Blood and Blood vessels and introduction to VM- Dr Manah Changmai.pptx

Histology of Blood Vessels and Blood film (Function of Blood cells) Dr Manah Changmai All images from: 1. Histology A Text and Atlas With Correlated Cell and Molecular Biology, Pawlina, W., Wolters Kluwer, London; Learning Objectives: At the end of the session, students should able to  Describe...

Histology of Blood Vessels and Blood film (Function of Blood cells) Dr Manah Changmai All images from: 1. Histology A Text and Atlas With Correlated Cell and Molecular Biology, Pawlina, W., Wolters Kluwer, London; Learning Objectives: At the end of the session, students should able to  Describe the histology of the blood and its various components, including plasma, erythrocytes, leukocytes and platelets.  Describe histological structure of various types of blood vessels.  Discuss the morphology, function, site of development and fate of erythrocytes.  Describe the morphology and function of neutrophils, eosinophils, basophils, monocytes, lymphocytes and platelets.  Discuss the hierarchy of stem cell types. Blood Vessels Blood vessels Arteries Elastic Arteries Capillaries Venules Muscular arteries Meta Arterioles Post Capillary venule Arterioles Terminal Arterioles veins The Blood Vascular System: Layers There is a basic 3 layer structure to the blood vessels:  Inner layer: Tunica intima, a single layer of squamous epithelial cells termed endothelial cells supported by a basal lamina and a thin layer of connective tissue.  Middle layer: Tunica media, made up predominately of smooth muscle. Thickness of this layer varies tremendously. From: 1  Outer layer: Tunica adventitia, made up of supporting connective tissue. The Blood Vascular System: Layers There is a basic 3 layer structure to the blood vessels:  The tunica intima is separated from the tunica media by a layer of elastic tissue called the internal elastic membrane.  The tunica media is separated from the tunica adventitia by a layer of elastic tissue called the external elastic membrane.  Elastic fibres are not stained using most From: 1 common stains (including H&E) but can be visualized with special stains like the one shown here – here the elastic fibres stain black. The Blood Vascular System: Layers There is a basic 3 layer structure to the blood vessels:  Inner layer: Tunica intima, a single T termed layer of squamous endothelial cells I epithelial cells supported by a basal lamina and a thin layer of connective tissue.  Middle layer: Tunica media, made TM up predominately of smooth muscle. Thickness of this layer tremendously. T varies made up of supporting A connective tissue.  Outer layer: Tunica From Dundee Virtual Microscope adventitia, There are variations in this general architecture. For example, in the largest arteries (e.g. aorta) a significant amount of the smooth muscle in the tunica media is replaced by sheets of elastic fibres. These are called ‘elastic arteries’. Blood Vessels: Elastic Arteries The very largest arteries (e.g. aorta) are termed elastic arteries because they have many sheets of elastic fibres (stained black here) in their tunica media to provide elastic recoil. Verhoeff’s/Masson trichrome stain: elastic fibres black, collagen green, and smooth muscle cells red Lume n Tunica adventi tia Tuni ca intim a Tunica media From 1 Blood Vessels: Elastic Arteries Note that in large arteries, only the inner part of the wall can obtain nutrients from the lumen, therefore these vessels will have their own vascular supply: the vasa vasorum. From 1 Blood Vessels: Arteriole Smallest division of muscular arteries As arteries become smaller they lose smooth muscle from the t. media, until arterioles have only one or two layers of smooth muscle in their tunica media and almost no adventitia. Typical diameter: 30- 200µm. These are particularly important in controlling blood flow in a tissue. Arteriole Terminal Arteriole;  No internal lamina  Covered by continuous coat of smooth muscle cells Meta Arteriole; Smooth muscle are replace by dis-continuous non-contractile cells called pericytes Terminates into capillaries From 1 Capillaries Capillaries are essentially composed of endothelial cells and a basal lamina. They have a diameter of 4- 8µm. (compare that to the dia. of an RBC) Capillaries are absent in:  Epithelial cells resting on basement membrane  Epidermis of skin, hair and nails  Cornea of the eye  Hyaline cartilage From: 1 Capillaries 3 Types: Continuous: muscle, nerve, lung, skin Fenestrated: have small pores (50nm), gut mucosa, endocrine glands, kidney Discontinuous or Sinusoidal: have large gaps, liver, spleen, bone marrow From: 1 Microvasulature Small arteriole Small arteriole connected to post capillary venule Through metarterioles (MT) Through thoroughfare channels (TC) Through capillaries (C) Through Postcapillary venule