Unit 4 Flashcards
Study
What are the consequences of a typical North American diet high in NaCl on body osmolarity without water intake?
Consuming 9g NaCl per day without additional water leads to an increase in [Na+] in the extracellular fluid (ECF), resulting in hyperosmolarity and potential cell shrinkage. If the kidneys are not clearing any salt, 1.1 L extra water per day is needed to maintain normal [Na+] in ECF.
How does the body respond to increased salt ingestion?
Ingested NaCl without change in volume leads to increased osmolarity, causing vasopressin secretion, thirst, increased water intake, increased renal water reabsorption, increased ECF volume, and increased blood pressure. Cardiovascular reflexes then lower blood pressure, and the kidneys excrete salt and water to normalize osmolarity and blood pressure.
Describe the reabsorption and secretion process in the nephron.
The nephron filters 180 L/day with 100% volume at Bowman’s capsule. Proximal tubule reabsorbs ~70% fluid and solute. Loop of Henle receives 30% volume, with the ascending loop being hypo-osmotic relative to plasma. Distal tubule and collecting duct fine-tune water/salt balance under endocrine control.
What happens to cell volume when high NaCl intake is not offset by water?
Cells shrink due to hyperosmolarity of the extracellular fluid.
Explain how the body’s osmoregulation mechanisms respond to high NaCl intake without an increase in volume.
Upon high NaCl intake, osmoregulation begins with the secretion of vasopressin and the sensation of thirst, leading to increased water intake and retention. This results in an increase in extracellular fluid volume, which elevates blood pressure. Cardiovascular reflexes and kidney excretion then act to reduce blood pressure and return osmolarity to normal.
How much fluid is reabsorbed in the proximal tubule of the nephron?
Approximately 70% of the fluid is reabsorbed in the proximal tubule.
What role does the loop of Henle play in urine concentration?
The loop of Henle establishes a concentration gradient that allows for the regulation of urine concentration and volume.
What stimulates aldosterone secretion and what are the implications of this secretion on ion balance and blood pressure?
Aldosterone secretion is stimulated by increased plasma [K+] and decreased blood pressure. It activates the renin-angiotensin-aldosterone system (RAAS) to increase Na+ reabsorption and K+ secretion, which in turn helps to increase blood volume and pressure.
What cellular mechanisms does aldosterone activate in the adrenal cortex?
Aldosterone acts on intracellular receptors to induce gene expression for new pumps and channels, particularly increasing the number of epithelial sodium channels (ENaC) and Na+/K+ ATPase pumps.
What are the specific roles of aldosterone at the apical and basolateral membranes of principal cells?
At the apical membrane, aldosterone increases Na+ import and K+ export, while at the basolateral membrane, it enhances the activity of Na+/K+ ATPase pumps.
Explain the dual impact of aldosterone on sodium and potassium homeostasis.
Aldosterone facilitates sodium reabsorption and potassium secretion in the distal nephron, aiding in fluid balance and preventing hyperkalemia.
How do the actions of aldosterone contribute to blood pressure regulation?
By increasing Na+ reabsorption, aldosterone contributes to water retention, which increases extracellular fluid volume and blood pressure.
What physiological conditions prompt the adrenal cortex to release aldosterone?
The adrenal cortex releases aldosterone in response to high plasma potassium levels or low blood pressure, as part of the body’s effort to maintain electrolyte balance and blood pressure.
What is the result of aldosterone-induced Na+ reabsorption in the distal nephron?
Enhanced Na+ reabsorption in the distal nephron leads to an increase in blood volume and pressure, as water passively follows the reabsorbed sodium.
Describe the process of aldosterone-mediated gene expression and its outcome in the distal nephron.
Aldosterone stimulates gene expression for sodium channels and pumps in the distal nephron, resulting in increased sodium reabsorption and potassium secretion.
What percentage of body potassium is found in the extracellular fluid (ECF)?
Only a small proportion (2%) of the body’s potassium is in the ECF, with the majority inside cells.
Why is it important to maintain ECF potassium concentrations within a narrow range?
ECF potassium concentrations are crucial in determining the resting membrane potential and excitability of excitable cells.
What are the effects of hyperkalemia on cellular function?
Hyperkalemia reduces the concentration gradient across the cell membrane, causing cells to be depolarized, which can lead to cardiac arrhythmias.
What is the role of the renin-angiotensin system (RAS)?
The RAS regulates blood pressure and fluid balance, where renin converts angiotensinogen to angiotensin I, which is then converted to angiotensin II by ACE, leading to aldosterone release.
What is the function of granular cells in the juxtaglomerular apparatus?
Granular cells secrete the enzyme renin, which is involved in salt and water balance regulation.
What condition can result from hypokalemia, and how does it affect cell function?
Hypokalemia can cause cells to become hyperpolarized, leading to muscle weakness.
Explain the pathophysiology of how hyperkalemia and hypokalemia can affect cardiac and muscle cell function.
