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NDM Trefor Morgan Renal Questions

1

Which is most closely associated with the lowest K+ concentration in filtrate?


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


The greatest amount or K+ is absorbed in the proximal tubule but the concentration stays the same as in plasma. The thick ascending limb of the Loop of Henle removes K+ and the concentration drops to 2 mmol/L or less by the macula densa. Most of the potassium excreted in the urine is secreted hy the distal nephron. Note the difference between excretion of a substance and the secretion of a substance. They do not necessarily correlate.

2

Which has the lowest Na+ concentration in filtrate?


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


Sodium can be transported out of the lumen throughout most parts of the nephron. The lowest concentration is reached in the collecting duct in the papilla at the end of the nephron, and under appropriate circumstances it is close to zero.

3

Which is most closely associated with changes im permeability to water?


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


Antidiuretic hormone increases the permeability of the collecting tubule and collecting duct to water.

4

Which is least permeable to urea?


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


The cortical portions of the distal nephron are almost impermeable to urea and this is important in allowing high urea concentration to develop, which is a secondary driving force for the concentration of the urine.

5

Which is most closely associated with the active W secretion.


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


The intercalated cells of the collecting tubule and duct actively secrete H+ by a H+ ATPase system.

6

Which has a transepithelial positive PD?


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


Owing to the triple transporter moving K+, Na+ and 2Cl- across the luminal membrane and a back leak of K+ into the lumen, the thick ascending limb has a lumen positive PD. A very small positive PD can exist in the latter part of the proximal tubule.

7

Which has a transepithelial negative PD?


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


Owing to transport of Na+ and a relative impermeability to Cl- and other anions, the collecting duct lumen has a negative potential difference. This is the driving force for K+ secretion and for some H+ secretion. A small negative PD is also found in the first part of the proximal tubule.

8

Which has the most most K+ reabsorption?


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


Sec Question 1. Most K+ is absorbed in the proximal tubule associated with Na+ and water absorption.

9

Which mediates 70% of Na+ absorption?


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


The proximal tubule absorbs about 70% of the sodium filtered, the Loop of Henle 20-25%, the distal nephron 7-10%. Less than l% or the sodium filtered is excreted in the urine.

10

Which has the highest urea concentration?


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


The highest urea concentration is developed in the papillary portion of the collecting duct, and the highest concentration is in the urine that is formed.

11

Which has the highest hydrostatic pressure?


  Proximal tubule.

  Thick ascending limb of the Loop of Henle.

  Cortical diluting segment.

  Collecting tubule and collecting duct.

  Thin limb of Loop of Henle.


The hydrostatic pressure in the proximal tubule is about 10-15 mmHg and is what causes fluid to to flow down the tubule.

12

All of the following statements related to glomerular filtrate are correct except for:


  GFR increases with increased capillary pressure.

  GFR decreases with increased plasma albumin concentration.

  GFR decreases with increased tubular pn::ssurc.

  The pressure drops significantly along the glomerular capillary.

  GFR may increase with increased renal blood flow.


GFR is the net result of capillary HP (out), tubular HP (in), plasma protein oncotic pressure (in), tubular oncotic pressure (out, but close to zero). Thus increased capillary pressure will increase filtration, while increased plasma albumin and increased tubular pressure will decrease filtration. Filtration equilibrium is reached before the end of the glomerular capillary, thus increased flow increases the functional surface are and filtration is increased. The glomerular capillary is a network and there is a minimal pressure drop along the glomerular capillary.

13

All of the following statements related to glomerular filtration are correct except for:


  There is little or no pressure drop along the glomerular capillary.

  Filtration rate increases if plasma albumin is low.

  Net filtration force is usually about 15 mmHg.

  Filtration rate depends upon the charge on the molecule.

  No substance with MW > 2000 is filtered.


See Question 12. The net fillration force is about 15 mmHg at the start of the capillary. If albumin is low the effective force is increased. -The glomerular capillary is very permeable. Substances with molecular weight less than 2000 are filtered in the same proportion as they are in the plasma unless they are protein bound. Substances up to 40 000 and even higher will be partially filtered. The filtration barrier has charged areas, thus charged particles are not filtered as readily as uncharged particles.

14

All of the following statements related to glomerular filtration are correct except for:


  GFR varies directly wiLh systolic blood pressure.

  GFR depends upon filu·ation area.

  GFR is increased by moderate efferent arteriole constriction.

  GFR is decreased by moderate afferent aneriole constriction.

  GFR is decreased by mesangial cell contraction.


