PATH 3610 unit 3

Epithelioid cells have an increased ability to:

secrete lysozyme

Caseous necrosis in granulomas caused by micro-organisms is related to:

a delayed type (Type IV) hypersensitivity reaction

Exudation refers to:

increased movement of fluid and proteins out of vessels due to increased permeability

Non-granulomatous chronic inflammation is seen with:

chronic viral infections

The two major components of the process of acute inflammation are:

vascular changes and cellular response

The increased blood flow into inflamed tissues is termed:

hyperemia

The synthesis of arachidonic acid metabolites is increased at inflammatory sites. T/F

true

Increased vascular permeability in inflammation will allow large protein molecules to leave the vascular space. These include:
a. albumin
b. fibrinogen
c. urea

b. fibrinogen

Persistence of an antigen or injurious stimulus will cause chronic inflammation to develop. T/F

true

In acute inflammation, the term 'pavementing' refers to the tendency for:

leucocytes to adhere to vessel walls

The marked active dilation of vessels in acute inflammation is due to:

release of chemical mediators by damaged cells

The fever associated with acute inflammation is a result of:

mediators such as interleukin-1 and prostaglandins causing a 'resetting' of core temperature

Neutrophil diapedesis is assisted by:

enlarged endothelial pores

The process by which certain inflammatory cells ingest and destroy particulate matter is termed:

phagocytosis

The type of inflammatory cell with the greatest role in inflammation is the:

Neutrophil

A focus of necrotic debris and dead neutrophils surrounded by a fibrous capsule is best termed:

abscess

The most common cause of osteomyelitis is:

bacterial seeding from the blood

Non-granulomatous chronic inflammation is characterized by sensitized lymphocytes, plasma cells and macrophages, together with:

areas of necrosis and fibrosis

Granulomatous inflammation is characterized by:

aggregation of activated (epithelioid) macrophages

Neutrophils leave capillaries in inflammation by the process of:

Diapedesis

In acute inflammation, leucocytes tend to 'stick' more to endothelial cells of the microvasculature. T/F

true

Neutrophils contain:

enzymes which can degrade biologic material

Exudate contains:

contains fluid, protein, and inflammatory cells

The specific movement of neutrophils toward a focus of inflammation is termed:

chemotaxis

The systemic fever response is a result of:

pyrogens influencing the hypothalamic thermoregulatory centre in the brain

Describe the composition of pus

degenerating neutrophils, plasma, tissue debris and dead microbes

The increased vascular permeability seen early in acute inflammation is primarily the result of:

widening of intercellular junctions between endothelial cells

Mast cells have an imporant role in inflammation because their granules release:

histamine

Fibrinous inflammation develops when:

vascular permeability has increased sufficiently to allow fibrinogen to leave the vessels

Opsonization refers to the:

enhanced recognition by leucocytes of injurious agents, due to coating with a variety of opsonins

Which of the following statements about acute inflammation is NOT true?
a) it is the first line of defense against an injury
b) the extent of the inflammatory reaction is proportionate to the degree of tissue damage
c) the leakiness of the vessels allows

c) the leakiness of the vessels allows fluids and proteins but not cells to escape

Septicemia refers to:

spread of bacteria and their toxins via the bloodstream

Relative to transudates, exudates are characterized by:

greater numbers of cells

The acute inflammatory process may cause an elevated number of:

white blood cells in the peripheral blood

The inflammatory mediators having the greatest role in the early phase of the acute inflammatory response are:

vasoactive amines (histamine and serotonin)

The cerebral plaque lesions of Alzheimer disease contain a specific type of amyloid. T/F

