tissues and disease - · pdf fileinjurious stimulus o if the stimulus is ... o cellular...

Tissues and Disease

Lecture 2

Pathology and Clinical

Science 1(BIOC211)

Department of

BioscienceText Reference:

Grossman, S.C. & Porth, C.M. (2014). Porth’s Pathophysiology: concepts of

altered health states, (9th ed.). Philadelphia, U.S.A. Walters Kluwer Health -

Lippincott, Williams & Wilkins.

© endeavour.edu.au

Session Learning Outcomes

This session aims to understand:

• The importance of homeostasis

• The effects of the loss of

homeostasis on the body’s cells,

organs and tissues

• The three outcomes of the body’s

response to changes in

homeostasis

© Endeavour College of Natural Health endeavour.edu.au 2


Session Learning Outcomes:

This session aims to understand

o The pathophysiology of inflammation

o The possible outcomes of inflammation to the healing

pathway

o Systemic and local clinical features of inflammation

o Treatment of inflammation

o The varying outcomes of the healing pathway


Homeostasis & Disease

o Homeostasis is the balance achieved when the

physiological needs of the body are met

o Disease will occur when the body can no longer

adapt to its internal or external environment

o A disease state is a descriptive term used to define

the status of the body when homeostasis is not

maintained


Homeostasis & Disease

o The degree of damage that occurs to the body

depends on the ability of the body to adapt to the

injurious stimulus

o If the stimulus is prolonged or severe and adaptation

mechanisms are exhausted, cellular injury will result

which may in turn lead to disease


What happens when

homeostasis is lost?

o At the cellular level

o At the tissue level

o At the organ level

o To the systems ability to function is lost


Cellular Response to a

Loss of Homeostasis

o Most diseases begin with inadequate adaptation.

o Cellular injury occurs if the cell cannot adapt.

o There are only two possible outcomes for injured tissue

• Recovery

• Death


Cellular Adaptation

o Cells adapt a changing environment

o The state of an adapted cell lies somewhere

between normal and injured but is neither

o Cellular function may be altered

o Cellular adaptation is a common and integral part of

many disordered states

o Cellular adaptation can be both normal or

pathophysiological


From Pathophysiology for the Health Professions (2nd ed), by B Gould, 2002. Philadelphia. W B Saunders Company.

Cellular Adaptation


Causes of Cell Death

Aging Decreased function

Apoptosis Programmed cell death

Injury Cell swelling

Physical Trauma etc.

Biological Pathogens

Metabolic Toxins / hypoxia

Chemical Poisons etc.


The Disease Process Overviewo The steps in the body response to injury or illness

include:

Inflammation

Immune responses

Neoplasia or a combination of these

o Outcomes are:

• Resolution

• Repair

• Adaptation

• Death


Mechanisms of Cell Injury

• Free Radical Injury

• Hypoxic Cell Injury

• Impaired Calcium Homeostasis


Overview of Tissue Response to Injury

Tissue damage

Acute inflammation

Cells can regrow

Resolution / Regeneration

Restoration of normal structure

and function

Cells cannot regrow

Healing by repair

Scar formation

Damaging agent persists

Chronic inflammation

Persistence


Overview of normal defences

o The immune system is organised

into lines of defence to protect the

body from microbial invasion

First (non specific)

Physical and chemical defences

(skin and mucous membranes)

Second (non specific)

Complement, neutrophils,

macrophages, inflammation

Third (specific)

Antibodies, B and T cell responses


Clinical Features of Inflammation

Injury

Chemical Mediator Release

Vasodilation of Arterioles Capillary Permeability

Local Hyperemia Leaky Capillaries

RED HEAT

PAINSWELLING

Jennifer Yeeles


Clinical Features of the

Inflammatory Response

1. Injury

2. Chemical mediator

release

3. Vasodilation

4. Capillary permeability

5. Leukocyte migration

6. Phagocytosis



Cellulitis

http://goodtoknow.media.ipcdigital.co.uk/111%7C000000046%7C1516_orh219w331_cellulitis-SPL-w.jpg

- Redness

- Heat

- Swelling

- Pain

- Immobility (if

joints

involved)


Causes of Inflammation

Causes of inflammation include:

o Tissue injury

o Infections

o Blood vessels damage

And may be due to:

» Trauma (cuts, sprains)

» Metabolic injury (ischemia, hypoxia)

» Cell death or infarction

» Allergic reaction

» Physical agents (thermal damage, radiation burns)

» Chemical agents ( acids, poisons, toxins)

» Foreign bodies (splinters, dirt)


The Acute

Inflammatory

Response

From Porth’s Pathophysiology: Concepts of Altered

Health States. (9th ed., p. 314), by

Sheila C. Grossman & Carol Mattson Porth.

