Cellular Injury and Hypoxia Basics
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Questions and Answers

What is the hallmark of irreversible injury in cells?

  • Increased protein synthesis
  • Membrane damage (correct)
  • Cellular swelling
  • Cytosolic enzyme activation

    • What occurs as a result of mitochondrial membrane damage?

  • Enhanced protein synthesis
  • Reduction of cytosolic calcium
  • Increased ribosome activity
  • Loss of the electron transport chain (correct)

    • What effect does plasma membrane damage have on the cytosolic environment?

  • Increased ATP production
  • Stabilization of lysosomal membranes
  • Decreased cellular calcium levels
  • Leakage of cytosolic enzymes (correct)

    • Which of the following is activated by high intracellular calcium due to lysosomal membrane damage?

    <p>Hydrolytic enzymes</p> Signup and view all the answers

    The ultimate outcome of irreversible cellular injury is primarily characterized by what?

    <p>Cell death</p> Signup and view all the answers

    Which type of injury is characterized by decreased blood flow through an organ?

    <p>Ischemia</p> Signup and view all the answers

    Which of the following is the final electron acceptor in the electron transport chain?

    <p>Oxygen</p> Signup and view all the answers

    What is the likely outcome of slowly developing ischemia, such as renal artery atherosclerosis?

    <p>Atrophy</p> Signup and view all the answers

    Which condition results from decreased arterial perfusion?

    <p>Atherosclerosis</p> Signup and view all the answers

    Which of the following is NOT a cause of hypoxia?

    <p>Nutritional excess</p> Signup and view all the answers

    What happens to ATP production when oxygen levels are decreased?

    <p>Decreases markedly</p> Signup and view all the answers

    Which scenario best describes a diffusion defect in relation to hypoxemia?

    <p>Interstitial pulmonary fibrosis affecting oxygen transfer</p> Signup and view all the answers

    Which condition may result from a right-to-left shunt?

    <p>V/Q mismatch</p> Signup and view all the answers

    What is the typical effect of carbon monoxide (CO) on hemoglobin?

    <p>It binds hemoglobin more avidly than oxygen.</p> Signup and view all the answers

    What physiological effect characterizes methemoglobinemia?

    <p>Oxidation of iron in heme to Fe3+.</p> Signup and view all the answers

    What is a classic finding associated with carbon monoxide poisoning?

    <p>Cherry-red appearance of the skin.</p> Signup and view all the answers

    What is the initial phase of injury in cellular damage characterized by?

    <p>Cytosol swelling and loss of microvilli.</p> Signup and view all the answers

    What happens to the Na+-K+ pump during hypoxia?

    <p>It is disrupted, causing sodium buildup in the cell.</p> Signup and view all the answers

    What is the treatment for methemoglobinemia?

    <p>Intravenous methylene blue.</p> Signup and view all the answers

    What metabolic change occurs due to lactic acid buildup in hypoxic conditions?

    <p>Decreased pH leading to protein denaturation.</p> Signup and view all the answers

    Which of the following is a consequence of significant carbon monoxide exposure?

    <p>Coma and potential death.</p> Signup and view all the answers

    The swelling of the rough endoplasmic reticulum (RER) is associated with increased ribosome activity and enhanced protein synthesis.

    <p>False</p> Signup and view all the answers

    Membrane damage is considered the hallmark of reversible injury in cells.

    <p>False</p> Signup and view all the answers

    Lysosomal membrane damage does not affect the release of hydrolytic enzymes into the cytosol.

    <p>False</p> Signup and view all the answers

    The leakage of cytochrome c into the cytosol activates apoptosis only in the absence of mitochondrial membrane damage.

    <p>False</p> Signup and view all the answers

    Damage to the plasma membrane allows cytosolic enzymes to leak into the serum, such as cardiac troponin.

    <p>True</p> Signup and view all the answers

    Ischemia can occur due to decreased venous drainage from an organ.

    <p>True</p> Signup and view all the answers

    Neurons are less susceptible to ischemic injury compared to skeletal muscle.

    <p>False</p> Signup and view all the answers

    Hypoxemia is characterized by a low partial pressure of carbon dioxide in the blood.

    <p>False</p> Signup and view all the answers

    Atherosclerosis can lead to decreased arterial perfusion and subsequent ischemia.

    <p>True</p> Signup and view all the answers

    Acute ischemia can lead to atrophy in affected tissues.

    <p>False</p> Signup and view all the answers

    Decreased oxygen delivery can impair ATP production by affecting oxidative phosphorylation.

    <p>True</p> Signup and view all the answers

    Hypoventilation can contribute to hypoxemia by increasing the partial pressure of oxygen in the blood.

    <p>False</p> Signup and view all the answers

    Anemia results in a decrease in red blood cell mass but does not affect the partial pressure of oxygen in the blood.

    <p>True</p> Signup and view all the answers

    Carbon monoxide binds hemoglobin less avidly than oxygen, resulting in normal Pao2 but decreased Sao2.

    <p>False</p> Signup and view all the answers

    A classic finding of methemoglobinemia is cyanosis with chocolate-colored blood.

    <p>True</p> Signup and view all the answers

    Early signs of carbon monoxide exposure include coma and death.

