Blood and Haemodynamics

Discuss Coagulation

Coagulation, the third stage of haemostasis, is a complex stage involving the activation of clotting factors (the clotting cascade) ultimately resulting in the conversion of soluble plasma proteins into insoluble fibers (the fibers of the ECM of blood). Phase 1: Two pathways to prothrombin activator: This phase is the most complex and involves two different pathways that lead to the production of prothrombin activator via activation of the clotting cascade. Both pathways require the presence of calcium (Ca2+): = Intrinsic pathway: platelets adhere to exposed collagen fibers in blood vessesl wall stimulating activation of clotting factors and release of platelet factor 3 (PF3), which facilitates the activation of some clotting factors. = Extrinsic pathway: blood is exposed to tissue factor (TF) from cells outside the blood vessel. TF also causes activation of some clotting factors. Together these pathways lead to the formation of prothrombin activator. Phase 2: Common pathway to thrombin: Prothrombin activator (the end result of phase 1) converts the plasma protein prothrombin into the active enzyme thrombin. Phase 3: Common pathway to fibrin mesh: Thrombin converts the soluble protein firbrinogen into fibrin. Fibrin molecules join together to form long insoluble fiber strands. Fibrin glues platelets together and forms a web-like mesh at the injury site that forms the structural basis of the blood clot.

Complete by listing the plasma solute related to the listed function/characteristic. Function/Characteristic: - Contribute most to plasma osmolarity - Heaviest plasma solutes - Homeostatic messengers - Include urea and creatinine - Obtained from GI tract - Participate in respiration

Contribute most to plasma osmolarity = Electrolytes Heaviest plasma solutes = Proteins Homeostatic messengers = Hormones Include urea and creatinine = Wastes Obtained from GI tract = Nutrients Participate in respiration = Gases

Compare and contrast the three formed elements of blood

Erythocytes: - No nucleus - Live for 120 days - Lacking most organelles - Contains hemoglobin Leukocytes: - Can move out of blood - Some contain storage vesicles - Live from minutes to years - Five cell types Thrombocytes: - Actually a cell fragment - Live up to two weeks

Explain Erthrocytes:

Erythrocytes, or red blood cells (RBCs), are biconcave, disc shaped cells. Lacking a nucleus (are anucleate) and most cellular organelles, RBCs are packed full of a protein called haemoglobin and various other structural proteins. Haemoglobin binds oxygen and carbon dioxide for transportation through the blood, a function that RBCs perform exclusively. The various structural proteins in RBCs are capable of de-forming and re-forming, making RBCs flexible and able to change their shape to fit through narrow blood vessels. Due to the mass of RBCs found in blood, they also increase blood viscosity (thickness). How many oxygen molecules can each hemoglobin protein carry? - 1 - 4 <----- Correct Answer - 40 - 100

Discuss Erythropoiesis & RBC life cycle

Erythropoiesis refers to the haematopoietic process that produces erythrocytes (RBCs). Because RBCs do not have a nucleus, they are only viable for around 120 days, thus they must be continuously replaced. Erythropoiesis produces new RBCs at a basal rate of approximately 2-3 million per second!! The production of RBCs from progenitor daughter cells of myeloid stem cells is stimulated by the hormone erythropoietin (EPO). EPO is released from the kidneys and maintains the basal rate of RBC production, however if blood oxygen levels drop, more EPO is released to stimulate an increase in the rate of erythropoiesis. The process of RBC production from myeloid stem cell to mature RBC in circulation takes approximately five (5) days. The production of RBCs requires all of the macronutrients (proteins, lipids and carbohydrates) plus iron, vitamin B12 and folic acid. Of the total amount of iron in the body, 65% is contained within hemoglobin (the rest is stored as ferritin in the liver, spleen and bone marrow which can be released as necessary to facilitate erythropoiesis). RBCs only live (function) for about 120 days in circulation. After this time they are broken down by macrophages (a type of white blood cell). Some of the breakdown products of RBCs will be recycled into new RBCs, and some will need to be eliminated from the body: 1. The haem pigment is separated from the globin. 2. Globin proteins are broken down into amino acids which are released back into blood circulation. 3. The iron (Fe) molecule is removed from the haem pigment and stored (in macrophages or liver) or released to circulate in blood bound to the plasma protein transferrin. 4. The remainder of the haeme pigment is degraded into bilirubin which will undergo a metabolic process for elimination from the body. Watch the video tutorial below outlining the processing of bilirubin in the body.

True or False? Erythropoiesis takes 3 months to complete

False

True or False? Haemoglobin is composed of 2 globin chains

False

True or False? RBCs contain 250 haemoglobin each

False

What is Haematopoiesis

Haematopoiesis is the process of blood cell formation. All blood cells (formed elements) originate from a common haematopoietic stem cell which undergoes a process of cell division to generate more stem cells and daughter cells. The daughter cells will then undergo a series of cell divisions and differentiation to produce the range of blood cells that enter blood circulation. Haematopoiesis occurs within red bone marrow on a continuous basis, with hundreds of billions of newly formed elements being produced each day!

