Acute Inflammation Flashcards
explain the essential functions of the immune system and the body’s response to infections and injuries
Destroys the source of infection: This refers to the immune system’s ability to recognize and eliminate pathogens (such as bacteria, viruses, or fungi) that have entered the body. Immune cells, like white blood cells, target and destroy these pathogens to prevent further infection.
Destroys harmful products made by infection or injury: In addition to directly combating pathogens, the immune system can also neutralize or eliminate harmful byproducts produced during the infection or injury, such as toxins or inflammatory molecules. This helps limit the damage caused by the immune response itself.
Breaks down damaged tissue: When tissues are damaged due to infection or injury, the body’s immune and repair mechanisms work to break down and remove the damaged tissue, allowing for the regeneration and healing of the affected area. This process is crucial for tissue repair and recovery.
Together, these functions are part of the body’s defense and recovery mechanisms, which help maintain health and well-being when faced with infections or injuries.
explain the inflammatory response
Response to tissue damage: Inflammation is a response triggered by tissue damage. It is the body’s way of trying to repair and protect the affected area.
Non-specific: Inflammation is a non-specific response, meaning it occurs in a similar manner regardless of the type of tissue damage or the specific cause.
Affects almost all tissues of the body: Inflammation can occur in virtually any tissue or organ in the body when there is damage or an infection.
Objectives:
Clear away dead tissue: Inflammation helps remove dead or damaged tissue from the site of injury.
Deal with local infection: Inflammation also plays a role in controlling and containing infections that may be present at the site of injury or damage.
Invites the immune system to attend: Inflammation signals the immune system to the site of injury to assist in the healing process. Immune cells are recruited to help fight infection and promote tissue repair.
Indicated by ‘itis’: Many medical conditions associated with inflammation are named with the suffix “-itis.” For example, “arthritis” refers to inflammation in the joints, “dermatitis” is inflammation of the skin, and “appendicitis” is inflammation of the appendix.
explain the various factors that can cause tissue damage and contribute to the inflammatory response
Anything that causes tissue damage: Inflammation can be triggered by various factors that result in tissue damage. This includes injuries, infections, and other sources of damage to the body’s tissues.
Microbial causes: Infections by viruses, bacteria, and parasites can lead to tissue damage. Additionally, microbial toxins produced by these pathogens can also be injurious to tissues.
Trauma: Trauma, which can be either blunt or penetrating, is a common cause of tissue damage. This can result from accidents, falls, or physical impacts. Foreign bodies, such as splinters or debris, can also cause tissue damage.
Chemical and physical causes: Various chemical and physical factors can lead to tissue damage, including burns, frostbite, and irradiation (exposure to radiation).
Immune reactions - hypersensitivity: Certain immune reactions, often referred to as hypersensitivity reactions, can lead to tissue damage. In these cases, the immune system overreacts to specific triggers, leading to inflammation and tissue injury.
Bleeding and hemostasis: If trauma is involved, such as a cut or injury that results in bleeding, the initial stages of the body’s response will include hemostasis. Hemostasis is the process of stopping bleeding and preventing excessive blood loss. This is achieved through mechanisms like blood clot formation.
Typically involves pain: Inflammation often results in pain at the site of tissue damage. Pain is a common symptom of the inflammatory response, serving as a signal that something is wrong and prompting protective behaviors.
explain how inflammation can lead to pain at the site of tissue damage or injury
Increased pressure from the swelling acting on nerve endings: During inflammation, the accumulation of fluid and immune cells at the site of injury or infection can lead to swelling. This swelling exerts pressure on nearby nerve endings, which can result in pain. The compression of nerves by the increased volume of tissue can cause discomfort and contribute to the sensation of pain.
Chemical mediators irritate nerve endings, e.g., bradykinin: Inflammatory responses involve the release of various chemical mediators, including bradykinin, which can directly stimulate or irritate nerve endings. These chemical signals can sensitize nerve fibers and enhance the perception of pain. Bradykinin, in particular, is known for its role in increasing pain sensitivity by affecting pain receptors (nociceptors) in the affected area.
explain the various components of the immediate early response to tissue damage or inflammation and their effects
Histamine:
Source: Released from mast cells, basophils, and platelets in response to various stimuli.
Effects: Primarily vascular effects, such as vasodilation and increased permeability, leading to redness and swelling. It can also induce pain. Histamine is not chemotactic, meaning it doesn’t attract immune cells to the site of inflammation.
Proteases: Enzymes that break down proteins. In the context of inflammation, they can contribute to tissue damage.
Kinins (Bradykinin and Kallikrein):
Source: Bradykinin is one of the kinins. Kallikrein is an enzyme involved in bradykinin formation.
