The Blood – Chapter 4

1. The Blood – Chapter 4 (c) Eleshia Howell, 2012. A&P 1 Tutor: Eleshia Howell

2. Blood is a fluid connective tissue circulating continuously around the body (pumped by the heart) allowing constant communication between tissues. Transports: • Oxygen from lungs to tissues, carbon dioxide from tissues to lungs • Nutrients from alimentary tract to tissues, cell waste to excretory organs (mainly kidneys) • Hormones secreted by endocrine glands to their targets organs/tissue • Heat, produced in active tissues to less active tissues • Protective substances, eg antibodies, to areas of infection • Clotting factors (c) Eleshia Howell, 2012.

3. Functions of Blood: • Transport of dissolved substances • Nutrients, hormones and metabolic wastes • Regulation of pH and ions • Diffusion between interstitial fluid and blood • Maintains localised homeostasis. • Restriction of fluid losses at injury sites • Initiation of clotting • Defense against toxins and pathogens • Transport of WBC; antibodies • Stabilization of body temperature • Absorbs heat from skeletal muscles and directs to cooler parts of the body. (c) Eleshia Howell, 2012.

4. Blood is composed of a clear, straw-coloured, watery fluid called PLASMA in which several different types of blood cells are suspended. • Plasma constitutes approx 55% of the blood volume • Remaining 45% is cellular portion • Blood makes up about 7% of body weight (5.6L in 70kg man). Proportion is greater in children, lesser in women. • Blood volume and the concentration of its constituents are kept within narrow limits by homeostatic mechanisms. (c) Eleshia Howell, 2012.

5. Plasma • 90% water, 10% dissolved / suspended substances • Plasma proteins • Inorganic salts • Nutrients (from digested food) • Waste materials • Hormones • Gases Plasma Proteins: • Make up about 7% of plasma • These large molecules remain in the blood as they are too big to cross into capillary beds. (c) Eleshia Howell, 2012.

6. The proteins help to maintain osmotic pressure , keeping plasma fluid within the circulation. When protein levels fall, osmotic pressure is reduced and fluid moves into the tissues (oedema) and body cavities. • Viscosity is due to plasma proteins, mainly albumin and fibrinogen. • With the exception of immunoglobulins, plasma proteins are formed in the Liver. (c) Eleshia Howell, 2012.

7. (c) Eleshia Howell, 2012.

8. Albumins: • The most abundant plasma proteins ~ approx 60% • Main function is to maintain normal osmotic pressure • Also act as carrier molecules for free fatty acids, some drugs and steroid hormones Globulins: • As antibodies (complex proteins produced by lymphocytes as part of immune system), they bind to & neutralise foreign material (antigens). • Transportation of some hormones & mineral salts • Inhibition of some proteolytic enzymes (c) Eleshia Howell, 2012.

9. Clotting Factors: • Are responsible for coagulation of blood; the most abundant clotting factor is fibrinogen • Serum is plasma without clotting factor. Electrolytes: • Electrically charged ions, eg sodium, potassium, chloride, bicarbonate, which help to conduct impulses. • Have a range of functions, including muscle contraction, transmission of nerve impulses and maintenance of pH in blood. (c) Eleshia Howell, 2012.

10. Nutrients: • Products of digestion eg glucose, amino acids, fatty acids, are absorbed into the blood from alimentary tract. Together with mineral salts and vitamins they are used by the body cells for energy, heat, tissue repair / replacement and for synthesis of other blood components. Waste Products: • Urea, creatinine and uric acid are the waste products of protein metabolism, formed in the liver and carried in the blood to the kidneys for excretion. (c) Eleshia Howell, 2012.

11. Hormones: • Passed from endocrine cells into the blood which then transports them to target organs/tissue. Gases: • Oxygen, carbon dioxide and nitrogen are transported around the body dissolved in the plasma. (c) Eleshia Howell, 2012.

12. Cellular Content • 3 types of blood cells ~ • Erythrocytes (red blood cells) • Platelets (thrombocytes) • Leukocytes (white blood cells) • Blood cells are mainly produced in the red bone marrow • Haemopoesis = blood cell formation (c) Eleshia Howell, 2012.

