Acute Inflammation (10/8a) [Biomedical]

Question 1

Inflammation

Answer 1

Response of vascularized tissues to infection and damage

Brings cells and molecules of host defense from the circulation to affected sites

Eliminate offending agents

Question 2

Goals of Inflammation

Answer 2

Rid the host of the initial cause of injury

Remove necrotic cells and tissues

Initiate the process of tissue repair (Inflammation → Proliferation → Maturation)

Question 3

The Five R’s of Inflammation

Answer 3

RECOGNITION of injury (turn on)

RECRUITMENT of white blood cells to area of injury (turn on)

REMOVAL of injurious agent and damaged tissue (turn on)

REGULATION of response (turn off)

RESOLUTION (turn off)

Question 4

Cardinal Signs of Inflammation

Answer 4

Rubor = redness

Calor = heat

Tumor = swelling

Dolor = pain

Functio laesa = loss of function

Question 5

___ ___ sensitizes specialized nerve endings to effects of Bradykinin and other pain mediators

Answer 5

Prostaglandin E2

Question 6

Inflammation - Cells in the Blood

Answer 6

Platelets (thrombocytes)

White blood cells (leukocytes)

• Neutrophils: most common
• Monocytes: become macrophages in tissue
• Lymphocytes: can be B or T lymphocytes

Question 7

Inflammation - Cells in the Tissues

Answer 7

Sentinel cells - immune cells that reside in tissue, sense microbes/tissue damage and can respond on their own

3 Types: Resident macrophages, Dendritic cells, Mast cells

3 Key Features

Question 8

3 Key Features of Sentinel Cells

Answer 8

Surface/cytosolic receptors recognize invading microbes/substances released by necrotic tissue

Bind, ingest, and phagocytize microbes and necrotic tissue

Release cytokines and other inflammatory mediators as signals to recruit help

Question 9

Substances and Inflammatory Mediators

Answer 9

Cytokines

Histamine

Prostaglandins and leukotrienes

Question 10

Cytokines

Answer 10

signaling molecules secreted by immune cells in response to injury/infection that induce and modulate immune response

Include interleukins, interferon, TGF-beta, TNF

Pro-inflammatory vs Anti-inflammatory

Question 11

Pro-inflammatory vs Anti-inflammatory

Answer 11

Pro-inflammatory induce fever, inflammation, tissue destruction in response to injury

Anti-inflammatory suppress actions of pro-inflammatory

Question 12

Histamine

Answer 12

released by mast cells

Causes vasodilation and increased capillary permeability

Question 13

Prostaglandins and Leukotrienes

Answer 13

produced in response to cytokines

Contribute to vasodilation, pain, and platelet activation

Question 14

Parts of Turning ON Inflammation

Answer 14

Hemostasis

Recognition of injury

Recruitment of WBCs

Removal of damaged tissues

Question 15

Hemostasis

Answer 15

Immediate response to traumatic injury to prevent blood loss

Damaged endothelial cells release mediators that cause
-Vasoconstriction — decrease blood flow to the area

• Platelet activation — adhere to lesion/each other, attract other platelets, initiate coagulation cascade → fibrin production
• Fibrin clot formation — fibrin stabilizes the clot, fibronectin provides initial scaffolding for infiltrating cells and ECM components

Question 16

Injury

Answer 16

trauma

necrotic tissue

infection by pathogens or foreign bodies

maladaptive immune response

Question 17

Recognition of Injury

Answer 17

Injury recognized by immune cells - sentinel cells in tissue, leukocytes in blood stream

Receptors on cell surface/interior recognize molecules

• On surface of invading microbes
• Released by damaged tissue (ATP, DNA, low K+)

Leukocytes ingest and phagocytize microbes and necrotic tissue

Recognition causes release of mediators that trigger recruitment

Question 18

Mediators that Trigger WBC Recruitment

Answer 18

cytokines
histamines
prostaglandins
bradykinins
leukotrienes

Question 19

Recruitment of White Blood Cells

Answer 19

Cytokines and inflammatory mediators act on endothelial cells of local blood vessels

Vasodilation — increase blood flow

• Histamine/mediators released by mast cells cause vessel relaxation
• Decreases velocity of blood flow

Increase vessel permeability

• Endothelial cell retraction creates holes in the vessel wall
• Plasma and proteins leak into tissue, causing edema

Vascular stasis

• Results from increased blood flow, decreased velocity, and hemoconcentration
• Accounts for redness and warmth of inflamed tissue
• Facilitates extravasation of leukocytes into tissues

Question 20

Hemoconcentration

Answer 20

increased concentration of RBCs due to decreased plasma/fluid volume

Question 21

Extravasation

Answer 21

movement of white blood cells from the capillaries to the tissues surrounding them

also known as diapedesis

Question 22

How are leukocytes recruited into tissues?

