Table 1.

Cardinal Signs of Acute Inflammation

Cardinal Sign Effect Chemical Mediators Table 3. Exudate vs Transudate
Rubor/Redness Vasodilation of blood Prostaglandins Exudate Transudate
vessels  hyperemia (PGE, prostacyclins) Capillary
Increased Normal
(increased blood flow) Permeability
Tumor/Swelling Increased vascular Vasoactive amines Specific Gravity > 1.02 < 1.012
permeability  (histamine, serotonin), Protein Content > 1.5 g/dL < 1 g/dL
extravascular C3a, C5a, bradykinin,
accumulation of fluid  leukotrienes (C4, D4,
edema E4, PAF) Table 4. Classes of Adhesion Molecules
Calor/Heat Increased blood flow Adhesion
Class Description
(hyperemia) Molecule
Dolor/Pain Increased pressure Prostaglandins, - Expressed on
exerted by edema and bradykinin endothelial cells
stimulation/impingement - Binds to CHO groups
E- Selectin
of pain-sensitive nerve on granulocytes,
endings monocytes, memory
Functio Laesa/ Pain leads to immobility T cells
Loss of of that body part leading - Expressed on
Function to loss of function Selectins leukocytes
(responsible for - Binds other surface
initial rolling molecules CD34,
interactions, for L- Selectin Sialyl-Lewis that are
Table 2. Differentiating points between Acute and Chronic Inflammation adhesion of upregulated on
Acute Chronic leukocytes to endothelium by
Duration Short latency Long latency endothelial cells) cytokines (TNF, IL-1)
(days/weeks), occurs (months/years), at injury sites
immediately or soon occurs over time or - Expressed on
after exposure long after exposure platelets and
Inflammatory Present Absent endothelial cells
P- Selectin
Edema - Binds neutrophils,
Predominant Polymorphonuclear Mononuclears: - T-lymphocytes,
Cells leukocytes (PMNs) or Lymphocytes, monocytes
neutrophils plasma cells, Integrins LFA-1 - 2 integrin
macrophages, (extracellular - Expressed on
fibroblasts glycoproteins cell Mac-1 leukocytes
Fibrosis/New Absent Present surface receptor
Blood Vessels that mediates cell
Reversibility Reversible as long as Many effects are adhesion through VLA-4
offending foreign irreversible specific
substance is removed interactions)
Exposure to High exposure (large Low exposure (small ICAM-1 - Expressed on
Injurious Agent dose) over a short doses) over a long (Intercellular endothelial cells
period period Adhesion - Binds to LFA-1 and
Effects Can be minor or Still unknown for Immunoglobulins Molecule) Mac-1
severe. For example, a many chemicals. For VCAM-1 (Vascular - Expressed on
small amount of example, most Cell Adhesion endothelial cells
ammonia can cause chemicals have not Molecule) - Binds to VLA-4
throat or eye irritation; been tested for
larger amounts can be cancer or
serious or even fatal reproductive effects
Relationship Generally obvious Difficult to establish
between due to long time
Chemical delay or latency
Exposure and period
Symptoms
Knowledge Human exposure Animal studies
often based on

Inflammatory
Present Absent
Cells
Pathologic fluid Physiologic fluid
Definition getting out of the getting out of the
blood vessel blood vessel
Formed during Formed when liquid
inflammation because leaks out because of
vascular permeability increased hydrostatic
Formation
increases as a result pressure or
of increased inter- decreased osmotic
endothelial spaces pressure
Table 5. Normal White Blood Cell Count (type 1
Condition Count hypersensitivity)
Lykocytosis increased WBC C5b-9
Leukopenia decreased WBC (membrane
Neutropenia decreased neutrophils attack complex):
Lymphopenia decreased lymphocytes attack unit to
Note: –tosis = increase; –penia = decrease destroy the
organism
2. NORMAL DIFFERENTIAL COUNT
Table 6. Normal Differential Count Table 9. Congenital Diseases of Defective Phagocytic Cell Function
Type of Cell Count Characterized by Recurrent Bacterial Infection (2020C *Not part of this year’s
Neutrophil (majority) 55 to 75% lecture*)
Lymphocytes 20 to 35 % DISEASE DEFECT
Monocytes 2 to 6% Leukocyte Adhesion Deficiency LAD-1 (defective B2-integrin
Eosinophils 1 to 3% (LAD) expression or function of
Basophils 0 to 1 % CD11/CD18)
LAD-2 (defective fucosylation,
selectin binding)
Table 7. Chemical Mediators. MEMORIZE!
Hyper-IgE-recurrent infection Poor chemotaxis
Reactions Mediators
(Job Syndrome)
Vasodilation Prostaglandins
Chediak-Higashi Syndrome Defective lysosomal granules,
Nitric Oxide
poor chemotaxis
Increased Vascular Vasoactive amines (histamine, Neutrophil-specific Granule
Permeability serotonin) Deficiency
C3a and C5a Absent neutrophil granules
Bradykinin
Chronic Granulomatous Disease ↓ NADPH oxidase with
Leukotrienes
absent H2O2 production
PAF
Myeloperoxidase Deficiency ↓ HOCl production
Chemotaxic Leukocytic C5a
Activation LTB
Chemokines
Fever IL-1, IL-6, TNF
Prostaglandins
Pain Prostaglandins
Bradykinin
Tissue Damage Neutrophil and macrophage
products
Lysosomal enzymes
Oxygen metabolites
Nitric oxide
Reactive Oxygen Species (ROS)

