1. Water homeostasis is closely related to sodium balance and is primarily regulated by the kidneys and hypothalamus. 2. Total body sodium accounts for over 90% of extracellular fluid content and osmotic activity, and changes in sodium concentration directly impact water distribution and balance. 3. The kidneys play a key role in maintaining sodium and water homeostasis through precise control of filtration, reabsorption and excretion in response to various hormones and physiological factors.

1. DR ADEDEJI T.A
DEPARTMENT OF CHEMICAL
PATHOLOGY
O. A. U, ILE IFE.

2.  Introduction
 Distribution of water in the body
 Functions of water
 Water balance
 Control of water balance
 Conclusion

3.  Water is the single most abundant body
constituent
 Often referred to as biological universal solvent
 it constitutes about 60% of the adult human weight
 This % actually decline with age
 The water contents of the tissues of the body varies
 Men tend to have higher % than women
 Water balance is closely related to that of Sodium

4.  In a 70kg man TBW is about 42L
 It is distribtd in three different compartments:
 ICC 24L 62.5%TBW 40%bw
 ECC 18L
 Interstitial 13L 30%TBW 15%bw
 Intravascular 5L 7.5%TBW
5%bw
 The TBW and its distribution is determined
mainly by the total body sodium.

5.  Medium for all chemical reactions
 Transport substs such as hormones and
nutrients
 Dilutes toxic and waste substances
 Distributes heat around the body

6.  Body water is in a constant state of motion
 In a normal healthy individual :
INPUT=OUTPUT
 ~ 90% come via the GIT
 ~ 10% = metabolic

7.  In a normal healthy adult water is lost from the
body via:
 Kidneys (urine) 62%
 Skin (diffusion & sweat) 19%
 Lungs (water vapour) 13%
 GIT (faeces) 6%

8.  Both intake and loss of water are controlled by
the osmotic gradient across the cell membs in
the hypothalamic centres
 Sodium is the predominant ecf cation and,
with its associated anions, accounts for more
than 90% of the osmotic activity of the ECF.
 Thus some of the factors involved in water
balance act via sodium control

9.  Neural factors: Thirst
Autonomic nervous system
 Renal factors: GFR
Renal interstitial tonicity
 Hormones: Arginine vasopressin
renin-angiotesin system
Aldosterone
Artrial natriuretic peptide

10.  Thirst
 A major determinant of intake
 normal functioning of thirst centre is influenced by:
 ECF tonicity
 Blood volume
 Others e.g. pain and stress

11.  Water output control is mainly via the kidney
 Other route of fluid loss cannot be controlled to
meet body requirement
 130-180L of water is produced as glomerular
filtrate
 Only about 1-2L finally appear as urine

12.  Proximal convoluted tubule
 Pars recta
 Loop of Henle
 Thin descending
 Thin ascending
 Thick ascending
 Distal convoluted tubule
 Collecting tubule and ducts

13.  Kidney has both diluting and concentrating
abilities
1. Ability to remove electrolytes
2. Ability to reabsorb water from the luminal fluid
in the collecting ducts

14.  There is a graded increase in medullary
interstitial osmolality
 This is provided for by the countercurrent
systems
 Multplier –loop of Henle
 Exchanger- vasa recta

15.  Involves 5 major steps:
a. Active transport of Na, K and Cl in the TAL =
b. The rise in outer medulla tonicity induce water
reabsobtion from the upper CD={urea}
c. Movt of urea along its conc. gradient from the
inner medullary CD=
d. Inner medullar interstitium draw water #from
the DTL of L. Henle=
e. NaCl passes out of ATL into the medullar

16.  Maintains the medullar interstitial tonicity
 There is exchange of solute and water btw the
vasa rectae and the medullar

17.  Decrease GFR leads to decease in the rate of
flow in the loop =increase conc. of urine

18.  Diluting segment of the loop of Henle
 The rate of fluid delivery from this segment is
about 30L /day
 Further processing involves reabsorbtion of
water the collecting duct influenced by AVP

19.  Aka ADH
 A nanopeptide synthesized in the supraoptic
and paraventricular nuclei of hypothalamus
 Acts on the collecting ducts resulting in
increased permeability
 It is released in response to a number of stimuli

20. 1. ECF tonicity
 Osmoreceptors –very sensitive mech that
responds to change in plasma tonicity as low as
1-2% i.e. abt 3mmol/L Na
2. Blood volume
 barroreceptors- responds to gross change as
much as 10% change in volume
 Can overide the effect of ECF tonicity on AVP
secretion in some condts

