PATH 3810 Acute and Chronic Inflammation

inflammation pros

beneficial host response to foreign invaders and necrotic tissue, helping to eliminate pathogens and initiate healing processes.

inflammation cons

inflammatory reaction and subsequent repair process can cause tissue damage

main components of inflammation are

• vascular reaction

• cellular response

  • activated by mediators derived from plasma proteins and cells

the 5 R’s of inflammation

• Recognition of injurious agent

• Recruitment of leukocytes

• Removal of agent

• Regulation (control) of response

• Resolution (repair)

the outcome of acute inflammation is either…

…elimination of the insult, followed by reduced inflammation and tissue repair, OR persistent cell injury leading to chronic inflammation

i looked at this diagram regarding arterioles, capillaries, and venules and inflammation and i understand

acute inflammation

rapid response to cell injury or invading microbes and other foreign substances that is designed to deliver leukocytes and plasma proteins to the site of injury

i looked at this diagram regarding normal vs abnormal capillary beds and i understand

stimuli for acute inflammation

• infections

• trauma: physical, chemical

• necrosis

• foreign bodies

• hypersensitivity reactions

vasodilation of arterioles results in…

…locally increased blood flow, which causes engorgement of downstream microcirculation, which leads to erythema and warmth of tissue

vasodilation cross-section

vasodilation longitudinal section

neutrophils

• most abundant leukocyte

• segmented nucleus (up to 5 lobes), heterochromatic chromatin, membrane-bound cytoplasmic granules, scarce organelles

• phagocytosis

phagocytosis involves…

…phagosome-lysosome fusion to form phagolysosome, generating H2O2 and superoxide radicals by respiratory burst

neutrophil degranulation

secrete granule contents (myeloperoxidase) into extracellular environment

neutrophils <3

eosinophils

• respond to parasitic infections and allergies

• migration stimulated by chemotactic factors produced by mast cells and basophils

• common in type 1 hypersensitivity reactions due to IgE receptors

• nucleus has 2-3 lobes

eosinophils!

lymphocytes

• smallest leukocyte (so petite)

• second most abundant

• circulate via blood and lymphatics between lymphoid tissues and all other tissues

• round, densely stained nucleus and small amount of agranular cytoplasm

• amount of cytoplasm depends on state of activity

B lymphocytes

produce antibodies, differentiate into plasma cells in tissues

T lymphocytes

secrete cytokines that modulate activities of other lymphocytes

natural killer cells

a type of large lymphocyte

lymphocytes !

monocytes

• largest leukocyte

• precursors of tissue macrophages (highly motile phagocytes)

• large eccentric, indented nucleus with nucleoli

• extensive cytoplasm with frequent pseudopodia on surface

• granules include myeloperoxidase, acid hydrolases, membrane adhesion proteins, TNF-a

• capable of continuous lysosomal activity using aerobic and anaerobic pathways

• antigen-presenting cell (APC)

monocyte

monocyte-macrophage system / mononuclear phagocyte system

consists of circulating monocytes, monocytic bone marrow precursors, and tissue macrophages both free and fixed

• includes Kupffer cells, microglia, Langerhans cells, alveolar macrophages, APCs of lymphoid tissues, and osteoclasts

basophils

• least abundant

• very similar to mast cells, but the exact relationship is unknown

• bilobed nucleus

• large basophilic cytoplasmic granules that are metachromatic when stained by toluidine/methylene blue

• granules are membrane-bound, round, and contain densely packed electron-dense material (contain proteoglycans and histamine)

• unclear function, but involved in allergic reactions

• very mysterious apparently

basophils

vascular changes of inflammation

• increased vascular permeability

• transudate and exudate (edema)

