lecture notes on Urinary system

1. School of medicine
Department of Medicine
Urinary system physiology
Zelalembanjaw9@gmail.com
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2. Outlines
 Functional Structure of the kidneys
 Glomerular Filtration and their Control
 Tubular reabsorption and secretion
 Urine concentration and dilution
 Control of ECF osmolarity and sodium concentration

3. 1. Multiple Functions of the Kidneys
1. Excretory function
Metabolic Waste Products
Foreign Chemicals
Drugs and
Hormone Metabolites
2. Regulatory function
Water and Electrolyte
Balances
Arterial Pressure
Acid-Base Balance
3. Endocrine function
secrete erythropoietin
4. Metabolic function
Activation of vitamin D
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4. 2. Physiological Anatomy of the Kidneys
2.1. General Organization of the Kidneys and Urinary tract
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5. 2.2. Renal Blood Supply
 Blood flow to the two kidneys is normally about 22% of the
cardiac output, or 1100 ml/min
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6. 2.2. Renal Blood Supply…
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The renal circulation is unique in:-
1. Having two capillary beds separated by arterioles
2. High hydrostatic pressure in glomerular capillaries (≈ 60 mmHg)

7. 2.3. Nephron: Functional Unit of the Kidney
 Each human kidney contains about 800,000 to 1,000,000 nephrons,
each of which is capable of forming urine.
 The kidney cannot regenerate new nephrons.
 After age 40 years, the number of functioning nephrons usually
decreases about 10 percent every 10 years.
Q: How aging old one do survive with that much loss of nephrons?
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8. 2.3. Nephron: Functional Unit of the Kidney…
Each nephron contains:-
1. Tuft of glomerular capillaries called ‘glomerulus’
 Through which large amounts of fluid are filtered from the blood
2. Long tubule
 In which the filtered fluid is converted into urine on its way to the
pelvis of the kidney
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9. 2.3. Nephron: Functional Unit of the Kidney…
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Fig: Microcirculation of each nephron Fig: Tubular segments of the nephron

10. Regional Differences in Nephron Structure
Cortical Nephrons
 Glomeruli located in the outer
cortex
 short loops of Henle that dip only a
short distance into the medulla
 Entire tubular system is surrounded
by an extensive network of
peritubular capillaries.
Juxta-medullary Nephrons
 Glomeruli that lie deep in the renal
cortex near the medulla
 Long loops of Henle that dip deeply
into the medulla (in some cases all the
way to the tips of the renal papillae)
 Efferent arterioles divide into
specialized peritubular capillaries
called vasa recta that extend
downward into the medulla, lying
side by side with the loops of Henle.
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11. Glomerular Filtration, Renal Blood Flow, and their Control

12. 1. Glomerular filtration
 Filtration of large amounts of fluid through the glomerular capillaries
into Bowman’s capsule
 (GFR Adult:180L/day or 125 ml/min)
 Most of this filtrate is reabsorbed, leaving only about 1 liter of fluid to
be excreted each day.
 Glomerular filtrate:-
 Protein free and devoid of cellular elements including RBC
 Few low molecular weight substances such as calcium and fatty acids
are not freely filtered because they are partially bound to the plasma
proteins

13. 1. Glomerular filtration…
Glomerular Capillary Membrane
 Glomerular capillary membrane is
similar to that of other capillaries,
except that it has three (instead of the
usual two) major layers:
1. Endothelium of the capillary
2. Basement membrane
3. Layer of epithelial cells (podocytes)

14. 1. Glomerular filtration…
 20 percent of the plasma flowing through the
kidney is filtered through the glomerular
capillaries
 Filterability depends on:
1. Size
 Filterability of solutes is inversely related to
their size
2. Charge
 Negatively charged large molecules are filtered
less easily than positively charged molecules of
equal molecular size
 Albumin is restricted from filtration, because
of its negative charge

