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ROLE OF KIDNEY IN SALT

AND WATER HOMEOSTASIS

Professor Harbindar Jeet Singh


Faculty of medicine
Universiti Teknologi MARA
Objectives

3. Explain the concept of water balance and the importance


of osmolality in its regulation.

2. The role of the kidney in water, sodium and potassium balance


Water is an important requirement of all living things.
Without water man cannot live for more than 72 hours

Two major sources of water

a) Daily water intake (1800 ml)


b) Water produced during metabolism

Approximately 200 ml is produced daily

Water loss from the body occurs via

a) Urine - 1000 ml

b) Sweat - 200 ml

c) Faeces - 200 ml

d) Breathing - 600 ml

>
Total body water in an adult is about 40-45 litres
(70 kg man)

i.e. 60-65 %total body weight

The percentage water in the body however varies slightly


with age and sex

Age (years) Male % Female %


Infants 80 75
1-5 65 65
10-16 60 60
17-39 60 60
40-59 60 55
60+ 55 50

>
Tissue composition of water (%)

TISSUE % Water
Kidney 83
Heart 79
Lungs 79
Skeletal muscle 76
Brain 75
Skin 72
Liver 68
Skeleton/bone 22
Adipose tissue 10

>
Body fluid compartments in humans
Water homeostasis

Water homeostasis represents a balance between the intake and


excretion of water

The mean water intake per day is about 2.3 - 2.8 L

The total excretion from both components is 2.4 - 2.8 L per day

There are two major mechanisms responsible for regulating


water homeostasis

a) Arginine vasopressin (ADH)

b) Thirst
(a) Arginine Vasopressin (AVP/ADH)

It is a nine-amino acid peptide with a molecular weight of 1099

It is synthesised in the hypothalamus and released from the


neurohypophysis or posterior pituitary

AVP secretion is influenced by many different stimuli, which can


be broadly grouped into two categories

1) Osmotic stimuli/osmotic regulation

2) Non-osmotic stimuli/non-osmotic regulation


1. Osmotic regulation

Changes in plasma osmotic pressure is the most important


stimulus for AVP release under physiologic conditions

The osmoreceptors are located in the anterior hypothalamus,


near organum vasculosum of the lamina terminalis

There is a discrete osmotic threshold for AVP secretion above


which a linear relationship between plasma osmolality and AVP
levels occur

At plasma osmolalities below the threshold, AVP secretion is


suppressed

In healthy adults, the osmotic threshold for AVP secretion


ranges from 280-285 mOsm/kg H2O
The sensitivity or the set-point may be altered during

a) acute changes in blood pressure

b) changes in effective blood volume

c) in pregnancy, where it is dramatically reduced


(possibly by placental hormone, relaxin)

AVP secretion is not equally sensitive to all plasma solutes

NaCl, mannitol and sucrose e.g. are more potent than urea and
glucose

This may be because, the osmoreceptors respond to osmotically


-induced changes in its water content.

Solutes that penetrate slowly cause a greater efflux of water from


osmoreceptor and therefore a greater stimulus
1) Non-osmotic regulation

i) Hemodynamic changes

Hypovolaemia - increases AVP release


(reductions of 5% or more)

Hypotension - increases AVP release


(reductions of 10-20%)

The effect of haemodynamic changes on AVP release is via


shifting of the sensitivity and threshold (set-point) to osmotic
stimuli

The haemodynamic influences on AVP secretion, particularly


changes in pressure, are mediated in part by the baroreceptors in
the aortic arch and carotid sinus.

Responses to hypovolaemia may involve the RAAS (Ang II),


altering the set-point at the osmoreceptors.
i) Drinking

Drinking lowers plasma AVP even before there is appreciable


decrease in plasma osmolality

? May involve sensory afferents from the oropharynx.

Suppression is also greater with colder fluids

i) Nausea
It is a very potent stimulus for AVP release whether accompanied by
vomiting or not.

e.g. a 20% increase in osmolality may increase AVP by 20 fold,


whereas nausea increases it by some 100-200 fold.

The pathway involves the chemoreceptor trigger zone in the brainstem

It can be activated by apomorphine and morphine and is inhibited following


pretreatment with fluphenazine and haloperidol
iv) Hypoglycaemia

Decreased plasma glucose concentration, though not so potent,


stimulates AVP secretion

v) RAAS
Blood-borne angiotensin II stimulates AVP release.

Angiotensin II binds to AT1 receptors in the brain at the circumventricular


subfornical organ (SFO), and through neural pathways from here to the
hypothalamic SON and PVN, mediate AVP secretion

i) Stress - pain, emotion, physical activity increase AVP

i) Hypoxia and Hypercapnia

Acute hypoxia and hypercapnia stimulate AVP secretion.

e.g. at PaO2 of 35 mm Hg or lower, plasma AVP increases markedly


i) Drugs and hormones

Stimulatory effect Inhibitory effect

Acetylcholine Fluphenazine
Nicotine Haloperidol
Apomorphine Promethazine
Isoproterenol Alcohol
Histamine Glucorticoids
Prostaglandin Phenytoin
Cyclophosphamide
Vincristine
Lithium
Naloxone
Cholecystokinin
Insulin
(b) Thirst

It is the body’s mechanism to increase drinking, defined as a conscious


desire to drink.

