Introduction to Inflammation

inflammation

local response to tissue injury (exogenous and endogenous injurious agents)

causes of inflammation

- physical agents
- chemical substances
- microbial infections
- tissue necrosis

Celsus signs

heat, swelling, redness, pain, loss of fxn

vascular rxn to inflammation

accumulation of fluid in extravascular space

cellular rxn to inflammation

migration and activation of leukocytes

systemic rxns to inflammation

regeneration + scarring

triple response injury

flush (cap dilation), flare (arterial dilation) + wheal (edema)

Phases of inflammation

1. tissue injury
2. Vasodilatation and exudation
3. Proliferative phase

Tissue injury phase

reversible or irreversible lesions upon to a cell, a tissue or an organ

exogenous causes of tissue injury

- mechanical, physical, chemical, foreign bodies
- infectious organisms
- exo/endotoxins
- immune mechanism

endogenous causes of tissue injury

- tissue necrosis, enzymes activation
- immune-mediated processes
- storage of substances

Proteolysis from tissue injury causes

metabolite storage, release of chem mediators, activation of coag. system and self-antigen formation

Storage of metabolites due to tissue injury leads to

acidosis, hyperionia (K+ ), hyperosmosis

release of chemical mediators due to tissue injury from _________, ________ and ___________ leads to :

from neural terminations, platelets and mast cells vascular reaction

Vasodilatation and exudation stage breaks into 3 parts

1. vascular rxn
2. formation of the inflammatory exudate and
phagocytosis
3. migration of neutrophils and bacterial phagocytosis

Vascular rxn of Vasodilatation and exudation stage

- arterioles + arteries - catecolamines cause spasm (vasoconstrict), serotonin releases -> paralytic dilation
- capillaries - stasis -> poststasis
all leads to hyperemia and cap congestion

exudate vs. transudate

Exudate
- extravascular fluid with high protein content and cellular debris (implies increased permeability and therefore inflammation)

Transudate
- extravascular fluid with low protein content, little to no cellular debris (no increased permeability and therefore NO inflammation)

Formation of the inflammatory exudate of Vasodilatation and exudation stage

Hyperionia, hyperosmosis, acidosis (h20 exudate) and Increasing of vascular permeability (serum+plasma exudate and leukodiapedesis)

Phagocytosis of Vasodilatation and exudation stage

Migration of neutrophils and monocytes

Secondary lymph vessels involvement (lymphangitis, lymphadenitis, lymphadenopathy) occurs in what stage of inflammation?

Vasodilatation and exudation stage

How does neutrophil migrate and bacteria is phagocytosed in the Vasodilatation and exudation stage

neutrophil ingests bacterium (in a phagosome), lysosomes fuse w/ vacuole and enzymes digest bacterium, bacterial debris released

Chemical mediators of vasodilatation

histamine, noradrenaline (a. spasm), serotonin, chemokines, anaphylatoxins, complements, prostaglandins

Chemical mediators of chemotaxis (exo + endogenous)

bacterial peptides (exo)
plasma and cell factors, lysosomal enzymes, lymphokines

Proliferative phase

repair of injured tissue

Early proliferative phase

granulation tissue forms, exudate removed, immunocompetent cells activated, migration of macrophages and fibroblasts, proliferation of the capillaries

Late proliferative phase

connective scar forms, proliferation of fibroblasts + connective fibers, decreasing # immunocompetent cells + capillaries

Acute inflammation

initial response of tissue to injury, rapid onset, pain + fever, leukocytosis, neutrophils migrate + edema + tissue injury

spread of acute inflammation

1. direct
2. into cavities
3. canalicular - asc/desc
4. into blood
5. into lymph vessels

healing of acute inflammation

regeneration
complete resolution (restoration)
reparation - fibrosis

Chronic inflammation

prolonged tissue reactions following the initial response, proliferation of immunocompetent cells + fibrosis

Complications of chronic inflammation

healing (fibrosis), scar, acutization (recurring), tissue atrophy

Types of chronic inflammation

exudative (-itis) vs productive (non-/specific + foreign body)

