APPP: L19/20 Inflammation, Tissue Repair, and Wound Healing

… is the protective response to eliminate the cause of cell injury and to remove damaged products/cells 

Inflammation 

The 2 major functions of inflammation is to … the attack and … the damage

stop, repair

What can trigger inflammation?

Infection, injury/foreign bodies/trauma, immunological, chemical agents, and radiation

What are the 3 types of inflammation?

Acute, systemic, and chronic

What are the 4 stages to acute inflammation?

Vasodilation, increase vascular permeability, chemotaxis, and systemic response

In acute inflammation, tissue … cells (such as mast cells) detect injury to nearby sites through … (such as the toll-like receptors) and release …, …, …, and others, initiating inflammatory response

resident immune, PRRs, histamine, nitric oxide, platelets

… increase blood flow to wound sites

Vasodilation

Increasing … causes wound to swell, redden, and become warm, and painful

vascular permeability

… brings in phagocytes and other immune cells

Chemotaxis

Systemic responses include … and …

pyrogenic and pain

… is the earliest response mediated by histamine and nitric oxide (15-30 mins)

Vasodilation

Dilation of blood vessels starts at the … → … → …

arteriole, capillary, venule

… occurs when enlarged vessels pack with cells. Normally, blood flows too fast for directed … movement 

Stasis, leukocyte

Increase blood flow cause local tissue … (redness) and …

erthyema, warmth

Increase in vascular permeability:

• … cells response to histamine and cytokines release

• … and … of endothelial cells allow protein-rich … to cross into interstitial tissue

• Results in … osmotic pressure in blood and … osmotic pressure in interstitial space

• Leakage of fluid out of blood vessels leads to …

• When infection is present, edema can spread to nearby lymph channels and lymph nodes (…)

• Increase delivery of … cells and mediators and clotting factors

Endothelial, Contraction, retraction, exudate, reduced, increase, edema, lymphadenopathy, immune

WBC migration steps in chemotaxis:

1. Rolling: …, intermittent contact with endothelium 

2. Adhesion: …, constant contact with endothelium

3. Transmigration: WBCs cross the … layer through gaps created by contracted endothelial cells

loose, tight, endothelial

… are recruited to site of insult in different phases:

• 6-24 hours post injury is dominated by …

  • … responders, fast arrival 

  • Phagocytes, apoptosis after response

• 24-28 hours post injury finds … (macrophages, APC), … (sometimes eosinophils)

Leukocytes, neutrophils, first, monocytes, lymphocytes 

… changes occurs only if necessary

Systemic

What are the preformed mediators released by mast cell degranulation?

Histamine, cytokines (TNF-alpha, IL-1, IL-6), chemokines for neutrophils and eosinophils, and enzymes 

What are the secondary mediators synthesized and secreted upon mast cell activation?

Eicosanoids (leukotrienes, prostaglandins, and thromboxanes) and Th2 cytokines (IL-4, IL-5, IL-13, GM-CSF)

What are the 5 cardinal signs of inflammation?

Redness, heat, swelling, pain, and loss of function

What are the 6 different types of exudates?

Serous, fibrinous, mucinous, purulent, sanguineous, and mixed type

What are 4 outcomes of acute inflammation?

Resolution, abscess formation, fibrosis (scar) formation, and chronic inflammation

In …, damaging agent is removed and damages are repaired, organ regeneration and full function restored, and is mediated through pro-resolving lipids such as … and …

resolution, lipoxins, resolvins 

An … is a walled off collection of pus (neutrophils and necrotic tissues)

abscess

A … is excessive or abnormal connective tissue (fibrosis)

scar

Systemic inflammation is caused by the … effects (local inflammation mediators and/or toxins reaching systemic circulation

spill over

What are 8 common clinical signs and symptoms of systemic inflammation?

Pyrexia, tachycardia, rigors, diaphoresis, leukocytosis, lethargy, confusion, and hypoxia

What does SIRS stand for?

Systemic inflammatory response syndrome

Infection + SIRS = …

Sepsis

What is the spectrum of systemic inflammation?

