CB Quiz 1 Flashcards
How are we able to observe the main components of blood?
Centrifugation
After Centrifugation, what main components of blood can be observed? Describe them.
We are able to observe blood through the centrifugation which will separate blood into 3 main parts with the lightest being on top. Blood is composed of:
• Plasma: Largest component of blood - Contains water, proteins, electrolytes - Serum may be produced after clotting removing proteins
• Buffy Coat: Smallest component of blood - Formed Element - Found in the middle of the centrifuge - Composed of Leukocytes and Platelets
• Erythrocytes: Heaviest component of blood - Contains RBCs
Describe Erythrocytes. Talk about what they contain, primary function, replication, structural significance, and where they are disposed of.
Erythrocytes:
• Also known as red blood cells, erythrocytes contain hemoglobin (Fe) and has the primary function of carrying and transporting oxygen (and some CO2) throughout the body.
• They do not replicate. They are disposed off in the spleen
• Erythrocytes have a flat, donut shaped, structure which allows for an increased surface area. This aids in the exchange of oxygen and CO2 between the blood and cell/tissue. It lacks a nucleus which allows for this shape to occur
Where are RBCs Disposed?
Spleen
Describe the Structure of Erythrocytes and it’s significance
• Erythrocytes have a flat, donut shaped, structure which allows for an increased surface area. This aids in the exchange of oxygen and CO2 between the blood and cell/tissue. It lacks a nucleus which allows for this shape to occur
What is the primary function of Leukocytes
Also known as white blood cells, leukocytes are large blood cells that serve the immune system function. Their primary function is to fend off and eliminate pathogens and infection
What are thrombocytes and what is their function
Also known as platelets, thrombocytes are non-cellular components of blood. Their primary function is clotting.
What is Thrombosis?
Blood clotting
LEARNING OUTCOME: Describe the sites of production of blood in embryos and adults.
In embryos, blastocysts have a yolk sack which is the first tissue to take the role of hematopoiesis. As it grows, the liver is formed and assumes function. Later, the spleen begins to form blood cells. Finally, 4 months into development, the bone marrow is formed.
In adults, hematopoiesis occurs in the blood marrow of bones in the axial skeleton
LEARNING OUTCOME: Describe the Main Components of Blood
We are able to observe blood through the centrifugation which will separate blood into 3 main parts with the lightest being on top. Blood is composed of:
• Plasma: Largest component of blood - Contains water, proteins, electrolytes - Serum may be produced after clotting removing proteins
• Buffy Coat: Smallest component of blood - Formed Element - Found in the middle of the centrifuge - Composed of Leukocytes and Platelets
• Erythrocytes: Heaviest component of blood - Contains RBCs
Erythrocytes:
• Also known as red blood cells, erythrocytes contain hemoglobin (Fe) and has the primary function of carrying and transporting oxygen (and some CO2) throughout the body.
• They do not replicate. They are disposed off in the spleen
• Erythrocytes have a flat, donut shaped, structure which allows for an increased surface area. This aids in the exchange of oxygen and CO2 between the blood and cell/tissue. It lacks a nucleus which allows for this shape to occur.
• Too many Erythrocytes cause a condition called erythrocytosis. Too little causes Anemia which causes fatigue due to the lack of oxygen
Leukocytes:
• Also known as white blood cells, leukocytes are large blood cells that serve the immune system function. Their primary function is to fend off and eliminate pathogens and infection
Thrombocytes:
• Also known as platelets, thrombocytes are non-cellular (non-living) components of blood with the primary function of clotting or thrombosis
Hematopoiesis
Hematopoiesis is the process in which hematopoietic stem cells give rise to blood cells
LEARNING OUTCOME: Outline the Derivation of Cellular Elements of Blood
Hematopoiesis is the process in which hematopoietic stem cells give rise to blood cells. Embryos have pluripotent stem cells that can turn into any type of cell (blood cell) but adults only have multipotent stem cells that can only turn into a select few. In both cases these stem cells become unipotent stem cells that undergo a process to become the desired blood cell type.
What are the Primary and Secondary lymphoid organs
Bone Marrow
Thymus
Lymph Nodes
Spleen
MALT
What are the main functions (not each one) of the lymphoid tissues/organs
Lymphoid tissues/organs are responsible for immune system function. Primary lymphoid tissues include the bone marrow and the thymus. They are responsible for the production and maturation of lymphocytes. The secondary lymphoid tissues include the lymph nodes, spleen and MALT. They are responsible for detecting infection, handling blood, maintenance, and protection against infection.
Describe the Location and Function of the Bone marrow. Also give the function of what they produce.
Bone marrow found in the axial skeleton is a primary lymphoid. It’s primary function is the production of B-lymphocytes.
