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Renal anatomy and overview of nephron function. (Continuing Education).

Editor's Note: This article introduces a renal physiology continuing education series to run in the Nephrology Nursing Journal. The articles, which are updates of manuscripts that previously appeared in the journal, are written by experts in nephrology and contain the most up-to-date information and research available.

The kidneys are paired vascular organs that perform excretory, regulatory, and secretory functions. In order to understand how these complex organs work, it is necessary to review renal anatomy and understand the renal processes involved in maintaining the body's internal milieu.

The renal system is comprised of the kidneys, ureters, bladder, and urethra (see Figure 1). Urine is formed by the kidneys and then flows through the other structures to be excreted from the body. The kidneys are located bilaterally in the retroperitoneal space at the level of T-12 to L-3. The organs are bean-shaped, measure approximately 12 cm in length, 6 cm in width, and 2.5 cm in thickness, and weigh 120 to 170 grams in the normal adult. The right kidney is slightly lower than the left because of the liver. The kidneys are protected, not only by their anatomical position within the rib cage, but also by the perinephric structures. A tough fibrous capsule covers each kidney. The renal fascia provides support and perirenal fat acts as a cushion.

[FIGURE 1 OMITTED]

The ureters are hollow fibromuscular tubes that begin at the renal pelvis, extend downward retroperitoneally, and join the bladder. Urine flows away from the kidneys by peristalsis. The urinary bladder, located in the pelvic region, is a spherical, muscular sac with a capacity of 300 ml to 500 ml in the normal adult. Urine enters via the ureteral orifices and is excreted through the urethra.

Vascular Supply

The kidneys are highly vascularized organs and receive approximately 20% of the resting cardiac output. Thus, renal blood flow is about 1,200 ml/min. Two characteristics of the renal vasculature make it different from most other vascular beds in the body. First, there are two capillary beds in series, the glomerular capillary bed and peritubular capillary bed. These capillary beds are separated by the efferent arteriole. This arrangement, a capillary bed surrounded by arterial vasculature, is referred to as a portal system. Second, the capillary bed is more porous. For example, it has a higher rate of fluid exudation than do the systemic capillaries and provides a size and charge barrier to large molecules such as albumin, unlike the systemic capillaries.

The aorta gives rise to the renal artery, which enters the kidney at the hilar region. This, in turn, branches to increasingly smaller vessels, that is, the intedobar, arcuate, and interlobular arteries. The interlobular arteries extend into the cortex and become the afferent arterioles that branch to form the glomerular capillary tufts (see Figure 2). The efferent arterioles receive blood from the glomerular capillaries. The presence of arteriolar structures on either end of the glomerular capillaries allows maintenance of an intracapillary pressure favoring the movement of fluid out of the capillary lumen. The efferent arterioles give rise to the second capillary bed, the peritubular network. These capillaries are a low pressure system that favors fluid movement into the capillary lumen. In the medulla, these capillaries, called the vasa recta, form long straight loops that run parallel to the loops of Henle of the juxtamedullary nephrons and play an important role in the concentration and dilution of urine. In the cortex, the peritubular capillaries form a network surrounding nephron segments located within the cortex. This meshwork is designed to efficiently pick up water and solutes reabsorbed from the nephron structures. Blood flow in the remainder of the venous system follows the same pattern as the arterial vessels and returns to the inferior vena cava.

[FIGURE 2 OMITTED]

Macroscopic Anatomy

The renal parenchyma consists of two distinct regions, the cortex and medulla (see Figures 3 and 4). The cortex has a granular appearance because of the structures contained in this layer, namely, the glomeruli, proximal and distal tubules, cortical collecting tubules, and adjacent peritubular capillaries. The medulla contains triangular wedges that have a striped appearance. These wedges are the renal pyramids formed by the long loops of Henle, medullary collecting tubules, and vasa recta. The tapered end of the pyramid, the papilla, directs urine toward the minor and major calyces. Urine then enters the hollow, funnel-shaped renal pelvis, which has a volume of 5 ml to 10 ml, before flowing into the ureters.

