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La Sangre. Funciones Fisiológicas
- 1. II.- Fisiología de la sangre Rafael Sirera, PhD
- 2. Rafael Sirera 2 II.- Fisiología de la sangre 1. Funciones fisiológicas de la sangre. Componentes del plasma. Elementos formes o celulares. Transporte plasmático. Tipos sanguíneos. 2. Hemostasia y coagulación de la sangre. Fibrinolísis.
- 3. II.1.- Fisiología de la sangre 1. Funciones fisiológicas de la sangre. Componentes del plasma: Proteínas plasmáticas, transporte de iones y metabolitos. Elementos formes o celulares: eritrocitos, plaquetas y leucocitos. Transporte plasmático. Tipos sanguíneos. Homeostasis.
- 4. Rafael Sirera 4 1.Conocer los componentes del plasma: 1. Proteínas plasmáticas, iones y metabolitos. 2.Identificar los elementos formes o celulares 1. eritrocitos, plaquetas y leucocitos. 3.Entender el transporte sanguíneo. 4.Conocer los tipos sanguíneos. 5.Estudiar los mecanismos de homeostasis. Objetivos de aprendizaje
- 5. Rafael Sirera 5 Funciones fisiológicas de la sangre • Transporte • Regulación del pH • Balance iónico • Coagulación • Defensa contra toxinas y patógenos • Regulación de la temperatura corporal
- 6. Rafael Sirera 6 Análisis de la sangre
- 7. Rafael Sirera 7 La sangre –Es un fluido • Mantiene el medio interno • Contiene células suspendidas en un matriz fluida coloidal • Muy viscosa • Ligeramente alcalina, pH 7.4 – Tansporta materiales “de y para” las células • Gases: O2 y CO2 • Nutrientes • Hormonas • Componentes del sistema inmune • Mecanismos de coagulación • Productos de desecho
- 8. Rafael Sirera 8 Características física de la sangre • Componentes – Plasma • Agua • Proteínas • Iones • metabolitos – Células • Eritrocitos (células rojas o hematíes) • Leucocitos (células blancas) • Plaquetas (trombocitos) • 7% del peso corporal: • 5-6 l hombre • 4-5 l mujer
- 9. Rafael Sirera 9 1 Withdraw blood and place in tube. 2 Centrifuge the blood sample. Plasma • 55% of whole blood • Least dense component Buffy coat • Leukocytes and platelets • <1% of whole blood Erythrocytes • 45% of whole blood • Most dense component Formed elements Hematocrit (Percent of blood volume that is RBCs) 47% ± 5% for males 42% ± 5% for females Componentes de la sangre
- 11. Rafael Sirera 11 Plasma • Origen de las proteínas plasmáticas –90% en el hígado –Los anticuerpos los producen las células plasmáticas –Las hormonas por las glándulas endocrinas • Diferencias entre el plasma y el líquido intersticial – Niveles de O2 y CO2 – Concentraciones y tipos de proteínas • Las proteínas del plasma no atraviesan el endotelio capilar
- 12. Rafael Sirera 12 Rafael Sirera Pérez Departamento de Biotecnología Proteínas Plasmáticas
- 13. Rafael Sirera 13 • Patrón electroforético de las proteínas del plasma en gel de agarosa • Se observan 5 fracciones • También se puede emplear la cromatografía y la precipitación Electroforesis del plasma Inmunoelectroforesis cruzada bidimensional
- 14. Rafael Sirera 14 Principales proteínas plasmáticas Proteína Conct. (g/l) Mr, (kDa) Función Acción Transtiretina (prealbúmina ) 0,15-0,36 62 Transporte Tiroxina, vitamina A Albúmina 39-51 66 Transporte Presión oncótica, Reservorio de amino ácidos Transportador de moléculas pequeñas 1-antitripsina 2-4 54 Inhibidor Inhibidor de proteasas 2-macroglobulina 1,5-3,5 725 Inhibidor Inhibidor de proteasas Haptoglobina 0,4-2,9 100 Transporte Fija Hemoglobina -lipoproteína 2,7-7,4 380 Transporte Transporta lípidos Transferrina 2-4 80 Transporte Transporta hierro C3 0,6-1,4 185 Defensa Componente mayoritario del complemento Fibrinógeno 1-4 340 Hemostasia Formación del coágulo IgG 7-15 150 Defensa Anticuerpo de tipo IgG IgA 0,4-3,5 320 Defensa Anticuerpo de tipo IgA IgM 0,25-2 850 Defensa Anticuerpo de tipo IgM
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- 21. Rafael Sirera 21 Células sanguíneas • Sólo los leucocitos son células completas • Los hematíes no tienen núcleo o orgánulos • Las plaquetas son fragmentos celulares • Viven pocos días en la sangre • Se originan en la médula ósea • No se dividen Platelets Neutrophils Lymphocyte Erythrocytes Monocyte
- 22. hematíes
- 23. Rafael Sirera 23 Anatomía de los hematíes
