W1 Histology of Blood (Reid, H).pdf

HISTOLOGY of Dr. Herman Reid Professor, Department of Medical Foundations BLOOD Office Hours: By appointment: 1 [email protected] Goals for our time together today • Cover the basics of blood histology • Discuss how this relates to wellness, and also a few examples of how disturbances in the norm...

HISTOLOGY of Dr. Herman Reid Professor, Department of Medical Foundations BLOOD Office Hours: By appointment: 1 [email protected] Goals for our time together today • Cover the basics of blood histology • Discuss how this relates to wellness, and also a few examples of how disturbances in the normal can lead to disease 2 Learning Objectives 1) Explain the differences between serum and plasma 2) List the basic composition and functions of blood 3) Discuss the structures and functions of each formed element in the blood (erythrocytes, neutrophils, eosinophils, basophils, lymphocytes, monocytes, and platelets) 4) Be able to recognize each of the formed elements of blood at the light microscopic level, and also be able to recognize those formed elements that have distinguishing characteristics (e.g. RBCs, platelets, eosinophils) at the EM level 5) Explain how acidophilic, basophilic, and azurophilic stains produce different colors on different cellular components, and know which cellular structures are stained with each 6) Explain how WBCs exit the bloodstream by diapedesis to enter tissues Sample questions can be found in lecture folder 3 WHAT IS BLOOD? The fluid consisting of plasma, blood cells, and platelets that is circulated by the heart, carrying oxygen and nutrients to, and waste materials away from all body tissues [from Old English blōd, meaning blood] hema (Greek) blood *Blood is considered to be a specialized connective tissue 4 FUNCTIONS OF THE BLOOD 1. Transports O2, CO2, hormones, waste, nutrients, enzymes 2. Stabilization of pH and electrolyte concentrations in interstitial fluids 3. Regulation of body temperature 4. Blood acts as a pathway for migration of white blood cells between various connective tissue compartments of the body Average adult has about 5-6 liters of blood About 7 - 8 % of total body weight Examples of the basic, functional interrelationships of blood Figure 1.3 6 Blood consists of three formed elements 1) Red blood cells (RBCs; erythrocytes) 2) White blood cells (WBCs; leukocytes) 3) Platelets (thrombocytes) 7 COMPONENTS OF BLOOD * In the body, the formed elements of blood are suspended in plasma When taken outside the body, blood will clot, leaving (the liquid) serum PLASMA VERSUS SERUM To remember the difference-plasma starts with a p, plasma contains all the proteins 8 blood clot: “strings” are insoluble fibrin that has been converted from soluble fibrinogen Colorized scanning EM of blood clot showing erythrocytes trapped in fibrin strands 9 BLOOD REVIEW 10 Blood - Plasma proteins (Albumins, Globulins, Fibrinogens) Consist of Albumins made in liver, smallest proteins, over ½ of the total plasma proteins responsible for exerting the concentration gradient between the blood and extracellular fluid represented by an osmotic pressure on the blood vessel wall, called the COLLOID OSMOTIC PRESSURE (COP) when albumins leak from blood vessels or are lost in urine or are not made in the liver osmotic pressure of blood drops, fluid accumulates in tissues and (O) EDEMA may result 11 Clinical Correlations - EDEMA • hypoproteinemia / loss of albumins → EDEMA • original causes for loss of albumins may vary • other causes of edema besides reduced COP Forces at work for the normal movement of fluid at the level of the blood and lymphatic capillaries Clinical Correlations - EDEMA Lower limb pitting edema Lymphatic Filariasis Edematous ankles – could be heart disease Lower limb - pregnancy Kwashiorkor Periorbital edema 13 Blood - Plasma proteins Globulins • immunoglobulins (gamma / γ globulins) largest component of globulins, antibodies (from Plasma Cells) • non-immune globulins (alpha / α, and beta / β) - secreted by liver - help maintain osmotic pressure - serve as carrier proteins for : - copper (ceruloplasmin) - iron (transferrin) - hemoglobin (haptoglobulin) - also include other molecules eg. lipoproteins, fibronectin and coagulation factors 14 Blood - Plasma proteins Fibrinogens • made in liver ▪ largest plasma protein ▪ blood clotting, transformed into insoluble FIBRIN ▪ fibrin fibers form a net that prevents further blood loss 15 We will now go through the three formed elements of blood (RBCs, WBCs, and platelets) and • learn what each does • and how to recognize each type under the microscope In the “Hematopoeisis” lecture you will learn about the production of each type in the bone marrow 16 MAKING A BLOOD SMEAR Blood smears are commonly stained with *WRIGHT STAIN- methylene blue and eosin 17 methylene blue • A basic dye (+ charge) • Stains (like hematoxylin) acidic cellular structures blue What cellular structures are acidic (- charge) ? 1) DNA in the nucleus 2) RNA in the cytoplasm 3) The specific granules of basophils • These structures are said to be basophilic (base-loving) WRIGHT STAIN methylene blue + eosin eosin • An acidic dye (- charge) (same as in H&E) • Stains basic cellular structures pink/red. What cellular structures are basic (+ charge) ? 1) Hemoglobin regions 2) The specific granules of eosinophils (contains the major basic protein) • These structures are said to be acidophilic or eosinophilic (acid- or eosin-loving) Other compounds are colored a reddish blue by binding to azures, substances formed when methylene blue is oxidized. The lysosomes (primary granules) of all leukocytes stain “AZUROPHILIC” 18 Normal stained blood smear 19 - which FORMED ELEMENTS are absent ? Figure 17.2 Normal stained blood smear - which FORMED ELEMENTS are absent ? - name the most numerous WBCs - note relative quantities of cells CBC hematology analyzer 20 FYI slide…. 21 FORMED ELEMENTS OF BLOOD 1) RED BLOOD CELLS (RBCS) aka ERYTHROCYTES (Greek erythros red, kytos cell) • Primary function is the transport of O2 and CO2 • No nucleus or organelles • RBCs are basically just bags of hemoglobin • RBCs make up 99% of all blood cells 22 HEMATOCRIT (PCV) (definition) The percentage by volume of packed red blood cells in a given sample of blood after centrifugation Males 40-50% Females 35-45% • Note that males have more erythrocytes per unit volume than females males 4.7-6.1 x 106/mm3 (1 mm3=1 ul) females 4.2-5.4 x 106/mm3 effects of menstruation? • And members of both sexes living at higher altitudes have more erythrocytes per unit volume than people living at lower altitudes….. Reason ? • • The number of RBCs in the circulation is regulated to meet O2 carrying needs. The hormone erythropoietin, secreted mainly by kidneys in adults and by the liver in the fetus, adjusts RBC production to match O2 demand. (see Hematopoiesis lecture) 23 **USMLE Step 1 normal Laboratory values-given with every mini, final, comp, step 1 These USLME Normal Lab Values are a resource that can be obtained on the portal- Portal/student resources/Center for Teaching and Learning/CTL Resources/Additional Study Resources/USMLE Normal Lab Values 24 CONTAINSALL THE BLOOD FACTS YOU DON’T HAVE TO MEMORIZE! 25 ERYTHROCYTES (RED BLOOD CELLS) Erythrocytes have mainly just 4 components (plus a few additional enzymes) 1) plasma membrane 2) cytoskeleton 3) hemoglobin- 95% of RBCs protein content, 30% weight of RBC ; Gives RBCs their red color (see Biochem lecture) 4) glycolysis enzymes* • During formation in bone marrow (erythropoiesis), developing erythrocytes lose nucleus and organelles, only keeping cytoskeleton • *Because RBCs don’t have any mitochondria, mature RBCs in blood make ATP exlusively through cytoplasmic glycolysis using glucose in the blood plasma RBCs have a limited life span- 120 days • • • The average RBC will pass through the heart ~500,000 times Cell membrane eventually ruptures; or aged cell is phagocytosed in spleen, liver