[FIGURES 3-4 OMITTED]

Microscopic Anatomy

The nephron is the basic functional unit of the kidney. There are approximately 1 million nephrons in each kidney. There are two types of nephrons, cortical and juxtamedullary, named according to the location of their glomeruli within the renal parenchyma (see Figures 3 and 4). The cortical nephrons, which comprise about 85% of the total nephrons, are subdivided into superficial and midcortical nephrons. The superficial cortical nephrons have their glomeruli in the outer cortex and have short loops of Henle. The midcortical nephrons, as their name suggests, have their glomeruli in the midcortex region. Their loops vary in length and may be either short (contained within the cortex) or long (extending partially into the outer medulla). The cortical nephrons perform excretory and regulatory functions. The juxtamedullary nephrons make up the remaining 15% of the nephrons. Their glomeruli are located deep in the cortex near the corticomedullary border. They have long loops of Henle that descend into the medulla often to the tips of the pyramids. These nephrons play an important role in the concentration and dilution of urine by generating a steep interstitial fluid osmotic gradient between the cortex and deep medulla. The vasa recta are responsible for maintaining this gradient.

Glomerulus. This specialized capillary bed is a network of interconnected loops surrounded by Bowman's capsule. As described above, the glomerular capillaries have unique characteristics that contribute to its filtering capabilities. The porosity of the endothelial layer increases capillary permeability, the meshlike structure of the basement membrane provides a barrier to large molecules, and the portal structure allows maintenance of an intracapillary pressure that favors filtration.

The glomerular membrane has three layers: (a) endothelial, (b) basement membrane, and (c) epithelial. The endothelium lines the capillary lumen and contains many pores, or fenestrae, that favor the filtration of fluid and small solutes. The glomerular basement membrane (GBM) is a matrix of collagen and similar proteins as well as glycosaminoglycans that provides a size and charge barrier to the movement of large particles out of the capillary lumen. The visceral epithelial cells of Bowman's capsule, or the podocytes, have cytoplasmic foot processes that extend over the basement membrane. Spaces between these foot processes are called slit-pores and allow the filtrate into Bowman's space. Mesangial cells are located between the capillary loops of the glomerulus and form a support network within the tuft. Some of these cells have phagocytic properties.

The glomerular membrane allows filtration of fluid and small molecules. Large molecules are prevented from entering the filtrate in two ways. First the size of the spaces in the glomerular epithelium and basement membrane limits the passage of these larger molecules and cells such as the white and red blood cells and albumin. Second, the podocytes and, to some extent, the GBM have a net negative charge that repels large negatively charged molecules, particularly the plasma proteins. Small anions that easily filter through the pores are not influenced by the negative electrical charge.

Bowman's capsule. Bowman's capsule is made up of two cell layers: the visceral layer that forms the epithelial layer (podocytes) of the filtration barrier and the parietal cell layer that forms the outer layer of the capsule. The space between the two cell layers, referred to as Bowman's space, collects the filtered fluid and solutes and directs this filtrate toward the proximal tubule.

Tubular system. The tubular system has four components: (a) proximal tubule (PT), (b) loop of Henle, (c) distal tubule (DT), and (d) collecting tubule. These components are divided further into subsegments each with specific cellular structures and functions. The kidneys filter about 180 liters of fluid per day with an electrolyte composition similar to that of plasma. Clearly, if all of this filtrate were excreted, total body water and electrolytes would be excreted in a few hours. Thus, the nephrons have the responsibility of handling this large volume of filtrate and separating that which must be conserved and that which needs to be excreted. The advantage of filtering such a large volume of fluid is that plasma clearance of waste products can occur rapidly. The disadvantage, however, is that the majority of the filtrate must be recycled back to the plasma, with little room for error.

In order to accomplish this tenuous task, the nephron is physically divided into subsegments with "assigned" specific tasks. In general, the proximal tubule can be thought of as the "bulk-phase" segment of the nephron as it transports water and solutes in bulk. It reabsorbs, and thus, returns to the plasma, up to 100% of the filtered solutes that the body does not routinely wish to discard, such as glucose, amino acids, and bicarbonate and reabsorbs a large percentage of solutes, such as sodium, potassium, chloride, calcium, and magnesium, and water whose amounts of excretion will vary throughout the day. This is not to say that regulation of transport of any of these solutes does not occur in the proximal tubule. In fact, transport of most of these solutes is tightly regulated, but the regulation involves a gross versus fine-me regulation.

