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Unit 3
inflammation
107
Pathology
Undergraduate 3
12/08/2014

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Term
What is the first line of defense against an injury?
Definition
acute inflammation
Term
What are the two main components of the acute inflammatory process?
Definition
Vascular Changes
-dilation
-increased permeability

Cellular Response
-leukocytes leave microcirculation, accumulate at site of injury
Term
What causes redness & swelling in acute inflammation?
Definition
Redness: vasodilation
Swelling: leaky vessels
Term
What causes active dilation of arterioles, capillaries & venules?
Definition
-release of chemical mediators from damaged & necrotic cells
e.g. vasoactivte amines, kinins etc.
Term
What are mast cells & where are they found in greatest concentrations?
Definition
cells with membrane bound vacuoles which contain histamine

-found concentrated around capillaries
Term
What does histamine do?
Definition
causes capillary dilation
Term
What is hyperemia?
Definition
-arteriolar dilation bringing more blood the the area, which dilation of capillaries to increase flow into the tissue
Term
What causes the increased permeability of capillaries & venules?
Definition
-widening of intercellular junctions of endothelial ccells
-inflammation increasing the permeability of the membrane allowing more fluid & larger proteins to pass through
Term
What is exudation?
Definition
more fluid & larger proteins moving from the vessel into extavascular space due to loss of mmb selective permeability
Term
What causes increased vascular permeability? (5)
Definition
-initial endothelial cell contraction of venules widens the junctions
-direct endothelial injury
-leukocyte-mediated endothelial injury
-increased transcytosis (movement across endothelial cells via vesicles)
-leakage from newly forming blood vessels
Term
True or False

Blood flow slows down as fluid moves into the interstitial space
Definition
True

-it becomes more viscous
Term
What are the differences between transudate & exudate?
Definition
Transudate
-primarily albumin, a few healthy cells, clear & colourless
-low protein content

Exudte
-high protein content
-albumin, globulins, fibrin
-lots of degenerate cells, neutrophils
-turbid, yellow/white, pink
Term
What effect does the loss of permeability have on swelling?
Definition
because more proteins are in the interstitium, osmotic pressure of the plasma will not be able to draw fluid back so swelling is increased
Term
What is peritonitis?
Definition
inflammation of the peritonium (membrane lining the abdominal cavity)
Term
How might you differentiated between ascites & peritonitis?
Definition
-pass a needle into the peritoneal space & take a sample
-transudate = ascites
-exudate = peritonitis
Term
True or False

Presence of an exudate indicates a change in vascular hydrostatic/oncotic pressure
Definition
False

it indicates an inflammatory process is taking place in the body
Term
What are the benefits of exudation?
Definition

-dilutes any offending agents

-brings immunoglobulins & complement proteins to the area

-increases lymphatic drainage to carry agents to lymph nodes

Term
What role does Factor XII play in fibrin formation?
Definition
it acts on fibrin monomers to form insoluble polymers of fibrin
Term
What is the role of fibrin in the tissue?
Definition
-forms a meshwork to localize the inflammatory process & aid neutrophil movement
Term
What are the characteristics of shipping fever?
Definition
-excess fibrin production in the lung & pleural surface
-causes adhesions between pleual mmbs
Term
What cell line do inlammatory cells derive from? What are the two branches?
Definition
myeloid cell line in bone marrow
-mononuclear cells & granulocytes
Term
What are granulocytes?
Definition
Neutrophils: phagocytosis of microorganisms, are motile, have degradation enzymes

Eosinophils: recruited to fight parasitic diseases
Term
What effects do dancer cells have on neutrophil function?
Definition
reduce levels of neutropphils, increasing the risk of infection
Term
What are mononuclear cells?
Definition
Lymphocytes
Plasma Cells
Monocytes
Macrophages
Term
Which are you more likely to see in acute inflammation, neutrophils or monocytes?
Definition
neutrophils
Term
What is the difference between monocytes & macrophages?
Definition
macrophages are monocytes which have migrated and become fixed in tissues
Term
What do macrophages do?
Definition
ingest microorganisms, phagocytosis, clean up cellular debris, secret epyrogens & complement components
Term
What are the steps of leukocyte recruitement? (5)
Definition
1. Margination, Rolling & Adhesion of leukocytes
2. Transmigration of neutrophils
3. Chemotaxis
4. Leukocyte Activation
5. Phagocytosis & Pathogen Degradation
Term
What is marginationm pavementing & adesion?
Definition
Margination: increased contact between leukocytes & endothelium

