week 5

• Etiology


  Causes of disease
• Pathogenesis


  Development and progression of disease
• Outcome of disease

  Survival, death
• Causes of disease

  • Endogenous (genetic defect, endocrine disorders)
  • Exogenous (microorganisms, chemicals, physical trauma)
  • Multifactorial (>1 etiological agent, e.g. diabetes)
  • Idiopathic (unknown cause, e.g. hypertension)
  • Iatrogenic (caused by treatment, e.g. cancers with cytotoxic drugs)
• Pathogenesis

  How etiological agents produce clinical and pathological changes, e.g. inflammatory reactions, carcinogenesis
• Natural history of disease

  Typical patterns of how a disease progresses, its effects (morbidity) and duration
• Progression of infectious disease

  1. Colonisation

  2. Crossing mucosal barrier

  3. Local invasion

  4. Invasion of bloodstream
• Examples of infectious disease progression

  • Sinusitis
  • Non-bacterial pneumonia
  • Meningitis
  • Sepsis
  • Bacterial pneumonia
• Subclinical stage of disease

  No sign or symptom is apparent but disease is established (laboratory test)
• Causes of disease manifestations

  • Decreased intake of food or catabolic state stimulated by release of factors from tumour
  • Release of neuropeptides following irritation of respiratory mucosa
  • Stimulation of nerve endings by trauma, chemicals or heat
  • Increase in number or size of cells or accumulation of tissue fluid
  • Actions of interleukin-1 and prostaglandins stimulate thermoregulatory centre in the brain
• Symptoms of disease

  • Pain
  • Swelling
  • Fever
  • Weight loss
  • Cough
• Prognosis

  Varies considerably for different diseases, influenced by treatments and patient
• Disease classification

  • Infectious (viruses, bacteria, fungi, protozoa, helminths)
  • Immunological (autoimmune thyroiditis, SCID)
  • Endocrine (under or overproduction of hormones, hormone resistance)
  • Homeostatic (disrupted secretion of hormones, e.g. vasopressin)
  • Genetic (defective gene, congenital disease)
  • Neoplastic (uncontrolled, abnormal cell growth)
  • Degenerative (progressive loss of tissue, aging)
  • Psychogenic (originate in the mind, psychological, emotional)
• Ancient Egypt had diseases like tuberculosis, trachoma, dental caries, cancer
• Plague (bubonic) was caused by Yersinia pestis and was a pandemic known as the black death
• HIV is the human immunodeficiency virus
• Influenza virus mutates
• Virulence factors

  Allow pathogenic microorganisms to infect specific body systems
• A small number of organisms can cause systemic disease
• Modes of transmission of infectious diseases

  • Direct contact between hosts or aerosols (cough/sneeze)
  • Food or water
• Long-term survival of pathogenic microorganisms is dependent on ability to maintain infectivity during transmission
• Zoonoses

  Diseases affecting animals and humans
• Types of infectious diseases

  • Skin infections (papillomaviruses, bacteria, fungi)
  • Ear, eyes and CNS infections (conjunctiva, protective tears, mumps, meningitis)
  • Respiratory system infections (inhaled microorganisms, influenza virus, Bordetella pertussis, Mycobacterium tuberculosis, pneumonia)
  • Gastrointestinal tract infections (actinomycosis, rotaviruses/adenovirus in ileum)
  • Urogenital tract infections (diabetes, kidney stones, catheters, cystitis, STDs)
  • Sepsis and systemic infections (progression from skin, GI or UTI to multi-organ failure)
• Infectious diseases are the most common cause of morbidity and mortality
• Immunodeficiency


  Failure of immune system, absence of immune system
• Factors contributing to immunodeficiency

  • Aging
  • Malnutrition
  • Immunosuppressive drugs
  • Physical trauma
• Autoimmune disorders


  Failure of immunological tolerance, 5-10% population affected
• Types of autoimmune disorders

  • Organ specific (type 1 diabetes, Graves disease, Addison's disease)
  • Systemic disease (Rheumatoid arthritis, multiple sclerosis)
• Allergic reactions


  Immune system overreacts or is hypersensitive to an antigen, IgE is produced by B cells and mast cells, mast cells secrete histamine, inflammation stimulated which could be fatal
• Endocrine system


  Consists of ductless glands producing hormones, regulates growth and development, stress responses, reproduction, homeostasis and energy metabolism
• Types of hormones


  • Amines (adrenaline, thyroid)
  • Peptides and proteins (insulin, growth hormone)
  • Steroids (cortisol, testosterone)
• Causes of endocrine disorders

  • Disruption - decreased (hypofunction) or increase (hyperfunction) hormonal activity; resistance to hormone action
  • Defects in synthesis (inherited deficiency)
  • Inappropriate stimuli to prevent or stimulate hormone release
  • Faulty inactivation or excretion of hormones in liver or renal disease
  • Excessive hormone secretion ectopically from non-endocrine source
  • Target tissue insensitivity (lack of receptors, dysfunctional receptors, defect in secondary messenger system)
• Growth hormone regulation


  GHRH (hypothalamus) -> Anterior pituitary -> GH -> Liver -> IGF-1, negative feedback
• Diabetes


  Characterised by hyperglycaemia, most common endocrine disorder, insulin dependent (type 1 - autoimmune) or insulin independent (type 2 - insulin resistance)
• A wide range of genetic diseases exist, from single gene disorders to multigenic diseases
• Single gene disorders


  • Congenital deafness (Connexin 26)
  • Tay-Sachs (hexosaminidase A)
  • Familial hypercholesterolemia (LDL receptor)
  • Sickle cell anemia (beta-globin)
  • Duchenne muscular dystrophy (dystrophin)
  • Cystic fibrosis (CFTR)
  • Hemochromatosis (HFE)
  • Huntington disease (Huntington)
• Multigenic traits and diseases

  Complex and poorly understood inheritance patterns, influenced by environmental factors
• Neural tube defects (spina bifida, anencephaly) are multigenic and complex, 5x more common in females than males, run in families
• Cancer


  The most common genetic disease, a multistage and multigenic disease
• 1 in two of the population will get cancer during their lifetime, incidence is increasing but mortality is decreasing