Week 1A (Inflammation & Healing) Flashcards
Clinical Manifestation
Signs (objective) & Symptoms (subjective)
Objective = can see/measure eg: jaundice, fever Subjective = reported by Pt eg: pain in chest
Diagnostic Investigation
Imaging (US/CT/MRI)
Etiology
Cause
Eg: high cholesterol level in bile –> formation of gallstones
Predisposing Factors
Risk Factors
Eg: High fat, low fiber diet
Pathophysiology
Mechanisms
Eg: Cholelithiasis obstruct flow of bile into cystic duct –> biliary colic and inflammation of GB
Course
Acute/Chronic
Acute: s&s appear suddenly, strong & last shortly
Chronic: s&s develop slowly & last longer
Treatment
Surgery/medications/fasting
Prognosis
Outcome/outlook
Eg: good with complete recovery if early surgical removal & bad if disease is life-threatening
Remission
Disappearance of S&S
Cellular Response to Stress & Injury
- Normal Cells (Homeostasis) –> Stress (Adaptation) & Injurious Stimulus (Cell Injury)
* inability to adapt –> cell injury
2A. Cell Injury (mild, transient) –> reversible injury (recover) –> normal cells
2B: Cell Injury (severe, progressive) –> irreversible injury –> necrosis & apoptosis AKA cell death
6 Types of Cellular Adaptation
- Atrophy
- Hypertrophy
- Hyperplasia
- Metaplasia
- Dysplasia
- Neoplasia (Malignancy)
Cellular Adaptation: Atrophy
Reduction in size NOT NUMBER
- vascular insufficiency
- malnutrition
- immobilization
- hormone level changes
Eg:
- bone loss
- muscle wasting
- brain cell loss
*reduced cell size DUE TO lower mass NOT reduced cell number
Cellular Adaptation: Hypertrophy
Increase in size NOT NUMBER
- increase functional demand
*2 cells –> 4 cells
Eg:
- heart & muscle hypertrophy
*All the hyper = increase functional demand
Cellular Adaptation: Hyperplasia
Increase in number of cells
- increase functional demand ONLY in cells capable of dividing (proliferate) / hormonal stimulation
*size small –> size large
Eg:
- during pregnancy, estrogen increases uterus thickness
*All the hyper = increase functional demand
Cellular Adaptation: Metaplasia
Change in morphology (form & structure) & function
*Square cells –> oval cells
Eg:
- smoke –> ciliated pseudostratified columnar epithelium TO stratified squamous epithelium
Cellular Adaptation: Dysplasia
Increase in numbers & change in cell types
- 2 cells –> 4 cells + changes in cell types
- Basal membrane integrity not breached
In chronically injured tissues, the cells are considered pre-neoplastic (pre-cancerous)
Cellular Adaptation: Neoplasia (Malignancy)
New growth (uncontrolled cell division)
*Basal membrane cell integrity breached
Eg:
- benign (non-cancerous)
- pre-malignant
- malignant (cancer)
Causes of Cell Injury
- Ischemia (lack of blood supply) –> Infarction (blood flow completely cut off –> cell death)
- Infection-m/o (bacteria, virus)
* bacteria invade tissue & release toxins –> cell lysis –> content spillage –> post-inflammatory rxn
* virus re-direct cell biosynthesis towards viral replication - Immune/allergic rxn
- Direct physical damage (thermal, tear, radiation)
- Chemical toxins (endogenous: internal OR exogenous: external)
- Genetics factors
- Nutritional factors
- Fluid/electrolyte imbalance
- Foreign bodies (splinter, glass)
Phases of repair in acute wound healing
- Haemostasis (formation of clot)
- Inflammation
- Proliferation
- Remodelling
Step 1: Haemostasis
Primary
- platelet activation
- platelet plug
Secondary
- coagulation cascade (add on to primary)
- fibrinogen –> fibrin
Mechanism of Haemostasis
Vessels injured –> blood spillage –> injured vessels constrict (slow/block) to limit blood loss
Primary haemostasis:
Platelet activation –> injured area –> platelet plug (NOT strong enough, just a temp mesh)
Seconday haemostasis:
Coagulation cascade adds on –> coagulation factor converts fibrinogen to fibrin (stronger mesh that adds on platelet plug) –> injured area sealed
*clot has alot of active ingredients that triggers inflammatory reaction
platelet activation + complement activation –> inflammatory response
Step 2: Inflammation Reponse
Tissue injury –> bradykinin released (stimulate pain)
Mast cells –> histamine, prostaglandins & leukotrienes released –> leading to 2 events
- Vascular events
- Vasodilation –> increase blood flow –> increase movement/delivery of active molecules (allow movements of histamine, prostaglandins) to injury site
- Increase capillary permeability –> endothelial cells having more gaps in between –> leaky –> swelling & redness (from increased diameter of vessels) - Cellular events
