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Microcirculation

            M1 โ€“ Cardiovascular/Respiratory
                       Sequence
                 Louis Dโ€™Alecy, Ph.D.




Fall 2008                                     3
Monday 11/10/08, 10:00
Microcirculation, Exchange
      25 slides, 50 minutes
1. Microcirculation
2. Diffusion
3. Exchange
     Delivery
     Removal
4. Ultra๏ฌltration
5. Starling hypothesis
                              4
Essential Role of Cardiovascular System in
                   Homeostasis
       ~ โ€œconstancyโ€ of internal environment




(1) Adequate blood ๏ฌ‚ow through capillaries

(2) Blood composition adequate for maintaining
interstitial ๏ฌ‚uid composition


                                                 5
Lungs
MICROCIRCULATION
 Site of:

  1. regulation of tissue
     blood flow

  2. nutrient & waste             venuoles
     exchange between
     blood and cells                  capillaries         arterioles
  3. fluid exchange
     between plasma &
     interstitialfluid

  4. Leukocyte migration
     between blood and
     interstitial fluid     lymph
                                                tissues
       Dโ€™Alecy              vessels                          6
Image of
                                  microcirculation
                                     removed




Please see: http://www.bg.ic.ac.uk/Staff/khparker/homepage/BSc_lectures/2002/Capillary_sketch.jpg




                                                                                               7
CAPILLARY BLOOD FLOW
Velocity: 300 -1000 m/sec
 capillaries 0.5 - 1.0 mm long (500-1000 m)
 mean resting transit time 1 sec (0.5 - 2 sec)
 exercise (increased CO) transit time 0.25 sec

Vasomotion: flow waxes and wanes at approximately
        15 second intervals due to local build up of
        metabolic vasodilators
Plug flow: capillary diameter 5-8 m,
               RBC diameter 7 m



     Dโ€™Alecy                                     8
McGraw-Hill   9
10
McGraw-Hill
Effective Capillary Surface Area (not fixed)
Capillary Number per unit volume varies in different tissues
          Thus so does total surface area cm2 /g tissue

Skeletal muscle = 100 cm2 /g vs. Heart & brain = 500 cm2 /g



Under resting conditions not all of capillaries are open
at same time nor do them have the same transit times.

      Increased metabolic activity by way of local
         metabolites can recruit capillaries ( #)
          - increasing exchange area ( A) and
     - decreasing diffusion distance ( L) to cells
                                                          11
Four Factors Determine the
   Rate of Diffusion (Xd )
1) Diffusion Coefficient (D)                  +

2) Surface area available for diffusion (A)   +

3) Concentration difference ( [ x ] )         +

4) Distance to diffuse (L)                    -
                                              12
Diffusion
           Xd = DA   [x]
                       L

Xd = rate of diffusion
D = diffusion coefficient
A = surface are available for diffusion
  [ x ] = concentration difference
L = distance to diffuse


                                    13
METABOLIC EXCHANGE
          Bulk Transport To:                Bulk Transport From:

          Delivery =                             Removal =
      Flow X Concentration                  Flow X Concentration


                                Capillary


 Artery                                                      Vein




Consumption                    Exchange         Production
(Utilization)

                                Cell
          Dโ€™Alecy
                                                             14
Tissue Delivery
          Delivery   =     F    x   Concentration
            (mg/min) = (L /min) x (mg/L)

     FLOW LIMITED EXCHANGE occurs when
 diffusing substance has high capillary permeability
             and exchange is increase by:
     1) increasing Conc. Or 2) increasing flow


    DIFFUSION LIMITED EXCHANGE occurs when
diffusing substance has low capillary permeability and
                exchange is increase by:
    1) increasing Conc. 2) increasing area by
                                  increasing number

                                                  15
Flow Limited Exchange (Diffusion)
     Exchange = Xd = DA                      [C p   - Cisf   ]
                                                    L
lower                         higher
 flow                          flow



