LESSON- 1 INFLAMMATION Flashcards
(133 cards)
1
Q
is a complex dynamic response of tissues to damaging (noxious) stimuli.
A
Inflammation
2
Q
It is a basic component of many disease processes
A
3
Q
An inflammatory stimulus may be
A
physical
biological
chemical
4
Q
comprises interrelated vascular and cellular changes in affected tissues, which are aimed at removing or neutralizing the offending stimulus, and repairing injured tissues.
A
Acute inflammation
5
Q
The response under such circumstance may then produce damage, which may constitute a disease process
A
(e.g. anaphylaxis, autoimmune hemolytic anemia and lupus erythematous)
5
Q
The acute inflammatory reaction has two main components:
A
(a) Innate non-immunological, and
(b) Acquired immunological
5
Q
Signs of Acute Inflammation
A
PAIN
ALTERED FUNCTION
redness
increased temperation
swelling
6
Q
Components of Inflammatory Reaction
A
- An innate non-immunological response
-Vascular events
-Cellular events - The acquired specific immune response
7
Q
Circulating neutrophils initially adhere to the swollen endothelial cells
A
margination
8
Q
then actively migrate through the basement membrane vascular epithelium, passing into the area of tissue damage
A
emigration
9
Q
Later, small numbers of blood —
migrate in a similar way.
A
monocytes (or macrophages) and lymphocytes
10
Q
This migration process, called
A
chemotaxis
11
Q
is caused by the attraction of leukocytes to chemical substances (—- ) produced in the site of tissue damage.
A
chemotoxins
12
Q
Functions of Acute Inflammation
A
- To dilute the offending noxious stimuli
(weakens the enemies)
2.To eliminate damaging agents
(gets rid of the enemies)
3.Removal of inflammatory tissue debris
(cleans up the battlefield)
13
Q
These events however constitute a continuum of inflammatory events of the cells involved in the inflammation some
- are normally present in tissues while
A
-vascular endothelial cells, —mast platelets, and
- tissue macrophages
14
Q
gain access into the tissue from the blood.
A
platelets, and leukocytes
15
Q
During inflammation the endothelial cells of the small arterioles are “activated” to secrete:
A
a. Nitric oxide (NO) and prostacyclin
b. Endothelin, plasminogen activator
c. express intercellular adhesion molecules (ICAM)
16
Q
leukocytes are classified into:
A
(a) Polymorphonuclear cells (neutrophils, basophils and eosinophils), and
(b) Mononuclear cells (monocytes and lymphocytes).
17
Q
Endothelial cell function also involved in
A
angiogenesis (formation of new blood vessels
18
Q
angiogenesis occur
A
wound repair,
chronic inflammation
cancer
19
Q
are characterized by having nuclei with varying shapes (banded, lobed or segmented).
A
Polymorphonuclear cells (PMNs)
20
Q
are the first of the leukocytes to enter the area of inflammation – the “first line” of defense
A
neutrophils
21
Q
but are predominantly found in tissues rather than in the circulating blood.
A
Mast cells
22
Q
Like neutrophils, they also adhere to endothelium, and migrate into the tissue in response to specific chemotaxic substances
A
chemokines
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. Mast cell’s membrane contains surface receptors for both
- immunoglobulin E (IgE)
- for complement components C3a and C5a
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Involved primarily in blood coagulation,
also play a role in inflammation
Platelets
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the neutrophils used to be called macrophages,
little eaters
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Other substances released by mast cells include:
(a) Heparin or (heparan)
(g) Peroxidases
(i) Prostaglandins
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in inflamed areas release inflammatory neuropeptides when appropriately stimulated. Type C and Aծ fibers transmit pain impulses to the central nervous system.
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In the tissue, monocytes are transformed into macrophages (literally
“big eaters”,
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Platelet-derived growth factor contributes to the repair processes following tissue damage.
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enter the area of inflammation at a later stage, several hours after the polymorphs
monocytes
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platelets also called
thrombocytes
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They kill target cells of NK
- virus-infected cells and - ----cancer cells that lack the major histocompatibility complex (MHC) molecules
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cells are specialized lymphocytes that are active in non-immunological reactions.
