ACUTE & CHRONIC INFLAMMATION - Increased permeability

(Based on Dr. Unas’ Presentation) o Cellular Response

- Margination
INFLAMMATION - Rolling
o A response of vascularized tissues to infections and tissue - Adhesion
damage that brings cells and molecules of host defense from the - Transmigration
circulation to where they are needed - Migration
o Consists of vascular responses, migration and activation of
leukocytes, and systemic reactions STEPS OF THE INFLAMMATORY RESPONSE
o A protective response 1. Recognition
- Its goal is to remove the initial cause of injury as well as the 2. Recruitment of Leukocytes
necrotic cells and tissues resulting from the original insult, 3. Removal of the agent
and to initiate the process of repair 4. Regulation or control of the response
- Removes the consequences of injury 5. Resolution or Repair
o Although it helps clear infections and other noxious stimuli and
initiates repair, the inflammatory reaction and the subsequent
repair process can themselves cause considerable harm
o Important in tissue repair:
- Destroys or dilutes the wall of infectious process
- Sets in motion tissue repair (regeneration and scarring)
o Has unique features:
- Reaction of blood vessels
- Accumulation of fluids and electrolytes in the extravascular
space

Disorders Cells & Molecules Involved in

Injury
CARDINAL SIGNS OF INFLAMMATION
Acute
o Heat (Calor)
Acute Respiratory Distress Neutriphils
Syndrome o Redness (Rubor)
Asthma Eosinophils; IgE antibodies o Swelling (Tumor)
Glomerulonephritis Antibodies and complement; o Pain (Dolor)
neutrophils, monocytes o Loss of Function (Functio Laesa)
Septic Shock Cytokines
Chronic *Inflammation is terminated when the inciting agent is eliminated and
Arthritis Lymphocytes, macrophages; the mediators have degenerated
antibodies
Artherosclerosis Macrophages; lymphocytes ACUTE INFLAMMATION
Pulmonary Fibrosis Macrophages; fibroblasts o A rapid response to an injurious agent that aims to rapidly bring
mediators of inflammation to the site of injury
CAUSES OF INFLAMMATION o Major components:
o Infections - Dilatation of small blood vessels >> increased blood flow
o Tissue necrosis - Increased vascular permeability >> plasma proteins and
o Foreign bodies leukocytes leave circulation
o Immune reaction - Emigration, accumulation, and activation of neutrophils
o Infiltration by polymorphonuclear cells (neutrophils, eosinophils,
INFLAMMATION CONT’D basophils)
o Tissues and cells are involved in this reaction
- Fluid and plasma proteins, blood vessels, circulating cells STIMULI FOR ACUTE INFLAMMATION
(WBCs), CT cells (mast cells, fibroblasts, macrophages), o Infections
extracellular matrix (collagen, elastin), adhesive o Trauma
glycoproteins o Physical and chemical agents
o The cells and molecules of host defense including leukocytes and o Tissue necrosis
plasma proteins, normally circulate in the blood and the goal of o Foreign bodies
inflammatory reaction is to bring them to the site of infection or o Immune reactions
tissue damage
MEDIATORS OF ACUTE INFLAMMATION
COMPONENTS OF INFLAMMATORY RESPONSE o Substances that initiate and regulate inflammatory reactions
o Vascular Reaction - Vasoactive amines (Histamine and Serotonin)
- Vasodilation - Kinins (Bradykinin)
 - Complement System (C3 and C3a) - Produced by proteolytic cleavage of precursors, mediate
vascular reaction, pain
Mediator Source Action
Vasodilation, ↑ Reaction of Inflammation Principal Mediators
Mast cells, vascular Vasodilation Histamine
Histamine basophils, platelets permeability, Prostaglandins
endothelial Histamine
activation Increased Vascular C3a and C5a (by liberating
Prostaglandins Vasodilation, pain, Permeability vasoactive amines from mast
fever cells, other cells)
Mast cells, ↑ vascular Leukotrienes 𝐶4 , 𝐷4 , 𝐸4
leukocytes permeability, TNF, IL-1
Leukotrienes chemotaxis, Chemotaxis, Leukocyte Chemokines
leukocyte adhesion, Recruitment and Activation C3a, C5a
and activation Leukotriene 𝐵4
Local: endothelial Fever IL-1, TNF
activation Prostaglandins
(expression of Pain Prostaglandins
Cytokines Macrophages, adhesion Bradykinins
(TNF, IL-1, IL-6) endothelial cells, molecules) Tissue Damage Lysosomal enzymes of
mast cells leukocytes
Systemic: fever, Reactive oxygen species
metabolic
abnormalities,
hypotension (shock)
Leukocytes, Chemotaxis,
Chemokines activated leukocyte activation
macrophages
Vasodilation, ↑
vascular
Platelet Activating Leukocytes, mast permeability,
Factor cells leukocyte adhesion,
chemotaxis,
degranulation,
oxidative burst
Leukocyte
chemotaxis and
activation, direct
Complement target killing
(membrane attack
Plasma complex),
(produced in the vasodilation (mast CLOTTING SYSTEM
liver) cell stimulation) 1. Arachidonic Acid Metabolites
Kinins ↑ vascular - Prostaglandin, Prostacyclin, Thromboxane A2, Leukotrienes
permeability, (B4, C4, D4, and E4)
smooth muscle 2. Oxygen Metabolites
contraction, 3. Platelet Aggregating Factor
vasodilation, pain 4. Nitric Oxide
5. Cytokines
PRINCIPAL MEDIATORS OF INFLAMMATION - Interleukins, TNF
o Vasoactive Amines
- Vasodilation and ↑ vascular permeability HALLMARK OF ACUTE INFLAMMATION
