Pathology: Acute Inflammation Flashcards
List the disease types described by acronym VINDICATE
V - Vascular I - Inflammation N - Neoplasia D - Drugs/toxins I - Iatrogenic C - Congenital A - Autoimmune T - Trauma E - Endocrine
What are the 2 main phases of acute inflammation?
Vascular phase
Cellular phase
Outline the vascular phase of acute inflammation
Vasodilation --> Stasis (blood slows, loss of laminar flow) --> White cell margination --> Rolling & Adhesion molecules --> Vascular permeability increases --> Diapedesis and transcytosis
Outline the cellular phase of acute inflammation
Chemotaxis --> Opsonization --> Phagocytosis & other "on-site immune functions"
Describe the vasodilation that is part of the vascular phase of acute inflammation
- Firstly arterioles vasodilate, then capillaries do
- Mediated by histamine and nitric oxide (NO)
- Results in increased calor and rubor
- Causes a decrease in blood rate of flow
Describe the stasis involved in the vascular phase of acute inflammation
- Normally blood flows centrally in the vessel
- Vasodilation causes a decreased rate of flow
- Allows cells white cell margination
Describe white cell margination
Due to a decreased blood flow rate in vessels
Larger cells (like white cells) move to the periphery of the vessels
Describe rolling and the expression of cell adhesion molecules
- Endothelial cells express Intracellular Adhesion Molecule (ICAM), Vascular adhesion molecule (VCAM) and selectins on their luminal surface
- They express them do to chemical signals
- These weakly bind to integrins and glycoproteins
- The bonds rapidly break and reform causing the leukocytes to roll along the vessel wall
Describe how leukocytes stop rolling and come to a halt
- Chemokines from the site of injury bind to prostaglandins on the endothelial cell surface
- These increase the affinity of VCAM and ICAM for integrins
- This binding with increased affinity halts the cell
What factors increase selectin expression?
What factors increase ICAM and VCAM expression?
Histamine and Thrombin increase selectin expression
Tumour necrosis factor (TNF) and Interleukin-1 (IL-1) increase VCAM and ICAM expression
Are selectin, ICAM, VCAM, integrin and glycoproteins on the endothelial cell or leukocyte?
Endothelial cell:
ICAM, VCAM, selectins
Leukocyte:
Integrin, glycoproteins
Describe the factors that can increase vascular permeability (“leakyness”)
Endothelial contraction - due chemical signals (histamine, bradykinin, substance P, leukotrienes)
Direct injury - burns, toxins
Leukocytes - self damage
Transcytosis - substances transported (via vesicles) through cells (due to VEGF)
New vessel formation - due to vascular endothelial growth factor (VEGF)
What is the clinical consequence of increased vascular permeability
Oedema
As fluid escapes the vessel
What is the role of vascular endothelial growth factor in increasing vascular permeability?
VEGF mediates transcytosis
Mediates new vessel formation
Describe how leukocytes migrate out of the vessels
By diapedesis
- Leukocyte extends pseudopods through gaps between endothelial cells
- Pulls itself through the epithelium into the intravascular space