Cellular Injury: BSc Podiatry, Year 1

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Questions and Answers

In the context of cellular function, if a cell's ability to synthesize lipids and nucleic acids is compromised, which of the following compensatory mechanisms is most likely to be initiated in the short term to maintain cellular homeostasis?

  • Selective autophagy targeting non-essential organelles to recycle precursor molecules. (correct)
  • Enhanced endocytosis of extracellular macromolecules to supplement intracellular synthesis.
  • Increased reliance on anaerobic respiration to spare resources for synthesis.
  • Upregulation of chaperones to prevent misfolding of partially synthesized molecules.

A researcher is investigating the relationship between mitochondrial dynamics and cellular adaptation to hypoxia. Which of the following experimental findings would most strongly suggest that mitochondrial fission is a critical early adaptive response?

  • Cells with constitutively inhibited mitochondrial fission show increased ATP production during hypoxia.
  • Knockdown of proteins regulating mitochondrial fusion leads to increased cell survival under hypoxic conditions.
  • Activation of mitochondrial fusion results in improved calcium buffering capacity in the endoplasmic reticulum during hypoxia.
  • Inhibition of mitochondrial fission impairs the selective removal of damaged mitochondria via mitophagy during hypoxia. (correct)

A podiatric physician observes significant atrophy in the calf muscles of a patient who has been immobilized in a cast for six weeks following a tibial fracture. Which cellular adaptation mechanism is primarily responsible for the observed muscle atrophy in this scenario?

  • Enhanced recruitment of satellite cells to facilitate myofiber regeneration.
  • Hyperactivation of mTOR signaling, promoting excessive protein synthesis and hypertrophy.
  • Reduced expression of autophagy-related genes, impairing the removal of damaged organelles.
  • Increased ubiquitin-proteasome activity leading to enhanced protein degradation. (correct)

Consider a scenario where a podiatric surgeon performs a tenotomy (tendon release) to correct a severe contracture. Post-operatively, the surrounding muscle tissue undergoes hypertrophy. Which molecular signaling pathway is most directly responsible for mediating this compensatory hypertrophy in response to the altered mechanical load distribution?

<p>mTOR (mammalian target of rapamycin) activation. (B)</p> Signup and view all the answers

In the context of reversible cellular injury, cellular swelling is often an early morphological change. Which of the following membrane transport mechanisms is the first to fail, leading to this swelling during ATP depletion?

<p>The Na+/K+ ATPase pump maintaining the ion balance across the plasma membrane. (D)</p> Signup and view all the answers

During an ischemic event in the lower limb, a critical threshold of ATP depletion is reached, triggering a cascade of cellular injury events. Assuming a closed system with limited collateral circulation, which of the following consequences of ATP depletion would directly initiate the process of cellular necrosis?

<p>Dysregulation of intracellular calcium homeostasis resulting in activation of degradative enzymes. (C)</p> Signup and view all the answers

A researcher is studying the effects of specific DNA damaging agents on cells and observes a distinct pattern of cell death characterized by chromatin condensation, DNA fragmentation, and the formation of apoptotic bodies, without significant inflammation. Which downstream effector mechanism is most likely directly responsible for the observed DNA fragmentation in these cells?

<p>Activation of executioner caspases, leading to cleavage of specific intracellular substrates. (B)</p> Signup and view all the answers

A patient with chronic venous insufficiency develops lower extremity edema and subsequent tissue hypoxia. Which statement BEST describes the cellular response to this hypoxic stress, particularly focusing on the balance between adaptation and injury?

<p>Upregulation of HIF-1α induces angiogenesis and glycolysis, representing an adaptive response if perfusion is restored, but prolonged hypoxia leads to necrosis. (C)</p> Signup and view all the answers

A patient presents with signs of tissue necrosis in the foot following exposure to frostbite. Histological examination reveals shrunken cells with pyknotic nuclei and disruption of the plasma membrane, alongside significant inflammatory infiltrate. Which type of cell death is most consistent with these findings?

