Inflammation and Repair Flashcards
inseparable and coexistent processes orchestrated
by leukocytes, chemical mediators, and GFs
present in tissue and blood
Inflammation and Repair
Follow a predictable sequence of events that includes:
- tissue injury
- vascular response
- cellular response
- resolution
Inflammation and Repair
- Response of living vascularized tissue to injury
- ROLE: destroy/isolate injurious agents to achieve healing and repair
Inflammation
Factors determining pattern of inflammation
- Inciting agent
- Time of observation
- Immune status of host
4 cardinal signs of inflammation
(D RCT = D Randomized Controlled Trials)
- Dolor – pain
- Rubor – redness
- Calor – warmth/heat
- Tumor – swelling
Fifth clinical sign of inflammation (later added by Virchow)
Functio laesa – loss of function
(iNIF)
Infections – bacterial, viral, fungal, parasitic and microbial toxins
Immune reactions/ hypersensitivity – autoimmune diseases, allergies
tissue Necrosis – ischemia, trauma, physical and chemical injury
Foreign bodies – splinters, dirt, sutures
Inciting agents/stimuli of inflammation
Typical Inflammatory Reactions: 5 Rs
- RECOGNITION of the injurious agent by macrophages, other sentinel cells in tissues
- RECRUITMENT of leukocytes and proteins – vasodilation, increased vascular permeability (edema)
- REMOVAL/Elimination of the agent – WBCs and CHONs activation
- REGULATION (control) of the response
- RESOLUTION/REPAIR of damaged tissue – fibroblasts, ECM and cells
Acute Inflammation: Hallmarks
Redness and Warmth – result of vessel dilatation and increased blood flow to the inflamed part
Swelling – caused by accumulation of fluid, esp exudate
Pain – due to increased pressure on nerve endings from swelling, and a direct effect of certain chemical factors which are released to mediate the response
Loss of function – When swelling and pain are marked, there is partial or complete loss of function of the inflamed structure
Immediate and early response to an injurious agent
Acute Inflammation
3 major components of acute inflammation
- Dilation of small vessels –> increase in blood flow
- Increased permeability of the microvasculature –> plasma proteins and leukocytes to leave the circulation
- Emigration of leukocytes from the microcirculation and their accumulation in the focus ofinjury, and their activation to eliminate the offending agent
- high protein content, may be with RBCs/WBCs
- formed in inflammation (vascular permeability
increases due to increased inter-endothelial spaces)
Exudate
- low protein content, few cells
- formed when fluid leaks out because of increased hydrostatic pressure or decreased oncotic pressure
Transudate
Vasodilation is induced by the action of several mediators, notably histamine on vascular smooth muscle
- involves first arterioles and opening of capillary beds resulting in increased blood flow
- redness (erythema) and warmth
Quickly followed by increased permeability of the microvasculature
Slowing of blood flow (stasis) - vascular congestion and localized redness
Leukocyte accumulation (principally neutrophils) along vascular endothelium
Vascular Changes (changes in blood flow and caliber) - Acute Inflammation
In inflammation, lymph flow is increased.
- secondarily inflamed lymphatics
- secondarily inflamed draining lymph nodes
¨ reactive or inflammatory lymphadenitis
Lymphangitis- secondarily inflamed lymphatics
Lymphadenitis- secondarily inflamed draining lymph nodes
*reactive or inflammatory lymphadenitis
Adhesion molecules and cytokines that mediate and control delivery of leukocytes to the site of injury
Chemokines
1) Slowing of blood flow promotes margination, rolling and adhesion of leukocytes to swollen endothelial cells
2) Transmigration (diapedesis: passage of blood cells through the intact walls of the capillaries) across the endothelium into the interstitial tissues.
3) Chemotaxis or migration in interstitial tissues toward
a chemical stimulus
4) Phagocytosis of the offending agent, which may lead to the death of the microorganism
Leukocyte Recruitment to Sites of Inflammation
Rolling – initial rapid and relatively loose adhesion involving the selectins
Stable (firm) adhesion – activation of leukocytes by chemical mediators resulting in increased avidity of integrins to bind to their ligands
Transmigration/ diapedesis – stable binding of integrins on activated leukocytes (LFA-1; MAC-1; VLA-4) to endothelial immunoglobulins (ICAM-1; VCAM-1); PECAM-1/CD31
Leukocyte Migration (Rolling, Adhesion, Transmigration)
Leukocyte Migration (*Rolling, Adhesion, Transmigration)
Rolling – initial rapid and relatively loose adhesion involving the selectins
Leukocyte Migration (Rolling, *Adhesion, Transmigration)
Stable (firm) adhesion – activation of leukocytes by chemical mediators resulting in increased avidity of integrins to bind to their ligands
Leukocyte Migration (Rolling, Adhesion, *Transmigration)
Transmigration/ diapedesis – stable binding of integrins on activated leukocytes (LFA-1; MAC-1; VLA-4) to endothelial immunoglobulins (ICAM-1; VCAM-1); PECAM-1/CD31
Directed migration of leukocytes towards chemical stimulus
- locomotion along a chemical gradient
Chemotaxis
Chemotaxis
______________ emigrate first (1st 6 to 24 hrs), followed by ______________ (24 to 48 hrs).***
Neutrophils emigrate first (1st 6 to 24 hrs), followed by monocytes (24 to 48 hrs).***
Chemotactic agents
¤ Bacterial derived N-Formyl peptides ¤ IL-8 ¤ C5a ¤ Leukotriene B4 ¤ Platelet Activating Factor
Chemotactic agents
¤ Bacterial derived N-Formyl peptides ¤ IL-8 ¤ C5a ¤ Leukotriene B4 ¤ Platelet Activating Factor
