PATUM (K5 – K6)

5, 6: INFLAMMATION
ꝱ Protective response involving immunocompetent cells, bv &
molecular mediators
ꝱ Goals to remove initial cause of cellular damage, clear necrotic
cells & damaged tiss fr initial damage & inflammatory process, &
to initiate tiss repair
Inflammation VS Adaptive Immune
Inflammation Adaptive Immune

• Natural immune defense (innate immunity) • Acquired immunity, i.e., vaccine

• Non-specific response • Specific immune response
• Body cell damage • Target only causative / antigen that bluffs
• Inhibit causative tiss damaged in Ab production
prolonged response (bac → • Long: 2 – 3 weeks b/4 causative target
inflammation/infection → bv dilate → eliminated
inflammatory cell exit → fluid exit → • Has memory system => faster response
accumulation (edema) (1 – 2 weeks): B & T cell memory
• Onset response (fast process mins – hrs) • Onset response (long time process 2 – 3
→ eliminate target → healing weeks) → eliminate → healing

Inflammation Defense of Innate Immunity System

• Programmed (genetic) inflammatory process until healing

• Body prepared inflammatory component
• Activated by causative factor
• Formation processes similar for all causative
• Quick start response, effect immediately w/o any adaptation process
• Localized inflammation forms to confine / fence off the cause
• Acute inflammation successful → healing
• Acute inflammation fails → x heals
o Extends to multifocal / extensive / systemic inflammation
o Active / chronic / granulomatous chronic local inflammation
o Delayed healing results in granulation tiss (fibrosis & angiogenesis)
o Systemic inflammation / septicemia
Sign

Swelling (tumor) Due to addition of blood vol

Red color (rubor)
Heat (calor)
Pain (dolor)
Disrupted tiss / organ function / a. Pneumonia: shortness of breath, ↓ gas , tiss
function laesa hypoxia, weakness, death
b. Arthritis: lame, diff to find food / drink, cachexia, poor
production

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PATUM (K5 – K6)

Swollen Spleen, Tumor

• Spleen inflammation common, affecting diff organs & x always associated w 1’ spleen disorder
• → ↑ in size – splenomegaly, due to significance ↑ in activity caused by infectious disease, even
disease locate in other organs
• Brittleness → splenic rupture
• Red mucosa = rubor = hyperemia, hemorrhage

Acute Local Inflammation Response

• Stimuli microvascular autonomy sympathetic nerve reflexes, temporary vasoconstriction of vas

lumen
• Main events:
o ∆ in vessel calibre: vasodilation → hyperemia
o ↑ vas permeability: vessels become leaky
o Leakage of plasma: fluid exudate rich in proteins
o Emigration of inflammatory cell: cellular exudate, mostly neutrophils
o Exudate target causative to destroy
• Lesion of many diseases, occur in any part of body system
• Inflammation (local) follows the name of organ / tiss added w -itis
Oral mucosa Stomatitis
Stomach Gastritis
Intestine Enteritis
Colon Colitis
Outer GIT / peritoneum Peritonitis
Brain Encephalitis
Cecum Typhlitis
Bird crop Ingluvitis
Lung Pneumonia
Subcutis Cellulitis
Systemin Widespread Inflammation Septicemia / sepsis
• Site of local inflammation begins where the response formed, in microcirculation area of
interstitium tiss (bet cells, cap area)
• Boils (abscess):
o 5 cardinal signs of inflame
o Yellow @ center of inflammation => pus / pyogenic exudate purulent / suppurative
o Exudate: inflammatory product composed over cellular & humoral
o Hyperemia: cap vasodilation fence off inflammatory center & sources exudate formation

Pathogenesis

• Inflammatory exudation (extravasation of blood plasma & leucocytes) influenced by contraction

of endothelial (shrink) & vasodilating lumen => venule & microcirculation cap
• Inflammatory mediator (MI) molecules → vasodilation: histamine, prostaglandins, nitric oxide
• MI → endothelial contraction, ↑ permeability: histamine, leukotrienes, bradykinin, platelet
activating factor, C3a + C5a = complement activation
• TNF (tumor necrosis factor), interleukin-1 (effect of MI is longer)