Hyperkalemia causes cells to depolarize prematurely, increasing the risk of arrhythmias, while hypokalemia leads to hyperpolarization, which decreases excitability and can result in muscle weakness.
Describe the regulatory mechanisms that the juxtaglomerular apparatus uses to control renal blood flow and filtration rate.
The juxtaglomerular apparatus regulates GFR by using the macula densa cells to detect changes in sodium chloride concentration, signaling granular cells to release renin, and altering arteriole resistance to adjust renal blood flow.
What are the components of the juxtaglomerular apparatus and their functions?
The juxtaglomerular apparatus includes the macula densa, which senses sodium chloride levels in the distal tubule, and the granular cells (JG cells), which secrete renin in response to low blood pressure.
How does the Renin-Angiotensin System (RAS) respond to a drop in blood pressure?
RAS responds to a drop in BP by releasing renin, which leads to the production of angiotensin II, causing vasoconstriction, increased aldosterone release, and a rise in BP.
What stimulates the release of renin from the juxtaglomerular cells?
Renin release is stimulated by low blood pressure detected by the granular cells, decreased NaCl transport across the macula densa, and sympathetic nervous system activation.
How does angiotensin II correct a drop in blood pressure?
Angiotensin II corrects low BP by causing vasoconstriction, increasing sympathetic activity, promoting aldosterone and antidiuretic hormone release, and triggering thirst and salt appetite.
What role does the liver play in the Renin-Angiotensin System?
The liver continuously produces angiotensinogen, which is the inactive precursor in the RAS pathway that is converted to active peptides by renin and ACE.
What is the significance of the RAS in treating hypertension?
RAS is targeted in hypertension treatment using ACE inhibitors, angiotensin receptor blockers, and direct renin inhibitors to reduce angiotensin II levels and its effects.
Describe the feedback loop involving the juxtaglomerular apparatus in regulating glomerular filtration rate (GFR) and blood pressure.
The juxtaglomerular apparatus regulates GFR and BP through a feedback loop where the macula densa senses changes in NaCl, and granular cells adjust renin release, influencing systemic blood pressure and nephron filtration rate.
Discuss the pharmacological interventions that target the RAS and their potential benefits in managing hypertension.
Pharmacological interventions in RAS include ACE inhibitors and angiotensin receptor blockers, which decrease angiotensin II activity, and direct renin inhibitors, which block the initial step in the RAS, each with potential benefits like fewer side effects and effective BP management.
What is the importance of blocking angiotensin II in the treatment of hypertension?
Blocking angiotensin II reduces vasoconstriction and sodium retention, thereby lowering blood pressure. This can be achieved with ACE inhibitors, angiotensin receptor blockers, and direct renin inhibitors.
What hormone opposes the actions of vasopressin and aldosterone, and what does it promote?
Atrial Natriuretic Peptide (ANP) opposes the actions of vasopressin and aldosterone by promoting the loss of sodium and water, aiding in reducing blood volume and pressure.
Who discovered ANP and what are its effects on the kidneys?
ANP was discovered by researchers, including Adolfo de Bold, in 1981. It increases sodium and water excretion by the kidneys, dilates afferent arterioles, and reduces aldosterone and vasopressin release, leading to decreased blood pressure.
How do natriuretic peptides, like ANP, affect the cardiovascular system and blood pressure?
Natriuretic peptides reduce blood volume and pressure by increasing sodium and water excretion in the kidneys and opposing the RAS and sympathetic nervous system.
What triggers the release of ANP from myocardial cells?
ANP is released from specialized myocardial cells, primarily in the atria, when these cells are stretched more than normal, typically due to increased blood volume.
How does ANP contribute to the regulation of blood pressure?
ANP contributes to blood pressure regulation by reducing sodium reabsorption in the kidneys, dilating the afferent arterioles to increase GFR, and suppressing renin and aldosterone secretion.
Explain the physiological mechanisms by which ANP serves as an antagonist to the renin-angiotensin-aldosterone system (RAS).
ANP antagonizes RAS by dilating the afferent arteriole of the glomerulus, reducing renin release, inhibiting aldosterone secretion, decreasing sodium reabsorption, and suppressing the sympathetic nervous system, all of which lead to decreased blood pressure.
Discuss the impact of ANP on the homeostatic balance of blood pressure in the context of RAS activation and its implications for therapeutic strategies in hypertension.
ANP counteracts RAS activation by promoting vasodilation, natriuresis, and diuresis, which leads to a decrease in blood volume and pressure. Therapeutically, this understanding has led to the development of drugs that mimic or enhance the effects of ANP, providing alternative strategies for managing hypertension and heart failure.
Elaborate on the physiological interplay between ANP and the sympathetic nervous system in the regulation of renal function and blood pressure.
ANP modulates renal function and blood pressure by inhibiting the sympathetic nervous system, leading to a decrease in renin release, vasodilation of the afferent arteriole, increased glomerular filtration rate, and enhanced excretion of sodium and water. This process effectively reduces blood volume and systemic vascular resistance, which are critical factors in the pathophysiology of hypertension.