    <p>False</p> Signup and view all the answers

    Reversible cellular injury is characterized by significant membrane damage and cell death.

    <p>False</p> Signup and view all the answers

    The treatment for methemoglobinemia involves intravenous methylene blue to restore Fe3+ to Fe2+ state.

    <p>True</p> Signup and view all the answers

    During hypoxia, the Na+-K+ pump's dysfunction leads to sodium and water accumulation in the cell.

    <p>True</p> Signup and view all the answers

    Lactic acid buildup during anaerobic glycolysis raises the pH of the cell.

    <p>False</p> Signup and view all the answers

    The classic finding associated with carbon monoxide poisoning is a cherry-red appearance of the skin.

    <p>True</p> Signup and view all the answers

    What role does oxygen play in oxidative phosphorylation?

    <p>Oxygen serves as the final electron acceptor in the electron transport chain.</p> Signup and view all the answers

    How does slowly developing ischemia differ from acute ischemia in its effects on tissues?

    <p>Slowly developing ischemia leads to atrophy of tissues, while acute ischemia results in immediate injury.</p> Signup and view all the answers

    What are the primary causes of hypoxemia mentioned in the content?

    <p>Hypoxemia can be caused by high altitude, hypoventilation, diffusion defects, and V/Q mismatch.</p> Signup and view all the answers

    How does decreased oxygen delivery lead to cellular injury?

    <p>Decreased oxygen delivery impairs ATP production due to disrupted oxidative phosphorylation.</p> Signup and view all the answers

    What physiological impact does a right-to-left shunt have on oxygenation?

    <p>A right-to-left shunt causes blood to bypass oxygenated lung areas, reducing oxygenation in the blood.</p> Signup and view all the answers

    Describe how trauma can lead to cellular injury.

    <p>Trauma causes direct physical damage, which can disrupt cellular integrity and function.</p> Signup and view all the answers

    How does anemia affect oxygen levels in the blood despite normal Pao2 and Sao2?

    <p>Anemia reduces the total red blood cell mass, affecting the blood's oxygen-carrying capacity.</p> Signup and view all the answers

    What condition can arise due to generalized hypotension and poor tissue perfusion?

    <p>Shock can result from generalized hypotension, leading to inadequate blood flow and cellular injury.</p> Signup and view all the answers

    How does lysosomal membrane damage contribute to cellular injury in the context of high intracellular calcium?

    <p>Lysosomal membrane damage leads to the leakage of hydrolytic enzymes into the cytosol, where they become activated by high intracellular calcium, exacerbating cell damage.</p> Signup and view all the answers

    Explain the consequences of mitochondrial membrane damage on apoptosis.

    <p>Mitochondrial membrane damage causes cytochrome c to leak into the cytosol, which triggers the apoptotic pathways, leading to programmed cell death.</p> Signup and view all the answers

    What role does plasma membrane damage play in the release of cardiac troponin into the serum?

    <p>Damage to the plasma membrane allows cytosolic enzymes, including cardiac troponin, to leak into the serum, indicating myocardial injury.</p> Signup and view all the answers

    Discuss the relationship between rough endoplasmic reticulum swelling and protein synthesis.

    <p>Swelling of the rough endoplasmic reticulum results in the dissociation of ribosomes, leading to decreased protein synthesis despite the organelle's initial role in producing proteins.</p> Signup and view all the answers

    What is the end result of irreversible cellular injury, and how is it identified?

    <p>The end result of irreversible cellular injury is cell death, which is identified by hallmark indicators such as membrane damage and enzyme leakage.</p> Signup and view all the answers

    How does carbon monoxide (CO) interfere with the body's ability to utilize oxygen?

    <p>Carbon monoxide binds to hemoglobin more avidly than oxygen, preventing effective oxygen transport.</p> Signup and view all the answers

    What clinical finding is commonly associated with carbon monoxide poisoning and why?

    <p>A classic finding is the cherry-red appearance of the skin, due to carboxyhemoglobin formation.</p> Signup and view all the answers

    What is the primary effect of hypoxia on cellular metabolism?

    <p>Hypoxia impairs oxidative phosphorylation, leading to decreased ATP production.</p> Signup and view all the answers

    What are the signs of reversible cellular injury, and what causes this condition?

    <p>Reversible injury is marked by cellular swelling and loss of microvilli, often due to low ATP levels.</p> Signup and view all the answers

    How does methemoglobinemia affect oxygen transport in the blood?

    <p>Methemoglobinemia occurs when iron in heme is oxidized to Fe3+, impairing oxygen binding.</p> Signup and view all the answers

    What metabolic shift occurs during anaerobic glycolysis as a consequence of hypoxia?

    <p>There is a switch to anaerobic glycolysis, leading to lactic acid buildup.</p> Signup and view all the answers

    What is a key treatment for methemoglobinemia, and how does it work?

    <p>Intravenous methylene blue is the treatment for methemoglobinemia, reducing Fe3+ back to Fe2+.</p> Signup and view all the answers

    What initial cellular response is observed in cases of hypoxia, and what is its significance?

    <p>The initial response is cellular swelling, which is a hallmark of reversible injury.</p> Signup and view all the answers

    Carbon monoxide binds hemoglobin more avidly than ______.

