**1. Microcirculation physiology**

The area of the circulation system where the metabolic requirements of tissues are met is called microcirculation. In other words, this is the point at which the arterial system and venous system join.

As a result of 6–8 branches occurring in the arterial structure entering a tissue, the width of the interior lumen reduces to 10–15 μm, and this structure is called an arteriole. The wall

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

structures of arterioles continue with metarterioles within the continuous surrounding smooth muscle, and capillary veins form from metarterioles. At the point where the capillaries emerge from the metarterioles, smooth muscle tissue forms a sphincter-like structure at the capillary entrance. Capillary structures continue to form venules. Venules have the larger diameter compared to arterioles though they have less muscle tissue. However, less muscle tissue causes low pressure within the venule and ensures severe contractile force (**Figure 1**).

requirement of the tissue. The precapillary sphincter found at the junction of the metarterioles with capillaries plays a role in the opening of closed capillaries and closure of open capillaries,

Microcirculation and Hyperbaric Oxygen Treatment http://dx.doi.org/10.5772/intechopen.75609 49

There may be nearly 12 l of fluid found in the interstitial area. This cavity found between cells is kept open by collagen fibres. Proteoglycans appear to be like a brush for the interstitium. Due to proteoglycans found in the interstitial fluid, it has a gel consistency. Water and electrolytes may rapidly diffuse within the gel. Free fluid is only found in collagen fibres and at cell

The size of exchange areas for material transfer between compartments in the microcirculatory environment is directly related to the transfer amounts. Additionally, other effective factors are fixed transfer, the presence of membrane carriers, channel-dependent transport,

According to Fick's first law, the solute transfer from a membrane only occurs in situations

is the solute flow rate, Pd is the diffusion permeability constant, and ΔC is the con-

Δ*x*,

According to Fick's second law, the amount of diffusion is linked to the thickness of the mem-

*dt* <sup>=</sup> <sup>−</sup>*DA* \_\_\_

About 97% of oxygen is bound to haemoglobin in blood and passes into tissues according to the Fick law. Oxygen presentation to tissues is dependent on the cardiac output and arterial oxygen content. Formula of arterial oxygen content is the sum of the multiplication of oxygen saturation, blood haemoglobin level and Hüfner number (amount of oxygen carried if haemoglobin is fully filled) with the multiplication of partial oxygen pressure by 0.003. There is 100 mmHg oxygen pressure at the arterial tip at the 1 atmospheric pressure while at the pressure of 3 atmospheres with 100% oxygen it increases according to the Henry law and reaches to the 2000 mmHg. Tissue oxygen pressure reaches from 55 to 500 mmHg at this point. At 1 atmosphere pressure, there is 3 ml per litre of free oxygen, and this amount reaches 60 ml where the tissues fulfil their needs without using haemoglobin-

Δ*C* Δ*X*

with concentration differences until concentration balance is achieved [4].

is the free diffusion constant, and Δx is the barrier thickness.

brane, the surface area over which diffusion occurs, molecular mass and size.

and this local control is called vasomotion [2].

barrier permeability, and soluble material transfer [3].

Js = P<sup>d</sup> S[ΔC]

*Pd* <sup>=</sup> *Df* \_\_\_

\_\_\_ *dn*

boundaries in the interstitial area.

where Js

where Df

centration difference

bound oxygen [5].

The total wall thickness of capillary structures is 0.5 μm. Shaped elements in the blood can only pass through by friction along the wall of the 9-μm lumen. There are openings of 6–7 nm width between the endothelial cells of the capillaries called fenestrations. These structures form 1/1000 of the total endothelial surface area but are areas where the transfer of water and water-soluble material occurs. These fenestrations may differ from organ to organ. These gaps are very narrow in the brain, while in the kidneys broad intervals ensure the necessary width for glomerular filtration of water and solutes [1].

