Mar 30- April 4th Renal

Question 1

16. State the percentage of the resting cardiac output that normally becomes renal blood flow, and compare the amount of renal blood flow that goes to the renal cortex vs. to the renal medulla

Answer 1

20% of the resting cardiac output goes to the kidneys; all blood is delivered to the cortex and a small fraction (5%) is directed to the medulla (low blood flow in the medulla permits an interstitial environment that is different from blood plasma)

Question 2

17. Put the following into the sequence encountered by blood flowing through the kidney:

cortical radial artery, afferent arteriole, arcuate artery, peritubular capillaries, glomerular 
capillaries, renal vein, efferent arteriole, renal artery

Answer 2

renal artery; arcuate arteries, cortical radial arteries, afferent arterioles, efferent arterioles, peritubular capillaries, renal vein

Question 3

Which part of the kidney is most vulnerable to ischemia and why?

Answer 3

there is limited blood flow via the vasa recta to maintain the concentration gradient, which means interstitial cells are particularly sensitive to changes in erythrocyte concentration (oxygen concentration) for erythropoietin levels

Question 4

18. Explain where vasa recta would occur, if they were on the list in the previous question

Answer 4

instead of branching to peritubular capillaries, vasa recta descend downward into the outer medulla, where they divide many times to form bundles of parallel vessels which penetrate deep into the medulla, then reform into ascending vasa recta that run in close association with the descending vasa recta

Question 5

19. Categorize all structures in the previous two questions as to whether they occur in the medulla or cortex of the kidney.: renal artery, arcuate arteries, cortical radial arteries, afferent arterioles, efferent arterioles, peritubular capillaries and vasa recta

Answer 5

Renal artery (medulla)
	Arcuate arteries (border between medulla and cortex)
	Cortical radial arteries (cortex)
	Afferent arterioles (cortex)
	Efferent arterioles (cortex)
	Peritubular capillaries (cortex)
	Vasa recta (medulla)

Question 6

20. List the average blood pressure inside glomerular and peritubular capillaries, and explain how the differences are important in their unique roles in renal function

Answer 6

arterial pressure is necessary to drive glomerular filtration whereas the low peritubular capillary pressure is equally necessary to permit the reabsorption of fluid; glomerular capillary pressure remains close to 60mmHg and 20 mmHg at the point where it feeds a peritubular capillary

Question 7

21. Describe the three layers that make up the glomerular filtration barrier.

Answer 7

1. Endothelial cells of capillaries (perforated and permeable to everything in blood except cells and platelets), carries a negative charge
2. Capillary basement membrane: acellular meshwork of glycoproteins and proteoglycans—selectivity around molecular size and charge
   3, Epithelial podocytes that surround the capillaries which include slit diagphragms– selectivity around molecular size and charge

Question 8

22. Draw a graph that demonstrates how both the size and charge of a solute molecule affect its permeability at the renal corpuscle.

Answer 8

p412 of phys text book

more positively charged particles are filtered than neutral particles (decreasing filtration with size); less negatively charged particles are filtered than neutral particles (decreasing filtration with size

Question 9

23. Using Ca2+ as an example, explain how binding to albumin affects the degree to which plasma substances are filterable.

Answer 9

plasma proteins are virtually unfilterable, so substances that bind to them- like Ca2+, do not filter freely, 40% of Ca2+ is bound to plasma proteins and does not get filtered; not positively charged macro molecules are filtered to a greater extent than negatively charge particles (this does not affect mineral anions or low-molecular weight organic anions)

Question 10

24. List the Starling’s forces that are most influential in determining net glomerular filtration pressure, and explain whether each one favors filtration or opposes filtration.

Answer 10

fluid pressure in Bowman’s space (disfavors filtration; Hydrostatic pressure in glomerular capillaries (favors filtration); plasma proteins in the capillaries (disfavor filtration)

Question 11

How would one calculate the rate of filtrations of glomerular capillaries based on its hydraulic permeability and surface area?