and bone marrow. (see Lymphoid Tissue lecture) 26 1% RBCs replaced daily, new ones reticulocytes (see Hematopoeisis lecture) STRUCTURE OF RBC ANISOCYTOSIS means that the red cells are of unequal size. • It is a feature of many anemias, and other blood conditions (see Pathology lectures) Histologic ruler also ! BICONCAVE SHAPE • Shape maximizes their surface area/ volume ratio, therefore maximizes O2 and CO2 exchange ~8 um normal <6 um MICROCYTE >9 um MACROCYTE 27 SCANNING EM OF RBC MOVING THROUGH CAPILLARY note the “TIGHT FIT” (arrow)*This maximizes membrane-membrane contact to facilitate gas exchange Collagen types in electron micrograph Collagen type I (C) Reticular Fibers (RF) - collagen type III, Found around many small blood vessels (also nerves and muscles) RBCs pass easily through the smallest blood vessels by folding on themselves and can thus pass through even the narrowest capillaries • In small vessels, RBCs often stack up in aggregates called rouleaux (French-”roll of coins” in a paper wrapping) 28 RBC MEMBRANE ORGANIZATION •The shape of the erythrocyte is maintained by a specialized cytoskeleton actin-spectrin that provides the mechanical stability and flexibility necessary to withstand forces experienced during circulation Integral membrane proteins are of two major families 1) Glycophorins 2) Band 3 proteins The carbohydrate groups on glycophorins and band 3 proteins (and on glycolipids) form the ABO blood group 29 antigens (sugar transferases determine ABO blood type) (see BIOCHEM lecture) RBC membrane organization Peripheral Membrane Proteins Organized as lattice network on the inner surface of the cell membrane spectrin, actin, band 4.1 protein, adducin, band 4.9 protein and tropomyosin lattice is bound to the lipid bilayer by the protein Ankyrin 30 HEREDITARY SPHEROCYTOSIS (HS) • Somatic dominant trait • Defective spectrin or ankyrin, which binds spectrin to plasma membrane • RBCs in HS do not form their normal biconcave shape (they are round and convex) • RBCs are abnormally fragile and rapidly break down • RBCs transport less O2 HS morphology: Red cells are more spherical, lack the central area of pallor on a stained blood film. NORMAL RBCS HEREDITARY SPHEROCYTOSIS 31 Hereditary Elliptocytosis Deficiency in band 4.1 proteins Elliptical erythrocytes result Both spherocytosis and elliptocytosis are conditions that result in an inability of RBCs to adapt to changes in their environment (osmotic pressure effects and mechanical deformations occur) HEMOLYSIS (breakdown / destruction of RBCs) therefore results 32 What may be other causes of hemolysis ? 33 Other causes of hemolysis ▪ incompatible blood transfusions ▪ hemolytic disease of the newborn ▪ snake venoms / toxins ▪ infectious agents / hemolytic anemias 34 Hemolysis: from RBCs placed in a hypotonic solution 35 Crenated RBCs Blood smear – malaria Malaria is a parasitic disease caused by the genus Plasmodium, of which there are four species that affect man. Shown here are "ring forms" of Plasmodium vivax in red blood cells. This disorder can produce hemolysis and anemia. 36 FORMED ELEMENTS OF BLOOD 2) WHITE BLOOD CELLS/LEUKOCYTES (Greek leukos white; kytos cell) • Much less abundant in blood than RBCs (~600 times less abundant) • Total number in peripheral blood is 6500 – 10,000/ul (versus RBC: male 4.7-6.1 x 106/ul, female 4.2-5.4 x 106/ul) **WBCS DO NOT FUNCTION IN THE BLOOD (UNLIKE RBCS), THEY FUNCTION IN TISSUES **WBC ARE A NORMAL COMPONENT OF CONNECTIVE TISSUE • They use blood to transport themselves from the bone marrow where they are made to their major sites of activity in tissues • They leave the bloodstream by migrating between endothelial cells of the blood vessels, diapedesis, see later in lecture A normal mature lymphocyte with a single large nucleus is seen on the left, compared to a segmented neutrophil on the right with multiple nuclear lobes connected by thin chromatin bridges, along with cytoplasmic granules. A RBC is seen to be about 2/3 the size of a normal lymphocyte. 