Inflammation and Fever Flashcards
Describe acute inflammation
Acute inflammation is the body’s immediate and rapid response to an injurious agent such as pathogens, damaged cells, or irritants. It’s characterized by the classical signs of pain, heat, redness, swelling, and loss of function. This type of inflammation is generally short-lived, lasting from a few minutes to a few days. Key features and processes of acute inflammation include:
- Vascular Changes: Initially, there’s a brief constriction of the small blood vessels at the injury site, followed by vasodilation, which leads to increased blood flow and warmth and redness at the site.
- Increased Permeability: Endothelial cells become “leaky” due to retraction or damage, allowing fluid, proteins, and white blood cells to escape from the blood vessels into the tissue spaces, causing swelling.
- Cellular Infiltration: Neutrophils are the first white blood cells to arrive, followed by monocytes and macrophages. These cells are responsible for phagocytosing (engulfing and digesting) pathogens and debris.
- Mediator Release: Numerous inflammatory mediators such as histamine, bradykinin, prostaglandins, and cytokines are released. These mediators increase blood flow and vascular permeability and attract immune cells to the site of injury.
Describe Chronic Inflammation
Chronic inflammation is a prolonged inflammatory response that can last for months or even years. It often begins when acute inflammation is unable to resolve the underlying cause of injury or when it is repeatedly triggered by persistent irritants or pathogens. Chronic inflammation can also arise without any preceding acute phase. Characteristics of chronic inflammation include:
- Persistent Infection, Autoimmune Reactions, or Long-Term Exposure to Toxic Agents: These can continually stimulate an inflammatory response.
- Tissue Destruction and Repair Co-occurring: The immune system’s prolonged response leads to tissue damage, which the body continuously attempts to repair. This can result in the formation of scar tissue.
- Cellular Infiltration: Unlike acute inflammation, which primarily involves neutrophils, chronic inflammation is characterized by the presence of lymphocytes, macrophages, and plasma cells.
- Granuloma Formation: Often, the immune system forms a granuloma, which is a small area of inflammation due to a cluster of macrophages surrounded by lymphocytes. This is a way to wall off and isolate the foreign substances that cannot be eliminated.
Chronic inflammation can lead to several diseases, such as heart disease, diabetes, cancer, and autoimmune disorders.
Explain the physiological changes responsible for the cardinal signs of inflammation
- Rubor (redness) and Calor (heat): Both redness and heat are caused by vasodilation, which is the widening of blood vessels at the site of injury. This response is primarily mediated by inflammatory mediators such as histamine, prostaglandins, and nitric oxide. Vasodilation increases blood flow to the affected area, bringing more blood cells to fight the injury, resulting in warmth and redness.
- Swelling: Swelling results from the increased permeability of the local blood vessels, allowing fluid to escape from the blood into the surrounding tissues. This vascular permeability is also mediated by histamine, bradykinin, and leukotrienes. The fluid, known as exudate, contains proteins such as fibrinogen, which clots to form a fibrin mesh. This mesh helps to localize the infection or injury, traps bacteria, and forms a scaffold for the repair process. Swelling can compress adjacent nerve endings and contribute to pain.
- Pain: Pain occurs due to the direct irritation of nerve endings by the injury itself or by the swelling that accompanies inflammation. Chemical mediators like prostaglandins (especially PGE2) and bradykinin enhance the sensitivity of pain receptors (nociceptors) in the affected area. Bradykinin, in particular, induces pain by binding to receptors on peripheral nerves and triggering pain signaling pathways.
- Loss of Function: The loss of function is often a consequence of the severity of the inflammation. Swelling and pain can limit mobility or normal activity, either as a result of mechanical disruption or through protective reflexes aimed at minimizing further damage. For example, joint inflammation can restrict movement to prevent damage to the joint.
What are the three primary plasma protein systems?
- Complement System
- Clotting (Coagulation) System
- Kinin System
Explain the complement system, its role, and how it contributes to inflammation/healing
The complement system is a group of proteins that, when activated, enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells, promote inflammation, and attack the pathogen’s cell membrane.
Its role in Inflammation and healing are:
- Enhances phagocytosis through opsonization (coating of pathogens to make them more recognizable to phagocytes).
- Stimulates histamine release from mast cells, increasing vascular permeability and facilitating the influx of immune cells to the site of infection or injury.
- Forms the membrane attack complex (MAC) that can lyse and kill pathogenic cells.
Explain the clotting (Coagulation) system, its role, and how it contributes to inflammation/healing
The clotting system involves proteins that, when activated, form a fibrin mesh that serves as a temporary barrier to control bleeding and provide a framework for repair and healing. The clotting cascade can be activated by:
- Intrinsic pathway: Triggered by damage within the blood vessel.
- Extrinsic pathway: Initiated by external trauma that causes blood to escape into the extracellular tissue.
Role in inflammation and healing:
- Prevents the spread of infection by trapping pathogens in the fibrin mesh.