True

Amyloid depositions seen in a wide variety of body tissues in association with chronic inflammatory disease are termed:

reactive amyloidosis

Amyloid deposition in renal glomeruli is associated with:

protein loss in urine

Which of the following is a cause of non-granulomatous chronic inflammation?
a) foreign material such as talc or sponge fibres
b) chronic viral infections
c) chronic mycobacterial infections

b) chronic viral infections

Amyloid consists of:

a) insoluble beta-pleated fibrillar proteins

Which of the following statements is NOT true of granulomatous inflammation?
a) it develops when macrophages phagocytose an "indigestible" agent
b) an active B cell-mediated immune response must occur
c) it is characterized by the presence of epithelioid

b) an active B cell-mediated immune response must occur

The role of T cells in granulomatous inflammation is to:

produce lymphokines which inhibit macrophage migration

Non-granulomatous chronic inflammation is seen with:

chronic viral infections

Osteomyelitis is a classic example of:

chronic suppurative inflammation

A surgical sponge (gauze) mistakenly left in the abdominal cavity during surgery would cause:

foreign body granuloma formation

Tuberculosis is characterized by:

granulomatous inflammation in lungs or other tissues

Chronic inflammation is characterized by: (4)

1) immune response
2) macrophages
3) granulation tissue
4) ongoing tissue necrosis

The immune response is indicated by the presence of:

mononuclear cells (plasma cells, lymphocytes, etc)

tissue healing through the development of granulation tissue is characterized by:

tissue fibrosis and angiogenesis

desired outcome of inflammation:

healing and repair, so function of injured tissue can be restored (if possible)

___________ is the predetermined/non-specific response to injury, consisting of microcirculatory response and mobilization of phagocytic cell

acute inflammatory response

acute inflammation is characterized by: (symptoms) (5)

redness, heat, swelling, pain and loss of function

-itis" is used to describe:

areas of inflammation

What's the first line of defence against injury?

acute inflammatory response

The extent of inflammation is proportionate to:

the degree of tissue damage

Once inflammation develops, the progression towards resolution and healing begins:

~ immediately

Healing time depends on: (4)

1) cause/nature of injury
2) extent of injury, tissue affected
3) genetic make-up of an individual
4) status of immune system

During the acute inflammatory response, vessels ______ to ________ to area, and become ________ to allow_______ to leave circulation and enter injured site

dilate
increase blood flow
more permeable
plasma proteins

The cellular response to acute inflammation is:

leukocytes leave microcirculation and accumulate at injury site

swelling is caused by:

leakiness - fluid moves out of vessels and into tissue spaces

Active dilation of arterioles, capillaries and venules caused by:

the release of chemical mediators from damaged and necrotic cells

Chemical mediators, including ________ and ______, are released during platelet aggregation.

vasoactive amines and kinins

Histamine is a chemical mediator released by _______, that causes ______.

mast cells
capillary dilation

mast cells contain _________ that contain histamine.

membrane bound vacuoles ("granules")

injury or activation of mast cells leads to:

mast cell degranulation (releasing histamine)

Normally, ________ remain closed, causing blood to pass through tissues via _________ (directly from arteries to veins)

precapillary sphincters
"freeway" channels

Precapillary sphincters open and blood is diverted from freeway channels to perfuse tissues in response to:

increased metabolism

Increased capillary and venular permeability initially occurs because of ___________ between endothelial cells

widening of intercellular junctions

When selectively permeable membrane is damaged by inflammation, spaces between endothelial cells become wider (increased vascular permeability) and increased amounts of fluid and proteins will pass out of vessels, into extravascular space. This describes:

exudation
the fluid = exudate

causes of increased vascular permeability: (5)

1) endothelial cell contraction
2) direct injury to endothelium
3) leukocyte-mediated endothelial injury
4) increased transcytosis
5) leakage from newly forming blood vessels

Endothelial cell contraction (the widening of intercellular junctions) is a transient process occurring primarily in ______, which is mediated by _______ and ________.

venules
tumor necrosis factor (TNF) and interleukin-1 (IL-1)

direct injury to endothelium causes:

endothelial cell necrosis and detachment

Leukocytes release ________ and _________ that further endothelial cell injury and detachment

proteolytic enzymes and toxic oxygen species

_________ is the movement of fluid across endothelial cells via vesicles

transcytosis

The movement of fluid into interstitial space that causes blood to become more viscid, which causes blood to slow down. This describes:

stasis

_______ is the fluid that leaves vessels due to increased hydrostatic pressure OR that fails to return to vasculature due to low osmotic pressure

