PR1153 IC1 to 7

• Cellular Adaptations


  Reversible changes in cell number or size in response to stimuli
• Types of Cellular Adaptation


  • Hyperplasia (↑ cell no.)
  • Hypertrophy (↑ cell size)
  • Hypoplasia (↓ cell no.)
  • Atrophy (↓ cell size)
  • Metaplasia (△ cell type)
• Skeletal Muscle


  • Hypertrophy
  • Stimulus: dedicated workout
• Skeletal Muscle


  • Atrophy
  • Stimulus: from disuse (reversible)
  • Stimulus: Poliomyelitis (irreversible, denervation)
• Uterine Enlargement in Pregnancy


  • Hypertrophy / Hyperplasia
  • Stimulus: Hormonal changes
• Heart - Left Ventricular


  • Hypertrophy
  • Stimulus: Hypertension
  • Clinical Consequence: Heart failure, cardiac arrest, ischemic stroke
• Benign Prostate


  • Hyperplasia
  • Stimulus: Androgen
  • Clinical Consequence: UTI (from urinary retention), Renal failure (from obstructive uropathy)
• Benign Endometrial


  • Hyperplasia
  • Stimulus: Oestrogen
  • Clinical Consequence: Abnormal menstrual bleeding, Higher risk of endometrial cancer
• Bone Marrow


  • Hypoplasia
  • Stimulus: Drugs/Chemicals, Ionising Radiation (Chemotherapy), Viruses
  • Clinical Consequence: Bone marrow failure (anemia, infection, bleeding)
• Metaplasia


  • Smoking: Bronchus Columnar epithelium → Stratified squamous epithelium
  • Barrett's oesophagus (from chronic acid reflux): Stratified squamous epithelium → Columnar epithelium
• Sources of free radicals


  • Normal redox reactions, cellular respiration
  • Ionising radiation (UV, X-rays) hydrolyse water into OH· and H·
  • Metabolism of exogenous chemicals (eg. CCl4)
• Protective molecules (antioxidant response)


  • Superoxide dismutase
  • Glutathione peroxidase
  • Vitamin E
  • Vitamin C
  • Catalase
• Sublethal Cell Damage


  Reversible cellular changes like swelling, intracellular accumulations
• Apoptosis


  Programmed cell death characterised by cell shrinkage, chromatin condensation, cytoplasmic blebs and phagocytosis by macrophages

  
• Physiological conditions for apoptosis


  • Fetal development
  • Involution of tissues with hormone withdrawal (eg. endometrial shedding in menstrual cycle or lactating breast regression)
  • Removal of self-reactive lymphocytes (at end of inflammatory response)
  • Removal of neutrophils (at end of inflammatory response)
• Pathological conditions for apoptosis


  • Cells with DNA mutations/damage
  • Cells with extensive improperly folded proteins
  • During infections (CD8+ T-cells induce apoptosis to eliminate infected cells)
  • Elimination of aberrant cells
  • Injurious process (eg. heat, radiation, cytotoxic drugs, hypoxia)
• Types of Necrosis


  • Coagulative (Infarction)
  • Liquefactive (Fungal/bacterial infections)
  • Caseous (TB infection)
  • Fat (Affects adipose tissue)
  • Fibrinoid (Follows damage to blood vessels)
  • Dystrophic Calcification (Deposition of calcium in damaged tissues)
• Changes during necrosis


  • Nuclear: Pyknosis (condensation of chromatin and shrinkage), Karyorrhexis (Fragmentation), Karyolysis (Complete dissolution)
  • Cytoplasmic: Eosinophilic (loss of cytoplasmic RNA, recognised by pink staining)
• Signs of Inflammation


  • Warmth (vasodilation)
  • Redness (vasodilation)
  • Swelling (oedema)
  • Pain (due to some mediators, stimulation of nerve endings)
  • Loss of Function (tissue damage, lack of use)
• Physiological Responses in Acute Inflammation


