4.2 Blood Flashcards
What is adult blood volume
5-6L
Give some functions of blood
- distribution of organic & inorganic substances
- transportation of gases (oxygen and carbon dioxide)
- acting as a buffer system
- maintenance of homeostasis
- maintenance of body temperature
Describe the composition of blood plasma
Blood plasma makes up 60% of total blood volume. It is made up of water (90%), proteins (8%), molecules (e.g glucose) and dissolved/bound chemicals
Describe haematopoiesis
Haematopoiesis is the synthesis of blood cells. The blood cells are produced in bone marrow from hematopoietic stem cells (HSCs), most active HSCs are found in the sinusoids. HSCs can differentiate or self renew into various specialised blood cells. Haematopoiesis is closely regulated by growth factors and cytokines. Once matured the blood cells then exit the bone marrow and enter the blood stream
Describe burst forming units and colony forming units
At first in haematopoiesis, he HSCs give rise to progenitors, which are still multipotent stem cells, but committed to certain blood cell lineages. Then the progenitors differentiate into either burst forming units (BFUs) or colony forming units (CFUs). BFUs give rise to many colonies but they are less committed and specific where as CFUs give rise to fewer but more committed and specific
What are some different blood cell types
erythrocytes, lymphocytes, neutrophils, eosinophils, basophils, monocytes and platelets
Describe erythrocytes
Erythrocytes (AKA red blood cells) are the most numerous cells in blood and their purpose is to transport oxygen and carbon dioxide around the body. They are biconcave discs with no nucleus, mitochondria or ribosomes, the nucleus is ejected during maturation in the bone marrow. They are adapted to gas exchange with a large surface area, flexibility and a haemoglobin rich cytoplasm.
Describe the mechanism of oxygen transport in erythrocytes
Erythrocytes contain many haemoglobin molecules. These proteins have 4 subunits with each one containing a haem group with an iron ion. Each haem group can bind to an oxygen molecule. In the lungs, a high oxygen concentration promotes oxygen binding to haemoglobin. In the tissues, a low oxygen concentration and high carbon dioxide concentration promotes the release of oxygen from haemoglobin. Haemoglobin proteins demonstrate cooperativity where one oxygen binding to one haem group increases the affinity of the other subunits in the haemoglobin for oxygen.
What is a dissociation curve
It is a typically S shaped curve, showing the relationship between the partial pressure of oxygen in the blood and the percentage of haem groups occupied with oxygen
Describe how carbon dioxide is transported in the blood
CO2 is transported in the blood as a waste product of metabolism in 3 ways;
- 7% as dissolved CO2 in the blood plasma
- 23% attached to haemoglobin and other blood proteins (forming carbamino compounds by attaching to NH2 groups)
- 70% as bicarbonate ions in the plasma
Red blood corpuscles contain the enzyme carbonic anhydrase which catalyses the reaction of co2 and h2o to form bicarbonate (hco3-) and hydrogen ions
What are leucocytes
Leucocytes (AKA white blood cells) are larger and less numerous than erythrocytes and they make up part of the immune system. There are many different types, categorised by their shape and the granules in their cytoplasms, granulocytes are leucocytes with cytoplasmic granules. Types of leucocytes include lymphocytes, neutrophils, eosinophils, basophils and monocytes.
What are neutrophils
Neutrophils are the most common leucocyte and one of the first to migrate to sites of infection/inflammation, they are a primary defence for bacteria and fungi. They have a lobed nucleus and a lifespan of 8-10 hours. Their cytoplasmic granules have proteolytic enzymes. There is a reserve pool of neutrophils in the bone marrow
What are eosinophils
Eosinophils are bi-lobed nuclei cells whose main function is to provide defence against helminth parasites. They are attracted to sites of inflammation in the tissues by antibodies, they’re also increased in times of allergy and asthma. They have large cytoplasmic granules that stain red with H&E.
