Cellular Adaptations: Atrophy & Hypertrophy

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Questions and Answers

A patient with a history of chronic alcohol abuse is found to have fat accumulation in their liver. This condition is an example of which type of cellular adaptation?

  • Atrophy
  • Metaplasia
  • Hypertrophy
  • Steatosis (correct)

Which of the following mechanisms contributes to the cellular changes seen in hypertrophy?

  • Increased synthesis of cellular components due to growth factor signaling (correct)
  • Reduced rate of protein synthesis, limiting cell growth
  • Activation of catabolic pathways, leading to cell shrinkage
  • Decreased workload reducing the cell stimulation

In a smoker, the columnar epithelium in the trachea is replaced by squamous epithelium. Which cellular adaptation is this an example of, and what is the primary risk associated with this change?

  • Hyperplasia, increased risk of infection
  • Hypertrophy, increased cell size
  • Metaplasia, increased risk of malignancy (correct)
  • Atrophy, decreased organ function

Following prolonged ischemia to the kidney, a biopsy shows cells with shrunken nuclei and fragmented DNA. Which of the following processes is most likely occurring?

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

A patient with hemochromatosis has increased iron accumulation in various organs, leading to cellular damage. Which mechanism directly contributes to this form of cell injury?

<p>Formation of free radicals via the Fenton reaction (C)</p> Signup and view all the answers

A researcher is studying the effects of a new drug on cancer cells and observes increased levels of cytochrome c in the cytoplasm. What cellular process is most likely to be initiated by this observation?

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

A biopsy of a lung lesion from a coal miner shows black pigment within macrophages. Which of the following terms best describes this condition?

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

A patient with hyperparathyroidism develops calcium deposits in multiple tissues. What is the underlying mechanism for this deposition?

<p>Metastatic calcification secondary to hypercalcemia (A)</p> Signup and view all the answers

Microscopic examination of the liver reveals Mallory bodies in hepatocytes. Which condition is most likely associated with this finding?

<p>Alcoholic liver disease (C)</p> Signup and view all the answers

Barrett's esophagus is characterized by the replacement of squamous epithelium with columnar epithelium containing goblet cells. Which cellular adaptation best describes this change?

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

In the context of cell injury, what is the role of glutathione reductase?

<p>Reduces oxidized glutathione back to its active form. (A)</p> Signup and view all the answers

What is the significance of detecting increased levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a patient?

<p>Suggests cell membrane disintegration and leakage of enzymes from damaged cells. (B)</p> Signup and view all the answers

A cell undergoing reversible injury due to hypoxia exhibits swelling. What is the primary mechanism contributing to this cellular swelling?

<p>Sodium-potassium pump dysfunction leading to ion and water imbalance (C)</p> Signup and view all the answers

What distinguishes metastatic calcification from dystrophic calcification?

<p>Metastatic calcification results from hypercalcemia; dystrophic calcification occurs in areas of cell injury or death. (C)</p> Signup and view all the answers

Which of the following is a key mechanism by which free radicals cause cellular damage?

<p>Attacking lipids in the cell membrane through lipid peroxidation (D)</p> Signup and view all the answers

Which enzyme is responsible for converting superoxide radicals into hydrogen peroxide?

<p>Superoxide dismutase (B)</p> Signup and view all the answers

If a liver biopsy shows an accumulation of pink globules within hepatocytes, which condition is most likely suspected?

<p>Alpha-1 antitrypsin deficiency (C)</p> Signup and view all the answers

A researcher exposes cells to ionizing radiation, leading to DNA damage. Which of the following processes is most directly involved in this type of cell injury?

<p>Formation of oxygen-derived free radicals (D)</p> Signup and view all the answers

A patient is diagnosed with ischemia-reperfusion injury following a myocardial infarction. What pathological process contributes to cell damage after blood flow is restored?

<p>Excessive generation of free radicals upon reintroduction of oxygen (D)</p> Signup and view all the answers

A patient with Wilson's disease has impaired copper excretion. What is the primary mechanism of cell injury in this condition?