B lymphocytes are responsible for the body’s Humoral Immune Response. This involves the production of antibodies against an antigen presented by pathogens or infecting bodies. They also produce memory cells which allow for a quicker and more efficient immune response if the same infection occurs again.
Describe the location and function of the Thymus gland. Also give the function of what it produces.
The Thymus gland is a primary lymphoid organs that is found in the front of the thorax anterior to the heart. T cells are responsible for the Cellular Immune Response where they identify and destroy already infected cells.
Where is the Thymus Gland Located
Found in the front of the thorax and anterior to the heart
What is the Humoral Immune Response
It is where B-lymphocytes produce antibodies in response to antigens presented by pathogens or an infecting body
What is the Cellular Immune Response
It is where T-lymphocytes identify and destroy already infected cells.
Where is the hematopoietic bone marrow located
Axial Skeleton
What are lymph nodes and where are they located? Indicate its functions.
Lymph nodes are secondary lymphoid tissues that are found within capillary beds that carry a high concentration of lymphocytes. Their functions are:
- Carry excess fluid back to the venous system
- Act as strainers filtering pathogenic material, cancer material, and large objects from entering the blood (causes swelling when infected)
Describe the spleen with its location. Explain it’s function
The spleen is a secondary lymphoid organ located behind the left ribs and next to the stomach. It is highly vascular which can cause heavy bleeding from trauma. The spleen is contained within a capsule and has white and red pulps where it stores a high concentration of lymphocytes and disposes of RBCs.
Describe MALT giving its location and function.
How is MALT different between children and adults
MALT or Mucosa Associated Lymphoid Tissue is located in the Tonsils and Peyer’s patch in the small intestine. It contains a large amount of B and T lymphocytes to fight infection.
More MALT is found in children when compared to adults as children explore the world with their mouth.
What Does MALT Stand For
Mucosa Associated Lymphoid Tissue
LEARNING OUTCOME: Describe the Primary and Secondary Lymphoid Organs
Lymphoid tissues/organs are responsible for the immune system function. The primary lymphoid tissues include bone marrow and thymus which are involved in producing and maturing lymphocytes (B and T cells). The secondary lymphoid tissues include lymph nodes, spleen, and MALT which are responsible for detecting infection, handling blood and maintenance, and protection against infection.
Bone Marrow: Primary lymphoid - Found in the Axial Skeleton - Responsible for the production of B lymphocytes (B cells) - B cells are responsible for the Humoral Immune Response which involves the production of antibodies in response to antigens presented by the pathogens or infecting body - Also responsible for the production of memory cells/antibodies which allow for a quicker and more efficient response if the same infection occurs again - Researchers are using this to fight COVID
Thymus Gland: Primary lymphoid - Found in the front of the thorax and anterior to the heart - Responsible for the production of T lymphocytes (T cells) - T cells are responsible for the cellular immune response where they identify and destroy already infected cells - Major components are Cortex (outer tissue, dark staining) and Medulla (inner tissue, paler staining)
Note: B cells cannot recognize when a pathogen has already invaded a cell, so the T cells handle infected cells
Lymph Nodes: Secondary lymphoid - Located within capillary beds - Responsible for carrying excess tissue fluid back to the venous system - High concentration of lymphocytes - They act as strainers preventing larger substances and infectious material from passing - Will enlarge when infected
Spleen: Secondary lymphoid - Located behind the left ribs, next to the stomach - Extremely vascular and can cause heavy bleeding after trauma - Young people can handle keeping BP stable with a sudden drop later but elders will have a steady decline in blood pressure - Responsible for filtering the blood from foreign antigens - The spleen is contained within a capsule and has white pulp for WBCs and red pulp for RBCs (check diagram)
MALT: Secondary Lymphoid - Located in the Tonsils and Peyer’s patches in the small intestine - Known as Mucosa Associated Lymphoid Tissue - Contains B cells and T cells to fight infection- More MALT is found in children rather than adults because they explore with their mouth and hence high risk of infection which causes extreme swelling of the tonsil. This does not affect adults that much if they are removed
LEARNING OUTCOME: Explain the Circulation of Lymphs
The lymphatic system is responsible for carrying tissue fluid back to the venous system. The fluid generally passes through lymph vessels located around the body to lymph nodes where they are filtered. Upon arriving to the lymph nodes, the lymph enters through afferents and pass through the Cortex, where B cells are located, the Paracortical, where T cells are located, and the Medulla, where Plasma cells are located. They then finally exit through efferents. These lymphs go across the body passing through several lymph nodes that are either Superficial lymphatics (run with veins) or Deep lymphatics(run with arteries)
Example: Lymphatics found in the leg will move up towards the superficial Inguinal lymph nodes found next to the pelvis and then move upwards towards the Deep lymph nodes found at the aorta which then feeds into the one found at the Thoracic duct and finally feed into the Subclavian veins
Where are the main lymph nodes located? Up top down
- Cervical Nodes: Along course of internal Jugular Vein
- Pericardial Ring: Base of Head
- Tracheal Nodes: Nodes along the trachea and bronchi
- Axillary Nodes: Arm pits (Axilla)
- Deep Nodes: Nodes along the Aorta, Celiac Trunk, and Superior and Inferior Mesenteric Arteries
- Inguinal Nodes: Along the Course of Inguinal ligament (near pelvis)
- Femoral Nodes: Along Femoral Vein
Describe the pathway of lymph within lymph nodes along with its parts
Upon arriving to the lymph nodes through the afferent vessel, it passes through the Cortex, where the B cells are located, the Paracortical, where the T cells are located, and the Medulla where plasma cells are located and then finally exit through the efferents
Draw the pathway of the Lymph from the leg till its end point.
