1. Nephron: functional unit of the kidney
Figure 26-3;
Guyton and Hall 1

2. Nephron Tubular Segments
Figure 26-4;
Guyton and Hall 2

3. Structure of the juxtaglomerular apparatus: macula densa
Figure 26-17;
Guyton and Hall 3

4. Cortical and Juxtamedullary Nephron Segments
Figure 26-5;
Guyton and Hall 4

5. 5

6. Summary of Kidney Functions
Excretion of metabolic waste products: urea, creatinine, bilirubin, hydrogen
Excretion of foreign chemicals: drugs, toxins, pesticides, food additives
Secretion, metabolism, and excretion of hormones
renal erythropoetic factor
1,25 dihydroxycholecalciferol (Vitamin D)
Renin
Regulation of acid-base balance
Gluconeogenesis: glucose synthesis from amino acids
Control of arterial pressure
Regulation of water & electrolyte excretion 6

7. Basic Mechanisms of Urine Formation
Figure 26-8;
Guyton and Hall 7

8. Renal Handling of
Different Substances
Figure 26-9;
Guyton and Hall 8

9. Renal Handling of Water and Solutes
Filtration Reabsorption Excretion
Water (liters/day) 1
Sodium (mmol/day) 25, ,410
150
Glucose (gm/day)
180
Creatinine (gm/day) 9

10. Glomerular Capillary Filtration Barrier
Figure 26-10;
Guyton and Hall 10

11. The Ability of a Solute to Penetrate the
Glomerular Membrane Depends on:
Molecular size ( small molecules > filterability)
Ionic charge (cations > filterability) 11

12. Effects of Size and Electrical Charge of Dextran on Filterability by Glomerular Capillaries
Figure 26-11;
Guyton and Hall 12

13. Clinical Significance of Proteinuria
Early detection of renal disease in at-risk patients
hypertension: hypertensive renal disease
diabetes: diabetic nephropathy
pregnancy: gestational proteinuric hypertension (pre-eclampsia)
annual “check-up”: renal disease can be silent
Assessment and monitoring of known renal disease
“Is the dipstick OK?”: dipstick protein tests are not very sensitive and not accurate: “trace” results can be normal & positives must be confirmed by quantitative laboratory test. 13

14. Figure 26-12;
Guyton and Hall

15. Glomerular Hydrostatic Pressure (PG)
Is the determinant of GFR most subject
to physiological control
Factors that influence PG
arterial pressure (effect is buffered by autoregulation)
afferent arteriolar resistance
efferent arteriolar resistance

16. Effect of Afferent and Efferent Arteriolar
Constriction on Glomerular Pressure Ra Re PG PG
Blood Flow
Blood Flow
GFR
GFR
Ra GFR Renal
Blood Flow
Re GFR Renal
Blood Flow

17. Effect of changes in afferent arteriolar or efferent arteriolar resistance
Figure 26-14;
Guyton and Hall

18. determined by : FF = GFR / RPF
RBF G _ RE
GFR PG +

19. Summary of Determinants of GFR
Kf GFR
PB GFR
G GFR
A G
FF G
PG GFR
RA PG
RE PG
GFR
GFR
GFR
(as long as RE < 3-4 x normal)

20. Assessing Kidney Function
Albumin excretion (microalbuminuria)
Plasma concentration of waste products
(e.g. BUN, creatinine)
Urine specific gravity, urine concentrating ability
Imaging methods (e.g. MRI, PET, arteriograms,
iv pyelography, ultrasound etc)
Isotope renal scans
Biopsy
Clearance methods (e.g. 24-hr creatinine clearance)
etc

21. Clearance Clearance is a general concept that describes the
rate at which substances are removed (cleared)
from the plasma.

22. Clearance Technique Renal clearance of a substance is the volume of
plasma completely cleared of a substance per min.
Cs x Ps = Us x V
Cs = Us x V Ps
Where: Cs = clearance of substance S
Ps = plasma conc. of substance S
Us = urine conc. of substance S
V = urine flow rate

23. Use of Clearance to Measure GFR
For a substance that is freely filtered, but not reabsorbed or
secreted (inulin, 125 I-iothalamate, ~creatinine), renal clearance
is equal to GFR
amount filtered = amount excreted
GFR x Pin
= Uin x V
GFR =
Pin
Uin x V
Copyright © 2006 by Elsevier, Inc.

24. Calculate the GFR from the following data:
Pinulin = 1.0 mg / 100ml
Uinulin = 125 mg/100 ml
Urine flow rate = 1.0 ml/min
GFR = Cinulin =
Pin
Uin x V
GFR =
125 x 1.0
1.0
= 125 ml/min

25. Steady-state relationship between
GFR and serum creatinine concentration
Figure 27-19;
Guyton and Hall

26. Clearances of Different Substances
Substance Clearance (ml/min)
inulin
glucose
sodium
urea
Clearance of inulin (Cin) = GFR
if Cx < Cin: indicates reabsorption of x
if Cx > Cin: indicates secretion of x
Clearance creatinine (Ccreat) ~ 140 (used to estimate GFR)

27. Control of Glomerular Filtration
1. Sympathetic Nervous System
RA + RE GFR + RBF
2. Catecholamines ( norepinephrine)
RA + RE GFR RBF
3. Angiotensin II
RE GFR + RBF
(prevents a decrease in GFR)

28. Control of Glomerular Filtration
4. Prostaglandins
RA + RE GFR RBF
5. Endothelial-Derived Nitric Oxide (EDRF)
RA + RE GFR RBF
6. Endothelin
RA + RE GFR RBF

29. Control of Glomerular Filtration
7. Autoregulation of GFR and Renal Blood Flow
Myogenic Mechanism
Macula Densa Feedback
(tubuloglomerular feedback)
Angiotensin II ( contributes to GFR but
not RBF autoregulation)

30. Renal Autoregulation 100 80 120 Renal Artery Pressure (mmHg)
Glomerular
Filtration Rate
Renal Blood
Flow 1 2 3 4 5
Time (min)
Copyright © 2006 by Elsevier, Inc.

31. Renal Blood Flow and GFR Autoregulation
Figure 26-16;
Guyton and Hall

32. Macula Densa Feedback GFR Distal NaCl Delivery
Macula Densa NaCl Reabsorption
(macula densa feedback)
Afferent Arteriolar Resistance
GFR (return toward normal)

33. Myogenic Mechanism Arterial Pressure Stretch of Blood Vessel Cell Ca++
Permeability
Vascular
Resistance
Blood Flow
Intracell. Ca++

34. Regulation of GFR by Ang II
Macula
Renin
GFR
Densa NaCl
Blood
AngII
Pressure
Efferent Arteriolar
Resistance

35. Macula densa feedback mechanism for GFR autoregulation Figure 26-18;
Guyton and Hall