Transudate
(the ultrafiltrate of plasma)

Large plasma proteins that are able to leave vessels during increased vascular permeability (inflammation) include:

immunoglobulins, complement and fibrinogen

Specific gravity of exudate is _______ than transudate because of ________.

greater
increased protein content in exudate

Movement of large molecules from plasma into interstitium __________ effect of plasma proteins, which favours _________, furthering swelling.

decreases osmotic pressure
fluid remaining in interstitium

Transudate form with ______. Exudates form with ______.

normal vascular permeability
increased vascular permeability

transudate is turbid, yellow/white/pink. T/F

False
Exudate is turbid, yellow/white/pink
transudate is clear

______ is effusion into peritoneal cavity

ascites

______ is an inflammation of the peritoneum

peritonitis

_________ is a systematic diagnostic method used to identify an entity where multiple alternatives are possible (process of elimination)

differential diagnosis

a _________ is the final diagnosis made after getting results of tests

definitive diagnosis

The fluid that accumulates in ascites is:

transudate

exudate suggests the presence of:

inflammation

Benefits of exudation: (3)

1) dilutes offending agent
2) brings defensive proteins into area (immunoglobulins and complements)
3) increases drainage of area via lymphatics
-lymphatic drainage takes agents to local lymph nodes, where protective immune response is facilitated

Fibrin is synthesized from _______ precursor ______, in the ______.

plasma
fibrinogen
liver

Inactive fibrinogen in plasma contributes to:

plasma osmotic pressure

_______ converts fibrinogen to fibrin

thrombin

thrombin is formed from:

tissue thromboplastin

When formed, fibrin exists in _______ form. Then _________ converts it to ________ polymer, "fibrin", that aids neutrophil movement

monomeric
coagulation factor XIII
insoluble fibrillary

________ is lobar pneumonia in cattle, caused by infection with Mannheimia hemolytica bacteria, characterized by ________ production within lung and at pleural surface, where it causes ______ between pleura of lung and ribcage

Shipping fever
abundant fibrin
adhesions

Shipping fever occurs in:

cattle that have been stressed by transportation

Vascular changes in acute inflammation establish:

infrastructural transit system that allows inflammatory cells to reach site of injury

Acute inflammation is characterized by: (cellular response)

active emigration of inflammatory cells from blood into area of tissue injury

leukocytes (white blood cells) are derived from:

myeloid cell line within bone marrow
-move into blood stream when mature

2 "arms" of the myeloid cell line:

-mononuclear cells: smoothly outlined, round cells
- granulocytes: contain multi-lobulated nucleus and cytoplasmic granules

Most leukocytes, RBCs and platelets undergo differentiation within:

bone marrow

Neutrophils, basophils and eosinophils are:

granulocytes

Characteristics of neutrophils: (4)

-seen in greatest numbers in early inflammation (granulocyte with greatest role in acute inflammation)
- actively motile
- capable of phagocytosis
- contain enzymes that degrade biologic material

The main function of the neutrophil is:

phagocytosis of microorganisms

________ describes low neutrophil numbers, often seen as a side effect of cancer therapy with cytotoxic drugs or radiation

neutropenia

lymphocytes, plasma cells, monocytes and macrophages are:

mononuclear cells

Mononuclear cells are most important in __________ of inflammation

later (more chronic) stages

Monocytes in blood can migrate into tissues, and become fixed into:

macrophages

________ are the mononuclear cells with the greatest role in acute inflammation. They _______ and _______ .

macrophages
ingest microoganisms(phagocytosis) and help clear cellular debris (debridement)

Stasis disorders __________ within vessel causing leukocytes to move __________, increasing contact between leukocytes and ________. This is called _________.

normal laminar flow
out toward vessel wall
endothelium
margination

Marginated leukocytes "roll" along endothelial surface, transiently sticking in place. This is mediated by:

selectins
-up-regulated after stimulation by inflammatory mediator

Endothelial cells become "sticky", causing leukocytes to adhere to vessel wall. This process is called ________ and is mediated by _______.

pavementing/adhesion
integrins (on leukocyte surface, interact with ligands on endothelial cells)

