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Lecture 7- Blood capillaries : Filtration and permeability 1.

Capillary structure - A single layer of endothelial cells located upon a basement membrane - Diameter of 3- 10 micrometer - Three forms of capillary classified according to the nature of the endothelium: Continuous ( least permeable) Fenestrated Discontinuous ( most permeable) In liver- sinusoids with wider lumen therefore sluggish blood flow therefore allow exchanges of nutrients to take place easily. A sinusoid is a small blood vessel that is a type of capillary similar to a fenestrated endothelium. Sinusoids are actually classified as a type of Open Pore Capillary (aka discontinuous) as opposed to fenestrated. Fenestrated capillaries have diaphragms that cover the pores whereas Open Pore Capillaries lack a diaphragm and just have an open pore. The open pores endothelial cells greatly increase their permeability. In addition, permeability is increased by large inter-cellular clefts and fewer tight junctions. The level of permeability is such as to allow small and medium-sized proteins such as albumin to readily enter and leave the blood stream. Sinusoids are found in the liver, lymphoid tissue, endocrine organs, and hematopoietic organs such as the bone marrow and the spleen.

2. Location of capillary Blood flow is regulated by resistance arteries and precapillary sphincters

3. Capillary exchange - Intercellular junctions

0.1-0.3% of capillary surface 15-20 nm wide

The rate of exchange of materials varies considerably between different capillary beds. The capillaries in the brain are the least permeable, whereas the sinusoids of the liver are among the 'leakiest'. The amount of protein in the lymphatics draining various tissues is often used as an indicator of the degree of exchange occurring across a capillary bed. Judged on this basis, the relative 'leakiness' of various capillary beds is: liver > other abdominal organs > thoracic organs > muscles and skin > eye and brain Substance exchange across capillary walls occurs mainly by diffusion (passive, down concentration gradient) Substance may undergo vesicular transport- Vesicular transport is reserved for the specific transport of large molecules, usually proteins, but not all capillaries are capable of this

New theory- caveolea-

Other additional routes include : fenestrae and gaps in discontinuos capillary basement membrane

4. Fluid Exchange : The Starling Hypothesis

States that : direction and rate of fluid transfer between blood plasma in the capillary and fluid in tissue spaces depend on hydrostatic pressure on capillary wall and osmotic pressure of protein in plasma and tissue fluid. Positive sign: force blood out and negative sign is reabsorption at the venous end. Net fluid flux is proportional to the net driving pressure. Several factors need to be considered which include reflection co-efficient Capillaries are not perfect semi-permeable membranes Reflection co-efficient is a measure of membranes molecular selectivity.

Thus will make up the full starling equation :

5. Clinical aspects : Oedema - Excessive accumulation of tissue fluid - Causative factors : High arterial pressure Venous obstruction or poor venous return Leak of plasma protein Usually the plasma protein cannot easily cross the capillary In conditions where plasma protein are reduced from being lost in the urine or from malnutrition, there will be reduction in oncotic pressure[it causes the fluid to get back into the capillary] and thus resulting excess fluid buildup in the tissues. Decreased plasma protein concentration Increased capillary permeability Lymphatic capillary blockage 6. Transcapillary solute exchange - Molecular permeability is determined by lipid solubility and molecular size - There are 3 types of solutes lipid soluble [can diffuse through endothelial cell membrane], small lipid insoluble (hydrophilic)[diffusion, convective transport=bulk transport], large lipid insoluble [vesicles, caveolae] - Hydrophilic molecules require water-filled channels to cross the capillary wall - There are two theories being proposed regarding aqueous channel Pappenheimers small pore theory Channels of 4-5nm radius

Channels occupy <0.1% of capillary surface area Grottes proposal Small number of larger pores of radis 20-30nm Cylindrically pores are merely concepts The most likely routes are intercellular junctions, fenestrae, caveole/transcellular channels The fibre matric theory propose that the glycocalyx reduce the effective width of the juctions and fenestrae. (by causing steric hindrance, electrostatic repulsion)