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54 Cards in this Set
- Front
- Back
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Differential diagnosis for nodules (lumps and bumps) |
NAG!
Neoplasia Abscess Granuloma |
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What are two subdivisions of cells of inflammatory exudate? |
Plymorphonuclear Luekocytes (i.e. granulocytes) - Neutrophils - Eosinophils - Basophils and Mast cells
Mononuclear Cells - lymphocytes and plasma cells - monocytes and macrophages - platelets |
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Which leukocytes do not normally inhabit circulating blood? |
Plasma cells and mast cells |
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Where do neutrophils develop? |
The bone marrow - maturation process takes about two weeks |
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Role of neutrophils: |
To eliminate: - microorganisms (mainly bacteria) - tumor cells - foreign material |
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Neutrophils are characterized by: |
- high motility due to rapid amoeboid movement - response to a wide variety of chemotaxic compounds - phagocytic and bactericidal |
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Neutrophil morphology: |
- Multilobed nucleus - Contain abundant cytoplasmic granules (two major classes)
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What are the two major classes of granules seen in neutrophils? |
1. Azurophil granules (primary granules) - large, oval and electron dense
2. Specific granules (secondary granules) - smaller, less dense, more numerous |
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What are neutrophils in rabbits, guinea pigs, rats, reptiles, fish and birds called? |
Heterophils - they have eosinophilic granules |
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Neutrophil functions: |
phagocytosis and secretion of pro-inflammatory substances
The purpose of phagocytosis is to ingest, neutralize and destroy the ingested particle (if possible)
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How do neutrophils kill microorganisms? |
- Produce oxygen free radicals - Hydrogen peroxide - Lysosomal enzymes |
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How do neutrophils regulate inflammatory response? |
By releasing chemical mediators such as leukotrienes and platelet activating factor (PAF)
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Eosinophils are abundant at sites of inflammation due to: |
Hypersensitivity (allergic reactions)
Parasitics (helminth worms)
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Eosinophil morphology: |
- Slightly larger than neutrophils - Cytoplasmic granules are pink (eosinophilic) - Lysosomal granules contain similar enzymes as neutrophils, except for lysozyme and phagocytin
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Eosinophil functions: |
- Modulate hypersensitivity reactions - especially immediate type - Defence against helminthic parasites (*main thing to know!) - Phagocytic but less efficient than neutrophils
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What does the major basic protein of eosinophils do? |
Is strongly toxic to parasites as well as other kinds of cells - causes histamine release from mast cells and basophils - neutralize heparin (which is an anti-coagulant)
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What does the eosinophilic cationic protein do? |
- Contributes to parasite killing - Shortens coagulation time - Alters fibrinolysis
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Examples of eosinophilic infiltration: |
- allergies such as contact dermatitis - nematode infections - eosinophils are also prominent in mast cells tumours, particularly in dogs |
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Localization of basophils and mast cells: |
Basophils are rare circulating granulocytes
Mast cells are found in pervascular sites (i.e tissues, near blood vessels)
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Similarities between basophils and mast cells: |
- Both come from bone marrow precursors - contain lots of granules with high content of heparin - cytoplasmic granules also contain histamine and proteases - main cellular sources of histamine and serotonin (especially mast cells) - major cell mediator of Immediate Hypersensitivity Reactions (type 1) |
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Differences between basophils and mast cells: |
Mast cells are: - in small number throughout connective tissue in most organs (skin, respiratory tract, GI tract) - numerous in perivascular sites
Basophils are: - found in small numbers in circulation |
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Basophil morphology: |
- Less than 1% of circulating leukocytes (eosinophils much more significant) - smaller than neutrophils, contain metachromatic (blue) granules)
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When are basophils recruited into tissues? |
Allergic reactions
Parasitic infections - increased number of circulating basophils seen with heartworm infection in dogs |
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Function of basophils: |