What body changes occur with the ingestion of hypertonic water?
Ingestion of hypertonic water increases extracellular fluid osmolarity, leading to water movement from intracellular to extracellular spaces, potentially causing cellular dehydration.
What is the effect of drinking large amounts of water without solute on the body?
It leads to a decrease in extracellular fluid osmolarity, resulting in hyponatremia and a potential shift of water into cells, causing cellular swelling.
How does the body compensate for sweat loss with plain water replacement?
Replacing sweat loss with plain water can dilute extracellular sodium, leading to hyponatremia and a decrease in osmolarity.
What is the physiological response to hemorrhage in terms of fluid volume and osmolarity?
Hemorrhage triggers a low volume response without changing osmolarity, prompting the body to conserve both water and sodium to maintain blood pressure.
How does dehydration from sweat loss or diarrhea affect the body?
Dehydration from sweat loss or diarrhea leads to a decrease in volume and an increase in osmolarity, causing the body to conserve water and increase thirst.
What are the similarities between the body’s response to hemorrhage and severe dehydration?
Both conditions trigger a low volume response, activating mechanisms to conserve water and maintain blood pressure, despite their differences in osmolarity changes.
Compare and contrast the homeostatic responses to hemorrhage versus severe dehydration and the implications for intracellular and extracellular fluid compartments.
Hemorrhage maintains osmolarity but reduces volume, leading to conservation of water and salt without cellular dehydration. Severe dehydration increases osmolarity and reduces volume, leading to water conservation and increased thirst, with a risk of cellular dehydration if not corrected.
How do the renin-angiotensin-aldosterone system and atrial natriuretic peptide (ANP) interact during disturbances in blood volume and osmolarity?
RAAS and ANP have opposing actions; RAAS conserves sodium and water to increase volume and blood pressure, while ANP promotes natriuresis and diuresis to decrease volume and blood pressure. During volume depletion, RAAS is activated, whereas ANP is suppressed; the opposite occurs during volume expansion.
What is the normal range for plasma pH and how does this compare to intracellular pH?
Normal plasma pH ranges from 7.38-7.42, and intracellular pH is similar, although fluids outside the body can have pH values outside this range.
How does an abnormal pH affect enzyme function and protein structure?
Hydrogen ion concentration affects the structure of proteins and consequently, enzyme function. Abnormal pH can denature enzymes and disrupt metabolic pathways.
What are the effects of acidosis and alkalosis on the nervous system?
Acidosis can make neurons less excitable, leading to CNS depression, while alkalosis can make them hyperexcitable, which can cause sensory changes, twitches, or even tetanus.
How are disturbances in pH often associated with potassium (K+) disturbances?
pH disturbances are frequently linked to K+ levels due to shared renal transport mechanisms, like the antiporter and H+/K+ ATPase.
What is the primary source of H+ in the body?
CO2 produced during aerobic respiration is the main source of acid in the body. The reaction CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+ occurs in all cells but is especially rapid in cells with high levels of carbonic anhydrase.
What are the three components of pH homeostasis in the body?
Buffers are the first line of defense against pH changes, ventilation is a rapid second line of defense that corrects 75% of disturbances, and renal regulation is slower but highly effective, involving direct excretion or reabsorption of H+.
Explain the role of bicarbonate as a buffer in plasma and how it interacts with ventilation and renal function to maintain pH homeostasis.
Bicarbonate acts as a buffer in plasma, neutralizing excess H+ to form carbonic acid, which can be exhaled as CO2. Ventilation adjusts the removal of CO2 to control pH, and the kidneys regulate the reabsorption or excretion of bicarbonate to maintain acid-base balance.
Describe the physiological processes that occur when plasma pH moves out of the normal range and the body’s buffering capacity is overwhelmed.
When plasma pH deviates from the norm and buffers are overwhelmed, the respiratory system alters CO2 exhalation to correct pH quickly. If the cause is respiratory, only renal mechanisms can compensate. If metabolic, both respiratory adjustments and renal modifications work to correct pH by altering bicarbonate and H+ concentrations.
How do the renal tubules compensate for acidosis?
Renal tubules compensate for acidosis by increasing the movement of H+/NH4+ into the tubule and HCO3- into the interstitium, which involves various transporters and exchangers.
How does respiratory compensation for acidosis work?
In response to increased plasma H+ (decreased pH), chemoreceptors stimulate the respiratory centers to increase the rate and depth of breathing, reducing plasma CO2 and thus lowering H+ concentration.
What triggers respiratory compensation in response to acidosis?
Increased plasma H+ concentration (decreased pH) triggers respiratory compensation, where chemoreceptors stimulate the respiratory centers to increase breathing rate and depth, thus lowering plasma CO2 and H+.
How does the kidney excrete hydrogen ions during acidosis?
The kidney secretes H+ ions, which are buffered in the urine by NH3 (ammonia) and HPO4^2- (dihydrogen phosphate), while reabsorbing bicarbonate to help buffer H+ in the extracellular fluid.
