Topic 10: Chpt 19-20 Flashcards
What is the most important function of the kidney?
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.
Why is waste removal not the most critical function of the kidney?
Disturbances in blood volume or ion levels cause serious medical problems before the accumulation of metabolic wastes reaches toxic levels.
How do kidneys maintain normal blood concentrations of ions and water?
Kidneys maintain normal blood concentrations by balancing the intake of these substances with their excretion in the urine, following the principle of mass balance.
What are the six general functions of the kidneys?
- Regulation of extracellular fluid volume and blood pressure
- Regulation of osmolarity
- Maintenance of ion balance
- Homeostatic regulation of pH
- Excretion of wastes
- Production of hormones
How do kidneys regulate extracellular fluid volume and blood pressure?
Kidneys work with the cardiovascular system to ensure blood pressure and tissue perfusion remain within an acceptable range, maintaining adequate blood flow to essential organs.
How do kidneys regulate osmolarity? What ions do the kidneys help to balance? How do kidneys contribute to pH homeostasis?
- Kidneys integrate with behavioral drives like thirst to maintain blood osmolarity close to 290 mOsM.
- Kidneys balance concentrations of sodium (Na+), potassium (K+), and calcium (Ca2+).
- Kidneys remove H+ and conserve bicarbonate ions (HCO3-) when ECF is too acidic and remove HCO3- and conserve H+ when ECF is too alkaline.
What wastes do the kidneys excrete?
Kidneys remove metabolic wastes like creatinine, urea, and uric acid, as well as xenobiotics like drugs and environmental toxins.
What gives urine its characteristic yellow color?
A metabolite of hemoglobin called urobilinogen .
How do kidneys contribute to hormone production?
Kidneys synthesize erythropoietin, release renin, and help convert vitamin D3 into a hormone that regulates Ca2+ balance.
What is erythropoietin and what is its role?
Erythropoietin is a cytokine/hormone synthesized by the kidneys that regulates red blood cell synthesis.
What is renin and what is its role?
Renin is an enzyme released by the kidneys that regulates the production of hormones involved in sodium balance and blood pressure homeostasis.
How do kidneys affect vitamin D3?
Renal enzymes help convert vitamin D3 into a hormone that regulates calcium (Ca2+) balance.
What is the reserve capacity of the kidneys?
You must lose nearly three-fourths of kidney function before homeostasis begins to be affected. Many people function normally with only one kidney.
What is the study of kidney function called?
The study of kidney function is called renal physiology, from the Latin word renes, meaning “kidneys.”
What are the components of the urinary system?
The urinary system is composed of the kidneys, ureters, bladder, and urethra.
How does urine production begin in the kidneys?
Urine production begins when water and solutes move from plasma into the hollow tubules (nephrons) that make up the bulk of the paired kidneys.
What is the pathway of urine from the kidneys to excretion?
Urine leaves the kidney through the ureter, passes into the urinary bladder, and is expelled through the urethra during micturition (urination).
Why are women more prone to urinary tract infections (UTIs) than men? What bacterium commonly causes urinary tract infections (UTIs)? What are the most common symptoms of a urinary tract infection (UTI)?
-Women have a shorter urethra and it is closer to bacteria from the large intestine, making them more susceptible to bacterial infections of the bladder and kidneys.
-The bacterium Escherichia coli (E. coli), a normal inhabitant of the human large intestine, commonly causes UTIs.
-Pain or burning during urination and increased frequency of urination. Urine may also contain red and white blood cells.
Where are the kidneys located in the body?
The kidneys are located on either side of the spine at the level of the 11th and 12th ribs, just above the waist, and are retroperitoneal (behind the peritoneal cavity)
What is the functional unit of the kidney? What are the two main layers of the kidney interior?
-The nephron is the functional unit of the kidney.
-The kidney interior is arranged in an outer cortex and an inner medulla.
What are the two types of nephrons in the kidney?
80% are cortical nephrons almost completely contained within the cortex, and 20% are juxtamedullary nephrons that dip into the medulla.
What is the renal portal system?
The renal portal system consists of two capillary beds in series: the glomerulus and the peritubular capillaries.
What is the function of the renal portal system?
To filter fluid out of the blood at the glomerular capillaries and reabsorb fluid from the tubule lumen back into the blood at the peritubular capillaries.
What is Bowman’s capsule?
Bowman’s capsule is a hollow, ball-like structure that surrounds the glomerulus and is part of the renal corpuscle.
What is the flow path of fluid through a nephron?
Fluid flows from Bowman’s capsule to the proximal tubule, then to the loop of Henle, then to the distal tubule, and finally to the collecting duct
What is the juxtaglomerular apparatus?
The juxtaglomerular apparatus is the region where the ascending limb of the loop of Henle passes between the afferent and efferent arterioles, allowing paracrine communication.
What is the role of the ureter?
The ureter is a smooth muscle tube that carries urine from the kidneys to the urinary bladder.
