Inflammation and Repair (Schoenwald) Flashcards
In degeneration, what are two reversible cellular responses to injury?
1) Cellular swelling (proteinaceous)
2) Fatty degeneration (fatty change in organ or cell, steatosis: i.e. fatty liver)
Define atrophy
Catabolic metabolism of cell, not immediately lethal to cell. Cell/organs shrink with or w/o accumulation of metabolic products
What can cause symmetric atrophy?
Old age
Reduced blood supply
Causes of asymmetric atrophy
- Decreased workload
- Nutritional deficiencies
- Neuro endocrine
- Chronic low-level injury (radiation, chemical toxins)
What is defined as symmetric atrophy of the entire body? (Can be caused by tumors, AIDs, TB)
Cachexia
What are two major purposes of apoptosis (programmed cell death)? What cell type is involved in the “clean up” after apoptosis?
1) natural cell turnover in development and aging
2) disposal of damaged or dysfunctional cells
- Macrophages clean up degraded cellular material
What process follows irreversible cell and tissue injuries?
Necrosis
What is the difference between coagulative necrosis and liquefaction necrosis?
Coagulative: tissue with normal protein content
Liquefaction: tissue poor in protein (brain and fat)
Autolysis involves ____-digestion, while ______ involves digestion of adjacent cells and tissues by enzymes released from ________ cells.
Autolysis involves self-digestion, while heterolyis involves digestion of adjacent cells and tissues by enzymes released from dying cells.
5 common causes of necrosis
1) Ischemia
2) Trauma
3) Toxin
4) Infection
5) Immunologic factors
Local changes of inflammation include _______ and ________ _________.
Local changes of inflammation include vasodilation and vascular permeability.
________ is the process that allows for WBC accumulation at the site of injury/inflammation.
Chemotaxis
Acute inflammation:
1) onset and duration
2) characterized by _______ fluid and ________
3) main cell type involved
Acute inflammation:
1) rapid onset, lasts minutes to days
2) characterized by exudative fluid and protein
3) Neutrophils are main cells involved
What are the 4 cardinal signs of acute inflammation?
1) Rubor- redness
2) Calor- heat
3) Dolor- pain
4) Tumor- mass effect
What are 6 causes of acute inflammation?
1) infection
2) trauma
3) physical/chemical agents
4) necrosis
5) foreign bodies
6) immune reactions
What are 3 mediators released by cells in acute inflammation that cause vasodilation? How do they work?
Histamine, prostacyclin, nitric oxide
Increases hydrostatic pressure by slowing blood flow–> causing margination of leukocytes along the vessel wall
What cell mediators are released causing vascular permeability in acute inflammation?
Histamine and leukotrienes
Increased leakiness of vessels caused by release of histamine and leukotrienes allows fluid to cross interstitial tissues —> causing (increased/decreased) protein at interstitial tissue which causes (increased/decreased) osmotic pressure in blood and (increased/decreased) osmotic pressure in tissue.
==>Causing _____ of interstitial tissue
Increased leakiness of vessels caused by release of histamine and leukotrienes allows fluid to cross interstitial tissues —> causing increased protein at interstitial tissue which causes decreased osmotic pressure in blood and increased osmotic pressure in tissue.
==>Causing edema of interstitial tissue
What are 5 mechanisms of increased vascular permeability?
1) endothelial contraction (short lived)
2) endothelial retraction (long-lived)
3) direct endothelial injury
4) Delayed prolonged response (UV light, xray, mild thermal injury)
5) leukocyte mediated damage
In endothelial contraction, what mediators are involved and what is their MOA?
Endothelial contraction:
Histamine, bradykinin, and leukotriene mediated
MOA: acts on postcapillary venules
TNF and interleukin are mediators in what type of mechanism of increased vascular permeability? What is their MOA?
Endothelial retraction
MOA: structural rearrangement of cytoskeleton
What mediates direct endothelial injury in order to increase vascular permeability? What vessels are affected and what is the MOA?
Direct endothelial injury:
Bacterial enzyme mediated
ALL vessels are affected
MOA: endothelial cell necrosis
What are 3 types of movement of WBCs from blood vessels to the site of inflammation?
1) Rolling: loose, intermittent contact of WBC with endothelium. Due to margination of WBC from stasis of blood
2) Pavementing: tight, constant contact of WBC with endothelium
3) Transmigration: WBC cross through endothelial layer. Platelet cell adhesion molecule mediated
Leukotrienes and IL-8 are exogenous/endogenous mediators while bacterial polysaccharides are exogenous/endogenous mediators in chemotaxis.
Leukotrienes and IL-8 are endogenous mediators while bacterial polysaccharides are exogenous mediators in chemotaxis.
________ are particles that bind to foreign material for WBC recognition. What are 3 mechanisms they use?
Opsonins
1) IgG-FC receptor site recognition on WBC
2) C3b (complement)
3) Collectins
Leukocytes recognize foreign particles through _______ detection and _________ receptors.
Leukocytes recognize foreign particles through mannose detection and scavenger receptors.
What are 2 mechanisms WBCs use to kill foreign substances? What chemical substances are involved?
1) Reduced NADPH oxidase: uses 2 oxygen molecules to produce superoxide radical which then converts to hydrogen peroxide –> kills bacteria
2) Myeloperoxidase: converts hydrogen peroxide and halogen (Cl-) to HOCl which causes lipid or protein peroxidation –> breaks down bacterial/invader cell wall
3 types of acute inflammation
1) serous inflammation
2) fibrinous inflammation
3) purulent inflammation
________ inflammation is typically seen in viral infectons and burns while _________ inflammation is seen with bacterial and fungal infections.
