General Pathology (inflammation & tissue healing / immunopathology & hypersensitivity) Flashcards
classification of inflammation via:
1) duration (acute/chronic)
2) Etiology
3) Location (local/systemic)
4) Morphology
1) DURATION
Acute or Chronic?
acute inflammation
short term process
immediate onset
swelling, redness, heat, altered/loss of function, pain
stops when “injurious” stimulus is:
a) removed
b) walled off (scarring/fibrosis)
c) broken down
acute inflammation process
Increased Vessel wall permeability of nearby BV
= Increased emigration of LEUKOCYTES
how do leukocytes emigrate?
via (along/up) CHEMOTACTIC gradient
combination of which systems?
cascade of events involving vascular system, immune system, and injured/damaged cells
conclusion of acute inflammation?
removal of stimuli = removal of inflammatory process
inflammatory response requires the presence of stimulus
Outcome?
either resolution
or
abscess formation
or
continued chronic inflammation
abscess define
An enclosed collection of pus in tissues, organs, or confined spaces in the body. An abscess is a sign of infection and is usually swollen and inflamed.
chronic inflammation
not necessarily classic symptoms/signs of inflammation (SHARP?)
delated onset
long duration
leads to tissue destruction/fibrosis
2) ETIOLOGY
infections
chemical
physical
immune
multifactorial etiology
infections as cause for chronic inflammation
bacteria, viruses, protozoa, fungi, helminthis (worms)
chemical cause for inflammation
Chemical – organic or inorganic, industrial, medicinal,
physical cause for inflammation
foreign bodies, heat, irradiation, trauma
immune cause for inflammation
..
3) LOCATION (classification of inflammation)
E.g. localized vs systemic
systemic can begin as localized
4) MORPHOLOGY (4th way to classify inflammation)
a) Serous
b) Fibrinous
c) Purulent
d) Ulcerative
e) Pseudomembranous
f) Chronic
g) Granulomatous
a) SEROUS INFLAMMATION
MILDEST TYPE
characterized by clear fluid
occurs in early stages of inflammation
typical in:
viral infections
arthritis
burns
generally “Self-limiting” (I.e. resolves without measure)
Resolves without consequences generally (E.g. Herpes)
b) FIBRINOUS INFLAMMATION
EXUDATE present
exudate rich in Fibrin
indicates severe inflammation
present in:
bacterial infections
E.g.
Strep throat, bacterial pneumonia, bacterial pericarditis
Doesn’t resolve easily
LEADS TO SCARRING IN “PARENCHYMA” (functional portion of organ)
Fibrosis of parenchyma = loss of function of tissue
parenchyma define
“In anatomy, parenchyma refers to the functional part of an organ in the body.”
“This is in contrast to the stroma or interstitium, which refers to the structural tissue of organs, such as the connective tissues.”
stroma define
the supportive tissue of an epithelial organ, tumor, gonad, etc., consisting of connective tissues and blood vessels.
interstitium define
Interstitium refers to the space or compartment between the cells in a tissue, particularly connective tissue. It is often filled with interstitial fluid and contains various structures such as collagen fibers, elastin fibers, and ground substance.
where is fibrinous inflammation seen (e.g.)?
present in:
bacterial infections
E.g.
Strep throat, bacterial pneumonia, bacterial pericarditis
c) PURULENT INFLAMMATION
PUS-forming bacteria
E.g.
Staphylococci
Streptococci
Pus accumulation @ mucosa, or skin, or @ internal organs
abscess = localized “collection” of pus
staphylococcus define
“a bacterium of a genus that includes many pathogenic kinds that cause pus formation, especially in the skin and mucous membranes.”
streptococcus define
“a bacterium of a genus that includes the agents of souring of milk and dental decay, and hemolytic pathogens causing various infections such as scarlet fever and pneumonia.”
d) ULCERATIVE INFLAMMATION
inflammation of body surfaces
or inflammation of mucosa
leads to ulceration or necrosis of epithelial lining
ulcer define
defect involving the epithelium;
can also extend into the connective tissue
“A break on the skin, in the lining of an organ, or on the surface of a tissue. An ulcer forms when the surface cells become inflamed, die, and are shed. Ulcers may be linked to cancer and other diseases.”
E.g.
Peptic Ulcer
e) PSEUDOMEMBRANOUS INFLAMMATION
combination of:
a) Ulcerative infl
b) Fibrinous infl
c) Purulent infl
Exudate present:
consist of:
Fibrin, pus, (cellular debris), mucous
–> Exudate forms pseudomembrane on the surface of ulcers
E.g. pathology
DIPHTHERIA
pseudomembranes form on throat
–> when scraped away, expose bleeding ulcers
inflammation type that is combination of purulent, fibrinous, and ulcerative
pseudomembranous inflammation
f) CHRONIC INFLAMMATION
Exudate present
contains:
monocytes, lymphocytes, (macrophage, plasma cell)
important feature of mechanism of Chronic inflammation
stimulation of proliferation of FIBROBLASTS
inflammation persists via constant recruiting of new inflammatory cells
Recall:
Loss of parenchyma via Scarring/fibrosis
fibroblasts and scar formation (fibrosis)
“Fibroblasts are expected to contract wounds and secrete ECM during the process, but uncontrolled proliferation of fibroblasts and excessive deposition of ECM contributes to the scar formation and should be avoided.”
