Gokng

1. White Blood Cell
Pathophysiology
Presented by: Wanda Lovitz, APRN

2. •Discuss the components of the hematologic system.
•Define and explain hematopoiesis.
•Compare and contrast the five types of leukocytes:
1.Neutrophils
2.Lymphocytes
3.Monocytes
4.Eosinophils
5.Basophils
•Differentiate between the two types of neutrophils:
1.Segs
2.Bands
•Describe how the hematologic system is clinically evaluated:
1.Bone marrow aspiration
2.Bone marrow biopsy
•Briefly describe the various medical disorders that result from alterations
in leukocyte function:
1.Infectious mononucleosis
2.Leukemia
3.Lymphoma (Hodgkins and non-Hodgkins)
Objectives: WBCs

3. Drugs to Know
 filgrastim (Neupogen)

4. Components of the
Hematologic System
 Composition of Blood:
 Plasma
 Plasma proteins
 albumin
 Blood cells
 FORMED IN BONE MARROW
 “HEMATOPOIESIS”
 Erythrocytes
 Leukocytes
 Thrombocytes

5. Plasma: 55%
Leukocytes & Thrombocytes: <1%
Erythrocytes: 45%
►►►
WBC/
Plts
Composition Of Blood Fresh Frozen Plasma
(FFP)

6. Primary Function of Blood Cells
 Erythrocytes = OXYGEN transport
 LEUKOCYTES = protect body from INFECTION
 Platelets = promote blood COAGULATION

7. Transfusing Blood Products:
platelets, whole blood, packed cells,
albumin, and fresh frozen plasma

8. Structure of the Immune System
 Skin - first line of defense
 Mucous membranes - first line of defense
 Mononuclear phagocyte system
 Lymphoid system (spleen, thymus, lymph nodes)
 Bone marrow
 All structures contain different types of WBCs that
control inflammation and immunity
 Chemical mediators aid in defense of the body
 complement
 kinins
 clotting factors
 cytokines
 chemokines

9. Lymphoid Organs:
(Link hematologic & immune
system)
 Lymphoid organs
 Primary
 THYMUS
 Key in newborn immune response
 BONE MARROW *
 Red/yellow; origin of hematopoiesis
 Secondary
 SPLEEN
 Fetal hematopoiesis; has phagocytes; has lymphocytes
(immune); blood reservoir
 LYMPH NODES
 Filters pathogens;
 enlarged/tender with infection (r/t  macrophages)
 TONSILS
 Mass of lymph tissue
 PEYER PATCHES of small intestine

10. Bone Marrow
 Confined to cavity of bone
 Red (active)
 Yellow (inactive)
 Not all bones have red marrow
 By adulthood the following do:
 Pelvic bone Ribs
 Vertebra Cranium
 Sternum
 Extreme proximal portion of humerus/femur
 Manufactures billions of WBC’s

11. Spleen Location = upper left quadrant
Enlarged spleen = spleenomegaly

12. Palpating For Splenomegaly

13. Development of Blood Cells
“HEMATOPOIESIS”
 Defined: blood cell production
 Originates in bone marrow
 Each type of cell has parent cells → “STEM CELLS”

 Two-stage process
 MITOTIC division (or proliferation)
 Replication of SAME cell
 MATURATION (or differentiation)
 Differentiates cells

14. Stem Cells: The Origin Of All Blood Cells

15. Pluripotential Stem Cell
MYELOID Stem Cells LYMPHOID Stem Cells
Granulocyte;
Macrophage
Stem Cells
Granulocyte
Stem Cells
NEUTROPHILS
EOSINOPHILS
& BASOPHILS
Monocytic
Stem Cells
agranulocytes
MONOCYTES &
MACROPHAGES
Megakaryocytic
Stem Cells
Megacaryocytes
& Platelets
Erythropoietic
Stem Cells
Erythrocytes LYMPHOCYTES
(T cells, B cells,
plasma cells)
HEMATOPOIESIS