Once adhered to endothelium, leukocytes squeeze out of vessel through intercellular junctions. This process is called:

diapedesis

Neutrophils are focally degraded by ________, enabling them to pass through basement membrane into tissue spaces. This occurs in __________.

secreted collagenases
venules in systemic circulation

diapedesis is mediated by:

cell adhesion molecules

_________ is the process by which inflammatory cells are attracted to injury sit by directional migration along chemical concentration gradient.

chemotaxis

chemical mediators that act as chemotactic signals in chemotaxis are: (4)

factor C3a, C5a, leukotriene and cytokines

_________ bind to receptors on leukocyte surfaces, leading to ________ and triggering assembly of intracellular contractile elements, that allow leukocytes to move by _________.

exogenous chemotactic molecules
increased intracellular calcium
extending pseudopods

________ must be activated for effector mechanisms to bear against invaders. They're activated by _______ released by inflammatory response.

leukocytes
cytokines

Leukocytes have surface receptors that recognize __________ on bacteria and pathogens

Pathogen-associated molecule patterns (PAMPs)

________ on leukocytes recognize PAMPs on viral, bacterial and fungal components.

Toll-like receptors

Opsonins, present normally in tissues, bind foreign substances and indirectly mediate leukocyte activation. This describes:

innate immunity

Because of innate immunity, introduction of a pathogen into tissue induces immediate response from leukocytes already in tissues without recognition and up-regulation of ___________

acquired immunity

initial activation of leukocytes in innate immunity leads to: (3)

1) phagocytosis
2) up-regulation of mechanisms for degradation and killing of microbes
3) production of inflammatory mediators

______ and ______ ingest/destroy particulate matter

neutrophils and macrophages

Neutrophils and macrophages undergo ________(large inert particles) or ________ (opsonized agents) of particulate matter

nonspecific or specific phagocytosis
-opsonization is the process of coating antigens in opsonins
-opsonins- antibody (IgG) or complement factor 3b (C3b)

______ are CHO-binding lectins in plasma that bind to microbial cell walls as opsonins

collectins

opsonization enhances:

phagocytosis

_______ phagocytosis dominates early acute inflammation, but when immune response develops ________ is more efficient.

nonspecific phagocytosis
immune phagocytosis

After opsonized particles are recognized and bound, they're _______, forming membrane-bound vacuoles within phagocytes cytoplasm, called _______.

engulfed
phagosome

Phagocytosis stimulates an increase in oxygen-dependant metabolism in leukocytes leading to the production of _________, which mediate pathogen destruction.

ROS (reactive oxygen species)

pathogens are further degraded by the fusion of the phagosome with ________, that release ________ to kill pathogens

lysosomes
hydrolase

________ give inflammatory exudate its cloudy/opaque appearance

inflammatory cells

Inflammatory mediators are __________ or formed when required

pre-formed and stored in cytoplasmic granules

__________, histimine and serotonin cause vasodilation and increased permeability, evoking __________ of the acute inflammatory response.

vasoactive amines (mediators)
the immediate phase

_________ are plasma-derived mediators initially activated by _________, a protein synthesized in the liver that circulates in plasma in inactive form - activated by endothelial injury. Activated form ___________.

plasma proteases
Hageman factor XII (XIIa = activated form)
cleaves protein substrates

In the kinin system, ________ enzyme converts precursor plasma protein into ________ that increases vascular permeability and mediates pain.

- Kallikrein (prod by XIIa from inactive plasma precursor prekallikrein)
bradykinin (the final product of the kinin system)

__________, initiated by XIIa, activates ________, ultimately leading to the production of fibrin.

the coagulation cascade
thrombin

________, released during the breakdown of fibrin, are chemotactic factors for _______, that increase vascular permeability.

fibrinopeptides
neutrophils

____ , formed in the compliment system, activates lipooxygenase pathway of the arachidonic acid metabolism and and is a phagocytosis activator

C5a

C3 and C5 are activated by:

proteolytic enzymes in inflammatory exudate
-their activation amplifies influx of neutrophils to the inflammatory site

