Lecture 6 Transcapillary Exchange
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- continued here from Lecture 5 Microcirculation on 01/25/11 at 11:35AM.
- test questions will come from objectives and clinical examples.
Transcapillary Exchange of Water and Solutes
Lecture Outline I. Capillary Structure and Capillary Exchange
II. The rules for capillary exchange of solutes
III. Rules for Capillary Exchange of Water
IV. Idealized concept of the balance of filtration and reabsorption forces ` across the capillary wall
V. The Lymphatic System: Tidies up the lost water and protein from the vascular system
Objectives 1. How is movement through the capillary wall much different for water soluble versus lipid soluble molecules? 2. Be able to describe a typical small water filled pore in the capillary wall in terms of its size, contents, and number of pores over the capillary surface and the role of the glycocalyx surface proteins. 3. How does the concentration difference of solutes across the capillary wall and the surface area of capillaries influence the rate of exchange of solutes? 4. What are two ways the capillary permeability can be pathologically increased? 5. How would the number of capillaries in an area of tissue and their distance apart influence the concentration of a solute within the tissue? 6. What are the two primary sources of force or pressure which determine the amount of water filtered or reabsorbed across capillaries? 7. How do tissue hydrostatic pressure and tissue oncotic pressure normally influence the amount of water filtered or reabsorbed across capillaries? 8. What does the term edema mean and how is edema generated? 9. Be able to describe how a lymph vessel uses external compression or contraction of its endothelial cells to move water from the interstitial spaces.
capillary cartoon I. Capillary Structure and Capillary Exchange
A. Lipid soluble materials 1. Pass through cell membranes 2. Huge surface area for exchange: Examples lung - 3500 cm2/gm HUMAN LUNG ~300-400 GM ~ 1050000 CM2 muscle - 100 cm2/ gm 3. Molecules involved a. Gases - Oxygen, Carbon Dioxide, Nitrogen b. Fatty acids, triglycerides c. Cholesterol based hormones
capillary structure cartoon
B. Water Soluble Materials
1. Must pass through water filled pores to reach interstitial environment a. Small pore system (1). 3-4 nanometer diameter: glucose and amino acids for example (2). 109 pores per cm2 of surface area (3). Approximately 0.02-0.05% of surface area b. Large pore system (1). 30-100 nanometer diameter: albumin and globulin proteins (2). 105 pores per cm2 of surface area
Break in Gap Junction Strand
B
Cross Section of joint between endothelial cells
Capillary Endothelial Cells
Cell A
Cell B
Glycocalyx
Tight Junction
Water filled space between cells
Cell B
Cell A
A
Capillaries
The capillaries
- Easy for lipids to go right through the endothelial cells.
- Huge surface areas for exchange.
- 1 gram of tissue has over 1000 square feet of SA.
- Lungs have even higher surface area
- Skeletal muscle caps have lowest SA for exchange.
- What gets across:
- Gasses
- FAs, TAG
- cholesterol-based hormones
Image
- There are tight jxns to link cells together so there is no leakage.
- There are also lots of invaginations.
- There are vacules
- Form on lumen of capilary and move outward (mostly).
- These are useful for things that can't get across the capillary.
Higher mag
- Glycocalyx sticks off endothelial cell into the plasma
- polysacc strands
- The tight jxns are longitudinally long between endothelial cells.
- There are small spots where they break so that things like glucose can get through.
- Small pore system:
- lets 3-4 nanometer things thorugh: glucose, mannose, arginine, etc.
- Na and K just go through.
- Billions and billions of pores.
- Don't take up much of the SA.
- lets 3-4 nanometer things thorugh: glucose, mannose, arginine, etc.
2. Materials leaving the capillary blood have many barriers to pass before passing between adjacent endothelial cells through physical holes known as pores.
- Glycocalyx is negatively charged as are most molecules int he body.
- So most things are repelled.
- The glycocalyx can be damaged.
- This can increase permeability.