<p>Necrosis induced by direct cellular damage from ice crystal formation. (D)</p> Signup and view all the answers

A researcher is investigating the role of free radicals in the pathogenesis of diabetic foot ulcers. Which experiment would BEST demonstrate the involvement of reactive oxygen species (ROS) in impaired wound healing?

<p>Administering antioxidants to reduce local levels of oxidative stress and assessing wound closure rate. (B)</p> Signup and view all the answers

A patient with chronic peripheral artery disease (PAD) experiences critical limb ischemia. The affected tissues are characterized by a loss of membrane integrity, release of intracellular contents, and subsequent inflammation. Which intracellular mechanism is most directly responsible for the initiation of the inflammatory response in this scenario?

<p>Release of damage-associated molecular patterns (DAMPs) from necrotic cells. (B)</p> Signup and view all the answers

In a study of cellular adaptation, researchers expose cultured cells to a gradually increasing concentration of a toxin. Initially, the cells exhibit increased expression of specific detoxification enzymes. However, at a higher toxin concentration, the cells undergo apoptosis. What is the MOST likely mechanism explaining this change from adaptation to cell death?

<p>The adaptive mechanisms become overwhelmed, leading to mitochondrial dysfunction and caspase activation. (B)</p> Signup and view all the answers

A patient develops a chronic foot ulcer infected with Staphylococcus aureus. The bacteria release toxins that cause direct lysis of host cells and stimulate a strong inflammatory response. Which of the following BEST describes the combined mechanisms of cellular injury in this scenario?

<p>Direct cellular damage by bacterial toxins, along with immune-mediated injury from the inflammatory response. (D)</p> Signup and view all the answers

A researcher is investigating the pathogenesis of Amyotrophic Lateral Sclerosis (ALS) and its effects on muscle atrophy. What aspect of denervation atrophy is LEAST likely to contribute to muscle fiber degradation?

<p>Enhanced mitochondrial biogenesis to compensate for reduced energy efficiency. (C)</p> Signup and view all the answers

Prolonged exposure to ionizing radiation can result in cellular injury through a variety of mechanisms. Which of the following cellular processes is MOST sensitive to damage from ionizing radiation, particularly in tissues with high proliferative capacity?

<p>DNA replication and repair mechanisms, leading to mutations and cell death. (C)</p> Signup and view all the answers

A group of researchers is studying the progression of metaplasia to dysplasia in the respiratory epithelium of smokers. Which of these changes would provide the STRONGEST evidence that the metaplastic cells are undergoing dysplastic transformation?

<p>Loss of cellular polarity and disordered arrangement of cells within the epithelium. (A)</p> Signup and view all the answers

In a study examining the effects of hyperglycemia on endothelial cells in diabetic patients, researchers observe increased apoptosis via the intrinsic pathway. Which intracellular event is MOST likely to initiate this apoptotic cascade?

<p>Mitochondrial outer membrane permeabilization (MOMP) and release of cytochrome c. (D)</p> Signup and view all the answers

A patient with a long-standing infection develops sepsis. Hypotension ensues, leading to widespread tissue hypoxia. What is the most detrimental effect of systemic hypoperfusion?

<p>Dysregulation of intracellular calcium and subsequent enzymatic degradation of the cell. (A)</p> Signup and view all the answers

Following a traumatic injury resulting in significant tissue damage, a patient exhibits elevated levels of intracellular proteins normally sequestered within cells. Which of the following mechanisms is most directly responsible for the presence of these proteins in the extracellular space?

<p>Disruption of plasma membrane integrity leading to uncontrolled leakage of intracellular contents. (A)</p> Signup and view all the answers

A researcher aims to study the effects of a newly identified toxin on cellular metabolism and observes that even at low concentrations, cells undergo a shift towards glycolysis, regardless of oxygen availability. Which specific cellular component is most likely directly targeted by the toxin?

