1. Altered Hematologic Function: Erythrocytes

2. Physical Characteristics of Blood
Heavier, thicker, and 3-4 X more viscous than water
38o C (100.4oF)
pH : 7.35 – 7.45
4-6 liters in an adult
Varies with electrolyte concentration and amount of adipose tissue

3. Blood Volume Blood volume is about 8% of body weight.
1 kg of blood ≈ 1 L of blood
70 kg X 0.08 = 5.6 Kg = 5.6 L
45 % is formed elements
55% plasma

5. Plasma 92 % Water 8% Solutes – organic and inorganic
Plasma proteins – largest proportion of solutes
Albumins – 58 % of the proteins – maintain osmotic (oncotic) pressure – hold water in the blood
Globulins – 38 % - antibodies synthesized by plasma cells
Clotting factors – fibrinogen – 4 %

6. Other components of plasma
Nutrients
Hormones
Electrolytes
Waste products
Dissolved gases

7. Formed elements Three types: Erythrocytes – red blood cells- RBC’s
Leukocytes – white blood cells – WBC’s
Thrombocytes – platelets – cell fragments

8. Hemopoiesis (Hematopoiesis)
All blood cells common from a common stem cell – Hemocytoblast
These are in the bone marrow (red) and develop into blood cells as needed by the body
Mitosis is signaled by biochemicals released from the body →
Stem cell is signaled to differentiate into the needed type of blood cell
Hematopoiesis / cell breakdown continue through life.

10. Erythrocytes (RBC’s) Most abundant blood cell type Transport gases
Shape is important
Large surface to volume ratio
Reversible deformability – can change shape
Development is called erythopoiesis
Erythropoietin is a hormone produced by the kidneys in response to low blood oxygen levels; signals bone marrow to increase RBC production

12. Cytoplasm is mostly hemoglobin (lacks organelles)
Made up of 4 peptide chains that form the globin portion and four molecules of the pigment heme which contains an atom of iron
Oxygen binds to iron in heme (also CO)
23 % of CO2 is bound to globin portion
If there is a problem with any part of the molecule it may not be functional.

14. RBC breakdown
Healthy RBC’s live about 120 days; we break down about 174 million per minute
RBC’s are removed from circulation by the liver and spleen
Broken down into heme and globin portions
Globin is broken down into amino acids
Iron is removed from heme and stored or recycled
Heme is broken down into biliverdin and then into bilirubin

16. Usually eliminated in bile.
To produce more RBC’s, the body needs sufficient iron and amino acids as well as the vitamins folate (folic acid) and vitamin B12

17. Abnormalities Anemias
Anemia is the inability of the blood to carry sufficient oxygen to the body.
low #’s of RBCs
lack of hemoglobin

18. Cinical Manifestations
Pallor
Fatigue
Weakness; exercise intolerance
Dyspnea
Syncope (fainting) and dizziness
Angina
Tachycardia (increased heart rate)
Organ dysfunctions

19. Classification of Anemias
Identified by their causes or by the changes that affect the size, shape or substance of the erythrocyte
Terms that end with –cytic refer to cell size, and those that end in –chromic refer to hemoglobin content.
Additional terms:
Anisocytosis – various sizes
Poikilocytosis – various shapes

20. Macrocytic / Megaloblastic Anemia
Characterized by abnormally large stem cells (megaloblasts) in the marrow that mature into erythrocytes that are unusually large in size, thickness and volume. The hemoglobin content is normal, so these are normochromic anemias.

21. These anemias are the result of:
Ineffective DNA synthesis
Commonly due to folate and B12 (cobalamin) deficiencies – malabsorption or malnutrition
These cells die prematurely, decreasing the numbers of RBC’s in circulation
DNA synthesis is blocked or delayed, but RNA replication and protein synthesis are normal.

