Transcript White Blood Cell Pathophysiology

White Blood Cell
Pathophysiology
Presented by: Wanda Lovitz, APRN
Objectives: WBCs
•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)
Drugs to Know

filgrastim (Neupogen)
Components of the
Hematologic System

Composition of Blood:

Plasma

Plasma proteins


albumin
Blood cells

FORMED IN BONE MARROW

“HEMATOPOIESIS”

Erythrocytes

Leukocytes

Thrombocytes
Composition Of Blood
Fresh Frozen Plasma
(FFP)
►►►
WBC/
Plts
Plasma: 55%
Leukocytes & Thrombocytes: <1%
Erythrocytes: 45%
Primary Function of Blood Cells



Erythrocytes = OXYGEN transport
LEUKOCYTES = protect body from INFECTION
Platelets = promote blood COAGULATION
Transfusing Blood Products:
platelets, whole blood, packed cells,
albumin, and fresh frozen plasma
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
 Lymphoid

Primary

THYMUS


Key in newborn immune response
BONE MARROW *


organs
Red/yellow; origin of hematopoiesis
Secondary

SPLEEN


Fetal hematopoiesis; has phagocytes; has lymphocytes
(immune); blood reservoir
LYMPH NODES

Filters pathogens;


TONSILS


enlarged/tender with infection (r/t  macrophages)
Mass of lymph tissue
PEYER PATCHES of small intestine
Lymphoid Organs:
(Link hematologic & immune
system)
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

Sternum

Extreme proximal portion of humerus/femur
Cranium
Manufactures billions of WBC’s
Spleen Location = upper left quadrant
Enlarged spleen = spleenomegaly
Palpating For Splenomegaly
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
Stem Cells: The Origin Of All Blood Cells
HEMATOPOIESIS
Pluripotential Stem Cell
MYELOID Stem Cells
Granulocyte;
Macrophage
Stem Cells
Granulocyte
Stem Cells
Megakaryocytic
Stem Cells
LYMPHOID Stem Cells
Erythropoietic
Stem Cells
Monocytic
Stem Cells
agranulocytes
NEUTROPHILS MONOCYTES &
EOSINOPHILS MACROPHAGES
& BASOPHILS
Megacaryocytes
& Platelets
Erythrocytes
LYMPHOCYTES
(T cells, B cells,
plasma cells)
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
Never Let Monkeys Eat Bananas!
The

five types of leukocytes, in order of prevalence
Never
(NEUTROPHILS)

Let
(Lymphocytes)

Monkeys
(Monocytes)

Eat
(Eosinophils)

Bananas
(Basophils)
Phagocytes = Neutrophils, Monocytes, Eosinophils, Basophils
The Process Of Phagocytosis
“Attack, Engulf, Destroy”
Clinical Evaluation of the
Hematologic System
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
Bone Marrow Aspiration/Biopsy: A Painful Procedure
Leukocytes:
2 Ways To Classify

Structure:

Granulocytes (Lifespan = 1-10 days)


Agranulocytes (Lifespan = days – months – years)


Neutrophils, eosinophils, basophils
Monocytes, lymphocytes
Function:

PHAGOCYTES (cells that ingest/digest bacteria)


Neutrophils, eosinophils, basophils, monocytes
IMMUNOCYTES (cells that create immunity)

Lymphocytes
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
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”
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
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%
“WBC W/Diff”:
What are we differentiating?

Granulocytes (phagocytes)




Lymphocytes


Neutrophils (50-67%)
Eosinophils (0-3%)
Basophils (0-2%)
(agranulocytes)
(24-40%)
Monocytes/macrophages (agranulocytes)

(4-9%)
{Remember…differential ALWAYS adds up to 100%}
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
Neutrophil: Segs & Bands

“Seg”mented neutrophils:


Band neutrophils:


Mature
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%
“Shift To The Left”: Many neutrophils, but not all of them mature
* Bands are horseshoe-shaped
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
S/P Organ Transplant: Neutropenic Precautions
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
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)
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)
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
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
Conditions That Alter WBC’s:

Leukocytosis ( WBC)




Leukopenia ( WBC)

Bone marrow depression
to physiologic stressors

Drug toxicity
(ie, surgery, anesthesia)

Autoimmune disease
Normal protective response

All types of infection
Tissue necrosis

(Lupus)
Malignancies,
Chemotherapeutic agents

Inflammatory disorders
CBC With Diff: NORMAL RANGES
CBC
(RBC, Hgb, Hct, Platelet count)
WBC count
5-10,000/mm³
WBC differential
SEGMENTED NEUTROPHILS
Band neutrophils
Lymphocytes
47-63%
0-4%
24-40%
Monocytes
4-9%
Eosinophils
0-3%
Basophils
0-2%
Example: WBC Diff With Bacterial Infection
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: Infectious Mononucleosis (Type of Virus)
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: Allergic Reaction With Resultant Asthma Attack
CBC
(RBC, Hgb, Hct, platelet count)
WBC count
11,700/mm³
WBC differential
Segmented neutrophils
39%
Band neutrophils
7%
Lymphocytes
Monocytes
Eosinophils
Basophils
Worms,Wheezes, and Weird Diseases
29%
3%
22%
1%
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
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
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
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
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
Mono: Sore throat with erythema & white exudate
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
Leukemias

Acute



ALL (acute lymphocytic leukemia)
AML (acute myelocytic leukemia)
Chronic


CLL (chronic lymphocytic leukemia)
CML (chronic myelocytic leukemia)
DEFINED BY:
1. SITE OF ORIGIN
a. myeloid stem cell
b. lymphoid stem cell
2. ACUTE VS CHRONIC
a. acute
b. chronic
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
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
HEMATOPOIESIS
Pluripotential Stem Cell
Myeloid Stem Cells
Granulocyte;
Macrophage
Stem Cells
Granulocyte
Stem Cells
Megakaryocytic
Stem Cells
Lymphoid stem cells
Erythropoietic
Stem Cells
Monocytic
Stem Cells
Neutrophils Monocytes &
Eosinophils Macrophages
& Basophils
Megacaryocytes
& Platelets
Erythrocytes
Lymphocytes:
(T cells, B cells,
plasma cells)
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
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)
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
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
Malignant Lymphomas:
Neoplasms Of Cells Derived From
Lymphoid Tissue

Hodgkin’s disease

Characterized by
Non-hodgkin’s
disease
PAINLESS, progressive,

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

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
Lymphadenopathy: Locations
Cell-specific Leukemias
Pluripotential stem cell
Acute undifferentiated leukemia
Lymphoid stem cell
Acute erytholeukemia
Hodgkins lymphoma
Acute lymphoblastic leukemia
Acute
megakaryocytic
leukemia
Erythroid stem cell
Chronic lymphocytic
Acute
myelocytic
leukemia
Granulocytic stem cell
Megakaryocytic
stem cell
Promonocyte
Chronic myelocytic
leukemia
Poycythemia
vera, chronic
myelocytic
leukemia
Monocyte
leukemia
Chronic granulocytic
leukemia
B-cell
T-cell
Erythrocyte
Multiple
myeloma
Eosinophil
Megakaryocyte
Non-Hodgkin
lymphoma
Myeloblast
Plasma cell
Basophil
Promyelocyte
Humoral immunity (antibody)
(IgG, IgM, IgA,
IgD, IgE)
Cell-mediated
immunity, graft vs
host response
Platelet
Myelocyte
Metamyelocyte
Segmented neutrophil