Answer 22

ACTIVATION
- Cytokines produced by mast cells and activated platelets “turn on” leukocytes

EXTRAVASATION
- Vascular endothelial cells express surface proteins that grab leukocytes, causing them to roll, adhere, and migrate through endothelium into tissue

CHEMOSTASIS
- Once in tissue, leukocytes migrate to the area of damage

Question 23

Removal of Damaged Tissue - 1st Wave

Answer 23

1ST WAVE — NEUTROPHILS

Ingest and destroy microbes and damaged tissues through phagocytosis

Die quickly via apoptosis, half life of only a few hours

Question 24

Removal of Damaged Tissue - 2nd Wave

Answer 24

2ND WAVE — MACROPHAGES

Phagocytize remaining microbes, necrotic tissue, and dead neutrophils

Clean up the mess made by damage and neutrophils

Produce anti-inflammatory cytokines that begin to downregulate inflammation

Question 25

Parts of Turning OFF Inflammation

Answer 25

Regulation of response Resolution

Question 26

Regulation of Inflammatory Response

Answer 26

Once activated, leukocytes have short half lives Anti-inflammatory signals activated to downregulate inflammation (EX: lymphocytes)

Question 27

Resolution of Inflammation

Answer 27

Leukocyte activation triggers proliferation and migration of fibroblasts Produce collagen and extracellular matrix components Main cell of proliferative phase

Question 28

Some sources of injury

Answer 28

``` chronic inflammation persistent injury autoimmune disease viral/bacterial infections infarction toxins trauma ```

Question 29

What can go wrong with inflammation?

Answer 29

Too little inflammation - Infections go unchecked, wounds/tissues don’t heal Misdirected inflammation - Against self/healthy tissues in autoimmune diseases (EX: rheumatoid arthritis) Inflammation in response to normally harmless stimuli - Hypersensitivity and allergies Inflammation is excessively prolonged or repetitive - Becomes chronic inflammation → more damage and scar tissue, fibrosis

Question 30

Inflammation - PT Key Observations

Answer 30

Look for cardinal signs and how exaggerated they are Impact on movement and gait

Question 31

Inflammation - PT History Questions

Answer 31

When and how did this happen? - When: to understand how long it’s been an issue - How: to understand the mechanism of injury and parts of body involved (traumatic vs nontraumatic) Ask if this repeated injury (acute vs chronic) Pain - location, type/quality, severity, aggravating/relieving factors - Scale of 0-10 (0 = no pain, 10 = worst pain you can imagine)

Question 32

Inflammation - PT Tests and Measures

Answer 32

Assessment of function (if region is stable) - ROM, strength, gait, standing, etc Edema assessment Joint stability - joint play assessment Test a joint above and below

Question 33

Inflammation - PT Prognosis

Answer 33

How long should acute inflammation last? If no change in signs and symptoms in 1-2 weeks, consider: - Repeated injury? - Another source of inflammation?

Question 34

Edema - Overview

Answer 34

Excess fluid in the interstitial space Increased girth of body part May also see: - tight, shiny skin - indentation of skin under clothing - weeping, leaking

Question 35

Edema - Why is it a problem?

Answer 35

Interferes with movement Decreased neuromuscular control and ROM, painful May indicate health problem - Tissue injury, DVT, heart failure, liver/kidney failure

Question 36

Edema - Types

Answer 36

Inflammatory - Red, hot, painful - Due to trauma, infection, or inflammatory reaction Non Inflammatory - Pitting = indentation in skin after applying pressure - Variety of causes

Question 37

Edema - Describing It

Answer 37

LOCATION - Limb/tissue - Unilateral vs bilateral DURATION - Acute = days to weeks - Chronic = weeks to months/years INFLAMMATORY/NONINFLAMMATORY - Are other signs of inflammation present? - Is there pitting? MEASUREMENT - girth measurements, volumetric

Question 38

Pitting Scale

Answer 38

press firmly into skin for 5 sec 1+ — indentation barely detectable 2+ — slight, returns to normal in 15 sec 3+ — deeper, returns to normal in 30 sec 4+ — indentation lasts > 30 sec