                    Fn                        Exchange
                                               Fn
        Cp                             Cp

             distance along             distance along
             capillary                  capillary

  arteriolar                  capillary              Exchange
 vasodilation                  flow
   Dโ€™Alecy
                                                                 16
More # capillaries    more diffusion
DIFFUSION LIMITED
     EXCHANGE


           Increase #
                                        Plus a little diffusion




                                        Plus a little diffusion




A little diffusion

                                         Plus a little diffusion
      Dโ€™Alecy
                                                         17
Cisf        O2, ,CO2, Etoh
                                             Diffusion
         capillary                  1   across membranes
        endothelial
           cell                                 slit pore
                                                between
                                               endothelial
                                                  cells
              Cisf           Cp                   Cisf
                 2                            3

Mediated transport                             bulk flow
 Ions, glu, drug                              & diffusion
                                             Na+, K+, Cl-,
   Vesicular transport                       H2O, glucose
                         4
   Plasma proteins
                             Cisf                        18
    Dโ€™Alecy
cell junction (slit pore)
continuous
capillary                                       endothelial cell

                                              basement membrane
    muscle, connective tissue, brain and exocrine glands




fenestrated
capillary                                           diaphragm

               kidney, intestines and endocrine glands



discontinuous                                       large gap
capillary                                                                 increasing
                                                                          capillary
                                                                          permeability
                    liver, bone marrow and spleen
                                                                                   19
     Source Undetermined
Endothelial Cell Junctions

JUNCTION                   blood
  FUNCTION
                                                   glycocalyx
1) Occluding                                        tight junctions
                                                    (zonula occludens)
2) Anchoring

                                                   zonula adherens
3) Communicating
                                                    gap junctions



                                                    basement membrane
                                                      (basal lamina)
                     interstitial fluid
                                                                     20
                             Source Undetermined
ULTRAFILTRATION



                            capillary slit pores

             Pc                   Pisf
          18 mm Hg             - 3 mm Hg

                     Bulk Flow Slit =       P = 21mm Hg
                                        R

                     Bulk Flow Slit = (Pc - Pisf)
Dโ€™Alecy
                                           Rslit 21
McGraw-Hill
              22
What determines capillary
hydrostatic pressure Pc ?
       โ€ข Arterial pressure Pc
       โ€ข Venous pressure Pc
       โ€ขClosure of arteriolePc
       โ€ขClosure of a venule Pc
โ€ข Local arteriolar vasoconstriction   Pc
     โ€ขLocal venoconstriction Pc

                                           23
24
McGraw-Hill
Arterial end
Interstitium




                             Venous end                                             25
    Mohrman and Heller. Cardiovascular Physiology. McGraw-Hill, 2006.   6th   ed.
What happens if you partially inflate a blood
pressure cuff on your own arm?

Did you ever leave one inflated too long?

Did your arm appear to swell?
How come?      Why partially inflated?

Does the hydrostatic pressure at the venous
end of the capillary can have a significant
effect on net filtration!!?

                                         26
McGraw-Hill

              27
Arterial end                  Venous end

Hydro - Osmo = ?           Hydro - Osmo = ?
(35-0) - (28-3) =10 fil    (15-0) - (28-3) = -10 abs




Place cuff & inflate       to 30 mmHg

        Arterial end                 Venous end

 Hydro - Osmo = ?            Hydro - Osmo = ?
 (35-0) - (28-3) =10 fil     (30-0) - (28-3) = 5 fil


    Dโ€™Alecy
                                               28
                            Interstitial Swelling
Additional Source Information
                                 for more information see: http://open.umich.edu/wiki/CitationPolicy