Capillaries are not continuously open structures. The number of open capillaries varies depending on the requirements of the tissue, and here the most important stimulus is the oxygen

**Figure 1.** The area of the circulation system.

requirement of the tissue. The precapillary sphincter found at the junction of the metarterioles with capillaries plays a role in the opening of closed capillaries and closure of open capillaries, and this local control is called vasomotion [2].

structures of arterioles continue with metarterioles within the continuous surrounding smooth muscle, and capillary veins form from metarterioles. At the point where the capillaries emerge from the metarterioles, smooth muscle tissue forms a sphincter-like structure at the capillary entrance. Capillary structures continue to form venules. Venules have the larger diameter compared to arterioles though they have less muscle tissue. However, less muscle tissue causes low pressure within the venule and ensures severe contractile force (**Figure 1**). The total wall thickness of capillary structures is 0.5 μm. Shaped elements in the blood can only pass through by friction along the wall of the 9-μm lumen. There are openings of 6–7 nm width between the endothelial cells of the capillaries called fenestrations. These structures form 1/1000 of the total endothelial surface area but are areas where the transfer of water and water-soluble material occurs. These fenestrations may differ from organ to organ. These gaps are very narrow in the brain, while in the kidneys broad intervals ensure the necessary width

48 Hyperbaric Oxygen Treatment in Research and Clinical Practice - Mechanisms of Action in Focus

Capillaries are not continuously open structures. The number of open capillaries varies depending on the requirements of the tissue, and here the most important stimulus is the oxygen

for glomerular filtration of water and solutes [1].

**Figure 1.** The area of the circulation system.

There may be nearly 12 l of fluid found in the interstitial area. This cavity found between cells is kept open by collagen fibres. Proteoglycans appear to be like a brush for the interstitium. Due to proteoglycans found in the interstitial fluid, it has a gel consistency. Water and electrolytes may rapidly diffuse within the gel. Free fluid is only found in collagen fibres and at cell boundaries in the interstitial area.

The size of exchange areas for material transfer between compartments in the microcirculatory environment is directly related to the transfer amounts. Additionally, other effective factors are fixed transfer, the presence of membrane carriers, channel-dependent transport, barrier permeability, and soluble material transfer [3].

According to Fick's first law, the solute transfer from a membrane only occurs in situations with concentration differences until concentration balance is achieved [4].

$$\mathbf{J}\_s = \mathbf{P}\_d \mathbf{S} \mathbf{[\Delta \mathbf{C}]} \mathbf{J}$$

where Js is the solute flow rate, Pd is the diffusion permeability constant, and ΔC is the concentration difference

$$P\_d = \frac{D\_f}{\Delta x'}$$

where Df is the free diffusion constant, and Δx is the barrier thickness.

According to Fick's second law, the amount of diffusion is linked to the thickness of the membrane, the surface area over which diffusion occurs, molecular mass and size.

$$\frac{dn}{dt} = -DA\frac{\Delta C}{\Delta X}$$

About 97% of oxygen is bound to haemoglobin in blood and passes into tissues according to the Fick law. Oxygen presentation to tissues is dependent on the cardiac output and arterial oxygen content. Formula of arterial oxygen content is the sum of the multiplication of oxygen saturation, blood haemoglobin level and Hüfner number (amount of oxygen carried if haemoglobin is fully filled) with the multiplication of partial oxygen pressure by 0.003. There is 100 mmHg oxygen pressure at the arterial tip at the 1 atmospheric pressure while at the pressure of 3 atmospheres with 100% oxygen it increases according to the Henry law and reaches to the 2000 mmHg. Tissue oxygen pressure reaches from 55 to 500 mmHg at this point. At 1 atmosphere pressure, there is 3 ml per litre of free oxygen, and this amount reaches 60 ml where the tissues fulfil their needs without using haemoglobinbound oxygen [5].

**Figure 2.** Diffusion according to the size and solubility of material.

The fat-soluble material does not need to pass through pores but reaches tissue directly by passing through endothelial cells. Water and water-soluble material use the pores between endothelial cells to diffuse and pass into the cell. For diffusion rate, the size of the molecule to be diffused is important (**Figure 2**).

