Chapter 19
What is the primary site for creation of dilute fluid?
Loop of Henle
At rest, what percent of blood flow (aortic flow) is directed to the kidneys?
a. At any given time, the kidneys receive 20-25% of the cardiac output
Of the 180 liters of fluid filtered per day, how much of it is excreted from the body?
a. 1.5 liters
What are the two major areas of the kidney?
a. A cross section through a kidney shows that the interior is arranged in two layers: an outer cortex and inner medulla
What is a cortical nephron vs. a juxtamedullary nephron?
a. About 80% of the nephrons in a kidney are almost completely contained within the cortex (cortical nephrons), but the other 20%—called juxtamedullary nephron dip down into the medulla.
What is the most important function of the kidneys?
a. Actually, the most important function of the kidney is the homeostatic regulation of the water and ion content of the blood, also called salt and water balance or fluid and electrolyte balance.
Give the equation for the amount of fluid excreted via the urinary system.
a. Amount filtered - amount reabsorbed + amount secreted = amount excreted
What is Tm? How does it affect glucosuria?
a. At substrate concentrations equal to or above the saturation point, transport occurs at a maximum rate. The transport rate at saturation is the transport maximum, or Tm. b. At normal plasma glucose concentrations, all glucose that enters the nephron is reabsorbed before it reaches the end of the proximal tubule. But what happens if blood glucose concentrations become excessive, as they do in diabetes mellitus? In that case, glucose is filtered faster than the carriers can reabsorb it. The carriers become saturated and are unable to reabsorb all the glucose that flows through the tubule. As a result, some glucose escapes reabsorption and is excreted in the urine.
Describe the portal system found in the kidney? What is the function of this physical arrangement?
a. Blood enters the kidney through the renal artery before flowing into smaller arteries and then into arterioles in the cortex. At this point, the arrangement of blood vessels turns into a portal system, one of three in the body. Blood flows from the afferent arteriole into a ball-like network of capillaries known as the glomerulus. b. The function of the renal portal system is first to filter fluid out of the blood and into the lumen of the nephron at the glomerular capillaries, then to reabsorb fluid from the tubule back into the blood at the peritubular capillaries.
What is clearance? How do we use inulin to measure GFR? What substance is used to estimate GFR in clinical setting?
a. Clearance of a solute is the rate at which that solute disappears from the body by excretion or by metabolism. b. For our example, we use inulin, a polysaccharide isolated from the tuberous roots of a variety of plants. Scientists discovered from experiments with isolated nephrons that inulin injected into the plasma filters freely into the nephron. As it passes through the kidney tubule, inulin is neither reabsorbed nor secreted. In other words, 100% of the inulin that filters into the tubule is excreted. c. In clinical settings, physicians use creatinine to estimate GFR. Normally, the production and breakdown rates of phosphocreatine are relatively constant, and the plasma concentration of creatinine does not vary much. Although creatinine is always present in the plasma and is easy to measure, it is not the perfect molecule for estimating GFR because a small amount is secreted into the urine. However, the amount secreted is small enough that, in most people, creatinine clearance is routinely used to estimate GFR.
Why is it so critically important to take penicillin at the prescribed time intervals when trying to eliminate a bacterial infection? How does probenecid prolong the activity of penicillin?
a. Demand for the drug was heightened by the fact that kidney tubules secrete penicillin. Renal secretion is so efficient at clearing foreign molecules from the blood that within three to four hours after a dose of penicillin has been administered, about 80% has been excreted in the urine. b. A synthetic compound named probenecid solves this problem. When probenecid is administered concurrently with penicillin, the transporter removes probenecid preferentially, prolonging the activity of penicillin in the body. Once mass-produced synthetic penicillin became available and supply was no longer a problem, the medical use of probenecid declined.
Name two hormone secretions of the kidneys.
a. Erythropoietin, renin
What is the mechanism of reabsorption of some of the small protein hormones and enzymes at the proximal convoluted tubule?
a. Filtration of plasma at the glomerulus normally leaves most plasma proteins in the blood, but some smaller proteins and peptides can pass through the filtration barrier. Most filtered proteins are reabsorbed in the proximal tubule, with the result that normally only trace amounts of protein appear in urine. b. Small as they are, filtered proteins are too large to be reabsorbed by carriers or through channels. Instead they enter proximal tubule cells by receptor-mediated endocytosis at the apical membrane.