Systemic effects of inflammation

fever, SAPR, leukocytosis, stress-related phase

Fever - exogenous pyrogens are ________ and endogenous pyrogens are ____________

exo - bacteria
endo - leukocytes

Systemic acute phase response

proteins of negative acute phase - albumin, transferin proteins of positive acute phase - globulines

Leukocytosis

increase in WBC, I: neutrophils II: monocytes macrophages III: lymphocytes

Alterative inflammation

tissue injury, lack of the exudation and proliferative phase, from metabolic disorders, can lead to necrosis

Causes of alterative inflammation

physical + chem substances
pathogens
anergy (lack of immunological response)

Evolution of alterative inflammation

severe functional disorders
healing with fibrosis

serous exudative inflammations

abundant protein-rich serous exudate

causes of serous (exudative) inflammation

perifocal inflammation, uremia, collagen diseases, allergies

evolution of serous (exudative) inflammation

- healing (absorption of exudate)
- transformation in serous-fibrinous, serous -purulent inflammation

rivalta probe is neg for ______ and pos for ______--

transudate, exudate

Catarrhal inflammation

serous (exudative) inflammation of mucosae (hyperemia + edema), hypersecretion

causes of catarrhal inflammation

- physical factors, chemical agents
- viruses (common cold)
- bacteria
- allergy

evolution of catarrhal inflammation

- healing (complete restitution)
- superinfection muco-purulent inflammation
- chronic transformation

in serous (exudative) inflammation, papules are due to __________- blisters - vesicles are due to __________ and bullae are due to __________

allergies, viruses, burns

fibrinous exudative inflammation

fibrinogen polymerization (fibrinous exudate in extracell space), on serosal surfaces there is thick fibrin coat

types of membranes - fibrinous pericarditis: _____________
fibrinous pleuritis: _________
fibrinous peritonitis, arthritis: _________

villous, winding, smooth

causes of fibrinous (exudative) inflammation

- perifocal inflammation)
- uremia, rheumatic fever, collagen diseases

evolution of fibrinous (exudative) inflammation

healing
resolution
organization (adherences)
transformation into another type of inflammation

Fibrinous inflammations of mucosa (pseudomembranous)

- dirty false membrane (fibrin+neutrophils+mucus), causes asphyxiation and during typhoid fever - Payer's plaques necrotic

causes of Fibrinous inflammations of mucosa (pseudomembranous)

diphtheria, uremia

evolution of Fibrinous inflammations of mucosa (pseudomembranous)

lysis of the membrane and healing, ulceration, obstruction

Purulent exudative inflammation

leukodyapedesis = pus = neutrophils, infecting organisms, liquefactive tissues and serum, on serosal surfaces

causes of purulent (exudative) inflammation

perifocal inflammation or perforation
pyogenic bacteria

evolution of purulent (exudative) inflammation

healing, organization - adhesions or capsulling of the pus septicemia

Purulent (exudative) inflammation of mucosa

hyperemic and swollen mucosa + covered w/ pus (empyema)

causes of Purulent (exudative) inflammation of mucosa

pyogenic bacteria + superinfection

evolution of Purulent (exudative) inflammation of mucosa

complete resolution (healing)
chronic transformation
pyemia
death

Phlegmon

diffuse acute purulent inflammation of tissues and organs, can lead to abscess or death

Abscess

a localized cavity with pus + necrotic tissue within a tissue or organ (purulent exudative inflammation)

acute vs chronic abscess

acute abscess: ill-defined cavity surrounded by neutrophils
chronic abscess: surrounded by a "pyogenic" membrane

types of abscesses

primary abscesses (solitary, multiples)
metastatic abscesses - during pyemia - multiple abscesses
cold abscesses - for TB, no celsus or neutrophils

evolution of abscess

- resolution, scarring or capsuling, calcification
- spontaneous discharge - fistula
- ulceration, pyemia, septicopyemia

