Podcast
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?
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?
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?
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?
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?
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?
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?
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?
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?
A biopsy of a lung lesion from a coal miner shows black pigment within macrophages. Which of the following terms best describes this condition?
A biopsy of a lung lesion from a coal miner shows black pigment within macrophages. Which of the following terms best describes this condition?
A patient with hyperparathyroidism develops calcium deposits in multiple tissues. What is the underlying mechanism for this deposition?
A patient with hyperparathyroidism develops calcium deposits in multiple tissues. What is the underlying mechanism for this deposition?
Microscopic examination of the liver reveals Mallory bodies in hepatocytes. Which condition is most likely associated with this finding?
Microscopic examination of the liver reveals Mallory bodies in hepatocytes. Which condition is most likely associated with this finding?
Barrett's esophagus is characterized by the replacement of squamous epithelium with columnar epithelium containing goblet cells. Which cellular adaptation best describes this change?
Barrett's esophagus is characterized by the replacement of squamous epithelium with columnar epithelium containing goblet cells. Which cellular adaptation best describes this change?
In the context of cell injury, what is the role of glutathione reductase?
In the context of cell injury, what is the role of glutathione reductase?
What is the significance of detecting increased levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a patient?
What is the significance of detecting increased levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a patient?
A cell undergoing reversible injury due to hypoxia exhibits swelling. What is the primary mechanism contributing to this cellular swelling?
A cell undergoing reversible injury due to hypoxia exhibits swelling. What is the primary mechanism contributing to this cellular swelling?
What distinguishes metastatic calcification from dystrophic calcification?
What distinguishes metastatic calcification from dystrophic calcification?
Which of the following is a key mechanism by which free radicals cause cellular damage?
Which of the following is a key mechanism by which free radicals cause cellular damage?
Which enzyme is responsible for converting superoxide radicals into hydrogen peroxide?
Which enzyme is responsible for converting superoxide radicals into hydrogen peroxide?
If a liver biopsy shows an accumulation of pink globules within hepatocytes, which condition is most likely suspected?
If a liver biopsy shows an accumulation of pink globules within hepatocytes, which condition is most likely suspected?
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?
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?
A patient is diagnosed with ischemia-reperfusion injury following a myocardial infarction. What pathological process contributes to cell damage after blood flow is restored?
A patient is diagnosed with ischemia-reperfusion injury following a myocardial infarction. What pathological process contributes to cell damage after blood flow is restored?
A patient with Wilson's disease has impaired copper excretion. What is the primary mechanism of cell injury in this condition?
A patient with Wilson's disease has impaired copper excretion. What is the primary mechanism of cell injury in this condition?
What role do metal carrier proteins, such as transferrin and ceruloplasmin, play in cellular defense against free radicals?
What role do metal carrier proteins, such as transferrin and ceruloplasmin, play in cellular defense against free radicals?
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?
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?
A new drug is found to cause cellular injury by damaging lysosomes. What intracellular consequence is most directly linked to this damage?
A new drug is found to cause cellular injury by damaging lysosomes. What intracellular consequence is most directly linked to this damage?
How does the production of lactic acid during anaerobic glycolysis contribute to cell injury?
How does the production of lactic acid during anaerobic glycolysis contribute to cell injury?
What is the role of NADPH in the context of free radical defense?
What is the role of NADPH in the context of free radical defense?
A patient with Alzheimer's disease shows neurofibrillary tangles in neurons. These tangles are composed of which protein?
A patient with Alzheimer's disease shows neurofibrillary tangles in neurons. These tangles are composed of which protein?
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?
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?
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?
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?
What is the significance of observing 'ghost cells' in a tissue sample?
What is the significance of observing 'ghost cells' in a tissue sample?
In the context of cellular adaptations, what distinguishes hyperplasia from hypertrophy?
In the context of cellular adaptations, what distinguishes hyperplasia from hypertrophy?
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?
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?
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?
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?
A biopsy of the gallbladder reveals cholesterol crystals and macrophages filled with lipid. Which of the following best describes this finding?