<p>Copper accumulation causing mitochondrial dysfunction and free radical formation. (D)</p> Signup and view all the answers

What role do metal carrier proteins, such as transferrin and ceruloplasmin, play in cellular defense against free radicals?

<p>They bind to metal ions, preventing them from catalyzing the Fenton reaction and generating free radicals. (B)</p> Signup and view all the answers

A biopsy from a chronic alcoholic patient's liver shows hepatocytes filled with lipid droplets. Which metabolic process is most directly disrupted, leading to this accumulation?

<p>Disruption of fatty acid oxidation (D)</p> Signup and view all the answers

A new drug is found to cause cellular injury by damaging lysosomes. What intracellular consequence is most directly linked to this damage?

<p>Release of hydrolytic enzymes, leading to autodigestion of the cell (B)</p> Signup and view all the answers

How does the production of lactic acid during anaerobic glycolysis contribute to cell injury?

<p>It lowers the cell's pH, potentially denaturing enzymes and damaging cellular structures. (C)</p> Signup and view all the answers

What is the role of NADPH in the context of free radical defense?

<p>It is required as an electron donor by glutathione reductase to regenerate reduced glutathione. (D)</p> Signup and view all the answers

A patient with Alzheimer's disease shows neurofibrillary tangles in neurons. These tangles are composed of which protein?

<p>Tau protein (A)</p> Signup and view all the answers

After a kidney transplant, the transplanted organ undergoes acute rejection due to immunological dysfunction. Which mechanism is primarily responsible for the cell injury in the rejected kidney?

<p>Immune-mediated attack by cytotoxic T cells. (C)</p> Signup and view all the answers

A researcher is studying the mechanism of cell death in a new autoimmune disease. They observe that affected cells undergo shrinkage, chromatin condensation, and formation of apoptotic bodies. Which type of cell death is most likely occurring?

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

What is the significance of observing 'ghost cells' in a tissue sample?

<p>Sign of irreversible cell injury and coagulative necrosis (D)</p> Signup and view all the answers

In the context of cellular adaptations, what distinguishes hyperplasia from hypertrophy?

<p>Hyperplasia involves an increase in cell number, while hypertrophy involves an increase in cell size. (C)</p> Signup and view all the answers

A patient's biopsy reveals tissue with cells containing an abnormal accumulation of amyloid protein. Which special stain is most appropriate to confirm the presence of amyloid?

<p>Congo red stain (B)</p> Signup and view all the answers

A researcher is investigating cellular adaptations in cardiac muscle cells subjected to chronic hypertension. Which of the following changes is most likely to be observed?

<p>Increased cell size without a change in cell number. (D)</p> Signup and view all the answers

A biopsy of the gallbladder reveals cholesterol crystals and macrophages filled with lipid. Which of the following best describes this finding?

<p>Cholesterol accumulation and phagocytosis by macrophages (D)</p> Signup and view all the answers

What is the primary role of Glucose-6-Phosphate Dehydrogenase (G6PD) in the context of cellular injury and free radical defense?

<p>It reduces NADP+ back to NADPH, which is essential for glutathione reduction. (A)</p> Signup and view all the answers

A researcher is studying the impact of chronic vitamin E deficiency on cell membranes. Which of the following outcomes is most likely to be observed?

<p>Increased lipid peroxidation in cell membranes due to reduced antioxidant protection (C)</p> Signup and view all the answers

Upon microscopic examination of a liver biopsy, a pathologist observes an increased number of Kupffer cells containing brown pigment. Which of the following conditions is most likely?

<p>Anemia and increased hemolysis (D)</p> Signup and view all the answers

Which cellular adaptation involves a change in cell phenotype and is most likely to occur in epithelial cells?

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

Which of the following mechanisms primarily accounts for cellular atrophy observed in skeletal muscle due to prolonged immobilization?

<p>Reduced stimulation (C)</p> Signup and view all the answers

Left ventricular hypertrophy (LVH) can arise from both physiologic and pathologic conditions. Which of the following represents a physiologic cause of LVH?

<p>Intense athletic training (A)</p> Signup and view all the answers

A researcher is investigating the mechanism by which a novel growth factor induces hyperplasia in liver cells. Which cellular process is most likely activated by this growth factor?

