Cells To Systems Week 4

Front 1

ACUTE INFLAMMATION

Back 1

Initial response to tissue damage.

Non specific

eliminates dead tissue, protects against local infection, allows immune system access.

Rapid onset, short duration

Increased blood flow, structural changes to vessels, oedema (Exudation of fluid and plasma proteins), emigration of leukocytes (mainly neutrophils) to eliminate agent.

Front 2

Restitution

Back 2

the ideal outcome of inflammation. Damaged area is replaced by organised tissue with normal structure and function.

Front 3

CHRONIC INFLAMMATION

Back 3

The damaging agent and tissue destruction persists

Ongoing attempts to repair

ongoing immune response.

Front 4

Causes of acute inflammation

Back 4

mechanical trauma

thermal and chemical injury

biological- viruses, fungi, immune response to foreign proteins.

Front 5

Functions of acute inflammation

Back 5

To bathe the area in inflammatory exudate which carries proteins, fluids and cells to mediate local defences. Biological agents are destroyed and eliminated, and damaged tissue broken down and debris removed.

Front 6

Cardinal Signs of inflammation

RHPLS

(ron harry please)

Back 6

1) redness (rubor) - increased blood flow under skin

2) heat (calsor)- too much heat causes damage. due to vessel dilation and increased blood flow.

4) pain (dolor) chemical mediators, pressure on nerves

5) loss of function (functio laesa) eg. can't put weight on limb

3) swelling (Fumor) - blood vessel dilation -> efflux of fluid to surrounding tissues.

Front 7

Autocoids

Back 7

Autacoids are biological factors which act like local hormones, have a brief duration, and act near the site of synthesis. Those involved in inflammation are often termed inflammatory mediators.

They Modulate activity of smooth muscle, glands, vascular permeability, and sensory nerves (pain and itch).

PARACRINE EFFECT (cell to cell)

Front 8

Notable autacoids

CHEP

Back 8

Cytokines

Histamine

Eicosanoids

Peptides (eg. bradykinin & substance P)

Front 9

Histamine

Back 9

-Stored in granules in mast cells (tissues), basophils (blood) and EC cells (GIT)

-Released in response to various stimuli... IgE, complement, neuropeptides. trauma...

-Act through G protein coupled receptors (GPCRs)

-RESPONSES

1) reddening- vasodilation

2) wheal- increase in vascular permeability

3) flare- spreading response through sensory fibres

TREATED WITH H1 receptor blockers (atopic dermatitis , anaphylaxis, bites, stings)

Front 10

Regulatory peptides

Back 10

Cause vasodilation, itch, pain.

Bradykinin: stimulates nerve endings to release substance P. Broken down by angiotensin converting enzyme (ACE), causes vasodilation.

Substance P: neurotransmitter sitting within nerve endings. Causes local itch, pain, vasodilation.

Front 11

Eicosanoids

Back 11

-Most anti-inflammatory drugs target these.

-Derived from arachidonic acid (breakdown of membrane phospholipids)- include prostaglandins, thromboxanes and leukotrienes.

- Different cells make different types

Front 12

Actions of eicosanoids

Back 12

Also act through GPRCs- in inflammation cause redness, swelling, pain, fever.

Also inhibit gastric acid secretion, and increase renal blood flow and water/ sodium excretion by kidney- therefore need to be careful how much we block prostaglandins.

Aspirin- the first non- steroidal anti-inflammatory targets eicosanoids.

Front 13

Cytokines

Back 13

- Small proteins produced mainly by WBCs (also endothelial, fibroblasts and stromal cells). Important role in inflammation.

- modulate the balance between humoral and cell-based immune responses

-Interleukins are the biggest group.

Front 14

Major processes in acute inflammation

VEE

Back 14

1) vasodilation

2) exudation (fluid coming out of bloodstream)

3) emigration of leukocytes (from blood to inflammation site)

Front 15

Vasodilation in acute inflammation

Back 15

-Of arterioles, capillaries and post capillary venules.

-stimulated by NO, histamine, prostaglandin I2 and bradykinin

-Local increase in blood flow causes heat and redness of inflammation.

Front 16

Exudation in acute inflammation

Back 16

Cells in endothelial layer retract from each other, leaving pores in the membrane, allowing water to come out under hydrostatic and oncotic pressure.

-stimulated by histamine, bradykinin and leukotrienes.

-May lead to outpouring of protein rich fluid called exudate, or a transudate (low protein)

Front 17

Effects of increased vascular permeability

Back 17

Fluids +/- cells leak into tissues.