- 24. Rafael Sirera 24 Características de los hematíes • Son el 99.9 % de las células de la sangre, 5x106µl – Confieren la viscosidad a la sangre • Discos bicóncavos, sin núcleo • Contienen hemoglobina (Hb), >97% (seco) • Alta relación membrana-volumen • Metabolismo anaerobio al carecer de mitocondrias • Morfología muy adaptativa, permite su paso por los capilares (espectrina) • Vida media de 120 días
- 25. Rafael Sirera 25 viscosidad de la sangre
- 26. Rafael Sirera 26 Hemoglobina • Estructura de la Hb • Globina: dos cadenas alpha y 2 beta • Un grupo Hemo en cada globina • Un átomo de Fe en cada hemo que una a una molécula de O2 • cada Hb transpota 4O2 • ↓pO2 libera O2 y une CO2
- 27. Rafael Sirera 27 Reciclado eritrocitos ferritin and hemosiderin Ferritin is a globular protein complex consisting of 24 protein subunits and is the primary intracellular iron-storage protein in both prokaryotes and eukaryotes, keeping iron in a soluble and non-toxic form. Ferritin that is not combined with iron is called apoferritin.
- 28. Rafael Sirera 28 Metabolismo del hierro La hepcidina es una hormona peptídica producida por el hígado, que parece ser el regulador central del metabolismo del hierro en humanos y otros mamíferos
- 29. Rafael Sirera 29 • Five Primary Functions of the Skeletal System • Support • Storage of Minerals (calcium) and Lipids (yellow marrow) • Blood Cell Production (red marrow) • Protection • Leverage (force of motion) Médula ósea
- 30. Rafael Sirera 30 Médula ósea
- 31. Rafael Sirera 31 Eritropoyesis Fases 1. Síntesis ribosomal 2. Acumulación de hemoglobina 3. Eyección del núcleo y formación del reticulocito Stem cell Hemocytoblast Proerythro- blast Early erythroblast Late erythroblast Normoblast Phase 1 Ribosome synthesis Phase 2 Hemoglobin accumulation Phase 3 Ejection of nucleus Reticulo- cyte Erythro- cyte Committed cell Developmental pathway
- 32. Rafael Sirera 32 Eritropoyesis • Regulación de la eritropoyesis • La síntesis de eritrocitos requiere • Aminoácidos, lípidos, carbohidratos… • Hierro • De la Hb (65%), hígado, bazo y médula • Almacenado en células como ferritina y hemosiderina • Tranportado por la transferrina • Vitaminas B12 (factor intrínseco), B6 y ácido fólico • síntesis de DNA, división y maduración celular
- 33. Rafael Sirera 33 Kidney (and liver to a smaller extent) releases erythropoietin.Erythropoietin stimulates red bone marrow. Enhanced erythropoiesis increases RBC count. O2- carrying ability of blood increases. Homeostasis: Normal blood oxygen levels Stimulus: Hypoxia (low blood O2- carrying ability) due to • Decreased RBC count • Decreased amount of hemoglobin • Decreased availability of O2 1 2 3 4 5 Homeostasis
- 35. leucocitos
- 36. Rafael Sirera 36 Leucocitos • Son <1% del volumen de la sangre – 5000 a 10,000 por microlitro • No tienen Hb pero sí núcleo y orgánulos • Salen de los capilares por diapédesis y tiene movimiento ameboide • Se mueven gracias a señales quimiotácticas • Funciones – Defensa de patógenos – Elimar toxinas y restos celulares – Atacar células anormales – Remodelado tisular • Leucocitosis: >11,000/mm3 – Respuesta a la invasión de patógenos
- 37. Rafael Sirera 37 Circulación y movimiento – La mayor parte está residente en tejidos • Conectivo • Órganos linfoides – Poca cantidad en sangre periférica • Pueden salir de la sangre • Son fagocíticos y citolíticos
- 38. Rafael Sirera 38 Formed elements Platelets Leukocytes Erythrocytes Differential WBC count (All total 4800 – 10,800/l) Neutrophils (50 – 70%) Lymphocytes (25 – 45%) Eosinophils (2 – 4%) Basophils (0.5 – 1%) Monocytes (3 – 8%) Agranulocytes Granulocytes Tipos de leucocitos
- 39. Rafael Sirera 39 Tipos de leucocitos
- 40. Rafael Sirera 40 Neutrófilos • Los más abundantes, 50–70% • Se denominan polimorfonuclears (PMNs) • Tienen gránulos azidófilos y basófilos con enzimas hidrolíticos • Son fagocíticos • Liberan prostaglandinas y leucotrienos • Forman el pus
- 41. Rafael Sirera 41 Eosinófilos • 2–4% • Núcleo rojo y bilobulado • Tienen gránulos acidófilos con enzimas hidrolíticos, citotóxicos y NO • Liberan el contenido de los gránulos – Atacan parásitos • Sensibles a los alérgenos
- 42. Rafael Sirera 42 Basófilos • Muy escasos, <1% • Grandes gránulos basófilos que contienen histamina – Vasodilatador – Quimitáctico • Liberan heparina • Funcionalmente son como los mastocitos