Filtration rate depends on the pressure (and other forces) in the glomerular capillary and the surface area. Mesangial cell contraction will reduce the surface area. Afferent arteriolar constriction will reduce the amount of arterial pressure transmitted to the glomerulus and reduce GFR. Efferent arteriolar constriction will increase the pressure in the glomerulus. The kidney autoregulates both renal blood flow and GFR, and changes in arterial pressure in the autoregulating range have little effect on GFR.

15

All of the following statements related to glomerular filtration are correct except for:


  Protein concentration in afferent arteriole is about 75 g/L.

  Protein conccnu·ation in efferent arteriole is about 90 g/L

  Proximal tubule oncotic pressure is about 5mmHg.

  Filtration fraction in humans is about 20%.

  Filtration fraction = GFR/RPF (renal plasma flow).


Filtration fraction is GFR/RPF and in humans is about 20% or 0.2. The removal of water without protein causes the plasma protein concentration to rise from about 75 to 90 g/litre as the same amount of protein that was in 1000 mL is now contained in 800 mL of plasma. Protein is only minimally filtered, and the oncotic pressure in the proximal tubule fluid is close to zero.

16

Which one of the following statements related to the glomerulus and glomerular filtration is most accurate?


  GFR is increased by moderate efferent arteriole constriction.

  Filtration rate varies directly with systolic blood pressure.

  Usual average net filtration force is 35 mm Hg.

  Glomerular capillaries arc not as permeahle as muscle capillaries.

  There is significant pressure drop along the glomerular capillary.


Note that this question says "Which one of the following statements is most accurate?", while the others say "All the following statements are correct except for,". It is very important that you read the question correctly. See Questions 12, 13 and 14. Glomerular capillaries are much more permeable than muscle capillaries.

17

All of the following statements related to proximal tubule reabsorption are correct except for:


  Exhibits a flow dependent increase in reabsorption.

  Low angiotensin II concentration inhibits Na+ reabsorption.

  Parathyroid hormone inhibits Na+ reabsorption.

  NaCl co-transport is important for Na+ reabsorption.

  Exhibits glomcntlotubular balance.


70% of filtered sodium is absorbed by the proximal tubule. The basolateral Na+-K+ ATPase provides the driving force for reabsorption, and Na+ enters across the luminal membrane by carriers. There is no NaCl co-transport carrier at this site. Angiotensin II stimulates sodium transpon probably by increasing entry via the Na+-H+ counter-transport. Parathyroid hormone decreases sodium absorption by increasing cellular cyclic AMP. The proxjmal tubule automatically adjusts its absorptive rate as GFR changes so that the percentage reabsorbed stays approximately the same. This is glomerulotubular balance.

18

All of the following statements related to proximal tubule reabsorption are correct except for:


  There are multiple entry steps for Na+ into the cells.

  The reabsorbate is hypotonic.

  Bicarbonate is reabsorbed more than chloride.

  Atrial natriuretic peptide reduces sodium and water reabsorption.

  Parathyroid hormone increases cyclic AMP in cells.


Sec Question 17. Na+ is primarily absorbed and the reabsorbatc is slightly hypertonic, providing the driving force for water reabsorptwn. Bicarbonate is reabsorbed hccause of the Na+-H+ counter-transport, and most bicarbonate is reabsorbed by the end of the proximal tubule and its concentration falls, while the concentration of Cl- rises. Natriuretic hormone inhibits the action of angiotensin II, thus reducing sodium and thereby water absorption.

19

All of the following statements related to proximal tubule reabsorption are correct except for:


  There is Na+-H+ counter-transport.

  There is Na+-amino acids co-transport.

  Approximately 70% of Na+ and water is reabsorbed.

  Reabsorption is increased by aldostcrone.

  Weak acids are actively reabsorbed.


Sec Questions 17 and 18. Aldosterone increases Na+ reabsorption in the distal nephron but not in this segment. Weak acids can be both actively reabsorbed and actively secreted. Na+ enters the cell across the luminal membrane by Na+-glucose, Na+-amino acid co-transport and Na+-H+ counter-transport.

20

All of the following statements related to proximal tubule reabsorption are correct except for:


  Transport is stimulated by low angiotensin II concentration.

  Carbonic anhydrase is in the luminal membrane.

  Weak bases are actively secreted.

  Non-Na+-K+ ATPase transport of Na+ exceeds Na+-K+ ATPase transport.

  Na+-K+-2Cl- co-transport is imponant for Na+ reabsorption.


There is no Na+-K+-2Cl- co-transport in the proximal tubule. This exists only in the Loop of Henle. Carbonic anhydrase is in the luminal membrane and 'speeds up' the Na+-H+ counter-transport exchange. More Na+ and water are absorbed paracellularly than through the cell.

