7. Role Of Kidney In Salt And Water Homeostasis

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 (reductions of 5% or more)

increases AVP release

Hypotension (reductions of 10-20%)

increases AVP release

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 Nicotine Apomorphine Isoproterenol Histamine Prostaglandin Cyclophosphamide Vincristine Lithium Naloxone Cholecystokinin Insulin

Fluphenazine Haloperidol Promethazine Alcohol Glucorticoids Phenytoin

(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 Hypovolaemic thirst

Osmotic thirst

Hypovolaemia

Plasma 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

Drinking

Increased tubular reabsorption of water

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 hormones

Post-prandial natriuresis caused by peptide produced in the GIT called guanylin and uroguanylin. It stimulates the release cGMP

Ingestion of isotonic saline

ECFV Atrial stretch receptors

ANP

Medullary centres

Inhibit aldosterone release

Renal sympathetic discharge Inhibit renal tubular Na+ reabsorption

decreased renal Na+ reabsorption

GFR

Renal Salt and water excretion

Restoration of ECFV to normal

IX & X AVP Inhibit renal H2O reabsorption

Disorders of water homeostasis Diabetes Insipidus (DI) Central DI

- Also called hypothalamic, neurogenic or neurohypophysial - there is insufficient secretion of ADH

Osmoreceptor dysfunction

- Also referrred to as essential hypernatraemia, adipsic hypernatraemia

Nephrogenic DI

- Defect within the V2 receptors in the kidney - Lithium induced

Hypotonic polyuria of pregnancy

Primary polydipsia

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

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

Tubular Na+ reabsorption

ADH

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