<p>The mitochondrial electron transport chain. (D)</p> Signup and view all the answers

Consider a cell undergoing apoptosis triggered by DNA damage. If a researcher introduces a mutation that inactivates caspase-9, what is the most likely outcome regarding the progression of apoptosis?

<p>Apoptosis will be blocked or significantly attenuated, preventing downstream caspase activation and DNA fragmentation. (C)</p> Signup and view all the answers

In the context of reversible metaplasia, which statement accurately captures the essential nature of this cellular adaptation, focusing on its potential impact on tissue function?

<p>Metaplasia involves a change from one fully differentiated cell type to another, providing better protection against a specific stress, though tissue function may be altered. (A)</p> Signup and view all the answers

A forensic pathologist discovers a high level of myeloperoxidase (MPO) in dead tissue. Select the most likely type of cell death pathway.

<p>Necrosis. (C)</p> Signup and view all the answers

A researcher is investigating the cellular mechanisms underlying the increased susceptibility of diabetic patients to infections. Which molecular alteration best explains heightened susceptibility?

<p>Impaired neutrophil chemotaxis and phagocytic activity. (C)</p> Signup and view all the answers

UV radiation leads directly to:

<p>Dangerous reactive oxygen species. (B)</p> Signup and view all the answers

A tissue sample shows a loss of size of cells within the given tissue. Select the most likely cellular process:

<p>Atrophy. (B)</p> Signup and view all the answers

A tissue sample shows an increase in the size of cells within the given tissue. Select the most likely cellular process:

<p>Hypertrophy. (A)</p> Signup and view all the answers

A tissue sample shows cells of one type being replaced by different cells. Select the most likely cellular process:

<p>Metaplasia. (D)</p> Signup and view all the answers

What cell death pathway leads most directly to activation of the inflammasome:

<p>Pyroptosis. (C)</p> Signup and view all the answers

A cell culture exhibits detachment from the extracellular matrix (ECM) leading to cell death. Which specific cell death process is in operation?

<p>Anoikis. (D)</p> Signup and view all the answers

Which statement accurately describes the difference between necrosis and apoptosis, specifically focusing on the involvement of the immune system?

<p>Necrosis is a form of cell death characterized by cell swelling, rupture, and inflammation, while apoptosis is a controlled process that does not trigger inflammation. (B)</p> Signup and view all the answers

Hypoxia prevents:

<p>Ability to carry out areobic oxidative respiration. (D)</p> Signup and view all the answers

A researcher is trying to determine if a population of cells is experiencing cellular injury. Which of the following indicates irreverisble cell injury?

<p>Irreversible membrane disruption. (D)</p> Signup and view all the answers

How do Clostridia damage tissue?

<p>Releasing phospholipase enzymes that disrupt cell membrane integrity. (D)</p> Signup and view all the answers

Which of the following is least commonly associated with cell death?

<p>Cellular Homeostasis. (C)</p> Signup and view all the answers

What best differentiates cellular metaplasia from dysplasia with regards to the reversibility of the condition?

<p>Dysplasia has no possibility for reversion, whereas metaplasia may be reversible. (B)</p> Signup and view all the answers

The process of histology is BEST described as:

<p>The study of tissues (E)</p> Signup and view all the answers

A tissue is removed and sent for histopathological assessment. Given this procedure, which is LEAST likely?

<p>There is no potential for metastasis. (D)</p> Signup and view all the answers

Tissue staining is MOST associated with:

<p>Histology. (D)</p> Signup and view all the answers

Within the context of cellular respiration, if a novel compound selectively inhibits the function of cytochrome c oxidase, yet ATP production is paradoxically maintained at near-normal levels, what compensatory allosteric mechanism is most likely upregulated to sustain cellular energy demands?

<p>Enhanced substrate-level phosphorylation during glycolysis and the citric acid cycle. (A)</p> Signup and view all the answers

If a cell is subjected to proteasome inhibition, which leads to an accumulation of misfolded proteins, what specific compensatory adaptation involving the unfolded protein response (UPR) would likely be activated that balances protein synthesis and degradation to maintain homeostasis?