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Process of Inflammation
1. Tiss damage
a. Chemicals (histamine, kinins, prostaglandins & leukotrienes) released by damaged cells
b. Blood clot forms
c. Abscess starts to form
2. Vasodilation & ↑ permeability of bv
3. Phagocyte migration & phagocytosis
a. Margination – phagocytes stick to endothelium
b. Emigration – phagocytes squeeze bet endo cell
c. Phagocytosis of invading bac
4. Tiss repair
Migration of neutrophil from cap to extravas networks
1. Exudates targets microcirculation
2. Plasma ‘extravasation’ phagocyte cell: phagocytosis, phagolysosome, O2 burst
3. Degranulation of toxic molecules (extra phagocytic killing)
4. Debris, clean causative
5. Healing
Microcirculation cap @ inflame areas
1. Constriction => speed of blood flow ↑
a. No exudate b/c WBC x coming out, → only edema
2. Vasodilation => more inflammatory cells needed to accommodate more blood flow and
inflammatory cells
3. Endothelial become ‘permeable’ / leaky
a. Granulomatome infection: chronic infection, takes weeks / yrs
b. Interleukin 6: form giant cells by causative agent
4. Exudation => albumin, H2O, PMN, RBC
a. Humoral exudate, plasma carrying albumin protein, nutrients, complement, fibrinogen,
fibrinolytic factor, antibodies, O2
b. Blood cells rupture
c. Fibrinogen form thrombus between endothelial cells → formation of pus
5. Inflammatory cells clean up by macrophages

Cause
1. Presence of foreign bodies in body tiss cells
a) Donor tissue: kidney, heart, skin
b) Biological / infectious / pathogenic agents: bac, viruses, parasites, molds, yeast, prions
(only if they damaged cells)
c) Inanimate objects: thread, implants, pacemakers, glass, metal, wood
2. Presence of damaged tiss:
a) Necrose, infraction, bleeding, thrombus clots, tumors
3. Due to infection, physical trauma, chemical toxins, immune response, radiation, biological toxins,
allergies, extreme temp, organic toxins, autoimmunity, nutritional deficiencies (Vit E, selenium)

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PATUM (K5 – K6)

Leucocyte Flow

• Margination (bring WBC to endothelium cell space => exit bv to work in edema (EC) space
• Rolling
• Adhesion
• Diapedesis
• Chemotaxis
• Phagocytosis
• Degradation
Leucocytes hv surface receptors compatible w chemotactic ML Molecules; move towards conc MI
molecules, sources of chemotactic molecules (Mast cell)
Mast cell inflammatory focus: PAMP, DAMP
Leucocyte margination in cap & arteriole (pavementing)
1. Blood cells flow slowly in micro/cap circulation => vasodilation
2. Leukocytes separates from erythrocytes
3. Located on edge, leukocytes approach endothelium wall

Acute Inflammation Mediators

Phase Chemical Mediators

Vas dilation • Histamine
• Prostaglandins
• Complement components C3a, C5a
↑ vascular permeability • Histamine
• Kinins
• Prostaglandin
Emigration of leukocytes • C5a
• Leukotrienes
• Cationic proteins of neutrophils

Complement: C

• Inflammatory focus K activated to become MI

• C = part of serous exudate stimulates release of histamine mast cells
• C3b: as bac opsonin => neutrophils & macrophages easier to phagocyte
• C5a: MI-releasing activator of neutrophils & macrophages, stimulate leukocyte adhesion to
endothelium & chemotactic to leukocytes
• C5-9: hydrophobic memb lysing fraction of target cells, i.e., bac memb, infected host cells
O2 Free Radicals

• Free radicals (H2O2, OH, superoxide) are burst (O2 burst) EC from leukocytes when activated
by:
o MI – chemotactic
o Immune complex
o Meet challenges, phagocytosis (in phagosome)
• Free radical activity:
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PATUM (K5 – K6)

o Damages endothelium => ↑ permeability

o Endothelial activation produces superoxide free radicals
o Cytotoxic for tumor cells, RBC & local parensim cells
o Deactivates local anti-protease, protease enzyme products rampant inflammation &
widespread tiss damage
Anti-free radicals

• Antioxidant in serum & tiss fluid => control free radical activity:
o Ceruloplasmin
o Transferrin
o Glutathione peroxidase (enzyme ↑ reaction, ↓ activity of other toxins)
o Superoxide dismutase (protect cell from damage
o Catalase
• Provide protection to cells => avoid toxic effects of O2 radicals
• Antioxidant balance free radical activity → tiss damage in inflammation focus can be localized