Philadelphia, U.S.A. Walters Kluwer Health - Lippincott,

Williams & Wilkins.


Chemical Mediators

from Mast Cells

Histamine- Vasodilation

- Capillary permeability

- bronchoconstriction

Platelet activating factor- Attracts leukocytes

- Capillary permeability

- Activated neutrophils

Cytokines- Attracts macrophages and

leukocytes

- Recruits platelets


Blood Vessel Damage

Kinin System

Effects:

Irritant

Increase

permeability

Chemical stimulus

for pain receptors

(cause pain)

Bradykinin

NO production by endothelium

damage

Effects:

Vasodilator

Increase permeability

Coagulation System

Effects:

Blood clotting

(thromboxane)

Decrease blood

loss

Trap pathogens


The Outcomes of Acute

Inflammation Tissue Injury

o Activation of mast cells & macrophages in

response to tissue injury aims to:

o Assist in the promotion of exudate which

• Prevents spread of potential pathogens

(infection)

• Supplies products needed for defence

• Supplies products needed in healing


Acute Inflammation

Response to Infection

o When cell damage is initiated by infection additional

mechanisms of acute inflammation are activated

o The detection of pathogens activates macrophages and

immune cells that sets in motion the pathways already

discussed


Acute

Inflammation

From Porth’s Pathophysiology: Concepts of Altered Health States. (9th ed., p.

308), by


Philadelphia, U.S.A. Walters Kluwer Health - Lippincott, Williams & Wilkins.


Acute Inflammation and Infection

Mast Cells

Complement

System

C5a

Activation of

Macrophages

Cytokines

Infection

(Pathogens)

Inc permeability

Inc cell adhesion

Tissue

injury

pathways

vascular changes

Chemical mediators


Acute Inflammation in Infection

o The inflammatory response is slightly different in

infection than tissue injury due to the additional

mechanisms activated

o In the clinical presentation there is

• more exudate

• a larger reaction in general in infected tissue

compared to injured tissue without infection

present

• More purulent (if bacterial)


Inflammatory Exudate

o The interstitial fluid formed in the effected area

o Shift of protein and fluid into the interstitial space causes

swelling (oedema)

o The characteristics of the exudate vary with the cause of

the trauma and the stage of the inflammatory response

Serous- Watery

- Burns

- Allergies

Fibrinous

- Thick

- Sticky

- Risk of

scar

tissue

Purulent

- Thick

- Pus

- Common in

bacterial

infection

Abscess

- Localised

pocket of

pus

Bloody

- Blood

vessel

damage


Local Manifestations of Acute

Inflammationo Dependent on tissue or organ involved

o Affects all vascularised tissue

o Healing can not occur without the inflammatory

response

o Cell death in heart, brain and liver results in different

effects;

• Heart – scar tissue

• Brain – abscess formation or liquefactive necrosis

• Liver – regeneration or scar tissue formation


Systemic Signs & Symptoms of

Inflammation

Malaise

Fatigue

Headache

Anorexia

Fever (dependent on cause of inflammation)

Leukocytosis

Increased plasma protein levels


The Course of the Inflammatory ResponseTis

sue inju

ry

Acute inflammation

Preparation for healing

Chronic inflammation

Repair (Fibrosis)Regeneration

Resolution/Regeneration

Cytokines

Complement and mast cells

Ecosanoids

Infe

ction

If cause persists

Healing

Cause removed


Chronic Inflammationo Prolonged inflammation where active

inflammation, tissue injury and healing proceed

together

o The causes of chronic inflammation include:

• Ineffective eradication of cause by the acute inflammatory response

• Can occur as a distinct process without much acute inflammation

–Specific bacteria

–Prolonged irritation (chemicals)– Long term abnormal immune responses


Chronic versus

Acute Inflammation

Characteristics of chronic inflammation

o Less oedema

o More lymphocytes, macrophages, fibroblasts

o Granuloma

o More collagen production resulting in more

fibrous scar tissue formation

o Generally more tissue destruction in chronic

inflammation

o Repair through regeneration


Tissue Repair



Treatment of Inflammation

-

DrugAspirin

- NSAID’s

- Glucocorticoids

Action- Anti-inflammatory

- Anti-pyretic

- Analgesic

- Anti-inflammatory

- Analgesic

- Anti-inflammatory

Side-Effects- Reactive peptic

ulcers

- Kidney disease

- Reactive peptic

ulcers

- Anaemia

- Arrythmia’s

- Hypertension


Healing After

Acute Inflammationo Tissue healing begins during the final stages of acute

inflammation

o The most desirable outcome is resolution / regeneration

(normal structure and function)

o If resolution / regeneration is not possible, healing is

through repair (scar tissue replacement)

o Three stages of Deep Wound Healing:

- Inflammatory phase

- Proliferative phase

- Remodelling phase


Inflammatory phase

o Brief vasoconstriction

followed by the

vasodilation

o Fluid moves out into

the tissue spaces

o Flow of blood to the

tissue reduces blood

clots

o WBCs enter the site

and cause

phagocytosis.

o Release of chemical

mediators.

