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Flashcards in Basic Pathology Deck (14):

List four types of cellular adaptation.

  1. Hypertrophy
  2. Hyperplasia
  3. Atrophy
  4. Metaplasia


Discuss cellular hypertrophy.

  • Hypertrophy is the increase in size of individual cells in response to a stress -> increased size of the organ.
  • Hypertrophy can be either physiologic or pathologic
  • Usually occurs in response to an increase in the functional demand of the affected cells, eg increased requirement to perform work -> hypertrophy of muscle cells.
  • If hypertrophy continues, it can reach a point where the cell is no longer able to perform its function -> eg in cardiac failure.


Discuss cellular hyperplasia.

  • Hyperplasia is an increase in the number of cells in an organ in response to a stressor -> inc'd size of the organ
  • Can be physiologic or pathologic:
    • Physiologic:
      • Hormonal - eg breast tissue during puberty
      • Compensatory - eg liver regeneration post partial hepatectomy
    • Pathologic: occurs in response to abnormal hormonal stimulus eg benign prostatic hypertrophy in response to androgens
  • Can be the result of:
    • Growth factor-driven proliferation of mature cells, and/or
    • Increased output of new cells from tissue stem cells.
  • Hypertrophy is distinct from neoplasia in that if the stimulus is removed, the proliferation abates.


Discuss cellular atrophy.

  • Atrophy is the decrease in the size and number of cells -> dec'd size of the organ
  • Results from decreased protein synthesis and inc'd protein degradation within cells
  • Can be physiologic or pathologic
    • Physiologic: shrinking of the uterus post partum
    • Pathologic: Many types, eg:
      • Dec'd workload - skeletal muscle atrophy in response to immobilisation
      • Loss of innervation - damage to nerves -> atrophy of the muscles supplied by them
      • Diminished blood supply - slowly progressive reduction in blood supply (as in atherosclerosis) results in atrophy of cells, eg neurons -> senile dementia
      • Inadequate nutrition - eg cachexia
      • Loss of endocrine stim'n - eg atrophy of breast and vaginal tissue in menopause
  • Can be compensated for by a reduction in size and/or number of intracellular organelles eg mitochondria, therefore red'd function can precede cell death.


Discuss cellular metaplasia.

  • Metaplasia is a reversible change which involves the replacement of one cell type by another. Usually, the replacement cell is more resistant to the causative stress.
  • Most common form is the substitution of columnar cells by squamous cells eg, bronchial cilliated columnar cells replaced by squamous cells
  • Often, the metaplastic cells are not able to perform the same function and, in some cases, are more predisposed to malignant transformation.
  • It results from a reprogramming of the stem cells to produce cells which proliferate down an altered pathway.


Discuss cell injury and the common causes.

  • Cell injury can be either reversible or irreversible 
  • Cell injury can be caused by any of the following:
    • oxygen deprivation (anoxia)
    • physical agents
    • chemical agents
    • infections agents
    • immunologic reactions
    • genetic defects
    • nutritional imbalances 
  • Reversible cell injury is characterised by:
    • Cell swelling (due to malfunction of membrane pumps -> electrolyte imbalance -> H20 ingress)
    • Reduced oxidative phosphorylation -> dec'd ATP
    • Changes in individual organelles
  • Irreversible cell injury is characterised by:
    • Progression to cell death by apoptosis or necrosis
    • Apoptosis usually ensues in response to degradation of cellular DNA or proteins and is characterised by:
      • Cell shrinkage
      • Nuclear dissolution
      • Cell fragmentation w/out complete loss of membrane integrity
      • Rapid removal of cellular debris
    • Necrosis usually ensues in response to severe damage to the cell's membranes -> release of lysosomal enzymes -> leaking of cell contents


Discuss the changes associated with reversible cell injury.

  • Cellular swelling and vacuoles formation (Hyodropic changes)
  • Changes at this stage are better appreciated by the EM that may show blebbing of the plasma membrane, swelling of mitochondria and dilatation of ER
  • Fatty changes 


Compare and contrast apoptosis and necrosis.

  • Both are a means of cell death
  • The cell shrinks in apoptosis and swells in necrosis
  • In necrosis, the nucleus undergoes pyknosis (small and dense), karyolysis (faint or dissolved) or karryohexis (fragmented). In apoptosis, the nucleus fragments into small fragments
  • In apoptosis, the cellular membrane remains intact whereas in necrosis it becomes disrupted
  • During necrosis, the cell contents are digested and may leak out of the cell, whereas in apoptosis the contents remain intact and may be released in apoptotic bodies
  • Adjacent inflammation is common in necrosis but does not occur in apoptosis
  • Necrosis is invariably pathologic (as the result of irreversible cell injury) whereas apoptosis may be physiologic or the result of some forms of cell injury



Discuss the six general mechanisms of cell death.

The mechanisms of cell death include:

  • ATP depletion
  • Loss of calcium homeostasis and free cytosolic calcium 
  • Free radicals
  • Defective membrane permeability
  • Mitochondrial damage
  • Cytoskeletal damage 

NB: Although the causative stressor may vary, the mechanisms of cell death are common to all


Discuss the common patterns of tissue necrosis.

Coagulative necrosis: the outline of the dead cells are maintained and the tissue is somewhat firm. Example: myocardial infarction 

Liquifactive necrosis: the dead cells undergo disintegration and affected tissue is liquified. Example: cerebral infarction.

Caseous necrosis: a form of coagulative necrosis (cheese-like). Example: tuberculosis lesions.

Fat necrosis: enzymatic digestion of fat. Example: necrosis of fat by pancreatic enzymes.