Exudates
Determines properties of flavor
For diagnosis: nature of exudate: fibrinous pleuritis, catarrhal enteritis, meningitis suppurative

Serous Plasma fluid (dominant)

- Clear ↓ fibrin
Neutrophils
Serosanguineous Serous contents of RBC
Neutrophils
Pus Neutrophils (pus cells)
- Cloudy Necrotic debris
Macrophages
Hemorrhagic RBC
Fluid / clots
Neutrophils
Fibrinous Neutrophil-dominant mixed fibrin
Catarrhal Predominantly mucous
Few leukocyte
Granulomatous Macrophages
Activated macrophages-2 forms (epithelioid cells & giant cells)
Lymphocytes
Pyogranulomatous Granulomatous mixed w neutrophil
Lymphocytic Lymphocytes + macrophages – viral causes
Eosinophilic Eosinophil – parasitic cause
Hypersensitivity

Edema

• Swollen feet, pressure test causes kicks (takes long time to return flat)
• Interstitium under skin / dermis excess fluid content (transudate)
Serous inflammation

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PATUM (K5 – K6)

• Finger blister by heat stroke, freezing, local friction / viral infection

• Group of epidermal cells undergo hydropic degeneration & necrotize
• Leaves a fluid-filled cavity, necrotic discharge, few inflammatory cells (serous exudates)
• Epidermal keratin as a blister wall

FLAD Manifestation in Various Organs – duration of inflammation occurs & exudates

• Serous arthritis
• Fibrino-purulent peritonitis
• Suppurative meningitis
o Thickening of meninges layer
o Hyperemia / congestion
• Non-suppurative encephalitis
o Perivascular Cuffing (PVC) - indicator: extravation flad celss entering Virchov-Robin
room (space bet cp wall & astrocyte barrier)
o Virchov-Robin rooms produce more room to enhance inflammatory reaction (if occurs)
b/c brain function is important
• Pyogenic exudate / pygenous mastitis
• Suppurative laryngitis @ trachea base of calves:
o 2 lesions of open wound (ulcers) on mucosa, coated w yellowish pus exudate
o Edge ulcers → red circles due to inflammatory hyperemia
o Indicating acute inflammation
o Cause in cattle: Fusobacterium necrophorum (calf diphtheria)
• Pneumonia (Pn) / alveolaris:
o Interalveolar cap hyperemia, ↑ permeability
o Plasma extravasation, few inflammatory cells (leukocytes)
o Serous pneumonia = early stage
o Alveoli neutrophils ↑ = Pn suppurative
o Exudate in interstitium interalveoli = Pn interstitialis
▪ Extravasated mononuclear Rader cells in interstitium (interalveoly)
▪ Virus infection causative, toxic hematogenous materials interstitium get thickens,
gas  ↓, blood ↓ O2, hypoxia body tiss
o Vasodilating interalveolar, ↑ permeability, extravasation of plasma protein & leukocytes
into alveoli, forming fibrin, phagocytic neutrophil = Pn alveolar / acute fibrinosuppurative
Pn
• Ancylostoma caninum → hemorrhagic enteritis
o Worms pierce the mucosa of small intestine, propria wounds, bleeding
o Worms hv anticoagulants, difficult to clot, chronic bleeding
o Bleeding & wound production of MI: vasodilation, ↑ permeability, extravasation of plasma
fluid, RBC, WBC
o Complications: anemia, bloody diarrhea, dehydration, if x acute hypoproteinemia,
general edema → die due to pulmonary edema
• Small intestine: hemorrhagic enteritis, multifocal
o Intestinal wall thickens, from serosa to mucosa layer
o Petechia, necrosis nest, white color, blood contents
o Causes of parasites protozoa Eimeria necatrix
o Complications: bloody diarrhea, anemia, dehydration, acute death → hypovolemic shock
/ intestinal hemorrhages

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PATUM (K5 – K6)

