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Questions and Answers
Albumin serves as a transport vehicle for _____ and ___
Albumin serves as a transport vehicle for _____ and ___
Albumin serves as a transport vehicle for fatty acids and steroid hormones
What is the function of fibrinogen in the blood?
What is the function of fibrinogen in the blood?
Which of the following is NOT a function of blood?
Which of the following is NOT a function of blood?
Which type of plasma protein is primarily responsible for maintaining fluid balance?
Which type of plasma protein is primarily responsible for maintaining fluid balance?
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What does serum consist of?
What does serum consist of?
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Which of the following is considered an electrolyte found in plasma?
Which of the following is considered an electrolyte found in plasma?
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Match to appropriate function
Match to appropriate function
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What is the primary growth factor involved in the proliferation and differentiation of erythroid precursors into rubriblasts?
What is the primary growth factor involved in the proliferation and differentiation of erythroid precursors into rubriblasts?
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Which nutrient is NOT required for the synthesis of heme in erythrocytes?
Which nutrient is NOT required for the synthesis of heme in erythrocytes?
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What feature of erythrocytes allows them to have a greater tolerance for osmotic swelling?
What feature of erythrocytes allows them to have a greater tolerance for osmotic swelling?
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What property of erythrocytes contributes to a larger surface area to volume ratio?
What property of erythrocytes contributes to a larger surface area to volume ratio?
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What is a common consequence of deficiencies in pyruvate kinase (PK) and phosphofructokinase (PFK) in erythrocytes?
What is a common consequence of deficiencies in pyruvate kinase (PK) and phosphofructokinase (PFK) in erythrocytes?
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What is the main function of erythrocytes in mammals?
What is the main function of erythrocytes in mammals?
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What are the determinants of aged erythrocytes that lead to their removal by splenic macrophages?
What are the determinants of aged erythrocytes that lead to their removal by splenic macrophages?
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What is the clinical significance of elevated direct bilirubin levels?
What is the clinical significance of elevated direct bilirubin levels?
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Which of the following is a sign associated with erythrocytosis?
Which of the following is a sign associated with erythrocytosis?
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What is the primary difference between hematocrit and packed cell volume (PCV)?
What is the primary difference between hematocrit and packed cell volume (PCV)?
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What change in plasma volume leads to relative polycythemia?
What change in plasma volume leads to relative polycythemia?
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Which of the following describes a common qualitative change in red blood cells?
Which of the following describes a common qualitative change in red blood cells?
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What distinguishes granulocytes from agranulocytes?
What distinguishes granulocytes from agranulocytes?
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Which type of white blood cell is primarily responsible for initiating the inflammatory response?
Which type of white blood cell is primarily responsible for initiating the inflammatory response?
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How long do neutrophils typically survive in the bloodstream?
How long do neutrophils typically survive in the bloodstream?
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What characteristic of neutrophils allows them to migrate rapidly into tissues?
What characteristic of neutrophils allows them to migrate rapidly into tissues?
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Which type of leukocyte would show granules that do not stain with any dye?
Which type of leukocyte would show granules that do not stain with any dye?
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What is the role of neutrophils in an inflammatory response?
What is the role of neutrophils in an inflammatory response?
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What is the main role of eosinophils in the immune response?
What is the main role of eosinophils in the immune response?
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Which type of cell is considered part of the adaptive immune response?
Which type of cell is considered part of the adaptive immune response?
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What distinguishes monocytes from lymphocytes?
What distinguishes monocytes from lymphocytes?
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What is an important non-immune function macrophages/monocytes have?
What is an important non-immune function macrophages/monocytes have?
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Which of the following is true regarding basophils?
Which of the following is true regarding basophils?
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Which statement about lymphocytes is accurate?
Which statement about lymphocytes is accurate?
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What is a significant characteristic of eosinophils in relation to allergic responses?
What is a significant characteristic of eosinophils in relation to allergic responses?
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Which type of cell primarily carries out phagocytic functions in the immune system?
Which type of cell primarily carries out phagocytic functions in the immune system?
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What percentage of T lymphocytes typically survive the selection process?
What percentage of T lymphocytes typically survive the selection process?
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What triggers naive T cells to stop migrating and start clonal replication?
What triggers naive T cells to stop migrating and start clonal replication?
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What is indicated by a left shift in neutrophils during a leukocyte evaluation?
What is indicated by a left shift in neutrophils during a leukocyte evaluation?
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Which lymphocytes primarily circulate and make contact with multiple antigen-presenting cells in lymph nodes?
Which lymphocytes primarily circulate and make contact with multiple antigen-presenting cells in lymph nodes?
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What is the primary role of B lymphocytes after their selection process?
What is the primary role of B lymphocytes after their selection process?
