Anatomy Ch. 25- The Urinary System

parathyroid hormone (PTH)

acting primarily at the DCT, PTH increases the reabsorption of Ca2+

three layers of tissue surrounding kidneys

from superficial to deep, these are: -the renal fascia, an outer layer of dense fibrous connective tissue that anchors the kidney and the adrenal gland to surrounding structures -the perirenal fat capsule, a fatty mass that surrounds the kidney and cushions it from blows -the fibrous capsule, a transparent capsule that prevents infections in surrounding regions from spreading to the kidney

three of the most common congenital abnormalities of the urinary system

horseshoe kidney, hypospadias, and polycystic kidney

urinary system

includes: -urine-forming kidneys -ureters-- paired tubes that transport urine from the kidneys to the urinary bladder -urethra-- a tube that carries urine from the bladder to the body exterior

male urethra

is approximately 20 cm (8 inches) long and has three regions: -the prostatic urethra, about 1.5 cm (1 inch) long, runs within the prostate -the intermediate part of the urethra (or membranous urethra), which runs through the urogenital diaphragm, extends about 2 cm from the prostate to the beginning of the penis -the spongy urethra, about 15 cm long, passes through the penis and opens at its tip via the external urethral orifice -has a double function: it carries semen as well as urine out of the body. we discuss its reproductive function in ch 27

tubular reabsorption of nutrients, water, and ions

the reabsorption of Na+ by primary active transport provides the energy and the means for reabsorbing almost every other substance, including water

renal failure

-GFR < 15 ml/min -filtrate formation decreases or stops completely -the clinical syndrome associated with it is called uremia (urine in the blood) and includes fatigue, anorexia, nausea, mental changes, and muscle cramps

regulation of glomerular filtration

-GFR is tightly regulated to serve two crucial and sometimes opposing needs -the kidneys need a relatively constant GFR to make filtrate and do their job of maintaining extracellular homeostasis -on the other hand, the body as a whole needs a constant blood pressure, and this is closely tied to GFR in the following way: assuming nothing else changes, an increase in GFR increases urine output, which reduces blood volume and blood pressure. the opposite holds true for a decrease in GFR -two types of controls serve these two different needs -intrinsic controls (renal auto regulation) act locally within the kidney to maintain GFR, while extrinsic controls by the nervous and endocrine systems maintain blood pressure -in extreme changes of blood pressure (mean arterial pressure less than 80 or greater than 180 mm Hg), extrinsic controls take precedence over intrinsic controls in an effort to prevent damage to the brain and other crucial organs -GFR can be controlled by changing a single variable-- glomerular hydrostatic pressure -all major control mechanisms act primarily to change this one variable -if the glomerular hydrostatic pressure rises, NFP rises and so does the GFR -if the glomerular hydrostatic pressure falls by as little as 18%, GFR drops to zero -clearly hydrostatic pressure in the glomerulus must be tightly controlled

sodium transport across the basolateral membrane

-Na+ is actively transported out of the tubule cell by primary active transport-- a Na+-K+ ATPase pump in the basolateral membrane -from there, the bulk flow of water sweeps Na+ into adjacent peritubular capillaries -this bulk flow of water and solutes into the peritubular capillaries is rapid because the blood there has low hydrostatic pressure and high osmotic pressure (remember, most proteins remain in the blood instead of filtering out into the tubule)`

internal gross anatomy of kidney

-a frontal section through a kidney reveals three distinct regions: a cortex, medulla, and pelvis -the most superficial region, the renal cortex, is light-colored and has a granular appearance -deep to the cortex is the darker, reddish-brown renal medulla, which exhibits cone-shaped tissue masses called medullary, or renal, pyramids -the broad base of each pyramid faces toward the cortex, and its apex, or papilla points internally -the pyramids appear striped because they are formed almost entirely of parallel bundles of microscopic urine-collecting tubules and capillaries -the renal columns, inward extensions of cortical tissue, separate the pyramids -each pyramid and its surrounding cortical tissue constitutes one of approx eight lobes of a kidney -the renal pelvis, a funnel-shaped tube, is continuous with the ureter leaving the hilum -branching extensions of the pelvis form two or three major calyces -each major calyx subdivides to form several minor calyces, cup-shaped areas that enclose the papillae -the calyces collect urine, which drains continuously from the papillae, and empty it into the renal pelvis -the urine then flows through the renal pelvis and into the ureter, which moves it to the bladder to be stored -the walls of the calyces, pelvis, and ureter contain smooth muscle that contracts rhythmically to propel urine by peristalsis

urethra

-a thin-walled muscular tube that drains urine from the bladder and conveys it out of the body -the epithelium of its mucosal lining is mostly pseudo stratified columnar epithelium -however, near the bladder it becomes transitional epithelium, and near the external opening it changes to a protective stratified squamous epithelium -at the bladder-urethra junction, the detrusor smooth muscle thickens to form the internal urethral sphincter -this involuntary sphincter, controlled by the autonomic nervous system, keeps the urethra closed when urine is not being passed and prevents leaking between voiding -the external urethral sphincter surrounds the urethra as its passes through the urogenital diaphragm -this sphincter is formed of skeletal muscle and is voluntarily controlled -the levator ani muscle of the pelvic floor also serves as a voluntary constrictor of the urethra -the length and functions of the urethra differ in the two sexes -in females the urethra is only 3-4 cm (1.5 in) long and fibrous connective tissue binds it tightly to the anterior vaginal wall -its external opening, the external urethral orifice, its anterior to the vaginal opening and posterior to the clitoris

anuria

-abnormally low urinary output (less than 50 ml/day) -may indicate that glomerular blood pressure is too low to cause filtration -renal failure and anuria can also result from situations in which the nephrons stop functioning, including acute nephritis, transfusion reactions, and crush injuries

sodium transport across the apical membrane

-active pumping of Na+ from the tubule cells results in a strong electrochemical gradient that favors its entry at the apical face via secondary active transport (cotransport) carriers , or via facilitated diffusion through channels -this occurs because 1) the pump maintains the intracellular Na+ concentration at low levels, and 2) the K+ pumped into the tubule cells almost immediately diffuses out into the interstitial fluid via leakage channels, leaving the interior of the tubule cell with a net negative charge -because each tubule segment plays a slightly different role in reabsorption, the precise mechanism by which Na+ is reabsorbed at the apical membrane varies

micturition

-also called urination or voiding -is the act of emptying the urinary bladder -for it to occur, three things must happen simultaneously: 1) the detrusor must contract 2) the internal urethral sphincter must open 3) the external urethral sphincter must open -the detrusor and its internal urethral sphincter are composed of smooth muscle and are innervated by both the parasympathetic and sympathetic nervous systems, which have opposing actions -the external urethral sphincter, in contrast, is skeletal muscle, and therefore is innervated by the somatic nervous system -is most easily understood in infants where a spinal reflex coordinates the process -as urine accumulates, distension of the bladder activates stretch receptors via visceral afferent fibers to the sacral region of the spinal cord -visceral afferent impulses, relayed by sets of interneurons, excite parasympathetic neurons and inhibit sympathetic neurons -as a result, the detrusor contracts and the internal sphincter opens -visceral afferent impulses also decrease the firing rate of somatic efferents that normally keep the external urethral sphincter closed -this allows the sphincter to relax so urine can flow -between ages 2 and 3, descending circuits from the brain have matured enough to begin to override reflexive urination -the pons has two centers that participate in control of it -the pontine storage center inhibits _________ whereas the micturition center promotes this reflex -afferent impulses from bladder stretch receptors are relayed to the pons, as well as to higher brain centers that provide the conscious awareness of bladder fullness -lower bladder volumes primarily activate the pontine storage center, which inhibits urination by suppressing parasympathetic and enhancing sympathetic output to the bladder -when a person chooses not to void, reflex bladder contractions subside within a minute or so and urine continues to accumulate -because the external sphincter is voluntarily controlled, we can choose to keep it closed and postpone bladder emptying temporarily -after additional urine has collected, the micturition reflex occurs again and, if urination is delayed again, is damped once more -the urge to void gradually becomes greater and greater, and micturition usually occurs before urine volume exceeds 400 ml -after normal micturition only about 10 ml of urine remains in the bladder