Chronic inflammation and loss of function
E.g.
Scarring of fallopian tubes associated with pelvic inflammatory disease can lead to infertility
E.g.
Fibrosis associated with chronic lung disease can impair passage of oxygen into lungs
g) GRANULOMATOUS INFLAMMATION
special type of chronic inflammation
NOT PRECEDED BY ACUTE INFLAMMATION
mechanism of granulomatous inflammation
accumulation at the site of injury by
–>T-lymphocytes and Macrophages
Cytokines released by lymphocytes
Cytokines transform macrophages into Epithelioid cells
what happens to epithelioid cells?
fuse together
form multinucleated “Giant cells”
Nodules are then formed
What are Nodules composed of? What are nodules called?
Multinucleated giant cells,
epithelioid cells,
and lymphocytes aggregate into nodules
called GRANULOMAS
–> “grain” “swelling”
what do granulomas do?
destroy tissue
persist for long time
E.g.
Syphilis
Tuberculosis
What are clinical findings (clinical correlations) of inflammation?
a) Fever
Leukocytosis
Constitutional symptoms
a) Fever
elevation in body temperature >37 degrees celsius
generally normal body temperature b/w 36-37
What causes fever? What is the mechanism?
Pyrogenic Cytokines:
–> Interleukin 1 (IL-1)
–> tumor necrosis factor (TNF)
interleukin define
“any of a class of glycoproteins produced by leukocytes for regulating immune responses.”
IL-1
“The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.”
insult
MEDICINE
“an event or occurrence that causes damage to a tissue or organ.”
E.g.
“the movement of the bone causes a severe tissue insult”
pyrogen
“A pyrogen is, by definition, a substance that produces a rise in temperature in a human or animal.”
“differentiated into exogenous and endogenous pyrogens”
exogenous pyrogen
“Exogenous pyrogens are substances that induce fever reactions after parenteral administration.”
parenteral
“situated or occurring outside the intestine.”
para-
distinct from, but analogous to.
exogenous pyrogens E.g.
“Exogenous pyrogens are molecules found outside of the body, such as endotoxins from gram-negative bacteria or pyrogenic prions.”
“Exogenous pyrogens either provoke endogenous pyrogen production to create a fever within the body or activate toll-like receptors (TLRs) to create a fever.”
endogenous pyrogens E.g.
“Interleukin-1 (IL-1), tumor necrosis factor, and prostaglandin E have all been shown to act as endogenous pyrogens. IL-1β, the most potent endogenous pyrogen, is balanced by the IL-1 receptor antagonist (IL-1Ra).”
what activates endogenous pyrogens
“Fever, a common symptom of many diseases, is elicited by exogenous pyrogens (such as bacterial LPS) or an inflammatory insult, which results in the production of cytokines such as IL-1β that act as endogenous pyrogens.
These cytokines then stimulate the neural pathways that increase body temperature.”
can fever occur without endogenous pyrogens, only exogenous?
yes (??)
are endogenous pyrogens always activated by exogenous pyrogens?
no
can fever occur without either?
??
b) Leukocytosis (Clinical findings/correlations of inflammation)
increase in circulating WBCs
Esp during infection
cytosis
“It essentially means ‘of the cell’.”
“sometimes refers to predominance of certain type of cells.”
TNF (Tumor necrosis factor) – a cytokine
“an inflammatory cytokine produced by macrophages/monocytes during acute inflammation”
“is responsible for a diverse range of signalling events within cells, leading to necrosis or apoptosis.”
SOME STUDIES SUGGEST TNF IS CRYOGENIC, OTHERS SUGGEST TNF IS PYROGENIC
–> controversy
TNF and IL-1 (CYTOKINES), the hypothalamus, and prostaglandins
“Interleukin-1 initiates fever by inducing an abrupt increase in the synthesis of prostaglandins, particularly prostaglandin E2, in the anterior hypothalamus.”
prostaglandin and fever
“Fever is thought to be initiated by pyrogenic cytokines inducing the production of prostaglandin E2 (PGE2) in the preoptic area (POA)”
“PGE2 may act as a paracrine mediator that stimulates the neural pathways that raise body temperature.”
c) Constitutional symptoms (Clinical findings/correlations of inflammation)
non-specific; include fatigue, weakness, depression, malaise, lack of appetite, achiness, etc.