Gangrenous necrosis: Necrosis (secondary to ischemia) usually with superimposed infection. Example: necrosis of distal limbs, usually foot and toes in diabetes. 

Fibrinoid necrosis: Usually involves the immune mediated death of blood vessels -> immune complexes combine with fibrin


What is apoptosis?

  • Apoptosis is programmed cell death. 
  • Cells undergoing apoptosis shrink and then break down into small fragments called apoptotic bodies which are easily phagocytosed.
  • The cell membrane remains intact and, thus, the cell contents do not leak out. This means that local inflammation does not occur.
  • It can occur physiologically, as in embryological development, or in response to a pathological process by which the cell is damaged and unable to adapt and is then triggered into apoptosis
  • The process consists of:
    1. Cell shrinkage
    2. Chromatin condensation
    3. Formation of cytoplasmic blebs and apoptotic bodies
    4. Phagocytosis by macrophages
  • Apoptosis can be initiated by:
    • an intrinsic pathway -> mediated by mitochondria, or
    • an extrinsic pathway ->  mediated by "death-receptors on the cell membrane

NB that both pathways result in a common "execution phase" which occurs by a cascade of capsase activation, followed by the removal of apoptotic bodies by macrophage phagocytosis.


What is autophagy?

Autophagy is the process by which cells devour their own contents during times of nutritional deficiency. The digested contents are recycled in order to maintain a level of function.


Discuss inflammation.

  • Inflammation is a crucial process that aims to eliminate a cause of cell injury eg microbe, toxin, foreign body etc.
  • Inflammation can be either acute (lasting hours to days) or chronic (lasting years)
  • Inflammation aims to increase blood flow to the affected area and, in doing so, deliver the following agents that can eliminate the harmful agent to the affected site:
    • leukocytes
    • plasma proteins
  • Inflammation normally abates rapidly once the causative agent has been eliminated
  • Inflammation also assits in the healing process which involves:
    • regeneration and/or
    • scarring
  • Inflammation can be harmful - lymphocytes and plasma proteins can damage normal cells


Describe the process of acute inflammation.

Acute inflammation consists of both vascular and leukocytic reactions:


  • Increase in blood flow and vessel calibre: 
    • Often a period of vasoconstriction (lasting just a few seconds) is the first change;
    • The arterioles then dilate -> inc'd flow -> erythema and heat (histamine and NO mediated)
    • Vascular permeability rapidly increases -> exudation of protein-rich fluid
    • Slower blood flow and inc'd blood viscosity -> stasis in small vessels. Stasis allows leukocytes to adhere to the vessel wall and migrate into the affected tissue
  • Increased vascular permeability:
    • ​Increased vascular permeability -> exudate -> oedema
    • ​Increased vascular permeability is due to:
      • Contraction of endothelial cells mediated by:
        • histamine
        • bradykinin
        • leukotrienes
        • Substance P
        • others
      • Usually an immediate response but can be delayed, as in sunburn
    • Endothelial injury -> necrosis and detachment. Can be due to the injurious agent or the action of leukocytes
    • Increased transport of fluids and proteins (transcytosis) across the endothelial wall
  • Lymph vessel proliferation and swelling -> lymphadenitis and lymphangitis


  • Marginalisation: leukocytes flow slowly along the endothelial wall
  • Rolling: Leukocytes adhere then release then adhere again as they move along the endothelial wall
  • Adherence: The leukocytes then bind strongly to the endothelial surface and remain stationary (mediated by cytokinessecreted by injured cells)
  • Migration through the endothelium: Leukocytes move through the wall by diapedesis toward the cytokine source
  • Chemotaxis: Chemoattractants (esp'lly cytokines, C5a and arachidonic acid metabolites) "attract" leukocytes  

NB: Neutrophils dominate the leukocytic reaction in the acute phase (6-24h) and then monocytes dominate after that (24-48h)

  • Recognition of offending agents/dead tissue: Leukocytes express several receptors that recognise foreign cells/material and deliver activating signals:
    • Toll-like receptors: Recognise microbial agents
    • Opsonin receptors: Recognise microbes that have been opsonised by antibodies, complement proteins or lectins
    • G-protein coupled receptors: Recognise bacterial cells and fragments of cell wall
    • Receptors for cytokines: Recogise cytokines that have been released and activate the leukocyte
  • Removal of offending agents: Once recognised and bound, the leukocytes must deal with the offending agents. They achieve this in by phagocytosis:
    • ​Phagocytosis consists of recognition, engulfment and degradation
    • Phagocytosis is greatly enhanced by opsonisation of the offending agent with:
      • IgG antibodies,
      • C3b complement, and/or
      • plasma lectins
    • ​Engulfment occurs by phagocytosis which encapsulates the agent within the leukocyte. The phagosome then binds to a lysosome containing lysosomal enzymes, forming a phagolysosome
    • The degradation, or killing, of the agent then occurs by either destruction by:
      • Lysosomal proteins, or
      • Reactive oxygen species.

​​​Additional effects of the acute inflammatory response:

  • Leukocytes, especially macrophages, release growth factors which stimulate fibroblasts and the synthesis of collagen which is important in the healing process.
  • Whilst much of the degradation of offending agents is carried out within the leukocyte, the process can result in collateral damage to normal host cells:
    • ROS and lysosomal proteins are released into the extracellular space and can damage neighbouring cells
    • The inflammatory response can be erroneously targeted at normal host cells -> autoimmune disease
    • The inflammatory response can be excessive, eg against relatively harmless agents such as dust in an asthmatic.

​Termination of the acute inflammatory response:

  • The response occurs only whilst the offending agent is present, once eliminated, the system quickly reverts to normal.
  • Neutrophils die quickly (after just a few hours) via apoptosis once they leave the blood