What is hemoglobin

Haemoglobin is composed of red haem (heme) pigments bound to the protein globin. The globin protein consists of four (4) polypeptide chains: = 2 alpha (α) chains = 2 beta (β) chains Each polypeptide chain binds one heme pigment, each of which contains a single iron (Fe) atom at it's center capable of binding one oxygen molecule (O2). Each RBC contains approximately 250 million haemoglobin molecules! Therefore a single RBC can carry up to 1 billion oxygen molecules!!!

What is Haemostasis

Haemostasis is the process of blood clotting. Blood clotting occurs to prevent blood loss when blood vessel walls have been damaged/ruptured. Haemostasis involves the thrombocytes, various plasma proteins and some other blood solutes. Haemostasis occurs in three stages: 1. Vascular spasm: Blood vessel constricts (smooth muscle contracts) to reduce blood loss through tear. 2. Platelet plug formation: Platelets are activated and become 'sticky', adhering to the torn vessel. This stimulates more and more platelets to activate and stick to the tear and each other, forming a small plug across the torn vessel. 3. Coagulation Reinforcement of the platelet plug with a network of fibers (fibrin) that 'glues' the platelet plug and seals larger breaks due to the activation of clotting factors and pro-coagulants. The fibrin meshwork incorporates more platelets and RBCs into the blood clot in the process of formation.

The ___________ pathway is activated by processes within the blood vessel lining. - extrinsic - common - intrinsic

Intrinsic

During coagulation, prothrombin: - Converts fibrinogen into fibrin. - Is converted into thrombin by prothrombin activator. - Converts plasminogen into plasmin. - Is required for the clotting cascade to occur.

Is converted into thrombin by prothrombin activator

Explain Leukocytes:

Leukocytes, or white blood cells (WBCs), are true blood cells, containing nuclei and cellular organelles. There are five types of leukocytes, however all together leukocytes are far, far less numerous than RBCs, accounting for <1% of total blood volume. WBC production and numbers can increase vastly, however, in the presence of inflammation or infection. WBCs function as part of the immune system of the body, helping to fight/prevent infections and take part in the inflammatory response. To facilitate this function, most WBCs can move out of the blood into body tissues. The five types of WBCs can be divided into two groups based on the presence or absence of granules (storage vesicles, e.g. lysosomes) in their cytoplasm - the granulocytes and the agranulocytes.

Discuss Clot retraction, blood vessel healing & clot degradation

Once a blood clot is formed, the clot retracts to further stabilize itself. The platelets in the clot contain contractile proteins which contract to compact the clot and pull the damaged edges of the torn blood vessel together. Once the clot is fully formed, tissue healing can begin- this process is driven by the platelets and endothelial cells of the blood vessels: = Platelets release platelet derived growth factor (PDGF) = Endothelial cells release vascular endothelial growth factor (VEGF) These growth factors stimulate the regeneration of new cells within the blood vessel wall. New cells will continue to be made until all of the damaged cells are replaced and the blood vessel wall is completely healed. Once this occurs, the blood clot is no longer needed and will be broken down and removed in a process known as fibrinolysis: = Healed endothelial cells release tissue plasminogen activator (TPA) = TPA converts the inactive protein plasminogen into the active enzyme plasmin = Plasmin degrades the clot by breaking down and digesting fibrin, while white blood cells will digest the remaining fragments of the blood clot Fibrinolysis typically begins within 2 days of clot formation (depending on the severity of damage) and will occur slowly over several days until the clot is completely dissolved.

Match each of the leukocytes with their correct function descriptions: Leukocytes: Eosinophils Neutrophils Monocytes T lymphocytes Basophils B lymphocytes Function: 1. Phagocytize (digest/destroy) bacteria, as well as some fungi and viruses 2. Attack parasitic worms by releasing digestive enzymes. Also involved in allergies and asthma responses 3. Attack/destroy viral infected body cells and tumour cells 4. Stimulates vasodilation and attracts other WBCs to the sits of inflammation or infection 5. Produce antibodies (immunoglobins), which recognize foreign antigens, and initiate immune response to these foreign antigens 6. Phagocytize bacterial parasites, viruses and other infectious microbes, as well as cellular debris and dead/dysfunctional cells in the body.