    <p>oxygen</p> Signup and view all the answers

    A classic finding of carbon monoxide poisoning is a ______-red appearance of the skin.

    <p>cherry</p> Signup and view all the answers

    Methemoglobinemia occurs when iron in heme is oxidized to ______ which cannot bind oxygen.

    <p>Fe3+</p> Signup and view all the answers

    Cellular injury occurs when a stress exceeds the cell's ability to ______.

    <p>adapt</p> Signup and view all the answers

    The treatment for methemoglobinemia is intravenous ______ to reduce Fe3+ back to Fe2+.

    <p>methylene blue</p> Signup and view all the answers

    Early signs of significant carbon monoxide exposure can lead to ______ and death.

    <p>coma</p> Signup and view all the answers

    Neurons are highly susceptible to ______ injury, whereas skeletal muscle is relatively more resistant.

    <p>ischemic</p> Signup and view all the answers

    Hypoxia is characterized by low oxygen delivery to ______.

    <p>tissue</p> Signup and view all the answers

    During hypoxia, a dysfunction in the Na+-K+ pump results in sodium and ______ accumulation in the cell.

    <p>water</p> Signup and view all the answers

    Decreased oxygen impairs oxidative phosphorylation, resulting in decreased ______ production.

    <p>ATP</p> Signup and view all the answers

    The hallmark of reversible injury in cells is ______ swelling.

    <p>cellular</p> Signup and view all the answers

    Lactic acid buildup during anaerobic glycolysis results in low ______, which can denature proteins.

    <p>pH</p> Signup and view all the answers

    Ischemia is defined as decreased blood flow through an ______.

    <p>organ</p> Signup and view all the answers

    Hypoxemia arises from a low partial pressure of oxygen in the ______.

    <p>blood</p> Signup and view all the answers

    Decreased O2-carrying capacity arises with hemoglobin loss or ______.

    <p>dysfunction</p> Signup and view all the answers

    A classic condition associated with decreased arterial perfusion is ______.

    <p>atherosclerosis</p> Signup and view all the answers

    Swelling of the rough endoplasmic reticulum (RER) results in dissociation of ______ and decreased protein synthesis.

    <p>ribosomes</p> Signup and view all the answers

    The hallmark of irreversible injury is ______ damage.

    <p>membrane</p> Signup and view all the answers

    Plasma membrane damage leads to cytosolic enzymes leaking into the serum, such as ______ troponin.

    <p>cardiac</p> Signup and view all the answers

    Mitochondrial membrane damage results in cytochrome c leaking into the ______, which activates apoptosis.

    <p>cytosol</p> Signup and view all the answers

    The end result of irreversible injury is ______ death.

    <p>cell</p> Signup and view all the answers

    Match the following conditions with their characteristics:

    <p>Carbon monoxide poisoning = Classic finding is cherry-red appearance of skin. Methemoglobinemia = Classic finding is cyanosis with chocolate-colored blood. Hypoxia = Impairment of oxidative phosphorylation resulting in decreased ATP. Reversible injury = Hallmarked by cellular swelling and membrane blebbing.</p> Signup and view all the answers

    Match the following causes with their associated symptoms:

    <p>Carbon monoxide exposure = Early sign includes headache and may lead to coma. Oxidant stress = Associated with methemoglobinemia due to drugs. Decreased ATP = Leads to sodium and water accumulation in the cell. Lactic acid accumulation = Results in low pH and protein denaturation.</p> Signup and view all the answers

    Match the following treatments with their applicable conditions:

    <p>Intravenous methylene blue = Treatment for methemoglobinemia. Oxygen therapy = Common intervention for carbon monoxide poisoning. Sodium replacement = Counteracts sodium buildup in hypoxic conditions. Antioxidants = Potential adjunct treatment in oxidant stress cases.</p> Signup and view all the answers

    Match the following types of injury with their effects:

    <p>Reversible cellular injury = Characterized by loss of microvilli. Irreversible injury = Ultimate outcome leads to cell death. Hypoxia = Causes a switch to anaerobic glycolysis. Chronic ischemia = Leads to atrophy in affected tissues.</p> Signup and view all the answers

    Match the following concepts with their correct definitions:

    <p>PaO2 normal = Partial pressure of oxygen remains unaffected. SaO2 decreased = Oxygen saturation is reduced. Lactic acidosis = Condition resulting from anaerobic metabolism. Cellular swelling = Initial phase of reversible cellular injury.</p> Signup and view all the answers

    Match the following symptoms with their related causes:

    <p>Headache = Early sign of carbon monoxide exposure. Dizziness = Resulting from hypoxia. Skin discoloration = Classic sign of carbon monoxide poisoning. Cyanosis = Classic sign of methemoglobinemia.</p> Signup and view all the answers

    Match the following effects with their corresponding cellular components:

    <p>Na+-K+ pump dysfunction = Causes sodium and water buildup. Ca2+ pump failure = Results in Ca2+ accumulation in cytosol. Oxidative phosphorylation impairment = Leads to decreased ATP production. Membrane blebbing = Indicator of reversible cellular injury.</p> Signup and view all the answers

    Match the following types of injuries with their underlying mechanisms:

    <p>Hypoxia = Decreased oxygen availability. Methemoglobinemia = Oxidation of iron in heme to Fe3+. Carbon monoxide poisoning = CO binds hemoglobin more avidly than O2. Chronic ischemia = Reduced blood flow affecting organ perfusion.</p> Signup and view all the answers

    Match the following causes of hypoxia with their descriptions:

    <p>Ischemia = Decreased blood flow through an organ Hypoxemia = Low partial pressure of oxygen in the blood Decreased O2-carrying capacity = Results from hemoglobin loss or dysfunction High altitude = Decreased barometric pressure resulting in decreased PAo2</p> Signup and view all the answers

    Match the following types of cellular injury with their characteristics:

    <p>Acute ischemia = Rapid tissue injury due to sudden loss of blood flow Chronic ischemia = Slow progressive tissue atrophy due to reduced blood supply Hypoxemia = Characterized by low oxygen saturation in blood Trauma = Physical damage leading to cell injury</p> Signup and view all the answers

    Match the terms related to oxidative phosphorylation with their roles:

    <p>Oxygen = Final electron acceptor in the electron transport chain ATP = Essential energy source for cellular functions Electron transport chain = Site of ATP production in cells Oxidative phosphorylation = Process that produces ATP using oxygen</p> Signup and view all the answers

    Match the following conditions with their causes:

    <p>Anemia = Decrease in red blood cell mass Hypoventilation = Increased partial pressure of carbon dioxide in blood Right-to-left shunt = Circulation problem where blood bypasses oxygenated lung Interstitial pulmonary fibrosis = Thickened diffusion barrier affecting oxygen transfer</p> Signup and view all the answers

    Match the following conditions with their effects on oxygen levels:

    <p>Atherosclerosis = Decreased arterial perfusion leading to ischemia Budd-Chiari syndrome = Decreased venous drainage from the liver Shock = Generalized hypotension affecting tissue perfusion Hypoxemia = Low oxygen levels in blood causing potential cellular injury</p> Signup and view all the answers

    Match the following physiological terms with their definitions:

    <p>V/Q mismatch = Ventilation problem or circulation problem affecting oxygenation Barometric pressure = Atmospheric pressure affecting oxygen levels at high altitude Partial pressure of oxygen = Measured as PAo2 in arterial blood Decreased venous drainage = Cause of ischemia from impaired blood return</p> Signup and view all the answers

    Match the following causes of cellular injury with the examples provided:

    <p>Inflammation = Can damage healthy tissue and lead to injury Nutritional excess = May result in cellular dysfunction and injury Genetic mutations = Cause of inherent cellular injuries leading to disease Trauma = Direct physical injury to cells causing immediate damage</p> Signup and view all the answers

    Match the following types of cellular metabolism with their requirements:

    <p>Aerobic metabolism = Requires oxygen to produce ATP Anaerobic glycolysis = Occurs in low oxygen conditions to generate energy Oxidative phosphorylation = Dependent on a sufficient oxygen supply Lactic acid production = Result of anaerobic conditions affecting pH</p> Signup and view all the answers

    Match the following types of membrane damage with their resulting effects:

    <p>Plasma membrane damage = Cytosolic enzymes leaking into serum Mitochondrial membrane damage = Loss of electron transport chain Lysosomal membrane damage = Hydrolytic enzymes leaking into cytosol Cytosolic calcium increase = Activation of apoptosis related to mitochondria</p> Signup and view all the answers

    Match the following descriptions with their corresponding membrane types affected during irreversible injury:

    <p>Plasma membrane = Allows cytosolic enzymes to leak out Mitochondrial membrane = Leads to the release of cytochrome c Lysosomal membrane = Releases hydrolytic enzymes upon damage Electron transport chain = Impacts ATP synthesis in the cell</p> Signup and view all the answers

    Match the following statements with the type of injury they describe:

    <p>Hydrolytic enzymes released = Lysosomal membrane damage Electron transport chain impairment = Mitochondrial membrane damage Cytosolic enzyme leakage = Plasma membrane damage Cell death = Final consequence of irreversible injury</p> Signup and view all the answers

    Match the following effects of membrane damage with their associated outcomes:

    <p>Cytosolic enzymes leaking = Resulting serum changes like cardiac troponin elevation Calcium influx = Events leading to cell dysfunction and apoptosis Cytochrome c leakage = Triggers the apoptotic process Hydrolytic enzyme leakage = Activation by high intracellular calcium</p> Signup and view all the answers

    Match the following irreversible injury phenomena with their descriptions:

    <p>Mitochondrial membrane damage = Loss of ATP production capacity Plasma membrane damage = Serum enzymatic alterations Lysosomal membrane damage = Increased cytosolic enzyme activity Cell death = Ultimate consequence of irreversible cell injury</p> Signup and view all the answers

    Study Notes

    Cellular Injury

    • Cellular injury occurs when a stress is too much for a cell to adapt to.
    • Factors determining injury severity:
      • Type of stress
      • Severity of stress
      • Type of cell affected
      • Examples: Neurons are highly susceptible to ischemic injury, while skeletal muscle is more resistant; Slowly developing ischemia (e.g., renal artery atherosclerosis) causes atrophy, while acute ischemia (e.g., renal artery embolus) causes injury
    • Common causes of cellular injury:
      • Inflammation
      • Nutritional deficiency or excess
      • Hypoxia
      • Trauma
      • Genetic mutations

    Hypoxia

    • Definition: Low oxygen delivery to tissue, a major cause of cellular injury.

