Inflammatory Response Quiz

PPSY 400: Unit 2

• Topics covered include inflammation, immune pathology, and pain.
• Chapters 5, 6, and 4 of the relevant textbook are pertinent.

Pain Pathway

• The pain pathway has six stages: pain, transduction, transmission, perception, expression, and modulation.
• Refer to slide 31 for more details.

Pain (Transduction)

• Nociceptors initiate pain transduction after a signal of injury.
• The initial response involves a chemical released into the central nervous system (CNS) to initiate the pain transmission process.
• Pain sensation is associated with a nociceptor (receptor). Page 3 has detail on the diagram, pathway and receptors involved.

Pain - Continued

• Perception (subjective): subjective experience of pain.
• Expression: expression of pain
• Modulation: modulation of pain (making it better ex. heat/cold)
• A-Delta fibers are myelinated and have faster transmission, associated with instant pain.
• C fibers are unmyelinated with slower transmission and are associated with throbbing pain experiences.
• Substance P is known for initiating pain actions
• A-beta fibers, created by touch, can have an inhibitory effect, blocking pain signals.

Synapsis

• Opioid receptors are crucial in the synapsis process
• Knowledge of mild vs. moderate pain is important

Pain Continued

• Acute pain is often associated with stress (flight/fight).
• Chronic pain has unknown origins.
• Visceral pain arises from organ dysfunction, including hypercontraction (muscle cramps).
• Referred pain is felt in an area away from damaged tissues.
• Phantom pain is felt in an area where there is no longer a body part.
• Intractable pain is unresponsive to treatment.

Immune System

• Structures of the immune system include skin, mucous membranes, monocytes, macrophages, lymphoid system (including spleen, thymus, and lymph nodes), and bone marrow.
• White blood cells (WBCs) or leukocytes mediate inflammation and immunity.
• Leukocytes locate and eliminate pathogens and foreign molecules.

Immune System (continued)

• Immune system uses macrophages to eliminate infectious agents (virus & bacteria) through positive feedback, continuing until the issue is resolved.
• Activities of suppressor T cells act as negative feedback to regulate the response.
• Innate immunity acts in tandem with adaptive immunity.
• Innate immunity works to provide an initial response for infection.
• B cells and T cells characterize the specific response.

Inflammation

• Inflammation is a protective mechanism that begins when cells are injured.
• The purpose of inflammation is to:
  • Neutralize or destroy harmful substances/invaders.
  • Limit the spread of harmful substances/invaders to other organs.
  • Prepare damaged tissues for repair (healing).
• Inflammation symptoms are generally characterized by redness, heat, swelling, pain, and loss of function.

Inflammation steps (Acute)

• Increased blood flow, due to pressure differences, aids in the immune response.
• White blood cells (neutrophils) respond initially as the first responders, with phagocytic behavior to eliminate harmful toxins and pathogens.
• Macrophages arrive to continue the process and remove toxins/pathogens, as they exist longer than neutrophils.
• Clotting/thrombosis formation occurs in the injured area for healing & injury repair.
• Inflammation stages (steps) are critical for the healing process

Wound Repair

• Inflammation is a critical first step.
• Hemostasis is a necessary process for wound repair.
• The intrinsic and extrinsic pathways contribute to the clotting process.

Wound Healing (types of cells)

• The three types of healing cells are labile, stable and fixed cells.
• Labile cells constantly undergo mitosis.
• Stable cells regenerate under certain circumstances.
• Fixed cells do not regenerate.

Wound Healing (steps)

• Initial stages involve inflammation and hemostasis.
• Proliferation follows, involving granulation tissue formation.
• Remodeling finally occurs, transforming granulation tissue into stronger scar tissue.
• The healing time varies based on factors such as injury type and individual conditions.

Signs of Inflammation

• Five classical signs of inflammation are redness, swelling, heat, pain, and loss of function.
• The term "-itis", is associated with inflammation in body parts and is used medically to describe a particular inflammation (for example, tendonitis or appendicitis).
• Inflammation may be present from infectious agents, but infection isn't the only cause of inflammation.

Inflammation (causes)

• Inflammation may be triggered by exogenous sources (outward factors), such as surgery, trauma, burns, etc.
• Inflammation may also be caused endogenously (inside factors). factors such as myocardial infarction (MI), ischemia, etc.

