Pathology Flashcards
What is the definition of inflammation?
a well organized cascade of fluid and cellular changes within vascularized tissue; host response to remove damaged/necrotic tissue or foreign invaders
What are the 5 cardinal signs of inflammation?
Heat
Redness
Swelling
Pain
Loss of function
How is inflammation part of the process of repair and healing?
destroys, dilutes or wall off injurious agents
initiates healing and tissue repair
How is inflammation a protective response?
It gets rid of pathogens
Removed nectrotic debris (phagocytosis
Repair the damage= return to normal structure/function
What are the types of inflammation?
Acute and Chronic
What are the characteristics of acute inflammation?
short duration (minutes to days)
exudation of fluid & plasma protein (edema)
emigration of leukocytes (mostly neutrophils)
What are the characteristics of chronic inflammation?
Longer duration (days to years)
Macrophages & lymphocytes
Proliferation of blood vessels & connective tissue
What are the 3 main components of acute inflammation?
1) vascular alteration leading to increased blood flow (hyperemia)
2) Changes in microvasculature permeability that allow plasma proteins & leukocytes to leave the circulation
3) Emigration of leukocytes into the perivascular area
What are the stimuli for acute inflammation?
Infections
Trauma
Physical & chemical agents
Tissue necrosis
Foreign body
Immune reactions
What is exudate and when does it form?
inflammatory extravascular fluid with:
high protein concentration (> 5 g/dL)
high cell content (> 5000 leukocytes/mL)
specific gravity >1.020
Formed when there is significant alteration in small blood vessel permeability at the site of injury (increased interendothelial spaces)
What is transudate and when does it form?
extravascular fluid with:
low protein concentration (< 2 g/dL)
low cell content (< 1500 leukocytes/mL)
specific gravity <1.012
Formed due to an ultrafiltrate of blood from either increased hydrostatic pressure or decreased oncotic pressure
What is edema?
accumulation of fluid in interstitial or serous cavities
What are the 4 main mechanisms that result in edema?
1) increased vascular permeability
2) increased intravascular hydrostatic pressure
3) decreased intravascular osmotic pressure
4) decreased lymphatic drainage
What is pus?
a purulent exudate rich in leukocytes (mostly neutrophils) and cell debris
What are some vascular changes in acute inflammation?
Vasodilation involves arterioles first, then results in opening new capillary beds
Increased permeability of microvasculature
loss of fluid results in concentration of RBCs in small vessles, increased blood viscosity & blood stasis
What are the 4 mechanisms for vascular leakage?
1) endothelial contraction
2) direct endothelial injury
3) leukocyte-dependent injury
4) increased transcytosis
What are the endothelial changes involved in contraction?
It increases in interendothelial space
It is mediated by histamine, bradykinns, leukotrienes
Rapid and short-lived
Occurs mainly in venules
Induced by histamine and NO
What are the endothelial changes associated with direct injury?
Direct damage to endothelium causes necrosis & detachment
Starts immediately, lasts until thrombosis occurs or endothelium repaired
Rapid and may be long lived
Occurs in arterioles, capillaries, venules
Caused by burns, & some microbial toxins
What are the endothelial changes associated with leukocyte-mediated injury?
Activated leukocytes may secrete free radicals & proteolytic enzymes, leading to cell damage
Occurs in venules, pulmonary capillaries
Associated with late stages of inflammation
Long lived (hours)
What are the endothelial changes associated with transcytosis?
Increased transport of fluid & protein through endothelial cells occurs in venules
What are the vasoactive amines?
Histamine
Seratonin
What are the arachidonic acid metabolites?
Nitric oxide (NO)
Cytokines
What are the plasma derived mediators?
Complement system
How is histamine presented?
Is a performed state in mast cells, basophils & platelets in cytoplasmic granules
Where are chemical mediators of inflammation formed?
Preformed in secretory granules within cells
Newly synthesized within cells
Liver
What are the actions of histamines?
Dilation of arterioles
Increased vascular permeability of venules which causes endothelial contraction
What is seratonin released in response to?
Platelet aggregation
How is arachidonic acid metabolites formed?
By the degradation of cell membrane phospholipids by phospholipases
What is a product of the arachidonic acid pathway and what do they do?
Eicosanoids which regulate inflammation and hemostasis
What are the two primary classes of inflammatory metabolites produced by eicosanoids?
Prostaglandins
Leukotrienes
What do corticosteroids do to the arachidonic acid pathway?
Inhibits phospholipases & the production of arachidonic acid
What produce prostaglandins?
Cyclooxygenases
What is lipoxygenase and what does it produce?
It is an enzyme that produces leukotrienes & lipoxins from arachidonic acid
What synthesizes nitric oxide (NO) and what produces it?
Synthesized by nitric oxide synthase and is produced by endothelial cells, macrophages, & neurons
What are the 2 functions of NO?
Vasodilation
Inhibits cellular inflammatory responses
How does NO inhibit the inflammatory response?
Inhibits leukocyte recruitment & migration
What can nitric oxide derivatives become and what do they do?
They become free radicals and kill microbes
What do cytokines primarily do?
Modulation of activities of other cells
What are the main cytokines involved in acute inflammation?
IL-1 & TNF
What are the local effects of IL-1 and/or TNF on vascular endothelium?
Expression of leukocyte adhesion molecules
Production of IL-1, chemokines
Procoagulation
Decrease anticoagulant activity
What are the local effects of IL-1 and/or TNF on leukocytes?
Activation of leukocytes
Production of cytokines
What are the local effects of IL-1 and/or TNF on fibroblasts?
Increase collagen synthesis
What are the systemic effects of IL-1 and/or TNF?
Fever
Leukocytosis
Increase acute-phase proteins
Decrease appetite
Increase sleep
How is complement used as a defense against microbes?
It forms the membrane attack protein which is like sticking a straw into a cell
What does the activation of complement cause?
Increased vascular permeability
Chemotaxis
Opsonization
What causes the activation of the classical complement pathway?
Reaction with IgG or IgM containing antigen-antibody complex
What causes the activation of the alternative complement pathway?
Contact with microbial surfaces & polysaccharides
What causes the activation of the lectin complement pathway?
Plasma mannose-binding lectin binds to microbes
What is the initial steps in complement activation lead to?
1) formation of C3 convertase which cleaves C3
2) Release of C3a
3)Covalent attachment of C3b which initiates formation of C5 convertase
4) formation of C5-9 (MAC)
What does C3a + C5a do?
Facilitate histamine release from mast cells (anaphylatoxins)
Vasodilation, increase permeability
What does C3b do?
Act as opsonis when fixed to bacteria; facilitate phagocytosis by neutrophils & macrophages (receptor)
What are the 3 possible outcomes for acute inflammation?
Complete resolution
Healing by connective tissue replacement (fibrosis)
Progression to chronic inflammation
What are the 4 morphological patterns of acute inflammation?
Serous inflammation
Fibrinous inflammation
Suppuration inflammation
Ulcers
What are the characteristics of serous inflammation?
Thin watery fluid derived from plasma mesothelioma cells
These mesothelial cells line the peritoneum, pleura, & pericardium
Fluid in these 3 cavities are called effusion
What are the characteristics of fibrinous inflammation?
Accumulation of fibrin
Usually found in body cavity linings
If fibrin is not removed it can lead to fibrosis
What are the characteristics of pus/purulent exudate?
Neutrophils, liquefactive necrosis, edema
What are the characteristics of ulcers?
Local defect or excavation of the surface of organ or tissue
What is the difference between an erosion and ulcer?
Erosion are superficial and do not go below the basement membrane
Ulcers go below the basement membrane or can go straight through and make a hole
