janeraf panthiah ernist
Karmen Mcarthun
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Exercise induces profound changes in the renal haemodynamics and in electrolyte and protein excretion. Effective renal plasma flow is reduced during exercise. The reduction is related to the intensity of exercise and renal blood flow may fall to 25% of the resting value when strenuous work is performed. The combination of sympathetic nervous activity and the release of catecholamine substances is involved in this process. The reduction of renal blood flow during exercise produces a concomitant effect on the glomerular filtration rate, though the latter decreases relatively less than the former during exertion. However, the degree of hydration has an important influence on the glomerular filtration rate. An antidiuretic effect is observed during intense exercise. Changes in urine flow are dependent on the plasma antidiuretic hormone levels which are increased by intense exercise. Heavy exercise has an inhibitory effect on most electrolytes (Na, Cl, Ca, P). With potassium, however, most studies report that potassium excretion is not consistently affected by moderate to heavy exercise. Increased aldosterone production helps the body to maintain sodium by increasing its reabsorption from the filtered tubular fluid. Recent studies suggest that sympathetic stimulation may be involved during exercise. Strenuous work leads to an increased excretion of erythrocytes and leucocytes in urine. Cylindruria has been regularly found in postexercise urine in different sports. Postexercise proteinuria is a common phenomenon in humans. It seems to be directly related to the intensity of exercise, rather than to its duration. This excretion of proteins in urine is a transient state with a half-time of approximately 1 hour. Postexercise proteinuria has a pattern different from normal physiological proteinuria. Immunochemical techniques demonstrate that postexercise proteinuria is of the mixed glomerular-tubular type, the former being predominant. The increased clearance of plasma proteins suggests an increased glomerular permeability and a partial inhibition of tubular reabsorption of macromolecules. Haemoglobinuria and myoglobinuria may be observed under special exercise conditions. The degree of hydration appears to be important to reduce these abnormalities.
Exercise induces profound changes in renal haemodynamics and protein excretion. The rate of ultrafiltration across the glomerular capillary is determined by the imbalance between the transcapillary hydraulic and colloid osmotic pressure gradients. Despite a major reduction in the renal plasma flow, the filtration fraction can double with maximal exercise, preserving the transfer of metabolites or substances through the glomerulus. Tubular processes and excretion rates are modified by exercise. Despite large increases in plasma lactate during strenuous exercise, renal excretion plays a limited role in lactate metabolism. Apparently, the mechanism of transcellular transport of lactate is saturated during severe exercise. Urea reabsorption is enhanced during prolonged exercise, and this process may act to limit the dehydration of an individual. As uric acid transport is also carrier-mediated, it appears that there is no saturation of the carrier system during prolonged exercise. Postexercise proteinuria is directly related to the intensity of exercise rather than to its duration. This excretion of excess proteins is a transient state with a half-time decay of about 1 hour. The increased clearance of plasma proteins suggests an increased glomerular permeability and a partial inhibition of tubular reabsorption. Studies suggest that exercise decreases the glomerular electrostatic barrier and facilitates transfer of macromolecules. Postexercise proteinuria appears to be age-dependent. Nephropathy is a common observation in the diabetic patient. In young and adult diabetic patients, exhaustive physical exercise does not provoke an enhanced dysfunction of the kidney to what is already found in healthy individuals. Heart and kidney transplant patients have a lesser postexercise proteinuria as compared with healthy individuals.
The renin-angiotensin-aldosterone system (RAAS) is a critical regulator of blood volume, electrolyte balance, and systemic vascular resistance. While the baroreceptor reflex responds short term to decreased arterial pressure, the RAAS is responsible for acute and chronic alterations. The classical understanding of RAAS is that it comprises three significant compounds: renin, angiotensin II, and aldosterone.[1][2] These three compounds elevate arterial pressure in response to decreased renal blood pressure, salt delivery to the distal convoluted tubule, and beta-agonism. The understanding of RAAS has expanded tremendously due to discoveries of newer system components over the last few decades. The discussion in this article will be limited to the components of the classical pathway of the renin-angiotensin-aldosterone system (Image 1).
In addition to the main physiological functions, the RAAS has a significant role in the pathophysiological conditions of hypertension, heart failure, other cardiovascular diseases, and renal diseases.[4][5] Blockade of the overactivation of RAAS by various medications has been shown to improve outcomes in various cardiovascular and renal diseases.