Natural killer (NK)
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The inflammatory exudate is composed of
fluids, electrolytes, proteins, cellular elements and some inflammatory mediators
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Components of Exudate
Fluid
Fribin
Neutrophils
Macrophages
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containing salts and high concentration of proteins including immunoglobulins
fluid
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from the white blood cell population
neutrophils
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which are phagocytic cells derived from blood monocytes, and
A few lymphocytes
macrophages
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in the acute inflammatory exudates carries nutrients, mediators and immunoglobulins.
fluids
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may dilute or buffer any locally produced toxins
fluids and salt
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Can diffuse into the area of inflammation to support the macrophages.
glucose and oxygen
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The fluid is constantly circulating to the local lymph nodes and assists in later development of a
specific immune response
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Immunoglobulins in the exudates may act as
opsonins
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main groups of lymphocytes
B- cell
t-cells
natural killers cells
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Responsible cell-mediated immune reactions
t cells
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Responsible for body production- the humoral immune response
b cells
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Specialized non-T and non-B lymphoid cells that are active in non-immune innate response
natural kiler cells
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The antigenic molecules are presented to the lymphocytes by the
antigenic-presenting cells
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This phase involves how the cells, which are produced in the induction phase, act to eliminate antigens. This action may be
cell mediated
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The production of --- during first exposure to antigen greatly accelerates and makes more effective the immunological response to subsequent exposure.
memory cells
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Antibodies or immunoglobulins have two functions;
- to recognize and interact
- activate one or more. host defense system
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The tissue reacts through vascular and cellular changes. These changes are mediated by substances, which are collectively called .
autocoids
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are substances present in the body and act near the sites of their synthesis. They are sometimes called
local hormones
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derived from the amino acid histidine
histamine
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which the blood of animals is relatively histamine
Goat and Rabbits
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the of this animals is low in histamines
blood of horse, dog cat and rat
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neurons in the brain.
histaminergic
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Non-mast-cell histamine is secreted by --- in the stomach
histaminocytes
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activates phospholipase C in the mast cell membrane, which catalyzes the breakdown of membrane phospholipids
antigen-antibody complex
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Histamine is stored mainly by mast cells, which are abundant in the
gastrointestinal mucosa, bronchial mucosa, and skin.
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histamine is released as a result of interaction of the
antigen and the antibody IgE
on the surface of mast cells (or basophils
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Some physiological roles of histamine
Histamine secreted by histaminocytes in the stomach regulates gastric acid secretion (excessive secretion causes hyperacidity and ulceration)
Histamine secreted by histaminergic neurons in the brain act as neurotransmitter in the CNC (involved in motion sickness)
Histamine secreted by mast cells acts as mediator of early inflammatory reactions
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Intradermally injected histamine produces the so-called
triple response
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triple response to histamine
reds spot
flare
wheal
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A few millimeters around the site of injection is due to immediate direct vasodilator effect of histamine.
Red spot
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A bright red irregular outline from the original red spot due to reflex dilatation of the adjacent small vessels.
flare
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A localized edema due to leakage of plasma fluid through the abnormality permeable walls of the small blood vessels.
wheal
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histamine also causes
not pain
pruritis
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Mediates most inflammatory and are antagonized by the classical anti-histamine
h1
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selective antagonist of H1
Mepyramine
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Has a role in gastric acid secretion; an action blocked by specific H2 antagonists
H2
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H2 Selective Antagonist
Cimetidine
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1. Prevent release of histamine by inhibiting the responses of sensitized cells basophils to specific antigen.
what drugs use ?
Epinephrine
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Description is still incomplete
H3
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selective antagonist of H3
Thloperamide
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The vasodilation and increased vascular permeability in response to histamine is mediated by both
H1 and H2 receptors on mast cells and basophils
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2. Physiologically antagonize histamine effects. drugs use?
epinephrine
Theophylline
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is poorly absorbed from the gut, and is usually given inhalation as nebulized solution or powder
cromolyn sodium
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is better absorbed than cromolyn sodium.
nedicromyl
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These xanthine derivatives are bronchodilators used in the management of attack of bronchospasm.
theophylline and aminophylline
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unwanted effect of of Theophylline and aminophylline
anorexia
Nausea and vomiting
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By acting on specific adrenergic receptors,
it causes peripheral vasoconstriction, bronchodilation and cardiac stimulation; effects that counter histamine effects.
epinephrine
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classical or H1 antihistamines are not as widely used in animals as in people because of two reasons:
antihistamines effectiveness in animals and
glucocorticoids are more effective
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the most abundant precursor of eicosanoids (eicosa – 20, may be derived by elongation of dietary linoleic acid (18 carbons), and is usually esterified to second carbon (C2) of cell membrane phospholipids
Arachidonic acid
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The prostaglandins (PG) are also called
prostanoids
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because they share the chemical features of a hypothetical substance 20-carbon prostanoic acid with a five-member cyclopentane ring and two hydrocarbon side-chains.
prostaglandins
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Prostaglandins are not stored in tissues, but are rapidly formed and released when tissue is damaged.