- Lymphatics begin in the legs
- Superficial Inguinal lymph nodes
- Deep Lymph nodes
- Thoracic Duct
- Subclavian Veins
Erythrocytosis
Too many RBCs
Define Anemia with one symptom
Erythrocytes below reference level, may cause fatigue due to lack of oxygen
Name the 5 types of Leukocytes
Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes
Describe Neutrophils (including staining and function) What does a high count of neutrophils indicate?
Most common type of WBC. It cannot be stained and hence neutral. They are the phagocytic and are the first line of defense against bacterial infection. Neutrophils last longer at the site of infection than when circulating in the blood. A high count of neutrophils indicates a site of infection.
Discuss Eosinophils.
Eosinophils are the second most common granulocyte and is basic, hence stained by Eosin (acidic). They have a clear multilobe nucleus when stained. Survival in tissue is a lot longer. Granules contain histamine, RNAase, and DNAase to combat viral and parasitic infections.
Describe Basophils
Least Common WBC and acidic hence stained by hematoxylin. When stained, it is hard to distinguish granules from nucleus as DNA is also acidic. It contains large cytoplasmic granules. It synthesizes and stores Histamine and Heparin. It’s release speeds up the removal of fat particles from the blood
Describe monocytes
Monocytes are phagocytes that
- Ingest bacteria by engulfing them.
- Enter tissues and become tissue macrophages.
- Process and remove aged RBCs.
- Are modulators of immune response
- Have a long lifespan when not in circulation. - Are characterized by it’s kidney-shaped nucleus
- Can differentiate into Dendritic Cells and Macrophages
Describe Thrombocytes along with their function.
Also known as platelets, thrombocytes are non-cellular components (cell fragments) of blood with the primary function of clotting or thrombosis. They are the second most numerous blood component and lack nuclei. They have cytosolic enzymes for generating energy. They are stored in blood-filled spaces in the spleen and are released when needed by sympathetically induced splenic contractions. It plats an important role in homeostasis as it seals leaks in blood vessels.
What are the formed elements of the blood
RBCs, WBCs, and Platelets
Erythrocytes, leukocytes, and thrombocytes.
Explain the bone marrow’s role in hematopoiesis/Hemopoiesis along with how it divides its role and why. Trace its production in the bone marrow.
The bone marrow (found in the axial skeleton) is the primary producer of RBCs and WBCs. It divides its work with 1/3 for RBC ans 2/3 for WBCs. Despite the fact that there are a lot more RBC than WBC in the blood, WBC have a much shorter life span. Progenitor Cells divide to produce erythrocytes, leukocytes and megakaryocytes (precursor of of platelets). All peripheral cells are derived from a single multipotent stem cell (adults). Stem cells grow and divide in the bone marrow and once differentiated, they lose their capacity for self-renewal and cell adhesion, which allows them to leave the marrow and enter circulation.
What are Progenitor Cells
They are cells found in the bone marrow that divide to produce RBC, WBC, and megacaryocytes
What are megakaryocytes
Precursors of platelets
What are the Growth Factors involved in Hemopoiesis
Erythropoietin: Stimulates erythrocyte production
Colony stimulating factors and Interleukins: Stimulate WBC production
Thrombopoietin: Stimulates the production of platelets or thrombocytes
The parts of the Axial skeleton where blood is produced is…
Pelvis, Cranium, and Sternum
When more blood is needed what organs assist in hematopoiesis?