13. Red Blood Cells: • Concave disc shape, with no nucleus and no organelles. • Main function is gas transport, predominantly oxygen, but also some CO2. • Shape increases surface area for gas exchange; the thinness of central portion allows fast entry/exit of gases. They are flexible and can squeeze through narrow capillaries. • Measurement of cell numbers, volume and haemoglobin content are routine diagnostic assessments in medical practice. (c) Eleshia Howell, 2012.

14. RBC’s are produced in the red bone marrow (present in long, flat and irregular bones) and undergoes several stages of development before entering circulation. (Erythropoiesis) • Life span is approx 120 days. Destruction of RBC is called haemolysis. • Vitamin B12 and folic acid are required for blood cell synthesis. (B12 must be bound to intrinsic factor to allow for absorption). • Erythropoiesis is controlled by negative feedback mechanism; regulated by hormone erythropoietin, produced mainly in the kidneys. (c) Eleshia Howell, 2012.

15. (c) Eleshia Howell, 2012.

16. Haemoglobin: • A large, complex protein containing a globular protein (globin) and a pigmented iron-containing complex called Haem. • Each molecule contains 4 x globin chains and 4 x haem units, each with 1 x atom of iron. As each iron atom can combine with an O2 molecule, haemoglobin can therefore carry up to 4 x O2 molecules. Each RBC carries approx 280 million haemoglobin molecules, theoretically giving each cell the capacity to carry over 1 billion oxygen molecules! • Iron is transported in the bloodstream bound to transferrin and stored in the Liver; a steady supply of Iron is required for normal RBC production. (c) Eleshia Howell, 2012.

17. (c) Eleshia Howell, 2012. Haemoglobin Molecule, p59

18. Oxygen Transport: • When all 4 oxygen binding sites on haemoglobin are full, it is said to be saturated. • Haemoglobin binds to oxygen to form oxyhaemoglobin. This is a loose bind, so that oxygen can be readily released when required, eg: low pH, hypoxia, metabolically active tissue. RBC Destruction: • Carried out by phagocyticreticuloendothelial cells, found mainly in the spleen, bone marrow and liver. As RBC’s age, their membranes become more fragile, more susceptible to haemolysis. • Iron released during this process is retained in the body and re-used in bone marrow to form new haemoglobin molecules. (c) Eleshia Howell, 2012.

19. Biliverdin is formed from the haem part and is almost completely reduced to the yellow pigment Bilirubin, before being bound to plasma globulin and transported to the Liver. In the liver it is converted from fat-soluble to water-soluble and excreted as a constituent of bile. (c) Eleshia Howell, 2012.

20. Blood groups • Different types of inherited antigens on the surface of the blood cell determine blood group. • The body also develops antibodies to the blood group antigens, but not to the individual’s own blood type (this would cause a potentially fatal transfusion reaction). • The antibodies circulate freely in the blood; transfusion of same blood type will not be recognised by the antibodies as foreign, however, a different blood group being introduced will initiate destruction of the foreign blood cells by the immune system. (c) Eleshia Howell, 2012.

21. Approx 55% of population have either A or B type antigens, or both AB. The remaining % have neither – known as O type. • Corresponding antibodies are called anti-Aand anti-B for types A and B respectively. Blood group AB makes neither antibodies; blood group O makes both antibodies. • AB people can receive either A or B group blood. • O people are often referred to as “universal donors” because their blood contains no antigens on the cell surface, can therefore be safely transfused into types A, B, AB or O. • Other antigens may be present in either person’s blood, so cross-matching still must occur to ensure a compatible donor / recipient. (c) Eleshia Howell, 2012.

22. (c) Eleshia Howell, 2012.

23. According to the Australian Red Cross Blood Service, the percentage of blood group frequency in Australia is: • O positive – 40 per cent • O negative – 9 per cent • A positive – 31 per cent • A negative – 7 per cent • B positive – 8 per cent • B negative – 2 per cent • AB positive – 2 per cent • AB negative – 1 per cent. (c) Eleshia Howell, 2012.

24. RHESUS SYSTEM: • Most clinically significant blood group system after ABO. Consists of 50 defined blood group antigens, but in the context of haemolytic disease the D antigen is the most important. • The Rhesus (Rh) antigen is present in about 85% of the population ~ Rh+ (don’t make anti-rhesus antibodies). • Remaining 15% are Rh- and are capable of making anti-Rh antibodies, but are stimulated to do so only in certain circumstances, eg pregnancy (placental transfusion), or incompatible blood transfusion. • Anti-D injections provided to immunise against potential haemolysis. (c) Eleshia Howell, 2012.