Where in the nephron does bicarbonate reabsorption occur?
Bicarbonate reabsorption primarily occurs in the proximal tubule, with indirect methods used due to the lack of direct transporters for bicarbonate on the apical membrane.
What is the function of intercalated cells in the distal nephron?
Intercalated cells in the distal nephron fine-tune acid-base balance. Type A intercalated cells secrete H+ and reabsorb bicarbonate to deal with acidosis, while type B cells do the opposite to compensate for alkalosis.
Explain the negative feedback loop involved in respiratory compensation for acidosis.
In respiratory compensation for acidosis, increased H+ stimulates chemoreceptors, which signal the respiratory centers to increase ventilation, reducing CO2 (and thus H+ via the law of mass action), which in turn decreases the stimulus on chemoreceptors, completing the feedback loop.
Discuss the renal adjustments in the secretion and reabsorption of ions that occur during acidosis and their impact on systemic pH levels.
During acidosis, renal adjustments include increased secretion of H+ and NH4+, enhanced reabsorption of bicarbonate, and increased production of buffer substances in urine. These changes lead to increased acid excretion and bicarbonate conservation, helping to raise systemic pH back towards normal levels.
What is the role of the Na+/H+ exchanger in the reabsorption of filtered bicarbonate in the proximal tubule?
The Na+/H+ exchanger facilitates the secretion of H+ into the tubular lumen, which combines with filtered bicarbonate to form CO2 and water, aiding in the reabsorption of bicarbonate.
How do Type A intercalated cells in the collecting duct contribute to acid-base homeostasis during acidosis?
Type A intercalated cells secrete H+ into the tubular lumen, helping to reabsorb bicarbonate and potassium, thereby reducing acidosis.
What is the difference between respiratory acidosis and alkalosis in terms of CO2 levels?
Respiratory acidosis is characterized by alveolar hypoventilation leading to CO2 retention and increased plasma PCO2, while respiratory alkalosis involves hyperventilation with decreased plasma PCO2.
Which conditions can lead to metabolic acidosis?
Metabolic acidosis can result from increased acidity or loss of bicarbonate due to conditions like lactic acidosis, ketoacidosis, ingestion of toxins, or loss of bicarbonate through diarrhea.
Contrast the mechanisms of acid excretion by Type A and Type B intercalated cells in the distal nephron.
Type A intercalated cells primarily excrete H+ and reabsorb bicarbonate and potassium to combat acidosis, whereas Type B intercalated cells excrete bicarbonate and potassium and reabsorb H+ to counteract alkalosis.
Discuss the compensatory role of the kidneys in respiratory acidosis versus metabolic acidosis.
In respiratory acidosis, the kidneys increase bicarbonate reabsorption to buffer the excess H+, whereas in metabolic acidosis, the kidneys enhance H+ excretion and generate new bicarbonate to replenish lost buffers and correct the pH balance.
What is the primary role of aldosterone in electrolyte balance?
Aldosterone regulates electrolyte balance by increasing sodium reabsorption and potassium excretion in the kidneys, which also impacts water retention and blood pressure.
How does the renin-angiotensin system (RAS) contribute to blood pressure regulation?
RAS increases blood pressure through vasoconstriction and aldosterone secretion, which promotes sodium and water retention, increasing blood volume and pressure.
Describe the body’s physiological response to hemorrhage.
In response to hemorrhage, the body triggers RAS activation, releases vasopressin, and increases heart rate and peripheral resistance to maintain blood pressure and volume.
Explain how the kidneys respond to dehydration.
The kidneys conserve water through increased reabsorption, facilitated by vasopressin, and minimize urine output, while the sensation of thirst is triggered to encourage water intake.
What are the key renal actions in maintaining acid-base balance?
The kidneys maintain acid-base balance by reabsorbing bicarbonate, secreting hydrogen ions, and producing ammonia to buffer excess acids in the urine.
How do disturbances in potassium homeostasis affect the body?
Imbalances in potassium levels can lead to serious cardiac and neuromuscular issues, as potassium is critical for membrane potential maintenance in cells.
What are the components of homeostasis of water and electrolyte balance, and what are the behavioral mechanisms that play an essential role in this process?
Homeostasis of water and electrolyte balance involves the regulation of sodium (Na+), chloride (Cl-), potassium (K+), hydrogen (H+), calcium (Ca2+), phosphate (HPO4 2-), and bicarbonate (HCO3-) ions, along with extracellular fluid (ECF) volume and osmolarity. Kidneys are the major route of elimination, but sweat, feces, and lungs also contribute. Behavioral mechanisms include thirst, which prompts drinking as the only way to replace lost water, and salt appetite.
Why is water and electrolyte homeostasis important?
It’s vital for cellular function, fluid balance, nerve transmission, and preventing health issues like dehydration or electrolyte imbalances.
How does the body react to decreased blood volume/pressure?
Increases cardiac output, vasoconstriction, and triggers thirst to conserve water.
