Blood as a Tissue Lecture Notes PDF

Blood as a tissue Dr Ashik Srinivasan ([email protected]) Last updated: 2024-04-15 Thank You to Dr Belal Chami. (Author and presenter of the previous version of this lecture) Learning Objectives Students should be able to: Describe...

Blood as a tissue Dr Ashik Srinivasan ([email protected]) Last updated: 2024-04-15 Thank You to Dr Belal Chami. (Author and presenter of the previous version of this lecture) Learning Objectives Students should be able to: Describe the many functions of blood Identify and describe the cellular constituents of blood Identify the major protein constituents of blood List and describe the function of plasma proteinase cascades Outline the process of haemostasis  Functional definition of ‘Tissue’ Tissues are groups of cells that have a similar structure and act together to perform a specific function. Hence blood can be called a tissue. Blood is possibly the most ‘simple’ tissue structurally. Blood cells of all types are made in the bone marrow. Function of blood Gas exchange i.e., oxygen and carbon-dioxide Carry nutrients from gut and storage sites to tissues Carry waste from tissues to kidneys, liver Carry signals through body (eg hormones, cytokines) Carry defensive chemicals (eg antibodies, complement) to sites of injury Carry defensive cells to sites of injury Maintaining osmotic pressure relative to tissues and cells Provides a mechanism for stopping leaks on injury (blood clotting) Carry heat Carry drugs Preparation of a blood film Blood is about 55% plasma 45% cells Red blood cells are seen (note: no nucleus) “Red cells” = Erythro cytes Erythrocytes Biconcave shape > more surface area > optimal for diffusion of oxygen Flexible, can fold and squeeze through tiny capillaries  Amongst the RBCs are a few immature RBCs (1-2 days old in the blood), called reticulocytes, still in the process of losing their nuclear material Dr Chaigasame https://www.ncbi.nlm.nih.gov/books/NBK542172/figure/article-28438.image.f1/  Erythrocytes made in bone marrow Hemocytoblast Start out as pro-erythroblasts Manufacture more hemoglobin Degradation of organelles Expulsion of the nucleus Acquisition of final shape Hemocytoblast --> Erythrocyte = 2 days A centrifuged blood sample shows: https://nci-media.cancer.gov/pdq/media/images/503952.jpg Different types of WBC (leukocytes): Neutrophils Monocyte Lymphocytes Platelets “Thrombocytes” misnomer Very tiny No nuclei Really just particles of cells (Megakaryocytes in bone marrow) Important for blood clotting Types of polymorphonuclear (PMN) cells Neutrophils (aka. Neutrophilic PMNs) Most prevalent leukocyte Kill Bacteria, form Pus Basophils Become mast cells Early response in injury Contribute to allergy Eosinophils Parasitic infections Contribute to asthma and allergy Neutrophils often incorrectly abbreviated to just “PMNs” or “polymorphs” Most numerous WBC Multi-lobed nucleus Many granules for phagocytosis and killing of bacteria Killing by production of oxygen radicals Degradation by lysosomal enzymes Eosinophils Pink granules (H&E) Bi-lobed nucleus Relatively low numbers Helps fight intestinal parasites (~ helminths), and some forms of gut-immunity Monocyte Kill bacteria, Eat debris Intracellular pathogens Wide role in controlling immunity and inflammation Become macrophages Types of lymphocytes T Cell, B Cells, NK Cells Specific Immunity, Viral immunity, Tumor protection Second most prevalent leukocyte Monocyte Moderately prevalent in blood Emigrate into tissues to become macrophages (“big eaters”) Many roles in inflammation, wound healing and immunity Control many aspects of host response Many macrophage forms Lymphocytes Many sub-types – T Cells – B Cells Plasma cells (produce antibodies) – Natural Killer Cells Specific immunity Produced in lymphoid tissues as well as bone marrow Plasma Equivalent to the Extracellular Matrix Fluid - Non-cellular component Proteins - About 5% W/V Salts Glucose Hormones Oxygen / CO2 Buffer Water Function of blood Gas exchange i.e., oxygen and carbon-dioxide – RBC & Plasma Carry nutrients from gut and storage sites to tissues – Plasma Carry waste from tissues to kidneys, liver - Plasma Carry signals through body (eg hormones, cytokines) - Plasma Carry drugs - Plasma Carry defensive chemicals (eg antibodies, complement) to sites of injury - - Plasma & recirculating lymphocytes Carry