Complement System, Granuloma & Exudate vs. Transudate

Complement is a system of circulating proteins which augment (or “compliment”) the action of phagocytes and antibodies during the immune response. It is important in acute and chronic inflammation. The complement system involves a complicated activation cascade, but you really don’t need to memorize it all for Step 1. The classic picture of this system involves C1 being activated first and subsequently moving through the cascade to C9, but there are other mechanisms by which the cascade can be triggered. Here is what you need to know.

  • C1 binds to antibodies (which are already bound to the pathogen) activating the complement cascade
  • C3b opsonizes (“tags”) pathogens to help phagocytes “find” them
  • C5a attracts neutrophils (AKA chemotactic factor)
  • Membrane Attack Complex (MAC), a combination of activated C5 through C9, forms a hole in the membrane of bacteria causing lysis.

Complement System Immune Sysem

There are two main types of extracellular fluid buildup (edema). Being able to distinguish between the two may help you figure out what is causing the fluid to buildup in the tissue. For example, when you are trying to figure out what is causing a pleural effusion the fluid make up helps you determine to the cause. Both transudate and exudate are made up of fluid that travels from within vessels into the tissue. However, they differ based on their cause and make up.

 

Transudates are caused by disturbances of hydrostatic forces like increased blood pressure or decreased oncotic pressure (Caused by having less protein in the blood). Exudates are caused by inflammation where post capillary venules open resulting in leukocytes, plasma proteins, and fluid to travel into the tissue. These cells and proteins give exudate a cloudy color and higher density.

Difference between trasudate and exudate

Think that TRANSudate is caused by differences in pressure on OPPOSITE sides of vessel wall and that EXudate has EXTRA stuff (cells, protein) in it.

 

Specific gravity is the ratio of the density of the fluid being tested to the density of water. So it makes sense that transudate, which is almost pure water, would have a density within about 1% of water. The extra cells and proteins present in exudates mean it has a higher density than water (at least 2% higher).

Specific gravity = density of fluid being tested / density of water

 

After acute inflammation has finished removing the noxious stimuli, the macrophages trigger the healing phase by releasing cytokine signals. For tissues, like skin or liver, that can undergo hyperplasia the damaged tissue can be replaced by fully functional tissue. However, most tissues lack the ability to undergo hyperplasia and will instead be replaced by non-functional scar during the healing process. The process of scar formation proceeds through 2 distinct steps.

  • Granulation Tissue – weak temporary connective tissue scar that begins forming within a couple days of injury. Characterized by angiogenesis (vessel formation), fibroblasts depositing Type III collagen and myofibroblasts (fibroblasts with smooth muscle properties) contracting the wound. Usually red and moist appearance due to the high amount of blood at the site.
  • Scar – strong permanent fibrotic healing that begins about a week after injury. Fibroblasts replace randomly weaved type III collagen with the stronger more organized and cross-linked Type I collagenHypertrophic Scars is when too much collagen is deposited in a scar. As a result, the scar can be raised above the level of the rest of the organ and may be a different color. Sometimes this is caused by an infection during healing or by the lack of stitches. A Keloid is an extreme version of a hypertrophic scar where the collagen mass can spread outside of the site of injury. Keloids can become cancerous and can be result from even small injuries (like getting your ear pierced). The cause of keloids is not well understood.

Keloid Hypertrophic Scar

Gliosis (AKA Astrocytosis) is the way healing takes place in the CNS following injuries like a stroke. It involves proliferation of glial cells (mainly astrocytes) to form a non-functional scar at the site of injury. In this case, astrocytes will fill the injured area with intermediate filaments and extracellular matrix that is not functional brain tissue.

 

When the body recognizes a material as foreign, but can’t eliminate it a circular “wall” of collagen and inflammatory cells is created around the material. This wall prevents the material from spreading and causing damage. Patients that have the ability to create these walled off areas can remain asymptomatic even though they are infected with foreign material because this noxious material is “quarantined”. This walled off area is called a Granuloma.  The key characteristic of granulomas is the presence of epitheliod histiocytes (activated macrophages that look sort of epithelial cells) and multinucleated giant/langerhan cells (multiple macrophages fused together). Both of these cells types are created when macrophages are exposed to interferon gamma (released by CD4 T-cells). Granulomas are present in Tuberculosis, many fungal infections, Sarcoidosis, Crohn’s Disease, Wegener’s Granulomatosis, Chronic Granulomatous Disease and many other diseases.

Granuloma pathology

 

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