    • Mechanism of cellular injury:

      • Oxygen is the final electron acceptor in the electron transport chain of oxidative phosphorylation.
      • Decreased oxygen impairs oxidative phosphorylation, leading to decreased ATP production.
      • Lack of ATP (the cell's energy source) causes cellular damage.

    • Causes of hypoxia:

      • Ischemia: Decreased blood flow through an organ
        • Can arise from:
          • Decreased arterial perfusion (e.g., atherosclerosis)
          • Decreased venous drainage (e.g., Budd-Chiari syndrome)
          • Shock (generalized hypotension leading to poor tissue perfusion)
      • Hypoxemia: Low partial pressure of oxygen in the blood (PaO2 < 60 mm Hg, SaO2 < 90%)
        • Can arise from:
          • High altitude (decreased barometric pressure leads to lower partial pressure of oxygen in the air)
          • Hypoventilation (increased partial pressure of carbon dioxide in the air leads to lower partial pressure of oxygen in the air)
          • Diffusion defect (a thicker diffusion barrier, like interstitial pulmonary fibrosis, prevents oxygen from moving from the air into the blood as efficiently)
          • Ventilation/perfusion mismatch (blood bypasses oxygenated lung, or oxygenated air cannot reach blood)
      • Decreased oxygen-carrying capacity of blood: Hemoglobin (Hb) loss or dysfunction
        • Examples:
          • Anemia (decrease in red blood cell mass) - PaO2 and SaO2 normal
          • Carbon monoxide poisoning
            • Carbon monoxide binds hemoglobin more avidly than oxygen, PaO2 normal, SaO2 decreased
            • Exposure sources: smoke from fires, exhaust from cars or gas heaters
            • Early sign: headache, more severe exposure: coma and death
            • Classic finding: cherry-red appearance of skin
          • Methemoglobinemia
            • Iron in heme is oxidized to Fe3+, which cannot bind oxygen, PaO2 normal, SaO2 decreased.
            • Seen with oxidant stress (e.g., sulfa and nitrate drugs) or in newborns
            • Classic finding: cyanosis with chocolate-colored blood
            • Treatment: intravenous methylene blue (helps reduce Fe3+ back to Fe2+)

    Reversible and Irreversible Cellular Injury

    • Hypoxia disrupts cellular functions:

      • Na+-K+ pump: Sodium and water build up inside the cell
      • Ca2+ pump: Calcium builds up in the cytosol of the cell
      • Aerobic glycolysis: Switches to anaerobic glycolysis, lactic acid production results in low pH, protein denaturation, and DNA precipitation

    • Initial phase of injury (reversible):

      • Hallmark: Cellular swelling
        • Cytosol swelling: loss of microvilli and membrane blebbing
        • Rough endoplasmic reticulum (RER) swelling: dissociation of ribosomes, decreased protein synthesis

    • Irreversible phase of injury:

      • Hallmark: Membrane damage
        • Plasma membrane damage:
          • Cytosolic enzymes leak into the serum (e.g., cardiac troponin)
          • Increase in calcium entry into the cell
        • Mitochondrial membrane damage:
          • Loss of the electron transport chain (inner mitochondrial membrane)
          • Cytochrome c leaks into cytosol (activates apoptosis)
        • Lysosome membrane damage:
          • Hydrolytic enzymes leak into the cytosol, activated by high intracellular calcium

    • End result of irreversible injury: Cell death.

    Cell Injury

    • Cellular injury occurs when stress exceeds the cell’s ability to adapt.
    • The likelihood of injury depends on the type of stress, its severity, and the type of cell affected.
      • Neurons are highly susceptible to ischemic injury, while skeletal muscle is relatively more resistant.
      • Slowly developing ischemia results in atrophy, whereas acute ischemia leads to injury.
    • Common causes of cellular injury include inflammation, nutritional deficiency or excess, hypoxia, trauma, and genetic mutations.

    Hypoxia

    • Low oxygen delivery to tissue, a significant cause of cellular injury.
      • Oxygen is the final electron acceptor in the electron transport chain of oxidative phosphorylation.
      • Decreased oxygen impairs oxidative phosphorylation, resulting in decreased ATP production.
      • Lack of ATP (essential energy source) leads to cellular injury.
    • Causes of hypoxia: ischemia, hypoxemia, and decreased O2-carrying capacity of blood.
    • Ischemia is decreased blood flow through an organ.
      • Decreased arterial perfusion (e.g., atherosclerosis)
      • Decreased venous drainage (e.g., Budd-Chiari syndrome)
      • Shock - generalized hypotension resulting in poor tissue perfusion.