Answer 11

Rate of filtration= NFP (net filtration pressure ) Kf (filtration coefficient)

Question 12

25. State which of Starling’s forces changes the most along the length of glomerular capillaries.

Answer 12

the oncotic pressure in the glomerular capillaries does change substantially along the length of the glomeruli

Question 13

26. Explain the variables that constitute the filtration coefficient (Kf), and how Kf influences the GFR.

Answer 13

Filtration coefficient is used to denote the product of the hydraulic permeability and the area, changes are most often by glomerular disease but also by normal physiological control via chemical messengers that cause contraction of capillary loops reducing filtration area and GFR; increases in Kf mean greater GFR

Question 14

Do the pressure in the glomerular capsule and the glomerular capillaries normally vary?

Answer 14

no. there is very little change throughout the capillary system, oncotic pressure has the greatest ability to change and there for affect GFR

Question 15

What is the average NFP (net filtration pressure)

Answer 15

16 mmHg (8x greater than other systemic capillaries)

Question 16

Describe a situation where changes in Kf (change in capillary surface area) causes variation in GFR.

Answer 16

with age and in disease, reduction in the number of functioning nephrons decreases, leads to decreased GFR

Question 17

How could pressure of the glomerular capillaries change GFR?

Answer 17

increased afferent resistance decreases GFR, increase in efferent resistance increases GFR, where as the converse of each situation is true

Question 18

27. For each Starling force and for the Kf, determine how the glomerular filtration rate would be affected if the variable increased or decreased.

Answer 18

Kf can change via chemically caused constriction may restrict flow through some of the capillary loops, effectively reducing area available for filtration
Hydrostatic pressure in the glomerular capillaries PGC is influenced by many factors, changing the diameter of vessels before or after the glomerulus can drastically change GFR depending on the spot. Upstream constriction can reduce GFR while downstream constriction can increase GFR
PBC changes are of minor importance save any obstruction in the urinary tract which will cause building pressure upstream
Oncontic pressure of the plasma in vessels of the glomerulus will increase slowly through the capillaries as water leaves—steep increases occur when RBF is very low; liver disease (lack of plasma proteins) will decrease pressure also; high oncotic pressure will decrease GFR

Question 19

28. Explain how increasing and decreasing the radius of afferent and efferent arterioles independently affects renal blood flow and glomerular filtration rate

Answer 19

Glomerular capillary pressure is regulated by the diameter changes in efferent and afferent vessels (sites of largest resistance); renal blood flow can remain constant despite pressure changes that cause change in the GFR by constriction and dilation

Question 20

29. Describe a clinical situation in which GFR is altered due to a change in the pressure within Bowman’s capsule (PBC).

Answer 20

If the urinary tract is blocked by a kidney stone, the increase of pressure in bowman’s capsule will oppose filtration and decrease GFR

Question 21

30. Detail the mechanism by which a reduction in the liver’s production of plasma proteins can affect renal function.

Answer 21

Decreasing liver production of plasma proteins decreases the oncotic pressure in the capillaries, which will increase overall filtration

Question 22

31. Explain how changes in renal plasma flow and the filtration fraction indirectly affect oncotic pressure in glomerular capillaries (πgc ) and thus GFR.

Answer 22

Slower flow can cause a greater amount of plasma to be removed, and a large concentration of plasma proteins in capillaries (decreasing filtration)

Question 23

32. Define “filtered load” and write the equation that can be used to calculate it for any given substance.

Answer 23

Filtered load is the amount of substance that is filtered per unit time, for freely filtered substances, this is the GFR and the plasma concentration (product)
Filtered Load = GFR x [substrate in plasma], filtered load is measured in mg/min of a given substrate NOTE concentration of the substrate needs to be correct if the substance is not freely filterable

Question 24

How do you calculate the filtration fraction?

Answer 24

GFR/RPF (renal plasma flow)

Question 25

33. Explain the overall purpose of renal autoregulation, and detail how the myogenic response plays a role in autoregulation.

Answer 25

Autoregulation (arteriolar myogenic mechanisms) is important for kidneys to keep the FGR at a level appropriate for the body in regards to salt and water levels; because GFR is so strongly influenced by renal arterial pressure so autoregulation protects the glomerular capillaries from hypertensive damage (autoregulation cannot totally offset the affects of hypertension) — affects are partly a result of myogenic response and a result of other complicated intrarenal signals that affect vascular resistance and mesangial cell contraction

Question 26

Given that the amount of Na+ that the nephron filters and reabsorbs varies with GFR and plasma concentration, how might the body actively change the Na+ levels in the body

Answer 26

Na+ balance can thus be altered by changes in GFR

Question 27

34. Compare the osmolarities of the glomerular plasma, filtrate in Bowman’s space, and filtrate at the end of the proximal tubule, and explain how these osmolarities are maintained despite reabsorption of large amounts of fluid.

