Erythrocytes (RBC s)

Transcription

1 Erythrocytes (RBC s)

2 RBCs are flattened biconcave discs Flexible structure Shape provides increased surface area for diffusion 7.5 µm diameter, 2.5 µm thick Life cycle 120 days

3 Lack a nucleus and other organelles. 33% of weight is hemoglobin molecules (Each RBC contains 280 million hemoglobins). Other proteins include antioxidants and those to maintain RBC shape (spectrin)

4 Erythrocyte Function Erythrocytes are dedicated to respiratory gas transport (transport O 2 to tissues and CO 2 from tissues) Hemoglobin reversibly binds with oxygen and most oxygen in the blood is bound to hemoglobin

5 Is a very elastic, semi-permeable lipid bi-layer supported by a mesh-like cytoskeleton Is a three layer structure: 1. an outer hydrophilic portion: glycolipid, glycoprotein and protein 2. a central hydrophobic layer: protein, cholesterol and PL 3. an inner hydrophilic layer: containing protein

6 Several proteins are present in the RBC s Integral membrane proteins: Extend from outer surface and transverse entire membrane to inner surface Peripheral proteins: Limited to cytoplasmic surface of membrane and forms the RBC cytoskeleton

7 Glycophorin: Is the principle RBC glycoprotein. Spans entire thickness of lipid bilayer and appears on external surface of RBC membrane Three types of glycophorins identified: A, B, and C All glycophorins carry RBC antigens and are receptors or transport proteins

8 Cytoskeleton: Network of proteins on the inner surface of the plasma membrane, called the peripheral membrane proteins Provides rigid support and stability to lipid bilayer Responsible for maintaining shape and deformability of RBC

9 1. Spectrin The most abundant peripheral protein Flexible, rod like molecule composed of an alpha helix of two polypeptide chains Microfilaments strengthen membrane, protecting cell from being broken Controls biconcave shape and deformability of cell Is an important factor in RBC membrane integrity because it binds with other peripheral proteins to form the skeletal network of microfilaments on the inner surface of RBC membrane

10 2. Ankyrin : Primarily anchors lipid bilayer to membrane skeleton 3. Protein 4.1: May link the cytoskeleton to the membrane by means of its associations with glycophorin 4. Actin: Responsible for contraction and relaxation of membrane

11 Erythrocyte membrane lipid consists of bilayer of phospholipids intermingled with molecules of cholesterol in nearly equal amounts. Also, small amounts of free fatty acids and glycolipids Different types of phospholipids are found on the inside layer than on the outside layer Abnormalities in the PL may result in decreased deformability and decreased red cell survival

12 Most of glycolipids are located in outer half of lipid bilayer and interact with glycoproteins to form many of RBC antigens Cholesterol equally distributed on both sides of lipid bilayer (25% of RBC membrane lipid content) RBC membrane cholesterol is in continual exchange with plasma cholesterol

13 Cholesterol plays important role in regulating membrane fluidity and permeability Accumulation of cholesterol results in decreased deformability and may lead to hemolytic anemia

14 They occur only on the external surface of the red cell They occur as glycoproteins or glycolipids The antigens of ABO blood groups are examples of carbohydrate membranes

15 Defective or absent spectrin molecule Leads to loss of RBC membrane, leading to spherocytosis Decreased deformability of cell Increased osmotic fragility

16 Normal biconcave red cell loses membrane fragments and adopts a spherical shape Inflexible cells are trapped in the splenic cords, phagocytosed by macrophages

17 Hereditary disorder of the RBCs (autosomal dominant trait) RBCs assume an elliptical shape, rather than the typical round shape.

18 Spectrin abnormality or deficiency of protein 4.1 RBC hemolysis occurs in the spleen, thus splenectomy corrects the hemolysis, but not the RBC membrane defect

19 Nonspecific test for inflammatory process Anticoagulated blood in calibrated tube; rate of sedimentation of RBCs in 1h X Normal: <15mm/hmale; <20mm/h female; add 10 past age 60

20 Any condition that elevates fibrinogen should elevate ESR. Dramatically with infection, malignancy, connective tissue disease. Also with pregnancy, inflammatory disease, and anemia. A ESR is associated with blood diseases in which red blood cells have an irregular or smaller shape that causes slower settling ie: sickle cell anemia

21 The term erythropoiesis (erythro = RBC, and poiesis = to make) is used to describe the process of RBC formation or production. In humans, erythropoiesis occurs almost exclusively in the red bone marrow

