0
Q
Monocytes & Macrophages
A
- monocytes->immature form of white blood cells in blood
- macrophages-> the mature cell in the tissues
- monocytes:
- largest normal cells & have a nucleus that is intended or horseshoe shaped
- produced in bone marrow, enter circulation, and migrate to inflammatory sites
- precursors of macrophages that are in fixed tissues
- Macrophages:
- larger and more active as phagocytes than their monocytic precursors
- enter to injury site 24 h after, or later & replace neutrophils
- better than neutrophils, more of a long term affect
- can divide and multiply in acidic inflammatory response
- orchestrate wound healing process by cleaning up site of injury by phagocytosis, promoting angiogenesis, releasing cytokines & growth factors to promote epithelial cell division, activating fibroblasts, & promoting synthesis of extracellular & collagen formation
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Q
Neutrophils
A
- member of WBC
- first phagocytic cells to arrive at site of tissue injury, usually 6-12 h
- bacteria components, C3a, C5a, and mast cell neutrophil chemotactic factor rapidly attract neutrophils from circulation & activate them
- they ingest bacteria, dead cells, and cellular debris and remove them from the area
- also release inflammatory mediators that participate inflammatory response: free oxygen radicals, proteolytic enzymes, arachidonic acid metabolites, and platelet activating factors
- it is short lived at the inflammatory site becomes a component of purulent exudate–>moved through the body through epithelium or drained from the infected site via lymphatic system
- primary role is removal of debris and dead cells in sterile lesions,such as burns, and destruction of bacteria in non-sterile lesion
- it is mature cell that is incapable of division and sensitive to acidic environments, it is short lived at the inflammatory site
2
Q
Macrophages-part 2
A
- some bacteria are resistant to killing of granulocytes & can survive in macrophages
- ex: TB, mycobacteriumleprae (leporasy), Salmonella typhi (typhoid fever), Brucella abortus (brucellosis) & listeria monocytogenes (listeriosis)
-can remain dormant or multiply inside the phagolysomes of macrophages
3
Q
Eosinophils
A
- 2 functions
- they serve as the body’s primary defense against parasites
- they help regulate vascular mediators released from mast cells
- mildly parasitic
- contain several enzymes that degrade vasoactive molecules–> controlling of the vascular effects of inflammation
- ex: histaminase, and arylsulfatase B which degrades lipid-derived mediators by mast cells
4
Q
Dendritic Cells & T-lymphocytes
A
- dendritic cells provide one of the major links between innate and acquired immune responses
- primary phagocytic cells located in peripheral organs and skin
- migrate through lymphatic vessels–to lymphoid tissues– >interact with T lymphocytes to start an acquired immune response
-T-lymphocytes are active during the proliferative phase of wound healing
5
Q
Phagocytosis
A
- process by which a cell ingests and dispose of foreign material, including microorganisms–> called phagocytes
- 2 most important phagocytes=neutrophils & macrophages
- both cells are already circulating in the blood and have to leave circulation & migrate to site of inflammation before starting phagocytosis
6
Q
Margination/Pavementing & Chemotaxis
A
- margination=when leukocytes & endothelial cells start expressing molecules that increase adhesion or stickiness causing leukocytes to adhere better to endothelial cells in walls of the capillaries
- chemotaxis= once leukocytes have under gone margination, they are attracted to the inflammatory site by chemotactic factors (neutrophils, complement fragement s and products of kinin system)
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Q
Process of Phagocytosis
A
- recognition and adherence of the phagocyte to its target
- engulfment (ingestion or endocytosis)
- formation of a phagosome
- fusion and phagosome with lysosomal granules within the phagocyte
- destruction of the target
- most phagocytes trap and engulf bacteria, but a slow process
- Opsonization enhances adherence by acting as a glue to tighten the affinity of adherence between the phagocyte and target cell
8
Q
Acute Inflammation-local manifestations
A
-self-limiting=continues only until the threat host is eliminated (usually 8-10 days)
- local manifestations: swelling, erythema, heat, redness begin b/c of vascular changes and the subsequent leakage of circulating components in tissue
- exudate:
- serous: water exudate, indicates early inflammation (burns, blisters)
- fibrinous: thick, clotted exudate; indicates more advanced inflammation (pneumonia, more debris, dead neutrophils, thick)
- purulent: pus; indicates bacterial infection (cysts, abcesses)
- hemorrhage: exudate contains blood; indicates bleeding
- exudate:
9
Q
Acute Inflammation-systemic manifestations
A
-Fever: caused by the endogenous and exogenous pyrogens that act directly on the hypothalamus [IL-1, cytokine pieces]
- Leukocytosis: increased number of circulating leukocytes, shift to the left (increases in bands)
- greater than 11,00ml3 in adults
-Increased plasma protein synthesis: acute phase reactance: pro-inflammatory or anti-inflammatory proteins synthesized by the liver
10
Q
Chronic Inflammation
A
- lasts longer than 2 weeks regardless of cause
- often r/t unsuccessful acute inflammatory response
- more macrophages and leukotrienes instead of histamine
- enlarge lymph nodes near site of injury
- Granuloma formation: if macrophages are unable to protect host from tissue damage, the body forms granulomas to wall off and isolate infected areas
- Epithelioid cell formation: takes up debris and other small particles