16. Leukocytes (WBCs)
 Defined:
 Are WBC’s that defend the body against
organisms that cause infection and remove debris,
including dead or injured host cells of all kinds
 Act primarily in TISSUES but are transported via
circulation
 Average number in adult:
 5,000-10,000/mm³

17. Never Let Monkeys Eat Bananas!
The five types of leukocytes, in order of prevalence
 Never
(NEUTROPHILS)
 Let
(Lymphocytes)
 Monkeys
(Monocytes)
 Eat
(Eosinophils)
 Bananas
(Basophils)

18. The Process Of Phagocytosis
“Attack, Engulf, Destroy”
Phagocytes = Neutrophils, Monocytes, Eosinophils, Basophils

19. Blood tests → CBC (# RBC, WBC & platelets)
Complete blood cell count WITH DIFFERENTIAL
includes:
→ RBC  Platelets WBC WITH differential count
CBC With Diff OR WBC With Differential
Clinical Evaluation of the
Hematologic System

20. Bone Marrow Aspiration/Biopsy: A Painful Procedure

21. Leukocytes:
2 Ways To Classify
 Structure:
 Granulocytes (Lifespan = 1-10 days)
 Neutrophils, eosinophils, basophils
 Agranulocytes (Lifespan = days – months – years)
 Monocytes, lymphocytes
 Function:
 PHAGOCYTES (cells that ingest/digest bacteria)
 Neutrophils, eosinophils, basophils, monocytes
 IMMUNOCYTES (cells that create immunity)
 Lymphocytes

22. WBC: Total Count
 5,000 -10,000/mm³
  WBC ↔ leukocytosis
  WBC ↔ leukopenia
  neutrophils ↔ neutropenia
 Marked  granulocytes ↔ agranulocytosis
 Total count:
 Indicates THE DEGREE of response to a pathologic process
 However, differential count will provide a more complete evaluation for
SPECIFIC DIAGNOSES

24. WBC: Differential
Why Reported in %?
  % in one type will ALWAYS mean  % in another type even
though absolute number for second type of cell does not 
 EXAMPLE:
 Client with WBC of 10,000/mm³
 neutrophil count is 60%
 lymphocyte count is 30% (& 10% of others)
 Even though lab doesn‘t report actual number of lymphocytes, one can
deduce this client has 3,000 lymphocytes/mm³
 called the “ABSOLUTE COUNT”

25. Example: Continued
 If this same client gets a severe BACTERIAL
infection, WBC →  20,000/mm³
 In a bacterial infection, almost all of  in WBC will
be 2°  NEUTROPHILS
 Diff count now shows:
 →75% neutrophils & 15% lymphocytes
 But does NOT mean man has fewer lymphocytes

26. Example: Continued
 He has 15% of 20,000
(or 3,000 lymphocytes/mm³, just as before)
 Only PROPORTIONS have changed
 Remember:
 Absolute numbers may change
 Proportions of each type of WBC may change, BUT…
 Percentage must ALWAYS add up to 100%

27. “WBC W/Diff”:
What are we differentiating?
 Granulocytes (phagocytes)
 Neutrophils (50-67%)
 Eosinophils (0-3%)
 Basophils (0-2%)
 Lymphocytes (agranulocytes)
 (24-40%)
 Monocytes/macrophages (agranulocytes)
 (4-9%)
{Remember…differential ALWAYS adds up to 100%}

29. Neutrophils aka “neuts”
 Most numerous and best understood of the granulocytes
 First to arrive at site of inflammation (within 90 mins)
 IMMATURE neutrophils → “bands”
 MATURE neutrophils → “segs”
 Segs (47-63%)+ bands (0-4%) = 47-67%
 CHIEF PHAGOCYTES OF ACUTE INFLAMMATION
  with acute bacterial infections & trauma