How does the urinary bladder function in the urinary system?
The bladder stores urine until it is expelled from the body through the urethra during urination (micturition).
How does the nephron’s structure facilitate its function?
The nephron twists and folds back on itself, allowing efficient filtering and reabsorption as fluid passes through different segments, closely associated with blood vessels.
What are peritubular capillaries and their function?
Peritubular capillaries surround the tubule and reabsorb fluid from the tubule lumen back into the blood. In juxtamedullary nephrons, they form the vasa recta.
What is the function of the renal arteries and veins?
Renal arteries supply blood to the kidneys, while renal veins carry blood away from the kidneys to the inferior vena cava.
Why do kidneys receive a high rate of blood flow?
Kidneys receive 20-25% of the cardiac output, which is critical for their function of filtering and regulating blood.
What is the significance of the nephron’s microvilli and tight junctions?
Microvilli increase surface area for absorption, and tight junctions regulate selective permeability for ions.
How does the nephron modify the composition of the fluid?
Through processes of filtration, reabsorption, and secretion as the fluid passes through its different segments.
How much plasma passes into the nephrons every day?
Approximately 180 liters of plasma pass into the nephrons each day.
What percentage of the fluid that enters nephrons is reabsorbed back into the blood?
More than 99% of the fluid that enters nephrons is reabsorbed back into the blood.
What are the three basic processes that take place in the nephron?
The three basic processes in the nephron are filtration, reabsorption, and secretion.
Where does filtration take place in the nephron?
Filtration takes place in the renal corpuscle.
What happens to the filtrate after it leaves Bowman’s capsule?
After leaving Bowman’s capsule, the filtrate is modified by reabsorption and secretion as it passes through the tubule.
Define reabsorption in the context of kidney function.
Reabsorption is the process of moving substances in the filtrate from the lumen of the tubule back into the blood flowing through peritubular capillaries.
Define secretion in the context of kidney function.
Secretion is the selective removal of molecules from the blood, adding them to the filtrate in the tubule lumen
What is the primary function of the proximal tubule?
The primary function of the proximal tubule is the isosmotic reabsorption of solutes and water.
What happens to the filtrate in the loop of Henle?
In the loop of Henle, more solute is reabsorbed than water, making the filtrate hyposmotic relative to plasma.
How much filtrate remains by the time it reaches the end of the collecting duct?
By the end of the collecting duct, the filtrate volume is about 1.5 liters per day.
What factors determine the final volume and osmolarity of urine?
The final volume and osmolarity of urine depend on the body’s need to conserve or excrete water and solute, under hormonal control.
What is the difference between secretion and excretion in the nephron?
Secretion refers to moving solutes from plasma to the tubule lumen, while excretion refers to removing a substance from the body.
What is the equation for the amount of a substance excreted in the urine?
Amount excreted = amount filtered - amount reabsorbed + amount secreted.
What is the function of filtration in the renal corpuscle?
Filtration in the renal corpuscle moves fluid from the capillaries of the glomerulus into Bowman’s capsule.
What occurs during reabsorption and secretion along the tubule?
During reabsorption and secretion, materials are transferred between the lumen and the peritubular capillaries.
How does the nephron modify fluid volume and osmolarity?
The nephron modifies fluid volume and osmolarity by reabsorbing water and solutes and secreting specific molecules at various segments.
What happens to filtrate in the distal tubule and collecting duct?
In the distal tubule and collecting duct, fine regulation of salt and water balance occurs under hormonal control.
What is the purpose of the juxtaglomerular apparatus in the nephron?
The juxtaglomerular apparatus facilitates paracrine communication between the ascending limb of the loop of Henle and the arterioles, aiding kidney autoregulation.
Why is it important for the kidneys to reabsorb most of the fluid filtered into Bowman’s capsule?
Reabsorption of most of the fluid is crucial to prevent dehydration, as the body must maintain proper fluid balance.
What happens to the osmolarity of filtrate as it passes through the loop of Henle?
The filtrate becomes hyposmotic relative to plasma as more solute than water is reabsorbed.
What processes determine the final composition of filtrate in the nephron?
The final composition of filtrate is determined by reabsorption and secretion processes in the distal tubule and collecting duct.
Why is it important to distinguish between secretion and excretion?
It is important because secretion involves transferring substances into the tubule, while excretion involves removing them from the body.
What role do the kidneys play in the homeostatic regulation of blood?
The kidneys maintain blood ion concentrations and water balance, regulate extracellular fluid volume and blood pressure, and manage waste removal and pH levels.
What is the first step in urine formation?
The first step in urine formation is the filtration of plasma into the kidney tubule
How does the composition of filtrate compare to plasma?
The filtrate is like plasma minus most of the plasma proteins.
What remains in the capillary under normal filtration conditions?
Blood cells remain in the capillary under normal filtration conditions.
What fraction of plasma filters into the nephrons?
Only about one-fifth of the plasma filters into the nephrons.