SIRS → sepsis → septic shock

… is caused by infection or trauma and contain all clinical signs of systemic inflammation

SIRS

… is a body’s inflammation response to a severe infection. It now includes … infection with organ dysfunction.

Sepsis, suspected 

… is the most severe form of sepsis with bacterial/infectious agents in blood, end organ damage and …, and typically leads to death

Septic shock, hypotension

Reduction or dysfunction in adaptive immune response, lead to:

1. Over-activity of the … system

2. Exaggerated … response

3. Compromised normal … functions

4. Coagulation dysfunction and other organ system failures

innate, cytokine, immune 

… inflammation may follow acute inflammation or may occur as a pathogenic process 

Chronic

Chronic inflammation involves … (B and T) and …

lymphocytes, macrophages

What are the causes of chronic inflammation?

Persistent viral or bacterial infection, autoimmune dysfunction, and chronic diseases

… = accumulation of mononuclear WBC (macrophage and lymphocytes), epithelioid cells and multinucleated giant cells in injured/damaged tissues 

Granuloma 

Granuloma formation is associated with … or … infections; chronic injury caused by foreign agents such as silica 

mycobacteria, fungal

Immune over-reaction such as autoimmune problems and allergic reactions are examples of …

hypersensitivity

Immune under-reaction such as cancer and infection are examples of …

immunodeficiency

… is the regeneration of parenchymal tissue or replacement of damaged tissue with scar, if complete repair is not possible

Repair

… is the replacement of damaged cells, with no scar formation (only possible in tissues that are able to replicate)

Regeneration

Regeneration is possible in tissues with high … rates (e.g. GI tract, skin)

renewal

Regeneration is not possible in tissues with …/… cell population (e.g. kidney, heart)

stable, post-mitotic

… is some replacement of cells combined with scarring and fibrosis

Healing

What are the 5 mediators of tissue repair?

Epidermal growth factor, vascular endothelial growth factor, platelet derived growth factor, fibroblast growth factor, and transformation growth factor beta

… stimulates granulation tissue formation

Epidermal growth factor

… stimulates formation of blood vessels

Vascular endothelial growth factors

… promotes growth of fibroblasts and smooth muscle cells

Platelet derived growth factor

… stimulates formation of blood vessels and wound repair

Fibroblast growth factor

… promotes collagen deposition and ECM growth

Transformation

What are the 3 phases in tissue repair?

Inflammation, proliferation, and remodelling

Wound healing timeline:

• Injury occurs and acute inflammatory response induced

• Repair starts within …h of onset of acute inflammation

• In … days granulation tissues forms, collagen deposition continues to week …, while edema and inflammatory cells disappear

• In … month, all inflammatory infiltrate is gone. Scar consists of mature collagen.

24, 3-5, 2, 1

Pink … tissue occurs in all wounds and is formed during the initial process of wound healing (first 24-72 hrs), but also in chronic inflammation

granular

… consists of fibroblasts, extracellular matrix, newly formed blood vessels (angiogenesis by endothelial cells) and immune cells (specifically macrophages but also other inflammatory cells)

Granulation tissue

Early granulation tissues are …, allowing passages of liquid and cells

leaky

As the wound heals, late granulation tissue …. Late granulation tissues are … during the remodelling process (e.g. replacement of temporary immature collagen with mature collagen)

dries up, replaced

Wound has clean edges, close proximity of margins, minimal tissue disruptions (no tissue loss, little to no scars) are kinds of … intention wound healing 

first

Wound has unclean and wide edges, extensive tissue disruption and necrosis, large and more prominent scar are kinds of … intention wound healing

second

What are the types of wound healing?

First and second intention

Surgical incision and clean cuts are examples of … intention wound healing

first

Pressure ulcers, trauma that affects large areas are examples of … intention of wound healing

second

What are 6 factors that delay/impair wound healing?

Infection, necrotic debris, poor tissue perfusion and hypoxia, nutritional deficiency, physical trauma, and drugs (glucocorticoids, immunosuppressive)