A biopsy of the gallbladder reveals cholesterol crystals and macrophages filled with lipid. Which of the following best describes this finding?
What is the primary role of Glucose-6-Phosphate Dehydrogenase (G6PD) in the context of cellular injury and free radical defense?
What is the primary role of Glucose-6-Phosphate Dehydrogenase (G6PD) in the context of cellular injury and free radical defense?
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?
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?
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?
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?
Which cellular adaptation involves a change in cell phenotype and is most likely to occur in epithelial cells?
Which cellular adaptation involves a change in cell phenotype and is most likely to occur in epithelial cells?
Which of the following mechanisms primarily accounts for cellular atrophy observed in skeletal muscle due to prolonged immobilization?
Which of the following mechanisms primarily accounts for cellular atrophy observed in skeletal muscle due to prolonged immobilization?
Left ventricular hypertrophy (LVH) can arise from both physiologic and pathologic conditions. Which of the following represents a physiologic cause of LVH?
Left ventricular hypertrophy (LVH) can arise from both physiologic and pathologic conditions. Which of the following represents a physiologic cause of LVH?
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?
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?
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?
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?
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?
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?
Hypoxia is a common cause of cell injury. Which of the following mechanisms directly leads to cellular swelling during hypoxia?
Hypoxia is a common cause of cell injury. Which of the following mechanisms directly leads to cellular swelling during hypoxia?
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?
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?
How do antioxidants, such as vitamins A, C, and E, protect cells from injury caused by free radicals?
How do antioxidants, such as vitamins A, C, and E, protect cells from injury caused by free radicals?
Which of the following enzymes is responsible for converting superoxide radicals into hydrogen peroxide, an intermediate step in neutralizing free radicals?
Which of the following enzymes is responsible for converting superoxide radicals into hydrogen peroxide, an intermediate step in neutralizing free radicals?
What is the primary role of metal carrier proteins like transferrin and ceruloplasmin in protecting cells from free radical damage?
What is the primary role of metal carrier proteins like transferrin and ceruloplasmin in protecting cells from free radical damage?
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?
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?
Which morphological feature is characteristic of reversible cell injury, and what cellular process underlies this adaptation?
Which morphological feature is characteristic of reversible cell injury, and what cellular process underlies this adaptation?
What is the sequence of nuclear changes observed during necrosis, representing the progression from reversible to irreversible cell injury?
What is the sequence of nuclear changes observed during necrosis, representing the progression from reversible to irreversible cell injury?
Which of the following best describes the histological appearance of 'ghost cells,' and under what conditions are they typically observed?
Which of the following best describes the histological appearance of 'ghost cells,' and under what conditions are they typically observed?
How does alcohol contribute to steatosis (fatty change) in the liver, and what outcome underscores the reversibility of this cell injury?
How does alcohol contribute to steatosis (fatty change) in the liver, and what outcome underscores the reversibility of this cell injury?
What is the mechanism by which cell swelling occurs due to dysfunction of the sodium-potassium pump after exposure to hypoxia?
What is the mechanism by which cell swelling occurs due to dysfunction of the sodium-potassium pump after exposure to hypoxia?
Which event involving mitochondria is a critical step in the initiation of apoptosis during irreversible cell injury?
Which event involving mitochondria is a critical step in the initiation of apoptosis during irreversible cell injury?
Why do accumulations of substances typically occur under pathological conditions, and how does recognizing these accumulations contribute to understanding disease?
Why do accumulations of substances typically occur under pathological conditions, and how does recognizing these accumulations contribute to understanding disease?
Steatosis involves fat accumulation within the liver. How does non-alcoholic steatohepatitis (NASH) differ from alcoholic steatosis in terms of causation and potential outcomes?
Steatosis involves fat accumulation within the liver. How does non-alcoholic steatohepatitis (NASH) differ from alcoholic steatosis in terms of causation and potential outcomes?
What is the pathological significance of finding cholesterol accumulations in the gallbladder, and how does this relate to the formation of atherosclerotic plaques?
