Renal Responses to Reduced Renal Perfusion

Renal Responses to Reduced Renal Perfusion Stage 1: Maintaining glomerular filtration – ‘pre renal’ phase        Nephron integrity is preserved in this stage and although GFR is reduced, it can be rapidly re-established if the perfusion is restored. (Biochemical markers of this stage include high urine osmolality, low urine output and low urinary sodium) Autoregulatory arteriolar responses mainly regulate blood flow and GFR in this stage through the use of general sympathetic nerve activation (autoregulation) to change afferent/efferent arteriole constriction o Afferent arteriole usually relaxes to maintain blood flow In response to low blood pressure, renin is released, activating renin-angiotensin-aldosterone system. o Angiotensin II preferentially constricts the efferent arteriole. Although this may reduce blood flow, it causes a higher filtration pressure, a higher filtration fraction and maintains GFR o Angiotensin II also increases aldosterone  causing sodium retention (due to increase expression of Na and K channels) + vasoconstriction of blood vessels  elevating blood pressure In the kidney, it preferentially constricts the efferent arteriole. Although this may reduce blood flow, it causes a higher filtration pressure, a higher filtration fraction and maintains GFR. In attempt to preserve intravascular volume, antidiuretic hormone (ADH, also called vasopressin) is being released from the posterior pituitary. ADH increases expression of water channels (Aquaporins) in cortical collecting duct, increasing water reabsorption = less urination AND urine concentrated with low sodium concentration There are also systematic responses in attempts to maintain the cardiac output (via maintaining cardiac filling by venoconstriction, increased pulse rate, increased contractility) and also systemic arteriolar vasoconstriction in order to increase vascular tone / peripheral vascular resistance. If these mechanisms are overwhelmed, ‘splanchnic’ vasoconstriction will occur where renal/gut perfusion is sacrificed to maintain ‘central’ circulation, thus this is bad for the kidneys If all the mechanisms mentioned above are overwhelmed, the renal adaptive response changes to one of self-preservation Stage 2: Turning off glomerular filtration    This is an adaptive response to maintain nephron viability and prevent further loss of perfusion at the expense of GFR The failing proximal tubular reabsorption (due to low perfusion) causes an increase in sodium delivery to the macula densa, which stimulates adenosine release. Adenosine then effectively turns off glomerular filtration by vasoconstricting the afferent arteriole, which dramatically reduces glomerular capillary pressure. Although this stops glomerular filtration, it helps to prevent further hypoxic injury to the tubules (no filtration, hence no need to expend energy on sodium reabsorption) Stage 3: Temporary renal injury (acute tubular necrosis)  Hypoxic injury to the renal tubules leads initially to ‘acute tubular necrosis’ (ATN)   However, not all nephrons are affected equally by the ATN – there is a mixture of viable but ‘switched off’ nephrons as well as the necrotic nephrons. Thus, repopulation of tubules can occur if life can be maintained Glomerular filtration remains turned off by adenosine so there is little urination and high sodium concentration Stage 4: Cortical necrosis  If there is severe and sustained loss of perfusion, this can eventually cause irreversible renal injury known as cortical necrosis Consequences of sustained loss of GFR   Retention of water soluble toxins such as potassium, hydrogen, urea/creatinine, phosphate Retention of water leading to volume overload Treatment/Management  In the setting of reduced perfusion, the initial aim of therapy is to restore perfusion and treat life threatening fluid and electrolyte disorders (especially hyperkalaemia). Assess the tubular integrity (urine biochemistry)  Urine tests may help to differentiate renal responses and aid management, and relieve any obstruction (i.e. in post-renal causes). Supportive therapy may require dialysis support.