Whole blood
solid Organic 1) Protein - albumin, globulin, fibrinogen, prothrombin 2) Internal secretion, antibodies, enzymes 3) Non proteins like urea, uric acid, creatinine 4) Neutral fat, cholesterol, glucose Inorganic
sodium chloride, sodium bicarbonate, calcium, iron Gases Oxygen, carbon diaoxide, nitrogen
RBC Major function – carries oxygen through
hemoglobin Contains carbonic anhydrase which catalyses reaction between water and carbon diaoxide and transport it from tissue to lung in the form of bicarbonate ion Responsible for buffering of the blood
Shape and size Shape – biconcave disc
shape changes while passing through capillaries It is like a bag which can change into any shape because of excess of cell membrane Size- Diameter -7.8 micrometer thickness- 2.5 micrometer at thickest 1 micrometer at the center
Production Early weeks of embryonic life- yolk sac Middle trimester – liver also spleen and lymph
node Last month and after birth- bone marrow Till 5 years – all the bone marrow After around 20 years – membranous bones like vertebra, sternum ribs
Concentration 5.2 million in male 4.2 million in female per cubic mililter Quantity of hemoglobin Whole blood contains 16 gm per deciliter in
males
in females
14 gm per deciliter
Factors controlling growth and reproduction
Growth inducers- IL1, IL6, IL3 IL3- promotes growth for all types of cells. Others only specific type of committed cells Growth factors promote growth but not
differentiation This function done by protein called as differentiation inducers Formation of growth and differentiation inducers in turn controlled by factors outside the marrow like low oxygen tension in case of RBC and infections in case of WBC
Regulation of RBC production Reduced tissue oxygenation - high altitudes,
destruction of marrow, circulation disorders • Erythropoietin Principle factor formed in kidney 90 % (renal tubular epithelial cells) and also in liver10% • Effect – hypoxia induces production of erythropoietin within minutes and RBC
Maturation – Vitamin B & Folic acid 12
Bone marrow cells are most rapidly
reproducing and growing cells. Maturation and rate of production are affected by nutritional status. For maturation Vit B12 and folic acid are needed Both are needed for synthesis of DNA as they are required in formation of thymidine phosphate which a building block of DNA Lack of Vit B12 and folic acid leads to failure of nuclear maturation and division
Forms larger than normal cells with normal
oxygen carrying capacity but fragile cell walls leading reduced life. This is called as maturation failure
Hemoglobin • Formation begins at proerythroblats and
continues into reticulocyte stage. • Steps - 2succinyl CoA + 2glycine -> pyrrole • 4 pyrrole-> protoporphyrine IX • protoporphyrine IX +Fe -> heme • heme + polypeptide -> hemoglobin chain Types of hemoglobin chains – alpha, beta, gamma chains and delta chains
Most common form of hemoglobin is hemoglobin a made up of 2 alpha and 2 beta chains Fetal hemoglobin ( hemoglobin F) is made up of a alpha and 2 gamma. This type facilitates movement of oxygen from maternal to fetal circulation and is replaced by adult circulation soon after the birth. There are 4 iron atoms attached in each Hb
molecule Each iron atom can bind to 1 molecule oxygen making it total of 4 molecules of oxygen.
Iron metabolism. Iron is absorbed from small intestine Transported in plasma by formation of
transferrin and can be released to any tissue cell. Excess amount of iron is stored mainly in hepatocytes in the form of ferritine
Destruction of RBC Life span of RBC is 120 days Metabolic system of RBC become
progressively less active with time and cell become more fragile. These fragile cell rupture while passing through tight spot in circulation mostly in spleen as the spaces between trabeculae is a very small. Destruction of hemoglobin – hemoglobin released during destruction of RBC is phagocytized by macrophages, mainly by
The iron is released back in circulation by
macrophages Which is carried by tranferrin to bone marrow for reuse or liver and other tissues for storage. The porphyrine portion is converted to bilirubin
Anemia Anemia means deficiency red blood cells with reduced oxygen carrying capacity. Causes Blood loss – acute and chronic Nutritional deficiency – Iron deficiency megaloblastic anemia hemolytic anemia – Spherocytosis sickle cell anemia Aplastic anemia - radiation, drugs like chloramphenicol
Leukocytes Granulocytes - neutrophil, eosinophil,
basophill Agranulocytes – lymphocyte and monocyte Granulocyte and monocyte are formed in bone marrow Lymphocyte are mainly produced in lymphogenous organ like thymus, lymph glands and spleen. Neutrophil 62% Eosinophil 2.3% Basophill 0.4%
Granulocytes Neutrophil, eosinophil, basophil The granules contain biologically active
substances Multilobed nucleus no of lobes increases with time Neutrophil Forms 1st line of defense takes part in inflammatory responses Average half life is 6 hours Neutrophil enter tissue spaces by diapedesis One in tissue spaces it moves around in
Chemotaxis – bacterial toxin, degenerated
products, complement complex
