Renal-Related Questions

Transcription

1 Renal-Related Questions 1) List the major segments of the nephron and for each segment describe in a single sentence what happens to sodium there. (10 points). 2) a) Describe the handling by the nephron (e.g., filtering, reabsorption, secretion) of a substance that could be given to a patient to determine renal plasma flow (RPF) rate. The substance would be monitored by both determining the amount excreted and the concentration in the systemic circulation. How would the handling of this substance by the kidney be different from a substance that could be used to determine GFR? (6 points). b) Using the above techniques to measure RFP and GFR, you determine that in a specific person GFR is 150 ml/min and RPF is 600 ml/min. You can then calculate the filtration fraction. What is the filtration fraction in this person? How does this compare to a typical filtration fraction? To the extent that this filtration fraction is not normal, what could account for it being altered in this manner? (6 points). 3) Which would be most effective as a chronic diuretic drug an inhibitor of the mineralocorticoid receptor, an inhibitor of the V2 vasopressin receptor, or an inhibitor of the V1 vasopressin receptor? Provide a rationale for your answer. (6 points). 4) A person emerging from being lost in the desert with nothing to drink for a few days was found to have a plasma osmolarity of ~325 mosm/l and a blood volume that was reduced by ~10%. Answer the following questions about this individual. (5 points). a) The individual s vasopressin levels would likely be closest to which of the following values: i) ~ 0.2pg/ml ii) ~2 pg/ml iii) ~20 pg/ml iv) ~200 pg/ml v) ~2000 pg/ml b) Compared to this person s aldosterone level before heading off to the desert, their level now would be: i) Lower ii) About the same Page 1

2 iii) Higher iv) Can t be determined from the information provided c) The individual s urinary excretion for the past 24 hours would be approximately what volume? 5) If somehow podocytes were damaged, causing the spaces between their end processes to separate a bit, what impact would there be on GFR? What impact would this damage have on the filtered load of sodium? What impact might this damage have on the excretion rate of sodium? Defend each of your answers. (8 points). 6) What effect would you expect that a kidney stone (i.e., salt crystals precipitating to form a partial obstruction in the tubule system) have on GFR? Provide a brief rationale for your answer. (5 points). 7) Despite the fact that GFR is highly dependent on glomerular capillary pressure, GFR is quite stable across a large range of arterial pressures. Describe the two mechanisms that are the most important for this stability of GFR. (8 points). 8) At normal blood glucose levels, no glucose is excreted in the urine. How would this change if the filtered load of glucose were doubled? What if it were increased 5-fold? Defend your answers. (6 points). 9) What are the two key physiological stimuli for aldosterone secretion? How do they act? How do they make sense physiologically? (5 points). 10) The osmotic gradient at the level of the deep renal medulla is not a constant, but varies depending on the level of ADH. What is the approximate extraceullar fluid osmolality at the deepest levels of the medulla under conditions of low and high ADH levels? Explain what accounts for this difference. (10 points). 11) A massive infection might cause a huge increase in circulating levels of immunoglobulins (i.e., antibody proteins). Describe how this might impact glomerular filtration rate. (Note to consider: In addition to there being an increase in plasma protein, immunoglobulins, because of their charge, may bind to the basement membrane.) (10 points). 12) The GFR in a patient is determined to be 180 ml/min, which is clearly abnormal. What might be wrong with this patient to cause this GFR? What other parameters might you measure to be able to identify the specific renal problem resulting in this abnormal GFR? (10 points). Page 2

