LECTURE 1: BLOOD Flashcards
Define the cardiovascular system. State the three main components.
There are three major constituents to the cardiovascular system:
Heart – pump to drive circulation of blood in vessels (vasculature)
Vasculature – vessels to transport blood
○ Arteries - transport blood away from heart to tissues
○ Veins - transport blood away from tissues toward the heart
Blood – liquid connective tissue
○ Contained in vasculature
○ Formed elements - cells and cell products
○ Plasma - fluid and dissolved substances
○ Exchanges materials with interstitial fluid
Understand the primary functions of blood.
The functions of blood are:
Transportation
○ oxygen and other gasses to and from tissue cells
○ hormones from endocrine glands
○ nutrients from GI tract
○ metabolites and waste products
Regulation
○ homeostasis (blood pH)
○ body temperature
○ water balance
Protection
○ immunity (white blood cells, antibodies)
○ blood clotting
Interstitial fluid is the medium through which blood and tissue cells exchange materials. Vasculature transports blood to and from metabolically active tissues where there is an exchange of materials (between blood, interstitial fluid, and tissues) at specialized vessels called capillaries. Blood is inside capillaries, while interstitial fluid is outside of capillaries and cells of metabolically active tissues.
Describe the physical characteristics of blood.
A person typically has between 4-6 liters of blood, accounting for roughly 8% of their total body weight.
Blood is primarily water with a substantial amount of
cells, cell products, biological macromolecules, nutrients, molecules, and other substances.
Circulating blood is approximately 38°C (100.4°F), and physiological processes maintain a range of blood pH typically between 7.35-7.45.
Explain the function of the carbonic acid-bicarbonate buffer system. Explain the ramifications of overly acidic or basic blood in relation to this buffer system.
How are excess carbon dioxide, bicarbonate ions, and protons cleared from the body?
Blood typically has a pH of 7.35-7.45, which is influenced by a variety of physiological processes involving the sequestering or release of various molecules.
The carbonic acid-bicarbonate ion buffer system (CA-BI) is among the principal ways in which the blood may resist drastic changes in pH. Carbonic acid (H2CO3) is
formed when carbon dioxide (CO2) is released by metabolically active tissues as a waste product of glucose catabolism and reacts with water (H2O).
Carbonic acid can also dissociate into bicarbonate ion (HCO3-) and hydrogen ion (H+). These two reactions are reversible and exist as a dynamic equilibrium. Any changes to the chemical environment of the blood will shift the direction of the reaction to promote homeostasis (pH within 7.35-7.45). Whenever the blood becomes more acidic (increased H+), the equation shifts to the left (toward producing more carbon dioxide). Whenever the blood becomes more basic, the equation shifts to the right (toward producing more hydrogen ions)
Lungs & Respiration
Among their major functions, lungs expel carbon dioxide from the body.
Faster breathing expels more carbon dioxide, whereas slower breathing expels less carbon dioxide.
As CO2 levels build in the blood, the rate of respiration can increase to help clear the CO2 from the body.
Kidneys & Urination
Kidneys are dynamic filters of the blood. In instances where the blood is too acidic, the kidneys can filter the excess hydrogen ions out of the blood and excrete them through urine.
Describe the components of blood. Discuss the contents of each component.
Blood consists of two parts: plasma & formed elements.
A solution has two components: a solute and a solvent. Blood plasma (55% of blood by volume) is a solution with water (91.5% of blood plasma by volume) as the solvent. Proteins are the most abundant solute. There are several types of proteins commonly found in blood:
Albumins – transport, maintain osmotic pressure
Globulins – immune function
Fibrinogens – clotting
The remaining solutes consist of nutrients, electrolytes, blood gases, hormones & cytokines, and waste products.
The addition of formed elements (45% of blood by volume), which include blood cells and cellular products, makes blood a mixture.
Define the formed elements of the blood. Which formed elements are the most and least abundant?
There are three types of formed elements:
Erythrocytes (ery=red), red blood cells (RBCs)
○ most abundant formed element
○ gas transport
Leukocytes (leuko=white), white blood cells (WBCs)
○ least abundant formed element
○ Immune responses
Thrombocytes (thrombus=clot), platelets
○ Clotting
Understand the function and clinical significance of a blood smear.
A blood smear is a simple clinical test using light microscopy to gauge the relative abundances and morphologies of the formed elements as well as to inspect for blood parasites. Blood is smeared on a slide and then stained to best visualize the numbers and shapes of cells.
