1. Alterations of Hematologic Function
Chapter 20

2. Anemia
Reduction in the total number of erythrocytes in the circulating blood or in the quality or quantity of hemoglobin
Impaired erythrocyte production
Acute or chronic blood loss
Increased erythrocyte destruction
Combination of the above

3. Anemia Classifications Etiology Morphology
Based on MCV, MCH, and MCHC values
Size
Identified by terms that end in “-cytic”
Macrocytic, microcytic, normocytic
Hemoglobin content
Identified by terms that end in “-chromic”
Normochromic and hypochromic

4. Anemia Anisocytosis Poikilocytosis
Red cells are present in various sizes
Poikilocytosis
Red cells are present in various shapes

5. Anemia Physiologic manifestation
Reduced oxygen-carrying capacity
Variable symptoms based on severity and the ability for the body to compensate
Classic anemia symptoms
Fatigue, weakness, dyspnea, and pallor

6. Macrocytic-Normochromic Anemias
Also termed megaloblastic anemias
Characterized by defective DNA synthesis
Caused by deficiencies in vitamin B12 or folate
Coenzymes for nuclear maturation and the DNA synthesis pathway

7. Macrocytic-Normochromic Anemias
Ribonucleic acid (RNA) processes occur at a normal rate
Results in the unequal growth of the nucleus and cytoplasm

8. Macrocytic-Normochromic Anemias
Pernicious anemia
Caused by a lack of intrinsic factor from the gastric parietal cells
Required for vitamin B12 absorption
Results in vitamin B12 deficiency

9. Macrocytic-Normochromic Anemias
Pernicious anemia
Typical anemia symptoms
Neurologic manifestations
Nerve demyelination
Absence of intrinsic factor
Others
Loss of appetite, abdominal pain, beefy red tongue (atrophic glossitis), icterus, and splenic enlargement

10. Macrocytic-Normochromic Anemias
Pernicious anemia
Treatment
Parenteral or high oral doses of vitamin B12

11. Macrocytic-Normochromic Anemias
Folate deficiency anemia
Absorption of folate occurs in the upper small intestine
Not dependent on any other factor
Similar symptoms to pernicious anemia except neurologic manifestations generally not seen
Treatment requires daily oral administration of folate

12. Microcytic-Hypochromic Anemias
Characterized by red cells that are abnormally small and contain reduced amounts of hemoglobin
Related to:
Disorders of iron metabolism
Disorders of porphyrin and heme synthesis
Disorders of globin synthesis

13. Microcytic-Hypochromic Anemias
Iron deficiency anemia
Most common type of anemia worldwide
Nutritional iron deficiency
Metabolic or functional deficiency
Progression of iron deficiency causes:
Brittle, thin, coarsely ridged, and spoon-shaped nails
A red, sore, and painful tongue

14. Microcytic-Hypochromic Anemias
Sideroblastic anemia
Group of disorders characterized by anemia
Altered mitochondrial metabolism causing ineffective iron uptake and resulting in dysfunctional hemoglobin synthesis
Ringed sideroblasts within the bone marrow are diagnostic
Sideroblasts are erythroblasts that contain iron granules that have not been synthesized into hemoglobin

15. Microcytic-Hypochromic Anemias
Sideroblastic anemia
Dimorphism
Myelodysplastic syndrome
Erythropoietic hemochromatosis

16. Normocytic-Normochromic Anemias
Characterized by red cells that are relatively normal in size and hemoglobin content but insufficient in number

17. Normocytic-Normochromic Anemias
Aplastic anemia
Pancytopenia
Pure red cell aplasia
Fanconi anemia
Posthemorrhagic anemia
Acute blood loss from the vascular space

18. Normocytic-Normochromic Anemias
Hemolytic anemia
Accelerated destruction of red blood cells
Autoimmune hemolytic anemias
Immunohemolytic anemia
Warm antibody immunohemolytic anemia
Drug-induced hemolytic anemia
Cold agglutinin immunohemolytic anemia
Cold hemolysin hemolytic anemia

19. Normocytic-Normochromic Anemias
Sickle cell anemia
Anemia of chronic inflammation
Mild to moderate anemia seen in:
AIDS, rheumatoid arthritis, lupus erythematosus, hepatitis, renal failure, and malignancies

20. Normocytic-Normochromic Anemias
Anemia of chronic inflammation
Pathologic mechanisms
Decreased erythrocyte life span
Ineffective bone marrow response to erythropoietin
Altered iron metabolism

21. Myeloproliferative RBC Disorders
Polycythemia
Overproduction of red blood cells
Relative polycythemia
Result of dehydration
Fluid loss results in relative increases of red cell counts and Hgb and Hct values

22. Polycythemia Absolute polycythemia Primary absolute Secondary absolute
Abnormality of stem cells in the bone marrow
Polycythemia vera (PV)
Secondary absolute
Increase in erythropoietin as a normal response to chronic hypoxia or an inappropriate response to erythropoietin-secreting tumors