What happens to the remaining four-fifths of the plasma?
The remaining four-fifths of the plasma flows into the peritubular capillaries.
What is the filtration fraction?
The filtration fraction is the percentage of renal plasma flow that filters into the tubule.
Where does filtration take place in the kidney?
Filtration takes place in the renal corpuscle.
What structures make up the renal corpuscle?
The renal corpuscle consists of the glomerular capillaries surrounded by Bowman’s capsule.
What are the three filtration barriers substances must pass through in the renal corpuscle?
Substances must pass through the glomerular capillary endothelium, the basement membrane, and the epithelium of Bowman’s capsule
Describe the first filtration barrier.
The first filtration barrier is the capillary endothelium, which has large pores (fenestra) that allow most plasma components to filter through.
What is the role of the glycocalyx in the first filtration barrier?
The glycocalyx, a layer of negatively charged glycoproteins, helps repel negatively charged plasma proteins and prevents blood cells from leaving the capillary.
What is the second filtration barrier?
The second filtration barrier is the basement membrane, an acellular layer that separates the capillary endothelium from Bowman’s capsule epithelium.
What is the composition and function of the basement membrane?
The basement membrane consists of negatively charged glycoproteins, collagen, and other proteins, and acts like a coarse sieve to exclude most plasma proteins from the filtrate.
Describe the third filtration barrier
The third filtration barrier is the epithelium of Bowman’s capsule, made up of podocytes with foot processes that interlace, leaving filtration slits closed by a slit diaphragm.
What is the function of the slit diaphragm in the third filtration barrier?
The slit diaphragm, containing proteins like nephrin and podocin, forms a two-layer sieve to regulate filtration.
What happens in congenital kidney diseases where nephrin or podocin are absent or abnormal?
The filtration barrier does not function properly, leading to protein leakage into the urine.
What is the role of glomerular mesangial cells?
Glomerular mesangial cells provide structural support, influence filtration by altering the surface area of filtration slits, and secrete cytokines involved in immune and inflammatory processes.
What drives filtration across the walls of the glomerular capillaries?
Filtration is driven by capillary blood pressure, capillary colloid osmotic pressure, and capsule fluid pressure.
What is the hydrostatic pressure (P H ) in glomerular capillaries and its effect?
Hydrostatic pressure in glomerular capillaries averages 55 mm Hg and favors filtration into Bowman’s capsule.
How does capillary colloid osmotic pressure (π) influence glomerular filtration?
Capillary colloid osmotic pressure averages 30 mm Hg, due to plasma proteins, and favors fluid movement back into the capillaries.
What is the hydrostatic fluid pressure (P fluid ) in Bowman’s capsule?
The hydrostatic fluid pressure in Bowman’s capsule averages 15 mm Hg and opposes filtration.
What is the net driving force for filtration in the glomerulus? What is the glomerular filtration rate (GFR)?
-The net driving force is 10 mm Hg, favoring filtration.
-GFR is the volume of fluid that filters into Bowman’s capsule per unit time, averaging 125 mL/min or 180 L/day.
How often is the entire plasma volume filtered by the kidneys?
The kidneys filter the entire plasma volume 60 times a day, or 2.5 times every hour.
What factors influence GFR?
GFR is influenced by net filtration pressure and the filtration coefficient, which includes surface area of the glomerular capillaries and permeability of filtration slits.
What determines filtration pressure?
Filtration pressure is determined primarily by renal blood flow and blood pressure.
How does the filtration coefficient affect GFR?
The filtration coefficient is determined by the surface area of the glomerular capillaries available for filtration and the permeability of the filtration slits.
Is GFR constant over different blood pressures? How is GFR controlled?
-Yes, GFR remains relatively constant as long as mean arterial blood pressure is between 80 mm Hg and 180 mm Hg.
-GFR is controlled primarily by regulation of blood flow through the renal arterioles.
What happens if resistance increases in the afferent arteriole? What is the effect of increased resistance in the efferent arteriole on GFR? Where does most regulation of GFR occur?
-If resistance increases in the afferent arteriole, hydrostatic pressure decreases on the glomerular side, leading to a decrease in GFR.
-Increased resistance in the efferent arteriole increases hydrostatic pressure in the glomerular capillaries, leading to an increase in GFR.
-Most regulation of GFR occurs at the afferent arteriole.
What is the average hydrostatic pressure in the glomerular capillaries?
The average hydrostatic pressure in the glomerular capillaries is 55 mm Hg.
What is the role of glomerular capillary endothelium in filtration?
The glomerular capillary endothelium, with large pores (fenestra), allows most plasma components to filter through.
How does the glycocalyx on the glomerular capillary endothelium function in filtration?
The glycocalyx, a negatively charged glycoprotein layer, helps repel negatively charged plasma proteins and prevents blood cells from leaving the capillary.
Describe the function of the basement membrane in filtration.
The basement membrane acts like a coarse sieve, excluding most plasma proteins from the filtrate due to its negatively charged glycoproteins, collagen, and other proteins.
