The kidneys are paired retroperitoneal organs of the urinary system. Their function is to filter blood and produce urine. Each kidney consists of a cortex, medulla and calyces. Nephrons are the main functional units of the kidney, in charge of removing metabolic waste and excess water from the blood. In this article we will explore the microanatomy of a nephron and learn how their function relates to their histological features.
Learning about kidney histology doesn’t have to be as painful as kidney stones! We have composed a simple step-by-step guide to help you master this complicated yet fascinating organ. If you need a little jump start, why not refresh your memory with our introduction to histology and gross anatomy of the kidney.
|Gross anatomy||Cortex (outer layer) and medulla (inner layer), calyces|
|Nephron||Main functional unit of the kidney:
- Renal corpuscle; glomerulus and glomerular capsule
- Renal tubule system; proximal tubule (convoluted and straight), nephron loop, distal tubule (convoluted and straight), collecting ducts
|Functions||Urine production; maintains body fluid and electrolyte balance, blood pressure, acid base balance|
- Kidney structure
- Cortex and medulla
- Secretion and reabsorption
The kidney is a bean shaped organ, with a convex lateral surface, concave medial surface and superior and inferior poles. The medial surface features the hilum of the kidney, which is the passageway for the renal vessels and the ureter. A connective tissue capsule (renal capsule) and a layer of perinephric (perirenal) fat protect and cushion the kidney. The capsule contains a layer of contractile cells called myofibroblasts, which make the capsule able to adapt to the constant pressure changes within the kidney. The suprarenal (adrenal) gland sits on the kidney’s superior pole, separated from it by the perinephric fat. Both the kidney and the suprarenal gland are covered by a layer of renal fascia.
The kidney parenchyma consists of two layers; an outer cortex and inner medulla. They comprise around one million urine-producing nephrons. Urine is collected into a system of renal calyces, which is a series of distinctive chambers within a kidney. Calyces gradually increase in size, starting with the minor calyces, which open into larger major calyces, which empty into the renal pelvis. From the renal pelvis, the urine passes into the ureter. The portion of the kidney which contains the calyces, renal pelvis, ureter and renal vessels is called the renal sinus.
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Cortex and medulla
Now let’s take a closer look at the parenchyma layers. The renal cortex is the outer layer of the kidney tissue. It is darker than its underlying renal medulla because it receives over 90% of the kidney blood supply. The cortex has a grainy appearance, as it mostly contains ovoid and coiled parts of the nephrons (renal corpuscles and convoluted tubules).
The renal medulla appears striped, as it contains vertical nephron structures (tubules, collecting ducts). It consists of renal (medullary) pyramids separated by projections of the renal cortex (renal columns). The apices of the pyramids project towards the renal pelvis and open into the minor calyces via perforated plates on their surfaces (area cribrosa). Each renal pyramid, with its surrounding cortical tissue, forms a renal lobe. Renal lobes are further divided into renal lobules. Each lobule consists of a group of nephrons emptying into one collecting duct. These structures can be observed in a coronal section of the kidney.
The nephron is the functional unit of the kidney. It produces concentrated urine by creating an ultrafiltrate from blood. A nephron consists of two main parts: a renal corpuscle and its associated renal tubule system.
Renal corpuscles are located in the renal cortex, while their tubular systems extend into the medulla. Depending on their distribution and morphology, there are two main types of nephrons in the kidney; cortical and juxtamedullary. Cortical nephrons have their corpuscles close to the kidney capsule. Their tubules are very short, extending only into the upper medulla. The corpuscles of the juxtamedullary nephrons are located close to the corticomedullary border. Their tubular systems are much longer, extending deep into the medulla.
Each nephron is surrounded by a network of capillaries. Branches from the renal interlobular arteries enter a nephron as the afferent arteriole, form a capillary tuft (glomerulus) then exit the nephron as the efferent arteriole. The capillary network then continues to surround the nephrons renal tubule system as peritubular capillaries, forming the vasa recta around the nephron loop. Did you know that these peritubular capillaries secrete erythropoietin (EPO)? A hormone that regulates red blood cell production.