Phagocytize (digest/destroy) bacteria, as well as some fungi and viruses = Neutrophils Attack parasitic worms by releasing digestive enzymes. Also involved in allergies and asthma responses = Eosinophils Attack/destroy viral infected body cells and tumour cells = T lymphocytes Stimulates vasodilation and attracts other WBCs to the sits of inflammation or infection = Basophils Produce antibodies (immunoglobins), which recognize foreign antigens, and initiate immune response to these foreign antigens = B lymphocytes Phagocytize bacterial parasites, viruses and other infectious microbes, as well as cellular debris and dead/dysfunctional cells in the body. = Monocytes Lymphocytes are most often found outside the blood, within lymphatic tissue where they regularly circulate. Lymphatic structures are also where T lymphocytes mature, after being released from the bone marrow during haematopoiesis. Monocytes regularly leave the bloodstream and are called macrophages when they leave the bloodstream or are actively engulfing/phagocytizing material.

What is plasma

Plasma is a sticky, straw-colored fluid composed mostly of water (>90% of plasma is water). However, plasma contains over 100 dissolved solutes! These include various proteins (some of which can polymerize to form the 'fibers' of the ECM), nutrients, electrolytes (salts), respiratory gases, hormones and wastes/by-products of cellular metabolism.

Discuss the different types of solutes found in plasma

Plasma proteins: With the exception of protein hormones and some globulins, plasma proteins are made by the liver. Albumin is the most abundant plasma protein. Plasma proteins serve a variety of functions, including: - Transportation of various molecules - Buffering of acids or other potentially toxic compounds - Facilitating coagulation (blood clotting) - Facilitating immune protection Plasma proteins are the heaviest solutes of plasma and therefore collectively they create an osmotic pressure within the plasma that 'pulls' water (or helps keep water in the plasma). If the number of plasma proteins increases, so does the osmotic pressure (and vice versa). Osmotic pressure plays a role in the leakage and filtration of plasma that occurs in blood capillaries. Nutrients: The digestion of our food and drink lead to the absorption of nutrients, vitamins and minerals into the plasma from the gastrointestinal (GI) tract. The nutrients absorbed are simple sugars (carbohydrates), amino acids (proteins) and fatty acids (lipids). The plasma will transport these nutrients and vitamins/minerals around the body until they are picked up by body cells as necessary. The plasma maintains a 'stock' of nutrients- so there is always some amount of glucose, fatty acids and amino acids floating around in the blood ready to be taken up by body cells. Levels of these nutrients in the blood are maintained within homeostatic limits under the influence of hormones. Electrolytes: Electrolytes are the charged solutes found in all body fluids, including acids and bases. Electrolytes are the most abundant type of solute found in the plasma and therefore they contribute the most to blood (plasma) osmolarity. The most abundant electrolyte in the plasma (and all ECF) is sodium (Na+) and therefore Na+ concentration contributes the most to blood osmolarity. The regulation of Na+ levels in blood is crucial to maintaining the balance of all body fluids. *Recall that osmolarity is the TOTAL concentration of all solutes in a solvent. As water is the body's solvent, osmolarity determines whether water moves into or out of fluid compartments- i.e. into or out of the ECF and ICF (or into/out of body cells). If too much water moves into or out of cells, they will swell or shrink, respectively, and this causes cellular dysfunction! Respiratory gases: The respiratory gases include oxygen (O2) and carbon dioxide (CO2). While red blood cells (RBCs) transport the majority of O2 and some CO2 , there is still a certain amount of each gas that is transported dissolved in plasma. CO2 is also considered a waste or by-product of cellular respiration. Hormones: All hormones are released into the blood from their endocrine organ. Dissolved in the plasma, hormones are transported to their target cells where they bind to their specific receptors to instigate cellular activities. As hormones are one of only two cellular messengers used for the maintenance of homeostasis, there are always hormones circulating in blood. Once released, hormones will be removed from the blood at varying rates, dependent on the hormone, it's half-life and the rate of hormone release. For many hormones (e.g. thyroid hormones), a certain level will always be homeostatically maintained at basal levels within the blood. Other hormones will have greater fluctuations in their blood levels based on the stimuli for hormone release and factors influencing its removal. Wastes/by-products of cellular metabolism: Cellular metabolism produces a variety of waste and by-products that need to be transported through the blood until they can be off-loaded from the body. These include the respiratory gas CO2 and various metabolic acids, but also compounds such as urea, uric acid, creatinine, amonium salts and nitrogen gas, bilirubin (by-product of RBC breakdown) and various other products of cellular breakdown.

Discuss formed elements

The formed elements include the erythrocytes (red blood cells), leukocytes (white blood cells) and thrombocytes (platelets). All three of these elements are formed by the process of haematopoiesis from the same stem cell, but they differentiate into drastically different cells which allow them to perform unique functions.

Explain ABO Blood Groups:

There are two antigens within the ABO blood group: = A antigen = B antigen Human red blood cells will contain either A antigens, B antigens, both antigens or neither, resulting in the four possible blood types for this antigen group. Unique to the ABO blood group are the presence (or absence) of pre-formed antibodies (immunoglobulins). Unlike other antibodies, the ABO antibodies are produced without exposure to foreign antigens, hence the antibodies being pre-formed. The antibodies formed reflect the antigens present on an individuals RBCs and will cause haemolysis of foreign RBCs that they are made to recognize as foreign. This antigen-antibody relationship determines the type of blood an individual could receive if a blood transfusion was necessary.

