Acute Inflammation Pathogenesis


Acute Inflammation Pathogenesis

What is the pathogenesis of acute inflammation?

Issues of Concern – Acute or Chronic Inflammation Acute inflammation has a rapid onset of minutes or hours, usually resolves in a few days, has classic signs and symptoms, and has cellular infiltrate primarily composed of neutrophils. The erythema seen in acute inflammation results from increased blood flow to the affected area due to vasodilation.

Cryotherapy is often an effective treatment for the acute inflammation caused by musculoskeletal injury with decreased pain and more rapid “return-to-participation.” Chronic inflammation has a slow onset of days, a long duration of years, less prominent classical signs and symptoms, and cellular infiltrate primarily composed of monocytes/macrophages and lymphocytes.

Chronic exposure to toxic chemicals and environmental agents such as cigarette smoke can cause chronic inflammation. Mediators and Biomarkers of Inflammation The discovery of cellular and molecular inflammatory mediators and the development of sensitive biomarkers have rapidly advanced our understanding of inflammation and its role in pathology.

Reactive oxygen and reactive nitrogen oxide species (ROS and RNOS) Formation of DNA adducts Cytokines (e.g., IL-6 and TNF-alpha) and chemokines Acute-phase proteins (e.g., C-reactive protein or CRP) Prostaglandins Cyclooxygenase (COX)-related metabolites Inflammation-related growth factors and transcription factors (e.g., NF-kappaB) Major immune cell types

The specific immune cells and mediators at play are variable and dependent upon the injury, the onset/duration of the injury, and multiple genetic loci. CRP is a widely used clinical inflammatory biomarker present in two forms with distinct functions.

  1. One form is a homopentamer termed native-CRP (nCRP), and the other is a monomer (mCRP).
  2. There are two clinical assays for CRP, a standard assay and a high-sensitivity assay (hs-CRP).
  3. Inflammation and Cardiovascular Disease Hs-CRP is often used to assess increased cardiovascular disease (CVD) risk.
  4. Increased plasma hs-CRP levels are a CVD risk factor in addition to LDL-cholesterol and the degree of metabolic syndrome.

Some suggested that increased inflammation from any cause (e.g., periodontal disease and arthritis) has a damaging effect on vascular endothelium. Central obesity, a risk factor for type 2-diabetes and CVD, is also associated with increased hs-CRP in metabolic syndrome.

  • It is not yet certain whether CRP plays an active pro-atherogenic role in CVD or that lowering hs-CRP is a valid goal for the primary prevention of CVD.
  • In contrast, the 2018 CANTOS trial on tertiary prevention in patients with a history of myocardial infarction showed that reducing hs-CRP levels by use of canakinumab was effective in reducing (by 25%) a major CVD event but primarily in those patients where treatment lowered hs-CRP to less than 2 mg/ml.
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Canakinumab is a monoclonal antibody that targets interleukin-1-beta and has no effect on plasma lipoprotein levels. It should be noted that most participants in the CANTOS trial were already on statin therapy. Statins, besides lowering LDL-C, also lower hs-CRP.

Nevertheless, a large-scale study found the effectiveness of simvastatin to lower a first major vascular event was unaffected by baseline CRP levels. Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic, antipyretic, antiplatelet as well as anti-inflammatory effects. They are among the world’s most used/prescribed medications.

The effects of NSAIDs on CRP levels are mixed and dependent upon the particular NSAID. In patients taking NSAIDs for rheumatoid arthritis, naproxen was associated with a decreased CRP; whereas, lumiracoxib was associated with an increased CRP. Lumiracoxib is a selective inhibitor of cyclooxygenase-2 (COX-2), the inducible form of COX, while naproxen is a nonselective COX inhibitor, inhibiting COX-2 as well as COX-1, the constitutively expressed form of COX.

The COX-2 selective inhibitors are collectively called coxibs. The more selective an NSAID is for COX-2, the greater its effect on increasing CRP. Due to the increased risk of severe CVD events, celecoxib is the only coxib available in the US market. The CVD risks posed by NSAIDs is an area of active research and are an under-recognized issue.

Inflammation, Aging, and Cancer Inflammation is closely associated with an increased production of ROS and RNOS, which can damage DNA. Chronic inflammation is, therefore, an ongoing process that can increase mutations and increase cancer risk. Increased cellular or tumor micro-environmental ROS production is associated with diminished control of cell growth.

  • For example, activated macrophages are a major source of ROS, and these inflammatory cells are located in the tumor microenvironment of breast cancer tumors, where they promote growth and metastasis.
  • Chronic inflammation is associated with many types of cancer and all stages of cancer.
  • Obesity, which increases chronic inflammation, is now recognized as a major (and preventable) increased cancer risk factor.

Increasing evidence supports a strong positive association between CRP levels and cancer. For example, elevated CRP (at the time of diagnosis) is associated with breast cancer, breast cancer subtypes, and poor outcome. The risk of epithelial cancers such as liver, lung, colorectal, endometrial, breast, and ovarian cancer are all positively associated with elevated CRP levels.

CRP levels have proven to be a valuable prognostic biomarker in a wide variety of adult tumors. Elevated CRP is linked with a shorter survival time for most solid tumors. Aging is a major risk factor for cancer, and systemic, sterile (non-infection-caused), age-related chronic inflammation (termed inflamm-aging or inflammaging) is thought to be an underlying etiological connection.

