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Physiological Processes

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Physiological Processes: Basic Concepts Systemic Inflammatory Response Syndrome (SIRS) Multiple Organ Dysfunction Syndrome (MODS)
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Page 1: Physiological Processes

Physiological Processes:Basic Concepts

Systemic Inflammatory Response Syndrome (SIRS)

Multiple Organ Dysfunction Syndrome (MODS)

Page 2: Physiological Processes

The Immune System Strives to:

• Eliminate infection and damaged tissue

• Maintain an appropriate response level

• Avoid or minimise disruption to homeostasis

• Promote healing

Page 3: Physiological Processes

Types of Immunity:

• Non-specific (innate):

– Natural barriers

– Inflammation

• Specific (acquired):

- T and B lymphocytes

Page 4: Physiological Processes

The Inflammatory Response

• The inflammatory response:

– A series of localised cellular responses

– Helps to eliminate invading antigens and damaged tissue,

and prevent them spreading to other areas of the body.

Complete the following multimedia tutorial on the basic concepts of inflammation.

http://www.nottingham.ac.uk/nmp/sonet/rlos/bioproc/inflam/index.html

Antigen - any substance that can trigger an immune response.

Page 5: Physiological Processes

The Innate Immune System and Homeostasis

Invasiveness of microbe.

Risk to Homeostasis

Action of innate immune system

skin surface

superficial tissue layers

circulation &

body systems

natural barriers

localised inflammation

systemic

inflammatory

response (SIRS)

BENEFICIAL

DETRIMENTAL

Page 6: Physiological Processes

Immunity is mediated by:

• Soluble molecules:

– cytokines e.g. interleukin (IL)

– others: prostaglandin (PG), reactive oxygen species (ROS)

• Cytokines:

– small proteins

– alter behaviour of other cells

– act via cell-surface receptors

– short-lived

– important examples in inflammation:

• IL-1, IL-6, IL-8, tumour necrosis factor–alpha (TNF-α).

Page 7: Physiological Processes

Trigger: e.g.invading bacteria

endothelium

Potent molecules released

e.g. ROS

Key effector cells:

neutrophil

Physiological changes associated with immunity i.e. inflammation

macrophageKey effector cell:

Chemical mediators of the inflammatory response

Page 8: Physiological Processes

Invading bacteria

endotoxin (lipopolysaccharide - LPS)

endotheliumplasma

macrophageIL-8

neutrophil

skin surface

tissue and interstitial fluid

Chemical mediators of the inflammatory response

IL-1 TNFα

activates endothelia

Page 9: Physiological Processes

vasodilation

permeabilityadhesion

rolling adhesion

Chemical mediators of the inflammatory response

Invading bacteria

macrophage

skin surface

tissue and interstitial fluid

endotheliumplasma

IL-1 TNFa

IL-8

Check NO

endotoxin (lipopolysaccharide - LPS)

Nitric oxide (NO)

Prostaglandin (PG)

Page 10: Physiological Processes

endotheliumplasma

diapedesis

Chemical mediators of the inflammatory response

Invading bacteria

macrophage

skin surface

tissue and interstitial fluid

IL-1 TNFa

IL-8

complement

fibrinogen

antibodies

endotoxin (lipopolysaccharide - LPS)

Nitric oxide (NO)

Prostaglandin (PG)

Page 11: Physiological Processes

skin surface

tissue and interstitial fluid

endotheliumplasma

migration and phagocytosis

more neutrophils and monocytes.

Chemical mediators of the inflammatory response

macrophage

skin surface

IL-1 TNFa

IL-8

Nitric oxide (NO)

Prostaglandin (PG)

complement

fibrinogen

antibodies

Invading bacteria

endotoxin (lipopolysaccharide - LPS)

Page 12: Physiological Processes

• reactive oxygen species (ROS)

• antimicrobial molecules

• hydrolytic enzymes

Chemical mediators of the inflammatory response

Neutrophils release powerful chemicals that

destroy the pathogen.

