Disorders of Volume Homeostasis

Disorders of Volume Homeostasis: Edema

Normal Hemodynamics

net effect: decreased effective circulating fluid volume (ECFV) leads to decreased renal sodium and water excretion

ß ECFV has three effects:

(1) Ý plasma oncotic pressure and ß hydrostatic pressure Þ ß GFR

(2) ß Plasma Volume Þ ß venous and arterial pressure Þ Ý sympathetic nervous system activity and Ý renin-angiotensin activity Þ ß GFR, Ý filtration fraction Þ Ý proximal and distal tubular sodium reabsorption

(3) Ý plasma osmolality Þ Ý ADH secretion (also increases due to ß Plasma Volume) Þ Ý distal nephron water reabsorption

thus, sodium and water excretion is decreased and ECFV is preserved

Pathological Conditions

Perturbation in salts and H2O regulatory mechanisms in each of the following conditions

Congestive Heart Failure

Backward Failure: Ý venous Pressure Þ Ý capillary hydrostatic pressure Þ shift in starling forces Þ Ý ECFV = Edema

Forward Failure: ß CO Þ ß Effective Blood VolumeÞ Systemic Hemodynamic Response Þ Ý Plasma Vol ¹ Ý COÞÝ ECFV = Edema

Hepatic Cirrhosis

Liver destruction Þ ß Albumin Synthesis Þ ß Capillary oncotic pressure Þ Ý ECFV, EDEMA, Ascites

Liver destruction Þ impedes splanchnic drainageÞ Ý portal venous pressure Þ arterio venous fistula Þ

Þ ß peripheral resistance Þ Ý CO and ß tissue perfusion Þ ß Effective circulating VolumeÞ Systemic Hemodynamic Response Þ Ý Plasma Vol Þ Ý ECFV = Edema, Ascites

Nephrotic Syndrome

Renal damage Þ massive urinary protein loss Þ ß plasma albumin concentration Þ ß capillary oncotic pressureÞ ß Effective blood vol Þ Systemic Hemodynamic Response Þ Ý Plasma Vol Þ Ý ECFV = Edema

In all three conditions the negative feedback loop of Ý ECFV does not occur, resulting in continued edema

Edema

palpable swelling produced by expansion of interstitial fluid volume.

can be localized or generalized (anasarca)

There are two steps in edema formation

(1) change in capillary hemodynamics that favors fluid movement from vascular to interstitial compartment

(2) Renal retention of Na and H₂O Þ expanding ECFV

Note: intracellular and extracellular fluid compartments are in osmotic equilibrium.

changes in Na do not determine movement of fluid from plasma to interstitium. In these compartments Na is an ineffective osmolyte; protein is an effective osmolyte.

Role of kidney in Edema Formation

Kidney is essential in edema formation. without a change in renal handling of Na and H₂O, edema does not occur.

Edema is not clinically apparent until 2-3 L of fluid moves from the vascular to the interstitial compartments.

Retention of Na by the kidney is an appropriate response in this setting, even though it promotes edema, because loss of 2-3 L from CO would otherwise result in shock.

This illustrates primacy of EVC (effective circulating volume-fullness of arterial circulation) in controlling ECFV

Capillary Hemodynamics and Starling’s Law

Fluid movement between the capillary and interstitium is determined by the hydraulic and oncotic pressures in each compartment:

Starling’s Law Net filtration = Kf(D hydraulic pressure - D oncotic pressure)

Or = Kf [(Pcap-Pis) – (p cap -p is)]

Kf is the product of the permeability or porosity of the capillary wall x the filtration surface area .

Oncotic pressures are determined primarily by albumin.

Interstitial fluid accumulation is additionally controlled by the rate of fluid removal by the lymphatics.

Net effect is small gradient (0.3mmHg) favoring filtration.

Starling’s Forces: Hydraulic Pressures

Capillary hydraulic pressure is generated by cardiac contraction, but auto regulation makes hydraulic pressure relatively insensitive to variation in mean arterial pressure

Capillary autoregulation is controlled primarily by the precapillary sphincter, which is under local baroreceptor and hormonal control (ie, endothelial-derived paracrine mediators).

Capillary autoregulation is so efficient that patients with hypertension rarely develop edema.

In contrast, resistance at the venous end is not well-regulated, and an Ý in venous pressure can Ý Pcap and Þ edema

Starling’s Forces: Oncotic Pressures

Oncotic pressure in capillary due mainly to plasma protein, ie, albumin. (Note: Na = ineffective osmolyte, freely crosses cap)
Effective interstitial solutes are filtered proteins (ie, albumin) > mucopolysaccharides.
A fall in plasma albumin will reduce the plasma oncotic pressure and favor fluid movement from the capillary into the interstitium.

Mechanisms and Causes of Edema Formation

2 Steps:

(1) Large change in Starling forces Þ fluid flow into interstitium

(2) Renal Na retention and expansion of ECFV

Most common change is increased Pcap, especially due to venous obstruction.

Less frequently, edema results from ß p _plasma, Ý capillary permeability, or lymphatic obstruction.

Renal Na Retention and Edema

wihtout renal Na retention edema will not form. 2 mechanisms account for renal retention.

(1) Compensatory response to depletion of ECV
(2) Primary retention of Na

Appropriate Na retention by kidney restores and preserves ECV: hormones = renin-Ang II-aldo, norepi, ADH
Primary Na retention occurs in advanced stages of renal disease.

Compensated state: mild disease (MI, CHF), renal response = restored ECV at new Steady state, but with edema.

Treatment of Edema

Dietary reduction in Na.

Prescribe diuretics to inhibit (control) Na retention by the kidney.