Liver, thymus, and spleen
What Are the stages of Erythropoiesis
- Proerythroblast: Large nucleus with DNA to make RNA
- Basophilic (early) Erythroblast: Staining is stronger as RNA production is increased
- Polychromatic (intermediate) Erythroblast: Hemoglobin (protein) is being produced
- Orthochromatic (late) Erythroblast: Nucleus becomes significantly smaller to make room for more hemoglobin and gets excluded
- Reticulocyte: RBC will enter circulation and still has ribosomes left to finish hemoglobin production
- Mature RBC: Loses ribosomes occupying all space by hemoglobin and forming biconcave shape
Describe the Characteristics of Erythrocytes
Erythrocytes have a flat, biconcave, disc shaped structure which allows for an increased surface area. This aids in the exchange of gas’s between the blood and cell/tissue making it more efficient. RBCs also lack a nucleus which allows for flexibility when passing through capillaries and more space for hemoglobin.
Describe the Life Cycle of Erythrocytes
The life span of erythrocytes is approximately 120 days. RBCs are removed by macrophages such as monocytes and hemoglobin components are recycled:
- Globin is reutilized in amino acid formation
- Iron is reutilized to form more RBCs
- Heme is excreted in bile
RBC count indicates
Anemia and Polycythemia
Reticulocytes indicate
Erythropoietic activity in the bone marrow
Packed cell volume/Hematocrit Measures….
The fraction of blood occupied by RBC
Hemoglobin count indicates…
Iron Binding Capability
Mean Cell Volume measures
Volume of average RBC
Mean Cell Hemoglobin measures
Concentration of Hb in average RBC
Mean Cell Hemoglobin Concentration measures…
Concentration of Hb per dL of RBC
Discuss Anemia (without classification)
Anemia is classified as the deficiency of Hemoglobin/RBC in the blood. It occurs with patients who have iron deficiency, blood loss, B12 deficiency, and/or folate deficiency This has several indications: Decreased rate of erythropoiesis Excessive loss of erythrocytes Deficiency in hemoglobin content of Erythrocytes Decrease in Hb (below reference level)
How can we classify Anemia and what are the classifications
We classify anemia based on size and color of RBC:
- Hypochromic (less than normal amount) and Microcytic (smaller than normal)
- Normochromic (Normal amount) and Macrocytic (larger than normal)
- Polychromatophilic (more than normal) amount) and Macrocytic (larger than normal)
Describe Hypochromic and Microcytic Anemia
It describes anemia with iron deficienct or chronic disease.
- Iron deficiency: Iron deficiency caused by blood loss in adults can occur through trauma/bleeding or chronic blood loss such as menstrual bleeding and digestive tract bleeding. These prevent the body from reusing the iron and hence more intake is required. Another cause is lack of iron in diet.
- Anemia of chronic disease:
- Inflammatory Diseases: Causes the impairment to erythropoietin which is the growth factor for RBC production. During these conditions, there is an increase in inflammatory cytokines such as interleukin-6 (IL-6) which would cause the increase of hepsidin which will block iron update and absorption.
- Malignancies: Also causes impairment of EPO (erythropoietin) response due to cytotoxic treatments used to treat cancer which targets bone marrow
- Chronic Kidney Disease/Chronic Heart Failure: This prevents stimulation of RBC production by reducing renal flow which decreased production of EPO
Describe Normochromic and Macrocytic Anemia
Caused by vitamin B12 and folate deficiency. This deficiency occurs due to the lack of the gastric intrinsic factor which forms a complex with vitamin B12 for absorption or malnutrition. This causes RBCs to grow large and with odd shapes. The effects of this deficiency with anemia include
- Symmetrical feeling of tingling in the feet
- Loss of the sense of vibration
Occasional muscle weakness which causes difficulty in walking
How is Vitamin B12 absorbed in the body?
B12 is only absorbed when in a complex with the Gastric Intrinsic Factor (GIF) which is a glycoprotein secreted by parietal cells in the stomach. This complex cannot be broken down and is absorbed by a specific receptor found on cells in the ileum.
Discuss Polychromatophilic and Macrocytic Anemia
This is caused by hemolytic anemia which causes the reduced lifespan of erythrocytes where the rate of destruction exceeds the rate of production. These anemias can occur through genetic disorders that affect the shape of the RBC such as sickle cell anemia as well as acquired disorders such as immune system disease where there is an ABO or Rh incompatibility with blood transfusion.
What is Polycythemia and what are the primary types of it?
Polycythemia is characterized by having too many circulating RBCs. It can be indicated by increased Hb or RBC count above reference levels. The 3 types are:
- Primary Polycythemia
- Secondary Polycythemia
- Relative polycythemia
Discuss Primary Polycythemia giving an example
This occurs due to intrinsic factors to RBC precursors caused by an acquired or inherited mutation showing a tumor-like condition of the bone marrow with uncontrollable rate of production.
An example of this is polycythemia Vera which is a genetic aberration in the RBC precursor cells. This causes for excess production beyond what is sufficient for plasma circulation causing sluggish and slow circulation which increases the workload of the heart. Chemotherapy treats this.
