Lisa's Acute And Chronic Inflammation Problem! Ouch!

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Inflammation

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The reaction of vascularized tissue to injury involving a complex process that changes blood vessels, connective tissue matrix, and interactions of a variety of cells

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Exudate, Ex?

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Any fluid that filters from the circulatory system into lesions or areas of inflammation. Ex. Pus

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Transudate

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Similar to exudates but are caused by disturbances of hydrostatic or colloid osmotic pressure, not by inflammation.

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Edema

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Swelling of any organ or tissue due to accumulation of excess lymph fluid, without an increase of the number of cells in the affected tissue.

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Pus

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A whitish-yellow or yellow substance (exudate) produced during inflammatory responses of the body that can be found in regions of pyogenic bacterial infections

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Margination

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A process of leukocyte accumulation that occurs during inflammation.

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Diapedesis

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The movement of leukocytes across the endothelial lining of blood vessels to interstitial fluid (IF). The process is driven by chemotactic factors which serve to upregulate adhesion molecules expresses on the leukocytes surface.

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What follows margination?

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Rolling does.

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Granuloma

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A group of epithelioid macrophages surrounded by a lymphocyte cuff

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Cellulitis

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An inflammation of the connective tissue underlying the skin, that can be caused by normal skin flora or by exogenous bacteria, and often occurs where the skin has previously been broken

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Lymphangitis

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An inflammation of the lymphatic channels that occurs as a result of infection at a site distal to the channel.

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Lymphadenitis

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This is the swelling of one or more lymph nodes (also called lymph glands). It is a recognised symptom of many diseases

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Bacteremia

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Blood poisoning from bacteria

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Abscess

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A collection of pus collected in a cavity formed by the tissue on the basis of an infectious process (usually caused by bacteria or parasites) or other foreign materials (e.g. splinters or bullet wounds). It is a defensive reaction of the tissue to prevent the spread of infectious materials to other parts of the body.

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Chemotaxis

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This is a kind of taxis, in which bodily cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment.

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Phagocytosis

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This is a form of endocytosis wherein large particles are enveloped by the cell membrane of a (usually larger) cell and internalized to form a "food vacuole."

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Opsonin

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Any molecule that acts as a binding enhancer for the process of phagocytosis, for example, by coating the negatively-charged molecules on the membrane

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Degranulation

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Understand degranulation -- not finished!

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Cytokine

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A group of proteinaceous signalling compounds that, like hormones and neurotransmitters, are used extensively for inter-cell communication

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Chediak-Higashi Syndrome

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This is a rare childhood autosomal recessive disorder that affects multiple systems of the body, which arises from a mutation in the lysosomal trafficking regulator gene, LYST. It is a disease with impaired bacteriolysis due to failure of phagolysosome formation. As a result of disordered intracellular trafficking there is impaired lysosome degranulation with phagosomes, so phagocytosed bacteria are not destroyed by the lysosome's enzymes.

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Leukocytosis

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This is an elevation of the white blood cell count above the normal range. This is very common in acutely ill patients. It occurs in response to a wide variety of conditions, including viral, bacterial, fungal, or parasitic infection, cancer, and exposure to certain medications or chemicals.

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Leukemoid reaction

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This describes an elevated white blood cell count, or leukocytosis, that is a physiologic response to stress or infection (as opposed to a primary blood malignancy, such as leukemia).

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Leukopenia

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A decrease in the number of circulating white blood cells (leukocytes) in the blood.

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Lymphocytosis

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An increase in the number of lymphocytes in the blood.It is common in acute viral infections, including glandular fever, but it may also be seen with intracellular bacterial infections, such as in tuberculosis

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Lymphopenia

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The condition in which there exists an abnormally low number of lymphocytes in the blood.

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Neutrophilia

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This is a condition where a person has a high number of neutrophil granulocytes in their blood.

Neutrophils are the primary white blood cells that respond to a bacterial infection, so the most common cause of marked neutrophilia is a bacterial infection.

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Neutropenia

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This is a hematological disorder characterized by an abnormally low number of neutrophil granulocytes (a type of white blood cell). Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defence against infections by destroying bacteria in the blood. Hence, patients with neutropenia are more susceptible to bacterial infections and without prompt medical attention, the condition may become life-threatening.