What is the pathological significance of finding cholesterol accumulations in the gallbladder, and how does this relate to the formation of atherosclerotic plaques?
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?
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?
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?
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?
Dystrophic calcification differs from metastatic calcification. Which condition is most closely associated with metastatic calcification?
Dystrophic calcification differs from metastatic calcification. Which condition is most closely associated with metastatic calcification?
What is the diagnostic utility of performing a Congo red stain, and what change observed under polarized light confirms the presence of amyloid protein?
What is the diagnostic utility of performing a Congo red stain, and what change observed under polarized light confirms the presence of amyloid protein?
How does Alpha-1 antitrypsin deficiency lead to protein accumulation within hepatocytes, and what is the impact of this accumulation on liver function?
How does Alpha-1 antitrypsin deficiency lead to protein accumulation within hepatocytes, and what is the impact of this accumulation on liver function?
A researcher discovers accumulation of lipid droplets within cells, but does not know the precise mechanism. Dysfunctional metabolism of which molecule is most likely?
A researcher discovers accumulation of lipid droplets within cells, but does not know the precise mechanism. Dysfunctional metabolism of which molecule is most likely?
A pathologist identifies several yellow streaks on the internal surface of the aorta during autopsy. What condition is characterized by this finding?
A pathologist identifies several yellow streaks on the internal surface of the aorta during autopsy. What condition is characterized by this finding?
A clinical sample contains macrophages laden with carbon pigment. The patient history should be checked for which exposure?
A clinical sample contains macrophages laden with carbon pigment. The patient history should be checked for which exposure?
Microscopic analysis of a liver biopsy reveals golden-brown pigment that can be further characterized with a Prussian blue stain. What is this pigment?
Microscopic analysis of a liver biopsy reveals golden-brown pigment that can be further characterized with a Prussian blue stain. What is this pigment?
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?
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?
Under what circumstances does metastatic calcification occur, and how does it differ from dystrophic calcification?
Under what circumstances does metastatic calcification occur, and how does it differ from dystrophic calcification?
A patient presents with neurofibrillary tangles found in neurons. Which protein is most closely associated?
A patient presents with neurofibrillary tangles found in neurons. Which protein is most closely associated?
Plasma cells are found histologically with globular endoplasmic reticula. What accumulates in cytoplasmic vesicles?
Plasma cells are found histologically with globular endoplasmic reticula. What accumulates in cytoplasmic vesicles?
During oxidative phosphorylation, which specific event leads to the formation of reactive oxygen species (ROS) or free radicals?
During oxidative phosphorylation, which specific event leads to the formation of reactive oxygen species (ROS) or free radicals?
During inflammation, phagocytes produce superoxide ions and hydrogen peroxide. Which enzyme primarily generates superoxide ions, initiating this respiratory burst used to kill pathogens?
During inflammation, phagocytes produce superoxide ions and hydrogen peroxide. Which enzyme primarily generates superoxide ions, initiating this respiratory burst used to kill pathogens?
How does ionizing radiation lead to the formation of free radicals, and what specific molecule is most directly affected by this process?
How does ionizing radiation lead to the formation of free radicals, and what specific molecule is most directly affected by this process?
During the metabolism of drugs like acetaminophen, how can free radicals be generated, and what organ is most susceptible to damage from this process?
During the metabolism of drugs like acetaminophen, how can free radicals be generated, and what organ is most susceptible to damage from this process?
In the context of cellular adaptation to chronic stress, which of the following best describes the role of transcription factors?
In the context of cellular adaptation to chronic stress, which of the following best describes the role of transcription factors?
Which of the following scenarios best illustrates a pathologic consequence of cellular hypertrophy?
Which of the following scenarios best illustrates a pathologic consequence of cellular hypertrophy?
Which cellular process is most directly inhibited by a reduction in ATP availability during cell injury?
Which cellular process is most directly inhibited by a reduction in ATP availability during cell injury?