___, ____, and _______ are important mediators of vascular permeability and pain

C3a, C5a, and bradykinin

Activated Hageman factor (XIIa) initiates: (4)

1) kinin system - producing vasoactive kinins
2) clotting system - inducing activation of thrombin, fibrinopeptides and factor X
3) fibrinolytic system - producing plasmin and deactivating thrombin
4) complement system - producing anaphylatoxins C3a and C

Roles of thrombin: (4)

1) cleaves circulating soluble fibrinogen and generates fibrin clot
2) binds to protease-activated receptors and enhances leukocytes adhesion
3) generate fibrinopeptides
4)cleaves C5, to generate C5a, linking coagulation with complement activation

______ generate toxic oxygen-based free radicals and protease

neutrophils

prostaglandin, leukotiene and lipoxin are produced in :

arachidonic acid metabolism

arachidonic acid metabolism is the target of:

anti-inflammatory agents

_________ is a phospholipid-derived inflammatory mediator, generated from cell membranes, by _________

Platelet-activating factor
phospholipase A2

cytokines (IL-1, TNF, etc) induce ______ and _______, and activate ______.

- endothelial activation
-systemic acute-phase responses (fever, lethargy, etc)
- tissue fibroblasts

Synthetic glucocorticoids (corticosteroids) can suppress/inhibit inflammation by:

by suppressing the immune response, by:
1) blocking conversion of cell membrane phospholipids to arachidonic acid
2) stabilizing lysosomal membranes of inflammatory cells, decreasing the release of enzymes/vasoactive amines

prednisone, dexamethasone and betamethasone are examples of:

corticosteroids

_________, like aspirin, ibuprofen or naproxen, inhibit conversion of of arachidonic acid to prostaglandins.

NSAIDs (non-steroidal anti-inflammatory drugs)
-anti-inflam and analgesic activity

__________ , fever-inducing agents, generated in acute inflammation, enter blood circulation at inflammation site and travel to brain, where they act at specific loci in hypothalamus, via prostaglandin synthesis, to reset body temperature

endogenous pyrogens
eg. interleukins, TNF, etc

________ increases with fever and decreases with hypothermia (not body temp)

metabolic rate

neuronal dysfunction and delirium occur at temperatures:

greater than 42.2�C
-death at ~43.3�C

Fever is good because it helps body combat infections by:

inhibiting some microorganism growth and by stimulating interferon production

neutrophilia:

increased neutrophil numbers

A ________ occurs when there's immature neutrophils in blood and indicates __________, reflecting extent of inflammation

left shift
heavy neutrophil demand

In acute viral infections, there's _______ (neutropenia) and _______ (lymphocytosis)

decreased neutrophils numbers
increased lymphocyte numbers

Leukocyte release from bone marrow is mediated by:

cytokines TNF and IL-1

In acute inflammation, increased acute phase reactant (plasma protein) levels is detected via:

increased erythrocyte sedimentation rate

___________ is the process of pus formation, resulting in a liquified mass of necrotic tissue, dead organisms, and neutrophils

suppurative/purulent inflammation

An ________ forms when an area of suppurative inflammation becomes "walled off" by fibrous tissue

abscess

If an abscess ruptures without draining enough, it may:

reform or remain as chronic inflammation

Chronic inflammation can progress from acute inflammation or:

arise directly in association with antigens, persistant injury or autoimmune disease

If an antigen persists for several days, _______, _______ and ______ accumulate at the site of inflammation.

activated T cells, plasma cells and macrophages

Immune response doesn't have time to develop in:

acute inflammation

____________ is characterized by aggregates of activated macrophages with scattered lymphocytes

granulomatous inflammation

_________ are activated macrophages with large foamy pale cytoplasms that are characteristic of chronic granulomatous inflammation

epithelioid cells

Granulomatous inflammation occurs when: (2)

1) causal agent is phagocytosed, but survives and persists within macrophages
2) phagocytosis of causal agent is impaired

Differential diagnoses for granulomatous inflammation: (5)

