Gross Anatomy

The kidneys lie anterior and lateral to the twelfth thoracic and first, second, and third lumbar vertebrae and behind the abdominal peritoneum; therefore they are retroperitoneal structures. The kidneys are embedded in a mass of fatty tissue called the adipose capsule, and each capsule is enclosed in the renal fascia (Fig. 13-1). The kidneys are not secured to the abdominal wall, but are held in position by the renal fascia and the large renal arteries and veins. The adipose capsule and the pararenal fat help to protect the kidney and keep it in place.

Fig. 13-1 Components of the urinary system.

(From Patton KT, Thibodeau GA: Anatomy and physiology, ed 7. St Louis, 2010, Mosby.)

The medial aspect of each kidney is curved away from the midline; at the center of this concavity is the hilus, where the renal artery and nerves enter the kidney and where the renal vein and ureter exit the kidney. Surrounding each kidney is a tough, nearly indistensible fibrous capsule, which becomes the outer lining of the renal calyces, renal pelvis, and ureter.

A longitudinal section of the kidney shows the three general areas of renal structure: the cortex, the medulla, and the pelvis (Fig. 13-2). The renal cortex is the outer portion of the kidney. It has a granular appearance and extends in fingerlike projections into the medullary areas. The cortex contains most of the nephrons, the smallest functioning unit of the kidney. The cortex also contains all glomeruli, the proximal and distal convoluted tubules, and the first parts of the loop of Henle and the collecting ducts.

Fig. 13-2 Cross-section of the kidney.

(From Patton KT, Thibodeau GA: Anatomy and physiology, ed 7. St Louis, 2010, Mosby.)

The renal medulla is composed predominately of the long loops of Henle from the juxtamedullary nephrons and the collecting ducts that grow progressively larger as they approach the renal pelvis. These structures give the medulla a striated, pyramidal appearance, with the apex of the pyramid pointing toward the renal pelvis and the base pointing toward the renal cortex.

The renal pelvis contains the outflow tract and a small amount of surrounding fat that acts as a cushion. The renal outflow tract begins with the minor calyces (Greek for cup) that receive urine from the collecting ducts. The urine flows from the minor calyces into the major calyces, into the renal pelvis, into the ureters and bladder, out of the bladder, and through the urethra to exit the body through the urethral meatus.

The functioning unit of the kidney is the nephron, which consists of a vascular component and a tubular component (Fig. 13-3). Each kidney contains approximately 1 million distinct nephrons. Eighty-five percent of all nephrons originate in the outermost area of the cortex. The remaining nephrons are the juxtamedullary nephrons that originate in the inner cortical area. The long loops of Henle from the juxtamedullary nephrons that extend deep into the medulla lie parallel to the medullary collecting ducts and play an important role in the concentration of urine (see Evolve Fig 13-1 in the Chapter 13 Supplement on the Evolve Website).

Fig. 13-3 Components of the nephron. A, One nephron. B, Cells of juxtaglomerular apparatus. C, Glomerulous and juxtaglomerular apparatus.

(A from Patton KT, Thibodeau GA: Anatomy and physiology, ed 7. St Louis, 2010, Mosby; B from Applegate E: The anatomy and physiology learning system, St Louis, 2011, Saunders; C from McCance K, Huether SE, editors: Pathophysiology: the basis for disease in adults and children, ed 6. St Louis, 2010, Mosby.)

Renal Vasculature

In most patients, each kidney is supplied with systemic arterial blood from a single artery. The renal arteries branch from the aorta at the level of the second or third lumbar vertebrae; together they receive approximately 20% of the total cardiac output. Each artery divides into an anterior and posterior artery. These arteries continue to branch into small arterioles. Some of these arterioles will supply nutrients to the renal medulla, cortical tissue, and capsule, while other arterioles enter the glomerular capsule.

The afferent arteriole enters the glomerular capsule and divides to form the glomerulus, a tuft of capillaries that allows filtration of plasma through the capillary membranes. The glomerular capillaries do not recombine into venous channels, but instead recombine into a second arteriole called the efferent arteriole (Fig. 13-4). Because arterioles are present at either end of the glomerular capillary system, constriction or dilation of these arterioles will alter the resistance to flow through the glomerular capillaries and thus will regulate glomerular filtration.

Fig. 13-4 Anatomy of the glomerulus and juxtaglomerular apparatus. A, Longitudinal cross-section of glomerulus and juxtaglomerular apparatus. B, Horizontal cross-section of glomerulus. C, Enlargement of glomerular capillary filtration membrane.

(From McCance K, Huether SE, editors: Pathophysiology: the basis for disease in adults and children, ed 6. St Louis, 2010, Elsevier, Figure 35-6, p. 1349).

After leaving the glomerulus, the efferent arterioles branch to form a network of capillaries that surround the convoluted tubules and the loop of Henle. These peritubular capillaries then converge into venules that will return renal venous blood to the systemic circulation via the inferior vena cava. Elements that the kidney reabsorbs from the filtrate to return to the circulation are reabsorbed into this peritubular capillary system.

Renal Tubules and Collecting Ducts

The tubular component of the nephron begins as a single layer of flat epithelial cells surrounding the glomerulus. This layer is known as Bowman’s capsule (Fig. 13-4, B). Filtered plasma from the glomerular capillaries will enter Bowman’s capsule and flow into a coiled tubule called the proximal tubule, also known as the proximal convoluted tubule (Fig. 13-5).

Fig. 13-5 Epithelial cells of the various segments of nephron tubules. The brush border and high number of mitochondria in the cells of the proximal convoluted tubule permit reabsorption of the 60% of the glomerular filtrate. Intercalated cells (rectangles) secrete either H⁺ (reabsorb HCO₃⁻) or HCO₃⁻ reabsorb K⁺. Principal cells (enlarged figures) reabsorb Na⁺ and water and secrete K⁺.

(From McCance K, Huether, SE, editors: Pathophysiology: the basis for disease in adults and children, ed 6. St Louis, 2010, Elsevier).

The structure and appearance of the proximal tubule changes as it descends toward the renal medulla. The tubular lumen narrows and the cells become flattened as the tubule makes a hairpin turn, called the loop of Henle. As the loop of Henle ascends from the medulla into the renal cortex, the tubular cells enlarge and again become cuboidal; in addition, the tubule coils, forming the distal convoluted tubule. The tubule then straightens and joins the collecting duct.

Collecting ducts are the terminus of many distal tubules; they are formed in the inner and outer renal cortex. These small collecting ducts enter the renal medulla where they form larger ducts, which in turn drain into a minor calyx in the renal pelvis. Approximately 8 to 10 minor calyces join into the major calyces, which combine to form the renal pelvis. The renal pelvis is the largest portion of the outflow tract proximal to the bladder.

Ureters

The two ureters conduct urine from the renal pelvis to the urinary bladder; they are located behind the peritoneum and they descend through the pelvic cavity, crossing over the common iliac arteries. The ureters are attached to the bladder at an oblique angle; they enter the bladder laterally and tunnel between the bladder mucosa and detrusor muscle, creating a flap-valve design that normally prevents reflux of urine into the ureters during bladder contraction.³⁰

Each ureteral wall has three layers: an inner epithelial lining, a middle muscular layer, and the outer fibrous layer that is continuous with the renal capsule. The middle muscular portion of the ureter consists of both a circular and a longitudinal muscle layer. The circular muscles propel the urine toward the bladder by peristaltic contraction, and they generate enough pressure to overcome the resistance caused by the oblique ureteral insertions into the bladder. Contraction of the longitudinal fibers opens the lumen of the ureter. These ureteral muscle fibers are innervated by fibers from the aortic, spermatic or ovarian, and hypogastric plexuses. Peristalsis persists even when the ureter is denervated, allowing ureters to be transplantable.⁵⁵

The Bladder and Urethra

The urinary bladder is a hollow, muscular organ that stores urine. There are three openings in the bladder wall: the entrances of the two ureters and the exit of the urethra. These openings form the corners of a triangle, called the trigone. There is a dense area of smooth (involuntary) muscle around the neck of the bladder at the orifice of the urethra; this muscle constitutes the internal sphincter. The urethra extends from the urinary bladder to the body surface. At the point where the urethra passes through the muscles of the pelvic floor, striated (voluntary) circular muscles form an external sphincter.⁵⁵

Micturition is the emptying of the stored urine from the bladder. The process normally involves both voluntary and involuntary nervous system activities in children beyond approximately 2 to 3 years of age. Once an adequate volume of urine has accumulated in the bladder, the bladder wall stretches, stimulating stretch receptors. Sensory signals are then conducted through afferent pelvic nerves to the spinal cord. Efferent nerves from the spinal cord return impulses through the parasympathetic fibers in the pelvic and hypogastric nerves to the bladder wall muscle and the neck of the bladder. Efferent nerve stimulation causes contraction of the bladder and relaxation of the internal sphincter. In addition, impulses from the central nervous system through the pudendal nerves innervate the voluntarily controlled external sphincter. If the external sphincter also relaxes, the bladder will then empty.