    Hypoxemia

    • Low partial pressure of oxygen in the blood (Pao2 < 60 mm Hg, Sao2 < 90%).
      • High altitude - Decreased barometric pressure results in decreased PAo2.
      • Hypoventilation - Increased PAco2 results in decreased PAo2.
      • Diffusion defect - PAo2 not able to push as much O2 into the blood due to a thicker diffusion barrier (e.g., interstitial pulmonary fibrosis).
      • V/Q mismatch - Blood bypasses oxygenated lung (circulation problem, e.g., right-to-left shunt), or oxygenated air cannot reach blood (ventilation problem, e.g., atelectasis).

    Decreased O2-carrying capacity

    • Arises with hemoglobin (Hb) loss or dysfunction.
      • Anemia (decrease in RBC mass) - Pao2 normal; Sao2 normal.
      • Carbon monoxide poisoning
        • CO binds hemoglobin more avidly than oxygen - Pao2 normal; Sao2 decreased.
        • Exposures include smoke from fires and exhaust from cars or gas heaters.
        • Classic finding is cherry-red appearance of skin.
        • Early sign of exposure is headache; significant exposure leads to coma and death.
      • Methemoglobinemia
        • Iron in heme is oxidized to Fe3+, which cannot bind oxygen - Pao2 normal; Sao2 decreased.
        • Seen with oxidant stress (e.g., sulfa and nitrate drugs) or in newborns.
        • Classic finding is cyanosis with chocolate-colored blood.
        • Treatment is intravenous methylene blue, which helps reduce Fe2+ back to the Fe2+ state.

    Reversible and Irreversible Cellular Injury

    • Hypoxia impairs oxidative phosphorylation resulting in decreased ATP.

    • Low ATP disrupts key cellular functions:

      • Na+-K+ pump, resulting in sodium and water buildup in the cell.
      • Ca2+ pump, resulting in Ca2+ buildup in the cytosol of the cell.
      • Aerobic glycolysis, resulting in a switch to anaerobic glycolysis. Lactic acid buildup results in low pH, which denatures proteins and precipitates DNA.

    • The initial phase of injury is reversible.

      • The hallmark of reversible injury is cellular swelling.
        • Cytosol swelling results in loss of microvilli and membrane blebbing.
        • Swelling of the rough endoplasmic reticulum (RER) results in dissociation of ribosomes and decreased protein synthesis.

    • Eventually, the damage becomes irreversible.

      • The hallmark of irreversible injury is membrane damage.
        • Plasma membrane damage:
          • Cytosolic enzymes leaking into the serum (e.g., cardiac troponin).
          • Additional calcium entering into the cell.
        • Mitochondrial membrane damage:
          • Loss of the electron transport chain (inner mitochondrial membrane).
          • Cytochrome c leaking into cytosol (activates apoptosis).
        • Lysosome membrane damage results in hydrolytic enzymes leaking into the cytosol, which, in turn, are activated by the high intracellular calcium.

    • The end result of irreversible injury is cell death.

    Cellular Injury

    • Cellular injury happens when stress exceeds the cell's ability to adapt.
    • The likelihood of injury depends on the type of stress, its severity, and the kind of cell.
    • Neurons are highly susceptible to ischemic injury while skeletal muscle is more resistant.
    • Slowly developing ischemia leads to atrophy, while acute ischemia results in injury.
    • Common causes of cellular injury include inflammation, nutritional deficiencies or excess, hypoxia, trauma, and genetic mutations.

    Hypoxia

    • Low oxygen delivery to tissue is a critical cause of cellular injury.
    • Oxygen is the final electron acceptor in the electron transport chain of oxidative phosphorylation.
    • Decreased oxygen impairs oxidative phosphorylation, leading to decreased ATP production.
    • Lack of ATP disrupts critical cellular functions, causing cell injury.

    Causes of Hypoxia

    • Ischemia: Decreased blood flow through an organ.
      • Decreased arterial perfusion (e.g., atherosclerosis).
      • Decreased venous drainage (e.g., Budd-Chiari syndrome).
      • Shock: Generalized hypotension resulting in poor tissue perfusion.
    • Hypoxemia: Low partial pressure of oxygen in the blood (Pao2 < 60 mm Hg, Sao2 < 90%).
      • High altitude: Decreased barometric pressure reduces PAo2.
      • Hypoventilation: Increased PAco2 reduces PAo2.
      • Diffusion defect: PAo2 struggles to push oxygen into the blood due to a thicker diffusion barrier (e.g., interstitial pulmonary fibrosis).
      • V/Q mismatch: Blood bypasses oxygenated lung (circulation problem, e.g., right-to-left shunt) or oxygenated air can't reach blood (ventilation problem, e.g., atelectasis).
    • Decreased O2-carrying capacity arises with hemoglobin (Hb) loss or dysfunction.
      • Anemia: Decreased red blood cell mass. Pao2 and Sao2 are normal.
      • Carbon monoxide poisoning: Carbon monoxide binds hemoglobin more avidly than oxygen. Pao2 is normal, but Sao2 is decreased.
        • Classic finding is a cherry-red appearance of the skin.
        • Early sign of exposure is headache; significant exposure leads to coma and death.
      • Methemoglobinemia: Iron in heme is oxidized to Fe3+, which cannot bind oxygen. Pao2 is normal, but Sao2 is decreased.
        • Seen with oxidant stress (e.g., sulfa and nitrate drugs) or in newborns.
        • Classic finding is cyanosis with chocolate-colored blood.
        • Treatment is intravenous methylene blue, which helps reduce Fe2+ back to Fe2+ state.