37 CLASSIFICATION OF LEUKOCYTES *based on the presence or absence of 2) AGRANULOCYTES specific granules 1) GRANULOCYTES neutrophils, eosinophils, basophils *Have specific granules Differentiated according to the color of their staining reaction with Wright stain lymphocytes, monocytes Do not have specific granules, ***however all WBCs possess small, nonspecific azurophilic granules (lysosomes) 38 PRIMARY AND SECONDARY (SPECIFIC) GRANULES •Primary and specific (secondary) granules each contain many enzymes **Each granulocyte has different set of enzymes/weaponsto fight different enemies! 39 DIFFERENTIAL WBC COUNT (% of total counted is WBC type) The differential counts the percentage of each type, will determine • If the cells are present in normal proportion to one another • If one cell type is increased or decreased, or • If immature cells are present **If there is a requirement for increased activity of any WBC type in the peripheral tissues, the number and proportion of that cell type rises markedly in the blood ex. Bacterial infection -neutrophil count goes up Parasitic infection - eosinophil count goes up Never Let Monkeys Eat Bananas LIFESPAN OF LEUKOCYTES Lifespan Neutrophils Few hours in blood, a few days in tissue Eosinophils A few days - 2 weeks Basophils Lymphocytes Monocytes A few days - Few days to a Few days in months number of years blood, several months to years in CT **Agranulocytes live much longer than granulocytes • All granulocytes are nondividing terminal cells with a life span of usually a few days after they are released from bone marrow, if they don’t “die in battle” first… see later • Withdrawal of growth factors when granulocytes leave the bone marrow triggers their 41 apoptosis in the connective tissue after a few days NEUTROPHILS - aka POLYMORPHONUCLEAR LEUKOCYTES (PMNs) • NEUTROPHILS are the most numerous of the white blood cells, constituting 60% to 70% of the total leukocyte population • The lobes of their multilobed nucleus (3-5 lobes) are connected to each other by slender chromatin threads • Neutrophils are motile cells: they leave the circulation and migrate to their site of action in the connective tissue • Neutrophils (and all WBCs) are inactive and spherical while circulating, but show an active ameboid movement upon adhering to a solid substrate. 42 NEUTROPHILS • 3-5 lobed nuclei *The key to identifying neutrophils is the shape of the nucleus • Azurophilic non-specific granules (lysosomes) • Neutral-staining specific granules • Neutrophils contain few mitochondria as they use mainly glycolysis to generate ATP *The ability of neutrophils to survive in an anaerobic environment is highly advantageous, because they can kill bacteria and help clean up debris in poorly oxygenated regions, eg, inflamed or necrotic tissue. Neutrophils contain a lot of glycogen- G 43 NEUTROPHILS • Neutrophils are active phagocytes of bacteria and other small particles • Neutrophils select bacteria/particles to be phagocytosed either because 1) they are coated with antibodies and/or complement (i.e. opsonized with “eat me” signals), or, 2) because they are emitting chemoattractors 1) 2) 3) 4) Chemoattractors/chemotactically active factors are important mediators of a number of processes because they attract the needed cell types to the area where they are needed. Immune responses Inflammation Wound healing Embryogenesis CHEMOTAXIS (definition) - Crawling along a soluble concentration gradient 44 towards its source 45 DIAPEDESIS (definition)- passage of blood cells (especially white blood cells) through intact capillary walls and into the surrounding tissue 19.2 Rolling_leukocytes.mov 46 NEUTROPHILS • Neutrophils defend tissues outside the blood by killing their targets • **The main function of neutrophils is to act as the first line of host cellular defense against bacterial infection • **Neutrophils are among the first cells to appear in acute bacterial infections • **Dead neutrophils and