Body Fluid Compartments
- H2o is 60% of body weight – 42L
- 40% is intracellular – 28L
- 20% extracellular – 14L
- 15% interstitial – 10.5L
- 5% plasma – 3.5L
Higher body fat means lower water content.
Osmolality is essentially identical between compartments.
Gibbs-Donnan explains unequal distribution in presence of nondiffusible ion. Concentration greatest in compartment containing nondiffusible, negatively charged protein. The side containing the protein will also have the same charge as that protein.
Infusing with normal saline in dehydration will overcompensate ECF and undercompensate ICF. However it is the proper treatment in the case of hemorrhage.
Control of Osmolality and Body Fluid Volume
Osmolality and volume of ECF is tightly regulated, mainly by kidney.
Osmolality regulated by changes in renal water handling – ADH (AVP)
ECF volume regulated by changes in renal Na handling – Renin-angiotension, sympathetics
- Water deprivation is sensed by Hypothalamus which stimulates thirst and ADH secretion.
Excess water is sensed by Hypothalamic Osmoreceptors:
- stimulate supraoptic and paraventricular nuclei suppress ADH release
- stimulate lateral pre-optic area supresses thirst
Medullary vasomotor center can also stimulate hypothalamus in response to decreased circulating volume.
ADH synthesized in hypothalamus as precursor, travels down axons to posterior pituitary where it is stored in granules in nerve terminals.
ADH metabolized in kidney and liver, short half-life, varies in plasma osmol range of 280-290
Diabetes Insipidus (tasteless). A defect in ADH secretion or action. There is Central DI and Nephrogenic DI where collecting tubule is unresponsive to ADH.
SIADH – plasma levels higher than normal – leads to negative free water clearance. Caused by cancer and injury.
ECF volume determined mainly by NaCl present.
Dietary Na intake will increase ECF volume, but you will also excrete more from kidney. ANP will decrease Na reabsorption.
Juxtaglomerular Apparatus
Renin secretion is stimulated by lowered afferent arteriolar pressure, increased sympathetic activity, decreased macula densa NaCl delivery.
Renin gets you to Angiotensin 1, ACE gets you to II, II binds to:
- AT1 (ARBs inhibit)
- increase aldosterone, vasoconstriction
- proximal Na reabsorption
- thirst
- ADH release
- lowers renal blood flow but maintains GFR
- AT2 receptors – vasodilation
Changes in volume that govern release of renin
- Baroreceptors in afferent arteriole
- Baroreceptors in heart and arteries with regulate sympathetic neural activity and circulating catecholamines
- Cells in macula densa in distal tubule
- as Cl falls, stimulates renin release via prostaglandins, but volume is dominating factor.
Aldosterone is made in the adrenal cortex and its release is stimulated by Angiotensin II and increased ECF K+.
- stimulates reabsorption of Na from late distal tubule, CCC, and TAL
- promotes K and H secretion
- stimulates Na absorption by colon
SNS activity evoked by reduced arterial pressure and reduced vascular volume. It causes constriction of arterioles, reducing RBF, but only slightly decreasing GFR, increasing FF (enhances reabsorption of Na in PT)
Angiotensin constricts efferent to help keep GFR up.
PGI2 released from JGA is a vasodilator that counteracts SNS and RAA. ACE inhibitors and NSAIDS problem here.
Factors that inhibit Na reabsorption:
- PGE2 in medulla oppose Na reabsorption.
- ANP – released from atria in response to stretch, increases cGMP
- Decreases reabsorption of Na in distal tubule and collecting tubule by blocking ENaC and inhibiting NaK ATPase.
- Inhibits release of aldosterone and renin
- Vasodilates afferent arteriole to increase GFR
- Urodilatin – released by kidney – identical to ANP
- Dopamine released by neurons to proximal tubules to inhibit NaK ATPase and Na/H exchange in proximal tubules.