15. 1. Glomerular filtration…
 The high filtration rate across the glomerular capillary membrane is due
partly to its special characteristics.
a. Capillary endothelium
 ‘Fenestrae’
Endothelial cell proteins are enriched with fixed negative charges
b. Basement membrane
Meshwork of collagen and proteoglycan fibrillae that have large space
Strong negative electrical charges associated with the proteoglycans
C. Epithelial cells (podocytes)
 Slit pores
 The epithelial cells also have negative charges

16. 2. Determinants of the GFR
 The GFR is determined by
1. Net filtration pressure
2. Glomerular Kf
 GFR= Kf x Net filtration pressure
 The net filtration pressure represents the
sum of:-
 Glomerular hydrostatic pressure (PG)
 Bowman’s capsule hydrostatic
pressure (PB)
 Colloid osmotic pressure of
glomerular plasma proteins (πG)
 Colloid osmotic pressure of
Bowman’s capsule plasma proteins
(πB)
 GFR = Kf (PG + πB) - (PB + πG)
Net filtration pressure = (PG + πB) - (PB + πG)
Net filtration pressure = (60mmHg+0mmHg)-
(18mmHg+32mmHg)
Net filtration pressure = +10mmHg
NB: This is estimated net filtration pressure in
humans (not directly measured in humans
instead in dogs & rats)

17. 2. Determinants of the GFR…
a. Filtration coefficient
 Kf is a measure of the product of
the hydraulic conductivity and
surface area of the glomerular
capillaries.
 Renal disease, Uncontrolled
Chronic hypertension and DM
gradually  ↑thickness of the
glomerular capillary basement
membrane ↓Kf  ↓GFR
b. Glomerular capillary hydrostatic pressure
 Changes in glomerular hydrostatic pressure serve
as the primary means for physiological
regulation of GFR
i. ↓ Systemic arterial pressure  ↓ PG ↓ GFR
ii. Constriction of afferent arterioles  ↓PG 
↓GFR
E.g. Sympathetic hormones (norepinephrine,
endothelin )↑afferent arteriole resistance↓GFR
iii. Constriction of efferent arterioles
 Modest constriction↑PG↑GFR
NB:↓Angiotensin-II (drugs that block
angiotensin II formation)↓RE↓PG

18. 2. Determinants of the GFR…
c. Glomerular capillary colloid osmotic pressure
 π G in glomerular capillaries is about 32 mmHg
 ↑plasma proteins↓GFR
d. Bowman’s capsule hydrostatic pressure
 Reasonable estimate PB of human is 18 mm Hg
 ↑PB  ↓GFR
 Urinary tract obstruction (e.g. Kidney stones) obstruct outflow↑PB
↓GFR Eventually can cause hydronephrosis (distention and dilation of the
renal pelvis and calyces)can damage or even destroy the kidney unless the
obstruction is relieved.

19. 3. Physiological control of glomerular filtration and renal blood flow
 The determinants of GFR that are:
 Sympathetic nervous system
 Hormones and autacoids
 Intrinsic feedback controls
a. Sympathetic nervous system control
 Strong activation of the renal
sympathetic nerves can constrict the
renal arterioles and decrease renal blood
flow and GFR.
 Moderate or mild sympathetic
stimulation has little influence on renal
blood flow and GFR
b. Hormones and autacoids
 Norepinephrine and epinephrine
 Constrict AA and EA ↓GFR and
RBF
 Endothelin
 Vasoconstrictor
 Angiotensin II
 Preferentially Constricts EA in Most
Physiological Conditions↑GFR
 Endothelial-Derived Nitric Oxide
 ↓Renal Vascular Resistance  ↑GFR
 Prostaglandins and Bradykinin
 ↓Renal Vascular Resistance ↑GFR

20. c. Autoregulation of GFR and renal blood flow
Renal autoregulation
 prevents large changes in GFR that
would otherwise occur
Glomerulo-tubular balance
 Adaptive mechanisms in the renal
tubules that cause them to increase
their reabsorption rate when GFR rises
 Even with these special control
mechanisms, ∆es in ABP still have
significant effects on renal excretion of
water and sodium; this is referred to as
pressure diuresis or pressure natriuresis
3. Physiological control of glomerular filtration and renal blood flow