<p>Selective upregulation of ER-associated degradation coupled with transient global protein synthesis inhibition. (C)</p> Signup and view all the answers

Following exposure to a sublethal dose of a novel alkylating agent that induces DNA adducts, a cell activates the nucleotide excision repair (NER) pathway. If this pathway is saturated, what specific downstream signaling cascade is most likely initiated to determine cell fate, balancing survival with the prevention of mutagenesis?

<p>Activation of ATR-Chk1 signaling to halt cell cycle progression and promote DNA repair, while simultaneously initiating pro-apoptotic signaling via p53 modulation. (C)</p> Signup and view all the answers

In a scenario involving chronic endoplasmic reticulum (ER) stress due to the accumulation of misfolded procollagen, which specific branch of the unfolded protein response (UPR) is most likely activated to restore ER homeostasis without inducing apoptosis?

<p>IRE1α-mediated splicing of XBP1 mRNA to enhance ER biogenesis and protein folding capacity. (A)</p> Signup and view all the answers

If a cell experiences a sudden increase in intracellular calcium concentration due to the activation of ionotropic receptors, which compensatory mechanism involving mitochondrial buffering would most efficiently sequester calcium and prevent excitotoxicity, influencing cell survival?

<p>Upregulation of the mitochondrial calcium uniporter (MCU) to facilitate rapid calcium uptake. (C)</p> Signup and view all the answers

Upon exposure to a specific growth factor, a quiescent fibroblast transitions into a proliferative state. If the cell's capacity for ribosome biogenesis is acutely limiting, which compensatory mechanism involving translational control would be initiated to prioritize the synthesis of cell cycle regulatory proteins?

<p>Internal ribosome entry site (IRES)-dependent translation of cell cycle regulatory proteins while suppressing cap-dependent translation. (B)</p> Signup and view all the answers

If a cell is subjected to a persistent hypoxic environment, leading to chronic activation of HIF-1α, what specific adaptation involving metabolic reprogramming would allow the cell to maintain ATP production while minimizing ROS generation?

<p>Increased expression of pyruvate dehydrogenase kinase (PDK) to inhibit mitochondrial entry of pyruvate and promote lactate fermentation. (B)</p> Signup and view all the answers

In response to chronic exposure to a non-genotoxic stressor, a population of cells undergoes adaptation. Which epigenetic modification is MOST likely to facilitate cellular adaptation?

<p>Site-specific histone methylation patterns that modulate gene expression related to the stress response. (A)</p> Signup and view all the answers

Following a localized ischemic event in skeletal muscle, autophagy is upregulated. Which signaling process involving nutrient acquisition, autophagy, and cellular survival is most closely related?

<p>Inhibition of mTOR signaling promotes autophagy and enhances cell survival during nutrient deprivation. (D)</p> Signup and view all the answers

If a cell is exposed to an inhibitor of the electron transport chain (ETC), leading to decreased ATP production, what compensatory mechanism would provide the MOST immediate, albeit temporary, source of ATP?

<p>Increase of creatine kinase activity to shuttle high-energy phosphates from phosphocreatine to ADP. (D)</p> Signup and view all the answers

Consider a cell undergoing ER stress and initiating the unfolded protein response (UPR). Which specific branch of the UPR would primarily mediate increased lipid biosynthesis to expand the ER membrane and accommodate the increased protein folding load?

<p>Activation of sterol regulatory element-binding protein (SREBP) to enhance lipid biosynthesis. (D)</p> Signup and view all the answers

If a population of cells is exposed to a persistent ROS source, resulting in chronic oxidative stress, what adaptation mechanism would be MOST effective in maintaining redox homeostasis and preventing cellular damage?

