Renal Physiology

05Sep07

RENAL PHYSIOLOGY

Introduction:

The anatomical design of the kidney and its functional unit, the nephron, provides the primary route for the elimination of the end products of metabolism and of ingested foreign substances. Of equal or greater importance, however, is the role that the kidney plays in the regulation of ECF volume, osmolarity, pH and electrolyte composition. Because changes in composition of the ECF influence the composition of the ICF renal function exerts its influence, albeit indirectly, on ICF volume and composition and therefore on TBF composition and volume.

The nephron is comprised of a series of anatomically unique segments whose activities are integrated to perform the functions cited above. In this chapter the elegant anatomical design of the nephron and the renal vasculature which support these remarkable functions will be discussed.

Objectives

After completing this chapter, students should be able to:

describe the surface anatomy (topography) of the kidney.

describe the structure of the kidney as observed in a longitudinal section of the organ.

identify and state the major function of each segment of the nephron,.

describe the renal vasculature naming its components and identifying unique structural differences as compared to other vascular beds

describe the filtration apparatus of the kidney.

describe the structure and major function of the loop of Henle

compare and contrast the structure and function of the proximal and distal nephron.

Gross Anatomy: Location and Dimensions:

In humans, the upper pole of each kidney is found opposite the 12th thoracic vertebra, and the lower pole lies opposite the 3rd lumbar vertebra. The kidneys are located in a retroperitoneal position, that is behind but not inside the abdominal cavity. Each kidney is covered by a strong fibrous capsule. In males each kidney weighs 150gm +20gm, and in females, each kidney weighs 135gm + 20 gm. The adult kidney is approximately 11 cm in length, 5 to 7 cm in width, and 2 to 3 cm thick.

Gross Anatomy: Topography:

Each kidney has a concave surface containing a slit called the hilus, allowing access to the renal sinus. Human kidneys are normally supplied by a single renal artery branching from the abdominal aorta, and entering the kidney through the hilus. Also entering the kidney through the hilus are the renal sympathetic nerves which arise from the celiac ganglia. The ureter, the renal vein and renal lymphatics exit through the renal hilus.

Gross Anatomy: Internal Structure:

If the kidney is bisected longitudinally, a lighter outer region, the cortex, and a darker inner region, the medulla, are clearly seen. The medulla is divided into 8 to 16 conical structures called renal pyramids. The base of each pyramid is at the interface between the cortex and medulla, and the apex of each pyramid forms a papilla that extends into the renal pelvis. Each papilla contains approximately 25 small holes representing the distal ends of the collecting ducts which drain into the renal pelvis which empties into the ureter. Elements of collecting ducts and straight segments of proximal and distal tubules extend into the cortex forming what are termed medullary rays (inappropriately as they are actually part of the cortex). The kidney is divided into lobules consisting of the cortical tissue surrounding a centrally positioned medullary ray.

Renal Vasculature: Major Arteries:

The renal arteries arise from the abdominal aorta. Within the renal sinus they divide approximately eight times to become the segmental or lobar arteries. The segmental arteries give rise to the interlobar arteries which ascend between the pyramids toward the cortex. At the junction of the cortex and the medulla, they curve over the renal pyramids of the medulla to form the arcuate arteries from which arise the interlobular arteries. The interlobular arteries give rise to the afferent arteriolar supply to the glomeruli.

Renal Vasculature: Afferent Arterioles:

The afferent arterioles arise from interlobular arteries extending into the cortex from the arcuate arteries. The capillaries of the renal glomerulus are supplied with blood by the afferent arterioles. Approximately 20% of the plasma perfusing the afferent arteriole, including water, electrolytes, and a host of other small molecules, but excluding protein, are filtered through the glomerulus.

Renal Vasculature: Glomerular Capillaries:

The glomerular capillaries are unique among the capillaries of the body. Within the glomerular capillary blood pressure is about 55 mm Hg, approximately double the pressure in most other capillaries. A unique aspect of the glomerular capillary bed is that it is situated between two arterioles, not between an arteriole and a venule as in other capillary beds. The high glomerular capillary pressure is due to the resistance afforded by the efferent arterioles. Because this pressure is always greater than the pressure in Bowman’s space, only filtration occurs. Fluid flow through the glomerular capillary membrane is unidirectional with no associated reabsorption by the capillaries.

Renal Vasculature: Efferent Arterioles & Peritubular Capillaries:

Eighty % of the plasma entering the glomerulus along with molecules too large to be filtered (particularly proteins and protein bound substances, such as Ca++) leave the glomerulus via the efferent arterioles. In the renal cortex the efferent arterioles of the glomeruli of cortical nephrons give rise to a peritubular capillary bed supplying the renal tubules of the cortical nephrons. These are nephrons whose glomeruli are situated in the outer or middle regions of the renal cortex and have short loops of Henle. A major function of the peritubular capillaries is to carry away in the renal veins water and solutes reabsorbed by the tubular epithelium. These peritubular capillaries also deliver blood to tubular secretory sites where certain substances are secreted from the plasma into the tubular fluid.