Effects: Bradykinin is a potent vasodilator, which increases blood flow to the injured area and can cause pain.
Complement system:
Source: A part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes.
Effects: It can lead to opsonization (marking microbes for destruction), inflammation, and direct lysis of pathogens.
Coagulation/fibrinolytic system:
Effects: Involved in the formation of blood clots to prevent excessive bleeding. It also plays a role in tissue repair and healing.
Prostaglandins/Leukotrienes:
Source: Derived from arachidonic acid.
Effects: Prostaglandins and leukotrienes are lipid mediators with various effects, including inflammation, pain, fever, and regulating blood flow.
Metabolites of arachidonic acid:
Synthesis blocked by NSAIDs (e.g., aspirin): These drugs inhibit the production of prostaglandins and related molecules, reducing inflammation and pain.
Cytokines and chemokines:
Examples: Interleukins, Platelet-activating factor (PAF), Tumor necrosis factor-alpha (TNF-alpha), Platelet-derived growth factor (PDGF), Transforming growth factor-beta (TGF-beta), Monocyte chemoattractant protein (MCP), and others.
Effects: These signaling molecules regulate and coordinate various aspects of the immune response, including cell activation, chemotaxis (attraction of immune cells to the site of inflammation), and the overall immune response.
explain some of the vascular and circulatory changes that occur during an inflammatory response
Arterioles dilate:
When inflammation occurs, arterioles in the affected area dilate or widen. This dilation is part of the body’s response to deliver more blood to the injured or inflamed site.
Increased blood flow leads to several effects: More oxygen is delivered to the area to support metabolic processes and immune responses.
Plasma, white blood cells (WBCs), and clotting factors are transported to the site, helping to address injuries and infections.
The increased blood flow makes the area warmer (increased temperature) and appear redder (caused by the influx of oxygenated blood).
Blood speed typically decreases as the arterioles dilate, allowing more time for interactions between blood components and the tissues.
Capillaries and venules become more permeable:
In response to inflammation, the walls of capillaries and venules become more permeable, allowing the escape of various substances, including plasma and blood components, into the surrounding tissues.
This increased permeability can lead to the accumulation of fluid in the tissue, resulting in edema. Edema can be either transudate (a clear, low-protein fluid) or exudate (a fluid rich in proteins, white blood cells, and other elements).
Lymphatic drainage increases:
The lymphatic system plays a crucial role in removing excess tissue fluid, filtering pathogens, and carrying immune cells to lymph nodes for further processing.
During inflammation, lymphatic drainage increases to help clear pathogens, cellular debris, and excess fluid from the inflamed site. This facilitates the transport of these substances to regional lymph nodes, where immune responses can be initiated.
explain the process of fever development during an immune response and inflammation
Red blood cell accumulation: Inflammation can lead to the accumulation of red blood cells in the affected area. This can occur due to the dilation of arterioles and increased blood flow to the inflamed site. The increased red blood cell presence contributes to the reddening of the area.
Release of pyrogens from bacteria and immune cells:
Pyrogens are substances that induce fever. They can be released by both bacteria and certain immune cells in response to infection or inflammation.
There are two types of pyrogens: exogenous (from external sources like bacteria) and endogenous (produced by the body’s own cells). Endogenous pyrogens are released by immune cells such as macrophages and include interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha).
Endogenous pyrogens, IL-1, and fever:
Interleukin-1 (IL-1) is an endogenous pyrogen that plays a significant role in inducing fever.
IL-1 can act on the hypothalamus, which is a region in the brain responsible for regulating body temperature.
When IL-1 stimulates the hypothalamus, it leads to the production of prostaglandins. Prostaglandins cause the hypothalamus to “reset” the body’s temperature to a higher level, resulting in fever.
Medications like aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce fever by inhibiting the production of prostaglandins, which effectively lowers the elevated body temperature.
explain the terms “transudate” and “exudate”
Transudate:
Transudate is a type of fluid that accumulates in body cavities or tissues.
It has a low protein content, usually due to minimal leakage of plasma proteins.
Transudate formation is typically the result of alterations in hydrostatic or oncotic pressure. These alterations can be caused by non-inflammatory factors such as heart failure, liver cirrhosis, or kidney disease.
Transudate does not typically contain a significant number of inflammatory cells or high levels of proteins, and it is often clear and watery.
Exudate:
Exudate, on the other hand, is a type of fluid that accumulates in response to inflammation or an injury.
It has a high protein content because the inflammatory process attracts various proteins, particularly albumin, and cells to the site.
The presence of high protein levels and inflammatory cells in exudate is indicative of an active inflammatory response. It can be cloudy or even purulent (containing pus) in appearance, depending on the severity of the inflammation and the specific cause.