Front 18

Transudate

Back 18

Transudate is fluid containing low protein and few cells. Results from mild change in endothelial integrity.

Front 19

Exudate

Back 19

Exudate is fluid and many cells, high protein. Can lead to deposition of proteins on the outside of organs.

May contain fibrinogen, which may be polymerised into insoluble fibrin protein forming a mesh in inflamed tissues (yellow, sticky looking). (holds damaged areas together, blocks bacterial migration, aids leukocyte migration).

Exudate fluid = salts, high protein, antibodies, dilution of toxins, diffusion of inflammatory mediators, circulation takes antibodies to lymph nodes.

Cells- neutrophils, macrophages.

Front 20

Emigration of leukocytes - how do leukocytes get from blood to tissues?

Back 20

1) cytokines/ inflame mediators stimulate endothelial cells to express adhesion molecules.

2) leukocytes stick to endothelium (leukocytes first)

3) Gradients of chemokines attract the leukocytes to the tissue.

4) in tissue, release free radicals and enzymes to clear dead tissue, kill bacteria- but can ultimately cause tissue damage and loss of function.

Front 21

Pain in inflammation

Back 21

caused by damage/ injury to peripheral nerve endings, pressure to them from peripheral swelling, or effects of mediators on nerve endings.

Front 22

Hightened pain sensitivity in inflammation

Back 22

inflammatory mediators can amplify pain by acting on the PNS and pain pathways in the spinal cord.

Front 23

Neurogenic inflammation

Back 23

Inflammation mediated by nerve endings. Eg. inflammatory mediator substance P release from nerve endings in response to eating chilli peppers

Front 24

Itch (pruritis)

Back 24

Unmyelinated axons for itch lie in the skin- leads to scratching, self trauma and more inflammation. Mediators such as histamine and substance p.

Front 25

Fever / pyrexia

Back 25

Body temperature increases.

This helps the healing process by...

1) Increasing mobility of leukocytes and phagocytosis.

2) Increasing T cell proliferation.

Front 26

Pyrogens

Back 26

Substances that induce fever.

Endogenous- cytokines (TNFa, ILs)

Exogenous- bacterial toxin, LPS.

Front 27

How pyrogens cause inflammation

Back 27

Cause release of PGE2

PGE2 acts on the hypothalamus

Sympathetic nervous system

Increased thyroid hormone

Heat increase.

Front 28

Pathological classification of acute inflammation

(nature of exudate)

SCFS - some cows feel sick

Back 28

1) serous

2) catarrhal

3) fibrinous

4) Suppurative

Front 29

serous acute inflammation

Back 29

Less severe. Mild inflammation. Water and low MW solutes pass out of plasma. A watery, straw coloured fluid in tissues.

aka. modified transudate.

burns injuries, skin blisters and effusions into body cavities (pleural, pericardial or peritoneal) related to viral infections.

Front 30

catarrhal acute inflammation

Back 30

formed on mucosal surfaces. Mucous, mixed with serous fluid, cell debris and inflammatory cells.

In airway or intestine where cells secrete mucous, will get serous fluid mixed in with a lot of mucous.

Front 31

Fibrinous acute inflammation

Back 31

A more severe change in vascular permeability.

Fibrinogen is converted to fibrin, which grossly appears as a yellow gel (yellow, buttery).

Occurs on serosal or mucosal surfaces.

characteristic of inflammation in body cavities such as pericardium and pleura

Front 32

Supperative

Back 32

A more extreme stage that occurs in particular when bacterially induced. Pussy exudate (lots of tissue damage) and large numbers of cells.

A characteristic response to certain types of bacteria that are termed “pyogenic” (pus producing)

Front 33

Pus

Back 33

creamy fluid composed of intact and disintegrating neutrophils, within a background of fragmented and liquified necrotic tissue elements.

Front 34

Abcess

Back 34

A localised collection of pus caused by supperative inflammation in a tissue. As the island of necrotic tissue and neutrophils grows, a wall of fibrous tissue is formed around it in an endeavour to confine it.

Front 35

Phlegmon

Back 35

- Spreading diffuse suppurative inflammation present in the loose connective tissue.

-Poorly defined margins

-progresses rapidly. acute pendicitis in humans, cellulitis.

Front 36

Empyema

Back 36

Accumulation of pus within a body cavity

Front 37

Resolution of inflammation

Back 37

1) apoptosis & leukocyte removal

2) macrophages switch from pro-inflammatory to phagocytic and antiinflammatory

3) Stop signals - resolvins, lipoxins, protectins

4) If resolution doesn't occur -> chronic inflammation.