What is the role of volume and baroreceptors?
They sense blood volume/pressure changes and activate reflexes to maintain balance.
True or false? kidneys restore lost water. AND WHY/HOW?
False. Kidneys conserve but cannot restore lost water; external water intake is necessary.
Discuss the relationship between ECF osmolarity and thirst.
Thirst regulates ECF osmolarity by prompting water intake to dilute increased osmolarity.
How does the body regulate blood pressure in hypervolemia?
Decreases sympathetic activity for vasodilation, reduces cardiac output, and increases renal excretion of salts and water.
What are the main structures of the kidney?
cortex,
medulla,
renal pelvis,
and nephrons (cortical and juxtamedullary),
supplied by the renal artery and drained by the renal vein.
How does osmolality change in the nephron?
Osmolality increases in the descending limb of the Loop of Henle (water reabsorbed), decreases in the ascending limb (solute reabsorbed), and is regulated by hormones in the collecting duct.
Explain the countercurrent multiplication system in the kidney.
The countercurrent multiplier in the Loop of Henle creates a gradient of increasing osmolality in the medulla, allowing for variable reabsorption of water and solutes and the production of urine with varying osmolality.
How does water cross cell membranes and what role do aquaporins play?
Water can leak through lipid bilayers but for rapid transport, cells use aquaporins. 13 types of aquaporins facilitate water movement, with 6 types found in renal tubules.
How do kidneys produce dilute and concentrated urine?
Dilute urine is made by reabsorbing solutes while making the tubules impermeable to water. Concentrated urine involves making tubular cells permeable to water, increasing aquaporin expression, and creating a salty interstitium.
What regulates water permeability in the distal nephron?
Water permeability in the distal nephron is regulated by ADH (antidiuretic hormone), which alters aquaporin expression on the cell surfaces and conserves water.
What is the effect of vasopressin on the collecting duct?
Vasopressin increases the permeability of the collecting duct to water, promoting reabsorption into the blood and leading to more concentrated urine.
Describe the mechanism by which vasopressin affects water reabsorption in the collecting duct.
Vasopressin binds to receptors on collecting duct cells, triggering cAMP signaling that leads to the insertion of aquaporin-2 water channels into the cell membrane, increasing water reabsorption.
Explain the synthesis and release of vasopressin.
Vasopressin is synthesized by magnocellular neurons in the hypothalamus, transported to the posterior pituitary, and released into the bloodstream, where it influences water reabsorption in the kidneys.
Why is regulating ECF osmolarity crucial?
ECF osmolarity regulation is vital as it affects cell volume and ionic strength, influencing macromolecule activity and overall cellular integrity.
What are the consequences of osmotic imbalances?
Osmotic imbalances can lead to neurological issues, with acute increases causing seizures or death, and decreases leading to confusion or coma.
Describe the function of osmoreceptors in maintaining ECF osmolarity.
Osmoreceptors, stretch-sensitive neurons, increase their firing rate with osmolarity changes, responding to cellular dehydration by stimulating vasopressin release.
Explain the defense mechanisms of osmolarity in the body.
The body defends ECF osmolarity by sensing changes through osmoreceptors, triggering responses like vasopressin release to adjust water reabsorption and maintain homeostasis.
How is vasopressin secretion controlled?
Decreased blood pressure/volume and increased plasma osmolarity signal to hypothalamic osmoreceptors, prompting the synthesis and release of vasopressin from the posterior pituitary.
What is the significance of central osmoreceptors?
Central osmoreceptors, found in the circumventricular organs like the OVLT and SON, are key regulators of thirst and vasopressin release in response to increased plasma osmolarity.
What are peripheral osmoreceptors and their role?
Peripheral osmoreceptors in the oropharyngeal cavity and blood vessels detect osmotic strength of ingested materials, triggering anticipatory responses to changes in ECF before plasma osmolarity is fully corrected.
What is the circadian rhythm of AVP secretion and its relation to nocturnal enuresis?
AVP secretion follows a circadian rhythm, with higher levels at night to concentrate urine. Disruption in this pattern can lead to nocturnal enuresis (bedwetting).
How is vasopressin secretion controlled?
Decreased blood pressure/volume and increased plasma osmolarity signal to hypothalamic osmoreceptors, prompting the synthesis and release of vasopressin from the posterior pituitary.
Describe the function of AVP and its synthetic analog desmopressin.
AVP regulates water reabsorption in the kidneys. Desmopressin, an AVP agonist, mimics this action and is used to treat conditions like diabetes insipidus and nocturnal enuresis.
Explain the mechanism of action of desmopressin in treating nocturnal enuresis.
What role do the kidneys play in water and electrolyte homeostasis?
The kidneys regulate water and electrolyte balance by adjusting urine concentration and composition in response to the body’s hydration status.
How is urine osmolarity regulated?
Urine osmolarity is regulated by varying the reabsorption of water and solutes in the renal tubules and collecting ducts, influenced by hormones like vasopressin.