30. Neutrophil: Segs & Bands
 “Seg”mented neutrophils:
 Mature
 Band neutrophils:
 IMMATURE; few normally found in peripheral blood
 A “SHIFT TO THE LEFT”:
 Signals ACUTE stage of infection
 Means that many band cells are present in peripheral blood
 Example: segs = 48%, bands = 14%

31. “Shift To The Left”: Many neutrophils, but not all of them mature
* Bands are horseshoe-shaped

32. Neutropenia
 Defined: low neutrophil count (absolute count < 1000/mm³)
 Most often cancer patients (as a result of disease or treatment)
 Susceptible to bacterial infection (can be life-threatening)
 “NEUTROPENIC PRECAUTIONS”
 Pt wears mask when outside of room
 Door closed/sign on the door
 Meticulous handwashing
 Ø sick visitors
 Ø raw fruit, veggies, fish
 Remove stagnant water BID
 Assess T q4h; any temp  is significant
 Often do not develop fever (or any other s/s infection) because do not have enough WBC to
produce these reactions; T > 100.4°? Antibiotics < 1 hr

33. S/P Organ Transplant: Neutropenic Precautions

34. Leukopenia:
Pharmacologic Treatment
 Hematopoietic agents (HA)
 Granulocyte - Colony stimulating factors (G-CSF)
 filgastrim (Neupogen)
 MOA: promotes proliferation, differentiation & activation of cells
that make granulocytes
 Indications  malignancies, chemo-induced leukopenia
 Given IV/SQ.
 Adverse Reactions: Bone pain
 Nursing Implication: Monitor CBC with differentiation

35. Lymphocytes
 24-40%
 The “IMMUNE” WBC
 Divided into 2 types: (both formed in bone marrow)
 1. T cells → mature in THYMUS; cell-mediated immune
response (attack & destroy specific foreign cells)
 2. B cells → mature in BONE MARROW
 produce ANTIBODIES that react against foreign antigens (ie., bacteria &
viruses)

36. Immune Response Cells
 T and B cells are the primary cells of immune response (create
immunity)
 Fight CHRONIC bacterial infection & ACUTE VIRAL
infections
 Most located in LYMPHOID tissue (NOT in bloodstream)

38. Monocytes
 4-9%
 Major function → potent phagocytosis
 Fight bacteria similar to neutrophils
 Second to arrive at the scene of an injury (occur
during LATE PHASE of infection)
 Only present in blood for a short time before they
migrate into tissues & become macrophages

39. Eosinophils
 0-3%
 Function: phagocytosis of antigen-antibody complexes
  with allergic reactions & parasitic infections
 Examples: Asthma, drug reactions, severe posion ivy reaction
 “Worms, Wheezes, and Weird diseases”
Basophils
 0-2%
 Function: PHAGOCYTOSIS

41. Conditions That Alter WBC’s:
 Leukocytosis ( WBC)
 Normal protective response
to physiologic stressors
(ie, surgery, anesthesia)
 All types of infection
 Tissue necrosis
 Inflammatory disorders
 Leukopenia ( WBC)
 Bone marrow depression
 Drug toxicity
 Autoimmune disease
 (Lupus)
 Malignancies,
Chemotherapeutic agents

42. CBC
(RBC, Hgb, Hct, Platelet count)
WBC count 5-10,000/mm³
WBC differential
SEGMENTED NEUTROPHILS 47-63%
Band neutrophils 0-4%
Lymphocytes 24-40%
Monocytes 4-9%
Eosinophils 0-3%
Basophils 0-2%
CBC With Diff: NORMAL RANGES

43. CBC
(RBC, Hgb, Hct, platelet count)
WBC count 13,300/mm³
WBC differential
Segmented neutrophils 70%
Band neutrophils 8%
Lymphocytes 15%
Monocytes 4%
Eosinophils 2%
Basophils 1%
Example: WBC Diff With Bacterial Infection