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What is the physiological consequence of neutrophilia?
What is the physiological consequence of neutrophilia?
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What percentage of B lymphocytes typically survives the selection process?
What percentage of B lymphocytes typically survives the selection process?
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What is the expected outcome of evaluating leukocytes?
What is the expected outcome of evaluating leukocytes?
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What is the primary function of platelets in hemostasis?
What is the primary function of platelets in hemostasis?
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What regulates thrombopoiesis?
What regulates thrombopoiesis?
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Which phase in primary hemostasis involves vascular constriction?
Which phase in primary hemostasis involves vascular constriction?
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What initiates the adhesion of platelets to the subendothelium during primary hemostasis?
What initiates the adhesion of platelets to the subendothelium during primary hemostasis?
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What is a direct effect of increased free thrombopoietin (TPO) on megakaryocytes?
What is a direct effect of increased free thrombopoietin (TPO) on megakaryocytes?
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What is the lifespan of a platelet in circulation?
What is the lifespan of a platelet in circulation?
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What is the primary function of von Willebrand Factor (vWF) during platelet activation?
What is the primary function of von Willebrand Factor (vWF) during platelet activation?
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In which blood component does platelet activation primarily occur?
In which blood component does platelet activation primarily occur?
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What structural change do platelets undergo during activation?
What structural change do platelets undergo during activation?
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What is a characteristic sign of von Willebrand Disease in affected dogs?
What is a characteristic sign of von Willebrand Disease in affected dogs?
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What is the role of phosphatidylserine during platelet activation?
What is the role of phosphatidylserine during platelet activation?
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How does vWF affect factor VIII in the bloodstream?
How does vWF affect factor VIII in the bloodstream?
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What is one of the main clinical challenges associated with von Willebrand Disease?
What is one of the main clinical challenges associated with von Willebrand Disease?
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Match to their correct function
Match to their correct function
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Aggregation to form a platelet plug is a reversible process
Aggregation to form a platelet plug is a reversible process
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Study Notes
Functions of Blood
- Transports dissolved gases (oxygen and carbon dioxide), nutrients, hormones, and metabolic wastes throughout the body.
- Plays a crucial role in maintaining fluid balance within the circulatory system.
- Regulates pH levels and ion composition of interstitial fluids, ensuring stability in cellular environments.
- Engages in hemostasis, which restricts fluid loss at injury sites to prevent excessive bleeding.
- Provides defense mechanisms against toxins and pathogens, contributing to immune function.
- Helps stabilize body temperature by redistributing heat throughout the body.
Plasma Proteins
- The primary types of plasma proteins are albumin, globulins, and fibrinogen.
- Albumin maintains osmotic pressure and transports various substances in the blood.
- Globulins serve critical roles in immune response and transport of ions and hormones.
- Fibrinogen, produced by the liver, is vital for the blood clotting process.
Serum and Plasma
- Serum is defined as plasma that has had fibrinogen removed, resulting in a liquid component without clotting factors.
Solutes in Plasma
- Electrolytes such as sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), bicarbonate (HCO3), phosphate (PO4), and sulfate (SO4) are crucial for numerous physiological functions.
- Non-protein nitrogen-containing compounds found in plasma include urea and creatinine, which are waste products.
- Nutrients like glucose, lipids, and amino acids are transported by the plasma to cells for nourishment and metabolism.
- Gases such as oxygen, carbon dioxide, and nitrogen are dissolved in plasma, facilitating respiration and metabolic processes.
- Additionally, plasma contains hormones and enzymes that regulate various body functions.
Hematopoiesis Overview
- Hematopoiesis involves the proliferation and differentiation of hematopoietic stem cells into mature blood cells.
- Key processes include erythropoiesis (red blood cells), leukopoiesis (white blood cells), and thrombopoiesis (platelets).
Erythrocytes (Red Blood Cells)
- Main functions:
- Oxygen transport to tissues
- Carbon dioxide transport from tissues
- Buffers hydrogen ions (H+)
- Structural characteristics:
- Mammalian erythrocytes are anucleate and lack organelles.
- Shape is circular, flattened, and bi-concave, enhancing surface area and minimizing diffusion distance.
- Diameter ranges from 4 to 8 µm, allowing for flexibility and plasticity.
- Possesses a cytoskeleton that supports shape changes and osmotic tolerance.
Erythropoiesis
- Stimulated by various growth factors:
- Local factors in bone marrow: stem-cell factor (SCF), IL-3, GM-CSF, and thrombopoietin (TPO).
- Peripheral tissue factor: erythropoietin (EPO) and triiodothyronine (T3).
- EPO is crucial for the proliferation and differentiation of erythroid precursor cells into rubriblasts, the first identifiable erythroid cells.