ureters

-are slender tubes that convey urine from the kidneys to the bladder -each ureter begins at the level of L2, as a continuation of the renal pelvis -from there, it descends behind the peritoneum and runs obliquely through the posterior bladder wall -this arrangement prevents backflow of urine because any increase in bladder pressure compresses and closes the distal ends of the ureters histologically, the ureter wall has three layers. from inside out: -the mucosa contains a transitional epithelium that is continuous with the mucosae of the kidney pelvis superiorly and the bladder medially -the muscularis is composed chiefly of two smooth muscle sheets: the internal longitudinal layer and the external circular layer. an additional smooth muscle layer, the external longitudinal layer, appears in the lower third of the ureter -the adventitia covering the ureter's external surface is typical fibrous connective tissue -the ureter plays an active role in transporting urine -incoming urine distends the ureter and stimulates its muscularis to contract, propelling urine into the bladder -the strength and frequency of peristaltic waves are adjusted to the rate of urine formation -both sympathetic and parasympathetic fibers innervate each ureter, but neural control of peristalsis appears to be insignificant compared to the way ureteral smooth muscle responds to stretch

urinary tract infection (UTI)

-is a common problem, with up to 50% of women experiencing one during their lives -the location of the female urethra near the anus predisposes it to colonization by fecal bacteria -sexual activity and the use of spermicides increase the risk -in both men and women, catheterization or any condition that obstructs the normal flow of urine also predisposes an individual to acquiring a UTI

nephrons

-are the structural and functional units of the kidneys (a functional unit is the smallest physical structure capable of carrying out the function of an organ) -each kidney contains about 1 million nephrons acting in parallel to make. urine -each nephron creates a cell- and protein-free filtrate from blood -from that filtrate, it recovers chemicals the body needs while also secreting into that filtrate selected chemicals that the body needs to get rid of -nearby nephrons empty their processed filtrate into one of the thousands of collecting ducts, which convey this fluid, now called urine, into the renal pelvis -each nephron consists of a renal corpuscle and a renal tubule -all of the renal corpuscles are located in the renal cortex, while the renal tubules begin in the cortex and then pass into the medulla before returning to the cortex

passive tubular reabsorption of solutes

-as water leaves the tubules, the concentration of solutes in the filtrate increases, and, if able, they too follow their concentration gradients into the peritubular capillaries -this phenomenon--solutes following solvent--explains the passive reabsorption of a number of solutes present in the filtrate, such as lipid-soluble substances, certain ions, and some urea -it also explains in part why lipid-soluble drugs and environmental pollutants are difficult to excrete: since lipid-soluble compounds can generally pass through membranes, they will follow their concentration gradients and be reabsorbed, even if this is not "desirable" -as Na+ ions move through the tubule cells into the peritubular capillary blood, they also establish an electrical gradient that favors passive reabsorption of anions (primarily Cl-) to restore electrical neutrality in the filtrate and plasma

tubuloglomerular feedback mechanism

-autoregulation by the flow-dependent tubuloglomerular feedback mechanism is "directed" by the macula densa cells of the juxtaglomerular complex -these cells, located in the walls of the ascending limb of the nephron loop, respond to filtrate NaCl concentration (which varies directly with filtrate flow rate) -when GFR increases, there is not enough time for reabsorption and the concentration of NaCl in the filtrate remains high -the macula densa cells respond to high levels of NaCl in filtrate by releasing vasoconstrictor chemicals (ATP and others) that cause intense constriction of the afferent arteriole, reducing blood flow into the glomerulus -this drop in blood flow decreases the NFP and GFR, slowing the flow of filtrate and allowing more time for filtrate processing (NaCl reabsorption) -in contrast, the low NaCl concentration of slowly flowing filtrate inhibits ATP release from the macula densa cells, causing vasodilation of the afferent arterioles. this allows more blood to flow into the glomerulus, thus increasing NFP and GFR -autoregulatory mechanisms maintain a relatively constant GFR over an arterial pressure range from about 80 to 180 mm Hg -consequently, normal day-to-day changes in our blood pressure do not cause large changes in water and solute excretion -however, the intrinsic controls cannot handle extremely low systemic blood pressure, such as might result from serious hemorrhage (hypovelmic shocks) -once the mean arterial pressure drops below 80 mm Hg, autoregulation ceases and extrinsic controls take over

developmental aspects of the urinary system (continued)

-because its bladder is very small and its kidneys are less able to concentrate urine for the first two months, a newborn baby voids 5 to 40 times daily, depending on fluid intake -by 2 months, infants void approximately 400 ml/day, and the amount steadily increases until adolescence, when adult urine output (about 1500 ml/day) is achieved -incontinence is normal in infants because their nervous systems have not matured enough to control the external urethral sphincter -reflex voiding occurs each time a baby's bladder fills enough to activate the stretch receptors -control of the voluntary urethras sphincter goes hand in hand with nervous system development -by 15 months, most toddlers know when they have voided -by 24 months, some children are ready to begin toilet training -daytime control usually is achieved first. it is unrealistic to expect complete nighttime control before age 4 -from childhood through late middle age, most urinary system problems are infectious conditions -escherichia coli bacteria are normal residents of the digestive tract and generally cause no problems there, but these bacteria account for 80% of all urinary tract infections -sexually transmitted infections can also inflame the urinary tract and clog some of its ducts -childhood streptococcal infections such as strep throat and scarlet fever, if not treated promptly, may cause long-term inflammatory renal damage -only about 3% of elderly people have histologically normal kidneys, and kidney function declines with advancing age -the kidneys shrink as the nephrons decrease in size and number, and the tubule cells become less efficient -by age 80, the GFR of healthy seniors is only about 70% that of young adults -diabetics are particularly at risk for renal disease, accounting for almost half of new cases -loss of bladder tone with age can cause an annoying increase in frequency of micturition -nocturia, the need to get up during the night to urinate, plagues almost two-thirds of this population -many people eventually experience incontinence, which can usually be treated with exercise, medications, or surgery

hematuria

-blood in the urine -the upper parts of both kidneys are protected by the thoracic cage, and the perirenal fat provides cushioning -however, the lower parts of the kidneys, especially the right kidney, are susceptible to blunt trauma such as from falls, motor vehicle accidents, or contact sports injuries -the renal artery is especially vulnerable to injury from rapid deceleration during car crashes, and may be lacerated (torn) or develop a thrombosis (blood clot) -the presence of _______ is an important sign of such renal trauma -occasionally, surgical treatment is required

intrinsic controls: renal auto regulation

-by adjusting its own resistance to blood flow, a process called renal auto regulation, the kidney can maintain a nearly constant GFR despite fluctuations in systemic arterial blood pressure -renal auto regulation uses two different mechanisms: 1) a myogenic mechanism 2) a tubuloglomerular feedback mechanism

diuretics

-chemicals that enhance urinary output -alcohol encourages diuresis by inhibiting release of ADH -other diuretics increase urine flow by inhibiting Na+ reabsorption and the obligatory water reabsorption that normally follows -examples include many drugs prescribed for hypertension or the edema of congestive heart failure -most diuretics inhibit Na+-associated symporters -"loop diuretics" are powerful because they inhibit formation of the medullary gradient by acting at the ascending limb of the nephron loop -thiazides are less potent and act at the DCT -an osmotic diuretic is a substance that is not reabsorbed and that carries water out with it

peritubular capillaries

-cling closely to adjacent renal tubules and empty into nearby venules -because they arise from the efferent arterioles (which have high resistance), they only experience low pressure -as a result, these low-pressure, porous capillaries readily absorb solutes and water from the tubule cells as these substances are reclaimed from the filtrate -renal tubules are closely packed together, so the peritubular capillaries of each nephron absorb substances from several adjacent nephrons

distal convoluted tubule (DCT)

