Physiology #23: Microcirculation

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Physiology #23: Microcirculation
2013-12-07 02:31:14
DVM 2017

DVM 2017
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  1. Microcirculation
    • refers to functions of the smallest vessels (capillaries, and lymph vessels)
    • -single cell layer
    • water-filled clefts between cells  
  2. Capillaries
    • are part of microcirculation
    • Capillaries are the site of exchange for gases, fluid, nutrients, and waste products
    • thin-walled structures that are a single endothelial cell thick
  3. Organisation from artery to capillaries
    arteries--> arterioles --> metarterioles --> capillaries
  4. What determines blood flow to the capillaries
    Degree of constriction or relaxation of the arterioles determines blood flow to capillaries

    it is also regulated by muscular precapillary sphincters present at the capillary opening (work as either on or off switch)
  5. Capillary structure
    Junctions between endothelial cells are interdigitating -- this allows passage of molecules up to 10nm (small leakage)

    • Cytoplasm of endothelial cells are attenuated to form pores or gaps that are 20-100nm in diameter, allowing for passage of relatively large molecules
    • Plasma proteins have diameters that are larger than pores (so cant get in)
    • Other molecules such as Na+, K+, Cl-, glucose and Ca++ can pass through these pores
    • O2 and CO2 are lipid soluble and pass directly through the cell membrane
    • Diameter of RBC's is just large enough for RBC's to pass through in single file (so they deform and RBC get stuck against capillary so RBC content can go into ISF)

    (in brain the interdigitating junctions are tighter permitting passage of only very small molecules)
  6. Capillary Blood Flow
    • Blood flow in the capillaries is intermittent, not continuous (start and stop movement)
    • Intermittent flow reflects contraction and relaxation of metarterioles and precapillary sphincters in alternating cycles of 6-12 times per cycle
    • *O2 is the most important determinant of the opening and closing of the metarterioles and precapillary sphincters   ("local autoregulation")
  7. What is the most important determinant of the opening and closing of metarterioles and precapillary sphincters?
    • O2 is the most important determinant of the opening and closing of the metarterioles and precapillary sphincters   ("local autoregulation")
    • ***************************
  8. local (tissue) autoregulation of blood flow
    -main regulator
    • O2 is the main regulator of tissue blood flow
    • Low O2 causes dilation of precapillary sphincters
    • In addition to the nutritive blood flow that is regulated by O2 there is also non-nutritive blood flow that is regulated by the ANS
    • AV shunt vessels are located in skin and provide mechanism to permit control of skin temp
  9. Fluid Movement
    • (passive process)
    • Solvent and solute movement across capillary endothelial cells occurs by diffusion and filtration (P grad for O2 and CO2 concentration gradients for Na etc...)
  10. Diffusion vs Filtration
    • diffusion: occurs in both directions along the entire length of the capillary membrane
    • filtration: Occurs as a result of the net movement of fluid out of the vessel at the arterial end of the capillary
    • *most important mechanism
    • is the most important mechanism for transfer of nutrients between plasma and interstitial fluid

    • Rate of diffusion of lipid-soluble substances is proportional to the concentration (or P) difference between the 2 sides of the membrane
    • For this reason, large amounts of O2 move from capillaries into tissues, whereas CO2 moves in the opposite direction  -- since they are lipid soluble, they diffuse readily across capillary membranes independent of pores
  12. Filtration
    • Important for water-soluble substances such as ions, glucose, aa that cannot cross endothelial cell membranes
    • diffusion of water-soluble substances is limited to the clefts between cells ---> surface area is much smaller than for gas
    • Transfer of these substances relies on "osmosis" --> driven by hydrostatic and osmotic P's
    • (hydrostatic: P in cap pushing fluid out, osmotic: presence of proteins that draw water towards them or fluids in)
  13. What are the 4 pressures that determine whether a fluid will move out of a capillary (filtration) or into the capillary (resorption) across the cell membranes:
    • 1. Capillary P (P fluid out of cap)
    • 2. Interstitial fluid P (fluid into cap out of ISF)
    • 3. Plasma colloid osmotic P (pull fluid into cap)
    • 4. Interstitial fluid colloid osmotic P (pulls fluid into ISF)
  14. Starling Equation
    • Net fluid movement = K(Pc-Pi)-σ(piep-piei)
    • K is the filtration (fluid out) coefficient
    • Pc is the capillary pressure
    • Pi is the interstitial fluid pressure
    • omega is the reabsorption coefficient
    • piep is the capillary colloid osmotic P
    • piei is the interstitial fluid colloid osmotic P
    • Changes of any of these variables can alter net movement of water into and out of the intravascular space
  15. net direction of fluid movement and its classification
    • fluid direction can be either in or out of the capillary
    • when net fluid movement is out of the capillary, we call it "filtration"
    • when net fluid movement is into the capillary, we will call it "absorption"
  16. Conductance
    • Relates to the filtration and reabsorption coefficients
    • is a measure of the permeability of the capillary to water
    • different value for different tissues, depending on the anatomic characteristics of the capillary wall (fenestrated, size of pores, etc...)
  17. Capillary Pressure
    • (1 of the 4 determinants of fluid flow direction)
    • determines filtration