3 13) If you could design a drug that would selectively constrict glomerular afferent arterioles, what impact would this action have on the renal handling (i.e., filtration, reabsorption, secretion, excretion) of sodium? How would this be different if the drug acted on both afferent and efferent arterioles? (10 points). 14) The following questions relate to the hormone aldosterone. (10 points). a) What are the two major actions of aldosterone? b) Which gland secretes aldosterone? c) Some physiology texts refer to a renin-angiotensin-aldosterone system. How are these three things tied together into a system? Do you like this notion of a renin-angiotensin-aldosterone system? 15) a) At a normal GFR and under normal resting conditions, describe the approximate flow (ml/min) and osmolality at each segment of the nephron beginning with Bowman's capsule. (10 points). b) How would the approximate flow and osmolality at each segment of the nephron be altered by the intravenous infusion of mannitol (a sugar molecule that acts as an osmotic diuretic)? (5 points). 16) Antidiuretic hormone acts on the kidney to promote water reabsorption. What is the site of action of ADH in the kidney, and how does it promote water reabsorbtion? (10 points) 17) What effect would liver damage resulting in a decrease in plasma albumin concentration have on glomerular filtration rate and renal plasma flow rate? (8 points) 18) The GFR in a patient is determined to be 180 ml/min, which is clearly abnormal. What might be wrong with this patient to cause this GFR? What other parameters might you measure to be able to identify the specific renal problem resulting in this abnormal GFR? (10 points) 19) Why does glomerular filtration not change when systemic arterial pressure falls by 10 mm Hg? (8 points) 20) What are the major stimuli controlling aldosterone secretion? Why do these stimuli make sense in terms of the major actions of aldosterone in the kidney? (10 points) 21) The clearance of inulin in a person was determined to be 125 ml/min. The clearance of substance A is 50 ml/min, substance B is 125 ml/min, substance C Page 3

4 is 200 ml/min, and substance D is 0 ml/min. What do you know about the renal handling of substances A, B, C, and D? (4 points) 22) Describe the renal handling of a compound that would be useful in the determination of renal plasma flow. How would renal plasma flow be determined using this substance? (4 points) 23) Consider the renal handling of hypothetical substance X. At a concentration of 1 mg/ml in blood and with a normal GFR, none of this substance is excreted in the urine. However, at a concentration of 2 mg/ml of substance X in plasma, approximately 100 mg/min of substance X shows up in the urine. What can you surmise about the renal handling of substance X? How would you expect the excretion of substance X be influenced by increases or decreases in ADH secretion? (6 points) 24) What effect would a drug that inhibits the Na, K, 2Cl transporter have on the kidney? What clinical usage might such a drug have? (10 points) 25) Diuretics are frequently used in clinical medicine as a way of decreasing blood volume by increasing fluid excretion. If designing a diuretic drug, would you think it is more safe and effective to block vasopressin receptors in the kidney or instead block aldosterone receptors in the kidney? Why? (10 points) 26) Compare and contrast the balance of hydrostatic and osmotic pressures in glomerular capillaries, peritubular capillaries, and muscle capillaries. (10 points) 27) The GFR in a patient is determined to be 180 ml/min, which is clearly abnormal. What might be wrong with this patient to cause this GFR? What other parameters might you measure to be able to identify the specific renal problem resulting in this abnormal GFR? (10 points) 28) A patient was discovered whose juxtamedullary nephrons had unusually short loops of Henle. What effect might this have on renal function? In your answer make sure you consider how this person might respond to 2 days of water deprivation and to rapidly drinking 2 liters of water. (10 points) 29) Both antidiuretic hormone and aldosterone play key roles in kidney function. Compare these two hormones in relationship to the following: (6 points) Nature of molecule Page 4 ADH Aldosterone

5 Site of release Key stimuli for release Site of action Duration of action Mechanism of action 30) The clearance of inulin in a person was determined to be 125 ml/min. The clearance of substance A is 50 ml/min, substance B is 125 ml/min, substance C is 200 ml/min, and substance D is 0 ml/min. What can you deduce about the renal handling of substances A, B, C, and D? (4 points) Page 5