25. LEUKOCYTES (White Blood Cells) • The largest of the blood cells, have an important function in defence and immunity. • Defend against pathogens • Remove toxins and wastes • Attack abnormal cells • They account for about 1% of blood volume • Contain nuclei and some have granules in their cytoplasm:- • Granulocytes – neutrophils, eosinophils, basophils. • Agranulocytes – monocytes, lymphocytes • Increased WBC numbers in blood usually indicates a physiological problem, eg infection, trauma, malignancy. (c) Eleshia Howell, 2012.

26. (c) Eleshia Howell, 2012. White Blood Cell

27. (c) Eleshia Howell, 2012.

28. Neutrophils: • Small, fast, active scavengers that protect the body against bacterial invasion and remove dead cells / debris from damaged tissues. • Attracted in large numbers to areas of damaged or infected tissue where they perform phagocytosis. • Forms pus (dead tissue cells, microbes and other cell debris). (c) Eleshia Howell, 2012.

29. Eosinophils: • Also capable of phagocytosis, but less active than neutrophils. • More specialised role of eliminating parasites, eg worms • Equipped with toxic chemicals (nitric oxide, cytotoxic enzymes) which they release into an infecting organism upon attachment. • Often found at sites of allergic inflammation; Control inflammation with enzymes that counteract inflammatory effects of neutrophils and mast cells • Helps to localise the inflammation response. (c) Eleshia Howell, 2012.

30. Basophils: • Closely associated with allergic reactions as they contain Heparin (anticoagulant), Histamine (inflammatory agent) and other substances that promote inflammation. Monocytes: • Largest of the WBC’s, some circulate in blood and others migrate into tissues becoming Macrophages. • Produce Interleukin-1which: • Acts on hypothalamus, causing ↑ body temp associated with microbial infections. • Stimulates production of globulins in Liver • Enhances production of activated T-lymphocytes (c) Eleshia Howell, 2012.

31. Monocyte-Macrophage System (or reticuloendothelial system) is the body’s complement of monocytes and macrophages providing defense at key locations throughout the body, eg: joints, skin, brain, liver, lungs, spleen, kidneys and bone. Macrophages are larger, longer lasting and more powerful cells that synthesize and release cytokines (cell-signalling proteins) and play an important role in specific and non-specific immunity. (c) Eleshia Howell, 2012.

32. Lymphocytes: • Circulate in the blood as well accumulate in lymphatic tissue / lymph nodes and the spleen. • Once activated they respond to antigens, such as abnormal cells, pollen, fungi, bacteria and some large molecule drugs (penicillin, aspirin). • Although all lymphocytes originate from one type of stem cell, when activated in lymphatic tissue there are 2 distinct types produced: • T-lymphocytes • B-lymphocytes (These will be discussed further when we look at Immune System) (c) Eleshia Howell, 2012.

33. Platelets (thrombocytes) • Very small, non-nucleated discs derived from red bone marrow. • Contain a variety of substances that promote blood clotting and haemostasis (cessation of bleeding). • Normal blood platelet count is 200,000-350,00/mm3 • The kidneys release thrombopoietin to stimulate platelet synthesis. Life span of platelet is 8-11 days; those not used are destroyed by macrophages, mainly in spleen. • An emergency store of platelets exists in the spleen (approx 1/3) in case needed to control excessive bleeding. (c) Eleshia Howell, 2012.

34. (c) Eleshia Howell, 2012. Full blood count parameters.

35. Haemostasis • When a blood vessel is damaged, loss of blood is stopped and healing occurs in a series of overlapping processes, in which platelets play an important role. • Vasoconstriction – the surface of platelets become sticky when they come into contact with damaged cells, adhering to the damaged wall. They then release serotonin, which constricts (narrows) the blood vessel, reducing blood flow. The damaged vessel also releases its own chemicals that cause vasoconstriction. (c) Eleshia Howell, 2012.

36. Platelet plug formation – the adherent platelets clump together and release other substances which attract more platelets to the site. This is a positive feedback mechanism, causing a rapid, response to vascular damage ~ plug formation is usually complete in 6mins after injury! • Coagulation (blood clotting) – this is a complex positive feedback system where numerous clotting factors activate each other in a specific order, eventually resulting in the formation of prothrombin activator, which activates the enzyme thrombin to convert fibrinogen to fibrin, laying down a 3-D mesh network to stabilise the platelet plug. (c) Eleshia Howell, 2012.