21. Tubular reabsorption and secretion
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22. a. Proximal tubular reabsorption…
Salt and water (65-70%)
 Apical/luminal membrane : via the Na/K/ATPase pump
 Basolateral membrane : transcellular transport (passive)
 H2O-via channels
Organic solutes (primarily glucose and amino acids (100%)
 Co-transporters driven by the Na+ gradient out of the
nephron (1st half of PCT) (Apical)
 SGLUT-1& GLUT-2 (Apical)
 GLUT (basolateral) & then passive diffusion
 Na+-H+ counter transport (? Function)
 Chloride concentration favors intercellular diffusion (2nd
half of PCT) )
 NB: Cl- in 1st half vs 2nd half : 105 mEq/L vs 140 mEq/L 22

23. b. Solute and water transport in the loop of Henle
i. The descending thin segment
 Highly permeable to water (20% of
reabsorbed) and moderately permeable to
most solutes, including urea and sodium.
 The function of this nephron segment is
mainly to allow simple diffusion of
substances through its walls.
NB: Both the thin and the thick ascending
limb, is virtually impermeable to water,
a characteristic that is important for
concentrating the urine.
ii. Thick segment ascending limb
 Has thick epithelial cells that have high
metabolic activity
 Capable of active reabsorption of
sodium, chloride, and potassium.
 About 25% of the filtered loads of
sodium, chloride, and potassium are
reabsorbed in the thick ascending limb.
 Considerable amounts of other ions,
such as calcium, bicarbonate, and
magnesium, are also reabsorbed in the
thick ascending loop of Henle.
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24. Late distal tubule and cortical collecting tubule
I. Both segments are almost completely impermeable to urea
II. Both segments reabsorb Na+
 rate of reabsorption is controlled by hormones, especially aldosterone.
III. The type A intercalated cells of these nephron segments can avidly secrete H+ by an active
hydrogen-ATPase mechanism in acidosis.
Type B intercalated cells secrete HCO3
- and actively reabsorb hydrogen ions in alkalosis
IV. The permeability of both segment to water is controlled by the concentration of ADH
(vasopressin)- controlling dilution or concentration of the urine
 With high levels of ADH permeable to water
 absence of ADH virtually impermeable to water.
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25. Medullary collecting duct
1. The permeability of the medullary collecting duct to water is
controlled by the level of ADH.
2. Unlike the cortical collecting tubule, the medullary collecting duct is
permeable to urea
3. The medullary collecting duct is capable of secreting H+ against a
large concentration gradient, as also occurs in the cortical collecting
tubule.
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26. 4. Use of clearance methods to quantify kidney function
 Renal clearance of a substance is the volume of
plasma that is completely cleared of the substance
by the kidneys per unit of time.
Cs=
UsXV
Ps
INULIN CLEARANCE CAN BE USED TO ESTIMATE GFR
 If a substance is freely filtered (filtered as freely as
water) and is not reabsorbed or secreted by the renal
tubules:
 The rate at which that substance is excreted in the
urine (Us × V) is equal to the filtration rate of the
substance by the kidneys (GFR × Ps)
Us × V= GFR X Ps
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27. Urine concentration and dilution: Regulation ECF
Osmolarity and sodium concentration
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28. 1. Formation of diluted urine
Proximal Tubule fluid
 Solutes and water are reabsorbed in equal proportions,
 So little change in osmolarity occurs
 Remains Isosmotic (300 mOsm/L)
Ascending Loop of Henle (Thick) fluid
 Na+, K+, Cl-are avidly reabsorbed.
 But impermeable to water even in the presence of
large amounts of ADH
 ADH is present or absent hypo-osmotic
(100mOsm/L)
Distal and Collecting Tubules fluid
 There is additional reabsorption of Nacl
 In the absence of ADH, it is also impermeable to water
 Decreasing its osmolarity to as low as 50 mOsm/L
Fig: Formation of dilute urine when
ADH levels are very low. 28