Appropriate contraction and voluntary intermittent emptying of the bladder require both inhibitory and facilitory impulses from the upper pons, the hypothalamus, the midbrain, and the cortex. The inhibitory centers prevent constant voiding, and the facilitory centers allow micturation to occur voluntarily (once bladder control is learned). If the inhibitory centers are injured, the patient can demonstrate an uninhibited neurogenic bladder and nearly constant urination.

Reflex bladder contraction and sphincter relaxation also require the presence of intact afferent nerves from the bladder to the second and third sacral spinal cord level and intact efferent nerves (including the hypogastric, pelvic, and pudendal nerves) from the first through the third sacral spinal level. If afferent nerves from the bladder to the spinal cord are injured or malformed, the patient can develop an atonic bladder, with loss of voluntary sphincter control. When an atonic bladder is present, the bladder fills to capacity and then overflow voiding begins.

If the spinal cord is damaged above the sacral spinal level, the patient initially loses all micturation reflexes because inhibitory and facilitory reflexes from the brain cannot be transmitted through the injured spinal cord. Later, however, simple spinal reflexes can return and the patient can void when bladder distension is sufficient. In this case, the bladder reflex will be initiated at the volume of urine that is usually present in the bladder during the patient’s convalescent period.⁴⁵

Physiologic Processes

The production of urine by the kidneys is accomplished through three physiologic processes: glomerular filtration, reabsorption, and secretion. The first and most important step in urine formation is the filtration of plasma out of the glomerular capillaries into Bowman’s capsule. The fluid that is filtered from the plasma, called filtrate, is then “acted on” by the renal tubular cells, through reabsorption or secretion.

Reabsorption is the process by which essential elements from the filtrate pass through the tubular cell back into the peritubular capillary plasma. Secretion is the transfer of substances from the peritubular capillary or the renal tubular cells to the filtrate so that it will be excreted. Secretion may be seen as an adjunct to filtration.

As the filtrate flows into the renal pelvis it becomes urine. The following discussion will detail the mechanisms involved in these three processes, glomerular filtration, reabsorption and secretion.

Filtration Physiology

The kidney receives its sympathetic nerve supply from the tenth through twelfth thoracic nerves and its parasympathetic nerve supply from branches of the vagus nerve. The renal blood vessels are innervated, but the renal tubules are not. Adjustment in the diameter of either or both of the afferent and efferent arterioles will affect the amount of fluid filtered in the glomerulus. As with any capillary, filtration of fluid in the glomerulus is affected by pressure gradients across the capillary bed and the intrinsic properties of the glomerular capillary membrane.

Capillary hydrostatic pressure is the pressure generated by the pumping action of the heart; it is maintained or altered by arterial resistance. Hydrostatic pressure in most capillaries is higher at the arterial end than at the venous end. This difference favors filtration of fluid out of the vascular space at the arterial end and favors reabsorption of fluid into the vascular space at the venous end. Because the glomerulus has an afferent arteriole at the proximal end and an efferent arteriole at the distal end, the glomerular capillary pressure is higher than in other capillary beds and is approximately equal to systemic arterial pressure. This high pressure favors fluid filtration out of the vascular space. The glomerular capillary pressure is altered by constriction or relaxation of the afferent or efferent arteriole.

Intravascular colloid osmotic pressure, or oncotic pressure, is the pressure opposing free water movement out of the vascular space. It is generated by dissolved proteins, ions, and other particles that are normally present in the blood. Larger particles such as proteins cannot move readily across a capillary membrane; therefore they remain in the vascular space, exerting an osmotic pressure of approximately 35   mm Hg. This oncotic pressure opposes hydrostatic filtration from the vascular space.⁵⁵

The hydrostatic pressure present in Bowman’s capsule is the pressure exerted on the glomerulus by fluid in the Bowman’s capsule and collecting ducts. This pressure is normally 10 to 15   mm Hg and opposes fluid filtration from the glomerulus. Because tubular fluid is normally protein-free, the oncotic pressure in Bowman’s capsule is normally negligible. (See Evolve Fig. 13-2 in the Chapter 13 Supplement on the Evolve Website for a diagram of these pressures.)

Net filtration pressure (NFP) within the nephron is the difference between forces favoring filtration (largely resulting from capillary hydrostatic pressure) and forces opposing filtration (largely caused by intravascular colloid osmotic pressure and the hydrostatic pressure within Bowman’s capsule) as follows:

Any change in the hydrostatic pressure in either Bowman’s capsule or the capillaries or any changes in serum colloid osmotic pressure can change the net filtration pressure and may result in a change in the glomerular filtration rate (GFR). For example, obstruction of a ureter increases resistance to urine drainage from the renal pelvis; this increases pressure in the tubules and in Bowman’s capsule and opposes filtration. The loss of a large volume of hypotonic fluid caused by diarrhea or unreplaced insensible losses during high fever will produce dehydration and hemoconcentration; this increases the colloid osmotic pressure and opposes filtration. If the child develops severe hypotension, capillary hydrostatic pressure will fall. All these changes oppose filtration and reduce the amount of glomerular filtrate. As noted previously, capillary hydrostatic pressure is determined by cardiac output (blood flow) and resistance in the arterioles. The relationship of flow, pressure, and resistance is described by the following equation (Poiseuille’s Law):

P = mean arterial pressure − venous pressure for that organ

This equation predicts that an increase in mean arterial pressure will increase blood flow if the resistance to flow remains constant. The kidney is designed to maintain glomerular hydrostatic pressure so it can create urine over a wide range of blood pressures. As a result, resistance to flow does not remain constant when the systemic arterial pressure changes. Instead, when mean arterial pressure increases, the afferent arterioles constrict; this constriction restricts renal blood flow and prevents transmission of the entire increase in arterial pressure to the glomerulus. When arterial pressure falls, sympathetic innervation to the afferent and efferent arterioles increases arterial tone and increases the resistance to flow into and out of the glomerulus; this vasoconstriction can maintain the GFR at near-normal levels despite a fall in systemic arterial pressure and renal blood flow.

The ability to respond to changes in flow into and out of the glomerulus allows the kidney to maintain solute and volume regulation at relatively constant levels, despite changes in systemic arterial blood pressure and renal blood flow; this ability is termed autoregulation. When the arterial pressure is extremely high or low, autoregulation fails and renal blood flow is proportional to arterial pressure.

Glomerular Filtration Rate (GFR)

Renal function can be evaluated by calculating the GFR. The GFR, in turn, is roughly equivalent to the creatinine clearance; therefore it can be estimated by calculating the creatinine clearance. This estimate should not, however, be the sole means of determining renal function.⁵⁶

Creatinine is a small molecule byproduct of skeletal muscle creatine metabolism. Creatinine is released at a near constant rate into the bloodstream, is filtered freely at the glomerulus, and is not broken down, reabsorbed, or synthesized by the renal tubules. Only a tiny amount of creatinine is secreted by the renal tubules. In effect, all of the creatinine that is filtered from the vascular space at the glomerulus remains in the urine and can be measured, and the creatinine clearance mirrors the GFR.⁶²

Calculation of creatinine clearance requires collection of a urine sample for a precise period of time. A blood sample is collected during that same time period. The sampling of blood and urine enables simultaneous determination of the concentration of creatinine in the plasma and in the urine, as well as calculation of creatinine clearance.

The relationship between the plasma and urine concentrations of creatinine (Cr), the urine volume formed per unit of time, and the glomerular filtration rate is expressed as follows:

It is important to note that laboratory determination of serum creatinine concentration may be affected by some cephalosporin antibiotics. For this reason the blood sample for analysis of the serum creatinine level should be obtained when antibiotic drug levels are at their lowest.⁷

The GFR is expressed as milliliters per minute per 1.73 square meter of body surface area, which allows a comparison of renal function among children and adults. The child’s GFR is approximately 55 to 65   mL/minute per 1.73   m² and will approach adult values (120   mL/minute per 1.73   m²) by approximately 3 years of age.