Precapillary sphincters (PS):composed of smooth muscle, at the beginning of the capillary help control flow through the network. Venul es Capillary networks drain into post-capillary venules (1030µm diameter), which are endothelial cell-lined and contain a thin layer of connective tissue. These are important sites for exchange, e.g. cells moving into the tissue in inflammation. Once the vessel begins to acquire intermittent smooth muscle cells in a tunica media layer, they are referred to as venules (generally >50µm). p.c. venule arterio le From 1 Vei ns Veins, in addition to a tunica intima, have a thin but continuous tunica media, typically consisting of a few layers of smooth muscle cells. There is an obvious tunica adventitia. The largest veins (e.g. vena cava) have a thick tunic adventitia which incorporates bundles of longitudinally oriented smooth muscle. Lumen of vessel TI (Tunica Intima) Many small veins have valves (inward extensions of the T.I.) to prevent backflow of blood. TM(Tunica media) TA (Tunica Adventitia From Lymph Vascular System System of relatively thin walled vessels that drain excess tissue fluid (lymph) into the blood stream Transports lymph to lymph immunological surveillance nodes for No central pump, but smooth muscle in walls, hydrostatic pressure in the tissue and compression of the vessels by voluntary muscle, combined with valves in the vessels, produces flow Venul e Arteriol e Lymphat ic vessel From 1 Bloo d Capillari es Where is the blood in the body? Peripheral Arteries Heart & Lungs Peripheral Veins Note: The cumulative volume of the capillaries is rather small, but their cumulative surface area is huge (estimated at 600m2). Blood Components up of: Average adult blood volume is 4.5-6 litres and is made Formed Elements (~45%) Red Cells White Cells Granulocyt es Platele ts Agranulocyt es Plasma (~55%) Water (~90%) Proteins (mostly albumin, immunoglobulins, clotting factors) Nutrients, Salts Neutrophils Eosinophils Basophils Lymphocytes Separating Blood Blood can be separated by spinning in a centrifuge.  The red cells are densest and after spinning are found at the bottom of the tube  The white cells are next  Plasma which is the liquid portion of blood, is found on top.  If the clotting factors are first removed from the blood, the liquid remaining is termed serum Serum is usually obtained by allowing the blood to clot, and then removing the clot before spinning the blood Before After Spinning From 1 Formed Elements of Blood: Erythrocytes Formed Elements of Blood: Erythrocytes Erythrocytes (often termed red blood cells or just RBC’s) are biconcave discs about 7µm in diameter Mature RBC’s are not true cells as they have no nucleus or organelles. They are basically deformable bags with about 1/3 of their volume taken up by the ironcontaining protein haemoglobin. They contain a network of flexible cytoskeletal elements that allow them to deform and slip through spaces smaller than themselves. Erythrocyt es From Dundee Virtual Microscope Erythrocyt es Erythrocytes last approximately 4 months in the circulation. Aged cells are removed chiefly by the spleen and liver. From: 2 From 1 The biconcave shape of RBCs is easily seen in this scanning electron micrograph. Hematocrit—the Proportion of Blood that is Red Blood Cells If a person has a hematocrit of 40, this means that 40% of the blood volume is cells, and the remainder is plasma. The hematocrit of adult men averages about 42, whereas that of women averages about 38 Modified from Guyton physiology In the above picture: Hematocrit values in a healthy (normal) person and in patients with anemia and polycythemia. The numbers refer to the percentage of the blood composed of red blood cells. Formed Elements of Blood: Leukocytes Leukocyt es Proportions of White Blood Cells: Neutrophils 4075% Eosinophils Basophils Lymphocyte s 5% 0.5% 2050% Monocytes 1-5% Leukocytes: Neutrophils Neutrophils are granulocytes and are the most common type of leukocyte. Their cytoplasm contains many granules but these stain poorly with either acidic or basic dyes (hence the ‘neutro’). They have a prominent, multi-lobed nucleus. Neutrophils circulate in an inactive state, but if stimulated, for example by the presence of bacteria or inflammation, they enter the tissue where they are highly motile phagocytes. From: 1 They are both abundant and short-lived which means that a significant portion of the bone marrow is devoted to their production. Leukocytes: Eosinophils Eosinophils typically have a bilobed nucleus. Their granules contain a variety of hydrolytic enzymes and they are important in inducing and maintaining inflammation, particularly in allergic reactions and asthma. They are also important in fighting parasitic infection. From: 1 The prominent granules in the cytoplasm of eosinophils have an affinity for