MEDICINE FOR ALL

JUXTA GLOMERULAR APPARATUS

Each nephron has a region called a juxtaglomerular apparatus, where the most distal portion of the ascending limb of the loop of Henle lies against the afferent arteriole feeding the glomerulus (and sometimes the efferent arteriole). Both the ascending limb and the afferent arteriole are modified at the point of contact.

The juxtaglomerular apparatus includes two cell populations that play important roles in regulating the rate of filtrate formation and systemic blood pressure. In the arterioles walls are the granular cells, also called juxtaglomerular cells, which are enlarged, smooth muscle cells with prominent secretory granules containing renin. Granular cells act as mechanoreceptors that sense the blood pressure in the afferent arteriole. The macula densa is a group of tall, closely packed cells of the ascending limb of the loop of Henle that lies adjacent to the granular cells. The macula densa cells are chemoreceptors that respond to changes in the NaCl content of the filtrate. A third population of cells, the extraglomerular mesangial cells, is also part of the juxtaglomerular apparatus. These cells are interconnected by gap junctions and may pass signals between macula densa and granular cells.

THE FILTRATION MEMBRANE

The filtration membrane lies between the blood and the interior of the glomerular capsule. It is a porous membrane that allows free passage  of water and solutes smaller than plasma proteins.

The filtration membrane layers are:

• The fenestrated endothelium of the glomerular capillaries
• The visceral membrane of the glomerular capsule, made of podocytes which have filtration slits between their foot processes
• The basement membrane composed of the fused basal laminae of the two other layers

The fenestrations (capillary pores) allow passage of all plasma components but not blood cells. The basement membrane restricts all but the smallest protein while permitting most other solutes to pass. The structural makeup of the gel-like basement membrane also confers electrical selectivity on the filtration process. Most of the proteins in the membrane  are negatively charged glycoproteins that repel other macromolecular anion and hinder their passage into the tubule. Because most plasma proteins also bear a net negative charge, this electrical repulsion reinforces the plasma protein blockage imposed by molecular size.

Almost all macromolecules that do manage to make it through the basement membrane are prevented from traveling further by thin membranes  (slit diaphragms) that extend across the filtration slits. Macromolecules that get “hung up” in the filtration membrane are engulfed and degraded by mesangial cells can also contract, changing the total surface area of the capillaries available for filtration.

The renal tubule of every nephron is closely associated with two capillary beds: the glomerulus and the peritubular capillaries. The glomerulus, in which the capillaries run in parallel, is specialized for filtration. It differs from all other capillary beds in the body in that it is both fed and drained by arterioles-the afferent arteriole and the efferent arterioles, respectively.

The afferent arterioles arise from the cortical radiate arteries that run through the renal cortex. The blood pressure in the glomerulus is extraordinarily high for a capillary bed because arterioles are high-resistance vessels and the afferent-arteriole has a larger diameter  than the efferent. This high blood pressure easily forces fluid and solutes out of the blood into the glomerular capsule. Most of the filtrating filtrate (99%) is reabsorbed by the renal tubule cells and returned to the blood in the peritubular capillary beds.

The peritubular capillaries arise from the efferen arterioles draining the glomeruli. These capillaries cling closely to adjacent renal tubules and empty into nearby venules. They are low-pressure, porous capillaries that readily absorb solutes and water from the tubule cells as these substances are reclaimed from the filtrate.

The efferent arterioles serving the juxtamedullary nephrons tend not to break up into meandering peritubular capillaries. Instead they form bundles of long straight vessels called vasa recta that extend deep into the medulla paralelling the longest loops of Henle. The thin -walled vasa recta play an important role in forming concentrated urine.

In summary, the microvasculature of the nephrons consists of two capillary beds separated by intervening efferent arterioles. The first capillary bed (glomerulus) produce the filtrate. The second (peritubular capillaries) reclaims most of that filtrate.

Blood flowing through the renal circulation encounters high resistance, first in the afferent and then in the efferent arterioles. As a result, renal blood pressure declines from approximately 95mmHg in the renal arteries to 9 mmHg or less in the renal veins. The resistance of the afferent arterioles protects the glomeruli from large fluctuations in systemic blood pressure. Resistance in the efferent arterioles reinforces the high glomerular pressure and reduces the hydrostatic pressure in the peritubular capillaries.

Nephrons are the structural and functional units of the kidneys. Each kidney contains over 1 million of these tiny blood-processing units, which carry out the process that form urine. In addition, there are thousands of collecting ducts, each of which collects fluid from several nephrons and conveys it to the renal pelvis.