2020A) Table 8. Chemical Mediators of Inflammation

Condition Count Mediators Source
Preformed Mast Cells,
Mediators in Histamine Basophils,
Secretory Platelets
Granules Serotonin Platelets
(You are born Lysosomal Neutrophil,
with it) Enzymes Macrophages
All leukocytes,
CELLULAR platelets,
Prostaglandins
IMMUNE Epithelial Cells
RESPONSE Newly (EC)
(cells are Synthesized Leukotrienes All leukocytes
stimulated) (only
Platelet
synthesized All leukocytes,
Activating
when your EC
Factors
immune
Activating
system is All leukocytes
Oxygen Species
challenged)
Nitric Oxide Macrophages
Lymphocytes,
Cytokines
Macrophages
Kinin system /
Bradykinin
Factor XII
Coagulation /
LIVER Activation
Fibrinolysis
(plasma fluid
System
is
C3a, C5a, C3b
synthesized
(anaphylatoxins):
from the
Complement complement
liver)
activation products
involved in
anaphylaxis
Table 10. Local and systemic factors that delay or retard wound healing
LOCAL SYSTEMIC
Retention of debris Deficiency of Vitamin C,
amino acid, zinc
Impaired circulation (blood supply) Excess of adrenal
glucocorticoids
Persistent infection or local Debilitating chronic diseases
infection (e.g. Diabetes Mellitus)
Denervation Hematologic Derangement
(anemia)
Hematoma Systemic Infection
Mechanical Stress Genetic disorders
(osteogenesis imperfecta,
Ehlers-Danlos syndromes,
Marfan syndrome)
Necrotic Tissue Drugs
Dressing on wound Malnutrition
Surgical Techniques Hormones
Type of tissue Temperature
Type, extent of injury Uremia
Location of injury Age (Older)
Foreign body Trauma, hypovolemia,
hypoxia
Table 14. Growth
Factors and Cytokines Involved in Regeneration
CYTOKINE
Epidermal Growth Factor (EGF)
Transforming Growth Factor Alpha
(TGF-α)
Transforming Growth Factor Beta
(isoforms 1 2 3); other members are
BMP and activin
(TGF-β)
Hepatocyte growth factor/scatter
factor (HGF)
Vascular endothelial cell growth factor
(isoforms A, B, C, D) (VEGF)
Platelet Derived Growth Factor
(Isoforms A, B, C,D) (PDGF)
Fibroblast Growth Factor-1 (Acidic), -
2(basic) and family (FGF)
Tumor Necrosis Factor (TNF)
Interleukins (IL-1, etc)
CYTOKINES ( Macrophage-Derived
Growth Factors)
SOURCE FUNCTIONS
Platelets, macrophages,  Mitogenic for fibroblast and keratinocytes
urine, milk, plasma, saliva  Growth of endothelial cells, fibroblablasts and hepatocytes
 stimulates keratinocyte and granulation tissue formation
 Receptor: EGFR/ ERB(epidermal growth factor receptor) with intrinsic
tyrosine kinase activity
- EGFR1: mutation testing among cancers of lung, head and neck
and breast
- ERB B2 (HER-2) targeted for treating breast cancer, for treatment
Macrophages, T lymphocytes,  Similar to EGF
keratinocytes, and many  Malignant transformation of normal cells to cancer cells
tissues migrating at the site of  Stimulates for replication of hepatocytes and epithelial cells
healing  Receptor: EGFR
Platelets, T lymphocytes,  chemotactic for PMNs, macrophages, lymphocytes, fibroblast and
macrophages, endothelial smooth muscle cells
cells, keratinocytes, smooth  inhibits growth of most epithelial cells
muscle cells, fibroblasts  increase expression of cell cycle inhibitors
 promote metastasis in mesenchymal cells
 increase collagen( via dec matrix proteases), fibronectin, and
proteoglycans formation
 fibrosis
 enhances In17 development
 stimulates TIMP (tissue inhibitor of MMPs) synthesis, keratinocyte
migration, angiogenesis, and fibroplasias
 inhibits production of MMPs (matrix metalloproteinases) and
keratinocyte proliferation
 regulates integrin expression and other cytokines
 induces TGF-B production
Mesenchymal cells  Enhances proliferation of epithelial cells and of hepatocytes
fibroblast  Necessary during embryonic devt
 increases cell motility i.e. cell scattering and migration
 receptor: C-Met, expressed in human tumors
Mesenchymal cells  vasculogenesis: blood vessel formation
 increases vascular permeability
 mitogenic for endothelial cells
- VEGFR 1: inflammation and mobilization
- VEGFR 2: vasculogenic and angiogenic
- VEGFR 3: lymphatic blood vessel production
Platelets, macrophages,  chemotactic for PMNs, macrophages, and smooth ms
endothelial cells,  activates PMNs, fibroblasts and macrophages
keratinocytes, smooth muscle  mitogenic for fibroblasts, endothelial cells and smooth muscle cells
cells  stimulate production of MMPs, fbronectic and hyaluronic acid
 stimulate angiogenesis and wound contraction; remodeling
 inhibits platelet aggregation; regulate integrin expression
- PDGFR B &C: ; Liver fibrosis and wound contraction
Macrophages, mast cells, T  (fibroblast: produces collagen)
lymphocytes, endothelial cells,  chemotactic for fibroblasts, mitogenic for fibroblasts and keratinocytes
fibrosis and many tissues  stimulates keratinocyte migration, angiogenesis, wound contraction
and matrix deposition
 cardiac and skeletal muscle development
 hematopoiesis: blood cell differentiation
 lung maturation
-
FGF-2 and 7: wound repair
-
FGF-2: angiogenesis
Macrophages, mast cells, T  activates macrophages
lymphocytes  regulate other cytokines
 multiple functions
Macrophages, mast cells,  chemotactic for PMNS (IL-1) and fibroblast (IL-4)
keratinocytes, T lymphocytes,  stimulation of MMP-1 synthesis (IL-1) , angiogenesis (IL-8) and TIMP
and many tissues synthesis (IL-6)
 regulation of other cytokines
 many other functions
T- lymphocytes  promote proliferation of fibroblast smooth muschl cells, and
endothelial cells
- IL 1, TNF: wound healing
- IL-6 TNF: liver regeneration
Table 15. Growth Factors and Cytokines Affecting Healing
Wound Healing Process GF/Cytokine
Collagenase secretion PDGF, EGF, FGF, TNF, TGF-β inhibitors
Fibroblast migration PDGF, EGF, FGF, TNF, TGF-β, IL-1
Fibroblast proliferation PDGF, EGF, FGF, TNF
Monocyte chemotaxis PDGF, FGF, TGF-β, Chemokines
Collagen synthesis PDGF, TGF-β
Angiogenesis PDGF, FGF, VEGF, angiopoietins