Slide 6: Dโ€™Alecy
Slide 7: Please see: http://www.bg.ic.ac.uk/Staff/khparker/homepage/BSc_lectures/2002/Capillary_sketch.jpg
Slide 8: Dโ€™Alecy
Slide 9: McGraw-Hill
Slide 10: McGraw-Hill
Slide 14: Dโ€™Alecy
Slide 16: Dโ€™Alecy
Slide 17: Dโ€™Alecy
Slide 18: Dโ€™Alecy
Slide 19: Source Undetermined
Slide 20: Source Undetermined
Slide 21: Dโ€™Alecy
Slide 22: McGraw-Hill
Slide 24: McGraw-Hill
Slide 25: Mohrman and Heller. Cardiovascular Physiology. McGraw-Hill, 2006. 6th ed.
Slide 27: McGraw-Hill
Slide 28: Dโ€™Alecy

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11.10.08(b): Microcirculation

  • 1. Author(s): Louis Dโ€™Alecy, 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attributionโ€“Non-commercialโ€“Share Alike 3.0 License: http://creativecommons.org/licenses/by-nc-sa/3.0/ We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it. The citation key on the following slide provides information about how you may share and adapt this material. Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, or clarification regarding the use of content. For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use. Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about your medical condition. Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
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  • 3. Microcirculation M1 โ€“ Cardiovascular/Respiratory Sequence Louis Dโ€™Alecy, Ph.D. Fall 2008 3
  • 4. Monday 11/10/08, 10:00 Microcirculation, Exchange 25 slides, 50 minutes 1. Microcirculation 2. Diffusion 3. Exchange Delivery Removal 4. Ultra๏ฌltration 5. Starling hypothesis 4
  • 5. Essential Role of Cardiovascular System in Homeostasis ~ โ€œconstancyโ€ of internal environment (1) Adequate blood ๏ฌ‚ow through capillaries (2) Blood composition adequate for maintaining interstitial ๏ฌ‚uid composition 5
  • 6. Lungs MICROCIRCULATION Site of: 1. regulation of tissue blood flow 2. nutrient & waste venuoles exchange between blood and cells capillaries arterioles 3. fluid exchange between plasma & interstitialfluid 4. Leukocyte migration between blood and interstitial fluid lymph tissues Dโ€™Alecy vessels 6
  • 7. Image of microcirculation removed Please see: http://www.bg.ic.ac.uk/Staff/khparker/homepage/BSc_lectures/2002/Capillary_sketch.jpg 7
  • 8. CAPILLARY BLOOD FLOW Velocity: 300 -1000 m/sec capillaries 0.5 - 1.0 mm long (500-1000 m) mean resting transit time 1 sec (0.5 - 2 sec) exercise (increased CO) transit time 0.25 sec Vasomotion: flow waxes and wanes at approximately 15 second intervals due to local build up of metabolic vasodilators Plug flow: capillary diameter 5-8 m, RBC diameter 7 m Dโ€™Alecy 8
  • 11. Effective Capillary Surface Area (not fixed) Capillary Number per unit volume varies in different tissues Thus so does total surface area cm2 /g tissue Skeletal muscle = 100 cm2 /g vs. Heart & brain = 500 cm2 /g Under resting conditions not all of capillaries are open at same time nor do them have the same transit times. Increased metabolic activity by way of local metabolites can recruit capillaries ( #) - increasing exchange area ( A) and - decreasing diffusion distance ( L) to cells 11
  • 12. Four Factors Determine the Rate of Diffusion (Xd ) 1) Diffusion Coefficient (D) + 2) Surface area available for diffusion (A) + 3) Concentration difference ( [ x ] ) + 4) Distance to diffuse (L) - 12
  • 13. Diffusion Xd = DA [x] L Xd = rate of diffusion D = diffusion coefficient A = surface are available for diffusion [ x ] = concentration difference L = distance to diffuse 13