• Lower resp tract infection:

o Exudate pus in bronchi, bronchus
o Hyperemia of lower resp tract mucosa
o Pus contains neutrophils (pus cells), bac, desquamated epithelial (peeled off)
o Suppurative bronchitis complications: sound breath, cough, spreading to
bronchopneumonia, fever, systemic infection / septicemia
• Ruminance lands:
o Rumen, reticulum, omasum: fermentation of feed (cellulage) using microbes
o Abomasum: true stomach, HCl production, enzyme, => kill microbes (become nutrients)
o Reticulitis traumatic w risk: walls of reticulum & diaphragm penetrating, carrying
microbes injuring the heart (pericarditis traumatic) / lungs (gangrenous pn)
• Fibrinous enteritis by clostridium chauvoei infection:
o Mucosal hyperemia, yellow fibrin bundles attached to intestinal mucosa
o Fibrin formed from extravasated plasma fibrinogen in propria, causing villous ischemia
& infraction
o The necrotic fibrin invites neutrophil inflammation cells
• Bovine jejunum w Johne’s disease: granuloma inflammation in proprio mucosa & edema in
submucosa → folding & thickening of intestine mucous
o Caused by mycobacterium avian spp paratuberculosis
o Enteritis granulomatous, ileum sheep, mucosa thickens by nest-2 granuloma epithelioid
in propria to crypta atrophy
o Villi swollen

Inflammation (SUMMARY)

• Pathogenic substances / agents / foreign bodies that destroy living body tiss / cell →
inflammatory defense response (inflammation)
• Local inflammatory response occurs in conn tiss vascular around the site of damage / foreign
body
• Inflammation quickly starts & reaches target:
o Dissolve & dilute substances / causative agent
o Causatives destroy & get rid
o Isolate the damaged location => x spread
o Trigger healing of damaged tiss

Tempo of Ongoing Inflammation

Acute End in 1 – 2 weeks of healing Acute Neutrophils
Chronic Acute inflammation x repair last Macrophages
over 2 weeks Lymphocytes
Per acute Inflammation forms rapid (hrs) Chronic Fibroblast
Subchronic States the initial phase of chronic Lymphocytes
inflammation (microscopy begins Granulomatous Lymphocytes
to show fibroblast cells producing Epithelioid
collagen) Giant cells
• To guide prognosis (3rd vocab) i.e., chronic fibrinous pleuritis, acute fibrinosuppurative
meningitis

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PATUM (K5 – K6)

Cause of inflammation
External Internal
Pathogen of microorg Toxin Damage cells
Foreign objectives

Infection VS Inflammation

Category Form Example Response

External (live) Microorganism Bac Infection
causative Virus
Mold
Yeast
Parasite
External causative Toxic irritant Chemical toxins Necrose, then
(dead) substance Biological toxins infection
Internal causative Cell necrose Donor cells / tiss / organ x Inflammation
(life) compatible
Bleeding
Autoimmune
Internal causative Toxins Ureum / kidney failure Inflammation
(dead) Metabolites

Causative Traits of Inflammatory Response

1. Infectious, causing illness = pathogens
2. Microbes cause infection: viruses, bacteria, molds, yeast, parasites
3. Infectious agent causing necrose & induce inflammatory stimuli
4. External / foreign causative damage, x-infectious → dead
a. Physical factors → necrosis, bleeding (extreme temp, radiation rays, trauma)
b. Implant
c. Donor cells / tiss / organs x compatible, pacemakers, artificial joints, implants, surgical
threads, glass fragments, bone fragments (complex fracture), burr splinters, nails, bullet
fragments
Cause of Inflammation x just Bac Infections:

• Causatives grouped based on pattern of foreign surface molecules, unlike the cells / tiss
• Host can ‘read’ (hv PRRs, Pattern Recognizing Receptors): leukocytes (including mast cells),
endothelial, epithelial, fibrocytes
• Reading: PRRs coupled by PAMP & DAMP molecules
• Pathogenic / infectious causative differ in molecular pattern & read by PRRs.
Pathogen ass molecular pattern (PAMP): Damages ass molecular pattern (DAMP):
o On surface of bac, virus, mold, yeast, o Surface of necrose cell, damaged cell that hv
parasites & their products / toxins x died (defects), infected cells & tumor cells |
o Molecules w same pattern Foreign objects: metal implants, wood chips,
o Mon & matched w PRRs = stimulus for bamboo, glass
initiation of inflammation o Different molecular pattern from healthy host
o Causative foreign cell (donor cells) / o Stimuli initiate inflammation
damaged host cells recognized b/c
same molecular pattern read by PRRs

