33.1: Introduction to the Renal System
By the end of this section, you should be able to:
- 33.1.1 Describe the structure and function of the renal system.
- 33.1.2 Name common conditions that affect the renal system.
Kidneys
The kidneys have three main functions: filtration, reabsorption, and secretion. The kidneys filter 200 liters of fluid daily to remove waste products that exit the body in the urine. Collecting important nutrients, ions, and proteins protects the body against deficiencies. The individual processes for the three main functions are listed here and explained in greater detail in later sections of this chapter:
- Removal of the waste products of metabolism
- Regulation of electrolytes and fluid
- Acid–base balance regulation
- Maintenance of systemic blood pressure
- Erythropoietin secretion
- Vitamin D 3 metabolism
- Gluconeogenesis
Kidneys’ Anatomical Structure
The kidneys are two bean-shaped organs positioned in the retroperitoneum slightly above the waist, between the T12 and L3 vertebrae. The right kidney sits slightly lower than the left to accommodate the liver. Each kidney weighs approximately 135–150 g and is approximately 10–12 cm long. The adrenal glands are located on the upper pole of each kidney, and the spleen is connected anteriorly to the upper pole of the left kidney by the splenorenal ligaments.
The exterior of the kidney has three protective layers: the renal fascia, which is the outermost layer; the perirenal fat capsule; and the renal capsule, which consists of fibrous connective tissue. The interior of the kidney is divided into three distinct areas: the outermost cortex, the medulla, and the renal pelvis. The renal cortex contains nephrons , the functional units of the kidney, which merge into the collecting ducts and the convoluted tubules. The renal medulla contains 8 to 18 renal pyramids with the bases located adjacent to the cortex and the apices connecting to the minor calyces (Sorano et al., 2023). The minor calyces drain into the major calyces, which are large collecting spaces near the ureters’ superior edge. The renal papillae are openings at the bottom of the renal pyramids where urine enters the collecting ducts. The renal columns are cortical tissues that separate the pyramids and provide space for the interlobar arteries. The urine moves from the pyramids to the funnel-shaped renal pelvis in the center of the kidney to the ureters (see Figure 33.2).
Kidneys’ Vascular Structure
The renal arteries branch off the aorta at the L1/L2 intervertebral disk level just inferior to the mesenteric artery. Each artery is 4–6 cm long and 5–6 mm in diameter. The renal artery divides into anterior and posterior branches before entering the kidney at the hilum , an indentation on the medial side of the organ that allows blood vessels, lymphatic vessels, and nerves to enter and exit the kidney. The segmental arteries eventually form the arterioles that supply the glomerular capillaries. The vasa recta is the network of capillaries that supply the proximal and distal tubules and the loop of Henle .
Kidneys’ Lymphatic Structure
Two separate lymphatic systems supply the kidney. One branch supplies the interior and the exterior of the renal capsule in the cortex, and the other surrounds the arterial blood vessels. Both systems drain from the hilum into the para-aortic lymph nodes.
Kidneys’ Neural Structure
The sympathetic division of the autonomic nervous system innervates the kidney. The splanchnic nerves from the renal plexus control the constriction of the arterioles in the renal cortex. These nerves travel from the renal vessels to the smooth muscle of the remaining areas of the nephron, including the juxtaglomerular cells that secrete renin. Sympathetic stimulation results in constriction of the renal vessels and the release of renin. In addition, there are pain receptors in the renal and urinary structures from the renal pelvis to the urinary meatus.
Link to Learning
This National Kidney Foundation video provides a brief overview of kidney function and kidney disease.
Nephrons
The nephron is the functional unit of the kidney and contains these structures (see Figure 33.3):
- Glomerulus and Bowman’s capsule, which together comprise the renal corpuscle
- Proximal convoluted tubule, located in the renal cortex
- Descending loop of Henle
- Ascending limb in the renal medulla
- Thick ascending limb
- Distal convoluted tubule
- Collecting duct
There are approximately 1 million nephrons in each kidney. There are two types of nephrons, which are labeled according to their anatomical position. Eighty-five percent of the nephrons are cortical nephrons , located in the outer renal cortex and extending partially into the medulla. The nephron loops are short and are supplied by the peritubular capillaries. The juxtamedullary nephrons are positioned at the junction of the renal cortex and the renal medulla. The nephron loop extends into the medulla and is surrounded by the vasa recta, a network of capillaries originating from the efferent arteriole. The cortical portion of the juxtamedullary nephron is also surrounded by the peritubular capillaries, which aid in the concentration and volume control of urine.
Blood is filtered by the globe-shaped renal corpuscle, which contains the glomerulus and Bowman’s capsule . The glomerulus is a tufted structure of fenestrated capillaries essential to filtration. The glomerulus is enclosed in a double-layered structure, the Bowman’s capsule, which has two surfaces, the exterior parietal layer and the interior visceral layer. The parietal layer is composed of squamous epithelial cells. The visceral layer is composed of specialized epithelial cells called podocytes that encircle the glomerular capillaries. Extensions of the podocytes called pedicles also surround the capillaries, forming filtration slits or pores that also aid filtration. The space between the visceral and parietal layers, the capsular space or Bowman’s space, becomes the lumen of the renal tubule. The fluid that is filtered from the glomerular capillaries moves to the renal tubule as filtrate.
The mesangial cells , located around the glomerular capillaries, regulate the surface area that is available for glomerular filtration. The cells contract in response to the stretch of increased blood in the capillaries, decreasing the surface area. Conversely, the filtration surface area increases when the cells are relaxed. The cells contract in response to angiotensin II and endothelin and relax in response to atrial natriuretic peptides (ANPs) and nitric oxide.
The renal tubule consists of three different areas with specialized structures and functions. Initially, the filtrate flows through the proximal tubule, which has straight sections and “convoluted” sections. This is the longest segment of the renal tubule, and the surface of the lumen has microvilli that increase the filtration surface area.
The second area, the nephron loop (loop of Henle), has two sections: the descending limb and the ascending limb. The descending limb, which consists of simple squamous cells, is often identified as the thin descending limb, whereas the ascending limb is mostly composed of cuboidal epithelial cells and is called the thick ascending limb.
The terminal portion of the nephron, the distal tubule, also contains straight and convoluted sections; however, the structure is composed of simple cuboidal epithelial cells without the microvilli. The fluid leaves the distal tubule and enters the collection system.
The Juxtaglomerular Apparatus
The macula densa cells are located at the boundary between the ascending loop of Henle and the distal tubules. These cells contact the juxtaglomerular cells of the smooth muscles of afferent and efferent arterioles to control glomerular filtration rate (GFR) and blood pressure.
Additional Regulatory Functions of the Nephron
Three additional functions of the nephron are important to discuss:
- Erythropoietin production : When the partial pressure of dissolved oxygen in the blood (pO 2 ) is decreased, erythropoietin (EPO), a hormone produced by the peritubular cells in the renal cortex, is released. The EPO stimulates the production of red blood cells by the bone marrow (Schoener & Borger, 2022).
- Gluconeogenesis : The proximal tubules of the kidney are responsible for producing 40% of the glucose needed to maintain homeostatic glucose levels. The kidney increases glucose production in response to acidosis or when stimulated by stress hormones such as cortisol (Legouis et al., 2022).
- Vitamin D 3 conversion : Vitamin D from the diet and skin absorption is converted to 25-hydroxyvitamin D (25[OH]D) in the liver and then to 1,25-dihydroxyvitamin D, the active form of the vitamin, in the kidneys. Deficient vitamin D levels are associated with altered calcium balance and bone metabolism (Kim et al., 2021).
Glomerular Filtration
Glomerular filtration is the initial step in removing waste and concentrating the urine. The filtration membrane consists of three layers: the fenestrated glomerular capillary endothelial cells, the basal lumina, and the podocytes in the visceral layer of the glomerular or Bowman’s capsule. The first layer, the openings in the fenestrated glomerular capillary endothelial cells, allows the movement of molecules up to 100 nanometers in size, which means that platelets and blood cells are not filtered from the capillaries. The basal lumina is a thin layer of tissue between the glomerular endothelial cells and the podocytes. The collagen fibers from this layer generate a mesh that creates a second barrier. This collagen mesh blocks most plasma proteins by size and also blocks negatively charged proteins regardless of size. The filtration slits or pores formed by the podocytes provide the third barrier to filtration. These openings block plasma proteins from entering the filtrate. The filtrate consists of the fluids and solutes that progress through the filtration membrane. Substances that are commonly included in the filtrate include water, glucose, electrolytes, amino acids, and smaller proteins.
The Glomerular Filtration Rate (GFR)
The kidneys filter approximately 200 liters of fluid every day (Ogobuiro & Tuma, 2022). The normal glomerular filtration rate is 120–125 mL per minute (Ogobuiro & Tuma, 2022). This value is influenced by the client’s age, weight, and muscle mass. Filtration is increased by the glomerular capillary hydrostatic pressure and Bowman’s capsule oncotic pressure, and filtration is opposed by the glomerular oncotic pressure and the Bowman’s capsule hydrostatic pressure. Note that the oncotic pressure in the Bowman’s capsule is normally near zero because proteins and cells do not enter the capsule.
Three elements determine the critical net filtration pressure required for homeostatic glomerular filtration:
- Glomerular capillary hydrostatic pressure : The pressure in the glomerular capillary bed is 55 mm Hg and is the major filtration force (Ogobuiro & Tuma, 2022).
- Glomerular capillary oncotic pressure : This pressure is determined by the oncotic pressure of the blood in the glomerulus. This pressure is higher than the average oncotic pressure because water is quickly filtered from the blood. This pressure opposes filtration because the increased osmotic pressure can pull the water from the filtrate into the arterioles.
- Bowman’s capsule hydrostatic pressure : The hydrostatic pressure is determined by the amount of fluid in the capsular space. The amount of fluid is determined by the rate at which the filtrate enters the capsular space, which is greater than the rate at which the filtrate empties into the lumen of the tubule. This pressure opposes filtration.
Autoregulation of the Glomerular Filtration Rate
Autoregulation of the GFR maintains homeostatic renal function when the systemic blood pressure (BP) is abnormally increased or decreased. There are two intrinsic or local renal responses that respond to these alterations: the myogenic response and tubuloglomerular feedback.
Myogenic Response
The myogenic response maintains the renal blood flow at homeostatic levels in response to the stretch of the vascular smooth muscles of the afferent arterioles. When the systemic BP is elevated, the afferent arterioles are stretched and the GFR is increased. The kidney responds by constricting the afferent arterioles, which decreases the blood being filtered, returning the GFR to normal. When the systemic BP is decreased, the afferent arterioles are stretched less than normal and the GFR declines. The kidney responds by dilating the smooth muscles of the arterioles, which increases the renal blood flow and the GFR.
The myogenic response rapidly addresses alterations in the GFR; however, the response only occurs when the systolic blood pressure is 80–180 mm Hg. When the systolic BP is above 180 mm Hg, additional smooth muscle constriction is not possible. Conversely, when the pressure falls below 80 mm Hg, additional dilation of the arterioles will not increase the GFR.
Tubuloglomerular Feedback
The macula densa cells located around the distal tubule react to the changes in the glomerular filtration rate. When the filtration rate increases the amount of sodium and chloride, the ultrafiltrate also increases, which results in additional absorption of these ions by the macula densa cells. The cells respond to these changes by releasing ATP (adenosine triphosphate) from the basolateral membrane, which directly or indirectly constricts the afferent arterioles. The ATP directly constricts the arterioles, and ATP converted to adenosine indirectly constricts the afferent arterioles. This constriction decreases renal blood flow and returns the GFR to normal. When the filtration rate decreases, less sodium and chloride are delivered to the macula densa cells, which triggers dilation of the afferent arterioles and constriction of the efferent arterioles. This results in increased hydrostatic pressure that returns the GFR to normal. In addition to autoregulation, the tubuloglomerular feedback mechanism also contributes to renal homeostasis by regulating sodium secretion and renin release.
Hormonal Actions Affecting the Glomerular Filtration Rate
Several hormones regulate kidney function by stimulating or inhibiting renal blood flow. Two of these processes are described below.
Renin-Angiotensin-Aldosterone System (RAAS)
The primary function of the RAAS is to control systemic blood pressure and fluid balance; however, the system also contributes to homeostasis of the glomerular filtration rate and tubular reabsorption of electrolytes. Three conditions can trigger the system: sympathetic nerve stimulation, decreased glomerular hydrostatic pressure, and feedback from the macula densa cells in the glomerular feedback system.
In response to decreased renal blood flow caused by decreased systemic blood pressure, the juxtaglomerular cells in the afferent arteriole trigger the release of renin. This action results in the conversion of angiotensinogen from the liver to angiotensin I. In the lung, the angiotensin-converting enzyme converts angiotensin I, activating angiotensin II. Angiotensin II constricts systemic and renal efferent arterioles; prompts reabsorption of sodium, chloride, and water by osmosis from the proximal tubule; releases aldosterone, which further increases sodium ion and water reabsorption in the distal tubule; and stimulates the thirst response.
Atrial Natriuretic Peptides
The atrial natriuretic peptide s (ANPs) are released from the atria in response to increased atrial blood volume. The primary purpose of the ANPs is regulation of the systemic blood pressure; however, one part of that process involves increasing the GFR. In the glomerulus, the ANPs dilate the afferent arterioles and constrict the efferent arterioles. This increases the glomerular hydrostatic pressure, resulting in increased GFR, which increases the urinary output and decreases the blood pressure.
Sympathetic Nervous System Effect on the GFR
Stimulation of the sympathetic nervous system regulates blood pressure by constricting systemic blood vessels, including the afferent arterioles. The effect of this stimulation on the GFR varies according to the level of sympathetic response. When the sympathetic stimulation is low due to mild exercise, the juxtaglomerular cells release a weaker form of angiotensin II, which increases the GFR and the systemic BP. Conversely, when sympathetic stimulation is high due to blood loss or strenuous physical activity, large amounts of angiotensin II are secreted, constricting both the afferent and efferent arterioles, which decreases the GFR. This response protects the circulating blood volume.
Link to Learning
Tubular Reabsorption
This article from Khan Academy discusses the process of tubular reabsorption in the nephron.
Tubular Reabsorption
The tubules are responsible for selective reabsorption of electrolytes, nutrients, and water from the filtrate and the return of these substances to the circulating blood volume. These mechanisms are responsible for moving water and substances from one area to another:
- Active transport: Active transport uses energy, ATP, to move a substance across a membrane from an area of low concentration to an area of higher concentration of that substance.
- Diffusion: Simple diffusion follows the concentration gradient and moves substances across a membrane from an area of higher concentration to an area of lower concentration. This process does not require energy expenditure.
- Facilitated diffusion: This process also moves substances along a concentration gradient; however, membrane receptors or channel proteins are required for the transfer (Ogobuiro & Tuma, 2022).
- Secondary transport systems: Secondary transport systems, including symport and antiport structures, each require energy. Symport structures move two or more substances in the same direction simultaneously. Antiport structures move two or more substances across the cell membrane in different directions.
The Proximal Tubule
Approximately 65% of the filtrate is reabsorbed in the proximal tubule. The active transport of elements by the sodium/potassium pumps consumes 6%–8% of the daily ATP expenditure. The microvilli lining the tubule facilitate rapid reabsorption of the following elements to support homeostasis (Zhang & Mahler, 2021):
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Proximal tubular reabsorption
- Glucose: Secondary active transport with sodium
- Proteins and amino acids: Secondary active transport with sodium
- Sodium: Two-thirds actively reabsorbed
- Chloride: Symport reabsorption with sodium, diffusion
- Vitamins and lactate: Reabsorbed
- Bicarbonate ions: Symport reabsorption with sodium
- Water: Two-thirds reabsorbed osmotically
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Loop of Henle reabsorption
- Water: Reabsorbed by osmosis
- Sodium: Reabsorbed by active transport
- Chloride: Reabsorbed by diffusion
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Distal convoluted tubule and collecting duct reabsorption
- Water: Reabsorbed by osmosis
- Sodium: Reabsorbed by active transport
- Chloride: By symport and diffusion
- Bicarbonate: By antiport with chloride
- Calcium: Reabsorbed
- Potassium and hydrogen: Directed by hormones
Concentration of the Urine
The cells in the distal convoluted tubule are responsible for the final concentration of water and solutes in the urine. The remaining water, sodium, chloride, calcium, and bicarbonate ions are reabsorbed as noted above. The cells are hormonally controlled by aldosterone, antidiuretic hormone (ADH), and ANPs. Aldosterone, released by the adrenal cortex, increases cellular permeability to sodium and increases the number of sodium and potassium pumps, which increases sodium reabsorption from the filtrate. ADH is released from the posterior pituitary gland and facilitates water reabsorption by opening the aquaporins in the tubular cells. These cells are impermeable to water when ADH is absent, resulting in large volumes of water in the urine. The ANPs inhibit the action of aldosterone and ADH, resulting in water retention and sodium absorption (Gewin, 2021).
Tubular Secretion
Tubular secretion is the movement of substances from the peritubular vessels into the tubular lumen to be excreted in the urine. The substances either are moved by passive diffusion from the peritubular capillaries into the interstitial space or are transported across the epithelial lumen of the nephron by active transport requiring ATPase. The proximal tubules secrete nitrogenous waste products such as urea, ammonia, and creatinine; excess hydrogen ions; and toxic substances including many protein-bound drugs that do not cross the glomerular basement membrane. The distal tubules secrete potassium and hydrogen ions in response to the hormonal control noted previously.
Common Conditions Affecting Kidney Function
Kidney function is affected by systemic disease, as discussed in the following section; however, several intrinsic/intrarenal conditions can affect renal homeostasis:
- Congenital abnormalities: These are alterations in anatomy or physiology that are present at birth. With renal agenesis and renal hypoplasia, the kidneys fail to develop in utero and the infant is born without kidneys (renal agenesis) or with only one kidney (renal hypoplasia). Renal agenesis is incompatible with extrauterine life, and the infant is often stillborn. The infant can survive with a single kidney; however, additional congenital abnormalities usually threaten the infant’s survival.
- Genetic disorders: Multiple forms of polycystic kidney disease can present in childhood or adulthood. These fluid-filled cysts interfere with urine formation and increase the risk of infection and hemorrhage. The disease course is complicated by hypertension, progressive loss of kidney function, and pain. Additional renal conditions, such as renal calculi, are also common in this client population.
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Neoplasms:
General risk factors for renal neoplasms are similar to other types of cancer: smoking, obesity, hypertension, history of renal dialysis or transplant, and exposure to environmental toxins.
- Wilms tumor/nephroblastoma : Presents in childhood with the onset of hypertension and kidney enlargement. It is the most common renal cancer in children and has a 90% five-year survival rate.
- Acute and chronic pyelonephritis (infection): The renal system has multiple protective mechanisms against infection; however, the most common infections ascend from the ureters, bladder, and urethra. The usual causative agent is Escherichia coli. Infections associated with indwelling urinary catheters are common in hospitalized clients, and these infections can progress to chronic renal failure in susceptible clients.
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Glomerulopathies
:
Glomerulopathies are disorders of the glomerular capillaries. These disorders can be due to systemic, autoimmune, or intrinsic renal alterations. Common manifestations include proteinuria, decreased GFR, hypertension, and edema. These disorders are progressive and commonly result in end-stage renal disease (ESRD).
- Nephrotic syndrome : A disorder associated with massive proteinuria, edema, and hypertension. It commonly progresses to ESRD.
- Renal calculi : Also called nephrolithiasis, urolithiasis, or kidney stones; are commonly composed of calcium crystals. Risk factors for stone formation include hypertension, red meat ingestion, obesity, family history of nephrolithiasis, prolonged immobility, vesicoureteral reflux, and hyperparathyroidism. Stones may be asymptomatic and excreted without further intervention; however, large stones can move from the kidney pelvis to the ureteral junction or further in the ureter, causing obstruction and pain ( renal colic ). Lithotripsy or endoscopy may be necessary to remove the obstruction. Preventive measures include maintaining oral fluid intake at 64–96 fluid ounces per day (or approximately 2–3 liters), avoiding additional calcium intake, and limiting dietary sodium and protein (National Kidney Foundation, 2019). Clients with recurrent stone formation require chemical analysis of the stones to address dietary restrictions.