Can be described under two broad categories.

(i) Osmotic thirst

The stimulus for osmotic thirst is the increase in plasma osmolality.

The thirst and AVP osmoreceptors are believed to be the same.

In healthy adults, a 2-3% increase in basal levels of effective


plasma osmolality levels produces a strong desire to drink.

The osmotic thirst threshold averages about 295 mOsm/Kg H2O

The intensity of thirst increases in direct proportion to serum [Na+]


or osmolality
(ii) Hypovolaemic thirst

This normally becomes evident when plasma volume decreases by


at least 5-8%.

The thirst appears to be stimulated by activation of low- or high-pressure


receptors and circulating Ang II

Osmotic thirst Hypovolaemic thirst

Plasma Hypovolaemia
osmolality
osmoreceptors Ang II

Thirst centre

Drinking
The body water content and composition is very finely maintained

The water component is primarily managed through ADH and thirst


mechanism

Increase water intake

GI absorption

Plasma osmolality

ADH suppression

Tubular reabsorption of water

Urine output
Dehydration Salt intake

Plasma osmolality

osmoreceptors
Increased ADH
release
Thirst centre
Increased tubular
reabsorption of water
Drinking

Decreased urine output


In addition to the osmoreceptors, there are also volume detectors
found in the vascular system that help maintain fluid volume
homeostasis

i) Atrial sensors (type B receptors) found at the entrance of


great veins into the atria

Stretch in the atria is detected by these receptors and impulses


travel along the cranial nerves IX and X to the hypothalamic
and medullary centres resulting in the inhibition of AVP/ADH,
decreased renal sympathetic discharge and decreased tone in
precapillary and postcapillary resistance vessels of the
vascular bed, and afferent arterioles of the kidney, increasing
GFR.

In addition to the neural activity, there is also the humoral


pathway, where atrial stretch releases ANP, which increases
sodium excretion by the kidney
i) Arterial sensors

a) Carotid baroreceptors

b) Renal sensors (e.g. the Juxtaglomerulus apparatus)

iii) Gastrointestinal tract reflexes

a) Hepatorenal reflex Hepatoportal region transduce


portal plasma Na+ conc into hepatic
nerve activity and reflexively
augment renal sodium excretion

a) Intestinal natriuretic Post-prandial natriuresis caused by


hormones peptide produced in the GIT called
guanylin and uroguanylin.

It stimulates the release cGMP


Ingestion of
isotonic saline ECFV

Atrial stretch receptors IX & X

ANP Medullary centres AVP

Inhibit Renal sympathetic discharge Inhibit renal


aldosterone H2O reabsorption
release
Inhibit renal GFR
tubular Na+
reabsorption

decreased renal
Na+ reabsorption Renal Salt and water excretion

Restoration of ECFV to normal


Disorders of water homeostasis

Diabetes Insipidus (DI)

Central DI - Also called hypothalamic, neurogenic or


neurohypophysial

- there is insufficient secretion of ADH

Osmoreceptor - Also referrred to as essential hypernatraemia,


dysfunction adipsic hypernatraemia

Nephrogenic DI - Defect within the V2 receptors in the kidney

- Lithium induced
Hypotonic polyuria - Due to increase rapid metabolism of AVP by
of pregnancy increased circulating oxytocinase/
vasopressinase (cysteine aminopeptidase).
Can be treated with desmopressin

Primary polydipsia a) Dipsogenic DI, where there is an


abnormality in the thirst mechanism

b) Psychogenic DI

There is depressed AVP secretion and


decreased AQP2 expression in the kidney
Sodium balance
Na+ intake

P Na+ Aldosterone
Increase plasma osmolality

Osmoreceptor stimulation ADH Tubular Na+


reabsorption
Thirst centre
ANF
Fluid intake

ECFV GFR H2O & Na+


excretion
Disorders in sodium metabolism
1. Hypernatraemia

1. Hyponatraemia
a) Hyponatraemia with ECFV depletion
e.g. diuretic-induced
adrenal insufficiency
a) Hyponatraemia with excess ECFV
e.g. CCF
Hepatic failure, Nephrotic syndrome
a) Hyponatraemia with normal ECFV
e.g. Psychosis
glucocorticoid deficiency
a) Syndrome of inappropriate ADH secretion
Daily potassium balance
During periods of low dietary intake the kidney reabsorbs as much as 98-99%
of the filtered load of potassium.

During normal or high potassium intake, when external K+ balance requires


that the kidneys excrete K+, the ‘distal K+ -secretory system’ consisting of
ICT, CCT and proximal portion of the MCD secrete K+ into the tubule.
Interaction of opposing factors on potassium secretion
(ADH, ECF and GFR)
THANK YOU
The renin-angiotensin-aldosterone axis

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