44. CBC
(RBC, Hgb, Hct, platelet count)
WBC count 14,200/mm³
WBC differential
Segmented neutrophils 26%
Band neutrophils 4%
Lymphocytes 59%
Monocytes 8%
Eosinophils 2%
Basophils 1%
Example: Infectious Mononucleosis (Type of Virus)

45. CBC
(RBC, Hgb, Hct, platelet count)
WBC count 11,700/mm³
WBC differential
Segmented neutrophils 39%
Band neutrophils 7%
Lymphocytes 29%
Monocytes 3%
Eosinophils 22%
Basophils 1%
Example: Allergic Reaction With Resultant Asthma Attack
Worms,Wheezes, and Weird Diseases

46. What else to look for with an
infection?
  temperature
 Fever is not a disease, but a sign that the
body is responding to an infection
 A fever may  or stop growth of some
microorganisms
 some can only survive within a narrow range of
temperature

47. Inflammation
 Increased vascular permeability
 Leukocyte recruitment and emigration
 CHEMOTAXIS- process by which neutrophils are attracted to
inflamed tissue
 Phagocytosis of ANTIGENS- neutrophils and macrophages produce
enzymes that digest protein structures
 CHRONIC INFLAMMATION
 Fibrosis and scarring can occur with prolonged inflammation when
normal tissue is replaced with fibrous tissue
 Ex. Pulmonary fibrosis
 Granuloma- accumulation of macrophages, fibroblasts and collagen
 EX: Tuberculosis

48. Inflammatory Exudates
 Functions: 1) transport leukocytes and antibodies; 2)
dilution of toxins; 3) transport of nutrients for repair
 Types:
 1) serous- watery, low protein, mild inflammation;
 2) serosanguineous- pink tinged fluid, small amounts of RBC;
 3) fibrinous- large amount of protein, increased inflammation,
sticky and thick, may need to be removed to allow healing- scar
tissue may develop;
 4) Purulent (pus)- severe inflammation, composed of neutrophils,
protein, and tissue debris;
 5) Hemorrhagic- large component of RBC, most severe
inflammation

49. Systemic Manifestations of
Inflammation
 C-reactive proteins (CRP)- an acute phase
protein that can be measured in the blood
 Erythrocyte sedimentation rate (ESR)- simple
measure of inflammation, measures how
quickly RBC settle to the bottom of a test
tube

50. Infectious Mononucleosis
 Self-limiting lymphoproliferative disorder
 Caused by Epstein-Barr virus (EBV)
 Most prevalent in adolescence/young adults
 Main mode of transmission → EBV-
contaminated saliva
 Pathogenesis: atypical lymphocytes proliferate
 Onset: insidious; incubation 4-8 weeks

52. Mono: Sore throat with erythema & white exudate

53. Infectious mononucleosis
 Clinical manifestations: lymphadenopathy,
hepatomegaly, splenomegaly
 Labs:
 WBC  (~ 12-18,000); 95% lymphocytes
 (viral infection)
 Acute phase: 2-3 weeks
 Treatment: symptomatic & supportive
 Some degree of debility/lethargy: 2-3 months

54. Leukemias
 Chronic
 CLL (chronic lymphocytic leukemia)
 CML (chronic myelocytic leukemia)
 Acute
 ALL (acute lymphocytic leukemia)
 AML (acute myelocytic leukemia)
DEFINED BY:
1. SITE OF ORIGIN
a. myeloid stem cell
b. lymphoid stem cell
2. ACUTE VS CHRONIC
a. acute
b. chronic

55. Leukemias
 Malignant neoplasms of cells originally derived from a
single hematopoietic cell line
 Leukemic cells:
 Are immature & unregulated
 Proliferate in bone marrow
 Circulate in blood
 Infiltrate spleen, lymph nodes & other tissues
 Disease of children & adults

56. Common feature of all leukemias:
Uncontrolled proliferation of immature leukocytes
results in crowding out of mature blood cells
including leuckocytes, red blood cells, and platelets
Pancytopenia = decrease in all functioning blood
cells: anemia, thrombocytopenia, neutropenia