21.  Stress e.g. pain and trauma
 Nausea e.g.post surgery
 Drugs e.g.opiates

22.  Depends on tonicity gradient across the cell
memb.
 In a normal healthy person ICF tonicity (K) and
ECF (Na) are similar (abt 300mmol/kg)
 ECF (and ICF) volume vary with total ECF Na
conc.
 Thus water balance depends on ECF {Na}

23.  Thus water balance depends on the extracellular sodium
content:
 ↑ECF sodium -> ↑ECF tonicity ->
 ↑Thirst (increase water intake)
 ↑AVP secretion (increase renal water re-absorption)
 Water shift from ICF to ECF
 a + b + c -> ↑ECF volume and ↓ICF volume
 ↓ECF sodium -> ↓ECF tonicity ->
 ↓Thirst (decrease water intake)
 ↓AVP secretion (decrease renal water REABSORPTION)
 Water shift from ECF to ICF
 a + b + c -> ↓ECF volume and ↑ICF volume
 Thus total body sodium (most of which is in the ECF) can
be said to control the extracellular volume (and water
balance) and, as will be seen later, the extracellular volume
controls the total body sodium (and sodium balance).

24.  Total body Na = 3000-3500millimoles
 Over 90% in the ECF
 Kidney is the main controller of homeostasis
 < 1% of filtered Na appear in the urine
 Na balance depend on rate of excretion

25.  Proximal tubule 70-75%
 Loop of Henle 15-25%
 DCT 1-5%
 CD 1-2% (fine tuner of Na homeostasis)

26.  GFR
 Renin-angiotensin system/ aldosterone
 Atrial natriuretic peptide ANP
 Increase GFR
 Natriuresis
 Kaliuresis
 Decrease renin and aldosterone secretion
 Diuresis

27.  Increased intravascular volume (or effective
arterial blood volume) results in increased renal
sodium excretion (decreased aldosterone plus
increased ANP).
 Decreased blood volume produces renal sodium
retention (increased aldosterone, decreased ANP)

28. EVERY STUDENT SHOULD BE ABLE TO AT
LEAST:
 Explaining the functions, distributions, factors
and mechanisms by which water homeostasis,
which is closely related to that of sodium, is
achieved.

30.  Na+ – most abundant ECF cation, accounts for
most of osmotic activity and this depends on
concentration. I.e. on relative amount of Na and
H2O in ECF rather than on absolute quantities of
each.
 90% of all ECF cations.
 Central role in maintaining normal distribution of
water and osmotic pressure in the ECF.
 Major contributor to plasma osmolality.
 At the cellular level, Na+/K+ ATPase pump= 3Na+
out and 2K+ in as ATP is converted to ADP

31.  Imbalance-hypo/hypernatraemia
 3000mmol Na in ECF; intake balance output
 60-150mmol of Na in an adult, output from
kidneys, lungs, GIT, sweat, faeces.
 It is almost completely absorbed from the GIT
 <30mmol of Na is lost in sweat
 Loss in sweat and lungs is controlled by GIT
(fine adjustments by the intestines) and
kidneys.

32.  Intake of water in response to thirst.
 Excretion of water =ADH release
 The renal regulation which depends on renal
blood flow and aldosterone secretion.
 Blood volume status = affects excretion –
aldosterone, angiotensin II, ANP

33.  The kidneys are the ultimate regulators of Na
balance.
 It is freely filtered by the glomeruli.
 99% of filtered Na is reabsorbed in the kidneys-
PCT and DCT/ collecting ducts.
 70-80% is actively absorbed with chloride and
water in an iso-osmotic and electrically natural
manner at the PCT.
 20-25% is reabsorbed at the loop of Henle
together with chloride and water.

34.  Fine aadjustment of the DCT through ADH
and aldosterone interaction – Na+/K+ and
Na+/H+ exchange systems, there is direct
sodium absorption and indirect chloride
absorption.
 Regulation by the DCT determines the amount
of sodium excreted in the urine.
 In kidneys (PCT), re-absorption of Na+ is
required for the re-absorption of H2O, Cl-,
glucose, bicarbonate, urea and amino-acids

35.  80% of Na entering the tubular cells exchanges
for H+ and therefore entry of Cl- and HCO-
3
into the cells.
 Na transport actively is regulated by;
 Protein kinase dependent phosphorylation
which increases the activity and number of
channels.
 DCT Na+/K+/H+ transport – aldosterone.
 Ion channels- modulated by ANP, enables
faster rates of transport than ATPase.