-the epithelial cells of the _____, like those of the PCT, are cuboidal and confined to the cortex, but they are thinner and almost entirely lack microvilli

hemodialysis

-current treatment options for uremia are hemodialysis or a kidney transplant -________ uses an "artificial kidney" apparatus, passing the patient's blood through a membrane tubing that is permeable only to selected substances -the tubing is immersed in a solution that differs slightly from normal cleansed plasma -as blood circulates through the tubing, substances such as nitrogenous wastes and K+ present in the blood (but not in the bath) diffuse out of the blood into the surrounding solution -meanwhile, substances to be added to the blood, mainly buffers for H+ (and glucose for malnourished patients) move from the bathing solution into the blood -in this way, it retains or adds needed substances, while removing wastes and excess ions

chronic renal disease

-defined as a GFR of less than 60 ml/ min for at least three months -often develops silently over many years -filtrate formation decreases gradually, nitrogenous wastes accumulate in the blood, and blood pH drifts toward the acidic range -the leading cause is diabetes mellitus (44% of new cases), with hypertension a close second -other causes include repeated kidney infections, physical trauma, and heavy metal poisoning

countercurrent multiplier

-depends on actively transporting solutes out of the ascending limb ("start" of the positive feedback cycle) -although the two limbs of the nephron loop are not in direct contact with each other, they are close enough to influence each other's exchanges with the interstitial fluid they share -the more NaCl the ascending limb extrudes, the more water diffuses out of the descending limb and the saltier the filtrate in the descending limb becomes -the ascending limb then uses the increasingly "salty" filtrate left behind in the descending limb to raise the osmolality of the medullary interstitial fluid even further -this establishes a positive feedback cycle that produces the high osmolality of the fluids in the descending limb and interstitial fluid -there is a constant difference in filtrate concentration between the two limbs of the nephron loop, and between the ascending limb and the interstitial fluid -this difference reflects the power of the ascending limb's NaCl pumps, which are just powerful enough to create a 200 most difference between the inside and outside of the ascending limb -a 200 mOsm gradient by itself would not be enough to allow excretion of very concentrated urine -because of countercurrent flow, the nephron loop is able to "multiply" these small changes in solute concentration into a gradient change along the vertical length of the loop (both inside and outside) that is closer to 900 mOsm -while much of the Na+ and Cl- reabsorption in the ascending limb is active (via Na+-K+-2Cl- cotransporters in the thick ascending limb), some is passive (mostly in the thin portion of the ascending limb)

what tubular secretion is important for

-disposing of substances, such as certain drugs and metabolites, that are tightly bound to plasma proteins. because plasma proteins are generally not filtered, the substances they bind are not filtered and so must be secreted -eliminating undesirable substances or end products that have been reabsorbed by passive processes. urea and uric acid, two nitrogenous wastes, are both handled in this way. urea handling in the nephron is complicated, but the net effect is that 40-50% of the urea in the filtrate is excreted -ridding the body of excess K+. because virtually all K+ present in the filtrate is reabsorbed in the PCT and ascending nephron loop, nearly all K+ in urine comes from aldosterone-driven active tubular secretion into the late DCT and collecting ducts -controlling blood pH. when blood pH drops toward the acidic end of its homeostatic range, the renal tubule cells actively secrete more H+ into the filtrate and retain and generate more HCO3-. as a result, blood pH rises and the urine drains off excess H+. conversely, when blood pH approaches the alkaline end of its range, Cl- is reabsorbed instead of HCO3-, which is allowed to leave the body in urine

collecting duct

-each ________ _______ contains two cell types -the more numerous principal cells have sparse, short microvilli and are responsible for maintaining the body's water and Na+ balance -the intercalated cells are cuboidal cells with abundant microvilli -there are two varieties of intercalated cells (types A and B), and each plays a role in maintaining the acid-base balance of the blood -each _______ ______ receives filtrate from many nephrons -the collecting ducts run side by side through the medullary pyramids, giving them their striped appearance -as the collecting ducts approach the renal pelvis, they fuse together and deliver urine into the minor calyces via papillae of the pyramids

juxtaglomerular complex (JGC)

-each nephron has a _______, a region where the most distal portion of the ascending limb of the nephron loop lies against the afferent arteriole feeding the glomerulus (and sometimes the efferent arteriole) -both the ascending limb and the afferent arteriole are modified at the point of contact includes three populations of cells that help regulate the rate of filtrate formation and systemic blood pressure -the macula densa is a group of tall, closely packed cells in the ascending limb of the nephron loop that lies adjacent to the granular cells. the macula densa cells are chemoreceptors that monitor the NaCl content of the filtrate entering the distal convoluted tubule -granular cells [also called juxtaglomerular (JG) cells] are in the arteriolar walls. they are enlarged smooth muscle cells with prominent secretory granules containing the enzyme renin. granular cells act as mechanoreceptors that sense the blood pressure in the afferent arterioles -extraglomerular mesangial cells lie between the arteriole and tubule cells, and are interconnected by gap junctions. these cells may pass regulatory signals between macula densa and granular cells

renal corpuscle

-each renal corpuscle consists of a tuft of capillaries called glomerulus and a cup-shaped hollow structure called the glomerular capsule (or bowman's capsule) -the glomerular capsule is continuous with its renal tubule and completely surrounds the glomerulus, much as a well-worn baseball glove encloses a ball

kidneys

-filter nearly 200 l of fluid from our bloodstream, allowing toxins, metabolic wastes, and excess ions to leave the body in urine while returning needed substances to the blood -are usually unappreciated until they malfunction and body fluids become contaminated maintain the body's internal environment by: -regulating the total volume of water in the body and the total concentration of solutes in that water (osmolality) -regulating the concentrations of the various ions in the extracellular fluids (even relatively small changes in some ion concentrations such as K+) can be fatal -ensuring long-term acid-base balance -excreting metabolic wastes and foreign substances such as drugs or toxins -producing erythropoietin and renin, important molecules for regulating RBC production and blood pressure, respectively

aldosterone

-fine-tunes the reabsorption of the remaining Na+ -decreased blood volume or blood pressure, or high extracellular K+ concentration (hyperkalemia), can cause the adrenal cortex to release aldosterone to the blood -except for hyperkalemia (which directly stimulates the adrenal cortex to secrete aldosterone), these conditions promote the renin-angiotensin-aldosterone mechanism -targets the principal cells of the collecting ducts and cells of the distal portion of the DCT (prodding them to synthesize and retain more apical Na+ and K+ channels, and more basolateral Na+-K+ ATPases) -as a result, little or no Na+ leaves the body in urine -in the absence of aldosterone, these segments reabsorb much less Na+ and about 2% of Na+ filtered daily can be lost-- an amount incompatible with life -physiologically, aldosterone's role is to increase blood volume, and therefore blood pressure, by enhancing Na+ reabsorption -in general, water follows Na+ if aquaporins are present -also reduces blood K+ concentrations because aldosterone-induced reabsorption of Na+ is coupled to K+ secretion in the principal cells of the collecting duct -that is, Na+ enters the cell, K+ moves into the lumen

