– Salt losing nephritis,
renal failure
2. Normal body Na with normal or
increased body water –
Euhydration
– Normal plasma osmolality:
pseudohyponatraemia –
glucose, hyperlipidaemia
– Low plasma osmolality: salt
poor fluids + stress,
hypovolaemia, SIADH, drugs
3. increased body Na and water
– Edematous states: CCF,
cirrhosis
– Renal failure: acute/chronic
renal failure with ▲water
intake (oral, IV)
Syndrome of Inappropriate ADH secretion (SIADH)
Continued and inappropriate secretion of ADH in face of plasma
hypo-osmolality & normal or slightly increased ECF volume

◆ Diagnostic Criteria: ◆ Common causes of SIADH:

◆ ▼plasma osmol (low [Na])
◆ Ur osmolality high relative to
plasma (e.g. > 200mmol/kg)
◆ ▲urinary [Na] ( > 30 mM)
without hypovolaemia
◆ Normal pituitary, adrenal,
cardiac & liver function &
absence of drugs/other
agents
◆ Respond to water restriction
by ▲ Posmol & [Na]
◆ ▲ plasma [ADH] (assumed)
◆ Malignancy: bronchogenic,
brain, renal, lymphoma
◆ Cerebral disorders: infections,
trauma, tumors
◆ Pulmonary disorders:
pneumonia, TB,
◆ Miscellaneous: porphyria,
Guillain-Barre syndrome
◆ Exclude Drugs: morphine,
chlorpropamide,
barbiturates, carbamazepine,
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]