Podcast
Questions and Answers
What primarily drives filtration in capillaries?
What primarily drives filtration in capillaries?
Which condition can lead to edema?
Which condition can lead to edema?
Which type of blood cell has the shortest lifespan?
Which type of blood cell has the shortest lifespan?
What is the diameter of an average red blood cell?
What is the diameter of an average red blood cell?
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What process refers to the production of white blood cells?
What process refers to the production of white blood cells?
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What role do plasma proteins play in blood physiology?
What role do plasma proteins play in blood physiology?
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Which cells are derived from the same multipotential stem cell?
Which cells are derived from the same multipotential stem cell?
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What is the approximate number of leukocytes per microliter of blood?
What is the approximate number of leukocytes per microliter of blood?
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What is the primary classification of Iron Deficiency Anemia?
What is the primary classification of Iron Deficiency Anemia?
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Which condition is characterized by an unknown etiology and exposure to radiation?
Which condition is characterized by an unknown etiology and exposure to radiation?
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What is the daily iron intake requirement for females who menstruate?
What is the daily iron intake requirement for females who menstruate?
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Which type of anemia results from deficiencies in Vitamin B12 and Folic Acid?
Which type of anemia results from deficiencies in Vitamin B12 and Folic Acid?
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What percentage of the body's total iron is found in hemoglobin?
What percentage of the body's total iron is found in hemoglobin?
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How much iron is normally absorbed from dietary intake by males?
How much iron is normally absorbed from dietary intake by males?
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What is NOT a characteristic of Diminished Production Anemia?
What is NOT a characteristic of Diminished Production Anemia?
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Which anemia is associated with renal disease resulting in less erythropoietin (EPO) production?
Which anemia is associated with renal disease resulting in less erythropoietin (EPO) production?
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Which nutrient source is essential for Vitamin B12?
Which nutrient source is essential for Vitamin B12?
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What is the term for the anemia caused by ineffective maturation of red blood cells?
What is the term for the anemia caused by ineffective maturation of red blood cells?
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What role does intrinsic factor play in vitamin B12 absorption?
What role does intrinsic factor play in vitamin B12 absorption?
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Which of the following is a characteristic of hemolytic anemias?
Which of the following is a characteristic of hemolytic anemias?
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What is the primary mechanism activated immediately after vascular injury?
What is the primary mechanism activated immediately after vascular injury?
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Which statement accurately describes the structure of platelets?
Which statement accurately describes the structure of platelets?
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In what scenario would a hematoma occur?
In what scenario would a hematoma occur?
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What condition is characterized by a deficiency in globin amino acid chain synthesis?
What condition is characterized by a deficiency in globin amino acid chain synthesis?
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Which of the following is a function of the platelet plug during hemostasis?
Which of the following is a function of the platelet plug during hemostasis?
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Which disorder is associated with an abnormal structure of red blood cells?
Which disorder is associated with an abnormal structure of red blood cells?
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What stimulates the synthesis of erythropoietin in the kidneys?
What stimulates the synthesis of erythropoietin in the kidneys?
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What is the primary function of erythropoietin in the body?
What is the primary function of erythropoietin in the body?
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What role do macrophages play in the lifecycle of red blood cells?
What role do macrophages play in the lifecycle of red blood cells?
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Which of the following components is produced from the hemoglobin of destroyed red blood cells?
Which of the following components is produced from the hemoglobin of destroyed red blood cells?
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Which factor decreases the release of erythropoietin from the kidneys?
Which factor decreases the release of erythropoietin from the kidneys?
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What is the life span of a red blood cell in circulation?
What is the life span of a red blood cell in circulation?
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What changes occur to erythropoiesis during severe accidental hemorrhage?
What changes occur to erythropoiesis during severe accidental hemorrhage?
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What hormone has an opposite effect on erythropoietin release compared to testosterone?
What hormone has an opposite effect on erythropoietin release compared to testosterone?
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What happens to erythropoiesis when the oxygen level in the plasma decreases?
What happens to erythropoiesis when the oxygen level in the plasma decreases?
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What is the end product of heme breakdown during the destruction of red blood cells?
What is the end product of heme breakdown during the destruction of red blood cells?
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Polycythemia occurs in which situation regarding red blood cell dynamics?
Polycythemia occurs in which situation regarding red blood cell dynamics?
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How are reticulocytes significant in the process of erythropoiesis?
How are reticulocytes significant in the process of erythropoiesis?
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Which storage form of iron is primarily found in the liver?
Which storage form of iron is primarily found in the liver?
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What consequence does excessive hemolysis have on bilirubin levels?
What consequence does excessive hemolysis have on bilirubin levels?
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What is the primary source of thrombopoietin involved in platelet production?