- a. Glycocalyx is proteineous structure of glycosaminoglycans, proteoglycans, and glycolipids
- b. Glycocalyx is negatively charged and repels negatively charged molecules
- c. Glyocalyx acts as a molecular sized filter to limit larger molecules reaching the physical pores between cells
- d. The physical pores are generally very small and would limit even most small proteins
3. What is a capillary pore
- a. Cleft between adjacent capillary endothelial cells
- b. Pore is not a straight tube but circuitous due to tight junctions
- c. Pore filled with fiber matrix mucopolysaccharide gel
- This generates an electrical barrier
- (1). Acts as partial barrier
- (2). Electrical charge (-) acts as barrier
- d. Basement membrane
- (1). Dense collagen and elastin material act as a filter for large molecules
- (2). May be barrier to lipid soluble materials: WATER FILLED BARRIER??
- e. The single greatest barrier is the extensive system of tight junctions between adjacent cells but the glycocalyx is a close second.
- (1). Areas between tight junctions are the water filled pores
- (2). In the brain and testes, tight junctions encircle the endothelial cells.
4. Endocytosis of macromolecules: caveolae form vesicles that move from the blood to tissue side of the endothelial cell
- A. Energy requiring system: hypoxia drastically decreases vesicle formation
- B. A major molecule moved by endocytosis is albumin and all the many materials attached to albumin.
- 1. albumin binding glycoprotein
- a. receptor type protein to attach albumin
- b. located predominately in caveolae
- c. binds or associates with caveolin-1 when albumin attaches
- d. vesicle forms, moves across endothelial cell, releases albumin
- 2. Many hormones and fatty acids are associated with albumin
- a. potential pathway for selective, controllable transport of hormones??
- b. diseases that influence caveolae formation likely impair this process - for example, mice with no caveoli have minimal albumin in lymph
- 1. albumin binding glycoprotein
- stopped here on 01/25/11 at 12PM.
II. The rules for capillary exchange of solutes
- A. Concentration difference from blood plasma to interstitial fluid is the energy source for diffusion
For each 1 mM difference in
concentration, energy equivalent to 17 mmHg
MOST CONCENTRATION DIFFERENCES ABOUT 1-50 µ.
Glucose 5 mM in plasma --- interstitial fluid concentration???
Js = solute transferred per minute
Cp = Plasma concentration
Ct = Tissue concentration
Js ~ (Ct - Cp)
capillary structure cartoon
B. Surface area available = A
(1). Lipid soluble - virtually entire capillary surface area
(2). Water soluble - only pore surface area
(3). Surface area influenced by
a. Surface area of a capillary: capillary diameter and length changes?
b. Number of perfused capillaries:
1. Active control perfuse different percentage of available capillaries
2. Grow new capillaries or lose capillaries by normal or disease
processes
Js ~ A (Ct - Cp)
capillaries three for area capillary structure cartoon
capillaries pores enlarged
C. Permeability of molecule to the capillary wall structure P (1). Lipid soluble materials are hundreds to thousands times more permeable than water soluble materials (2). Permeability for water soluble materials is regulated by tightness of junctions between endothelial cells a. Histamine can cause endothelial cells to “contract” and widen “pores” b. Hypoxia and anoxia increase permeability either by damage or cell shape changes
P = moles / minute / area
Js ~ P A (Cp - Ct)
D. Distance the molecules must diffuse into the tissue
(1) Primarily determined by the amount of tissue each capillary must serve (2) Greatly influenced by the number of capillaries in service and perfused
Js = (P A (Cp - Ct)) / D
oxygenation by capillaries to sk muscle
E. Rules for regulation of capillary permeabilty: Primarily an issue of decreasing the contact proteins between adjacent endothelial cells. 1. Common causes of increased capillary permeability a. Hypoxia – inadequate blood flow provides too little oxygen for endothelial cells to maintain contacts between cells. Fortunately, endothelial cells tolerate hypoxia and even anoxia quite well b. Reperfusion injury – formation of oxygen radicals when blood flow restored to a tissue.