<p>Upregulation of the pentose phosphate pathway (PPP) to enhance NADPH production and glutathione reduction. (B)</p> Signup and view all the answers

Following an acute inflammatory stimulus, specific immune cells are recruited to the site of injury. What mechanism involving cellular metabolism enables immune cells to meet this energy demand?

<p>Metabolic shift toward aerobic glycolysis (Warburg effect) to support rapid ATP production and macromolecule synthesis. (B)</p> Signup and view all the answers

Epithelial cells in the respiratory tract are exposed to chronic cigarette smoke, leading to metaplasia. What intracellular process is MOST likely responsible for this conversion?

<p>Changes in histone methylation patterns, leading to altered gene expression. (D)</p> Signup and view all the answers

After exposure to high levels of ionizing radiation, certain cells undergo apoptosis. Which is the MOST likely target?

<p>DNA. (C)</p> Signup and view all the answers

Following chronic exposure to a toxin, endoplasmic reticulum (ER) stress occurs. Which adaptation method is most closely related.

<p>Reduction in protein synthesis. (C)</p> Signup and view all the answers

Which statement BEST describes irreversible cell death?

<p>The cell cannot recuperate. (A)</p> Signup and view all the answers

In an environment of chronic hypoxia, cells begin to undergo functional changes. Which mechanism is most plausible?

<p>Upregulation of of enzymes. (D)</p> Signup and view all the answers

Describe the relationship between cell injury and cell survival.

<p>Cells can adapt, experience injury, or die based on the degree of a stressor. (D)</p> Signup and view all the answers

Toxins lead to damage through what mechanism?

<p>Disruption of cell structure. (A)</p> Signup and view all the answers

Flashcards

Morphology

The appearance of a cell or tissue related to its form and structure.

Morphological changes

Alteration to a cell or tissue in response to a stimulus, considering structural and functional changes.

Cytology

The study of cells, including their structure, function, and interactions.

Enzymes

Cells must produce and respond to them to speed up metabolism and chemical reactions.

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Transport Metabolites

Cells are responsible for moving them across membranes and within compartments to maintain homeostasis.

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External membranes

The plasma membrane controls what enters and exits the cell.

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Glycolysis

A process involving glucose breakdown in the cytoplasm.

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Cell division

Cells divide to produce new cells for growth, occurring via mitosis or meiosis.

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Cellular injury

Disruption of cellular homeostasis leading to abnormal cell function or cell death.

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Mitochondrial Dysfunction

Mitochondria are essential for energy production.

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Reversible cellular injury

When a cell has been injured but is able to survive.

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Cellular adaptation

Cells undergo this when confronted with stresses to normal structure/function.

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Atrophy

Decrease in size of an organ/tissue due to a decrease in cell size.

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Hypertrophy

Increase in tissue size due to an increase in cell size.

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Hyperplasia

Increase in the number of cells in a tissue or organ due to increased cell division.

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Metaplasia

Reversible change of one differentiated cell type to another.

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Dysplasia

Abnormal cell growth and development which results in changes in cell size, shape, appearance and organisation.

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Neoplasia

Uncontrolled and abnormal growth of cells, which leads to the formation of a tumour.

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Irreversible cellular injury

Where a cell has been injured, and the affected cell is unable to survive the injury.

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Hypoxia

Refers to the loss of the ability to carry on sufficient aerobic oxidative respiration.

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Free Radicals

Chemical species with an unpaired electron in the outer shell.

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chemical Injury

Contact with toxic substances that causes subtle causes of cell injury.

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Radiation

The cell is most sensitive to radiation during mitosis.

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Apoptosis

The body is removing unwanted cells as a part of normal cell turnover

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Necrosis

Anatomic changes that result from abnormal cell death within a living creature.

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Study Notes

Lecture 7: Cellular Injury

  • Cellular injury is being discussed as part of the BSc Podiatry Programme, Year 1, Pathology.
  • The lecturer is Sophie Hartfield, Lecturer in Podiatry.