Each nephron consist of a glomerulus, which is a tuft of capillaries, and a renal tubule. The renal tubule has a cup shaped-end, the glomerular capsule (or Bowman’s capsule), which is blind and completely surrounds the glomerulus, much as a well-worn baseball glove encloses a ball. Collectively, the glomerular capsule and the enclosed glomerulus are called the renal corpuscle.

The endothelium of the glomerular capillaries is fenestrated (penetrated by many pores), which makes them exceptionally porous. This allows large amounts of solute-rich, virtually protein-free fluid to pass from the blood into the glomerular capsule. This plasma-derived fluid or filtrate is the raw material that the renal tubules process to form urine.

The external parietal layer of the glomerular capsule is simple squamous epithelium. This layer simply contributes to the capsule structure and plays no part in forming filtrate.

The visceral layer, which clings to the glomerular capillaries, consist of highly modified, branching epithelial cells called podocyte. The octopus-like podocytes terminate in foot processes, which intertwine as they cling to the basement membrane of the glomerulus. The clefts or opening between the foot processes are called filtration slits. Through these slits, filtrate enters the capsular space inside the glomerular capsule.

The remainder of the renal tubule is about 3 cm long and has three major parts. It leaves the glomerular capsule as the elaborately coiled proximal convulated tubule, make a hairpin loop called the loop of Henle (also called the nephron loop or Henle’s loop), and then winds  and twists again as the distal convoluted tubule before emptying into a collecting duct. The terms proximal and distal indicate relationship of the convoluted tubules to the renal corpuscle-filtrate from the renal corpuscle passes through the proximal convulated tubule first and then the distal convulated tubule, which is thus “further away” from the renal corpuscle. The meandering nature of the renal tubule increases its length and enhances its filtrate processing capabilities.

The collecting ducts, each of which receives from may nephrons, run through the medullary pyramids and give them their striped appearance. As the collecting ducts approach the renal pelvis, they fuse together and deliver urine into the minor calyces via papillae of the pyramids.

The U-shaped loop of Henle has decending and ascending limbs. The proximal part of the decending limb is continuous with the proximal tubule and its cells are similar. The rest decending limb, called the thin segment, is a simple squamous epithelium freely permeable to water. The epithelium becomes cuboidal or even low columnar in the ascending part of the loop of Henle, which therefore becomes the thick segment. In some nephrons, the thin segment is found only in the descending limb. In others, it extends into the ascending limb as well.

Nephrons are generally divided into two major groups. Cortical nephrons represent 85% of the nephrons in the kidneys. Except for small parts of their loops of Henle that dip into the outer medulla, they are located entirely in the cortex. The remaining juxtamedullary nephrons originate close to the cortex-medulla junction, and they play an important role in the kidneys ability to produce concentrated urine. Their loops of Henle deeply invade the medulla, and their thin segments are much more extensive than those those of cortical nephrons.

The kidneys continuosly cleanse the blood and adjust its composition, so it is not surprising that they have a rich blood supply. under normal resting conditions, the large renal arteries deliver one-fourth of the total cardiac output (about 1200 ml) to the kidneys each minute.

The renal arteries issue  at right angles from the abdominal aorta and the right renal artery is longer than the left because the aorta lies to the left of the midline. As each renal artery approaches a kidney, it divides into five segmental arteries. Within the renal sinus, each segmental artery branches further to form several interlobar arteries.

At the medulla-cortex junctions, the interlobar arteries branch into the arcuate arteries that arc over the bases of the medullary pyramids. Small cortical radiate arteries radiate outward from the arcuate arteries to supply the cortical tissue. More than 90% of the blood entering the kidney perfuses the renal cortex.

Afferent arterioles branching from the cortical radiate arteries begin a complex arrangement of microscopic blood vessels. These vessels are key elements of kidney function, and we will examine them in detailed later when we describe the nephrons.

Veins pretty much trace the pathway of the arterial supply in reverse. Blood leaving the renal cortex drains sequentially into the cortical radiate, arcuate, interlobar and finally renal veins (there are no segmental veins). The renal veins issue from the kidneys and empty into the inferior vena cava. Because the inferior vena cava lies to the right of the vertebral column, the left renal vein is about twice as long as the right.