In a patient with chronic obstructive pulmonary disease (COPD) due to smoking, squamous metaplasia in the trachea serves primarily as:
In a patient with chronic obstructive pulmonary disease (COPD) due to smoking, squamous metaplasia in the trachea serves primarily as:
Which of the following molecular events is most critical in initiating apoptosis following irreversible cell injury?
Which of the following molecular events is most critical in initiating apoptosis following irreversible cell injury?
Which mechanism directly accounts for cellular swelling during the initial stages of reversible cell injury due to hypoxia?
Which mechanism directly accounts for cellular swelling during the initial stages of reversible cell injury due to hypoxia?
In the context of free radical injury, how do metal carrier proteins like transferrin and ceruloplasmin protect cells from damage?
In the context of free radical injury, how do metal carrier proteins like transferrin and ceruloplasmin protect cells from damage?
After an ischemic event, reperfusion can paradoxically exacerbate cell injury. Which of the following mechanisms primarily accounts for this reperfusion injury?
After an ischemic event, reperfusion can paradoxically exacerbate cell injury. Which of the following mechanisms primarily accounts for this reperfusion injury?
Why does steatosis (fatty change) frequently occur in the liver of chronic alcohol abusers?
Why does steatosis (fatty change) frequently occur in the liver of chronic alcohol abusers?
What is the role of glucose-6-phosphate dehydrogenase (G6PD) in protecting cells against oxidative stress?
What is the role of glucose-6-phosphate dehydrogenase (G6PD) in protecting cells against oxidative stress?
How does ionizing radiation cause cellular injury?
How does ionizing radiation cause cellular injury?
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?
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?
In the context of accumulation disorders, what is the underlying mechanism in alpha-1 antitrypsin deficiency that leads to protein accumulation in hepatocytes?
In the context of accumulation disorders, what is the underlying mechanism in alpha-1 antitrypsin deficiency that leads to protein accumulation in hepatocytes?
What is the role of NADPH oxidase in phagocytes during the inflammatory response?
What is the role of NADPH oxidase in phagocytes during the inflammatory response?
What is the significance of observing 'ghost cells' in histological samples?
What is the significance of observing 'ghost cells' in histological samples?
Dystrophic calcification often occurs in areas of tissue damage or necrosis. What is the primary mechanism by which calcium is deposited in these areas?
Dystrophic calcification often occurs in areas of tissue damage or necrosis. What is the primary mechanism by which calcium is deposited in these areas?
Congo red staining is used to identify amyloid deposits in tissues. What specific change observed under polarized light confirms the presence of amyloid?
Congo red staining is used to identify amyloid deposits in tissues. What specific change observed under polarized light confirms the presence of amyloid?
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?
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?
Patients taking acetaminophen may be at risk for liver damage. Why?
Patients taking acetaminophen may be at risk for liver damage. Why?
Flashcards
Cellular Adaptations
Cellular Adaptations
Reversible changes in response to persistent stress, allowing cells to adapt. Number, size, phenotype, or metabolic activity of cells
Atrophy
Atrophy
Decrease in organ size or cell number, often due to reduced demand or blood supply.
Hypertrophy
Hypertrophy
Increase in cell size, leading to enlarged organ size, without cell division.
Hyperplasia
Hyperplasia
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Metaplasia
Metaplasia
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Hypoxia
Hypoxia
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Free Radicals
Free Radicals
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Reperfusion Injury
Reperfusion Injury
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Antioxidants
Antioxidants
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Reversible Cell Injury
Reversible Cell Injury
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Irreversible Cell Injury
Irreversible Cell Injury
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Pyknosis
Pyknosis
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Karyorrhexis
Karyorrhexis
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Karyolysis
Karyolysis
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Necrosis
Necrosis
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Calcium Accumulation
Calcium Accumulation
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Cellular Accumulations
Cellular Accumulations
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Steatosis
Steatosis
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Anthracosis
Anthracosis
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Dystrophic Calcification
Dystrophic Calcification
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Metastatic Calcification
Metastatic Calcification
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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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