Answer 27

Most of the reabsorption in the the proximal tubules are nearly iso-osmotic, by the end of the proximal tubule is filtrate is still isosmotic because solutes are reabsorbed in equal amounts to water

Question 28

What happens to GFR and blood flow with increased blood pressure?

Answer 28

both flow and GFR do increase with increased blood pressure but they do so slowly due to compensation of auto regulation

Question 29

What is not filtrated into Bowman’s capsule? (the catch to “virtually isoosmotic”)

Answer 29

larger proteins do not leave the circulation (generally speaking)

Question 30

Where does regulated reabsorption occur, compared to areas where reabsorption is iso-osmotic?

Answer 30

iso-osmotic reabsorption occurs in the proximal tubules, regulated absorptions occurs in distal tubules, collecting ductules and collecting tubules

Question 31

35. Describe all possible routes by which substances can be reabsorbed from tubular lumen to renal interstitial fluid, defining the terms transcellular, paracellular, apical and basolateral.

Answer 31

Transcellular (through cells), paracellular (around cells- through the matrix of tight junctions that link cells); transcellular route requires two steps, transport across the apical membrane and transport across the basolateral membrane

Question 32

36. List the steps that link Na+ transport to that of anions and water in the proximal tubule.

Answer 32

1. sodium is actively extruded into the interstitial from the tubule epithelial cell (Na, K-ATPase), 2. Sodium enters passively from the tubular lumen (mostly through sodium- proton antiporter), 3. Anions follow the sodium, 4. Water follows the solute (aquaporins) 5. Water and solutes move by bulk flow into the peritubular capillary (process of cell polarization causes movement of other substances through transcellular transport)

Question 33

37. Explain how Starling’s forces favor the bulk-flow reabsorption of fluid from the renal medullary interstitium into the peritubular capillaries.

Answer 33

low pressure in capillary, high interstitial pressure and high peritubular capillary oncotic pressure (concentrated proteins that were not filtrated)

Question 34

Exit of water concentrates many solutes, like __,___,___,___ and ____ which diffuse down their concentration gradients through _______

Answer 34

urea, K+, Cl-, Mg2+ and Ca2+; tight junctions

Question 35

38. Distinguish between a gradient-limited reabsorption mechanism and a tubular maximum-limited one, using specific examples of substances handled in one way or the other.

Answer 35

gradient limited systems- when tight junctions are very leaky to a given substance, it is impossible for the removal of the substance from the lumen to reduce its luminal concentration very much below that in the cortical interstitium (substance can leak back as fast as it is removed) (ie. Na+)

tubular maximum-limited systems feature systems in which the tight junction is impermeable to the solutes in question (no leak), the limit on the transport rate is placed on the capacity of the transporters ro remove the subsance (ie. Glucose)

Question 36

T/F Flow at the afferent arterioles is less then the efferent arterioles

Answer 36

false, plasma volume is lost to filtration between the afferent and efferent arterioles

Question 37

39. List examples of organic molecules that kidney mechanisms prevent from being excreted, and note the region(s) of the nephron in which those mechanisms act.

Answer 37

glucose, amino acids, acetate, Krebs cycle intermediates, some water soluble vitamins, lactate and many other are actively reabsorbed, the proximal tubules are the major site for reabsorption

Question 38

40. Explain why there is not a 1:1 ratio between the number of essential amino acids and the number of transporters that reabsorb amino acids.

Answer 38

Two or more closely related substances may use the same transporter

Question 39

41. Describe the mechanism by which most organic nutrients are moved from the nephron lumen into epithelial cells.

Answer 39

They are actively transported up their respective electrochemical gradients by transport proteins usually coupled symport with Na+, most are Tm- limited systems (max rate much higher than the normal filtration rate) (example: drug that inhibits SGLUT can cause osmotic diaeresis)

Question 40

42. Detail the mechanisms by which glucose is transported across each barrier from the proximal tubule lumen into the peritubular capillaries.