  • 14. METABOLIC EXCHANGE Bulk Transport To: Bulk Transport From: Delivery = Removal = Flow X Concentration Flow X Concentration Capillary Artery Vein Consumption Exchange Production (Utilization) Cell Dโ€™Alecy 14
  • 15. Tissue Delivery Delivery = F x Concentration (mg/min) = (L /min) x (mg/L) FLOW LIMITED EXCHANGE occurs when diffusing substance has high capillary permeability and exchange is increase by: 1) increasing Conc. Or 2) increasing flow DIFFUSION LIMITED EXCHANGE occurs when diffusing substance has low capillary permeability and exchange is increase by: 1) increasing Conc. 2) increasing area by increasing number 15
  • 16. Flow Limited Exchange (Diffusion) Exchange = Xd = DA [C p - Cisf ] L lower higher flow flow Fn Exchange Fn Cp Cp distance along distance along capillary capillary arteriolar capillary Exchange vasodilation flow Dโ€™Alecy 16
  • 17. More # capillaries more diffusion DIFFUSION LIMITED EXCHANGE Increase # Plus a little diffusion Plus a little diffusion A little diffusion Plus a little diffusion Dโ€™Alecy 17
  • 18. Cisf O2, ,CO2, Etoh Diffusion capillary 1 across membranes endothelial cell slit pore between endothelial cells Cisf Cp Cisf 2 3 Mediated transport bulk flow Ions, glu, drug & diffusion Na+, K+, Cl-, Vesicular transport H2O, glucose 4 Plasma proteins Cisf 18 Dโ€™Alecy
  • 19. cell junction (slit pore) continuous capillary endothelial cell basement membrane muscle, connective tissue, brain and exocrine glands fenestrated capillary diaphragm kidney, intestines and endocrine glands discontinuous large gap capillary increasing capillary permeability liver, bone marrow and spleen 19 Source Undetermined
  • 20. Endothelial Cell Junctions JUNCTION blood FUNCTION glycocalyx 1) Occluding tight junctions (zonula occludens) 2) Anchoring zonula adherens 3) Communicating gap junctions basement membrane (basal lamina) interstitial fluid 20 Source Undetermined
  • 21. ULTRAFILTRATION capillary slit pores Pc Pisf 18 mm Hg - 3 mm Hg Bulk Flow Slit = P = 21mm Hg R Bulk Flow Slit = (Pc - Pisf) Dโ€™Alecy Rslit 21
  • 23. What determines capillary hydrostatic pressure Pc ? โ€ข Arterial pressure Pc โ€ข Venous pressure Pc โ€ขClosure of arteriolePc โ€ขClosure of a venule Pc โ€ข Local arteriolar vasoconstriction Pc โ€ขLocal venoconstriction Pc 23
  • 25. Arterial end Interstitium Venous end 25 Mohrman and Heller. Cardiovascular Physiology. McGraw-Hill, 2006. 6th ed.
  • 26. What happens if you partially inflate a blood pressure cuff on your own arm? Did you ever leave one inflated too long? Did your arm appear to swell? How come? Why partially inflated? Does the hydrostatic pressure at the venous end of the capillary can have a significant effect on net filtration!!? 26
  • 28. Arterial end Venous end Hydro - Osmo = ? Hydro - Osmo = ? (35-0) - (28-3) =10 fil (15-0) - (28-3) = -10 abs Place cuff & inflate to 30 mmHg Arterial end Venous end Hydro - Osmo = ? Hydro - Osmo = ? (35-0) - (28-3) =10 fil (30-0) - (28-3) = 5 fil Dโ€™Alecy 28 Interstitial Swelling
  • 29. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicy Slide 6: Dโ€™Alecy Slide 7: Please see: http://www.bg.ic.ac.uk/Staff/khparker/homepage/BSc_lectures/2002/Capillary_sketch.jpg Slide 8: Dโ€™Alecy Slide 9: McGraw-Hill Slide 10: McGraw-Hill Slide 14: Dโ€™Alecy Slide 16: Dโ€™Alecy Slide 17: Dโ€™Alecy Slide 18: Dโ€™Alecy Slide 19: Source Undetermined Slide 20: Source Undetermined Slide 21: Dโ€™Alecy Slide 22: McGraw-Hill Slide 24: McGraw-Hill Slide 25: Mohrman and Heller. Cardiovascular Physiology. McGraw-Hill, 2006. 6th ed. Slide 27: McGraw-Hill Slide 28: Dโ€™Alecy