Process of Inflammation

• Regardless of cause, inflammation follows predictable stages: increased vascular permeability, leukocyte recruitment, phagocytosis.
• Note: there is vasoconstriction(quick contraction of arterioles) immediately following an injury as a response to decrease blood loss..

Increased Vascular Permeability

• The underlying mechanism involves the release of chemical mediators (histamine, prostaglandins, bradykinin, leukotrienes) from mast cells at the injury site.
• The increased blood flow, hydrostatic pressure, and capillary permeability result in fluid being pushed out of blood vessels into surrounding tissues, leading to swelling.

Increased Vascular Permeability (continued)

• Histamine is a key vasodilator during inflammation and is released in high amounts as a strong response to inflammation.
• Exudates or the fluid that accumulates during inflammation is critical to inflammation and healing.

Increased Vascular Permeability (continued)

• Platelets move to the injury site and release fibronectin.
• Fibronectin helps form a meshwork/trap that reduces bleeding.
• Platelets release growth factors to boost cell proliferation.
• The release of fibrin in lymph vessels wall off the site of injury to reduce the spread of toxins.

Emigration of Leukocytes

• Neutrophils adhere to the capillary wall through selectins and integrins
• Chemokines enhance the binding of integrins
• Neutrophils migrate through the endothelial cells into inflamed tissues via diapedesis.

Emigration of Leukocytes - Chemotaxis

• Neutrophils are guided to damaged tissues by chemical signals (bacterial toxins, degenerative byproducts, etc.)
• Neutrophils initiate phagocytosis and release collagenases that break down dead tissues.
• Macrophages, eosinophils, and NK cells also participate by contributing to inflammation and eliminating infected tissues.

Phagocytosis

• Neutrophils and monocytes (macrophages) initiate phagocytosis, consuming cellular debris and harmful cells at the injured tissue site.
• Phagocytic enzymes (lysozymes, neutral proteases, elastase, etc.) digest engulfed material.
• Neutrophils eventually die at the site and form pus (a collection of dead neutrophils, bacteria, and debris).
• Macrophages remain longer to eliminate dead neutrophils and assist in tissue repair/healing.

Acute Inflammation

• Acute inflammation can cause damage to tissues due to degradative enzymes and oxidative agents.
• Antiproteases, produced in the liver, inhibit the destructive proteases released from activated neutrophils.

Alterations in Immune Function

• The immune system defends against invading foreign substances (antigens).
• Immune disorders are classified into excessive and deficient immune responses.

Excessive Immune Responses

• Autoimmunity is characterized by the immune system attacking its own tissue as if it's a foreign substance.
• Hypersensitivity describes a normal immune response becoming inappropriate & causing an excessive or undesirable effect on the body.
• Unknown causes typically trigger autoimmune responses.

Treatments for Autoimmunity

• Immunosuppressive therapies, such as corticosteroids and cytotoxins, aim to control excessive immune responses.
• Medication like corticosteroids may reduce (or decrease) the lymphocytes and alter their function; antibodies may also decrease with these medications..

Hypersensitivity

• Type I hypersensitivity involves allergic reactions mediated by mast cells, leading to immediate hypersensitivity or anaphylactic reactions. (Symptoms such as vasodilation, increased vascular permeability, hypotension, bronchoconstriction, hives, increased mucus secretion, itching, occur 15-30 minutes after exposure to the antigen or allergen)
• Type II hypersensitivity (ex. blood transfusion) is tissue-specific, causing the immune system's cells to attack foreign antigens.
• Type III hypersensitivity refers to immune complex reactions, where the immune system fails to eliminate antigen-antibody complexes in the tissues.
• Type IV hypersensitivity involves delayed-type reactions (such as contact dermatitis) initiated by T-cells; no antibodies are involved. Symptoms appear 24 hours after exposure and last up to 14 days.

Deficient Immune Responses

• Primary immunodeficiency disorders (PID) arise from inborn errors in immune cell development or maturation (congenital) or from acquired conditions such as HIV/AIDS.
• Secondary immunodeficiency disorders arise from non-immune system factors (such as nutritional deficiencies, stress, or drugs that interfere with/suppressed immune function).

Pain

• Pain is a subjective experience and difficult to define.
• Nociception involves the physiological mechanisms underlying pain perception.

Nociception - Stages

• Transduction is the conversion of a painful stimulus to an electrical signal.
• Transmission involves the movement of action potentials from sensory neurons to the spinal cord and brain.
• Perception occurs when the brain interprets the signal as pain.
• Modulation involves mechanisms that alter pain signal transmission.