- 43. Rafael Sirera 43 Monocitos • Son grandes, esféricos y el 2–8% de los WBCs • Núcleo en forma de riñón • Salen de la circulación y se convierten en macrófagos • Células fagocíticas muy activas • Activan a los linfocitos • Inducen quimiotáxis
- 44. Rafael Sirera 44 Linfocitos • 20–30% de los WBCs circulantes • Núcleo grande y púrpura. Gran relación núcleo-citoplasma • Principalmente en los tejidos • Pieza clave de la inmunidad adaptativa • Dos tipos – Células B – Células T
- 45. Rafael Sirera 45 Clases de linfocitos – T • Inmunidad mediada por células (citocinas) • Citotoxicidad – B • Inmunidad humoral (Abs) • plasma cells – Natural killer (NK) • Destruyen células aberrantes • Inmunidad innata
- 46. Rafael Sirera 46 Hemocytoblast Myeloid stem cell Lymphoid stem cell Myeloblast Myeloblast MonoblastMyeloblast Lymphoblast Stem cells Committed cells Promyelocyte PromyelocytePromyelocyte Promonocyte Prolymphocyte Eosinophilic myelocyte Neutrophilic myelocyte Basophilic myelocyte Eosinophilic band cells Neutrophilic band cells Basophilic band cells Developmental pathway Eosinophils NeutrophilsBasophils Granular leukocytes (a) (b) (c) (d) (e) Monocytes Lymphocytes Agranular leukocytes Some become Some become Leucopoyesis Regulado por: •Interleuquinas (e.g., IL-1, IL-2) •Colony-stimulating factors (CSFs)
- 47. Plaquetas
- 48. Rafael Sirera 48 Plaquetas • 150,000 - 500,000 por microlitro • Fragmentos celulares de megacariocitos – Los no mamíferos tienen núcleo • Implicados en la coagulación • Circulan durante 9–12 días – Eliminados por el bazo • Los gránulos contiene serotonina, calcio, enzimas, ADP y PDGF
- 49. Rafael Sirera 49 Hematopoyesis, trombopoyesis Thrombopoietina (TPO) Interleuquina-6 (IL-6) Multi-CSF
- 51. Rafael Sirera 51 Tipaje sanguíneo • Si los donantes no son compatibles – La sangre se aglutina y hemoliza – Los Abs del plasma se encuentran con su ligando en la superficie de los hematíes • Los tipos sanguíneos – Están determinados genéticamente (30 tipos de glicoproteinas) – Los antígenos en la superficie de los RBCs • A, B, Rh (ó D)
- 52. Rafael Sirera 52 Tipos • El factor Rh – Antígeno D – Rh positivo (Rh+ ) – Rh negativo (Rh- ) • Sólo las personas Rh- sensibilizadas tienen Abs anti-Rh
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- 55. Rafael Sirera 55 Rh y embarazo
- 56. Rafael Sirera 56 Datos poblacionales
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Notas del editor
- La función más importante es el transporte, y en este sentido el de oxígeno, pero hay más. Transfusiones!!! Necesario y BTC. Partes útiles de la sangre. Herramienta no invasive diagnóstica Among blood’s many functions, transport of oxygen to the tissues is the most important. In order for cells to run aerobic metabolism, they require oxygen. Without oxygen, the tissues begin to break down. Blood is also needed in trauma situations. In just the United States alone, millions of units of whole blood are needed each week Collected whole blood is also broken down into various other products. The plasma from whole blood can be used for transfusion, or it can be fractionated into other medications, such as clotting factors for hemophiliacs Diagnostic Blood Tests A. Changes in some of the visual properties of blood can signal diseases such as anemia, heart disease, and diabetes B. Differential white blood cell counts are used to detect differences in relative amounts of specific blood cell types C. Prothrombin time, which measures the amount of prothrombin in the blood, and platelet counts evaluate the status of the hemostasis system D. SMAC, and a complete blood count (CBC) give comprehensive values of the condition of the blood
- Recall for the students that blood is a fluid connective tissue. That is, blood nicely fits the cardinal properties of connective tissue, a population of cells—the RBCs and WBCs—scattered within an acellular matrix—the plasma. There are striking differences between blood and the other connective tissues, however: The cells were not formed within the connective tissue, and the matrix was not produced by the blood cells but by many other cells past which the blood flows.
