Podcast
Questions and Answers
What is the primary component of the pulmonary extracellular matrix?
What is the primary component of the pulmonary extracellular matrix?
- Fibronectin
- Elastin
- Glycoproteins
- Collagen (correct)
Which metabolic process provides energy for lung tissue functions?
Which metabolic process provides energy for lung tissue functions?
- Glucose oxidation (correct)
- Amino acid catabolism
- Protein synthesis
- Fatty acid metabolism
What role do proteoglycans play in pulmonary tissue?
What role do proteoglycans play in pulmonary tissue?
- Mediating cell growth
- Supporting oxygen transport
- Facilitating immune response
- Regulating fluid dynamics (correct)
What is the end product of glycolysis?
What is the end product of glycolysis?
Which pathway can metabolic intermediates from glycolysis enter?
Which pathway can metabolic intermediates from glycolysis enter?
What is the estimated rate of glucose oxidation in lung tissue?
What is the estimated rate of glucose oxidation in lung tissue?
Which of the following best describes the role of integrins in pulmonary tissue?
Which of the following best describes the role of integrins in pulmonary tissue?
What is a product of the tricarboxylic acid (TCA) cycle?
What is a product of the tricarboxylic acid (TCA) cycle?
What is an effect of prolonged exposure to high altitude on red blood cells?
What is an effect of prolonged exposure to high altitude on red blood cells?
How can the decrease in 2,3-BPG in red blood cells be prevented when storing blood?
How can the decrease in 2,3-BPG in red blood cells be prevented when storing blood?
What is the effect of the amino acid substitution in hemoglobin S?
What is the effect of the amino acid substitution in hemoglobin S?
What typically characterizes β-thalassemia major?
What typically characterizes β-thalassemia major?
Which of the following factors increases sickling in individuals with sickle cell disease?
Which of the following factors increases sickling in individuals with sickle cell disease?
Patients with hemoglobin C disease generally experience which of the following?
Patients with hemoglobin C disease generally experience which of the following?
What is one consequence of α-thalassemia if all four α-globin genes are defective?
What is one consequence of α-thalassemia if all four α-globin genes are defective?
In sickle cell disease, what type of genetic inheritance is observed?
In sickle cell disease, what type of genetic inheritance is observed?
What happens to hemoglobin levels in patients with hemoglobin SC disease compared to those with sickle cell disease?
What happens to hemoglobin levels in patients with hemoglobin SC disease compared to those with sickle cell disease?
What occurs when carbonic acid dissociates in the blood?
What occurs when carbonic acid dissociates in the blood?
What is the primary function of the chloride shift in red blood cells?
What is the primary function of the chloride shift in red blood cells?
What characterization best describes the binding affinity of carbon monoxide to hemoglobin?
What characterization best describes the binding affinity of carbon monoxide to hemoglobin?
What condition does methemoglobin represent concerning hemoglobin function?
What condition does methemoglobin represent concerning hemoglobin function?
Which statement about fetal hemoglobin (Hb F) is accurate?
Which statement about fetal hemoglobin (Hb F) is accurate?
What typically happens to the affinity of hemoglobin for oxygen when pH decreases?
What typically happens to the affinity of hemoglobin for oxygen when pH decreases?
Which factor stabilizes the T state of hemoglobin?
Which factor stabilizes the T state of hemoglobin?
What is the role of 2,3-bisphosphoglycerate (BPG) in the context of oxygen transport?
What is the role of 2,3-bisphosphoglycerate (BPG) in the context of oxygen transport?
What physiological condition leads to an increase in 2,3-BPG levels?
What physiological condition leads to an increase in 2,3-BPG levels?
What happens during the exchange of bicarbonate and chloride ions in red blood cells?
What happens during the exchange of bicarbonate and chloride ions in red blood cells?
What clinical symptoms are likely at a carbon monoxide level of 20% to 50%?
What clinical symptoms are likely at a carbon monoxide level of 20% to 50%?
How does carbon dioxide concentration impact hemoglobin's oxygen release?
How does carbon dioxide concentration impact hemoglobin's oxygen release?
At what stage of pregnancy does Hb A synthesis begin?
At what stage of pregnancy does Hb A synthesis begin?
What is the underlying mechanism of the Haldane effect?
What is the underlying mechanism of the Haldane effect?
What proportion of glucose consumed by the healthy rat lung is converted to lactate under normal oxygen conditions?
What proportion of glucose consumed by the healthy rat lung is converted to lactate under normal oxygen conditions?
Which metabolic pathway is primarily utilized by the lungs during times of nutrient deprivation?
Which metabolic pathway is primarily utilized by the lungs during times of nutrient deprivation?
How many molecules of O2 are consumed to break down one molecule of glucose completely?