Under normal conditions, what is the clearance of glucose? How are urea and penicillin usually handled at the kidney?
a. For any solute, its clearance reflects how the kidney tubule handles it. For example, 100% of the glucose that filters is reabsorbed, and glucose clearance is zero. On the other hand, urea is partially reabsorbed; four molecules filter, but two are reabsorbed and two are excreted. Consequently, urea clearance is 50 mL plasma per minute. Urea and glucose clearance are both less than the inulin clearance of 100 mL/min, which tell you that both glucose and urea have been reabsorbed b. As you learned earlier, penicillin is filtered, not reabsorbed, and additional penicillin molecules are secreted from plasma in the peritubular capillaries. Four penicillin are filtered, but six are excreted. An extra 50 mL of plasma have been cleared of penicillin in addition to the original 100 mL that were filtered. The penicillin clearance therefore is 150 mL plasma cleared per minute. Penicillin clearance is greater than the inulin clearance of 100 mL/min, which tells you that net secretion of penicillin occurs.
Describe the structure and function of the mesangial cells.
a. Glomerular mesangial cells lie between and around the glomerular capillaries. Mesangial cells have cytoplasmic bundles of actin-like filaments that enable them to contract and alter blood flow through the capillaries. In addition, mesangial cells secrete cytokines associated with immune and inflammatory processes. Disruptions of mesangial cell function have been linked to several disease processes in the kidney.
GFR is controlled mainly by regulation of blood flow. What are the two main sites of control of blood flow at the nephrons, and what is the result of their regulation?
a. If resistance increases in the afferent arteriole, hydrostatic pressure decreases on the glomerular side of the constriction. This translates into a decrease in GFR. If resistance increases in the efferent arteriole, blood "dams up" in front of the constriction, and hydrostatic pressure in the glomerular capillaries increases. Increased glomerular pressure increases GFR. The opposite changes occur with decreased resistance in the afferent or efferent arterioles. Most regulation occurs at the afferent arteriole.
What percentage of the population has only one kidney? What are the component parts of the urinary system?
a. Many people function perfectly normally with only one kidney, including the one person in 1000 born with only one kidney b. The Urinary System Consists of Kidneys, Ureters, Bladder, and Urethra
Where does most reabsorption take place? What is the mechanism of reabsorption of sodium at the proximal tubule cell? How does glucose move from the lumen of the tubule to the interstitial fluid?
a. Most of this reabsorption takes place in the proximal tubule, with a smaller amount of reabsorption in the distal segments of the nephrons. b. Active transport of Na+ from the tubule lumen to the extracellular fluid creates a transepithelial electrical gradient in which the lumen is more negative than the ECF. Anions then follow the positively charged Na + out of the lumen. The removal of Na + and anions from lumen to ECF dilutes the luminal fluid and increases the concentration of the ECF, so water leaves the tubule by osmosis. c. Sodium- linked secondary active transport in the nephron is responsible for the reabsorption of many substances, including glucose, amino acids, ions, and various organic metabolites. Na+-dependent glucose reabsorption across the proximal tubule epithelium. The apical membrane contains the Na+-glucose cotransporter (SGLT) that brings glucose into the cytoplasm against its concentration gradient by harnessing the energy of Na+ moving down its electrochemical gradient. On the basolateral side of the cell, Na+ is pumped out by the Na+-K+-ATPase, while glucose diffuses out with the aid of a facilitated diffusion GLUT transporter.
Name one nervous and one endocrine-related control of GFR.
a. Neural control of GFR is mediated by sympathetic neurons that innervate both the afferent and efferent arterioles. Sympathetic innervation of a-receptors on vascular smooth muscle causes vasoconstriction. If systemic blood pressure drops sharply, as occurs with hemorrhage or severe dehydration, sympathetically induced vasoconstriction of the arterioles decreases GFR and renal blood flow. This is an adaptive response that helps conserve fluid volume. b. A variety of hormones also influence arteriolar resistance. Among the most important are angiotensin II, a potent vasoconstrictor, and prostaglandins, which act as vasodilators. These same hormones may affect the filtration coefficient by acting on podocytes or mesangial cells. Podocytes change the size of the glomerular filtration slits. If the slits widen, more surface area is available for filtration, and GFR increases. Contraction of mesangial cells apparently changes the glomerular capillary surface area available for filtration.
What is the primary function of the proximal tubule?
a. Reabsorption occurs when proximal tubule cells transport solutes out of the lumen, and water follows by osmosis. Filtrate leaving the proximal tubule has the same osmolarity as filtrate that entered. For this reason, we say that the primary function of the proximal tubule is the reabsorption of isosmotic fluid.