What is the action of vasopressin on the distal nephron?
Vasopressin increases the permeability of the distal nephron to water, enhancing reabsorption and concentrating urine.
How does the Loop of Henle contribute to the formation of a salt gradient in the medulla?
The Loop of Henle utilizes a countercurrent multiplication mechanism to create a high osmolarity in the medulla, which is crucial for water reabsorption.
Describe the countercurrent multiplier system in the renal medulla.
The countercurrent multiplier system in the Loop of Henle generates a concentration gradient in the renal medulla by actively reabsorbing ions and allowing more water to be reabsorbed from the collecting ducts.
Explain the significance of the NKCC symporter in the thick ascending limb of the Loop of Henle.
The NKCC symporter in the thick ascending limb transports Na+, K+, and 2 Cl- ions into the cell, contributing to the dilution of the filtrate and the generation of the osmotic gradient.
Why doesn’t the osmolarity of the interstitium decrease as water is reabsorbed?
The counter-current exchange system between the loop of Henle and the vasa recta maintains high osmolarity in the interstitium while allowing for water reabsorption.
How does the counter-current mechanism compare to a heat exchanger?
Similar to a heat exchanger, where warm blood transfers heat to cooler blood returning to the body, the counter-current mechanism in the kidney allows for the exchange of water and solutes instead of heat.
Easy recap: What is the primary role of the kidneys in homeostasis?
The kidneys regulate water and electrolyte balance by filtering blood and producing urine
How does vasopressin affect the kidneys?
Vasopressin increases water reabsorption in the distal nephron, concentrating the urine
What creates the osmotic gradient in the kidney?
The Loop of Henle’s countercurrent multiplier system creates an osmotic gradient in the renal medulla.
What mechanism do the kidneys use to regulate urine osmolarity?
The kidneys use a countercurrent mechanism and hormonal regulation, including vasopressin, to alter urine concentration.
How do peripheral osmoreceptors function?
Peripheral osmoreceptors detect osmotic strength of ingested materials, inducing an anticipatory response for hydration.
What triggers the release of vasopressin?
Increased plasma osmolarity and decreased blood volume or pressure trigger vasopressin release.
Where are central osmoreceptors located and what is their function?
Central osmoreceptors are located in the hypothalamus and trigger thirst and vasopressin release in response to osmolarity changes.
What is the circadian pattern of vasopressin release?
Vasopressin release follows a circadian rhythm, with higher levels during the night to conserve water.
Hard flashcard: Explain how the thick ascending limb of the Loop of Henle contributes to urine concentration
It actively reabsorbs ions, particularly Na+ and Cl-, making the filtrate hypotonic by the time it leaves the loop.
How does the countercurrent exchange system in the vasa recta preserve the medullary gradient?
It efficiently exchanges water and solutes between incoming and outgoing blood, preventing washout of the gradient.
Describe the role of NKCC symporters in the thick ascending limb.
NKCC symporters facilitate the reabsorption of Na+, K+, and 2 Cl- ions from the filtrate, contributing to the generation of a dilute urine and the osmotic gradient.
What is the significance of aquaporin expression in the collecting duct?
Aquaporin expression, regulated by vasopressin, allows water to be reabsorbed or excreted, affecting urine concentration and volume.
What is the main purpose of renal reabsorption?
Renal reabsorption primarily allows the kidney to reclaim essential compounds from the filtrate back into the blood. Approximately 180 liters are filtered daily, but only 1.5 liters are excreted; the rest is reabsorbed.
How does filtration contribute to substance clearance in the kidneys?
Filtration removes foreign and toxic substances alongside endogenous materials. Due to the high rate of filtration, these substances are cleared quickly without the need for specific transport mechanisms.
What drives tubular reabsorption in the nephron?
Tubular reabsorption is driven by active transport of Na+ out of the tubule, creating a gradient that facilitates the reabsorption of other solutes and water by osmosis.
Differentiate between active and passive transport in the nephron.
Active transport requires energy (ATP) to move solutes against a concentration gradient, while passive transport follows the gradient without additional energy input.
Describe the role of vasopressin in renal water handling.
Vasopressin increases water reabsorption in the collecting ducts of the kidney by increasing the permeability of the ducts to water, thus concentrating the urine and reducing water excretion.
What principles govern tubular reabsorption?
To reclaim solute, tubular cells create gradients (chemical or electrical) by active transport. Pumping Na+ out leads to anions and water following, and other solutes like K+ and Ca2+ move into the interstitium if the tubular epithelial cells are permeable to them.
Compare para-cellular and trans-cellular pathways for crossing the epithelial layer in the nephron.
The para-cellular pathway involves movement between cell junctions, relying on passive diffusion, whereas trans-cellular transport involves moving across the apical and basolateral membranes, which can be active or passive.
Explain the Na+-linked reabsorption process in the proximal tubule.
Na+ moves down its electrochemical gradient via various membrane proteins into the cell, then is pumped out on the basolateral side by Na+/K+-ATPase, providing the driving force for reabsorption of glucose and other solutes.