22. Pernicious Anemia Common megaloblastic anemia
Caused by a Vitamin B12 deficiency
Pernicious means highly injurious or destructive – this condition was once fatal

23. Can be congenital – baby born with a deficiency in a protein , intrinsic factor, necessary to absorb B12 from the stomach
Adult onset – one example is an autoimmune dysfunction - type A chronic atrophic gastritis – where there is destruction of the gastric mucosa
Most commonly affects people over 30
Females are more prone to PA , and black females have an earlier onset.

24. Pernicious Anemia is also associated with:
Heavy alcohol consumption
Hot tea
Cigarette smoking
Other autoimmune conditions
Complete or partial removal of the stomach can cause intrinsic factor deficiency

25. Develops slowly – over 20 - 30 years
Usually severe by the time individual seeks treatment
Early symptoms ignored because they are nonspecific and vague- infections, mood swings, and gastrointestinal, cardiac or kidney ailments.
Usually a degree of neuropathy occurs
Untreated, it is fatal, us. due to heart failure

26. Folate deficiency anemias
Folic acid also needed for DNA synthesis
Demands are increased in pregnant and lactating females
Absorbed from small intestine and does not require any other elements for absorption.
Folate deficiency is more common than B12 deficiency

27. Folate deficiency is more common than B12 deficiency , esp
Folate deficiency is more common than B12 deficiency , esp. in alcoholics and those who are malnourished because of fad diets or diets low in vegetables.
Estimated that 10 % of North Americans are folate deficient.
Specific manifestations include cheilosis, (scales and fissures of the mouth), inflammation of the mouth, and ulceration of the buccal mucosa and tongue.

28. Microcytic – Hypochromic Anemias
Characterized by abnormally small RBC’s that contain reduced amounts of hemoglobin.
Possible causes:
Disorders of iron metabolism
Disorders of porphyrin and heme synthesis
Disorders of globin synthesis

29. Iron Deficiency Anemia
Most common type of anemia throughout the world.
High risk:
Individuals living in poverty
Females of childbearing age
Children
Common causes
Insufficient iron intake
Chronic blood loss – even 2- 4 ml/ day
In men –gastrointestinal bleeding
In women – profuse menstruation, pregnancy

30. Other causes: Use of medications that cause GI bleeding
Surgical procedures that decrease stomach acidity, intestinal transit time, and absorption
Eating disorders such as pica

31. Clinical manifestations:
Early symptoms are nonspecific
Later - changes in epithelial tissue:
Fingernails become brittle and concave (koilonychia)
Tongue papillae atrophy and cause soreness, redness and burning
Corners of mouth become dry and sore
Difficulty in swallowing due to web of mucus and inflammatory cells at opening of esophagus

34. Treatment
Stop blood loss
Iron replacement therapy

35. Sideroblastic Anemia
Due to inefficient iron uptake, resulting in abnormal hemoglobin synthesis
Characterized by the presence of ringed sideroblasts in the bone marrow – red cells containing iron granules that have not been synthesized into hemoglobin, but instead are arranged in a circle around the nucleus.

37. Can be acquired or hereditary Acquired SA is the most common
May be idiopathic or associated with other disorders
Reversible - secondary to alcoholism, drug reactions, copper deficiency and hypothermia
Hereditary SA –rare, almost always in males – probably X-linked recessive gene.

38. Clinical manifestations
Along with cardiovascular and respiratory manifestations of anemia, may also show signs of iron overload (hemosiderosis)
Enlargement of spleen and liver
Bronze tint to skin
Heart rhythm disturbances
Impaired growth and development in young children

39. Treatment Drug therapy – pyridoxine
Iron overload requires repeated blood removal – phlebotomies
Iron chelating agents in anemic individuals who require transfusions

40. Normocytic –Normochromic Anemias
RBC’s are normal in size and hemoglobin content, but are too few in number.
Less common than the macrocytic and microcytic anemias

41. Several types that do not have anything else in common:
Aplastic
Posthemorrhagic
Hemolytic
Sickle cell
Anemia of chronic inflammation

