Inflammation in organs without blood vessels.

The inflammation-organism relationship (beneficial and

harmful effects of inflammation; outcome of the acute inflammation, systemic sings of acute

inflammation)

Special type of inflammation

• Organs without blood vessels

• Examples:

– cornea, cartilage, heart valves

• No real circulatory response

• Only regressive changes

• Reflex action of the surrounding

tissue

Cornea

• From the neighboring conjuctiva

– Circulatory response

• blood plasma flows into tissue spaces

– Exudative and infiltrative processes

• granulocytes migrate into the cornea

(Recognition: difficult - elongated shape)

• Persistent stimulus

– vascularisation opacity of the cornea

Intact cornea

Cornea

H.-E.; 100x

Epithelium Corneal connective tissue (substantia propria)

Fibroblast cells

Collagen fibers

H.-E.; 200x

Epithelium

Corneal connective tissue (substantia propria)

Fibroblast cells

Collagen fibers

H.-E.; 400x

Cornea

• From the neighboring conjuctiva

– Circulatory response

• Blood plasma flows into tissue spaces

– Exudative and infiltrative processes

• Neutrophil granulocytes migrate into the

cornea

(Recognition: difficult - elongated shape)

• Persistent stimulus

– Vascularisation (neoangiogenesis) opacity of the

cornea Pannus

Keratitis/Pannus

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https://www.google.hu/search?q=keratitis+pannus&client=firefox-

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Keratitis, elongated neutrophil

granulocytes

Pannus

Pannus

In ophtalmology, pannus is a progressive change occurs

where blood vessels and scar tissue invade the cornea.

In normal individuals, the cornea is avascular.

Chronic inflammation or local hypoxia may lead to

corneal vascularization, or pannus.

H.-E.; 40x

Pannus

H.-E.; 100x

Pannus

H.-E.; 200x

Pannus

H.-E.; 400x

Pannus

Chronic Superficial Keratitis (Pannus) is a disease seen

most commonly in the German Shepherd, but does occur

in other breeds.

Cartilage

• Chondritis

• Monochodritis

• Polychondritis

• Feline auricular chondritis

Feline auricular chondritis

Pinna: Marked multifocal, chronic lymphoplasmacytic

and neutrophilic chondritis and dermatitis with

degeneration splitting and necrosis of auricular cartilage.

• Auricular chondritis has been reported in rats, mice,

cats, dogs, in a horse and very rarely in cattle.

• It has been classified among the immune-mediated

diseases due to similarities to rheumatoid arthritis

and lupus erythematosus as well as its favorable

response to immunomodulatory therapy.

• Clinical signs include pain, swelling, erythema and

deformation of the pinnae.

• Other organs such as joints, eyes and heart may be

present as well.

• Histologically, lesions consist of lymphoplasmacytic

infiltrates and loss or necrosis of cartilage.

Valves

• neutrophil migration is missing

• proliferative processes

– proliferation of the basic cells

– endothels

– fibrin

• vascularisation from the neighboring

tissues

– blood vessels from the heart muscles

Valves/Endocarditis

• Endocarditis

– Mostly bacterial: E. rhusiopathiae, streptococci, staphylococci, klebsiella, C. pyogenes (rarely parasital, fungal)

– valvular - parietal endocarditis

– acute - chronic (vegetative - verrucosus)

– mitral > aortic > tricuspid > pulmonary

• Consequences of endocarditis

– acute cardiac failure

– chronic cardiac failure

– septic thromboembolism

Inflammation

The inflammation-organism relationship

(1) Complex pathological process.

(2) Congenital non-specific protective mechanism.

(3) Aim: elimination of different exogenous and endogenous non-infective physical, chemical and infective biological (viral, bacterial infections) agents + necrotic tissues and cells. Keep the integrity of the organism, minimisation of the destruction of the tissues and cells.

(4) Rapid protection until effective immune response (in the fibrovasculare tissues; duration: few hours-days).

The inflammation-organism relationship

(4) Rapid protection until effective immune response.

- Few seconds after injury!

The inflammation-organism

relationship

(4) Rapid protection until effective immune

response.

- Effective immune response: acquired, specific

protective mechanism based on lymphocyte

proliferation.

- Specific for the inflammatory agents (antigens).

- Specific clonal proliferation (expansion) of the

T- and/or B-lymphocytes (cellular and/or

humoral immune response => 3-5 days after

inflammatory injury!).

Effective immune response

= Subacute inflammation Lymphocytes

The inflammation-organism

relationship

(5) This protective

inflammatory reaction

tries to restrict

(localize) the

destructive, cytotoxic

effect of the infective,

and non-infective

inflammatory stimuli to

the site of entry.

The inflammation-organism

relationship

(6) Diluting, inactivating biologic

and chemical toxins.

(7) Killing and sequestrating

microbes and neoplastic cells.

(8) Degrading foreign body.

(9) Providing wound healing

(growth) factors to ulcerated

surfaces and traumatised tissue.

