Acute Inflammation (10/8a) [Biomedical] Flashcards
Inflammation
Response of vascularized tissues to infection and damage
Brings cells and molecules of host defense from the circulation to affected sites
Eliminate offending agents
Goals of Inflammation
Rid the host of the initial cause of injury
Remove necrotic cells and tissues
Initiate the process of tissue repair (Inflammation → Proliferation → Maturation)
The Five R’s of Inflammation
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)
Cardinal Signs of Inflammation
Rubor = redness
Calor = heat
Tumor = swelling
Dolor = pain
Functio laesa = loss of function
___ ___ sensitizes specialized nerve endings to effects of Bradykinin and other pain mediators
Prostaglandin E2
Inflammation - Cells in the Blood
Platelets (thrombocytes)
White blood cells (leukocytes)
- Neutrophils: most common
- Monocytes: become macrophages in tissue
- Lymphocytes: can be B or T lymphocytes
Inflammation - Cells in the Tissues
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
3 Key Features of Sentinel Cells
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
Substances and Inflammatory Mediators
Cytokines
Histamine
Prostaglandins and leukotrienes
Cytokines
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
Pro-inflammatory vs Anti-inflammatory
Pro-inflammatory induce fever, inflammation, tissue destruction in response to injury
Anti-inflammatory suppress actions of pro-inflammatory
Histamine
released by mast cells
Causes vasodilation and increased capillary permeability
Prostaglandins and Leukotrienes
produced in response to cytokines
Contribute to vasodilation, pain, and platelet activation
Parts of Turning ON Inflammation
Hemostasis
Recognition of injury
Recruitment of WBCs
Removal of damaged tissues
Hemostasis
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
Injury
trauma
necrotic tissue
infection by pathogens or foreign bodies
maladaptive immune response
Recognition of Injury
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
Mediators that Trigger WBC Recruitment
cytokines histamines prostaglandins bradykinins leukotrienes
Recruitment of White Blood Cells
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
Hemoconcentration
increased concentration of RBCs due to decreased plasma/fluid volume
Extravasation
movement of white blood cells from the capillaries to the tissues surrounding them
also known as diapedesis
How are leukocytes recruited into tissues?
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
Removal of Damaged Tissue - 1st Wave
1ST WAVE — NEUTROPHILS
Ingest and destroy microbes and damaged tissues through phagocytosis
Die quickly via apoptosis, half life of only a few hours
Removal of Damaged Tissue - 2nd Wave
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
Parts of Turning OFF Inflammation
Regulation of response
Resolution
Regulation of Inflammatory Response
Once activated, leukocytes have short half lives
Anti-inflammatory signals activated to downregulate inflammation (EX: lymphocytes)
Resolution of Inflammation
Leukocyte activation triggers proliferation and migration of fibroblasts
Produce collagen and extracellular matrix components
Main cell of proliferative phase
Some sources of injury
chronic inflammation persistent injury autoimmune disease viral/bacterial infections infarction toxins trauma
What can go wrong with inflammation?
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
Inflammation - PT Key Observations
Look for cardinal signs and how exaggerated they are
Impact on movement and gait
Inflammation - PT History Questions
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)
Inflammation - PT Tests and Measures
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
Inflammation - PT Prognosis
How long should acute inflammation last?
If no change in signs and symptoms in 1-2 weeks, consider:
- Repeated injury?
- Another source of inflammation?
Edema - Overview
Excess fluid in the interstitial space
Increased girth of body part
May also see:
- tight, shiny skin
- indentation of skin under clothing
- weeping, leaking
Edema - Why is it a problem?
Interferes with movement
Decreased neuromuscular control and ROM, painful
May indicate health problem
- Tissue injury, DVT, heart failure, liver/kidney failure
Edema - Types
Inflammatory
- Red, hot, painful
- Due to trauma, infection, or inflammatory reaction
Non Inflammatory
- Pitting = indentation in skin after applying pressure
- Variety of causes
Edema - Describing It
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
Pitting Scale
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
