Nephron

Fig.2) Schematic of the glomerular filtration barrier (GFB). A. The endothelial cells of the glomerulus; 1. endothelial pore (fenestra).
B. Glomerular basement membrane: 1. lamina rara interna 2. lamina densa 3. lamina rara externa
C. Podocytes: 1. enzymatic and structural proteins 2. filtration slit 3. diaphragm

The renal corpuscle is the site of the filtration of blood plasma. The renal corpuscle consists of the glomerulus, and the glomerular capsule or Bowman's capsule.[3]^: 1027

The renal corpuscle has two poles: a vascular pole and a tubular pole.[4]^: 397 The arterioles from the renal circulation enter and leave the glomerulus at the vascular pole. The glomerular filtrate leaves the Bowman's capsule at the renal tubule at the urinary pole.

The glomerulus is the network known as a tuft, of filtering capillaries located at the vascular pole of the renal corpuscle in Bowman's capsule. Each glomerulus receives its blood supply from an afferent arteriole of the renal circulation. The glomerular blood pressure provides the driving force for water and solutes to be filtered out of the blood plasma, and into the interior of Bowman's capsule, called Bowman's space.

Only about a fifth of the plasma is filtered in the glomerulus. The rest passes into an efferent arteriole. The diameter of the efferent arteriole is smaller than that of the afferent, and this difference increases the hydrostatic pressure in the glomerulus.

The Bowman's capsule, also called the glomerular capsule, surrounds the glomerulus. It is composed of a visceral inner layer formed by specialized cells called podocytes, and a parietal outer layer composed of simple squamous epithelium. Fluids from blood in the glomerulus are ultrafiltered through several layers, resulting in what is known as the filtrate.

The filtrate next moves to the renal tubule, where it is further processed to form urine. The different stages of this fluid are collectively known as the tubular fluid.

The renal tubule is long pipe like structure containing the tubular fluid filtered through the glomerulus.[5] After passing through the renal tubule, the filtrate continues to the collecting duct system.[6]

The components of the renal tubule are:

• Proximal convoluted tubule (lies in cortex and lined by simple cuboidal epithelium with brush borders which help to increase the area of absorption greatly.)
• Loop of Henle (hair-pin like, i.e. U-shaped, and lies in medulla)
  • Descending limb of loop of Henle
  • Ascending limb of loop of Henle
    • The ascending limb of loop of Henle is divided into 2 segments: Lower end of ascending limb is very thin and is lined by simple squamous epithelium. The distal portion of ascending limb is thick and is lined by simple cuboidal epithelium.
    • Thin ascending limb of loop of Henle
    • Thick ascending limb of loop of Henle (enters cortex and becomes the distal convoluted tubule.)
• Distal convoluted tubule
• Collecting tubule

Blood from the efferent arteriole, containing everything that was not filtered out in the glomerulus, moves into the peritubular capillaries, tiny blood vessels that surround the loop of Henle and the proximal and distal tubules, where the tubular fluid flows. Substances then reabsorb from the latter back to the blood stream.

The peritubular capillaries then recombine to form an efferent venule, which combines with efferent venules from other nephrons into the renal vein, and rejoins the main bloodstream.

Cortical nephrons (the majority of nephrons) start high in the cortex and have a short loop of Henle which does not penetrate deeply into the medulla. Cortical nephrons can be subdivided into superficial cortical nephrons and midcortical nephrons.[7]

Juxtamedullary nephrons start low in the cortex near the medulla and have a long loop of Henle which penetrates deeply into the renal medulla: only they have their loop of Henle surrounded by the vasa recta. These long loops of Henle and their associated vasa recta create a hyperosmolar gradient that allows for the generation of concentrated urine.[8] Also the hairpin bend penetrates up to the inner zone of medulla.[9]

Juxtamedullary nephrons are found only in birds and mammals, and have a specific location: medullary refers to the renal medulla, while juxta (Latin: near) refers to the relative position of the renal corpuscle of this nephron - near the medulla, but still in the cortex. In other words, a juxtamedullary nephron is a nephron whose renal corpuscle is near the medulla, and whose proximal convoluted tubule and its associated loop of Henle occur deeper in the medulla than the other type of nephron, the cortical nephron.

The juxtamedullary nephrons comprise only about 15% of the nephrons in the human kidney.[1]^: 24 However, it is this type of nephron which is most often depicted in illustrations of nephrons.

