7. Role of Kidney in Salt and Water Homeostasis
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Transcript of 7. Role of Kidney in Salt and Water Homeostasis
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ROLE OF KIDNEY IN SALT AND WATER HOMEOSTASIS
Professor Harbindar Jeet SinghFaculty of medicine
Universiti Teknologi MARA
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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
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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
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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
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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
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(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
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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
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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
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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.
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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
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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
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viii) Drugs and hormones
Stimulatory effect
AcetylcholineNicotineApomorphineIsoproterenolHistamineProstaglandinCyclophosphamideVincristineLithiumNaloxoneCholecystokininInsulin
Inhibitory effect
FluphenazineHaloperidolPromethazineAlcoholGlucorticoidsPhenytoin
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(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.
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(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
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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
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Plasma osmolality
osmoreceptors
Dehydration Salt intake
Thirst centre
Drinking
Increased ADH release
Increased tubularreabsorption of water
Decreased urine output
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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
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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
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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
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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
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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
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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
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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
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Daily potassium balance
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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.
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Interaction of opposing factors on potassium secretion(ADH, ECF and GFR)
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THANK YOU
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The renin-angiotensin-aldosterone axis