o Arachidonic Acid Metabolites (PGs and Leukotrienes) o Dilation of small blood vessels
- Involved in vascular reactions, leukocyte chemotaxis and o Accumulation of leukocytes and fluid in the extravascular tissue
other reactions of inflammation
o Cytokines EDEMA
- Proteins produced by many cell types, multiple effects o Refers to an excess fluid in the interstitial tissue or serous cavities
mainly in leukocyte recruitment and migration
o Complement
EXUDATION
- Leads to generation of multiple breakdown products >>
o The escape of fluid, proteins and blood cells from the vascular
leukocyte chemotaxis, opsonization and phagocytosis
system into interstitial tissue or body cavities
o Kinins
o 2 types: exudate and transudate
 Exudate Transudate
Protein Content High Low (Albumin) MUCINOUS/ CATARRHAL
Specific Gravity >1.020 <1.020 o When mucus hypersecretion accompanies acute inflammation
Cellular Inflammatory cells, None of a mucous membrane
Components cellular debris o Contains a large amount of mucous and epithelial cells
o Inflammatory conditions like allergenic rhinitis are common
PUS
o An exudate rich in inflammatory cells (leukocytes) and cellular TYPES OF INFLAMMATION ACCORDING TO LOCATION
debris ABSCESS
o Localized collection of pus in a part of the body surrounded by
MORPHOLOGIC PATTERNS an inflamed area
SEROUS o The area will most likely look like a giant boil or cyst that can
o Exudation of cell poor fluid into spaces created by cell injury or become extremely red and infected
into body cavities lined by the peritoneum, pleura or
pericardium ULCER
o May be derived from plasma (increased vascular permeability) o An open sore of the skin, eyes or mucous membrane often
or from mesothelial cells (local irritation) caused by an initial abrasion and generally maintained by an
o Accumulation of fluid >> effusion inflammation and/or an infection
o Early inflammation, heart failure, pleural effusions
CATARRHAL
PURULENT/ SUPPURATIVE o Mucosal surface
o The terms “suppurative” and “purulent” denote the production o Thick mucous and white blood cells
of pus, an exudate composed of neutrophils, liquefied debris of
necrotic cells and edema fluid MEMBRANOUS
o Caused by pyogenic bacteria o An epithelium becomes coated by fibrin, desquamated epithelial
o The pus may become walled-off by granulation tissue or fibrous cells and inflammatory cells
tissue to produce an abscess (a localized collection of purulent o An example is the grey membrane seen in pharyngitis or
inflammatory tissue) buried in a tissue, an organ or a confined laryngitis due to Corynebactrium diptheriae
space
o If a hollow viscus fills with pus, this is called an empyema PSEUDOMEMBRANOUS
o Formed by the fibrin and necrotic cell surface epithelium
FIBRINOUS o A structure which resembles the luminal surface of the tissue
o Increased vascular permeability >> large molecules pass out of (looks like the affected tissue is covered by a membrane)
the blood >> fibrin is deposited in extracellular space
o Develops when vascular leaks are large or there is a local TYPES OF INFLAMMATION ACCORDING TO DISTRIBUTION/
procoagulant stimulus LOCATION
o Characteristic of inflammation in the lining of the body cavities
FOCAL
(meninges, pericardium, pleura)
o Single abnormality/ inflamed area w/in tissue
o Forms eosinophilic meshwork of threads or sometimes as an o Size varies from 1mm to several centimeters in diameter
amorphous coagulum
o May be dissolved by fibrinolysis, if not lead to fibrosis MULTIFOCAL
o Often seen in acute pericarditis giving the parietal and visceral
o Arising from one/ pertaining to many foci (several foci separated
pericardium a “bread and butter” appearance
from one another)
o Size is variable
MEMBRANOUS o Each focus of inflammation is separated from the other
o Contains fibrinous or fibrinopurulent material with necrotic cells
o Often found in mucous membranes, some microbial infection LOCALLY EXTENSIVE
o Involvement of considerable area w/in an organ
SEROSANGUINOUS o Aka focally extensive
o Contains both serous and hemorrhagic materials o Possible origin:
o Caused by bleeding, serous exudation like injury and burns - Severe local rxns that spread into adjacent tx
- Coalescence of foci in a multifocal rxn
EXUDATES IN INFLAMMATORY PROCESSES
HEMORRHAGIC DIFFUSE
o Contains a large amount of RBCs and other cells o Involve all the tx/ organ in w/c the inflammation is present
o Damaged or vascular injury or permeable blood vessels or o Variations in severity may exist
depletion of coagulation factors o Interstitial pneumonia
o Acute pancreatitis due to proteolytic destruction of vascular
walls, and in meningococcal septicemia due to disseminated OUTCOMES OF ACUTE INFLAMMATION
intravascular coagulation
o Complete resolution SIMPLE RESOLUTION
o Healing by connective tx replacement (scarring/ fibrosis) o No destruction of normal tx
- Tissues incapable of regeneration o Offending agent is neutralized
- Abundant fibrin exudation in tissues/ cavities o Vessels return to their normal permeability state
o Progression to chronic inflammation o Excess fluid is reabsorbed
o Clearance of mediators & inflammatory cells