<p>Cell proliferation (D)</p> Signup and view all the answers

In a patient with chronic reflux esophagitis, Barrett's esophagus develops as a result of metaplasia. What cellular change is characteristic of Barrett's esophagus?

<p>Squamous to columnar (B)</p> Signup and view all the answers

A patient presents with wheezing, crackles, cyanosis, and ankle edema, and is diagnosed with chronic bronchitis due to long-term smoking. How does squamous metaplasia contribute to the patient's respiratory symptoms?

<p>Impeding particle removal (A)</p> Signup and view all the answers

Hypoxia is a common cause of cell injury. Which of the following mechanisms directly leads to cellular swelling during hypoxia?

<p>Dysfunction of sodium-potassium pump (B)</p> Signup and view all the answers

Free radicals cause damage to cells via several mechanisms. Which process involves the abstraction of electrons from lipids in the cell membrane, leading to a chain reaction?

<p>Lipid peroxidation (D)</p> Signup and view all the answers

How do antioxidants, such as vitamins A, C, and E, protect cells from injury caused by free radicals?

<p>Donating electrons to neutralize free radicals (B)</p> Signup and view all the answers

Which of the following enzymes is responsible for converting superoxide radicals into hydrogen peroxide, an intermediate step in neutralizing free radicals?

<p>Superoxide dismutase (D)</p> Signup and view all the answers

What is the primary role of metal carrier proteins like transferrin and ceruloplasmin in protecting cells from free radical damage?

<p>Binding and sequestering metal ions (A)</p> Signup and view all the answers

A patient is diagnosed with ischemia-reperfusion injury following a myocardial infarction. Which of the following processes contributes to cell damage after blood flow is restored?

<p>Exacerbated inflammation (B)</p> Signup and view all the answers

Which morphological feature is characteristic of reversible cell injury, and what cellular process underlies this adaptation?

<p>Membrane blebbing due to cytoskeleton damage (B)</p> Signup and view all the answers

What is the sequence of nuclear changes observed during necrosis, representing the progression from reversible to irreversible cell injury?

<p>Pyknosis → Karyorrhexis → Karyolysis (A)</p> Signup and view all the answers

Which of the following best describes the histological appearance of 'ghost cells,' and under what conditions are they typically observed?

<p>Cellular outlines with loss of nuclei, seen in coagulative necrosis (A)</p> Signup and view all the answers

How does alcohol contribute to steatosis (fatty change) in the liver, and what outcome underscores the reversibility of this cell injury?

<p>Disrupting fatty acid oxidation, reversible with alcohol abstinence (C)</p> Signup and view all the answers

What is the mechanism by which cell swelling occurs due to dysfunction of the sodium-potassium pump after exposure to hypoxia?

<p>Influx of sodium ions drawing water into the cell (D)</p> Signup and view all the answers

Which event involving mitochondria is a critical step in the initiation of apoptosis during irreversible cell injury?

<p>Release of cytochrome c (A)</p> Signup and view all the answers

Why do accumulations of substances typically occur under pathological conditions, and how does recognizing these accumulations contribute to understanding disease?

<p>Accumulations disrupt normal cell function and indicate underlying metabolic or pathological processes; recognizing these helps in diagnosing and managing diseases. (B)</p> Signup and view all the answers

Steatosis involves fat accumulation within the liver. How does non-alcoholic steatohepatitis (NASH) differ from alcoholic steatosis in terms of causation and potential outcomes?

<p>NASH involves triglyceride fat metabolism issues not related to alcohol and can lead to liver damage. (A)</p> Signup and view all the answers

What is the pathological significance of finding cholesterol accumulations in the gallbladder, and how does this relate to the formation of atherosclerotic plaques?

<p>Cholesterol in the gallbladder may lead to gallstone formation; fatty streaks in the aorta indicate initial cholesterol deposits under the intima. (A)</p> Signup and view all the answers

How does lipofuscin accumulation in the myocardium relate to cellular aging and injury, and why is it often referred to as 'wear-and-tear' pigment?

