ROLE OF KIDNEY IN SALT AND WATER HOMEOSTASIS

Professor Harbindar Jeet SinghFaculty of medicine

Universiti Teknologi MARA

Objectives

1. Explain the concept of water balance and the importanceof 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

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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

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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

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Body fluid compartments in humans

Water homeostasis

Water homeostasis represents a balance between the intake andexcretion 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 regulatingwater 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 theneurohypophysis or posterior pituitary

AVP secretion is influenced by many different stimuli, which canbe 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 issuppressed

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 fromosmoreceptor and therefore a greater stimulus

2) 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 viashifting 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.

ii) Drinking

Drinking lowers plasma AVP even before there is appreciabledecrease in plasma osmolality

? May involve sensory afferents from the oropharynx.

Suppression is also greater with colder fluids

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

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

vii) Hypoxia and Hypercapnia

Acute hypoxia and hypercapnia stimulate AVP secretion.

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

viii) Drugs and hormones

Stimulatory effect

AcetylcholineNicotineApomorphineIsoproterenolHistamineProstaglandinCyclophosphamideVincristineLithiumNaloxoneCholecystokininInsulin

Inhibitory effect

FluphenazineHaloperidolPromethazineAlcoholGlucorticoidsPhenytoin

(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

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

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

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

(ii) Hypovolaemic thirst

This normally becomes evident when plasma volume decreases byat least 5-8%.

The thirst appears to be stimulated by activation of low- or high-pressure receptors and circulating Ang II

Osmotic thirst

Thirst centre

Hypovolaemic thirst

osmoreceptors

Plasmaosmolality

Hypovolaemia

Ang II

Drinking

The body water content and composition is very finely maintained

The water component is primarily managed through ADH and thirstmechanism

Increase water intake

GI absorption

Plasma osmolality

ADH suppression

Tubular reabsorption of water

Urine output

Plasma osmolality

osmoreceptors

Dehydration Salt intake

Thirst centre

Drinking

Increased ADH release

Increased tubularreabsorption of water

Decreased urine output

In addition to the osmoreceptors, there are also volume detectorsfound in the vascular system that help maintain fluid volumehomeostasis

i) Atrial sensors (type B receptors) found at the entrance ofgreat veins into the atria

Stretch in the atria is detected by these receptors and impulsestravel along the cranial nerves IX and X to the hypothalamicand 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, increasingGFR.

In addition to the neural activity, there is also the humoral pathway, where atrial stretch releases ANP, which increases sodium excretion by the kidney

ii) Arterial sensors

a) Carotid baroreceptors

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

iii) Gastrointestinal tract reflexes

a) Hepatorenal reflex Hepatoportal region transduceportal plasma Na+ conc into hepaticnerve activity and reflexively augment renal sodium excretion

b) Intestinal natriuretic hormones

Post-prandial natriuresis caused bypeptide produced in the GIT called guanylin and uroguanylin.

It stimulates the release cGMP

ECFVIngestion of isotonic saline

Atrial stretch receptors

ANP AVPMedullary centres

Renal sympathetic discharge

GFR

Renal Salt and water excretion

Inhibit renaltubular Na+

reabsorption

Inhibit aldosteronerelease

Inhibit renal H2O reabsorption

Restoration of ECFV to normal

IX & X

decreased renalNa+ reabsorption

Disorders of water homeostasis

Diabetes Insipidus (DI)

Central DI

Nephrogenic DI

- Also called hypothalamic, neurogenic or neurohypophysial

- there is insufficient secretion of ADH

- Defect within the V2 receptors in the kidney

- Lithium induced

Osmoreceptor dysfunction

- Also referrred to as essential hypernatraemia, adipsic hypernatraemia

Hypotonic polyuriaof pregnancy

- Due to increase rapid metabolism of AVP by 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

Increase plasma osmolality

Osmoreceptor stimulation

Thirst centre

Fluid intake

ECFV

ADH

P Na+

GFR H2O & Na+

excretion

Aldosterone

Tubular Na+

reabsorption

ANF

Disorders in sodium metabolism

1. Hypernatraemia

2. Hyponatraemia

a) Hyponatraemia with ECFV depletion

b) Hyponatraemia with excess ECFV

c) Hyponatraemia with normal ECFV

d) Syndrome of inappropriate ADH secretion

e.g. diuretic-inducedadrenal insufficiency

e.g. CCFHepatic failure, Nephrotic syndrome

e.g. Psychosisglucocorticoid deficiency

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 requiresthat 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)

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The renin-angiotensin-aldosterone axis