The distal nephron, including all subsegments between the thin descending limb of the loop of Henle and the inner-medullary collecting tubule, is the site of fine-tune regulation of all solutes and water that leave the proximal tubule. In the articles that follow in this series, the nephron segments specifically handling these solutes and water will be discussed in detail, along with discussions of the regulation of solute and water excretion. In total, these processes govern maintenance of a systemic homeostatic milieu with regards to volume regulation, acid-base balance, and electrolyte balance. The next section of this article introduces the nephron subsegments, describing their anatomic differences, and summarizing their roles in water and solute regulation.

Proximal tubule. The PT, which drains the glomemlar filtrate from Bowman's space, is located in the renal cortex. The pars convoluta is the convoluted section of the PT, and the pars recta is the straight section that descends toward the medulla. The cellular structures of the PT give evidence of its high transport capacity. The flattened epithelial cells have microvilli on the luminal border, which create a brush border and increase surface area available to solute and fluid transport. The cells contain a large number of mitochondria, which are necessary for active transport.

The PT is the major site of reabsorption in the nephron. Sixty-five percent of the filtered water and sodium is reabsorbed here. Other substances reabsorbed include all of the filtered glucose and amino acids; some of the water soluble vitamins; 50% of the filtered chloride; potassium, and urea; 80%-90% of the filtered bicarbonate; 75% of the filtered phosphate; 60% of the filtered calcium; and one third of the filtered magnesium and remaining solutes. The PT also secretes substances into the tubular fluid. Secretion occurs primarily in the pars recta and includes many endogenous and exogenous organic anions and cations. As a result of these reabsorptive and secretory processes, the osmolarity of the tubular fluid at the end of the PT is isosmotic, that is, essentially equivalent to plasma, or approximately 300 mOsm/L.

Loop of Henle. The loop of Henle is the next component of the tubular system and consists of the thin descending limb, thin ascending limb, and thick ascending limb. Of note, these segments differ between the cortical and juxtamedullary nephrons. Superficial cortical nephrons, with their short loops, do not have a thin ascending segment. This is also true of the midcortical nephrons with short loops. However, the juxtamedullary nephrons and those midcortical nephrons with loops extending into the inner medulla do have a thin ascending limb. In the juxtamedullary nephrons, the long loops of Henle together with the vasa recta are components of the countercurrent mechanism responsible for urine concentration and dilution.

In the thin descending limb and thin ascending segment, the cells are flat with few microvilli and mitochondria. Movement of solutes is by diffusion rather than by active transport. There are functional differences between the two thin segments. The thin descending limb is highly permeable to water but much less permeable to urea, sodium, and most of the other solutes. The thin ascending limb is virtually impermeable to water but transports sodium, chloride, and urea.

The epithelial cells of the thick ascending limb become thick and are similar to those in the PT but with fewer microvilli. The thick ascending limb, like the thin ascending limb, is impermeable to water. Although sodium and chloride are the major solutes reabsorbed, other ions including potassium, bicarbonate, magnesium, and calcium are also reabsorbed. Because of the high solute but low water reabsorption in this segment, the tubular fluid becomes hypoosmotic.

Distal tubule. The DT is located in the cortical region of the kidney. The initial section of the DT immediately after the thick ascending limb of the loop of Henle contains specialized cells, the macula densa cells, which are a component of the juxtaglomerular apparatus. Following this specialized region, there are two sections of the DT, the distal convoluted segment or early DT and the late distal segment. The tubular epithelial cells of these subsegments are thick and have both microvilli and mitochondria.

The early DT transports a number of solutes including sodium, chloride, bicarbonate, potassium, calcium, and magnesium. However, it is quite impermeable to water. With reabsorption of solutes but virtually no reabsorption of water, the tubular fluid remains hypo-osmotic.

The late DT is a site for regulation of sodium, chloride, bicarbonate, potassium, and calcium transport. These processes are regulated in a variety of manners, including hormonal, physical factors, and/or systemic acid-base or electrolyte balance.

