Session 11: Outcomes of Inflammation

Session 11: Outcomes of Inflammation

• Felician Sikujua (MD)

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Learning tasks

Learning tasks

At the end of this session, students are expected to be able to:

Explain outcomes of acute inflammation.

Identify beneficial effects of acute inflammation.

Identify harmful effects of acute inflammation.

Explain systemic effects of acute inflammation.

Identify outcomes of chronic inflammation.

Identify systemic effects of chronic inflammation.

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Outcomes of Acute Inflammation

Outcomes of Acute Inflammation

Resolution (complete healing).

Occurs when tissue damage is minimal or process is short lived and the tissue has the ability of regeneration.

Progression to chronic inflammation.

When the tissue damage is extensive or when the exudates is not completely eliminated.

Fibrosis.

This occurs when there is extensive tissue damage, exudates are not timely cleared and tissue involved has no capacity to regenerate.

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Outcomes of Acute Inflammation cont…

Outcomes of Acute Inflammation cont…

Spread to different tissues by

Direct e.g. in cellulitis.

Lymphatic e.g. lymphangitis, acute lymphadenitis.

Blood vessels e.g. pyaemia, septicaemia.

Death

It can result from

Septicaemia, e.g. endotoxic shock and its complications.

Involvement of vital organs, e.g. encephalitis, myocarditis.

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Beneficial effects of Acute Inflammation

Beneficial effects of Acute Inflammation

Dilution of toxins.

Provide protective antibodies as present in exudates.

Fibrin formation, preventing bacteria spreading.

Plasma mediator systems provisions to the area of injury.

Cell nutrition as exudates brings with it glucose, oxygen to the cells.

Promotion of immunity as micro-organisms and their toxins stimulate antibodies production.

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Harmful effects of Acute Inflammation

Harmful effects of Acute Inflammation

Tissue destruction

Inflammation may result in tissue necrosis.

Swelling

Caused by inflammation may have serious mechanical effects at certain locations.

Inappropriate response

The inflammatory seen in hypersensitivity reactions is inappropriate (i.e. exaggerated).

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Systemic effects of Acute Inflammation

Systemic effects of Acute Inflammation

Also called the acute-phase reaction or the systemic inflammatory response syndrome.

Cytokines that are most important mediators of the acute-phase reaction

Tumor Necrotic Factor (TNF).

Interleukin-1 (IL-1).

Interleukin-6 (IL-6).

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Systemic effects of Acute Inflammation cont…

Systemic effects of Acute Inflammation cont…

Tumor Necrotic Factor (TNF) and Interleukin-1 (IL-1) have similar biologic actions, inducing fever and leukocytosis.

Interleukin-6 (IL-6) stimulates the hepatic synthesis of a number of plasma proteins.

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Acute-phase reactions

Acute-phase reactions

The acute-phase response consists of several clinical and pathologic changes including

Fever.

Elevated plasma levels of acute-phase proteins.

Leukocytosis.

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Fever

Fever

It is characterized by an elevation of body temperature.

It is one of the most prominent manifestations of the acute-phase response.

Fever is produced in response to substances called pyrogens that act by stimulating prostaglandin synthesis in the vascular and perivascular cells of the hypothalamus.

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Fever cont…

Fever cont…

Bacterial products, such as lipopolysaccharide (LPS) (exogenous pyrogens), stimulate leukocytes to release cytokines such as Tumor Necrotic Factor (TNF) and Interleukin-1 (IL-1) (endogenous pyrogens).

Tumor Necrotic Factor (TNF) and Interleukin-1 (IL-1) increase the levels of prostaglandins.

In the hypothalamus the prostaglandins, especially PGE2, stimulate the production of neurotransmitters, which reset the temperature set point at a higher level.

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Elevated plasma levels of acute- phase proteins

Elevated plasma levels of acute- phase proteins

These plasma proteins are mostly synthesized in the liver.

Increase concentrations in acute inflammation.

These proteins include

C-reactive protein (CRP).

Fibrinogen.

Serum amyloid A (SAA) protein.

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Elevated plasma levels of acute- phase proteins cont…

Elevated plasma levels of acute- phase proteins cont…

Synthesis of these molecules by hepatocytes is stimulated by cytokines, especially Interleukin-6 (IL-6).

Many acute-phase proteins, such as CRP and SAA, bind to microbial cell walls, and they may act as opsonins and fix complement, thus promoting the elimination of the microbes.

An increased CRP is a measure of acute inflammation.

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Leukocytosis cont…

Leukocytosis cont…

Leukocytosis is a common feature of inflammatory reactions, especially those induced by bacterial infection.

The leukocytosis occurs because of accelerated release of cells from the bone marrow post mitotic reserve pool.

Influenced by Tumor Necrotic Factor (TNF) and Interleukin-1 (IL-1) cytokines.

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Leukocytosis cont…

Leukocytosis cont…

Prolonged infection also stimulates production of colony stimulating factors (CSFs), which increase the bone marrow output of leukocytes.

Most bacterial infections induce an increase in the blood neutrophil count, called neutrophilia.

Viral infections are associated with increased numbers of lymphocytes (lymphocytosis).

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Leukocytosis cont…

Leukocytosis cont…

Bronchial asthma, hay fever, and parasite infestations cause increase eosinophils, creating an eosinophilia.

Certain infections (typhoid fever and infections caused by some viruses, rickettsiae, and certain protozoa) are paradoxically associated with a decreased number of circulating white cells (leukopenia).

Because of cytokine-induced sequestration of lymphocytes in lymph nodes.

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Other manifestations of the acute-phase response

Other manifestations of the acute-phase response

Increased heart rate and blood pressure.

Decreased sweating.

Rigors (shivering).

Chills (perception of being cold).

Anorexia.

Somnolence.

Malaise.

Septic shock.

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Outcomes of Chronic inflammation

Outcomes of Chronic inflammation

Scarring (healing by fibrosis).

Chronic discharging sinus commonly seen in chronic osteomyelitis.

Pathological fractures.

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Systemic effects of Chronic inflammation

Systemic effects of Chronic inflammation

Fever.

Anaemia.

Leukocytosis.

Elevated Erythrocytes Sedimentation Rate (ESR).

Amyloidosis.

Weight loss.

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Key points

Key points

Death in acute inflammatory conditions is mainly due to septicemia.

In acute inflammation complete healing is common seen in the tissue which can regenerate .

Fibrosis is seen in tissue which cannot regenerate.

TNF and IL-1 induce fever and leukocytosis.

An increase CRP is a marker for acute inflammation

An increase in ESR is a marker for chronic inflammation.

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Review questions

Review questions

Explain five (5) outcomes of acute inflammation

Explain mechanisms causing an increase of body temperature in acute appendicitis.

List three (3) plasma proteins produced in acute inflammatory reaction.

List specific leukocytes raised in bacterial, viral and parasitic infections.

Mention three (3) outcomes of chronic inflammation.

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References

References

Bezabeh M.; Tesfaye A.; Ergicho B. et al (2004): General pathology lecture notes for Health Sciences students. Ethiopia Public Health Training Initiative. Pg. 33-34.

Kumar V.; Abbas A. K.; Aster J. C.;(2013): Robbins and Contran Pathologic Basis of Disease (9th Ed.) Elsevier Saunders, China. Pg. 41-42, 57-58.

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