Acute Inflammation: Vascular Events and Outcomes

• Inflammation, the inflammatory response, and fever are important topics in pathophsiology

Causes of Inflammation

• Exogenous causes are from outside the body

• Endogenous causes are from within the body

• Biological/infectious exogenous causes include bacteria, viruses, fungi and parasites

• Non-infectious exogenous causes include physical trauma, foreign bodies, contact to heat/burns, frostbite, extreme temperatures, radiation injury, chemical accidents, chemotherapeutic drugs, and alcohol

• Endogenous causes include autoimmune reaction, damaged cells/tissue necrosis, neoplasm, endogenous protease release, and psychological excitement

What is Inflammation?

• Inflammation is how the body's white blood cells and the substances they produce protect against injury or infection.
• Inflammation works against outside invaders like bacteria and viruses
• Inflammation is an automatic, complex immuno vascular response of vascularized tissues to cell injury.
• It neutralizes harmful agents, removes deal tissue, and helps generate new tissue (healing).
• Inflammation is characterized by the development of inflammatory mediators and fluid movement from blood vessels to tissues
• This plays a key role in a number of diseases.
• Inflammatory conditions can be named by adding the suffix "-itis" to the affected organ or system
• Inflammation can be acute or chronic

Types of White Blood Cells

• Granulocytes
  • Neutrophils help with phagocytosis
  • Eosinophils fight against parasitic infection
  • Basophils produce inflammatory and allergic reactions
• Agranulocytes
  • Lymphocytes produce specific immune responses
  • Monocytes fight off bacteria, viruses, and fungi
    • B Lymphocytes
    • T Lymphocytes
    • Natural Killer Cells

Types of Inflammation

• Inflammation can be acute or chronic

Acute Inflammation

• Involves Pathogens, injured tissues
• Major cells invovled are Neutrophils, mononuclear cells like monocytes and macrophages.
• The primary mediators are vasoactive amines, eicosanoids
• Onset is immediate
• Duration is a few days
• Outcomes include resolution, abscess formation, chronic inflammation

Chronic Inflammation

• Involves persistent acute inflammation due to non-degradable pathogens

• The major cells involved mononuclear cells, lymphocytes, plasma cells, fibroblasts

• Primary mediators consist of IFN-y and various other molecules.

• Onset is delayed.

• Duration can be months or years.

• Outcomes include tissue destruction and fibrosis.

Cardinal Signs of Acute Inflammation

• Rubor (redness) is caused by increased blood flow to the injured area.

• Tumor (swelling)

• Calor (heat) due to vasodilation and increased blood flow.

• Dolor (pain)

• Functio laesa (loss of function)

• In acute inflammation, damaged cells release inflammatory mediators, which stimulates inflammation.

• ECM components are also involved in the inflammatory response.

• Cells like WBCs are also mobilized

• Damaged cells release inflammatory mediators.

• Acute inflammation delivers mediators of host defense leukocytes & plasma protein

The 3 Main Events of Acute Inflammation

• Hemodynamic changes
  • Vascular changes in physiology to increase blood flow
• Increased vacular permability
  • Microvascular changes allow WBC's + plasma proteins through.
• Migration of WBC's
  • Move to the site of injury

Stages of Inflammation

• Vascular Stage for Local Early Responses

  • Affect blood vessels through prostaglandins and leukotrienes
  • Vasoconstriction followed quickly by vasodilation
  • Arterioles and venules dialate
    • This increases blood flow to injured area
    • Causes redness and warmth

• Capillaries becoming more permeable

  • Allows exudate to escape into tissues
  • This causes swelling and pain

• Exudates that leak out contain cells, proteins, and solid materials.

• Results for acute inflammation include resolution, chronic inflammation, tissue scaring and fibrosis

• After a transient period following cell injury, vasoconstriction occurs.

Vascular Flow Caliber

• This leads to arteriolar vasodilation, increasing blood flow to the capillary bed, causing hotness and redness in the area.
• Protein-rich fluid moves into extravascular areas, concentrating blood by RBCs, which increases viscosity and slows circulation, known as stasis.
• After stasis, leukocytes (neutrophils) change their flow in vessels and accumulate along the vascular endothelial surface (margination).

Immediate Transient Response of the Vascular Stage

• Common form of vascular permeability increase following minor injury.
• Limited to post-capillary venules.
• Reversible and mediated by histamine, bradykinin, and leukotrienes.
• Endothelial cell contraction leads to intercellular gaps.
• Rapid and short-lived reaction (minutes), hence immediate transient response.

Immediate Sustained Response of the Vascular Stage

• Response occurs with serious injury
• Endothelial cell necrosis and detachment are caused by severe injury like burns
• Leak begins immediately after an injury and persists for hours or days.
• It effects venules, capillaries and arterioles.

Delayed Hemodynamic Response of the Vascular Stage

• Response is due to radiation injury.
• Beginning 2-12 hours after direct injury to endothelial cells and can last for days.
• It affects venules and capillaries and is caused by mild to moderate thermal injury, radiation, and bacterial toxins.

Inflammatory Mediators

• Damaged cells release inflammatory mediators.
• The types of local, early responses are vascular and cellular stages.

The Cellular Stage

• White blood cells enter the injured tissue
• This destroys infective organisms, removes damaged cells, and releases more inflammatory mediators.
• Leukocyte activation leads to Phagocytosis
• Leucocytes squeeze between cells which is also known as transmigration or diapedesis

Leukocytes

• Leukocytes express adhesive proteins

• Leukocytes follow the inflammatory mediators to the injured area which is also refered to as chemotaxis

• Leukocytes engulf and breakdown the injurious agents

• Leukocyte activation leads to cell recruitment and phagocytosis

Chemical Mediators of Inflammation

• Cell-derived mediators are either preformed such as histamine or synthesized from arachidonic acid.

Synthesized Cell-Derived Mediators

• Metabolites. Platelet activating factors, NO, reactive oxygen species, cytokines, and chemokines

Plasma-derived Mediators

• The liver synthesizes and releases inflammation mediators
• These travel in the plasma proteins
• Kinins
• Coagulation and fibrinolysis proteins
• Complement system
• C-reactive protein

Cell-Derived Inflammatory Mediators

• Includes histamine, serotonin, platelet-activating factor, cytokines, and nitric oxide.

Plasma-Derived Mediators of Inflammation

• Plasma derivatives are synthesized in the liver.
• Kinins
• Coagulation and fibrinolysis proteins
• Complement system
• C-reactive protein.
• C-reactive protein (CRP) increases 1000 fold or more during an injury, inflammation, or tissue death

Acute Phase Response

• Clinical Manifestations of Acute Inflammation Systemic Responses including;
  • An acute phase response, change in WBC count, fever (pyrexia), and lymphadenitis.

More Clinical Manifestations of Systemic Responses

• Altered plasma protein concentrations (e.g., SAA, CRP, Fibrinogen).
• Skeletal muscle catabolism.
• Increased ESR.
• Increased leukocyte count.
• Fever.
• Increased heart rate.
• Anorexia.
• Somnolence.
• Malaise.
• Body temperature rises due to upward displacement of the set point of the hypothalamic thermoregulatory center.
• This is induced by cytokines and bacteria endotoxins

Explore the vascular events of acute inflammation, including redness, warmth, and increased permeability. Understand the roles of prostaglandins, leukotrienes, and hemodynamic changes. Learn about different types of exudates and outcomes like resolution and fibrosis.