Water-permeability of the late distal tubule is influenced by antidiuretic hormone (ADH), which is produced by the hypothalamus and released in response to input by systemic baroreceptors, osmoreceptors, and angiotensin II. In the presence of ADH, the late DT is impermeable to water and the tubular fluid remains hypo-osmotic as solutes, not water, are reabsorbed.

Collecting tubule. A number of DTs join together to form the collecting tubules, which extend from the cortex through the medulla and empty into the papilla. The collecting tubule has three subsegments: the cortical collecting tubule, the outer medullary collecting tubule, and the inner medullary collecting tubule. For the first two subsegments, there are two predominant cell types, the principal cells and intercalated cells. The principal, or light cells, is the predominant cell in the cortical collecting tubule, comprising approximately 90% of the epithelial cells. These cells are involved in the transport of sodium and potassium. The intercalated, or dark cells, are the predominant cell type in the outer medullary collecting tubules, and account for about 10% of the epithelial cells in the cortical collecting tubule. These cells are involved in the transport of hydrogen and bicarbonate and play an important role in the acidification of urine.

In the inner medullary collecting tubules, some intercalated cells are still present, but a different cell type, called the inner medullary collecting duct cells, appears. The exact role of this latter cell type is not fully known, but since sodium, chloride, potassium, and ammonia transport all occur in this segment, this cell may be involved in these processes.

All along the collecting tubule, water permeability is ADH dependent. In the absence of ADH, water absorption along the collecting tubule is minimal and a dilute urine is excreted. In the presence of ADH, water absorption occurs. When ADH secretion is maximal, osmotic equilibration can occur between the collecting tubule fluid and the surrounding interstitium, which can lead to a maximally concentrated urine of > 1000 mOsm/L depending on the interstitial osmolality. Urine osmolalities between these extremes occur with submaximal ADH secretion.

Juxtaglomerular Apparatus

This autoregulatory structure participates in maintaining systemic blood pressure and, consequently, intraglomerular pressure and glomerular filtration. It involves the interplay between vascular and tubular components in the nephron. As the ascending limb of the loop of Henle moves upward, the initial portion of the DT passes between the afferent and efferent arterioles that proceed or form from, respectively, the glomerulus of that nephron. Specialized cells, the macula densa cells, are found in the walls of the tubule juxtapositioned to the glomerular hilus (see Figure 3). This region of the distal tubule "touches" the cells of the afferent arteriole, feeding the glomerular capillary associated with that nephron. At this point, the afferent arteriole basement membrane is absent so that the macula densa cells and the afferent arteriole cells "touch," forming a synsitium that allows communication between these specialized cells. These granular smooth muscle cells of the afferent arteriole are called juxtaglomerular cells, which synthesize and store renin, a proteolytic enzyme.

[FIGURE 3 OMITTED]

Renal Processes

As blood flows through the kidneys, approximately 20% of the plasma passes from the glomerulus into Bowman's space, forming the glomerular filtrate. This fluid contains no red blood cells, has approximately 0.03% small molecular weight proteins (primarily albumin), and has essentially the same concentration of electrolytes and other small molecules as the plasma. This filtrate undergoes many changes in the tubular system before it is excreted as urine.

Glomerular filtration is the initial process in the formation of urine. The glomerular membrane is highly permeable and allows fluid and small molecular weight solutes to pass into Bowman's space. The glomerular capillary tuft with its interconnected loops increases available surface area. Finally, arterioles at both ends of the glomerulus modulate intraglomerular pressure.

Tabular reabsorption is the movement of fluid and solutes from the tubular system into the peritubular capillaries. This process allows the body to retain fluid and desired solutes. At a glomerular filtration rate of 125 mi/min., the kidneys produce 180 liters of filtrate daily. Yet the average urine output is only 1000 to 1500 ml. Through reabsorption, 99% of the glomerular filtrate is returned to the bloodstream.