21

All or the following statements related to the thick ascending limb of the Loop of Henle are correct except for:


  High concentration of Na+-K+ ATPase on luminal membrane.

  Na+-K+-2Cl- co-transport at luminal membrane.

  K+ leaks back into the lumen.

  Cl- leaks hack into lumen hy paracellular pathway.

  Na+ reabsorbed by paracellular pathway.


Na+-K+ ATPase exists in high concentrations on the basolateral membrane and is the active transport step that drives transport. Na+, Cl- and K+ enter across the luminal membrane by the Na+-K+-2Cl- co-transporter. K+ leaks back into the lumen, creating a positive PD. This creates an electrogenic force that allows Na+ to go from the lumen to the interstitium by the paracellular pathway and some Cl- leaks back into the lumen by the paracellular pathway. There is also additional movement of Na+ through the cell by mechanisms not involving Na+-K+ exchange. Thus transport of Na+ depends on Na+-K+ ATPase as a driving force, but the effect is amplified.

22

All of the following statements related to absorption from the thick ascending limb or the Loop of Henle are correct except for:


  The lumen PD is positive compared to plasma.

  Transport depends upon primary active chloride transport.

  Cl- leaks hack into lumen by paracellular pathway.

  Relatively impermeable to water.

  High concentration of Na+-K+ ATPase on basolateral membrane.


Sec Question 21. While the lumen has a positive PD compared with plasma, this is not due to primary active chloride transport but is created as stated in the answer to Question 21. The thick ascending limb is relatively impenncable to water, allowing Lhe luminal contents to become hypotonic compared to plasma and thus the reabsorbate is hypertonic. This is the driving force for the counter-current system.

23

All of the following statements related to absorption from the thick ascending limb or the Loop of Henle are correct except for:


  Frusemide binds to the Na+-K+-2Cl- receptor inhibiting transport.

  ADH increases reabsorptive capacity.

  ADH increases water permeability.

  Net transport can he increased hy a high Na+ diet.

  Calcium reabsorption increased by parathyroid hormone.


ADH has no effect on water permeability of this segment, but it does increase the total capacity to reabsorb sodium. A high sodium intake can increase the number of Na+-K+ ATPase sites and increase transport. Frusemide acting from the luminal side binds to one of the chloride receptorss of the triple co-transporter and stops transport. Calcium is reabsorbed also in this segment, and the reabsorption is increased by parathyroid hormone.

24

All of the following statements related to the macula densa and tubuloglomerular (TG) feedback are correct except for:


  Renal blood flow autoregulation and TG feedback have the same controlling mechanisms.

  Low NaCl at macula densa leads to increased renin release.

  Low NaCl at macula densa leads to increased GFR.

  Low NaCl at macula densa leads to dilation of afferent arteriole.

  Macula densa transport depends on Na+-K+-2Cl- co-transporter.


The macula densa moitors NaCl in the lumen, probably by transport via the Na+-K+-2Cl- co-transporter. A low NaCl causes renin to be released and GFR to increase, but the renin release is not the cause of the GFR rise. The rise in GFR is due to dilatation of the afferent arteriole. The mechanism of TG feedback will have some effect on renal blood flow, but there are other mechanisms (e.g. myogenic, neural) involved in renal blood flow autoregulation.

25

All of the following statements related to the juxta-glomerular apparatus and tubuloglomerular feedback are correct except for:


  Renin is present predominantly in the afferent arteriole.

  Angiotensin II is present preformed in the renin granules.

  Angiotensin II mediates TG feedback.

  Afferent arteriole tone is the main mediator of TG feedback.

  Efferent arteriole is more sensitive to circulating angiotensin II than the afferent arteriole


See Question 24. Renin is present together with angiotensin II in granules in the afferent arteriolar cells. Renin is released in response to a low NaCl al the macula densa at the same time as the afferent arteriok dilates. The efferent arteriole is more sensitive to circulating angiotensin II than the afferent arteriole. Angiotensin II is not the mediator of TG feedback because it would contract the afferent arteriole. However, it appears to be important to provide tone to the efferent arteriole, permitting some other factor to dilate Lhe afferent arteriole and mediate tubuloglomerular feedback.

26

Which one of the following statements related to the macula densa, juxtaglomerular apparatus and tubuloglomerular feedmack is most accurate?


  Renin granules predominantly in efferent arteriole.

  Renin secretion controls TG feedback.

  Efferent arteriole is the main controller of TG feedback.

  Low NaCl at macula densa leads to increased renin release.

  Renal blood flow autoregulation and TG feedback have the same controlling mechanisms.


Note question says is most accurate. See Questions 24 and 25.

27

All of the following statements related to the cortical diluting segment of the distal nephron are correct except for:


  Less that 7% of sodium filtered is reabsorbed in this segment.

