HCT lab module 1.2 Flashcards
A protective response, designed to remove the organism of both the initial cause of cell injury
(e. g. microbes, toxins) and the consequences of such injury (e.g. necrotic cells and
tissues) .
Inflammation
The local response of living mammalian tissues to injury due to any agent that disturb the normal steady state.
inflammation
A dynamic process, evolving through several
phases that last from a few minutes to days or even months and years.
inflammation
Inflammation of sudden onset and short duration
acute inflammation
Inflammation lasts a long time
chronic inflammation
[T or F] Inflammation occurs only in multicellular organisms that are capable of mounting a neuromuscular and cellular response to injury
True
[T or F] Inflammation occurs only in living tissues.
True
[T or F] The inflammatory response is not closely intertwined with the process of repair.
false
4 cardinal signs of inflammation
State both roman and english name:
✓ rubor (redness)
✓ tumor (swelling);
✓ calor (heat); and
✓ dolor (pain)
Who presented the 4 cardinal signs of inflammation? When was it introduced?
Roman writer Celsus in 1st century A.D.
Fifth sign of inflammation added by Virchow
functio laesa (loss of function)
[T or F] The word inflammation means flaming.
False - burning
is of short duration (lasting less than 2weeks) and represents the early body reaction, resolves quickly and is usually followed by healing.
Acute inflammation
is of longer duration and occurs either after the causative agent of acute inflammation persists for
a long time, or the stimulus is such that it induces chronic inflammation from the
beginning.
Chronic Inflammation
the type of chronic inflammation in which
during the course of the disease, there are acute exacerbations of activity.
chronic active inflammation
The three major components of acute inflammation are:
✓ alterations in vascular caliber that lead to an increase in blood flow;
✓ structural changes in the microvasculature that permit plasma proteins and leukocytes to leave the circulation; and
✓ emigration of leukocytes from the microcirculation, their accumulation in the focus of injury, and their activation to eliminate the offending agent
The major manifestations of acute
inflammation, compared to normal.
1 , Vascular dilation and increased blood flow (causing erythema and warmth);
2, extravasation and extravascular deposition of
plasma fluid and proteins(edema);
3, leukocyte emigration and accumulation in the site of injury.
Acute inflammatory response process can be divided into two:
I. Vascular events
II. Cellular events
The earliest response to tissue injury is the alteration in the microvasculature
- alterations include: hemodynamic changes and changes in vascular permeability
Vascular events
earliest features of inflammatory response result from changes in the vascular flow and calibre of small blood vessels in the injured tissue.
Hemodynaic Changes
Progression of hemodynamic changes:
- Transient vasoconstriction
- Persistent progressive vasodilation
- local hydrostatic pressure
- Slowing or stasis
- Leukocyte margination
occur immediately irrespective of the type of
injury. Mild form injury, the blood flow may be reestablished in 3-5 seconds, and in more
severe injury, the vasoconstriction may last for about 5 minutes.
Transient vasoconstriction
involves mainly the arterioles, but to a
lesser extent, affects other components of the microcirculation like venules and
capillaries. This can be seen within half an hour of injury.
- results in increased blood volume, which is responsible for the redness and warmth at the site of acute inflammation.
Persistent progressive vasodilation
results in transudation of fluid into the extracellular space. This is responsible for the swelling at
the local site of acute inflammation.
local hydrostatic pressure
causes increased concentration of
red cells raising blood viscosity.
Slowing or stasis
also known as the peripheral orientation of
leukocytes (mainly neutrophils) along the vascular endothelium.
Leukocyte margination
The leukocytes briefly sticks to the vascular endothelium before moving and migrating through the gaps between the endothelial cells and into extravascular space.
Emigration
In and around the inflamed tissue, there is accumulation of edema fluid in the interstitial
compartment which comes from blood plasma by escaping through the endothelial wall
of the peripheral vascular bed.
