Water, sodium and potassiuWater, sodium and potassium-1.pptxm-1.pptx

※ Percentage of water in the body changes with the
development of the body:
-As high as 75-80% of the body mass in infants
-50%–60% in normal adults
  60% of body weight in men
 50-55% in women, the difference reflecting the
typically greater body fat content in women
-As low as 45% in older adults
※ Weight of total body water accounts for:
-60% of lean weight in men
-50% of lean weight in women

ᴓ The total body water is distributed primarily between 2
compartments, namely, extracellular fluid (ECF) and
intracellular fluid (ICF) compartments.
ᴓ ECF is present outside cells:
– Makes up about ⅓ (33%) of total body water
– ECF includes:
• Intravascular fluid (¼ of ECF): primary component of plasma
• Interstitial fluid (¾ of ECF): lies outside blood vessels(interstitial)
ᴓ ICF is present inside cells:
– Makes up about ⅔ (66%) of total body water
– Principal component of the cytoplasm of cells

ʘ The major body constituent is water. An .average,
person, weighting 70 kg, contains about 42 litres of
water in total.
ʘ 2/3(28L) of this is intracellular fluid ,
ʘ 1/3(14L) is extracellular fluid(ECF).
ʘ The ECF can be further subdivided into
ʘ plasma (3.5 L)
ʘ interstitial fluid (10.5 L).
ʘ The term dehydration simply means that fluid loss has
occurred from body compartments
ʘ Overhydration occurs when fluid accumulates in body
compartments.

electrolytes distribution in the body fluid compartment

Na & K distribution
 The body of an adult man contains  4000 mmol Na, 70% of which
is freely exchangeable, the remainder being complexed in bone.
 The majority of the exchangeable Na is ECF (135–145 mmol/L), ICF
(4–10) mmol/L.
 Most cell membranes are relatively impermeable to Na, but some
leakage into cells occurs by active pumping of sodium from the ICF to
the ECF by Na+
,K+
-ATPase (the sodium–potassium pump).
 K is the predominant intracellular cation.
  90% of the total body K is free and therefore exchangeable, whereas
the remainder is bound in RBC, bone and brain tissue.
 only approximately 2% (50–60 mmol) of the total is located in the
extracellular compartment (3.5-5.5 mmol/L)
 Plasma potassium concentration is not, therefore, a reliable index of
total body potassium status

Water and Sodium Homoeostasis
 Fluid is separated into compartments by semipermeable membranes.
The membranes are highly permeable to water but require energy to
transport ions.
 Distribution of fluid between intracellular and extracellular
compartments is determined by the concentration of Na+
, chloride,
and other electrolytes.
 Water moves between compartments following osmotic gradients.
 A change in the concentration of solute or water will cause water to
shift between compartments.
 2 processes are responsible for the movement of fluid across
membranes:
– Diffusion: A substance passes from an area of higher concentration to an
area of lower concentration.
– Osmosis: Water is drawn across a membrane toward a region where there is
a higher solute concentration

osmolality vs osmolarity
⁕ Technically different but functionally the same for normal use ( is
the measure of solute concentration)
⁕ Osmolality (with an "l") is defined as the number of osmoles (Osm)
of solute per kilogram of solvent (osmol/kg or Osm/kg),
⁕ Osmolarity (with an "r") is defined as the number of osmoles of
solute per liter (L) of solution (osmol/L or Osm/L).
⁕ As such, larger numbers indicate a greater concentration of solutes
in the plasma, irrespective to the size or nature of the particles

۩ Calculated osmolality
2 [Na]+ 2[K]+ [glucose]+ [urea]
۩ (all concentrations must be in mmol/L)
۩ the reference ranges for serum osmolality are as
follows : Adult/elderly: 275-295 mOsm/kg
H 2O or 275-295 mmol/kg (SI units)
۩ Urine osmolality: can range from 50 - 1400
mOsm/kg water, but average is about 500 - 800
mOsm. After an overnight fast

Arginine vasopressin (AVP) and the regulation of osmolality

reduces the urine flow rate to as little as 0.5
ml/minute in order to conserve body water

Arginin vasopressin (AntiDiuretic Hormone [ADH]).