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Eosinophilia

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The state of having high eosinophil granulocytes in the blood

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Effusion

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This is the process where individual molecules flow through a hole without collisions

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Serous inflammation

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inflammation from mild injuries such as sun burn. Inflam liquid is watery with small proteins and few cells

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Fibrous inflammation

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Severe injuries. Inflammatory liquid (exudate) has large proteins such as fibrinogen where can be deposited in body cavities lined by serous membranes.

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What is Purulent/suppurative inflammation?

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injury to tissue caused by bacteria. Exudate is rich is proteins, neutrophils, and macrophages.

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VIP

What are three examples of the ramifications of purulent/suppurative inflammation?

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1. Abscess - liquifactive necrosis - collection of PUS
2. Cellulitis - spreading of inflammation of skin and subcutaneous tissue.
3. Ulcer - crater or excavation of a body surface or organ lining caused by sloughing off of necrotic tissue. Here you will see acute and chronic cells since its an acute exasserbation of a chronic problem.

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Are there macrophages seen in acute inflammation?

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NO!

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Is any tissue destruction or repair attempts being made in chronic inflammatio? How about acute?

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Not in acute but in CHRONIC!

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Example of a disorder where chronic inflammation occurs before any acute happened?

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Systemic Lypus Erythematosus

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What cell type induces tissue destruction and angiogenesis or fibrosis?

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Macrophages

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Four cells that come to site during chronic inflammation?

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1. Macrophages
2. Lymphocytes
3. Plasma cells - in chronic!! NOT A FIRST LINE DEFENSE
4. Eosinophils - for acute and also for parasites which are chronic

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VIP VIP VIP

What is granulomatous inflammation?

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A distinct pattern of chronic inflammation characterized by the presence of granuloma which are aggregations of activated macros that look like epithelial cells and are surrounded by a collar of leukocytes and lymphocytes (some times Giant cells)

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VIP VIP VIP

What are two types of granulomas?

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1. foreign body
2. immune

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VIP VIP

Explain what happens to the vasculature during an acute inflammation?

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1. vasoDILATION
2. increased vascular permeability with leakage of plasma proteins such as albumin
3. water follows proteins
4. causes extravascular swelling (edema)
5. bradykinin and prostaglandins which cause pain.

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What are the three mechanisms of vascular leakage?

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1. immediate and transcient - allergic rxn
2. delayed and prolonged - sunburn
3. immediate and prolonged - severe sunburn

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CORRECT:

Margination

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The loss of intravascular fluid causing increased blood viscosity which slows the blood. Leukocytes then congregate along the endothelium or margin of the vessel lumen.

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What immune cell is the most common one that rolls/adheres/and transmigrates?

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Neutrophil

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How to leukocytes move from a blood vessel to the point of injury?

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Using chemotaxis (unidirectional movement of leukocytes along a gradient to a site of tissue injury) that occurs through chemo attractants released at the site of injury.

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VIP

What does the leukocyte do at the site of injury?

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Mainly phagocytosis!
-Neutrophil recognizes the organism (usually through the organisms opsonin coat - IgG and C3b)
-Neutrophils attaches
-Neutrophils engulf pathogen starting with the extension of pseudopods around the microbe (requires nrg). When the tips of the pseudopods fuse the microbe is enclosed in an intracellular vacule called a phagolysosome
-Degranulation: lysosomal granules are attached to the wall of the phagosome and release their contents into the vacuole.
-As neutrophil degranulates using OXIDASE the pathogen is killed.

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Knowing what you know about neutrophils process of phagocytozing - what would happen if a patient was deficient in immunoglobulins or complement components?

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Frequeny and repeated bacterial infections

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VIP

What four things are formed during the chemical mediation in killing and degradation of phagocytosis?

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1. oxygen metabolites
2. superoxide ion
3. hydrogen peroxide

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VIP VIP VIP

Explain the myeloperoxidase system:

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The hydrogen peroxide (weak microbial) made during phagocytosis combines with Cl in the presence of a myeloperoxidase to form a very powerful antimicrobial agent called HYPOCHLORITE. This H2O2-Halide-Myeloperoxidase systems forms O2 radicals that are the major mechanism used to destroy phagocytosed bacteria.

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What disorder has problems with their myeloperoxidase system?

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Diabetics

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VIP

What would result from a congenital defect in the NADPH-oxidase? Name of acquired disorder that does this?

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Patient would not be able to form H202 (neutrophils used NADPH-oxidase to make H2O2) which will join with myeloperoxidase and Cl to kill microbes efficiently. They will still be killed just not as fast (diabetes)