How many molecules of O2 are consumed to break down one molecule of glucose completely?
What initiates the fatty acid synthesis process after acetyl-CoA is formed?
What initiates the fatty acid synthesis process after acetyl-CoA is formed?
Which cells secrete surfactant in the lungs?
Which cells secrete surfactant in the lungs?
Why is hemoglobin necessary in the blood?
Why is hemoglobin necessary in the blood?
What is the role of elastic fibers in the alveoli?
What is the role of elastic fibers in the alveoli?
What is the consequence of breaking down fatty acids in lungs regarding oxidative stress?
What is the consequence of breaking down fatty acids in lungs regarding oxidative stress?
What is the total surface area of the alveoli in the lungs?
What is the total surface area of the alveoli in the lungs?
What is the yield of ATP from breaking down one palmitate molecule?
What is the yield of ATP from breaking down one palmitate molecule?
What are heme-proteins primarily made of?
What are heme-proteins primarily made of?
What kind of gases are exchanged during the gas exchange process in the alveoli?
What kind of gases are exchanged during the gas exchange process in the alveoli?
How many heme groups are present in one molecule of hemoglobin?
How many heme groups are present in one molecule of hemoglobin?
What is the main function of myoglobin in muscle tissue?
What is the main function of myoglobin in muscle tissue?
How many heme groups are present in hemoglobin?
How many heme groups are present in hemoglobin?
What is the effect of oxidation of Fe2+ in myoglobin or hemoglobin?
What is the effect of oxidation of Fe2+ in myoglobin or hemoglobin?
What is the difference between the T form and R form of hemoglobin?
What is the difference between the T form and R form of hemoglobin?
What shape is the oxygen dissociation curve for myoglobin?
What shape is the oxygen dissociation curve for myoglobin?
Which of the following describes the cooperative binding of oxygen by hemoglobin?
Which of the following describes the cooperative binding of oxygen by hemoglobin?
Which condition leads to a lower affinity for oxygen in hemoglobin?
Which condition leads to a lower affinity for oxygen in hemoglobin?
What is the role of carbonic anhydrase in the transport of CO2 in blood?
What is the role of carbonic anhydrase in the transport of CO2 in blood?
What type of structure does adult hemoglobin (HbA) have?
What type of structure does adult hemoglobin (HbA) have?
How does the affinity of hemoglobin for oxygen change during its transition from T form to R form?
How does the affinity of hemoglobin for oxygen change during its transition from T form to R form?
What is the primary storage location of myoglobin in the body?
What is the primary storage location of myoglobin in the body?
What is the primary way carbon dioxide is transported in the blood?
What is the primary way carbon dioxide is transported in the blood?
Which groups are found at the -positions of heme?
Which groups are found at the -positions of heme?
What is the role of the distal histidine in myoglobin and hemoglobin?
What is the role of the distal histidine in myoglobin and hemoglobin?
Which statement about the oxygen dissociation curve of hemoglobin is true?
Which statement about the oxygen dissociation curve of hemoglobin is true?
Flashcards
Pulmonary Extracellular Matrix (ECM)
Pulmonary Extracellular Matrix (ECM)
A complex network of proteins and other molecules, including collagen, elastin, and proteoglycans, that provides structural support, elasticity, and organization to lung tissue.
Proteoglycans
Proteoglycans
Large, complex molecules composed of a core protein covalently attached to one or more glycosaminoglycan chains, important for fluid dynamics in the lung.
Versican
Versican
A large chondroitin sulfate proteoglycan found in the interstitial space of the lung, forming aggregates with hyaluronic acid.
Integrins
Integrins
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Glucose Oxidation
Glucose Oxidation
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Glycolysis
Glycolysis
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Pentose Phosphate Pathway (PPP)
Pentose Phosphate Pathway (PPP)
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Oxygen
Oxygen
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Lactate Production in the Lung
Lactate Production in the Lung
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β-oxidation in Lungs
β-oxidation in Lungs
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Biosynthesis of Lipids in Lungs
Biosynthesis of Lipids in Lungs
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Lipid Synthesis in Type II Alveolar Cells
Lipid Synthesis in Type II Alveolar Cells
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Gas Exchange
Gas Exchange
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Alveoli
Alveoli
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Ventilation
Ventilation
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Diffusion of Gases in the Alveoli
Diffusion of Gases in the Alveoli
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Perfusion of Oxygenated Blood
Perfusion of Oxygenated Blood
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Hemoglobin
Hemoglobin
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Why is Hemoglobin Needed?
Why is Hemoglobin Needed?
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Heme-proteins
Heme-proteins
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Myoglobin
Myoglobin
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Hemoglobin
Hemoglobin
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What is 2,3-BPG (2,3-Bisphosphoglycerate)?