What is the primary source of thrombopoietin involved in platelet production?
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Which sequence correctly describes the stages of platelet plug formation?
Which sequence correctly describes the stages of platelet plug formation?
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What role does exposedcollagen play in platelet activation?
What role does exposedcollagen play in platelet activation?
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What condition is characterized by a platelet count of less than 75,000/µL?
What condition is characterized by a platelet count of less than 75,000/µL?
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Which factor provides a positive feedback mechanism in the coagulation process?
Which factor provides a positive feedback mechanism in the coagulation process?
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What is the main difference between white thrombus and red thrombus?
What is the main difference between white thrombus and red thrombus?
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Which of the following is NOT a function of platelets?
Which of the following is NOT a function of platelets?
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How does aspirin affect platelet function in relation to thromboxane A2?
How does aspirin affect platelet function in relation to thromboxane A2?
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What initiates the intrinsic pathway of coagulation?
What initiates the intrinsic pathway of coagulation?
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What is the primary role of plasminogen in clot lysis?
What is the primary role of plasminogen in clot lysis?
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What is a key factor that contributes to coagulation initiation?
What is a key factor that contributes to coagulation initiation?
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Which vitamin is critical for the synthesis of several crucial clotting factors?
Which vitamin is critical for the synthesis of several crucial clotting factors?
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What do anticoagulants do in the context of hemostasis?
What do anticoagulants do in the context of hemostasis?
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Which pathway of coagulation has a faster response time?
Which pathway of coagulation has a faster response time?
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Which of the following best describes pernicious anemia?
Which of the following best describes pernicious anemia?
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Which of the following conditions is most likely associated with hemolytic anemias?
Which of the following conditions is most likely associated with hemolytic anemias?
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What is a primary cause of ineffective maturation in anemias?
What is a primary cause of ineffective maturation in anemias?
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Which type of anemia is characterized by abnormal hemoglobin structure?
Which type of anemia is characterized by abnormal hemoglobin structure?
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What distinguishes the secondary hemostatic response from the primary hemostatic response?
What distinguishes the secondary hemostatic response from the primary hemostatic response?
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Which condition is characterized by increased destruction or reduced survival of red blood cells?
Which condition is characterized by increased destruction or reduced survival of red blood cells?
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Which mechanism primarily facilitates vascular response to blood vessel injury?
Which mechanism primarily facilitates vascular response to blood vessel injury?
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What role do granules within platelets play during hemostasis?
What role do granules within platelets play during hemostasis?
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What is a common consequence of hereditary spherocytosis regarding red blood cells?
What is a common consequence of hereditary spherocytosis regarding red blood cells?
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How does the term 'hematoma' relate to the context of blood loss?
How does the term 'hematoma' relate to the context of blood loss?
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In the context of vitamin B12 absorption, what is the critical role of intrinsic factor?
In the context of vitamin B12 absorption, what is the critical role of intrinsic factor?
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What is the primary distinction between primary hemostasis and homeostasis?
What is the primary distinction between primary hemostasis and homeostasis?
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What is a primary reason for hemoglobin being contained within red blood cells instead of being dissolved in plasma?
What is a primary reason for hemoglobin being contained within red blood cells instead of being dissolved in plasma?
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What is the approximate carrying capacity of oxygen per 100 ml of blood when hemoglobin is fully saturated?
What is the approximate carrying capacity of oxygen per 100 ml of blood when hemoglobin is fully saturated?
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Which factor does NOT affect the ability of hemoglobin to bind and release oxygen?
Which factor does NOT affect the ability of hemoglobin to bind and release oxygen?
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Which locations are primarily involved in the postnatal production of red blood cells?
Which locations are primarily involved in the postnatal production of red blood cells?
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What is the duration of time required for a reticulocyte to develop into a fully matured red blood cell?
What is the duration of time required for a reticulocyte to develop into a fully matured red blood cell?
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What is the primary role of hematopoietic growth factors in red blood cell production?
What is the primary role of hematopoietic growth factors in red blood cell production?
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What process accurately describes the conversion of a myeloid precursor to a red blood cell?
What process accurately describes the conversion of a myeloid precursor to a red blood cell?
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What is a unique feature of the erythropoietin hormone in the regulation of red blood cell production?
What is a unique feature of the erythropoietin hormone in the regulation of red blood cell production?
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What is the primary role of hematopoietic growth factors (HGFs) in the body?
What is the primary role of hematopoietic growth factors (HGFs) in the body?
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Which enzyme in red blood cells is crucial for CO2 transport?
Which enzyme in red blood cells is crucial for CO2 transport?
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In which anatomical locations does postnatal hematopoiesis primarily occur?