<p>It reflects the accumulation of indigestible cellular debris and signifies oxidative stress and wear-and-tear on the cells. (A)</p> Signup and view all the answers

Anthracosis is the accumulation of carbon pigment in lung tissue. How does the process of anthracosis occur, and what role do macrophages play in this condition?

<p>Macrophages phagocytose the pigment and transport it to connective tissue or lymph nodes. (D)</p> Signup and view all the answers

Dystrophic calcification differs from metastatic calcification. Which condition is most closely associated with metastatic calcification?

<p>Elevated serum calcium levels (D)</p> Signup and view all the answers

What is the diagnostic utility of performing a Congo red stain, and what change observed under polarized light confirms the presence of amyloid protein?

<p>Congo red stains amyloid protein red, with polarized light showing green birefringence. (D)</p> Signup and view all the answers

How does Alpha-1 antitrypsin deficiency lead to protein accumulation within hepatocytes, and what is the impact of this accumulation on liver function?

<p>A mutated protein accumulates within hepatocytes; it cannot be excreted so is retained, leading to cellular injury. (B)</p> Signup and view all the answers

A researcher discovers accumulation of lipid droplets within cells, but does not know the precise mechanism. Dysfunctional metabolism of which molecule is most likely?

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

A pathologist identifies several yellow streaks on the internal surface of the aorta during autopsy. What condition is characterized by this finding?

<p>Cholesterol accumulation leading to fatty streaks (B)</p> Signup and view all the answers

A clinical sample contains macrophages laden with carbon pigment. The patient history should be checked for which exposure?

<p>Air pollution exposure (C)</p> Signup and view all the answers

Microscopic analysis of a liver biopsy reveals golden-brown pigment that can be further characterized with a Prussian blue stain. What is this pigment?

<p>Iron-containing hemosiderin (D)</p> Signup and view all the answers

Clusters of cells are found to have died, in an otherwise benign sample, and calcium accumulates in circular clusters (psammoma bodies). These structures are most likely to be observed in which condition?

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

Under what circumstances does metastatic calcification occur, and how does it differ from dystrophic calcification?

<p>Resulting from hypercalcemia as calcium deposits and accumulates in tissues (C)</p> Signup and view all the answers

A patient presents with neurofibrillary tangles found in neurons. Which protein is most closely associated?

<p>Tau protein (A)</p> Signup and view all the answers

Plasma cells are found histologically with globular endoplasmic reticula. What accumulates in cytoplasmic vesicles?

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

During oxidative phosphorylation, which specific event leads to the formation of reactive oxygen species (ROS) or free radicals?

<p>Incomplete transfer of electrons to oxygen (B)</p> Signup and view all the answers

During inflammation, phagocytes produce superoxide ions and hydrogen peroxide. Which enzyme primarily generates superoxide ions, initiating this respiratory burst used to kill pathogens?

<p>NADPH oxidase (C)</p> Signup and view all the answers

How does ionizing radiation lead to the formation of free radicals, and what specific molecule is most directly affected by this process?

<p>Knocks off electrons from water molecules, converting them into hydroxyl radicals (A)</p> Signup and view all the answers

During the metabolism of drugs like acetaminophen, how can free radicals be generated, and what organ is most susceptible to damage from this process?

<p>Liver breaking down the drug produces toxic chemicals after metabolism (B)</p> Signup and view all the answers

In the context of cellular adaptation to chronic stress, which of the following best describes the role of transcription factors?

<p>They regulate gene expression, altering protein synthesis to promote cell survival or adaptation. (D)</p> Signup and view all the answers

Which of the following scenarios best illustrates a pathologic consequence of cellular hypertrophy?

<p>Cardiac enlargement in response to chronic hypertension, leading to heart failure. (B)</p> Signup and view all the answers

Which cellular process is most directly inhibited by a reduction in ATP availability during cell injury?

<p>Active transport of ions across the plasma membrane. (C)</p> Signup and view all the answers

In a patient with chronic obstructive pulmonary disease (COPD) due to smoking, squamous metaplasia in the trachea serves primarily as:

<p>An adaptive response to protect against heat and chemical irritants, albeit at the cost of mucus secretion. (D)</p> Signup and view all the answers

Which of the following molecular events is most critical in initiating apoptosis following irreversible cell injury?