REGENERATION
o Replacement of lost/ necrotic tx w/ a new tx that is structurally
& functionally similar to those that were destroyed
o The intact, healthy neighboring cells surrounding the dead cells
will proliferate to replace the affected cells

REPLACEMENT BY A CT SCAR
o Formation of a new type of tx that causes fibrous scar production
w/ some loss of tx fxn
o Angiogenesis
o Migration & proliferation of fibroblasts
o Deposition of ECM
o Remodeling (reorganization of the fibrous tx, contraction of
CHRONIC INFLAMMATION wound edges)
o An inflammation of prolonged duration o Cicatrization
o Infiltration by mononuclear cells (macrophages, lymphocytes, - Formation of the mature scar
plasma cells) - Cicatrix
 Scar
CAUSES OF CHRONIC INFLAMMATION  Less vascular, pale, contracting scar tx
o Follows an acute inflammation o Epithelialization
o Repeated bouts of acute inflammation
- Persistent infections of intracellular microbes (tubercle SYSTEMIC EFFECTS OF INFLAMMATION
bacilli, viral infections) o Fever, increase in pulse & blood pressure, decreased in
- Prolonged exposure to non-degradable but potentially sweating, rigors, chills, anorexia, somnolence, malaise,
harmful substances (silicosis, asbestosis) lymphadenopathy
- Immune rxns (autoimmune diseases) o Increase plasma levels of acute phase proteins (CRP, serum
amyloid A protein)
MORPHOLOGIC OF CHRONIC INFLAMMATION o Leukocytosis
o Infiltration of mononuclear cells (macrophages, lymphocytes, o Sepsis
plasma cells, mast cells, eosinophils) o Shock
o Tx destruction
o Attempts at healing by CT replacement (angiogenesis & fibrosis) FACTORS MODIFYING THE INFLAMMATORY-REPARATIVE
RESPONSE
GRANULOMATOUS INFLAMMATION o Adequacy of blood supply
o A distinctive pattern of chronic inflammation o Nutritional status of the patient
o Characterized by formation of granulomas o Presence/ absence of infection
o Granuloma o Presence/ absence of diabetes mellitus
- Focal aggregation of activated macrophages w/c are o Presence/ absence of immunosuppressive drugs (ex.
transformed in an epithelial-like (epithelioid) cells glucocorticosteroids)
- Have an abundant pink cytoplasm o Adequate levels of circulating, normal fxning WBCs
- Surrounded by numerous lymphocytes & plasma cells
o Tuberculosis, leprosy, syphilis
o 2 types of granuloma:
- Foreign body granuloma
 Caused by inert foreign bodies
 Material (talc), sutures
 No inflammatory/ immune rxns present
- Immune granuloma
 Caused by immune T-cell mediated rxns
 Insoluble particles (microbial parts)
 Inflammatory rxns present

RESOLUTION INFLAMMATION (HEALING)