List the six subdivided areas of kidney function.
a. Regulation of ECF volume and blood pressure b. Regulation of osmolarity c. Maintenance of ion balance d. Homeostatic regulation of pH e. Excretion of wastes f. Production of hormones
Name the filtration barriers at the renal corpuscle.
a. Substances leaving the plasma must pass through three filtration barriers before entering the tubule lumen: the glomerular capillary endothelium, a basal lamina (basement membrane), and the epithelium of Bowman's capsule
Name the two components which may affect the filtration coefficient.
a. The filtration coefficient has two components: the surface area of the glomerular capillaries available for filtration and the permeability of interface between the capillary and Bowman's capsule.
What are the roles of the internal and external sphincters with regard to micturition?
a. The internal sphincter is a continuation of the bladder wall and consists of smooth muscle. Its normal tone keeps it contracted. The external sphincter is a ring of skeletal muscle controlled by somatic motor neurons. Tonic stimulation from the central nervous system maintains contraction of the external sphincter except during urination.
What is the functional unit of the kidney?
a. The nephron is the functional unit of the kidney.
The basal lamina does not have cells. How does it filter materials?
a. The second filtration barrier is the basal lamina, an acellular layer of extracellular matrix that separates the capillary endothelium from the epithelial lining of Bowman's capsule. The basal lamina consists of negatively charged glycoproteins, collagen, and other proteins. The lamina acts like a coarse sieve, excluding most plasma proteins from the fluid that filters through it.
Name two important ions that are secreted into the tubule of the nephron.
a. The secretion of K+ and H+ by the distal nephron is important in the homeostatic regulation of those ions.
Name the specialized cells of the Bowman's capsule which allow only about 20% of the plasma to be pass through. How did these cells obtain their name?
a. The third filtration barrier is the epithelium of Bowman's capsule. The portion of the capsule epithelium that surrounds each glomerular capillary consists of specialized cells called podocytes. Podocytes have long cytoplasmic extensions called foot processes that extend from the main cell body.
Give approximate values for GFR in L/day and ml/min.
a. The volume of fluid that filters into Bowman's capsule per unit time is the glomerular filtration rate (GFR). Average GFR is 125 mL/min, or 180 L/day, an incredible rate considering that total plasma volume is only about 3 liters.
Name the three basic processes in the nephron, and define each.
a. Three basic processes take place in the nephron: filtration, reabsorption, and secretion b. Filtration is the movement of fluid from blood into the lumen of the nephron. Filtration takes place only in the renal corpuscle, where the walls of glomerular capillaries and Bowman's capsule are modified to allow bulk flow of fluid. c. After filtrate leaves Bowman's capsule, it is modified by reabsorption and secretion. Reabsorption is the process of moving substances in the filtrate from the lumen of the tubule back into the blood flowing through peritubular capillaries. d. Secretion removes selected molecules from the blood and adds them to the filtrate in the tubule lumen. Although secretion and glomerular filtration both move substances from blood into the tubule, secretion is a more selective process that usually uses membrane proteins to move molecules across the tubule epithelium.
Explain the mechanism and result of increased fluid flow through the distal tubule regard to GFR autoregulation.
a. Tubuloglomerular feedback is a local control pathway in which fluid flow through the tubule influences GFR. The twisted configuration of the nephron, causes the final portion of the ascending limb of the loop of Henle to pass between the afferent and efferent arterioles. The tubule and arteriolar walls are modified in the regions where they contact each other and together form the juxtaglomerular apparatus. b. The modified portion of the tubule epithelium is a plaque of cells called the macula densa. The adjacent wall of the afferent arteriole has specialized smooth muscle cells called granular cells (also known as juxtaglomerular cells or JG cells). The granular cells secrete renin, an enzyme involved in salt and water balance. When NaCl delivery past the macula densa increases as a result of increased GFR, the macula densa cells send a paracrine message to the neighboring afferent arteriole. The afferent arteriole constricts, increasing resistance and decreasing GFR.
What is micturition?
a. Urination, the process by which urine is excreted
The glomerular capillaries are ______________ capillaries with large pores which are still small enough to prevent the passing of ___________________.
fenestrated blood cells
The hydrostatic pressure of blood flowing through glomerular capillaries, the colloid osmotic pressure inside glomerular capillaries, and the hydrostatic fluid pressure that opposes fluid movement into the Bowman's capsule result in ___________________________________________.
rapid fluid filtration
The collecting duct dumps into the _____________________ which connects to the _____________________ to deliver urine to the bladder.
renal pelvis ureter