Conditions like infections, injuries, and inflammatory diseases can lead to the formation of exudate.
explain the cardinal signs of inflammation
Rubor (redness): Inflammation often leads to an increase in blood flow to the affected area. This increased blood flow can make the area appear red or flushed. It’s a result of dilated blood vessels and increased delivery of oxygen and immune cells to the site of inflammation.
Tumor (swelling): Swelling is another common feature of inflammation. It occurs due to the accumulation of fluid (edema) in the tissues at the site of injury or infection. Swelling is a response to the increased permeability of capillaries and venules, allowing fluids, proteins, and immune cells to enter the affected area.
Calor (heat): Inflammation can make the affected area feel warm to the touch. This warmth is a result of increased blood flow and metabolic activity in the area. The higher blood flow and metabolic processes generate heat.
Dolor (pain): Pain is a common symptom of inflammation. It is caused by the activation of pain receptors (nociceptors) in response to tissue damage, pressure from swelling, and the release of chemical signals like bradykinin. Pain serves as a warning signal, discouraging further injury and encouraging rest.
Loss of movement: Inflammation may lead to a temporary loss of movement in the affected area. This is often due to pain, swelling, and tissue damage. The loss of movement serves as a protective mechanism to prevent further harm and to promote healing.
outline the roles of various components of blood in the body, particularly in the context of tissue repair and defense against infections
Red blood cells (RBCs):
RBCs are primarily responsible for transporting oxygen from the lungs to the body’s tissues and organs.
They also help transport carbon dioxide, a waste product of metabolism, from the body’s tissues back to the lungs for exhalation.
Salts and proteins for construction:
Blood contains essential nutrients, including salts (electrolytes) and proteins, which are required for various bodily functions, including tissue repair and construction. These nutrients are transported via the bloodstream to the cells and tissues that need them for growth and repair.
Fibrin and clotting factors:
Fibrin and clotting factors are essential components of the blood’s clotting system. When blood vessels are damaged, these components work together to form a blood clot to prevent excessive bleeding.
Fibrin, in particular, creates a mesh-like structure that traps blood cells and forms the clot.
White blood cells (WBCs):
WBCs are a crucial part of the immune system and play a central role in defending the body against infections and foreign invaders.
Different types of WBCs, such as neutrophils, lymphocytes, and macrophages, have specific functions in identifying and attacking pathogens, such as bacteria, viruses, and fungi.
outline some of the key vascular and cellular changes that occur during the inflammatory response
Dilation of vessels (arterioles mainly, also capillaries): During inflammation, arterioles (small arteries) and capillaries in the affected area dilate or widen. This dilation is a response to various signals, including chemical mediators like histamine and prostaglandins. Dilation increases blood flow to the site of injury or infection, which is a crucial step in delivering necessary resources to the area.
RBCs and white cells slow down: As blood vessels dilate, the flow of both red blood cells (RBCs) and white blood cells (WBCs) may slow down. This reduction in blood flow velocity allows these cells to interact with the endothelium and migrate into the tissue.
Endothelium (and basement membrane) becomes more permeable: In response to inflammatory signals, the endothelial cells that line blood vessels become more permeable. This increased permeability allows various substances, including immune cells and fluid, to move from the bloodstream into the surrounding tissue. The basement membrane, which underlies the endothelium, may also become more permeable.
Fluid and white cells move into the interstitium: The increased permeability of the endothelium and basement membrane allows fluid, white blood cells, and other molecules to exit the bloodstream and enter the interstitium (the space between cells and tissues). This movement of fluid and immune cells is a fundamental part of the inflammatory response, as it brings immune cells to the site of injury or infection and allows them to combat pathogens and initiate tissue repair.
explain the process of margination and the interactions between endothelium and phagocytes (white blood cells) during the early stages of inflammation
Margination:
Margination refers to the process where white blood cells (such as neutrophils and monocytes) move closer to the inner wall of the blood vessel (endothelium) in response to chemical signals.
Endothelium-Phagocyte Interactions:
These interactions involve adhesion molecules on both the endothelium (the lining of blood vessels) and phagocytes (white blood cells). The interactions are crucial for the recruitment of phagocytes to the site of inflammation or infection.
Activation of Adhesion Molecules:
Various chemical signals can activate adhesion molecules on both endothelial cells and phagocytes. Some of the key adhesion molecules involved in this process include:
P-selectin: Histamine and thrombin can activate P-selectin on the endothelium. This activation occurs relatively quickly, within minutes.
E-selectin: Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) can activate E-selectin on the endothelium. This activation takes hours to occur.
