Untitled Quiz

Course Information

• Course Code: 301
• Instructor: Dr. Ayesha Ilyas
• Semester: Spring 2020
• Reference Text: Robbins Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster-Robbins, and Cotran (2015)

Overview

• The course material involves an overview of the topic
• It covers intracellular accumulations

Intracellular Accumulations

• Accumulations of normal cell metabolites (e.g., fats, proteins, carbohydrates)
• Accumulations of abnormal substances (e.g., storage diseases, inborn errors of metabolism)
• Accumulations of pigments (e.g., endogenous pigments, exogenous pigments)

Acute Inflammation: Vascular and Cellular Events

• The study material covers the topic of acute inflammation, focusing on vascular and cellular events.
• Images of inflammation (e.g., swollen ankles, hands, burns) are presented.

Introduction to Inflammation

• Survival of organisms depends on eliminating foreign invaders, like pathogens and damaged tissues.
• This function is mediated by a complex host immune response called inflammation
• Inflammation is a protective mechanism that removes harmful stimuli and initiates the healing process.
• Without inflammation, injuries and infections would not heal.

Definition of Inflammation

• The word inflammation is derived from Latin "inflammare," meaning "to set on fire."
• Inflammation is a response of vascularized tissues to infection or injury.
• It brings cells and molecules of host defense from the circulation to the affected site to eliminate the offending agent.
• Inflammation is a protective response, not harmful

Mediators of Defense

• Phagocytic leukocytes
• Antibodies
• Complement proteins
• The inflammatory process delivers these elements to damaged/necrotic tissues & foreign invaders (e.g., microbes)
• These elements activate recruited cells/molecules to eliminate harmful substances

Historical Background

• Celsus (30 BC – 45 AD), a Roman physician, identified the four cardinal signs of inflammation: rubor (redness), tumor (swelling), calor (heat), and dolor (pain).
• Virchow (1871) added a fifth sign: loss of function (functio laesa).
• Cohnheim (1873) described diapedesis (movement of cells out of blood vessels).
• Lewis (1927) described inflammation as "triple response" to injury.

Cardinal Signs of Inflammation

• Rubor (Redness): Increased blood flow
• Tumor (Swelling): Exudation of fluid
• Calor (Heat): Increased blood flow, exudation of fluid, release of inflammatory mediators
• Dolor (Pain): Stretching of pain receptors & nerves, inflammatory exudates, chemical mediators
• Functio Laesa (Loss of Function): Pain, disruption of tissue structure, fibroplasia, and metaplasia

Steps of Inflammation (5R's)

• Recognition of injurious agent
• Recruitment of leukocytes
• Removal of agent
• Regulation of the response
• Resolution

Types of Inflammation

• Acute inflammation
• Chronic inflammation

Acute Inflammation

• Rapid response to microbes or injury
• Designed to deliver leukocytes and plasma proteins to injury sites
• Stimuli for inflammation include: Infections, trauma, physical/chemical agents, foreign bodies, immune reactions.

Components of Acute Inflammation

• Vascular changes
• Cellular events

Vascular Changes

• Changes in vascular caliber and flow
• Increased vascular permeability

Changes in Vascular Caliber and Flow

• Changes in blood vessels start rapidly after infection or injury.
• Development rate varies based on the severity and nature of the stimulus.

Increased Vascular Permeability

• Endothelial cell contraction increases interendothelial spaces.
• This is primarily triggered by histamine, leukotrienes, and bradykinin.
• Endothelial injury - resulting in endothelial necrosis and detachment
• Endothelial damage is caused by direct damage, microbes, microbial toxins and neutrophils.

Responses of Lymphatic Vessels and Lymph Nodes

• Lymphatic vessels proliferate to handle increased load.
• Lymphatics become inflammed (lymphangitis/lymphadenitis)
• This inflammation leads to redness/swelling

Pathophysiology of Inflammation

• Inflammation causes vasodilation, increasing blood flow (manifested as rubor).
• Increased permeability lets protein-rich fluid enter the extravascular tissues.
• Red blood cells (RBCs) concentration increases, leading to blood viscosity and stasis.
• Leukocytes accumulate along vessels' endothelium.

Cellular Events

• Leukocytes delivery to injury site is crucial for inflammation.
• Leukocytes activation following transmigration, chemotaxis, phagocytosis.
• Phagocytosis involves: recognition & attachment, engulfment (phagocytic vacuole), killing/degradation (ingested material).

Resolution of Inflammation

• Phagocytes clear dead tissue and leukocytes during inflammation.
• Lymphatic drainage and macrophages remove fluid/proteins.
• Macrophages release growth factors for new blood vessels and fibroblasts, aiding fibrosis & scarring.

Patterns of Acute Inflammation

• Morphologic manifestations of acute inflammation (e.g., serous, purulent, fibrinous).
• Key features differentiate these patterns.

Different Morphological Patterns

• Serous inflammation
• Purulent inflammation (pus)
• Fibrinous inflammation
• Ulcer

Serous, Fibrinous, and Purulent Inflammation

• These are morphologic classifications of acute inflammation
• Serous inflammation: Characterized by a watery, low protein fluid. This fluid can appear as a blister
• Fibrinous inflammation: Occurs as a consequence of significant injury. This type of inflammation results in high vascular permeability, allowing large molecules (fibrin) to leak out into the tissues.
• Purulent inflammation (suppurative inflammation): Characterized by a large amount of purulent exudate or pus. This fluid consists mainly of neutrophils, necrotic cells and edema fluid.

Home Task

• Study the principle mediators of inflammation.