Erythrocyte shapes may fall into one of three categories:
Microcytic - abnormally small RBCs
Normocytic - typical RBCs
Macrocytic - abnormally large RBCs
Explain the origin and differentiation of blood cells.
Describe the process of hematopoiesis, where it occurs in the body, and when.
Describe the general pathway of formation of a blood element from a stem cell.
Formed elements arise from hematopoietic connective tissue. Hematopoiesis (aka hemopoiesis) refers to the process of creating new formed elements. A variety of tissues may participate in hematopoiesis, depending on the developmental state at the time.
Prenatal hematopoiesis occurs primarily in the yolk sac (1st trimester), liver & spleen (2nd trimester), and bone marrow (3rd trimester). Postnatal hematopoiesis primarily occurs in the bone marrow with some contributions from lymph nodes.
Pluripotent stem cells give rise to either myeloid stem cells or lymphoid stem cells. Myeloid stem cells give rise to erythrocytes, thrombocytes, granular leukocytes, mast cells, & monocytes. Lymphoid stem cells give rise to agranular leukocytes (excepting monocytes).
Discuss the various hematopoietic growth factors, which cells they act on, and what prompts their secretion.
Hematopoietic growth factors are substances that regulate the proliferation and differentiation of the formed elements of the blood. Hematopoietic growth factors are specific types of cytokines called hematopoietic cytokines.
Cytokines are a broad category of regulatory substances that play an important role in modulating the immune system. Specific cytokines that stimulate the growth and/or development of formed elements are known as hematopoietic cytokines.
Hematopoietic cytokines include:
Colony stimulating factors (CSFs)
Induce differentiation of myeloid stem cells into colony forming units
Targets progenitor cells, include CFU-E, CFU-Meg, CFU-GM
Interleukins (ILs); inter = between, leuko = WBCs
Vast, diverse
Increase production of white blood cells
Secreted in response to inflammation and immune response
Erythropoietin (EPO)
Promotes the production of erythrocytes
Secreted in response to hypoxia
Thrombopoietin (TPO)
Increases production of thrombocytes (platelets)
Secreted in response to cellular damage
List the broad categories of hematological malignancies and what tissue or cells are affected.
A malignancy is a condition where abnormal cells divide uncontrollably and can spread to other parts of the body. We colloquially refer to malignancies as cancers. There are three categories of blood cancers, each of variable diversity and prognosis. These include:
Leukemias
Arise from blood-forming tissues
Bone marrow and leukocytes (‘blasts)
Lymphomas
Arise from lymphatic tissues
Myelomas
Arise from bone marrow & plasma cells
Describe the basis for the ABO blood grouping system. Understand the broad, foundational characteristics and functions of antibodies. What are the ramifications of receiving the wrong blood type during a blood transfusion?
Blood group systems categorize blood based on erythrocyte plasma membrane surface antigens. The ABO blood group is named for the presence of A, B, AB, or the absence (O) of antigens on the RBC surface.
Type A – A antigens, Anti-B antibodies
Type B – B antigens, Anti-A antibodies
Type AB – A & B antigens, No anti-A or anti-B antibodies (Universal recipient)
Type O – No A or B antigens, Anti-A & Anti-B antibodies (Universal donor)
Receiving the wrong blood type causes agglutination, which can lead to obstructed blood flow and life-threatening complications.
Describe the basis for the ABO blood grouping system.
Understand the broad, foundational characteristics and functions of antibodies. What are the ramifications of receiving the wrong blood type during a blood transfusion?
Blood group systems are categorizations of blood (blood types) based on erythrocyte plasma membrane surface antigens. Antigens are substances that can generate an immune response. The two most commonly used blood types include the ABO and Rh groups.
The ABO blood group is named for the presence of A, B, AB, or the absence (O) of antigens on the surface of RBCs. In general, there are various types of antibodies, each with different functions. A person’s blood plasma typically includes antibodies for whichever antigen(s) doesn’t match their blood type. A person may have the following blood types:
Type A
A antigens on RBC surface
Anti-B antibodies in plasma
Type B
B antigens on RBC surface
Anti-A antibodies in plasma
Type AB
A & B antigens on RBC surface
No anti-A or anti-B antibodies in plasma
Type O
No A or B antigens on RBC surface
Anti-A and anti-B antibodies in plasma
When a blood donation recipient receives the wrong blood type, the antibodies associated with their own blood type will bind to the foreign RBC antigens. One antibody can bind to an antigen on multiple RBCs, which causes clumping of the cells (an immune response called agglutination). Agglutination reactions lead to obstructed blood flow within the vasculature, which can be life-threatening.