- - EL plasma es muy parecido al espacio extracellular. Sólo se diferencia en las proteinas - The plasma proteins play the main role of providing the “colloid” osmotic pressure that sucks fluid back into capillaries from the interstitial space. Inadequate levels, due to liver disease or malnourishment, result in ascites, accumulation of fluid in the peritoneal cavity.
- Emphasize that the hematocrit is an indirect measurement of the O2-carrying capacity of the blood. More red blood cells mean more O2 carried by the same volume of blood. As a point of interest, mention that well-oxygenated blood is bright red; normal deoxygenated blood (at the tissue level) is dark red. Mention that serum is essentially plasma without clotting proteins If a sample of blood is drawn into a tube with an anticoagulant (heparin or citrate) to prevent clotting, then allowed to stand, the heavier blood cells will settle to the bottom. The clear straw-yellow fluid remaining on top is plasma. Occasionally, abnormal appearance of the plasma indicates a pathology. Patients with excessively high concentrations of lipid in the blood may have cloudy rather than clear plasma. In extreme cases, a fat layer floats to the top of the plasma, much like the layer of cream that forms at the top of bottles of unpasteurized milk. If a blood sample is collected without anticoagulant and allowed to clot, the fluid that remains when the clot settles to the bottom is called serum.
- Serum albumin, often referred to simply as albumin is a globular protein. is the most abundant plasma protein in mammals. Albumin is essential for maintaining the oncotic pressure needed for proper distribution of body fluids between intravascular compartments and body tissues. It also acts as a plasma carrier by non-specifically binding several hydrophobic steroid hormones (thyroid hormones) and as a transport protein for hemin and fatty acids. Albumin is a soluble, monomeric protein which comprises about one-half of the blood serum protein. Albumin functions primarily as a carrier protein for steroids, fatty acids, and and plays a role in stabilizing extracellular fluid volume. Albumin is a globular un-glycosylated serum protein of molecular weight 65,000. Albumin is synthesized in the liver as preproalbumin which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin Albumin (when ionized in water at pH 7.4, as found in the body) is negatively charged. The glomerular basement membrane is also negatively charged in the body; some studies suggest that this prevents the filtration of albumin in the urine. According to this theory, that charge plays a major role in the selective exclusion of albumin from the glomerular filtrate. A defect in this property results in nephrotic syndrome leading to albumin loss in the urine. Nephrotic syndrome patients are sometimes given albumin to replace the lost albumin. All globulins fall into one of the following four categories: Alpha 1 globulins Alpha 2 globulins Beta globulins Gamma globulins (one group of gamma globulins are the immunoglobulins, which are also known as "antibodies") Alpha 1 globulins[edit source | editbeta] α1-antitrypsin Alpha 1-antichymotrypsin Orosomucoid (acid glycoprotein) Serum amyloid A Alpha 1-lipoprotein Alpha 2 globulins[edit source | editbeta] Haptoglobin Alpha-2u globulin α2-macroglobulin Ceruloplasmin Thyroxine-binding globulin Alpha 2-antiplasmin Protein C Alpha 2-lipoprotein Angiotensinogen Beta globulins are a group of globular proteins in plasma that are more mobile in alkaline or electrically charged solutions than gamma globulins, but less mobile than alpha globulins.[1][2][3] Examples of beta globulins include: beta-2 microglobulin plasminogen angiostatins properdin sex hormone-binding globulin transferrin Fibrinogen (factor I) is a soluble, 340 kDa plasma glycoprotein, that is converted by thrombin into fibrin during blood clot formation. Fibrinogen is synthesized in the liver by the hepatocytes. The concentration of fibrin in the blood plasma is 200-400 mg/d Regulatory Coagulation factors Complement and regulators Hormones Cytokines, GF,
- Bone marrow cultures (BMC) can be used for cancer patients in whom chemotherapy will kill their stem cells. A bone marrow sample is taken from a matched donor or from the patient (if patient’s marrow is used, the transplant is called autologous; if from a matched donor, homologous). The stem cells are separated out and grown up in long-term BMC. The procedure must either include growth factors or stromal cells in the culture. The ECF matrix of marrow binds growth factors and is necessary for normal development. Stromal cells secrete growth factors necessary to maintain multipotent stem cells and to promote their growth and division into committed stem cells of various lines. In culture, myeloid stem cells can differentiate into adipocytes, the same transformation that occurs normally in inactive marrow regions of adults. Stromal cells secrete CSF-1 (=M-CSF), GM-CSF, and G-CSF, but not IL-3, the most potent stimulator of multipotent stem cells.
