The functions of the kidney arevital to life and are regulated by the endocrine system by hormones such as antidiuretichormone (ADH), aldosterone, and parathyroid hormone (PTH). The importantfunctions that the kidneys serve including: (1)1.
Filtration and excretion of metabolic wasteproducts2. Regulation of necessary electrolytes, fluid,and acid-base balance 3. Controlling reabsorption of water andmaintaining intravascular volume ,also kidneys reabsorb glucose, amino acids4. Stimulation of red blood cell (RBC) production.5.
Regulation of blood pressure via therenin-angiotensin-aldosterone system, 6. Hormonalfunctions via erythropoietin, calcitriol, and vitamin D activation. The kidney is considered as themost important organ for the excretion of water soluble drugs and/or theirmetabolites in to the urine.
(2) Nephrons are urine-producing functionalstructures of the kidney (1) which are distributed at the cortex andmedulla. A normal human kidney contains 800,000 to 1.5 million nephrons.(3) Each nephron is composed of (Figure 1): · The renalcorpuscle (Bowman capsule): containing the glomerulus. · The Proximalconvoluted tubule (PCT), located in the renal cortex.· loop of Henle(LOH) :descending limb and ascending limb located in renal medulla· The distalconvoluted tubule.· Collecting duct Figure(1): structure of the nephronTwo general classes of nephrons are: · Cortical nephrons havetheir loop of Henle in the renal medulla near its junction with the renalcortex.· Juxtamedullarynephrons have their the loop of Henle deep in the renalmedulla.
(5)1.1.2.
Renal bloodsupply (6) Normally, the kidneys receive 1,000 to1,250 mL/min of blood in the adult person which is about 25% of the cardiacoutput (COP). This amount far exceeds that needed to provide the kidney’sintrinsic oxygen requirement but ensures optimal clearance of all wastes anddrugs from the body. Essentially, all blood passes through glomeruli, and about10 % of renal blood flow is filtered (a glomerular filtration rate GFR of 125mL/min in the normal adult). The basal normal blood flow is 3 to 5 mL/min/g oftissue, greater than in most other organs. The vascular structure of the renal cortex iscomplex. The renal artery enters the kidney at the hilum, where itdivides into five interlobar arteries, each an end artery.
The afferentarterioles, which arise from the interlobular arteries, divide within thecortical tissue to form the glomerular capillary network. The capillaries thenreunite to form the efferent arterioles. Vessels from the efferent arteriolessupply the proximal and distal tubules and portions of the loops of Henle andthe collecting ducts. The juxtaglomerular apparatus is between the afferent andefferent arterioles (Figure 2) and the macula densa, a specialized groupof cells which are located in the distal convoluted tubule. The point atwhich the afferent arterioles enter the glomerulus and the efferent arterioleleaves it, the tubule of nephron return back to touch the arterioles of theglomerulus of the same nephron from which it exists. At this position, thickascending limb of loop of Henle, there is a specific modified region of tubularepithelium called the Macula densa.
1.1.3.Factors contributing to renal ischemia/reperfusion (7)Simplythe term ischemia means that there is a deficient blood supply to tissues dueto obstruction of arterial blood inflow.
Thebody is able to adapt to a reduction in blood flow to a certain level, but whendelivery of oxygen and nutrient substrates becomes inadequate, cellular injuryleads to organ dysfunction.The Kidney is considered as one of the most susceptible body organs toischemia. Renal parenchymal oxygenation is graded with the highest oxygenlevels noted in the cortex, medium levels in the outer medulla, and the lowestlevels in the papillae. As a consequence, cortical cells are the most sensitiveto ischemia, while cells in the outer medulla can shift to oxygen-independentmetabolism making them less sensitive to a hypoxic environment.
Inner medullaryand papillae cells use predominantly glucose to generate ATP via anaerobicglycolysis. Thus, these regions demonstrate a reduced sensitivity to ischemia.(12)Reperfusioncould paradoxically induce and exacerbate tissue injury and necrosis. Renal ischemia/reperfusion injury (IRI)(13,14)results from a generalized or localized impairment of oxygen and nutrientdelivery to, and waste product removal from, cells of the kidney.(15)There is a mismatch of local tissue oxygen supply and demand and accumulationof waste products of metabolism. As a result of this imbalance, the tubularepithelial cells undergo injury and, if it is severe, death by apoptosis andnecrosis (acute tubular necrosis ATN), with organ functional impairment ofwater and electrolyte homeostasis and reduced excretion of waste products ofmetabolism. (15).
There are major clinical settings or medicationuse which may lead to deposition of ischemia reperfusion injury 🙁 7, 11)· Acute renal failure caused by medications forthe treatment of hypertension,especially with angiotensin converting enzyme inhibitors (ACEIs)· Progressive azotemia · Acute pulmonary edema · Renal transplantation.· Vasoconstrictive drugs · Cyclosporine use · Tacrolimus use · Overuse of NSAIDs· Radiocontrast agents· Hypotension linked to sepsis or bloodloss after surgery and trauma. · Renal vascular diseases 1.1.4. Cellular changes duringischemic acute kidney injury (AKI)1.
1.4.1.
Endothelial dysfunction (17)Endothelial cells contribute to:· Vascular tone· Vascular permeability· Participate in coagulation and regulation of blood flow tolocal tissue beds · Modulation ofinflammation . Here we will discuss the changes thatoccur in the endothelium during ischemic injury