In which anatomical locations does postnatal hematopoiesis primarily occur?
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What is the typical RBC count range for females in microliters of blood?
What is the typical RBC count range for females in microliters of blood?
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Which property of hemoglobin contributes to a high oxygen solubility in blood?
Which property of hemoglobin contributes to a high oxygen solubility in blood?
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What is the maximum number of oxygen molecules that can bind to one hemoglobin molecule?
What is the maximum number of oxygen molecules that can bind to one hemoglobin molecule?
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What is the main advantage of red blood cells lacking organelles such as nuclei and mitochondria?
What is the main advantage of red blood cells lacking organelles such as nuclei and mitochondria?
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Which component of red blood cells is responsible for generating energy anaerobically?
Which component of red blood cells is responsible for generating energy anaerobically?
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What role does spectrin play in the structure of red blood cells?
What role does spectrin play in the structure of red blood cells?
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How does hypoxia influence erythropoietin production in the kidneys?
How does hypoxia influence erythropoietin production in the kidneys?
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What role do macrophages play in the destruction of red blood cells?
What role do macrophages play in the destruction of red blood cells?
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Which hormone increases the sensitivity of RBC precursors to erythropoietin?
Which hormone increases the sensitivity of RBC precursors to erythropoietin?
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What is the effect of increased oxygen levels in plasma on erythropoietin release?
What is the effect of increased oxygen levels in plasma on erythropoietin release?
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What happens to erythropoiesis during severe accidental hemorrhage?
What happens to erythropoiesis during severe accidental hemorrhage?
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What does the presence of reticulocytes indicate in erythropoiesis?
What does the presence of reticulocytes indicate in erythropoiesis?
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Which substance is produced from the breakdown of hemoglobin during RBC destruction?
Which substance is produced from the breakdown of hemoglobin during RBC destruction?
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What is the lifespan of a red blood cell in circulation?
What is the lifespan of a red blood cell in circulation?
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What typically triggers the synthesis of erythropoietin in the kidneys?
What typically triggers the synthesis of erythropoietin in the kidneys?
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What occurs to the components of hemoglobin during the phagocytosis of old RBCs?
What occurs to the components of hemoglobin during the phagocytosis of old RBCs?
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What factors can contribute to the development of jaundice?
What factors can contribute to the development of jaundice?
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What type of feedback mechanism regulates erythropoietin levels in the body?
What type of feedback mechanism regulates erythropoietin levels in the body?
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Where is the primary site of iron storage in the body?
Where is the primary site of iron storage in the body?
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What happens to erythropoiesis when the body experiences a decrease in oxygen levels?
What happens to erythropoiesis when the body experiences a decrease in oxygen levels?
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What is the relationship between the concentration of a protein and the osmotic pressure it exerts?
What is the relationship between the concentration of a protein and the osmotic pressure it exerts?
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How does molecular weight affect the osmotic pressure generated by a protein?
How does molecular weight affect the osmotic pressure generated by a protein?
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Which protein fraction has the lowest concentration in plasma according to the provided data?
Which protein fraction has the lowest concentration in plasma according to the provided data?
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What factor does NOT influence the osmotic pressure of a solution?
What factor does NOT influence the osmotic pressure of a solution?
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Given the molecular weight of globulins ranges from 90 to 800 kDa, what can be inferred about their potential osmotic pressure effects?
Given the molecular weight of globulins ranges from 90 to 800 kDa, what can be inferred about their potential osmotic pressure effects?
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What percentage of fluid filtered out from capillaries is reabsorbed back into them?
What percentage of fluid filtered out from capillaries is reabsorbed back into them?
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What term describes the process that pulls fluid into capillaries due to plasma proteins?
What term describes the process that pulls fluid into capillaries due to plasma proteins?
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Which structure is characterized by being a network of blind-ended tubules that collect lymph?
Which structure is characterized by being a network of blind-ended tubules that collect lymph?
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How much total blood flow occurs daily in liters?
How much total blood flow occurs daily in liters?
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What primarily determines the distribution of extracellular fluid volume between plasma and interstitial fluid?
What primarily determines the distribution of extracellular fluid volume between plasma and interstitial fluid?
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What is the volume of fluid that is typically drained from tissues by lymphatic vessels daily?
What is the volume of fluid that is typically drained from tissues by lymphatic vessels daily?
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Which option best defines the process that tends to push fluid out of the capillaries?
Which option best defines the process that tends to push fluid out of the capillaries?
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What is the role of lymphatic vessels in relation to interstitial fluid constituents?
What is the role of lymphatic vessels in relation to interstitial fluid constituents?
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What primarily determines the flow of water into or out of capillaries?
What primarily determines the flow of water into or out of capillaries?