<p>Release of cytochrome c from the mitochondria into the cytoplasm. (D)</p> Signup and view all the answers

Which mechanism directly accounts for cellular swelling during the initial stages of reversible cell injury due to hypoxia?

<p>Dysfunction of the sodium-potassium pump, resulting in an influx of sodium and water. (A)</p> Signup and view all the answers

In the context of free radical injury, how do metal carrier proteins like transferrin and ceruloplasmin protect cells from damage?

<p>By binding to transition metals, preventing them from catalyzing the formation of free radicals. (D)</p> Signup and view all the answers

After an ischemic event, reperfusion can paradoxically exacerbate cell injury. Which of the following mechanisms primarily accounts for this reperfusion injury?

<p>Increased neutrophil infiltration, leading to the release of additional free radicals. (C)</p> Signup and view all the answers

Why does steatosis (fatty change) frequently occur in the liver of chronic alcohol abusers?

<p>Alcohol impairs the synthesis of proteins needed for lipoprotein metabolism, leading to fat accumulation. (D)</p> Signup and view all the answers

What is the role of glucose-6-phosphate dehydrogenase (G6PD) in protecting cells against oxidative stress?

<p>It regenerates NADPH, which is essential for the reduction of glutathione. (A)</p> Signup and view all the answers

How does ionizing radiation cause cellular injury?

<p>By interacting with water molecules to produce hydroxyl radicals, which damage DNA. (B)</p> Signup and view all the answers

In Alzheimer's disease, neurofibrillary tangles are a key pathological feature. Which protein primarily comprises these tangles, and what is its role in neuronal function?

<p>Tau protein, which stabilizes microtubules involved in axonal transport. (D)</p> Signup and view all the answers

In the context of accumulation disorders, what is the underlying mechanism in alpha-1 antitrypsin deficiency that leads to protein accumulation in hepatocytes?

<p>Impaired folding and transport of mutant alpha-1 antitrypsin within the endoplasmic reticulum. (D)</p> Signup and view all the answers

What is the role of NADPH oxidase in phagocytes during the inflammatory response?

<p>It generates superoxide radicals to kill ingested pathogens. (A)</p> Signup and view all the answers

What is the significance of observing 'ghost cells' in histological samples?

<p>They are remnants of necrotic cells characterized by loss of the nucleus and cellular architecture. (C)</p> Signup and view all the answers

Dystrophic calcification often occurs in areas of tissue damage or necrosis. What is the primary mechanism by which calcium is deposited in these areas?

<p>Release of phosphate from necrotic cells that binds to calcium, forming calcium phosphate crystals. (C)</p> Signup and view all the answers

Congo red staining is used to identify amyloid deposits in tissues. What specific change observed under polarized light confirms the presence of amyloid?

<p>An apple-green birefringence. (C)</p> Signup and view all the answers

A biopsy of the lung from a city resident reveals numerous macrophages containing black pigment. What is this pigment likely to be, and what is the process of its accumulation called?

<p>Carbon, resulting from anthracosis. (C)</p> Signup and view all the answers

Patients taking acetaminophen may be at risk for liver damage. Why?

<p>Acetaminophen metabolism in the liver generates free radicals that cause cellular damage. (C)</p> Signup and view all the answers

Flashcards

Cellular Adaptations

Reversible changes in response to persistent stress, allowing cells to adapt. Number, size, phenotype, or metabolic activity of cells

Atrophy

Decrease in organ size or cell number, often due to reduced demand or blood supply.

Hypertrophy

Increase in cell size, leading to enlarged organ size, without cell division.

Hyperplasia

Increase in cell number, often in response to hormonal signals or increased workload.

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Metaplasia

Change in cell phenotype from one type to another, usually in response to chronic irritation or stress.

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Hypoxia

Most common cause of cell injury due to lack of blood flow, heart failure, or decreased oxygen carrying capacity.

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Free Radicals

Unstable molecules with unpaired electrons that damage DNA, proteins, and lipid membranes.

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Reperfusion Injury

Damage to cells from the restoration of blood flow after ischemia due to the generation of free radicals.