- leukocytes following chemotaxis
- leukocytes leave circulatory system –> injury site
- phagocytosis
Results of Immediate Vascular Event Post Injury
- Redness (increase vasodilation)
- Heat (increase vasodilation)
- Swelling (increase capillary permeability & protein leakage)
- Pain (bradykinin)
- Loss of function
Cellular Event
- Exudate of fluid from blood vessels
- Stasis (slowing/stopping of flow due to engorgement of RBC)
- Margination (WBC accumulate & adhere to vessel wall due to adhesion molecules)
- Diapedesis (oozing of WBC out of blood vessel)
- Chemotaxis (diretional migration of WBC to source of injury)
Order of WBC
- Neutrophils (last 24 hours)
2. Monocytes & Macrophages
Innate Immunity Cells
Non-specific & non-memory
- Neutrophils (WBC)
- Basophils (WBC)
- Eosinophils (WBC)
- Macrophages (Lymphocytes)
*WBC have granules to release active agents
Activity of Neutrophils
Phagocytosis of m/o
*High neutrophils = pyogenic (pus producing) bacterial infection
Activity of Basophils
Release histamine –> inflammatory response
*Histamine boost blood flow to area of injury
**High basophils = parasitic infection
Activity of Eosinophils
Increase allergic response
*High eosinophils = allergic reaction
Activity of Macrophages
Mature monocytes that migrate into tissues from blood (active in phagocytosis)
Adaptive Immunity Cells
Memory cells
- T lymphocytes
- B lymphocytes
*High lymphocytes = viral infection
Activity of T lymphocytes
Cell mediated immune response
Activity of B lymphocytes
Produce AB
Cell Differential Counts
Determine the number of cells for each types. Eg: high eosinophils will be reflected when allergic reactions are high
Goals of inflammation
Early non-specific response to tissue injury
- Degradation & removal of necrotic tissues (neutrophils and macrophages)
- Secretion of chemical mediators and growth factors by inflammatory cells & macrophages
- GF are essential for cell division during proliferative phase
Diagnostic test for inflammation
- Leukocytosis
- higher than normal value of WBC (esp neutrophils) - Differential count
- distinguish viral from bacterial infection - Plasma proteins
- increased fibrinogen and prothrombin - CRP
- not normally in blood but appears with acute inflammation - Increased ESR (RBC sedimentation rate)
- usually blood settle slowly at the bottom of test tube
- if quickly = inflammation - Cell enzymes
- indicative of site of inflammation
- 3,4 and 5 = serve as screening/monitoring parameters, unable to tell cause/site of inflammation
- 6 = may be useful in locating site of necrotic cells (eg: ALT - liver, CK-MB - heart). However some may not be specific (eg: AST elevated in both liver diease & acute MI)
Potential Complications of Inflammation
- Infection
- m/o more easily penetrate into oedematous tissues
- inflammatory exudate is an excellent medium for m/o growth - Skeletal Muscle Spasm
- protective response to pain - Deep ulcers
- Cell necrosis/lack of cell regeneration
- Lead to complications: perforation of viscera & scar tissue formation
*Inflamamtion by itself is good (meant for cleaning & planning for wound healing –> remodelling phase) BUT when out of control = complications
Local Effects of Inflammation
- Redness
- Heat
- Swelling
- Pain
Systemic Effects of Inflammation
- Low grade fever
- Malaise (unwell)
- Fatigue
- Headache
- Anorexia (LOA)
Acute Inflammation
Sudden onset + short duration
Characteristics
- exudation of fluids & plasma protein (edema)
- migration of WBC (esp neutrophils)
Chronic Inflammation
Follows acute episode of inflammation with continued tissue destruction
Characteristics
- less swelling & exudate
- more lymphocytes, macrophages and fibroblasts
- severe tissue destruction
- more collagen and fibrous scar tissue
Causes of Chronic Inflammation
- Persistent infection
- Persistent indigestible material
- endogenous (internal)
- exogenous (external) - Immune mediated reactions
- autoimmune reactions
- organ transplant rejection
- hypersensitivity reactions - Repeated episodes of acute inflammation
Acute Management of Inflammation
RICE
- Rest
- Ice
- Compression
- Elevate
Drugs Used to Treat Inflammation
- ASA (eg: aspirin)
- Acetaminophen (eg: paracetamol)
- NSAID (non-steroidal anti-inflammatory)
- COX-2 (part of NSAID)
- Glucocorticoid (steroid)
Anti-inflammatory: all except acetaminophen
Analgesia (pain): all except glucocorticoids
Antipyretic (temperature): all except glucocorticoids & COX-2