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Two major enzyme systems
use in arachidonic substance
cyclo-oxygenage and lipoxygenase
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Arachidonic acid is converted by cyclo-oxygenase (COX; also called
Endoperoxide
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A constitutive enzyme, which sub serve a number of physiologic role.
cyclooxygenase-1
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are unstable and may be converted to their corresponding hydroxyl fatty acid, known for short
HETE
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is a powerful chemotactic agent for bit neutrophils and macrophages.
It also increase the formation of membrane adhesion molecules and production of toxic oxygen products and release of granules enzyme.
LTB₄
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are rapidly metabolized (bio transformed) in the lungs by prostaglandin dehydrogenase.
Prostanoids, PGE and PGF
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The factors that inhibit prostaglandins dehydrogenase include:
*nitrate
*IRRADIATION
*bacterial Endotoxins
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are a heterogeneous group of compound which are often chemically unrelated.
Non-steroidal Anti-inflammatory Drugs
(NSAID)
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is converted to 20-hydroxy LTB₄ by special membrane-bound P450 enzyme, which occur in neutrophils
Leukotrienes LTB₄
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NSAID’s are used as:
analgesic
antipyretic
anti inflammatory
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is used to reduce thromboembolus (intravascular clot) formation associated with heartworm disease in dog and with hypertrophic cardiomyopathy in cats.
aspirin
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The prototype of these agents is aspirin, hence they are also called
aspirin like drugs
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are used systemically in the management of non-ulcerative keratitis (inflammation of cornea) in the horse.
Flunixin and Phynebutazone
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Elimination is most rapid in herbivores, slowest in carnivores and intermediate in omnivores
aspirin
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* Similar to aspirin, but less commonly used
* Do not use in animals less than 30 days old.
sodium salicylate
67
Used externally as a counter-irritant.
oil of wintergreen
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* Recommended in horses for treatment of inflammatory conditions involving pain and lameness, such as “tying up” syndrome
naproxen
68
* A simple derivative of phenylpropoinic acid
* Metabolized in the liver and may cause gastrointestinal irritation and bleeding but less frequently than with aspirin.
Ibuprofen
69
* Inhibits both the cyclooxygenase and some lipoxygenase.
ketoprofen
70
* Usually not included with NSAIDs for it is devoid of anti-inflammatory effects but retains antipyretic and analgesic effects
paracetamol
71
* Used to treat acute or chronic osteoarthritic disease in the horse and chronic musculoskeletal disease in the dog, slow onset action
meclofenamic acid
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* Effective for the most colic cases excluding severe bowel distension or displacement.
* Useful in treatment of endotoxin shock
flunixin maglumine
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* Not to be given in dogs of fetal effect
* In horsed it causes CNS disorder
indomethacin
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* Frequently beneficial in the treatment of soft-tissue or non-articular rheumatism including capsulitis, laminitis and bursitis.
* Most widely used in horses
phenylbutazone
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* Widely used to treat equine colic and other condition of GI spasm or hypermobility in both large and small animals
Dipyrone
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* Inhibits chondrocyte and synoviacyte synthesis of PGE₂
entodoplac
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* It is a metabolite phenylbutazone has similar properties as phenylbutazone
oxyphenbutazone
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* Rapidly absorbed in the stomach and reaches 80% of its peak plasma concentration in 1 hour
* The long half-life (45 h) of his compound permits once a day or longer dosing interval
piroxicam
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* A new NSAIDs similar to Ibuprofen, specifically used to treat arthritis in dog.
caprofen
80
is a polar lipid released from leukocytes and causes platelets to aggregate
Platelets activiting factors
81
are polypeptide production released by connective tissue and activated lymphocytes and monocytes.
cytokines
82
oxide is a small molecule that is locally synthesized by endothelium and macrophage through the activity of the enzyme, nitric oxide synthesis.
nitric oxide
83
is a nonpeptide
brachykinin
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has an additional lysine and amino terminal.
kallidin
85
are activated by protease enzyme kallikrein.
kinins
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initially activated on exposure to collagen, cleave pre-kallikreins into active kallikreins.
factor XII (Hageman factor)
87
has been used in treatment of acute pancreatitis and carcinoid syndrome
aprotinin
87
Bradykinin acts on at least three types of receptors:
1. B1
2. B2, and
3. B3
88
Complement can be activated either by:
1. The Classical Complement Activation Pathway or
2. The Alternative Complement Activation Pathway
88
is a collective term referring to heat labile factor in the extra cellular fluids
complement
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* This dissociation is regulated by a serum protein called
which acts to stabilize the C3bBb complex
properdin
89
is initiated by activation of Hageman factor (Factor XII).
blood clotting
90
The best “anti-inflammatory” agent in such clinical setting
heparin ( anti coagulant )
91
derived from endothelium by the action of bradykinin generates plasmin, a thrombolytic enzyme.
plasminogen activator