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Which of the following best defines filtration in the context of capillary dynamics?
Which of the following best defines filtration in the context of capillary dynamics?
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What role do plasma proteins play in capillary dynamics?
What role do plasma proteins play in capillary dynamics?
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Which of the following correctly describes the relationship between hydrostatic pressure and osmotic pressure in capillary exchange?
Which of the following correctly describes the relationship between hydrostatic pressure and osmotic pressure in capillary exchange?
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What is the primary function of Starling forces in transcapillary dynamics?
What is the primary function of Starling forces in transcapillary dynamics?
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In the context of capillary dynamics, the term 'bulk flow' refers to?
In the context of capillary dynamics, the term 'bulk flow' refers to?
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Which factor is least likely to affect the colloidal osmotic pressure of plasma?
Which factor is least likely to affect the colloidal osmotic pressure of plasma?
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What is the impact of hydrostatic pressure on transcapillary fluid movement?
What is the impact of hydrostatic pressure on transcapillary fluid movement?
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What is the primary role of plasma as a component of blood?
What is the primary role of plasma as a component of blood?
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Which statement most accurately describes the composition of blood volume occupied by red blood cells in a healthy individual?
Which statement most accurately describes the composition of blood volume occupied by red blood cells in a healthy individual?
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What characterizes the osmolality of a 0.9% NaCl solution in terms of physiological relevance?
What characterizes the osmolality of a 0.9% NaCl solution in terms of physiological relevance?
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What process is involved in the measurement of hematocrit in a clinical setting?
What process is involved in the measurement of hematocrit in a clinical setting?
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Which blood component's concentration is significantly affected by liver disease?
Which blood component's concentration is significantly affected by liver disease?
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What is the effect of increased colloidal osmotic pressure (COP) in plasma on fluid distribution?
What is the effect of increased colloidal osmotic pressure (COP) in plasma on fluid distribution?
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In the context of blood plasma, what is the major contributor to colloidal osmotic pressure?
In the context of blood plasma, what is the major contributor to colloidal osmotic pressure?
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What fluid balance condition is characterized by decreased blood volume?
What fluid balance condition is characterized by decreased blood volume?
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How is the osmotic pressure of a solution primarily influenced, according to physiological principles?
How is the osmotic pressure of a solution primarily influenced, according to physiological principles?
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What method is used to separate plasma proteins based on their charge and molecular weight?
What method is used to separate plasma proteins based on their charge and molecular weight?
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What is the predominant mechanism of fluid transport across capillary walls?
What is the predominant mechanism of fluid transport across capillary walls?
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What effect does the removal of fibrinogen from plasma have on the analysis of serum?
What effect does the removal of fibrinogen from plasma have on the analysis of serum?
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What is the significance of the interstitial fluid's composition in relation to plasma?
What is the significance of the interstitial fluid's composition in relation to plasma?
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What is the potential consequence of extreme hemolysis within the bloodstream?
What is the potential consequence of extreme hemolysis within the bloodstream?
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Study Notes
Hemoglobin Accumulation
- Normal hemoglobin accumulation is 7 µm
Anaemia Classification
- Anaemia is categorized by its origin: diminished production, ineffective maturation, increased destruction or reduced survival
- Diminished production can be caused by abnormalities at the site of production, insufficient stimulus, or inadequate raw materials
- Ineffective maturation can be caused by deficiencies in vitamin B12 or folic acid, or a deficiency in iron.
Aplastic Anemia
- Aplastic anemia is a type of diminished production anaemia
- Its cause is unknown
- It's often associated with exposure to radiation, chemicals, or drugs.
- The classification is normocytic and normochromic.
Stimulation Failure Anemia
- Stimulation failure anemia is another type of diminished production anaemia
- It's caused by renal disease, leading to reduced production of erythropoietin.
- Its classification is normocytic and normochromic.
Iron Deficiency Anemia
- Iron is essential for production of red blood cells.
- Iron deficiency anemia is the most common type of anaemia
- The body's total iron content is 4g
- Iron needed for normal erythropoiesis is 25mg/day.
- This is met by the destruction of aging red blood cells which release 25mg of iron per day.
- 1mg of iron is lost daily while 24mg is recycled.
- Iron deficiency anemia is caused by an increased need for iron, like during infancy, adolescence, and pregnancy.
- It can also be caused by an inadequate supply of iron from dietary deficiency or the inability to absorb iron.
- It can also stem from hemorrhaging and resulting loss of iron.
- Iron Deficiency Anemia is classified as microcytic and hypochromic.
Pernicious Anemia
- This is a type of ineffective maturation anaemia
- It's caused by an inability to absorb Vitamin B12.