1) Atypical bacteria
2) fungal pathogens within tissues
3) parasites within tissues
4) inert foreign bodies
5) immune-mediated diseases

________ develops in patients with _________. It is characterized by nodular skin thickening and extensive tissue destruction, with disfiguring lesions on figures and face

leprosy
poor T cell responsiveness

Functional tissue around a granuloma is lost by ______ and replaced by _______.

necrosis
scar tissue

T cell mediated Type IV hypersensitivity causes central areas of:

caseous necrosis

When foreign materials that are inert, non-antigenic and indigestible enter tissues:

foreign body granulomas develop
- inert: doesn't elicit inflammatory response
- non-antigenic: doesn't elicit immune response
-indigestible: too large to be phagocytosed by single macrophage

Langhans giants cells have:

nuclei at periphery

_______ is inflammation caused by an ingrown hair/pimple, which occurs when immune system doesn't recognize keratin as a "self-protein

furunculosis

Any chronic inflammation NOT characterized by epithelioid cells =

non-granulomatous inflammation
characterized by: lymphocytes, plasma cells and macrophages scattered through affected tissue, along with areas of necrosis and fibrosis

Causes of non-granulomatous chronic inflammation: (5)

1) Chronic viral infections
2) other chronic infections
3) Chronic autoimmune disease
4) allergic conditions and parasitic infections
5) chronic toxic diseases

Chronic active", "recurring acute", "subacute" and "chronic suppurative" describe inflammation which has:

characteristics of BOTH chronic AND acute inflammation

Chronic suppurative inflammation develops when:

the body's unable to clear strong pyogenic stimulation
- pyogenic=pus producing

Initial injection of bacteria into subcutaneous tissues results in _______ that becomes exuberant, forming large pus pockets. If infection persists, body attempts to prevent infection spread by ______________, resulting in an abscess.

local suppurative inflammation (cellulitis)
walling damaged tissue off with granulation tissue
-abscesses are typically the result of pyogenic bacterial infection lasting > a week

Abscesses appear as roughly round ______ structures, with ________ walls and a central cavity filled with ______, ______ and sometimes_______.

cyst-like
thick white fibrous
large quantities of pus, necrotic debris
fibrin

Osteomyelitis results from infections with:

pyogenic bacteria

In ___________, bacteria enter through skin, subcutaneous tissues, GI tracts or umbilicus and are carried to bone by bloodstream

hematogenous osteomyelitis

_______ may occur 2� to implantation of bacteria into bone through open fracture site

2� osteomyelitis

________ progresses to chronic phase more often than other pyogenic bacterial infections

osteomyelitis

________ disrupt blood supply, causing bone ischemia, which results in the formation of a _________, a fragment of dead infected bone that persists despite attempts of inflammatory response to clear it out.

Subperiosteal abscesses
sequestrum

Chronic osteomyelitis is difficult to resolve because of destruction of local blood supply, which is necessary to: (2)

1) deliver leukocytes to destroy infection and clear bulk of necrotic tissue
2) deliver systemic antibiotics to infection site
-surgical debulking is often important for healing

_____ is caused by decreased transport of stored iron into plasma

anemia
-when hemoglobinization is inadequate

_______ refers to a group od diseases characterized by the deposition of insoluble protein in interstitium of tissues

amyloidosis

_______ is an amorphous eosinophilic �-pleated fibrillar protein

amyloid

3 most common amyloid forms:

1) serum amyloid-associated non-immunoglobulin protein - derived (AA-amyloid)
2) immunoglobulin light chain-derived amyloid (AL-amyloid)
3) A�-amyloid - characterize cerebral plaque lesions of alzheimers

3 classes of amyloidosis:

1)systemic
2) localized
3) familial

In 1� systemic amyloidosis, the formation of ______ amyloid is associated with ________ or ________.

AL-type
multiple myeloma
B cell dysfunction

______ is often associated with chronic inflammation produced in autoimmune diseases

2�(reactive) amyloidosis

Amyloid depositions seen in endocrine tumors are derived from:

peptide hormone precursor molecules

________ are inherited disorders in which amyloid is deposited locally in organs

familial amyloidosis