The juxtaglomerular (JG) cells, present within the afferent arterioles of the kidney, contain prorenin. Activation of JG cells causes the cleavage of prorenin to renin. The activation of prorenin occurs in the kidney by enzymes like proconvertase 1 and cathepsin B.[6][7] Mature renin is stored in the granules of the JG cells and released into circulation by four main stimuli: [8][9][10]
Therefore, conditions leading to decreased renal perfusion and reduced tubular sodium content lead to renin enzyme release into the bloodstream. The half-life of renin activity in circulation is 10-15 minutes.[11] Renin is the rate-limiting enzyme in RAAS.[12]
This enzyme is expressed on plasma membranes of vascular endothelial cells, primarily in the pulmonary circulation.[14] It cleaves the two amino acids from the C-terminal of angiotensin I to make the peptide angiotensin II.
ACE generates angiotensin II by cleaving the two amino acids at the C-terminal of angiotensin I. Angiotensin II is the primary mediator of the physiologic effects of RAAS, including blood pressure, volume regulation, and aldosterone secretion.[15] The half-life of angiotensin II in circulation is very short, less than 60 seconds.[16] Peptidases degrade it into angiotensin III and IV. Angiotensin III has been shown to have 100% of the aldosterone-stimulating effect of angiotensin II but 40% of the pressor effects, while angiotensin IV has further decreased the systemic effect.[17]
Angiotensin II is also implicated in many pathophysiological states and is known to induce oxidative stress, vascular smooth muscle contraction, endothelial dysfunction, fibrosis, and hypertrophic, anti-apoptotic, and pro-mitogenic effects.[24][25][26] Angiotensin II has been implicated in the pathogenesis of hypertension, atherosclerotic disease, heart failure, and kidney disease through these effects.[27][28][29][30]
The physiological and pathophysiological effects of angiotensin II are mediated by two types of receptors: type 1 and type 2.[31] These receptors have different and often opposing physiological responses.[32]
AT1-R is a G-protein coupled receptor.[33] It is widely distributed in many cell types, including the heart, vasculature, kidney, adrenal glands, pituitary, and central nervous system.[34][35][36][37] Angiotensin II mediates its physiological effects of vasoconstriction and sodium and water reabsorption through the AT1-R.[38] In pathogenic states, the activation of the AT1-R leads to inflammation, fibrosis, oxidative stress, tissue remodeling, and increased blood pressure.[39] The dysregulation of this receptor is central to the pathophysiology of cardiac and renal diseases.[38][40][41]
AT2-R is a G-protein coupled receptor.[33] It is mainly expressed in fetal tissues, and expression decreases in adulthood.[42][32] In adults, it is distributed in the heart, kidney, adrenal glands, and brain.[43][44][45] AT2-R mediates the opposing and protective effects of angiotensin II via the AT1-R. These actions inhibit inflammation, fibrosis, and central sympathetic outflow and cause vasodilation.[46][47] Stimulation of the AT2-R by angiotensin II leads to vasodilation and natriuresis, opposite to the vasoconstriction and anti-natriuresis caused by angiotensin II via the AT1-R.[48][32][49]
Aldosterone is synthesized primarily in the zona glomerulosa of the adrenal cortex. The synthesis and secretion of this hormone are primarily regulated by angiotensin II, ACTH, and extracellular potassium concentration.[50][51] The effects of aldosterone are mediated through nuclear cytosolic receptors.[52] The half-life of aldosterone in plasma is less than 20 minutes.[53]
Aldosterone mediates its effects on electrolyte and renal homeostasis by binding to the MR receptors on principal epithelial cells in the renal cortical collecting duct. Sodium is reabsorbed via the ENaC (epithelial sodium channel) on the apical membranes of principal cells in the collecting tubules. Aldosterone leads to increased concentrations of ENaC channels at the apical membrane, resulting in increased sodium reabsorption.[53][54] Na-K ATPase activation at the basolateral membrane of apical cells occurs by the effect of aldosterone.[55] This leads to sodium transport in the extracellular space and increases potassium uptake in the apical cells. Aldosterone also influences salt and water homeostasis by regulating thirst and salt appetite via the mineralocorticoid receptors present in various regions of the brain.[56][57][58][59]
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