• endothelial cells contraction

transudate

ultrafiltrate of blood plasma which moves from capillaries into tissues

exudate

protein-rich fluid and cells move into interstitium

edema

fluid accumulation in extravascular spaces which may be transudate or exudate

margination of neutrophils along endothelial surface as stasis

stasis

occurs as protein-rich fluid moves into extravascular tissue, erythrocytes become more concentrated, blood viscosity increases, circulation slows

i looked at this poor resolution diagram of transudate vs exudate and i understand

electron micrograph of a capillary

lymphatic vessel

V = valve

lymphatic vessels

lymph flow is increased during inflammation to help drain edema from extravascular space

diapedesis / transmigration

special characteristic of leukocytes that allows then to migrate through vessel walls

they squeeze through intercellular junctions between endothelial cells

leukocytes degrade basement membranes with collagenases

chemotaxis

migrate toward sites of injury in extracellular tissues along a chemical gradient

mediators include bacterial products, cytokines, complement, and leukotrienes

endothelial injury

results in vascular leakage due to endothelial cell necrosis and detachment due to direct injury to endothelial cells or leukocyte-mediated endothelial injury

irreversible

begins immediately after injury and persists for hours or days until repair: immediate sustained response

may induce delayed prolonged leakage

electron micrograph of cell migration from microcirculation

leukocyte emigration

type of emigrating leukocyte varies with age of inflammatory response

neutrophils predominate during the first 6 to 24 hours and are replaces with monocytes in 24-48 hours

early (neutrophilic) infiltrates and congested blood vessels

later (mononuclear) cellular infiltrates

kinetics of edema and cellular infiltration

outcomes of acute inflammation

• resolution

• progression to chronic inflammation

• scarring/fibrosis

• abscesses (which leads to fibrosis)

fibrosis means…

…scarring

morphologic patterns of acute inflammation

• serous inflammation

• fibrinous inflammation

• suppurative/purulent inflammation

• ulcer: a local defect or excavation of the surface of an organ or tissue that is produced by necrosis of cells and sloughing of necrotic inflammatory tissue

serous inflammation

serous inflammation

characterized by outpouring of watery, protein-poor fluid, derived from serum or secretions of mesothelial cells lining peritoneal, pleural, or pericardial cavities

fibrinous pericarditis (gross)

fibrinous pericarditis (microscopic)

F = exudate

P = pericardial surface

bacterial abscess of the lung (gross)

bacterial abscess of the lung (microscopic)

abscess

focal collections of pus caused by seeding of pyogenic organisms into a tissue or by secondary infections of necrotic tissue

duodenal ulcer (gross)

duodenal ulcer (microscopic)

ulcers occur when…

…tissue necrosis and resultant inflammation exist on or near a mucosal surface.

features of the acute phase of ulcers

neutrophils and vascular dilations

features of the chronic phase of ulcers

scarring at lateral margins and along the base

chronic inflammation

inflammation of prolonged duration in which active inflammation, tissue injury, and healing proceed simultaneously

chronic inflammation is characterized by…

…infiltration with mononuclear cells, tissue destruction, and repair with angiogenesis and fibrosis

acute inflammation of the lung

chronic inflammation of the lung

granulomatous inflammation

characterized by patterned aggregation of activated macrophages that assume epithelioid appearance

granulomatous inflammation causes

• persistent T cell responses to certain microbes

  • M. tuberculosis

  • T. pallidum

  • Fungal infection

• foreign bodies

granuloma

keys to granuloma formation

1. chronic macrophage activation by T cell derived cytokines

2. morphologically typical and characteristic arrangement of epithelioid macrophages and multinucleated giant cells

systemic effects of inflammation / acute phase reaction

consist of cytokine-mediated effects on a variety of organ systems and manifests as

• fever

• elevated acute phase proteins in plasma

• leukocytosis

• tachycardia/hypertension

• septic shock

What are the two main components of inflammation?

Vascular reaction and cellular response

Which of the following best describes acute inflammation?

A rapid response to cell injury or invading microbes that delivers leukocytes and plasma proteins to the site of injury

What can occur when an injurious stimulus persists following acute inflammation?

Persistent cell injury leading to chronic inflammation

Choose from the pictures: which leukocyte is the precursors of tissue macrophages? ​

Picture B

Which statement is FALSE regarding the White blood cells?​

Eosinophils are decreased in numbers in parasitic infections and allergies 

Which of the following is increased in order to remove edema from extravascular space?​

lymph flow

Which of the following types of inflammation is characterized by the accumulation of a watery, protein-poor fluid?​

Serous

Which of the following best describes the process shown in the images provided?​ 

Fibrinous inflammation

 Which of the following is NOT observed in a typical granuloma?

central core of lymphocytes

An abscess is a localized form of which type of inflammation​

Suppurative ​

Regarding the image, which of the following best describes the distribution of the pathologic process shown (HINT: look at arrows)? 

Multifocal