1. RENAL PHYSIOLOGY PHYSIOLOGY 551 Advanced Physiology I
Lecturer: Ruben Markosyan, PhD
Office: b Jelke
Office Phone: x27011

2. Why is urine yellow?
Why does urine smell?

3. What about drinking urine?
Is “holding it” or voluntarily delaying urination bad?

4. Lecture 1 BASIC RENAL STRUCTURES AND FUNCTIONS

5. → Kidneys receive about 20-25% of the cardiac output.
Basic Kidney Facts
→ Kidneys are <1% of body weight but use ~7% of all oxygen used in body.
This high O2 consumption is due to huge amount of energy used
by the numerous active membrane transport processes in the kidney.
→ Kidneys receive about 20-25% of the cardiac output.
For comparison… Brain gets ~13%… Heart gets ~4%
Point here is that kidneys receive much more blood flow than they need
to stay alive. Thus, the high blood flow accomplishes something else.
So….What do kidneys do?
1) Kidneys filter waste out of blood.
2) Kidneys make urine.
3) Kidneys rid body of excess water.
Fact is…..the kidneys have many functions (beyond these).

6. Basic Kidney Facts General Categories of Kidney Functions
1) Maintenance of a Relatively Constant Extracellular Fluid Composition
2) Generation of Hormones
3) Miscellaneous Other Functions

7. General Categories of Kidney Functions
Basic Kidney Facts
General Categories of Kidney Functions
1) Maintenance of a Relatively Constant Extracellular Fluid Composition
● Balance Concept: input = output (substances gained via diet/metabolism/catabolism
need to be eliminated via feces, sweat or urine)
● Kidney’s Functional Unit: Nephron (each kidney has ~1 million nephrons)
blood
filtration
reabsorption
secretion
urine
Filtered Fluid = 180 L/day (47.5 gallons/day)
Urine Output = 1.4 L/day (0.37 gallons/day)
● Kidney’s Handle Many Substances: H20, Na, K, Cl, Ca, P04, glucose, urea, etc.
Regulation of water and electrolytes (salts) levels
Control of plasma osmolality (via adjusting total body H20 & salt)
Elimination of many metabolic waste products
Ridding body of abnormal substances (e.g. drugs, antibiotics, pyrogens, etc.)
Regulation of normal acid/base balance (secrete acid, reabsorb base)
protein in diet generates acids
the urine is usually acidic
Modulation of blood pressure
renin-angiotensin system (kidney generate renin)
kidneys ultimately control blood volume
► Some Specific Maintenance Sub-Functions:

8. Basic Kidney Facts General Categories of Kidney Functions
1) Maintenance of a Relatively Constant Extracellular Fluid Composition
2) Generation of Hormones
3) Miscellaneous Other Functions

9. Basic Kidney Facts General Categories of Kidney Functions
1) Maintenance of a Relatively Constant Extracellular Fluid Composition
2) Generation of Hormones
● The kidney secretes renin……as just mentioned
Renin cleaves Angiotensinogin (which is made in liver) into Angiotensin-1.
Angiotensin-1 is converted into angiotensin-2 by ACE (angiotensin converting enzyme)
Angiotensin-2 is a powerful vasoconstriction agent
● The kidney secretes erythropoietin
Low plasma O2 levels trigger erythropoietin release
Circulating erythropoietin promotes RBC production in bone marrow
This has been (and is) abused as “blood doping agent”
● The kidney generates calcitriol (active form of vitamin D)
Sunlight promotes formation of the inactive form of Vitamin D in skin
(the inactive form of Vitamin D may also be ingested)
Two chemical reactions needed to make active vitamin D (one occurs in kidney)
Active vitamin D promotes Ca uptake by G.I. tract

10. Basic Kidney Facts General Categories of Kidney Functions
1) Maintenance of a Relatively Constant Extracellular Fluid Composition
2) Generation of Hormones
3) Miscellaneous Other Functions

11. → Gluconeogenisis: synthesis of glucose
Basic Kidney Facts
General Categories of Kidney Functions
1) Maintenance of a Relatively Constant Extracellular Fluid Composition
2) Generation of Hormones
3) Miscellaneous Other Functions
→ Gluconeogenisis: synthesis of glucose
→ Catabolism of small peptide hormones (Ang. II, ADH, insulin, etc.)
Keep “balance” of numerous substances
Regulate of osmolality, blood pressure, acid/base status
Generate renin, erythropoietin & calcitriol
Catabolism of peptide hormones
Gluconeogenisis
Point: Kidneys do much more than just filter waste from blood.