57. Pluripotential Stem Cell
Myeloid Stem Cells Lymphoid stem cells
Granulocyte;
Macrophage
Stem Cells
Granulocyte
Stem Cells
Neutrophils
Eosinophils
& Basophils
Monocytic
Stem Cells
Monocytes &
Macrophages
Megakaryocytic
Stem Cells
Megacaryocytes
& Platelets
Erythropoietic
Stem Cells
Erythrocytes Lymphocytes:
(T cells, B cells,
plasma cells)
HEMATOPOIESIS

58. Leukemia: Classifications
 Classified according to their PREDOMINANT CELL type
 LYMPHOCYTIC or MYELOCYTIC AND
 whether dx is ACUTE or CHRONIC
1. Acute lymphocytic (lymphoblastic) leukemia (ALL)*
2. Chronic lymphocytic leukemia (CLL)**
3. Acute myelocytic leukemia (AML)
4. Chronic myelocytic leukemia (CML)
* Most common childhood leukemia
**Most common leukemia of older adults

59. Leukemia: Pathogenesis
 Causes:
 Unknown;  exposure to radiation
 Pathogenesis – Leukemic cells:
 Are an immature type of WBC
 Capable of  rate of proliferation/have prolonged
life span
 Cannot perform function of mature leukocytes →
are ineffective as phagocytes
 Interfere with maturation of normal bone marrow cells
(including RBC & platelets)

60. Leukemia: Acute vs Chronic
 Acute:
 Sudden, stormy onset
 S/S related to  (mature) WBC,  RBC,  platelets
 ALL → 80% childhood acute leukemias
 AML → chiefly an adult disease
 Diagnosis based on:
 Blood/bone marrow tissue ↔ presence of immature WBC’s (blasts) –
may constitute 60-100% of cells

61. Leukemias: Acute vs Chronic
 Chronic
 More insidious onset
 May be discovered during a routine medical exam by a blood
count
 CLL → older adults
 Relatively mature lymphocytes that are immunologically incompetent
 CML → adults & children
 Leukocytosis with immature cell types

62.  Hodgkin’s disease
 Characterized by
PAINLESS, progressive,
rubbery enlargement of a
single node or group of
nodes – usually in neck
area
 Reed-Sternberg cell –
distinctive tumor cell found
with lymph biopsy
 GOOD PROGNOSIS
 Non-hodgkin’s
disease
 Also neoplastic disorder of
lymphoid tissue
 However, SPREADS EARLY
→ liver, spleen & bone marrow
 Also characterized by painless,
superficial lymphadenopathy;
also extranodal symptoms
 POORER PROGNOSIS than
Hodgkin’s
Malignant Lymphomas:
Neoplasms Of Cells Derived From
Lymphoid Tissue

63. Lymphadenopathy: Locations

64. Pluripotential stem cell
Acute undifferentiated leukemia
Lymphoid stem cell
Hodgkins lymphoma
Acute lymphoblastic leukemia
Acute erytholeukemia
Erythroid stem cell
Chronic granulocytic
leukemia
Erythrocyte
Chronic lymphocytic
leukemia
T-cell B-cell
Multiple
myeloma
Plasma cell
Humoral immunity (antibody)
(IgG, IgM, IgA,
IgD, IgE)
Non-Hodgkin
lymphoma
Cell-mediated
immunity, graft vs
host response
Acute
megakaryocytic
leukemia
Acute
myelocytic
leukemia
Megakaryocytic
stem cell
Chronic myelocytic
leukemia
Megakaryocyte
Platelet
Granulocytic stem cell
Promonocyte Monocyte
Poycythemia
vera, chronic
myelocytic
leukemia
Myeloblast
Eosinophil
Basophil
Promyelocyte
Myelocyte
Metamyelocyte
Segmented neutrophil
Cell-specific Leukemias