The efferent arterioles of the juxtamedullary nephrons give rise to two different capillary beds. The glomeruli of these nephrons are located at the junction of the cortical and medullary regions of the kidney. They have long loops of Henle which extend deep into the renal medulla.

One branch of their efferent arteriole gives rise to a peritubular capillary network which envelops the proximal and distal convoluted tubules.

A second branch of the juxtamedullary efferent arteriole parallels the long loops of Henle extending deep into the medulla where they divide repeatedly into vascular bundles which form the vasa recta. The vasa recta are composed of the descending (arterial) limbs which gives rise to a capillary network that envelopes the loops of Henle and the collecting ducts. These medullary capillary beds drain into the ascending (venous) limb of the vasa recta. These structures play a critical role in the mechanism of urinary concentration and dilution.

The Nephron: Overview:

The nephron is the basic functional unit of the kidney. Each kidney contains approximately 1 million nephrons, and each nephron has the ability to transport water and solutes and to produce urine. The nephron consists of a glomerulus and the renal tubule to which it is attached. The figure illustrates the basic anatomy of a nephron. The renal tubule may be divided by functional and histological criteria into the proximal convoluted tubule, the proximal straight tubule (pars recta), the loop of Henle, the juxtaglomerular apparatus (JGA), the distal convoluted tubule, the connecting tubule, and the collecting duct.

The Nephron: Glomerulus, Bowman’s Capsule & Mesangium:

The figure shows a section of a renal glomerulus. The glomerulus is a ball of capillary loops that are surrounded by the blind end of the renal tubule called Bowman’s capsule. Between the loops are cells called mesangial cells which together with the surrounding matrix form the mesangium. The mesangium is mesenchymal in origin and contains myofilaments that resemble smooth muscle in structure. The contractile nature and location of the mesangium permits it to function as a regulator of glomerular filtration by altering the capillary surface area available for filtration. Mesangial cells are also known to take up immune complexes.

The Nephron: Glomerular Capillaries:

The basal lamina of the glomerular capillaries are lined by endothelial cells that contain pores or fenestrations of ~0.1 m m in diameter. On the outer surface of the glomerular capillaries, in the space between the capillary loops and Bowman’s capsule, there are epithelial cells called podocytes. The podocytes possess long finger-like projections called pedicels. The interdigitation of the projections creates 25 nm wide slit pores. These slit pores are lined with a thick layer of negatively charged proteins and at the surface of the basement membrane the pore is covered by a very thin membrane. The slit pores therefore play a role in restricting filtration of large molecules.

The combined barrier of the endothelial cells, basal lamina, and epithelial cells create a filtration apparatus which exhibits molecular sieving in which size and charge play a role. Water and neutral substances of less than 3.0 nm in diameter pass freely. The filtration rate for larger molecules decreases progressively with increasing size. In terms of molecular weight inulin at about 5500 is the upper limit for free permeability. Larger substances, such as albumin (3.6 nm radius) at a molecular weight of 70000, are essentially impermeant. Due to the negative charge in the slit pores anions are less permeant than cations of equal weight and size.

The Nephron: Proximal Tubule, Pars Convoluta & Pars Recta:

The outer basement membrane of Bowman’s capsule is continuous with the basement membrane of the remainder of the renal tubule. The portion of the tubule directly adjacent to Bowman’s capsule is the proximal convoluted tubule, (pars convoluta). The proximal convoluted tubule winds randomly within the cortex, and then straightens to become the proximal straight tubule, (pars recta), as it turns and descends into the medulla.

The Nephron: Proximal Tubule Epithelium:

The epithelial cells of the proximal tubule are also continuous with the epithelial cells of Bowman’s capsule, but they differ in their morphology. The cells lining the proximal tubule are cuboidal epithelial cells with deep basal membrane invaginations that provide a large basal surface area. The long microvilli (the brush border) lining the tubule lumen, maximize luminal surface area and make these cells ideally suited for both reabsorptive and secretory functions. Furthermore the leaky nature of the apical tight junctions facilitates the paracellular transport of water by osmosis, of solutes moving down electrochemical concentration gradients and of solutes moving by solvent drag.

Located in the luminal and basolateral membranes are enzymatic and protein carriers, primary and secondary active transport systems, which together with its permeability characteristics, make the proximal tubule the major site of reabsorption of the glomerular filtrate. About 65 % of the filtrate including all essential nutrients are reabsorbed by the proximal tubule.