What is 2,3-BPG (2,3-Bisphosphoglycerate)?
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Why does stored blood have lower oxygen-releasing ability?
Why does stored blood have lower oxygen-releasing ability?
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What is the solution to the problem of lower oxygen-releasing ability in stored blood?
What is the solution to the problem of lower oxygen-releasing ability in stored blood?
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What are hemoglobinopathies?
What are hemoglobinopathies?
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What is sickle cell disease?
What is sickle cell disease?
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What is the specific amino acid substitution in sickle cell disease?
What is the specific amino acid substitution in sickle cell disease?
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How do sickle cells form?
How do sickle cells form?
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What is hemoglobin C disease?
What is hemoglobin C disease?
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What are thalassemias?
What are thalassemias?
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What are beta-thalassemias?
What are beta-thalassemias?
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Heme
Heme
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Heme-Iron Bonds
Heme-Iron Bonds
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Proximal Histidine
Proximal Histidine
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Distal Histidine
Distal Histidine
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Helical Structure of Myoglobin
Helical Structure of Myoglobin
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Hemoglobin A (HbA)
Hemoglobin A (HbA)
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T-form (Taut) of Hemoglobin
T-form (Taut) of Hemoglobin
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R-form (Relaxed) of Hemoglobin
R-form (Relaxed) of Hemoglobin
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Hemoglobin-Oxygen Cooperative Binding
Hemoglobin-Oxygen Cooperative Binding
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Oxygen Dissociation Curve
Oxygen Dissociation Curve
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Carbaminohemoglobin
Carbaminohemoglobin
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CO2 Transport in Blood
CO2 Transport in Blood
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Carbonic Anhydrase (CA)
Carbonic Anhydrase (CA)
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Carbonic Acid
Carbonic Acid
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Bicarbonate Ions
Bicarbonate Ions
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Chloride Shift
Chloride Shift
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CO2 Hydration Reaction
CO2 Hydration Reaction
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Carbon Monoxide (CO)
Carbon Monoxide (CO)
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Carboxyhemoglobin
Carboxyhemoglobin
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Methemoglobin
Methemoglobin
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Methemoglobinemia
Methemoglobinemia
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Hemoglobin A2 (Hb A2)
Hemoglobin A2 (Hb A2)
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Fetal Hemoglobin (Hb F)
Fetal Hemoglobin (Hb F)
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Allosteric Effects
Allosteric Effects
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Bohr Effect
Bohr Effect
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Haldane Effect
Haldane Effect
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2,3-Bisphosphoglycerate (BPG)
2,3-Bisphosphoglycerate (BPG)
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Study Notes
Pulmonary Extracellular Matrix (ECM)
- Composed primarily of collagen, elastic fibers, and proteoglycans
- Proteoglycans influence capillary membrane sieving and interstitial tissue compliance
- Epithelial and mesenchymal cells interact with ECM via integrins, transmembrane receptors facilitating cell-cell and cell-ECM adhesion
- Proteoglycans are multidomain core proteins linked to glycosaminoglycans
- Versican, a large chondroitin sulfate proteoglycan, aggregates with hyaluronic acid in the interstitial matrix.
Pulmonary Metabolic Processes
- The lung is metabolically active, involved in secretion, clearance, and maintenance
- These activities require reducing potential, energy, and biosynthetic substrates
- Glucose is the primary fuel utilized by lung tissue
- Lung tissue can metabolize glucose, fatty acids, amino acids, lactate, and glycerol, with glucose oxidation being the most prolific (40-50 μmol/(h·g) dry lung weight)
- Glycolysis, a 10-step cytoplasmic process, converts glucose into pyruvate
- Pyruvate is converted to lactate or enters the TCA cycle as acetyl-CoA, generating NADH and FADH2. NADH and FADH2 are utilized in the electron transport chain to generate ATP
- Glycolysis intermediates can also be utilized in the pentose phosphate pathway (PPP) to produce NADPH and ribose-5-phosphate
- Lactate production is elevated in the normal rat lung with approximately 40% of glucose consuming cells converting glucose to lactate under normal oxygen conditions. This suggests lactate production may be an energy source for certain lung cells.
β-Oxidation in Lungs
- β-oxidation is a primary energy source during nutrient deprivation
- Less efficient than glycolysis in oxygen consumption (23 O2 molecules to break down palmitate vs 6 O2 molecules for glucose)
- Fatty acid breakdown can cause oxidative stress.
Lipid Biosynthesis in Lungs
- Lung cells can synthesize necessary lipids for internal and external membranes
- Fatty acid synthesis uses intermediates from glycolysis (pyruvate) and the TCA cycle (citrate)
- Acetyl-CoA, obtained from pyruvate and citrate, initiates fatty acid synthesis, proceeding via a four-step reaction: condensation, reduction, dehydration, and reduction
- Fatty acyl chains are incorporated into triglycerides, phospholipids, and cardiolipins, vital components of plasma membranes, lipid droplets, and other organelles.