Phagocytosis Cellular ingestion of offending agent Slective process Opsonisation –C3 molecule of complement
system Neutrophil attaches itself with to the particles and then project pseudopodia which meet at opposite side and fuse The enclosed chamber is then filled with neutrophillic granule and digested. The granules contain defensin which are
In addition to this NADPH oxidase is activated
which produces large amount of toxic oxygen metabolites Also myelopeoxidase is discharged which produces potent oxidants Neutrophil kills bacteria with hydrogen peroxide and hydroxyl ion
Eosinophil Like neutrophil it releases proteins, cytokines
and chemokines which kills bacteria and also causes inflammation Active against parasite because of larvacidal polypeptide called major basic protein Numbers increase in allergic reaction like
Basophill Releases protein and cytokines Resembles mast cells and contains heparin
and histamine Takes part in in immediate type of
hypersensitive reaction
Monocytes after leaving bone marrow it gets fixed in
tissue and acts a macrophages Skin- histiocyte Liver – kupffer cell
Combination of monocyte, tissue
macrophage, mobile macrophage and specialized cells endothelial cell in marrow, spleen and lymph node is called as reticuloendothelial system
Lymphocyte Key element in production of immunity 2 types – B lymphocyte and T lymphocyte Originates from bone marrow and are
processed in thymus or brusal equivalent Located more extensively in lymph nodes also in spleen, GIT, bone marrow
T lymphocyte Processed in thymus Provides cell mediated immunity Divide extensively in thymus and develops
specificity against antigens This continues till there are different lymphocyte with specificity against millions of different antigens Now it leaves thymus and gets lodge in different lymph node in body Once T lymphocyte comes in contact with specific antigens the same type of lymphocytes are produced in large no called as clone of lymphocytes
T cell marker – these are surface receptor
proteins present on the T lymphocyte. It is highly specific against the antigens
B lymphocyte Destined to form antibodies it is processed in liver during fetal life and in
bone marrow after birth This population of cell was first seen in birds where it is processed in bursa of fabricus and that’s why it is called as B lymphocyte.
Disorders of leucocyte Nonneoplastic - Leucopoenia – reduced
number Leucocytosis – increased in number Neoplastic - Malignant lymphoma (hodgkins and non hodgkins lymphoma) Lymphomas are malignant neoplasm of cell native to lymphoid tissue Leukemia's – malignant neoplasm of stem cells characterized by diffuse replacement of bone marrow by malignant cells Acute – acute lymphoblastic and acute myeloblastic leukemia
Platelets 3oo,ooo/ùL Half life about 4 days 60 – 75% of platelet are in circulation and
remainder are in spleen There membrane contain receptor for collagen , von Willibrand factor and fibrinogen Cytoplasm has granules containing non
proteins like serotonin, ADP And proteins like clotting factor and PDGF.
Platelet production controlled by colony
stimulating factor acting on megakaryocye And by thrombopoietin a circulating protein factor When platelet count is low – thrombocytopinic purpura When circulating platelets are abnormal – thrombasthenic pupura
Blood groups There At least 30 group systems most of
them are weak Two particular types are most likely than others – OAB and Rh system
OAB system There two antigens A & B occur on the
surface of RBC These are also called as agglutinogen
Major types Type A when agglutinogen A is present Type B when agglutinogen B is present Type AB when agglutinogen A & B both are present Type O when both are absent Agglutinins - antibodies when particular type of antigens are missing, antibodies against it develops Antibodies are IgM and IgG types
Blood type
Agglutinoge n
Agglutinin
O
-
Anti-A and Anti B
A
A
Anti B
B
B
AB
A and B
Anti A -
Rh blood types Difference - Agglutinin are formed instantly in
OAB system but in Rh system it is not In Rh system there must be massive blood transfusion for formation of antibodies. Rh positive and Rh negative Six common type of antigens C, D, E, c, d, and e The person having C antigen does not have c antigen and vice a versa. Same is true for other antigens Type D is widely present and more antigenic than other Rh factors
Therefore person having D antigen is called
as Rh positive and person not having D antigen is called as Rh negative About 85% of population is Rh positive and 15% Rh negative. If Rh negative person receives Rh positive blood for first time then immediate reaction will not occur. Mild reaction develops after 2 to 4 weeks. But on subsequent transfusion reaction will be greatly enhanced
Erythroblastosis Fetalis Rh negative mother having Rh positive child First child no does not develop complication Second Rh positive child develop
erythroblastosis fetalis due to presence of antibodies in mothers blood which act against child's RBC Antibody diffuse through placental membrane and causes agglutination Jaundice, anemia, kernicterus Treatment – replacement with Rh negative blood.