The PT is the major site of reabsorption in the tubular system although reabsorption in the tubular system occurs throughout the nephron. Reabsorption involves both passive and active transport mechanisms. Passive transport includes osmosis and diffusion while active transport mechanisms, such as primary and secondary transport and endocytosis, require the use of energy to move substances against an electrochemical gradient. Reabsorption of fluid and solutes is regulated to meet the body's physiological needs, through a number of hormonal and neural systems including ADH, aldosterone, angiotensin II, parathyroid hormone, prostaglandins, and alpha and beta adrenergics.

Tabular secretion is the movement of solutes from the peritubular capillaries into the tubular system. It is the process by which the body secretes unwanted or excess substances. Like reabsorption, secretion occurs by both passive and active transport mechanisms. As with reabsorption, secretion of substances is regulated by a number of factors, many of them hormonal in nature.

With regard to active transport mechanisms in both tubular reabsorption and secretion, reference is made to the maximal transport capacity (Tm). Specific carriers exist in the tubular epithelium that are responsible for the movement of substances in and out of the tubular system. However, there is a maximum rate at which substances can be transported in this way. This is known as the maximal transport capacity, or Tm, of the substance. Once the threshold or maximal solute transport rate has been reached, the presentation of larger amounts of solute results in the substance remaining in the tubular fluid (not reabsorbed) or in the plasma (not secreted). All substances actively transported have a Tm. As with all physiological processes, the Tm is subject to regulatory factors, most notably physiological, pathological, and pharmacological.

Excretion is the process by which unwanted substances are eliminated from the body through the passage of urine. These substances include the end products of metabolism such as urea, creatinine, uric acid, drugs, and foreign chemicals, and unwanted ingested substances such as sodium, potassium, and phosphate.

Conclusion

The kidneys are responsible for performing various roles in the maintenance of the body's internal environment. A thorough understanding of the renal system with its components and specialized functions is necessary to grasp not only its role in the healthy individual but also in the individual with renal disease.

This article is the basis for the physiology series. Subsequent articles will deal with renal functions in more detail. Topics include renal hemodynamics and glomerular filtration, urine concentration and dilution, renal acidification, renal regulation of extracellular volume, osmolality and electrolytes, and the effect of aging on the kidney.

Renal Anatomy and Overview of Nephron Function

Christine Chmielewski MS, CRNP, CNN, CS

Posttest--1.5 Contact Hours Posttest Questions

(See posttest instructions on the answer form, on page 192.)

1. The kidneys, paired vascular organs

A. are located in the peritoneal space.

B. are located at the level of T-10-L-1.

C. measure approximately 12 cm in length, 6 cm in width.

D. weigh 75-100 grams.

2. The kidneys are highly vascular organs that

A. receive approximately 10% of resting cardiac output.

B. consist of two capillary beds in parallel.

C. have renal blood flow of approximately 1000 ml/min

D. consist of the peritubular and glomerular capillary beds.

3. The basic functional unit of the kidney is the

A. nephron.

B. tubules.

C. Bowman's capsule.

D. Vasa recta.

4. The glomerular capillaries have unique characteristics that contribute to its filtering capabilities, This includes:

A. decreased porosity of the endothelial layer.

B. a basement membrane that provides a barrier to large molecules.

C. a positively charged membrane that limits passage of molecules.

D. a portal structure that maintains intracapillary pressure that limits filtration.

5. The tubular system has four components. The filtrate passes through the components in the what order from first to last?

A. Collecting tubule, proximal tubule, loop of Henle, distal tubule

B. Proximal tubule, loop of Henle, distal tubule and collecting tubule

C. Loop of Henle, proximal tubule, collecting tubule and distal tubule

D. Proximal tubule, collecting tubule, distal tubule and loop of Henle.

6. The following is a true statement about the filtrate reabsorption in the proximal tubule.

A. Twenty five percent (25%) of the water and sodium are reabsorbed.

B. Fifty percent (50%) of the calcium and phosphate are reabsorbed.

C. Seventy five (75%) of the chloride, potassium and urea are reabsorbed.

D. One hundred percent (100%) of the glucose and amino acids are reabsorbed.

7. In the loop of Henle, the movement of

A. solutes is by active transport.

B. water is equal in all limbs.

C. sodium and chloride causes hypo-osmotic fluid.

D. water causes hyper-osmotic tubular fluid.

8. In the distal tubule in the presence of antidiuretic hormone (ADH), the tubular fluid becomes hypoosmotic because

A. water is reabsorbed.

B. water is not reabsorbed.

C. solutes are secreted.

D. solutes are not secreted.

9. The juxtaglomerular apparatus participates in maintaining system blood pressure via communication between the

A. afferent and efferent arterioles.

B. vascular and tubular components of the nephron.

C. efferent arteriole and the macula densa.

D. juxtaglomerular cells and the glomerulus.

10. Through reabsorption, what part of the glomerular filtrate is returned to the blood stream and where does the majority of the reabsorption occur?