Urinary Sodium Output Is Regulated By Two Hormones
I. Aldosterone
2. Atrial natriuretic peptide (ANP).
⸎Sodium intake is variable, a range of <100 mmol/day to >300
mmol/day
⸎In health, total body sodium does not change even if intake
falls to as little as 5 mmol/day or is >750 mmol/day.
⸎Sodium losses are just as variable
⸎ln practical terms, urinary sodium excretion matches sodium
intake.
⸎Most sodium excretion is via the kidneys.
⸎Some sodium is lost in sweat (≈ 5 mmol/day) and in the faeces
(≈ 5 mmol/day).

Aldosterone
 Aldosterone  urinary Na+
excretion by  Na+
reabsorption in
the renal tubules at the expense of K+
or H+
.
 A major stimulus to aldosterone secretion is the volume of the
ECF in response to activation of the renin-angiotensin-
aldosterone system (RAAS).
 The renin-angiotensin-aldosterone system (RAAS) is a critical
regulator of blood volume and systemic vascular resistance. It is
composed of three major compounds renin, angiotensin II, and
aldosterone. The conversion of angiotensin I to angiotensin II is
catalyzed by an enzyme called angiotensin converting enzyme
(ACE)
 Specialized cells in the juxtaglormerular apparatus of the nephron
sense  in blood pressure and secrete renin, the first step in a
sequence of events that leads to the secretion of aldosterone by
the glomerular zone of the adrenal cortex

Atrial Natriuretic Peptide (ANP)
֎ Atrial natriuretic peptide is a polypeptide hormone
predominantly secreted by the cardiocytes of the right atrium
of the heart.
֎ It increases urinary sodium excretion apparently by causing
a marked increase in GFR and by
inhibiting renin and aldosterone secretion.
֎ Other structurally similar peptides have been identified,
including brain or B-type natriuretic peptide (BNP), secreted
by the cardiac ventricles and with similar properties to ANP,
and both promote vasodilation and natriuresis.

Causes of water depletion
Decreased intake
 Infancy
 old age
 Unconsciousness
 Dysphagia
Increased loss
 from kidneys: DI
 from skin: Sweating
 from lungs: Hyperventilation
 from gut: diarrhoea (in infants)
Diabetes insipidus:
- Central failure of AVP
secretion,
- Nephrogenic renal tubules
do not respond to AVP.

Water depletion
 Water depletion will occur if water intake is inadequate or if
losses are excessive.
 Excessive loss of water without any sodium loss is unusual, except
in diabetes insipidus
 Loss of water from the ECF causes in osmolality, which, in turn,
causes movement of water from the ICF to the ECF.
 in ECF osmolality will be sufficient to stimulate the thirst centre
and vasopressin secretion.
 Plasma sodium concentration increases; plasma protein
concentration and the haematocrit are usually only slightly
elevated.
 The urine becomes highly concentrated and there is a rapid
decrease in its volume. Because water loss is borne by the total
body water pool, and not just the ECF, signs of a reduced ECF
volume are not usually present.

Causes sodium depletion
֎ Excessive loss
 from kidneys
diuretic phase of acute kidney injury
Drugs (ACEI, AIIRAs)
 from skin
Excessive sweating
Burns
Dermatitis
 from gut: vomiting, diarrhoea, fistulae
֎ Inadequate intake: very rare

Sodium depletion
• In Na depletion, there will be a decrease in ECF
volume
• The normal responses to hypovolaemia are an
increase in aldosterone secretion renal Na
reabsorption in the distal convoluted tubules and
collecting ducts, and  in urine volume as a
consequence of a decreased GFR.
•  vasopressin secretion, which stimulates the
production of highly concentrated urine, occurs
only with more severe ECF volume depletion

Hyponatremia
 Hyponatremia is defined as a serum sodium concentration below
the reference interval of (l35-145 mmol/L)
 Hyponatraemia can arise either because of loss of Na+
or retention
of water.
1) Loss of Na+
Na is the main extracellular cation and plays a critical role in the
maintenance of blood volume and pressure, by osmotically
regulating the passive movement of water. Thus, when significant
Na+
depletion occurs. water is lost with it
2) Water retention:
Retention of water in the body compartments dilutes the constituents
of the extracellular space including Na+
, causing hyponatremia.
Water retention occurs much more frequently than Na+
loss, and
where there is no evidence of fluid loss from history or examination

Pseudohyponetrremia
⁂ Hyponatraemia is sometimes reported in patients with
severe hyperproteinaemia (large increases in total protein
concentration caused by paraproteinaemia) or
hyperlipidaemia (when the plasma will usually appear
turbid to the naked eye)  fractional water content of
plasma.
⁂ In such patients, the increased amounts of protein or
lipoprotein occupy more of the plasma volume than usual,
and the water less.
⁂ Plasma osmolality should be normal in a patient with
pseudohyponatraemia.