Pavementing: selectins on both mediate the leukocytes sticking to the endothelium

Adhesion: integrins integrate the leukocytes into tissues
Term
Describe the transmigration of neutrophils
Definition
Diapedesis: neutrophils have adhered to the endotheliun, now need to squeeze between intercellular junctions
-secrete collagenases to degrade basement membrane & enter the intersitium
Term
Where does diapedesis typically occur?
Definition
in venules of systemic circulation
Term
What is chemotaxis? How does it work?
Definition

the attraction of inflammatory cells based on concentration gradient

-chemotactic molecules bind to leukocyte receptors, increasing Ca and triggering intracellular contractile elements to allow leukocytes to move

Term
True or False

Cytokines are chemotactic
Definition
true
Term
What is leukocyte activation? What does it lead to?
Definition
Toll-like receptors recognize PAMPS, activating leukocytes to initiate the inflam process
Cytokines can also activate leukocytes after inflam process is underway

Leads to:
Phagocytosis
Upregulation of mechanisms for degradaing microbes
Produces inflammatory mediators
Term
What is opsonization?
Definition
recognition of an antibody or complement factor by phagocytic cells to enhance phagocytosis
Term
What are the steps of phagocytosis/pathogen degradation
Definition
1. Recognition
2. Opsonization
3. Engulfing (phagocytosis)
4. ROS kill pathogens
5. Phagosome fuses with lysosome for hydrolysis
Term
What effect does phagocytosis have on aerobic metabolism in leukocytes?
Definition
increases it

-results in lots of ROS being produces, which kills pathogens
Term
What are the 6 types of inflammatory mediators?
Definition
Vasoactive Amines
Plasma Proteins
Lysosomal Constituents
Arachidonic acid metabolism
Platelet-activating factor
Cytokines
Term
What are the 2 vasoactive amines discussed and what do they do?
Definition
Histamine & seratonin
-vasodilation & increase permeability
Term
What activates plasma proteases?
Definition
Hageman factor (Factor XII)
Term
What are the 3 plasma proteases?
Definition
Kinin system
-bradykinin increases permeability

Coagulation Cascade
-activates thrombin to produce fibrin

Complement System
-C5a & C3a stimulate histamine release
-C5a is chemotactic & mediates arachidonic metabolism
-C3a is an opsonin
Term
What do Bradykinin, C3a & C5a have in common?
Definition
they mediate vascular permeability
Term
What is the role of lysosomal constituents?
Definition
oxygen-based free radicals & proteases increase vascular permeability (damage mmbs) & kill/degrade microorganisms
Term
What is the importance of arachidonic metabolism?
Definition
-produces prostaglandins, leukotrienes & lipoxins (eicosanoids)
Term
If you are using an anti-inflam agent, which mediator if inflammation are you likely targeting?
Definition
metabolism of arachidonic acid
Term
What does platelet-activating factor originate from?
Definition
phospholipids
Term
Which two cytokines are of particular importance? How are they produced & what do they do?
Definition
Interleukin 1 & Tumour Necrosis Factor

-produced by activated macrophages
-induce endothelial activation & activate tissue fibroblasts
-induce systemic acute-phase responses e.g. fever & lethargy
Term
What do corticosteroids do?
Definition
-suppress/inhibit inflam response by blocking conversion of mmb phospholipids to arachidonic acid
-reduce vasodilation & permeability to reduce exudation
-suppress almost all aspects of the inflam response to the injurious agent
Term
What do NSAIDs do?
Definition
-inhibit conversion of arachidonic acid to prostaglandins
-anti inflam & analgesic effects
Term
What are the local signs of inflammation?
Definition
redness, heat, swelling, pain
Term
What polypeptides signal pain?
Definition
bradykinin
histamine
seratonin
Term
Aside from polypeptides of low molecular weight, what else signals pain?
Definition
increased pressure due to swelling
stimulation of nerve endings
Term
True or False

Fever is a local finding indicating inflammation
Definition
false

it is a systemic finding
Term
What is the acute phase reaction to inflammation? (4)
Definition
fever
malaise
changes in peripheral WBC count
changes in plasma proteins
Term
What is the difference between a sign & a sympton?
Definition
Sign = objective e.g. enlarged lymph nodes, blood test