When the amount of fluid filtered by the glomerulus is expressed as a fraction (ratio) of the total renal plasma flow (600   mL/minute per 1.73   m² in the adult), this provides an estimate of the percentage of total renal plasma flow that is filtered into Bowman’s capsule. This ratio is termed the filtration fraction and equals approximately 20% of total renal plasma flow. Plasma that is not filtered (i.e., plasma that remains in the vascular space) continues through the glomerulus into the efferent arteriole, through the peritubular capillaries, and into venules and interlobular veins.

The glomerular filtrate in Bowman’s capsule is an ultrafiltrate of blood. Its composition, like interstitial fluid from other capillaries, is usually free of proteins and cells. Animal micropuncture studies have established that all of the solutes (such as ions and amino acids) measured in the glomerular filtrate are present in virtually the same concentrations as their free, unbound concentrations in the plasma. If a substance is bound even partially to protein, that restricts its glomerular filtration because proteins normally cannot pass through the glomerular capillary membrane.

The urine that ultimately is formed by the kidneys is not merely the ultrafiltrate of plasma, because excretion of an ultrafiltrate through the urine would soon deplete the body of solutes and water. To modify the volume and content of the urine, the tubules selectively reabsorb and secrete substances.

Reabsorption

Table 13-1 summarizes the work of the renal tubular cells in the process of reabsorption. An average of 180   L of water (protein-free plasma) is filtered through the glomerulus of an adolescent per day, and yet the average urine output is 1.5   L/day. This means that 178.5   L of water is reabsorbed out of the tubular lumen back into the body’s circulation per day.

Secretion

Although most substances enter the tubules through filtration at the glomerulus, other substances actually can be secreted into the urine by the tubular cells. Like tubular reabsorption, tubular secretion can be either an active or a passive transport process. Substances dissolved in the serum of the peritubular capillaries cross into the tubular cell and then can be transported into the tubular lumen and excreted in the urine.

Substances most commonly secreted by the tubules include organic acids and bases, food additives, and many drugs and chemicals. A transport maximum for secretion is known for only three substances; therefore tubular secretory functions may be less limited than reabsorptive functions.

Reabsorption and Secretion in the Proximal Tubule

The selective reabsorption of solute begins in the proximal tubules. Approximately 67% of the filtered water, Na⁺, Cl⁻, K⁺, and other solutes such as bicarbonate are reabsorbed in the proximal tubule. In addition, the proximal tubules normally reabsorb all filtered amino acids and glucose.⁶³

The most important function of the proximal tubule is the reabsorption of the filtered sodium and water. The proximal tubule neither concentrates nor dilutes the urine; its primary responsibility is the reabsorption of sodium, water, and electrolytes.

Bicarbonate and Hydrogen Ions

Because the kidney is responsible for bicarbonate reabsorption and is also responsible for generating new bicarbonate ions, it plays an important role in the regulation of acid-base balance. Sodium and bicarbonate ions in the glomerular filtrate enter the proximal tubule. There, as noted previously, the sodium passively diffuses by concentration gradient into the proximal tubular cell and then is actively transported out of the tubular cell. To maintain electrical balance, another positively charged ion—hydrogen—is pumped actively from the tubular cells into the tubular lumen.

Once the hydrogen ion enters the tubular lumen, it combines with the bicarbonate in the filtrate to form carbonic acid. The carbonic acid in the tubule quickly disassociates to form carbon dioxide and water. The carbon dioxide easily diffuses back through the tubular cell membrane where it recombines with water, forming carbonic acid. Subsequent disassociation of the carbonic acid within the tubular cell again forms the hydrogen ions and bicarbonate ions; and the process is repeated. The tubular cell will again actively secrete the hydrogen ions into the lumen in exchange for sodium ions, and the bicarbonate ions will then diffuse passively out of the tubule cell into the peritubular interstitial fluid in response to concentration and electrical gradients.

As a result of this process, for every bicarbonate ion that combines with a hydrogen ion in the lumen of the tubule, a bicarbonate ion ultimately will diffuse into the peritubular capillaries (Fig. 13-6). This secretion of hydrogen ions and reabsorption of bicarbonate ions occurs along the length of the renal tubules, but 90% of bicarbonate reabsorption occurs in the proximal tubule. (See section, Regulation of Acid-Base Balance.)

Fig. 13-6 Renal excretion of acid. 1. Conservation of filtered bicarbonate. Filtered bicarbonate combines with secreted hydrogen in the presence of carbon anhydrase (CA) to form carbonic acid (H₂CO₃), which then dissociates to water (H₂O) and carbon dioxide (CO₂); both diffuse into the epithelial cell. The CO₂ and H₂O combine to form H₂CO₃ in the presence of CA, and the resulting bicarbonate (HCO₃⁻) is reabsorbed into the capillary. 2. Formation of titratable acid. A hydrogen ion is secreted and combines with dibasic phosphate (HCO₄⁻) to form monobasic phosphate (H₂PO₄⁻). The secreted hydrogen is formed from the dissociation of H₂CO₃, and the remaining HCO₃⁻ is reabsorbed into the capillary. 3. Formation of ammonium. Ammonia (NH₃) is produced from glutamine in the epithelial cell and diffuses to the tubular lumen, where it combines with H⁺ to form ammonium (NH₄⁺). Once NH₄⁺ has been formed, it cannot return to the epithelial cell (diffusional trapping), and the bicarbonate remaining in the epithelial cell is reabsorbed into the capillary.

(From McCance K, Huether SE, editors: Pathophysiology: the basis for disease in adults and children, ed 6. St Louis, 2010, Elsevier).

The Loop of Henle

Reabsorption of sodium and water from the proximal tubule significantly reduces the volume of the glomerular filtrate. However, because the sodium and water are reabsorbed at approximately the same rate, the osmolality of the filtrate remains unchanged as it passes through the proximal tubule; it is neither concentrated nor diluted. The function of the loop of Henle is to remove more solute and water from this filtrate.

The loop of Henle, located within the renal cortex and the medulla, provides a countercurrent mechanism for urine concentration. The descending limb of the loop of Henle does not transport sodium or chloride actively, but it is highly permeable to sodium and water. Thus, as the filtrate passes through the descending limb of the loop, it becomes progressively more concentrated. The osmolality can increase from 300 to 1200   mOsm/L between the beginning of the descending limb and the tip of the loop of Henle (Fig. 13-7).

Fig. 13-7 Countercurrent mechanism for concentrating and diluting urine. ADH, Antidiuretic hormone (Note: Numbers in illustration represent milliosmoles).

(From McCance K, Huether, SE, editors: Pathophysiology: the basis for disease in adults and children, ed 6, St Louis, 2010, Elsevier).

As the filtrate begins to pass through the ascending limb of the loop of Henle, chloride is actively pumped out of the tubule, and sodium follows passively. Water, however, must remain in the tubule because the ascending limb is impermeable to water. The solute loss from the tubule produces a fall in the osmolality of the filtrate and a rise in the osmolality of the interstitial fluid surrounding the loop. Thus, the osmolality of filtrate arriving in the distal tubule is lower than that of filtrate entering the loop of Henle and lower than that of the interstitial fluid in the medulla.

The loop of Henle removes approximately 25% of filtered sodium and 15% of filtered water from the tubule, leaving approximately 10% of the filtered sodium and 20% of the filtered water to enter the distal tubule.

The blood vessels surrounding the loop of Henle form a hairpin loop structure, called the vasa recta. The vasa recta consists of capillaries that run parallel to the loop of Henle and the collecting ducts (for an illustration, see Evolve Fig. 13-1 in the Chapter 13 Supplement on the Evolve Website). As these capillaries follow the loop of Henle into the interstitium of the renal medulla, where osmolality is high (as the result of the tubular countercurrent mechanism), water shifts out of capillaries into the interstitial fluid, and sodium and chloride move from the interstitial fluid into the capillaries.

The vasa recta does not contribute to the creation of a concentration gradient; its content is affected by the osmotic gradients surrounding the loop of Henle. This capillary loop mechanism is termed a countercurrent exchanger; the term reflects its passive nature. By this mechanism, the solute and water in the interstitial fluid surrounding the loop of Henle and the collecting ducts are reabsorbed into the circulation while maintaining the interstitial osmolality.

The Distal Tubule and Collecting Ducts

The distal tubule arises from the ascending limb of the loop of Henle; its thick cellular structure is distinct from the thin cells of the ascending loop. Thick cuboidal cells continue up through the renal cortical area to a point where the distal tubule is in direct contact with the afferent arteriole of its glomerulus. At this junction, the distal tubule cells become more densely packed and more columnar, and the muscle cells of the arteriole enlarge and take on a granular appearance. This point of contact between the distal tubule and the glomerular afferent arteriole is called the juxtaglomerular apparatus (see Fig. 13-3).

The juxtaglomerular apparatus consists of the columnar cells of the distal tubule (called the macula densa because of their prominent nuclei) and large cells of the afferent arteriole (called polkissen or polar cushion). The term juxtaglomerular cells most commonly refers to the cells of the afferent arteriole; these cells are able to sense pressure and secrete the hormone renin.

Beyond the juxtaglomerular apparatus, the distal tubule joins the collecting duct. The collecting duct will in turn descend from the renal cortex through the medulla and into the renal calyces. The filtrate present in the early distal tubule has a lower osmolality and lower sodium concentration than the plasma and the surrounding interstitial fluid. As the urine filtrate passes through the distal tubule and the collecting ducts, more water will be removed to further concentrate the urine. The final concentration of urine in the distal tubule and the collecting ducts is adjusted by the active transport of sodium out of the distal tubule and changes in the relative permeability of the collecting ducts to water (e.g., under the influence of antidiuretic hormone).

The distal tubule is the site of final adjustments in the urine sodium and potassium content. The distal tubule actively reabsorbs approximately 10% of the filtered sodium. This active transport process occurs against a high electrical and concentration gradient and is influenced by the volume and character of the fluid arriving from the loop of Henle, as well as by hormones, especially aldosterone.

Renin, Aldosterone, and Antidiuretic Hormone

Renin is secreted from the polkissen cells of the afferent arteriole in the juxtaglomerular apparatus. In turn, renin forms angiotensin I from renin substrate (a circulating peptide from the liver). The amounts of renin released and angiotensin formed are determined by the renal perfusion pressure, sympathetic nervous system stimulation, circulating vasoactive substances, and changes in electrolyte concentration.⁵⁵

Angiotensin I circulates to the lung and is converted enzymatically to angiotensin II. Angiotensin II produces peripheral vasoconstriction and an increase in aldosterone secretion, which increases renal sodium and water reabsorption. These effects should increase intravascular volume (Fig. 13-8). Angiotensin I and II are destroyed by angiotensinase, an enzyme that is present in plasma and secreted by a variety of organs, such as the kidney, intestine, and liver.

Fig. 13-8 Renal response to changes in extracellular fluid volume and electrolyte concentration or stress.

The quantity of sodium that is excreted in the urine when aldosterone is absent totals approximately 2% of the total filtered sodium. If aldosterone is absent (e.g., in patients with untreated adrenal insufficiency), excretion of that sodium will be associated with excretion of a large volume of water that can produce hypovolemic shock. Thus, aldosterone is responsible for the reabsorption of a very small but significant portion of the filtered sodium.

Aldosterone is secreted by the adrenal cortex in response to pituitary adrenal corticotropic hormone (ACTH) secretion and a variety of other stimuli. A fall in the pulse pressure, decreased stretch of the right atrium, and an increased serum potassium concentration all stimulate aldosterone secretion.⁶³ An important stimulus for aldosterone is formation of angiotensin from renin released by the juxtaglomerular apparatus. Aldosterone stimulates epithelial cell transport of sodium in the renal tubular epithelium, along the intestinal lumen, and in sweat and saliva. Increased aldosterone levels increase the active reabsorption of sodium and decrease potassium reabsorption. The increased sodium reabsorption produces water reabsorption; this increases intravascular volume and reduces the juxtamedullary secretion of renin. The reduction in potassium tubular reabsorption increases potassium excretion in the urine and should result in a fall in the serum potassium concentration. These responses to aldosterone should in turn reduce the stimulus for aldosterone secretion (see Fig. 13-8).

Antidiuretic hormone (ADH), or arginine vasopressin (AVP), secretion also affects the final concentration of urine. ADH is produced by the supraoptic and paraventricular nuclei in the hypothalamus and is transported to the posterior lobe of the pituitary, where it is released in response to an increase in serum osmolality. ADH secretion is stimulated by serum osmolality greater than 280 to 285   mOsm/L (or a rise in serum osmolality of 2% or more). It also is secreted in response to significant (10%-15%) volume depletion, a fall in blood pressure, painful stimuli, fear, and exercise. Hemoconcentration, diabetic ketoacidosis,⁹⁰ and mannitol administration increase ADH secretion, and administration of hypertonic glucose often inhibits ADH secretion.^34,54 The predominant stimulus for ADH secretion is a rise in serum osmolality sensed by osmoreceptors in and around the supraoptic nucleus of the hypothalamus.

If ADH is present, the renal distal tubule and collecting ducts become highly permeable to water. As the collecting ducts descend through the hypertonic interstitium in the renal medulla, water will move from the collecting ducts into the medullary interstitium to be reabsorbed into the circulation. Thus, ADH secretion reduces urine volume and increases urine concentration.

If ADH levels are low, ADH secretion is absent (i.e., neurogenic diabetes inspidus [DI]), or the kidney is unresponsive to ADH (i.e., nephrogenic DI), the distal tubule and collecting ducts remain relatively impermeable to water, so water will remain in the filtrate that flows into the renal calyces. Large quantities of dilute urine will then be excreted.

Regulation of Acid-Base Balance

The kidney plays a critical role in balancing serum acids and bases. A substance is labeled as an acid or a base according to its ability to lose or gain a hydrogen ion (a proton). Strong acids dissociate freely in solution, readily yielding a hydrogen ion; therefore they will contribute to the development or progression of acidosis. Weak acids only partially dissociate into a solution that will then contain both acid and base; thus, they do not contribute to changes in acidity. Bases are substances that will accept a free hydrogen ion; they reduce the hydrogen ion concentration, increasing the pH.

The pH is the inverse of the logarithm (log) of the hydrogen ion concentration; as the hydrogen ion concentration rises, the pH falls (the serum becomes more acid). The normal range of pH is 7.35 to 7.45. If the pH is less than 7.35, acidosis is present; if the pH exceeds 7.45, alkalosis is present. Even slight changes in hydrogen ion concentration or serum pH can alter metabolic and cell functions.

Calcium Regulation

The serum (extracellular) ionized calcium concentration normally is maintained within very narrow limits by renal regulatory mechanisms and by adjustments in bone deposition or demineralization and vitamin D reabsorption in the gastrointestinal tract. Serum ionized calcium concentrations also are affected by serum albumin concentration and acid-base balance.

Precise regulation of the serium extracellular calcium is necessary because calcium imbalance can exert a profound effect on neuromuscular excitability and cardiovascular function. In addition, calcium plays an important role in the chemical reactions necessary for thrombin formation and coagulation. Finally, calcium ions react with phosphate ions to form bone salts; these bone salts give the bones rigidity.

Approximately 99% of the total body calcium stores are deposited in the bones, and the remaining 1% resides in the plasma and the interstitial fluid. If the serum pH is normal, approximately half of the total plasma calcium is bound to serum albumin, does not enter into chemical reactions, and does not filter into the glomerular filtrate. The remaining half of the total plasma calcium is present in the ionized form; this constitutes the biologically active form of calcium.

The normal total serum calcium concentration is 9 to 11   mg/dL, and normal ionized calcium concentration is approximately 4.4 to 5.3   mg/dL.⁸⁰ The serum calcium concentration is evaluated in light of the serum protein concentration. An increase in the serum albumin and globulin will increase the amount of calcium bound to proteins, so will reduce the amount of the serum calcium that is present in the ionized form. For each 1   g/dL increase in serum albumin, 0.8   mg/dL of calcium is removed from its ionized state and is bound to the albumin. Increases in serum globulin level, however, will lower the ionized calcium concentration by only 0.16   mg/dL. If serum albumin and globulin concentrations are reduced, a relatively greater portion of the patient’s total serum calcium will be present in the ionized form. As a result, the patient with a low total serum calcium concentration and a reduction in serum albumin may have a normal serum ionized calcium concentration.

Changes in the serum pH also will affect the amount of calcium bound by proteins. An increase of 0.1 in serum pH will increase protein-bound calcium by 0.12   mg/dL. Conversely, when the serum pH falls, more calcium is removed from the protein binding sites and is ionized, and available to participate in chemical reactions. Thus, when a decreased total serum calcium concentration is present in a patient with alkalosis, the serum ionized calcium concentration is probably extremely low. Alternatively, if the total serum calcium concentration is low in a patient with acidosis, the serum ionized calcium concentration may not be reduced significantly.¹⁰³

Calcium homeostasis requires regulation of the amount of calcium filtered and reabsorbed by the kidneys, the amount of calcium absorbed from and excreted by the gastrointestinal tract, and the mobilization or deposition of calcium phosphate and other minerals in the bone matrix. These three methods of calcium regulation are controlled by parathyroid hormone (PTH), which is secreted by the four parathyroid glands. When serum ionized calcium levels fall, PTH is released, increasing the renal reabsorption of calcium and the gastrointestinal absorption of calcium. PTH enhances the movement of calcium and phosphate from the bone into the extracellular fluid. In addition, PTH decreases renal tubular reabsorption of phosphate, resulting in excretion of the phosphate that was released when calcium was mobilized from the bone.⁵⁴

Prenatal and Postnatal Development of Renal Function

During fetal life, the placenta performs many of the functions of the kidney, so congenital renal malformations may not cause fetal distress. Urine secretion into the amniotic fluid begins during the ninth through twelfth weeks of gestation. Most kidney growth occurs during the last 20 weeks of gestation, and the GFR increases rapidly between the twenty-eighth and thirty-fifth weeks of gestation. All nephrons of the mature kidney are formed by the twenty-eighth week of gestation.⁴⁰

After birth, kidney size increases in proportion to body length. Kidney weight doubles in the first 10 months of life, more as the result of proximal tubular growth than from an increase in glomerular size. The GFR also increases significantly after birth. The GFR of the full-term neonate (per square meter of body surface area) is approximately one third the GFR of an adult. Renal blood flow and the GFR double during the first 2 weeks of life, and GFR is nearly equal to adult values within the first 3 years of life.⁴⁰

Immediately after birth, the neonate normally has a high urine volume with low osmolality, thought to be the result of immaturity of renal sodium and fluid regulatory mechanisms. Because increases in systemic arterial pressure and systemic vascular resistance also result in an increase in renal blood flow and GFR during this time, these factors also may be responsible for the high urine volume. Beyond the first several hours of life, urine volume normally falls and urine concentration gradually rises.⁴⁰

The newborn kidney is able to excrete amino acids and conserve sodium and glucose as well as the adult kidney. However, the newborn kidney is less able to excrete free water and to concentrate urine than is the adult kidney.⁴⁰ As a result, the infant kidney may be less able to excrete a large water load and may be unable to concentrate urine in response to dehydration.

Regulation of the acid-base balance by the newborn kidney is relatively efficient, although it has less ability to secrete hydrogen ions or fixed acid than does the adult kidney; this is exacerbated by limited dietary protein intake. As a result, renal compensation for metabolic acidosis may be limited in the neonate. Dehydration, hypotension, and hypoxemia all produce a marked fall in the infant’s GFR; therefore renal function may become compromised quickly during critical illness.

Serum Osmolality

Osmotic pressure in a fluid is measured in milliosmoles and is the force exerted by particles in solution that will draw water across a semipermeable membrane. The normal serum osmolality is approximately 275 to 295   mOsm/L. Sodium and its chief anions, chloride and bicarbonate, account for 90% of the total osmolality of the plasma. The serum osmolality can be calculated by adding the concentrations of the solutes (including sodium, potassium, calcium, magnesium, sulfate, creatinine, glucose, protein, and urea) per unit of solvent. For simplicity, the total serum osmolality is estimated using the serum concentrations of sodium, glucose, and blood urea nitrogen (BUN) as follows⁸⁶:

*This formula does not reflect the influence of plasma proteins or administered osmotic agents, such as mannitol. It may be inaccurate in the presence of severe hyperglycemia and hyperlipemia.

If the serum glucose and BUN are normal, the serum osmolality will be slightly more than double the serum sodium concentration.

Factors Influencing Water Movement Between Body Compartments

Under normal conditions, free water is distributed within the intracellular and the extracellular (including intravascular and interstitial) compartments, so that osmolality is equal within all spaces.³⁴ Acute changes in the osmolality of any one body fluid compartment will result in free water movement across the semipermeable vascular and cell membranes until osmotic equilibrium is restored. Acute changes in serum sodium and osmolality can cause acute water shifts between the intracellular and extracellular spaces. Sudden, significant water shifts are tolerated poorly.

An acute fall in serum sodium and the resulting intracellular water shift can cause cerebral edema. If neurologic symptoms develop, urgent treatment is needed. An acute rise in serum sodium and osmolality can cause a water shift from the cells to the extracellular space. A significant extracellular water shift can cause cerebral dysfunction and intracranial bleeding. For further information, see Chapter 12.

Changes in Body Fluid Composition and Distribution During Critical Illness

Critically ill patients have a tendency to retain fluids, because antidiuretic hormone and aldosterone secretion are typically increased. Catecholamine release, hypotension, fright, or pain can stimulate antidiuretic hormone (ADH), renin, and aldosterone release. ADH release also is known to be stimulated by any condition that reduces left atrial pressure (including hemorrhage, positive pressure ventilation, and severe pulmonary hypertension), and the administration of general anesthetics, morphine, or barbiturates.⁵⁴

ADH secretion promotes water reabsorption in the renal tubules and collecting ducts, so that intravascular volume will increase and intravascular osmolality will fall. Aldosterone secretion enhances renal sodium reabsorption; water follows, contributing to an increase in intravascular volume. As a result of the actions of these hormones, postoperative patients often demonstrate decreased urine volume and increased urine concentration in the presence of hemodilution. Because the newborn kidney has a limited ability to concentrate urine, neonates may demonstrate decreased urine volume and only moderate urine concentration.

Postoperative fluid administration must be tailored to prevent fluid overload or sodium imbalance. Typical fluid and electrolyte losses in the urine most closely resemble 0.45% sodium chloride, whereas insensible losses through the skin and respiratory tract are more similar to 0.2% sodium chloride. For this reason, 0.2% or 0.45% sodium chloride with 5% or 10% glucose may be administered during the postoperative period to replace insensible and urine losses only, but not for the provision of maintenance fluids. Recent reports of hyponatremia in critically ill children have led to caution in the use of hypotonic fluids, and greater use of isotonic crystalloids (see Chapter 12).

The stressed patient will tend to retain sodium and water as a result of renin, aldosterone, and ADH secretion; therefore administration of hypotonic solutions (e.g., 5% dextrose and water) should be avoided unless sodium intake is restricted (e.g., in postoperative patients with congenital heart disease). Excessive gastrointestinal fluid and electrolyte losses should be replaced with a solution approximating the electrolyte concentration in the gastrointestinal fluid lost.⁴³ These recommendations should serve only as guidelines and must, of course, be adjusted to meet the patient’s individual requirements.

Urine volume should be monitored closely and should average more than 1   mL/kg per hour if fluid administration is adequate. If severe fluid restriction is imposed, urine volume will likely be lower and can average 0.5-1.0   mL/kg per hour. Urine concentration is evaluated through measurement of urine specific gravity and osmolality. The specific gravity of the urine reflects the combined weight of all the particles in the urine. The specific gravity of water is 1.000, and the specific gravity of normal urine ranges from 1.010 to 1.030. The higher the solute content of urine, the higher the urine specific gravity.

The urine specific gravity usually correlates with the urine osmolality. However, if an excessive number of large particles such as glucose, protein, mannitol, or contrast agent is present in the urine, then the urine specific gravity will increase disproportionate to its true osmolality, rendering the specific gravity measurement useless. Because the urine osmolality best indicates the renal ability to concentrate urine above the serum osmolality, it is a more reliable indicator of renal function than the measurement of urine specific gravity.

Normal urine osmolality is approximately 300   mOsm/L when plasma osmolality is approximately 275 to 295   mOm/L. If renal function is good, the ratio of urine to plasma osmolality should be 1.1:1 or higher (i.e., urine osmolality should always be higher than plasma osmolality). When renal failure is present, urine osmolality often is equal to plasma osmolality.

Potential Effects of Drugs and Solutions on Renal Function

Some drugs and solutions used in the evaluation or treatment of critically ill patients may be nephrotoxic. Antibiotics such as the cephalosporins, the aminoglycosides, and the sulfonamides may be nephrotoxic in infants and children.^23,99 Alpha adrenergic medications that produce renal vasoconstriction can result in decreased renal perfusion and oliguric renal failure. Indomethacin administration to promote constriction of the neonatal ductus arteriosus can produce a fall in GFR or a decrease in urine output.

The use of hypertonic angiographic contrast agents can result in renal vein thrombosis, medullary hypoperfusion, renal ischemia, and renal insufficiency. Because these agents have an osmolality of 1300 to 1940   mOsm/L, they should be administered carefully in low doses and only to well-hydrated infants. If possible, low-osmolality radiocontrast agents should be used, and other nephrotoxic drugs should be avoided.²³ Use of nephrotoxic drugs in children also should be restricted if circulatory compromise or renal insufficiency is present.

Proximal Tubule Diuretics

Distal Tubule Diuretics

Most agents that act on the distal convoluted tubule will be ineffective if the GFR less than 40   mL/min or less than 40% of normal.³¹

Loop of Henle Diuretics

The loop diuretics, furosemide (Lasix) and ethacrynic acid (Edecrin) are the most potent and popular diuretics used in the care of critically ill children. Both drugs inhibit sodium chloride transport in the ascending limbs of the loop, so that natriuresis and diuresis result. These drugs are often effective in patients responding maximally to other diuretics, and they will be effective despite a decrease in glomerular filtration rate.³¹ Both drugs can be administered intravenously, and they have a rapid onset.

Loop diuresis results in increased urinary potassium, hydrogen, and calcium ion loss. Potassium supplementation often will be required to prevent hypokalemia. The child’s serum electrolytes should be monitored closely.

Large diuresis can decrease plasma volume, causing a contraction alkalosis. The increased hydrogen ion excretion that results from the administration of loop diuretics can further contribute to the alkalotic state (Box 13-4).

In large doses, both furosemide and ethacrynic acid can cause an increase in renal blood flow with an accompanied increase in perfusion to the outer renal cortical areas. These drugs are useful in patients with marginal renal perfusion or in patients with both cardiovascular and renal disease. Both drugs have been associated with ototoxicity, although the reported incidence of this complication seems to be higher with ethacrynic acid. The ototoxicity may not be reversible even after the drug is discontinued.

Etiology

An increase in serum potassium can result from excessive potassium administration, intravascular accumulation of potassium ions caused by changes in the acid-base balance or significant cell destruction (and release of intracellular potassium), or reduced renal excretion of potassium ions.

Pathophysiology

The serum potassium concentration should be evaluated in light of the serum pH. Acidosis (or a fall in serum pH) produces a rise in the intravascular potassium ion concentration, because potassium ions will move from the cells into the vascular space in exchange for hydrogen ions. Thus, a modest elevation in the serum potassium concentration in the acidotic patient may not represent significant hyperkalemia. When acidosis is corrected (i.e., the serum pH rises), the serum potassium concentration will fall.

Alkalosis (or a rise in serum pH) produces a fall in the serum potassium concentration. Therefore if the serum potassium concentration is high despite the presence of alkalosis, significant hyperkalemia is present.

Hyperkalemia can complicate renal failure because renal potassium excretion decreases. When chronic renal failure is present, the serum potassium concentration can remain normal if the child does not have a high potassium load (such as can result from increased potassium intake, acidosis, or potassium release from injured cells). If the child has acute kidney injury and decreased urine volume, the child’s serum potassium concentration may rise quickly.

Clinical Signs and Symptoms

The manifestations of hyperkalemia affect neuromuscular function, because the membrane potential in excitable tissue is determined by the ratio of extracellular to intracellular potassium concentration. Therefore hyperkalemia causes muscle weakness and paralysis.

Hyperkalemia can produce characteristic changes in the electrocardiogram. Initially a tall, peaked T wave develops; this is followed by a widening of the QRS complex, ST-segment depression, and decreasing amplitude of the R wave. As the serum potassium concentration continues to rise, the P-R interval is prolonged, the amplitude of the P wave decreases, and finally the P wave disappears. Ventricular arrhythmias or ventricular fibrillation can develop at any point during this progression (Fig. 12-3).

Management

The best way to prevent hyperkalemia is to identify at-risk patients so that potassium administration can be curtailed. In addition, providers should frequently assess the at-risk child’s serum potassium concentration and monitor for signs of clinically significant hyperkalemia. Finally, the child’s fluid intake and output and acid-base status should be monitored, because these also affect serum potassium concentration.

Once the child’s serum potassium concentration exceeds 6.5-7.0   mEq/L, there is a high risk of serious cardiac arrhythmias, and immediate intervention is required. Although the evidence supporting emergent therapies for hyperkalemia is largely anecdotal, widely accepted goals are: stabilize the myocardial cellular membrane, expand the extracellular fluid volume, shift potassium into the cells, and remove potassium from the body (see “Acute Kidney Injury” later in this chapter and Chapter 12, Table 12-4 for more information).

Calcium chloride or calcium gluconate is administered to transiently counteract adverse effects of hyperkalemia on cardiac cells. Calcium chloride (20   mg/kg) is infused intravenously over 1 to 5 minutes (calcium gluconate is used in neonates). During the calcium infusion, the nurse should monitor for bradycardia. In the presence of arrhythmias, an immediate improvement in the patient’s electrocardiogram (ECG) may be observed as the calcium is given; these effects last approximately 30   min.⁵⁰ During this 30-minute window, additional therapy is provided to reduce the serum potassium concentration.

If hyperkalemia is associated with contraction of intravascular volume or hemoconcentration (e.g., with hypovolemic shock or severe dehydration), reexpansion of the intravascular volume should produce a dilutional reduction in the serum potassium concentration.

Because a rise in serum pH produces a shift of potassium ions into the cells, sodium bicarbonate may be administered (1.0   mEq/kg) over a 30- to 60-minute period to alkalinize the serum and enhance the intracellular potassium shift. Full-strength (8.4%) sodium bicarbonate typically is diluted to half strength before administration to infants and young children, to prevent vascular irritation and the development of increased intravascular osmolality and hypernatremia. Sodium bicarbonate should not be used to treat hyperkalemia in patients with respiratory failure and hypercarbia, because the buffering action of the bicarbonate will result in more carbon dioxide formation.

The administration of sodium bicarbonate does not reduce the total body potassium and may have a minimal effect on the serum potassium concentration of the nonacidotic patient. If the drug is effective, the serum potassium should begin to fall within 5 to 10 minutes, and the effects usually are apparent for several hours.

Cellular uptake of potassium from the extracellular (including intravascular) fluid is enhanced with the infusion of glucose plus insulin, one of the most effective methods of reducing hyperkalemia in critically ill children. A hypertonic glucose solution is administered (1-2   mL/kg of 25% dextrose [1   g/kg]) with a dose of regular insulin (0.1   U/kg).⁵⁰ The serum potassium concentration should begin to fall within 15 to 30 minutes, and effects may be apparent for about an hour.

The half-life of regular insulin is longer than the half-life of hypertonic glucose. Therefore late hypoglycemia often is observed after administration of the glucose and insulin. The child’s serum glucose concentration should be monitored and point-of-care glucose testing should be used (if available), especially 1 to 2 hours following administration. Supplementary glucose should be administered as needed.⁵

Removal of potassium from the body can be accomplished via the gastrointestinal tract because potassium is present in intestinal fluids. The ion exchange resin, sodium polystyrene sulfonate (Kayexalate) will exchange potassium for sodium ions on an ion-for-ion basis when it is administered orally or as a retention enema.

Sodium polystyrene sulfonate is administered as a 20% suspension in a 5% glucose solution. The dose of 1.0   g/kg can be repeated as often as two or three times in 24   hours.⁵² Because the greatest exchange of sodium for potassium occurs in the large intestine, an oral or nasogastric dose of 1.0   g/kg (given in divided doses) can reduce the serum potassium 1   mEq/L over a 24-hour period. The enema dose is somewhat higher and usually totals 2   g/kg, given once or twice per day. The serum sodium will rise following sodium polystyrene sulfonate administration, and fluid retention may develop.

Inhaled albuterol causes rapid movement of potassium into the cells by stimulating the beta 2 adrenergic receptors, which in turn increase activity of the sodium-potassium-adenosine triphosphatase pump in the cell membrane, increasing cellular uptake of potassium. Albuterol stimulates the release of insulin, which also promotes cellular uptake of potassium.⁸³ Albuterol may provide rapid but unpredictable lowering of the serum potassium.

If all other measures to reduce serum potassium concentration fail, then hemofiltration, exchange transfusion, or hemodialysis may be required (see section, Care of the Child During Dialysis, Hemoperfusion, and Hemofiltration).

Etiology

There are many causes of AKI in critically ill children. Critically ill neonates can develop AKI as a result of asphyxia, hypoxia, shock, and sepsis.⁶ AKI also can occur as a complication of umbilical artery or vein catheterization and subsequent thrombosis of the aorta, the renal artery, or the renal vein. Critically ill children most commonly develop AKI as a complication of major surgical procedures, multisystem organ failure, drug toxicity, or toxic ingestions.^9,27

Causes of AKI are classified according to the location of the primary disorder. The categories to describe these etiologies are prerenal, postrenal and intrarenal (intrinsic). Ostensibly, prerenal and postrenal causes of AKI, if not prolonged, do not involve damage to the renal parenchyma, and correction or reversal of these causes should allow renal function to return to normal. However, severe prerenal or postrenal failure can produce damage to the nephron unit, so that normal renal function might not return after correction of the underlying cause, and intrinsic renal failure occurs. Intrinsic renal failure can also result from primary kidney disease.

Pathophysiology

The most common cause of AKI is an acute reduction in renal perfusion. As noted in the Etiology section above, this reduction can be caused by hypovolemia, hypotension, other forms of shock, or renal artery or aortic thrombosis. When renal perfusion is compromised, renal efferent arteriolar constriction can initially maintain glomerular filtration. However, if the compromise in perfusion is severe or acute, efferent arteriolar constriction cannot maintain glomerular capillary pressure sufficiently, and glomerular filtration falls.

Postrenal failure can develop as the result of obstruction to the ureters or urethra with obstruction to urine flow. Urine obstruction increases the volume and pressure of fluid in the collecting system and ultimately will increase the pressure in Bowman’s capsule. This increase in pressure will impede glomerular filtration. Once the obstruction to urine flow is relieved, a natriuresis often is present for several days or weeks (up to 2 weeks is common). Renal function ultimately is restored unless the obstruction has been prolonged.

If both prerenal and postrenal causes have been ruled out in the patient with AKI, the cause is assumed to be injury to the kidney’s functional components—the renal parenchymal cells. This damage can occur through direct injury to the glomeruli, tubules, or renal vasculature. Glomerular damage is associated more commonly with the glomerulonephropathies; tubular damage is more commonly a result of ischemia or nephrotoxins.

Obstruction and damage to the renal vasculature can complicate umbilical artery or vein catheterization in the neonate; however, this is an uncommon cause of ARF in children. Renal vasculature pathology in children is most frequently the result of hemolytic uremic syndrome and other pathologies, including sickle cell disease, Kawasaki disease, and Henoch-Schonlein Purpura.⁵⁸

Tubular lesions caused by nephrotoxins temporarily disrupt the tubular structure, because they produce necrosis of the tubular epithelium down to, but not including, the supporting basement membrane. Ischemic lesions may affect any segment of the nephron, and injured areas may be interspersed with normal segments of tubular epithelium. Healing of both ischemic and nephrotoxic injury occurs through re-epithelialization. If the basement membrane is intact, tubular morphology can be reestablished after healing. If the basement membrane has been fragmented, however, the lack of supportive structure prevents regrowth of organized tubules. Connective tissue can extend through the ruptured basement membrane and fibrosis can replace the tubules.

The unpredictability of tubular healing makes it impossible to predict the rate of recovery of nephron function after ischemic or nephrotoxic injury.²⁷ Renal failure can be complicated by the development of backleak of fluid through the damaged tubular basement membrane. Backleak prevents elimination of the filtrate and results in reabsorption of the creatinine and other nitrogenous wastes back into the circulation.⁷⁹

Although the precise pathophysiology of AKI is not understood, almost all theories include a severe reduction in renal blood flow by 25% to 50%. This reduction in renal blood flow often occurs despite a normal systemic arterial pressure and is thought to result from intense renal vasoconstriction²⁷ that reduces GFR and renal cortical blood flow. This reduction stimulates renin and aldosterone secretion and produces sodium and water retention and decreased urine volume.

The development of AKI usually indicates the presence of renal tubular damage and reduced renal blood flow. In addition, there may be destruction of the glomerular capillary membrane, increased tubular permeability, or obstruction of the tubules.

Clinical Signs and Symptoms

AKI is characterized by a steady increase in the BUN and serum creatinine levels. Oliguria (urine output <300   mL/m² body surface area per day) is a common but not a constant clinical sign of AKI. Anuria is less common, and it often indicates more severe renal damage. Some children who develop AKI have nonoliguric renal failure, which is characterized by a rise in serum BUN and creatinine without a fall in urine volume. Children with AKI may even exhibit polyuria.

Clinical signs produced by uremia include an altered level of consciousness, seizures, anorexia, nausea, vomiting, abnormal platelet function, diminished white blood cell function, and pericarditis.⁷¹ Once AKI develops, the ability of the kidneys to regulate fluid volume and potassium, calcium, and glucose concentrations is severely impaired. In addition, renal regulation of acid-base balance is reduced. Finally, many patients with AKI develop anemia and coagulopathies, and they are at risk for the development of gastrointestinal hemorrhage and infection.⁷¹ As a result, assessment of children with AKI must include assessment of the reversible causes of renal failure as well as the recognition and management of its complications.

Management

Nutrition

If the child can tolerate oral or nasogastric feedings, these should be instituted as soon as possible to prevent excess protein catabolism. If oral or nasogastric feedings are impossible, parenteral alimentation should be instituted within the limits of the child’s daily fluid restriction.

Any form of nutrition should provide calories in the form of glucose or essential amino acids to minimize the accumulation of metabolic waste products.⁹⁸ The child’s daily caloric requirements will total approximately 50% to 75% of normal daily maintenance requirements when AKI is present, because a large portion of the daily maintenance calories are used for basal requirements and growth (Table 13-5).

Table 13-5 Estimated Normal Maintenance Caloric Requirements for Infants and Children

Age	Kcal/kg per 24 hours
0-6 months	90-110
6-12 months	80-100
12-36 months	75-90
4-10 years	65-75
>10 years, male	40-45
>10 years, female	38-30

Nutrient	Percent of total daily calories
Carbohydrates Fat		Combined 85-88
Protein	7-15

Psychosocial Aspects

When the child develops AKI, the child and the family are usually frightened. At the same time that the nurse must provide the most thorough observations and skilled care, the child and family are most in need of reassurance and support. If the child’s physical care requires the nurse’s undivided attention, the nurse should request assistance from a colleague or additional supportive staff (e.g., chaplain, social worker, patient ombudsman). The child requires explanations and preparation for uncomfortable treatments or procedures (as age appropriate), gentle handling, and soothing verbal and nonverbal interaction. (See Chapter 2 for further information.) Box 13-8 summarizes the care of the child with AKI.

Box 13-8 Nursing Care of the Child with Acute Kidney Injury (Acute Renal Failure)

1 Potential Acute Prerenal Failure Related to:

• Poor systemic perfusion

• Inadequate renal perfusion

Expected Patient Outcomes

• Patient will demonstrate effective systemic perfusion.

• Patient will demonstrate normal urine output with good renal concentrating ability (specific gravity greater than 1.005) when urine volume is reduced.

• Patient will demonstrate adequate, but not excessive, intravascular volume.

• Patient will demonstrate normal serum electrolyte concentration (including BUN and creatinine).

Nursing Interventions

• Record urine volume and total fluid intake hourly and notify provider if urine output <l-2   mL/kg per hour or if fluid intake greatly exceeds output.

• Insert and maintain urinary catheter—ensure that catheter is functioning properly. Irrigate per physician (or other on-call provider) order or unit policy if patency is questionable. Maintain aseptic technique when manipulating catheter.

• Ensure that catheter tubing is placed to facilitate gravity drainage of urine.

• Record urine osmolality and specific gravity every 2-4   hours (or per orders or unit policy); notify on-call provider if urine osmolality and specific gravity do not rise when urine volume falls.

• Monitor color of urine; notify on-call provider of cloudy or rusty urine. Cloudy urine can indicate infection or the presence of cell casts in the urine. Rusty urine can indicate hemolysis.

• Assess patient’s systemic perfusion: skin should be warm, peripheral pulses should be strong, capillary refill should be brisk, and mucous membranes should be pink. If the skin is cool, peripheral pulses are difficult to palpate, and capillary refill is sluggish, or color is pale or mottled, notify the on-call provider. Monitor urine output; a fall in urine output in the presence of poor systemic perfusion may indicate inadequate renal perfusion, and on-call provider should be notified.

• Support cardiovascular function as needed (and ordered) to maintain urine output greater than 1   mL/kg per hour. Fluid challenge of 20   mL/kg isotonic crystalloid or colloid initially may be ordered to improve systemic perfusion. If systemic perfusion does not improve despite the presence of a CVP greater than 5-10   mm Hg and signs of adequate intravascular volume (see Box 13-11), administration of inotropic agents or vasodilators may be necessary.

• Administer diuretic agents (furosemide [1-2   mg/kg IV] or mannitol [0.25-0.5   g/kg]) as ordered; monitor patient response and notify on-call provider if response is inadequate.

• Obtain urine samples as ordered for laboratory analysis of osmolality, sodium concentration, BUN and creatinine. Simultaneous serum samples must also be obtained.

• If prerenal failure is present, serum BUN will usually begin to rise before serum creatinine.

• When hypovolemia produces prerenal failure, urine sodium content will fall to less than 10   mEq/L (sodium is actively reabsorbed by functioning kidneys in presence of hypovolemia), and urine osmolality will exceed 500   mOsm/L (kidneys conserving water).

• After urine and serum electrolytes are obtained, calculate FE_Na

Where

U_Na = Urine sodium concentration

P_Na = Plasma (serum) sodium concentration

U_Cr = Urine creatinine concentration

P_Cr = Plasma (serum) creatinine concentration

An FE_Na of less than 1% in children and less than 2.5% in neonates is associated with prerenal failure, and an FE_Na greater than 1% to 3% is usually associated with intrinsic AKI.

NOTE: This calculation will not provide a valid indicator of the type of AKI present if diuretics, including mannitol, are administered before measuring urine and serum sodium and creatinine, because these drugs will increase urine sodium content regardless of the effectiveness of renal function.

2 Potential Hypervolemia/Fluid Volume Excess Related to:

• Oliguria

• Excessive fluid administration

• Sodium and water retention

Expected Patient Outcomes

• Patient will not demonstrate signs of hypervolemia, including high CVP, hepatomegaly, systemic edema, tachycardia, hypertension, tachypnea or increased requirement for ventilation support, pulmonary edema, high pulmonary artery wedge pressure, full (tense) fontanelle in infants, hyponatremia.

• Patient will not demonstrate excessive weight gain (greater than 50   g/24   hours in infants, greater than 200   g/24   hours in children, greater than 500   g/24   hours in adolescents).

Nursing Interventions

• Measure and record all fluid intake and output hourly; notify on-call provider immediately if urine output falls or positive fluid balance is present.

• Limit fluid intake (as ordered) once AKI is suspected. Typically, fluid intake is restricted to 300-400   mL/m² BSA per day plus urine output if renal failure is present. Minimize fluid used to flush monitoring lines and dilute medications. Closely supervise oral intake, if allowed or tolerated.

• Administer diuretic therapy as ordered. Monitor patient’s urine response and monitor electrolyte balance closely.

• Monitor for signs of hypervolemia including tachycardia, high CVP or PAWP, systemic and pulmonary edema and hypertension, possible signs of congestive heart failure.

• Measure child’s weight daily or twice daily (as ordered or per unit policy); utilize same scale each time and ensure consistent weighing time. Use bed scales for unstable patients. Notify provider of excessive weight gain.

• Be prepared to assist in initiation of CRRT if clinically significant hypervolemia develops.

3 Potential Electrolyte Imbalance Related to:

• Decreased renal potassium excretion

• Increased renal sodium excretion

• Decreased renal excretion of phosphate, calcium phosphate precipitation and decreased renal activation of vitamin D

Expected Patient Outcome

• Patient will demonstrate normal serum electrolytes.

Nursing Interventions

• Monitor patient’s serum electrolytes closely; notify on-call provider of abnormal results, including high or rapidly rising potassium concentration.

• Limit potassium intake (as ordered).

• Monitor for clinical signs of hyperkalemia, including peaked T wave, arrhythmias, diarrhea, and muscle weakness. If hyperkalemia is suspected, notify on-call provider, obtain serum sample for measurement of potassium concentration, and prepare to institute emergency measures to reduce serum potassium concentration.

• If significant hyperkalemia is present, administer (as ordered):

Calcium chloride (10% solution: 20   mg/kg) or calcium gluconate (10% solution: 60-100   mg/kg)

Sodium bicarbonate: 1   mEq/kg

Concentrated glucose: 1-2   mL/kg of 25% dextrose or glucose plus insulin (0.1 U/kg): combine 6 units regular insulin with 25% Dextrose to total 100   mL; administer 1-2   mL/kg (for further information, see Box 13-6)

Administer sodium polystyrene sulfonate (Kayexalate) enema as ordered (0.5   g/kg of 20% solution) approximately two to three times per day to reduce serum potassium approximately 1   mEq/L per 24   hours.

• If symptomatic hyperkalemia persists, prepare to assist with initiation of hemofiltration or dialysis.

• Be prepared to support cardiovascular function as needed.

• Monitor serum sodium concentration; notify provider of hyponatremia or hypernatremia.

• Monitor for clinical evidence of hyponatremia, including change in level of consciousness, muscle cramps, anorexia, abnormal reflexes, Cheyne-Stokes respiration, or seizures. Notify on-call provider if these are observed, obtain serum sample to evaluate sodium concentration, and prepare to administer 3% saline if ordered (2-4   mEq/kg).

• Monitor serum calcium concentration; notify physician of reduced total or ionized calcium concentration.

• Monitor for clinical signs of hypocalcemia, including muscle tingling or change in muscle tone, seizures, tetany, positive Chvostek sign (twitching of the side of the face when the facial nerve is tapped in front of the ear), or compromised cardiovascular function. If these signs are observed, notify the on-call provider, draw a serum sample for measurement of total and ionized serum calcium concentrations, and prepare to administer calcium chloride (20   mg/kg of 10% CaCl; use calcium gluconate in infant).

• Administer antacid-phosphate binders (as ordered) to reduce serum phosphate levels.

• Administer vitamin D as ordered to enhance calcium absorption.

4 Potential Metabolic Acidosis Related to:

• Poor systemic perfusion associated with prerenal failure

• Decreased renal ability to excrete hydrogen ions

Expected Patient Outcomes

• Serum pH, serum lactate and serum bicarbonate within normal levels

• Anion gap less than 15   mEq/L

Nursing Interventions

• Monitor arterial blood gases and serum lactate, and notify provider of development of acidosis.

• If metabolic acidosis develops, administer sodium bicarbonate as ordered (1   mEq/kg or mEq dose to correct part or all of the calculated deficit: base deficit × Weight in kg × 0.3).

• Administer sodium bicarbonate only if ventilation is effective or effectively supported.

• Monitor serum potassium concentration, because acidosis will produce a rise in serum potassium concentration.

• Calculate anion gap (AG):

Anion gap exceeding 11-14   mEq/L can be associated with metabolic acidosis or alteration in serum potassium, calcium, or magnesium ions.

5 Potential Drug Toxicity Related to:

• Reduced renal excretion of drugs or drug metabolites

Expected Patient Outcomes

• Patient will not demonstrate clinical or laboratory evidence of drug toxicity.

Nursing Interventions

• When renal failure develops, review patient’s drug doses and drug administration schedule, and discuss these with on-call provider (doses of drugs excreted by kidneys will be reduced as renal function is reduced).

• Note clinical signs of toxicity of all drugs child receives in the nursing care plan, and monitor for these signs; notify on-call provider of any signs of drug toxicity.

6 Potential Infection, Related to:

• Multiple invasive catheters

• Compromised immune system

• Compromised nutritional intake

• Poor nutritional status

Expected Patient Outcome

• Patient will demonstrate no leukocytosis, fever, or localizing signs of infection, sepsis or septic shock (see Chapter 6).

Nursing Interventions

• Perform meticulous hand washing before and after patient contact; ensure that hand washing is performed by every member of the healthcare team.

• Change all dressings and IV tubing per unit policy.

• Monitor patient temperature and white blood cell count, and notify physician (or on-call provider) of fever, leukocytosis, or leukopenia.

• Assess all skin puncture sites and notify provider of any erythemia, drainage, or fluctuance of wound edges, obtain cultures of urine, skin puncture sites, and blood (as ordered) if infection or sepsis are suspected.

• Monitor appearance of urine and peritoneal dialysis fluid; notify physician of cloudiness and obtain cultures as ordered.

• Administer antibiotics as ordered (check dose in light of compromised renal function).

7 Potential Patient/Family Anxiety Related to:

• Limited understanding of patient condition

• Patient fluid and electrolyte imbalance

• Severity of patient condition

Expected Patient Outcomes

• Child will be able to cooperate (as age-appropriate) with treatment plan and will not demonstrate any self-destructive behavior.

• Family members will demonstrate understanding of the child’s illness, prognosis, and treatment and will be able to participate in the child’s care.

Nursing Interventions

• Provide the child (as age-appropriate) and family with consistent explanations and support (see Chapter 2).

• Provide the child with positive reinforcement and encouragement.

• Provide explanations before any treatments are performed, and prepare the child for painful therapy with truthful information.

• Plan activities that will allow the child (as age-appropriate) to demonstrate anger, frustration, or sadness; encourage expression of these feelings if the child is willing to discuss them.