  Relatively impermeable to water.

  Relatively impermeable to urea.

  Dilutes the urine.

  Na+-K+-2CL- co-transporter is present in the luminal membrane.


NaCl is reabsorbed in the cortical diluting segment, and as the membrane is relatively water impermeable this provides some dilution of the urine. Only a small amount of the filtered sodium (1- 3%) is absorbed at this site and NaCl moves across the luminal membrane by a NaCl co-transporter, which is inhibited by a thiazide diuretic. The impermeability to urea means that urea is retained in the nephron, and its conccnlrntion gradually increases. It provides more and more or the tubular fluid eventually urine osmolality.

28

All ofthe following statements related to he cortical diluting semgnet of the distal nephron are correct except for:


  Thiazide diuretics block sodium absorption.

  Amiloride inhibits sodium transport.

  Relatively impermeable to urea.

  Relatively impermeable to water.

  Dilutes the urine.


Sec Question 27. Amiloride blocks Na+ channels and some Na+-H+ counter-transport. As these are not present in the luminal membrane of this segment it will have no effect on its transport.

29

ll of the following statements related to transport in the collecting tubule or collecting duct are correct except for:


  Intercalated cells secrete H+.

  H+ ATPase causes H+ secretion

  H+ is secreted down an electrochemical gradient.

  Total H+ secretion is greater than in the proximal tubule.

  K+ is secreted down an electrochemical gradient.


H+ ions are secreted by the intercalated cells by an H+ ATPase and enter the lumen down the elctrochemical gradient. A high concentration of H+ compared to the cell can be reached (pH 5.4 compared to 7.5, i.e. 100 times gradient), but many more H+ are secreted in the proximal tubule by Na+-H+ counter-transport. However, the H+ ions secreted in the proximal tubule are all reclaimed in the absorption of HCO3- and thus are not excreted (lost from the body). K+ is secreted by the chief cells down an electrochemical gradient.

30

All of the following statements related to transport in te collecting tubule or collecting duct are correct except for:


  HCO3- in lumen increases H+ excretion.

  Na+ reabsorption is less than 7& of sodium filtered.

  The permeability to water is altered by ADH.

  K+ permeability is increased by ADH.

  Na+ absorption is increased by aldosterone.


Sodium is absorbed in Lhe collecting duct and collecting tubules and enters the cell from the lumen by an amiloride-sensitive sodium channel. Chloride and bicarbonate are relatively impermeable and a negative PD up to 70mV develops. Sodium absorption is increased by aldosterone which increases the number of membrane Na+-K+ ATPase units and sodium permeability. Less man 7% of the sodium that is filtered comes to this site. This sement can reduce the sodium concentration to zero. The epilhelium is normally impermeable to water, but ADH will increase water permeability. In ADH absence the epithelium is relatively impermeable to K+. ADH increases K+ permeability. If HC03- is in the tubule fluid the amount of H+ secreted increases but it will be used to reabsorb bicarbonate and hence will not be is important to distinguish between secretion and excretion.

31

All of the following statements related to transport in the collecting tubule or collecting duct are correct except for:


  HCO3- in lumen increases H+ secretion.

  HCO3- in lumen decreases H+ excretion in the urine.

  HCO3- in lumen increases Na+ reabsorption.

  Lumen PD is made more negative by aldosterone.

  Lumen PD is made more negative by SO4^2- in lumen.


HCO3- in the lumen makes the lumen more electronegative. This will cause positively charged ions (e.g. H+, K+, Na+) to enter or be retained in the lumen. Thus Na+ reabsorption will be decreased and H+ secretion will be increased. However, H+ excretion is not increased as the H+ reacts with the bicarbonate which is reabsorbed. Aldosterone increases Na+ transport and makes the lumen more negative. SO42- is very impermeably and the lumen is also made more negative.

32

All of the following statements related to transport in the collecting tubule or collecting duct are correct except for:


  There can be net K+ secretion.

  There can be net K+ reabsorption.

  Na+ absorption is increased by aldosterone.

  K+ secretion is decreased by aldosterone.

  Permeability to water is increased by ADH.


K+ can be secreted or absorbed in the collecting tubule and duct. Aldosterone increases sodium absorption and increases K+ secretion. The membrane is impermeable to water unless ADH is present.

33

Which one of the following statements related to transport in the collecting tubule or collecting duct is most accurate?


  H+ secretion is greater than in the proximal tuble.

  HCO3- in lumen increases Na+ reabsorption.

  HCO3- in lumen increases H+ excretion.

  Low plasma K+ increases K+ secretion.

  Low plasma K+ increases H+ secretion.


