DIAPÉDESIS: PROCESS, BLEEDING - ANATOMY AND PHYSIOLOGY - 2024

The diapedesis or transmigration is the process output the formed elements of the blood, mainly the white blood cells, through the intact blood vessel walls, by small windows called fenestrations.

The movement of leukocytes (white blood cells) and erythrocytes (red blood cells) from the veins or arteries to different tissues and organs depends on this phenomenon.

The ability of these cells to migrate is of great importance. Diapédesis is necessary for the entry of immature lymphocytes into the thymus for its correct development.

It then plays a vital role in its transfer to the lymph nodes to activate and act on sites of inflammation or infection that have already become mature effector lymphocytes.

Diapédesis process

As long as there is no tissue damage, the white blood cells are circulating through the blood vessels in a state of rest but alert to any event. Everything changes the moment an injury occurs.

Immediately, local macrophages are activated, releasing a series of substances that adhere to the inner wall of the vessels - the endothelium - and this attracts lymphocytes to the affected or infected site. Once there, diapédesis or leukocyte extravasation occurs.

The leukocytes or white blood cells pass through the vessel wall through special windows or pores and thus reach the area where they must exert their protective and attack functions against the elements that cause damage or local infection.

Diapédesis consists of four well-studied and recognized stages:

- Bearing

- Signaling

- Firm adhesion

- Diapédesis

All these steps are regulated by a series of interactions between the endothelium and the cells that participate in the inflammatory response such as lymphocytes, macrophages, and even platelets and red blood cells.

Bearing

This first stage begins with the contact of the lymphocyte to the vascular endothelium (the endothelium is the innermost layer that covers the blood vessel).

This process is mediated by different substances called selectins, which are found in the aforementioned endothelium and interact with its receptors on the surface of lymphocytes.

Signaling

When selectins interact with their respective receptor, a signal is sent into the cell and other adhesion molecules are immediately activated, paving the way for the lymphocyte to "stick" to the endothelium.

Firm adhesion

As adhesion molecules are activated, the lymphocyte narrows with the endothelium, exposing more sites for that binding in the vascular wall, allowing the lymphocyte to adhere firmly and prepare for subsequent exit.

Diapédesis

Leukocyte extravasation or transmigration is a strictly regulated process, since lymphocytes must enter specific tissues and activation for this to occur requires precision.

This precision is achieved because the small veins in the affected sites have unique combinations of adhesion molecules and substances on their surface, so that only the specific lymphocytes that recognize this combination are the ones that cross the vascular walls and reach their destination.

Commentary

It is important to note that all white blood cells have this recognition capacity, which is necessary to cross the walls of blood vessels and thus defend our body. As already mentioned, this process takes place in blood capillaries and venules.

There are certain substances that induce or activate the diapédesis process: histamine, interferon, tumor necrosis factor, selectins, and integrins. These substances are present in any inflammatory process.

Diapedesis hemorrhage

Let's start by defining hemorrhage: it is the outflow of blood from the circulatory system, either by the rupture of a blood vessel (vein, artery or capillaries) or by increased permeability of it (inflammation, infection or systemic or local disease).

Vessel injuries can be due to:

- Rexis: is the regular damage or solution of continuity of the vascular wall.

- Dieresis: it is the injury caused intentionally during a surgery without the intention of abuse.

- Diabrosis: it is the erosion of the total thickness of the vascular wall. This lesion presents irregular margins.

The increase in vascular permeability would correspond to the diapédesis itself.

Hemorrhage due to diapédesis is understood as the increase in vascular permeability of the red blood cells without the presence of anatomical damage to the vessel, which causes the erythrocytes to escape and the consequent evidence of bleeding.

This form of hemorrhage occurs basically in small-caliber capillaries, without compromising the small venules or arterioles.

Physiopathologically, what occurs is a non-pathological alteration of the endothelium, which causes an increase in vascular permeability so important that it allows the red blood cells to pass from the interior of the lumen to the tissue, without there being real damage to the vessel.

Causes

The most frequent causes of endothelial stimulation and consequent capillary bleeding are intoxications by certain substances and hypoxia.

A similar phenomenon that tends to be confused is the hemorrhagic process produced in some cases of inflammation such as contamination by heavy metals, certain infections and trauma.

Another cause of alteration of the basement membrane is the deficiency of vitamins C, E and v, the latter being necessary in the production of certain elements that participate in coagulation.

There are also basement membrane disorders in skin hemorrhages, diabetic neuropathy, immune diseases, and cancer.

Manifestations

When diapédesis bleeding is accentuated and perpetuated, it is known as hemorrhagic diathesis and is difficult to manage.

The clinical manifestations are varied, but the most frequent is the presence of petechiae, small pinpoint hemorrhages on the skin that are red or purple in color. There may also be significant bleeding such as layer hemorrhages, bruises, and ecchymoses.

Conclusions

Despite the name, hemorrhagic diapédesis, it is not really a transmigration scenario, since red blood cells do not have their own motility like lymphocytes, which is essential in the diapédesis process itself.

Considering that the permeability of the vascular endothelium allows only the exit of fluid and small molecules, and that this changes in inflamed tissues regardless of the cause, when the increase in capillary permeability and extravasation of erythrocytes is triggered, we are in the presence of bleeding due to diapedesis.

References

1. Filippi, Marie-Dominique (2016). Mechanism of Diapedesis: Importance of the Transcellular Route. Advances in Immunology, volume 129, 25-53.
2. Petri, B. and Bixel MG (2006). Molecular events during leukocyte diapedesis. The FEBS Journal, 273 (19), 4399-4407.
3. Ebnet, K. and Vestweber, D. (1999). Molecular mechanisms that control leukocyte extravasation: the selectins and the chemokines. H istochemistry and Cell Biology Journal, 112 (1), 1-23.
4. Vestweber, D. (2012). Novel insights into leukocyte extravasation. Current Opinion in Hematology, 19 (3), 212-217.
5. Wikipedia (nd). Leukocyte Extravasation. Recovered from en.wikipedia.org.
6. Svensson, Marcus (nd). T Lymphocyte transmigration. British Society for Immunology, bitesized immunology. Recovered from immunology.org.
7. Catholic University of Chile (nd). Hemorrhage. Manual of General Pathology, chapter 3: circulatory disorders. Recovered from publicationsmedicina.uc.cl.