Microcirculation PDF

The Microcirculation and lymphatics Jutta A. Ward, PhD  Objectives The Microcirculation and Lymphatics Explain how water and solutes traverse the capillary wall. Describe how changes in capillary surface area affect the capacity for fluid exch...

The Microcirculation and lymphatics Jutta A. Ward, PhD  Objectives The Microcirculation and Lymphatics Explain how water and solutes traverse the capillary wall. Describe how changes in capillary surface area affect the capacity for fluid exchange. Define the Starling equation and discuss how each component influences fluid movement across the capillary wall. Predict how altering pressure or resistance in pre- and post-capillary regions alters capillary pressure and the consequence of this change on transmural fluid movement. Using the components of the Starling equation, explain why fluid does not usually accumulate in the interstitium of the lungs. Describe how histamine alters the permeability of the post capillary venules and how the loss of albumin into the interstitial space promotes localized edema. Describe the lymphatics, and explain how the structural characteristics of terminal lymphatics allow the reabsorption of large compounds, such as proteins  Objectives The Microcirculation and Lymphatics Explain how water and solutes traverse the capillary wall. Describe how changes in capillary surface area affect the capacity for fluid exchange. Define the Starling equation and discuss how each component influences fluid movement across the capillary wall. Predict how altering pressure or resistance in pre- and post-capillary regions alters capillary pressure and the consequence of this change on transmural fluid movement. Using the components of the Starling equation, explain why fluid does not usually accumulate in the interstitium of the lungs. Describe how histamine alters the permeability of the post capillary venules and how the loss of albumin into the interstitial space promotes localized edema. Describe the lymphatics, and explain how the structural characteristics of terminal lymphatics allow the reabsorption of large compounds, such as proteins Contrast the structure of lymphatic capillaries and systemic capillaries Diagram the relationship between interstitial pressure and lymph flow. Explain why edema does not normally develop as interstitial pressure increases. Explain how edema develops in response to: a) venous obstruction, b) lymphatic obstruction, c) increased capillary permeability, d) heart failure, e) tissue injury or allergic reaction  Microcirculation Extends from 1st order arteriole to 1st order venule with a network of true capillaries in between them Flow thru capillaries may be altered by contraction or relaxation of small arteries, arterioles and metarterioles. Levy & Pappano Fig 8-1 Capillaries fall into three groups depending on their “leakiness” G & H Fig 16-4  Transcapillary exchange Movement across capillary Continuous capillary Most common capillary. Diffusion – promotes exchange Has inter-endothelial junctions 10- of gases, substrates and waste 15 nm wide. Special exception, the blood brain Filtration – net transfer of fluid barrier is achieved by filtration and – Clefts are absent – instead capillaries have tight absorption. junctions Capillary permeability varies in different tissues. Also venous end of capillary more permeable than arterial end. Fenestrated capillary Sinusoidal (discontinuous) Endothelial cells are thin In addition to fenestrae, and perforated with these capillaries have large fenestrations. gaps. Found in surrounding epithelia. Found primarily in the – Small intestine sinusoids of the liver – exocrine glands – Glomerular tufts of kidney  Diffusion of water-soluble, non-lipids: Fick’s law of diffusion J = -DA (dc/dx) J: flux of substance per unit time D: diffusion coefficient of molecule A: cross sectional area Dc/dt: concentration gradient Fick’s law as it relates to the vasculature J = S Px([C]o – [C]i) – S: capillary surface area – Px: capillary permeability to X – ([C]o – [C]i): Difference between concentration in capillary and concentration outside capillary Depends largely on molecular size and concentration difference Relative permeability in skeletal muscle capillary pores Relative permeability (Px) varies in different capillary beds J = S * Px * ([X]c – [X]if) Substance Molecular Weight Permeability Water 18 1.00 NaCl 58.5 0.96 Molecules move across the Urea 60 0.8 capillary membrane at a Glucose 180 0.6 rate that is inversely Sucrose 342 0.4 proportional to their size Inulin 5,000 0.2 until MW ~ 60,000. Myoglobin 17,600 0.03 Beyond this size molecules Hemoglobin 68,000 0.01 do not pass thru the membrane Albumin 69,000 0.001  Diffusion of substances Lipid insoluble molecules move thru pores of the capillaries For small molecules, capillaries have little restriction to diffusion (small reflection coefficient). Diffusion is rapid. – Flow limited: for small molecules, the only limit to net movement is the rate of blood flow. – Diffusion limited: for large molecules, capillary permeability to the large molecules limits its transport across the capillary wall. Lipid soluble molecules pass readily thru endothelial cells.  Exchange of water Water can travel via transcellular and paracellular pathways. Aquaporins (AQP1) are the principle trans-cellular pathway Water moves via convection. According to Starling, 2 driving forces for movement of water – 1) trans-capillary hydrostatic pressure difference (blood pressure) – 2) effective osmotic pressure difference (colloid osmotic pressure or oncotic pressure)  Hydrostatic pressure is the principle force in capillary filtration P = (Pc – Pif) Pc = capillary hydrostatic pressure Pif = interstitial fluid hydrostatic pressure Arterial side Venous side Pc = 35 mmHg Pc = 17 mmHg Pif = 0 mmHg Pif = 0 mmHg P = 35mmHg P = 17mmHg If Pc is greater than Pif, fluid leaves Hydrostatic pressure promotes filtration  Factors effecting capillary pressure (Pc ) 1) resistance  Factors effecting Pc 2) changes in upstream and downstream pressure Parteriolar Pcapillary Pvenous Control 60 25 15 arteriolar 70 27 15 venular 60 33 25  Factors effecting Pc 3) location – ie in kidney very high Pc of near 50mmHg required for ultrafiltration – Retinal capillaries that bathe vitreous humor ~20mmHg – Pulmonary capillaries very low between 5-15mmHg to avoid edema in alveolar air spaces 4) time – capillary pressure varies over time at any given site. Primarily due to factors that influence arteriolar diameter and pre-capillary sphincter. 