- Giant cell formation: active phagocytes that engulf large particles, formed by fusion of macrophages
11
Q
Wound Healing
A
- Resolution & Repairing
- Regeneration–> resolution: returning injured tissue to the original structure and function
- Repair: replacement of destroyed tissue with scar tissue (composed primarily of collagen that fills the lesion & restores strength but can’t carry out physiologic functions of destroyed tissue)
- if damage is minor, no complications occur and destroyed tissues are capable of regeneration (resolution). Resolution may not be possible if extensive damage is present. If the tissue is not capable of regeneration, infections result in the abscess or granuloma formation, or if fibrin persists in the lesion, repair takes place (collagen that fills in the lesion and restores strength but cannot carry out physiologic functions of destroyed tissue)
12
Q
Phase 1: inflammation (wound healing)
A
- begins during acute inflammation and usually lasts for 1 to 2 days
- includes coagulation and the infiltration of cells that participate in wound healing including platelets, neutrophils, and macrophages
- the fibrin mesh of blood clots acts as a scaffold for cells that participate in healing
- neutrophils clear the wound of debris & bacteria and later released by macrophages
- platelets contribute to clot formation, and as they degranulate they release growth factors
- macrophages release wound healing mediators and growth factors, recruit fibroblasts, and help promote angiogenesis during the proliferative phase
13
Q
Phase 2: Proliferation & New Tissue Formation
A
- begins 2-3 days after injury and continues for as long as 2 weeks
- the wound is sealed & fibrin clot is replaced by normal tissue or scar tissue during this phase
- proliferative phase is characterized by macrophage recruitment of fibroblasts (connective tissue cells) and fibroblast proliferation, followed by fibroblast collagen synthesis, epithelialization, contraction of the wound and cellular differentiation
- Macrophages invade & dissolve the clot & clear away debris & dead cells to begin wound healing; also secretes biochemical mediators
- transformation growth factor-beta; stimulates fibroblasts entering the lesion to synthesize & secrete the collagen precursor pro-collagen
- angiogenesis factors: such as vascular endothelial growth factor & fibroblast growth factor-2; stimulate vascular endothelial cells to form capillary buds that grow into the lesion; decreased pH & decreased wound oxygen tension also promote angiogenesis
- matirix metalloproteinases (MMPs); degrade & remodel extracellular matrix proteins (collagen & fibrin) at site of injury
-granulation tissue grows into the wound from surrounding healthy connective tissue
14
Q
Phase 3: wound healing
A
-tissue remodeling and maturation begins several weeks after injury and normally completed in 2 years
-during this phase, there is continuation of cellular differentiation , scar formation, and scar remodeling
-the fibroblasts is the major cell of tissue remodeling w/the deposition of collagen into organized matrix
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15
Q
Dysfunctional wound healing
A
-may occur during any phase of the wound healing process
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16
Q
Hypertrophic Scar
Keloid
A
- hypertrophic scar=raised but remains within the original boundaries of the wound and tends to regress over time
- keloid=a raised scar that extends beyond the original boundaries of the wound, invades the surrounding tissue, and is likely to recur after surgical removal
17
Q
Wound Disruption
A
- dehiscence=wound pulls apart at suture line, caused by excessive strain, obesity, etc
- increases risk of sepsis
- usually occurs 5-12 days suturing, when collagen synthesis is at its peak
- usually is heralded by increased serous drainage from the wound and patients perception that “something gave way”=
18
Q
Impaired Contraction
A
- wound contraction may become pathological when contraction is excessive, resulting in a deformity or contracture of scar tissue
- contractures, especially at joints
19
Q
Dysfunction during reconstructive phase
A
-impaired collagen matrix assembly: excessive production of collagen, causing surface over healing, leading to hypertrophic scar or keloid
- impaired epithelialization:
- anti-inflammatory steroids: prevent macrophages from migrating to the site of injury and inhibit release of collagenase and plasminogen activator, also inhibit fibroblast migration into the wound during proliferative phase
- Hypoxemia: makes wound susceptible to infection & delays wound healing
- Nutritional deficiencies
- Medications: delay wound healing, slow cell division and angiogenesis
- healing prolonged if there is excessive bleeding
- excessive fibrin deposits: detrimental to healing, fibrin is released in response to injury and must be reabsorbed to prevent organization into fibrous adhesions, adhesions formed in the pleural, pericardial, or abdominal cavities can bind organs together by fibrous bands and distort or strangulate the affected organ
20
Q
Dysfunction during inflammatory response
A
- wound sepsis: delays wound healing
- hypovolemia: vessel constriction rather than dilation to deliver inflammatory cells to the site of injury
- hypoproteinemia: inhibits fibroblasts proliferation and collagen synthesis
- anti-inflammatory: steriods
- hemorrhage: clots increase the amount of space that granulation tissue must fill and serve as a mechanical barrier to oxygen diffusion. Accumulated blood is a good culture medium for bacteria and promotes infection
- fibrous adhesion
- infection
- excessive scar formation
- diabetes, malnutrition, drugs (steriods), NSAIDs, tobacco smoke, HIV
Patho-class 4-inflammation
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