Introduction to Blood, Erythrocytes and Anemia

1. Introduction to Blood, Erythrocytes and Anemia Clinical Pathology Ms. Canga

2. Introduction to Blood, RBCs, and AnemiaTopics for discussion: • Function of blood and various components • Composition • Fluid • Cellular (Specific to erythrocytes) • Anemia • Staining

3. The Function of Blood • Classified as a _____________________ tissue • Fun Fact: Approximately ___% of animals body wt. is blood. • _________________________ • _________________________ • _________________________

4. Function: Transportation • Carries _______, nutrients, etc… • To every living cell in the body. • Carried by _______ in erythrocytes • Nutrients, etc. are dissolved and delivered via ____________ • Carries waste products of cellular metabolism • Primary waste product is ___________ • Carried to disposal organs that excrete from body • __________________&____________

5. Transportation continued • Transports _______________________ • From ______________ glands to target _________ • Transports _______________________ • From _______________________ in to circulation • Final destination is the _____________ as needed • Transports _______________________ • To site of ______________ within _________________ • Clump together to prevent further escape.

6. Function: Defense • Leukocytes (Will be covered in more detail later) • Defense from foreign invaders • _______________________ • _______________________ • Platelets (Will be covered in more detail later) • Work along side 13 clotting factors in the blood • Are activated when a _______________________wall is damaged. • Very complex process in which ALL factors must be activated in ____________ and __________________ in order for clot to form. • Each factor depends on the _____________ factor to activate it.

7. Function: Regulation • Regulatory system • _______________________ • _______________________ • _______________________

8. Regulation • Acid-base balance • Regulation of blood ______. • Normal range is ________________(IDEAL = _____) • Higher pH = _______________________ • Lower pH = _______________________ • Required for _______________________ • Assists with neutralizing acidic waste products of cellular metabolism. • Which blood is MORE alkaline? Arterial or venous? • Why?

9. Regulation continued • Body temperature • Regulators located in the _____________are influenced by temperature of the blood that passes over them. • Most dogs and cats average 101.0 – 102.5oF • Homeostasis • Body tissue fluid is maintained as __________________ as possible. • If fluid is lost in large amounts, fluid moves from ________________________ into tissues to compensate. • Leaves less plasma in bloodstream, causing _______________________. • If fluids are given or excessive fluids are present, fluid moves from ______________________ into bloodstream. • Excessive fluid in bloodstream causes _______________________.

10. Composition of Blood • _______________________ tissue • Composed of ____________and __________ • Cellular portion is composed of: • _____________– Responsible for gas exchange • _____________– Responsible for defense and immunity • _____________– Prevent leakage of blood from vessels • Liquid portion of whole blood is called __________ • Whole Blood: Blood in cardiovascular system, OR blood that contains plasma and all other components. • Plasma is ~90% water.

11. “Recipe” for an RBC • __________ • __________ (for the synthesis of heme-) • __________ is also important in release of iron from tissues into plasma • ____________________ (formation of -globin) • Essential ______________ (phospholipid bilayer) • __________________: helps form RBC • __________________: also helps in RBC formation • ____________________: works with B12 to help form RBC.

12. Formation of RBCs • Formerly known as ‘__________’ • Process of formation is called _______________. • Erythropoiesis takes place in __________________ and is initiated by the cytokine called __________________ (EPO). • EPO: produced by __________, is released when kidney cells detect __________in blood. • EPO acts on __________ ______and causes it to begin undergoing __________divisions, developing into several RBC precursors.

13. Maturation Cycle of an Erythrocyte

14. Morphological Changes during Maturation • Rubriblast: • Is very large, with royal blue __________. • Contains a large purple nucleus in a loose __________ pattern. • Prorubricyte: • Is slightly smaller, with a __________ cytoplasm. • The __________ composing the nucleus is slightly smaller and __________ and stains __________. • Rubricyte: • Is smaller still, with either a __________or slightly __________ cytoplasm as it begins to acquire the __________molecules.

