Pathology

• Pathology


  The study of disease
• What will be covered?

  • Mechanisms of Disease
  • Inflammation
  • Neoplasia
  • Cell Injury, Aging and Death
  • Thrombosis and Embolism
• Mechanisms of Disease


  What is behind the symptoms - use this like a sieve if you can't quite work out what is going on
• Mechanisms of Disease


  • Vascular
  • Infection/Inflammation
  • Neoplasia
  • Drug/toxins
  • Iatrogenic
  • Congenital
  • Autoimmune
  • Trauma
  • Endocrine/metabolic
• Acute Inflammation


  Response to any insult i.e. infection, injury, foreign body, immune reaction
• Acute Inflammation


  1. Vasodilation of arterioles and capillary beds mediated by histamine and Nitric Oxide

  2. Endothelial contraction = leaking of fluid into interstitial space causing swelling

  3. Pro inflammatory mediators = increased expression of ICAM and Selectin on endothelial cells which bind glycoproteins and Integrins respectively on white blood cell surface

  4. WBC then stops and flattens against the vessel wall = PAVEMENTING

  5. WBC can then extend pseudopods through gaps in endothelial wall and move out of the vessel = MIGRATION / DIAPEDESIS
• Chemotaxis


  White blood cells following a concentration gradient towards the site of injury established by chemokines
• Neutrophils


  • Multi lobed nucleus = polymorph
  • Granules in the cytoplasm = granulocyte
• Neutrophil phagocytosis


  1. Recognition and attachment

  2. Engulfment

  3. Killing and degradation
• Outcomes of Inflammation


  • Resolution
  • Suppuration
  • Organisation
  • Fibrosis and Scarring
  • Chronic Inflammation
• Resolution


  Restoration to normal function
• Suppuration


  Formation of pus - a collection of fluid containing mix of inflammatory cells, bacteria or inflammatory products
• Organisation


  Occurs if there is poor blood supply, extensive cell death and necrosis, a lot of fibrin has been produced, and tissue type has limited regenerative capacity
• Granulation tissue

  Formation of capillaries and delivery of myofibroblasts to lay down collagen and smooth muscle and build scaffold for healing
• Fibrosis and Scarring

  Loss of function, classic example is heart following MI
• Chronic Inflammation


  Predominant cell is the lymphocyte, also involves macrophages
• Granulomas


  Aggregate of epithelioid histiocytes or organised collection of macrophages, formed when immune system cannot eliminate perceived foreign material
• Caseous necrosis


  Cheesy necrosis, classically found in TB
• Types of Necrosis

  • Coagulative
  • Liquefactive
  • Caseous
• Necrosis

  Always pathological and requires no energy
• Apoptosis

  Programmed cell death in response to a signal and requires energy, can be physiological or pathological

  
• Extrinsic pathway of apoptosis

  Cell membrane receptors with Death domain, i.e. Fas or TNF bind and activate caspases

  
• Intrinsic pathway of apoptosis

  Loss of growth signals = replacement of anti-apoptotic molecules on mitochondrial surface with Bak and Bax, increase permeability of the mitochondria, releases proteins that stimulate caspases

  
• Hyperplasia

  Increase in cell number, always in response to a stimulus and will regress on withdrawal of that stimulus
• Hypertrophy


  Increase in size of cell, can be alongside hyperplasia or isolated in non dividing tissue
• Atrophy


  Reduction in cell size, causes include loss of blood supply, loss of innervation, lack of use, degenerative conditions
• Neoplasia

  A new growth, can be benign or malignant/cancerous

  
• Tumour


  A growth or swelling, a descriptive not diagnostic term
• Malignant


  Cancer, invasive and has spread past the basement membrane with the possibility of becoming metastatic
• Metastases


  The spread of a cancer to a site distant from its origin
• Precursor lesions to cancer

  • Metaplasia
  • Dysplasia
  • Carcinoma in Situ
  • Hyperplasia

  
• Metaplasia


  Reversible change from one mature cell type to another mature cell type, high risk of cancer development
• Dysplasia


  Disordered cell growth, cells are abnormal and are not changing in response to a stimulus, no invasion past basement membrane
• Carcinoma in Situ

  Dysplasia affecting the whole basement membrane, last stage before becoming invasive
• Differences between Benign and Malignant Tumours

  • Symmetrical vs Poorly defined and irregular
  • Encapsulated vs Heterogeneous - areas of haemorrhage and necrosis
  • Homogeneous - all of the tumour looks the same vs Pleomorphism
  • Well differentiated vs High nucleus: cytoplasm ratio
  • Hyperchromasia
  • Mitotic figures
  • Poorly differentiated - will not resemble the cell type expected for that organ/tissue
• Tumour Naming

  Usually by cell of origin, e.g. Squamous epithelium: Benign = papilloma, Malignant = carcinoma; Glandular epithelium: Benign = adenoma, Malignant = adenocarcinoma; Mesenchymal/Connective Tissue: Benign = ______oma, Malignant = _____sarcoma
• Grading of Malignancies


  How differentiated is the tumour? Low grade = better differentiated, High grade = poorly differentiated
• Staging of Malignancies


  How far has the tumour spread? Done via the TNM staging system - Tumour, Nodes, Metastases
• Hallmarks of Cancer


  Usually follows 2 hit hypothesis - a genetic susceptibility then exploited by environmental factors and further genetic damage
• Risk Factors for Cancer


  • Chemical exposure
  • Radiation
  • Viral infection
  • Chronic inflammation