Sympton = subjective e.g. general pain, headacehe
Term
What are the endogenous pyrogens and how do they work?
Definition
Interleukins IL-1 & IL-6 & TNF

-enter systemic circulation, travel to brain, stimulate prostaglandin synthesis to 'reset' the core body temperature
Term
What is the difference between leukocytosis & neutrophilia?
Definition
Leukocytosis = increased WBC count

Neutrophilia = increased neutrophil #s specifically
Term
Why would you see an increase in immature neutrophils during acute inflammation?
Definition
-they are being released from bone marrow before completely mature in an effort to keep up with demand
Term
What mediates the release of leukocytes from bone marrow?
Definition
TNF & IL1
Term
True or False

In viral infections, you are likely to see a decrease in WBC count
Definition
true
Term
What changes would you see in plasma protein levels in acute inflammation?
Definition
increases in acute phase reactants
-C reactive protein, fibrinogin etc.
Term
Is an increase in acute phase reactants a specific or non-specific indication of inflammation?
Definition
non specific
Term
What is resolution?
Definition
occurs when acute inflammation is uncomplicated, the swelling & cellular debris are removed by macrophage activity & lymphatic flow relatively quickly with no signs of it ever having happened
Term
When is 'repair' required to fix acute inflammation?
Definition
if the inflammation cannot be quickly resolved, and some tissue necrosis/introduction of bacteria has occured
Term
What is liquefactive necrosis & what causes it?
Definition
-exaggerated inflow of neutrophils due to bacterial presence in the injury
-liquified mass of necrotic tissue, dead organisms & neutrophils

PUS!
Term
What is suppurative inflammation?
Definition
the process of forming liquefied necrotic tissue
Term
What causes an abscess to form?
Definition
-fibrous tissue walls off an area of suppurative inflammation
Term
What is cellulitis?
Definition
local spread of infection as bacteria 'escapes' the original site of infection and travels to surrounding tissues
Term
What is septicemia?
Definition
-spread of bacteria & their toxins in their bloodstream
Term
What is bacteremia?
Definition
the travel of just bacteria in the bloodstream (bacteremia)
Term
Which organ is particularly susceptible to abscess formation due to bacteremia?
Definition
the valves of the heart
Term
What characterizes chronic inflammation vs acute inflammation?
Definition
Chronic = lots of mononuclear cells, occurs if acute inflam cannot be resolved promptly, persistence of the antigen/injurious stimulus

Acute = lots of neutrophils
Term
Coughing, hemoptysis, fever, weight loss & fatigue are all signs of _____ resulting from chronic inflammation & necrosis of lung tissue
Definition
tuberculosis
Term
What causes chronic inflammation?
Definition
a continued inflammatory responses combined with an immune response against a persistent injurious agent
Term
What is chronic inflammation?
Definition
inflammation of prolonged duration in which active inflammation, tissue injury & healing take place simultaneously
Term
What are the characteristics of chronic inflammation? (4)
Definition
1. An immune response (monouclear cells such as plasma cells & lymphocutes)
2. Accumulation of macrophages
3. Healing through development of granulation tissue (tissue fibrosis & angiogenesis(
4. Ongoing tissue injury & necrosis
Term
What happens if an antigen persists for several days in a tissue?
Definition
activated T cells, blasma cells & macrophages will accumulate

tissue necrosis

fibrosis
Term
What determines whether chronic inflammation is successful?
Definition
Degree of:

-activation & killing by T cells
-antibody formation by plasma cells
-activation of macrophages & lymphokines
Term
What characterizes granulomatous inflammation?
Definition
aggregates of activated macrophages that assume an epitheloid appearance
Term
What are epitheloid cells?
Definition
activated macrophages which characterize granulomatous inflamation

-pale foamy cytoplasm due to lots of RER
Term
What causes granulomatous inflammation to develop?
Definition
Impaired ability to phagocytise/destroy a causal agent

