Fluid Homeostasis

Definitions

Osmolyte – osmotically active solute

Osmole – mole of osmolytes

Osmolarity – Osmole/liter

Osmolality – Osmole/Kg water

Introduction

In the steady state, our total body water and salt content remain constant

An increase or decrease in H₂O and salt intake is paralleled by an Ý or ß in renal H₂O and salt excretion

Homeostasis is achieved through the process of glomerular filtration of plasma to produce an ultrafiltrate of » 174 L/day

The tubules then process this ultrafiltrate so that the final urine flow rate and solute excretion meet the homeostatic needs of the body.

intake (mL/day): total 2600

Fluid 1400
In Food 850
Metabolically 350

output (mL/day): total 2600

Lungs 400
Skin 500
Feces 200
Urine 1500

Minimum daily fluid intake is 400mL (assuming normal food intake and metabolism)

The minimum urine that can be produced in a day to wash out salt urea and other solutes is 400-500mL.

Plasma osmolality (Posm)

In health, the Posm can be estimated by 2X plasma sodium concentration (an estimate of Na + attendant anions)

Posm = 2 x [Na]_plasma = 290mOsm/kg H₂O

because plasma is in equilibrium with ICF, an Ý or ß in Posm results in a corresponding change in plasma Volume until homeostatic Posm is reached

Urine osmolaity (Uosm) is varied by the kidney to maintain volume and osmolar homeostasis in the plasma, so Uosm and volume can vary independently.

Symptoms of both hypo- and hyperosmolality are Neurological resulting from brain cell swelling (hypo) or dessication (hyper);

nausea, malaise, headache, confusion, seizures, coma, lethargy, even death

Determinants of Water Flow

Water flow is always passive, and is determined by Starling forces: flow = k (D P - D p ) .

Because D p (colloid pressure) is dominant in tubules, water flow is secondary to solute transport.

The magnitude of ‘k’, and its regulation, determine the magnitude of water flow. The molecular basis of ‘k’ are: surface area, lipid bilayer permeability, and aquaporins.

Water equilibration is quickest in the proximal tubule and descending loop of Henle because here water permeability is high and solute absorption is not regulated, and it is slowest in the distal tubule and collecting duct because here water permeability is low and solute absorption can be regulated by ADH.

Antidiuretic Hormone (ADH)

The kidney Controls H₂O excretion largely through Antidiuretic Hormone (ADH)

ADH is a 9 aa polypeptide secreted by the supraoptic and paraventricular hypothalamic cells with axons ending in posterior pitutary

Half life = 5-20 minutes: this allows for rapid adaptation to fluctuation in osmolality

ADH acts to retain H₂O and blood volume by:

Ý H₂O permeability in the principle cells of the cortical and medullary collecting ducts by promoting insertion of aquaporins

Ý urea permeability in the medullary collecting duct.

change in H₂O reabsorption in antidiuresis to early CCD: maintaining bulk flow of H₂O reabsorption in cortex-keeps osmogradient intact without washing out medullary interstitium.

Ý Ý amounts of ADH released in response to significant change in plasma volume (Vasopressin) cause vasoconstriction

The two major classes of ADH receptors are found in the basolateral membrane of the nephron (V2) and in the vasculature (V1):

V2 receptor Þ Ý cAMP activityÞ insertion of intracytoplasmic Auquaporin-2 to apical membrane; and Auquaporin-3 to basolateral membrane allowing water to flow through the cell. With the removal of ADH (t_1/2=5-20 minutes) the aquaporins are reinternalized

also increases Na and urea flow via the Na/K/2Cl and an unidentified urea transporter (uses cAMP for both) – augments concentrating ability

V1 receptor (not affected by dDAVP) Þ Vasoconstriction linked to calcium

Secretion of ADH is controlled by :

(1) Osmoreceptors (hypothalamic -near thirst center).

High sensitivity (change of 1-2% PosmÞ greatest change in ADH)

low gain

Only responds to solutes that are effective osmoles (ie Na⁺), not ineffective osmoles (ie urea)

(2) Baroreceptors (carotids, aortic arch, left atrium ).

Low sensitivity (5-10% decrease in volume or BP Þ greatest change in ADH)

high gain

Note: though the body will try to control osmolality more than volume, if the volume drops dangerously low the kidney will conserve water at the expense of osmolality, i.e. even though water conservation will reduce the osmolality of body fluids.

(3) Non-osmotic factors (narcotics, pain, stress, nicotine, chloropropamide, cytoxan, clofibrate, carbamazepine, nausea, angiotensin II)

(4) Release inhibited by ethanol, hypothermia, and atrial natriuretic peptide

Thirst

an Ý of only 2% to 3% in plasma osmolality will produce a strong desire to drink

a ß of 10% to 15% in blood volume and arterial pressure are required to produce the same response

the thirst center is located in the anterolateral region of the hypothalamus (subfornical organ and vasculosm of lamina terminalis)

thirst center cells respond to effective osmoles. Angiotensin II stimulates Subfornical organ cell evoked thirst

Clinical Syndromes

Diabetes Insipidus: caused by ADH deficiency or resistance causes inappropriately low collecting duct permiability; causes excessive excretion of dilute urine and dehydration (if unable to drink to correct)

Inadequate response to ADH (i.e., defect in the renal cellular apparatus such as ADH receptor) = Nephrogenic Diabetes Insipidus.
Inadequate ADH release = central diabetes insipidus

Syndrome of inappropriate ADH secretion = Ý Ý [ADH] Þ ß renal excretion and retained H₂OÞ hyposmotic body fluids and [ ] urine

dehydration Þ Ý urine and plasma osmolality and ß volume of each.

polydipsia Þ ß urine and plasma osmolaity and Ý volume of each.