Acute/Chronic Inflammation

• Acute inflammation is part of innate immunity, and chronic inflammation is part of the adaptive immune response.
• The distinction between acute and chronic inflammation comes from the time course of the inflammation.
• Acute inflammation starts in a few minutes, becomes maximal after several hours, and then lasts for a day or two. If an acute inflammatory response lasts for more than two days, it begins to change, and starts having some of the attributes of a chronic inflammatory reaction.
• Chronic inflammation can last for weeks or months, sometimes even years or decades.
• The inflammatory cells associated with an acute inflammation response are predominantly neutrophil polymorphs, whereas in chronic inflammation, at a histological level, the predominant cells are mononuclear cells, lymphocytes, and macrophages.
• Acute inflammatory responses tend to be stereotypic, irrespective of the initial cause. Once the acute inflammatory response as started, the process is similar, irrespective of the cause.

  In chronic inflammation however, because the process goes on for a longer period of time, many factors can modify the histological appearances, which consequently mean that there are different types of chronic inflammatory responses.
• Inflammation is the reaction of vascularised, living tissue to local injury. In higher animals (organisms with some form of a blood system), it's the reaction of the blood vessels to local injury that lead to accumulation of fluid and cells that characterises inflammation.

  Tissues that aren't vascularised, such as the cornea of the eye, don't become inflamed according to the classical definition. For the cornea to be inflamed, there has to be new blood vessel formation; neoangiogenesis - bringing blood vessels onto the corneal surface.
• The process of inflammation are followed by the processes of repair. Repair is the replacement of injured tissue either by regeneration of the tissue, or by scar tissue.

  What determines whether the damaged tissue is repaired by regeneration or scar tissue is whether or not the damaged cells can divide and be replaced by similar cells of the same type.

  An example of repair via regeneration is a superficial laceration of the epidermis; the basal layer of cells are able to divide and replace the damaged keratinocytes.
• Repair by regeneration is the ideal method, but it can only be done if the cells form one of the stable cell populations, such as blood vessels and big internal organs, or one of the label cell populations, such as cells of the bone marrow or skin.

  Cells in the permanent cell populations of the body, such as cardio myocytes and CNS neurons, cannot be replaced by regeneration, because these cells can't go back into the cell cycle beyond foetal life. In these situations, damaged cardiac or brain tissue gets replaced by fibroblastic scar or a glial scar.
• Glial scars are in the CNS, while fibroblastic scars are outside the CNS proliferate and produce collagen.

  A scar will damage the surrounding the structures in the skin, and within a scar, although there is replacement of the epidermis and the collagen of the underlying dermis, the hair follicles, sebaceous glands, and sweat glands won't be replaced in the scar.
• Inflammatory and repair processes can contribute to disease states. An example of this is rheumatoid arthritis, a persistent autoimmune inflammation. In rheumatoid arthritis, there is a deformity that particularly affects the small joints of the hands in a bilateral and symmetrical distribution. The inflammatory cells in the synovium are responsible for producing the rheumatoid factor, which is one the findings in patients with rheumatoid arthritis.
• Another example where inflammatory or repair responses that contribute to disease states are fibrous adhesions between loops of bowel following abdominal surgery. Many fibrous bowel adhesions don't cause any significant issues, but in some situations, loops of bowel can become twisted around these fibrous adhesions and cause bowel obstruction.
• Many diseases that affect the kidney - the glomerulonephritis family of diseases specifically- are due to immune complexes being deposited within the renal glomeruli.
• Rheumatoid arthritis, bowel obstruction from a fibrous adhesion, and renal inflammation are examples of cases where the inflammatory or repair response contributes to the disease present.
• There are 4 stages to an acute inflammation, known as the 4 cardinal signs of inflammation:

  • redness because of increase blood flow to the area.
  • swelling because of the oedema fluid accumulating as an exudate in the affected tissue, and because of the inflammatory cells accumulating in the area.
  • heat because of the increased blood flow into the inflamed area.
  • pain caused by the oedema fluid stretching the sensory cutaneous nerve endings in the inflamed tissue.
• Acute inflammation is mediated by the innate immune system. It's a relatively rapid onset and short duration. If it persists for more than a few days, then its nature beings to change, and become sub-acute, and then eventually become chronic.

  Irrespective of the cause, whether it's an inflammatory process due to infection, chemical injury, or physical injury, once the inflammatory response has been triggered, it follows a stereotypic course.
• The vascular changes that are present in acute inflammatory response involve a transient vasoconstriction of the arterioles (which are seen perhaps after an acute injury) for a couple of seconds, followed by a prolonged vasodilation of the arterioles and capillaries. This increases the blood flow to the inflamed tissue.
• After blood flow has been increased to the inflamed site, gaps in the endothelium of the capillaries then begin to open, and as they open, fluid flows out to create an inflammatory extravascular fluid in the surrounding tissue. As fluid flows out of the capillaries, there is a slowing of the circulation. In some situations, the flow of the blood becomes so slow that it becomes static. The exudation of fluid carries with it plasma proteins. These protein rich fluids within the extravascular tissue are oedema.
• In some types of acute inflammation, the accumulation of fluid is such a dominant feature, that it's given a specific term: acute serous inflammation. This gets across the idea that the fluid has become the dominant feature of the inflammation. There are relatively few cells present.
• Acute serous inflammation is observed in friction blisters and in burns.
• Acute inflammation may be accompanied by exudates, which are inflammatory extravascular fluids with a high concentration of protein and a lot of cellular debris. Because of the high protein concentration, the specific gravity of the exudate is high (above 1012/1.012)
• In contrast to exudates, the transudates are ultrafiltrates of plasma that contain low amounts of protein and most of those proteins have a low molecular weight, such as albumin. Since protein concentration is low, the specific gravity of transudates is low (below 1012/1.012). An example of a transudate is the fluid that fills the Bowman's capsule outside the glomerulus.
• Pus is a purulent - a thick exudate - that is rich in leukocytes, mostly neutrophils and a lot of parenchymal cell debris.
• Neutrophils are short-lived cells that only live for 2-3 days. As they die, the polymorpholibated appearance of the nucleus may become quite difficult to see, and so in tissue sections, degenerate neutrophils won't show such good polylibation as in peripheral blood smear.
• Normally, blood cells are arranged within the centre of a column of blood, next to the endothelial cell walls. The plasma is relatively low in cells, and all the leukocytes and erythrocytes are present in a column in the middle of the bloodstream.