15. Morphological Changes during Maturation • Metarubricyte: • Cytoplasm is similar in color to __________ RBC. • Nucleus is now considered __________ (becoming more dense) and stains dark blue. • (____________________ may be seen here) • Reticulocyte: • __________is “pushed out” of cell leaving behind ____________________ composed of RNA. • Cytoplasm stains slightly blue, and ____________________ may be seen if stained with Wright’s stain. (Deff-Quick is a modified Wright’s stain) • Mature RBC is seen after all ____________________ is lost from reticulocyte.

16. Morphological Changes During RBC Maturation

17. The End Result: Erythrocytes

18. Erythrocytes • Mature RBC is ____________________ sac. • Contains ~ _____ % water and _____ % solids (mainly __________) • Canines have __________RBCs; ~__________ in diameter • μ = a micron. One micron is one millionth of a meter (VERY TINY) • Cats, horses, cows, sheep and goats are smaller; ~__________ in diameter.

20. Erythrocytes - Morphology • Membrane is “____________________” • Can change shape, but is not __________. • _______________ shape provides more ____________________ to allow for gas exchange to take place. • Disk shape allows for shorter __________ distance in and out of cell compared to a sphere. • Animals with __________ biconcave shape usually have __________ number of RBCs on average.

21. Erythrocytes & Hemoglobin • Carry __________ to all tissues of the body. • O2 carried through hemoglobin, which binds to the oxygen. • __________ = pigment portion • produced in __________ • __________ = protein portion • Produced by __________

22. Hemoglobin - structure • For every heme group, there is one __________ molecule • Four __________ groups attach to each globin molecule. • This means that each hemoglobin molecule can carry __________ molecules of oxygen.

23. Hemoglobin molecule

24. Hemoglobin Types • __________ hemoglobin (HbE) • __________ hemoglobin (HbF) • __________ hemoglobin (Hb) • Each type of hemoglobin is found during different stages of development in the animal.

25. Embryonic and Fetal hemoglobin • Embryonic hemoglobin (HbE): is found in early developing __________. • Fetal hemoglobin (HbF): is present in fetal blood during mid to late __________. • Is also present up to a couple of months after birth. • Highest concentration of HbF is at __________.

26. Adult Hemoglobin (Hb) • Found in the RBCs of all animals beginning a couple of weeks to months after birth. • Gradually replaces __________ as primary type being produced by the body. • Inside normal RBCs, Hb is ___________________.

27. Function of (Adult) Hemoglobin • Transports __________to the tissues • Exists in two normal physiological states. • ____________________: Carrying oxygen • One oxygen molecule is associated with each iron molecule. • pH, temperature, and O2 and CO2 levels influence ability of Hb to carry O2 • ____________________: Has given up oxygen. • Also known as __________ hemoglobin. • CO2 is transported directly and indirectly in the RBC and is dissolved in the __________.

28. RBC Life Span and Destruction • Average in dogs is ~____ days • Average in cats is ~____ days • As an RBC ages, they are replaced by young, but mature RBCs from __________ in constant ______________________ cycle. • Process of aging is called ____________________.

29. Senescence • The process of cellular __________ • Enzyme activity __________ • Cell loses ____________________ and becomes __________ as its volume decreases. • 90% of destruction of senescent RBCs occurs through ____________________. • Takes place __________ the cardiovascular system via macrophage ____________________. • Macrophages of __________ are especially active in removal of senescent RBCs

30. Extravascular Hemolysis • Once inside a macrophage, the __________________ of the RBC is destroyed. • Contents are recovered from the macrophages and ________is transported back to red bone marrow. • Heme is eliminated from the body by being converted to ____________. Bilirubin binds to ___________ (plasma protein) and is carried to the liver. • Because it is not ____ soluble, it is called ________________________ or free bilirubin.

31. Extravascular Hemolysis, cont’d. • Once in the liver, bilirubin is _________________ to ________________________, making the combination water soluble. • Conjugated bilirubin is excreted as a ______ pigment into the intestines. • Some conjugated bilirubin is converted into _____________________ by bacteria and eliminated in the ____________ as urobilin. • Other conjugated bilirubin is converted into ______________________ and excreted in the __________ as stercobilin.