Note this question asks "Which is most accurate</em?". HCO3- in the lumen causes an increased PD, which means there is less Na+ absorption and more K+ and more H+ secretion. K+ excretion also goes up, but H+ excretion does not rise as H+ combines with HCO3-. A low K+ in plasma will decrease secretion of K+ as the equilibrium concentration of K+ reached in the lumen will be less. K+ and H+ have an interaction of each other's secretion. Thus alow K+ increases H+ secretion and a low H+ increases K+ secretion.

34

AL of the following statements related to vasopressin (ADH) are correct except for:


  Is produced in the hypothalamus.

  Is stored in the posterior pituitary

  Release is increased by alcohol.

  Release is increased in response to pain and emotion.


Vasopressin is produced in the hypothalamus and is stored in the posterior pituitary. The normal physiological control is the plasma osmolality, and a high osmolality causes more ADH release, which means that more water is retained. Its release is inhibited by a low plasma osmolality and by alcohol. Pain and emotion also cause its release owing to effects on cortical neurons affecting its secretion.

35

All of the following statements related to vasopressin (ADH) are correct except for:


  Increases collecting duct permeabilty to water.

  Stimulated Na+ transport in the Loop of Henle.

  Increases K+ permability in the collecting tubule.

  Increases proximal tubule reabsorption of Na+ and water.

  Causes arterial vasoconstriction.


Vasopressin's principal renal action is to increase the permeability or the collecting duct to water. It also stimulates Na+ transport by the thick ascending lumb of the Loop of Henle, and increases K+ permeability of the collecting tubule. It contracts blood vessels, but this is in concentrations above the usual physiological range. Vasopressin has no significant effect on the proximal tubule.

36

All of the following statements related to vasopressin action in the kidney (ADH) are correct except for:


  Increases cyclic GMP concentration.

  Increases collecting duct permeability to water.

  Activates adenyl cyclase.

  Increases cyclic AMP concentration.

  Ation depends on activation of microfilaments.


Vasopressin binds to a receptor on the basolateral membrane of the collecting duct activating adenyl cyclase which causes increased cyclic AMP. This activates phosphokinases and causes calcium release, which causes microfilaments to contract thus inserting water channels into the luminal membrane. Cyclic GMP is not involved in the water permeability action or vasopressin.

37

All of the following statements related to the concentrating diluting mechanism of the kidneys are correct except for:


  Vasopressin increases collecting duct permeability to water.

  Urea is a major contributor to urine osmolality.

  Loop of Henle is essential for urine dilution.

  Loop of Henle is essential for urine concentration.

  Concentrating aility depends on the integrity of the papilla.


The transport of sodium out of the thick ascending limb of the Loop of Henle is the driving force for urine concentration and also causes urine dilution. However, the other distal nephron segments also cause dilution of the urine. The papilla needs to maintain its integrity for the concentrating mechanism to work, and the change in water permeability of the collecting system with ADH enables urine to be concentrated. Urea becomes a major component of urine, and urea gradients and movement are an important secondary driving force for urine concentration. particularly in the papilla as opposed to the outer medulla.

38

All of the following statements related to water balance and theconcentrating diluting mechansm are correct except for:


  Diluting ability is abolished by frusemide.

  Concentrating ability depends on the integrity of the papilla.

  Concentrating ability is abolished by frusemide.

  Free water clearance = V(Posm-Uosm)/Posm.

  Too little ADH causes hypernatraemia.


See Question 37. Diluting ability may be decreased by frusemide but is not destroyed, as the distal tubule and the collecting duct system can remove sodium and contribute to urine dilution.

39

All o the following statements related to acid-base balance are correct except for:


  H+ comes from fatty acids.

  Normal diet gives approximate 50mmol H+/day to be excreted in the urine.

  H+ comes from protein.

  ANimal protein metabolism gives H+.

  A vegetarian usually has an alkaline urine.


A person on a normal omnivore diet has a load of ahout 50 mmol of H+/day to be excreted. These come from the metabolism of sulfur containing amino acids that are more common in animal proteins. Fatty acids do not contribute to the excess load of acid that needs to be excreted by the kidney.

40

All of the following statements related to acid-base balance and its control are correct except for:


  A vegetarian usually has an alkaline urine.

  Most people's urine pH < 7.0.

  NH4+ is the major excretory mechanism of an acid load.

  H+ concentration in blood is about 400nmol/L

  pH = pK+log(HCO3-/H2CO3)


See Question 39. Most people are omnivores and their urine is acid (pH < 7.0). The major way H+ is excreted is bound to NH3 to give NH4+. The kidney helps maintain the plasma pH between 7.3 and 7.4 which is a H+ concentration of about 40 nmol/L. The bicarbonate buffer system prevents rapid fluctuations in the pH and can adjust by blowing off CO2 by the lungs.