ICAM-1 (Intercellular Adhesion Molecule-1) and VCAM-1 (Vascular Cell Adhesion Molecule-1): These molecules are also upregulated on the endothelium and play important roles in phagocyte adhesion.
LFA-1 (Lymphocyte Function-Associated Antigen-1) and VLA-4 (Very Late Antigen-4): These are adhesion molecules on the surface of neutrophils that become activated, allowing them to bind to their respective ligands on the endothelium.
explain the sequence of events that occur during the process of white blood cell recruitment from the bloodstream to the site of inflammation or infection
Margination & Rolling:
During the initial phase of inflammation, white blood cells (such as neutrophils and monocytes) undergo a process called “margination,” where they move closer to the blood vessel’s inner wall (endothelium) in response to chemical signals.
Following margination, these white blood cells start “rolling” along the endothelium. This rolling is facilitated by interactions between cell adhesion molecules on both the white blood cells and the endothelial cells.
Tight Binding:
After rolling, white blood cells firmly adhere to the endothelium by forming strong bonds with adhesion molecules on the endothelial cells. This process is called “tight binding” or “adhesion.”
Diapedesis:
Once tightly bound, white blood cells undergo “diapedesis,” which is the process of migrating through the endothelial cells and basement membrane to enter the surrounding tissue. Diapedesis allows white blood cells to leave the bloodstream and reach the site of inflammation or infection.
Migration:
After successfully crossing the endothelial barrier, white blood cells continue to move through the tissue, guided by chemical signals and gradients, to reach the specific area of injury or infection. This step is referred to as “migration” and is essential for the immune response to target and combat pathogens effectively.
explain diapedesis
Diapedesis, also known as extravasation, is the process by which white blood cells (leukocytes) exit the bloodstream and move into the surrounding tissue during an inflammatory response. It is a crucial step in the immune system’s ability to target and combat infections or respond to tissue damage.
The process of diapedesis involves the following key steps:
Relaxation of Inter-Endothelial Cell Junctions: White blood cells, such as neutrophils and monocytes, interact with the endothelial cells that line the blood vessel walls. Chemical signals, such as cytokines and other inflammatory mediators, trigger the relaxation or loosening of the tight junctions between endothelial cells. This loosening allows gaps or openings to form between the endothelial cells.
Digestion of Vascular Basement Membrane: In addition to the relaxation of endothelial cell junctions, white blood cells secrete enzymes (proteases) that help digest the vascular basement membrane. The basement membrane is a thin, supportive structure that underlies the endothelium. By breaking down the basement membrane, white blood cells can access the interstitium, which is the space between cells and tissues.
Transmigration: With the junctions between endothelial cells relaxed and the basement membrane partially degraded, white blood cells can migrate through these openings and enter the surrounding tissue (interstitium). Once in the tissue, they can respond to pathogens, remove damaged cells, and participate in the immune response.
outline the process of phagocytosis
Pathogen Interaction with Phagocyte Receptors:
When a pathogen, such as a bacterium or virus, enters the body, it contains specific molecular patterns (pathogen-associated molecular patterns or PAMPs) that can be recognized by receptors on the surface of phagocytes.
These receptors, like Toll-like receptors (TLRs) or pattern recognition receptors (PRRs), bind to the pathogen’s PAMPs, triggering a series of signaling events within the phagocyte.
Phagocyte Engulfment of the Pathogen:
The interaction between the pathogen’s PAMPs and the phagocyte’s receptors initiates a process known as phagocytosis. During this process, the phagocyte extends pseudopods (protrusions of the cell membrane) to surround and engulf the pathogen.
The pathogen is encapsulated within a phagosome, an intracellular vesicle formed during phagocytosis.
Digestion of the Pathogen:
After the pathogen is enclosed within the phagosome, it fuses with lysosomes, which are specialized organelles containing enzymes and antimicrobial substances.
Within the phagolysosome, these enzymes digest the pathogen, breaking it down into its constituent molecules.
Pathogen Breaks Down into Proteins and Molecules:
As the pathogen is broken down within the phagolysosome, it disintegrates into its basic components, which can include proteins, nucleic acids, lipids, and other molecules.
Antigen-Presenting Cell:
Some of the degraded pathogen’s proteins and molecules can serve as antigens. Antigens are substances that can trigger an immune response.
The phagocyte, which has ingested and digested the pathogen, becomes an antigen-presenting cell (APC). It presents fragments of the pathogen’s antigens on its cell surface, bound to major histocompatibility complexes (MHC).
By presenting these antigens, the APC can activate other immune cells, such as T cells, which play a central role in orchestrating an immune response tailored to combat the specific pathogen.