hypospadias

-found in male infants only -is the most common congenital abnormality of the urethra -it occurs when the urethral orifice is located on the ventral surface of the penis -this problem may be corrected surgically when the child is around 12 months old

urine physical characteristics

-freshly voided urine is clear and pale to deep yellow -its yellow color is due to urochrome, a pigment that results when the body destroys hemoglobin -the more concentrated the urine, the deeper the color -an abnormal color (such as pink, brown, or a smoky tinge) may result from eating certain foods (beets, rhubarb) or from the presence of bile pigments or blood in the urine -additionally, some commonly prescribed drugs and vitamin supplements alter the color of urine -cloudy urine may indicate a urinary tract infection -fresh urine is slightly aromatic, but if allowed to stand, it develops an ammonia odor as bacteria metabolize its urea solutes -some drugs and vegetables alter the odor of urine, as do some diseases -for example, in uncontrolled diabetes mellitus the urine smells fruity because of its acetone content -is slightly acidic (around pH 6) but changes in body metabolism or diet may cause the pH to vary from about 4.5 to 8.0 - a predominantly acidic diet that contains large amounts of protein and whole wheat products produces acidic urine -a vegetarian (alkaline) diet, bacterial infection of the urinary tract, or prolonged drainage of the stomach via a nasogastric tube all cause the urine to become alkaline -the ratio of the mass of a substance to the mass of an equal volume of distilled water is its specific gravity -because urine is water plus solutes, a given volume has a greater mass than the same volume of distilled water -the specific gravity of distilled water is 1.0 and that of urine ranges from 1.001 to 1.035, depending on its solute concentration

urinary incontinence

-in adults, it is usually a sign of weakened pelvic muscles following childbirth or surgery, physical pressure during pregnancy, or nervous system problems -in stress incontinence, a sudden increase in intra-abdominal pressure (during laughing and coughing) force urine through the external sphincter -this condition is common during pregnancy when the heavy uterus stretches the muscles of the pelvic floor and the urogenital diaphragm that support the external sphincter -in overflow incontinence, urine dribbles from the urethra whenever the bladder overfills

developmental aspects of the urinary system

-in an embryo, three different sets of kidneys develop from the urogenital ridges, paired elevations of the intermediate mesoderm that gives rise to both the urinary organs and reproductive organs -only the last set persists to become adult kidneys -during the fourth week of development, the first tubule system, the pronephros, forms and then quickly degenerates as a second, lower set appears -although the pronephros never functions and is gone by the sixth week, the pronephric duct that connects it to the cloaca persists and is used by the later-developing kidneys (the cloaca is the terminal part of the gut that opens to the body exterior) -as the second renal system, the mesonephros claims the pronephric duct, it comes to be called the mesonephric duct -the mesonephric kidneys degenerate (with remnant incorporated into the male reproductive system) once the third set, the metanephros, makes its appearance -the metanephros starts to develop at about five weeks as hollow uteric buds that push superiorly from the mesonephric duct into the urogenital ridge, inducing the mesoderm there to form nephrons -the distal ends of the uteric buds from the renal pelves, calyces, and collecting ducts, and their unexpanded proximal parts, now called the uteric ducts, become the ureters -because the kidneys develop in the penis and then ascend to their final position, they receive their blood supply from successively higher sources -although the lower blood vessels usually degenerate, they sometimes persist, and for this reason multiple renal arteries are common -the metanephric kidneys excrete urine by the third month of fetal life, and most of the amniotic fluid that surrounds a developing fetus is fetal urine -nonetheless, the fetal kidneys do not work nearly as hard as they will after birth because exchange through the placenta allows the mother's urinary system to clear most of the undesirable substances from the fetal blood -as the metanephros is developing, the cloaca subdivides to form the future rectum and anal canal and the urogenital sinus, into which the urinary and genital ducts empty -the urinary bladder and the urethra then develop from the urogenital sinus

atrial natriuretic peptide (ANP)

-in contrast to aldosterone, which acts to conserve Na+ , ________ reduces blood Na+, thereby decreasing blood volume and blood pressure -released by cardiac atrial cells when blood volume or blood pressure is elevated, it exerts several effects that lower blood Na+ content, including direct inhibition of Na+ reabsorption at the collecting ducts

cystitis

-infection of the urinary bladder -causes urinary frequency and dysuria (painful urination) -the urine may be blood tinged or foul smelling -if the infection ascends to the kidney, the more serious pyelonephritis results, accompanied by fever, back pain, and other symptoms of systemic illness -after the offending bacteria are identified by culturing the urine, antibiotics are used to treat the problem

pyelonephritis

-infections or inflammations that affect the kidney -kidney infections in females are usually caused by fecal bacteria that spread from the anal region to the urinary tract -less often they result from blood-borne bacteria (traveling from other infected sites) that lodge and multiply in a kidney -in severe cases, the kidney swells, abscesses form, and the pelvis fills with pus -untreated, the kidney may be severely damaged, but antibiotic therapy can usually treat the infection successfully

antidiuretic hormone (ADH)

-inhibits diuresis or urine output -makes the principal cells of the collecting ducts more permeable to water by causing aquaporins to be inserted into their apical membranes -the amount of ADH determines the number of aquaporins, and so regulates the amount of water that is reabsorbed there -when the body is over hydrated, extracellular fluid osmolality decreases, decreasing ADH secretion by the posterior pituitary and making the collecting ducts relatively impermeable to water -also decreases urea reabsorption by the collecting ducts

polycystic kidney disease (PKD)

-is a group of disorders characterized by the presence of many fluid-filled cysts in the kidneys these disorders can be grouped into two general forms based on their pattern of inheritance: -autosomal dominant PKD, the less severe form, is much more common, affecting 1 in 500 people. the cysts develop so gradually that they produce no symptoms until about 40 years of age -autosomal recessive PKD is more severe and much less common, affecting 1 in 20,000 people. almost half of newborns with recessive PKD die just after birth, and survivors generally develop renal failure in early childhood

glomerular filtration

-is a passive process in which hydrostatic pressure forces fluids and solutes through a membrane -the glomeruli can be viewed as simple mechanical filters because filtrate formation does not directly consume metabolic energy

urinary bladder

-is a smooth, collapsible, muscular sac that stores urine temporarily -is located retroperitoneally on the pelvic floor just posterior to the pubic symphysis -the prostate (part of the male reproductive system) lies inferiorly to the bladder neck, which empties into the urethra -in females, the bladder is anterior to the vagina and uterus -the interior of the bladder has openings for both ureters and the urethra -the smooth, triangular region of the bladder base outlined by these three openings is the trigone, important clinically because infections tend to persist in this region -the bladder wall has three layers: a mucosa containing transitional epithelium, a thick muscular layer, and a fibrous adventitia (except on its superior surface, where it is covered by the peritoneum) -the muscular layer, called the detrusor, consists of intermingled smooth muscle fibers arranged in inner and outer longitudinal layers and a middle circular layer -is very distensible. when empty, it collapses its basically pyramidal shape -its walls are thick and the mucosa is thrown into folds (rugae) -as urine accumulates, the bladder expands, becomes pear shaped, and rises superiorly in the abdominal cavity -the transitional epithelium and muscular wall stretch and thin, and rugae disappear -these changes allow the bladder to store more urine without a significant rise in internal pressure -usually, a moderately full bladder holds approximately 500 ml ( 1 pint) of urine -however, if urine flow has been partially obstructed for a long time (as by an enlarged prostate), then the bladder can become enlarged to hold more than twice that amount -when tense with urine, it can be palpated well above the pubic symphysis -the urinary bladder and ureters can be seen in a special X ray called a pyelogram

