a) Histamine
– Vasoactive amine that causes dilation of post-capillary venules
– Binds specific receptors on the other cells
– DEGRANULATION PRODUCT
b) Chemotactic factors
– Neutrophil chemotactic factor
– Eosinophil chemotactic factor
– DEGRANULATION PRODUCT
c) Prostaglandins and leukotrienes
– Products of arachidonic acid pathway
– Induce pain, inhibited by ASA/NSAIDS
– Similar effect to histamine
– Can also act as hormones (chem)
– SYNTHESIS PRODUCT
d) Platelet-activating factor
– Similar effect to leukotrienes + platelet activation
– SYNTHESIS PRODUCT 
Endothelium
Lines blood vessels
Attached to underlying connective tissue matrix
Critical in pathophysiology of inflammation
Interact with circulating cells, platelets, plasma proteins
Endothelial injury initiates platelet adherence
Release/regulate inflammatory mediators
Simple squamous cells lining blood vessel; have tight
junction which can be loosened 
Platelets
Activated by rough endothelium, tissue destruction and inflammation
Activation leads to interaction with coagulation factors and activates the cascade
– The cascade is only activated when there is tissue factor release
They have no nucleus
Mother cell is megakaryocyte in bone marrow
Normal count: 150,000-450,000 /L
Life span: 8-11 day
Pathology of Acute Inflammation
Vascular changes
– Vessels become more porous and leak fluid
“Acute” refers to the increase in neutrophils as part of the inflammatory response
Types of Exudative Fluids
In acute inflammation there is a leakage of circulating fluid into tissue (exudative fluids)
The four types of exudative fluids are:
a) Serous:
– watery. Indicates early inflammation
b) Fibrinous:
– Thick, clotted. Indicates advanced inflammation.
c) Purulent (suppurate):
– Pus. Indicates bacterial infection
d) Hemorrhagic:
– Bloody; Indicates bleeding 
Manifestations of Acute Inflammation
Local
Heat, swelling, redness, pain, loss of function
Systemic
Fever
– Caused by exogenous and endogenous pyrogens
– Pyrogens act directly on the hypothalamus
Leukocytosis
– Increased numbers of circulating leukocytes
– Normal count: 4-11 x 109/L
General lab markers inflammation: ESR, CRP
– ESR: erythrocyte sedimentation rate. Basic non-specific test. Examines the sedimentation of red cell mass vertically over time
– CRP: C-reactive protein measured in blood. Pathology of Chronic inflammation, acute phase reactant
Acute inflammation lasting ~2 weeks (more neutrophils infiltration) and chronic lasts longer (more lymphocytes infiltration)
Chronic Inflammation
Causes of Chronic Inflammation:
Unresolved acute inflammation
Microbe surviving inside macrophage
Persistence of stimulus
– Toxins, chemicals, particulate matter, or physical irritants
Pathophysiological features of chronic inflammation
Dense infiltration of lymphocytes, fibroblasts and macrophages
– If macrophages are unable to protect the host from tissue damage, the body will attempt to wall off and isolate the infected area, thus forming a granuloma.
– TNF-alpha primarily drives the formation of a granuloma. 
Giant cell infiltration and granuloma formation
– When macrophages form, they can make a giant cell. Which is active phagocyte that can engulf very large particles.
– The giant cell and epithelioid cell form the centre of the granuloma and are surrounded by wall of lymphocytes.
Simultaneous destruction and healing of tissues
Examples of chronic inflammatory conditions:
TB
Rheumatoid arthritis 
Wound Healing
The process where the skin (or organ/tissue) repair themselves after injury
Requires healthy blood vessels and connective tissue
Three phases of wound healing:
I. Inflammation (including coagulation) (1-2 days)
Infiltration of cells of inflammatory response, phagocytosis of debris
Release of cytokines and inflammatory mediators 
II. Proliferation and new tissue formation (3-4 days)
Angiogenesis (new blood vessel formation)
Fibroblasts grow and form new connective tissue (granulation tissue)
Re-epithelialization: epithelium crawl to provide a cover for new tissue
III. Remodeling and maturation (few weeks – 2 years)
Collagen is remodeled and realigned along tension line
Myofibroblasts decrease wound size (wound contraction)
Un-necessary cells undergo apoptosis 
Dysfunctional/Complications of Wound Healing
Dysfunctional inflammation
Caused by:
– Bleeding, hypovolemia, poor inflammatory response
Results in:
– Fibrous adhesion/infection
Deficient scar:
Caused by:
– Inadequate granulation tissue
Results in:
– Wound dehiscence, rupture, increase risk of infection
Excessive scar:
Caused by:
– Impaired collagen matrix remodeling
Results in:
– Keloid/hypertrophic scar
Impaired epithelialization
Caused by:
– Steroids, hypoxemia, nutritional deficiencies
Results in:
– Incomplete healing
Impaired contraction
Deficient: decreases engraftment in skin grafts
Excessive (contracture): impairs joint function post burns
Others:
Calcification
Pigmentation
Pain
Incisional hernia
Pathophysiological conditions of impaired wound healing
Diabetes Mellitus
Worst of chronic conditions that can impair wound healing
Impaired due to:
– Neuropathy
– Vascularization (angiopathy)
– Impaired coagulation
– Hyperglycemia impairs cell function 
Stress
Extremes of age
Disease involving hypoxemia
Obesity
Alcoholism
Poor nutrition
Smoking
Medications
– Steroids
– Chemotherapy 
Wound Healing and Extremes of Age
Neonates
Transient depression of inflammatory and immune function
Inefficient neutrophils chemotaxis
Complement deficiency
Increased susceptibility to sepsis
Elderly:
Impaired function of innate immune cells (eg. Phagocytes)
Increased susceptibility to infections
Impaired inflammation likely due to:
– Associated chronic illness: DM, CVD, etc.
– Polypharmacy
Impaired healing due to loss of regenerative ability of skin