- why the kidney is the logical organ to control the release of erythropoietin. This fact is probably puzzling until you let them know that the kidney receives almost 25 percent of cardiac output and is profoundly dependent on good blood flow to function and remain healthy. Point out that the kidney secretes erythropoietin in response to decreased levels of oxygen, not to decreased levels of RBCs. That is, the kidney is measuring a chemical property and NOT doing a blood count! During fetal development, the liver also produces significant amounts of EPO, but that contribution diminishes with age. In an adult, the liver produces no more than 15% of the EPO found in the body.
- Erythrocyte Disorders a. Anemias are characterized by a deficiency in RBCs that may originate from several causes: i. Hemorrhagic anemia resulting from excessive blood loss. ii. Iron-deficiency, pernicious, or renal anemia resulting from nutritional deficiency in either iron or vitamin B12, or a lack of EPO, which leads to underproduction of erythrocytes. iii. Hemolytic anemias in which erythrocytes are prematurely destroyed. iv. Thalassemias, characterized by an abnormality in one or more globin chains that compromises the oxygen-carrying ability of RBCs. v. Sickle-cell anemia, in which hemoglobin changes shape when oxygen levels are low, causing cells to rupture easily and block small blood vessels. b. Polycythemia is characterized by an excess of RBCs due to oxygen deficiency or disease, which may increase blood viscosity, causing poor blood flow and oxygen delivery. Some cases of polycythemia vera occur in people who live in hypoxic conditions at high altitude, while in other cases the etiology of the disease is unknown. Regardless of cause, polycythemia vera is easily treated by removing some blood if the hematocrit goes above 55%. Phlebotomy (phleps, vein + (o)tomos, cutting) is the removal of blood from a vein, a procedure performed nowadays with a needle by modern health care practitioners. This treatment is almost the only reason for therapeutic bloodletting practiced today. La anemia macrocítica es un término generalizado que incluye a un grupo de anemias caracterizadas por eritrocitos con un volumen corpuscular medio (VCM) mayor de 100 micras cúbicas Anemia perniciosa debido a una deficiencia en el factor intrínseco. Deficiencia de vitamina B12.2 Deficiencia de ácido fólico. During a gastric bypass, the stomach is stapled and reattached to the small intestines at the level of the jejunum. As a consequence of this procedure, iron absorption may be impaired. Also, vitamin B12 reabsorption may be impaired owing to decreased concentrations of intrinsic factor (produced by the stomach) released into the stomach Anemia microcítica es un término genérico para cualquier tipo de anemia caracterizada por glóbulos rojos pequeños. Normalmente el volumen corpuscular medio (abreviado como VCM en el los resultados del hemograma) es de 76 a 100 fl anemia ferropénica,1 por lejos, la causa más común de anemia en general y de la anemia microcítica, en particular talasemia A normocytic anemia is defined as an anemia with a mean corpuscular volume (MCV) of 80-100 which is the normal range. However, the hematocrit and hemoglobin is decreased an increased destruction or loss of red blood cells (e.g., hemolysis, posthemorrhagic anemia); an uncompensated increase in plasma volume (e.g., pregnancy, fluid overload); a B2 (riboflavin) deficiency[2] a B6 (pyridoxine) deficiency
- A moderate elevation of WBCs (leukocytosis) is often a sign of infection. Very high counts may indicate leukemia
- Leukemias—cell division out of control: Retroviruses have been linked to some types of leukemias. Human T cell lymphotropic virus (HTLV) causes T cell leukemia/lymphoma or hairy cell leukemia. When the marrow of patients with leukemia is put into culture, about 50% of the time, the abnormal leukemia cells will die off but the normal cells will grow and thrive. This occurs because these strains of leukemic cells require growth factors that are not present in the stromal cells of the culture. This technique can be used to make cancer-free marrow for autologous transplant. In the remaining leukemias, the abnormal cells do not require colony-stimulating factors for growth, resulting in uncontrolled replication.