36.  Rennin, a proteolytic enzyme, stored and
secreted by cells of the juxtaglomerular
apparatus of the kidney.
 Secretion is stimulated by decreased renal
perfusion, stimulation of sympathetic nerves to
the kidney and decreased Na concentration in
the fluid of the DCT.

37.  Angiotensinogen ------------›Renin---------------›Angiotensin I
 (α2 globulin renine substrate)
(decapeptide)
 (synthesized in liver) ↓
 ACE
(proteolytic)
 ↓
 Aldosterone ‹---------------- Angiotensin II

 Vasoconstriction
 Stimulates aldosterone release
 Stimulates thirst centre
 Affects ADH secretion

38.  ANP (Atrial), released from cardiac atria in
response to increase stretch and from ventricles in
heart failure.
 BNP (Brain), released from brain ventricles in
response in response to pressure within or
stretching of ventricles.
 Both promote loss of Na through the kidneys,
induce vasodilation and inhibit release of rennin
and aldosterone.
 CNP (C type), synthesized in the vascular
endothelial cells and in the brain.


39.  Urodilatin
 Peptide similar in structure to ANP
 Formed in the kidneys.
 Renal regulation of sodium balance thus increases Na loss

 Na+ K+ - ATPase inhibitory substance
 Also called digitalis like substance.
 Inhibits Na pump responsible for sodium re-absorption by the
renal tubules.

 Water Control-important in sodium balance, affects sodium
balance indirectly.
 Hypothalamus
 Anti Diuretic Hormone.


40.  Regulatory centers for H2O intake and output are
located in separate areas of the hypothalamus.
 Neurons respond to increase in ECF osmolarity,
decrease in intravascular volume and to angiotensin II.
 Increase ECF osmolarity stimulates neurons and causes
shrinkage of the cells.
 Decreased ICF volume causes decreased activity of
distension receptors located in the atria, inferior vena
cava and pulmonary veins and a decrease in activity of
blood pressure receptors in the aorta and carotid
arteries.
 Relay of this information stimulates neurons in the
water intake areas-produces a conscious sensation of
thirst and therefore increase water intake.

41.  Angiotensin II acts directly on the water control areas to increase water
intake.
 ADH is synthesized in the hypothalamus and transported to the post pit
where it is stored and released in response to increase ECF.
 Stretch receptors of the left atria and baroreceptors in the aortic arch and
carotid sinus influence ADH secretion in response to low intravascular
pressure and volume of hypovolaemia.
 Neurons in the water output areas are stimulated and this results in the
release of ADH from the posterior pituitary gland.
ADH causes re-absorption of H2O from the Distal Convoluted tubules with
formation of hypertonic urine and decreased output of free H2O.


42.  Inadequate water intake.
 Impaired water retension- DI, DM, Uraemia.
 Excess Na intake- drugs- metronidazole,
carbenicillin.
 Excess Na retension- Conn’s syndrome (1°), 2°
hyperaldosteronism.


43.  Main intracellular action.
 Average concentration is 150mmol/L, in erythrocytes
it is 105mmol/L which is about 23 times that in
plasma.
 High intracellular concentration because K+ diffuses
slowly outward through the cell membrane while
Na+/K+ ATPase pump continuously transports
potassium into the cell against a concentration
gradient.
 This maintains and adjusts ionic gradients on which
nerve impulse transmission and contractility of cardiac
and skeletal muscle depend on.
 Total body potassium is 3000mmol/L.

44.  98% is intracellular.
 Normal- Plasma=3.0-5-5mmol/L, Urine=25-125mmol/day.
 K+ intake 60-150mmol/day.
 Almost completely absorbed by the GIT, small amounts
taken up by the cells and most excreted by kidneys
depending on patient’s need.
 Routes of control:- Intestine, kidneys, membranes of allcells.
 Diffusion of K+ out of cell into plasma exceeds pump
mediated uptake when pump activity is low: reduced
metabolic substances (glucose for ATP prod.), competition
for ATP between pump and other energy consuming
activities of the cell and slowing down of cellular
metabolism e.g. refrigeration.