Discuss Secondary Polycythemia
Physiological type of polycythemia which occurs as a mechanism to improve the blood’s oxygen-carrying capacity in response to prolonged reduction in oxygen delivery to the tissue. This occurs in high altitude athletes
What is Relative Polycythemia
This occurs when the body loses fluid and not RBCs. Too little plasma but good amount of RBCs
LEARNING OUTCOME: Explain the Clinical Evaluation of Anemia
Anemia is classified as the deficiency of hemoglobin in the blood. During clinical evaluation several indices may be examined:
- Blood Count (RBC indices), Hemoglobin concentrations in MCV, MCH, and MCHC
- Reticulocyte index
- Determination of acuteness or chronicity
Clinical signs of anemia include the following:
• Fatigue and weakness
• Pallor: Abnormal loss of skin or mucous membrane layer (ex. The eye)
• Koilonychia: Upward curvature of nails
• Angular stomatitis: Deep cracks and splits formation at the corners of the mouth
• Glossitis: Inflammation or infection of the tongue
LEARNING OUTCOME: Discuss the role of Heme in Oxygen Binding
Multicellular organisms need to transport and store O2 for aerobic metabolism. The heme group (found in both Hb and Mb) is tightly bound to proteins and allows them to bind oxygen to them. The heme group consists of a Protoporphyrin Ring consisting of Fe2+ which is held into position by 4 Nitrogen atoms
LEARNING OUTCOME: Describe the Structure and Function of Myoglobin
Structure: Compact protein
- Consists largely of alpha helices
- Hydrophilic exterior and hydrophobic interior with the exception of histidines
- Heme group positioned between 2 His groups binding to the proximal His and intermolecularly bound to the distal His
- Oxygen binds between the heme group and the distal His causing structural change between the heme and proximal His.
Function: O2 reservoir within heart & skeletal muscle cells to be released when O2 supply is insufficient
LEARNING OUTCOME: Describe the Structure and Function of Hemoglobin
3- Describe the Structure and Function of Hemoglobin (Hb):
Structure: 4 identical polypeptide chains (2 alpha and 2 beta chains or one alpha dimer and one beta dimer) - Each chain consists of a heme group => can bind 4 oxygens - Subunits held together by intermolecular interactions (non-covalent) => can be flexible and hence adds to the flexibility of the RBC
Function: Transports O2 to tissues and Transports CO2 and protons (H+) away from tissues
What does the Oxygen dissociation curve represent?
It represents how Hb and Mb bind to oxygen and their affinities.
Describe the normal dissociation Trend of Mb as PO2 increases
As PO2 increases there is a steep increase in % saturation with O2 and since Mb can only bind with one O2 there is no further binding and hence no co-cooperativity.
Compare Adult and Fetal Hb Values
Adults have less affinity than fetal Hb (To the right) and hence O2 can pass from maternal RBCs to Fetal RBCs.
What are the Co-Cooperativity and Allosteric Effects of Hb
- Heme-Heme Interaction
- Bohr Effect
- 2,3 Bisphosphoglycerate (2,3-BPG)
Discuss Heme-Heme interactions and the dissociation curve of Hb
Since Hb has 4 oxygen binding sites, it also has a sigmoid curve which is indicative of it’s COOPERATIVE BINDING. When one oxygen binds to a heme group, the other heme groups become more receptive and will bind following oxygen to other heme groups a lot easier. This is due to the structural changes that occur in Hb when oxygen binding occurs. Hb is in a Tense Form when there are no O2 molecules bound to the Hb and hence low affinity to O2 yet high affinity when in the relaxed form with up to 4 O2 molecules bound to it.
Discuss the Bohr Effect:
As cellular respiration increases, PCO2 increased which causes the pH to decrease which then causes the affinity to O2 to decrease. This allows O2 to be released more easily which shifts the curve to the right. This maximizes the efficiency of oxygen handling by Hb as it releases oxygen to cells that require O2 the most.
Discuss the effects of Bisphosphoglycerate
It is present in erythrocytes at equimolar concentration to Hb. It binds to deoxygenated Hb only forming salt bridges with positively charged residues between the Beta polypeptide chains in the central cavity decreasing its affinity for O2. This binding stabilized the Taut conformation (T) which causes the curve to move to the right. This can be reverted through oxygenation removing the cavity allowing Hb to have even higher affinity than it originally had. The body regulates the amount of 2,3-BPG in the blood to regulate oxygen affinity.
NOTE: As concentrations of 2,3-BPG increases, affinity of O2 decreases and hence O2 delivery to tissues increases. This tends to occur at high altitudes just.
What is included in CADET and what does this do?