Learning Objectives

  • An outline of normal cellular functions and the objectives will be provided.
  • Cellular injury and relevance to the lower limb will be reviewed.
  • Mechanisms of cellular injury are to be discussed.
  • Cellular adaptations and changes which may occur will be described.
  • Types of cellular death will be examined.
  • Diagnostic testing and assessment of cellular injury will be discussed.

Morphology & Cell Structure

  • Morphology refers to the appearance of a cell or tissue related to its form and structure.
  • Morphological changes refer to alterations to a cell or tissue in response to stimuli, accounting for structural and functional changes that can be characteristic of a disease or diagnostic of its cause.
  • Cytology is the study of cells, focusing on their structure, function, and interactions.

Typical Cellular Function

  • Cells must perform key activities to remain functional.
  • Cellular activities are inter-related, so a problem with one function can have a knock-on effect on others.
  • Cells must synthesize nucleic acids, proteins, lipids, and ATP, as well as repair genetic material.

Key Functions of the Cell

  • Cells produce and respond to enzymes.
  • They transport metabolites.
  • Cells maintain external and internal membranes.
  • Respiration occurs aerobically to produce energy.
  • Cells divide to create new cells.
  • All this ensures a cell can function, grow, respond to environmental changes and replicate.
  • Successful cellular activities require coordination.

Enzyme Role

  • Enzymes are proteins that speed up metabolic and chemical reactions.
  • Enzymes are produced by the cell to speed up biological reactions lowering the energy required to carry out processes
  • These are strictly regulated by cells; activity is controlled in response to environmental or intracellular conditions.

Transport of Metabolites

  • Cells move metabolites across and within membranes, maintaining homeostasis and supporting cellular processes.
  • Transport mechanisms involve passive transport, active transport, endocytosis, and exocytosis.
  • These are critical for nutrient acquisition, waste removal, and ion concentration regulation.

Importance of Cell Membranes

  • External membranes control what enters/exits the cell, protecting internal components.
  • Internal membranes compartmentalize functions within organelles like ER, Golgi apparatus, and mitochondria.
  • Membranes are constantly being repaired and remodelled.

Aerobic Respiration

  • Aerobic respiration occurs in the mitochondria, breaking down glucose in the presence of oxygen to produce ATP.
  • ATP is the main energy source for the cell.
  • Glycolysis (in the cytoplasm)
  • Cytric acid cycle (in the mitochondria)
  • Electron Transport Chain (on the inner mitochondrial membrane)

Cell Division and Proliferation

  • Cells divide for growth, repair, and reproduction via mitosis & meiosis.
  • The cell cycle is regulated to control cell division; cells may rest or undergo apoptosis (programmed cell death) if damaged.

Cell Survival

  • Cells can adapt to changes.
  • They may be injured, which can be reversible.
  • Cells may be injured or killed by severe stress like lack of oxygen or bacterial toxins.

Cellular Injury

  • Cellular injury disrupts cellular homeostasis, causing abnormal function or death.
  • The lower limb is susceptible to injuries through trauma, fractures, ischaemia, infections, and chronic diseases. -These injuries directly impact cellular health.

Irregular Cellular Function

  • A disruption to Homeostasis occurs when cells are stressed or injured.
  • Normal mechanisms break down, leading to swelling, metabolic disturbances and loss of function.
  • Cells in pathological states become unresponsive or hypersensitive to signals. -It leads to abnormal growth (hyperplasia) or cell death (apoptosis).
  • Mitochondria are essential for energy production. -Mitochondrial dysfunction can lead to cell death (necrosis) or insufficient energy production
  • Injured cells may accumulate misfolded proteins.

Mechanisms of Cellular Injury

  • Reversible cellular injury: the affected cell is able to survive and leads to adaptation of the cells and tissue.
  • Irreversible cellular injury: a cell has been injured, and it cannot survive.

Reversible Cellular Injury Details

  • Reversible cellular injury occurs when an injured cell is able to survive.
  • It leads to adaptation of the cells and tissue and recovery is possible if the stressor is removed.
  • Examples include cell swelling, fatty changes, or accumulation of intracellular material.
  • If stress continues, it may progress to irreversible damage.