Gas Exchange in Lungs
- Gas exchange occurs across alveoli (300 million, 60-80 m2 total surface area)
- Alveoli contain collagen and elastic fibers enabling stretching during inhalation and returning to their original state during exhalation.
- Type I alveolar cells form air sacs, and Type II alveolar cells secrete surfactant and regulate sodium and water absorption.
- Ventilation is the movement of air in and out of the lungs, and gas diffusion occurs between alveoli and blood.
- Cellular respiration utilizes inhaled oxygen and produces carbon dioxide, which is transported via the blood to be exhaled.
Hemoglobin
- Hemoglobin is vital for oxygen transport due to its high oxygen solubility compared to plasma
- Hemoglobin in one liter of blood can carry 200 mL of oxygen—87 times more than plasma alone.
- The efficiency and control of oxygen delivery are enhanced by hemoglobin within red blood cells.
Heme/Heme-Proteins
- Heme is a complex of protoporphyrin and ferrous iron (Fe2+)
- Heme contains a ferrous iron (Fe2+) atom at its center, facilitating oxygen binding to myoglobin or hemoglobin.
- The planar network of conjugated double bonds in heme absorbs visible light, causing the deep red color.
- Oxidation to the ferric state (Fe3+) destroys heme activity.
- Heme-proteins such as myoglobin and hemoglobin are involved in oxygen transport.
Myoglobin
- Stores oxygen in red muscle
- Releases oxygen during oxygen deprivation (e.g., exercise) for muscle ATP synthesis
- Location: Skeletal and cardiac muscles -Function: Oxygen storage.
- Structure: Single polypeptide chain with high helical content (80%).
Hemoglobin
- Transports oxygen from the lungs to tissues
- Removes carbon dioxide from tissues
- Acts as a buffer in red blood cells
- Location: Red blood cells
- Structure: Quaternary, with four polypeptide chains.
- Forms two states: -Taut (T) state: low oxygen affinity, stabilized by ionic bonds. -Relaxed (R) state: high oxygen affinity, unstable ionic bonds.
Oxygen Dissociation Curve
- Myoglobin curve is hyperbolic (high oxygen affinity at all pO2 values)
- Hemoglobin curve is sigmoidal (cooperative binding, increasing oxygen affinity with each binding event)
Carbon Dioxide Transport in Blood
- CO2 is transported in three main ways:
- As bicarbonate ions (70%)
- As carbaminohemoglobin (20%)
- Dissolved in plasma (10%)
- Carbonic anhydrase converts CO2 into bicarbonate ions, maintaining blood pH.
Carbon Monoxide Toxicity
- CO binds to hemoglobin more strongly than oxygen, effectively displacing oxygen and inhibiting its delivery.
Methemoglobinemia
- Methemoglobin is an oxidized form of hemoglobin unable to bind oxygen
- This condition results in a deficiency in oxygen delivery to tissues.
Minor Hemoglobins
- HbA is one member of a family of hemoglobin proteins. All hemoglobins are tetramers.
- Fetal hemoglobin (HbF) has a higher oxygen affinity than HbA due to different globin chains (γ chains instead of β chains).
- HbF is the major hemoglobin in the fetus and newborn.
Allosteric Effects
- Interaction at one site affects oxygen binding at other sites
- Allosteric effectors influence hemoglobin oxygen affinity.
Bohr Effect
- Decreased oxygen affinity at low pH or high CO2 concentrations. This shifts the oxygen dissociation curve to the right.
2,3-Bisphosphoglycerate (BPG)
- BPG stabilizes the deoxyhemoglobin T state, decreasing oxygen affinity.
- BPG concentration increases in conditions like chronic hypoxia or anemia.
Hemoglobinopathies
- Group of genetic disorders involving abnormal hemoglobins
- Sickle cell disease (HbS), a homozygous recessive disorder with a single nucleotide mutation in the β-globin gene. This causes a substitution of valine for glutamic acid.
- HbS polymerizes, deforming red blood cells into a sickle shape, impairing blood flow and potentially triggering anoxia and tissue damage.
Thalassemias
- Hereditary hemolytic diseases due to defects reducing or eliminating globin chain synthesis.
- Classified into α and β thalassemias with various degrees of severity based on globin chain deficiencies.
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Description
Test your knowledge on the pulmonary extracellular matrix, metabolic processes, and the role of proteoglycans in lung tissue. This quiz covers key concepts related to lung metabolism and extracellular components. Assess your understanding of glycolysis and the TCA cycle as they relate to pulmonary health.
