Urinary System: Kidney

Kidney is divided into two regions:

• Cortex, whose main components are the renal corpuscles, convoluted tubules, straight tube, cortical collecting ducts, and extensive vascular supply. The first three make up the nephron, which is the functional and structural unit of the kidney. Sections of the kidney reveal a series of vertical striations, which appear to emanate from the medulla called medullary rays (consisting of straight tubules and cortical collecting ducts). Regions between the medullary rays are called cortical labyrinths, consisting of convoluted tubules, renal corpuscles, and interlobular arteries and veins.
• Medulla, which are characterized by the presence of straight tubules, medullary collecting ducts and vasa recta (blood vessels that run parallel to the straight tubules of the loop of Henle and collecting ducts). The three structures constitute the countercurrent exchange system, regulating urine concentration.
• Medullary straight tubules, due to differences in length and arrangement. They form a number of conical structures (the renal pyramids).
• Caps of cortical tissue over pyramids extend down around lateral portions of the pyramid, called renal columns.

Kidney lobes and lobules:

The number of lobes equals the number of renal pyramids (8-18 lobes). A lobe consists of one renal pyramid, which is associated with cortical tissue at its base and sides. Lobation is most evident in fetal kidneys., and disappears after birth (although may exist until a teenager). Each lobe is composed of lobules, which consists of one medullary ray and half of the surrounding cortical labyrinth on either side.

Arterial blood supply:

Each kidney is supplied by a renal artery. The renal artery branches into interlobar arteries. Which travel between the lobes (pyramids) up to the level of the cortex. Then they turn to follow an arched course between the cortex and medulla, hence they are then called arcuate arteries. Arcuate arteries then branch into intralobular arteries, which ascend in the cortex towards the capsule. They give off afferent arterioles, one to each renal corpuscle. These then give rise to the capillary network that forms the glomerulus, which is then drained by the efferent arterioles. This gives rise to a second network of capillaries, the peritubular capillaries, that surround the convoluted tubules. The efferent arterioles from the juxtamedullary glomeruli descent to the medulla, forming the vasa recta, which is part of the countercurrent multiplier system.

There are 2 million Nephrons per kidney, They consist of a renal corpuscle (aka malpighian corpuscle) and a tubule system.

• Renal corpuscle is at the beginning of the nephron and is made of:
• Glomerulus, which is a tuft of 10-20 capillary loops, arising from the afferent arteriole and drinking into the efferent arteriole.
• Bowman’s (renal) capsule is a cup where blood undergoes ultrafiltration. The ultrafiltrate accumulates in the urinary space (i.e. Bowman’s space). The urinary space is surrounded by two layers of epithelial cells: parietal layer (simple squamous epithelium) and visceral layer (cytoplasmic processes of podocyte cells). Bowman’s capsule has two poles: vascular pole (where afferent and efferent arterioles penetrate and exit the capsule, respectively) and urinary pole (beginning of the proximal convoluted tubule).

Following the Bowman’s capsule are:

• Proximal thick segment, made of the proximal convoluted tubule and the proximal straight tubule
• Thin segment, made of the thin limb of Loop of Henle
• Parts of the Loop of Henle include the descending (proximal) thick segment, the descending thin limb, and its hairpin turn, the ascending thin limb, and the ascending (distal) thick segment)
• Distal thick segment, made of the distal straight tubule and the distal convoluted tubule

Types of nephrons include:

• Cortical or subcapsular nephrons, whose corpuscles are located in the outer cortex and have short loops of Henle
• Juxtamedullary nephrons, whose corpuscles are located in proximity to base of the medullary pyramid and have long loops of Henle
• Intermediate nephrons, whose renal corpuscles in the mid region of the cortex and loops of Henle of intermediate length

Filtration apparatus is located in the renal corpuscles and consists of three components:

• Endothelium of glomerular capillaries, possesses numerous large fenestration. Fenestration has no diaphragm. Endothelial cells possess a large number of water channel aquaporin-1 (AQP-1). They restrict movement of blood cells & formed elements of blood.
• Glomerular basement membrane (GBM) is located between the endothelial cells and the podocytes. It’s the joint product of these cells. It serves as a physical barrier and an ion-selective filter. It consists of:
• Lamina rara interna, which is adjacent to the capillary endothelium.
• Lamina rara external, which is adjacent to the podocyte processes. Both interna and externa are rich in polyanion GAGs, such as heparan sulfate. These impede passage of negatively charged molecules.
• Lamina densa, which is a fused portion of the basal lamina. Sandwiched between the lamina rara. It is made of type IV collagen, organized into feltwork (fibrous network) that acts as a physical filter.
• Visceral layer of Bowman’s capsule, which consists of specialized cells called podocytes. Podocytes constitute the visceral (inner) layer of Bowman’s capsule. They send primary processes around glomerular capillaries that branch into Secondary processes, which gives rise to pedicels or foot processes (Interdigitate with pedicels from another podocyte). Spaces between adjacent pedicels are called filtration slits.
• Filtration slits are spaces between two pedicles, about 40nm wide. They allow blood filtrate to enter Bowman’s space. They exclude plasma proteins and permit water, glucose, amino acids, and metabolic waste products to pass. They act as physical barriers to bulk flow and free diffusion. The slits are closed by a filtration slit membrane, formed by the transmembrane protein nephrin. Nephrin is anchored to actin filaments of podocyte cytoplasm. Nephrins from adjacent pedicels interdigitate with each other.
• Podocyte foot processes contain actin filaments to regulate slits.

Mesangial cells are a group of cells in the renal corpuscle. The mesangium is the mesangial cells & their ECM. They are located in the vascular stalk of glomerulus. Like pericytes, they are enclosed by basal lamina of glomerular capillaries. Some mesangial cells are located outside the renal corpuscle, along the vascular pole. They are called Lacis Cells, and form part of the Juxtaglomerular Apparatus. Mesangial cells functions include:

• Provide structural support at sites where the GBM is incomplete
• Primary function is to clean the GBM (phagocytotic, not monocytic)
• Secrete interleukin-1 and platelet-derived growth factor (PDGF), which has a role in the response to glomerular injury
• Contractile, which regulates glomerular blood flow
• They are derived from smooth muscle precursors

Juxtaglomerular Apparatus consists of three cell types:

• Juxtaglomerular cells are modified smooth muscle cells of the afferent arterioles at the site of entry into the renal corpuscle. They are occasionally found in the efferent arterioles. They are mechanoreceptors and contain secretory granules (containing renin) They are in intimate contact with endothelial cells of the afferent arteriole, due to a lack of internal elastic lamina. They have spherical nuclei (unlike smooth muscle).
• Renin is synthesized, stored and released from JC cells. In blood, renin catalyzes hydrolysis of angiotensinogen to produce Angiotensin I. Angiotensin I is then converted to Angiotensin II in the lung by the angiotensin-converting enzyme on endothelial cells of lung capillaries. Angiotensin II is the active agent in blood pressure regulation. It stimulates synthesis & release of aldosterone. Aldosterone increases reabsorption of water from DCT and collecting ducts (i.e., renin regulates blood pressure).
• Macula densa is a group of distinctive cells that are narrower and usually taller than the other cells of the distal convoluted tubule. The nuclei appear crowded and superimposed over each other. It marks the very beginning of the distal convoluted tubule (DCT) of the nephron. It monitors Na+ concentration in DCT (osmoreceptors) and regulates renin secretion from the juxtaglomerular cells.
• Extraglomerular mesangial cells (lacis cells) are located in a notch between the afferent and efferent arterioles. They are in close association with the macula densa and juxtaglomerular cells. They show extensive interdigitations and are interconnected by means of gap junction with each other and with the juxtaglomerular cells. There is a suggestion of a functional cooperation between the three types of cells.