Relation between sodium and water homeostasis

It has been emphasized that plasma sodium concentration
depends on the amounts of both sodium and water in the plasma,
so a low sodium concentration does not necessarily imply
sodium depletion.
Indeed, hyponatraemia is more frequently a result of a defect in
water homoeostasis that causes water retention and hence
dilution of plasma sodium.
One of three mechanisms is usually primarily responsible for the
development and maintenance of hyponatraemia, These
mechanisms are:
1) sodium depletion (hypovolaemic hyponatraemia) (diarrhea and
vomiting
2) water excess (euvolaemic hyponatraemia) (SIAD, polydepsia)
3) water and sodium excess (hypervolaemic hyponatraemia)
(CHF, liver cirhosis).

Control of vasopressin secretion

Other causes of hyponatraemia
Addition of a solute to the plasma that is confined to the ECF
will tend to increase ECF osmolality.
As in hyperglycaemia: a decline in plasma sodium is a normal
response to hyperglycaemia (hyperosmolal hyponatraemia in
type 2 DM), and it is essential to measure plasma glucose
concentration in all patients with unexplained hyponatraemia.
there is a shift of water from the ICF to the ECF,  the ECF
sodium concentration, and the  in ECF osmolality stimulates
vasopressin secretion, water retention.
 ECF volume inhibits aldosterone secretion  natriuresis.
Movement of water from the ICF to the ECF does not occur
in uraemia because urea equilibrates between the ECF and the
ICF, thus preventing an osmotic imbalance.

sick cell syndrome
※ osmolal gap = measured serum osmolality−calculated osmolality
A normal osmol gap is < 10 mOsm/kg
※ “sick cell syndrome”  in the permeability of cell membranes to
Na+ and  active removal of Na+
from the cells by energy
dependent cations exchange pump leads to redistribution
hyponatremia with  osmolar gap (> 10)and  in K+
(hyperkalemia).
※ Any transmembrane shift of Na+
would be expected to be
accompanied by an iso-osmotic movement of water, and thus should
not affect plasma Na+
concentration, thus nullifying its effect on
osmolality.
※ Hyponatraemiais frequently observed in patients with either acute or
chronic illness (traumatic shock, DKA, lactic acidosis and multiple
organ failure)
※ Many sick patients may have a degree of stress related  vasopressin
secretion or another cause of SIAD.

Water excess
 Water excess causes dilutional hyponatremia with reduced plasma
osmolality . Either:
1) Usually results from impaired water excretion and
2) Rarely from increased intake (compulsive water drinking, acutely
purely because of excessive water intake, but this is rare
(psychoses) or occur in people who drink large quantities of weak
beer.
3) The acute development of water excess and hyponatremia is a
result of a combination of excessive hypotonic fluid intake and
impairment of diuresis  either continued (and inappropriate)
production of vasopressin (or the presence of a drug having a
vasopressin-like action)
 Most patients who are hyponatraemic due to water retention have the
so-called syndrome of inappropriate antidiuresis (SIAD)

⸙SIAD was previously called ‘syndrome of inappropriate antidiuretic
hormone secretion “SIADH”, but because inappropriate secretion of
the hormone is not always present in patients satisfying its diagnostic
criteria, and vasopressin is now the accepted name for ‘antidiuretic
hormone’, the newer term syndrome of inappropriate antidiuresis is
more appropriate.
⸙There are at least four different types of SIAD:
۩ tumors may produce the hormone (ectopic production)
۩ abnormal regulation of vasopressin release, as in artificial
ventilation  stimulation of thoracic volume receptors
۩ incomplete suppression of vasopressin release when osmolality
falls (a ‘vasopressin leak’)
۩ inappropriate activation of the aquaporin water channel, because
of genetic mutations of the vasopressin

