Acute and Chronic Inflammation

• The presentation discusses both acute and chronic inflammation

Learning Objectives

• Explain inflammation by describing the cells involved and its relationship to symptoms like redness, heat, swelling, pain, and restricted movement
• Familiarize with inflammation terminology, concepts, cardinal signs, and significance
• Understand the inflammation process, event sequence, and components
• Differentiate between the two main types and morphological patterns of inflammation
• Get acquainted with inflammation outcomes

Definition of Inflammation

• Originates from the Latin term “inflammare”
• It is a primary defense of the innate immune system in response to tissue injury
• The goal is to eliminate the cause of injury and facilitate tissue repair
• Key components include stimulus, vessels, cells, and mediators
• It involves a complex process with recognition of stimulus, vascular and cellular events, and resolution or repair
• In clinical terms, the suffix "itis" denotes inflammation, like in cellulitis, arthritis, and appendicitis

Components of Inflammation

• There are four major components: stimulus, vessels, cells, and mediators
• The prominence of these components varies between acute and chronic inflammation

Inflammation Process: Steps

• The inflammation process includes presence of stimulus, vascular changes , cellular events and resolution
• Vascular changes include vasodilatation and increased vascular permeability, leading to leakage
• Cellular events involve leukocytes and mediators.

Cellular Events

• Recruitment of leukocytes occurs through margination, migration, and chemotaxis
• Recognition of stimuli by leukocytes involves their attachment and activation via receptors
• Removal of the stimuli involves phagocytosis carried out by leukocytes, followed by killing and degradation
• Resolution involves regeneration or repair of local tissues

Inflammation Sequence

• Presence of stimulus, vasodilation, recruitment, recognition, removal, and resolution
• Or presence of stimulus, vasodilation, margination, chemotaxis, attachment, activation, phagocytosis, degradation, and repair

Stimulus

• The initial step to initiate inflammation
• Types of stimuli include vascular issues, infections, neoplasm, drugs, iatrogenic factors, congenital issues, autoimmunity, trauma, and environmental factors
• Stimuli sources can be either exogenous or endogenous

Stimulus Sources

• Exogenous sources include physical, chemical, environmental, and biological factors
• Endogenous sources include immune reactions

Vascular Changes

• The goal of vascular changes is to bring cells and chemical mediators to the injury site
• Injury induces transient vasoconstriction, with histamine and nitric oxide then opening arterioles and capillaries within 4-6 hours, leading to vasodilation
• Dilated vessels hold more blood, causing vessel engorgement, known as hyperaemia, resulting in redness and swelling
• Endothelial cell contraction, histamine, cause transcytosis and leakage of fluid and plasma proteins through gaps between endothelial cells, leading to ODEma
• Vascular permeability leads to swelling, clinically known as edema

Lymphatic Changes

• Lymphatic vessels dilate and proliferate (lymphangitis) to drain leaked fluids, cells, debris to lymph nodes for removal, leading to lymph node inflammation (lymphadenitis)
• Lymphangitis presents as red streaks on the skin from the injury site
• This is common in intravenous drug users, leading to swollen regional lymph nodes

Recruitment: Margination & Migration

• Neutrophils predominate in acute inflammation
• Lymphocytes predominate in chronic viral inflammation
• Eosinophils predominate with allergic reactions and parasites
• Neutrophils arrive first within 6-24 hours and are then replaced by monocytes/macrophages

Chemotaxis

• Directional movement of leukocytes towards the injury site
• This movement follows a chemical gradient created by chemokines

Chemokines

• Chemokines are chemicals that mediate kinesis, produced by bacteria, blood, and cells
• Bacteria produces bacterial peptides, blood produces Complement-C5, and cells produce cytokines like IL-1 and TNF

Recognition

• Leucocytes recognize stimuli like microbes or dead cells in tissues
• This recognition is facilitated by sensors on leucocytes that detect microbes, chemicals, and dead cells

Removal

• Involves phagocytosis and killing of pathogens

Cardinal Signs of Inflammation

• There are five cardinal signs: rubor (redness), tumor (swelling), calor (heat), dolor (pain), and functio laesa (loss of function)
• Rubor is caused by vasodilation and increased blood flow
• Tumor is caused by vasodilation and leakage of cells, plasma, and proteins
• Calor is caused by vasodilation, increased vascularity and flow, and chemical mediators
• Dolor is caused by stretching of pain receptors, inflammatory exudate and mediator-kinin
• Functio laesa is caused by Disruption of tissue structure, Loss of tissue due to injury or repair by fibrosis

Types of Inflammation

• Acute inflammation is quick, lasting minutes to days, is caused by short stimulus is primarily caused by neutrophils
• Whereas, chronic inflammation is slow lasting weeks/months/years, is caused by persistent stimulus is primarily driven by lymphocytes and macrophages
• Acute inflammation contains stimuli vascular and cellular events and resolution
• Chronic inflammation contains stimuli vascular and cellular events tissue destruction resolution (fibrosis)
• 5 cardinal signs in acute inflammation are prominent
• Loss of function is prominent in chronic inflammation
• Acute inflammation stems from trauma/infections/vascular issues
• Chronic stems from infections/autoimmune/chemical

Outcomes of Inflammation

• The outcomes depend on stimulus, its intensity/duration, site of injury, affected tissue, and the host's ability to respond
• The outcomes include resolution, pus formation, healing, and fibrosis

Significance of Inflammation

• Treats beneficial effects i.e. neutralizes/disposes of the injurious stimulus and cell debris
• Treats limits the damage extent
• Treats sets the stage for tissue repair, and alerts the adaptive immune system
• Trick has harms, trick entails tissue damage
• Trick consists of spread and excessive repair, and can act as a precursor for cancers