As such:
A person with Type A blood may only receive blood from a donor with Type A or Type O blood.
A person with Type B blood may only receive blood from a donor with Type B or Type O blood.
A person with Type AB blood may receive blood from any blood type (universal recipient).
A person with Type O blood may only receive blood from another Type O donor, but can donate to any blood type (universal donor).
Explain the Rh factor and what it could mean for an Rh- individual who becomes pregnant. Know which antigen is present on the surface of Rh+ individuals.
Rh factor (D antigen) is a protein on RBC surfaces.
Rh+ – D antigen present.
Rh- – D antigen absent.
Rh status is crucial in pregnancy. If an Rh- mother carries an Rh+ fetus, she may develop anti-Rh antibodies during delivery. In a second pregnancy, these antibodies can cross the placenta and attack fetal RBCs, causing hemolytic disease of the newborn (HDN). This is prevented with RhoGAM injections.
Blood types have an associated + or -, which indicate Rh factor type. Rh factor (D antigen) is a type of plasma membrane protein found on RBCs. An individual with D antigens present on the surfaces of their RBCs is Rh+, while the absence of D antigens is Rh-. The majority of the population is Rh+.
While most antibodies in the maternal blood cannot cross the placental barrier, a special category of antibodies (called IgG) can cross the placental barrier from the mother to the developing fetus.
Rh status is predominantly an issue for an Rh- mother carrying an Rh+ fetus and typically is most problematic for a second pregnancy. What may happen is that any tearing during delivery of the first pregnancy could lead to mixing of the maternal and fetal blood, exposing the mother to Rh factor (D antigens). This causes the mother to produce anti-Rh antibodies which will circulate in the blood plasma. These IgG antibodies can cross the placenta of the second pregnancy and attack fetal RBCs. This is known as hemolytic disease of the newborn (HDN).
HDN is preventable through a simple series of injections with RhoGAM, a substance that stops the mother from producing anti-Rh antibodies. This therapy is the standard of care for all Rh- pregnancies.
Describe the physical properties and structure of an erythrocyte. What is the role of oxygen in the body? How can an erythrocyte transport oxygen without utilizing any of it?
Erythrocytes (RBCs) are anucleate, biconcave, and filled with hemoglobin (33% of cell volume). They have a 120-day lifespan and are specialized for oxygen transport.
Oxygen is required for ATP production via aerobic respiration. RBCs lack mitochondria and generate ATP anaerobically, ensuring they do not consume the oxygen they transport.
Erythrocytes (red blood cells; RBCs) are the most abundant formed element in the blood. RBCs are without nuclei (anucleate) and lack other organelles (e.g. mitochondria). RBCs are shaped like biconcave discs that are 7-8 μm in diameter. The major constituents of a RBC are water and hemoglobin (33% of cell volume). As anucleate cells, RBCs have a short life-span, typically lasting only 120 days. RBCs are the principal agents in gas transportation in the blood. Oxygen is required to produce energy (ATP) through aerobic cellular respiration in metabolically active tissue cells. Red blood cells are highly specialized for their oxygen transport function, and since mature red blood cells lack a nucleus, all their internal space is available for transporting oxygen. Since RBCs generate ATP anaerobically (without oxygen), they do not expend any of the oxygen they are transporting for energy production. This allows for maximum transport of oxygen.
What is the physical structure of hemoglobin?
Hemoglobin is a heterotetramer composed of 4 globin proteins, each with a heme group that binds oxygen. The primary adult hemoglobin (HbA) consists of 2 alpha (Hbα) and 2 beta (Hbβ) chains.
What is the physical structure of hemoglobin?
Hemoglobin is a heterotetrameric molecule of 4 globin proteins (polypeptide chains). At the center of each globin is heme, an iron-containing pigment that reversibly bonds to oxygen and other gasses. Heme is what gives blood its red color. Each hemoglobin molecule contains 2 identical pairs of globin proteins. While other globin proteins exist, the most common are: Hbα (alpha) & Hbβ (beta). 98% of adult hemoglobin is formed from 2 Hbα & 2 Hbβ = 2α2β. 2α2β is known as HbA (adult hemoglobin).
How do hemoglobin and oxygen interact? How much oxygen can a hemoglobin molecule transport at one time? What can affect hemoglobin’s affinity for oxygen?
