Water Balance and Control of Body Fluid Osmolarity

Antidiuretic Hormone -ADH or arginine vasopressin(AVP)

Retains water

ADH increases:

1. H2O permeability- late distal tubule and collecting duct

2. Urea permeability- inner medullary collecting duct

3. Na+ reabsorption- thick ascending limb of Henle loop

Renin -angiotensin-aldosterone system

retains Na+

Atrial Natriuretic Peptide (ANP)

increases Na+ and H2O excretion

The role of ANP: decrease blood volume and osmolarity

Urine Concentration and Dilution: Kidneys maintain ECF osmolarity within a narrow range by regulating water excretion :a. when water intake is high, a large volume of diluted urine is produced -

diuresis

hyposmotic or diluted urine

Urine Concentration and Dilution: Kidneys maintain ECF osmolarity within a narrow range by regulating water excretion :when water intake is low, our body conserves H2O, and a small volume of concentrated urine is formed -

antidiuresis

hypersmotic or concentrated urine

Urine concentration and dilution: Plasma osmolarity is about

290 mOsM when it enters the nephron.

Urine osmolarity can range from 50 mOsM (diuresis) to 1200 mOsM (antidiuresis).

Urine volume varies between 0.5 to 20 L per day, it depends on plasma

ADH

ADH is produced in the

hypothalamus and released in capillaries of the pituitary gland

ADH is produced in the hypothalamus and released in capillaries of the pituitary gland: Osmoreceptors

specialized neurons in the hypothalamus, are activated by an increase in ECF osmolarity and stimulate ADH production by neurons of the supraoptic and paraventricular nuclei (another hormone, oxytocin, is also produced in these nuclei)

ADH is released in the blood by

axonal terminals in the posterior lobe of the pituitary gland

Only substantial decrease in blood pressure can stimulate ADH release

Mechanism of ADH action =

Insertion of Aquaporins (AQP) in the Distal Nephron

Vasopressin (AVP) binds to the basolateral membrane receptor (V2)

.c-AMP is activated and specialized protein AQP2, a channel for transport of water molecules, is inserted on the apical membrane.

Different AQPs are present on the basolateral membrane

Urea helps to reabsorb

more water

ADH enables H2O (not urea) reabsorption in the distal tubule, cortical and medullary collecting duct.

As a result, tubular urea concentration rises and reaches its maximum at the level of inner medulla.

There, ADH allows diffusion of urea molecules into the interstitium, which contributes to the build up of the cortico-medullary osmotic gradient, increasing water reabsorption.

Urea helps to reabsorb more water: Urea is produced in the

liver (protein metabolism).

Filtered urea is reabsorbed regardless of ADH mainly in the proximal tubule

Water is driven out of the renal tubule by

osmosis

and carried away from the interstitium via the peritubular capillaries and (or) ascending vasa recta

Urea and other solutes diffuse into the vasa recta and peritubular capillaries drawing water back into circulation.

Eventually, this water influx returns blood osmolarity to~ 300 mOsM at the cortical

Vasa recta removes electrolytes, urea and water from the

interstitium

Electrolytes and urea diffuse from the interstitium into the vasa recta down the concentration gradient.

Influx of urea in the inner medulla helps to maximize plasma osmolarity (1200mOsM) and water uptake by osmosis into the ascending vasa recta. High oncotic pressure also adds to reabsorption

*Urea recycling (passage from the medullary collecting duct into the interstitium, and then into the ascending limb) helps to maintain

high osmolarity in the inner medulla

After water ingestion osmolarity of urine

decreases and it becomes hypo-osmotic

(i.e. urine osmolarity is less than plasma osmolarity), while urine flow rate increases, prompting excretion of a large volume of dilute urine

The total amount of solute excreted by the kidneys increases only slightly, i.e. lowered ADH release helps to excrete mostly water. This response of the kidneys prevents plasma osmolarity from decreasing markedly during excessive water ingestion

An increase in ADH release is stimulated by

loss of bodily fluids or a decrease in water intake

Increase in plasma osmolarity (decreased water intake) =

major stimulus for ADH secretion

- most sensitive (1-2% change)

- detected by osmoreceptors in the hypothalamus

Decrease in ECF volume or blood pressure

Other regulators of ADH secretion: Increased ADH secretion

a. angiotensin II (hemorrhage, hypotension etc.)

b. stress and heat

c. pain, nausea and vomiting

Other regulators of ADH secretion: Decreased ADH secretion

a. atrial natriuretic peptide

b. cold temperature

c. ethanoL

Diseases of water balance related to abnormalities in ADH production: Diabetes insipidus

Symptoms

- abnormally large volume of dilute urine

- diuresis, polyuria

- constant sensation of thirst, desire for drinking

- polydipsia (does not increase blood volume or pressure)

- even short lasting cut in water supply may result in severe problems (e.g. hypovolemic shock)

Major consequence

- Water loss and high plasma osmolarity!

(Na+ is not lost)

Constant sensation of thirst* and excessive drinking are also features of another illness - polydipsia (called primary or psychogenic polydipsia).

Water deprivation decreases volume of urine in patients with polydipsia, but not so in patients with diabetes insipidus

Two types of Diabetes insipidus: Central (neurogenic, hypothalamic)

insufficient ADH release from the hypothalamus- plasma ADH - low

Causes: head injury, CNS infection, stroke in the pituitary gland

Two types of Diabetes insipidus: Nephrogenic

decreased renal response to ADH due to abnormal vasopressin receptors or aquaporins in the renal tubule

- plasma ADH high (or normal with plentiful water intake) Causes: kidney disease, drugs (lithium, amphotericin B),

hereditary

Used to treat central diabetes insipidus

Desmopressin (DDAVP)

a synthetic analog of ADH (AVP)

Patients with pure nephrogenic diabetes insipidus do not respond to DDAVP.

ADH excess

syndrome of inappropriate ADH secretion (SIADH)

Abnormally high ADH release from hypothalamus (and other cites)

Major consequence - water retention!

- low plasma osmolarity and plasma Na+

(hyponatremia - severe cases "water intoxication")

- high urine osmolarity

(paradoxically, Na+ excretion with urine increases despite its low plasma level)

syndrome of inappropriate ADH secretion (SIADH) causes

lung diseases (tumor, tuberculosis, pneumonia)

CNS diseases

- (tumor, trauma, infection),

drugs (3,4 methylendioxymethamphetamine “ecstasy”, carbamazepine)

Possible hazards of ecstasy and high water intake

hyponatremia (due to water intoxication)

can be fatal

cerebral oedema- brain edema

Even low doses of MDMA and fluids may lead to a serious out come.

The only risk factor is female gender

Water intoxication

Excessive sweating, vomiting, or diarrhea coupled with voluminous intake of water (hypotonic gain)

Decreased Na+ concentration of plasma (hyponatremia)

Decreased plasma osmolarity

Osmosis of water from plasma into intracellular fluid

Cell swelling, brain edema and compression

Convulsions, coma and possible death

Which of the following is expected in a patient with diabetes insipidus placed on overnight water restriction

A.Hyponatremia

B.Hypernatremia

C. Urine osmolarity of 800 mOsM/ kg or more

D.Anuria

B. Hypernatremia

A healthy young man runs several-mile race on a hot summer day and got dehydrated. Assuming that his ADH level is high, in which segment of the renal tubule water is reabsorbed at the highest rate?

A. Distal tubule

B.cortical collecting duct

C.medullary collecting duct

D.proximal tubule

Proximal tubule