22 A hemocytoblast is transformed into a committed cell called the proerythroblast Proerythroblasts develop into early erythroblasts The developmental pathway consists of three phases Phase 1: ribosome synthesis in early erythroblasts Phase 2: hemoglobin accumulation in late erythroblasts and normoblasts Phase 3: ejection of the nucleus from normoblasts and formation of reticulocytes Reticulocytes then become mature erythrocytes

23 Increases O 2 -carrying ability of blood Normal blood oxygen levels Start: Stimulus: Hypoxia / decreased availability of O 2 to blood/or increased tissue demands for O 2 Reduces O 2 levels in blood Enhanced erythropoiesis increases RBC count Erythropoietin stimulates red bone marrow Kidney (and liver to a smaller extent) releases erythropoietin

24 Hemolysis is the breakage of the RBC s membrane, causing the release of the hemoglobin and other internal components into the surrounding fluid. Hemolysis is visually detected by showing a pink to red tinge in serum or plasma In-vivo hemolysis may be due to pathological conditions, such as autoimmune hemolytic anemia or transfusion, drugs and infections

25 (a) without hemolysis: red blood cell suspension seems red and opaque. (b) without hemolysis: RBCs sedimented spontaneously for 60 min. Note that the supernatant is not colored. (c) hemolysis: RBC suspension become transparent by hemolysis. (a) (b) (c)

26 RBC membranes have glycoprotein antigens These antigens are: 1. Unique to the individual Human Blood Groups 2. Recognized as foreign if transfused into another individual 3. Promoters of agglutination and are referred to as agglutinogens Presence or absence of these antigens is used to classify blood groups Humans have 30 varieties of naturally occurring RBC antigens but the important ones are the ABO and the rhesus (Rh) blood systems

27 ABO blood grouping system According to the ABO blood typing system there are four different kinds of blood types depending on the antigen of the RBC membrane: A, B, AB or O

28 Is the precursor of both A substance (A antigen) and B substance (B antigen) Is formed by the action of Fucosyl Transferase that catalyses addition of fucose residue to the terminal galactose residue of H substance precursor H antigen Fucose Added by Fucosyl transferase

29 Is formed by the action of N-acetyl-D GalactosamineTransferase (GalNAC transferase) that catalyses addition of GalNAC to the terminal Gal residue of H substance GalNAc (N-Acetyl-D galactosamine) A antigen

30 Is formed by the action of Galactosyl Transferase that catalyses the transfer of Gal residue to the terminal galactose residue of H substance D-Galactose Added by Galactosyl transferase B antigen

31 AB0 blood grouping system Blood group A you have A antigens on the surface of your RBCs and B antibodies in your blood plasma Blood group B you have B antigens on the surface of your RBCs and A antibodies in your blood plasma

32 AB0 blood grouping system Blood group AB you have both A and B antigens on the surface of your RBCs no A or B antibodies at all in your blood plasma Blood group O you have neither A or B antigens on the surface of your RBCs but you have both A and B antibodies in your blood plasma

33 Blood transfusions who can receive blood from whom? People with blood group O: "universal donors People with blood group AB: "universal receivers"

34 How common is your blood type? 46.1% 38.8% 11.1% 3.9%

35 Is the second most significant blood group system in human transfusion Rh antigens are transmembrane proteins The D antigen (RhD) is the most important If it is present, the blood is RhD positive (~80% of the population), if not it's RhD negative So, for example, some people in group A will have it, and will therefore be classed as A+ (or A positive), while the ones that don't, are A- (or A negative) and so it goes for groups B, AB and O

36 A person with Rh+ blood can receive blood from a person with Rh- blood without any problems

37 A person with Rh - blood can develop Rh antibodies in the blood plasma if he or she receives blood from a person with Rh + blood, whose Rh antigens can trigger the production of Rh antibodies

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40 hemolysis

41 Rh - mothers who have had a pregnancy with/are pregnant with a Rh + infant are given Rh immune globulin (RhIG) at 28 weeks during pregnancy and within 72 hours after delivery to prevent sensitization to the D antigen. It works by binding any fetal red cells with the D antigen before the mother is able to produce an immune response and form anti-d IgG 41

42 Maternal antibodies destroy fetal red blood cells Results in anemia. Anemia limits the ability of the blood to carry oxygen to the baby's organs and tissues. Baby's responds to the hemolysis by trying to make more red blood cells very quickly in the bone marrow and the liver and spleen. Organs enlarge - hepatosplenomegaly. New red blood cells released prematurely from bone marrow and are unable to do the work of mature red blood cells. 42