renin-angiotensin-aldosterone mechanism

-is the body's main mechanism for increasing blood pressure -without adequate blood pressure (as might be due to hemorrhage, dehydration, etc.), glomerular filtration is not possible, so this mechanism regulates GFR indirectly low blood pressure causes the granular cells of the juxtaglomerular complex to release renin. there are three pathways that stimulate granular cells: -sympathetic nervous system. as part of the baroreceptor reflex, renal sympathetic nerves activate B1-adrenergic receptors that cause the granular cells to release renin -activated macula densa cells. low blood pressure or vasoconstriction of the afferent arterioles by the sympathetic nervous system reduces GFR, slowing down the flow of filtrate through the renal tubules. when macula densa cells sense the low NaCl concentration of this sluggishly flowing filtrate, they signal the granular cells to release renin. they may signal by releasing less ATP (also thought to be the tubuloglomerular feedback messenger) by releasing more prostaglandin PGE2, or both -reduced stretch. granular cells act as mechanoreceptors. a drop in mean arterial blood pressure reduces the tension in the granular cells' plasma membranes and stimulates them to release more renin

glomerular filtration rate (GFR)

-is the volume of filtrate formed each minute by the combined activity of all 2 million glomeruli of the kidneys is directly proportional to each of the following factors: -net filtration pressure. NFP is the main controllable factor. of the pressures determining NFP, the most important is hydrostatic pressure in the glomerulus. this pressure can be controlled by changing the diameter of the afferent (and sometimes the efferent) arterioles -total surface area available for filtration. glomerular capillaries have a surface area (collectively) equal to the surface area of the skin. glomerular mesangial cells, surrounding these capillaries can fine-tune GFR by contracting to adjust the total surface area available for filtration -filtration membrane permeability. glomerular capillaries are thousands of times more permeable than other capillaries because of their fenestrations -the high surface area and high permeability of the filtration membrane explain how the relatively modest 10 mm Hg NFP can produce huge amounts of filtrate -furthermore, the NFP in the glomerulus favors filtration over the entire length of the capillary, unlike other capillary beds where filtration occurs only at the arteriolar end and reabsorption occurs at the venous end -as a result, the adult kidneys produce about 180 L of filtrate daily, in contrast to the 2 to 4 L formed daily by all other capillary beds combined -this 180 L of filtrate per day translates to the normal GFR of 120-125 ml/ min

the kidneys create and use an osmotic gradient to regulate urine concentration and volume

-kidneys make adjustments to keep the solute concentration of body fluids constant at about 300 most, the normal osmotic concentration of blood plasma -maintaining constant osmolality of extracellular fluids is crucial for preventing cells, particularly in the brain, from shrinking or swelling from the osmotic movement of water -a solute's osmolality is the concentration of solute particles per kg of water -because 1 osmol is a fairly large unit, the milliosmol (most), equal to 0.01 osmol, is generally used -the kidneys keep the solute load of body fluids constant by regulating urine concentration and volume -when you dehydrate, your kidneys produce a small volume of concentrated urine -when you overhydrate, your kidneys produce a large volume of dilute urine -the kidneys accomplish this feat using countercurrent mechanisms -in the kidneys, the term countercurrent means that fluid flows in opposite directions through adjacent segments of the same tube connected by a hairpin turn -this arrangement makes it possible to exchange materials between the two segments

kidneys location and external anatomy

-lie in a retroperitoneal position (between the dorsal body wall and the parietal peritoneum in the superior lumbar region -extending approx from T12 to L3, the kidneys receive some protection from the lower part of the rib cage -the right kidney is crowded by the liver and lies slightly lower than the left -an adult's kidney has a mass of about 150 g and its average dimensions are 11 cm long, 6 cm wide, and 3 cm thick -the lateral surface is convex -the medial surface is concave and has a vertical cleft called the renal hilum that leads into an internal space called the renal sinus -the ureter, renal blood vessels, lymphatics, and nerves all join each kidney at the hilum and occupy the sinus -atop each kidney is an adrenal (or suprarenal) gland, an endocrine gland that is functionally unrelated to the kidney

filtration membrane

-lies between the blood and the interior of the glomerular capsule -it is a porous membrane that allows free passage of water and solutes smaller than plasma proteins its three layers are: -fenestrated endothelium of the glomerular capillaries. the fenestrations (capillary pores) allow all blood components except blood cells to pass through -basement membrane. lies between the other two layers and is composed of their fused basal laminae. it forms a physical barrier that blocks all but the smallest proteins while still permitting most other solutes to pass. the glycoproteins of the gel-like basement membrane give it a negative charge. as a result, the basement membrane electrically repels many negatively charged macromolecular anions such as plasma proteins, reinforcing the blockade based on molecular size -foot processes of podocytes of the glomerular capsule. the visceral layer of the glomerular capsule is made of podocytes that have filtration slits between their foot processes. if any macromolecules manage to make it through the basement membrane, slit diaphragms-- thin membranes that extend across the filtration slits-- prevent almost all of them from traveling farther macromolecules that get "hung up" in the filtration membrane are engulfed by specialized pericytes called glomerular mesangial cells -molecules smaller than 3 nm in diameter-- such as water, glucose, amino acids, and nitrogenous wastes-- pass freely from the blood into the glomerular capsule -as a result, these substances usually have similar concentrations in the blood and the glomerular filtrate -larger molecules pass with greater difficulty, and those larger than 5 nm are generally barred from entering the tubule -keeping the plasma proteins in the capillaries maintains the colloid osmotic (oncotic) pressure of the glomerular blood, preventing the loss of all its water to the capsular space -the presence of proteins or blood cells in the urine usually indicates a problem with the filtration membrane

classes of nephrons

-nephrons are generally divided into two major groups, cortical and juxtamedullary -cortical nephrons account for 85% of the nephrons in the kidneys. except for small parts of their nephron loops that dip into the outer medulla, they are located entirely in the cortex -juxtamedullary nephrons originate close to the cortex-medulla junction, and they play an important role in the kidneys' ability to produce urine that is concentrated (which conserves water). they have long nephron loops that deeply invade the medulla, and their ascending limbs have both thin and thick segments

sympathetic nervous system controls

-neural renal controls serve the needs of the body as a whole-- sometimes to the detriment of the kidneys -when the volume of the extracellular fluid is normal and the sympathetic nervous system is at rest, the renal blood vessels are dilated and renal autoregulation mechanisms prevail -however, when the extracellular fluid volume is extremely low (as in hypovelmic shock during severe hemorrhage), it is necessary to shunt blood to vital organs, and neural controls may override auto regulatory mechanisms -this could reduce renal blood flow to the point of damaging kidneys -when blood pressure falls, norepinephrine released by sympathetic nerve fibers (and epinephrine released by the adrenal medulla) causes vascular smooth muscle to constrict, increasing peripheral resistance and bringing blood pressure back up towards normal (this is the baroreceptor reflex) -as part of this reflex, the afferent arterioles also constrict -constriction of the afferent arterioles decreases GFR and so helps restore blood volume and blood pressure to normal)