The Nephron: Loop of Henle

Henle’s loop consists of a thin descending limb, a thin ascending limb characterized by a thin flat squamus epithelial cell, and a thick ascending limb with somewhat taller squamous epithelial cells. The thin limb begins at the end of the pars recta, descends into the medulla, makes a hairpin turn becoming the thin ascending limb which parallels the course of the descending limb back towards the cortex. At the junction of the outer and inner medulla the epithelial cells of the ascending limb become cuboidal , the tubule diameter increases and the segment becomes the thick ascending limb of Henle’s loop. At this point it is necessary to distinguish between three types of nephrons.

Superficial cortical nephrons have glomeruli located in the outermost cortex, have short loops of Henle extending only a short way into the medulla, and lack thin ascending limbs.

Mid cortical nephrons have glomeruli located between the superficial and the juxtamedullary nephrons, and may have short or long loops of Henle.

Juxtamedullary nephrons have glomeruli located in the cortex just above the junction of cortex and medulla and all have long loops of Henle which descend deep into the medulla.

The thin descending limb is water permeable and relatively impermeant to solutes. Both thin and thick ascending limbs are impermeable to water. The thin ascending limb is permeable to solutes and the thick ascending limb has a high capability for active salt reabsorption. The loop of Henle and the closely associated vasa recta play a critical role in the mechanism for urinary concentration or dilution. Salt reabsorption in the water impermeable thick ascending limb dilutes the tubular fluid, concentrates the medullary ISF and generates a cortico-medullary osmolar gradient in the renal ECF which provides the force for passive water reabsorption from the collecting duct. The permeability of the collecting duct is determined by ADH which increases water permeability of the duct. When the duct is permeable the urine is concentrated, when it is impermeable the urine is dilute.

The Nephron: Juxtaglomerular Apparatus:

The juxtaglomerular apparatus (JGA), located in the renal cortex, is a unique segment of the nephron where the thick ascending limb of the loop of Henle passes between the afferent and efferent arterioles of its own glomerulus. The macula densa is the specialized area of the thick ascending limb which makes contact with the vascular elements of the JGA. The vascular elements of the JGA contain modified smooth muscle cells of the arterioles (granular cells) which contain secretory granules that synthesize and secrete the enzyme renin. A second group of JGA cells, called the lacis cells or extraglomerular mesangial cells, are not granular but also secrete renin.

The JGA plays a major role in the renin-angiotensin-aldosterone system. One theory holds that the macula densa senses changes in the Na+ or Cl? concentration and changes the rate of renin secretion. A second theory states that renin secretion is controlled by changes in volume and stretch of the afferent arteriole. The JGA has also been implicated in the autoregulation of GFR. It has been proposed that changes in Na+ or Cl? transport by the macula densa causes release of an unidentified vasoconstrictor which acts locally to control filtration pressure and GFR.

The Nephron: Distal Convoluted Tubule & Connecting Tubule:

The distal convoluted tubule begins at the end of the macula densa. It has short epithelial cells with highly invaginated basal membranes. It empties into the connecting tubule which in turn drains to the cortical collecting duct. The cells of the connecting tubule resemble those of the distal convoluted tubule but are taller and appear under light microscopy to be more textured. Both the distal convoluted tubule and the connecting tubule contain a few apical microvilli on each cell, but no distinct brush border as in the proximal tubule. With regard to permeability and transport these segments are similar in most respects to the thick ascending limb of Henle’s loop.

The Nephron: Collecting Duct:

The collecting duct is divided into the cortical collecting duct, the medullary collecting duct, and the papillary collecting duct, based on location. The epithelial cells of the cortical collecting duct are cuboidal shaped and become progressively more elongated toward the papillary collecting duct.

The collecting duct cells are of two types.

1. The intercalated cells are involved primarily in acidification of the urine and regulation of acid base balance.

2. The principal cells are involved mainly with sodium reabsorption and have a major role in sodium balance and regulation of ECF volume. The sodium transport activity of these cells is controlled by aldosterone.

The water permeability of the collecting duct is variable depending on the level of ADH activity and so plays a role in regulation of body fluid osmolarity.

Renal tubule

The flow of the renal tubule is as follows:

Name Description
Proximal tubule The proximal tubule as a part of the nephron can be divided into an initial convoluted portion and a following straight (descending) portion. 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).
loop of Henle The loop of Henle (sometimes known as the nephron loop) is a tube, it is often u-shaped in diagrams for simplicity but in reality it looks more like one loop of a coil (hence, ‘loop’). It extends from the proximal tube and it 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 not similar to the proximal convoluted tubule in structure and function. 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 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 traveling the length of the distal convoluted tubule, only about 1% of water remains, and the remaining salt content is negligible.

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