1. Functions of the kidney
1. Regulation of inorganic ions (Na+, K+, Ca++, Cl-, Pi, Mg++)
2. Regulation of water balance & osmolality
3. Excretion of nitrogenous wastes (urea, creatinine)
4. Excretion of foreign chemicals (drugs, pollutants, etc.)
5. Regulation of pH, and HCO3-
6. Synthesis of renin
7. Synthesis of erythropoietin; activation of vitamin D3
8. Gluconeogenesis (liver much more important)

2. Structure of urinary system
fig 14-1

3. Structure of kidney
fig 14-4

4. Structure of nephron & blood supply
Bowman’s capsule (C)
proximal tubule (C)
loop of Henle (M)
distal tubule (C)
collecting duct (C, M)
Blood supply
afferent arteriole (C)
glomerular capillaries (C)
efferent arteriole (C)
peritubular capillaries (C)
vasa recta (M)
venule (C)
(C) = cortex
(M) = medulla
fig 14-2

5. Structure of glomerulus (renal corpuscle)
Blood flow:
afferent arteriole  glomerular capillaries  efferent arteriole
Filtration: from glomerular capillaries into Bowman’s capsule
Cell types:
juxtaglomerular apparatus (macula densa + juxtaglomerular cells)
podocytes
fig 14-3

6. Direction of filtration
From plasma through capillary endothelial cell fenestrae & podocyte filtration slits into Bowman’s capsule.
Fluid in Bowman’s capsule is protein-free filtrate of plasma
fig 14-3b

7. Juxtaglomerular apparatus
Macula densa: specialized cells in wall of distal tubule
Juxtaglomerular cells: contain renin, sympathetic nerves
fig 14-5

8. Filtration, reabsorption, secretion, excretion
Filtration: glomerular capillaries  Bowman’s capsule
Secretion: peritubular capillaries  tubular fluid
Reabsorption: tubular fluid  peritubular capillaries
Excretion = filtration + secretion – reabsorption
fig 14-6

9. Kidney handling of various substances
Substance X: filtered & entirely secreted (rare)
Substance Y: filtered & partially reabsorbed (Na+, K+, water)
Substance Z: filtered & entirely reabsorbed (glucose, amino acids)
fig 14-7

10. Glomerular filtration barrier
fig 14-3c

11. Forces of filtration
Compare with Starling forces in muscle capillaries
fig 14-8

12. Important numbers Resting cardiac output: ~5L/min
Renal blood flow: ~1.2 L/min (i.e. about 25% of CO)
Renal plasma flow: ~650 ml/min (~55% of blood is plasma)
Glomerular filtration rate: ~120 ml/min (i.e. about 20% of renal plasma flow)
Therefore, of plasma flowing through glomerular capillaries, ~20% is filtered into Bowman’s capsule and only 80% enters the efferent arteriole
GFR of 120 ml/min = ~180 L/day (i.e. plasma is filtered 60x each day)
Urine flow rate = ~1 ml/min (i.e. 99+% water reabsorbed)
fig 14-8

13. Reabsorption
reabsorption
fig 14-10

14. Reabsorption of glucose & amino acids
Glucose & amino acids are freely filtered
At normal plasma concentrations they are all entirely reabsorbed
Hence, urine [glucose] & [amino acid] are zero (see substance Z fig 14-7)
Mechanism:
Na+ linked co-transport at the luminal membrane of the proximal tubule
In an untreated diabetic, plasma [glucose] is high, therefore the amount of glucose filtered is greater then the maximum transport rate of the transporters; hence glucose appears in the urine.

15. Reabsorption of urea Urea is freely filtered
As water is reabsorbed, the tubular [urea] rises
Urea is passively reabsorbed down its concentration gradient
(see substance Y fig 14-7)
About half the filtered urea is excreted

16. Measurement of glomerular filtration rate
Inulin (~5000 M.Wt. polysaccharide) prepared from plants
Inulin is filtered, not reabsorbed, not secreted
Therefore all the inulin that is filtered is excreted
Inulin filtered = GFR x [inulin]plasma
Inulin excreted = urine flow rate x [inulin]urine
Therefore GFR = urine flow rate x [inulin]urine
[inulin]plasma
Clinically, creatinine is used to measure GFR
Creatinine is released at a constant rate from muscle
Creatinine properties are similar, but not identical, to inulin