Altered Vascular Permeability
Filtrate of blood plasma without changes in
endothelial epermeability
Transudate
Edema of inflamed tissue associated with
increased vascular permeability
Exudate
Characterizes a Non-inflammatory edema
Transudate
Characterizes an inflammatory edema
Exudate
protein content: Low (less than 1g/dL); mainly albumin, low fibrinogen; hence no tendency to coagulate
Transudate
Protein content: High 2.5-3.5 g/dL), readily coagulates due to high content of fibrinogen and other coagulation factors
Exudate
Glucose Content: Same as in plasma
Transudate
Protein content: Low (less than 60 mg/dL)
Exudate
Specific gravity: Low (<1.015)
Transudate
Specific gravity: High (>1.018)
Exudate
pH: >7.3
pH: <7.3
Transudate
Exudate
Few cells, mainly mesothelial cells and
cellular debris
Example is edema in congestive heart failure
Transudate
Many cells, inflammatory as well as
parenchymal
Purulent exudate such as pus
Exudate
[T or F] In acute inflammation, normally non-permeable endothelial layer of the microvasculature becomes leaky
true
The mechanisms of increased vascular permeability are
Hint: 5 mechanisms
- Contraction of endothelial cells (contraction)
- Retraction of endothelial cells (retraction)
- Direct injury to endothelial cells (direct injury)
- Endothelial injury mediated by
leukocytes (Endothelial injury by leukocytes) - Leakiness in neovascularisation (leakiness)
most common mechanism of increased leakiness that affects venules exclusively
while capillaries and arterioles remain unaffected
Contraction of endothelial cells
It is mediated by the release of histamine, bradykinin and other chemical mediators.
Contraction of endothelial cells.
The response begins immediately after injury, usually reversible, and for short duration only
(15-30 minutes).
Contraction of endothelial cells
In this mechanism, there is structural reorganization of the cytoskeleton of endothelial cells that causes reversible retraction at the intercellular junctions.
Retraction of endothelial cells
This change affects venules and is mediated by cytokines like interleukin-1 (IL-1) and tumor necrosis factor (TNF)-α.
Retraction of endothelial cells
The onset of response takes 4-6 hours after injury and lasts for 2-4 hours or more (somewhat delayed and prolonged leakage).
Retraction of endothelial cells
Example of such immediate transient leakage is mild thermal injury of skin of forearm.
Contraction of endothelial cells
The example of this type of response
exists in vitro experimental work only
Retraction of endothelial cells
results to cell necrosis and appearance of
physical gaps at the sites of detached
endothelial cells
Direct injury to endothelial cells
The increased permeability may either appear immediately after injury and last for several hours or days (immediate sustained leakage), or may occur after a delay of 2-12 hours and last for hours or days (delayed prolonged leakage).
Direct injury to endothelial cells
The examples of immediate sustained leakage are severe bacterial infections while delayed prolonged leakage may occur following moderate thermal injury and radiation injury.
Direct injury to endothelial cells
- Occurs mainly in venules
- Induced by histamine. NO. other mediators
- Rapid and short-lived (minutes)
Retraction of endothelial cells
- Occurs in arterioles, capillaries, venules
- Caused by burns, some microbial toxins
- Rapid, may be long-lived (hours to days)
Direct injury to endothelial cells/ Endothelial injury
Adherence of leukocytes to the
endothelium at the site of inflammation
may result in activated leukocytes
which release proteolytic enzymes and toxic oxygen species causing this and increased vascular easiness affects mostly venue and is a late response.
Endothelial injury mediated by
leukocytes
- Occurs in venules, pulmonary capillaries
- Associated with late stages of inflammation
- Long-lived (hours)
Endothelial injury mediated by
leukocytes/LEUKOCYTE-MEDIATED
VASCULAR INJURY
- Occurs in venules
* Induced by VEGF
Leakiness in neovascularisation/INCREASED
TRANSCYTOSIS
The cellular phase of inflammation consists of 2 processes:
exudation of leukocytes
phagocytosis
most important feature of inflammatory response.
consists of normal axial flow, margination of pavementing, rolling and adhesion, and emigration and diapedesis
Exudation of Leukocytes
In acute inflammation,
___________________ comprise the first line of body defense, followed later by monocytes
polymorphonuclear neutrophils (PMNs)
Due to slowing and
stasis, the central stream of cells widens and peripheral plasma zone becomes
narrower due to loss of plasma by exudation. This is called?
margination
Neutrophils of the central column come close to the vessel wall
pavementing
consists of central stream of cells comprised by leukocytes and RBCs and peripheral cell-free layer of plasma close to the vessel wall
Normal axial flow
substances responsible for Rolling and Adhesion
Selectins, integrins and immunoglobulin gene superfamily adhesion molecule (ICAM)
Peripherally marginated and pavemented neutrophils slowly roll over the endothelial
cells lining the vessel wall
Rolling phase
The transient bond between
the leukocytes and endothelial cells becomes firmer
Adhesion phase
neutrophils lodged between the endothelial
cells and basement membrane cross the basement membrane by damaging it locally
with secreted collagenases and escape out into the extravascular space
(damage is repaired immediately)
Emigration
[T or F] Neutrophils are the dominant cells in acute inflammatory exudate in the first 24 hours,
and monocyte-macrophages appear in the next 24-48 hours.