From Porth’s Pathophysiology: Concepts of Altered Health States. (9th ed., p. 321), by




Proliferation phase

o Fibroblasts deposit

more fibers and cells

o Multiplication of the

cells

o Fibroblasts release

growth factors.

o Final stage of

proliferative phase is

epithelialization.





Remodelling phase o New tissue is formed

to fill the wound

o Scar tissue

development.

o It is formed from the

fibroblasts and

epithelial cells. It

contains new blood

vessels.

o The tissue is soft and

pink.

o This stage begins

after about 3 weeks.





Resolution / Regeneration

o Begins during acute inflammation

o Debridement:

• Clean up of lesion

o Draining exudate and toxic products and reversal of permeability of vasculature

o Clearance of inflammatory mediators

o Capillary budding

o Regeneration of tissue cells and resolution of tissue function occurs if there are cells present capable of mitosis

o May have adaptive changes


Replacement / Repairo Begins during acute inflammation

o Debridement:

• Clean up of lesion

o Draining exudate and toxic products and reversal of

permeability of vasculature

o Capillary budding

o Repair occurs with 3 processes:

• Filling of the wound

• Sealing or covering the wound

• Shrinkage of the wound

o Fibroblast activity results in scar tissue formation

o Replacement of tissue with another tissue type


Factors that promote / delay healing

o Nutrition

o Circulation

o Age

o Infection

o Hygiene

o Medications

o Genetics

http://alyasfitclub.files.wordpress.com/2011/09/vitamins1.jpg


Complications of Healingo Infection

• septicaemia

o Chronic inflammation

o Loss of function

o Contractures

o Obstructions

o Adhesions

o Dysfunctional wound healing

• Hypertrophic scar tissue

• Keloid scars

o Ulcerations

o Local complications- site dependent

• Diffusion of oxygen in the lungs

• Inhibited ROM in joint

Keloid Scar





Chronic Peptic Ulcer



Chronic Venous Stasis Ulcer

http://www.unchealthcare.org/site/woundmanagement/images/SC000301.JPG/image_preview


Effects of Scarring & Obstruction



Readings and ResourcesResources:

o Set Textbooks:

Colledge, N.R., Walker, B.R. & Ralston S.H. (2014). Davidson’s Principles and Practice of Medicine, (22nd ed.). Edinburgh.

Churchill Livingstone.

Grossman, S.C. & Porth, C.M. (2014). Porth’s Pathophysiology: concepts of altered health states, (9th ed.). Philadelphia,

U.S.A. Walters Kluwer Health - Lippincott, Williams & Wilkins.

o Additional textbooks:

Davies, A. & Moores, C. (2010). The respiratory system: basic science and clinical conditions, (2nd ed.). Edinburgh. Churchill,

Livingstone, Elsevier.

Field, M., Pollock, C., Harris, D. (2010). Systems of the Body: The Renal System; Basic Science and Clinical Conditions. (2nd

ed.). United Kingdom: Churchill Livingstone.

Jamison, J.R. (2006) Differential Diagnosis for Primary Care: a handbook for health care practitioners. (2nd ed.). Edinburgh.

Churchill Livingstone.

McCance, K.L. & Huether, S.E. (2014). Pathophysiology: the biological basis for disease in adults and children, (7th ed.). St.

Louis, MO. Elsevier.

Murphy, K. (2011). Janeway’s immunobiology, (8th ed.). New York. Garland Science.

Noble, A., Johnson, R. & Bass, P. (2010). The cardiovascular system: basic science and clinical conditions, (2nd ed.).

Edinburgh. Churchill, Livingstone, Elsevier.

Pagana, K.D. & Pagana, T.J. (2013). Mosby’s diagnostic and laboratory test reference, (11th ed.). St. Louis, MO. Elsevier.

Smith, M.E. & Morton, D.G. (2010). The digestive system: basic science and clinical conditions, (2nd ed.). Edinburgh.

Churchill, Livingstone, Elsevier.

VanMeter, K.C. & Hubert, R. (2014). Gould’s pathophysiology for health professions, (5th ed.). St. Louis, MO. Elsevier.


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