INFLAMMATORY DISORDERS
Immune disorders
Infections
Injuries
Arthritides
Cancer
HEALING AND REPAIR, vs inflammation
inflammation may result in tissue loss
consequence of tissue loss (via inflammation) depends on the type of cell
(in terms of regenerative/dividing capabilities)
3 types
1) continuously dividing, mitotic
–> “LABILE” cells
2) “quiescent cells”
Aka “Facultative mitotic” / “stable” cells
3) non-dividing cells – “post-mitotic” cells – “permanent” cells
“Labile cell”
cells that continuously multiply and divide throughout life
quiescent cell
Quiescence is a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide.
“stable” cell
“In cellular biology, stable cells are cells that multiply only when needed. They spend most of the time in the quiescent G0 phase of the cell cycle”
facultative cell
BIOLOGY
“capable of but not restricted to a particular function or mode of life.”
permanent / post-mitotic cells
Permanent cells are defined as cells that are unable to replicate in postnatal life.
E.g.
Nervous cells
skeletal muscles
cardiac cells
1) continuously dividing (labile / mitotic)
“Undifferentiated stem cells divide by mitosis”
differentiate and replace los cells
E.g.
skin cells
resolution – minimal tissue damage – tissue returns to normal
(Note visible scars / scar tissue can still occur depending on severity of injury to skin)
2) Quiescent cells (facultative mitotic / stable cells)
I.e. cells in G0 phase
Do not divide regularly
can be stimulated to divide to replace lost cells
E.g. Hepatocytes (liver cells)
Outcome?
regeneration –> damaged tissue is replaced
–>
However, replacement can still be limited depending on extent of damage
3) Non-dividing cells (permanent / post-mitotic cells)
E.g. neurons, skeletal/cardiac muscle cells
No division/mitosis
Outcome?
Parenchymal tissue gets replaced with Scar tissue (connective tissue)
I.e.
Leads to loss of function
HEALING
(by first intention / by second intention)
.
healing by first intention
wound is clean
free of foreign materials
free of necrotic tissue
edges are closed together
healing by second intention
large break in tissue
more inflammation
longer inflammation
more scar tissue
presence of foreign bodies / bacteria
more “Granulation tissue”
granulation tissue define
“Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process.”
intention define
MEDICINE
“the healing process of a wound.”
granulation tissue, fibroblasts, myofibroblasts
“In the granulation tissue, fibroblasts are activated and acquire α-SM actin expression and become myofibroblasts.”
“These myofibroblastic cells synthesize and deposit the ECM components that eventually replace the provisional matrix”
“Myofibroblasts mediate wound contractions, but their persistent presence in tissues is central to driving fibrosis”
Cells participating in wound healing
a) Leukocytes (i.e.WBC)
b) CT cells
c) Epithelial cells
d) Macrophage
a) Leukocytes (i.e.WBC)
Leukocytes (i.e.WBC)
–> Esp polymorphonuclear neutrophils —> “scavenging at the initial site of injury”
b) CT cells
produce scar tissue
E.g. Fibroblasts/myofibroblasts
c) Epithelial cells
undergo mitosis and extend across the wound
(except for permanent / non-mitotic cells)
d) Macrophages
stay @ site of healing
produce:
growth factors
cytokines
mediators
all act on connective tissue cells
CT cells participating in wound healing
a) myofibroblast
b) angioblast
c) fibroblasts
a) myofibroblast
hybrid b/w smooth muscle cell and fibroblast
can contract and secrete ECM
function of contraction in myofibroblasts
“The contraction is considered one of the important events in wound healing because it results in the closure of the wound”
b) Angioblasts
precursor to blood vessels
fibroblasts
produce most ECM
THE HEALING PROCESS – events
1) blood clot forms, seals area
2) inflammation develops
3) phagocytes (including monocytes & macrophages) remove debris
4) Granulation tissue forms in gap (highly vascular – brings new blood supply)
5) tissue is fragile
THE HEALING PROCESS – events (continued)
6) mitosis of epithelial cells
7) fibroblasts enter area – produce collagen (basic component of scar tissue)
8) macrophages/fibroblasts produce cytokines to attract more fibroblasts
THE HEALING PROCESS – events (3)
9) Fibroblasts also stimulate epithelial cell division –> and increase ANGIOGENESIS
10) cross-linking of collagen fibres = tight, strong scar
11) capillaries in area decrease
12) Note that scar tissue is not normal functional tissue
what increases effeciency of healing?
Young age
Good nutrition
Adequate hemogloblin
Effective circulation
Clean wound
No foreign bodies
No complications
Small wound
Site of wound
what deceases effeciency of healing?
Advanced age
Poor nutrition
Anemia
Poor circulation
Presence of other disorders (diabetes)
Irritation or excessive mobility
Infection, foreign materials
Large sized wound
COMPLICATIONS OF WOUND HEALING
1) Loss of function
2) Deficient scar formation
3) Excessive scar formation
4) Infection
1) Loss of function
scar tissue replaces parenchymal tissue
2) deficient scar formation
?
age/genetic/medications/nutrition/infection?