What are podocytes and their role in filtration?
Podocytes are specialized cells with foot processes that wrap around glomerular capillaries, creating filtration slits closed by a slit diaphragm to regulate filtration.
What happens in congenital kidney diseases related to nephrin or podocin?
In these diseases, where nephrin or podocin are absent or abnormal, the filtration barrier does not function properly, causing protein leakage into the urine.
What is the role of glomerular mesangial cells in filtration?
Glomerular mesangial cells provide structural support, influence filtration by altering the surface area of filtration slits, and secrete cytokines involved in immune and inflammatory processes.
What is autoregulation of glomerular filtration rate (GFR)?
Autoregulation is a local control process in which the kidney maintains a relatively constant GFR despite normal fluctuations in blood pressure. This protects the filtration barriers from high blood pressures that could cause damage.
What are the mechanisms involved in GFR autoregulation?
The mechanisms involved in GFR autoregulation include the myogenic response and tubuloglomerular feedback
Describe the myogenic response in GFR autoregulation.
The myogenic response is the intrinsic ability of vascular smooth muscle to respond to pressure changes. Increased blood pressure stretches smooth muscle in the arteriole wall, opening stretch-sensitive ion channels, causing depolarization, and opening voltage-gated Ca²⁺ channels. This results in muscle contraction and vasoconstriction, reducing blood flow and filtration pressure in the glomerulus.
What happens to the afferent arteriole during decreased blood pressure?
During decreased blood pressure, the tonic level of arteriolar contraction disappears, and the arteriole becomes maximally dilated. However, vasodilation is less effective at maintaining GFR because the afferent arteriole is normally relaxed.
What is tubuloglomerular feedback in the context of GFR autoregulation?
Tubuloglomerular feedback is a local control pathway in which fluid flow through the tubule influences GFR. The macula densa in the thick ascending limb of the loop of Henle sends paracrine messages to the afferent arteriole to regulate GFR based on NaCl delivery.
What is the juxtaglomerular apparatus, and what are its components?
The juxtaglomerular apparatus is the region where the thick ascending limb of the loop of Henle contacts the afferent and efferent arterioles. It includes the macula densa (tubule epithelium) and granular cells (smooth muscle cells in the afferent arteriole).
What role does the macula densa play in tubuloglomerular feedback?
The macula densa senses increased NaCl delivery due to increased GFR and sends paracrine signals to the afferent arteriole, causing it to constrict and decrease GFR.
How does paracrine signaling between the macula densa and the afferent arteriole work?
Paracrine signaling involves multiple signals, including ATP, adenosine, and nitric oxide, which pass from the macula densa to the afferent arteriole, influencing GFR.
How do hormones and autonomic neurons influence GFR?
Hormones and autonomic neurons influence GFR by changing resistance in the arterioles and altering the filtration coefficient. Sympathetic neurons cause vasoconstriction, decreasing GFR and renal blood flow, especially during low blood pressure conditions.
Which hormones affect arteriolar resistance and how?
Angiotensin II, a potent vasoconstrictor, and prostaglandins, which are vasodilators, influence arteriolar resistance. These hormones also affect the filtration coefficient by acting on podocytes and mesangial cells.
What is the role of podocytes in regulating GFR?
Podocytes can change the size of the glomerular filtration slits. If the slits widen, more surface area is available for filtration, increasing GFR.
How does the kidney conserve blood volume when mean blood pressure drops below 80 mm Hg?
When mean blood pressure drops below 80 mm Hg, GFR decreases to conserve blood volume by reducing the potential for fluid loss in the urine.
What are primary cilia on renal tubule cells and their function?
Primary cilia on renal tubule cells act as flow sensors and signal transducers for normal development, playing a role in sensing fluid flow in the tubules.
What happens during sympathetically induced vasoconstriction of the arterioles?
During sympathetically induced vasoconstriction, GFR and renal blood flow decrease to help conserve fluid volume, especially during conditions like hemorrhage or severe dehydration.
How much filtered fluid enters the kidney tubules each day, and how much is excreted in urine?
180 liters of filtered fluid enter the kidney tubules each day, but only about 1.5 liters are excreted in the urine. More than 99% of the fluid is reabsorbed into the blood.
Where does most reabsorption occur in the nephron?
Most reabsorption occurs in the proximal tubule, with a smaller amount in the distal segments of the nephron.
Why is there a high daily filtration rate if most of the filtrate is reabsorbed?
The high filtration rate helps clear unwanted substances from the plasma rapidly and simplifies the regulation of ions and water, allowing rapid excretion or reabsorption as needed for homeostasis.
How does reabsorption maintain homeostasis?
Reabsorption in the distal nephron is regulated to selectively return ions and water to the plasma as needed to maintain homeostasis.
What happens to foreign substances filtered into the nephron?
Foreign substances filtered into the nephron are not reabsorbed and are excreted in the urine, helping clear such substances from the plasma.