The increase of CO2, Acid, DPG (another word for 2,3-BPG), Exercise, and Temperature shift the curve to the right which causes less oxygen affinity and more oxygen delivery
Outline the Metabolic Capability of RBCs
Erythrocytes have the ability to perform the Pentose-Phosphate Pathway which allows for the prevention of Oxidative stress by ROS (Reactive Oxygen Species) which, in turn, prevents hemolysis
LEARNING OUTCOME: Discuss the Molecular Basis of Sickle Cell Anemia giving rise to its clinical consequences, diagnosis, and treatment
Sickle Cell Anemia: Sickle cell anemia is caused by a point mutation that occurs in the beta chain in Hb from Glutamate to Valine. This causes the valine to adopt a Sticky patch in low O2 conditions which significantly reduces cell flexibility. This causes hydrophobic interactions to occur between Hb subunits which leads to stacking into long fibers. These fibers distort the erythrocyte into a sickle shape causing the blockage of capillaries and Anoxia (or lack of oxygen reaching tissues) which, in turn, causes pain and cell death. It is precipitated (occurs more often, other than genetically) through dehydration and infection.
Clinical Consequences:
• Bone pain (sickle cells stuck in capillary beds)
• Chronic anemia (destruction of erythrocytes)
• Organ damage (kidneys, heart, & lungs)
• Cerebrovascular accidents
Diagnosis: Protein or DNA analysis
Treatment:
• Treat symptoms
• Hydration, Analgesics (pain killers), and aggressive antibiotics
• Blood transfusion
• Hydroxyurea (raises fetal hemoglobin levels HbF)
Explain Sickle Cell Anemia
Sickle cell anemia is caused by a point mutation that occurs in the beta chain in Hb from Glutamate to Valine. This causes Valine to adopt a sticky patch in low O2 conditions which significantly reduces cell flexibility. This then causes hydrophobic interactions to occur between Hb subunits which leads to stacking in long fibers. These fibers distort the erythrocyte into a sickle shape causing blockage of capillaries and Anoxia (lack of oxygen reaching tissues) which causes pain and cell death.
It can occur non-genetically through dehydration and infection.
What is Anoxia
Lack of Oxygen reaching tissues
What are the Clinical Consequences of Anemia (name 3)
- Bone pain (sickle cells stuck in capillary beds)
- Chronic Anemia (Destruction of Erythrocytes)
- Organ Damage (Kidneys, heart, and lungs)
- Cerebrovascular accidents
How is Sickle Cell Anemia Diagnosed
Through Protein or DNA analysis
How do you Treat Sickle Cell Anemia Patients (mention 3)
- Treat symptoms (clinical consequences)
- Hydration
- Analgesics (pain killers)
- Aggressive antibiotics
- Blood transfusion
- Hydroxyurea (Must include this)
LEARNING OUTCOME: Discuss the Molecular Basis of Glucose-6-Phosphate Dehydrogenase Deficiency
It is a metabolic enzyme that affects NADPH production. NADPH minimizes damaging effects of ROS (Reactive Oxygen Species) such as H2O2. ROS causes Oxidative Stress on cells by attacking DNA, protein, and lipids.
Deficiency of G6PD impairs the ability of the Erythrocyte to form NADPH which results in Hemolysis (cell death). Oxidative stress leads to Hemolytic Anemia (where body destroys more RBC than it produces)
Factors that increase Oxidative Stress include:
- Oxidant Drugs
- Favism (ingestion of Fava beans)
- Infection which causes inflammatory response leading to the generation of free radicals
- Neonatal Jaundice: Impaired catabolism of heme or increased production of Bilirubin
Hemolysis
Cell Death
Analgesics
Pain Killers
Neonatal Jaundice
Impaired catabolism of heme or increased production of bilirubin
What factors increase oxidative stress
Factors that increase Oxidative Stress include:
- Oxidant Drugs
- Favism (ingestion of Fava beans)
- Infection which causes inflammatory response leading to the generation of free radicals
- Neonatal Jaundice: Impaired catabolism of heme or increased production of Bilirubin
What does an increase of Oxidative Stress cause in terms of RBCs
Hemolytic Anemia (where the body destroys more RBCs than it produces)
LEARNING OUTCOME: Explain the Mechanism of Action of Hydroxyurea in the Treatment of Sickle Cell Disease
Hydroxyurea is traditionally a cancer treatment that changes gene expression levels and is used to increase fetal hemoglobin levels which are not expressed in adults. This allows for production of a normally functioning oxygen supplier to the body to assist in oxygen delivery.
