GENPATH Inflamation and Repair Flashcards
4 Causes of Inflammation
- […] (and toxins) –> bacteria, virus, fungi, parasite
- […] –> Ischemia, trauma, chemical injury
- […]
- […] –> Autoimmunity, hypersensitivity
4 Causes of Inflammation
- Infection (and toxins) –> bacteria, virus, fungi, parasite
- **Tissue Necrosis **–> Ischemia, trauma, chemical injury
- Foreign bodies
- Immune Reactions –> Autoimmunity, hypersensitivity
5 Cardinal Signs of ACUTE Inflammation (IMPT)
- […] (Calor) –> vasodilation (Prostaglandin, Histamine)
- […] (Rubor) –> vasodilation (Prostaglandin, Histamine)
- […] (Tumor) –> exudation secondary to increased vascular permeablity (Histamine, Serotonin, Leukotrines, C3a, C5a)
- […] (Dolor) –> stimulation of nerve endings (prostaglandin, Bradykinin)
- […] (Functio Laesa) –> voluntary or damaged tissue
Fever is systemic, caused by […] and cytokines ([…], […])
5 Cardinal Signs of ACUTE Inflammation (IMPT) **
- *Warmth (Calor) –> vasodilation (Prostaglandin, Histamine)
- *Redness (Rubor) –> vasodilation (Prostaglandin, Histamine)
- Swelling (Tumor) –> exudation secondary to increased vascular permeablity (Histamine, Serotonin, Leukotrines, C3a, C5a)
- Pain (Dolor) –> stimulation of nerve endings (prostaglandin, Bradykinin)
- **Loss of Function **(Functio Laesa) –> voluntary or damaged tissue
Fever is systemic, caused by prostaglandin and cytokines (IL-1, TNF)
Acute inflammation is characterised by
- […]
- […]
- […]
- […]
Chronic inflammation is characterised by
- […]
- […]
- […]
- […]
Acute inflammation is characterised by
- exudation
- Fast onset
- Neutrophil accumulation
- Mild and self-limited tissue damage and fibrosis
Chronic inflammation is characterised by
- also exudation
- Slow onset
- Monocyte/macrophages and lymphocyte accumulation
- Severe and progressive tissue damage and fibrosis
Angiogenesis in wound healing repair is important for vessels to bring
- […]
- […]
Angiogenesis in wound healing repair is important for vessels to bring
- oxygen and other nutrients to injured cells/tissues
- To bring WBCs to counter injurious foreign stimuli
Before healing and repair can take place, macrophages need to
- […]
- […]
Before healing and repair can take place, macrophages need to
- Clear the inflammatory site of cell debris, including removal of neutrophils and their secreted products.
- secrete cytokines/growth factors for ECM synthesis
Therefore, macrophages are impt not only in chronic inflammation, but also in wound healing. depleted macrophage leads to delayed wound healing!
M1 macrophages –> pro-inflammatory
M2 macrophages –> pro-healing
TLDR, M2 macrophages Clean up and build a solid ECM!!
Watch “Cells At Work!” if you wanna take a break. Really cute, very zen.
Capacity for proliferation
Labile Tissue: Dividing cells that are always in cell cycle
- readily regenerates after injury
- eg. blood cells, epithelial cells
Stable Tissue: Usually in G0, can be stimulated to enter cell cycle
- Limited capacity to regenerate after injury
- eg. hepatocytes
Permanent Tissue: Always in G0, cannot divide
- Terminally differentiated and non-proliferative
- Almost no capacity of regeneration
- eg. neurons, myocytes
Collagen Synthesis and Maturation
- Initially type […] collagen, which is later removed and replaced by type […]
- As remodelling occurs, collagen fibres and bundles are […] along new lines of stress
- Requires Vit […]
Collagen Synthesis and Maturation
- Initially type III collagen, which is later removed and replaced by type I
- As remodelling occurs, collagen fibres and bundles are re-organized along new lines of stress
- Requires Vit C
Criterias for Regeneration
[…]
Criterias for Regeneration
1. Tissue contains pluripotent stem cells capable of dividing
2. Underlying ECM - extracellular matrix scaffold must remain intact as a good support base
TLDR,
U need sturdy soil (ECM) and a budding that is alive (capable of dividing) for growth (regeneration)
Got sturdy soil but dead bud –> no grow
No sturdy soil but alive bud –> no grow
ok bad analogy but u gets!!