The renal corpuscle is the filtration apparatus of the nephron. Each corpuscle consists of two main elements; the glomerulus and glomerular (Bowman's) capsule. The glomerulus is a network of capillaries formed by branches of the renal artery (afferent and efferent arterioles).
The glomerular capsule surrounds the glomerulus. It consists of two layers (parietal and visceral), which bound a cavity called the glomerular capsular space (Bowman’s / urinary space). The inner visceral layer is made of special cells called podocytes. Podocytes cover the walls of glomerular capillaries, interdigitating with each other and forming narrow slits between their projections. The outer parietal layer is made of simple squamous epithelium and is continuous with the nephron tubules. The afferent and efferent arterioles enter the renal corpuscle at the vascular pole, while the site where the glomerular capsule narrows and continues as the proximal thick segment of the nephron is called the urinary pole.
The renal corpuscle is the starting point of urine formation. Systemic blood passes through the glomerular capillary system, and is filtered to form primary urine (ultrafiltrate). It does this via a special filtration barrier which selectively filters water and solutes from the blood passing through the glomerular capillaries. The glomerular ultrafiltrate is collected by the glomerular space, and passes into the kidney tubules.
The kidney filtration apparatus is formed by three layers of tissue; endothelium of the glomerular capillaries, glomerular basement membrane (GBM) and podocytes (visceral layer of renal capsule). Glomerular capillaries are composed of fenestrated endothelium. Fenestrations function as pores. The GBM is more complex than other epithelial basal membranes. It consists of three layers; a thick central lamina densa and two thinner layers (lamina rara interna and lamina rara externa).
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Podocytes cover the walls of the glomerular capillaries. Their finger like projections (pedicles) interdigitate, with narrow filtration slits (filtration slit diaphragm) forming between the projections. Together, these three layers function as a selective filter, allowing only molecules below a certain size, and of a certain charge, to pass from the blood and enter the renal tubular system. For example, blood cells, platelets, some proteins and some anions are prevented from leaving the glomerular capillaries, while water and solutes pass through. The remaining unfiltered blood is carried out of the glomerulus by the efferent arteriole, and passes back into the venous system.
Renal tubule system
The tubule system is the part of the nephron which processes glomerular ultrafiltrate into urine by reabsorbing necessary molecules and secreting the unnecessary and waste substances. It consists of three parts;
- Proximal tubule; convoluted proximal tubules and straight proximal tubule
- Nephron loop; descending and ascending limbs
- Distal tubule; straight distal tubule and convoluted distal tubule
The proximal tubule is the first part of the tubular system. It consists of convoluted and straight segments. The proximal convoluted tubule is located within the renal cortex and is continuous with the capsular space.
The straight proximal tubule (or thick descending limb) extends down into the medulla. Both parts are composed of simple cuboidal epithelium, rich in mitochondria and microvilli (brush border). This morphology is adapted to the proximal tubule function of absorption and secretion. More than half of the previously filtered water and molecules are returned to the blood (reabsorption) by the proximal tubules.
The nephron loop is the U-shaped bend of a nephron which extends through the medulla of the kidney. Histologically, it consists of two parts; thin descending and thin ascending limbs.
Both limbs are composed of simple squamous epithelium. The cells have few organelles, little to no microvilli and low secretion abilities. The two limbs work in parallel, with the surrounding vasa recta capillaries, to adjust the filtrate’s salt (e.g. sodium, chloride, potassium) and water levels. More specifically, the descending limb is highly permeable to water, less permeable to solutes, while the ascending limb is the opposite. Some authors consider the nephron loop to be synonymous with the loop of Henle, while other authors include the proximal straight tubule, nephron loop and distal straight tubule in this term.
The distal tubule also consists of straight and convoluted segments. The straight distal tubule (thick ascending limb) continues on from the thin ascending limb of the nephron loop at the level between the inner and outer medulla. The convoluted distal tubule projects into the cortex. Both parts of the distal tubule are composed of simple cuboidal epithelium, similar in morphology to the proximal tubule.
A key difference between them is that the epithelium of the distal tubule has less well-developed microvilli. Reabsorption and secretion occurs here, albeit to a lesser degree than in the proximal tubule. By having lots of mitochondria the straight distal tubules can reabsorb any useful substances (electrolytes), and secrete any remaining waste products using active transport. Of particular note is the absorption of sodium, under the regulation of aldosterone.
