W4 Pain and inflammation Flashcards
Define inflammation and its role in body protection.
The immune system is divided into two catergories.
Innate (nonspcific) & Adaptive.
1st line, 2nd line, 3rd line
Innate - First-line Skin: has a strong keratinized epidermis Mucous membranes: aids to trap bacteria Secretions: acts to kill bacteria
Second-line: Phagocytic cells: engulf foreign particles antimicrobial proteins: (complement, interferon)
Inflammatory response: defense against pathogens, bleeding and healing.
ADAPTIVE: third line
Identify the roles of immune cells in the inflammatory process.
Phagocytic cells: macrogphages, neutrophils & dendritic cells. Phagocytose enguld foreign cells.
Granulocytes release chemical mediators to amplify the inflammatory response but also to initiate the adaptive immune response.
List the cardinal signs of inflammation and explain why they manifest
Signs of acute inflammation.
- Redness
- Swelling
- Heat
- Pain
- Loss of function. - Systemic manifestations of inflammation may also occur
Describe the three stages of the acute-phase of the inflammatory process.
- Injury/initiation: blood clotting; haematostasis.
- Tissue injury/irritation.
- May coincide with bacterial infiltration
- Local release of histamine form mast cells located within the affected tissue. (Granulocyte) (Mast cells reside in most itssues.
* THey respond to the presence of pathogens, allergens and some signalling factors to release histamine, proteoglycans, and proteases to initiate inflammatin..*
Tissue damage → permits foreign body and entry of bacteria into the tissue →mast cells respond by releasing histamine → from storage granules.
2. Vascular phase: Histamine ( & later prostaglandins and leuotrienes) affect blood vessels.
→ Arterioles and venules dilate
- ↑ blood flow to injured area - redness and warmth result. Capillaries become more permeable
- Allowing exudate (water, blood or pus) to escape into the tissues
- Swelling and pain result
3. Cellular phase:White cells enter the injured tissue.
- Platelets: release blood-clotting proteins at the wound site.
- Mast cells secrete histamine that mediate vasodilation and vascular permeability
- Neutrophils and macrophages secrete chemotacic factors to recruit more WBC and adhesive fact that allow them to attach to site of injury; they remeove pathogens by phagocytosis.
- Macrophages secrete cytokins that attract immune cells. Secretory cells: granulocytes
- Phagocytic cells: neutrophils and macropages
Outline the roles of chemical mediators and plasma proteins in the inflammatory process.
- Damaged cells release inflammatory mediators..
- Those are derived from membrane phospholipids are called eicosanoids → these stimulate inflammation but also promote onset of healing,
Prostaglandins: ↑ vascular permeability and oedema, sensitise nociceptors to other inflammatory mediators, smooth muscle contraction.
Thromboxanes: platele taggregation and vasoconstriction Leukotrienes: bronchoconctriction, ↑ vascular permeability.
- Leukocytes release many inflmmatory mediates at the injured area - histamind and seotonin (vasodilation, ↑ vascular prmeability - platelet-activating factor (clotting)
Cytokines - Colony-stimulating factors
x Interleukins [fever]
x Interferons [fever]
x tumor necrosis factor [fever]
Nitric oxcide (vasodilation)
- Plasma proteins of innate immunity: normal protein comonent of blood, lymph, ECF, circulating in inactive form.
- Coagulation system: blood clotting)
- The kinin system induce pain ↑ vascular permeability
- The complement system: on exposure to foreign bodies they become activated, carrying out innate defence fnctions:
- trigger inflammation (inducing histamine release)
- attract phagocytes to the infection site
- promote the attachment of antigens to phagocytes
- causes lysis (breaking down the cell wall and membranes) of gram negative bacteria
- participates in the activation of naive B-lymphocytes.
- C-reative protein (facilitates clotting bind to pathogens, moderate inflammatory responses).
Compare and contrast chronic from acute inflammation.
Acute inflammation:
- short duration
- restrains tissue damage
- characterized leukocytosis and presence of fluid exudation
Chronic inflammation: occurs when tissue repair (healing) in achieve by acute inflammation is counter-acted by the re-injury of the same tissue:
- the orginial damaging stimulus has not been eradicated or
- the area is for some reason pre-disposed to re-injury.
- longer duration
- characterized by infiltration of lymphocytes and macrophages
- often causes tissue damage
Macrophages accumulate in the damaged area and keep releasing inflammatory mediators BY:
- Non-specific chronic inflammation
- Fibroblasts proliferate
- scar tissue forms,
Granulomatous inflammation - macrophages mass together around foreign bodies - connective tissue surrounds and isloates the mass
Describe the three phases of wound healing.
Aim to restore structural and function integrity of tissue. healed by primary or seconday intent.
- Haemostasis (inflammatory phase)
- Proliferative phase
- Remodelling phase
Describe the three phases of wound healing.
Aim to restore structural and function integrity of tissue. healed by primary or secondary intent.
- Haemostasis (inflammatory phase) blood clotting. Inflammation: brings WBCs that secretechemical mediators that initate healing.
Phagocytosis: (macrophages and neutrophils)
- infectious agents (if wound is exposed).
- debridement of injured tissue (cleans up dead cells.
- Proliferative phase: starts 2-3 days after injury, lasts upto 3 weeks. RE-EPITHELIAISATION of wound surfances closes the wound edges.
- Formuation of granulation tissues (fills up the ound with hihgly vascular CT
- Angiogenesis (new blood and lymphatic vessels)
Fibrogenesis (fibroblasts proliferate in the area)
3. Remodelling phase: 3> weeks after injury >>6 weeks. Remodelling of scar tissue to restore tensile strength.
- Tissue regeneration: injured tissue is replaces by the same kind of cells.
