Inflammation: an engine in the Journey of UCTD

So what is happening in my body on this Journey of UCTD? As I have said in the earlier blogs and in the ones about allergies, the body has the ability to recognise something as foreign and attempts to get rid of it. The allergen gets attacked by the white blood cells and produces an inflammatory response. This process is called inflammation.  Thus the inflammatory response takes place when there is injury to the cells from micro-organisms, any physical or chemical agents as well as those perceived as foreign in the body.

Physiology of inflammation

Inflammatory response is the body’s natural defence mechanism. It protects by neutralising and destroying any toxic substances. It helps to limit the spread of these toxins to other parts of the body and restore homeostasis. There are 4 main characteristics of inflammation – redness, swelling, heat and pain. If inflammation occurs over a part that is involved in mobility then it also will cause restriction or loss of mobility of that part.  

When injury occurs, and in case of UCTD the injury is caused by the damage to connective tissue which is not recognised as self, a number of changes take place to form the inflammatory response. The site will release substances like histamine and bradykinin. Histamine is released from any injured cells that contains it as well as by in response to the chemicals produced by neutrophils (a type of white blood cell). Bradykinin is help to attract neutrophils to the site of injury. There is also an increase in the production of chemicals called prostaglandins. These prostaglandins are potent vasodilators and they enhance the effect of histamine and bradykinin.

These chemicals increase dilation of the blood vessels causing more blood to flow into the area. This gives redness to the area. It also increases the permeability of the blood capillaries allowing fluid and defensive substances to ooze out into the extra cellular space of the surrounding tissues. This causes the swelling seen in the inflammatory response. The defensive products are white blood cells and clot forming chemicals. The white blood cells will destroy any micro-organisms, damaged tissue and foreign substances. The increased blood supply also helps to remove the toxins and dead cells from the site. A clot forms around the site to prevent the micro-organisms and its toxins from spreading.

Another response by the body is to increase metabolism and heart rate so that blood can reach the injured site quickly. The warmth at the site of inflammation is due to the warm blood gathering in the area as well as increased metabolism. The other symptom, pain, occurs due to the irritation of nerve endings by the toxic chemicals and due to pressure caused by the swelling. Prostaglandin also intensifies and prolongs the pain caused during inflammation. The bradykinin also causes the intense pain by affecting the nerve endings. I will discuss pain in more detail in another blog.

Lastly the loss of function or mobility can take place if this inflammation is over or near a joint, its tendons and ligaments.

What does this mean in UCTD?

Once we understand what normally happens in the body as a defence then we can understand what happens in UCTD. Within this autoimmune disease which has not differentiated into any specific kind, the entire body’s connective tissue is open to having an antigen – antibody response. This means there can be injury due to this antigen-antibody response and inflammation will result. So from the realms of general body defence we move to understand the specific body defence.

What is Immune response?

When the resistance is specific to a disease or organism then it is called immunity. When a particular antigen (organism or protein) enters the body and it is recognised as foreign, the body will produce an antibody specific to that antigen. Mostly antigens are proteins of some kind, nucleoproteins, lipoproteins, glycoproteins and some large polysaccharides. With regards to bacteria the flagella, the wall and even the toxins can be the antigen, but non microbial kind varies widely, from pollen, egg white, nuts, oils, perfumes, incompatible blood cells to transplanted organs.

Antibodies are formed against specific sites on the surface of the antigen. Generally antigens are substances that are not usually part of the body. The body has the capacity to recognise itself and so only substances that are ‘non self’ will stimulate antibody production. Need I point out that this is where things go haywire in UCTD? The body cannot differentiate between self and non self, and thinks the connective tissue is an antigen!

The antibody produced is also a protein that is able to combine with a specific antigen. The collective name for antibodies is immunoglobulins as the antibodies are made of proteins called globulins. There are 5 types of immunoglobulins – IgG (increases phagocytosis, neutralizes toxins and protects foetus and new born), IgA (provides protection on the mucosal surface), IgM (effective against microorganisms), IgD (stimulated the antibody production) and IgE (participate in an allergic reaction). These also can be not recognised by the body and can produce antibodies of its own.

When the antibody attaches itself to the antigen, it forms the antigen-antibody complex that the body will destroy and remove. When the antigen happens to be ‘self’ then it will produce an inflammatory response to this perceived injury to its tissue. 

So where is this connective tissue in the body?

Connective tissue is formed by cells and large amount of intercellular matrix and extracellular elements. It forms the framework, connecting, supporting and packing tissue in the body. There are 6 types of connective tissues:

Tissue with cells floating in a fluid matrix – Blood.

Tissue with cells in a semi-solid matrix – mesenchyme, found in embryo and subsequently gives rise to all other connective tissue. 

Tissue with cells in semi-solid matrix with a fine network of reticular fibres in the extracellular space. The tissue forms a 3 dimensional framework for organs such as spleen, bones and lymph nodes. The cells within are capable of ingesting particles, that is they are phagocytes.

Tissue with cells in semi-solid matrix with thicker collagenous and elastic fibres. These are 5 types –

·        Loose Fibrous tissue which form the packing between organs, sheaths of muscles, nerves and blood vessels.

·        Dense Fibrous tissue which is strong and inelastic but pliable and is found in ligaments, capsules of joints and heart valves.

·        Elastic tissue is strong, flexible and extensible and found in blood vessels and air passages.

·        Adipose tissue contains fat and forms a protective cushion around the organs as well as function as an insulating layer in the skin.

·        Tendon is tough and formed by inelastic cords of dense fibrous tissue that allows muscles to be attached to bones.

Tissue with cells in solid elastic matrix with fibres – cartilage which is also of 3 different kinds-

·        Hyaline cartilage which is firm yet resilient and us seen in air passages and ends of bones at joints.

·        White fibro-cartilage is tough but resistant to stretching and found between vertebrae where it acts as shock absorber.

·        Elastic or Yellow fibro-cartilage is more flexible but resilient and found in larynx and the ear.
 
T   Tissue with cells in a solid rigid matrix which is impregnated with calcium and magnesium salts – bone, which forms the rigid framework of the body.

Making sense of UCTD

Now you can connect all three sections – connective tissue, immune response and the process of inflammation and it will give you a fair understanding of what is happening to the body in an autoimmune disease. When specific connective tissue involvement is there, it gives a particular pattern of symptoms and changes to blood constituents and so categorised to a particular autoimmune disease. However, luckily or unluckily, within Undifferentiated Connective Tissue Disease there is no specific pattern or blood changes and so does not allow a specific diagnosis. It is almost as if the body has not decided on which parts are not self. The symptoms fluctuate randomly between various symptoms and so we say that the disease has not differentiated itself. 

One must not assume that the title reflects the inability of the medical profession to make a diagnosis. It is actually a disease in its own right and pretty difficult to pin down as there is no pattern of either the symptoms or of blood and body changes. However, the inflammatory response is seem pretty strongly and can comprise of the whole body. You can look back at the symptoms I have described in the previous blogs to make sense of the pathophysiology of this disease. The medical profession do take a long time to make a diagnosis not only because the investigation results fluctuate but also it takes time for the disease to develop and most would rather wait and see than label the disease immediately. About a quarter of the patients are likely to achieve remission and be disease free. About a quarter will develop and differentiate into one or 2 specific diseases over 5 years. The rest will remain in the undifferentiated category.