Explain Thrombocytes:

Thrombocytes, or platelets, are not cells, but are fragments of a much larger cell called a megakaryocyte. Platelets are part of the process of haemostasis, or blood clotting, that occurs when blood vessel walls are damaged or ruptured. Platelets are always in circulation, available for haemostasis, but in an inactive form. When a blood vessel wall is damaged, collagen fibers are exposed which cause the platelets to stick to them and activate, or become 'sticky'. When platelets are activated and sticky, they stick to the damaged blood vessel wall, and to each other, to form a platelet plug that can temporarily stop blood loss from the damaged site. The activation of platelets occurs through a positive feedback cycle, where the activation of a few platelets stimulates the activation of more and more platelets until a final conclusion (blood clot) results. Platelets also activate the process of coagulation which reinforces the platelet plug and creates a blood clot.

True or False? Erythropoietin is released from the kidney

True

True or False? Haem pigment is degraded into bilirubin

True

True or False? RBCs lack a nucleus

True

True or False? RBCs live for about 4 months

True

Explain Rh Blood Groups

Within the Rh blood group there are 52 Rh antigens, referred to as Rh factors. Only three Rh factors are fairly common: the C, D and E antigens, with the D antigen being the most common of all the Rh factors. RBCs either have an Rh factor or not. In the case of the D antigen, it will either exist on the RBCs or be absent to give the following Rh blood types: = Rh positive (Rh+): D antigen present on RBCs = Rh negative (Rh-): D antigen absent on RBCs There are no pre-formed antibodies for Rh factors, however an Rh- individual will produce anti-D antibodies if exposed to Rh+ RBCs.

Fill in the specific type of formed element that performs the listed function. Function: - Attack parasitic worms - Attract other WBCs to infection site - Takes part in blood clotting - Create antibodies - Phagocitize bacteria - Transports oxygen

Attack parasitic worms = Eosinophils Attract other WBCs to infection site = Basophils Takes part in blood clotting = Platelets Create antibodies = B Lymphocytes Phagocitize bacteria = Neutrophils Transports oxygen = RBCs

Discuss the functions and components of blood:

Blood facilitates numerous functions necessary to cellular performance and homeostasis. The functions of blood include: = Transportation of nutrients, respiratory gases, waste products, hormones and various proteins. = Regulation of body temperature, fluid volume and pH balance. = Prevention of blood loss and infection. As a connective tissue, blood is composed of cells, more specifically referred to as the formed elements, and the extracellular matrix (ECM). The ECM of blood is called plasma. Plasma makes up 1/5 of the total amount of extracellular fluid (ECF) of the body (the remaining 4/5 of ECF is found in the other types of connective tissues of the body). The formed elements of blood are suspended in the plasma. The different components of blood can be seen when a sample of blood is centrifuged, allowing the components to be separated.

Discuss Blood Groups

Blood grouping (blood types) is based on the presence, or absence, of antigens on red blood cells (RBCs). Antigens = Glycoproteins within the cell membrane that have a specific and unique structure that identify cells as belonging to a particular individual. There are numerous antigens on RBCs and various antigens are 'grouped' according to their structure, giving rise to the various blood groups. The two most common blood groups are the ABO blood groups and the Rh blood groups.

Blood and Haemodynamics Conclusion

Blood is a fluid connective tissue coursing through our blood vessels and penetrating almost every tissue in the body. It is essential for many functions and delivers the necessary molecules to body cells for cellular metabolism. Blood provides transportation of many substances, regulates body temperature, fluid volumes and ph and plays a crucial role in the body's defense mechanisms. The various components of blood- plasma and its solutes and the formed elements- all have particular roles to play in these various functions of blood.

Blood and Haemodynamics Introduction

Blood is a type of connective tissue, and like all connective tissues it contains cells and an extracellular matrix (ECM) composed of water, dissolved solutes and fibers. The liquid nature of blood means it can be easily moved around the body, and this is continuously accomplished by the heart which pumps blood through a network of blood vessels which permeate almost all body tissues (with a few exceptions such as the epidermis of the skin and cartilage). The adult body contains approximately 5L of blood, and this entire volume moves through the heart twice each minute! This motility of blood is necessary for the numerous and varied functions performed by this connective tissue. Blood plays a crucial role in many homeostatic processes of the body, and due to it's continuous circulation around the body provides the means for a variety of interactions with all body parts. It is the communication pathway used by hormones, and it allows for a variety substances to be supplied or removed from other body structures. It is also regularly filtered by two other body systems for efficient and effective functionality.