defensive cells to sites of injury - Plasma & leukocytes Carry heat - Plasma Maintaining osmotic pressure relative to tissues and cells – Plasma proteins Must have a mechanism for stopping leaks on injury (blood clotting) – Platelets & Plasma clotting factors Buffy coat Pietrowska, M., et al., (2019). ‘Emerging sample treatments in proteomics Plasma Proteins Albumin is the major protein, about 50% of all plasma prot and about 4% w/v Transport protein Clotting Cascade proteins (Generates fibrin) Fibrinolytic Cascade proteins (Lyses fibrin) Kinin cascade proteins (roles in inflammation & blood pressure regulation) Complement cascade proteins (roles in inflammation) Antibodies / anti-microbials (specific immunity) Transport proteins (solubility / availability) Hormones Inflammatory mediators  Proteinase Cascades Involved in proteolysis – the breakdown of proteins into smaller polypeptides Inactive proteinase substrates are activated by proteinase activity Sequential products become enzymes Amplification of an initially small signal Explosive production of products Final product is produced in vast amounts relative to small initial activation event Normal Haemostasis 1. Transient arteriolar vasoconstriction: Reflex neurogenic stimulation Endothelin release (potent endothelium-derived vasoconstrictor) 2. Primary haemostasis: Platelet adhesion and activation by extracellular matrix Platelet flattening & release of secretary granules (ADP, TxA2, serotonin) Recruitment of additional platelets (aggregation) serotonin Forms a temporary primary haemostatic plug. Robbins Pathological Basis of Disease: Fig 5.5 Transmission Electron Microscopy Platelets as a micro-aggregate in a blood vessel and a single unactivated platelet Platelets get activated when vessels are damaged. Activation induces shape change, degranulation, aggregation to form early clot Platelets Activated by contact with extravascular material Adhesion to surface Activation (Shape change,/degranulation) Aggregation  3. Secondary haemostasis Exposure of tissue factor (TF), located on endothelium, fibroblasts & WBCs, binds Factor VII & activates Extrinsic Coagulation Cascade Activation of the coagulation cascade results in activation of thrombin Thrombin converts soluble fibrinogen in the blood into insoluble fibrin in the thrombus Thrombin recruits further platelets, yielding a solid permanent plug, the permanent secondary haemostatic plug Robbins Pathological Basis of Disease: Fig 5.5 4. Counter-regulatory mechanisms established: Restricts inappropriate extension of the haemostatic plug beyond the site of injury, by release from the endothelium of: Tissue plasminogen activator [t-PA] – fibrinolytic [generates fibrinolytic plasmin] Thrombomodulin - interferes with the coagulation cascade So at the very end of the very end of the coagulation cascade starts a counter- regulatory mechanism: the fibrinolytic cascade! Robbins Pathological Basis of Disease: Fig 5.5 This 6-min long YouTube video explains hemostasis quite well for starters, before you go for a deeper dip later… https://www.youtube.com/watch?v=OEbDDtcN4qI The contents of the video link on this page is for your interest only (will not be tested). The details of the coagulation cascade is for your interest only.  COAGULATION CASCADE This page is for your interest only, to demonstrate an enzyme cascade (proteinase cascade) Fibrin degradation products https://litfl.com/wp-content/uploads/ 2019/01/coagulation-cascade.jpg and D-dimers Fibrin clot (crosslinked, stable) with erythrocytes and platelets Plasma Proteinase Cascades Coagulation cascade (makes fibrin) Fibrinolytic cascade (degrades fibrin) Complement cascade (inflammation) Kinin cascade (inflammation) Other Enzyme Cascades Phosphorylation / dephosphorylation cascades (Intracellular signalling) Caspase cascade (apoptosis)  Summary about Blood: Delivering plasma-borne substances to tissues Removing waste, delivering O2, carrying heat Delivering defensive leukocytes to tissues Aids hemostasis in case of blood vessel injury Coagulation and Fibrinolytic cascades, when in balance, ensure we don’t clot too much or bleed too much! Please remember: for hemostasis to be achieved, we need: 1.Reflex Vasoconstriction 2.Initial Platelet plug 3.Coagulation cascade ending in fibrin deposition 4.Fibrin stabilisation in the final clot. We did it! We did it! We did it! Yay!