- This can stem from a deficiency in intrinsic factor, a protein crucial for vitamin B12 absorption, or damage or disease in the ileum, a part of the small intestine responsible for Vitamin B12 absorption.
Hemolytic Anemia
- This is a class of anaemia characterized by the increased destruction or reduced survival of red blood cells.
- This can be caused by an abnormality in the structure of the red blood cell membrane, a faulty metabolism due to an abnormal enzyme system, or an abnormal hemoglobin structure.
Hemostasis
- Hemostasis is the process of stopping or preventing blood loss after an injury to a blood vessel
- Vasoconstriction, platelet plug formation, and blood clot formation are the steps involved.
Red Blood Cell Life-span
- Red blood cells circulate in the body for 120 days.
- Old RBCs are then recognized and removed from the circulation by macrophages in the liver and spleen.
- There is no known method to prolong the life span of red blood cells.
Jaundice
- Jaundice is a yellowing of the skin and whites of the eyes due to the accumulation of bilirubin in the blood.
- Bilirubin is a yellowish pigment produced when heme, a component of hemoglobin, is broken down.
- It is usually processed and eliminated by the liver. Jaundice arises when the liver fails to remove bilirubin from the blood.
- This can occur due to several conditions, including: excessive destruction of red blood cells (hemolysis), liver damage, and blockage of the bile ducts.
- Neonatal jaundice is a common condition in newborns, usually harmless and resolves within a few weeks.
Red Blood Cell Dynamics
- Normal red blood cell dynamics involve a balance between production and destruction.
- Polycythemia occurs when there is an excess of red blood cell production than destruction.
- Anemia results when the production of red blood cells is less than their destruction rate.
Blood Cell Progenitors
- All blood cells originate from a common pluripotent or multipotent hematopoietic stem cell.
- Red blood cells, platelets, and white blood cells are derived from this common stem cell.
- Red blood cells (erythrocytes) are responsible for oxygen transport.
- Platelets (thrombocytes) are responsible for blood clotting.
- White blood cells (leukocytes) are responsible for fighting infection.
Erythropoiesis
- Erythropoiesis is the process of red blood cell production.
- Erythropoietin (EPO) plays a key role in regulating erythropoiesis.
- EPO is primarily produced in the kidney.
- It is stimulated by hypoxia, a condition in which the body’s tissues lack sufficient oxygen.
- EPO acts on committed red blood cell precursors in the bone marrow, accelerating their maturation, proliferation, and ultimately, maturation into mature red blood cells.
Erythropoietin Hormonal Effects
- Testosterone increases both the release of erythropoietin and the sensitivity of red blood cell precursors to erythropoietin.
- Estrogen has the opposite effect.
Platelets
- Platelets are small, anuclear cells that are essential for hemostasis (the process by which bleeding is stopped)
- Platelets are formed in the bone marrow from megakaryocytes
- Many filaments, microtubules, mitochondria, and smooth endoplasmic reticulum are contained in platelets
- Average platelet count: 250,000 per microliter
- Platelets have a lifespan of 7-10 days
Hematopoiesis
- Hematopoiesis is the process of blood cell formation
- Hematopoietic stem cells that are found in bone marrow are able to create all hematopoietic cell types
Platelet Production
- Thrombopoietin is the hormone that stimulates platelet production
- Thrombopoietin is primarily released from the liver
Platelet Plug Formation
- Platelets are essential for the initial phase of hemostasis, known as primary hemostasis
- Platelet plug formation involves the following steps:
- Adhesion: Platelets adhere to the damaged blood vessel wall, specifically to exposed collagen.
- Activation and release of cytokines: This triggers the release of substances including ADP, serotonin, and thromboxane A2.
- Aggregation: The released substances attract more platelets to the site of injury and cause them to clump together, forming a platelet plug.
- Consolidation: The platelet plug is further stabilized by fibrin, which is a protein generated as part of secondary hemostasis
Blood Clot Formation (Secondary Hemostasis)
- Blood clot formation, also known as secondary hemostasis, involves the activation of a cascade of clotting factors in plasma
- Exposed collagen binds to and activates platelets
- Platelets release factors that attract more platelets and initiate the coagulation pathway
- The coagulation pathway consists of a complex series of enzymatic reactions involving various clotting proteins, which culminate in the formation of a stable fibrin clot
Intrinsic and Extrinsic Pathways of Coagulation
- The coagulation pathway has two main pathways:
- Intrinsic Pathway: This pathway is initiated by the exposure of collagen in the blood vessel wall.
- Extrinsic Pathway: This pathway is initiated by the release of tissue factor from damaged cells outside the vessel wall.