CRP and other inflammatory biomarkers increase with age. Gut microbiota is thought to become more pro-inflammatory with aging and contribute to systemic chronic inflammation. Diet, Exercise, and Inflammation Levels Over the last decade, a fairly consistent view has emerged in the relationship between lifestyle and inflammation.

Individuals with high CRP levels of greater than 3.0 mg/L tend to be physically inactive, have higher plasma glucose levels, less likely to follow the Mediterranean diet, have a higher incidence of hypertension, have a lower HDL-cholesterol (anti-atherogenic), and increased abdominal obesity. Adopting a Mediterranean diet combined with a medium level of physical activity markedly reduces the incidence of high CRP by 72%.

The dietary inflammatory index (DII) is a flexible tool for accessing the relationship between diet and inflammation (smartphone apps are available).

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What are the stages of pathogenesis of inflammation?

What are the Stages of Inflammation? – G4 Physiotherapy & Fitness

  • Inflammation is a result of damage to body tissues and can be caused by a number of factors including trauma, repetitive use and those conditions affected by age such as Osteoarthritis.
  • The are three main stages of inflammation which can each vary in intensity and duration:
  1. Acute -swelling stage
  2. Sub-acute – regenerative stage
  3. Chronic – scar tissue maturation and remodelling stage

During the acute inflammatory stage, there is evident redness (erythema) and swelling due to vascular changes. Exudation of cells and chemicals cause swelling and pain. A haematoma may form if there is bleeding within the tissues. Secondarily, chemical irritants are neutralized and the area is sealed off from surrounding tissues and circulation is impaired.

There is early fibroblastic cell activity. Pain is normally present at rest over a diffuse area and can be aggravated by activity. Secondary muscle spasm and guarding normally restrict passive movement. During range of movement testing, pain is felt before the tissue resistance is reached. Injuries to deep structures or poorly vascularised areas can lead to surface swelling and oedema but may not be noticeable.

The sub-acute stage is the commencement of healing and repair. Noxious chemicals are further neutralized and new capillary beds growing into the damaged areas are supported by connective tissue growth (collagen fibres) and together form granulation buds.

Visible signs of inflammation start to subside and range of movement increases with pain felt at the point of tissue resistance. The chronic inflammatory stage is the period when tissue remodelling takes place. Signs of inflammation are absent and scar tissue is maturing. Pain is felt further into the range of movement after the tissue resistance has been reached.

Maturation refers to the growth of the fibroblasts to fibrocytes and remodelling refers to the organization of and shrinking of collagen fibres along the lines of stress. The skill of the physiotherapist is to identify the exact stage of the inflammation and then intervene to enhance the healing process with the most appropriate form of treatment.

What are the 5 stages of pathogenesis?

The stages of pathogenesis include exposure, adhesion, invasion, infection, and transmission.

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What are the 4 steps of pathogenesis?

Pathogenesis – Pathogenesis is the process by which an infection leads to disease. Pathogenic mechanisms of viral disease include (1) implantation of virus at the portal of entry, (2) local replication, (3) spread to target organs (disease sites), and (4) spread to sites of shedding of virus into the environment.

What are the stages of pathogenesis?

Stages of Pathogenesis – To cause disease, a pathogen must successfully achieve four stages of pathogenesis to become an infection: exposure, adhesion (also called colonization), invasion, and infection. The pathogen must be able to gain entry to the host, travel to the location where it can establish an infection, evade or overcome the host’s immune response, and cause damage (i.e., disease) to the host.

What is acute vs chronic inflammation pathophysiology?

During acute inflammation, innate immune cells form the first line of immune defense and regulate activation of adaptive immune responses. By contrast, during chronic inflammation, these roles can be reversed — adaptive immune responses can cause ongoing and excessive activation of innate immune cells.

What is the pathogenesis of chronic inflammation?

Etiology – Chronic inflammation can result from the following:

  1. Failure of eliminating the agent causing an acute inflammation such as infectious organisms including Mycobacterium tuberculosis, protozoa, fungi, and other parasites that can resist host defenses and remain in the tissue for an extended period.
  2. Exposure to a low level of a particular irritant or foreign material that cannot be eliminated by enzymatic breakdown or phagocytosis in the body including substances or industrial chemicals that can be inhaled over a long period, for example, silica dust.
  3. An autoimmune disorder in which the immune system recognizes the normal component of the body as a foreign antigen, and attacks healthy tissue giving rise to diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE).
  4. A defect in the cells responsible for mediating inflammation leading to persistent or recurrent inflammation, such as auto-inflammatory disorders (Familial Mediterranean Fever).
  5. Recurrent episodes of acute inflammation. However, in some cases, chronic inflammation is an independent response and not a sequel to acute inflammation for example diseases such as tuberculosis and rheumatoid arthritis.
  6. Inflammatory and biochemical inducers are causing oxidative stress and mitochondrial dysfunction such as increased production of free radical molecules, advanced glycation end products (AGEs), uric acid (urate) crystals, oxidized lipoproteins, homocysteine, and others.

What are the three major components of acute inflammation?

Functions and Components of Inflammatory Response – The main function of inflammation is to trigger an immune response in an area of the body that needs it to fight off pathogens that may cause an infection or to help heal an injury. The main symptoms of acute inflammation are swelling, redness, pain, loss of function, and heat.