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Antioxidants

Vitamins A, C, and E neutralize free radicals by donating electrons.

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Reversible Cell Injury

Initial cellular changes that are reversible if the stressor is removed in time. Sodium-Potassium Pump Dysfunction, Membrane blebbing and organelle swelling.

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Irreversible Cell Injury

Point where the cell cannot recover from injury, leading to cell death. Nuclear Damage, Plasma Membrane Breakdown.

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Pyknosis

Enzyme causes chromatin condensation (nuclear shrinkage).

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Karyorrhexis

Enzyme causes nuclear fragmentation.

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Karyolysis

Fading or obliteration of the nuclear content. Happens in necrosis

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Necrosis

Cell death due to injury with inflammation, leaking of contents and enzymes.

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Calcium Accumulation

Cell death via enzyme activation: Proteases, DNAases

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Cellular Accumulations

Pathological conditions leading to intracellular or extracellular buildup of substances.

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Steatosis

Fat accumulation within the liver cells (hepatocytes).

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Anthracosis

Accumulation of carbon pigment from air pollution inhaled into the lung tissue.

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Dystrophic Calcification

Calcium deposits from cell injury and necrosis (especially in atherosclerosis or atheromas.).

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Metastatic Calcification

Calcium deposits from hypercalcemia.

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Study Notes

Cellular Adaptations

  • Cellular adaptations are reversible changes to cells in response to persistent environmental stress.
  • Cells adapt to prevent injury or death and return to homeostasis when stress is removed.
  • Adaptations include changes in number, size, phenotype, and metabolic activity, potentially altering cell function.

Atrophy

  • Atrophy is a decrease in organ size or cell number.
  • Causes include lack of stimulation, reduced blood supply, disuse, malnutrition, or pressure.
  • Mechanisms involve decreased synthesis or increased breakdown of organelles and apoptosis.
  • Examples include post-partum uterus (physiologic), disuse from a cast, aging, or atherosclerosis (pathologic).

Hypertrophy

  • Hypertrophy is an increase in cell or organ size due to increased cell size.
  • Occurs in cells that cannot divide.
  • Mechanisms include increased workload, agonists, growth factors, and mechanical sensors activating signaling pathways.
  • Results in growth factors, vasoactive agents, agonist production, and transcription factor activation.
  • Physiologic causes include athlete's heart, while pathologic causes include left ventricular hypertrophy due to a stenotic valve.
  • Pregnant uterus experiences both hypertrophy and hyperplasia.
  • Signaling leads to changes in gene and protein expression, sometimes reverting to embryonic stages for better mechanical performance.
  • Production of atrial natriuretic factor increases sodium excretion, decreasing blood volume and pressure.

Hyperplasia

  • Hyperplasia involves an increase in cell number due to increased workload or stimuli.
  • Hormones and growth factors stimulate cell proliferation.
  • Can be physiologic or pathologic.

Metaplasia

  • Metaplasia is a reversible change in cell phenotype where stem cells differentiate into a new cell type.
  • Primarily occurs in epithelial cells.
  • Can increase malignancy risk or reduce normal function.
  • Squamous metaplasia, seen in smokers, transforms columnar cells into squamous cells.
  • Columnar metaplasia occurs in Barrett's esophagus due to chronic reflux.
  • Connective tissue metaplasia, such as myositis ossificans, is rare and involves muscle cells changing into bone cells.

Clinical correlation of squamous metaplasia

  • Clinical correlation of squamous metaplasia is seen in smokers who exhibit wheezing, crackles, cyanosis, and ankle edema.
  • Normal ciliated epithelium is destroyed, replaced by squamous metaplasia, impairing mucus clearance.
  • Submucosal glands undergo hyperplasia to increase mucus production.

Overview of Cellular Adaptations

  • Hypertrophy involves cells "pumping up" by increasing their size.
  • Atrophy involves cells decreasing ("if you don't use it, you lose it").
  • Hyperplasia involves increasing the cell number ("strength in numbers").
  • Metaplasia involves cells transforming and differentiating into a different phenotype.