The collecting system of the kidney is a series of tubes that moves urine from the nephrons into the minor calyces. Several distal convoluted tubules from neighbouring nephrons drain into a collecting duct via connecting/collecting tubules. Collecting ducts then travel through the kidney medulla, converging at the apex of each renal pyramid. Here, several ducts merge to form a single large papillary duct (of Bellini), which opens into the minor calyx through the area cribrosa.
Collecting ducts are termed cortical or medullary, depending on which part of the kidney parenchyma that part of the duct is located. They are made of epithelial cells, which get progressively taller as the ducts get larger.
- Cortical collecting ducts - simple cuboidal epithelium
- Medullary collecting ducts - simple columnar epithelium
- Papillary ducts - simple columnar epithelium
Two additional types of cells are distinguishable in these ducts. The principal cells, which are pale staining and play a role in ion transport. Darker staining intercalated cells are scattered amongst the principal cells and are responsible for acid-base balance. Collecting ducts are the last chance site for water and electrolyte reabsorption from the filtrate further concentrating the urine, particularly under the influence of antidiuretic hormone (ADH). No more reabsorption takes place past the medullary collecting ducts.
Nestled into the vascular pole of the nephron is a collection of cells called the juxtaglomerular apparatus (JGA). It is formed by 3 types of cells; macula densa, juxtaglomerular granular (JG) cells and extraglomerular mesangial (Lacis) cells.
The macula densa are located in the wall of the distal tubule, at the point where the tubule comes in contact with the glomerulus. Here the regular cuboidal epithelium of the distal tubule crowd together and become columnar in shape. The juxtaglomerular granular (JG) cells are modified smooth muscle cells found surrounding the afferent, and sometimes efferent, arteriole. The third cell type of the JGA are the extraglomerular mesangial (Lacis) cells. These are located in the triangular space between the afferent and efferent arterioles.
The juxtaglomerular apparatus has two key functions;
- regulates glomerular blood flow and filtration rate
- regulates systemic blood pressure
Glomerular blood flow is regulated by a feedback mechanism, whereby the macula densa responds to high sodium chloride levels in the filtrate by releasing vasoconstrictor chemicals. These chemicals cause the afferent arteriole to vasoconstrict, thus lowering glomerular pressure and, in turn, filtration rate. This system maintains a mostly constant pressure within the nephrons. Systemic blood pressure is regulated through the renin-angiotensin-aldosterone system. Low systemic blood pressure, recognised by baroreceptors, triggers the juxtaglomerular granular cells to secrete an enzyme called renin. Renin, in turn, activates the renin-angiotensin-aldosterone system, raising systemic blood pressure through the actions of angiotensin and aldosterone.
Secretion and reabsorption
The nephron function is to maintain homeostasis of the body fluids, by excreting unwanted products in urine. Nephron anatomy is specialised to create urine from the blood through 4 key activities; filtration, reabsorption, secretion and excretion.
Filtration occurs in the renal corpuscle of the nephron, and is described above. Reabsorption and secretion are activities that occur in the nephrons renal tubular system. These processes fine tune what substances are excreted and what are kept, by the body. Reabsorption is the process by which water and molecules, lost from the blood during filtration, are reabsorbed back into the capillaries surrounding the nephron. Secretion is where water and molecules leave the peritubular capillaries and enter (or re-enter) the urine filtrate. The remaining product, urine, is then excreted from the kidney via the ureters.
Reabsorption and secretion are finely controlled processes, whereby the epithelial cells of each segment of the tubular system reabsorbs and secretes different substances in order to achieve maximum control over the urine concentration. Regulation of these processes includes; passive (countercurrent exchange system), nervous (sympathetic nervous system) and hormonal (angiotensin, aldosterone and antidiuretic hormone) mechanisms. The result of this process is urine, a fluid highly concentrated with body metabolic waste and excess substances. In healthy individuals, urine normally contains ions, urea, creatinine and variable amounts of water. Healthy urine is free of microorganisms, glucose, blood cells and blood proteins.
Now that you’ve mastered the histology of the kidney, why not challenge yourself with our nephron quiz: