Chapter 21
Filtration, Urine Formation, and Fluid Regulation
After reading this chapter you will be able to:
• Describe the anatomy of the nephron
• Differentiate between the terms filtrate and urine and reabsorption and secretion
• Explain how glomerular filtration rate and urine output are related
• Explain how autoregulation of the glomerular filtration rate and renal blood flow are related
• Explain how the nephron processes the tubular filtrate to excrete a concentrated or dilute urine
• Describe why it is important that the kidney’s countercurrent multiplier mechanism maintains a high osmotic pressure deep in the medulla
• Explain how aldosterone, natriuretic peptides, and antidiuretic hormone influence extracellular fluid volume
• Describe the mechanisms whereby various classes of diuretic drugs work
Functional Anatomy of the Kidneys
Gross Anatomy
The kidneys are paired, bean-shaped organs that are located on the posterior abdominal wall behind the peritoneal membrane; hence, the kidneys are called retroperitoneal organs (Figure 21-1, A). A fat pad surrounding the renal capsule protects the kidneys from mechanical shock (Figure 21-1, B). Blood vessels and nerves enter the medial concave border of the kidney at the hilum (Figure 21-2). The kidney contains an outer cortex and inner medulla (see Figure 21-2). A ureter from each kidney carries urine to the bladder.
Nephron Anatomy
The nephron is the basic functional unit of the kidney. This structure is responsible for filtering the blood plasma, eliminating only the unwanted substances, and returning the remainder to the circulation. These unwanted substances include urea (a by-product of amino acid metabolism), creatinine (from muscle cells), uric acids (from nucleic acids), bilirubin (from hemoglobin breakdown), and metabolites of assorted hormones; in addition, the kidneys eliminate various toxins and foreign substances, whether produced by the body or ingested.1
Each kidney contains between 0.4 million and 1.2 million nephrons.2 Because the kidney cannot regenerate new nephrons, normal aging and disease reduce their number such that a normal 80-year-old individual has about 40% fewer functioning nephrons than he or she did at age 40.1 The nephron is composed of the following structures, listed in the order in which fluid flows through them: (1) Bowman’s capsule, (2) proximal convoluted tubule, (3) loop of Henle, (4) distal convoluted tubule, and (5) collecting duct (Figure 21-3).
Bowman’s Capsule
The beginning of the proximal tubule is called Bowman’s capsule (a hollow sphere composed of epithelium, deeply indented to form a double-walled pouch). A small afferent arteriole enters this spherical pouch and branches diffusely to form a dense tuft of capillaries called the glomerulus. The glomerulus is in intimate contact with the inner capsular wall. Glomerular capillaries contain thousands of minute pores, or fenestrations, rendering them highly permeable to all plasma constituents except large protein molecules. Blood leaves the glomerulus by way of the efferent arteriole, formed by the convergence of the glomerular capillaries. The glomerulus and its surrounding double-walled capsule are collectively called the renal corpuscle (see Figure 21-3). This entire structure is located in the renal cortex. The epithelial layer forming the inner pouch of Bowman’s capsule (the visceral layer) and the fenestrated glomerular capillary endothelium form the glomerular filtration membrane. The first step of urine formation occurs when glomerular hydrostatic pressure (about 60 mm Hg)1 forces plasma through the glomerular filtration membrane. The resulting filtrate enters Bowman’s capsule.
Proximal Convoluted Tubule
The tubule draining the filtrate from Bowman’s capsule follows a curved, twisted path and is called the proximal convoluted tubule. Its terminal end approaches the medullary border, where it forms the beginning of the loop of Henle. (It is called the proximal tubule because it is located before the loop of Henle.) The tubule’s epithelium has a brushlike border of numerous fine microvilli facing its luminal side (see Figure 21-3). These microvilli greatly increase the luminal wall surface area.
Loop of Henle
The loop of Henle consists of a straight descending limb, a sharp hairpin turn, and an ascending limb (see Figure 21-3). About 70% to 80% of the glomeruli are located in the outer cortex (cortical nephrons) and have short loops of Henle that never reach the medulla.1 The remaining nephrons located deeper in the cortex near the medullary border are called juxtamedullary nephrons. These nephrons have long loops dipping deep into the medulla.
Renal Vasculature
Because the kidneys must eventually filter all the blood plasma, they receive an extremely high blood flow relative to their mass (about 20% of the cardiac output).1 Renal arteries enter the hilum and eventually subdivide to form afferent arterioles entering Bowman’s capsule (see Figure 21-3).
The kidneys have two capillary beds: the glomerulus and peritubular capillaries. The peritubular capillaries are branches of the efferent arteriole, which was formed by the convergence of the glomerular capillaries. The peritubular capillaries closely surround proximal and distal convoluted tubules. The vasa recta are a branch of the peritubular circulation that surrounds the loop of Henle (see Figure 21-3).
Because of the moderately high resistance of the efferent arteriole, the glomerular capillaries are a high-pressure bed, and the peritubular capillaries are a low-pressure bed. As a result, glomerular capillaries act as filtration vessels, and peritubular capillaries act as absorption vessels. The vasa recta receive only 1% to 2% of the renal blood flow.1 Medullary blood flow is quite sluggish, in contrast to rapid cortical blood flow.
Juxtaglomerular Apparatus
Near their glomerular entry and exit points, afferent and efferent arterioles contain cuffs of smooth muscle that control vessel diameter. At these points, the distal convoluted tubule abuts both arterioles.1 The densely packed distal tubular cells in this area are called the macula densa; the smooth muscle cuffs of the afferent and efferent arterioles are called juxtaglomerular cells. The macula densa and juxtaglomerular cells are collectively known as the juxtaglomerular apparatus (see Figure 21-3). When systemic blood pressure decreases, cells of the juxtaglomerular apparatus secrete renin, an enzyme that activates angiotensin, which ultimately leads to widespread systemic arteriole constriction.
Basic Theory of Nephron Function
The nephron accomplishes its function in the following way: First, it filters about 20% of the renal blood plasma through the glomerular membrane into the proximal tubules1; next, it reabsorbs most of the filtrate’s water and electrolytes and all of the glucose back into the peritubular capillaries. The remaining filtrate (water and waste products) stays in the tubules and is eliminated in the urine. In addition, the nephron actively secretes certain substances directly into the tubular filtrate; urine contains both filtered and secreted substances.
Formation of Glomerular Filtrate
Filtration Pressure
Filtration is the movement of water and solutes from the plasma in the glomerulus, across the glomerular membrane, and into Bowman’s capsule. Filtration occurs because of a pressure gradient between glomerular capillary blood and the capsular filtrate. The main factor establishing this pressure gradient is the hydrostatic pressure of the glomerular blood (Figure 21-4). This pressure is about 60 mm Hg, much higher than capillary pressures anywhere else in the body.1