How are nutrients like glucose and citric acid cycle intermediates handled by the nephron?
These nutrients are filtered in large amounts and efficiently reabsorbed by transporters in the proximal tubule.
What is the advantage of filtering ions and water into the tubule?
Filtering ions and water into the tubule simplifies their regulation. If they are not needed, they are excreted. If they are needed, they are reabsorbed and returned to the blood.
What are the main processes involved in reabsorption?
Reabsorption involves both active and passive transport, with active transport creating concentration or electrochemical gradients that drive the movement of water and solutes from the tubule lumen to the extracellular fluid.
How does active transport of Na+ facilitate reabsorption?
Active transport of Na+ from the tubule lumen to the extracellular fluid creates an electrical gradient, attracting anions, which leads to water following by osmosis. This increases the concentration of other solutes in the lumen, facilitating their diffusion.
What are the pathways for reabsorption?
Reabsorption can occur through transepithelial (transcellular) transport, where substances cross the apical and basolateral membranes of epithelial cells, or through the paracellular pathway, where substances pass through cell-cell junctions.
What determines the route a solute takes during reabsorption?
The permeability of the epithelial junctions and the electrochemical gradient for the solute determine whether a solute uses transepithelial transport or the paracellular pathway.
How does passive transport of solutes occur in the nephron?
Solutes moving down their concentration or electrochemical gradients use open leak channels or facilitated diffusion carriers to cross cell membranes.
How are molecules moved against their gradient during reabsorption?
Molecules are moved against their gradient by primary active transport or secondary (indirect) active transport, often involving Na+.
What is the primary driving force for renal reabsorption?
The active reabsorption of Na+ is the primary driving force, with Na+ entering tubule cells passively and being actively transported out across the basolateral membrane.
How does secondary active transport work in the nephron? What is an example of sodium-linked secondary active transport?
-Sodium-linked secondary active transport uses the energy from Na+ moving down its gradient to transport other substances, like glucose, into tubule cells.
-An example is Na+-dependent glucose reabsorption in the proximal tubule, where the Na+-glucose cotransporter (SGLT) brings glucose into the cytoplasm against its gradient.
How does the Na+-glucose cotransporter (SGLT) work?
SGLT uses the energy of Na+ moving down its electrochemical gradient to bring glucose into the cytoplasm against its concentration gradient.
How does glucose exit the tubule cells after being reabsorbed?
On the basolateral side, Na+ is pumped out by the Na+-K+-ATPase, while glucose diffuses out with the aid of a facilitated diffusion GLUT transporter.
What other molecules are reabsorbed by sodium-linked secondary active transport?
Other molecules include amino acids, lactate, citric acid cycle intermediates like citrate and α-ketoglutarate, and ions like phosphate and sulfate.
How is urea reabsorbed in the nephron?
Urea is reabsorbed passively by diffusion through epithelial junctions when a concentration gradient is created by the reabsorption of Na+ and other solutes.
How does the concentration gradient for urea develop?
When Na+ and other solutes are reabsorbed from the proximal tubule, the transfer of osmotically active particles makes the extracellular fluid more concentrated, creating a gradient for urea to diffuse out of the lumen.
How are plasma proteins reabsorbed in the nephron?
Filtered plasma proteins are reabsorbed by receptor-mediated endocytosis in the proximal tubule, digested in lysosomes, and the resulting amino acids are absorbed into the blood.
Why is the reabsorption of small filtered proteins significant?
The renal digestion of small filtered proteins is a significant method by which peptide signal molecules are removed from the circulation, contributing to homeostasis.
Describe the characteristics of mediated transport in the nephron.
Most transport in the nephron uses membrane proteins and exhibits three key characteristics: saturation, specificity, and competition. Saturation refers to the maximum rate of transport that occurs when all available carriers are occupied by substrate. Specificity means that transporters are specific to certain substrates. Competition occurs when different substrates compete for the same transporter.
What is saturation in the context of nephron transport, and why is it significant?
Saturation in nephron transport occurs when all available transporters are fully occupied. At substrate concentrations below the saturation point, the transport rate is directly related to substrate concentration. However, at substrate concentrations equal to or above the saturation point, transport occurs at a maximum rate, known as the transport maximum (T_m). This is significant because it limits the amount of substrate that can be reabsorbed or secreted by the nephron.
How does glucose reabsorption in the nephron illustrate the concept of saturation?
Glucose reabsorption in the nephron is a prime example of saturation. At normal plasma glucose concentrations, all glucose entering the nephron is reabsorbed before it reaches the end of the proximal tubule, as the tubule epithelium has enough carriers to capture the glucose. However, in conditions like diabetes mellitus, where blood glucose levels become excessive, glucose is filtered faster than the carriers can reabsorb it. Once the carriers are saturated, any additional glucose cannot be reabsorbed and is thus excreted in the urine.
Explain the analogy of glucose reabsorption in the nephron using a moving train at Disney World.
