2. Renal Epithelial Cell (cells exposed to interstitium and urinary space)
“luminal” membrane (urinary space) specific transport proteins(reabsorption/
secretion area), villi, microvilli (surface area).Absent Na-K ATPase, Tight junctions
Abundant Na-K ATPase
Exposed to interstitium
Apical membrane:
Basolateral membrane

5. Proximal Nephron
Proximal convoluted tubule and Proximal straight tubule
The Loop of Henle: thin descending limb, thin ascending limb, medullary thick ascending limb, cortical thick ascending limb
The proximal nephron is considered to end at the macula densa segment which occurs at the end of the cortical thick ascending limb

6. Proximal Tubule Proximal convoluted tubule (cortex)
Proximal straight tubule (descends to the corticomedullary junction)

8. Loop of Henle Thin descending limb Thin ascending limb
Thick ascending limb (medullary and cortical portions)
Note: cortical nephrons are “short loop”
juxtomedullary nephrons are “long loop” nephrons

10. Distal Nephron Distal convoluted tubule Connecting segment
Cortical collecting duct
Medullary collecting duct (outer and inner portions)

12. Proximal Tubule Functions
Reabsorption occurs in an isotonic manner (isotonic fluid enters and isotonic fluid exits, but the composition is altered)
Bulk reabsorption: ~50-55%NaCl and H20
~90% NaHCO3
Organic nutrients: 100% glucose, amino acids
Organic anion and cation secretory pathways
PO4 and urate reabsorption
Major site of NH3 production (via glutamine metabolism)
Major site of glomerulotubular balance

13. Definitions Filtered Load:
The amount of a substance, X, that is deposited in Bowman’s space by filtration: (GFR) x (Px)
Transport Maximum
The maximal amount of substance X that can be reabsorbed or secreted: Tmx

14. Glomerulotubular balance
Normal matching of proximal tubule reabsorptive capacity to the filtering capacity of its glomerulus (euvolemic conditions)
Alternative meaning: The phenomenon that the fraction of filtered Na+ that is reabsorbed by the proximal tubule is constant
Incr GFR, incr FL, but 50-55% reabsorbed
Decr GFR, decr FL, but 50-55% reabsorbed

18. Thin descending limb
H20 permeable (aquaporins- H20 channels)
Minimal NaCl permeability
Thin ascending limb
H20 impermeable (absent H20 channels)
NaCl permeable
(NaCl reabsorption, passive)

19. Thick Ascending Limb Active NaCl transport ~ 20-25% NaCl reabsorption
Oxygen requiring
H20 impermeable (absent H20 channels)
Responsible for producing hypertonic medulla
Essential for dilution and concentration of urine
Major site of calcium and magnesium reabsorption
Major site of NH4+ reabsorption (medullary trapping)

20. Loop of Henle Thin ascending limb Thick ascending limb
Combined: ~ 35% of total NaCl reabsorption

24. Tubuloglomerular feedback (TGF)
Autoregulation of single nephron GFR by the rate of fluid delivery to the macula densa
Example: Decreased renal perfusion pressure, decreased GFR, decreased delivery to macula densa, local response (adenosine, NO), afferent arteriolar dilatation, increased glomerular capillary pressure, increased GFR, return to normal delivery to macula densa segment

25. Tubuloglomerular feedback
Example: increased renal perfusion pressure (which increases GFR)
Afferent arteriole constricts and GFR falls in the presence of increased renal perfusion pressure
TGF contributes to maintaining distal delivery of tubular fluid at a relatively constant rate.