urine formation, step 2: most of the filtrate is reabsorbed into the blood

-our total plasma volume filters into the renal tubules about every 22 min, so all our plasma would drain away as urine in less than 30 min were it not for tubular reabsorption, which quickly reclaims most of the tubule contents and returns them to the blood -tubular reabsorption is a selective trans epithelial process that begins as soon as the filtrate enters the proximal tubules -to reach the blood, reabsorbed substances follow either the transcellular or paracellular route -the transcellular route is just like the route we described for absorption in the gut -transported substances move through the apical membrane, the cytosol, and the basolateral membrane of the tubule cell and then the endothelium o the peritubular capillaries -movement of the substances in the paracellular route--between the tubule cells-- is limited by the tight junctions connecting these cells -in the proximal nephron, however, these tight junctions are "leaky" and allow water and some important ions (Ca2+, Mg2+, K+, and some Na+) to pass through the paracellular route -given healthy kidneys, virtually all organic nutrients such as glucose and amino acids are completely reabsorbed to maintain or restore normal plasma concentrations -in contrast, the reabsorption of water and many ions is continuously regulated and adjusted in response to hormonal signals -depending on the substances transported, the reabsorption process may be active or passive

renal clearance

-refers to the volume of plasma from which the kidneys clear (completely remove) a particular substance in a given time, usually 1 min -tests are done to determine the GFR, which allows us to detect glomerular damage and follow the progress of renal disease -the renal clearance rate (C) of any substance, in ml/min, is calculated from the equation C= UV/P where U=concentration of the substance in urine (mg/ml) V= flow rate of urine formation (ml/min) P=concentration of the substance in plasma -because it is freely filtered and neither reabsorbed nor secreted by the kidneys, inulin is the substance used to determine the GFR -inulin is a plant polysaccharide that has a renal clearance value equal to the GFR -when inulin is infused such that its plasma concentration is 1 mg/ml (P= 1 mg/ml), then generally U=125 mg/ml, and V= 1 ml/min -therefore, its renal clearance is C= (125 x 1) 1=125 ml/min, meaning that in 1 min the kidneys have cleared all the inulin present in 125 ml of plasma

myogenic mechanism

-reflects a property of vascular smooth muscle-- it contracts when stretched and relaxes when not stretched -rising systemic blood pressure stretches vascular smooth muscle in the arteriolar walls, causing the afferent arterioles to constrict -this constriction restricts blood flow into the glomerulus and keeps the GFR at a level ideal for kidney function -declining systemic blood pressure causes dilation of afferent arterioles and raises glomerular hydrostatic pressure -both responses help maintain normal NFP and GFR

other factors affecting GFR

-renal cells produce a battery of chemicals, many of which act as paracrines (local signaling molecules) affecting renal arterioles -these include adenosine and prostaglandin E2 (PGE2) -in addition, the kidney makes its own locally acting angiotensin II that reinforces the effects of hormonal angiotensin II

active tubular reabsorption

-requires ATP either directly (primary active transport) or indirectly (secondary active transport) for at least one of its steps

tubular reabsorption of sodium

-sodium ions are the single most abundant cation in the filtrate, and about 80% of the energy used for active transport is devoted to reabsorbing them -sodium reabsorption is almost always active and via the transcellular route

secondary active transport

-substances reabsorbed by secondary active transport (the "push" comes from the gradient created by Na+ -K+ pumping at the basolateral membrane) include glucose, amino acids, some ions, and vitamins -in nearly all these cases, an apical carrier moves Na+ down its concentration gradient as it cotransports another solute -cotransported solutes move across the basolateral membrane by facilitated diffusion via other transport proteins before moving into the peritubular capillaries

clearance value

-tells us about the net handling of a substance by the kidneys. there are three possible cases: 1) a clearance value less than that of inulin means that the substance is reabsorbed. for example, C is normally 70 ml/min for urea, meaning that of the 125 ml of glomerular filtrate formed each minute, approx 70 ml is completely cleared of urea, while the urea in the remaining 55 ml is recovered and returned to the plasma -if C is zero (such as for glucose in health individuals), reabsorption is complete or the substance is not filtered 2) if C is equal to that of inulin, there is no net reabsorption or secretion 3) if C is greater than that of inulin, the tubule cells are secreting the substance into the filtrate. this is the case with most drug metabolites. knowing a drug's renal clearance value is essential because if it is high, the drug dosage must also be high and administered frequently to maintain a therapeutic level -creatinine, which has a C value of 140 ml/min, is freely filtered but also secreted in small amounts -nevertheless, its measured blood value is often used to give an estimate of GFR -this is convenient because creatinine does not need to be intravenously infused into the patients as does inulin

nephron loop

-the U-shaped nephron loop (formerly called the loop of Henle) has descending and ascending limbs -the proximal part of the descending limb is continuous with the proximal tubule and its cells are similar -the rest of the descending limb, called the descending thin limb, consists of a simple squamous epithelium -the epithelium becomes cuboidal or even low columnar in the ascending part of the nephron loop, which is therefore called the thick ascending limb -in most nephrons, the entire ascending limb is thick, but in some nephrons, the thin segment extends around the bend as the ascending thin limb -the thick and thin parts of the nephron loop are also referred to as thick and thin segments -beyond the PCT, the permeability of the tubule epithelium changes dramatically -here, for the first time, water reabsorption is not coupled to solute reabsorption -water can leave the descending limb of the nephron loop but not the ascending limb, where aquaporins are scarce or absent in the tubule cell membranes -these permeability differences play a vital role in the kidneys' ability to form dilute or concentrated urine -the rule for water is that it leaves the descending limb of the nephron loop -the opposite is true for solutes -virtually no solute reabsorption occurs in the descending limb, but solutes are reabsorbed both actively and passively in the ascending limb -in the thin segment of the ascending limb, Na+ moves passively down the concentration gradient created by water reabsorption -in the thick ascending limb, a Na+-K+-2Cl- symporter is the main means of Na+ entry at the apical surface -a Na+-K+ATPase operates at the basolateral membrane to create the ionic gradient that drives the symporter -the thick ascending limb also has Na+-H+ antiporters -in addition, some 50% of Na+ passes via the paracellular route in this region

urinanalysis

-the analysis of urine -can aid in the diagnosis of diseases or detect illegal substances -however, to measure how well the kidneys are functioning, we need to analyze both blood and urine -renal function can quickly be assessed by measuring levels of nitrogenous wastes in blood -but to precisely measure kidney function, we need to determine the renal clearance, which requires that both blood and urine be tested

urinary retention

-the bladder is unable to expel its contained urine -is common after general anesthesia (it takes a little time for the detrusor to regain its activity) -_______ _______ in men often reflects hypertrophy of the prostate, which narrows the urethra, making it difficult to void -when it is prolonged, a slender drainage tube called a catheter must be inserted through the urethra to drain the urine and prevent bladder trauma from excessive stretching

filtration, absorption, and secretion are the key processes of urine formation

-the body "dumps" cell- and protein- free filtered blood into a separate "waste container" -from this container, it reclaims everything the body needs to keep (which is almost everything in the container) -finally, the kidney selectively adds specific things to the container, fine-tuning the body's chemical balance -anything left in the container becomes urine. this is basically how nephrons work

two types of countercurrent mechanisms that determine urine concentration and volume