Imagine the glucose carriers as seats on a train at Disney World. Passengers (glucose molecules) board the train via a moving sidewalk that rolls them past the train. If the number of passengers exceeds the number of available seats, some passengers will not find seats and will be carried past the train to the exit. Similarly, if glucose molecules filter into the tubule faster than they can be transported, the excess glucose remains in the lumen and is excreted in the urine.
Describe the relationship between the filtration rate of glucose and plasma glucose concentration.
The filtration rate of glucose from plasma into Bowman’s capsule is directly proportional to the plasma concentration of glucose. Filtration does not exhibit saturation, meaning the graph of filtration rate against plasma glucose concentration is a straight line extending infinitely, indicating that the filtrate glucose concentration is always equal to the plasma glucose concentration.
How does the reabsorption rate of glucose in the nephron relate to plasma glucose concentration?
The reabsorption rate of glucose in the proximal tubule is plotted against plasma glucose concentration. Reabsorption shows a maximum transport rate (T_m) when the carriers reach saturation. Under normal plasma glucose levels, the concentration is well below the saturation point, allowing complete reabsorption of glucose. However, as plasma glucose concentration increases beyond the saturation point, the carriers cannot reabsorb all the glucose, leading to excretion.
Explain the excretion rate of glucose in relation to plasma glucose concentration
The excretion rate of glucose in urine is the result of the balance between filtration and reabsorption. At low plasma glucose concentrations, all filtered glucose is reabsorbed, and no glucose is excreted. Once the plasma glucose concentration reaches the saturation point of the transporters, excess glucose begins to appear in the urine. Thus, excretion of glucose starts when filtration exceeds the reabsorption capacity of the nephron.
What is the renal threshold for glucose, and why is it important?
The renal threshold for glucose is the plasma concentration at which glucose first begins to appear in the urine. This threshold indicates the point at which the glucose carriers in the nephron become saturated, and any additional glucose cannot be reabsorbed, leading to its excretion. It is important because it marks the limit of the kidney’s ability to reabsorb glucose and reflects the body’s glucose management capacity.
Define glucosuria and discuss its causes.
Glucosuria, or glycosuria, is the presence of glucose in the urine. This condition usually indicates an elevated blood glucose concentration, often seen in diabetes mellitus when the renal threshold for glucose is exceeded. In rare cases, glucosuria can occur even with normal blood glucose levels due to a genetic disorder that results in insufficient glucose transporters in the nephron, preventing complete reabsorption.
How do peritubular capillary pressures favor reabsorption in the nephron?
Reabsorption from the tubule lumen to the interstitial fluid is facilitated by the pressure differences in the peritubular capillaries. The hydrostatic pressure in these capillaries is low, averaging 10 mm Hg, while the colloid osmotic pressure is higher, at 30 mm Hg. This results in a net pressure gradient of 20 mm Hg, favoring the movement of fluid from the interstitial space back into the capillaries, ensuring that reabsorbed substances are efficiently returned to the blood circulation.
Describe the pathway and process of reabsorbed fluid in the nephron.
Fluid reabsorbed from the tubule lumen first enters the interstitial fluid. From there, it moves into the peritubular capillaries, driven by the favorable pressure gradient. The peritubular capillaries, with their lower hydrostatic pressure and higher colloid osmotic pressure, facilitate the uptake of reabsorbed fluid. This fluid then joins the venous circulation, eventually returning to the heart, thus maintaining overall fluid balance in the body.
What is secretion in the nephron, and what is its importance?
Secretion in the nephron is the transfer of molecules from the extracellular fluid into the lumen of the nephron. It relies on membrane transport systems and is crucial for the homeostatic regulation of ions like K+ and H+. Secretion also helps eliminate many organic compounds, both endogenous and xenobiotics, enhancing the excretion of substances filtered by the nephron.
How does secretion in the nephron enhance excretion efficiency?
Secretion enhances excretion efficiency by adding substances directly into the nephron lumen from the peritubular capillaries. If a substance is filtered into the nephron but not reabsorbed, its excretion is very efficient. However, if the substance is also secreted into the lumen after filtration, the efficiency of its excretion is further increased.
What is the role of the organic anion transporter (OAT) family in nephron secretion?
The OAT family is responsible for the secretion of a wide variety of organic anions, including endogenous compounds like bile salts and exogenous substances like benzoate from preservatives and salicylate from aspirin. These transporters use tertiary active transport, where the energy from ATP is two steps removed from the actual transport process.
Describe the process of tertiary active transport in the secretion of organic anions.
Tertiary active transport in the secretion of organic anions involves three steps:
- Direct active transport: ATP is used to maintain low intracellular Na+ concentration.
- Na+ gradient: This gradient drives the Na+-dicarboxylate cotransporter (NaDC), concentrating dicarboxylates inside the tubule cell.