Factors that affect wound healing
Local:
- […] –> incision vs laceration, depth of cut
- […] –> patients with venous congestion (varicose veins) and diabetes (peripheral vascular disease) –> poor wound healing
- […] –> poor healing if infectious injury is ongoing (importance of wound debridgement)
- […] –> excessive movement before maturation of fibrous scar = tearing of collagen fibres
- Others –> radiation causing destruction of both tumour and normal body cells
Systemic:
- […]
- […] –> good blood supply = better healing
- […] –> malnutrition = poor healing, need for essential elements in diet (zinc, vit C, etc)
- […] –> Pt w DM and hypothyroidism –> poor healing
- […] –> corticosteroids inhibits collagen synthesis, but thyroxine, androgens, estrogens and growth hormone enhances healing.
Factors that affect wound healing
Local:
- Type, size and location of wound –> incision vs laceration, depth of cut
- Local vascular supply –> patients with venous congestion (varicose veins) and diabetes (peripheral vascular disease) –> poor wound healing
- Secondary infection –> poor healing if infectious injury is ongoing (importance of wound debridgement)
- Movement –> excessive movement before maturation of fibrous scar = tearing of collagen fibres
- Others –> radiation causing destruction of both tumour and normal body cells
Systemic:
- **Age of Pt **
- Circulatory status –> good blood supply = better healing
- Nutrition –> malnutrition = poor healing, need for essential elements in diet (zinc, vit C, etc)
- Metabolic status –> Pt w DM and hypothyroidism –> poor healing
- Hormones –> corticosteroids inhibits collagen synthesis, but thyroxine, androgens, estrogens and growth hormone enhances healing.
Don’t memorize cuz all can deduce!! #understandingisnumber1
Granulation Tissue formation
- Vascular connective tissues composed of […], […] and mix of […] cells
- grows from […] to fill wound
- Angiogenesis, (myo)fibroblast cell proliferation, deposition of new immature collagen and other ECM
- Regulatory mechanisms not understood but probably involve FGF, ECG, PDGF, etc
Granulation Tissue formation
- Vascular connective tissues composed of vascular capillaries, fibroblast/myofibroblasts **and mix of inflammatory cells
- grows from basement membrane to fill wound
- Angiogenesis, (myo)fibroblast cell proliferation**, deposition of new immature collagen and other ECM
- Regulatory mechanisms not understood but probably involve FGF, ECG, PDGF, etc
Granulomatous inflammation occurs when there is an aggregation of activated macrophages ([…]) and scattered lymphocytes that walled off the infection loci
- activated macrophages may fuse into […]
- Sometimes with central necrosis
- Infection is walled off but causal agent is not eradicated
- Limits the scale of infection but can be a cause of organ dysfunction
Granulomatous inflammation occurs when there is an aggregation of activated macrophages (epitheloid histocytes) and scattered lymphocytes that walled off the infection loci
- activated macrophages may fuse into multinucleated giant cells
- Sometimes with central necrosis
- Infection is walled off but causal agent is not eradicated
- Limits the scale of infection but can be a cause of organ dysfunction
Healing by first intention vs second intention
First intention:
- Minimal tissue damage
- Wound edges […]
- less wound contraction, faster healing
- eg. surgical incision
Second intention:
- large gaping wound
- wound edges are […], healing tissues exposed
- more wound contraction, […] healing
- more […], more […] formation
- eg. lacerations, burns
Healing by first intention vs second intention
First intention:
- Minimal tissue damage
- Wound edges closely apposed
- less wound contraction, faster healing
- eg. surgical incision
Second intention:
- large gaping wound
- wound edges are far apart, healing tissues exposed
- more wound contraction, prolonged healing
- more inflammation, more granulation tissue (angiogenesis) formation
- eg. lacerations, burns
How does excessive scarring lead to disease?
- […]
- […]
- […]
How does excessive scarring lead to disease?
- Defective scar formation
-
Excessive scar formation
-* Excessive contraction*
In chronic inflammation, prolonged […], […] and […] occurs simultaneously!!