bacteria are the main ingredients of pus 47 HOW DO NEUTROPHILS KILL THEIR PREY AFTER THEY HAVE HUNTED THEM DOWN? Neutrophils contain 2 main types of granulesWhich contain hundreds of proteins, “weapons” used to kill bacteria After phagocytosis, both types of granules fuse with the phagosome 1) Azurophilic granules (aka primary granules) • These are the lysosomes of the neutrophil and contain myeloperoxidase, which helps to generate highly reactive bactericidal hypochlorite and chloramines (see neutrophil oxidative burst later in lecture) 2) Specific granules (aka secondary granules) • “neutral”-colored in neutrophils • The smallest granules which contain various enzymes and antimicrobial agents (examples: lysozyme, lactoferrin) *NOTE THAT EOSINOPHILS AND BASOPHILS CONTAIN DIFFERENT SUBSTANCES IN THEIR GRANULES 48 Neutrophils and phagocytosis Cells such as monocytes, macrophages, lymphocytes, eosinophils, plasma cells, basophils and fibroblasts are also involved in inflammation ! Appearance of large numbers of various WBCs in an inflamed tissue section ID the PMNs and other cells in this section 49 NEUTROPHIL IMAGES REVIEW 50 EOSINOPHILS • Have a sausage-shaped, bilobed nucleus • The two lobes are connected by a thin chromatin strand and nuclear envelope • Are round cells (in the blood), • Have large, salmon pink colored specific granules **major basic protein causes eosinophilic/acidophilic staining of specific granules • Eosinophils also contain azurophilic non-specific granules (lysosomes) **Eosinophils function in 1) parasitic infections 2) asthma and allergies (together with mast cells and basophils) “EOSINOPHILIA”-An increase in the number of eosinophils in the blood is associated with: 1) parasitic infections 51 2) allergic reactions • EOSINOPHILS Contain different “weapons” than neutrophils because they are hunting different “prey” (not bacteria) • Eosinophil specific granules contain major basic protein (50% of total granule protein) • The highly basic nature of the protein contributes to its toxicity by causing it to “gum up” and denature proteins on the plasma membrane of other eukaryotes • Major basic protein causes eosinophilia (acidophilia) of specific granulesgives eosinophils their name! 52 *On EM, can recognize eosinophils because of dark stripe on specific granules 53 Parasite: An organism that grows, feeds, and is sheltered on or in a different organism while contributing nothing to the survival of its host. Parasites are of different types and range in size from tiny, single-celled, microscopic organisms (protozoa) to larger, multi-cellular worms (helminths) that may be seen without a microscope. * Eosinophils generally fight multicellular parasites like worms, which can be quite large (a tapeworm, for example, may be up to 20 feet long) The way that eosinophils attack their prey is based on two considerations: 1) Their prey are (usually) eukaryotes like themselves 2) Their prey are (usually) much bigger than they are, and too big to be phagocytosed EOSINOPHILS Eosinophils therefore attach to the surfaces of parasites and extrude the contents of their granules (both specific and non-specific) into the extracellular space. **Eosinophils are often (importantly) first attracted to surface of parasite by bound antibodies, they then release their granules +major basic protein 55 EOSINOPHILS *When eosinophils release the major basic protein (and other substances) into tissue, in addition to killing the parasites can also cause damage to surrounding normal tissue (collateral damage) eosinophils would be increased in the lamina propria of this intestine example- If this happens in the intestine, can cause diarrhea and other irritations mouse eosinophils coat a worm.mp4 (no soundtrack) Speeded up from real life, but exact speed unknown (from YouTube) 56 A SECOND MAJOR ROLE OF EOSINOPHILS IS TO CONTROL MECHANISMS ASSOCIATED WITH ALLERGY AND ASTHMA • A hallmark of allergic disease is infiltration of the tissues with