Nephron

A nephron is the basic structural and functional unit of the kidney. Its chief function is to regulate water and soluble substances by filtering the blood, reabsorbing what is needed and excreting the rest as urine. Nephrons eliminate wastes from the body, regulate blood volume and pressure, control levels of electrolytes and metabolites, and regulate blood pH. Its functions are vital to life and are regulated by the endocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.

Each nephron is composed of an initial filtering component (the renal corpuscle) and a tubule specialized for reabsorption and secretion (the renal tubule). The renal corpuscle filters out large solutes from the blood, delivering water and small solutes to the renal tubule for modification.

Anatomy and function

Renal corpuscle

Composed of a glomerulus and Bowman's capsule, the renal corpuscle (or Malphigian corpuscle) is the beginning of the nephron. It is the nephron's initial filtering component.

Glomerulus

The glomerulus is a capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. The glomerular blood pressure provides the driving force for fluid and solutes to be filtered out of the blood and into the space made by Bowman's capsule.

The remainder of the blood not filtered into the glomerulus passes into the narrower efferent arteriole. It then moves into the vasa recta, which are collecting capillaries intertwined with the convoluted tubules through the interstitial space, and which the reabsorbed substances will also enter. This then combines with efferent venules from other nephrons into the renal vein, and rejoins the main bloodstream.

Bowman's capsule

Bowman's capsule (also called the glomerular capsule) surrounds the glomerulus and is composed of visceral (simple squamous epithelial cells) (inner) and parietal (simple squamous epithelial cells) (outer) layers. The visceral layer lies just beneath the thickened glomerular basement membrane and is made of podocytes which send foot processes over the length of the glomerulus. Foot processes interdigitate with one another forming filtration slits that, in contrast to those in the glomeruluar endothelium, are spanned by diaphragms. The size of the filtration slits restricts the passage of large molecules (eg, albumin) and cells (eg, red blood cells and platelets). In addition, foot processes have a negatively-charged coat (glycocalyx) that limits the filtration of negatively-charged molecules, such as albumin.

The parietal layer of Bowman's capsule is lined by a single layer of squamous epithelium. Between the visceral and parietal layers is Bowman's space, into which the filtrate enters after passing through the podocytes' filtration slits. Unlike the visceral layer, the parietal layer does not function in filtration. Rather, the filtration barrier is formed by three components: the diaphragms of the filtration slits, the thick glomerular basement membrane, and the glycocalyx secreted by podocytes.

The process of filtration of the blood in the Bowman's capsule is ultrafiltration (or glomerular filtration), and the normal rate of filtration is 125 ml/min, equivalent to ten times the blood volume daily. Measuring the glomerular filtration rate (GFR) is a diagnostic test of kidney function. A decreased GFR may be a sign of renal failure.

Any proteins under roughly 30 kilodaltons can pass freely through the membrane, although there is some extra hindrance for negatively charged molecules due to the negative charge of the basement membrane and the podocytes. Any small molecules such as water, glucose, salt (NaCl), amino acids, and urea pass freely into Bowman's space, but cells, platelets and large proteins do not. As a result, the filtrate leaving the Bowman's capsule is very similar to blood plasma in composition as it passes into the proximal convoluted tubule.

Renal tubule

Proximal tubule

The proximal tubule can be anatomically divided into two segments: the proximal convoluted tubule and the proximal straight tubule. The proximal convoluted tubule can be divided further into S1 and S2 segments based on the histological appearance of its cells. Following this naming convention, the proximal straight tubule is commonly called the S3 segment.

Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the peritubular capillaries, including approximately two-thirds of the filtered salt and water and all filtered organic solutes (primarily glucose and amino acids). This is driven by sodium transport from the lumen into the blood by the Na⁺/K⁺ ATPase in the basolateral membrane of the epithelial cells. Much of the mass movement of water and solutes occurs in between the cells through the tight junctions, which in this case are not selective.

The solutes are absorbed isotonically, in that the osmotic potential of the fluid leaving the proximal tubule is the same as that of the initial glomerular filtrate. However, glucose, amino acids, inorganic phosphate, and some other solutes are reabsorbed via secondary active transport through cotransport channels driven by the sodium gradient out of the nephron.

Loop of Henle

The loop of Henle (sometimes known as the nephron loop) is a U-shaped tube that consists of a descending limb and ascending limb. It begins in the cortex, receiving filtrate from the proximal convoluted tubule, extends into the medulla, and then returns to the cortex to empty into the distal convoluted tubule. Its primary role is to concentrate the salt in the interstitium, the tissue surrounding the loop.

=Descending limb

= Its descending limb is permeable to water but completely impermeable 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. Longer descending limbs allow more time for water to flow out of the filtrate, so longer limbs make the filtrate more hypertonic than shorter limbs.

=Ascending limb

= Unlike the descending limb, the ascending limb of Henle's loop 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.

Distal convoluted tubule

The distal convoluted tubule is similar to the proximal convoluted tubule in structure and function. Cells lining the tubule have numerous mitochondria, enabling active transport to take place by the energy supplied by ATP. 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 excretes more phosphate. When aldosterone is present, more sodium is reabsorbed and more potassium excreted. Atrial natriuretic peptide causes the distal convoluted tubule to excrete more sodium. In addition, the tubule also secretes hydrogen and ammonium to regulate pH.

After travelling the length of the distal convoluted tubule, only 3% of water remains, and the remaining salt content is negligible. 97.9% of the water in the glomerular filtrate enters the convoluted tubules and collecting ducts by osmosis.

Collecting duct system

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. Though the collecting duct is normally impermeable to water, it becomes permeable in the presence of antidiuretic hormone (ADH). As much as three-fourths 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 dilute. Dehydration results in an increase in ADH, while water sufficiency results in low ADH allowing for diluted urine. Lower portions of the collecting duct are also permeable to urea, allowing some of it to enter the medulla of the kidney, thus maintaining its high ion concentration (which is very important for the nephron).

Urine leaves the medullary collecting ducts through the renal papilla, emptying into the renal calyces, the renal pelvis, and finally into the bladder via the ureter.

Because it has a different embryonic origin than the rest of the nephron (the collecting duct is from endoderm whereas the nephron is from mesoderm), the collecting duct is usually not considered a part of the nephron proper.

Juxtaglomerular apparatus

The juxtaglomerular apparatus occurs near the site of contact between the thick ascending limb and the afferent arteriole. It contains a tightly-packed area of cells in the thick ascending limb, the macula densa, as well as specialized smooth muscle cells, the juxtaglomerular cells, in the wall of the afferent arteriole. Juxtaglomerular cells are the site of renin synthesis and secretion and thus play a critical role in the renin-angiotensin system.

Clinical relevance

Because of its importance in body fluid regulation, the nephron is a common target of drugs that treat high blood pressure and edema. These drugs, called diuretics, inhibit the ability of the nephron to retain water, increasing the amount of urine produced.

External links

Science aid: Kidney Nephron About the kidney nephron for teen understanding.

Kidney | Urinary system

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