What are basophils
Basophils are the least common of the circulating leucocytes, containing dense cytoplasmic granules that stain dark blue with H&E, this staining usually obscures the nucleus under a microscope. These granules have many mediators of inflammation such as histamines, leukotrienes and proteases. The basophils are rapidly recruited to the skin, lung or nose following antigen challenge in humans and are found in high numbers during asthma, allergic rhinitis, atopic dermatitis and nasal polyps.
What are lymphocytes
Lymphocytes are the second most common leucocytes and have have Natural Killer, B cell and T cell subtypes (which can not be differentiated under an H&E stain). They have a a dense nucleus with little cytoplasm and they circulate between the blood, peripheral tissues and the lymphatic system. Unlike other leucocytes, they have a lifespan that can last years and they can act as memory cells
What are monocytes
Monocytes are the largest leucocytes in peripheral blood and have an eccentrically placed kidney shaped nucleus. They ingest pathogenic material, degrade it and present peptides or peptide fragments to T lymphocytes (antigen presenting cells). They also kill microorganisms such as listeria, mycobacteria and some fungi. After a short time in circulation, they move into the tissues as macrophages.
What are the 3 phases of haemostasis
vasoconstriction then the formation of a platelet plug and then coagulation
What are platelets
Platelets are small cell fragments formed in the bone marrow by the fragmentation of large megakaryocyte cells. They contain mitochondria and specialised granules which contain essential compounds for haemostasis (preventing blood loss). Their primary function is to initiate coagulation (clot forming) in response to injury and haemostasis.
Describe vasoconstriction in haemostasis
Vasoconstriction is when the blood vessels constrict to reduce blood flow to the bleeding area. There is local contraction of the vessel wall due to damage to smooth muscle cells. This vasoconstriction is induced by pain an injury triggers via sympathetic nerve activation, release of endothelins from endothelial cells and activated platelets releasing vasoconstrictors.
Describe the formation of a platelet plug in haemostasis
The platelets adhere to the injury site and aggregate to form a temporary “plug”, the endothelial damage exposes the collagen, this initiates platelet activation. The activated platelets adhere to the collagen and begin to aggregate at the site of the injury, the von Willebrand Factor (a glycoprotein) helps platelets bind to the vessel wall via glycoprotein 1b receptors on the platelet surface. There is then an activation cascade where the platelets release ADP and other factors that activate additional platelets. Glycoprotein 2b/3a receptors become active on the platelet surface. There is then platelet aggregation where fibrinogen then binds to the active glycoprotein receptors to link the platelets together to form a platelet plug.
Describe coagulation in haemostasis
A cascade of clotting factors leads to the formation of a stable fibrin clot, reinforcing the platelet plug. The cascade of clotting factors leads to the formation of a stable fibrin clot, reinforcing the platelet plug. Thrombin does this by cleaving fibrinopeptides from the fibrin monomer, enabling polymerisation so soluble fibrin can form, factor XIII then catalyses covalent bond formation so the molecule turns insoluble.
What are some key clotting factors in the coagulation cascade
coagulation factors: series of serine proteases
calcium ions: activate and stabilise stages in the cascade
phospholipd surface: provided by the activated platelets, supports the assembly of the coagulation factors
Discuss the 2 different models for the coagulation cascade
Traditional model:
-seperate activation routes that eventually merge into one common pathway causing clot formation
-can be divided into the intrinsic and extrinsic pathway, which then converge into the final common pathway
Cell based model:
-gives more accurate understanding of clot formation
-focuses on role of cell surfaces (especially platelets and tissue factor expressing cells) in organising and localising the coagulation reactions
-Initiation: Tissue factor on damaged cells initiates clotting and produces some thrombin (similar to the extrinsic pathway).
-Amplification: Activated platelets gather at the injury site, thrombin activates factors in the intrinsic pathway, which form on platelet surfaces
-Propagation: Large amounts of thrombin are generated, leading to fibrin formation and a stable clot.
Describe fibrinolysis
Fibrinolysis is the removal of the clot. Plasminogen is a plasma protein trapped in the clot, overtime, injured endothelial cells release a protease called tPA which activates plasminogen and converts it to plasmin. The plasmin then degrades the fibrin mesh, producing circulating degradation products (FDPs).
