PATH 3610 Lecture Notes - Lecture 3: Granuloma, Tumor Necrosis Factor Superfamily, Transudate

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1 May 2018

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Inflammation

Unit Outline:

1. name the cardinal signs of inflammation

2. describe the role of the acute inflammatory response

3. describe the acute inflammatory response in terms of vascular changes and the

cellular response

4. explain how inflammatory exudate forms

5. describe the differences between transudates and exudates

6. describe the differences between granulocytes and mononuclear cells

7. describe how inflammatory cells reach the site of inflammation

8. give a general explanation of the role of chemical mediators in inflammation

9. describe the systemic signs of acute inflammation

10. describe the possible outcomes of acute inflammation, including abscess formation

11. describe how chronic inflammation in response to antigenic agents develops

12. characterize granulomatous inflammation

13. describe why granulomatous inflammation develops

14. list the five general causes of non-granulomatous chronic inflammation

15. describe how chronic inflammation develops in response to non-antigenic agents

such as foreign material

16. describe and give an example of chronic suppurative inflammation

17. define and describe the significance of amyloid deposition in tissues

Chronic inflammation is characterized by:

• Some degree of immune response, indicated by the presence of mononuclear cell

types (like plasma cells and lymphocytes)

• Infiltration and accumulation of macrophages (which mediate phagocytosis)

• Healing of tissue through development of granulation tissue (characterized by tissue

fibrosis and angiogenesis aka formation of new blood vessels)

• Ongoing tissue injury and necrosis

Introduction

Inflammation:

• Implies a complex, predetermined and nonspecific response to injury, consisting of a

microcirculatory response as well as mobilization of phagocytic cells (=acute inflammatory

response)

◦ It is characterized by factors above with redness, heat, pain, swelling and loss of

function also considered cardinal signs

• If prolonged, chronic inflammation is used to describe a complex of tissue changes of

a combined inflammatory and immune response against the foreign agent

• Wherever inflammation occurs, it is described by adding the suffix "-itis"

◦ Appendix - appendicitis

◦ Colon - colitis

◦ Skin - dermatitis

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◦ Stomach - gastritis

Acute Inflammatory Response

Acute inflammation is essentially the first line of defense against an injury.

• The changes occurring in inflammation are predictable, but the extent of the

inflammatory reaction is proportionate to the degree of tissue damage

• The changes occurring in blood vessels lead to "leakiness" of the vessels, such that

fluid, chemicals (produced by the body) and leucocytes can move into tissue spaces

• The ultimate benefit of these changes is that the causative agent is destroyed, and

debris is removed to allow repair

Tissue Injury

Tissue Injury --> Inflammation

Once inflammation has developed, the progression towards resolution and healing begins almost

immediately, though time to reach these endpoints is extremely variable

There are two major components to acute inflammation:

A. Vascular Changes

◦ Vessels dilate to increase blood flow to the area

◦ Vessels become more permeable, to allow plasma proteins to leave the circulation

and enter the injured site

B. Cellular Response

◦ Leukocytes leave the microcirculation and accumulate at the injured site

*read pages 29-31

Vascular Changes

• The basic vascular changes occurring in inflammation occur in the microcirculation,

capillaries, arterioles and venules

◦ These vessels become dilated (vasodilation), so there is more blood in the are (cause

of redness)

◦ The vessels become leaky so fluid moves out of the vessels and into the tissue spaces

(cause of swelling)

• Following an injury, one of the first reactions is transient vasoconstriction, but it is

not very significant

◦ More important is the marked active dilation of arterioles, capillaries and venules

caused by the release of a variety of chemical mediators from damaged and necrotic cells, such

as:

• Vasoactive amines (histamine and serotonin)

▪ Histamine - released by mast cells and is a derivative of amino acid histadine that

generally causes capillary dilation

• Kinins

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Mast Cells:

• Mast cells are found throughout the body, but in greater concentration in

damaged/necrotic cells

• Generally causes capillary dilation

• Contain membrane bound vacuoles (granules) which contain histamine

• Injury to the surface of the mast cell (or activation by external stimuli) leads to

degranulation of the mast cell, with subsequent release of histamine

*Normally only some capillaries within a tissue contain a stream of blood

• Precapillary sphincters of remaining capillaries are closed, causing blood to pass

through tissue via "freeway" channels (directly from arterioles to venules)

• As you become more active, the precapillary sphincters open and blood is diverted to

perfuse to tissues in response to an increased metabolism

• Dilation of arterioles also brings more blood into the area

Hyperemia = increased blood flow in the tissue (causes the inflamed tissue to appear red)

Increased permeability of capillaries and venules occurs initially due to a widening of

intercellular junctions between endothelial cells

• Recall: fluid normally leaves capillaries at the arteriolar end under the influence of

hydrostatic pressure and returns to vascular space at the venular end of capillary bed due to

osmotic pressure

• If the normally selectively permeable barrier of the endothelium is damaged by

inflammation, the spaces between endothelial cells are much wider than usual, increased

amounts of fluid as well as larger molecules (proteins) will pass out of the vessels and into the

extravascular space (=exudation)

• This causes the swelling and accumulation of inflammatory exudate

Therefore, acute inflammation is an important cause of localized edema

*see Figure 2-4 (page 33)

Increased vascular permeability is the result of more than just the initial widening of intercellular

gaps (pages 33-34):

• The initial endothelial cell contractions, which widens the intercellular junctions, is a

transient process occurring primarily in venules

◦ A more prolonged retraction of endothelial cells (mediated by tumour necrosis factor

and interleukin) also occurs

• Direct injury to endothelium causes endothelial necrosis and detachment, which

contributes to leakage from vessels

◦ Primarily after severe injuries

• Leukocyte-mediated endothelial injury

◦ Leukocytes release proteolytic enzymes and toxic oxygen species which further

endothelial cell injury and detachment

• Increased transcytosis

◦ Transcytosis refers to fluid movement across endothelial cells via vesicles

• Leakage from newly formed blood vessels (UNIT 5)

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Document Summary

Chronic inflammation is characterized by: types (like plasma cells and lymphocytes) fibrosis and angiogenesis aka formation of new blood vessels) Infiltration and accumulation of macrophages (which mediate phagocytosis) Healing of tissue through development of granulation tissue (characterized by tissue. Some degree of immune response, indicated by the presence of mononuclear cell. It is characterized by factors above with redness, heat, pain, swelling and loss of. Implies a complex, predetermined and nonspecific response to injury, consisting of a. If prolonged, chronic inflammation is used to describe a complex of tissue changes of. The changes occurring in inflammation are predictable, but the extent of the. The ultimate benefit of these changes is that the causative agent is destroyed, and. The changes occurring in blood vessels lead to leakiness of the vessels, such that: vascular changes. Vessels dilate to increase blood flow to the area. Vessels become more permeable, to allow plasma proteins to leave the circulation.