Pathology Overview Quiz

Pathology Definition

• Pathology is the study of the causes and effects of diseases on cells, tissues, and organs.
• It aims to understand how changes in structure and function contribute to disease symptoms.

Pathology Divisions

• General Pathology: Focuses on the basic cellular and tissue responses to stimuli like injury, inflammation, and repair.
• Systemic Pathology: Studies the specific responses of different organs to disease processes, such as heart attacks, brain infarctions, etc.

Etiology

• Diseases can have a single cause or multiple etiologic factors.

Pathogenesis

• The mechanisms by which the cause of the disease leads to the structural and functional changes in cells, tissues, and organs.

Morphology

• The gross and microscopic changes in cells and tissues caused by a disease.

Clinical Symptoms and Signs

• The features that lead a patient to seek medical advice.

Natural History

• The disease's origin, progression, outcome, and prognosis.

• Cell Injury*

• Cells can survive and function within a narrow range of physiological parameters.

• Adaptation: Cells attempt to achieve a new steady state and preserve viability under stress.

• Reversible Injury: Injury can be reversed if the stimulus is removed and the limits are not exceeded.

• Irreversible Injury: Leads to cell death, either through necrosis or apoptosis.

Homeostasis and Environment

• Cells maintain a balance within their environment to sustain life.
• When stress exceeds adaptation capacity, cell injury occurs.

Causes of Cell Injury

• Hypoxia (Oxygen Deprivation): Interferes with aerobic respiration, commonly caused by ischemia.
• Ischemia: Loss of blood supply due to impaired blood flow or drainage.
• Chemicals: Both known toxic agents and normal substrates in abnormal concentrations can cause injury.
• Infectious Agents: Bacteria and viruses.
• Immunological Reactions: Hypersensitivity reactions and autoimmune disorders.
• Genetic Defects: Examples like Down syndrome.
• Nutritional Imbalances: Over or under nutrition, including vitamins and minerals.
• Physical Agents: Trauma, heat, electricity, and radiation.
• Aging: Cellular senescence impairs cell repair and replication.

Cellular Adaptation

• Enables cells to maintain function in the face of stress.
• Can be physiological (e.g., breast and uterine enlargement during pregnancy) or pathological (e.g., endometrial hyperplasia caused by tumor hormones).

Types of Adaptive Responses

• Atrophy: Decrease in cell size due to loss of cell substances, leading to diminished function.
• Hypertrophy: Enlargement of individual cells.
• Hyperplasia: Increase in cell number.
• Metaplasia: Transformation of one cell type into another.

Atrophy

• Occurs when cells lose substances and shrink in size.
• The cells remain alive, and the process is reversible.
• Can involve individual cells or whole organs.

Causes of Atrophy

• Physiological:
  • Thymic involution (shrinkage of the thymus with age).
  • Normal aging.
• Pathological:
  • Decreased workload (disuse).
  • Loss of innervation (denervation).
  • Reduced blood supply (ischemia).
  • Inadequate nutrition.
  • Loss of hormonal stimuli.

Mechanisms of Atrophy

• Imbalance between protein synthesis and degradation, with degradation playing a dominant role.
• Autophagy: Lysosomes break down cellular components.
• Ubiquitin-proteasome Pathway: Degrades cytoplasmic and nuclear proteins.
• Cell number can also be reduced by apoptosis.

General Biochemical Mechanisms of Cell Injury

• Mitochondrial Damage and ATP Depletion: Damage to mitochondria disrupts ATP production, leading to loss of cell function.
• Oxygen Changes: Hypoxia/ischemia impairs oxidative respiration, while free radical formation damages cells through oxidative stress.

Hypoxic/Ischemic Injury

• Reduced oxygen supply disrupts cellular function.
• Leads to:
  • Decreased ATP production.
  • Impaired Na/K pump function, causing cell swelling.
  • Increased anaerobic glycolysis, leading to lactate accumulation and decreased pH.
  • Detachment of ribosomes, impairing protein synthesis.
• Reversible if the stimulus is removed, but becomes irreversible if the stress continues.

Ischemia/Reperfusion Injury

• Paradoxical increase in cell death after blood flow is restored.
• Attributed to:
  • Calcium influx into injured cells.
  • Inflammation.
  • Free radical production from damaged mitochondria.

Apoptosis

• Programmed cell death, often referred to as "cellular suicide."
• Can be physiological or pathological.

Physiological Apoptosis

• During embryogenesis: Cell death is a normal part of development.
• Hormone-dependent involution: E.g., shedding of the endometrium during menstruation.
• Cell deletion in proliferating tissues: E.g., cells in the gastrointestinal tract.
• Immune cell death: Destruction of autoreactive T-lymphocytes, elimination of virally infected cells.

Pathological Apoptosis

• Mild injurious stimuli: E.g., heat, radiation, toxic chemicals.
• Elimination of neoplastic cells in tumors.
• Neuron death in diseases: E.g., Alzheimer's disease.

Mechanisms of Apoptosis

• Mediated by caspases and mitochondrial proteins like the BCL-2 family.

Caspases

• Cysteine proteases that play a key role in apoptosis.
• Exist in an inactive form in the cytoplasm.
• Classified as initiators or effectors.

Initiator Caspases

• Found in specific cell types and commit cells to apoptosis when activated.

Effector Caspases

• Present in all cell types.
• Break down cellular components and contribute to the characteristic morphology of apoptosis.

Mitochondrial Proteins: BCL-2 Family

• Regulate mitochondrial membrane permeability, influencing apoptosis.
• Some promote apoptosis (e.g., Bax, Bad), while others inhibit it (e.g., BCL-2, BCL-XL).

BCL-2

• Protects against apoptosis by stabilizing the mitochondrial membrane, preventing the release of cytochrome-C, and inhibiting Apaf activation.

Mitochondrial Damage and Apoptosis

• Stimuli like toxins, radiation, and anoxia can open the permeability transition pore complex (PTPC) in mitochondria.
• This releases cytochrome-C into the cytosol, activating the effector caspases and initiating apoptosis.

Test your knowledge on the fundamental concepts in pathology, including general and systemic pathology. Explore topics such as etiology, pathogenesis, and clinical symptoms. This quiz provides a comprehensive overview of how diseases affect cells, tissues, and organs.