- The regulation of red blood cell (RBC) mass is dependent on cellular oxygen levels.
Nutritional Requirements for Erythropoiesis
- Essential nutrients include:
- Iron: necessary for heme synthesis.
- Vitamins B6, B9, B12: critical for various metabolic processes.
- Copper and cobalt: play roles in erythropoiesis.
- Due to the absence of mitochondria, erythrocytes utilize anaerobic metabolism and do not consume the oxygen being transported.
Hemoglobin Structure and Function
- Hemoglobin binds oxygen reversibly for efficient transport.
- Composed of globin and heme; includes four polypeptide chains (two alpha and two beta chains).
Biochemical Components of Erythrocytes
- Important enzymes and compounds include:
- Pyruvate kinase (PK): vital for glycolysis.
- Phosphofructokinase (PFK): crucial in regulating glycolytic flux.
- Phosphorus: integral for ATP generation.
- Deficiencies in these components can result in decreased glycolytic rates, reduced ATP production, and premature death of red blood cells.
Removal of Aged Erythrocytes
- Erythrocytes circulate for several months before removal.
- Aging triggers oxidative injury and ATP depletion, leading to surface membrane changes.
- Senescent erythrocytes become denser and less deformable.
- Key modifications include phosphatidylserine exposure and altered Band 3 proteins.
- Membrane carbohydrate residues also change with age.
- Splenic macrophages are responsible for the removal of aged erythrocytes.
Bilirubin Metabolism
- Indirect bilirubin is produced in the mononuclear phagocyte system (MPS) and binds to albumin in the bloodstream.
- Direct bilirubin is formed through glucuronidation in the liver.
Clinical Importance of RBC Evaluation
- Quantitative changes observed in conditions like anemia, which is characterized by a decrease in RBCs.
- Causes of anemia include blood loss, decreased production, and increased destruction.
- Clinical signs of anemia: pale mucous membranes, weakness, lethargy, rapid pulse, and rapid breathing.
- Erythrocytosis results from an increase in RBCs and can be categorized into absolute and relative forms.
- Absolute polycythemia can be primary (EPO-independent) or secondary (EPO-dependent).
- Signs include increased thirst/urination (PU/PD), lethargy, and brick red mucous membranes, with an elevated risk of thrombotic events.
- Relative polycythemia occurs due to decreased plasma volume.
Hematocrit vs. PCV
- Both hematocrit and Packed Cell Volume (PCV) denote the percentage of total blood volume occupied by RBCs.
- PCV is manually measured via microhematocrit after centrifugation.
- Hematocrit is calculated based on RBC number and size.
Qualitative Changes in RBCs
- Abnormal morphology and the presence of inclusions can indicate qualitative changes in erythrocytes.
Leukocytes (WBCs)
- Heterogeneous population involved in the immune response.
- Classified morphologically based on nucleus shape: mononuclear or polymorphonuclear.
- Presence of cytoplasmic granules distinguishes granulocytes from agranulocytes.
- Critical for both innate and adaptive immunity and hold significant diagnostic value.
Granulocytes
- Named according to staining properties showing affinity for different dyes.
- Eosinophils: Stain with acidic dyes, involved in combating parasitic infections and allergies.
- Neutrophils: Most abundant WBC, critical in the inflammatory response, with a segmented nucleus allowing quick tissue migration.
- Basophils: Rare, involved in allergic responses and reacting to parasites; functionally similar to mast cells.
Neutrophils
- Primary responders in inflammation, capable of phagocytosing pathogens and enhancing inflammation through pro-inflammatory substances.
- Short lifespan in bloodstream (5-10 hours) and limited survival in tissues (few days).
- Serve as a primary indicator for inflammatory processes.
Eosinophils
- Predominantly located in the gastrointestinal mucosa.
- Play a significant role in responses to parasitic infections and Type I hypersensitivity reactions.
- Release toxic granules to destroy pathogens and assist in inflammation.
Basophils
- Present in very low numbers and associated with allergic reactions.
- Less effective than eosinophils in response to parasites.
Mononuclear/Agranulocytes
- Characterized by a single large nucleus with fewer visible granules compared to granulocytes.
- Monocytes: Larger than lymphocytes with variable nuclei shapes; differentiate into macrophages.
- Lymphocytes: Generally possess round nuclei; key players in adaptive immunity.
Monocytes/Macrophages
- Monocytes differentiate into macrophages, which are vital for phagocytosis and immune coordination.
- Activated macrophages inform other immune cells of infections and present antigens to lymphocytes.
- Undertake non-immune tasks, such as recycling dead cells, without triggering immune responses.
Lymphocytes
- Diverse group essential for adaptive immunity.
- B cells: Contribute to antibody production (10-40% of lymphocytes).
