1. % of Filtered Load Reabsorbed
Reabsorption:
> large amounts are filtered
>for many substances, large amounts are reabsorbed, so little is excreted
Amount Filtered
Amount Reabsorbed
Amount Excreted
% of Filtered Load Reabsorbed
glucose
180
100
Bicarbonate (mEq/day)
4,320
4,318 2
>99.9
Sodium (mEq/day)
25,560
25,410
150
99.4
Chloride (mEq/day)
19,440
19,260
99.1
Potassium (mEq/day)
756
664 92
87.8
urea
46.8
23.4 50
Creatinine (g/day)
1.8
Urea
Table Filtration, Reabsorption, and Excretion Rates of Different Substances by the Kidneys
Glucose
Table 27-1

2. Reabsorption across tubular epithelial cells
Brush border
Reabsorption across tubular epithelial cells
PC=proximal convoluted
DC=distal convoluted
BB=brush border
Figure 27-1

3. Brush border
Scanning EM of proximal tubule cell

4. Pressures favoring reabsorption by bulk flow into peritubular capillaries
Figure 27-15

5. Sodium reabsorption in the proximal tubule
Figure 27-2

6. Secondary active transport
Version from the Silverthorn text
Figure 27-3

7. Passive reabsoprtion of some substances
Glomerulus
Peritubular
capillary
Bowman’s
capsule
125 ml of
filtrate
Beginning of
proximal
tubule
Na+ (active)
H2O (osmosis)
Na+ (active)
H2O (osmosis)
End of
proximal
tubule
44 ml of
filtrate
Passive diffusion
of urea down its
concentration gradient
= Urea molecules
Figure Page 534

8. Importance of transport maxima
Substance Transport Maximum
Glucose 375 mg/min
Phosphate 0.10 mM/min
Sulfate 0.06 mM/min
Amino acids 1.5 mM/min
Urate 15 mg/min
Lactate 75 mg/min
Plasma protein 30 mg/min
Transport Maximums for Substances That Are Actively Secreted. Substances that are actively secreted
Creatinine 16 mg/min
Para-aminohippuric acid 80 mg/min
Figure 27-4

9. Silverthorn Figure 19-15 - Overview

10. Different segments are specialized for different things:
Proximal Tubule: REABSORBTION, secretion
Figure 27-6

11. Figure 27-7

12. We’ll save loop of Henle for next time
Figure 27-8

13. Distal tubule and collecting duct: regulated reabsorption and secretion
Figure 27-11

14. (a wonderful figure; pay attention to:
Glucose and amino acids
Na+, K+, Cl-
Urea
Inulin and creatinine
PAH
Figure 27-14

15. Key hormones involved in the regulation of reabsorption
Site of Action
Effects
Aldosterone
Collecting tubule and duct
↑ NaCl, H2O reabsorption, ↑ K+ secretion
Angiotensin II
Proximal tubule, thick ascending loop of Henle/distal tubule, collecting tubule
↑ NaCl, H2O reabsorption, ↑ H+ secretion
Antidiuretic hormone
Distal tubule/collecting tubule and duct
↑ H2O reabsorption
Atrial natriuretic peptide
↓ NaCl reabsorption
Parathyroid hormone
Proximal tubule, thick ascending loop of Henle/distal tubule
↓PO4--- reabsorption, ↑ Ca++ reabsorption
Table 27-3
(we’ll focus on aldosterone and antidiuretic hormone during the next two classes)

16. For a substance that is freely filtered, but not reabsorbed or secreted:
Silverthorn Figure 19-16

17. Figure 27-19

18. Silverthorn Table 19-2

19. Clearance Rate (ml/min)or
Substance
Clearance Rate (ml/min)
Glucose    
Sodium
0.9
Chloride
1.3
Potassium
12.0
Phosphate
25.0
Inulin
125.0
Creatinine
140.0
Silverthorn Figure Overview

20. Don’t worry about memorizing these formulas, but understand what they represent
Table 27-4
Term
Equation
Units
Clearance rate (Cs)
                       
ml/min
Glomerular filtration rate (GFR)
                                 
Clearance ratio
                                            
None
Effective renal plasma flow (ERPF)
                                                 
Renal plasma flow (RPF)
                                                                
Renal blood flow (RBF)
                                         
Excretion rate
Excretion rate = Us × V
mg/min, mmol/min, or mEq/min
Reabsorption rate
                                                                                              
Secretion rate
Secretion rate = Excretion rate - Filtered load
S, a substance; U, urine concentration; V, urine flow rate; P, plasma concentration; PAH, para-aminohippuric acid; PPAH, renal arterial PAH concentration; EPAH, PAH extraction ratio; VPAH, renal venous PAH concentration.

21. 21
Silverthorn 19-2

22. If we are denied water, we need to excrete less
If we drink a lot of water, we need to excrete more
(while still excreting the appropriate amounts of various solutes)
If water moves only by diffusion, how can this be accomplished?