41

all of the following statements related to acid-base balance and its control are correct except for:


  Aldosterone can cause an alkalosis.

  HCO3- reabsorption in the proximal tubule varieswith volume status.

  HCO3- loss corrects alkalosis.

  Volume depletion prevents correction of alkalosis.

  Free H+ ions int he urie are an important mode of excretion of the acid load.


Aldosterone increases Na- transport and thereby the PD in the collecting system, and more H+ is secreted down a concentration gradient. If they are excreted the person becomes H+ depleted and alkalotic. If a person is alkalotic the condition is corrected by the loss of bicarbonate. Bicarbonate is absorbed by the proximal tubule and its threshold varies with the volume status. If a person is volume-depleted more bicarbonate is reabsorbed and the alkalosis may not be corrected. Even if the pH is 5.0 in the urine this is less than 1 mmol of H+/litre. Most H+ is excreted as NH4+ or titratable acidity.

42

All of he following statements related to acid-base balance and its control by the kidney are correct except for:


  Most people's urine pH < 7.0.

  H+concentration in blood is about 40 nmol/L

  HPO4^2- in the urine contributs to titratable acidity.

  H+-K+ ATPase causes H+ secretion in the distal nephron.

  Na+-H+ counter-transport is important in the proximal tubule.


H+ enteres the tubule lumen by Na+-H+ counter-transport in the proximal tubule and by H+ ATPase in the collecting system, and if H+ is in excess an acid urine is formed to maintain blood pH between 7.3 and 7.4, which is a concentration of 40 mmol/litre. Titratable acidity relates to the amount of NaOH required to bring pH of urine back to 7.4. HPO42- has a pH > 7.4 and thus does not contribute to titratable acidity. H2PO4 has a pH < 7.4, so that NaOH can be added to restore pH to 7.4. Thus H2PO4 contributes to titratable acidity and is one mechanism for excretion of H+.

43

All of the following statements related to plasma volume and its regulation are correct except for:


  Most blood is in the heart and arteries.

  Plasma volume is about 3 litres.

  Plsma albumin is an important determinant of blood volume.

  Low plasma volume activates sympathetic nerves.

  Low plasma causes renin release.


Blood volume is about 5 litres and plasma makes up 3 litres of this. Most blood is in the veins. Plasma albumin maintains water in the vascular department owing to the Starling's forces at the capillary level. If volume is low the sympathetic nervous system is activated and renin is released by the kidney because of direct baroreceptor effects and inreased sympathetic activity.

44

ll of the following statements related to plasma volume, its composition and regulation are correct except for:


  Plasma albumin is an important determinant of blood volume.

  A high plasma sodium is an important determinant of blood volume.

  Low plasma volume causes aldosterone release.

  Low plasma volume causes renin release.

  Low plasma volume cases ADH release.


See Question 43. A low plasma volumne, which may b due to a low plasma albumin, causes release of renin, aldosterone and ADH, which causes salt and water reabsorption to correct the plasma volume. A high plasma sodium has little effect on the blood volume.

45

All of the following statements related to low plasma volume are correct except for:


  Low plasma volume increases heart rate.

  Low plasma volume activates sympathetic nerves.

  Low plasma volume causes renin release.

  Low plasma volume causes atrial natriuretic peptide release.

  Low plasma volume causes ADH relase.


See Questions 43 and 44. A low plasma volume causes increased sympathetic nerve activity, which causes an increased heart rate and constriction of blood vessels. It releases ADH and renin. Renin causes angiotensin II to increase, which releases aldosterone. Angiotensin II and ADH can also cause vasoconstriction. Atrial peptide release is caused by increased plasma volume. It causes Na+ excretion and vasodilatation, which would be an unwanted effect in a person who was volume-depleted.

46

All of the following statements related to aldosterone synthesis and secretion are correct except for:


  Formed from cholesterol.

  Release from adrenal medulla.

  Rease stiulated by angiotensin II.

  Release stimulated by high plasma K+.

  Release stimulated by low sodium in diet.


Aldosterone is formed from cholesterol in the adrenal cortex. Its release is stimulated by angiotensin II, by a high plasma K+, and weakly by a low plasma Na+. It causes increased Na+ to be reabsorbed owing to aldosterone's action in the kidney.

47

All of the following statements related to aldosterone action are correct except for:


  Binds to basolateral membrane of collecting tubule cells.

  Increases K+ permeability of distal nephron.

  Increases amount of distal nephron Na+-K+ ATPase.

  Increases distal nephron Na+ transport.