Aulus Cornelius Celsus

- Clinical features of acute

inflammation were

described by Celsus (dated

around 2000 BC)

- Four cardinal signs of acute

inflammation: rubor, tumor,

calore and dolore, redness,

swelling, heat, and pain.

Rudolf Virchow

-A fifth clinical sign, loss

of function (functio

laesa) was later added

by Rudolf Virchow

(1858).

The inflammation-organism relationship

• beneficial and harmful effects of inflammation

• outcome of the acute inflammation

• The systemic sings of acute inflammation

• rubor (redness)

• tumor (swelling)

• calor (warming up)

• dolor (pain)

1st century AD Celsus

• functio lesa (decreased function)

Galenus

Cytokines

Cytokines are a broad and loose category of small

proteins (~5–20 kDa) that are important in cell

signaling.

Cytokines are produced by a broad range of cells,

including immune cells like macrophages, B-

lymphocytes, T- lymphocytes and mast cells, as well as

endothelial cells, fibroblasts, and various stromal cells.

Cytokines include chemokines, interferons, interleukins,

lymphokines, and tumour necrosis factors but generally

not hormones or growth factors.

Cytokines

They act through receptors, and are especially important in the

immune system.

They are important in health and disease, specifically in host

responses to infection, immune responses, inflammation,

trauma, sepsis, cancer, and reproduction.

Virtually all nucleated cells, but especially endo/epithelial cells

and resident macrophages are potent producers of IL-1, IL-6,

and TNF-α.

The action of cytokines may be autocrine or paracrine in

chemotaxis or chemokinesis and endocrine as a pyrogen.

Cytokines

Cytokines have been classed as lymphokines,

interleukins, and chemokines, based on their presumed

function, cell of secretion, or target of action.

The term interleukin was initially used by researchers

for those cytokines whose presumed targets are

principally leukocytes. Lymphokines, produced by

lymphocytes

Monokines, produced exclusively by monocytes.

Interferons, involved in antiviral responses.

Chemokines mediate chemoattraction (chemotaxis)

between cells.

Macrophages

Proinflammatory

cytokine

Proinflammatory cytokines are cytokines that are important

in cell signaling and promote systemic inflammation.

They are produced predominantly by activated macrophages

and are involved in the upregulation of inflammatory

reactions.

IL-1, TNF-alpha, and chemokines are examples of

proinflammatory cytokines.

Proinflammatory cytokines are used to activate neutrophils.

Pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α

function to be a part of pathological pain.

Hypercytokinemia

„Cytokine storm”

- When the immune system is fighting pathogens, cytokines

signal immune cells such as T-cells and macrophages to

travel to the site of infection.

- In addition, cytokines activate those cells, stimulating them to

produce more cytokines.

- Normally, this feedback loop is kept in check by the body.

However, in some instances, the reaction becomes

uncontrolled, and too many immune cells are activated in a

single place.

- Uncontrolled release of more than 150 known inflammatory

mediators (IL-1, IL-6, TNF-alpha).

Clinical signs of inflammation

• the pathopysiologic background of the lesions were described at the end of the 19th century by Cohnheim

• Inflammation is not an independent, isolated process

– Although it develops on circumscribed parts of the body

• in an organ or on a part of an organ

– in regional lymph nodes

– it can have distant effect in the body

• fever, lack of appetite, depression

Clinical signs of inflammation

• in regional lymph nodes always similar lesions to the primary process

– circulatory disturbance: active hyperaemia

– exudation: leakage of serum to the sinusoids

– infiltration: detached endothelial cells, granulocytes, lymphocytes in the sinusoids

– proliferative process: proliferation of the reticular cells and lymphocytes

– alterative process : necrosis occurs too

Organism - inflammation

• 1. CNS

– coordination

• 2. Endocrine system

– Mineralo- and glycocorticoids

• 3. Immunological state

– Allergic reaction

• 4. Others (condition)

General condition and inflammation

• hormonal factors (inhibitory, stimulatory)

- anterior pituitary (adenohypophysis): ACTH

- cortex of the adrenal gland : glyco corticoids

(hydrocortizone, cortizone)

- anterior pituitary (adenohypophysis): STH

- cortex of the adrenal gland: mineralo corticoids

(dezoxy-corticosterone)

General condition and inflammation

• hormonal factors (inhibitory, stimulatory)

• STH - increases cell proliferation

– glyco corticoids from the adrenal gland:

• decrease

– the permeability of the cell membrane and the wall of the capillary

– the exudation

– the proliferation of the fibroblasts

– the increased permeability effect of the hyaluronidase

– the tissue antigen-antibody reaction

• inhibit the migration of the granulocytes

Effects of the antigens

• Normergia

– the organism did not meet the antigen yet

• Hyperergia

– the organism did meet the antigen already

(seroconversion)

– sudden severe inflammatory reaction

• severe hyperaemia, exudation, fibrinoid degeneration

• eosinophil cellular infiltration, proliferative processes

– Immunity (antibodies)