23. Figure 28-1 Water diuresis in a human after ingestion of 1 liter of water. Note that after water ingestion, urine volume increases and urine osmolarity decreases, causing the excretion of a large volume of dilute urine; however, the total amount of solute excreted by the kidneys remains relatively constant. These responses of the kidneys prevent plasma osmolarity from decreasing markedly during excess water ingestion

24. If water can’t follow the solute, then excess water relative to solute can get excreted

25. As a result, can excrete ~20L/day of 50 mOsm/L urine
If water can’t follow the solute, then excess water relative to solute can get excreted
This transporter is a Na-K-2Cl transporter, which is very active in the ascending limb of the loop of Henle
As a result, can excrete ~20L/day of 50 mOsm/L urine

26. + - Loop of Henle Sodium Reabsorption – thick ascending limb Na+ 2K+
Ascending Thick Limb of the Loop of Henle Epithelial Cell
Capillary Lumen (blood)
Tubular Lumen
(urine)
Na+
2K+
ATP
2 Cl-
3 Na+ K+
K+ recycling K+
Cl-
ROMK
channel + -
Na+ Ca+2 Mg+2
Paracellular Pathway 26

27. or 4
Adding water channels back into the collect duct, would allow some of that water to get reabsorbed, and that’s what ADH (or vasopressin) does
Germann 18.10

28. A slightly different version of the previous slide:

29. A slightly more complicated version of the previous slide:
Brown D, et al, Traffic Mar;10(3): Sensing, signaling and sorting events in kidney epithelial cell physiology.

30. Section of kidney collecting duct triple-immunostained to show AQP2 (green) and AQP4 (red) in vasopressin-sensitive principal cells, and the proton-pumping V-ATPase (blue) in acid-secreting intercalated cells. In the region of the kidney shown here, the inner stripe of the outer medulla, A-IC express V-ATPase apically. In response to systemic acidosis, V-ATPase pumps accumulate in the apical plasma membrane and proton secretion is activated to help excrete the acid load (Bar = 5 μm).
Brown D, et al, Traffic Mar;10(3): Sensing, signaling and sorting events in kidney epithelial cell physiology.

31. Kidney collecting duct
V-ATPase
AQP2
AQP4 PC IC H+
H2O

32. ADH is made in the hypothalamus (paraventricular and supraoptic nuclei) and released from the posterior pituitary

33. Hyperosmolarity sensed by osmoreceptors:
Central osmoreceptors (hypothalamic)
Hepatic portal osmoreceptors ??
Hypovolemia
Atrial baroreceptors
Hypotension
Arterial baroreceptors
?? Role of angiotensin

34. Brain osmoreceptors are neurons that are endowed with an intrinsic ability to detect small changes in ECF osmolality
a | MRI images in the horizontal (upper image) and sagittal (lower image) planes, highlighting areas that show a significantly increased blood-oxygen-level-dependent (BOLD) signal under conditions in which thirst was stimulated in a healthy human by infusion of hypertonic saline. The arrows point to increased BOLD signals in the anterior cingulate cortex (ACC; left-hand arrow) and in the area of the lamina terminalis (right-hand arrow) that encompasses the organum vasculosum laminae terminalis (OVLT). b | Plots showing changes in thirst (upper plot) and changes in the BOLD signals in voxels of interest in the ACC (middle plot) and the lamina terminalis (lower plot) of the subject imaged in part a. The values of plasma osmolality shown in the upper plot represent average changes that were observed in a group of subjects that all underwent the same treatment. The traces show that osmoreceptors in the OVLT stay activated as long as plasma osmolality remains elevated, whereas the activation of cortical areas correlates with the sensation of thirst. c | Frequency plots showing examples of changes in firing rate that were detected during extracellular single-unit recordings obtained from three OVLT neurons in superfused explants of mouse hypothalamus. d | A scatter plot showing the changes in firing rate (relative to baseline) that were recorded from many mouse OVLT neurons during the administration of hyperosmotic stimuli of various amplitudes. The data indicate that osmoreceptor neurons in the OVLT encode increases in extracellular fluid osmolality through proportional increases in firing rate. This plot only shows data from osmoresponsive neurons (approximately 60% of the total neuronal population in the OVLT). Part a modified, with permission, from Ref. 27 ©(2003) National Academy of Sciences. Part b modified, with permission, from Ref. 27 © (2003) National Academy of Sciences and Ref.197 © (1999) National Academy of Sciences. Parts c and d reproduced, with permission, from Ref. 89 © (2006) Society for Neuroscience.
C.W. Bourque. Nature Reviews Neuroscience 9, (July 2008)
Central mechanisms of osmosensation and systemic osmoregulation

35. Two actions of ADH:
Antidiuretic
Action on kidney
Very sensitive (1-15 pM
Action on V2 receptors to cause insertion of aquaporin 2 into epithelial cell members in the collecting ducts
Vasopressor
Higher concentrations required than for antidiuresis
Action on V1 receptors in arterioles
(discrepancy between vasocontrictor and vasopressor effects)
Figure 28-9 Neuroanatomy of the hypothalamus, where antidiuretic hormone (ADH) is synthesized, and the posterior pituitary gland, where ADH is released.