17. Measurement of glomerular filtration rate
fig 14-11

18. Sodium balance Most NaCl intake added during food preparation
Sweat output depends on body temperature
Urine output of NaCl is regulated by blood pressure

19. Water balance
Metabolically produced by oxidation of H-containing nutrients
Insensible loss: expiration of 37 saturated air, evaporation through skin (different from sweat)
Urine output regulated by vasopressin (antidiuretic hormone ADH)

20. Total body NaCl and extracellular volume
 extracellular osmolality
 vasopressin release
water retention by kidneys
 extracellular volume
Because vasopressin release is sensitive to changes in osmolality, any change in total body NaCl will result in a proportional change in extracellular volume

21. Sodium handling by the kidney
Of the sodium filtered ~99.5% is reabsorbed, 0.5% excreted
Sympathetic nervous system regulates glomerular filtration rate
Sodium reabsorption:
~70% from proximal tubule (unregulated)
~20% from ascending limb of loop of Henle (unregulated)
~5% from distal tubule (unregulated)
3-5% from collecting duct
(regulated by aldosterone & atrial natriuretic peptide-less important)

22. Regulation of sodium excretion

23. Sympathetic nervous system on sodium excretion
1. action on glomerular filtration rate
 blood pressure  discharge from carotid sinus  SNS activity  glomerular filtration rate  Na+ filtered  Na+ excreted
action on renin release
 blood pressure  afferent arteriole pressure  renin 
 angiotensin I,II  aldosterone  Na+ reabsorbed 
 Na+ excreted

24. Renin angiotensin aldosterone system
fig 14-19

25. Renin angiotensin aldosterone system on Na+ excretion
fig 14-20

26. Renin angiotensin aldosterone system on Na+ excretion
Renin release stimulated by:
1.  sympathetic nervous activity
2.  blood pressure in afferent arteriole
 Na+ and Cl- in tubular fluid at macula densa
Angiotensin II actions:
general vasoconstriction
stimulates aldosterone release from adrenal cortex
Aldosterone release stimulated by:
1.  plasma angiotensin II levels
2.  plasma potassium concentration

27. Actions of aldosterone
fig 14-13
Aldosterone actions:
 Na+ channel activity,  K+ channel activity,  Na+/K+ ATPase pump
Note: large Na+, K+ shows high concentration & vice versa

28. Atrial natriuretic peptide on Na+ excretion
ANP actions:
 Na+ reabsorption from deep medullary collecting duct
2.  glomerular filtration rate
Both actions  Na+ excretion
fig 14-21

29. Water transport & vasopressin (ADH) dependence
Transport mechanism:
passive diffusion through aquaporin channels down osmotic gradient
Reabsorption:
~99% of filtered water is reabsorbed
Sites of reabsorption:
~70% from proximal tubule
~15% from descending limb of loop of Henle
0% from Henle’s ascending limb & distal tubule
0-15% from collecting duct depending on plasma vasopressin level

30. Vasopressin (ADH) release & actions
Vasopressin release stimulated by:
slight (1%) increase in plasma osmolality
large (~15%) reduction in plasma volume
Vasopressin action:
increases permeability of collecting duct to water
Renal medulla
has osmotic gradient from 300 mOsm/kg at cortical border to 1200 mOsm/kg at deepest part of medulla (mechanism not necessary)
 ADH levels  collecting duct permeability  water reabsorption  urine volume with  osmolality

31. Vasopressin action
fig 14-15

32. Water transport & vasopressin actions
fig 14-23
fig 14-22

33. Sweating without water replacement
fig 14-24
Sweat is hypotonic (i.e. osmolality < plasma)
Gatorade story

34. Regulation of thirst Sensation of thirst stimulated by:
1%  osmolality
2. >15%  blood volume
 angiotensin II
4. dry mouth, throat
Sensation of thirst inhibited by:
1. GI metering of water intake
fig 14-25

35. Potassium excretion Reabsorption from: proximal tubule
Henle’s ascending limb
(collecting duct)
Secretion into:
collecting duct (regulated process)
fig 14-26

36. Regulation of potassium excretion
fig 14-27