- Organic anion transport: OAT transporters use the dicarboxylate gradient to move organic anions into the tubule cell against their gradient, followed by apical OAT4 exchanging the organic anion into the lumen for a dicarboxylate.
What are dicarboxylates, and how do they contribute to the secretion process?
Dicarboxylates are the anion forms of dicarboxylic acids, such as citrate, oxaloacetate, and α-ketoglutarate (αKG), which are intermediates in the citric acid cycle. The NaDC cotransporter uses the Na+ gradient to concentrate these dicarboxylates inside the tubule cell, driving the secretion of organic anions by the OAT transporters
How does competition affect the secretion of organic anions, and what is a historical example of this?
The broad specificity of the OAT family means that different substrates compete for transporter binding sites. An important historical example is the competition between penicillin and the synthetic compound probenecid. Probenecid competes with penicillin for OAT binding, reducing penicillin secretion and prolonging its activity in the body. This was crucial during World War II when penicillin supply was limited.
What is the overall net result of organic anion secretion in the nephron?
The net result of organic anion secretion is the reabsorption of desirable metabolic intermediates in exchange for the secretion of unwanted organic anions. This process ensures that beneficial substances are retained while harmful or excess organic anions are efficiently excreted from the body through the urine.
What happens to fluid by the time it reaches the end of the nephron?
By the time fluid reaches the end of the nephron, it bears little resemblance to the filtrate that started in Bowman’s capsule. Glucose, amino acids, and useful metabolites are reabsorbed into the blood, and organic wastes are more concentrated. The concentrations of ions and water in the urine vary depending on the body’s state.
Why can’t excretion alone tell us the details of renal function?
Excretion by itself cannot tell us the details of renal function because it only shows what the body is eliminating. The excretion rate of a substance depends on its filtration rate and whether it is reabsorbed, secreted, or both, as it passes through the tubule.
What is clearance in the context of renal physiology?
Clearance is the rate at which a solute disappears from the body by excretion or by metabolism. It is expressed as the volume of plasma from which the solute is completely cleared per minute (mL/min)
How is the clearance of a solute calculated?
Clearance of a solute is calculated using the formula:
Clearance of X = Excretion rate of X (mg/min) / [X]plasma (mg/mLplasma)
What is inulin, and why is it used to measure GFR?
Inulin is a polysaccharide that filters freely into the nephron and is neither reabsorbed nor secreted. This means 100% of inulin that filters is excreted, making inulin clearance equal to GFR, providing a precise measure of filtration rate.
How does the concept of filtration load relate to inulin clearance?
Filtration load of inulin is calculated by multiplying its plasma concentration by GFR. Since all filtered inulin is excreted, inulin clearance equals the filtration rate, thus GFR can be calculated using inulin clearance.
How can clearance values determine renal handling of solutes?
By comparing the filtered load of a solute (plasma concentration * GFR) with its excretion rate, one can determine if net reabsorption or net secretion has occurred. If the excretion rate is lower than the filtered load, reabsorption has occurred; if higher, secretion has occurred.
Describe the handling of glucose in the nephron.
Glucose is filtered at the glomerulus and completely reabsorbed in the proximal tubule under normal conditions, resulting in no glucose in the urine. In cases of high plasma glucose, such as diabetes mellitus, not all glucose is reabsorbed, and it appears in the urine.
What does it mean if the clearance of a solute is less than the clearance of inulin?
If the clearance of a solute is less than the clearance of inulin, it indicates that the solute has been reabsorbed. Inulin clearance represents GFR because it is neither reabsorbed nor secreted.
What does it mean if the clearance of a solute is greater than the clearance of inulin?
If the clearance of a solute is greater than the clearance of inulin, it indicates that there has been net secretion of the solute into the tubule lumen. More plasma is cleared of the solute than filtered.
How is urea handled by the nephron?
Urea is partially reabsorbed in the nephron. If 4 molecules of urea are filtered and 2 are reabsorbed, the clearance of urea is 50 mL/min. Urea clearance being less than inulin clearance indicates net reabsorption.
How is penicillin handled by the nephron?
Penicillin is filtered but not reabsorbed, and additional penicillin is secreted into the tubule. If 4 molecules are filtered and 6 are excreted, penicillin clearance is 150 mL/min, indicating net secretion.
How is clearance used to estimate renal plasma flow with PAH? What is the significance of PAH clearance?
-PAH is completely cleared from the plasma in one pass through the kidneys. By administering PAH and measuring its clearance, renal plasma flow can be determined. If 100 mL of plasma with 100 mg PAH enters the kidney, and all PAH is excreted, the clearance equals the renal plasma flow (100 mL/min).
-PAH clearance equals renal plasma flow because PAH is completely cleared from the plasma in one pass through the kidneys, making it a valuable tool for measuring renal blood flow.
What is the role of secretion in renal function?
Secretion is the transfer of molecules from extracellular fluid into the lumen of the nephron. It depends on membrane transport systems and enhances the excretion of substances. Secretion is an active process, often involving indirect active transport.