In chronic inflammation, prolonged inflammation, tissue injury and healing occurs simultaneously!!
Inflammatory Cells and Mediators BUFFET!!! (vvv. IMPT)
Cells that are involved in acute inflammation include […], […], […] and […]
Key principal mediators include
- Cell-derived mediators: […], lipid mediators ([…], […]), Cytokines ([…], […], […], […]), and
- Plasma- derivede mediators: […], […], […]
Inflammatory Cells and Mediators BUFFET!!! (vvv. IMPT)
Cells that are involved in acute inflammation include Mast cells, macrophages, neutrophils and leukocytes
Key principal mediators include
- Cell-derived mediators: histamine, lipid mediators (prostaglandins, Leukotrienes), Cytokines (**TNF, IL-1, IL-6, chemokines), **and
- Plasma- derivede mediators: complement, kinins, coagulation system
List some tissue/organs that can undergo regeneration following injury
[…]
[…]
[…]
[…]
[…]
[…]
List some tissue/organs that can undergo regeneration following injury
Liver (classic example)
Skin
Pancreas
Thyroid
Lung
Adrenal gland
Regeneration = Proliferation
Regeneration is NOT Repair.
one of the earliest mediator of inflammation is […]
one of the earliest mediator of inflammation is histamine (it’s preformed)
Outcomes of acute inflammation?
[…]
[…]
[…]
Outcomes of acute inflammation?
Resolution
Fibrosis
Chronic Inflammation
Note that chronic inflammation doesn’t have to start with acute inflammation!
Processes in Tissue Healing & Repair (IMPT)
- […], […]
- […]
- […] (ECM) synthesis and maturation
- Epithelial cell […]
- Scar maturation and […]
Processes in Tissue Healing & Repair (IMPT)
- Granulation Tissue Formation, Angiogenesis
- Wound contraction
- Collagen (ECM) synthesis and maturation
- Epithelial cell regeneration/proliferation
- Scar maturation and remodelling
“What are the processes in tissue healing and repair?”
“GAW CPR?”
HAHAHHAHA man is going bonkers
Scar maturation and remodelling
- As repair progresses, collagen synthesis […] degradation –> accumulation of collagen
- Tensile strength of collagen increases due to development of […]
- Vascular involution/resorption continues, giving rise to eventual pale and stable avascular scar
Scar maturation and remodelling
- As repair progresses, collagen synthesis exceeds degradation –> accumulation of collagen
- Tensile strength of collagen increases due to development of cross linkages
- Vascular involution/resorption continues, giving rise to eventual pale and stable avascular scar
Suppurative or Purulent inflammation is indicative of […]
contents of purulent exudates:
[…]
Suppurative or Purulent inflammation is indicative of pyogenic bacteria
contents of purulent exudates:
neutrophils
cell debris
microbes
Tissue Regeneration and Repair
Regeneration: Dead cells are replaced either by […] of residual uninjured cells or by […] of available stem cells
Repair: Remaining cells are incapable of regeneration and the region is replaced by […] that provides structural stability for uninjured tissue to continue to function
Tissue Regeneration and Repair
Regeneration: Dead cells are replaced either by proliferation of residual uninjured cells or by differentiation of available stem cells
Repair: Remaining cells are incapable of regeneration and the region is replaced by connective tissue that provides structural stability for uninjured tissue to continue to function
So yah regeneration and repair are not the same. Repair will result in some loss of function as original cells are replaced by scars
Unlike acute inflammation, chronic inflammation does not involve […]. Instead, they are primarily driven by […]
Unlike acute inflammation, chronic inflammation does not involve neutrophil. Instead, they are primarily driven by macrophages
Wound Contraction
- […] express smooth muscle […] and […], secrete ECM incl collagen
- Arise from resident/circulating fibroblasts and mesenchymal transformation of regenerating immature epithelial cells/endothelial cells
- Undergo apoptosis after healing completed
- Shrinks size of wound (and hence size to be healed)
Wound Contraction
- Myofibroblasts express smooth muscle actin and myosin, secrete ECM incl collagen
- Arise from resident/circulating fibroblasts and mesenchymal transformation of regenerating immature epithelial cells/endothelial cells
- Undergo apoptosis after healing completed
- Shrinks size of wound (and hence size to be healed)