  Important regulator of plasma K+ concentration.


Aldosterone enters the collecting tubule cell and links to a cytosolic receptor. It enters the nucleus and causes increased production of proteins, which increase sodium reabsorption by increasing the amount of Na+-K+ ATPase. Sodium transport is increased by this mechanism and by a direct effect increasing luminal membrane sodium entry. K+ permeability is increased at the luminal membrane and this, associated wilh the greater PD, causes increased K+ loss. This will eventually cause low plasma K+.

48

All of the fllowing statements related to aldosterone secretion and action are correct except for:


  Release stimulated by low sodium in diet.

  Important regulator of plasa sodium concentration.

  Increases distal nephron sodium transport.

  Increases sweat duct sodium transport.

  Increases colonic Na+ transport.


A person on a low sodium diet has a high renin, which increases angiotensin II and thus aldosterone levels. Aldosterone increases te absorption of sodium in the distal nephron, sweat ducts and colon. Aldosterone causes an increased sodium content in the body but concentration is not altered to any significant extent as ADH is released, increasing water retention and maintaining Na+ concentration constant. Aldosterone is a regulator of total body sodium and plasma volume, not of sodium concentration.

49

All of the following statemenst related to aldosterone synthesis secretion and action are correct except for:


  Formed from cholesterol.

  Metabolised by the liver.

  Synthesis is stimulated by angiotensin II.

  Excess amounts cause hypernatraemia (plasma Na+ > 155mmol/L)

  Excess amounts case hypokalaemia (K+ < 3.2 mmol/L)


Aldosterone is formed in the adrenal cortex from cholesterol and is destroyed by the liver. Its synthesis is stimulated by angiotensin II. Excess amounts cause sodium to be reabsorbed, but plasma Na+ does not rise excessively owing to concomitant retention of water, which is due to ADH release. Plasma volume and BP may both rise. The increased Na+ reabsoption gives more negative pD in the distal nephron and K+ is lost, causing hypokalaemia.

50

All of the following statements related to the renin-angiotensin systems are correct except for:


  Angiotensinogen (A) is produced by the liver.

  AI is a decapeptide.

  AII is an octapeptide.

  AI causes vasoconstriction.

  AII causes vasoconstriction.


Angiotensinogen is produced by the liver, and AI, a decapeptide, is split off by renin. Ai is converted to AII, an octapetide, by converting enzyme. AII is the active substance causing vasoconstriction, aldosterone release and increased proximal tuble sodium absorption. AI does not have these actions. AII may also have important effects on growth of heart cells and vascular smooth muscle.

51

All of the following statements related to angiotensin II (AII) systems are correct except for:


  AII concerted to bradykinin by converting enzyme.

  AII causes vasoconstriction.

  AII stimulates aldosterone secretion.

  AII increases proximal tubule sodium reabsorption.

  AII stimulates thirst.


See Question 50. AII in the brain stimulates thurst. Converting enzyme converts AI to AII and also breaks down bradykinin. If converting enzyme is not present bradykinin will accumulate.

52

All the following statements to renal function clearance are correct except for:


  Inulin clearance gives an accurate estimate of GFR.

  PAH clearance gives an estimate of renal plasma flow.

  Clearance = (urine volume x urine concentration)/plasma concentration.

  Creatinine clearance gives an estimate of GFR.

  Urea clearance gives an estimate of GFR.


The clearance of a suhstancc is the volume of blood from which all of a suhstance would he removed in a given time. The amount excreted in the urine is the flow rate (volume in a given time) x concentration in urine. If you know the plasma concentration then: Clearance = amount secreted in urine in a given time/concentration in plasma or Clearance = (urine volume x urine concentration)/plasma concentration All values must he put in the same units. Clearance is expressed us mL/min or mL/sec. If you know how a substance is handled you can obtain certain values. Inulin is freely filtered but not secreted or reabsorbed. Thus it gives a value for GFR. PAH is filtered but in addition the proximal tubule removes all of it from plasma, so that an estimate of renal plasma now can he obtained. If the haematocrit is known renal blood flow can be calculated. Creatinine is filtered. There may be a small amount reabsorbed but it gives an approximation of GFR. Urea is freely filtered but a large amount is reabsorbed in the proximal tubule. Thus it is not an estimate of GFR.

53

A person aged 18, weight 65kg, has the following values estimated: plasma creatinine 0.10mmol/L; plasma urea 5.0 mmol/L. In 1 hour the amount of creatinine excreted in the urine was 0.72mmol and the amount of urea excreted was 18mmol. Which one of the following statements related to this person's renal function is most accurate?


  The clearance of urea is greater than that of creatinine.

  Urea clearance was 90mL/min.

