Mechanisms of Disease: Aetiology and Injury

• Mechanisms of diseases are being discussed

Terminology Revision

• Aetiology is the cause of a disease.
• Pathogenesis refers to how a disease or lesion develops.
• Morphological changes are the structural changes resulting from a disease.
• A lesion is any alteration from normal that is detectable grossly or histologically.

Aetiology

• Infectious causes of disease include bacteria, viruses, parasites, and fungi.
• Non-infectious causes of disease include genetic, metabolic, physical, nutritional, and toxic factors.
• Damage to cells, tissues, and organs leads to reactions and consequences.

Stressors of Injury

• Stressors of injury listed, include:
  • Increased metabolites
  • Decreased nutrients/O2
  • Decreased blood flow
  • Free radical injury
  • Telomeric shortening
  • Age
  • Ischaemic
  • Hypoxia
  • Genetic factors
  • Physical trauma
  • Temperature
  • Irradiation
  • Natural compounds
  • Drugs
  • Nutritional factors
  • Biological factors
  • Chemical factors
  • Immunological factors
  • Auto-immune factors
  • Allergies
  • Viruses, bacteria, fungi, prions, and parasites.
• Reactions and consequences follow from stressors.

Processes/Mechanisms of Disease

• Adaptive Tissue Responses
• Vascular Disturbances
• Cell Degeneration (necrosis)
• Inflammation
• Healing and Repair
• Neoplasia
• Teratology

Adaptive Tissue Responses

• Adaptive Tissue Responses shows the normal cell, the injured cell, the irreversibly injured cell, and the dead cell in a continuum of function and structure with minimal structural change.
• Stresses on cells often cause modification without cell death.
• Stressors can be pathological or physiological.
• The ability of cells and tissues to adapt varies depending on vulnerability to certain agents, degree of differentiation, metabolic requirements, nutrition, and previous state of the cell.
• Adaptive changes only occur in mature cells and tissues after growth has occurred.
• Adaptive changes include Atrophy, Hypertrophy, Hyperplasia and Metaplasia
• Reversible Changes include: Atrophy, Hypertrophy, Hyperplasia, Metaplasia
• Irreversible Changes include: Dysplasia, Neoplasia, Death, Decreased Function
• Pathological Stressors are exogenous or endogenous
• Physiological Stressors are physical, hormonal

Atrophy

• Atrophy involves a reduction in the size of the organ, tissue, or cell.
• Atrophy is due to a decrease in the size or number of its specialized cells or organelles.
• Atrophy results from physiological or pathological stimuli.
• Atrophy mechanisms include an increase in apoptosis, and remaining cells surviving at a smaller size with fewer mitochondria, myofilaments and ER.
• Atrophy is associated with catabolism exceeding anabolism.
• Causes of Atrophy: Examples include:
  • Inadequate nutrition
  • Decreased blood supply
  • Loss of innervation
  • Decreased workload or disuse
  • Prolonged pressure
  • Decreased aberrant hormonal stimulation
  • Physiological factors such as regression of the thymus
  • Aging

Hypertrophy

• Hypertrophy increases the size of an organ or tissue, usually due to an increase in the size of its specialized cells.
• Hypertrophy occurs in cells with increased workload but that cannot divide, e.g. muscle.
• Hypertrophy involves a limited general increase in the number of organelles, increasing the cell's size.
• Compensatory hypertrophy examples include removal of one kidney, or increased workload in muscle.
• Hormonal hypertrophy is exemplified by pregnancy, which causes uterine hypertrophy.
• Mechanisms:
  • Physical triggers lead to this.
  • Trophic triggers such as growth factors, hormones, and cytokines, may be produced endogenously or exogenously to cause increased gene expression
  • Cause is uncertain in Ideopathic hypertrophy.

Hyperplasia

• Hyperplasia results in an increase in the size of an organ or tissue due to an increase in the number of its specialized cells
• Aetiology may be due to physiological or pathological causes
• Physiological Hyperplasia are:
  • Compensatory or reactive, like haematopoietic system after blood loss, or mesenteric lymph nodes.
  • Hormonal, such as cyclical changes in the mammary gland or endometrium
• Pathological Hyperplasia are:
• Hormonal excess, like excess Erythropoietin causing Polycythemia, excess Estrogen causing Dysmenorrhea, and nutritional and renal secondary parathyroid gland hyperplasia.
• It is reparatory to restore architecture or function.
• Infectious organisms may be the cause.

Metaplasia

• In metaplasia, one type of specialized, fully differentiated adult cell changes to another adult cell type, often less specialized.
• Metaplasia is often a protective response, but some functions are lost.
• Metaplasia requires reprogramming of stem cells involving altered cytokines, growth factors (TGF-β), and extracellular matrix components.
• Metaplasia is a reversible change in cell structure or type following a specific signal or loss of one normally present.
• Vitamin A deficiency can cause reversible squamous metaplasia of respiratory epithelium.

Summary

• Both infectious & non-infectious agents can cause cell and tissue injury.
• The nature of the injury determines the consequences and how the body reacts to the insult
• Adaptive Tissue Reactions include: Atrophy, Hypertrophy, Hyperplasia, Metaplasia

Pathological jargon

• Jargon listed: aplasia, hypoplasia, hyperplasia, metaplasia, dysplasia, neoplasia
• Adaptive changes are not the same as, Developmental Anomalies
• Conditions such as AGENESIS, APLASIA, ATRESIA and HYPOPLASIA occur during the original development & maturation of tissues, these will be considered under Teratology.