37. (c) Eleshia Howell, 2012. p64

38. Fibrinolysis – after the clot has formed, the process of removing it and healing the damaged blood vessel begins. The breaking down of the clot (fibrinolysis) is the first stage. The enzyme plasmin initiates breakdown of fibrin to soluble products that are treated as waste material and removed by phagocytosis. The healing process restores the integrity of the blood vessel wall. (c) Eleshia Howell, 2012.

39. Pathophysiologies related to blood Anaemias– not enough haemoglobin available to carry sufficient oxygen to the tissues. Rate of production of mature RBC’s doesn’t keep up with rate of haemolysis. Classification of anaemia is based on: • Impaired RBC production: iron deficiency, megaloblasticanaemias, hypoplasticanaemias. • Increased RBC loss: haemolytic anaemia, normocytic anaemia. • Anaemia can cause abnormal changes in the size or colour of RBC’s • Symptoms relate to the inability of blood to supply body cells with adequate oxygen and may represent adaptive changes. (c) Eleshia Howell, 2012.

40. e.g: tachycardia, palpitations, angina, breathlessness /  respiratory rate. • Iron deficiency anaemia – most common form . Normal daily RDI for men is 1-2mg, women 3mg. Caused by deficiency of iron in the bone marrow due to dietary insufficiency, excessively high requirements or malabsorption. RBC’s become smaller and paler. • Megaloblastic anaemia – caused by deficiency in vitamin B12 and/or folic acid which impairs RBC maturation. Size of RBC’s are abnormally large and fragile, with a short life span. Their depressed function and early lysis causes anaemia. Pernicious anaemia is the most common B12 related; it is an autoimmune disease where antibodies destroy intrinsic factor and parietal cells in the stomach. (c) Eleshia Howell, 2012.

41. Aplastic anaemia – results from bone marrow failure. Since the bone marrow also produces leukocytes and platelets, their numbers are also low in conjunction with the RBC’s. When all 3 types of cells are low, the condition is called pancytopenia and is accompanied by anaemia, diminished immunity and tendency to bleed. • Haemolytic anaemia – occur when circulating blood cells are destroyed or removed prematurely from the blood because the cells are abnormal or the spleen is overactive. • Sickle cell anaemia • Congenital disorders • Blood transfusion reactions • Injuries, diseases, toxins. (c) Eleshia Howell, 2012.

42. Leukopenia – low white blood cell count. May be caused by drugs, irradiation, disease, severe microbial infection. • Leukaemia – a malignant proliferation of WBC precursors by the bone marrow resulting in the uncontrolled increased production of leukocytes, crowding out other blood cells. The WBC’s released into the blood are immature, immunity is reduced and infection risk is high. There are numerous types of Leukaemia. • Thrombocytopenia – low blood platelet count due to reduced production or increased rate of destruction. (c) Eleshia Howell, 2012.

43. Haemophilia – a group of inherited clotting disorders carried by faulty genes present on the X- chromosome (female = XX, male = XY). People with haemophilia experience repeated episodes of severe and prolonged bleeding at any site, with little evidence of trauma. Recurrent bleeding into joints is common, causing severe pain and cartilage damage. Disorder ranges from mild to severe. (c) Eleshia Howell, 2012.

44. Plasma expanders • Are used to temporarily increase blood volume over a period of hours, allowing diagnostic tests and stabilisation of body systems to occur, preventing further deterioration of a medical condition / emergency. Delivered via I.V. • Normal saline – isotonic sodium solution • Ringer’s Solution – saline containing lactate, potassium chloride and calcium chloride ions; often used for fluid resuscitation after a blood loss due to trauma, surgery, or a burn injury. • Hartmann’s Solution – similar to Ringer’s, used to replace body fluid and mineral salts that may be lost for a variety of medical reasons (c) Eleshia Howell, 2012.

45. Dextrose solution – sugar solution. • The effects of these solutions are relatively short lived as the contents are absorbed and used by the body (as intended). • They do not increase the amount of oxygen carried by the blood. This completes our study of the Blood. (c) Eleshia Howell, 2012.