Collaboration between the three cell types to maintain blood pressure:

Cells of the juxtaglomerular apparatus work together to maintain blood pressure through the Renin – Angiotensin – Aldosterone System (RAAS). Low Na+ concentration in DCT stimulates macula densa cells (osmoreceptors) to secrete mediators such as: ATP, adenosine, nitric oxide (NO), and prostaglandins (PGE2). Mediator molecules act in paracrine manner and their signals are distributed to JC (probably via the gap junctions of Lacis cells). JC are stimulated to secrete renin and RAAS is activated. RAAS activation results in aldosterone secretion from the adrenal gland. Aldosterone increases Na absorption from the DCTs and Collecting ducts. Water absorption increases as a result and blood pressure is maintained.

Kidney Tubules:

• Proximal convoluted tubules (PCT) are located in the cortical labyrinth and are wider in diameter than the DCT. Line with cuboidal cells and have long microvilli apically.
• Junctional complex includes Zonula occludens (tight junction) and zonula adherens, which seal off intercellular space from lumen of duct.
• Plicae (folds), which are large flattened processes on lateral surface of cells alternating with processes of other cells.
• Interdigitation of basal processes, from basal infoldings.
• Basal striations, from elongated mitochondria in basal processes.
• Proximal (descending) thick segment of Loop of Henle, also called thick descending limb of the Loop of Henle. Found in the medullary rays. The epithelial cells are cuboidal and they have fewer short microvilli. Wider in diameter than the distal thick segment of the loop of Henle.
• Thin Segment of loop of Henle, which is located in the medulla. The length varies with the location of the nephron's corpuscle in the cortex. The longest thin segment found in the juxtamedullary nephrons. The shortest is found in the subcapsular nephrons. In LM, cells appear squamous. TEM reveals 4 epithelial cell types, but specific function of each cell type is not clear. The thin segment is part of the countercurrent exchange system.
• Distal (ascending) thick segment of Loop of Henle, which is located in the medullary ray. It contains large cuboidal cells with extensive basal-lateral plications. There are numerous mitochondria located in basal infolds with less-developed microvilli. Narrower in diameter than the descending segment. The nucleus is apical, and may cause cells to bulge into lumen.
• Distal convoluted tubule (DCT) is in the cortical labyrinth. It is shorter in length than proximal convoluted tubule and has fewer and shorter microvilli than those of the PCT. The lumina surface is smooth and clean. It is under the influence of aldosterone, ADH, and Angiotensin II. DCT is also under the influence of atrial natriuretic factor (ANF), which is released during stretching of atrial muscles. It stimulates Na+ and K+ excretion and inhibits renin and aldosterone secretions (i.e., inhibits renin-angiotensin-aldosterone system) and decreases blood pressure.
• Collective tubules and collecting ducts are under the influence of ADH and aldosterone. The collecting tubules last part of each nephron, with small tributaries of the branching collecting ducts made up of simple cuboidal cells. The collecting ducts have tributaries of the main collecting ducts (papillary ducts [of Bellini]) that empty into the minor calyces. Cells of the collecting ducts are simple columnar. The essential function is to reabsorb water. Along the entire length of the collecting tubules and ducts are two cell types:
• Light cells (also called principal cells), which are the main cells of the system. They have pale staining, possess water channels, and have basal membrane infoldings. They have a role in ion transportation and possess a single cilium with few microvilli.
• Dark Cells (also called intercalated cells) are few in number and have many mitochondria/dense cytoplasm. They help in secretion of H+ and have microvilli & folds apically. No basal infolds.

Countercurrent Multiplier System creates hypertonic urine. It’s found in the medulla and consists of the Loop of Henle, Vasa recta, and Medullary collecting ducts.

Interstitial Cells are minimal in health tissue. They increase in amount from cortex (7%) to medulla (20%).

• In the cortex, 2 cell types are seen:
• Cells resembling fibroblasts, located between the basement membrane of tubules and adjacent peritubular capillaries. They synthesize and secrete collagen (type III) and GAGs. There is evidence of erythropoietin production.
• Occasional macrophages seen.
• In medulla, interstitial cells resemble myofibroblasts. Contain bundles of actin filaments and are parallel to tubules. May have role in compressing the tubules.