Chapter Review

The kidney glomerulus filters blood mainly based on particle size to produce a filtrate lacking cells or large proteins. Most of the ions and molecules in the filtrate are needed by the body and must be reabsorbed farther down the nephron tubules, resulting in the formation of urine. Urine characteristics change depending on water intake, exercise, environmental temperature, and nutrient intake. Urinalysis analyzes characteristics of the urine and is used to diagnose diseases. A minimum of 400 to 500 mL urine must be produced daily to rid the body of wastes. Excessive quantities of urine may indicate diabetes insipidus or diabetes mellitus. The pH range of urine is 4.5 to 8.0, and is affected by diet. Osmolarity ranges from 50 to 1200 milliosmoles, and is a reflection of the amount of water being recovered or lost by renal nephrons.

The urethra is the only urinary structure that differs significantly between males and females. This is due to the dual role of the male urethra in transporting both urine and semen. The urethra arises from the trigone area at the base of the bladder. Urination is controlled by an involuntary internal sphincter of smooth muscle and a voluntary external sphincter of skeletal muscle. The shorter female urethra contributes to the higher incidence of bladder infections in females. The male urethra receives secretions from the prostate gland, Cowper’s gland, and seminal vesicles as well as sperm. The bladder is largely retroperitoneal and can hold up to 500–600 mL urine. Micturition is the process of voiding the urine and involves both involuntary and voluntary actions. Voluntary control of micturition requires a mature and intact sacral micturition center. It also requires an intact spinal cord. Loss of control of micturition is called incontinence and results in voiding when the bladder contains about 250 mL urine. The ureters are retroperitoneal and lead from the renal pelvis of the kidney to the trigone area at the base of the bladder. A thick muscular wall consisting of longitudinal and circular smooth muscle helps move urine toward the bladder by way of peristaltic contractions.

As noted previously, the structure of the kidney is divided into two principle regions—the peripheral rim of cortex and the central medulla. The two kidneys receive about 25 percent of cardiac output. They are protected in the retroperitoneal space by the renal fat pad and overlying ribs and muscle. Ureters, blood vessels, lymph vessels, and nerves enter and leave at the renal hilum. The renal arteries arise directly from the aorta, and the renal veins drain directly into the inferior vena cava. Kidney function is derived from the actions of about 1.3 million nephrons per kidney; these are the “functional units.” A capillary bed, the glomerulus, filters blood and the filtrate is captured by Bowman’s capsule. A portal system is formed when the blood flows through a second capillary bed surrounding the proximal and distal convoluted tubules and the loop of Henle. Most water and solutes are recovered by this second capillary bed. This filtrate is processed and finally gathered by collecting ducts that drain into the minor calyces, which merge to form major calyces; the filtrate then proceeds to the renal pelvis and finally the ureters.

The functional unit of the kidney, the nephron, consists of the renal corpuscle, PCT, loop of Henle, and DCT. Cortical nephrons have short loops of Henle, whereas juxtamedullary nephrons have long loops of Henle extending into the medulla. About 15 percent of nephrons are juxtamedullary. The glomerulus is a capillary bed that filters blood principally based on particle size. The filtrate is captured by Bowman’s capsule and directed to the PCT. A filtration membrane is formed by the fused basement membranes of the podocytes and the capillary endothelial cells that they embrace. Contractile mesangial cells further perform a role in regulating the rate at which the blood is filtered. Specialized cells in the JGA produce paracrine signals to regulate blood flow and filtration rates of the glomerulus. Other JGA cells produce the enzyme renin, which plays a central role in blood pressure regulation. The filtrate enters the PCT where absorption and secretion of several substances occur. The descending and ascending limbs of the loop of Henle consist of thick and thin segments. Absorption and secretion continue in the DCT but to a lesser extent than in the PCT. Each collecting duct collects forming urine from several nephrons and responds to the posterior pituitary hormone ADH by inserting aquaporin water channels into the cell membrane to fine tune water recovery.

The entire volume of the blood is filtered through the kidneys about 300 times per day, and 99 percent of the water filtered is recovered. The GFR is influenced by hydrostatic pressure and colloid osmotic pressure. Under normal circumstances, hydrostatic pressure is significantly greater and filtration occurs. The hydrostatic pressure of the glomerulus depends on systemic blood pressure, autoregulatory mechanisms, sympathetic nervous activity, and paracrine hormones. The kidney can function normally under a wide range of blood pressures due to the autoregulatory nature of smooth muscle.

The kidney regulates water recovery and blood pressure by producing the enzyme renin. It is renin that starts a series of reactions, leading to the production of the vasoconstrictor angiotensin II and the salt-retaining steroid aldosterone. Water recovery is also powerfully and directly influenced by the hormone ADH. Even so, it only influences the last 10 percent of water available for recovery after filtration at the glomerulus, because 90 percent of water is recovered before reaching the collecting ducts. Depending on the body’s fluid status at any given time, the collecting ducts can recover none or almost all of the water reaching them.