Serous inflammation is typically seen in viral infectons and burns while Purulent inflammation is seen with bacterial and fungal infections.
What are some characteristics of serous inflammation?
Serous inflammation:
- relatively clear, watery fluid
- Transudative- few cells, protein poor, specific gravity <1.012
- Viral infections and burns
What are characteristics of fibrinous inflammation?
Fibrinous inflammation:
- finely particulate, thick fluid
- exudative- protein-rich fluid, specific gravity >1.020
- postmyocardial infarction pericarditis
What are characteristics of purulent inflammation?
Purulent inflammation:
- Pus
- neutrophil, protein-rich exudative
- bacterial and fungal infections
What is the term for a walled off collection of pus that can occur in any organ?
Abscess
What are the 4 microscopic layers involved in ulcers?
From superficial to deep:
- fibrin
- neutrophils
- granulation tissue
- fibrosis
What is a fistula? How does it relate to inflammation?
A connection between 2 organs (typically organs with a lumen, i.e. colon, bladder)
-inflammatory process involving full thickness wall of an organ, duct or blood vessel can lead to a fistula. The wall adheres to adjacent organ wall which allows for communication between the two organs
Chronic inflammation results in proliferation of new _______ and _________, production of __________, which leads to __________.
Chronic inflammation results in proliferation of new capillaries and fibroblasts, production of collagen, which leads to scarring.
Acute inflammation is more (neutrophil/leukocyte) mediated and chronic inflammation is (neutrophil/leukocyte) mediated.
Acute inflammation is more neutrophil mediated and chronic inflammation is leukocyte mediated.
Lymphohistiolytic infiltration with increasing fibroblast activity are associated with what type of inflammation? What type of tissue does this typically develop into?
Chronic inflammation
lymphohistiolytic infiltration with increasing fibroblasts–> granulation tissue
Granuloma formation may result from what type of mediated response in chronic inflammation?
T-cell immune response–> granuloma formation (i.e. TB)
What are 4 causes of chronic inflammation?
1) viral
2) persistent microbial infection
3) prolonged exposure to toxin
4) autoimmune dysfunction
Proteases, IL-1, TNF, arachidonic acid metabolites, and nitric oxide (NO) are produced by what type of cells in chronic inflammation?
Activated macrophages
What is a collection of activated macrophages called? These are seen in response to TB, fungal infections, sarcoidosis, foreign materials, and silica exposure
Granulomatous inflammation (granuloma)
What is the difference between regeneration and healing?
Regeneration: complete replacement of damaged cells- NO scar formation. Can occur is skin, GI tract, compensatory tissue of liver and kidney
Healing: regeneration of cells combined with scarring and fibrosis
What are 5 growth factors involved in repair?
1) epidermal growth factor
2) vascular endothelial growth factor
3) platelet derived growth factor
4) fibroblast derived growth factor
5) transforming growth factor -B
Match the growth factor with its function:
1) Epidermal growth factor, 2) Vascular endothelial growth factor, 3) Platelet derived growth factor, 4) Fibroblast derived growth factor, 5) Transforming growth factor -B
a: stimulates blood vessel formation and wound repair through macrophages, fibroblast, and endoethelial cell migration
b: induces blood vessel formation
c: acts as growth inhibitor for epithelium
d: stimulates granulation tissue formation
e: promotes migration and proliferation of smooth muscle cells
1) Epidermal growth factor- d: stimulates granulation tissue formation
2) Vascular endothelial growth factor- b: induces blood vessel formation
3) Platelet derived growth factor- e: promotes migration and proliferation of smooth muscle cells
4) Fibroblast derived growth factor- a: stimulates blood vessel formation and wound repair through macrophages, fibroblast, and endoethelial cell migration
5) Transforming growth factor -B- c: acts as growth inhibitor for epithelium
What are 4 requirements of replacement by a scar?
1) angiogenesis
2) migration and proliferation of fibroblasts
3) deposition of extracellular matrix
4) maturation and reorganization of fibrous tissue
Time frame for a scar:
______ = granulation tissue
________ = collagen deposition continues
______= inflammatory infiltrate absent and collagen starts to strengthen
Time frame for a scar:
3-5 days = granulation tissue
Week 2 = collagen deposition continues
1 month = inflammatory infiltrate absent and collagen starts to strengthen
Healing by _(_primary/secondary) intention involves healing of a wound with clean edges, close margins, and minimal tissue disruption. This leaves a (small/large) scar.
Healing by primary intention involves healing of a wound with clean edges, close margins, and minimal tissue disruption. This leaves a small (to nonexistent) scar.
Healing by (primary/second) intention involves a wound with unclean edges, extensive tissue disruption and necrosis. It results in a (small/large) scar. Debridement is usually necessary for healing.
Healing by second intention involves a wound with unclean edges, extensive tissue disruption and necrosis. It results in a large or prominent scar. Debridement is usually necessary for healing.
True/False: A fully healed wound is just as strong as normal skin
False: Fully healed wounds will never be as strong. They are about 2/3rd the strength of normal skin
What are 5 factors that impair wound healing?
1) Nutritional deficiency (protein, Vit C)
2) Infection
3) Steroid therapy
4) Poor blood flow
5) Pressure
