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Alterations of Leukocyte,
Lymphoid, and Hemostatic
Function
Chapter 27
1
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
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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
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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
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
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Neutropenia


Reduction in circulating neutrophils
Causes:




Prolonged severe infection
Decreased production
Reduced survival
Abnormal neutrophil distribution and
sequestration
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Granulocytopenia
(Agranulocytosis)

Causes:




Interference with hematopoiesis
Immune mechanisms
Chemotherapy destruction
Ionizing radiation
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Eosinophilia



Hypersensitivity reactions trigger the
release of eosinophilic chemotactic factor of
anaphylaxis from mast cells
Increased in allergic disorders
Increased in parasitic invasions
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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
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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
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Monocytes

Monocytosis




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
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Lymphocytes

Lymphocytosis

Acute viral infections


Epstein-Barr virus
Lymphocytopenia

Immune deficiencies, drug destruction, viral
destruction
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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
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Infectious Mononucleosis


Symptoms: fever, sore throat, swollen cervical
lymph nodes, increased lymphocyte count, and
atypical (activated) lymphocytes
Serious complications are infrequent (<5%)



>50% lymphocytes and at least 10% atypical
lymphocytes
Diagnostic test


Splenic rupture is the most common cause of death
Monospot qualitative test for heterophilic antibodies
Treatment: symptomatic
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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
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Leukemias




Acute lymphocytic leukemia (ALL)
Acute myelogenous leukemia (AML)
Chronic myelogenous leukemia (CML)
Chronic lymphocytic leukemia (CLL)
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Leukemias
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Leukemias

Signs and symptoms of leukemias

Anemia, bleeding purpura, petechiae,
ecchymosis, thrombosis, hemorrhage, DIC,
infection, weight loss, bone pain, elevated uric
acid, and liver, spleen, and lymph node
enlargement
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Philadelphia Chromosome
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Myeloma



Proliferation of plasma cells
The tumor may be solitary or multifocal (multiple
myeloma)
The malignant plasma cells produce abnormally
large amounts of one class of immunoglobulin or
incomplete immunoglobulin

The unattached light chains of the immunoglobulins
(Bence Jones proteins) can pass through the glomerulus
and damage the renal tubular cells
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Myeloma


Multiple myeloma causes increased
osteoclastic bone destruction
Clinical manifestations



Cortical and medullary bone loss
Skeletal pain
Recurring infections due to loss of the humoral
immune response
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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
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Lymphadenopathy
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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
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Hodgkin Lymphoma

Characterized by the presence of ReedSternberg 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
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Hodgkin Lymphoma

Physical findings


Symptoms


Fever, weight loss, night sweats, pruritus
Laboratory findings


Adenopathy, mediastinal mass, splenomegaly,
and abdominal mass
Thrombocytosis, leukocytosis, eosinophilia,
elevated ESR, and elevated alkaline phosphatase
Paraneoplastic syndromes
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Hodgkin Lymphoma
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Hodgkin Lymphoma
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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
Non-Hodgkin lymphomas are linked to
chromosome translocations, viral and
bacterial infections, environmental agents,
immunodeficiencies, and autoimmune
disorders
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Non-Hodgkin Lymphoma


Clonal expansion of B cells, T cells, and/or
NK cells
Changes in proto-oncogenes and tumorsuppressor genes contribute to cell
immortality and thus an increase in
malignant cells
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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
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Burkitt Lymphoma
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Alterations in Splenic Function




Splenomegaly
Hypersplenism
Congestive splenomegaly
Infiltrative splenomegaly
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Disorders of Platelets

Thrombocytopenia

Platelet count <100,000/mm3




<50,000/mm3—hemorrhage from minor trauma
<15,000/mm3—spontaneous bleeding
<10,000/mm3—severe bleeding
Causes:

Hypersplenism, autoimmune disease, hypothermia,
and viral or bacterial infections that cause
disseminated intravascular coagulation (DIC)
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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
Manifestations

Petechiae and purpura, progressing to major
hemorrhage
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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
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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
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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
Manifestations


Petechiae, purpura, mucosal bleeding, gingival
bleeding, and spontaneous bruising
Disorders can be congenital or acquired
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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
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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
Endothelial damage is the primary initiator
of DIC
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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
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Disseminated Intravascular
Coagulation (DIC)



By activating the fibrinolytic system
(plasmin), the patient’s fibrin degradation
product (FDP) and D-dimer levels will
increase
Due to the patient’s clinical state, the
disorder has a high mortality rate
Treatment is to remove the stimulus
41
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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
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