- Induce vascular changes at sites of acute inflammation - Release of mediators to aid in expulsion of parasites - Histamine may modulate some delayed reactions through receptors on T cells |
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Lymphocytes and plasma cells (ABC): |
- Antibody production - Both cells are involved in immune reactions - Cellular mediators of immediate and delayed hypersensitivity responses |
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Lymphocyte and plasma cell morphology: |
- Vary in size and morphology but typically smaller than neutrophils - Have a densely staining nucleus and not very much cytoplasm - Lymphocytes are subdivided by molecules on their surface in B and T cells and then into more sub-classes |
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Lymphocyte function: |
- Appear later than neutrophils, may be more prominent cell in subacute and chronic inflammation
B lymphocytes: differentiate into plasma cells that produce antibody (humoral immunity)
T lymphocytes: responsible for cell mediated immunity. Produce lymphokines (a type of cytokine) which modulate and expand local inflammatory reactions |
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Macrophages/Monocytes: |
- Macrophages are made from circulating blood monocytes (bone marrow origin) - small portion may originate from immature resident mononuclear phagocytes in tissue (also bone marrow origin) - unlike neutrophils they do not have large reserve pool in bone marrow - remain longer in circulation than neutrophils (24-72 hours)
- monocytes require activation under influence of various mediators before becoming active macrophages |
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What are the names for macrophages in different areas of the body? |
Liver: Kupffer cells Spleen and lymph nodes: Sinus Histiocytes Lungs: Alveolar and capillary macrophages CNS: Gitter cells |
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Life span of macrophages: |
Monocytes stay in circulation for 24-72 hours
Once they migrate to tissue they are called macrophages: - can live 30-60 days - may proliferate at sites of inflammation (they maintain mitotic capability in tissues) - sluggishly motile and are responsive to chemotactic influences |
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Activated macrophages are involved in: |
Inflammation and Tissue injury: - reactive oxygen and nitrogen species - proteases - cytokines, including chemokines - coagulation factors - AA metabolites
Repair: - growth factors - fibrogenic cytokines - angiogenic factors - "remodeling" collagenesis |
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4 functions of macrophages: |
Phagocytosis: major scavengers in inflammatory response
Modulation: of inflammatory and repair processes
Regulation: of immune response (especially in some delayed-type hypersensitivity responses)
Production: of interluekin-1 (major inflammatory mediator that increases vascular permeability, chemotactic, induces fever, nausea etc) |
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Macrophage morphology: |
- Larger than neutrophils - Prominent, central nuclei that may be folded or bean-like - Azurophilic granules and ingested material |
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What are epithelioid macrophages? |
Large, pale staining activated macrophages that have an ovoid nucleus and resemble epithelial cells
- found in granulomas - become the multi-nucleated giant cells of granulomas |
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Function of platelets as inflammatory cells: |
- Enhance coagulation (primary role!) and fibrin deposition - Primary haemostasis - Release mediators that increase vascular permeability
*lysosomal-like granules *respond to vascular injury/accumulate in vessels adjacent to inflamed areas *interact with immune-complexes and microorganisms *initiate intravascular inflammation *enzymes can further damage endothelium *adhesion to subendothelium (collagen) *promote local microvascular thrombosis |
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What are the 4 out comes of acute inflammation? |
1. Complete resolution 2. Healing by scarring - after substantial tissue destruction or when inflammation occurs in tissues that do not regenerate, or when there is abundant fibrin exudation 3. Abscess formation: particularly in infections with pyogenic organisms 4. Progression to chronic inflammation |
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Complete resolution of acute inflammation: |
Involves: - neutralization of the chemical mediators - return of normal vascular permeability - cessation of leukocytic infiltration - removal of edema fluid, leukocytes, foreign agents and necrotic debris |
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Healing by formation of scar tissue: |
- see a "plug" of tissue made of fibroblasts and collagen - also contains blood vessels - epithelium has grown back over the surface
i.e. repair has taken place |
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Abscess formation: |
Capsule of fibrous tissue - can have something like caseous necrosis or liquid pus inside, depending on level of dehydration - the longer the abscess is there the more consolidated it becomes |
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What is chronic inflammation? |