  • Vascular Response: Increased blood flow (vasodilation), Increased vascular permeability (loss of endothelial cell integrity, leakage of fluid/plasma proteins, results in oedema), Increased endothelial cell adhesiveness (adhesion molecules, chemokine production)
  • Leukocyte Recruitment: Adhesion to endothelial cells (Margination, Rolling, Arrest), Diapedesis (transmigration), Chemotaxis (migration to site of damage, directed by chemokines)
• Inflammatory Mediators


  • Histamine
  • Complement
  • Arachidonic Acid Metabolites (Prostaglandins, Thromboxanes, Leukotrienes, Lipoxins)
  • Chemokines (eg. IL-8)
  • Cytokines (TNF and IL-1)

  
• Acute Phase Proteins


  Plasma proteins from liver (eg. c-reactive protein (CRP)) released within hours of injury, triggered by IL-1, IL-6, TNF, act as indicators of disease severity
• Forms of Acute Inflammation


  • Suppurative or Purulent Inflammation
  • Serous Inflammation
  • Fibrinous Inflammation
  • Ulceration (usually in chronic inflammation)
• Causes of Chronic Inflammation


  • Persistent infection
  • Immune-mediated disease
  • Prolonged exposure to injurious agents (exogenous or endogenous)
  • Lowered host resistance
• Characteristics of Chronic inflammation


  Infiltration of mononuclear cells (macrophages, lymphocytes, plasma cells), Tissue destruction, Attempts at healing
• Granulomous Inflammation


  Chronic inflammatory response characterised by aggregation of macrophages
• Steps of Tissue Renewal


  • Scavenging (removal of debris by macrophages)
  • Regeneration (replacement by cells of same type)
  • Repair (scar formation, use of connective tissue to "fill the hole")

  
• Growth of Granulation Tissue


  Grows from the edge (healthy area) into the damaged area, involves macrophage secretion of angiogenic and fibrogenic factors, angiogenesis, fibroblast migration and proliferation, collagen synthesis
• Scar Maturation and Remodeling


  Increasing amounts of cross-linked collagen, reabsorption of capillaries, deactivation and decrease in fibroblasts, scar tissue is not as strong as normal skin

  
• Factors influencing wound healing


  • Growth Factors (PDGF, TGFβ)
  • Cytokines (TNF-α, IL-6)
  • Extracellular Matrix (Agrin)
  • Cell adhesion molecules
  • Age
  • Nutrition
  • Metabolic status
  • Circulatory status
  • Hormones
  • Infection
  • Mechanical Factors
  • Foreign Bodies
  • Size, location, type of wound
• Complications of wound healing


  • Deficient scar formation (wound dehiscence, ulceration, incisional hernias)
  • Formation of contractures
  • Excessive scar formation (hypertrophic scar, keloids, excessive granulation tissue)

  
• Hyperaemia


  Arterial vasodilation resulting in more blood in blood vessels, can be physiological or pathological
• Congestion


  Venous outflow obstruction resulting in more blood in blood vessels, causes enlarged, cyanotic, firm & heavy organs
• Primary Causes of Oedema


  • Increased hydrostatic pressure
  • Decreased oncotic pressure
  • Increased endothelial permeability
  • Lymphatic obstruction
  • Sodium and water retention by kidney
• Types of Oedema


  • Localised oedema (impaired venous drainage, increased vascular permeability & hyperaemia, obstruction / destruction of lymphatics)
  • Generalised oedema (cardiac oedema, renal oedema, hepatic oedema)
• Exudate


  Fluid that leaks out of blood vessels into nearby tissues, high protein content, due to inflammatory response
• Transudate


  Fluid that passes through membrane or squeezes through extracellular space or tissues, low protein content, not due to inflammatory response
• Causes of Haemorrhage


  • Trauma
  • Abnormal vessels
  • Abnormality in platelets (in number & quantity)
  • Coagulation factor deficiency
• Types of Haemorrhage


  • Petechiae, Purpura
  • Ecchymoses (big bruises)
  • Bleeding into joints
  • Intracranial haemorrhage
• Types of Shock


  • Hypovolemic shock
  • Cardiogenic shock
  • Septic shock
  • Distributive shock