HISTOPATH Lec Mod 1

• In single-celled organisms, substances can easily enter the cell due to a short distance
• In multicellular organisms, the distance for substances to enter the cell is larger because of a higher surface area to volume ratio
• Multicellular organisms require specialised exchange surfaces for efficient gas exchange of carbon dioxide and oxygen due to their higher surface area to volume ratio
• Pathology is the study of disease, focusing on the structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease
• The purpose of pathology includes explaining the signs and symptoms manifested by patients and providing a rational basis for clinical care and therapy
• Pathology serves as a bridge between the basic sciences and clinical medicine, forming the scientific foundation for all of medicine
• General Pathology is concerned with common reactions of cells and tissue to injurious stimuli, not tissue-specific, such as inflammation caused by bacterial infection
• Systemic Pathology examines alterations and underlying mechanisms in organ-specific diseases, like ischemic heart disease
• The core aspects of pathology include Etiology (cause), Pathogenesis (sequence of events following exposure to injurious agents), Morphologic changes (structural alterations), and Clinical Manifestations (functional consequences of the disease)
• Disease, Disorder, Syndrome:

  • Disease: a pathophysiological response to internal and external factors, leading to abnormalities in systemic functions
  • Disorder: a disruption of normal functions in the body or a part of the body
  • Syndrome: a disease or disorder with more than one identifying feature or symptom
• Diagnosis, Prognosis:

  • Diagnosis: determination of the nature of a disease
  • Prognosis: probable outcome of a disease in a living individual
• Acute, Chronic:

  • Acute: sudden onset or rapid course, short clinical course, usually respond to therapy
  • Chronic: slow onset or long duration, examples include asthma, COPD, and diabetes mellitus
• Idiopathic, Iatrogenic, Nosocomial, Community acquired:

  • Idiopathic: a disease with no identifiable cause
  • Iatrogenic: pathology caused by a physician and their treatment
  • Nosocomial: hospital-acquired infection
  • Community-acquired infection: infection acquired outside a healthcare facility
• Non-communicable, Communicable, Infectious, Contagious:

  • Non-communicable diseases (NCD): not transmitted through contact with an infected person, caused by genetic, physiological, environmental, and behavioral factors
  • Communicable diseases: spread from one organism to another, including infectious diseases that affect someone with pathogenic microorganisms
• In multicellular organisms, the distance for substances to enter cells is larger due to a higher surface area to volume ratio
• Multicellular organisms require specialised exchange surfaces for efficient gas exchange of carbon dioxide and oxygen
• Metaplasia is the transformation of one cell type into another cell type
• Different types of metaplasia include:

  • Osseous metaplasia: formation of new bone at sites of tissue injury
  • Cartilaginous metaplasia
  • Myeloid metaplasia (extramedullary hematopoiesis): proliferation of hematopoietic tissue at sites other than the bone marrow
• Metaplasia does not result from a change in the phenotype of an already differentiated cell type; instead, it is the result of a reprogramming of stem cells or undifferentiated mesenchymal cells
• Cell injury occurs when:

  • Cells are exposed to injurious agents or stress beyond their adaptive responses
  • Essential nutrients are deprived
  • Mutations affect essential cellular constituents
• Cell injury is reversible up to a point, but if the injurious stimulus is persistent or severe, irreversible injury and cell death may occur
• Cell death can occur through two pathways:

  • Necrosis
  • Apoptosis
  • Nutrient deprivation can trigger autophagy, leading to cell death
• Causes of cell injury include:

  1. Hypoxic cell injury

  • Oxygen deprivation reduces aerobic oxidative respiration
  • Causes include reduced blood flow, inadequate oxygenation, and decreased oxygen-carrying capacity
  • Cells may adapt, undergo injury, or die
  • Early stage effects include mitochondrial dysfunction and decreased ATP synthesis
  • Late stage effects include membrane damage and irreversible injury

  2. Free radical injury

  • Free radicals have unpaired electrons and can be generated by various mechanisms
  • Mechanisms that degrade free radicals include intracellular enzymes and antioxidants