Oxygen molecules bind to the heme groups (specifically the iron portion) of hemoglobin molecules. Since there are 4 heme groups in a hemoglobin molecule, each hemoglobin molecule can transport 4 oxygen molecules. As blood flows through the tissue capillaries, the binding of iron and oxygen reverses and the oxygen diffuses into the interstitial fluid and then into the tissue cells. The affinity for oxygen to bind to the heme groups can change according to different conditions, and there are different types of binding through which oxygen attaches to hemoglobin. Hemoglobin has a higher affinity for oxygen in areas of the body or conditions where blood needs to hold tightly onto the oxygen molecules in order to transport it. One such place is in the lungs where oxygen first enters the bloodstream. This is done through cooperative binding, where an increase in oxygen binding to hemoglobin increases hemoglobin’s affinity for oxygen (and vice-versa). When hemoglobin has a decreased affinity for oxygen, hemoglobin holds oxygen less tight and is more likely to dump oxygen into the blood. This occurs in areas of metabolically active tissue, where there is a higher temperature, lower pH, and an increased amount of carbon dioxide.
Outline the process of erythropoiesis. What stimulates this process? Explain the process and types of blood doping.
Outline the process of erythropoiesis. What stimulates this process? Explain the process and types of blood doping.
Erythropoiesis is the process of erythrocyte formation. In fetal development, erythropoiesis begins in the yolk sac, then the liver and spleen. Post-birth, erythropoiesis occurs in red bone marrow. At the start of erythropoiesis in adults, precursor cells (proerythroblasts) in the red bone marrow divide several times, producing multiple erythroblasts. Erythroblasts further divide and eject their nuclei to form reticulocytes. It’s the loss of the nucleus that causes the center of the cell to indent and form a biconcave shape. The reticulocytes then pass from the bone marrow into the bloodstream. About 1-2 days after the reticulocyte enters the bloodstream, it develops into a mature red blood cell. Usually, erythropoiesis and normal red blood cell destruction proceed at about the same rate. However, if this balance is disturbed and the blood isn’t able to carry enough oxygen due to a decrease in red blood cells, erythropoiesis is increased. A variety of conditions could lead to low levels of oxygen in the blood (hypoxemia), including medical reasons (e.g. anemia), or hypoxic environments (e.g. high altitude). Hypoxemia stimulates the kidneys to ramp up the release of the hormone erythropoietin (EPO). With low levels of blood oxygen (hypoxia), levels of circulating EPO rise rapidly and significantly. EPO circulates through the blood to the red bone marrow where it increases the rate of development of proerythroblasts into reticulocytes. When the number of mature red blood cells increases, more oxygen can then be delivered to various tissues of the body. From the onset of hypoxia to an increased production of mature red blood cells, erythropoiesis takes about 10 days. Blood doping is a process to elevate the amount of erythrocytes, usually to gain an unfair athletic advantage. Blood doping may be accomplished through transfusions of RBCs either from one’s own stored supply or from another person. Blood doping may also be accomplished through injections of exogenous EPO. Athletes may also choose to train under hypoxic conditions (e.g. high elevations) to increase their RBCs naturally, although this generally isn’t viewed as cheating. A major risk of blood doping is polycythemia, or having too many RBCs. Whenever the total volume of RBCs exceeds 60% of blood volume, a person is at risk for spontaneous clotting (stroke).
What is hematocrit? What happens when hematocrit is out of normal range? Describe sickle cell disease as it relates to anemia. Define hypoxemia.
Hematocrit is the percentage of RBCs by blood volume. Typical hematocrit in an adult is 38-54%. Hematocrit below 38% is called anemia (a=without, -emia=blood). Hematocrit above 54% is called polycythemia. Critical thresholds for hematocrit include:
<15%: risk of cardiac failure
60%: risk of spontaneous clotting As hematocrit is a percentage of blood volume, it may be affected by either the number of RBCs or the amount of plasma. Decreased hematocrit is anemia, which is the state of reduced oxygen carrying capacity of the blood. There are many different types of anemia, including, but not limited to:
Sickle cell disease (anemia):
Mutation of the beta globin in the hemoglobin molecule
Causes sickling of RBCs
RBCs rupture easily
RBCs form clumps in vasculature Anemia may also be the result of hemorrhage, menstruation, dehydration, etc. Side note (not tested): It is important to note that post-hemorrhage blood plasma may rebound quickly (to keep blood pressure up), but hematocrit is slow to rebound as the process of erythropoiesis takes about 10 days. Hypoxia is the condition of having generally too little oxygen in the tissues. This can be the result of being in a hypoxic environment (insufficient environmental oxygen), or there being a pathological issue preventing the distribution of oxygen. Hypoxia is sometimes used interchangeably with hypoxemia, which is decreased oxygen levels in the blood. Anemia often causes hypoxia.