- T cells: Attack foreign or cancerous cells (50-75% of lymphocytes).
- NK cells: Kill tumor and infected cells, representing the innate immune response (5-10%).
- Majority inhabit lymphoid organs rather than circulating in the blood (only 2-10%).
Lymphocyte Formation
- Precursors of T cells migrate to the thymus, while B cell precursors either move to the Bursa of Fabricius or remain in the bone marrow in mammals.
- Only 1-2% of T lymphocytes survive the selection process, indicating a strong selection mechanism.
- Less than 20% of B lymphocytes manage to survive; only a few selected lymphocytes enter circulation and reach peripheral lymphoid organs.
Lymphocyte Circulation
- Naive T cells circulate and are attracted to lymph nodes by chemotactic factors, making contact with numerous antigen-presenting cells daily.
- Likelihood of a naive T cell being specific for a particular antigen ranges from 1 in 10,000 to 1 in 1,000,000.
- If a naive T cell is not primed by an antigen, it recirculates to attempt activation in another lymph node.
- Primed T cells, upon recognition of specific antigens, stop migrating, initiate cytokine release, and begin clonal replication for a few days.
- Armed effector T cell clones exit the lymphoid organ and are directed to infection sites.
Leukocyte Evaluation
- Assessment of white blood cells (WBCs) focuses on count and morphology.
- Key objectives include detection of inflammation, identifying infections, determining prognosis, and recognizing hematopoietic neoplasia.
- Diagnosis of leukemia can also be made through leukocyte evaluation.
Neutrophils and Shift Analysis
- Neutrophilia refers to an increased number of neutrophils in the bloodstream, ranging from mild to severe conditions.
- Neutropenia indicates a reduced number of neutrophils in the blood.
- A "left shift" signifies an increase in immature neutrophils, regardless of total neutrophil count, often serving as an indicator of severe inflammatory responses.
- Normally, only a small number of band forms are expected; a significant left shift with more immature neutrophils indicates a more intense inflammatory stimulus.
Platelets
- Small, anucleated, round to oval thin discs.
- Lifespan of 4-10 days, crucial for primary hemostasis.
Thrombopoiesis
- Platelet precursor is the megakaryocyte, found in bone marrow and sometimes lungs.
- Long proplatelet processes fragment into individual platelets.
- Megakaryocytes are absent in nonmammalian species; these species use normal mitosis for precursors.
- Regulated by thrombopoietin (TPO), produced by the liver, kidneys, and muscle.
- Free TPO levels increase megakaryocyte production and differentiation; low platelet counts lead to increased free TPO.
Hemostasis
- Physiological process halting bleeding at injury sites while maintaining blood flow.
- Involves primary hemostasis (platelet plug formation), secondary hemostasis (clot formation), and tertiary hemostasis (fibrinolysis and clot dissolution).
Primary Hemostasis
- Vascular phase involves vascular constriction.
- Platelet phase includes:
- Platelet adhesion to subendothelium, reliant on von Willebrand Factor (vWF).
- Activation leading to shape changes, membrane alterations, and granule secretion.
- Aggregation into an irreversible platelet plug, aided by ADP and Thromboxane A2.
Von Willebrand Factor (vWF)
- Synthesized by endothelial cells and platelets, circulates as multimeric strings.
- Composed of over 100 subunits, molecular weights ranging from 500 to 20,000 kDa.
- Functions as "platelet glue" by binding to subendothelial collagen, facilitating platelet interactions.
- Binds and prolongs the half-life of factor VIII in blood.
Platelet Activation
- Triggered by adhesion (to collagen) and ligation (to thrombin and TXA2).
- Shape change transforms smooth discs into spheres with extensive filopodia, increasing surface area.
- Membrane flip moves negatively charged phosphatidylserine to the outer surface, enhancing procoagulant activity.
- Granule secretion includes ADP, calcium, and factors V and VIII to facilitate further platelet activation.
Secondary Hemostasis
- Provides surfaces for fibrin formation and deposition necessary for clot stability.
- Facilitates clot retraction through actomyosin contractions, aiding in wound closure and vessel patency.
Role in the Immune System
- Platelets contribute to immune responses apart from hemostatic functions.
Clinical Correlation - Von Willebrand Disease
- Most common inherited bleeding disorder in dogs, characterized by reduced, non-functional, or absent vWF.
- Certain breeds, such as Doberman Pinschers and Poodles, are more susceptible.
- Symptoms include skin bruising, prolonged bleeding from minor wounds, and excessive bleeding during surgery.
- Diagnosis through vWF antigen assay and genetic testing.
- No cure; management includes avoiding risky activities and pre-surgery plasma transfusion to prevent hemorrhage.
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Understand the function and composition of blood, clinical relevances etc