12. We begin our dive into the details by reviewing renal “functional anatomy”
Rembrandt Harmenzoon van Rijn: "The Anatomy Lesson of Dr. Nicolas Tulp"

13. Urinary System Gross Anatomy
X-ray w/ contrast media cartoon
Angiogram

14. Kidney Functional Anatomy
Normal
Polycystic
Polycystic Kidney Disease is the most
common life threatening genetic disease.
PKD prevalence as high as 1 in 500 people.

15. The Nephron (kidney’s functional unit)
JuxtaGlomerular Apparatus (JGA)
Renal tubule “revisit” its glomerulus !
(point where feedback control can occur)

16. Kidney Gross Circulation

17. Micro Circulation & 2 Nephron Types

18. Renal Corpuscle Vascular Cast of Renal Cortex
Renal Corpuscle = Glomerular Capillaries + Bowman’s Capsule

19. Filtration Barrier What Goes Through the Filtration Barrier?
Podocyte Foot Processes
→ Filter Layer 1 : capillary endothelial cell pores (~70 nm holes)
→ Filter Layer 2 : glomerular basement membrane (charge field)
→ Filter Layer 3 : slits b/w podocyte foot processes (~8 nm holes)
What Goes Through the Filtration Barrier?

20. What Goes Through the Filtration Barrier?
Electrolytes
K nm radius
Na nm
Ca nm
ammonium nm
Organics
urea nm
glucose nm
Mannitol nm
Inulin nm
creatinine nm
Proteins
Albumin (60% of blood proteins) 3.6 nm
globulin (35% of blood proteins) nm
fibrinogen (4% of blood proteins) 5.8 nm
angiotensin very small & 100% filtered
insulin small & 100% filtered
growth hormone larger & 60% filtered
Cells
platelets 3,000 nm
RBC 7,000 nm
neutrophil 12,000 nm
Layer 1 : capillary endothelial cell pores (~70 nm holes)
Layer 2 : glomerular basement membrane (charge field)
Layer 3 : slits b/w podocyte foot processes (~8 nm holes)
Size is not the only important thing.
Endothelial Pores
Podocyte Foot
Processes
Basement
Membrane
Real Image of Filtration Barrier

21. Before Moving On: Another View of the Renal Corpuscle
E = endothelial cells (E)
PO = podocytes
GBM = glomerular basement membrane
M = mesangial cells
MM = mesangial matrix
Mesangial cells serve a “cleansing function”
in the renal corpuscle. They can also
contract/constrict (under autonomic control)
changing how fluid moves in renal corpuscle
(i.e. changing filtration rate).

22. Afferent & Efferent Arterioles
Pressure ?
filtered fluid
Blood
If pinch afferent arterial, then what happens to pressure?
2) If pinch efferent arterial, then what happens to pressure?
Thus, pressure will depend on the relative pinching of each.
Bottom Line: Hydrostatic pressure in glomerulus
controlled by relative vasoconstriction of
afferent & efferent arterioles

23. Juxtaglomerular Apparatus (JGA)
Macula Densa (senses flow rate of distal tubular fluid
and secretes a vaso-active agent)
Mesangial cells
Tubuloglomerular Feedback

24. Review of Basic Renal Processes
Filtration (F)
Reabsorption (R)
Secretion (S)
Excretion = F + S - R

25. Review of Basic Renal Processes
Filtration (F)
Reabsorption (R)
Secretion (S)
Excretion = F + S - R
Filtration
Reabsorption
Secretion
Forming Urine
Afferent Arteriole
Efferent Arteriole
Glomerulus
Bowman’s
Capsule
Renal
Tubule
Peritubular
Capillary

26. Review of Basic Renal Processes
Filtration (F)
Reabsorption (R)
Secretion (S)
Excretion = F + S - R
Filtration
Reabsorption
Secretion
Forming Urine
Afferent Arteriole
Efferent Arteriole
Glomerulus
Bowman’s
Capsule
Renal
Tubule
Peritubular
Capillary

27. Review of Basic Renal Processes
Filtration (F)
Reabsorption (R)
Secretion (S)
Excretion = F + S - R
Filtration
Reabsorption
Secretion
Forming Urine
Afferent Arteriole
Efferent Arteriole
Glomerulus
Bowman’s
Capsule
Renal
Tubule
Peritubular
Capillary

28. Review of Basic Renal Processes
Filtration (F)
Reabsorption (R)
3. Secretion (S)
Excretion = F + S - R
Filtration
Reabsorption
Secretion
Forming Urine
Afferent Arteriole
Efferent Arteriole
Glomerulus
Bowman’s
Capsule
Renal
Tubule
Peritubular
Capillary