    Reversible and Irreversible Cellular Injury

    • Hypoxia impairs oxidative phosphorylation, resulting in decreased ATP.
    • Low ATP disrupts critical cellular functions.
      • Na+-K+ pump: Leads to sodium and water buildup in the cell.
      • Ca2+ pump: Results in Ca2+ buildup in the cytosol of the cell.
      • Aerobic glycolysis: This shifts to anaerobic glycolysis, leading to lactic acid buildup which lowers pH, denatures proteins, and precipitates DNA.

    Reversible Injury

    • The initial phase of injury is reversible.
    • The hallmark of reversible injury is cellular swelling.
      • Cytosol swelling causes loss of microvilli and membrane blebbing.
      • Swelling of the rough endoplasmic reticulum (RER) results in dissociation of ribosomes and decreased protein synthesis.

    Irreversible Injury

    • Eventually, the damage becomes irreversible.
    • The hallmark of irreversible injury is membrane damage.
      • Plasma membrane damage leads to:
        • Cytosolic enzymes leaking into the serum (e.g., cardiac troponin).
        • Additional calcium entering the cell.
      • Mitochondrial membrane damage results in:
        • Loss of the electron transport chain (inner mitochondrial membrane).
        • Cytochrome c leaking into the cytosol (activates apoptosis).
      • Lysosome membrane damage causes hydrolytic enzymes to leak into the cytosol, which are activated by the high intracellular calcium.

    Cell Death

    • The end result of irreversible injury is cell death.

    Cellular Injury

    • Cell injury occurs when stress exceeds the cell's ability to adapt.
    • The type and severity of stress and the type of cell determine injury likelihood.
      • Neurons are highly susceptible to ischemic injury, while skeletal muscle is more resistant.
      • Slow ischemia leads to atrophy, while acute ischemia results in injury.
    • Common causes of cellular injury include inflammation, nutritional deficiency or excess, hypoxia, trauma, and genetic mutations.

    Hypoxia

    • Low oxygen delivery to tissue is a significant cause of cellular injury.
      • Oxygen is the final electron acceptor in oxidative phosphorylation.
      • Reduced oxygen impairs oxidative phosphorylation, leading to decreased ATP production.
      • Lack of ATP causes cellular injury.
    • Hypoxia can result from ischemia, hypoxemia, or decreased oxygen-carrying capacity of the blood.

    Ischemia

    • Ischemia is reduced blood flow through an organ.
    • It can arise from:
      • Decreased arterial perfusion (e.g., atherosclerosis)
      • Reduced venous drainage (e.g., Budd-Chiari syndrome)
      • Shock - generalized hypotension resulting in poor tissue perfusion

    Hypoxemia

    • Hypoxemia is a low partial pressure of oxygen in the blood (PaO2 < 60 mm Hg, SaO2 < 90%).
    • It can arise from:
      • High altitude - Decreased barometric pressure lowers PAO2
      • Hypoventilation - Increased PAco2 lowers PAO2
      • Diffusion defect - Thicker diffusion barrier (e.g., interstitial pulmonary fibrosis) hinders oxygen transfer from alveoli to blood.
      • V/Q mismatch - Blood bypasses oxygenated lung (circulation problem) or oxygenated air cannot reach blood (ventilation problem).

    Decreased O2-carrying Capacity

    • Decreased oxygen-carrying capacity occurs with hemoglobin loss or dysfunction.
    • Examples include:
      • Anemia (reduced RBC mass) - PaO2 normal; SaO2 normal
      • Carbon monoxide poisoning
        • CO binds to hemoglobin more avidly than oxygen - PaO2 normal; SaO2 decreased.
        • Exposures include smoke from fires and exhaust from cars or gas heaters.
        • Cherry-red skin appearance is a classic finding.
        • Early sign of exposure is headache; significant exposure leads to coma and death.
      • Methemoglobinemia
        • Iron in heme is oxidized to Fe3+, which cannot bind oxygen - PaO2 normal; SaO2 decreased.
        • Seen with oxidant stress (e.g., sulfa and nitrate drugs) or in newborns.
        • Cyanosis with chocolate-colored blood is a classic finding.
        • Treatment is intravenous methylene blue, which helps reduce Fe3+ back to Fe2+ state.

    Reversible and Irreversible Cellular Injury

    • Hypoxia disrupts oxidative phosphorylation, decreasing ATP production.
    • Low ATP affects key cellular functions, leading to:
      • Sodium and water buildup in the cell due to disruption in Na+-K+ pump
      • Calcium buildup in the cytosol of the cell due to Ca2+ pump disruption
      • Switch to anaerobic glycolysis, causing lactic acid buildup and lowering pH, which denatures proteins and precipitates DNA.

    Reversible Injury

    • The initial phase of injury is reversible.
    • Cellular swelling is the hallmark of reversible injury.
      • Cytosol swelling results in loss of microvilli and membrane blebbing
      • Rough endoplasmic reticulum (RER) swelling disrupts ribosomes and decreases protein synthesis.