Key Coagulation Factors
- The coagulation pathways involve many protein factors, identified with Roman numerals, as well as other critical components like:
- Calcium (Ca++)
- Phospholipid
Clotting Factor Deficiencies
- Coagulation factor deficiencies can lead to prolonged bleeding
-
Congenital Deficiencies: These are inherited deficiencies of single or multiple clotting factors.
- Hemophilia A is a deficiency of factor VIII
-
Acquired Deficiencies: These deficiencies are acquired due to conditions such as:
- Liver disease: Liver synthesizes many coagulation factors
- Vitamin K deficiency: Vitamin K is a cofactor in the synthesis of several clotting factors, including prothrombin (factor II), VII, IX, and X.
Clot Retraction
- Clot retraction is the process by which the blood clot shrinks, drawing the edges of the wound together
- Clot retraction is facilitated by the release of a contractile protein called thrombosthenin by platelets
Regulation of Coagulation
- Coagulation is tightly regulated by a balance of pro-coagulant and anti-coagulant mechanisms
- Inhibitors of platelet adhesion: These substances prevent platelets from adhering to the blood vessel wall and forming a platelet plug (e.g. aspirin in low doses).
- Anticoagulants: These substances block different stages in the coagulation cascade. For instance, heparin inhibits the activity of thrombin.
- Natural Anticoagulants: The body produces several naturally-occurring chemicals that act as anticoagulants.
Clot Lysis (Fibrinolysis)
- Clot lysis, also known as fibrinolysis, is the process by which the blood clot dissolves
- The key enzyme in fibrinolysis is plasmin.
- Plasmin is formed from its inactive precursor, plasminogen, activated by plasminogen activator
Clot Lysis Mechanisms
- Intrinsic Pathway: The intrinsic pathway is mediated by factor XIIa and endothelial cell factors.
- Extrinsic Pathway: The extrinsic pathway is initiated by tissue factors released from damaged cells.
Drugs that Interfere with Coagulation
-
Anticoagulant Drugs:
- Coumarin (e.g., warfarin): Coumarins inhibit the synthesis of prothrombin and other vitamin K-dependent clotting factors.
- Heparin: Heparin acts by promoting the inhibition of thrombin.
-
Thrombolytic Drugs:
- Tissue Plasminogen Activator (t-PA): t-PA is a natural enzyme that activates plasmin to dissolve clots
- Streptokinase: Streptokinase is a bacterial enzyme that activates plasmin.
Summary of Lecture Notes
- Platelets: involved in primary hemostasis
- Hemostasis: The process of stopping bleeding
- Platelet Plug: The first step in hemostasis
- Blood Clot: The second step in hemostasis
- Thrombin: Crucial enzyme in blood clot formation
- Intrinsic Pathway: Initiated by contact with exposed collagen
- Extrinsic Pathway: Initiated by release of tissue factor
- Coagulation Factors: Proteins involved in coagulation
- Clot Retraction: Process of clot shrinking
- Anticoagulants: Drugs that inhibit coagulation
- Thrombolytic Drugs: Drugs that dissolve clots
Red Blood Cell Production
- Erythropoiesis refers to the creation of red blood cells (RBCs)
- RBCs are produced in the bone marrow, specifically the axial skeleton, flat bones of the skull, shoulder blades, sternum, vertebrae, ribs, pelvis, and the proximal epiphyses of long bones.
- RBCs are produced in the bone marrow under the influence of hematopoietic growth factors (HGFs), which are cytokines (proteins or peptides) released by one cell to influence the growth, development and activity of another cell.
- Erythropoietin (EPO) is a key HGF in RBC production, a hormone produced in the renal cortex, and stimulated by hypoxia (reduced oxygen levels)
- The life span of RBCs is approximately 120 days.
- During their lifespan, RBCs travel the equivalent of 300 miles.
- Old RBCs are removed from circulation by highly phagocytic cells known as macrophages, found in the liver and spleen.
RBC Function And Structure
-
RBCs are "biconcave" shaped, meaning they are concave on both sides. RBCs are approximately 0.8 µm thick and 2.6 µm in diameter.
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The "biconcave" shape is due to the presence of spectrin, a fibrous protein that forms a flexible network linked to the cell membrane.
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The "biconcave" shape offers the following advantages:
- Maximal surface area: facilitates the efficient diffusion of oxygen and carbon dioxide
- Minimal diffusion distance
- High degree of flexibility: allows RBCs to squeeze through narrow capillaries
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RBCs contain no subcellular organelles, including a nucleus and mitochondria.
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RBCs have important enzyme systems to generate energy (anaerobically through glycolytic enzymes) and transport carbon dioxide (through the enzyme carbonic anhydrase)
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Hemoglobin (Hb) is found inside RBCs.