43 Baby's responds to the hemolysis by trying to make more red blood cells very quickly in the bone marrow and the liver and spleen. Organs enlarge - hepatosplenomegaly. New red blood cells released prematurely from bone marrow and are unable to do the work of mature red blood cells. The heart begins to fail and large amounts of fluid build up in the baby's tissues and organs resulting in a condition known as Hydrops Fetalis. A fetus with hydrops is at great risk of being stillborn. 43

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45 Type of Blood Transfusion Whole Blood Blood Component RBC; PLT(platelets); FFP (Fresh Frozen Plasma); Leukocyte; concentrate Use of whole blood is considered to be a waste of resources

46 The preparation of blood components from whole blood Cellular components Fresh plasma Fresh frozen plasma Red cells Platelets White cells Cryoprecipitate Cryosupernatant Factor VIII Albumin Concentrate Immunoglobulins other concentrates

47 Blood type and Rh factor status crossmatched Blood transfusion reactions: Fever and chills within first 15 minutes hives and itching during or after transfusion

48 Most dangerous: ABO incompatibility RBCs clump and block capillaries Decreased blood flow to vital organs Manifestations: lumbar, abdominal and/or chest pain, fever, chills, urticaria, nausea and vomiting Occurs after ml of incompatible blood infused

49 1. Stop transfusion immediately 2. Continue IV infusion with normal saline 3. Notify physician of client s signs and symptoms 4. Provide care for client as indicated 5. Complete reaction form according to institution protocol. 6. Obtain urine specimen from client and send for free hemoglobin.

50 No organelle no mitochondria Generate energy through anaerobic breakdown of glucose (2ATP+lactate) ATP is used as substrate for Na +, K + or the Ca 2+ dependant ATPases that maintain intracellular concentrations of these cations The glucose uptake by RBC s through high affinity glucose transporter is independent on insulin

51 Four pathways involved in RBC metabolism: 1. Pentose Phosphate Pathway 2. Glycolysis pathway 3. Methemoglobin reductase pathway 4. 2,3 BPG pathway is unique for RBC

52 In red cells 1,3 BPG is converted to 2,3BPG which unites with oxy Hb and helps release of oxygen at tissues. The rate of synthesis and hydrolysis of 2,3 DPG are very sensitive to ph: a fall of ph inhibits mutase and stimulates phosphatase causing decrease of 2,3 DPG 2,3 BPG pathway

53 H 2 O 2 Aerobic respiration Drugs, fava beans Superoxide radicals Hydrogen peroxide 2 GSH NADP + glutathione peroxidase glutathione reductase The major role of PPP in RBCs is the production of NADPH which protect these cells from oxidative damage by providing GSH for removal of H 2 O 2 pentose pathway Detoxification 2 H 2 O GSSG NADPH + H + Pentose Phosphate Pathway When erythrocytes are exposed to chemicals that generate high levels of superoxide radicals, GSH (Reduced Glutathione) is required to reduce these damaging compounds Glutathione Peroxidase catalyzes degradation of organic hydroperoxides by reduction, as two glutathione molecules are oxidized to a disulfide GSSG The PPP is responsible for maintaining high levels of NADPH in red blood cells for use as a reductant in the glutathione reductase reaction.

54 Important in maintaining heme iron in the reduced or ferrous functional state The methbfe 3+ is reduced to deoxyhbfe 2+ by the flavoprotein, MetHb reductase (MW 185Kda) (NADH cytochrome b 5 reductase) NADH+H + 2 cytob 5 Fe 3+ (Glycolysis) 2 Hb Fe 2+ NAD + 2 cytob 5 Fe 2+ 2 met Hb Fe 3+

55 RBC Metabolic Pathways Disorders Mutations causes a deficiency in G6PDH (X-linked), with consequent impairment of NADPH production Detoxification of H 2 O 2 is inhibited, and cellular damage results - lipid peroxidation leads to erythrocyte membrane breakdown and hemolytic anemia. Most G6PD-deficient individuals are asymptomatic - only in combination with certain environmental factors (sulfa antibiotics, herbicides, antimalarials, *divicine) do clinical manifestations occur. *toxic ingredient of fava beans

56 This deficiency causes the entire glycolysis pathway to cease working so that little to no ATP is produced Consequently, the defective red cells are destroyed in the spleen causing anaemia and the spleen enlarges (splenomegaly) because it is overworked The excessive destruction of red blood cells (hemolysis) results in the breakdown of hemoglobin stored in these cells