6 31) Compare the effects on GFR of constricting a) the afferent arteriole; b) the efferent arteriole; c) and both the afferent and efferent arterioles. (9 points) 32) Patient A is determined to have an inulin clearance of 200 ml/min and a PAH clearance of 640 ml/min. a. What is the filtration fraction in this patient? (If not enough information is provided to answer this, state what additional information is needed, and estimate it as best you can. Don t worry too much about the math; feel free to round off numbers, as long as it is clear what you did.) (4 points) b. How does the filtration fraction in this patient compare to a normal filtration fraction? (3 points) c. Describe what might be going on with the kidneys in this patient to account for these numbers, and how might you determine whether your diagnosis is correct? (8 points) 33) Antidiuretic hormone (vasopressin) and aldosterone are very different hormones that have very different effects on the kidney. Compare these two hormones along the following dimensions: a. Chemical structure and site of production (4 points) b. Stimuli that control their secretion (4 points) c. Location of receptors for the hormone (4 points) d. Renal actions of the hormone (4 points) 34) A researcher at a drug company notices that the compound he was given to test produced a large increase in urine production, which was maintained with chronic treatment with the test compound. Water intake also increased. Describe 4 distinct mechanisms by which this drugs might be acting, and present a series of experiments that this researcher might conduct to further elucidate the mechanism by which this drug is increasing urine flow. What is the very first measurement you would make in trying to narrow down the correct mechanism of action? (20 points) 35) Describe the concentration of Na + in each segment of the nephron under conditions where plasma ADH levels are set experimentally at 0.5 pg/ml and 50 pg/ml, in the presence of either high or low levels of aldosterone (i.e., there are 4 conditions involving the two ADH and the two aldosterone levels). Assume a normal plasma Na + concentration in each case. (15 points) Page 6

7 36) Despite GFR being very dependent upon glomerular capillary pressure, GFR remains constant over a wide range of systemic arterial blood pressure. Briefly described the primary mechanism(s) allowing this to occur. (10 points) 37) Patient A is determined to have an inulin clearance of 75 ml/min and a PAH clearance of 750 ml/min. (15 points) a. What is the filtration fraction in this patient? (If not enough information is provided to answer this, state what additional information is needed, and estimate it as best you can.) b. How does the filtration fraction in this patient compare to a normal filtration fraction? c. Describe what might be going on with the kidneys in this patient to account for these numbers. d. Patient B also has an inulin clearance of 75 ml/min but has a PAH clearance of 375 ml/min. What might account for these numbers? 38) A normal fasting subject is studied while receiving intravenous infusions of glucose to raise plasma glucose levels to 100 mg/100 ml, 200 mg/ 100 ml, or 500 mg/100 ml. Assuming a normal GFR (rounding it off to 100 ml/min to simplify the math) and normal renal function, discuss the renal handling of glucose in each condition. Make sure that your answer includes a discussion of the filtered load, reabsorption and secretion, excretion, and clearance. (10 points) 39) Spironolactone, a competitive antagonist of aldosterone receptors, is sometimes used as a diuretic. Why is this drug an effective diuretic? (5 points). At which segment(s) of the nephron does it act to produce its diuretic action? (1 point). 40) Describe 3 factors that would influence GFR. For each factor that you list, describe a condition under which it might change. (6 points). 41) Under conditions of profound hypotension, 3 mechanisms contribute to the large increase in renin secretion from the JG cells. List the 3 mechanisms, in order of the extent to which they are thought to contribute to the increased renin secretion (i.e., indicate the most important mechanism first). (6 points). Page 7

8 42) During a physiology lab experiment, a subject is asked to drink a few liters of water. What effect, if any, would the water consumption have on the osmolality of the renal medullary interstitial fluid? Why? (8 points). 43) What is meant by renal filtration fraction? How might it be determined in clinical tests? (9 points). 44) As a result of some disease process, the osmolality of the interstitial fluid of the deepest levels of the renal medulla became 600 milliosmolar. Compared to a normal individual, what effect would that have on urine volume and urine osmolality at different levels of ADH? Why? Include in your answer a graphical representation of these relationships, making the graphs as quantitative as possible. (For example, consider making a graph that has plasma ADH levels on the x axis and urine volume or osmolality on the y axis and including a line for a normal subject and a line for this patient.) (15 points). 45) What is the macula densa? What role does it play in the regulation of GFR? What role does it play in the regulation of renin secretion? (10 points) 46) Describe what might occur physiologically or pathophysiologically to cause each of the following: (16 points total) a) A very large volume of hypotonic urine (4 points) b) Protein in the urine (4 points) c) Profound natriuesis (4 points) d) High amounts of the amino acid phenylalanine in the urine (4 points) 47) In the table below, indicate the expected osmolality of tubular fluid given the plasma concentration of ADH indicated. Assume that the plasma osmolality is 300 mosm/kg and the osmolality of the renal medullary interstitial fluid is 1200 mosm/kg. (12 points) Bowman s capsule 0 pg/ml ADH 50 pg/ml ADH 500 pg/ml ADH Proximal tubule (middle section) Beginning of descending limb of Page 8