-the countercurrent multiplier is the interaction between the flow of filtrate through the ascending and descending limbs of the long nephron loops of juxtamedullary nephrons -the countercurrent exchanger is the flow of blood through the ascending and descending portions of the vasa recta -these countercurrent mechanisms establish and maintain an osmotic gradient extending from the cortex through the depths of the medulla -this gradient-- the medullary osmotic gradient--allows the kidneys to vary urine concentration dramatically

vasa recta

-the efferent arterioles serving the juxtamedullary nephrons tend not to break up into meandering peritubular capillaries -instead they form bundles of long straight vessels called ________ ______ that extend deep into the medulla paralleling the longest nephron loops -like all blood vessels, the _______ ___ supply oxygen and nutrients to the tissue through which they pass (the renal medulla) -however, the thin-walled ______ _____ also play an important role in forming concentrated urine

glomerulus

-the endothelium of the glomerular capillaries is fenestrated by many pores, which makes these capillaries exceptionally porous -this property allows large amounts of solute-rich but virtually protein-free fluid to pass from the blood into the glomerular capsule -this plasma-derived fluid or filtrate is the raw material that the renal tubules process to form urine -capillaries run parallel -is specialized for filtration -it differs from all other capillary beds in the body in that it is both fed and drained by arterioles-- the afferent arteriole and efferent arteriole, respectively -this arrangement maintains the high pressure in the glomerulus that is needed for filtration -filtration produces a large amount of fluid, most (99%) of which is reabsorbed by the renal tubule cells and returned to the blood in the peritubular capillary beds -the afferent arterioles arise from the cortical radiate arteries that run through the renal cortex -the efferent arterioles feed into either the peritubular capillaries or the vasa recta

proximal convoluted tubule

-the entire renal tubule is involved in reabsorption to some degree, but the PCT cells are by far the most active reabsorbers and the events just described occur mainly in this tubular segment -normally, the PCT reabsorbs all of the glucose and amino acids in the filtrate and 65% of the Na+ and water -the bulk of the electrolytes are reabsorbed by the time the filtrate reaches the nephron loop -nearly all of the uric acid and about half of the urea are reabsorbed in the proximal tubule, but both are later secreted back into the filtrate

glomerular capsule

-the glomerular capsule has an extended parietal layer and a visceral layer that clings to the glomerular capillaries -the parietal layer is simple squamous epithelium. this layer contributes to the capsule structure but plays no part in forming filtrate -the visceral layer, which clings to the glomerular capillaries, consists of highly modified, branching epithelial cells called podocytes. the octopus-like podocytes have foot processes that align to the basement membrane of the glomerulus -the clefts or openings between the foot processes are called filtration slits. through these slits, filtrate enters the capsular space inside the glomerular capsule

outward pressures

-the hydrostatic pressure in glomerular capillaries (HPgc) is essentially glomerular blood pressure. it is the chief force pushing water and solutes out of the blood and across the filtration membrane. the blood pressure in the glomerulus is extraordinarily high (approx. 5 mm Hg compared to an average of 26 mm Hg or so in other capillary beds) and it remains high across the entire capillary bed. this is because the glomerular capillaries are drained by a high-resistance efferent arteriole whose diameter is smaller than the afferent arteriole that feeds them -as a result, filtration occurs along the entire length of each glomerular capillary and reabsorption does not occur as it would in other capillary beds -theoretically, the colloid osmotic pressure in the capsular space of the glomerular capsule would "pull" filtrate into the tubule. however, this pressure is essentially zero because virtually no proteins enter the capsule, so we will not consider it further

kidney blood and nerve supply

-the kidneys continuously cleanse the blood and adjust its composition, so it is not surprising that they have a rich blood supply -under normal resting conditions, the large renal arteries deliver one-fourth of the total cardiac output to the kidneys-- about 1200 ml/min -the renal arteries exit at right angles from the abdominal aorta, and the right renal artery is longer than the left because the aorta lies to the left of the midline -as each renal artery approaches a kidney, it divides into five segmental arteries -within the renal sinus, each segmental artery branches further to form several interlobar arteries -at the cortex-medulla junction, the interlobar arteries branch into the arcuate arteries that arch over the bases of the medullary pyramids -small cortical radiate arteries radiate outward from the arcuate arteries to supply the cortical tissue -more than 90% of the blood entering the kidneys perfuses the renal cortex -afferent arterioles branching from the cortical radiate arteries begin a complex arrangement of microscopic blood vessels. these vessels are key elements of kidney function -veins mostly trace the pathway of the arterial supply in reverse -blood leaving the renal cortex drains sequentially into the cortical radiate, arcuate, interlobar, and finally renal veins -the renal veins exit from the kidneys and empty into the inferior vena cava -because the inferior vena cava lies to the right of the vertebral column, the left renal vein is about twice as long as the right -the renal plexus, a variable network of autonomic nerve fibers and ganglia, provides the nerve supply of the kidney and its ureter -an offshoot of the celiac plexus, the renal plexus is largely supplied by sympathetic fibers from the most inferior thoracic and first lumbar splanchnic nerves, which course along with the renal artery to reach the kidney -these sympathetic vasomotor fibers regulate renal blood flow by adjusting the diameter of renal arterioles and also influence the formation of urine by the nephron

urine formation, step 3: certain substances are secreted into the filtrate

-the most important way to clear plasma of unwanted substances is to simply not reabsorb them from the filtrate -another way is tubular secretion-- essentially, reabsorption in reverse -tubular secretion moves selected substances from the peritubular capillaries through the tubule cells into the filtrate -also, some substances (such as HCO3-) that are synthesized in the tubule cells are secreted -the urine eventually excreted contains both filtered and secreted substances -with one major exception (K+), the PCT is the main site of secretion, but the collecting ducts are also active

passive tubular reabsorption of water

-the movement of Na+ and other solutes establishes a strong osmotic gradient, and water moves by osmosis into the peritubular capillaries -transmembrane proteins called aquaporins aid this process by acting as water channels across plasma membranes -in continuously water-permeable regions of the renal tubules, such as the PCT, aquaporins are always present in the tubule cell membranes -their presence "obliges" the body to absorb water in the proximal nephron regardless of its state of over- or under-hydration -this water flow is referred to as obligatory water reabsorption -aquaporins are virtually absent in the apical membranes of the collecting duct unless antidiuretic hormone (ADH) is present -water reabsorption that depends on ADH is called facultative water reabsorption

renal tubule and collecting duct

-the renal tubule is about 3 cm (1.2 inches) long and has three major parts -it leaves the glomerular capsule as the elaborately coiled proximal convoluted tubule, drops into a hairpin loop called the nephron loop, and then winds and twists again as the distal convoluted tubule before emptying into a collecting duct -the terms proximal and distal indicate the relationship of the convoluted tubules to the renal corpuscle ,filtrate from the renal corpuscle passes through the proximal convoluted tubule first and then the distal convoluted tubule, which is thus "further away" from the renal corpuscle -the meandering nature of the renal tubule increases its length and enhances its filtrate processing capabilities -throughout their length, the renal tubule and collecting duct consists of a single layer of epithelial cells on a basement membrane -however, each region has a unique histology that reflects its role in processing filtrate

nephron capillary beds

-the renal tubule of every nephron is closely associated with two capillary beds -the first capillary bed (the glomerulus) produces the filtrate -the second (a combo of peritubular capillaries and vasa recta) reclaims most of that filtrate

