Pre-renal AKI: Pathophysiology

00:01 So let's talk a little bit more about pre-renal and the causes behind it.

00:07 The two major causes as we've mentioned before are true volume depletion.

00:12 True volume depletion means that we have a loss of sodium from the extracellular fluid volume.

00:17 Remember, sodium is the primary cation that expands that ECF so it's critical in order to maintain our volume status to have sodium.

00:27 If we have a situation where our patient has GI losses, they develop gastroenteritis, they have significant emesis or diarrheal losses, they lose a lot of sodium and therefore become hypovolemic.

00:39 If our patient loses volume through hemorrhagic shock, renal losses if they're on excessive amounts of diuretics or cutaneous losses with burns, these can all result in hypovolemia.

00:50 We can also see renal hypoperfusion when there's a decrease in effective arterial blood volume.

00:56 And when I talk about a decrease in effective arterial blood volume, I'm really referring to the extracellular fluid volume in the arterial circulation.

01:05 So it may be such that our patient's total extracellular fluid volume is actually high or increased.

01:12 But what's actually circulating in the arterial volume and perceived by baroreceptors is actually on the lower side.

01:19 So again, if I have arterial blood volume that's low, my baroreceptors in the carotid sinus, the glomerular afferent arterioles are very low perceiving that I don't have volume and this really includes our edematous states.

01:33 That's heart failure, hepatic cirrhosis and portal hypertension and sepsis.

01:40 So, before we move on, I think it's really important to talk about what our kidneys are able to do in order to maintain our GFR when we do have a decrease in renal artery perfusion.

01:51 So if you look at our schematic here on the right, you can see that we have a picture of our glomerulus.

01:58 We have the afferent arteriole located at the left.

02:01 We have our glomerular capillary network in the middle and then we have our efferent arteriole on the right.

02:06 And remember that through changes in the afferent and efferent arteriole, we can change that hydrostatic pressure in the glomerular capillary network and we can change the filtration.

02:16 So when we have a decrease in renal perfusion, our bodies are so smart, they develop homeostatic mechanisms in order to activate and maintain that GFR.

02:26 We do this through the afferent arteriole that can vasodilate because of the generation of vasodilatory prostaglandins.

02:33 We have an increase in vasodilation which can then increase the glomerular capillary hydrostatic pressure.

02:41 At the efferent arteriole, we have things like angiotensin II which can actually cause renal vasoconstriction of that particular arteriole.

02:50 And again, if I have vasodilation and I have constriction at the efferent arteriole then I'm maintaining or increasing my hydrostatic pressure in the glomerular capillary network.

03:02 When we have this autoregulation phenomena, we can increase our filtration fraction leading to an increase in oncotic pressure in the post glomerular capillaries with a resultant increase in salt and water absorption in the proximal tubule.

03:15 Activation of angiotensin II and antidiuretic hormone will lead to also an increase in salt and water absorption so our patients tend to have a low urine sodium and a very concentrated urine.

03:30 Now, what happens when our patient comes in and they're taking a medication like a non-steroidal anti-inflammatory drug, something like ibuprofen or Aleve.

03:40 That is going to antagonize those vasodilatory prostaglandins and therefore in a situation where a patient is having a decrease in renal artery perfusion, we don't have that mechanism of vasodilation in order to increase or maintain that glomerular capillary hydrostatic pressure and that patient will have a reduction in GFR.

04:02 Similarly, what if the patient was on an ACE inhibitor or an ARB? Those are fantastic medications but if our patient is on that medication in the setting of hypovolemia, then we don't have that autoregulatory control to constrict the efferent arteriole again either maintaining or increasing hydrostatic pressure in that glomerular capillary network and then we have a resultant fall in GFR.