Edema formation in congestive heart failure and the underlying mechanisms

Abstract

Congestive heart failure (HF) is a complex disease state characterized by impaired ventricular function and insufficient peripheral blood supply. The resultant reduced blood flow characterizing HF promotes activation of neurohormonal systems which leads to fluid retention, often exhibited as pulmonary congestion, peripheral edema, dyspnea, and fatigue. Despite intensive research, the exact mechanisms underlying edema formation in HF are poorly characterized. However, the unique relationship between the heart and the kidneys plays a central role in this phenomenon. Specifically, the interplay between the heart and the kidneys in HF involves multiple interdependent mechanisms, including hemodynamic alterations resulting in insufficient peripheral and renal perfusion which can lead to renal tubule hypoxia. Furthermore, HF is characterized by activation of neurohormonal factors including renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), endothelin-1 (ET-1), and anti-diuretic hormone (ADH) due to reduced cardiac output (CO) and renal perfusion. Persistent activation of these systems results in deleterious effects on both the kidneys and the heart, including sodium and water retention, vasoconstriction, increased central venous pressure (CVP), which is associated with renal venous hypertension/congestion along with increased intra-abdominal pressure (IAP). The latter was shown to reduce renal blood flow (RBF), leading to a decline in the glomerular filtration rate (GFR). Besides the activation of the above-mentioned vasoconstrictor/anti-natriuretic neurohormonal systems, HF is associated with exceptionally elevated levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). However, the supremacy of the deleterious neurohormonal systems over the beneficial natriuretic peptides (NP) in HF is evident by persistent sodium and water retention and cardiac remodeling. Many mechanisms have been suggested to explain this phenomenon which seems to be multifactorial and play a major role in the development of renal hyporesponsiveness to NPs and cardiac remodeling. This review focuses on the mechanisms underlying the development of edema in HF with reduced ejection fraction and refers to the therapeutic maneuvers applied today to overcome abnormal salt/water balance characterizing HF.

Cardiorenal Interactions in Acute Heart Failure; Renal Proximal Tubules in the Spotlight

“…Similarly, it should be noted that low GFR is associated with enhanced proximal tubular absorption of sodium; an increase in GFR (e.g., through improvement in hemodynamics) may facilitate urinary sodium excretion [45]. Finally, the changes in renal hemodynamics and renal venous congestion induced by increased intra-abdominal pressure would lead to lower GFR and enhanced proximal tubular sodium absorption that may be reversed after reduction of pressure [46].…”

Anaemia and Congestion in Heart Failure: Correlations and Prognostic Role

“…Indeed, fluid retention in HF is a complex physiopathologic condition with many actors [ 45 ]. The renin–angiotensin–aldosterone system (RAAS) principally impacts systemic fluid regulation: it is responsible for tubular sodium reabsorption and concomitant water retention; the action of angiotensin II on angiotensin receptor 1 (AT1) induces glomerulus hypoperfusion due to the vasoconstriction of the afferent and efferent arterioles: this reduces the filtration rate of the kidney and promotes systemic fluid accumulation [ 46 ].…”

“…The NP system is also able to impact both fluid retention and anaemia in patients with HF [ 45 ]. HF increases the production of both atrial (ANP) and BNP, which in turn activate natriuretic peptide receptor B (NPR-B).…”

Left labial edema after kidney transplantation

“…General medical conditions can also result in edema formation [4][5][6]. Changes in normal fluid homeostasis that cause an increased secretion or impaired removal of fluid can cause edema.…”

“…Changes in normal fluid homeostasis that cause an increased secretion or impaired removal of fluid can cause edema. In the case of kidney failure, there is impaired removal of fluid from the body, causing an increase in intravascular hydrostatic pressure and edema [4,6,7]. Areas with loose, distensible skin are particularly at risk for fluid collection, the genitalia included [7].…”