Table 12. Summary of Mediators

Action
Mediator Source
Vascular Leakage Chemotaxis Other
Histamine and Serotonin Mast Cells, Platelets + –
Bradykinin Plasma substrate + – Pain
C3a Plasma protein via liver + – Opsonic fragment (C3b)
Macrophages + + Leukocyte adhesion,
C5a
activation
Mast cells, from Potentiate other – Vasodilation, pain, fever
Prostaglandins membrane mediators
phospholipids
Leukocytes – + Leukocyte adhesion,
Leukotriene B4
activation
Leukocytes, Mast cells + – Bronchoconstriction,
Leukotriene C4, D4, E4
vasoconstriction
Leukocytes + – Endothelial damage,
Oxygen metabolites
tissue damage
Leukocytes, Mast Cells + + Bronchoconstriction,
PAF
leukocyte priming
Macrophages, other – + Acute-phase reactions,
IL-1 and TNF
endothelial activation
Chemokines Leukocytes, others – + Leukocyte activation
Macrophages, + + Vasodilation, cytotoxicity
Nitric Oxide
Endothelium

Table 13. Role of Mediators in Different Reactions of Inflammation

Reaction Mediators
Vasodilation Prostaglandins
Nitric oxide
Histamine
Increased vascular permeability Vasoactive amines
C3a and C5a (through liberating amines)
Bradykinin
Leukotriene C4, D4, E4
PAF
Substance P
Chemotaxis, leukocyte recruitment, and activation C5a
Leukotriene B4
Chemokines
IL-1, TNF
Bacterial products
Fever IL-1, TNF
Prostaglandins