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PATUM (K5 – K6)

• If PAMP / DAMP in body, cells w PRRs will read & signal the inflammation begins (in area where
pathogen / defective cell is located).
• Important PRRs cells: mast cells
• Cell / damaged tiss categorized as necrose: bleeding clots, tiss infraction, thrombo-embolism,
gangrene, hypersensitivity (repeated immune contact w same antigen → excessive
inflammatory response, esp IgE)
• Cell & body interstitium tiss whose surface molecules ∆: autoimmune, virus-infected cells, tumor
cells, crystal/mineral deposits, amyloid, necrose collagen fibers

PRR Sensor Mon Inflammation

• Inflammation has sensor system => able to mon arrival of danger from damaging body tiss cells
• Sensory molecules = PRR, present in mast cell memb, macrophages, neutrophils, endothelium,
epithelium, fibroblast, cells & EC (humoral)
• PRR + causative pathogens / danged cells / occupied by virus / foreign / tumor = activation to
initiate inflammation
• PRR family:
o Transmembrane receptors
o Toll-like receptors (TLRs)
• Intracellular compartments:
o Nucleotide-binding oligomerization domain- (NOD-)
o C-type lectin receptors (CLRs), like receptors (NLRs), retinoic acid-inducible gene- (RIG),
I-like receptors (RLRs)
o AIM2-like receptors

Mast cell Initiate Inflammation

• Embedded in conn tiss, near bv: mucosal layers (digestion, resp, urogenital, eye) & serosa
(peritoneum, joints)
• Prepared to occupy important posts of body tiss, ready to give command to initiate inflammation
• Surface has receptors molecules for inflammatoru signals activation
• Causative inflammation / its product bind to receptors, → degranulation, exocytosis of various
MI: histamine, serotonin, TNF alpha
• Mast cell receptors + causative agent = PRRs
Dead Infected Necrotic cell Spilling Dendritic cell (DC)
cell cells inflammation
Shrunk Apoptotic Macrophage / clearance DC tolerance, x
cells inflammation
Apoptotic Small fragment of blebs, DC inflammation
cells impaired clearance

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Phagocytosis

• Fusion of phagosome w 1’, 2’ granules & lysosomes

1’ granules: 2’ granules: Toxic O2 compound that kill
bac during O2 burst
• Antimicrobial peptides • Phagocyte oxidase
• Lysozyme (degrades Superoxide anion O2-
peptidoglycan) Hydrogen peroxide H2O2
Singlet oxygen 1O
•
2
Proteases (elastase) Lysosomes: Hydroxyl radical OH
Toxic hypochlorite OCl-
• Digestive enzymes

Complications of Suppurative Inflammation:

Phlegmon • Exudate pus in interstitium tiss
• Neutrophils under skin are necrotic, rapid expand & become diff
• Suppurative cellulities
Acute abscess / • Accumulation of pus exudate w local tiss margins
abscess • Chronic abscess, conn tiss fibrosis border abscess
• Causative bac reproduce, chemotaxis against neutrophils continues,
become bigger
• Military abscess (metastatic abscess)
Empyema • Accumulation of pus exudate in a cavity
• Chest cavity empyema: chronic suppurative peritonitis
• Pyometra: accumulation of purulent exudate in uterine lumen by
chronic suppurative endometritis
Fistula • Exudate pus (abscess-like) to form artificial channel to drain pus
• Purulent arthritis from skin outlet of joint area
• Suppurative meningitis, artificial fistula => exudate comes out through
the skull & scalp

Suppurative Inflammation & Complications

• In vas, 2nd inflammation (metastatic inflammation) & sepsis / septicemia (massive bacteriemia
b/c x controlled by antibiotics:
o Thrombophlebitis: inflammation of veins forming thromboembolism
o Lymphangitis / lymphadenitis: embolic pathogen in lymphatic vessels
o Endocarditis: metastatic pathogens participate in the bloodstream of the heart
Pus exudate accumulates in large #:

• Generate extensive tiss necrose by protease / ROS from neutrophils, => inflammation gets
bigger
• Presence of pathogens & extensive necrose debris inhibits recovery

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Neutrophils

• Adult neutrophils / PMN leukocyte (Polymorphonuclear)