36. And then there is this issue with oxytocin: what does it do?
Effect of drinking on mean ± SE values of plasma osmolality (Posmol; A), plasma vasopressin (pVP;B), and plasma oxytocin (pOT; C) in rats infused with 1 M NaCl (2 ml/h iv for 240 min).
This slide from a study we conducted on osmoregulation in rats is included to make two points :
While we typically think about negative feedback reflexes, feedforward control is important too!
And then there is this issue with oxytocin: what does it do?
Effect of drinking on mean ± SE values of plasma osmolality (Posmol; A), plasma vasopressin (pVP;B), and plasma oxytocin (pOT; C) in rats infused with 1 M NaCl (2 ml/h iv for 240 min). Baseline values (BL) before start of the infusion and of the drinking test (0 min) are given. A drinking test began after 220 min of infusion, at which time each of the 3 variables was already significantly increased (allP < 0.01). Then rats were given either water (n = 6), 0.15 M NaCl solution (n = 4), or nothing to drink (n = 8) for 5 min (horizontal bar), and additional blood samples were taken 5 and 15 min later. Differences in Posmol among the 3 groups were not statistically significant. pVP and pOT each decreased abruptly in rats drinking water (all P < 0.05), but no significant changes were observed in the other 2 groups.
Wan Huang et al. Am J Physiol Regul Integr Comp Physiol 2000;279:R756-R760 36

37. Central – problem with ADH synthesis or secretion
Diabetes Insipidus
Central – problem with ADH synthesis or secretion
Nephrogenic – problem with renal response to ADH
~20 L/day of a very hypotonic urine (~ 50 mOsm/L)
Insipidus = Latin for lacking taste

38. How can we make a urine that’s more concentrated than 300 mOsm/L?
and we can: ~ 1200 mOsm/L !!

39. Germann 18.9

40. The ascending limb of the loop of Henle pumps solute, but is impermeable to water
The adjacent descending limb of the loop of Henle is permeable to water but does not transport solute.

42. Silverthorn 19-4

43. Germann 18.9

44. Silverthorn 19-10

45. Figure 28-4 Formation of a concentrated urine when antidiuretic hormone (ADH) levels are high. Note that the fluid leaving the loop of Henle is dilute but becomes concentrated as water is absorbed from the distal tubules and collecting tubules. With high ADH levels, the osmolarity of the urine is about the same as the osmolarity of the renal medullary interstitial fluid in the papilla, which is about 1200 mOsm/L. (Numerical values are in milliosmoles per liter.)

46. Figure 28-5 Recirculation of urea absorbed from the medullary collecting duct into the interstitial fluid. This urea diffuses into the thin loop of Henle, and then passes through the distal tubules, and finally passes back into the collecting duct. The recirculation of urea helps to trap urea in the renal medulla and contributes to the hyperosmolarity of the renal medulla. The heavy dark lines, from the thick ascending loop of Henle to the medullary collecting ducts, indicate that these segments are not very permeable to urea. (Numerical values are in milliosmoles per liter of urea during antidiuresis, when large amounts of antidiuretic hormone are present. Percentages of the filtered load of urea that remain in the tubules are indicated in the boxes.)

47. Figure 28-7 Changes in osmolarity of the tubular fluid as it passes through the different tubular segments in the presence of high levels of antidiuretic hormone (ADH) and in the absence of ADH. (Numerical values indicate the approximate volumes in milliliters per minute or in osmolarities in milliosmoles per liter of fluid flowing along the different tubular segments.)

48. Notice that even in the presence of maximal ADH, some water is lost: obligate water loss. Consider that we cannot make a urine that is more concentrated than ~1200 mOsm/L and that there is a certain amount of organic waste that needs to be excreted in the urine, ~600 mOsm per day. Thus, under those conditions, the minimal urine volume would be 0.5 L/day. (Note that the calculations don’t quite work out with the values presented in this figure.)

49. Negative feedback loop controlling plasma osmolality.

50. What about feedforward regulation?
Negative feedback loop controlling plasma osmolality.
What about feedforward regulation?

51. Note the difference in threshold for
VP secretion and thirst.

52. Figure Effect of large changes in sodium intake on extracellular fluid sodium concentration in dogs under normal conditions (red line) and after the antidiuretic hormone (ADH) and thirst feedback systems had been blocked (blue line). Note that control of extracellular fluid sodium concentration is poor in the absence of these feedback systems.

53. Diabetes Mellitus: Large volume of glucose-containing urine
Why is there glucose in the urine?
Why is urine volume increased? 53