Answer 40

Taking up glucose from the tubular lumen via a sodium-dependent glucose symporter SGLUT across apical proximal convoluted tubule epithelial cells, followed by its exit across the basolateral membrane into the interstitium via a glucose transporter GLUT

Question 41

Contrast the fate of organic wastes v. organic nutrients in the afferent arterioles.

Answer 41

both are filtered, organic wastes can also be actively secreted (esp. important if bound to carrier molecules) and nutrients are actively reabsorbed

Question 42

What is the characteristic sign that someone has osmotic diuresis (ie. from diabetic ketoacidosis)?

Answer 42

large volume of urine that is highly concentrated

Question 43

42. Detail the mechanisms by which glucose is transported across each barrier from the proximal tubule lumen into the peritubular capillaries.

Answer 43

Na/K ATPase sets up a Na+ gradient first (K+ cycles passively through channel); glucose is taken up from the tubular lumen via a sodium-dependent glucose symporter SGLUT across apical proximal convoluted tubule epithelial cells, followed by its exit across the basolateral membrane into the interstitium via a glucose transporter GLUT

Question 44

43. Draw a graph showing the filtration, reabsorption and excretion rates of glucose at different plasma concentrations, and use it to explain the concept of a transport maximum (Tmax).

Answer 44

p430 in book for diagram: Excretion of glucose begins after the transport maximum has been exceeded (reabsorption can no longer match the growing glucose load). After transport maximum is exceeded, the amount of secretion parallels the filtered load as they both increase

Question 45

44. Calculate the filtered load of glucose in a person with a normal GFR and a blood glucose concentration of 350 mg/dL, and from this, estimate the rate of glucose excretion (in mg/min) in the urine. Explain how this situation might cause the urine flow rate to change, compared to when the blood glucose is in its normal range (90-100 mg/dL).

Answer 45

1.25 dL/min x 350 mg/dL = 437.5 mg/min, this would exceed the Tm of 375 for glucose and lead to 62.5 mg/min excretion and this osmotically active substance in the urine can lead to osmotic diuresis

Question 46

45. Describe the handling of proteins and peptides by the kidney, including the types and amount filtered, and the mechanisms that normally prevent large quantities of protein from appearing in the urine. Under what circumstances does urinary protein increase?

Answer 46

Urine has a total protein content much lower than plasma; peptides and smaller proteins are filtered in considerable quantities while there is extremely limited amount of large plasma proteins cross into glomerular filtrate (normally enzymatically degraded to their constituents and amino acids are returned to the blood); larger proteins require endocytosis at the apical membrane (energy requiring) and is degraded into small fragments which exit the basolateral membrane

Question 47

46. Explain the normal role of the kidney in regulating peptide hormone levels in the blood, and what occurs when glomerular filtration mechanisms are impaired.

Answer 47

Total mass of filtered hormone is insignificant, however because even tiny levels in the plasma have important signaling function in the body, renal filtration becomes an important influence on the concentrations in the blood; the kidneys are major sites of catabolism of many plasma proteins, including polypeptide hormones and decreased rates of degradation occurring in renal disease may result in elevated plasma hormone concentrations NOTE: proteinuria can be normal after exercise esp. running

Question 48

47. Detail the mechanism by which the kidney excretes wastes and toxins that are organic anions, including the events at both apical and basolateral membranes

Answer 48

Na/K ATPases set up the proton gradient that powers cotransport by OAT isoforms that transport organic substances into the epithelial cell on the apical side and is then pumped by cotransporter OAT and MRP2 isofrom into the tubule through the basolateral membrane

Question 49

47.3 List some examples of endogenous and exogenous organic anions

Answer 49

endogenous: bile salts, fatty acids, hippurates, oxalate, prostaglandins, and urate; exogenous: acetazolaminde, furosemide, penicillin, saccharine, salicylates etc.