  The endothelial cells normally don't normally express cell adhesion molecules on their luminal surface. But the leukocytes present in the central column of blood do.
• In normal circumstances, the blood cells normally pass the endothelial cells and don't stick to them. In inflammation, in response to histamine and thrombosis factors, subcellular organelles within the endothelial cells, called Weibel Palade bodies, release cell adhesion molecules, specifically stored p-selectin, which is then expressed on the surface of the endothelial cells.
• This expression of p-selectin and e-selectin on the surface of endothelial cells causes the neutrophils to slow down, because it interacts with carbohydrate receptors on the endothelial cells. They being to roll along the endothelium, and this processes is described as margination.

  Margination is the increased adhesion of inflammatory cells to endothelium and rolling along the endothelium.
• Once the neutrophil is marginated with the endothelium, it will eventually lose momentum, causing it to stop and stick to the endothelial cells.

  There is then a release of chemokines, such as interleukin-8, that attract neutrophils along a concentration gradient in response to stimuli.
• Neutrophils migrate towards the chemokines in the process of chemotaxis (the unidirectional migration of cells towards a chemokine). The main inducers of chemotactic agents for neutrophils can be put into 3 categories:

  • bacterial products, particularly bacterial cell wall products that act as chemokines
  • components of the complement system; in particularly activated c5a acts as a chemotactic agent for neutrophils
  • products of a lipoxygenase pathway of arachidonic acid metabolism, particularly leukotriene B4.
• Interaction between integrin molecules present on the surface of neutrophils, and cell adhesion molecules on the endothelial cells (such as ICAM-1) makes a very firm connection that permits diapedesis (movement across the endothelium), and extravasation (movement of cells into tissues following the chemokine gradient.
• Neutrophiles have to find a gap in the endothelial wall and go through that gap to enter the extravascular space. The driver for extravasation is the chemokine gradient.
• Alongside acute serous inflammation, there are other types of acute inflammation, such as acute suppurative inflammation. This is where the accumulation of neutrophils is the dominant feature (as opposed to the accumulation of fluid), and so much pus accumulates within the tissues that the pus can be seen with the naked eye.

  Suppuration means an outpouring of pus.
• In most situations, to show that a tissue or organ is inflamed, the suffix -itis is added onto the name of the organ or tissue involved. To make it clear that acute inflammation, rather than chronic inflammation, is what's being addressed, 'acute' would be placed in front of the condition name.

  An exception to this naming rule is acute inflammations of the lung, which are referred to as a pneumonia. Pneumonitis does exist, but its inflammation is restricted to the alveolar septi, not involving the air spaces.
• Pneumonias can affect certain parts of the lungs, or can affect the whole lobe of the lung.

  Lobar pneumonia is when a whole lobe of the lung is affect, and usually it's only one lobe that affected, but it can be more than one. The air spaces are filled with neutrophiles, and the capillaries are dilated and filled with erythrocytes, showing increased blood flow to the area.
• Acute fibrinous inflammation is when the coagulation cascade has been triggered, alongside acute inflammation, with the production of fibrin.
• Another form of acute inflammation is when an inflammatory membrane forms over the inflammatory tissue. This is known as an acute membranous inflammation. This can be seen in a disease called pseudomembranous colitis, caused by patients being given antibiotics that alter their gut bacteria, and allow a particular species of bacteria to proliferate and overgrow. This bacteria produces a toxin that destroys part of the mucosa of the colon produce an inflamed pseudo-membrane.
• After an acute inflammation, ideally, the injury will be healed. Sometimes, the accumulation of pus is so extensive, that an abscess forms in the tissues. Once an abscess has formed, it needs to be surgically drained, since antibiotics will rarely penetrate into the centre of an abscess.

  Acute inflammation may be followed by scarring, and other sorts of regeneration if the cell populations cannot be repaired by replication.
• Some sorts of acute inflammation will, with the passage of time, turn into chronic inflammation.

  Chronic inflammation is a relatively long-term. It's associated with the presence of lymphocytes, plasma cells, and macrophages within the tissues. In this case, lymphocytes, plasma cells, and macrophages are collectively referred to as mononuclear cells to distinguish them from the polylibated neutrophiles.
• Because chronic inflammation goes on for a long time, there is enough time for neoangiogenesis, and the proliferation of connective tissue; for fibroblasts to proliferate and synthesis collagen to be laid down and produce fibrous scar tissue.

  Chronic inflammation isn't stereotypic. Many factors can modify the cause and histological appearance of chronic inflammation, so it's possible to recognise different types of chronic inflammation.
• Chronic inflammation may follow acute inflammation, usually when the acute inflammatory response hasn't been able to deal with the injury agent.

  Chronic inflammation can also begin as a low-grade smouldering response that doesn't go through an acute inflammatory stage. This can be seen when there are persistent infections due to organisms that are able to live inside cells. A example of this would be the bacillus that causes TB. It lives inside macrophages.