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Structure and roles of capillaries Role of capillary
-oxygen and other essential substances leave the blood to enter tissue cells and carbondioxide and other metabolites are removed
-capillaries are small in size: 500-1000 micrometers long and 4-8 micrometers wide
-there are a large number of capillaries so the total combined surface area is largethis increases the rate of exchange of solutes, gases and waste products with the tissue
-large number of capillaries means they are distributed throughout the tissue-all regions of the tissue are exposed to the vasculature Structure
-one endothelial cell thick -300nm (small diffusion distance)
-Adv: combination of large surface area and thinness of the capillary wall ensures that solute flux across a capillary is fast- this is shown by Fick's law of diffusion
-based on ultrastructure: three types of endothelial cells defined by pores within and between endothelial cells. Types of pores determines the permeability of the capillary rather than the channels
-found in all types of muscle, lungs, connective tissue. In the blood brain barrier the continuous capillary is extremely tight
-there are numerous tight junctions (main determinant of permeability) between the endothelial cells: proteins-occludin, claudin which bind to each other tightly. Tightness is determined by claudin 5 as prevention of expression of the claudin 5 gene increases the permeability of capillaries at the blood brain barrier. Tight capillaries become leaky. If Red dye is injected-in a transgenic mouse everything can be seen as a red dye.
-abundant ion channels and aquaporins- mostly transcellular transport
-continuous capillaries are less permeable than the other two types of capillaires
-found in renal glomeruli, glands, ciliary body, intestinal mucosa
-intracellular fenestrations (holes) - 30-50nm wide. In glomerular capillaries the fenestrations occupy 10-30% of the wall area
-fenestrations can be regulated with a thin diaphragm that can result in an open and closed fenestration
-found in bone marrow, liver and spleen
-large intercellular gaps.
-macromolcules and blood cells can permeate- very leaky, very large gaps Breakdown of capillary structure leads to disease: E.g- multiple sclerosis, there is a destruction of myelin in the CNS-triggered by immune cells (T lymphocytes) which cross the blood brain barrier and initiate an inflammatory response Transport of solute and fluid mechanisms across capillaries Movement of solutes: Transcellular: movement of substances from the capillary lumen to the interstitial space by passing through the endothelial cell
-endothelia have large surface area, are thin, so small lipophilic molecules can diffuse across them easily- this is the major route for gases like O2 and CO2
-endothelial plasma membrane contains ion channels for calcium, potassium, chloride as well as Na-K ATPase pump, Na-Ca exchange. There are also waterpermeable channels (aquaporins)
-permeability of a cell depends on the size and number of pores in the capillariesthe channels are more important for the transcellular movement of negatively charged ions.
-a form of vesicular transport (transcytosis) has also been found and might be important for passage of large proteins Paracellular: movement of substances from the capillary lumen to the interstitial space by passing through gaps between endothelial cells. Endothelia are coated by glycocalyx-so substances have to cross this barrier.
-Glycocalyx-protrudes into the lumen on either side of the capillary wall. It is made up of Glycoproteins (podocalyxin) , proteoglycans (Heparan sulphate ,chondroitin sulphate) , Hyaluronic acid (many negative charges)
-These components are arranged as a complex polymer- 100-500 nm thick- forms a molecular sieve or barrier to movement of molecules
-permeation depends on size and charge
-Small substances are able to pass more easily than larger ones- this is shown through using dextran molecules of different size.
-permeability sequence for substances of the same size is positive > neutral
> negative- shown through dextran molecules of different charge- this is because the glycocalyx has a net negative charge
-we know that the glycoclax is a charged sieve because using enzyme that digest the glycocalyx increases the permeability to anions.
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