Question 50

47.2 What is the role of water solubility of the substance, the role of the liver, the concept of tubular maximum, and which region of the nephron is involved

Answer 50

the concept of tubular maximum is important with drug therapy- concentrations must exceed Tm in order to persist in the blood stream; other molecules that are transported by the same transporters can compete for transport and slow secretion of drugs; the water solubility of the substance relates back to how easily it can leak back across the membrane and different areas of the tubules have different permeabilities to give substances

Question 51

48. List three ways by which altered renal function can lead to the condition gout.

Answer 51

1. decreased filtration of urate secondary to the GFR, 2. Excessive reabsorption of urate and 3. Diminished secretion of urate

Question 52

49.2 List some examples of endogenous and exogenous organic

Answer 52

endogenous substances: chine, creatinine, dopamine, epinephrine (many neurotransmitters) and exogenous: atropine, isoproterenol, morphine procaine etc.

Question 53

49. Compare the mechanisms by which the kidney secretes organic cations to how it handles organic anions.

Answer 53

Organic cations enter across the basolateral membrane via one of the several uniporters, members of the organic cation transporter family and exit into the lumen via an antiporter, which exchanges a proton for the organic cation

Question 54

50. Explain how acidifying or alkalinizing the urine affects the excretion rate of drugs and endogenous organic substances that are weak acids or bases, and explain how this mechanism can be used to reduce or enhance the impact of a drug.

Answer 54

State of ionization affects both the aqueous solubility and membrane permeability of the substance; neutral forms of organic acids and bases are more permeable in lipid membranes (this can trap ions in the lumen), the lower the pH the greater the amount in the neutral acid form; protonation of weak bases makes them impermeable to renal tubular cells (are not reabsorbed) highly acidic urine tends to increase passive reabsorption of weak acids – many medically useful drugs are weak organic acids and bases for which these factors have important clinical consequences

Question 55

51. Describe the production of urea in the body, and the role of the kidneys in maintaining urea balance.

Answer 55

In most people, urea production proceeds continuously as a result of protein catabolism in the liver, urea constitutes about half of the normal solute content of urine and is a crucial player in osmotic concentrations within the renal medulla; in urea balance, the kidney excretes as much urea as is excess with only transient fluctuations urea levels

Question 56

What is the TF/Plasma ratio.

Answer 56

it is the ratio of the tubular fluid concentration of a substance compared to the plasma concentration of that same substance

Question 57

53. Rank the urea concentration in the following locations in descending order of urea concentration in a typically hydrated person: Medullary collecting duct, distal convoluted tubule, Bowman’s space, beginning of the descending loop of Henle.

Answer 57

distal convoluted tubules (110% secreted in ascending limb), Bowman’s space(100% freely filtered), Medullary collecting duct (50% reabsorbed for counter-current multiplier in cortex), beginning of the descending loop of Henle (50% secreted into ascending loop)

Question 58

54. State the typical percentages of total body water found in the intracellular fluid (ICF) and extracellular fluid(ECF) compartments. Compare those percentages to the percentage of total body osmotic particles found in these two compartments.

Answer 58

Body water is typically 60% of body weight is in ICF, the remaining 1/3 is in ECF *** (needs more)

Question 59

55. Draw a diagram showing the effects on ECF and ICF volumes of ingesting: a)pure water, b)isotonic saline, or c)pure NaCl

Answer 59

p 438: ingestion of pure water will equally distribute into all three compartments, infusion of isotonic saline solution will lead to inflated ECF volume and a pure NaCl addition will steal water for the ICF and cause dehydration of cells

Question 60

56. List the sources of intake and the routes of output of Na+ and water, and explain for each which route is regulated physiologically to keep the body in balance.

Answer 60

Intake: food; output: sweat, feces, urine—urine content is physiologically regulated to keep the body in balance NOTE: total body NaCl determines ECF volume so kidney’s excretion rate must regulate balance for homeostasis of blood volume and pressure

Question 61

57. Compare the amount of Na+ and H20 filtered each day to the amounts that typically are excreted into the urine.

Answer 61

Typically a person could ingest 20-25g of sodium chloride per day with 630 g Na/day filtered and only 4g excreted (<1% filtered), the healthy kidney can readily alter excretion of salt over this range, urinary water excretion can be varied physiologically from approximately 0.4 to 25 L a day

Question 62

58. List the typical percentages of filtered Na+ and Water (separately) that are reabsorbed in the proximal tubule, descending loop of Henle, Ascending loop of Henle, distal convoluted tubule, and collecting duct.