How is urea passively reabsorbed in the kidneys?
Urea is passively reabsorbed in the kidneys because it can move across the membrane down its gradient without transporters. Up to 40% of the filtered urea is reabsorbed in the proximal tubule, following the osmotic gradient created by the reabsorption of Na+ and other solutes.
What factors determine the passage of molecules directly through cell membranes?
The passage of molecules through cell membranes depends on their size, polarity, and charge. Small, polar, uncharged molecules like urea can passively diffuse, while ions like Na+ require specific transporters due to their low permeability.
Why is a portion of the filtered urea reabsorbed?
About 40% of the filtered urea is reabsorbed because urea is a small, neutral molecule that is a key intermediate in nitrogen metabolism (urea cycle). The kidney reabsorbs it passively due to its chemical properties and its role in nitrogen balance.
What is the sequence of events in tubular reabsorption?
Na+ is actively reabsorbed, which drives anion reabsorption. This creates an osmotic gradient that allows water to follow by osmosis. Other solutes, such as K+, Ca2+, and urea, are then reabsorbed either through membrane transporters or paracellularly.
How does the transfer from interstitial fluid to plasma occur in the kidneys?
The lower hydrostatic pressure in peritubular capillaries compared to the pressure in the tubule lumen creates a net driving force, favoring the reabsorption of interstitial fluid back into the plasma.
Identify and describe the significance of the different cellular components in renal histology.
The distal convoluted tubule (DC) has fewer cells than the proximal convoluted tubule (PC), which is characterized by a brush border (BB). These structures relate to the different functions of solute and water reabsorption.
How does the kidney handle proteins and what is the cut-off for filtration at the glomerulus?
Protein concentrations in urine are normally low, at about 1/1000th of plasma. The kidney is the major route of elimination for small proteins. The general cut-off for proteins filtered at the glomerulus is 50 kDa; proteins smaller than this are typically filtered.
What happens when renal transport mechanisms become saturated?
Most renal transport involves membrane proteins and can become saturated, meaning there is a maximum transport capacity (Tm). The renal threshold is the plasma concentration at which saturation occurs, beyond which substances will appear in the urine.
Describe the relationship between filtration, reabsorption, and excretion of glucose at the nephron.
Glucose is filtered at the glomerulus and then reabsorbed in the proximal tubule by Na+-linked secondary active transport. The Tm for glucose is about 375 mg/min; above this plasma glucose level, glucose starts to appear in the urine due to transport saturation.
How does the graph of glucose handling at the nephron illustrate renal threshold and Tm?
The graph shows that as plasma glucose levels increase, the rate of glucose reabsorption reaches a plateau (Tm). The renal threshold is the plasma glucose concentration at which glucose first appears in the urine, indicating that Tm has been exceeded.
What are some examples of ‘small’ proteins that get filtered by the kidneys?
Glycoprotein hormones such as FSH, LH, hCG (around 30 kDa), and many protein hormones like GH (22 kDa) and insulin (6 kDa) are considered small enough to be filtered by the kidneys.
Describe the main functions occurring at different parts of the nephron.
In the nephron, filtration occurs at the glomerulus. Reabsorption of water and solutes primarily happens in the proximal tubule, Loop of Henle, and distal tubule. Secretion occurs mainly in the proximal tubule and distal tubule, moving substances from blood to tubular fluid. Excretion is the final elimination of urine to the bladder.
What is the mechanism behind renal secretion?
Renal secretion is the transfer of substances from the plasma into the tubular fluid. It depends on membrane transporters and receptors. For example, K+ and H+ are secreted by epithelial cells of the distal nephron, which is essential for acid-base balance.
How are proteins secreted in the kidneys?
Small proteins and peptide hormones are secreted from peritubular capillaries into the proximal tubule. This requires receptors on the basolateral face of epithelial cells and involves indirect active transport mechanisms.
How are organic anions secreted at the proximal tubule?
Organic anions are secreted into the tubular fluid via the organic anion transporter (OAT) family. This system has broad specificity and can transport a range of endogenous and exogenous compounds, such as bile salts and drugs like penicillin.
How do OAT transporters affect drug interactions?
Compounds that compete with drugs for OAT transporters can slow the clearance of these drugs from the blood. Probenecid is a drug that inhibits OAT transporters and is used to prolong the effect of penicillin and prevent drug nephrotoxicity.
What is the formula for excretion and what does it represent?
Excretion = filtration - reabsorption + secretion.
It represents the process of eliminating waste from the body, with urine composition differing from the original filtrate due to these processes.
How is clearance defined in renal physiology?
Clearance is the rate at which a substance disappears from the body by excretion or metabolism, calculated as the excretion rate of a substance divided by its concentration in plasma. It helps to understand how well the kidneys are removing a substance from the bloodstream.
Why is inulin clearance used as an indicator of GFR?