    Irreversible Injury

    • Once the damage becomes irreversible, it results in membrane damage.
    • The hallmark of irreversible injury is membrane damage:
      • Plasma membrane damage leads to:
        • Cytosolic enzymes leaking into the serum (e.g., cardiac troponin)
        • Additional calcium entering the cell
      • Mitochondrial membrane damage results in:
        • Loss of the electron transport chain (inner mitochondrial membrane)
        • Cytochrome c leaking into cytosol (activates apoptosis)
      • Lysosome membrane damage releases hydrolytic enzymes into the cytosol, which are activated by high intracellular calcium.

    Cell Death

    • Irreversible injury ultimately leads to cell death.

    Cellular Injury

    • When stress exceeds a cell's ability to adapt, cellular injury occurs.
    • The likelihood of injury depends on the type of stress, its severity, and the cell type.
    • Neurons are very vulnerable to ischemic injury, while skeletal muscle is more resistant.
    • Slow developing ischemia (e.g., renal artery atherosclerosis) results in atrophy, whereas acute ischemia (e.g., renal artery embolus) results in injury.
    • Common causes of cellular injury include inflammation, nutritional deficiency or excess, hypoxia, trauma, and genetic mutations.

    Hypoxia

    • Low oxygen delivery to tissue is an important cause of cellular injury.
    • Oxygen is essential for the electron transport chain in oxidative phosphorylation.
    • Decreased oxygen impairs oxidative phosphorylation, leading to decreased ATP production.
    • Lack of ATP disrupts cellular function.
    • Causes of hypoxia include ischemia, hypoxemia, and decreases oxygen-carrying capacity of blood.

    Ischemia

    • Ischemia is reduced blood flow to an organ.
    • It can arise from decreased arterial perfusion (e.g., atherosclerosis), decreased venous drainage (e.g., Budd-Chiari syndrome), and shock, which is generalized hypotension resulting in poor tissue perfusion.

    Hypoxemia

    • Hypoxemia is a low partial pressure of oxygen in the blood (Pao2 < 60 mm Hg, Sao2 < 90%).
    • It arises from:
      • High altitude - Decreased barometric pressure results in decreased PAo2
      • Hypoventilation - Increased PAco2 results in decreased PAo2
      • Diffusion defect - PAo2 struggles to push O2 into the blood due to a thicker diffusion barrier (e.g., interstitial pulmonary fibrosis)
      • V/Q mismatch - Blood bypasses oxygenated lung (circulation problem, e.g., right-to-left shunt), or oxygenated air cannot reach blood (ventilation problem, e.g., atelectasis).

    Decreased O2-Carrying Capacity

    • This arises with hemoglobin (Hb) loss or dysfunction.
    • Examples include:
      • Anemia (decrease in RBC mass)-Pao2 normal; Sao2 normal
      • Carbon monoxide poisoning
        • CO binds hemoglobin more avidly than oxygen-Pao2 normal; Sao2 decreased
        • Exposures include smoke from fires and exhaust from cars or gas heaters.
        • Classic finding is cherry-red appearance of skin.
        • Early sign of exposure is headache; significant exposure leads to coma and death.
      • Methemoglobinemia
        • Iron in heme is oxidized to Fe3+, which cannot bind oxygen-Pao2 normal; Sao2 decreased
        • Seen with oxidant stress (e.g., sulfa and nitrate drugs) or in newborns
        • Classic finding is cyanosis with chocolate-colored blood.
        • Treatment is intravenous methylene blue, which helps reduce Fe2+ back to Fe2+state.

    Reversible and Irreversible Cellular Injury

    • Hypoxia impairs oxidative phosphorylation resulting in decreased ATP.
    • Low ATP disrupts key cellular functions, including:
      • Na+-K+pump, resulting in cellular sodium and water buildup.
      • Ca 2+pump, resulting in Ca2+ buildup in the cytosol.
      • Aerobic glycolysis, resulting in a switch to anaerobic glycolysis. Lactic acid buildup results in low pH, which denatures proteins and precipitates DNA.
    • The initial phase of injury is reversible. The hallmark of reversible injury is cellular swelling.
      • Swelling of the cytosol results in the loss of microvilli and membrane blebbing.
      • Swelling of the rough endoplasmic reticulum (RER) results in dissociation of ribosomes and decreased protein synthesis.
    • Eventually, the damage becomes irreversible. The hallmark of irreversible injury is membrane damage.
      • Plasma membrane damage results in:
        • Cytosolic enzymes leaking into the serum (e.g., cardiac troponin)
        • Additional calcium entering the cell
      • Mitochondrial membrane damage results in:
        • Loss of the electron transport chain (inner mitochondrial membrane)
        • Cytochrome c leaking into the cytosol (activates apoptosis).
      • Lysosome membrane damage results in hydrolytic enzymes leaking into the cytosol, which are then activated by the high intracellular calcium.
    • The end result of irreversible injury is cell death.

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    Growth Adaptations, Cellular Injury, and Cell Death PDF

    Description

    This quiz explores the concepts of cellular injury and hypoxia, focusing on various factors determining injury severity and the mechanisms behind oxygen deficiency. Understand the common causes of cellular injury and their implications for different cell types. Prepare to deepen your understanding of these critical biological processes.

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