5) gravity – Capillary bed below heart greater Pc than one that is at level of heart.  The interstitium and interstitial fluid 2 types of solid structures – Collagen fiber bundles Strong and provide tensile strength of the tissues. – Proteoglycan filaments Forms fine reticular filaments G & H Fig 16-4 Gel – Similar to plasma but lower concentration of protein. – This fluid is trapped in the proteoglycan filaments and is gel-like – Fluid does not flow through the gel but moves via diffusion, one molecule at a time. This occurs 95-99% as rapidly as through free fluid “free” fluid: not trapped in the gel – Usually less than 1%. – During edema the free fluid pockets expand so that over half the fluid is free of the proteoglycan filaments  Interstitial fluid pressure (Pif) Usually negative in loose tissues due to fluid removal by the lymphatic system May be positive in rigid compartment like bone marrow or brain May be positive in encapsulated organs like kidney. In general however, Pif is close to zero or slightly negative  Colloid osmotic pressure  π or oncotic pressure The difference in colloid osmotic pressure between plasma proteins and interstitial fluid proteins. Colloids are those molecules with MW greater than 30,000. Only those molecules that do not move across the capillary wall contribute to the oncotic pressure Plasma proteins are the key factor that retain fluid loss from capillaries Remember, when Pc is greater than Pif, this promotes filtration and fluid leaves. However, when π c is greater than πif, this promotes absorption and fluid wants to enter the capillary  Oncotic pressure is the principle force in capillary absorption  π = (π c – π if) π c = capillary oncotic pressure π if = interstitial fluid oncotic pressure Arterial side Venous side π c = 26 mmHg π c = 26 mmHg π if = 1 mmHg π if = 1 mmHg  π = 25mmHg  π = 25mmHg The oncotic pressure helps retain fluid in the vessel Factors effecting πc Composition of plasma proteins. Reported as g/dl but due to diff molecular wgts π c can πc vary considerably (mmHg) (mmol amount of each is what matters) Average πc ~25 mmHg  Combine P and π for NFP NFP = (Pc – Pif) + (πc –πif) For arterial side (35-0) – (26-1) = 35 – 25 = +10 mmHg For venous side (17–0) – (26-1) = 17 - 25 = - 8 mmHg Net Filtration Pressure (NFP) Figure 19.15  Variations in NFP Intestinal mucosa – Pc always much lower than πc so that re-absorption occurs continually In kidney, glomerular capillary Pc exceeds πc so that filtration occurs almost continuously In general 2-4 liters of fluid per day are lost from the plasma to the interstitium. This must be returned to the plasma and is done so via the lymphatic system.  Lymph system Consists of two semi- independent parts – A meandering network of lymphatic vessels – Lymphoid tissues and organs scattered throughout the body Returns interstitial fluid and leaked plasma proteins back to the blood at right and left subclavian veins Lymph – interstitial fluid once it has entered lymphatic vessels  General functions of lymphatics Maintaining fluid balance – Transports interstitial fluid back to circulation – Transports protein back to circulation Purification and defense – Clears extra-cellular space of particulate matter, exudates and bacteria – Brings immune cells in contact with invaders Nutrition – Absorption of fats from small intestine  Lymph Transport The lymphatic system lacks an organ that acts as a pump Vessels are low-pressure conduits Uses the same methods as veins to propel lymph – Pulsations of nearby arteries – Contractions of smooth muscle in the walls of the lymphatics  Lymphatics Filtration at arteriolar end > reabsorption at venular end of capillaries, resulting net loss of fluid from plasma. Lymphatics return excess interstitial fluid to blood stream Terminal lymphatics are open to the liquid phase of the interstitium They are absent or reduced in myocardium and brain Prevalent in skin, respiratory, urogenital and gastrointestinal regions. G & H Fig 16-11  Factors effecting lymph flow Factors influencing interstitial pressure – Capillary hydrostatic pressure – Plasma protein – Interstitial protein – Capillary permeability – Interstitial hydrostatic pressure Lymphatic pumping – Intrinsic pumping by smooth muscle – Extrinsic pumping by surrounding tissues  Circulation of extra-cellular fluid 1) cardiovascular loop – 5 l/min = 7200 l/day 2) trans-vascular loop – Filter 20 l at arteriolar end – Re-absorb 16-18 l at venule end 3) lymphatic loop – Returns 2-4 l back to venous system  Movement of solutes Glucose – Diffusion at capillary is primary site for delivery to tissue – None absorbed Proteins – Plasma ~7g/dL of protein so 3L plasma contains 210g protein – CO if of plasma 2.75 L/min so 277,000 g of protein circulated daily – 100-200 g protein lost through large pores. – most proteins returned to blood stream via lymphatics  Edema In most cases edema is the result of increased fluid accumulation in the interstitial space, but it can also occur as a result of increased fluid inside of cells. Extracellular – A disruption in the balance of Starling forces – An increase in capillary permeability Intracellular – ↓ activity of Na+-K+ ATPase (due to ↓ O2) can result in an increase in sodium inside the cell, which draws water into cell