Inulin is a storage carbohydrate from plant roots used in medicine to measure GFR because it is freely filtered at the glomerulus, not reabsorbed or secreted by the kidneys, so its clearance is directly proportional to the GFR.
How can creatinine clearance be used to estimate GFR?
Creatinine is produced at a constant rate by the body and is filtered by the kidneys, with some also being secreted. Since it’s not reabsorbed, measuring creatinine clearance gives an estimate of GFR.
Why is glucose excretion normally zero?
Under normal conditions, all the glucose filtered by the glomerulus is reabsorbed in the proximal tubule, which means glucose clearance is zero because no glucose is excreted in the urine.
How is urea handled by the kidneys and how does this affect urea clearance?
The kidneys filter urea, but about 50% of it is reabsorbed back into the blood. The rest is excreted, resulting in a urea clearance rate that is lower than the GFR.
How can penicillin clearance be greater than GFR?
Penicillin is filtered by the glomerulus, but additional penicillin is also secreted into the renal tubule from the blood, making the penicillin clearance greater than the GFR.
What are some useful equations in renal physiology?
Normal GFR is 100-125 ml/min. The filtration rate of a substance (X) is the product of its plasma concentration and GFR. Clearance of X is the excretion rate of X divided by its concentration in plasma.
Describe the process of micturition.
Micturition, or urination, is the process of emptying the bladder. It involves the relaxation of the internal and external sphincters, and is controlled by a spinal reflex as well as conscious control from the CNS.
Explain the micturition reflex.
The micturition reflex is triggered when stretch receptors in the bladder wall are activated as the bladder fills. This sends signals to the spinal cord, activating parasympathetic neurons that contract the bladder muscle and relax the internal sphincter.
What if the body experiences high levels of hydration?
• The body would exhibit _____(low,high) levels of vasopressin, leading to ______(decreased,increased) reabsorption of water in the collecting ducts, resulting in a _______________…
What if the body experiences high levels of hydration?
• The body would exhibit low levels of vasopressin, leading to decreased reabsorption of water in the collecting ducts, resulting in a larger volume of more dilute urine.
What if the proximal tubule could not reabsorb glucose?
If the proximal tubule failed to reabsorb glucose, glucose would appear in the urine, indicative of a condition known as renal glycosuria.
What if the secretion mechanisms in the proximal tubule were inhibited?
• Inhibition of secretion in the proximal tubule would lead to reduced ….. (like certain drugs or organic compounds), potentially causing ……….
What if the secretion mechanisms in the proximal tubule were inhibited?
• Inhibition of secretion in the proximal tubule would lead to reduced clearance of substances normally secreted (like certain drugs or organic compounds), potentially causing their accumulation in the body.
What if the glomerular filtration rate (GFR) significantly increased?
An increase in GFR could potentially _______ the reabsorption capacity of the _______, leading to …..
An increase in GFR could potentially overwhelm the reabsorption capacity of the tubules, leading to the excretion of substances that are normally fully reabsorbed, like glucose.
What if the Loop of Henle was not functioning properly? (think: what would it affect)
A malfunctioning Loop of Henle would disrupt the countercurrent multiplication system, affecting the kidney’s ability to concentrate urine and maintain water balance.
What determines the renal threshold for glucose and how does it relate to diabetes?
The renal threshold for glucose is determined by the maximum reabsorption capacity of the renal tubules. In diabetes, blood glucose levels can exceed this threshold, resulting in glycosuria.
How do changes in blood pressure affect renal clearance?
Renal clearance is influenced by blood pressure through changes in glomerular hydrostatic pressure. High blood pressure can increase filtration, while low pressure can decrease it, affecting the clearance of substances.
What role does the organic anion transporter play in drug interactions?
The organic anion transporter (OAT) can influence drug interactions by mediating the clearance of multiple drugs. Competitive inhibition at OAT can increase the plasma levels of these drugs, affecting their efficacy and toxicity.
Broad: How do the concepts of filtration, reabsorption, secretion, and excretion integrate to form the urinary excretion rate?
• The urinary excretion rate is the net result of _______ (input into the tubules), minus _______ (substances returned to the blood), plus ______ (additional substances added to the tubules), reflecting kidney function.
Broad: How do the concepts of filtration, reabsorption, secretion, and excretion integrate to form the urinary excretion rate?
• The urinary excretion rate is the net result of filtration (input into the tubules), minus reabsorption (substances returned to the blood), plus secretion (additional substances added to the tubules), reflecting kidney function.
Broad: How does the kidney’s handling of substances like urea, glucose, and proteins reflect its role in homeostasis?
• The kidney’s selective reabsorption or excretion of substances like urea, glucose, and proteins is crucial for maintaining homeostasis by regulating _____ _____, _______, and removing ______
Broad: How does the kidney’s handling of substances like urea, glucose, and proteins reflect its role in homeostasis?
• The kidney’s selective reabsorption or excretion of substances like urea, glucose, and proteins is crucial for maintaining homeostasis by regulating blood composition, osmolarity, and removing waste.