Answer 62

Proximal tubule  65% salt
Descending loop of Henle
Ascending loop of Henle  25% salt
Distal convoluted tubule  5% salt
Collecting duct 0-5% salt

Question 63

How is the magnitude of Cl- reabsorption related to Na+ reabsorption

Answer 63

because Cl- reabsorption is dependent on Na+ reabsorption, the tubular locations that reabsorb Cl- and the percentages of filtered Cl- that are reabsorbed are similar to those for Na_

Question 64

59. Given that the average total osmoles of waste products that need to be eliminated each day, and that the maximum osmolarity of urine the kidney can produce is 1400 mOsm/L, calculate the minimum volume of urine that must be excreted in a day to keep the body in balance. Describe the environmental circumstances in which this amount and type of urine would be produced, and explain why you shouldn’t drink seawater.

Answer 64

Cannot drink saltwater because the obligatory water loss contributes to dehydration when a person is deprived of water intake, to excrete all the salt in seawater plus the obligatory solute would require more urinary water than was contained in the seawater consumed

The minimal volume of water in which the required amount of wastes is excreted is roughly 0.43 L per day (600mOsm waste / 1,400 mosm/L max concentration), this small amount of super concentrated urine might be produced under situations of highly dehydrated situations

Question 65

60. Draw a proximal tubule cell and include the principal transporters and channels in the apical and basolateral membrane that are responsible for reabsorbing Na+, Cl- and H20.

Answer 65

1. Sodium is transported to the interstitium mostly via the basolateral Na/K-ATPase but also in symport with bicarbonate, active pumping creates a Na gradient within the cell
2. Na/H antiporter on the apical side transports most of the Na+ into the epithelial cell from the proximal tubule
3. Organic nutrients are reabsorbe with Na+ via a variety of specific transporters (glucose, phosphate, amino acids, etc
4. Note in order to maintain electroneutraility, Cl- always follows Na+ in nearly equal proportions mostly paracellularly, with some in antiport with bases

Sodium entry via the apical membrane is coupled to the secretion or uptake of a variety of substances, the major one being hydrogen ions, which are secreted in exchange for sodium via the NHE3 anitporter. Additional sodium enter is symport with glucose, amino acids and phosphate.

Chloride that enters in antiport with organic vase leaves mostly via channels, in addition a substantial amount of chloride is reabsorbed paracellularly; active chloride transport in the later proximal tubule using parallel Na-H and Cl-base antiporters and in exchange for antiport of small organic molecules (secretion of organic molecules)

Water moves both paracellularly and intracellularly via aquaporins

Question 66

61. Explain how, in addition to reducing the reabsorption of water, an osmotic diuretic reduces the reabsorption of Na+ and other solutes in the proximal tubule. Name a common disease in which this occurs.

Answer 66

Proximal tubule is very permeable to water and small difference in osmolality can create water reabsorption ie. reabsorption of NaCl

If sodium transport across tubule walls is blocked, it is osmotically active in the filtrate and “holds” water in the filtrate, during diuresis there is less reabsorption of water and less concentration of other luminal solutes which are not pushed to move down their concentration gradients out of tubules; this can occur as a result of pathology as in uncontrolled diabetes mellitus where filtered load of glucose exceeds the tubular maximum and glucose remains as a osmotically active substance

Question 67

62. Compare the fraction of filtered NaCl reabsorbed in the loop of Henle to the fraction of filtered water reabsorbed in the loop of Henle, and describe how this affects the osmolarity of the fluid entering the distal convoluted tubule.

Answer 67

NaCl reabsorption in Henle’s loop is greater than reabsorption of water, unlike in the proximal tubule where water and NaCl are absorbed in equal amounts, therefore the urine leaving the loop of Henle is diluted

Question 68

63. Describe the differential permeability to water of the descending and ascending portions of the loop of Henle

Answer 68

descending limb reabsorbs water but not sodium or chloride and the ascending limb reabsorbs very little water

NOTE between the PCT and the bottom of the loop osmolarity increases and flow decreases only slightly, where as in the ascending tubule, osmolarity decreases while flow stays the same

Question 69

Does movement out of the tubule change osmolality of flow of the filtrate.

