Questions and Answers
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?
Which of the following is NOT a function of blood?
Which type of plasma protein is primarily responsible for maintaining fluid balance?
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What does serum consist of?
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Which of the following is considered an electrolyte found in plasma?
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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?
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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?
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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?
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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?
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What is the clinical significance of elevated direct bilirubin levels?
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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)?
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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?
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What distinguishes granulocytes from agranulocytes?
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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?
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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?
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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?
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Which type of cell is considered part of the adaptive immune response?
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What distinguishes monocytes from lymphocytes?
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What is an important non-immune function macrophages/monocytes have?
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Which of the following is true regarding basophils?
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Which statement about lymphocytes is accurate?
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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?
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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?
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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?
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What is the primary role of B lymphocytes after their selection process?
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What is the physiological consequence of neutrophilia?
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What percentage of B lymphocytes typically survives the selection process?
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What is the expected outcome of evaluating leukocytes?
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What is the primary function of platelets in hemostasis?
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What regulates thrombopoiesis?
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Which phase in primary hemostasis involves vascular constriction?
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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?
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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?
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In which blood component does platelet activation primarily occur?
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What structural change do platelets undergo during activation?
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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?
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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?
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Match to their correct function
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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