  Creatinine clearance was 72mL/min.

  Creatinine clearance was 12mL/min.

  GFR was 120mL/min.


You need first to calculate the clearance of each substance. Here we are given the excretion in 1 hour. Conrect to excretion in 1 minute by dividing by 60, the plasma concentrations are per litre. These need to be divided by 1000 to make it per mL. Clearance = amount secreted (mmol/min)/concentration (mmol/min) = mL/min Creatinine = 0.72/60 x 1000/0.10 = 720/6 = 120mL/min Urea = 18/60 x 1000/50 = 18000/300 = 60mL/min Creatinine clearance gives an estimate of GFR. Thus the statement that GFR was 120 mL/min is correct, and the clearance of creatinine is greater than urea. None of the other calculated clearance values are correct, but creatinine clearance gives an indication of GFR, which is 120 mL/min.

54

Questions 54 to 59 refer to the following case. A person aged 48, weight 70kg, has the following values measured in their plasma and urine. An infusion of PAH and inulin has been given to achieve constant blood levels. 100mL of urine was collected over 2 hours. The patient's haematocrit is 40%.

Plasma concentrationUrine concentration
Creatinine0.10 mmol/L10.8 mmol/L
Urea4 mmol/L240 mmol/L
PAH0.05 mmol/L30 mmol/L
Inulin0.05 mmol/L6 mmol/L
Drug A1 umol/L360 umol/L
Drug B10 umol/L120 umol/L
All of the following statements related to clearance in this patient are correct except for:


  Creatinine clearance was 90mL/min.

  Urea clearance was 50mL/min

  PAH clearance was 500mL/min.

  Inulin clearance was 100mL/min.

  Drug A clearance was 360mL/min.


YOu must first calculate the clearance of all substances, making certain all values are in the same units. Clearance = ((Vol*Uc)/Pc)x(100/120)x(Uconc/Pconc) e.g. Creatinine = (100/120)x(10.8/0.10) = 90mL/min The clearances of the other substances are urea, 50; PAH, 500; inulin, 100; Drug A, 300; and Drug B, 10 mL/min. The concentrations in the urine and the total amount excreted give little information about clearance since plasma concentrations are different.

55

This question relates to the patient described in Q54. Which one of the following statments related to this person's renal function is most correct?


  GFR is 90mL/min.

  GFR is 50mL/min.

  GFR is 100mL/min.

  Inulin clearance was 100mL/min.

  Drug clearance was 360mL/min.


lnulin clearance gives the best guide to GFR. Thus Answer 3, 100 mL/min, is Lhe right response. Creatinine clearance gives a guide but is not as accurate as some creatinine can be reabsorbed.

56

This question relates to the patient described in Q54. Which one of the following statements related to the percentage of the water in the glomerular filtrate that is reabsorbed is most accurate?


  90%.

  95%.

  99%.

  99.2%.

  99.5%.


GFR is 100 mL/min. In 1 minute 100/120 = 0.825 mL of urine is formed. Thus approximately 99.2 mL and in this case 99.2% of water in the glomerular filtrate is reabsorbed.

57

This question relates to the patient described in Q54. All of the following statements related to this patient are correct except for:


  GFR is 100mL/min.

  Renal plasma flow is 500mL/min.

  Filtration fraction is 0.20.

  Drug A must be secreted.

  Drug B must be secreted.


GFR, renal plasma flow (i.e. PAH clearance) and filtration fraction GFR/RPF=100/500=0.2 are all correct. The clearance of Drug A is 300mL/min which is greater than GFR. Thus it must be secreted. The clearance of Drug B is about 10% of the GFR. It could be filtered and reabsorbed to obtain this value. It is feasible that it could be secreted but the statement that it must be secreted is incorrect.

58

This question relates to the patient described in Q54. All of the following statements related to this patient are correct except for:


  PAH is filtered and secreted.

  Inulin is filtered and not reabsorbed.

  Creatinine is filtered and some is reabsorbed.

  Drug A is filtered ad not secreted.

  If Drug B is filtered it must be reabsorbed.


See Questions 52, 53 and 54

59

THis question relates to the patient described in Q54. All of the following statements related to the two drugs could be correct except for:


  Drug B is protein bound.

  Drug A could not be protein bound.

  Drug B could be filterd.

  Drug B could be reabsorbed.

  Drug A could be secreted.


Drug B could be protein bound so that only a certain amount is filtered. If tightly protein bound none might be filtered but some could be secreted. Thus answers A, C or D related to this drug could all be correct. Drug A must be handled by secretion as the clearance is greater than GFR. It may be both filtered and secreted but even if protein bound, which would prevent filtration, it could still be secreted.