Mechanisms of solute recovery include active transport, simple diffusion, and facilitated diffusion. Most filtered substances are reabsorbed. Urea, NH₃, creatinine, and some drugs are filtered or secreted as wastes. H⁺ and HCO₃^– are secreted or reabsorbed as needed to maintain acid–base balance. Movement of water from the glomerulus is primarily due to pressure, whereas that of peritubular capillaries and vasa recta is due to osmolarity and concentration gradients. The PCT is the most metabolically active part of the nephron and uses a wide array of protein micromachines to maintain homeostasis—symporters, antiporters, and ATPase active transporters—in conjunction with diffusion, both simple and facilitated. Almost 100 percent of glucose, amino acids, and vitamins are recovered in the PCT. Bicarbonate (HCO₃^–) is recovered using the same enzyme, carbonic anhydrase (CA), found in erythrocytes. The recovery of solutes creates an osmotic gradient to promote the recovery of water. The descending loop of the juxtaglomerular nephrons reaches an osmolarity of up to 1200 mOsmol/kg, promoting the recovery of water. The ascending loop is impervious to water but actively recovers Na⁺, reducing filtrate osmolarity to 50–100 mOsmol/kg. The descending and ascending loop and vasa recta form a countercurrent multiplier system to increase Na⁺ concentration in the kidney medulla. The collecting ducts actively pump urea into the medulla, further contributing to the high osmotic environment. The vasa recta recover the solute and water in the medulla, returning them to the circulation. Nearly 90 percent of water is recovered before the forming urine reaches the DCT, which will recover another 10 percent. Calcium recovery in the DCT is influenced by PTH and active vitamin D. In the collecting ducts, ADH stimulates aquaporin channel insertion to increase water recovery and thereby regulate osmolarity of the blood. Aldosterone stimulates Na⁺ recovery by the collecting duct.

The kidneys are innervated by sympathetic nerves of the autonomic nervous system. Sympathetic nervous activity decreases blood flow to the kidney, making more blood available to other areas of the body during times of stress. The arteriolar myogenic mechanism maintains a steady blood flow by causing arteriolar smooth muscle to contract when blood pressure increases and causing it to relax when blood pressure decreases. Tubuloglomerular feedback involves paracrine signaling at the JGA to cause vasoconstriction or vasodilation to maintain a steady rate of blood flow.

Endocrine hormones act from a distance and paracrine hormones act locally. The renal enzyme renin converts angiotensinogen into angiotensin I. The lung enzyme, ACE, converts angiotensin I into active angiotensin II. Angiotensin II is an active vasoconstrictor that increases blood pressure. Angiotensin II also stimulates aldosterone release from the adrenal cortex, causing the collecting duct to retain Na⁺, which promotes water retention and a longer-term rise in blood pressure. ADH promotes water recovery by the collecting ducts by stimulating the insertion of aquaporin water channels into cell membranes. Endothelins are elevated in cases of diabetic kidney disease, increasing Na⁺ retention and decreasing GFR. Natriuretic hormones, released primarily from the atria of the heart in response to stretching of the atrial walls, stimulate Na⁺ excretion and thereby decrease blood pressure. PTH stimulates the final step in the formation of active vitamin D3 and reduces phosphate reabsorption, resulting in higher circulating Ca⁺⁺ levels.

The major hormones regulating body fluids are ADH, aldosterone and ANH. Progesterone is similar in structure to aldosterone and can bind to and weakly stimulate aldosterone receptors, providing a similar but diminished response. Blood pressure is a reflection of blood volume and is monitored by baroreceptors in the aortic arch and carotid sinuses. When blood pressure increases, more action potentials are sent to the central nervous system, resulting in greater vasodilation, greater GFR, and more water lost in the urine. ANH is released by the cardiomyocytes when blood pressure increases, causing Na⁺ and water loss. ADH at high levels causes vasoconstriction in addition to its action on the collecting ducts to recover more water. Diuretics increase urine volume. Mechanisms for controlling Na⁺ concentration in the blood include the renin–angiotensin–aldosterone system and ADH. When Na⁺ is retained, K⁺ is excreted; when Na⁺ is lost, K⁺ is retained. When circulating Ca⁺⁺ decreases, PTH stimulates the reabsorption of Ca⁺⁺ and inhibits reabsorption of ${\text{HPO}}_4^{2-}$. pH is regulated through buffers, expiration of CO₂, and excretion of acid or base by the kidneys. The breakdown of amino acids produces ammonia. Most ammonia is converted into less-toxic urea in the liver and excreted in the urine. Regulation of drugs is by glomerular filtration, tubular secretion, and tubular reabsorption.

The effects of failure of parts of the urinary system may range from inconvenient (incontinence) to fatal (loss of filtration and many others). The kidneys catalyze the final reaction in the synthesis of active vitamin D that in turn helps regulate Ca⁺⁺. The kidney hormone EPO stimulates erythrocyte development and promotes adequate O₂ transport. The kidneys help regulate blood pressure through Na⁺ and water retention and loss. The kidneys work with the adrenal cortex, lungs, and liver in the renin–angiotensin–aldosterone system to regulate blood pressure. They regulate osmolarity of the blood by regulating both solutes and water. Three electrolytes are more closely regulated than others: Na⁺, Ca⁺⁺, and K⁺. The kidneys share pH regulation with the lungs and plasma buffers, so that proteins can preserve their three-dimensional conformation and thus their function.