Forces controlling fluid transfer in capillaries were defined by Starling. While capillary pressure (Pc) and interstitial fluid oncotic pressure (πif) ensure water and solutes leave the vein, plasma oncotic pressure (Pπ) and interstitial hydrostatic pressure (Pif) attempt to prevent water and solute transfer in the interstitial area. In conclusion, net filtration pressure (NFP)

Capillary 10 Interstitial −5.3 Subtotal (positive = outwards) 15.3

Microcirculation and Hyperbaric Oxygen Treatment http://dx.doi.org/10.5772/intechopen.75609 51

Capillary −28 Interstitial −6 Subtotal (positive = outwards) −22 Total (positive = outwards) −6.7

According to the Starling equation, there is 0.3 mmHg net outward pressure for 2 ml/min outward flow. The difference is removed from the interstitial area by the lymphatic system. Filtration occurs in the arteriole sections of the capillaries. Fluid reabsorption is clear at the

Lymphatic capillaries include endothelial flaps, and these flaps prevent reverse leakage of fluid. Fluid flow is ensured by skeletal muscle contractions with flow rates in the interval 4–150 ml/hr. Interstitial fluid pressure and lymph fluid rate determine lymphatic flow.

In eukaryotes, transfer of oxygen and nutrition into the cell and removal of carbon dioxide and waste material occurs at the cell surface. In multicellular organisms, this event occurs in

In humans, blood flow follows the path: left ventricle large- and medium-diameter arteries small arteries known as precapillary resistance arterioles and terminal arterioles capillary beds not containing contractile elements and where oxygen and solute exchange occurs postcapillary resistance venules and collecting veins capacitance veins and large veins

Tissue oxygenation (DO2) is calculated as being equal to arterial oxygen saturation (SaO2

The result is that it takes 30–60 s for oxygen entering blood in the lungs to reach tissues. However, for oxygen to reach peripheral tissues, it is necessary for there to be sufficient

blood haemoglobin level cHb × 1.39 × cardiac output (CO).

) ×

develops as NFP = Pc−Pif−π P + πif. The pressure distribution is shown in **Table 1**.

venule tips [3].

**2. Microcirculation regulation**

Venous end Hydrostatic pressure

**Table 1.** Pressure distribution in microcirculation.

Osmotic pressure

the interstitial area [3].

right atrium.

With the Donnan effect, negatively charged proteins responsible for oncotic plasma pressure may attach to glycocalyx structures due to charge; however, they cannot bind, and plasma oncotic pressure remains high [6].



**Table 1.** Pressure distribution in microcirculation.

The fat-soluble material does not need to pass through pores but reaches tissue directly by passing through endothelial cells. Water and water-soluble material use the pores between endothelial cells to diffuse and pass into the cell. For diffusion rate, the size of the molecule to

With the Donnan effect, negatively charged proteins responsible for oncotic plasma pressure may attach to glycocalyx structures due to charge; however, they cannot bind, and plasma

> Capillary 17 Interstitial −5.3 Subtotal (positive = outwards) 22.3

> Capillary −28 Interstitial −6 Subtotal (positive = outwards) −22 Total (positive = outwards) 0.3

> Capillary 30 Interstitial −5.3 Subtotal (positive = outwards) 35.3

> Capillary −28 Interstitial −6 Subtotal (positive = outwards) −22 Total (positive = outwards) 13.3

Mean values Hydrostatic pressure mm Hg

Osmotic pressure

Osmotic pressure

be diffused is important (**Figure 2**).

**Figure 2.** Diffusion according to the size and solubility of material.

50 Hyperbaric Oxygen Treatment in Research and Clinical Practice - Mechanisms of Action in Focus

oncotic pressure remains high [6].

Arterial end Hydrostatic pressure

Forces controlling fluid transfer in capillaries were defined by Starling. While capillary pressure (Pc) and interstitial fluid oncotic pressure (πif) ensure water and solutes leave the vein, plasma oncotic pressure (Pπ) and interstitial hydrostatic pressure (Pif) attempt to prevent water and solute transfer in the interstitial area. In conclusion, net filtration pressure (NFP) develops as NFP = Pc−Pif−π P + πif. The pressure distribution is shown in **Table 1**.

According to the Starling equation, there is 0.3 mmHg net outward pressure for 2 ml/min outward flow. The difference is removed from the interstitial area by the lymphatic system. Filtration occurs in the arteriole sections of the capillaries. Fluid reabsorption is clear at the venule tips [3].

Lymphatic capillaries include endothelial flaps, and these flaps prevent reverse leakage of fluid. Fluid flow is ensured by skeletal muscle contractions with flow rates in the interval 4–150 ml/hr. Interstitial fluid pressure and lymph fluid rate determine lymphatic flow.