Type of inflammation resulting from persistent injurious stimuli (weeks or months) - leads to predominantly proliferative (leukocytes and fibroblasts), rather than exudative (pus/neutrophils), reaction
*Fibrosis is hallmark of chronic inflammation in most tissues |
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Chronic inflammation originating as low-grade smouldering response includes: |
- Persistent infection by intracellular microorganisms (low toxicity but evoke an immunologic reaction i.e. delayed hypersensitivity) - Prolonged exposure to non-degradable but potentially toxic substances (e.g. asbestosis in lungs) - Aberrant immune reactions, especially those perpetuated against host tissues (autoimmune disease) |
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Hallmarks of chronic inflammation vs acute inflammation: |
Acute inflammation: - vascular changes, edema, leukocytic infiltration
Chronic inflammation: - Infiltration by mononuclear cells (macrophages, lymphocytes, plasma cells) - Proliferation of fibrobalsts and often small blood vessels - Increased connective tissue (fibrosis) - Tissue destruction |
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What other features besides phagocytosis do macrophages possess that make them important in chronic inflammation? |
Potential to be activated that results in: - increase in cell size - increased levels of lysosomal enzymes - increased metabolism - greater ability to phagocytose and kill ingested microbes |
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What are some activation signal of macrophages? |
Complex multistep sequential process
Activation signals include: - Lymphokines secreted by sensitized T lymphocytes - Bacterial endotoxins - Contact with fibronectin-coated surfaces - Variety of chemicals generated during acute inflammation
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What is granulomatous inflammation? What are the two types? |
Accumulation of activated macrophages (epithelioid cells) in a distinctive pattern of chronic inflammation - initiated by variety of infectious and non-infectious agents
1. Diffuse infiltration (as seen in Johne's disease) 2. Nodular type (as in tuberculosis) |
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Inciting stimuli/Etiology of granulomatous inflammation: |
Stimuli resistant to phagocytic killing and degradation
Etiology include: - inert particles (silica, asbestos) - lipids resistant to metabolism (mineral oil) - bacteria resistant to lysosomal degradation (mycobacterium sp.) - systemic fungal agents (Histoplasma sp., Blastomyces sp., Coccidioides sp.) - Foreign bodies (wood splinters, suture material, hair shafts) |
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Cells involved in granulomatous inflammation: |
- Epithelioid cells (macrophages) - Multinucleated giant cells (macrophages) - Lymphocytes |
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Features of epithelioid cells: |
Specialized macrophages
- lightly eosinophilic - lots of cytoplasm rich with ER, golgi apparatus, vesicles and vacuoles - eccentrically located round to oval nucleus - specialized for extracellular secretion - less phagocytic activity than non-specialized macrophages |
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What are multinucleated giant cells? What are the two types? |
Formed by coalescence and fusion of epithelioid cells which is induced by cytokines - may have over 50 nuclei
1. Langhan's-type Giant cells: - nuclei arranged around the periphery in a horseshoe pattern - often seen in TB granulomas
2. Foreign-body type Giant cells: - nuclei aggregated in the centre
Multinucleated cell function is similar to epithelioid cell |
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What are the roles of T-lymphocytes? |
Often present in granulomatous inflammatory reactions:
- produce lymphokines and interferon - attract and activate macrophages - induce formation of multinucleated giant cells |
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What are the histologic features of chronic inflammation? |
Dense accumulation of macrophages, epithelioid cells, giant cells and lymphocytes
Neutrophils and plasma cells are often present: - Pyrogranulomatous inflammation: lots of neutrophils present in the centre of a granulomatous reaction - Eosinophilic granuloma: lots of eosinophils present - associated with parasite migration through tisues |
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2 types of granulmoas: |
Simple granuloma: organized accumulation of macrophages and epithelioid cells, rimmed by lymphocytes, then fibroblasts
Complex granuloma: central area of necrosis - necrosis may lead to calcification/mineralization - necrosis may be due to: - release of oxygen free radicals - release of lysosomal enzymes - ischemia
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What does sequelae mean? |
A sequela is a pathological condition resulting from a disease, injury, therapy, or other trauma - a secondary, chronic condition |
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Sequelae of chronic inflammation/granulomatous inflammation? (2) |
Destruction of stimuli -> resolution of inflammation -> repair of tissue
Persistence of stimuli -> progression of inflammatory reaction -> fibrosis |