In humans, cortical nephrons have their renal corpuscles in the outer two thirds of the cortex, whereas juxtamedullary nephrons have their corpuscles in the inner third of the cortex.[1]^: 24

The proximal tubule as a part of the nephron can be divided into an initial convoluted portion and a following straight (descending) portion.[10] Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the peritubular capillaries, including 80% of glucose,more than half of the filtered salt, water and all filtered organic solutes (primarily glucose and amino acids).[4]^{: 400–401}

The loop of Henle is a U-shaped tube that extends from the proximal tubule. It consists of a descending limb and an ascending limb. It begins in the cortex, receiving filtrate from the proximal convoluted tubule, extends into the medulla as the descending limb, and then returns to the cortex as the ascending limb to empty into the distal convoluted tubule. The primary role of the loop of Henle is to enable an organism to produce concentrated urine, not by increasing the tubular concentration, but by rendering the interstitial fluid hypertonic.[1]^: 67

Considerable differences aid in distinguishing the descending and ascending limbs of the loop of Henle. The descending limb is permeable to water and noticeably less permeable to salt, and thus only indirectly contributes to the concentration of the interstitium. As the filtrate descends deeper into the hypertonic interstitium of the renal medulla, water flows freely out of the descending limb by osmosis until the tonicity of the filtrate and interstitium equilibrate. The hypertonicity of the medulla (and therefore concentration of urine) is determined in part by the size of the loops of Henle.[1]^: 76

Unlike the descending limb, the thick ascending limb is impermeable to water, a critical feature of the countercurrent exchange mechanism employed by the loop. The ascending limb actively pumps sodium out of the filtrate, generating the hypertonic interstitium that drives countercurrent exchange. In passing through the ascending limb, the filtrate grows hypotonic since it has lost much of its sodium content. This hypotonic filtrate is passed to the distal convoluted tubule in the renal cortex.[1]^: 72

The distal convoluted tubule has a different structure and function to that of the proximal convoluted tubule. Cells lining the tubule have numerous mitochondria to produce enough energy (ATP) for active transport to take place. Much of the ion transport taking place in the distal convoluted tubule is regulated by the endocrine system. In the presence of parathyroid hormone, the distal convoluted tubule reabsorbs more calcium and secretes more phosphate. When aldosterone is present, more sodium is reabsorbed and more potassium secreted. Ammonia is also absorbed during the selective reabsorption. Atrial natriuretic peptide causes the distal convoluted tubule to secrete more sodium.

A part of Distal nephron. This is the final segment of the tubule before it enters the collecting duct system. Water, some salts and nitrogenous waste like urea and creatinine are passed out to collecting tubule.

Fig.6) Cross-sectional histologic preparation showing (b)small connecting tubules with simple columnar epithelium and (a) large connecting tubules with simple cuboidal epithelium.

Each distal convoluted tubule delivers its filtrate to a system of collecting ducts, the first segment of which is the connecting tubule. The collecting duct system begins in the renal cortex and extends deep into the medulla. As the urine travels down the collecting duct system, it passes by the medullary interstitium which has a high sodium concentration as a result of the loop of Henle's countercurrent multiplier system.[1]^: 67

Because it has a different origin during the development of the urinary and reproductive organs than the rest of the nephron, the collecting duct is sometimes not considered a part of the nephron. Instead of originating from the metanephrogenic blastema, the collecting duct originates from the ureteric bud.[11]^: 50–51

Though the collecting duct is normally impermeable to water, it becomes permeable in the presence of antidiuretic hormone (ADH). ADH affects the function of aquaporins, resulting in the reabsorption of water molecules as it passes through the collecting duct. Aquaporins are membrane proteins that selectively conduct water molecules while preventing the passage of ions and other solutes. As much as three-quarters of the water from urine can be reabsorbed as it leaves the collecting duct by osmosis. Thus the levels of ADH determine whether urine will be concentrated or diluted. An increase in ADH is an indication of dehydration, while water sufficiency results in a decrease in ADH allowing for diluted urine.[4]^: 406

Fig.7) Cross-sectional diagram of the juxtaglomerular apparatus and adjacent structures: 1) top, yellow - distal convoluted tubule; 2) top, brown -macula densa cuboidal cells surrounding arterioles; 3) small blue cells - juxtaglomerular cells; 4) large blue cells - mesangial cells; 5) tan - podocytes lining Bowman's capsule adjacent to capillaries, and parietal layer of capsule, 6)center - five glomerular capillaries, and the 6)bottom, purple - exiting tubule. Structures (2), (3), and (4) constitute the juxtaglomerular apparatus.

Lower portions of the collecting organ are also permeable to urea, allowing some of it to enter the medulla, thus maintaining its high concentration (which is very important for the nephron).[1]^: 73–74

Urine leaves the medullary collecting ducts through the renal papillae, emptying into the renal calyces, the renal pelvis, and finally into the urinary bladder via the ureter.[4]^{: 406–407}

The juxtaglomerular apparatus (JGA) is a specialized region associated with the nephron, but separate from it. It produces and secretes into the circulation the enzyme renin (angiotensinogenase), which cleaves angiotensinogen and results in the ten amino acid substance angiotensin-1 (A-1). A-1 is then converted to angiotensin-2, a potent vasoconstrictor, by removing two amino acids: this is accomplished by angiotensin converting enzyme (ACE). This sequence of events is referred to as the renin–angiotensin system (RAS) or renin-angiotensin-aldosterone system (RAAS). The JGA is located between the thick ascending limb and the afferent arteriole. It contains three components: the macula densa, juxtaglomerular cells, and extraglomerular mesangial cells.[4]^: 404