Capillary Blood Pressure Notes

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 large- this 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

-continuous

-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

-fenestrated

-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

-sinusoidal (discontinuous)

-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 water-permeable channels (aquaporins)

-permeability of a cell depends on the size and number of pores in the capillaries- the 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.

-for molecules with the same size and charge, permeability is not identical due to deformability: this is shown as protein which are relatively rigid have a lower permeability than dextran which is flexible.

-the glycocalyx is not just a barrier but also a mechano-transducer as it links shear stress to the production of the gaseous vasodilator nitric oxide

-glycocalyx acts as a lubricant which is gel like and it minimises the damage due to fluid leaking out due to hydrostatic pressure

-the glycocalyx also binds to things and leads to accumulation as molecules become trapped.

Movement of fluid:

-determined by STARLING FORCES (only applies to water) across the capillary: balance between the capillary hydraulic pressure (driving fluid out) and capillary plasma osmotic pressure (net fluid movement into the capillary)- leads to plasma ultrafiltration across a...

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