- Hb molecules can bind up to 4 oxygen molecules per molecule of Hb
- Hb is comprised of the protein globin and the heme molecule, which contains a ferrous ion (Fe++)
- Hb binds to oxygen to form oxyhemoglobin (HbO2) and when oxygen is released it becomes deoxyhemoglobin.
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The blood's oxygen carrying capacity is 20 ml O2/100 ml blood.
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The average person has approximately 25 x 1012 RBCs in their blood.
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The rate of RBC production is approximately 2 x 106 RBCs per second.
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The rate of RBC destruction is approximately 2 x 106 RBCs per second.
Hemoglobin Function
- Hemoglobin functions in:
- Oxygen transport
- Carbon dioxide transport
- Acts as a buffer
- Hb is vital since oxygen is not very soluble in plasma (~0.3 ml O2/100ml plasma)
- Hb helps increase oxygen solubility in the blood (~20 ml O2 / 100 ml blood)
Hemolytic Anemia
- Hemolytic anemia is caused by the premature destruction of RBCs in the blood.
- Hemolytic Anemia can be:
- Congenital - caused by genetic factors
- Acquired - caused by toxins, drugs, antibodies
- Hemolytic anemia can be caused by:
- Abnormal RBC membrane structure: an example is Hereditary Spherocytosis; RBCs are less flexible and more fragile
- Abnormal enzyme systems: abnormal metabolism
- Abnormal Hb structure - examples include Sickle Cell Disease and Thalassemia, which has deficient synthesis of globin amino acid chains
- Hemolytic anemia can be accompanied by Jaundice.
Jaundice
- Jaundice is caused by a buildup of bilirubin in the blood, which is the pigment released when the body breaks down heme.
- Jaundice is a condition that causes a yellowing of the skin and eyes.
- Causes of Jaundice:
- Excessive hemolysis - the breakdown of RBCs
- Liver damage - the liver is where bilirubin is processed and excreted
- Bile duct obstruction - blocks bilirubin from exiting the body
- There are two main types of Jaundice:
- Neonatal jaundice: is common in newborns, especially premature infants, and usually resolves on its own within a few weeks.
- Adult jaundice: can be caused by a variety of conditions such as cirrhosis, hepatitis, and gallstones.
Polycythemia
- Polycythemia is a condition characterized by an increase in the number of red blood cells (RBCs) in the blood.
- This means that the body produces more RBCs than it needs.
- Polycythemia can be physiological (appropriate) or abnormal.
- Polycythemia can be caused by:
- Chronic hypoxia - long-term low oxygen levels
- Genetic factors - such as congenital polycythemia
- Certain tumours - which can produce EPO
Anemia
- Anemia is a condition characterized by a deficiency of red blood cells or hemoglobin in the blood.
- Anemia can be caused by:
- Decreased RBC production
- Ineffective RBC maturation
- Increased RBC destruction or reduced RBC survival
Erythropoiesis Regulation
- Erythropoiesis can increase or decrease depending on the oxygen content of the blood via a negative feedback loop.
- The kidneys detect changes in oxygen levels; if oxygen levels are low, they release erythropoietin, a hormone that stimulates RBC production in the bone marrow.
- This increases the RBC count in the blood, which in turn increases the blood's oxygen carrying capacity.
- As oxygen levels normalize, the body decreases erythropoietin production, which slows RBC production.
Vitamin B12 and Erythropoiesis
- Vitamin B12 is essential for the normal production of RBCs.
- Vitamin B12 is absorbed in the ileum, the last part of the small intestine.
- Vitamin B12 deficiency can lead to pernicious anemia.
- Pernicious anemia is caused by the body's inability to absorb vitamin B12 due to a lack of intrinsic factor, a protein produced by the stomach that binds vitamin B12 and allows it to be absorbed.
Blood Loss - Hemostasis
- Hemostasis is the process of stopping bleeding, which is initiated by vascular injury.
- Hemostasis is divided into three stages:
- Vascular response: injured blood vessels constrict to reduce blood flow
- Platelet response: platelets adhere to the site of injury and form a platelet plug to help seal the wound
- Blood clot formation: the coagulation cascade is activated, resulting in the formation of a fibrin clot.
- Fibrin is an insoluble protein that forms a mesh-like structure that traps blood cells, platelets, and other debris to make a blood clot.
Hemostasis - Clot Formation
- Clot formation involves the following steps:
- Damaged blood vessels expose collagen to the blood
- Platelets adhere to the exposed collagen and become activated.
- Activated platelets release factors that enhance coagulation.
- The coagulation cascade is initiated. A complex series of enzymatic reactions involving clotting factors.
- Clotting factors sequentially activate each other.
- The final product of the coagulation cascade is a fibrin clot.