The renal plexus, a variable network of autonomic nerve fibers and ganglia, provides the nerve supply of the kidney and its ureter. An offshoot of the celiac plexus, the renal plexus is largely supplied by symphatetic fibers from the most inferior thoracic and first lumbar sphlanchnic nerves, which course along with the renal artery to reach the kidney. These sympathetic vasomotor fibers regulate renal blood flow by adjusting the diameter of renal arterioles and also influence the urine-forming role of the nephrons.

Location and external anatomy

The bean-shaped kidneys lie in retroperitoneal position (between the dorsal body wall and the parietal peritoneum) in the superior lumbar region. Extending approximately from T12 to L3, the kidneys receive some protection from the lower part of the rib cage. The right kidney is crowded by the liver and lies slightly lower than the left. An adult kidney has a mass about 150g (5 ounces) and its average dimensions are 12 cm long, 6cm wide and 3 cm thick – about the size of a large bar of soap. The lateral surface is convex. The medial surface is concave and has a vertical cleft  called the renal hilum that leads into an internal space within the kidney called the renal sinus.  The ureter, renal blood vessels, lymphatics and nerves all join each kidney at the hilum and occupy the sinus. Atop each kidney is an adrenal (or suprarenal) gland, an endocrine gland that is functionally unrelated to the kidney.

Three layers of supportive tissue surround each kidney:

• The renal fascia, an outer layer of dense fibrous connective tissue that anchors the kidney and the adrenal gland to surrounding structures
• The perineal fat capsule, a fatty mass that surrounds the kidney and cushions it against blows
• The fibrous capsule, a transparent capsule that prevents infections in surrounding regions from spreading to the kidney

The fatty encasement of the kidneys is important in holding the kidneys in their normal body position. If the amount of fatty tissue dwindles (as with extreme emaciation or rapid weight loss), one or both kidneys may drop to a lower position, an event called renal ptosis. renal ptosis may cause a ureter to become kinked, which creates problems because the urine, unable to drain, backs up into the kidney and exerts pressure on its tissue. Back up of urine from ureteral obstruction or other causes is called hydronephrosis. Hydronephrosis can severely damage the kidney, leading to necrosis (tissue death) and renal failure.

Internal Anatomy

A frontal section through a kidney reveals three distinct regions: cortex, medulla and pelvis. The most superficial region, the renal cortex, is light in color and has a granular appearance.  Deep to the cortex is the darker, reddish-brown renal medulla, which exhibits cone-shaped tissue masses called medullary or renal pyramids. The broad base of each pyramids faces toward the cortex, and its apex, or papilla, points internally. The pyramids appear striped because they are formed almost entirely of parallel bundles of microscopic urine-collecting tubules and capillaries. The renal columns, inward extensions of cortical tissue, separate the pyramids. Each pyramid and its surrounding cortical tissue constitutes one of approximately eight lobes of a kidney.

The renal pelvis, a funnel-shaped tube, is continuos with the ureter leaving the hilum. Branching extensions of the pelvis form two or three major calyces. Each one subdivides to form several minor calyces, cup-shaped areas that enclose the papillae.

The calyces collect urine, which drains continuosly from the papillae, and empty it into the renal pelvis. The urine then flows through the renal pelvis and into ureter, which moves it to the bladder to be stored. The walls of the calyces, pelvis and ureter contain smooth muscles that contracts rhytmically to propel urine along its course by peristalsis.

Every day the kidneys filter nearly 200 liters of fluid from the blood stream, allowing toxins, metabolic wastes and excess ions to leave the body  in urine while returning needed substances to blood. Much like a water purification plant that keep a city’s water drinkable and disposes of its wastes, the kidneys are usually unappreciated until they malfunction and body fluids become contaminated. Although the lungs and skin also participate in excretion, the kidneys are the major excretory organs.

As the kidneys perform these excretory functions, they also act as essential regulators of the volume and chemical makeup of the blood, maintaining the proper balance between water and salts and between acids and bases. Frankly, this would be tricky work for a chemical engineer, but the kidneys do it effeciently most of the time.

Besides the urine-forming kidneys, the urinary system includes the urinary bladder, a temporary storage reservoir for urine, plus three tubelike organs-the paired ureters and the urethra, all three of which furnish transportation channels for urine.

Other renal functions include:

• Gluconeogenesis during prolonged fasting
• Producing the hormons renin and erythropoetin. Renin acts as an enzyme to help regulate blood pressure and kidney function. Erythropoetin stimulates red blood cell production
• Metabolizing vitamin D to its active form