  3. Chemical cell injury

  • Chemical agents and drugs can cause cell injury
  • Examples include salt in hypertonic concentrations and toxic oxygen levels
• Other causes of cell injury:

  • Infectious agents
  • Immune system reactions
  • Genetic abnormalities
• Morphological alterations in cell injury are at the ultrastructural level, visible only on electron microscopy, not on light microscopy
• Changes in cell injury may also be seen through histochemistry, which determines chemical changes in the cell using stains, indicators, and microscopy
• By the time changes are observed using ultrastructural and histochemical techniques, irreversible cell injury may have already occurred
• Reversible cell injury:

  • All stresses and noxious influences affect the molecular and biochemical level first
  • Time lag between stress and morphologic changes of cell injury
  • Reversible cell injury is due to decreased ATP generation, loss of cell membrane integrity, defects in protein synthesis, cytoskeletal damage, and DNA damage
• Morphology of reversible cell injury (Ultrastructural):

  • Plasma membrane: Generalized swelling of the cell and its organelles, blebbing, blunting, and loss of microvilli
  • ER: Dilation with detachment of polyribosomes, intracytoplasmic myelin figures
  • Mitochondrial changes: Swelling and appearance of amorphous densities
  • Clumping of nuclear chromatin
• Morphology of reversible injury under the light microscope:

  • Cellular swelling due to failure to maintain ionic and fluid homeostasis
  • Manifests with pallor, increased turgor, weight, small clear vacuoles in the cytoplasm, increased eosinophilic staining
  • Fatty change: Appearance of lipid vacuoles in the cytoplasm, seen in cells involved in fat metabolism like hepatocytes and myocardial cells
• Cell death:

  • Tissue death has two contrasting morphologic patterns: necrosis and apoptosis
  • Necrosis is the result of degradative and inflammatory reactions after tissue death caused by injury
• Patterns of necrosis:

  1. Coagulative necrosis: Results from a sudden cutoff of blood supply, characterized by preservation of tissue architecture, increased cytoplasmic eosinophilia, nuclear changes like pyknosis, karyorrhexis, karyolysis, and ultimately removal by heterolysis

  2. Liquefactive necrosis: Characteristic digestion, softening, and liquefaction of tissue, seen in CNS ischemic injury and suppurative infections

  3. Caseous necrosis: Part of granulomatous inflammation, has cheese-like consistency, amorphous eosinophilic appearance, often caused by tuberculosis

  4. Gangrenous necrosis: Affects lower extremities or bowel, secondary to vascular occlusion, can be wet or dry gangrene, gas gangrene if caused by Clostridium perfringens

  5. Fibrinoid necrosis: Associated with immune-mediated vascular damage, deposition of fibrin-like material in arterial walls
• 6. Fat necrosis: Traumatic or enzymatic, seen in severe tissue injury with high fat content or as a complication of acute hemorrhagic pancreatitis
• In multicellular organisms, the total number of cells is regulated by controlling the rate of cell division and cell death
• When cells are no longer needed or become a threat to the organism, they undergo a programmed cell death called apoptosis
• Cells that die by necrosis swell and burst due to loss of cell membrane integrity, causing inflammation and injury to neighboring cells
• Apoptosis is an orderly cell death process that causes the cell to shrink, condense, disassemble its cytoskeleton, and alter its cell surface for phagocytic cells to attach and digest it rapidly
• Physiological Apoptosis:

  • Destruction of cells during embryogenesis, organogenesis, and developmental involution
  • Involution of hormone-dependent tissues upon hormone withdrawal
  • Cell loss in proliferating cell populations to maintain a constant number
  • Elimination of potentially harmful self-reactive lymphocytes
  • Death of host cells that have served their useful purpose
• Pathological Apoptosis:

  • Eliminates cells that are injured beyond repair without eliciting a host reaction
  • Caused by DNA damage, radiation, cytotoxic drugs, hypoxia, accumulation of misfolded proteins, certain infections, and pathologic atrophy
• Morphology of Apoptosis:

  • Cell shrinkage, chromatin condensation, formation of cytoplasmic blebs and apoptotic bodies, phagocytosis of apoptotic cells or cell bodies by macrophages