True
[T or F] neutrophils are short-lived (24-48 hours) while monocyte-macrophages survive much longer
True
passive phenomenon where RBCs are being forced out either by raised hydrostatic pressure or may escape through the endothelial defects left after emigration of leukocytes.
-gives hemorrhagic appearance to the
inflammatory exudate.
Diapedesis
Defined as locomotion oriented along a chemical gradient.
Chemotaxis
[T or F] In Chemotaxis, Both exogenous and
endogenous substances can act as chemoattractants.
True
agents that act as potent chemotactic substances or chemokines for neutrophils:
- Leukotriene B4 (LT-B4)
- Components of complement system (C5a and C3a)
- Cytokines (Interleukins, IL-8)
- Soluble bacterial products (formylated peptides)
a product of lipooxygenase pathway of arachidonic acid metabolites
Leukotriene B4 (LT-B4)
Aside from neutrophils, other inflammatory cells respond and participate in inflammation and there are also chemokines for them. State the examples:
- eotaxin chemotactic for eosinophils
- NK cells for recognizing virally infected cells,
Defined as the process of engulfment of solid particulate material by the cells.
Phagocytosis
The cells engulfing of solid particulate material are called:
Phagocytes
2 main types of phagocytes:
Polymorphonuclear neutrophils (PMNs) Macrophage
Polymorphonuclear neutrophils (PMNs) which appear early in acute inflammatory
response
2. Circulating monocytes and fixed tissue mononuclear phagocytes, commonly known as
macrophage
Type of phagocyte which appear early in acute inflammatory response
Polymorphonuclear neutrophils (PMNs)
[type of phagocyte] other term for macrophage
Circulating monocytes and fixed tissue mononuclear phagocytes
Proleolytic enzymes produced by neutrophils and macrophages which degrade collagen and extracellular matrix.
hint: [mnemonic] LPCELPGA
lysozyme, protease, collagenase, elastase, lipase, proteinase, gelatins, and acid hydrolyses.
Stages of phagocytosis
A, Opsonization of the particle.
B, Pseudopod engulfing the opsonized particle.
C, Incorporation within the cell (phagocytic vacuole)
and degranulation.
D, Phagolysosome formation after fusion of lysosome of the cell.
[recognition and attachment] Phagocytosis is initiated by the expression of surface receptors on macrophages which recognize microorganisms: __________ and __________
mannose receptor and scavenger receptor
[recognition and attachment] The process of
phagocytosis is further enhanced when the microorganisms are coated with specific
proteins called:
Opsonins
[recognition and attachment] establish a bond between bacteria and the cell membrane of phagocytic cell.
Opsonins
After a particle is bound to phagocyte receptors, extensions of the cytoplasm
(pseudopods) flow around it, and the plasma membrane pinches off to form a vesicle
(phagosome) that encloses the particle. The phagosome then fuses with a lysosomal
granule, resulting in discharge of the granule’s contents into the phagolysosome.
Engulfment
[killing and degradation] The microorganisms being killed by antibacterial substances are degraded by _________.
Hydrolytic enzymes
[T or F] The substances acting as chemical mediators of inflammation may be released from the cells, the plasma, or damaged tissue itself.
True
The substances acting as chemical mediators of inflammation is broadly classified into to groups, this are:
mediators released by cells
mediators originating from plasma
Cell-derived mediators
- Vasoactive amines (Histamine, 5 hydroxytryptamine, neuropeptides)
- Arachidonic acid metabolites (Eicosanoids)
• Metabolites via cyclo-oxygenase pathway (prostaglandins, thromboxane A2, prostacyclin
resolvins)
• Metabolites via lipo-oxygenase pathway (5-HETE, leukotrienes, lipoxins) - Lysosomal components (from (PMNs, macrophages)
- Platelet activating factor
- Cytokines (IL-1, TNF-a, TNF-B, IFN-ɣ, chemokines)
- Free radicals (Oxygen metabolites, nitric oxide)
Plasma-derived mediators (Proteases)
Products of:
- The kinin system
- The clotting system
- The fibrinolytic system
- The complement system
[T or F] The cells participating in acts and chronic inflammation are stationary leukocytes, plasma cells and tissue macrophages.