26. Juxtaglomerular apparatus
TGF (macula densa)
Renal renin secretion (afferent arteriole)
(decreased renal perfusion pressure results in enhanced renin secretion and activation of TGF)
Both contribute to maintaining GFR and to maintaining a normal distal tubular flow rate.
Proximal nephrons segments: Bulk reabsorption. Distal nephron segments: Fine tuning of final urine composition

27. Distal Convoluted Tubule
5-8% of NaCl reabsorption
H20 and urea impermeable
Major site of calcium reabsorption (stimulated by PTH)
Important for maximal urinary diluting ability (i.e., for maximal free H20 excretion)

31. Collecting Duct Cortical and medullary segments
2-3 % NaCl reabsorption
Built for fine tuning of solute and H20 handling
Not built for bulk reabsorption

32. Collecting duct
Principal cells (cortical collecting duct and inner medullary collecting duct) Sodium chloride and water reabsorption, potassium secretion
Intercalated cells (cortical collecting duct and outer medullary collecting duct) acid-base maintenance
Alpha intercalated cells -H+ secretion (H+ATPase)
Beta intercalated cells- HCO3 secretion (Cl-HCO3 exchanger

36. Final Urinary Contents Are Greatly Influenced by Collecting Duct reabsorption And/or Secretion
H20
(Uosm mOsm/kg)
Na+ and CL-
(Una < 10 mEq/L to >100 mEq/L)
NH4+
(renal acidification, urine pH – 4.5 – 8.0) K+
(secretion, especially cortical collecting duct)
Urea
(influenced by urine flow rate and AVP)

40. Solute and water excretion
Solute excretion obligates H20 excretion
“diuretics” increase solute excretion by inhibiting tubular NaCl reabsorption
Currently used “diuretics” are natriuretic
Osmotic diuretics (hyperglycemia, mannitol, excessive urea excretion)
See syllabus re diuretics

42. Multiple mechanisms exist within the proximal nephron which function to avoid excessive delivery of filtrate to the distal nephron. These mechanism include:
glomerulotubular feedback
tubuloglomerular feedback
autoregulation of arteriolar resistance at the afferent and efferent arterioles
ability to shift cortical blood flow from superficial cortical nephrons to juxtamedullary nephrons which have a greater capacity for salt and water reabsorption

44. Effect of Angiotensin II
Vasoconstriction (especially efferent arteriole)
Stimulates aldosterone secretion
Enhances proximal tubule Na+ reabsorption
Augments sympathetic stimulation
May augment vasopressin secretion
Contraction of mesangial cells which decreases glomerular capillary surface area and reduces permeability; thus,decreasing single nephron GFR

45. Slides to augment small groupsessions
The following slides are to supplement the small group sessions, Problems 1 and 2 and the sodium chloride and water problems (3-8)

51. Creatinine
Serum creatinine is a function of GFR, but also influenced by skeletal muscle mass
Increased age, female gender, malnutriton, cirrhosis lead to less muscle mass
20 yr old male, creatinine 1.0mg/dl has higher GFR than 60yr old female with creatinine of 0.9mg/dl

52. Neuro-endocrine responses to volume changes
↓ ECFV ↑ ECFV
Renin ↑ ↓
Angiotensin II ↑ ↓
Aldosterone ↑ ↓
Plasma ANP ↓ ↑
SANS ↑ ↓
Non-osmotic AVP ↑ ↓

53. Glomerular Responses to Volume Changes
↓ ECFV ↑ ECFV
RPF ↓ ↑
GFR (Creat. Clearance) unchanged unchanged
FF ↑ ↓
Aff. Arteriole Vasodilated unchanged or vasoconstricted
Eff.Arteriole Vasoconstricted Vasodilated
Glomerular capillary Unchanged Unchanged
pressure

54. Tubular Response to Volume Changes
↓ ECFV ↑ ECFV
Peritubular capillary ↓ ↑
hydrostatic pressure
Peritubular capillary ↑ ↓
oncotic pressure
Proximal reabsorption ↑ ↓
Na excretion ↓ ↑
H20 excretion ↓ ↑
Urea excretion ↓ ↑ or unchanged
Urine flow rate ↓ ↑
FENA ↓ ↑
Urine osmolality ↑ approaches plasma osmolality
(~300 mOsm/kg H20)