23. Alterations of Leukocyte Function
Quantitative disorders
Increases or decreases in cell numbers
Bone marrow disorders or premature destruction of cells
Response to infectious microorganism invasion
Qualitative disorders
Disruption of cellular function

24. Quantitative Alterations of Leukocytes
Leukocytosis
Leukocytosis is a normal protective physiologic response to physiologic stressors
Leukopenia
Leukopenia is not normal and not beneficial
A low white count predisposes a patient to infections

25. Granulocytosis (Neutrophilia)
Neutrophilia is evident in the first stages of an infection or inflammation
If the need for neutrophils increases beyond the supply, immature neutrophils (banded neutrophils) are released into the blood

26. Granulocytosis (Neutrophilia)
This premature release is detected in the manual WBC differential and is termed a shift to the left
When the population returns to normal, it is termed a shift to the right

27. Neutropenia Reduction in circulating neutrophils Causes
Prolonged severe infection
Decreased production
Reduced survival
Abnormal neutrophil distribution and sequestration

28. Granulocytopenia (Agranulocytosis)
Causes
Interference with hematopoiesis
Immune mechanisms
Chemotherapy destruction
Ionizing radiation

29. Eosinophilia
Hypersensitivity reactions trigger the release of eosinophilic chemotactic factor of anaphylaxis from mast cells
Increased in allergic disorders
Increased in parasitic invasions

30. Eosinopenia Decrease in circulation numbers of eosinophils
Usually caused by migration of cells to inflammatory sites
Other causes
Surgery, shock, trauma, burns, or mental distress

31. Basophils Basophils account for only 0% to 1% of the circulating WBCs
Basophilia
Response to inflammation and hypersensitivity reactions
Basopenia
Occurs in acute infections, hyperthyroidism, and long-term steroid therapy

32. Monocytes Monocytosis Monocytopenia Poor correlation with disease
Usually occurs with neutropenia in later stages of infections
Monocytes are needed to phagocytize organisms and debris
Monocytopenia
Very little known about this condition

33. Lymphocytes Lymphocytosis Lymphocytopenia Acute viral infections
Epstein-Barr virus
Lymphocytopenia
Immune deficiencies, drug destruction, viral destruction

34. Infectious Mononucleosis
Acute, self-limiting infection of B-lymphocytes transmitted by saliva through personal contact
Commonly caused by the Epstein-Barr virus (EBV)—85%
B cells have an EBV receptor site
Others viral agents resembling IM
Cytomegalovirus (CMV), hepatitis, influenza, HIV

35. Infectious Mononucleosis
Symptoms: fever, sore throat, swollen cervical lymph nodes, increased lymphocyte count, and atypical (activated) lymphocytes
Serious complications are infrequent (<5%)
Splenic rupture is the most common cause of death

36. Infectious Mononucleosis
>50% lymphocytes and at least 10% atypical lymphocytes
Diagnostic test
Monospot qualitative test for heterophilic antibodies
Treatment: symptomatic

37. Leukemias Malignant disorder of the blood and blood-forming organs
Excessive accumulation of leukemic cells
Acute leukemia
Presence of undifferentiated or immature cells, usually blast cells
Chronic leukemia
Predominant cell is mature but does not function normally

38. Leukemias Acute lymphocytic leukemia (ALL)
Acute myelogenous leukemia (AML)
Chronic myelogenous leukemia (CML)
Chronic lymphocytic leukemia (CLL)

39. Leukemias

40. Leukemias Signs and symptoms of leukemia
Anemia, bleeding purpura, petechiae, ecchymosis, thrombosis, hemorrhage, DIC, infection, weight loss, bone pain, elevated uric acid, and liver, spleen, and lymph node enlargement

41. Philadelphia Chromosome

42. Lymphadenopathy Enlarged lymph nodes that become palpable and tender
Local lymphadenopathy
Drainage of an inflammatory lesion located near the enlarged node
General lymphadenopathy
Occurs in the presence of malignant or nonmalignant disease

43. Lymphadenopathy

44. Malignant Lymphomas
Malignant transformation of a lymphocyte and proliferation of lymphocytes, histiocytes, their precursors, and derivatives in lymphoid tissues
Two major categories
Hodgkin lymphoma
Non-Hodgkin lymphomas

45. Hodgkin Lymphoma
Characterized by the presence of Reed-Sternberg cells in the lymph nodes
Reed-Sternberg cells are necessary for diagnosis, but they are not specific to Hodgkin lymphoma
Classical Hodgkin lymphoma
Nodular lymphocyte predominant Hodgkin lymphoma

46. Hodgkin Lymphoma Physical findings Symptoms Laboratory findings
Adenopathy, mediastinal mass, splenomegaly, and abdominal mass
Symptoms
Fever, weight loss, night sweats, pruritus
Laboratory findings
Thrombocytosis, leukocytosis, eosinophilia, elevated ESR, and elevated alkaline phosphatase
Paraneoplastic syndromes