29. 2. Formation of concentrated urine…
Requirements for excreting a concentrated urine:
1. High level of ADH
 ↑permeability of the distal tubules and collecting ducts to water, allowing
tubular segments to avidly reabsorb water
2. Hyperosmotic renal medulla interstitial fluid
 provides the osmotic gradient necessary for water reabsorption to occur
in the presence of high levels of ADH
 Renal medullary interstitium surrounding the collecting ducts is normally
hyperosmotic
 So when ADH levels are high water moves through the tubular
membrane by osmosis into renal interstitiumvasa recta back into
the blood
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30. 2. Formation of concentrated urine…
Countercurrent multiplier mechanism
 Process by which renal medullary interstitial fluid becomes
hyperosmotic
 It depends on the special anatomical arrangement of the loops of
Henle and vasa recta.
 The osmolarity of interstitial fluid in almost all parts of the body is
about 300 mOsm/L .
 The osmolarity of interstitial fluid is about 1200-1400 mOsm/L in the
pelvic tip of the medulla.
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31. 2. Formation of concentrated urine…
 The major factors that contribute to the buildup of solute concentration
into the renal medulla are as follows:
1. Active transport of Na+ and co-transport of K+, Cl-and other ions out of the
thick ascending limb of the loop of Henle into the medullary interstitium
2. Active transport of ions from the collecting ducts into the medullary
interstitium
3. Facilitated diffusion of urea from the inner medullary collecting ducts into
the medullary interstitium
4. Diffusion of only small amounts of water from the medullary tubules into
the medullary interstitium— far less than the reabsorption of solutes into
the medullary interstitium
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32. b. Role of distal tubule and collecting ducts in excreting concentrated urine
 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.
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33. 4. Control of ECF osmolarity and sodium concentration
 Regulation of ECF osmolarity and Na+ concentration are closely linked
because Na+ is the most abundant ion in the extracellular compartment.
 Estimating plasma osmolarity from plasma sodium concentration:
Posm= 2.1×PNa
+ (mmol/L
 Normally, Na+ and associated anions (primarily HCO3-and Cl-) represent
about 94% of the extracellular osmoles, with glucose and urea contributing
about 3-5%of the total osmoles.
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34. 4. Control of ECF osmolarity and sodium concentration…
 Multiple mechanisms control the amount of sodium and water
excretion by the kidneys, two primary systems are especially involved
in regulating the concentration of sodium and osmolarity of
extracellular fluid:
1. Osmoreceptor-ADH system &
2. Thirst mechanism
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35. 5. Osmoreceptor-ADH feedback system
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36. 5. Osmoreceptor-ADH feedback system…
Factors that Increase ADH
 ↑Plasma osmolarity
 ↓ Blood pressure
 ↓ Blood volume
 Nausea
 Drugs: Morphine ,Nicotine, Cyclophosphamide
Q: Effect of alcohol on ADH release?
 Generally The kidneys minimize fluid loss during water deficits through
the osmoreceptor-ADH feedback system.
Q: Pathophysiology & Clinical manifestation Diabetes Insipidus ?
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37. 6. Importance of thirst in controlling ECF osmolarity and sodium
concentration
 preoptic nucleus stimulation: immediate thrist as long as stimulus lasts
Stimuli Increase Thirst
 ↑ Plasma osmolarity
 ↓ Blood volume
 ↓ Blood pressure
 ↑ Angiotensin II (How?)
 Dry mouth & mucous membranes of the esophagus
Threshold for osmolar stimulus of drinking
 When the sodium concentration increases only about 2mEq/L above normal, the
thirst mechanism is activated, causing a desire to drink water. This is called the
threshold for drinking 37

38. Thank you!
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