- Forms a clot that stops bleeding and provides a scaffold for cell migration during the healing process.
- Supports the restoration of normal tissue architecture and function.
Explain the Kinin system, its role, and how it contributes to inflammation/healing
The kinin system generates bradykinin, a potent peptide that causes blood vessels to dilate (increase in diameter) and become more permeable. It is activated by the action of kallikrein on high-molecular-weight kininogen (HMWK) to produce bradykinin.
Role in inflamation and healing:
- Bradykinin increases vascular permeability, allowing more fluid and cells to reach the injured tissue.
- Induces smooth muscle contraction, pain, and vasodilation.
- Helps in delivering components necessary for tissue repair to the site of injury.
What is the pathophysiology of fever
Fever is an elevation of body temperature that is controlled by the hypothalamus, acting as the body’s thermostat. It is a common physiological response to infection or illness, particularly from bacterial or viral causes. The process typically starts when an infection stimulates immune cells to release pyrogens. Pyrogens can be either exogenous (originating from outside the body, such as bacterial toxins) or endogenous (produced by the body, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF)).
These pyrogens act on the hypothalamus, leading it to raise the body’s set-point temperature. The body responds by generating and conserving heat through various mechanisms, such as shivering, increasing metabolism, and constricting peripheral blood vessels, which minimizes heat loss.
What are the benefits of fever
Despite its discomfort, fever has several potential benefits in the context of an immune response:
- Increased Immune Efficiency: Higher body temperatures can enhance the function of certain immune cells. For example, fever can increase the mobility of leukocytes, enhance phagocytosis, and optimize the activity of enzymes involved in the immune response.
- Inhibiting Pathogen Growth: Many pathogens have optimal growth temperatures close to the human body’s normal temperature. A rise in body temperature can inhibit the growth of some bacteria and viruses.
- Facilitation of Repair Mechanisms: Fever can potentially speed up the healing process by enhancing enzymatic reactions that occur faster at higher temperatures.
What is the difference between fever and hyperthermia
While fever and hyperthermia both involve an increase in body temperature, they are fundamentally different processes:
Fever: As described above, fever is a regulated increase in body temperature, set by the hypothalamus in response to pyrogens. It is a purposeful response by the body’s immune system to fight infection or illness.
Hyperthermia: Unlike fever, hyperthermia occurs when the body’s mechanisms for controlling temperature are overwhelmed by heat production, environmental conditions, or impaired heat dissipation. This can happen due to external heat exposure (heat stroke), strenuous physical activity (heat exhaustion), or dysfunction in thermoregulatory mechanisms (as seen in malignant hyperthermia). In hyperthermia, the body temperature rises above the set point regulated by the hypothalamus.
What are the 4 stages of wound healing?
- Hemostasis phase
- Inflammatory phase
- Proliferative phase
- Remodeling phase
Explain the Hemostasis phase
(1st phase) This initial phase begins immediately after the injury and is aimed at stopping the bleeding. Key events include:
Vasoconstriction: Blood vessels at the injury site constrict to reduce blood loss.
Platelet Aggregation: Platelets adhere to the injury site, forming a platelet plug.
Coagulation: Clotting factors are activated in a cascade that leads to the formation of a fibrin mesh. This fibrin clot not only staunches bleeding but also provides a temporary matrix for cellular components of healing.
Explain the Inflammatory Phase
(2nd phase) Following hemostasis, the inflammatory phase begins, typically lasting a few days. This phase is characterized by:
Vasodilation and Increased Permeability: This allows immune cells, nutrients, and growth factors to reach the wound site.
White Blood Cell Migration: Neutrophils arrive first to clear the wound of debris and bacteria, followed by macrophages which further clean the wound and release cytokines and growth factors that promote the next phase of healing.
Explain the Proliferative Phase
(3rd phase) Starting a few days after the injury and lasting up to several weeks, this phase focuses on building new tissue to fill the wound:
Fibroblast Proliferation: Fibroblasts migrate into the wound, proliferate, and produce collagen and extracellular matrix, which provide strength and structure to the tissue.
Angiogenesis: New blood vessels form to restore vascular supply to the tissue, a process critical for bringing oxygen and nutrients necessary for continued healing.
Granulation Tissue Formation: This is the formation of a new, pink, vascular tissue that fills the wound bed.
Epithelialization: New skin cells (epithelial cells) migrate across the new tissue to form a barrier between the wound and the environment.
Explain the Remodeling Phase
(4th phase) The final phase of wound healing can begin several weeks after the injury and last up to two years. During this phase:
Collagen Remodeling: The collagen deposited in the proliferative phase is rearranged and converted from type III to type I, increasing the tensile strength of the wound.
Contraction: The wound decreases in size as myofibroblasts, which are contractile cells that develop from fibroblasts, pull the edges of the wound together.
Maturation: The new tissue slowly gains strength and flexibility, though healed skin may only regain 70-80% of its original strength.