What are the differences between Hb and Mb
- Mb is a storage protein whereas Hb is not
- Mb binds to O2 avidly and dissociates slowly whereas Hb carries Oxygen and transports them through RBC to the tissues to be released
- Mb is not co-operative as it only has one Heme group when compared to Hemoglobin’s 4 heme groups where when one oxygen binds to the protein, the next will bind more easily and better
- Mb is only 1 polypeptide whereas Hb has 4.
- Hb dissociates at a higher partial pressure than Mb
What is the distribution and composition of Body fluids in the body?
Extracellular fluids make up 20% but is split into plasma (5%) and interstitial fluid (15%). Plasma and interstitial fluid have the same electrolyte composition but plasma has additional protein anions. The dominant cation is Na+ and the dominant anion is Cl- with a smaller amount of HCO3-
Intracellular fluid make up 40%. Dominant cation is K+ and dominant anion is PO4^3- with a smaller amount of protein anions.
How is the composition of fluids in the ECF maintained at a constant level? Give an Example
Constancy of ECF composition is critical for cell function and is maintained by homeostasis. Everyday activities of the body changes the composition of the ECF. Homeostasis is controlled by Negative feedback ex. Glucose and insulin
How is the composition of body fluids in the ICF maintained at a constant level? Give an Example
Constancy of ICF is important for cell function as ionic strength has a major influence on Cellular Reactions. This constancy is maintained by Cell Mechanisms. The cell membrane separates ICF from ECF which maintains concentrations of electrolytes and hence water by osmosis. Ex Na/K pump
What is Osmotic Pressure?
The Osmotic Pressure of body fluids is a measure of the tendency of water to move into that solution due to relative concentrations but does not tend to happen since the osmotic pressure of ICF and ECF are similar. It is determined by number of particles and not mass. It is measured by OSMOLES (osm)=1 mole (mol)
What is the osmole concentration of 1 mole of glucose
1
What is the osmole concentration of 1 mol of NaCl
2
What is the osmole concentration of 1 mole of Na2SO4
3
What is the osmole concentration of CaCl2
2
What is the difference between Osmolarity and Osmolality
Osmolarity is expressed in Osmol/L of a SOLUTION
Osmolality is expressed in Osmol/Kg do a SOLVENT
The Osmolarity of body fluid is…
283 +/- 11 mOsmol/L
What is used clinically Osmolarity or Osmolality
Osmolality
Disturbances to water balance control are caused by:
- Diabetes Mellitus
- Dehydration
- Diabetes Insipidus
How does Diabetes Mellitus affect Water Balance
Diabetes Mellitus results from a deficiency of circulating insulin characterized by Hyperglycemia. Glucose is osmotically active and hence an increased amount of glucose causes water to shift into the plasma causing intracellular dehydration which affects cell function. This will also cause the patient to have Polyurea or glucose in urine, increased urination, and suffer from dehydration.
Hyperglycemia
High levels of glucose
How does Dehydration affect water balance
Due to insufficient water intake or excessive water loss due to heavy sweating, vomiting, or diarrhea. This causes water deficiency in the blood and in the tissues impairing cell function and metabolism
How does Diabetes Insipidus Affect water balance distribution
Diabetes Insipidus is characterized by a deficiency in Vasopressin which reduces urinary output to conserve water in the body. This leads to dehydration.
What are the Effects of Dehydration
Effects of Dehydration: Symptoms are mainly neurological as water loss from brain cells leads to shrinkage of cells:
Water content of ECF decreases -> Osmolarity of ECF increases -> Water leaves cells -> Osmolarity of ICF increases -> Disruption of cellular function
1. Mild Cases: Dry skin, Dry tongues, and Sunken Eyeballs
2. Moderate Cases: Mental confusion, Irrationality
3. Severe: Delirium, Convulsions, Coma
4. Non-Neural Symptoms: Circulatory disturbances: Vary from slight lowering of blood pressure to circulatory shock and death
What are the effects of Overhydration
Effects of Overhydration: Excess Excess water in ECF => Osmolarity of ECF decreases => Water moves into cells => Osmolarity of ICF decreases => Disruption of cellular function. Usually does not occur as any surplus of water is excreted immediately through urine. It does occur, however in:
- Patients with Renal Failure
- Low body mass infants
- Marathon runner who drink water only (must take electrolytes with it)
- Overheating (Overexertion/MDMA-Ecstacy)
- Syndrome of Inappropriate Vassopression/ADH Secretion (Opposite of Diabetes Insipidus => too much secretion)
What are the Symptoms of overhydration
Symptoms Include: Symptoms related mainly to water entry into brain cells making them swell
- Mild & Moderate: Confusion, Lethargy (fatigue), headache, dizziness, vomiting
- Severe: Coma and death
- Non-Neural Symptoms: Weakness (swelling of muscle cells) and Circulatory disturbances (Expansion of plasma volume)
Explain how Tonicity of Solutions is determined
Tonicity is a measure of the osmotic pressure gradient of 2 solutions seperated by a semi-permeable membrane. Solutes that are able to flow freely across plasma do not affect tonicity as they will automatically reach equilibrium. WATCH THE UNIT
Talk about hypertonic, isotonic, and hypotonic cuz you know it already lmao
LEARNING OUTCOME: Describe the Main Components of Blood
We are able to observe blood through the centrifugation which will separate blood into 3 main parts with the lightest being on top. Blood is composed of:
• Plasma: Largest component of blood - Contains water, proteins, electrolytes - Serum may be produced after clotting removing proteins
• Buffy Coat: Smallest component of blood - Formed Element - Found in the middle of the centrifuge - Composed of Leukocytes and Platelets
• Erythrocytes: Heaviest component of blood - Contains RBCs
Erythrocytes:
• Also known as red blood cells, erythrocytes contain hemoglobin (Fe) and has the primary function of carrying and transporting oxygen (and some CO2) throughout the body.
