Class 2 - Inflammation, Cell Injury and Wound Healing

Question 1

Cellular Injury

Answer 1

• Reversible injury, cell recovery, and then a return to normal function.
  1. Apoptosis: programmed cell death
• parts are reused by the body, very useful
  2. Necrosis
• Triggers inflammation
• Can be reversible before the progressive injury stage
• Gangrene

Question 2

Cell Injury Mechanisms

Answer 2

1. Free radicals / reactive oxygen species
2. Hypoxic Injury
3. Reperfusion injury
4. Chemical injury (drugs, alcohol, lead, carbon monoxide)
5. Physical forces (trauma, temperature, electrical forces)
6. Other (changes in atmospheric pressure, radiation injury, environment)

Question 3

Free Radicals / Reactive Oxygen Species

Answer 3

• An atoms or groups of atoms have an unpaired electron
• Causes oxidative stress to the body
• Free radicals are by products of normal metabolism
• Causes aging. Counteracted by antioxidants. When under stress, antioxidants are overwhelmed
• Char, stress, cigarette smoke, infections, inflammation, UV and pollution increase free radicals
• Causes membrane damage, breakdown, misfolding and mutations
• Occurs in every metabolic process that uses oxygen

Question 4

Hypoxic Injury

Answer 4

• Decreased oxygen to tissues
• Decreased oxygen in the blood (hypoxemia)
• Decreased blood flow (ischemia)
• Decrease of dysfunctional hemoglobin

Question 5

Cerebral Palsy

Answer 5

Hypoxic Injury

• A group of non-progressive syndromes causing varying degrees of motor dysfunction
• Due to brain damage often resulting from hypoxic injury before, during or shortly after brith
• One of the most crippling disorders ofchildhood
• May have cognitive impairement

Question 6

Reperfusion Injury

Answer 6

• Occurs when there has been ischemia
• Restoration of circulation causes inflammation and release of free radicals
• Can happen in the heart or brain

Question 7

Results of Cellular Injury

Answer 7

• Mitochondrial damage and ATP depletion
• Damage to the cell membrane (Na-K pump fails, water comes into the cell, Ca2+)
• Ribosome damage; leads to protein misfolding
• DNA damage

Question 8

Systemic Manifestations of Cellular Injury

Answer 8

• Fatigue
• Malaise (feeling sick)
• Fever
• Loss of appetite (anorexia)
• Elevated plasma enzymes
  1. Lactic dehydrogenase (LDH)
  2. Creatine kinase (CK)
  3. Troponin
• Triggers the inflammatory response

Question 9

Local Manifestations of Inflammation

Answer 9

5 signs of inflammation

1. Redness
2. Swelling
3. Heat
4. Pain
5. Loss of function
   - Pressure will increase if there’s no room for swelling (brain swelling in the skull)

Question 10

Inflammatory Response

Answer 10

• Inflammation ends in “itis”
• Second line of defence. Important part of innate immunity and is activated within seconds.
• Non-specific

Activated by cellular injury or necrosis due to:
- hypoxia, reperfusion, free radicals, mechanical damage, temperature extremes, radiation, chemicals nutrient deprivation, infection etc.

Question 11

Goals of the Inflammatory response

Answer 11

• Prevents infection and further damage, contains the bacteria to the location
• Limits and controls the inflammatory process; prevents it from spreading to healthy areas
• Initiate adaptive immune responses
• Initiates healing

Question 12

Vascular Response - Inflammation

Answer 12

• Blood vessel dilation
• Increased vascular permeability
• Fluid moves into tissues
• Blood becomes more viscous
• Clotting occurs

Question 13

Cellular Response - Inflammation

Answer 13

• White blood cells adhere to capillaries
• Then they squeeze through emigration
• Chemotaxis
• Phagocytosis
• Exudates: fluid, RBC’s, WBC’s, tissue debris (pus)

Question 14

Acute Inflammatory Response

Answer 14

• Cellular components: neutrophils, macrophages, others (mast cells, platelets, plasma proteins)
• Main chemical component is Histamine
• Systemic manifestations
  1. Fever: caused by exogenous and endogenous pyrogens. Acts directly on the hypothalamus.
  2. Leukocytosis: increased number of circulating leukocytes
  3. Fatigue, anorexia and lymphadenitis (inflammation of the lymph nodes)
  4. Elevated “markers” like erythrocyte sedimentation rate (ESR) and C-reactive protein

Question 15

Chronic Inflammation

Answer 15

• Inflammation lasting 2 weeks or longer
• Persistence of an irritant (infection, antigen, foreign body)
• Or due to an unsuccessful acute inflammatory response
• Long-term, perpetuation and often debilitating
• Phagocytes cells are different; neutrophils die and lymphocytes are activated
• Immune and inflammatory substances can further injure cells and delays healing
• Fibroblasts and scar tissue formation leading to a loss of function.
• Major risk factor for many cancers, coronary artery disease and other chronic diseases

Question 16

Rheumatoid Arthritis

Answer 16

• Occurs when scar tissue replaces regular tissue

- Chronic inflammation

Question 17

Systemic Manifestations of Chronic Inflammation

Answer 17

• Same as acute (fever, fatigue, anorexia)
• Hyperplasia (enlargement) of spleen or lymph nodes
• Anemia
• Pain
• Activity intolerance
• Depression
• Insomnia
• Weight loss (prolonged anorexia)

Question 18

Phases of Healing

Answer 18

1. Inflammation
   - First stage of wound healing
   - Neutrophils and macrophages clean up injured area
   - Blood clot acts as a scaffold for new tissue
2. Proliferation and New Tissue Formation
   - Building of new tissue
   - Fibroblasts secrete collagen, growth factors
   - New epithelial cells and granulation tissue
   - If it is interrupted, the healing process is delayed
3. Remodelling and Maturation phase
   - Scar tissue formation
   - Scar remodelling; continuous synthesis and breakdown of collagen
   - Can take 2 years for scars to fade

Question 19

Cutaneous Wound Healing

Answer 19

1. Primary intention
   - Wounds that heal under conditions of minimal tissue loss
   - eg. sutured surgical wound, small scars.
   - edges of the wound are “well approximated”
2. Secondary intention
   - wounds that require a great deal more of tissue replacement
   - eg. pressure ulcer, burns
3. Tertiary intention
   - covered in other classes

Question 20

Factors Affecting Healing and Tissue Repair

Answer 20

• Age
• Blood supply / temperature. Areas with lower blood supply are cooler
• Moisture
• Nutrition
• Tension on tissue (obesity). If there’s a lot of tension on the tissue it’ll be harder for the tissue to come together
• Drugs and stress hormones
  1. corticosteroids
  2. non-steroidal anti-inflammatories (NSAID) like ibuprofen and advil
  3. anticoagulants
• Chronic diseases like diabetes

Question 21

Dysfunctional Wound Healing

Answer 21

• Adhesions
• Strictures: narrowing of a tube, typically due to scar tissue
• Contracture’s: can occur to the skin after burns
• Infection
• Excess scar formation; keloids. They are more prevalent in the neck/chest area, and more common with those of African and Asian ancestry.
• Dehiscence: when the wound begins healing, but splits apart in the middle
• Evisceration: when the organs of the abdomen begin spilling out