The laboratory criteria for the diagnosis of SIAD are:
۞ hyponatraemia
۞ decreased plasma osmolality
۞ continued natriuresis (>30 mmol/L)
۞ inappropriately concentrated urine
۞ no clinical evidence of volume depletion (e.g. due to diuretics) or
oedema
۞ normal renal function
۞ normal adrenal function
۞ normal thyroid function

cerebral salt wasting and SIAD
⸎Cerebral (or central) salt wasting (CSW) describes the
combination of hyponatremia and natriuresis in the presence of
cerebral pathology.
⸎Associated with brain injury and cranial surgery. The
pathogenesis is uncertain: mechanisms may include release of
natriuretic peptides by the brain. It is sometimes mistaken for
SIAD.
⸎The difference between (CSW) and SIAD is that patients with
(CSW) should have clinical and biochemical features of
hypovolemia and marked natriuresis (urine sodium >100
mmol/L) and diuresis while patients with SIAD are typically
euvolemic,

NOTE 1
 Oedema is not a feature of SIAD:
the excess of water is distributed
throughout both the ICF and the
ECF, and the effect on ECF volume
is insufficient to cause oedema.
 Measurement of vasopressin
concentration is seldom helpful in
differential diag nosis: raised
values are present in the majority
of patients with hyponatraemia,
irrespective of the cause.
NOTE 2
 Severe hyponatraemia has
been reported in individuals
undertaking endurance athletic
events, such as marathon
running.
 This is due to stress-mediated
secretion of vasopressin
combined with an
inappropriately high intake of
low-solute fluids.

Combined water and sodium excess
• Combined water and sodium excess is a frequent cause of
hyponatraemia associated with cardiac failure (cardio-renal
syndrome), hypoalbuminaemia and hepatic cirrhosis.
• The fact that there is sodium excess is indicated by signs of
increased ECF volume (e.g. peripheral oedema or ascites).
• cardio-renal syndrome: CHF COP  prerenal hypoperfusion 
stimulate RAAS and non-osmotic release of AVP together with 
secretion of ANP, counters the sodium-retaining action of
aldosterone

Sodium excess and Hypernatraemia
⁑ Sodium excess can result from increased intake or decreased excretion, more
often due to impaired excretion than to excessive intake
⁑ Hypernatraemia is less common than hyponatraemia but is much more
frequently of clinical significance. The causes include pure water depletion,
combined sodium and water depletion with water loss predominating, or
sodium excess; of these, excess sodium is the least common
⁑ frequent finding in elderly people, as a result of inadequate water intake; in
hospitals, it is often iatrogenic.
⁑ Usually the cause is obvious from the history and clinical observations as in
DI or in The pathophysiological condition of:
1) primary hyperaldosteronism (Conn's syndrome), where there is excessive
aldosterone secretion and consequent Na+
retention by the renal tubules.
2) Similar findings may be made in the patient with (Cushing's syndrome),
where there is excess cortisol production. Cortisol has weak
mineralocorticoid activity.
However, in both these conditions the serum Na+
concentration rarely rises
above 150 mmol/L

Potassium Homoeostasis
urinary potassium excretion depends on several factors:
⁕ the circulating concentration of aldosterone
⁕ intravascular volume (reduction stimulates aldosterone secretion)
⁕ the relative availability of hydrogen and K+
in the cells of the distal
tubules and the collecting ducts
⁕ the capacity of these cells to secrete hydrogen ions
⁕ the rate of flow of tubular fluid: a high flow rate favours the transfer
of K+
into the tubular lumen
⁕ the amount of sodium available for reabsorption in the distal
convoluted tubules and the collecting ducts
⁕ dietary potassium intake (the kidneys’ capacity to retain K+
is
enhanced by low intake, and vice versa)
⁕ Mg+
status: Mg+
depletion  K+
secretion from the distal nephron (it
also impairs the action of the Na+
–K+
pump responsible for the
uptake of K+
into the ECF) as in GIT or renal loss.