Overview of Causes of Cell Injury

  • Cell injury happens when cells can't adapt to stress, leading to death and affecting organ systems.
  • Common causes include hypoxia, pathogens, immunologic dysfunction, genetic mutations, chemical toxins, physical injury, nutritional imbalances, and aging.

Oxygen-Derived Free Radicals Mechanisms of Cell Injury

  • A key mechanism of cell injury is the damage to DNA, proteins, and lipid membranes by oxygen-derived free radicals.
  • Protective factors, such as vitamins A, C, and E, and enzymes like glutathione and catalase, can counteract free radicals.
  • Inflammation and ionizing radiation can also cause DNA damage and increase oxygen-derived free radicals.

ATP Depletion Mechanism of Cell Injury

  • ATP depletion from ischemia or hypoxia leads to dependency on anaerobic glycolysis, decreasing cell pH and increasing lactic acid.
  • Severe injury results in increased cell membrane permeability and calcium influx through dysfunctional ion channels.
  • Calcium influx activates destructive enzymes such as proteases, ATPases, phospholipases, and endonucleases.

Mitochondrial Dysfunction Mechanism of Cell Injury

  • Mitochondrial dysfunction reduces ATP production and releases cytochrome c, triggering apoptosis.

Free Radicals

  • Free radicals are molecules with unpaired electrons that destabilize other molecules by stealing electrons.
  • Formed physiologically during cellular respiration and pathologically during inflammation or exposure to radiation.
  • Reactive oxygen species (ROS) include superoxide, hydrogen peroxide, and hydroxyl radicals.

Pathological conditions where free radicals are generated

  • Phagocytes produce free radicals during inflammation to destroy pathogens.
  • Exposure to ionizing radiation converts water into hydroxyl radicals.
  • Metal buildup, like in hemochromatosis, generates free radicals through Fenton reactions.
  • Ischemia-reperfusion injury results in additional free radical production when blood flow returns to ischemic tissue.
  • Chemical or medication metabolism by the liver can also generate free radicals.

Free Radical Defense Mechanisms

  • Antioxidants such as vitamins A, C, and E neutralize free radicals by donating electrons.
  • Glutathione neutralizes hydrogen peroxide and is regenerated by glutathione reductase using NADPH.
  • Glucose-6-phosphate dehydrogenase (G6PD) replenishes NADPH.
  • Metal carrier proteins such as transferrin and ceruloplasmin bind to metal ions, preventing participation in free radical reactions.
  • Superoxide dismutase converts superoxide to hydrogen peroxide, while catalase and glutathione peroxidase convert hydrogen peroxide into water.

Outcomes of Cell Damage Due to Free Radicals

  • Lipid peroxidation damages cell membranes through chain reactions.
  • Oxidative modification of proteins alters enzyme and structural protein function.
  • DNA oxidation causes strand breaks and mutations, increasing cancer risk.
  • Free radicals damage lipids, proteins, and DNA and are produced physiologically and pathologically.
  • The body defends against them with antioxidants, glutathione, metal carriers, and scavenging enzymes.

Cellular Injury Morphology

  • Cells unable to adapt to stress undergo reversible or irreversible injury.
  • In reversible injury, cells can recover if the stressor is removed, while irreversible injury leads to cell death.
  • Cell death occurs through apoptosis or necrosis.
  • Mechanisms of injury include DNA damage, free radicals, increased permeability, calcium influx, and mitochondrial damage.

Reversible Cell Injury Morphology

  • With reversible cell injury morphology cells experience dysfunction of the sodium-potassium pump, causing water influx, cell swelling, membrane blebbing, and organelle swelling, as well as lipid accumulation.

Irreversible Cell Injury Morphology

  • In irreversible cell injury morphology, cells experience membrane breakdown leads to leakage of contents and enzymes, nuclear damage causing loss of DNA.
  • Necrosis involves nuclear pyknosis, karyorrhexis, and karyolysis.

Histologic light microscopy images

  • Histologic light microscopy images of renal tubules show normal state, cytoplasmic blebbing, and cell swelling with reversible injury.
  • With irreversible injury, cells show loss of nuclei, ghost cells, and necrosis.
  • Lipid accumulation in hepatocytes, as seen in fatty liver disease, is reversible if the cause (e.g., alcohol) is removed.