Blood transfusion Indications 2) Acute haemorrhage 3) Major surgeries 4) Deep burns – destruction of rbc and
hemolysis 5) Preoperatively for anaemic patient 6) Anaemic patient with Hb below 10gm/100ml 7) Coagulation disorders and also during chemotherapy for malignant diseases there is bone marrow depression
Collection of blood Screen the donor for diseases which can be
transferred through blood like HIV and hepatitis Donor lies down sphygmomanometer is applied and inflated to 80mm h\Hg 15 gauge needle is inserted in medial cuboidal vein Blood is collected n plastic bag containing 70 ml of anticoagulant. About 410 ml of blood is collected Anticoagulants – 2 types 1) CPD containing trisodium citrate, citic acid and sodium dihydrogen phosphate
Stored at 4 degree Celsius in refrigerator Shelf life is 3 to 5 weeks RBC loose ability to release oxygen in 7 days Platelets useful up to 24 hours Types of blood transfusion 6) CPD stored blood 7) Warm blood – cardiopulmonary operations to
reduce risk of cardiac arrest 8) Filtered blood to filter off platelet and leukocyte aggregate 9) Auto transfusion 10)Exchange transfusion – erythroblastosis fetalis
Packed red cells – chronic anemia, low cardiac
reeve. Old patient Amount of blood transfusion – 500ml of blood raises Hb by 10% Complications 1)incompatibility - after expiry date, already hemolysed blood 2) Pyerexial reactions 3) allergic reaction to plasma products 4) sensitisation to leucocytes and platelets 5) transmission of diseases
Reaction caused by massive
transfusions Acid base imbalance Hyperkalaemia- shift of potassium out of rbc Citrate toxicity Hypothermia Failure of coagulation due to dilution Blood substitutes 8) Fresh frozen plasma – factor V and VIII 9) Platelet rich plasma - - thrombocytopinic
purpura 10)Fibrinogen – stored in powdered form and mixed with distilled water. Used in DIC
4) Cryoprecipitate – if frozen plasma is allowed to bring at a temperature of 4 degree Celsius it divides into precipitate and plasma this precipitate is called cryoprecipitate it is a rich source of factor VIII Synthetically prepared solutions Dextran - increases plasma volume, used in restoring plasma volume for longer time Gelatin- less effective than dexran Hydroxyethylstarch- plasma volume expander Fluorocarbons- colorless, odorless, dens liquid inert and soluble It binds and release oxygen. Also considered as red cell substitute
Capillary circulation It is also called a microcirculation Transport of nutrients Extremely thin structure with highly
permeable endothelial cells.
Structure Artery ( Divides 6 – 8 times ) Arteriole ( Divides 2- 5 times) Meta arteriole Capillary Preferential arteriole capillaries
True
Structure of capillary wall Wall – unicellular layer of endothelial cells. Pores – intercellular cleft- thin slit between
5) 6)
7)
endothelial cells .the size is slightly smaller than albumin protein molecule. Special types of pores. Brain – tight junction of cells – Blood- brain barrier Liver- wide open junction – so all dissolved substances including plasma protein can pass In kidney special arrangement for filtering the blood
Vasomotion Flow is not continuous instead it is
intermittent It is because of contraction of metarterioles and precapillary sphincters Regulation – Depends on oxygen demand
Lymphatic system Accessory rout by which fluid can flow from
interstitial spaces into the blood. Carries protein and large particulate matter away from blood which can not be removed by capillaries This is essential function without which person can die in 24 hours.
Lymph channels of body All lymph from lower part flows up thoracic
duct and empties into venous system at the junction of left internal jugular vein and subclavian vein
Lymph from right side of head , neck right
arm and parts of chest enters right lymph duct which empties in to junction between right subclavian and internal jugular vein.
• Terminal lymphatic capillaries
and its permeability 1/10th of fluid from capillary system enters lymphatic system Total quantity is about 3 liters per day. This minute quantity is very important as high molecular weight substances can pass through easily which can not be reabsorbed in any other way
Rate of lymph flow 100 ml/hour flows through thoracic duct More the interstitial fluid pressure more is the
flow elevated capillary pressure increased capillary permeability increased fluid protein Lymphatic pump increases lymph flow – valves Intrinsic pumping by lymph vessels Extrinsic compression by surrounding muscle of body movement of body, arterial pulsation,
Role of lymphatic
protein leaks into the interstitium increased osmotic pressure
and
fluid is pulled in to interstitium this causes raised fluid volume pressure this leads to increased rate of
lymph flow and excess fluid and protein is
Lymphatic disorders Lymphengitis – infection spreading into
lymphatics mainly caused by beta hemolytic streptococci Lymphedema Primary secondary Congenital Obstruction removal fibrosis filariasis