False - circulating
Commonly called as neutrophils or polymorphs
Polymorphonuclear Neutrophils (PMNs)
Contain granules in their cytoplasm (contains proteases, myeloperoxidase, lysozyme,
esterase, aryl sulfatase, acid and alkaline phosphatase, and cationic proteins.
Polymorphonuclear Neutrophils (PMNs)
These cells comprise 40-70% of circulating leukocytes and their number is increased in
blood (neutrophilia) and tissues in acute bacterial infections
Polymorphonuclear Neutrophils (PMNs)
Functions:
✓ “Initial phagocytosis” of microorganisms as they form the first line of body defense in
bacterial infection.
✓ “Engulfment” of antigen-antibody complexes and non-microbial material
✓ “Harmful effect” of neutrophils in causing basement membrane destruction of the
glomeruli and small blood vessels.
Polymorphonuclear Neutrophils (PMNs)
These are larger than neutrophils but are fewer in number, comprising 1-6% of total blood
leukocytes
Eosinophils
Granules in the cytoplasm contain a variety of enzymes, of which major basic protein
and eosinophil cationic protein are the most important which have bactericidal and toxic
action against helminthic parasites
Eosinophils
conditions where eosinophils are increased:
✓ allergic conditions;
✓ parasitic infestations;
✓ skin diseases; and
✓ certain malignant lymphomas
comprise about 1% of circulating leukocytes
Basophils (Mast Cells)
These cells contain coarse basophilic granules in the cytoplasm and a polymorphonuclear
nucleus.
Basophils (Mast Cells)
These granules are laden with heparin and histamine
Basophils (Mast Cells)
Have receptors for IgE and degranulate when cross-linked with antigen
Basophils (Mast cells)
Functions:
✓ In immediate and delayed type of hypersensitivity reactions; and
✓ release of histamine by Ig-E sensitized basophils.
Basophils (Mast cells)
Next to neutrophils, these cells are the most numerous of the circulating leukocytes
(20-45%).
Lymphocytes
They have scanty cytoplasm and consist almost entirely of nucleus
Lymphocytes
Function:
✓ In tissues, they are dominant cells in chronic inflammation and late stage of acute
inflammation.
✓ In blood, their number is increased (lymphocytosis) in chronic infections like
tuberculosis.
Lymphocytes
These cells are larger than lymphocytes with more abundant cytoplasm and eccentric
nucleus which has cart-wheel pattern of chromatin
Plasma cells
inflammatory cells normally not seen in peripheral blood.
Plasma cells
[T or F] There is an interrelationship between plasmacytosis and hyperglobulinemia
True
These cells are most active in antibody synthesis
Plasma cells
plasma cells are increased in conditions like:
✓ prolonged infection with immunological responses (e.g. syphilis, rheumatoid arthritis,
tuberculosis);
✓ hypersensitivity states; and
✓ multiple myeloma
This cell system includes cells derived from 2 sources with common morphology, function
and origin
Mononuclear-Phagocyte System (Reticuloendothelial System)
Mononuclear-Phagocyte System (Reticuloendothelial System) is derived from 2 sources. What are they?
Blood monocytes
Tissue macrophages
These comprise 4-8% of circulating leukocytes
Blood monocytes
[Mononuclear-Phagocyte System (Reticuloendothelial System)] source of the cell system which includes the following] • Macrophages in inflammation • Histiocytes in connective tissues • Kupffer cells in liver cells • Alveolar macrophages in lungs • Osteoclasts in the bones • Microglial cells of the brain • Langerhans’ cells/dendritic histiocytes of the skin • Mesangial cells of glomerulus
Tissue macrophages
These are the scavenger cells of the body as well as participate in immune system of the body
Mononuclear-Phagocyte System (Reticuloendothelial System)
Functions:
✓ Phagocytosis
✓ Macrophages on activation by lymphokines
Mononuclear-Phagocyte System (Reticuloendothelial System)
In chronic inflammation, when the macrophages fail to deal with particles to be removed,
they fuse together and form multinucleate ________.
Giant cells
Giant cells observed in inflammation:
✓ Foreign body giant cells
✓ Langhans’ giant cells
✓ Touton giant cells
✓ Aschoff giant cells
Giant cells observed in tumors:
✓ Anaplastic cancer giant cells
✓ Reed-Sternberg cells
✓ Giant cell tumor of the bone