47. Hodgkin Lymphoma

48. Hodgkin Lymphoma

49. Hodgkin Lymphoma

50. Non-Hodgkin Lymphoma Generic term for a diverse group of lymphomas
The lymphomas can be differentiated based on etiology, unique features, and response to therapies

51. Non-Hodgkin Lymphoma
Non-Hodgkin lymphomas are linked to chromosome translocations, viral and bacterial infections, environmental agents, immunodeficiencies, and autoimmune disorders

52. Non-Hodgkin Lymphoma
Clonal expansion of B cells, T cells, and/or NK cells
Changes in proto-oncogenes and tumor-suppressor genes contribute to cell immortality and thus an increase in malignant cells

53. Burkitt Lymphoma Most common type of non-Hodgkin lymphoma in children
Burkitt lymphoma is a very fast-growing tumor of the jaw and facial bones
Epstein-Barr virus is found in nasopharyngeal secretions of patients

54. Burkitt Lymphoma

55. Multiple Myeloma (MM)
Infiltrate bone marrow and aggregate into tumor masses in skeletal system
M-proteins
Hypercalcemia, renal failure, bone lesions

56. Multiple Myeloma (MM)

57. Lymphoblastic Lymphoma (LL)
Clone of immature T cells that become malignant in the thymus
Lymphadenopathy of the neck

58. Alterations in Splenic Function
Splenomegaly
Hypersplenism
Congestive splenomegaly
Infiltrative splenomegaly

59. Disorders of Platelets
Thrombocytopenia
Platelet count <150,000/mm3
<50,000/mm3—hemorrhage from minor trauma
<15,000/mm3—spontaneous bleeding
<10,000/mm3—severe bleeding

60. Disorders of Platelets
Thrombocytopenia
Causes
Hypersplenism, autoimmune disease, hypothermia, and viral or bacterial infections that cause disseminated intravascular coagulation (DIC), HIT

61. Disorders of Platelets
Immune thrombocytopenic purpura (ITP)
IgG antibody that targets platelet glycoproteins
Antibody-coated platelets are sequestered and removed from the circulation
The acute form of ITP that often develops after a viral infection is one of the most common childhood bleeding disorders

62. Disorders of Platelets
Immune thrombocytopenic purpura (ITP)
Manifestations
Petechiae and purpura, progressing to major hemorrhage

63. Disorders of Platelets
Thrombotic thrombocytopenic purpura (TTP)
A thrombotic microangiopathy
Platelets aggregate, form microthrombi, and cause occlusion of arterioles and capillaries
Chronic relapsing TTP
Acute idiopathic TTP

64. Disorders of Platelets
Essential (primary) thrombocythemia
Thrombocythemia is characterized by platelet counts >600,000/mm3
Myeloproliferative disorder of platelet precursor cells
Megakaryocytes in the bone marrow are produced in excess
Microvasculature thrombosis occurs

65. Alterations of Platelet Function
Qualitative alterations in platelet function demonstrate an increased bleeding time in the presence of a normal platelet count
Platelet function disorders result from platelet membrane glycoprotein and von Willebrand factor deficiencies

66. Alterations of Platelet Function
Manifestations
Petechiae, purpura, mucosal bleeding, gingival bleeding, and spontaneous bruising
Disorders can be congenital or acquired

67. Alterations of Coagulation
Vitamin K deficiency
Vitamin K is necessary for synthesis and regulation of prothrombin, the prothrombin factors (II, VII, XI, X), and proteins C and S (anticoagulants)
Liver disease
Liver disease causes a broad range of hemostasis disorders
Defects in coagulation, fibrinolysis, and platelet number and function

68. Disseminated Intravascular Coagulation (DIC)
Complex, acquired disorder in which clotting and hemorrhage simultaneously occur
DIC is the result of increased protease activity in the blood caused by unregulated release of thrombin with subsequent fibrin formation and accelerated fibrinolysis

69. Disseminated Intravascular Coagulation (DIC)
Endothelial damage is the primary initiator of DIC

70. Disseminated Intravascular Coagulation (DIC)
The amount of activated thrombin exceeds the body’s antithrombins and the thrombin does not remain localized
The widespread thromboses created cause widespread ischemia, infarction, and organ hypoperfusion

71. Disseminated Intravascular Coagulation (DIC)
By activating the fibrinolytic system (plasmin), the patient’s fibrin degradation product (FDP) and D-dimer levels will increase
Because of the patient’s clinical state, the disorder has a high mortality rate
Treatment is to remove the stimulus

72. Disseminated Intravascular Coagulation (DIC)
Clinical signs and symptoms demonstrate wide variability
Bleeding from venipuncture sites
Bleeding from arterial lines
Purpura, petechiae, and hematomas
Symmetric cyanosis of the fingers and toes