Cell Response to Oxygen Deprivation

  • Cells need oxygen to produce ATP via oxidative phosphorylation.
  • Without oxygen, cells undergo hypoxia, leading to ATP deficiency.
  • The sodium-potassium pump fails without ATP, causing sodium and water influx, resulting in cell swelling, loss of surface area, and protein synthesis disruption.
  • Cells use anaerobic glycolysis as a backup ATP source, which produces lactic acid, lowering pH and damaging enzymes.

Calcium Accumulation Resulting From Hypoxia

  • Calcium accumulates due to failure of the calcium pump, activating destructive enzymes (proteases, endonucleases, hydrolases, and phospholipases).
  • Mitochondrial damage results from calcium leakage, leading to the release of cytochrome c and initiation of apoptosis.
  • Lack of oxygen leads to cell dysfunction and death.

Accumulations

  • Accumulations, which are the accumulation of substances, occur under the setting of abnormal conditions.
  • Accumulations can be either intracellular or extracellular.
  • Accumulations include lipids, cholesterol, glycogen, pigments, calcium, and proteins.

Lipid or Cholesterol Accumulations

  • Fat accumulation within the liver, fatty changes in the liver, can either be due to alcohol or Non-Alcoholic Steatohepatitis (NASH).
  • Triglyceride fat metabolism within hepatocytes can be altered. Increased fats in the liver can alter the normal function of hepatocytes.
  • Cholesterol can accumulate in the gallbladder where bile contains cholesterol and bile salts.
  • Extra cholesterol can be phagocytosed by macrophages.
  • Fatty streaks, which are the precursors of an atheroma and atherosclerosis, are caused by fat deposits underneath the intimal layer of the aorta.

Glycogen, Lipofuscin, and Anthracosis Accumulations

  • Glycogen can accumulate within the lysosomes due to genetic conditions.
  • Lipofuscin accumulation in the myocardium can indicate cell injury and aging, and is also seen on the skin as age spots.
  • Anthracosis refers to the accumulation of carbon pigment in the lungs, particularly in urban settings.
  • Macrophages phagocytose the pigment and transport it to connective tissue or lymph nodes.

Tattoo Pigments, Hemosiderin, and Calcium Accumulations

  • Tattoo pigments accumulate in the dermis of the skin.
  • Hemosiderin, found in the liver, stains brown or golden-brown in normal hematoxylin stain.
  • Calcium accumulates due to cell death (dystrophic calcifications) from atherosclerosis. Accumulations can also result from hyperparathyroidism (metastatic calcification).
  • Metastatic calcification can be due to hyperparathyroidism, which causes hypercalcemia, calcium will flow through the bloodstream and deposit into various tissues of the body.

Calcium Accumulation:

  • With dystrophic calcifications calcium accumulates as a product of cell death, Over time, cells die out, and calcium remains as a remnant of that cell injury. So calcium accumulates due to cell death from atherosclerosis.
  • With metastatic calcification this is caused by hyperparathyroidism, which causes hypercalcemia where the calcium will flow through the bloodstream and deposit into various tissues of the body.

Alpha-1 Antitrypsin, Neurofibrillary Tangles, Plasma Cells Protein Accumulations

  • Amyloid, stained with Congo red, can be observed where polarization causes fluorescent chartreuse coloration and it deposits the blood vessel wall and the tissue proper.
  • Alpha-1 antitrypsin results in pink globules in hepatocytes, while nuerofibrillary tangles are composed of Tau protein and are associated with Alzheimer's.

Alpha-1 Antitrypsin, Irregular Protein and Tau Proteins Accumulations

  • Alpha-1 antitrypsin deficiency causes mutated proteins that remain with the cell that cannot be removed to protect the lung. The accumulations can be seen as pink globules within hepatocytes.
  • Dying liver cells have cytokeratin intermediate filaments which show the basic structure of the cell is disrupted, but not removed
  • Alzheimer's patients have neurofibrillary tangles, which are comprised of Tau proteins.

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