• They do not replicate. They are disposed off in the spleen
• Erythrocytes have a flat, donut shaped, structure which allows for an increased surface area. This aids in the exchange of oxygen and CO2 between the blood and cell/tissue. It lacks a nucleus which allows for this shape to occur.
• Too many Erythrocytes cause a condition called erythrocytosis. Too little causes Anemia which causes fatigue due to the lack of oxygen
Leukocytes:
• Also known as white blood cells, leukocytes are large blood cells that serve the immune system function. Their primary function is to fend off and eliminate pathogens and infection
Thrombocytes:
• Also known as platelets, thrombocytes are non-cellular (non-living) components of blood with the primary function of clotting or thrombosis
Hematopoiesis
Hematopoiesis is the process in which hematopoietic stem cells give rise to blood cells
LEARNING OUTCOME: Outline the Derivation of Cellular Elements of Blood
Hematopoiesis is the process in which hematopoietic stem cells give rise to blood cells. Embryos have pluripotent stem cells that can turn into any type of cell (blood cell) but adults only have multipotent stem cells that can only turn into a select few. In both cases these stem cells become unipotent stem cells that undergo a process to become the desired blood cell type.
What are the Primary and Secondary lymphoid organs
Bone Marrow
Thymus
Lymph Nodes
Spleen
MALT
What are the main functions (not each one) of the lymphoid tissues/organs
Lymphoid tissues/organs are responsible for immune system function. Primary lymphoid tissues include the bone marrow and the thymus. They are responsible for the production and maturation of lymphocytes. The secondary lymphoid tissues include the lymph nodes, spleen and MALT. They are responsible for detecting infection, handling blood, maintenance, and protection against infection.
Describe the Location and Function of the Bone marrow. Also give the function of what they produce.
Bone marrow found in the axial skeleton is a primary lymphoid. It’s primary function is the production of B-lymphocytes.
B lymphocytes are responsible for the body’s Humoral Immune Response. B cells proliferate to generate antibodies against an antigen presented by pathogens or infecting bodies. They also produce memory cells which allow for a quicker and more efficient immune response if the same infection occurs again.
Describe the location and function of the Thymus gland. Also give the function of what it produces.
The Thymus gland is a primary lymphoid organs that is found in the front of the thorax anterior to the heart. T cells are responsible for the Cellular Immune Response where they identify and destroy already infected cells.
Where is the Thymus Gland Located
Found in the front of the thorax and anterior to the heart
What is the Humoral Immune Response
It is where B-lymphocytes produce antibodies in response to antigens presented by pathogens or an infecting body
What is the Cellular Immune Response
It is where T-lymphocytes identify and destroy already infected cells.
Where is the hematopoietic bone marrow located
Axial Skeleton
What are lymph nodes and where are they located? Indicate its functions.
Lymph nodes are secondary lymphoid tissues that are found within capillary beds that carry a high concentration of lymphocytes. Their functions are:
- Carry excess fluid back to the venous system
- Act as strainers filtering pathogenic material, cancer material, and large objects from entering the blood (causes swelling when infected)
Describe the spleen with its location. Explain it’s function
The spleen is a secondary lymphoid organ located behind the left ribs and next to the stomach. It is highly vascular which can cause heavy bleeding from trauma. The spleen is contained within a capsule and has white and red pulps where it stores a high concentration of lymphocytes and disposes of RBCs.
Describe MALT giving its location and function.
How is MALT different between children and adults
MALT or Mucosa Associated Lymphoid Tissue is located in the Tonsils and Peyer’s patch in the small intestine. It contains a large amount of B and T lymphocytes to fight infection.
More MALT is found in children when compared to adults as children explore the world with their mouth.