45.  Almost completely absorbed in the PCT.
 In DCT, K+ is secreted in DCT in exchange for Na+
or H+
 K+ lossin kidney depends on Na+ available, H+
concentration, aldosterone levels.
 K+ is absent in small intestine.
 It is re-absorbed from intestinal secretions: net loss
is <10mmol/day in faeces.
 Excess loss from intestinal lumen is derived more
from fluid entering lumen from body rather than
from dietary intake.

46.  Tubules respond promptly to potassium
loading by increasing potassium output but
respond slowly to potassium conversion.
 Factors regulating DCT secretion of potassium-
intake of Na+, K, and water flow in distal
tubules, plasma mineralo-corticoid levels, acid-
base balance.
 Slow conversion therefore leads to early
consequences of decreased potassium intake.

47.  Na+/ K+ ATPase pump on cell surfaces.
 Several chemicals exist to maintain negative
cell membrane potential.
 Regulate intracellular volume.
 Recycling of potassium across apical and
basolatral membranes to supply Na-2Cl- K co-
transport.
 Na K ATPase – active transport process,
located on the basolatral membrane of
tuboepithelial cells.

48.  3 Na+ out for 2K+=in.
 K is also exchanged for H+
 K+ shift is usually accompanied by Na shift but
% change in ECF Na is much less than that of
K+.
 Increased uptake of K by cells increased with
increased pump activity (insulin and
catechoamines, alkalosis due increased uptake
by cells and increased urinary loss

49.  Net loss of K+ from cells: K loss from ECF accompanied by replenishment
from ICF, inefficient pump e.g. Hypoxia, acidosis with displacement of K+
by H+.
 ECF H+ affects K+ entry into cells, proportions of K+ and H+ ions in the
DCT affects urinary loss of K+.
 Acidosis: increased uptake of K+ into cells and increased urinary loss-
hypokalaemia.
 If there is K+ depletion, Na is exchanged for more H+ than HCO3, for each
H+ formed one HCO3 is also formed, with more H+ being secreted into
the urine, more HCO3 is being passed into ECF by Na+, therefore ECF is
alkalotic and urine acidic.
 Chronic potassium depletion is usually accompanied by high HCO3 level.

50.  Hypokalaemia and high plasma bicarbonate is
likely due to K+ depletion than to met. Alkalosis.
 Hyperkalaemia and low HCO3 is most likely due
to metabolic acidosis than K+ excess.
 Decreased glomerular filtration in renal failure
leads to potassium retension.
 Potassium in plasma and whole blood is 0.7-
1.0mmol/L lower than serum, increased K+ in
serum is as a result of platelet rupture in the
coagulation process, plasma is the sample of
choice.

51.  Chilling whole blood slows down glycolysis
and NaKATPase pump is made inactive
therefore gradient is not maintained and K
leaks from the cells.
 K+ increased by 2mmol/l after 5hrs at 40°C,
0.2mmol/L in 1.5hrs at room temperature.
 If stored at 37°C, glycolisis occurs and K+ shifts
inside, false decreas.


52.  Glucose/insulin therapy
 Increased catecholamine secretion e.g.
treatment of MI
 Familial
 Prolonged vomiting/diarrhea
 Habitual purgative users.
 Chronic starvation

53.  Hyperaldosteronism
 Cushing’s syndrome
 Liquorice/tobacco with mineralocorticoid
effect.
 Prolonged saline infusion.
 Diurectics
 Tubular dysfunction

54.  In vitro-haemolysis
 Severe tissue damage.
 Familial
 Renal failure.
 Drugs-spinolactne, ACE inhibitors.
 Hypoaldostronism-addisons.
 DKA/Metabolic acidosis.

55.  Clinical features: Vague muscle weakness,
flaccid paralysis, paraesthesia, cardiac
arrythmia, ECG changes- Tall peaked T-waves,
abnormal QRS waves, Fusion of QRS and T-
waves
 Laboratory findings:- depends on the cause: e.g
Increased plasma K, Ure, and Creatinine in
renal failure. etc

56.  Treatment:
1. Calcium gluconate: 10%, 10-20ml over 2-3 minutes
but has transient effect.
2. Sodium bicarbonate infusion: 100-200mmol over
30minutes, effect lasts 2-3hrs.
3. Glucose and insulin infusion: 50 units of soluble
insulin infused with i.v 100ml of 50% glucose, lasts
several hours.
4. Resonium A (sodium polystyrene sulphonate), a
cation exchange resin, given orally or as enema, 30-
60g B.d
5. Heamodialysis in ARF.

57.  Thanks……………………
 Comments?..............
 Questions……………….