    • Force that favors fluid moving out of the capillary -*HIGHEST at the arterial end of the capillary
    • capillary pressure at the arterial end is ~30mmHg while pressure at venous end is about ~10mmHg
    • Venous P has a more important impact than arterial
  18. Arterial or venous P effects on capillary pressure
    • changes in arterial blood pressure have little effect on capillary pressure due to adjustments in precapillary resistance vessels
    • venous pressure can have a more important effect
    • (venous system can be overloaded whereas arterial always remains the sameish)
  19. Interstitial Fluid P
    • (1 of the 4 determinants of blood flow direction)
    • Force that theoretically opposes filtration of fluid out of the capillary (if it was positive)

    • Interstitial fluid is the gel matrix that surrounds the cells
    •   -has a negative P of about -6mmHg
    •   -acts as a 'vacuum' to hold tissues together and maintain minimal distance for diffusion of nutrients
    • However because it is a NEGATIVE P it actually encourages fluid to move out of the capillary ****
  20. Edema and interstitial fluid P
    loss of negative ISF P allows fluid to accumulate in tissue spaces as "edema"
  21. Plasma Colloid Oncotic Pressure
    • (1 of the 4 determinants of blood flow direction)
    • Force that favors fluid moving INTO the capillary

    • Plasma proteins generate osmotic P that draws fluid into the capillary through the membrane  ---ALBUMIN accounts for nearly 70% of this force (globulins and fibrinogen account for smaller component)
    • Negative charge on proteins requires more positive ions (Na+) to be on same side of the membrane as the proteins -- this results in more osmotically active substances and further increases colloid osmotic P (called "Donna Equilibrium") and acconts for colloid osmotic P being 50% greater than that caused by proteins alone
    • (so changes in protein concentration - changes a lot of fluid content because of oncotic P and Na that brings fluid along too)
  22. Interstitial Fluid Colloid osmotic pressure
    • Force that favors fluid moving OUT of the capillary
    • Proteins in the interstitial fluid are responsible for this pressure of -3mmHg (not as large of P as plasma colloid oncotic P as there is not a lot of protein in the interstitial space)
    • caused by albumin leakage out of capillaries but not globulins (they are too large)
  23. Net effect of the 4 P's (Cap P, ISF P, Plasma colloid osmotic P, Interstitial fluid colloid osmotic P)
    • Net effect of these pressures is a positive filtration pressure at the ARTERIAL end of the capillary
    • *fluid moves out of the capillary into the ISF spaces (IE FILTRATION)

    Net effect of these P's at the VENOUS end of the capillary is that fluid moves back into the capillary (REABSORPTION)

    Overall the mean values of the 4 pressures are nearly ID so that the amount of fluid filtered is nearly the same as the amount that is reabsorbed

    ***any fluid not reabsorbed enters the lymph vessels
  24. Lymphatic system
    responsible for returning interstitial fluid and proteins to the vascular compartment

    • lymph capillaries lie in the interstitial space and collect fluid and protein that is not (or cannot be) reabsorbed
    • Very important in certain tissues (esp GIT and LIVER b/c of leaky fenestrations)
    • bacteria that enter the lymph vessels are removed and destroyed in the lymph nodes
    • lymph nodes-- [] of immune cells that kill bacteria
  25. what does the lymphatic system empty into
    thoracic duct (which drains into the systemic circulation ie eventually caudal vena cava)
  26. doe lymph vessels have backflow?
    NO lymph vessels contain flap like valves that prevent backflow of fluid
  27. how does lymph flow
    Skeletal muscle contraction and passive movements of the limbs facilitate flow of lymph
  28. Lymph vessels
    • The most important function is to return protein to the systemic circulation to maintain low protein concentrations in interstitial fluids *******************
    • without lymph vessels present proteins would become more concentrated in the ISF
    • This would result in increased interstitial fluid colloid osmotic P, pull more fluid from circulation, and cause life-threatening edema within a few hours (ESPEC if it develops in the lungs)
  29. EDEMA
    • The presence of excess Interstitial fluid in peripheral tissues, resulting in POSITIVE pressure in the interstitial fluid space (instead of negative)
    • The V of the extra fluid exceeds the ability of the lymph vessels to transport it away to the tissues
    • when this occurs, external P in one area will displace fluid to another area: this is called "pitting edema"
  30. Causes of Edema
    • INCREASED capillary pressure
    • INCREASED permeability of capillaries
    • DECREASED plasma protein concentrations 
    • OBSTRUCTION of lymph vessels
  31. How does increased capillary P cause edema
    • Accompanies impaired venous return due to cardiac failure 
    •     -results in increased filtration of fluid from capillaries that exceeds capillary reabsorption and lymph transport

    Histamine release may contribute to increased capillary pressure by dilating the arterioles and constricting the venules (may also see increased cap permeability)
  32. How does decreased protein concentration caus edema?
    • Decreases the colloid osmotic P such that the capillary pressure predominates and excess fluid leaves the circulation
    • most often due to low albumin levels as a result of burns, GI disease, renal disease
  33. How does obstruction of lymph vessels lead to edema
    • results in accumulation of protein in the interstitial fluid
    • the increased interstitial fluid colloid osmotic pressure results in excess fluid accumulation in the interstitial space

    May occur secondary to neoplasia, surgery, etc.... typically regresses as new lymph node develops
    • The peritoneal cavity frequently accumulates edema fluid because any increased pressure in the liver (heart failure or liver disease) causes leakage of protein-containing fluids out of the liver and into the peritoneal cavity
    • also remember that the liver capillaries are more 'leaky' than other capillaries to begin with

    accumulation of fluid in the peritoneal cavity is referred to as ascites