Transduction

• Nociceptors are stimulated by noxious stimuli, responding to harmful stimuli at injury sites, responding to damage or chemicals.

Transduction — Chemicals (continued)

• Pain chemicals include K+, H+, lactate, histamine, serotonin, bradykinins, and prostaglandins.
• These chemicals depolarize nociceptor membranes, triggering a pain signaling cascade.

NSAIDs

• NSAIDs (NonSteroidal AntiInflammatory Drugs) inhibit cyclooxygenase, an enzyme involved in prostaglandin production.
• Inflammation often triggers prostaglandin release, increasing nociceptor sensitivity to pain signals.

Transmission

• Action potentials travel from sensory neurons to the spinal cord and brain via Aδ fibers (larger, myelinated, rapid transmission) and C fibers (smaller, unmyelinated, slower transmission).
• Aδ fibers generally transmit sharp, acute pain
• C fibers typically transmit dull, chronic pain

Transmission (Continued)

• Collaterals from sensory afferent fibers carrying pain signals spread up & down the spinal cord, activating reflex postural adjustments.

Transmission to Brain

• The anterolateral tract is the primary pathway for pain signals to the brain.
• The tracts travel through the spinal cord white matter and cross to the opposite side of the spinal cord (contralateral).
• It divides into the spinothalamic and paleospinothalamic tracts.

Anterolateral Tract

• The neospinothalamic tract involves Aδ fibers, sending signals rapidly to the thalamus for location processing of pain stimuli but no emotional component.
• The paleospinothalamic tract carries signals from C fibers and to the thalamus but also reaches the cerebral cortex, limbic system and brainstem for emotional processing of pain more extensively.

Pain Identification

• The brain localizes pain sensations through specific pathways (nociceptors) that connect to the spinal cord and somatosensory cortex.
• Sensory dermatomes illustrate the relationship between spinal nerves and the body's surface areas they innervate.
• Nerve damage (injury/pinching) can cause characteristic pain patterns specific to the affected or damaged nerve.

Perception

• Perception involves the brain interpreting pain signals as 'pain'.
• Pain perceptions encompass pain awareness & understanding/interpretation of the meaning behind the sensations.
• Expectations, attention, distraction, anxiety, previous experience, past or current conditions, fear, fatigue, etc., impact pain perception.
• The primary somatosensory cortex and related association areas play a crucial role in localizing and interpreting pain.
• Front brain / limbic structures are also involved in the perception of pain.

Perception of Pain (continued)

• Pain threshold refers to the intensity of stimulation required to trigger pain perception (roughly similar across individuals).
• Pain tolerance refers to the intensity of pain someone can endure before seeking relief, highly variable between individuals.
• Pain expression is the way in which pain is communicated to others (ex. facial grimacing, crying, moaning).

Modulation

• Modulation is a complex process altering pain signal transmission.
• Rubbing, shaking, or pressing apply pressure to areas to lessen pain.
• The gate-control theory suggests that large myelinated nerve fibers can block or decrease pain signals by inhibiting small unmyelinated fibers (C fibers).
• Brain pathways, such as the descending pathway from the brainstem (raphe magnus nucleus), help to modulate pain perception.
• Opioids, like endorphins, and opioid medications, inhibit substance P release to interfere with pain signal transduction.

Nociceptive Inhibition

• During pain and stress, body functions modulate pain with chemicals such as serotonin, endorphins, and norepinephrine.
• Endogenous opiates, like enkephalins, inhibit substance P release.

Acute vs Chronic Pain

• Acute pain is temporary, resolving after tissue healing, and usually lasts less than 3 months. Short term therapies (non-opioid, opioid drugs) may be effective.
• Chronic pain persists beyond healing and expected recovery time, often lacking a known cause.

Other Types of Pain

• Cancer-related pain stems from tumor infiltration or treatment complications.
• Neuropathic pain is chronic pain stemming from nerve damage or dysfunction.
• Ischemic pain stems from reduced blood flow and often involves aching, burning or pricking sensations.
• Referred pain is perceived in areas distant from the actual injury site due to shared nerve pathways.

Test your knowledge about the inflammatory response and innate immune system functions. This quiz covers various aspects of inflammation, including its signs, causes, and components. Perfect for students studying biology or health sciences.