transport maximum

-the transcellular transport systems for the various solutes are quite specific and limited -there is a transport maximum (Tm) for nearly every substance that is reabsorbed using a transport protein in the membrane -the Tm reflects the number of transport proteins in the renal tubules available to ferry a particular substance -in general, there are plenty of transporters for substances such as glucose that need to be retained, and few or no transporters for substances of no use to the body -when the transporters are saturated-- that is, bound to the substance they transport-- the excess is excreted in urine -this is what happens in individuals who become hyperglycemic because of uncontrolled diabetes mellitus -as plasma levels of glucose approach and exceed 180 mg/dl, the glucose Tm is exceeded and large amounts of glucose may be lost in the urine even though the renal tubules are still functioning normally

countercurrent exchanger

-the vasa recta act as countercurrent exchangers -countercurrent exchange does not create the medullary gradient, but preserves it by 1) preventing rapid removal of salt from the medullary interstitial space, and 2) removing reabsorbed water -as a result, blood leaving and reentering the cortex via the vasa recta has nearly the same solute concentration -the water picked up by the ascending vasa recta includes not only water lost from the descending vasa recta, but also water reabsorbed from the nephron loop and collecting duct -as a result, the volume of blood at the end of the vasa recta is greater than at the beginning

proximal convoluted tubule (PCT)

-the walls of the _________ are formed by cuboidal epithelial cells with large mitochondria -their apical (luminal) surfaces bear dense microvilli -just as in the intestine, this brush border dramatically increases the surface area and capacity for reabsorbing water and solutes from the filtrate and secreting substances into it

urine chemical composition

-water accounts for about 95% of urine volume; the remaining 5% consists of solutes -the largest component of urine by weight, apart from water, is urea, which is derived from the normal breakdown of amino acids -other nitrogenous wastes in urine include uric acid (an end product of nucleic acid metabolism) and creatinine ( a metabolite of creatinine phosphate, which is found in large amounts in skeletal muscle tissue where it stores energy to regenerate ATP) -normal solute constituents of urine, in order of decreasing concentration, are urea, Na+, K+, PO4^3-, SO4^2-, creatinine, and uric acid -much smaller but highly variable amounts of Ca2+, Mg2+, and HCO3- are also present -unusually high concentrations of any solute, or the presence of abnormal substances such as plasma proteins, WBCs (pus), or bile pigments, may indicate pathology

horseshoe kidney

-when ascending from the pelvis, the kidneys are very close together, and in 1 out of 600 people they fuse across the midline, forming a single, U-shaped _______ _____ -this condition is usually asymptomatic, but it may be associated with other kidney abnormalities, such as obstructed drainage, that increase the risk of frequent kidney infections

renal calculi

-when calcium or magnesium salts or uric acid are concentrated in urine, they may crystallize and precipitate as "kidney stones" or renal calculi -if stones obstruct urine flow, they cause excruciating pain radiating from the flank to the abdomen -nephrolithiasis refers to calculi in the kidney, whereas ureterolithiasis refers to calculi lodged in the ureters -while most small calculi pass without intervention, larger calculi or those that lodge in the ureter can be removed endoscopically or surgically -many calculi, especially those in the kidney, can be treated by lithotripsy, a noninvasive procedure that uses acoustic wave energy to break stones into smaller pieces that may be passed more easily -obesity and elevated blood calcium are risk factors for the formation of renal calculi -the best way to prevent recurrence is to maintain dilute urine by adequate hydration

formation of dilute or concentrated urine

-when we are over hydrated, ADH production decreases and the osmolality of urine falls as low as 100 mOsm -if aldosterone is present, the DCT and collecting duct cells can remove Na+ and selected other ions from the filtrate, making the urine that enters the renal pelvis even more dilute -the osmolality of urine can plunge as low as 50 mOsm, about one-sixth the concentration of glomerular filtrate or blood plasma -when we are dehydrated, the posterior pituitary releases large amounts of ADH and the solute concentration of urine may rise as high as 1200 mOsm, the concentration of interstitial fluid in the deepest part of the medulla -with maximal ADH secretion, up to 99% of the water in the filtrate is reabsorbed and returned to the blood, and only half a liter per day of highly concentrated urine is excreted -the ability of our kidneys to produce such concentrated urine is critically tied to our ability to survive for a limited time without water

uremia

-while once attributed to accumulation of nitrogenous wastes (particularly urea), we now know that urea is not especially toxic -rather, this multi organ failure is caused by an interplay of multiple factors -these include ionic and hormonal imbalances (including anemia due to lack of erythropoietin) as well as metabolic abnormalities and accumulation of various toxic molecules that interfere with normal metabolism

distal convoluted tubule and collecting duct

-while reabsorption in the PCT and nephron loop does not vary with the body's needs, hormones fine-tune reabsorption in the DCT and collecting duct -because most of the filtered water and solutes have been reabsorbed by the time the DCT is reached, only a small amount of the filtered load is subject to this fine tuning (about 10% of the originally filtered NaCl and 25% of the water)

urine formation and adjustment of blood composition involves three processes

1) glomerular filtration. takes place in the renal corpuscle and produces a cell- and protein- free filtrate 2) tubular reabsorption. this is the process of selectively moving substances from the filtrate back into the blood. it takes place in the renal tubules and collecting ducts. tubular reabsorption reclaims almost everything filtered--all of the glucose and amino acids, and some 99% of the water, salt, and other components. anything that is not reabsorbed becomes urine 3) tubular secretion is the process of selectively moving substances from the blood into the filtrate. like tubular reabsorption, it occurs along the length of the tubule and collecting duct -the kidneys process an enormous volume of blood each day -of the approximately 1200 ml of blood that passes through the glomeruli each minute, some 650 ml is plasma, and about one-fifth of this is forced into the glomerular capsules as filtrate -this is equivalent to filtering your entire plasma volume more than 60 times each day -the kidneys (which account for only 1% of body weight) consume 20-25% of all oxygen used by the body at rest -filtrate and urine are quite different -filtrate contains everything found in blood plasma except proteins -urine contains unneeded substances such as excess salts and metabolic wastes -the kidneys process about 180 L of blood-derived fluid daily -of this amount, less than 1% typically leaves the body as urine; the rest returns to the circulation

urea recycling and the medullary osmotic gradient

1) urea enters the filtrate by facilitated diffusion in the ascending thin limb of the nephron loop 2) as the filtrate moves on, the cortical collecting duct usually reabsorbs water, leaving urea behind 3) when filtrate reaches the portion of the collecting duct in the deep medullary region, the now highly concentrated urea moves by facilitated diffusion out of the collecting duct into the interstitial fluid of the medulla. these movements form a pool of urea that recycles back into the ascending thin limb of the nephron loop. in this way, urea contributes substantially to the high osmolality in the medulla -antidiuretic hormone enhances urea transport out of the medullary collecting duct -when ADH is present, it increases urea recycling and strengthens the medullary osmotic gradient, allowing more concentrated urine to be formed

passive tubular reabsorption

encompasses diffusion, facilitated diffusion, and osmosis-- processes in which substances move down their electrochemical gradients

extrinsic controls: neural and hormonal mechanisms

the purpose of extrinsic controls regulating the GFR is to maintain systemic blood pressure

inward pressures

two inward forces inhibit filtrate formation by opposing HPgc -the hydrostatic pressure in the capsular space (HPcs) is the pressure exerted by filtrate in the glomerular capsule. HPcs is much higher than hydrostatic pressure surrounding most capillaries because filtrate is confined in a small space with a narrow outlet -the colloid osmotic pressure in glomerular capillaries (OPgc) is the pressure exerted by the proteins in the blood that "sucks" water into the capillary