A. 25%, distal tubule

B. 49%, proximal tubule

C. 75%, distal tubule

D. 99% proximal tubule

11. What would you expect to happen to a substance that has reached its maximal transport capacity?

A. No secretion from the glomerulus

B. No reabsorption from the tubules

C. Reabsorption from the urine

D. Secretion from the plasma

12. The process of urine formation includes

A. glomerular filtration only.

B. glomerular filtration and tubular reabsorption only.

C. glomerular filtration, tubular reabsorption, and tubular secretion only.

D. glomerular filtration, tubular reabsorption, tubular secretion, and excretion.

ANSWER FORM

Renal Anatomy and Overview of Nephron Function

Christine Chmielewski, MS, CRNP, CNN, CS

Posttest Instructions

* Select the best answer and circle the appropriate letter on the answer grid below.

* Complete the evaluation.

* Send only the answer form to the ANNA National Office; East Holly Avenue Box 56; Pitman, NJ 08071-0056; or fax this form to (856) 589-7463.

* Enclose a check or money order payable to ANNA

* Posttests must be postmarked by April 20, 2005. If you receive a passing score of 70% or better, a certificate for 1.5 contact hours will be awarded by ANNA.

* Please allow 2-3 weeks for processing. You may submit multiple answer forms in one mailing, however, because of various processing procedures for each answer form, you may not receive all of your certificates returned in one mailing.

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References/Readings

Brenner, B.M., & Rector, F.C. (2000). The kidney (6th edition), Volume I. Philadelphia: W.B. Saunders Company.

Dolan, J.T. (1991). Anatomy and physiology of the renal/urinary system. In J.T. Dolan, Critical care nursing: Clinical management through the nursing process (pp. 399-416). Philadelphia: F.A. Davis.

Guyton, A.C., &Hall, J.E. (2000). Unit V: The kidneys and body fluids. In A.C. Guyton & J.E. Hall, Textbook of medical Physiology (10th edition) (pp. 264-379). Philadelphia: W.B. Saunders Company.

Hladsky, S.B., & Rink, T.J. (1986). Physiological principles in medicine series: Body fluid and kidney physiology. London: Edward Arnold Publishers Ltd.

Vander, A.J. (1994). Renal physiology (5th edition). New York: McGraw-Hill.

This offering for 1.5 contact hours is being provided by the American Nephrology Nurses' Association (ANNA), which is accredited as a provider and approver of continuing education in nursing by the American Nurses' Credentialing Center-Commission on Accreditation (ANCC-COA). This educational activity is approved by most states and specialty organizations that recognize the ANCC-COA accreditation process. ANNA is an approved provider of continuing education in nursing by the California Board of Registered Nursing, BRN Provider No. 00910; the Florida Board of Nursing, BRN Provider No. 27F0441; the Alabama Board of Nursing, BRN Provider No. P0324; and the Kansas State Board of Nursing, Provider No. LT0148-0738. This offering is accepted for RN and LPN relicensure in Kansas

The Nephrology Nursing Certification Commission (NNCC) requires 60 contact hours for each recertification period for all nephrology nurses. Forty-five of these 60 hours must be specific to nephrology nursing practice. This CE article may be applied to the 45 required contact hours in nephrology nursing.

Christine Chmielewski, MS, RNP, CNN, CS, is a Nephrology Nurse Practitioner with Edward J. Filippone, MD, PC, and Associates in Philadelphia, PA. She is a member of ANNA's Keystone Chapter.
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Author:Chmielewski, Christine
Publication:Nephrology Nursing Journal
Geographic Code:1USA
Date:Apr 1, 2003
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