increased numbers of eosinophils (eosinophilia) • Result of the co-ordinated action of cytokines causing selective trafficking of eosinophils into allergic tissue Examples: 1)Allergy, cow’s milk intolerance, and gluten sensitivity cause increased numbers of eosinophils in the bowel mucosa 2) Asthma causes increased numbers of eosinophils in lung tissue (slide at right) LUNG, H&E-At high magnification, the numerous eosinophils are prominent from their bright red cytoplasmic granules in 57 this case of bronchial asthma. EOSINOPHILS IMAGE REVIEW 58 BASOPHILS • The rarest leukocyte, less than 1% of the total leukocyte population • Numerous basophilic (blue) granules in the cytoplasm that usually make it difficult to see the nucleus clearly • Has an S-shaped nucleus, but you usually can’t see it in light micrographs because of the granules • The specific granules of basophils contain heparin and histamine (like mast cells) 59 BASOPHILS FUNCTION: Basophil function is very similar to those of mast cells however basophils and mast cells are different cell types ➢ 😇Basophils leave the blood and accumulate at the site of infection or other inflammation There they release a variety of mediators such as histamine, serotonin, prostaglandins and leukotrienes which increase the blood flow to the area and in other ways add to the inflammatory process ➢ 👿SIDE-EFFECT: Basophils have immunoglobulin E (IgE) receptors (like mast cells), and the mediators released by basophils play an important part in some allergic responses such as hay fever and in anaphylactic response to insect stings 60 BASOPHILS VERSUS MAST CELLS • Basophils closely resemble mast cells of connective tissue • Their basophilic granules look like those of mast cells; Granules also contain histamine and heparin. **tell these two cell types apart primarily by their location If it is in blood, it is a basophil If it is in connective tissue, odds are it is a mast cell because basophils are very rare there basophil in a blood smear mast cells in connective tissue 61 BASOPHILS / MAST CELLS IMAGE REVIEW 62 GRANULOCYTES REVIEW NEUTROPHILS EOSINOPHILS BASOPHILS 63 AGRANULOCYTE (1 of 2) MONOCYTES • The largest of the circulating blood cells (range in size from 12-20 um) • ~2-3 times the diameter of RBCs • Constitute 3% to 8% of the leukocyte population • Have large, acentric, indented or kidneyshaped nucleus • The chromatin network is coarse but not overly dense • Their cytoplasm is bluish gray and has numerous azurophilic granules, (lysosomes) but • No specific granules **note size of monocytes relative to RBCs (~2-3x) 64 MONOCYTE FUNCTIONS 1) Avid phagocytes, they phagocytose and destroy dead and defunct cells as well as antigens and foreign particulate matter (such as bacteria). 2) Antigen presenting cells They play a major role in the immune response Mononuclear phagocyte system- members of family play a major role all over the human body • • • All develop as monocytes in bone marrow, Then enter the bloodstream Then leave the blood and enter connective tissue where they develop into macrophages • ***The characteristics of the connective tissue surrounding the newly formed macrophages determine their exact final differentiation, i.e. if it is dermis they can further differentiate into Langerhan’s cells and then they enter the epidermis; if it is bone, they can become osteoclasts etc… (NB: diagram to the right !) AGRANULOCTE (2 of 2)- LYMPHOCYTES • Lymphocytes constitute 20% to 25% of the total circulating leukocyte population • Round cells • Slightly indented • Dense (heterochromatic), round nucleus that occupies most of the cell • Thin rim of cytoplasm stains light blue and contains a few azurophilic, but no specific granules • The 3 group of lymphocytes (B, T, and NK cells) all look the same by histological staining 66 AGRANULOCTE (2 of 2)- LYMPHOCYTES • Lymphocytes vary in life span; ✓ some live only a few days, ✓ others survive in the circulating blood for many years • Are 20-25% of leukocytes