9 the loop of Henle Beginning of ascending limb of the loop of Henle End of collecting duct Urine 48) What effect would surgical removal of both adrenal glands have on blood volume and its regulation. (10 points) 49) Diuretic drugs are used in the treatment of a variety of conditions. Answer the following questions regarding diuretics. (15 points total) a) Name one condition for which a diuretic drug would be useful (1 point) b) Why do carbonic anhydrase inhibitors act as diuretics? (3 points) c) Why aren't carbonic anhydrase inhibitors typically used as diuretic drugs? (2 points) d) Why wouldn't an inhibitor of antidiuretic hormone be a good choice of a diuretic drug in most instances? (4 points) e) If you were to design an ideal diuretic drug, what mechanism of action would you target? Why? (5 points) 50) Two hormones, aldosterone and antiduiretic hormone, play dominant roles in regulating renal function. Compare and contrast these two hormones in terms of (2 points each): a) Site of secretion: b) Chemical class: c) Stimuli for secretion: d) Half-life in blood: e) Site of action in the nephron: f) Nature of the receptor on which they act: g) Key actions: Page 9

10 h) Duration of action: 51) Glomerular blood vessels are unusual for several reasons compared to blood vessels in other tissues. One of the more unique features is the presence of afferent and efferent arterioles capable of constriction and dilation. Describe the importance of this arrangement of having both afferent and efferent arterioles. (7 points) 52) While the molecular mechanism of Na+ sensing of macula densa cells is currently unknown, describe what you expect the effects would be of a defect in this mechanism rendering the macula densa insensitive to Na+. (10 points) 53) The Na/K/2Cl transporter plays a unique role in renal physiology. Describe the physiological impact of selective inhibition of this transporter. (10 points) 54) Draw a graph with the plasma concentration of substances on the X- axis and the rate of renal excretion on the Y-axis. Now, draw a line representing a substance that is filtered in the nephron but neither reabsorbed or secreted. Label this line substance A. Make sure the graph extends from very low levels of this substance to very high levels of this substance in blood. Now include two more substances on this graph: Substance B is filtered and secreted, whereas Substance C is filtered and, at low physiological levels, completely reabsorbed. (12 points) 55) Infections producing very high levels of immunoglobulin class G (IgG) in blood can interfere with renal function. Provide two reasons why high levels of IgG might decrease GFR. (10 points) 56) Antidiuretic hormone (vasopressin) and aldosterone are both important in renal function. Compare these two hormones along the following dimensions: a) General chemical structure and site of production (2 points). b) Stimuli that control their secretion. (2 points). Page 10

11 c) Location of receptors for the hormone. (2 points). d) Renal actions of the hormone. (4 points). 57) a) Describe how renal filtration fraction can be determined. (5 points). b) Using that approach, you determine that filtration fraction in a patient is 12%. This is (circle one): low normal high (1 point). c) To the extent that this is not normal, explain what factors might cause this abnormal filtration fraction. If it is normal, describe one factor that might cause it to increase and one that might cause it to decrease. (4 points). 58) Liddle s syndrome results from a gain in function mutation in ENaC (i.e., ENaC becomes more effective). What would the major symptoms of this syndrome be? (5 points). 59) Compare the average protein osmotic pressure among: glomerular capillaries, peritubular capillaries, muscle capillaries, and pulmonary capillaries. (5 points). 60) Compare and contrast the transport properties of the proximal tubule, ascending limb of the loop of Henle, and collecting ducts for the following: (1 point each). Glucose Transport Proximal Tubule Ascending Limb of Loop of Henle Collecting Duct Na-K-2Cl Transporter Water Permeability Amino Acid Transport Page 11

12 Sodium Reabsorption Action of Atrial Natriuretic Hormone Aldosterone Receptors Potassium Secretion or Reabsorption Reabsorption of Creatinine Protein Secretion or Reabsorption 61) What is the macula densa and what are its key roles in renal function? (10 points). Page 12