Answer 69

it changes both, while movement of solutes will only affect the osmolality

Question 70

64. Draw a picture of an epithelial cell in the thick ascending limb of the loop of Henle showing the apical and basolateral transport mechanisms that result in Na+ and Cl- reabsorption. Contrast that mechanism with how NaCl is reabsorbed in the thin ascending limb.

Answer 70

1. Na/K ATPase sets up gradient on basolateral membrane
2. NCCK transporter trasports both Na+, 2Cl- and K+ into the apical membrane, K+ exits through channels back into the tubules
3. Cl- and K+ travel down their concentration gradients out of channels on the basolateral membrane

Tight junctions between cells prevents paracellular movement of water

Question 71

65. List two commonly used loop diuretics, and describe their specific target protein and how they result in diuresis

Answer 71

Loop diuretics include furosemide (Lasix) and bumetanide which both target the NKCC transporters and limit the reabsorption of ions, particularly Na, Cl and K

Question 72

66. Draw an epithelial cell of the distal convoluted tubule, showing the apical and basolateral transport mechanisms that result in Na+ and Cl- reabsorption, and point out the protein that is a target of the thiazide diuretics.

Answer 72

generally salt reabsorption occurs without significant water permeability

1. Na/K ATPase creates gradient on basolateral membrane
2. Na/Cl cotransporter transports NaCl across the apical membrane along with sodium channels

Distal tubule reabsorption uses Na-Cl symporter and is specifically sensitive to thiazide diuretics. The end result is that DCT further dilutes the filtrate because the distal tube is not permeable to water

Question 73

67. Draw a principal cell as found in the cortical collecting duct, showing the apical and basolateral transport mechanisms that result in Na+, Cl- and water reabsorption. Explain how water reabsorption varies, depending upon the presence of antidiuretic hormone (ADH).

Answer 73

1. Na/K ATPase creates gradient (pump regulated by aldosterone) on basolateral membrane
2. Aldosterone controls Na, K and ADH controls H20 channels in the apical membrane
3. Basolateral membrane also includes K and H20 channels

In collecting duct the principal cells’ main function is aldosterone-mediated NaCl absorption and K+ secretion

when ADH is present, water reabsorption occurs in principal cells, and tubular fluid osmolarity comes to match that of the cortical interstitial fluid

Question 74

68. Compare the urea and NaCl concentrations in the renal medullary interstitium under conditions of water deprivation (dehydration) and water excess.

Answer 74

when you are dehydrated, there is a steep gradient in the renal interstitium, most of the water available is reabsorbed in the cortex DCT before it can dilute the medullary interstitum (controlled by ADH); when you drink lots of water the gradient is destroyed a bit by the water that persists in the tubule into the medulla

Question 75

69. Explain how the countercurrent anatomy of the vasa recta prevents the washout of the renal medullary interstitial osmotic gradient, including the importance of the magnitude of blood flow in the vasa recta.

Answer 75

Vasculature that minimizes removal of sodium form the medullary interstitium due to both to a low rate of blood flow is important to develop the medullary osmotic gradient and the arrangement of descending components in close apposition to ascending components; medullary sodium recirculates, diffusing out of ascending vessels and reentering nearby descending vessels developing a countercurrent exchange

Question 76

Name the 4 conditions that help to build the countercurrent exchanger?

Answer 76

1. active transport of salt from the ascending limb into the medullary interstitium
2. water impermeability of the ascending limb
3. water absorption from the descending limb
4. urea from the collecting duct into the medullary interstitium, which is regulated by ADH

Question 77

70. Compare the pattern of water reabsorption and tubular filtrate osmolality in maximum antidiuretic and maximum diuretic states; also compare the final urine flow and osmolality.

Answer 77

in the absence of ADH:

1. PCT: flow decreases, osmolality is constant
2. descending tubule: flow decreases slightly, osmolality increases
3. ascending tubules: flow is constant, osmolality decreases
4. DCT: flow decreases, osmolality is constant
5. Collecting ducts: flow is constant, osmolality decreases

In the presence of ADH the only thing that changes is that H2O and urea reabsorption from the collecting ducts is increased, which reduces flow and increases osmolality in the collecting ducts

Medullary blood flow is lowest in conditions where medullary osmolality is highest, so there is no “washing out” the gradient