Blood Functions
- Transports nutrients, respiratory gasses, wastes, hormones, temperature regulation
- Acid-base balance, normal pH range 7.35 - 7.45
- Protection via white blood cells and plasma proteins
Blood Composition
- Composed of plasma, "Buffy coat" (WBCs and platelets), and red blood cells (RBCs)
- Hematocrit is the percentage of blood volume occupied by RBCs, normal value: ~45%
Plasma Composition
- Contains proteins: Albumins, Globulins, Fibrinogen
- Plasma proteins can be separated by differential precipitation by salts, sedimentation in an ultracentrifuge, immunological characteristics, and electrophoretic mobility
- Electrophoresis is a fractionation method based on the movement of charged particles along a voltage gradient
- Rate of migration is influenced by the number and distribution of charges, molecular weight (MW) of each protein
- Each protein migrates at its own characteristic rate
- Serum is plasma with fibrinogen removed.
Plasma Protein Synthesis
- Most plasma proteins are synthesized in the liver.
- Gamma globulin is synthesized in lymphoid tissue
Plasma Protein Characteristics
- Plasma proteins play a major role in determining the distribution of fluid between plasma and interstitial fluid (ISF) compartments.
Body Water Compartments
- Extracellular fluid (ECF) comprises interstitial fluid (ISF) and plasma
- Intracellular fluid (ICF) is the fluid inside the cells
- Cell membrane is relatively impermeable to ions while the capillary wall is freely permeable to water and ions, but impermeable to proteins
Body Fluid - Ionic Composition
- ECF is approximated by a 0.9% solution of NaCl, 300 mOsm
- ECF osmotic pressure is 6.7 atmospheres or ~5100 mm Hg
- Plasma has more protein than ISF, ~7 g/dl
Osmolarity of Extracellular Fluid
- 1 M solution of NaCl has 58.5 g NaCl/L
- 0.9% NaCl = 9 g/L NaCl = ~ 0.15 M
- NaCl dissociates into 2 ions, so its osmolarity = 2 x molarity = ~ 0.3 Osm = ~ 300 mOsm = 6.7 atmospheres = ~ 5100 mm Hg
Colloidal Osmotic (Oncotic) Pressure
- Only non-diffusible solutes contribute to the effective osmotic pressure of a solution
- Plasma proteins are non-diffusible and exert an osmotic effect
- The colloidal osmotic pressure (C.O.P.) of plasma is ~25 mm Hg
Starling Forces
- Hydrostatic Pressure: "pushing out" force due to pressure in the blood vessel
- Osmotic Flow: "pulling in" force due to plasma proteins
- These determine the distribution of ECF volume between plasma and ISF
Simplified Circulatory System
- Heart pumps blood throughout the body
Capillary Bed
- Site where exchanges between plasma and ISF take place
Starling's Transcapillary Dynamics
- The net movement of fluid across the capillary wall is determined by the balance of hydrostatic pressure and colloidal osmotic pressure.
- The hydrostatic pressure tends to push fluid out of the capillary, while the colloidal osmotic pressure tends to pull fluid back into the capillary.
- The net movement of fluid is usually out of the capillary at the arteriole end and into the capillary at the venule end.
Lymphatic System
- Network of blind-ended terminal tubules
- Coalesce to form larger lymphatic vessels
- Converge to form large lymphatic ducts
- Drain into large veins in the chest
- Lymphatic vessels are highly permeable to all ISF constituents, including proteins
Lymphatic vs Blood Flow Volumes
- Daily blood flow: ~6,000 L
- Volume filtered into ISF: ~20 L
- Volume returned by absorption: ~17 L
- Volume returned by lymph drainage: ~3 L
Colloidal Osmotic Pressure (C.O.P.)
- C.O.P. is determined by the concentration and molecular weight of proteins
- Albumin contributes the most to C.O.P. due to its high concentration and moderate molecular weight
Summary: Capillary Exchanges
- Nutrients, wastes, O2, and CO2 move by simple diffusion
- Starling's Transcapillary Dynamics determine the ECF volume distribution between plasma and ISF
- Filtration pushes fluid out of the capillaries
- Osmotic flow pulls fluid into the capillaries
Net Filtration vs Net Absorption
- Exchanges of filtration and absorption occur along the whole length of the capillary bed
- ~90% of the fluid filtered out is reabsorbed back into capillaries
- ~10% is drained by lymphatic vessels
Excess Fluid
- Excess fluid in the ISF is returned to the bloodstream via lymphatic vessels
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Explore the various classifications of anaemia, including aplastic anemia and iron deficiency anemia. Learn about causes, classifications, and the role of hemoglobin accumulation in anemia. This quiz provides a comprehensive understanding of diminished production and stimulation failure anemia.