32. Senescence • ____% of RBC destruction takes place through _________________________ hemolysis • Takes place within _____________________________. • Results in blood cell fragmentation and/or destruction • When RBC membrane ruptures in blood vessel, _____ is released directly into the blood. • ____________________ Hb is picked up by transport protein called __________. • __________carries unconjugated Hb to macrophages in the __________ for breakdown. • Once in liver, ____________________hemolysis continues.

33. Senescence • When ____________________is filled with ____________________ hemoglobin, the excess unconjugated Hb has nothing to bind to. • Excess Hb is carried to __________ for excretion in urine. • _________________ ____hemolysis results in plasma that is pink, red, or brownish. • C/S will be ____________________. • Urine will be pink, red, or brownish in color.

34. Anemia • Anemia: a pathological condition resulting in decreased oxygen-carrying capacity of the blood. • May be caused by: • Low number of circulating mature RBCs • Increased __________ (RBC parasites/radiation therapy) • Decrease __________ (Bone marrow suppression) • Inappropriate __________ (hemorrhage) • Not enough ____________________being produced for normal RBCs present. (Iron deficiency) • Appropriate # of RBCs are present • Insufficient Hb to fill each cell.

35. Classifying Anemia • Anemia may be classified as either: • Regenerative: Usually caused by hemorrhage or hemolysis. • Non-regenerative: Involves the bone marrow (More on Anemia in next presentation)

36. Polycythemia • An __________ above normal in the number of RBCs. • Three common types: • _______________________________________ • _______________________________________ • _______________________________________

37. Relative Polycythemia • Seen in ____________________ • Common in __________ animals due to sensible and insensible losses such as: • Excessive __________, __________, __________or reduced __________intake. • You will learn more about sensible and insensible losses in Special Topics.

38. Treatment of Relative Polycythemia • Correction of cause of _____________________ • Use of ____________________ • Managing __________ intake is critical

39. Compensatory Polycythemia • Also known as __________ Polycythemia • Result of __________ • Bone marrow is stimulated to produce more RBCs because tissues aren’t getting enough oxygen. • Animals living in ____________________ often develop this type of polycythemia. • Patient in heart failure may develop this type of polycythemia because heart isn’t pumping enough blood to tissues, resulting in __________.

40. Treatment of Compensatory Polycythemia • ____________________may be required if no inappropriate physiological cause • If there is an underlying __________, surgical correction, followed by __________ treatment is required. (phlebotomy to normalize PCV may also be required)

41. Polycythemia Rubra Vera • Rare ____________________ disorder • Characterized by increased _______________ of RBCs • EPO levels are __________. Bone marrow is producing __________ stimulation from EPO.

42. Treatment of Polycythemia Rubra Vera • __________is required • ~__________mLs/kg • Simultaneous __________therapy to maintain overall blood __________. • Treatment with Rx: Hydroxyurea will help to suppress the production of RBCs.

43. Staining of Blood • Different __________ within cell stain specific colors. • Many different hematology stains • Different names but similar staining characteristics. • Many are _________________-_________stains (Wright’s stain, Giemsa, Leishman’s, Wright-Giemsa, and May-Grunwald are all Romanovsky-type stains) • Also called ____________________ stains because they stain more than one color. • Combination of basic blue and acidic red dyes dissolved in __________alcohol. • Allows ____________________ structures to stain blue • Allows ____________________ structures to stain red.

44. Staining Blood • Stain depends on ________ you are performing. • Each test we do in here will have specific stain instructions. • ____________________stain is the most widely used hematology stain. • Alkaline part is ____________________ blue • Acidic part is __________ • Modified Wright’s stains offer faster staining times but don’t stain some cellular structures as effectively. • ____________________ is a Modified Wright’s stain.

45. Sources • http://compepid.tuskegee.edu/syllabi/pathobiology/pathology/clinpath/chapter2.html • Clinical Anatomy and Physiology for Veterinary Technicians: Colville and Bassert. Second Edition • Merckvetmanuals.com