in blood **but, the main type of cell found in lymph, hence the name lymphocyte • Lymphocytes recirculate between blood, tissues, and lymph They do this as part of the immune system that monitors the tissues see Immunology lectures and the Lymphoid Tissue lecture for descriptions of lymphocyte homing 67 LYMPHOCYTE (in blood), not secreting anything PLASMA CELL (in tissue) B lymphocytes can transform into antibody-secreting plasma cells *note extensive rER and “clockface” nucleus 68 REVIEW MONOCYTES LYMPHOCYTES *note the size of each relative to RBCs 69 CLL • These mature lymphocytes are increased markedly in number. • They are indicative of chronic lymphocytic leukemia (CLL), a disease most often seen in older adults. • This disease responds poorly to treatment, but it is indolent. 70 PLATELETS • Blood platelets (aka thrombocytes) are not cells, they are pieces of a cell • Derived in the bone marrow from a giant precursor cell megakaryocyte (see Hematopoeisis lecture) • Their life span is about 10 days IN A BLOOD SMEAR, PLATELETS (ARROWS) ARE OFTEN FOUND AS AGGREGATES ***The primary function of platelets is to prevent excessive internal or external bleeding after an injury by helping to form blood clots71 Thrombocytes / Platelets • Platelet demarcation channel membranes are invaginations of the plasma membrane of the megakaryocytes • the channels are continuous with the extracellular space • PLATELETS therefore form from segmentation of parts of the megakaryocyte cytoplasm 72 • Platelets are nonnucleated, disklike cell fragments 2-4 um in diameter containing ✓ lysosomes ✓ mitochondria ✓ some ER ✓ some Golgi ✓ three types of granules ✓ extensive cytoskeleton Platelet granules contain • VON WILLEBRAND FACTOR promotes adhesion of platelets to endothelial cells; also produced by endothelial cells • PLATELET FACTOR IV stimulates blood coagulation • and other factors PLATELETS students-figure details fyi only 73 1st FUNCTION OF PLATELETS- BLOOD CLOTTING 1) To Seal Wounded Endothelium • Platelets help to temporarily seal off the site of a wound by sticking to the exposed, damaged edges of blood vessels • Platelets are activated upon exposure to collagen of basal lamina and connective tissue underlying endothelial cells of blood vessels, **which is normally hidden except when endothelium is injured • When platelets bind to wounded endothelium: ✓ They become activated ✓ Release their granules ✓ These factors react with the clotting factors in the blood (like fibrinogen) to form blood clot See Biochemistry blood clotting lecture for details 74 Thrombocytes / platelets Platelets are involved with blood clot formation ▪ Fibrinogen is converted to fibrin ▪ Red blood cells trapped in fibrin forming a hemostatic plug 75 2ND FUNCTION OF PLATELETS- WOUND • REPAIR The blood clot is only a temporary solution to stop bleeding, vessel repair is therefore needed • The aggregated platelets help this process by secreting chemicals, primarily platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF beta) • These substances promote the invasion of fibroblasts from surrounding connective tissue into the wounded area to form a scar and also repair of blood vessel endothelium • Local applications of these factors in increased concentrations through platelet-rich plasma (prp) has been used as an adjunct to wound healing for several decades 76 Example of the result of abnormal blood clot formation within a blood vessel resulting in a STROKE -- fyi 77 Images of thrombi / thromboemboli - fyi 78 THE END OF THE LECTURE ! HIGHLY RECOMMENDED!!! Digital Histology https://digitalhistology.org/ For studying and they also have quizzes to test you Additional reading if required and reference: Junquiera’s Basic Histology (in Vital Source package) Chapter 12, “Blood” Note: I don’t recommend Digital Histology for the Hematopoeisis lecture. They cover recognizing the stages of development of the different lineages of blood cells, which you are not required to know. 79