-causal agent may be phagocytized but persist within the macrophages
-may not be able to phagocytize the agent
Term
What is required for granulomatous inflammation to develop? Why?
Definition
An active T-cell mediated immune response
-T cells produce lymphokines which cause macrophages to remain in the area, forming granulomas
Term
What causes granulomatous inflammation in tuberculosis?
Definition
mycobacteria survive inside macrophages in the lungs, forming granulomas
Term
What are some differential diagnoses for granulomatous inflammation? (5)
Definition
1. Atypical bacteri
2. Fungal pathogens within tissues
3. Parasites within tissues
4. Inert foreign bodies
5. Immune-mediated diseases
Term
What are the two types of leprosy?
Definition
Tuberculoid
-strong T cell response causing development of granulomas

Lepromatous
-poor T cell response so bacillus multiplies in the macrophages
Term
What happens to tissue affected by granulomas?
Definition
-surrounding tissue will be lost due to necrosis
-scar tissue will replase it
-caseous necrosis is common
-adjacent granulomas may fuse & form large masses
Term
What are foreign body granulomas?
Definition
inert, non-antigenic foreign material enters a tissue
-lots of macrophages congregate around to phagocytise it
Term
What is furunculosis?
Definition
-immunologically privileged keratin (hairs) embedded within tissues induce a foreign body reaction causing a granulomatous response

ingrown hair!
Term
What characterizes non-granulomatous chronic inflammation?
Definition
-sensitize lymphocytes
-plasma cells
-macropages
-areas of necrosis & fibrosis

(no epitheloid cells!)
Term
What are some causes of non-granulomatous chronic inflammation?
Definition
Chronic viral infections
Other chronic infections
Chronic autoimmune diseases
Allergic conditions & parasitic infections
Chronic toxic dieases (alcohol consumption)
Term
What is chronic suppurative inflammation?
Definition
-body cannot clear a strong pyogenic (pus-producing) stimulus
-may have thick fibrous walls surrounding an area of suppurative inflammation & necrosis
Term
What is granulation tissue?
Definition
mixture of fibrous connective tissue & new capillaries

-often walls off damaged tissue to form an abcess
Term
_______ are round cyst-like structures with a thick fibrous wall & central cavity filled with large quantities of pus & debris
Definition
abcesses
Term
What is osteomyelitis?
Definition
infection of bone with pyogenic bacteria
Term
What are the two types of osteomyelitis?
Definition
Hematogenous
-bacteria carried by bloodstream

Secondary Osteomyelitis
-bacteria develop secondary from a wound/adjacent site of infection e.g. open fracture site
Term
Why are children at risk of hematogenous osteomyelitis?
Definition
their epiphyseal cartilage (growth plates) are highly vascular, increasing the likelihood of 'seeding' with bacteria
Term
What is sequestrum?
Definition
fragment of dead, infected bone that persists despite inflammatory response trying to clear it out
Term
Why is chronic osteomyelitis difficult to resolve?
Definition
destruction of local blood supple means leukocytes & systemic antibodies cannot access the site of infection
Term
Why would you see anemia with chronic inflammation?
Definition
-limited production of RBCs due to decreased transport of Fe into the plasma
-reduces formation of hemoglobin-Fe complexes leading to anemia
Term
Why are antibiotics often not effective in resolving chronic suppurative inflammation?
Definition
the bacteria involved are often isolated to an area with no blood supply, allowing them to continue to grow & multiply
Term
What is amyloid? What are the 3 common derivatives?
Definition
beta-pleated fibrillar protein

Derived from
-serum amyloid-associated non-immunoglobullin protein (produced by liver) AA type
-immunoglobulin light chains (produced by plasma cell or B cell tumours) AL type
-amyloid beta (cerebral plaque in Alzheimers) AB type
Term
What are the classifications of amyloidosis? (3)
Definition
Systemic
Localized
Familial
Term
What is systemic amyloidosis? (2)
Definition
Primary
-AL type
-associated with cancer

Reactive
-depositions of amyloid widely in body associated with chronic inflammatory diseases e.g. tuberculosis
Term
What is localized amyloidosis? (2)
Definition
-associated with amyloid plaques in the brain (Alzheimers)
-depositions in some endocrine tumours
Term
What is familial amyloidosis?
Definition
inherited disorders causing local deposition of amyloid in heart/kidney/nervous tissue
Term
Why is amyloid deposition significant?
Definition
-can cause enlarged tissues, less flexible
-inhibits diffusion of nutrients across interstitium
Term
What would be the effect of amyloi in the renal glomerulus?
Definition
inhibited filtration mechanism, causing protein loss in the urine
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