How does secretion enhance excretion efficiency?
If a substance is filtered and not reabsorbed, it is efficiently excreted. If it is additionally secreted into the tubule from peritubular capillaries, excretion efficiency increases further.
Describe the secretion of organic anions in the nephron.
The secretion of organic anions involves the organic anion transporter (OAT) family. It uses tertiary active transport, where ATP is used indirectly. Na+-dicarboxylate cotransporters concentrate dicarboxylate inside the tubule cell, driving the OAT to exchange dicarboxylate for organic anions.
Explain tertiary active transport in the secretion of organic anions.
Tertiary active transport involves three steps: (1) ATP is used to maintain low intracellular Na+ concentration, (2) the Na+ gradient is used to concentrate dicarboxylates inside the cell, and (3) OATs use the dicarboxylate gradient to exchange dicarboxylate for organic anions.
What role does the organic anion transporter (OAT) play in the kidney?
OATs transport a variety of endogenous and exogenous anions. They use the gradient of dicarboxylates to move organic anions into the tubule cell against their concentration gradient, which are then secreted into the lumen.
What does the excretion rate of a substance depend on?
The excretion rate of a substance depends on its filtration rate and whether it is reabsorbed, secreted, or both as it passes through the tubule.
Define clearance in renal physiology.
Clearance is the rate at which a solute disappears from the body by excretion or metabolism. It is calculated as the excretion rate of the solute divided by its plasma concentration, expressed as mL of plasma cleared per minute.
What is creatinine, and why is it used to estimate GFR?
Creatinine is a breakdown product of phosphocreatine, produced at a constant rate in muscles. It is used to estimate GFR because it is always present in the plasma and easy to measure, despite a small amount being secreted.
What happens to filtrate once it leaves the collecting ducts?
Once filtrate leaves the collecting ducts, it can no longer be modified. The filtrate, now called urine, flows into the renal pelvis and then down the ureter with the help of rhythmic smooth muscle contractions that spurt urine into the bladder.
Describe the structure and function of the bladder
The bladder is a hollow organ with well-developed layers of smooth muscle. It stores urine until released in urination, voiding, or micturition. The bladder can expand to hold about 500 mL of urine.
What are the sphincters that control the release of urine from the bladder?
The internal sphincter is a continuation of the bladder wall and consists of smooth muscle, normally kept contracted. The external sphincter is a ring of skeletal muscle controlled by somatic motor neurons, maintained in contraction by tonic stimulation from the CNS.
Explain the process of micturition.
Micturition is a simple spinal reflex controlled by both conscious and unconscious signals from the brain. As the bladder fills and stretches, sensory neurons send signals to the spinal cord. This excites parasympathetic neurons, causing the bladder to contract and inhibit somatic motor neurons, leading to the relaxation of the external sphincter.
How does the micturition reflex work in infants? What changes in micturition occur with toilet training?
-In infants, the micturition reflex is primarily a simple spinal reflex. Stretch receptors in the bladder send signals to the spinal cord, initiating parasympathetic stimulation of the bladder muscle and inhibition of the external sphincter, resulting in urination.
-With toilet training, a learned reflex develops that inhibits the micturition reflex until a conscious decision to urinate is made. This involves additional sensory fibers in the bladder, signaling fullness to the brainstem and cerebral cortex, which then override the reflex by inhibiting parasympathetic fibers and reinforcing the external sphincter contraction.
Describe the conscious control of micturition in trained individuals
In trained individuals, brain centers in the brainstem and cerebral cortex receive information about bladder fullness and inhibit the micturition reflex until the person decides to urinate. At the appropriate time, these centers remove the inhibition and facilitate urination by relaxing the external sphincter.
How does the bladder signal fullness to the central nervous system?
As the bladder fills and stretches, stretch receptors send signals via sensory neurons to the spinal cord. This information is integrated and sent to brain centers, signaling the degree of bladder fullness and helping to control the micturition reflex.
What happens when the micturition reflex is facilitated? What is the role of the parasympathetic and somatic motor neurons in micturition?
-When the micturition reflex is facilitated, the parasympathetic fibers stimulate bladder contraction, and inhibition of the somatic motor neurons relaxes the external sphincter. This coordinated action allows urine to pass through the urethra and out of the body.
-The parasympathetic neurons stimulate the contraction of the bladder’s smooth muscle, increasing pressure and aiding in urination. The somatic motor neurons control the external sphincter, maintaining its contraction until urination is consciously desired.
What are the four parameters aimed at maintaining fluid and electrolyte balance in the body?
The four parameters are fluid volume, osmolarity, concentrations of individual ions, and pH.
How much fluid and NaCl does the human body ingest daily?
The human body ingests about 2 liters of fluid containing 6–15 grams of NaCl daily.
What are the routes for excreting ions and water in the body?
The primary route is through the kidneys. Small amounts are also lost in feces and sweat, and the lungs lose water and help remove H+ and HCO3- by excreting CO2.