• Polymorphic / multilobes core (3 – 5 lobes)
• Young neutrophils (stab, juvenile)
• Core = horseshoes x formed a lobe
• Ed cytoplasmic granules  digestive materials:
o MPO (myeloperoxidase)
o ALP (leukocyte alkaline phosphate)
o NADPH oxidase
o H2O2
o HOCl
• Acute inflammatory cells = 1st acute inflammatory exudate
• Active phagocitation & digestion → neutrophils die
• Shedding of enzymes & oxidative materials on site of inflammation: necrose of surrounding tiss
• Neutrophils & tiss necrose invite monocytes arriving @ inflammation site
• Excessive accumulation indicates pus exudate (suppurative / pus)
• Formation:
o Bone marrow stem cells & proliferative → Myeloblast, Promyelocytes, Myelocytes,
Metamyelocytes → adults neutrophils w/in 5 days (x-proliferative)
• Compartment in body:
Blood Into circulation; age 10 – 12 hrs
Margination of cap endo
Tiss Live 1 – 2 days, x returns to circulation
Bone marrow Metamyelocyte marrow, stab, adult neutrophils

Macrophages

• In bone marrow: early cells, monoblast & proliferative promonocytes, => monocytes enter blood
cir as phagocyte w viability of 2 – 6 days
• Activation by MI:
o Migration to inflammatory sites as macrophages
o Large form & phagocytic power of monocyte
o Able to multiply @ inflammation site
o Forming giant cell of matter = difficult to digest
o Forming epithelioid cells
• Post-inflammatory live monthly as tiss macrophages & occasionally when activated, migrates to
another location w/o entering the blood
• As tiss permanent macrophages:
o Kudffer cells in sinusoid cap of liver
o Pulmonary interalveolar cap macrophages
o Microglial cells, substance of brain & spinal cord
o Ag-presenting macrophages in lymphoid follicles
• Acute pn: gram (+) cocci phagocytized by PMN exudate into alveolar space. Opsonin IgG & Csb
facilitate attachment of PMN to offending agents: bacteria, phagocytosis by PMN

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Inflammation focus after experiencing debris cleaning (crush of cells, collagen & foreign
objectives):

• Parenchymal cells of local tiss, mitosis to fill post inflame area

Interstitium network update:

• Fibroplasia: mitosis fibroblast & forming collagen

• Neovascularization: new growing cap network
• End nerve also regeneration

Chronic Inflammation

• X heal after 2 weeks

• Results of unsuccessful acute inflammatory response:
o Causative difficult to destroy
o Extensive necrose tiss
o Repeated causative attacks
o Immune suppressive host
• Other cause:
o Microorg w ↑ lipid & wax content
o  live in leucocytes
o Toxins: cytolytic (cell lyses)
o Chemical & dissolved substances that are irritant (caustic)
o Physical irritant materials (metals)
• Features:
o Inflammatory focus infiltrated by lymphocytes & macrophages, plasma cells, fibroblast,
angioblast & collagen
o Inflammation form granuloma
o Epithelioid macrophages form @ inflammatory focus when focus enlarged, epithelioid
cells necrose
o Giant cells appear bet epithelioid cells
o Causative resides in epithelioid, giant cells / scattered in inflammatory focus outside
macrophage
o Fibrocyte tiss surr the granuloma focus

Systemic Inflammatory Syndrome / Acute Phase Respond

• Septicemia: serious bloodstream infection. = blood poisoning.

• occurs when bac infection in body, lungs / skin, enters bloodstream.
• Dangerous b/c bac & toxin carried thru’ whole body
• Sever sepsis: occur when several vital organs damaged resulting in ↓ organ function
• Etiology: pathogen, trauma, burn, acute pancreatitis, spreading infection
• Septic shock: serious sepsis case, body goes into shock (life threatening, ↓ BP/hypotension)
• Hypotension when body fluids x reduced
• Indicator:
o Tachycardia (↑ heart rate)
o Fever = response to emergence of

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▪ Internal pyrogens: hypothalamic prostaglandin (PGE-2) / MI (IL-1 &TNF)

▪ External pyrogens: LPS (lipopolysaccharides) infectious bac products
o Presence of hypothermia
o Leucocytes ↑ (leukocytosis) w emerging immature-2 forms (donut core neutrophils,
horseshoes nuclei)
• Steps:

Fibrous Repair:
1. Phagocytosis of necrotic tiss debris by inflammatory cells
2. Proliferation of endothelial cells forming small cap => grow into necrotic area
3. Proliferation of fibroblast & myofibroblasts that synthesize collagen & cause wound contraction
Mixture of cap, inflammatory cells & fibroblast = granulation tiss

• Open wound/ulcers have chronic healing w formation of granulation (fibrogenesis &

angiogenesis 2-cell collection)

Tiss healing depends on type of local organ cells

1. Unstable cells
a. Always ready to renew b/c growing points / cells w unconditional mitotic power
b. Epidermis of skin constantly being renewed from the lowest layer, basal cell layer.
Epithelium of small intestinal villi mucosa is always renewed from crypta cells
c. If damaged is accompanied by mucosal dermis / propria layer, healing is accompanied
by fibrosis (reparative healing)
2. Stable cell
a. Cells w mitosis if death of adjacent cells, provide the supporting tiss framework x
defective / damage
Hepatic Hepatocytes when acute local inflammation:
i. After causative & necrose debris cleansing, → adjacent hepatocyte undergo mitosis, filling the
gap
ii. Supporting tiss framework of liver lobules damages, hepatocytes mitosis accompanied by
fibrotic conn tiss formation (reparative healing)
Tiss Healing
1. Tiss repair = restoration of tiss architecture & function following an injury

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2. Tiss regeneration = new growth completely restores portion of damaged tiss to normal state
a. Acute inflammation heals retentively if supporting tiss x damaged, exp when local
parensim cell of permanent cell type x regenerative / mitotic properties.
b. If damaged accompanied by supporting tiss, healing accompanied by fibrosis
c. Acute inflammation delayed healing (→ chronic inflammation), experience reparative
healing (healing accompanied by fibrosis)
3. Permanent / non-mitotic cells: cardiac muscle & adult animal neurons, neutrophils
a. Death by necrosis (inflammation) / apoptosis (w/o inflammation) replaced by fibrosis
(reparative healing)
b. CNS, fibrosis process carried out by astrocytes (Astrocytosis)

General pattern of tiss healing preceded by local inflammation. Local perensim cell healing
accompanied by fibrosis.

Weeks ltr, after supporting tiss is strong, remodeling cap ↓, fibroblast contract myofibroblasts →
fibrocytes again w ↓ production of collagen fibers

Fibrous repair:

• As repair continues, granulation tiss becomes ↓ vas & matures into fibrous scar tiss
characterized by abundant collagenous fibrous tiss
• Maturation accompanied by shrinkage of scar, mediated by contraction of fibrils w/in
myofibroblast
• Fibrous scarring gradually develops directly in areas of ongoing chronic inflammation

Complication of reparative healing:

• Accompanied by fibrosis
• Organ adhesions, bet lungs lobes / chest wall after chronic pleurisy
• ↓ organ function, myocardial fibers after infraction replaced by granulation tiss
• ↓ heart pump capacity (fatigue, dilation of ventricles of heart)
• ∆ in anatomical patterns, interfere with functions
• Hepatitis spreads, fibrosis ↑, hepatocyte regeneration distorted, liver cirrhosis occurs (liver
shrinks, uneven surface & hard consistency)
• Granulation tiss formation can be excessive especially collagen formation
• Skin form keloids (nodulation of skin), although epidermis heals, excessive dermal collagen x
experience remodeling

Local healing disorder

• Poor blood supply (post vasculitis, arteritis, atherosclerosis, narrowed vas lumen)
• Systemic infection (leukocytes used up, process debridement of phagocytosis slow)
• Excessive mechanical stretching (surgical wound healing tear)
• Pathogens / foreign bodies still implanted in wound (suture head, bone fragments, tampon
residue)
• Necrose tiss in nest excessive inflammation, takes long time to clean (debridement)
• Repetitive causative (radiation / x-rays, friction i.e.: decubitus sores on elbow or large dogs)

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Internal healing disorder

• Old age (apoptotic ↑, regeneration capacity ↓)

• Hormonal disorder (recovery rqd growth hormone)
• Nutritional deficiencies: protein, ess fatty acids, vit, esp Vit C (collagen formed abnormally, x
strong, easily damaged)
• Chronic disease (diabetics, wounds difficult to heal when sugar level ↑)
• Drug abuse

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