MICROVASCULAR CELL INJURY
LACK OF OXYGEN OXIDANTS PROTEASES
ATP ACTIVATE NEUTROPHILS
ADP INFLAMMATORY CYTOKINES
XANTHINE
AMP DEHYDROGENASE TISSUE DAMAGE
ADENOSINE -OH*
INOSINE XANTHINE Fe+3
OXIDASE
HYPOXANTHINE URATE + O2* + H2O2
REPERFUSION
OXYGEN
III. Rules for Capillary Exchange of Water
A. Capillary blood pressure attempts to push water out of capillary through pores 1. Pc = Capillary Pressures are 15-35 mmHg. Intestinal mucosa 14-17 mmHg Brain 20-25 mmHg Muscle 23-30 mmHg 2. When standing, capillary pressures in lower body could be 80-150 mmHg
capillary albumin and Pcapillary
B. Plasma albumin and globulin large proteins resist having water removed from its sphere of influence:
1. Plasma Oncotic Pressure = Plasma Colloidal Osmotic Pressure = COPp
About 22-27 mmHg is normal
2. Attempts to reabsorb water from tissue spaces
3. Albumin accounts for about 60% of the oncotic pressure
C. A small amount of albumin is in the interstitial environment.
Interstitial Tissue Oncotic Pressure
About 3-6 mmHg is normal and pulls water out of capillary
capillary albumin and Pcapillary
D. Interstitial Tissue hydrostatic pressure Pif 1. In most tissues, slightly negative 2. Varies from assisting filtration if negative to assisting reabsorption if positive 3. Excessive fluid causes edema, or free fluid in the interstitium 4. External compression can be used to prevent filtration or enhance reabsorption of water Support stockings Massage interstitial pressure and volume
capillary hydrostatic vs oncotic forces E. The Starling - Landis Equation for filtration - reabsorption of water
1. Filtration forces
(Pcap + COPif)
2. Reabsorption forces
(COPp - Pif)
3. Hydraulic Conductivity - a measure of water permeability per unit area
and per mmHg
K = ml/min/area/mmHg
IV. Idealized concept of the balance of filtration and reabsorption forces across the capillary wall
1. Capillary pressure is gradually dissipated by friction of flow along the capillary 2. Plasma oncotic pressure gradually increases along capillary as water is filtered out 3. Reality - most organs filter plasma water such that in a 24 hour period, the entire plasma volume is lost at least once. Also, the capillaries leak a mass of albumin equal or greater than the blood mass of albumin
CAPFILTR
V. The Lymphatic System: Tidies up the lost water and protein from the vascular system
Problem: Once albumin or any large protein is out of the capillary, it must be physically carried back to the blood by lymph
Solution: Suck interstitial fluid into the terminal lymphatic vessels
1. Contract or compress lymphatic structures to push lymph through valves to next lymphatic tube
2. Recoil of lymphatic structure generates negative pressure to assist filling of lymph vessel
3. Recoil aided by anchoring filaments on edges of lymphatic endothelial cells
LYMPH
Clinical Example Mrs. Clark was washing her windows when she broke a large glass pane. A glass shard cut her arm and leg. She lost a great deal of blood. A neighbor brought her to the emergency department. The first blood sample before infusion of saline solution indicated a hematocrit of 33% and past records indicate her hematocrit is normally 39-40%. A probable cause of the decrease in hematocrit is A. loss of more red blood cell than plasma volume. B. contraction of the spleen and liver veins to add plasma. C. absorption of interstitial water to dilute the blood. D. decreased excretion of water by the kidneys. E. increased absorption of water from the intestinal contents.
NORMAL VOLUME AND RED CELL MASS
INITIAL BLOOD VOLME LOSS
PHYSIOLOGICAL
COMPENSATION
ELECTROLYTE FLUID ADDED