Necrotizing and gangrenous (exudative) inflammation

presence of necrosis + bacterial putrefaction
necrotizing - fetid exudate + putrefaction
gangrenous - putrefaction w/o exudate

causes of necrotizing + gangrenous (exudative) inflammation

- anaerobic bacilli + body anergy
- hematological disorders

Hemorrhagic (exudative) inflammation

severe vascular injury or depletion of coagulation factors

evolution of hemorrhagic (exudative) inflammation

erythrodiapedesis -> sanguineous exudate

subserosal hemorrhages are caused by

TB, metastases

Hemorrhagic inflammation of skin -

anthrax + variola (smallpox)

hemorrhagic inflammation of organs -

pneumonia, encephalitis, DIC, anthrax, plague

Primary (Inherited) Immunodeficiencies

antibody deficiency
T-cell defects

acquired immunodeficiencies

leukemia
HIV/AIDS
imunosuppressive drugs
transplant
malnutrition

Opportunistic infections in immunocompromised

- CMV and Pneumocytis carinii (in aids)
- cystic fibrosis
- bacterial infections
- T-cell defects
- S. Pneumoniae (asplenism), Neisseria, S. Aureus, Herpes virus

Granulation tissue

reparation w/ inflammatory cells
fibroblasts, capillary endothelial cells + collagen fibers proliferate
fibroblasts became myofibroblasts
capillary neoformed vessels

Granuloma

aggregation of lymphocytes and macrophages, sometimes w/ giant cells

Scarring/fibrosis

substitution of damaged tissue with connective tissue

Organization

replacement of the chronic exudate by the formation of a fibrous scar

process of healing

1. Elimination of lytic cells
2. Migration of immunocompetent cells
3. Genesis of new blood vessels - neoformed capillaries
4. Proliferation of fibroblasts
5. Fibrous tissue remodelling

Angiogenesis

formation of new blood vessels, process of healing injury, dev of collateral circulations @ ischemia + allowing tumors to grow

Wound healing by first intention

incised wound, platelets aggregate + scab forms, neutrophils/macrophages chemotaxis, proliferation of epidermal then dermal cells - secrete collagen

Wound healing by second intention

open wound, foreign material in it, persistent bleeding, infection

risk factors of open wounds

diabetes, atherosclerosis, nutritional deficiencies, steroid drugs

steps of wound healing by second intention

tissue loss
neutrophil/macrophage chemotaxis
phagocytosis to remove the debris
granulation tissue
organization and scar formation
epithelial regeneration

keloid nodules

In healing by second intention, excessive fibroblast proliferation and collagen production

Chronic ulcers

loss of the tissue continuity in organs covered by mucosa or on leg

stages of chronic ulcer healing

surface - covered with fibrin layer + necrotizing exudate
phagocytosis of the dead tissue
granulation tissue
regeneration of the mucosa
connective scar

Productive inflammation of the mucosa and organs - leads to

chronic inflammations, hyperplasia, mucosal fold thickening + atrophy

labile tissues

formed by cells which retained the ability to proliferate in post-natal life and have a high rate of turnover (hematopoietic cells)

stable tissues

good regenerative ability but low rate of turnover (hepatocytes, bone, renal tubes)

permanent/differentiated tissues

formed by cells which have lost the ability to proliferate being divided only during fetal life (neurons, muscle cells)

physiological regeneration

epithelial cells, hematopoietic cells

regeneration in liver

only hepatocyte loss (they are stable cells)

regeneration of kidney

tubular epithelium can be regenerated but not architecture

foreign body granuloma

chronic granulomatous inflammation (accumulation of activated macrophages and inflammatory cells around foreign bodies which cannot be phagocytosed)
- giant multinucleated cells (macrophage fusion)

lipogranuloma vs oleogranuloma

lipo - lipid deposits
oleo - from oil injection

Tuberculosis

tubercles (specific granulomatous inflammation)

Mycobacterium tuberculosis - phtyonic acid

central caseous necrosis and epithelioid hystiocytes (langhans)

exudative tubercle

in anergy and normal immunity, caseous necrosis, evolves to liquefaction and cavity