 In renal tubules, K+
is secreted in exchange for either Na+
or H+
: 
delivery of Na+
 the potential secretion of K+
.
 Aldosterone stimulates K+
excretion both:
─ indirectly, by increasing the active reabsorption of Na+
in renal tubules
by activation of the RAAS in response to hypovolaemia, and
─ directly, by  active K+
secretion in renal tubules hyperkalaemia.
 Because both H+
and K+
can neutralize the nephron membrane potential
generated by active Na reabsorption, there is a close relationship
between K+
and H+
ion homoeostasis.
 In an acidosis, H+
will tend to be secreted in exchange to K+

hyperkalaemia in acidosis and same in systemic acidosis(buffering)
 In alkalosis, fewer H+
will be available for excretion and there will be
an  in K+
excretion  hypokalaemia in alkalosis.
 An exception, renal tubular acidosis (RTA) caused by defective renal
H+
excretion. In this condition, because of the  in H+
excretion, K+
secretion must  to balance Na+
reabsorption. The result is the unusual
combination of hypokalaemia with acidosis.

• Healthy kidneys are less efficient at conserving K+
than Na+
: even on
a K+
free diet, urinary excretion remains at 10–20 mmol/24 h.
• Because there is also an obligatory loss from the skin and gut, the
kidneys cannot compensate if intake declines to much less than 40
mmol/24 h.
• Movement of K+
between the ICF & ECF can have a profound effect
on plasma K+
concentration. K+
move into cells from the ECF in
exchange for Na+
, via the transmembrane, (Na+
,K+
-ATPase).
Hyperkalaemia can result if the activity of this pump is impaired or if
there is damage to cell membranes.
• K+
uptake into cells is stimulated by insulin.
• K+
uptake is impaired In Mg depletion

Decreased K+
intake
Transcellular K+
movement
alkalosis
insulin administration
Increased K+
excretion
Renal
diuretics
diuretic phase of ARF
Aldosteronism (1ry & 2ry)
Cushing syndrome
Renal tubular acidosis (types 1 and 2)
Mg+
depletion
Extrarenal
diarrhoea
vomiting,
gastric aspiration
fistulae
excessive sweating
Potassium Depletion
and Hypokalaemia
Hypokalaemia is more
common than hyperkalaemia
K+ depletion occurs when
output exceeds intake. Except
in patients who are fasting,
inadequate intake is rarely the
sole cause of K depletion.
 loss of K+
, either from the gut
or kidneys.
Clinical features and
investigation

Potassium Excess and Hyperkalaemia
 K+
excess can be caused by:
─ excessive intake always iatrogenic
─ or decreased excretion (kidney failure).
 Drugs are causes of hyperkalaemia:
─ combinations of K+
-sparing diuretics with angiotensin-converting
enzyme inhibitors (ACEIs),
─ Angiotensin II receptor blockers (ARBs) or
─ Non-steroidal anti-inflammatory drugs (NSAIDs) tend to  renal
K+
excretion.
 Hypoaldosteronism
 Redistribution of K+
from the ICF to the ECF even in a patient with
k+
depletion
─ diabetic ketoacidosis (DKA)
─ K release from damaged cells e.g, rhabdomyolysis, extensive trauma
─ Insulin deficiency

Pseudohyperkalaemia
⁋Caused by the leakage of K+
from blood cells in vitro,
⁋Although often caused by frank haemolysis, if there has been a delay
in separation of the plasma from the blood cells.
⁋The normal clotting process releases K+
from white cells and
platelets: this normally contributes a negligible amount to serum K+
concentration, but the effect is exaggerated in patients with high
WBC or platelet counts (e.g. in leukaemia).
⁋Measurement of K+
using a blood tube containing heparin
anticoagulant with rapid centrifugation and separation of the plasma
may identify this cause

Investigation of hyperkalaemia
 Chronic mild hyperkalaemia, with a serum k+
concentration of 5.3–
6.0 mmol/L, is a relatively common finding, especially in elderly
patients.
 History and examination
 DM, kidney disease, ACTH, drug history, leukaemia, ….etc
 Hemolysis  report the case
 Transtubular potassium gradient (TTKG): if the patient may have
hyporeninaemic hypoaldosteronism.
─ in the elderly and often a feature of early (e.g. diabetic)
nephropathy, with hyperkalaemia.
─ Measure paired serum and urine K+
concentrations and osmolalities
to calculate the transtubular K+
gradient (TTKG), a measure of the
ability of the nephrons to excrete K+
appropriately.
─ In hyporeninaemic hypoaldosteronism, the TTKG is low.

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