- Fibrous tissue repair: injured tissue is replaced by CT. Regeneration depends on cell type; [Epithelial and CT: ↑ capacity for regeneration] [Mature muscle and nervous tissue: limited]
Outline factors that may affect wound healing.
- Malnutrition
- Blood flow and oxygen delivery
- Impaired inflammatory and immune responses
- Infection, would separation & foreign bodies
- Age
Describe the anti-inflammatory mechanisms of action of corticosteroids and NSAIDs.
1. Non-sterodial anti-inflammatory drugs (NSAIDS)
Asprin
prototype NSAID - anti-inflammatory - antri-pyretic - anti=platelet inhibit COX enzymes → inhibition of prostaglandin production.
x do no cause tolerance or dependence
x adverse reactions include GIT disorder, asthma, rashs, sodium retention, renal damage.
Compound analgesia: may be used in combination with other drugs - antihistamines - codeines - caffin -antacids Sterodial anti-inflammatory *
Glucocorticoids - Powerful anti-inflammatory and immune suppressant - used for both systemic and toical applications
MECHANISIM OF ACTION:
- Suppress production of inflammatory mediators by inhibiting danger sensors in tissue cells,
- Reduc blood flow to inflammatory sites
- Attenuate leukocyte diapedesis (mobilisation phase)
- Regulate adaptive immunity x may inhibit many wound healing processes
- Corticosteroids x Other agents address
Define pain.
Pain is a mechanisim of defense, constructed in the brain, to protect the body from danger. Unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
- Reflex
Describe the neural pathways that determines the discriminative aspects of pain.
Step 1. Reflex loops
Step 2. Conscious awareness. *Reporter* Info reaches the brain and processes (discriminative process. → not “painful” yet. Type of stimulus differentiation
SOMATOSENSORY SYSTEM: Sensory receptor/neuron → Secondary order (relay) neurons → higher-order (process) neurons Sensory receptor: functional, receptive, field, modal and
Define nociceptors and describe the different types present in the human body.
Pain in somatosensory pathway is stimulated by a nociceptor.
A nociceptor is a receptor selectively activated by noxious stimuli (potential to cause tissue damage).
- Nociceptors are free nerve endings that serve as the primary sensory receptors for pain. Carrying impulses to the spinal cord.*
1. Acute or fast: sharp pain that takes your pain away - usually from superficial areas such as the skin, mucous membranes → somatic pain,
2. Chronic or slow: dull or aching pain such as stimuli arising from deep visceral areas → visceral pain.
Pain can be exacerbated by stimulation of mechanoreceptors (trauma/pressure)’ thermoreceptors (burning) and special senses intense light or sound.
Describe how pain is generated by stimulating nociceptors.
Myelinated (fast action potentials)
AB: mostly non-noxious, mechanical stimuli (itch, touch)
Ao fibres: Interpreted as sharp and well-localised pain Unmyelinated C fibre (slow action potentials) - Linked to sensations of dull, aching pain - difficult to pinpoint Dimensions of pain
- Modality 2. Intensity 3. Duration 4. Location
Describe the neural pathway that determines the emotional aspect of pain.
Spino-parabrachial-amigdaloyd pathway. Spinal cord → brainstem → amygdala (limbic system).
Amygdala processes sensory in to produce an emotional response. → activates hypothalamus = ( ↑ BP, HR, or behaviors crying, freezing in danger) Behaviour, hormonal and autonomic responses. The amygala → noxious responses
Explain how pain is processed by the nervous system.
- Activation of Nociceptors (or sensory receptors above a pain threshold).
* Nociceptors: receptors deeper in the skin that respond to mechanical, thermal or multimodal stimuli and conduct primarily via the fast conducting Ao fibres or the slower C fibres. - Activation of spinal neurons: spinal neurons in the doral horn are the second order neurons.Axons ascend and decuss (cros smidline) and contact the 3rd order sensory neurons in the thalamus.
- Spinothalmic tract: to thalamus then onto somatosensory cortex where received as a topographical sensory experience
- Spino-parabrachial-amygdaloid pathway: to parabrachial nucleous of the brainstem → amygdala → emotional response
- Corical and amygdaloid processing
- Processing in somatosensory cortex to provide the discriminatory awareness of the pain.
- Processing in the amygdala to provide the emotional response.
- Processing in other cortical and limbic structures (the neuromatrix) to provide the conscious perception or construction of the entire experience.
Distinguish between different types of pain.
. Nociceeptive pain vs Neuropathic pain
Nocicptive pain in pain xpereinced when noxious stimulus activates a sensory receptor neuron. Working normally. -
Neuropathic pain is where the pain pathway neurons generate pain because of neuronal dysfunction. These neurons are not working normally. SHooting, burning, tingling pain. Associated with paresthesias/allodynia.
Causes: pressure on nerve, infection of neuron
Somatic pain
- Originats in skin, mucosal surfaces, bones, joints, pleura and peritoneum.
- Throbbing, burning, stinging or dull.
Visceral (splanchnic pain - Arises from visceral organs and large muscle masses
neurological mechanisms and perception of pain different to somatic pain mechanisms.
- Deep, diffuse, nagging.
- Maybe referred pain.
Acute pain: usually results from tissue damage. ANS responses.
Chronic pain: > 3 months
utline the main analgesic drugs currently utilised to manage pain.
Opioids: Codeine, morphine, pethidine, fentanyl, tramadol
Non-opioids: asprings, and other salicylates, paracetamol
Others: GABAergics (ketamine)
Adjuvants: tricyclic anti-depressants, corticosteriods, psychotropic drugs