Cellular Adaptation

  • Cells undergo adaptation when confronted with stresses that threaten normal structure and function
  • These adaptive changes permit survival and maintenance of function
  • Cells may adapt by undergoing changes in size, number and type.

Atrophy

  • Atrophy is a decrease in the size of an organ/tissue due to a decrease in cell size.
  • It occurs due to decreased workload or adverse conditions, such as lack of nutrition, aging, or reduced blood supply.
  • Reversible if the cause is addressed, and cells may regain original size.

Hypertrophy

  • Hypertrophy refers to increased tissue size due to an increase in cell size.
  • Seen in muscle cells because of increased workload.
  • Reversible in response to stress such as increased mechanical loading, so cells adapt by growing in size.

Hyperplasia

  • Hyperplasia refers to an increase in the number of cells in a tissue or organ, due to increased cell division.
  • It occurs in response to stimuli like hormonal changes or chronic irritation.
  • Its a compensatory mechanism to increased demand, reversible if the stimulus is removed, the tissue may return to its original state.

Metaplasia

  • Metaplasia refers to the reversible change of one differentiated cell type to another adult cell type.
  • Usually, occurs due to chronic irritation and inflammation: substitution of better cells that are able to survive.

Dysplasia

  • Dysplasia refers to abnormal cell growth that changes cell size, shape, appearance, and organization.
  • Minor changes to cells (dysplasia) are associated with chronic irritation or inflammation
  • It is considered to be a precursor to malignancy (cancer).

Neoplasia

  • Neoplasia refers to uncontrolled and abnormal growth of cells, leading to the formation of a tumor.
  • Process can be benign or malignant.
  • Neoplasia can lead to metastasis.

Irreversible Cellular Injury

  • Irreversible cellular injury occurs when a cell has been injured and is unable to survive.
  • Leads to cell death and tissue damage.
  • Has no possibility of recovery
  • Examples include necrosis and apoptosis, characterized by the loss of structural integrity and function.

Mechanisms of Cellular Injury.

  • Hypoxia.
  • Free radical induced.
  • Toxins and Chemicals
  • Radiation.
  • Metabolic and Nutritional Deficiencies.
  • Infectious Agents and Inflammation.

Hypoxia

  • Hypoxia refers to the loss of the ability to carry on sufficient aerobic oxidative respiration;
  • The most common cause of cell injury and death.
  • Disruption of ATP production, ion pump failure, and accumulation of metabolites.
  • Local causes are fractures.
  • Systemic causes are failure of the heart to pump enough blood or haemoglobin problems,

Hypoxaemia

  • Hypoxaemia refers to the reduced amount of oxygen within the blood.

Results of Hypoxia

  • Neurons undergo frank necrosis after being deprived of oxygen for 3-5 minutes.
  • Heart muscle cells can last 30-60 minutes.
  • Liver cells and renal tubular cells can last for 1-2 hours.
  • A leg can last for many hours!

Free Radicals

  • Free Radicals are chemical species with an unpaired electron in the outer shell.
  • They are highly reactive and have low chemical specificity, reacting with proteins, lipids, carbohydrates, and DNA.
  • Attack nucleic acids
  • They are unstable cells that have the ability to damage cells and DNA

Free Radicals - More Information

  • DNA damage by oxygen free radicals accelerates the degradation of mitochondrial function.
  • Accumulating mutations in genes decrease transfer efficiency and higher production of superoxide and hydroxyl free radicals.
  • Aging may be caused by cumulative free radical damage
  • Genetic mutations have been implicated in many degenerative diseases e.g. Alzheimer's disease, ischaemic heart disease and diabetes.

