PATHOPHYSIOLOGY OF ACUTE KIDNEY DISEASE (AKD)

AKD, or Acute Kidney Injury, occurs when there is a sudden decrease in kidney function. It can be caused
by various factors like dehydration, low blood flow to the kidneys, or certain medications. This leads to a
disruption in the normal filtration and waste removal process of the kidneys. In the case of AKD, there
are three main mechanisms that can cause it: prerenal, intrinsic renal, and postrenal.

1. Prerenal AKD occurs when there is a decrease in blood flow to the kidneys. This can happen due to
conditions like dehydration, low blood pressure, or heart failure. When the kidneys don't receive
enough blood, they can't filter and remove waste properly, leading to AKD.

2. Intrinsic renal AKD happens when there is damage to the kidney tissue itself. This can be caused by
conditions like infections, inflammation, or certain medications. The damage to the kidney tissue impairs
its ability to function properly, resulting in AKD.

3. Postrenal AKD occurs when there is a blockage in the urinary tract, preventing the normal flow of
urine out of the kidneys. This can be due to conditions like kidney stones, tumors, or an enlarged
prostate gland. The blockage causes a buildup of pressure in the kidneys, leading to AKD.

The most common cause of AKI is ischaemia, which can occur for a number of reasons). Physiological
adaptations, in response to the reduction in blood flow can compensate to a certain degree, but when
delivery of oxygen and metabolic substrates becomes inadequate, the resulting cellular injury leads to
organ dysfunction. The kidney is highly susceptible to injury related to ischaemia, resulting in
vasoconstriction, endothelial injury, and activation inflammatory processes.This susceptibility can be
explained in part from structural associations between renal tubules and blood vessels in the outer
medulla of the kidney, with ischaemia compromising blood flow to critical nephron structures present
therein. Following the reduction in effective kidney perfusion, the epithelial cells are unable to maintain
adequate intracellular ATP for essential processes. This ATP-depletion leads to cell injury and if it is
severe enough can lead to cell death by necrosis or apoptosis. During an ischaemic insult, all segments
of the nephrons can be affected but proximal tubular cells are the most commonly injured. In addition,
the nephron’s natural function is to filter, concentrate and reabsorb many substances from tubular
lumen, and the concentration of these substances may reach toxic levels for the surrounding epithelial
cells.