the red acidic dye eosin. These cells are released from the marrow and circulate for 8-12 hours and then move into the tissue (particularly spleen, lymph nodes and GI tract) where most eosinophils live. Eosinophils are slightly larger than neutrophils (use the RBC’s as rulers). Leukocytes: Basophils Basophils are the rarest of the granulocytes. The prominent granules in their cytoplasm have an affinity for basic dyes such as methylene blue and with this dye, stain intensely blue-purple. The cells have a bilobed nucleus but this is often obscured by the granules. These granules contain histamine, heparin and other inflammatory mediators From: 1 Basophils act as effector cells in allergic reactions. High affinity IgE receptors in their cell membrane are directed against a particular allergen and when they bind their antigen the cell is stimulated to release its granules (termed degranulation). This leads to hayfever, allergic asthma, allergic dermatitis etc. Leukocytes: Monocytes Monocytes serve as the precursors of tissue macrophages and together they form what is termed the mononuclear phagocyte system.Macrophages are widely distributed in the body, but are particularly found in loose connective tissue From: 1 Monocytes have numerous small lysosomal granules in their cytoplasm. They are the largest cells circulating in the blood and have a non-lobulated nucleus which often appears kidney bean-shaped. Monocytes/ Macrophages Many members of the mononuclear phagocytic system are ‘wanderers’ but some remain resident within particular tissues, for example Kupffer cells in the liver, microglia in the brain and Langerhan’s cells in the skin. An activated tissue From: 1 Leukocytes: Lymphocytes Lymphocytes have a round nucleus surrounded by a thin to moderate rim of cytoplasm that does not have visible granules. There are two general classes of lymphocytes, B cells and T cells, however these cannot be distinguished in routine stained sections. From: 1 Both types of lymphocyte arises in the bone marrow, but T cells differentiate in the thymus. Both cell types participate in the specific immune response. B cells give rise to antibody secreting plasma cells while T cells form a complex set of cells that perform many defense functions (aiding other immune cells, killing defective cells, etc). Formed Elements of Blood: Platelets Platele ts In addition to RBC’s and leukocytes, the formed elements of blood include platelets. These are small cell fragments about 2µm in diameter found in large numbers in the blood. Platelets play a key role in hemostasis (the prevention of blood loss). From Dundee Virtual Microscope Platele ts  Platelets have a well developed cytoskeleton, which participates in extrusion of granules and in clot retraction.  Platelets have some organelles, but no nucleus.  They have conspicuous granules that include, among other things, somecoagulation factors From: 1 Hemopoie sis Developme nt Earliest site for erythrocyte formation is outside the embryo in the yolk sac beginning at about 3 weeks gestation. Later, the liver and to some extent the spleen is colonized by hemopoietic stem cells. Thus during the second trimester the liver is the principal site of blood formation. Gray’s anatomy 40th edition Hemopoiesis in a fetal liver. Note the hemopoietic cells (small arrows) between the pink clumps ofliver cells. From: 1 Developme nt By birth the bone marrow is the main site of blood formation and essentially all bones participate. As bones enlarge there is excess capacity and so hemopoiesis is shut down in many bones. By the time the skeleton reaches maturity, only the vertebrae, ribs, skull, pelvis and proximal femurs retain hemopoiesis. Marrow in other bones is largely adipose tissue, although in an emergency, they can revert to blood formation. Bone Marrow Hemopoiet ic cells Bloo d Megakaryocytes are large (30100µm) cells of bone marrow that produces platelets. It undergoes multiple duplications of its nuclear material but doesn’t undergo nuclear or cell division – so the nucleus is very large. The platelets are formed as extensions at the outer margin of the cell which fragment from the cell. Lineages of Blood Cells In Bone marrow, a very small number of self renewing pluripotent stem cells which are capable of giving rise to all blood cell types, including lymphocytes The committed progenitor cells are often termed colony-forming units (CFU) of the lineage Development of granulocytes and monocytes. Haemopoietic stem cells give rise to colonyforming units (CFUs). CFU-GEMMs have the potential to give rise to all blood cells except lymphocytes. These are granulocytes (G), erythrocytes (E), monocytes (M) and megakaryocytes (M), which each develop in response to specific cytokines and hormones. Intermediate CFUs or, for erythrocytes, burst-forming units (BFUs), THANK YOU