42. Aplastic anemia
Fortunately, this condition is rare; it means the RBC’s are not being produced. Bone marrow stem cells are not functioning.
Can result from disorders of the bone marrow, such as cancer; autoimmune diseases; renal failure due to lack of erythropoietin; B12 or folate deficiency; congenital problems; or it may be induced by radiation, toxins or the use of some drugs, such as chloramphenicol.
Treatment – treat the underlying disorder, blood transfusions, and possibly bone marrow transplant

43. Posthemorrhagic Caused by sudden loss of blood.
Can be fatal if loss exceeds % of plasma volume.
Treatment is to restore blood volume by intravenous administration of saline, dextran, albumin, plasma or whole blood.

44. Hemolytic Anemia Red blood cells are formed, but are broken down.
May be acquired or hereditary.
Acquired hemolytic anemia is extrinsic, due to factors outside the red blood cell, such as an abnormal autoimmune response that targets red cells, or by improper matches during transfusions; or due to infection, systemic diseases, or drugs or toxins.

45. Hereditary or intrinsic hemolytic anemias:
Sickle cell anemia – due to a change in one amino acid in each of the beta-chains in the globin, under conditions of low oxygen the hemoglobin forms insoluble threads that change the shape of the erythrocyte into a crescent. This shape is not as flexible and tend to be trapped in the capillaries, where they obstruct blood flow and cause ischemic injury.

46. The life span of a sickled cell is only 20 days rather than 120, and is removed from circulation by the spleen.
Either mechanism causes a chronic anemia.
Sickle crisis: episodes of acute sickling that block blood flow, posing the threat of widespread and possibly life-threatening ischemic organ damage.

48. This is an inheritable condition.
If a person has only one defective gene, it is called sickle cell trait, and the person is essentially normal. This condition tends to persist because it protects against malaria. When a cell becomes infected by the parasite, the cell sickles and is removed from circulation, preventing reproduction of the parasite.
Only when a person inherits two defective genes does sickle cell anemia occur.

49. Thalassemia is another hemolytic disorder where the alpha or beta chains of the globin are defective, or the beta chain is not produced. When the beta protein is lacking, the alpha protein accumulates and causes destructive membrane effects, causing these cells to be rapidly removed from the circulation.
Highest incidence in populations around the Mediterranean and Southeast Asia.
Problem occurs when two defective genes are inherited; heterozygotes are essentially normal.

50. Thalassemia major is an inherited form of hemolytic anemia, characterized by red blood cell (hemoglobin) production abnormalities. This is the most severe form of anemia, and the oxygen depletion in the body becomes apparent within the first 6 months of life. If left untreated, death usually results within a few years. Note the small, pale (hypochromic), abnormally-shaped red blood cells associated with thalassemia major.

51. Myeloproliferative Disorders
The opposite of anemias – here we have too many RBC’s.
Polycythemia – excessive production of RBC’s
Primary polycythemia – cause is unknown, but is in effect, a benign tumor of the marrow, leading to increased numbers of stem cells and therefore RBC’s, and splenomegally.
Polycythemia vera – rare, mostly Northern European Jewish males between 60 – 80 yrs.

52. Secondary Polycythemia
Due to the overproduction of erythropoietin caused by hypoxia. This is more common.
Seen in:
Persons living at high altitudes
Smokers
COPD patients
Congestive heart failure patients

53. Polcythemia leads to : Increased blood volume and viscosity
Congestion of liver and spleen
Clotting
Thrombus formation
(last two may be due increased numbers of platelets along with the increase in RBC’s due to bone marrow dysfunction.)

54. Clinical manifestation of Polycythemia
Headache
Dizziness
Weakness
Increased blood pressure
Itching / sweating

55. Treatment of polycythemia
Reduce blood volume by phlebotomy – ml.
Treat underlying condition - Stop smoking
Radioactive phosphorus injections
Prevent thrombosis