What are leukocytes and what are the major ways to categorize them? What are their functions? Which types of leukocytes do myeloid and lymphoid stem cells give rise to? Identify the characteristics of monocytes and lymphocytes.
Leukocytes (leuko=white, cytes=cells)/white blood cells/WBCs are a diverse group of blood cells involved in immune protection from pathogens and foreign substances. They include basophils, neutrophils, eosinophils, monocytes, and lymphocytes. WBCs are classified by their developmental lineage and their physical characteristics. WBCs exist as formed elements in the blood. Some may emigrate from the blood to interstitial tissues for the rest of their lifespan, and some pass back and forth between blood and tissues. When dealing with pathogens and foreign substances, there are two major approaches: innate (present at birth; no previous exposure to pathogens) & acquired (adaptive; requires experience with pathogens) immunity. Most WBCs function as part of innate immunity, whereas some (e.g. most lymphocytes) are the basis for acquired immunity. There are three common actions of WBCs that enable them to be effective as part of innate immunity:
Degranulation: granular leukocytes are able to store substances (granules) in their cytoplasm to release and facilitate a defense mechanism
Phagocytosis: some WBCs can engulf and destroy materials
Chemotaxis & emigration: some WBCs can ‘detect’ the presence of a pathogen through chemical signals and exit the bloodstream to deal with it
Myeloid stem cells give rise to: granular leukocytes, monocytes, and mast cells. Lymphoid stem cells produce lymphocytes: T cells (adaptive), B cells (adaptive), and Natural Killer cells (innate).
Monocytes:
Derived from myeloid stem cells
Agranular
Puffy, kidney-shaped nucleus
May differentiate into macrophages (in tissues)
Fixed or wandering
Immunity, tissue repair, homeostasis
May differentiate into dendritic cells (skin, mucosa)
Adaptive immunity
Antigen presenting cells
Mediate immune responses
Pathogen is broken down via phagocytosis
Pathogen pieces presented on cell membrane
~10% of WBCs
Lymphocytes:
Derived from lymphoid stem cells
Agranular
Large round nucleus
Not phagocytic
Acquired immunity
T cells
B cells
Innate immunity
Natural killer cells
~25% of WBCs
Define and explain the purpose of a differential white blood count. Understand what may cause a white blood cell count to exceed normal limits.
A common blood test is a differential white blood count, which looks at the relative abundances of all WBCs and their morphologies to determine potential issues or infections. Elevated levels of leukocytes is known as leukocytosis, whereas low levels of leukocytes is known as leukopenia. You do not need to memorize the below chart, but understand that a variety of pathogens, substances, and circumstances can affect the white blood count, including: infections, radiation exposure, drugs, pregnancy, etc.
What is a platelet (thrombocyte) and how is it formed? What stimulates the production of platelets? Describe the physical characteristics of platelets. What are their functions?
Thrombocytes (thrombo=clot, cyte=cell), better known as platelets, are irregularly shaped cell fragments that arise from myeloid stem cells. This process is stimulated by the hormone thrombopoietin, which induces myeloid stem cells to develop into megakaryocyte colony-forming-units. Megakaryocyte CFUs develop into precursor cells called megakaryoblasts. The blast cells transform into megakaryocytes, which are large cells with projections called proplatelets. Megakaryocytes are located in spaces of the bone marrow and project these proplatelet processes into the bloodstream. The flow of the bloodstream causes the proplatelets to splinter off and become platelets within the blood. Typically, a megakaryocyte produces 2-3 thousand platelets. Platelets don’t contain a nucleus, but they do contain granules, and the chemicals within these granules promote blood clotting.
Aged and dead platelets are removed from the circulation by fixed macrophages located in the spleen and liver. Platelets are constantly produced, and this production can be stimulated even more at times, especially in the instance of vascular injury.
How are blood clots formed to repair vascular injury?
Coagulation (clotting) is an important protective process for when there is vascular injury. Blood clots act as a cork to prevent further blood loss, while also pulling the edges of the ruptured vessel together to assist in damage repair.
When a vascular injury occurs, a structural protein within the wall of the vessel called collagen becomes exposed and attracts the platelets to the site of the injury. Platelets can initiate a series of interactions that result in a network of fibrin that has transformed and become insoluble protein threads. Together, the webbing of fibrin threads, platelets, and associated trapped red blood cells form a blood clot.
Clotting is further promoted by a clotting protein in the blood called the von Willebrand factor, which acts as a glue to help the platelets stick to one another.
What are the components of the cardiovascular system?
Heart, vasculature, blood