Chemical Injury

  • Cells may be injured by contact with toxic substances e.g. mercury poisoning, medication e.g. chemotherapy.
  • Some substances cause damage as a result of toxic breakdown substances e.g. carbon tetrachloride
  • Some causes of cell injury is Chemical agents and physical agents including fire, freezing, electricity and ionizing radiation.
  • Sometimes, cell destruction is deliberate, e.g., cryotherapy and caustics.

Radiation and Cell Injury

  • Cell damage will depend on the type and dose of radiation.
  • Cell cycle when radiation occurs - just before and during mitosis, the cell is most sensitive.
  • The presence of chemical agents may potentiate radiation, or free radicals may be present.
  • Radiation can cause dilation and increased permeability of microvasculature
  • Leads to atrophy, scarring and ulceration e.g. in gut.
  • Radiation can lead to Skin - erythema, hair loss & dryness, with later hyperkeratosis.

Inadequate Nutrition

  • Poor nutrition affects cells as it does people and Different cells react differently to starvation conditions.
  • Lack of glucose produces the same brain damage as does hypoxia and other cells simply waste away and die.

Infectious Agents

  • Injure cells in a variety of ways.
  • Certain clostridia produce phospholipase enzymes which break down cell membranes and enable bacteria to flourish,
  • Viruses and some rickettsiae explode cells when they multiply.
  • Bacterial toxins can cause cell lysis e. gas gangrene or block nerve transmission e.g. botulinum toxin or tetanus toxin.
  • Bacteria also leads to cellulitis, osteomyelitis or septic arthritis. –Release of free radicals which can damage tissue and cause cell death.

Immune Injury

  • Antibody or T-cell mediated.
  • Damage to the body's own "innocent bystanders"
  • Routinely occurs in serious inflammation, even when lymphocyte-mediated immunity is not

Cell Death

  • Cell death is an irreversible process. -There are 2 primary pathways, necrosis occurring within living tissue and apoptosis referring to programmed cellular death

Necrosis Details

  • Necrosis refers to the anatomic changes resulting from abnormal cell death in a living creature.
  • The first light-microscopic proof that a cell is dead is shrivelling and fragmentation of the nucleus.
  • Most necrosis results from loss of blood supply to part of the body.
  • There are various types of necrosis that display different features depending on the cause of tissue death.

Apoptosis

  • Apoptosis is essentially a program for single-cell death for removing unwanted cells
  • When the proper signal is given, the involved cell activates mechanisms that cause it to die, fragment and be removed from the tissue. -Requires the expenditure of energy: Doesn't cause an inflammatory response to the cell death.

Stages of Apoptosis (Cell Suicide)

  • Cells separate from adjacent cells.
  • They shrink as nucleus and cytoplasm condense.
  • Mitochondria breaks down with the release of cytochrome c.
  • Cells develop bubble-like blebs on their surface.
  • They have chromatin (DNA and protein) degraded.
  • They break into small, membrane-wrapped fragments.

Apoptosis and DNA Damage

  • Damage to cell genome can cause disruption of proper embryonic development leading to birth defects or cause a cell to become cancerous.
  • Cells respond to DNA damage by increasing their production of p53, a potent inducer of apoptosis.
  • Mutations in the p53 gene, produce a defective protein and are often found in cancer.

Cell Suicide Via Apoptosis

Generated by signals arising within the cell or triggered by death activators binding to receptors at the cell surface

  • TNF-alpha –Lymphotoxin (TNF-beta) –Fas ligand (FasL) -Triggered by dangerous reactive oxygen species e.g. UV

Histology and Histopathology

  • Histology refers to study of tissues.
  • Histopathology refers to the examination and diagnosis of a pathologic tissue affected by a disease process or structural concern.

Tissue Preparation and Staining

  • Request Form and sample Must be labelled with:Unique Number (MRN or NHS Number), Surname, First Name, Date of Birth.
  • Signature and Date and TimeClinical Details/Reasons for transfusion

Post Lecture Consolidation

  • Review and recap lecture and consider key terminology.
  • Attempt the MCQ quiz at the end of this learning unit and test knowledge.

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