Some ROS may leak onto nearby tissues

Page 13: Physiological Processes

TNF-alpha (TNFα) is a powerful pro-inflammatory mediator

Activates endothelium:

- adhesion molecules are displayed

- active substances released

Increases vascular permeability

Releases C-reactive protein

Induces fever via hypothalamus

Mobilises neutrophils from bone marrow

TNFα

with

IL-1 and IL-6

Chemical mediators of the inflammatory response

Page 14: Physiological Processes

pro-inflammatory mediators

TNFα

IL-1

IL-6

anti-inflammatory mediators

IL-10

IL-4

glucocorticoids

Maintains inflammation at an appropriate

magnitude to promote health

Regulation of the inflammatory response by

chemical mediators.

Page 15: Physiological Processes

What happens if local inflammatory responses fail?

Natural barriers and local

inflammatory response

Specific immune

response

Chronic inflammation:

infiltration of lymphocytes

and plasma cells

But cannot prevent

microbial invasion into

the blood.

Acute inflammation:

infiltration of neutrophils and

macrophages

Immediate 2-4 days

Potential outcome

bacteraemia / septicaemia

systemic inflammatory response (SIRS)

multiple organ dysfunction syndrome (MODS)

Page 16: Physiological Processes

What could happen if local inflammatory responses fail

L

H

L

H

1. Macrophages activated inthe liver and spleen secreteTNFα into the blood.

2. Systemic shift of fluid from plasma to tissue spaces causesa drop in blood volume and collapse of dilated blood vessels.

L

H

3. Disseminated intravascularcoagulation leads to wastingand multiple organ dysfuction.

L

H

Page 17: Physiological Processes

Systemic Inflammation:

A systemic inflammatory response causes:

1. systemic vasodilation

2. increased capillary leak due to:(b) altered endothelial integrity

(c) endothelial injury

3. microvascular occlusion

Page 18: Physiological Processes

bacterial

LPS

macrophages in

liver, spleen

TNFα, IL-1, IL-6

vascular

endothelium

nitric oxide prostaglandin

Systemic Inflammation: 1. systemic vasodilation and vasopermeability

hypotension, circulation problems

fluid resuscitation

remedy remedy

vasopressor

medication

Page 19: Physiological Processes

pro-inflammatory mediators

TNFα

IL-1

IL-6

anti-inflammatory mediators

IL-10

IL-4

glucocorticoids

Maintains inflammation at an appropriate

magnitude to promote health

Systemic Inflammation: 1. systemic vasodilation and vasopermeability (regulation)

Page 20: Physiological Processes

* Compensatory anti-inflammatory response syndrome (CARS)

magnitude of

response

excessive PRO -

inflammatory response

*excessive ANTI-

inflammatory response

adequate inflammatory

response

Shock: early mortality

Immunodepression: later mortality

Time

Systemic Inflammation: 1. systemic vasodilation and vasopermeability (regulation)

Page 21: Physiological Processes

plasma

endothelium

interstitial fluid

TNFα, IL-1

capillary leak

Systemic Inflammation: 2. Increased capillary leak (b) Altered endothelial integrity

Page 22: Physiological Processes

ROS

proteinases

destroys

capillary leak

Systemic Inflammation: 2. Increased capillary leak (b) Endothelial injury

plasma

endothelium

interstitial fluid

neutralises

anti-proteinases

Page 23: Physiological Processes

TNFα, IL-1ROS

intrinsic coagulation

pathway activated

blood clotting

factor VIIa

extrinsic coagulation

pathway activated

disseminated Intravascular Coagulation

microvascular

occlusion

collagen matrix exposed

Systemic Inflammation: 3. microvascular occlusion

Page 24: Physiological Processes

Organ

Blood vessel

capillary leak and build-up of IF increases diffusion distance

“sticky” neutrophils form a plug

thrombus

ischaemia

Functional

inadequate supply / movement of gases & metabolites

organ dysfunction

Development of Multiple Organ Dysfunction Syndrome (MODS)

Interstitial

Fluid (IF)

Oxygen and nutrients

Carbon dioxide and wastes


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