alterations of leukocyte, lymphoid, and hemostatic function chapter 27 mosby items and derived items...

Alterations of Leukocyte, Lymphoid, Alterations of Leukocyte, Lymphoid, and Hemostatic Functionand Hemostatic Function

Chapter 27Chapter 27

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

Alterations of Leukocyte FunctionAlterations of Leukocyte Function Deficiencies in the quality and quantity of Deficiencies in the quality and quantity of

leukocytes (leukopenia) leukocytes (leukopenia) Increased numbers of leukocytes Increased numbers of leukocytes

(leukocytosis) (leukocytosis) Many hematologic disorders are Many hematologic disorders are

malignanciesmalignancies Many nonhematologic malignancies metastasize Many nonhematologic malignancies metastasize

to bone marrow, affecting leukocyte productionto bone marrow, affecting leukocyte production


Alterations of Leukocyte FunctionAlterations of Leukocyte Function Quantitative disordersQuantitative disorders

Increases or decreases in cell numbersIncreases or decreases in cell numbers Bone marrow disorders or premature destruction Bone marrow disorders or premature destruction

of cellsof cells Response to infectious microorganism invasionResponse to infectious microorganism invasion

Qualitative disordersQualitative disorders Disruption of cellular functionDisruption of cellular function


Quantitative Alterations Quantitative Alterations of Leukocytesof Leukocytes

LeukocytosisLeukocytosis Counts higher than normalCounts higher than normal Leukocytosis is a normal protective physiologic Leukocytosis is a normal protective physiologic

response to stressorsresponse to stressors LeukopeniaLeukopenia

Counts lower than normalCounts lower than normal Leukopenia is always abnormalLeukopenia is always abnormal Low WBC count predisposes to infectionsLow WBC count predisposes to infections


Granulocytosis (Neutrophilia)Granulocytosis (Neutrophilia)

Evident in first stages of infection/inflammation Evident in first stages of infection/inflammation If need for neutrophils increases beyond the If need for neutrophils increases beyond the

supply, immature neutrophils (banded supply, immature neutrophils (banded neutrophils) released into the bloodneutrophils) released into the blood

Premature release detected in manual WBC Premature release detected in manual WBC differential and is termed a shift to the leftdifferential and is termed a shift to the left Leukemoid reactionLeukemoid reaction

When the population returns to normal, it is When the population returns to normal, it is termed a shift to the righttermed a shift to the right


Neutropenia Neutropenia

Reduction in circulating neutrophilsReduction in circulating neutrophils PrimaryPrimary

• Congenital Congenital Cyclic neutropenia and neutropenia with congenital Cyclic neutropenia and neutropenia with congenital

immunodeficiency diseasesimmunodeficiency diseases Multiple syndromesMultiple syndromes

• AcquiredAcquired Multiple conditions (hypoplastic anemia, aplastic anemia, Multiple conditions (hypoplastic anemia, aplastic anemia,

leukemias, lymphomas [Hodgkin, non-Hodgkin]; leukemias, lymphomas [Hodgkin, non-Hodgkin]; myelodysplastic syndrome)myelodysplastic syndrome)

SecondarySecondary


Neutropenia Neutropenia

CausesCauses Prolonged severe infectionProlonged severe infection Decreased productionDecreased production Reduced survivalReduced survival Abnormal neutrophil distribution and sequestration Abnormal neutrophil distribution and sequestration


Granulocytopenia Granulocytopenia (Agranulocytosis)(Agranulocytosis)

CausesCauses Interference with hematopoiesis Interference with hematopoiesis Immune mechanismsImmune mechanisms Chemotherapy destructionChemotherapy destruction Ionizing radiationIonizing radiation

Sepsis caused by agranulocytosis often Sepsis caused by agranulocytosis often results in death within 3 to 6 daysresults in death within 3 to 6 days


EosinophiliaEosinophilia

Hypersensitivity reactions trigger the Hypersensitivity reactions trigger the release of eosinophilic chemotactic factor of release of eosinophilic chemotactic factor of anaphylaxis from mast cells anaphylaxis from mast cells

Increased in allergic disorders Increased in allergic disorders Increased in parasitic invasionsIncreased in parasitic invasions


EosinopeniaEosinopenia

Decrease in circulation numbers of Decrease in circulation numbers of eosinophilseosinophils

Usually caused by migration of cells to Usually caused by migration of cells to inflammatory sitesinflammatory sites

Other causes Other causes Surgery, shock, trauma, burns, or mental Surgery, shock, trauma, burns, or mental

distress distress


BasophilsBasophils

Basophils account for only up to 1% of the Basophils account for only up to 1% of the circulating WBCscirculating WBCs

BasophiliaBasophilia Response to inflammation and hypersensitivity Response to inflammation and hypersensitivity

reactionsreactions BasopeniaBasopenia

Occurs in acute infections, hyperthyroidism, and Occurs in acute infections, hyperthyroidism, and long-term steroid therapylong-term steroid therapy


MonocytesMonocytes MonocytosisMonocytosis

Poor correlation with diseasePoor correlation with disease Usually occurs with neutropenia in later stages of Usually occurs with neutropenia in later stages of

infections infections Monocytes are needed to phagocytize organisms and Monocytes are needed to phagocytize organisms and

debrisdebris MonocytopeniaMonocytopenia

Very little known about this conditionVery little known about this condition• Prednisone treatmentsPrednisone treatments

• Hairy cell leukemiaHairy cell leukemia


LymphocytesLymphocytes LymphocytosisLymphocytosis

Acute viral infectionsAcute viral infections• Epstein-Barr virusEpstein-Barr virus

LymphocytopeniaLymphocytopenia Immune deficiencies, drug destruction, viral Immune deficiencies, drug destruction, viral

destructiondestruction


Infectious Mononucleosis (IM)Infectious Mononucleosis (IM) Acute, self-limiting infection of B Acute, self-limiting infection of B

lymphocytes transmitted by saliva through lymphocytes transmitted by saliva through personal contactpersonal contact

Commonly caused by the Epstein-Barr virus Commonly caused by the Epstein-Barr virus (EBV)—85%(EBV)—85% B cells have an EBV receptor siteB cells have an EBV receptor site Others viral agents resembling IMOthers viral agents resembling IM

• Cytomegalovirus (CMV), hepatitis, influenza, HIVCytomegalovirus (CMV), hepatitis, influenza, HIV


Infectious MononucleosisInfectious Mononucleosis Symptoms: fever, sore throat, swollen cervical Symptoms: fever, sore throat, swollen cervical

lymph nodes, increased lymphocyte count, and lymph nodes, increased lymphocyte count, and atypical (activated) lymphocytes; may affect atypical (activated) lymphocytes; may affect multiple systemsmultiple systems

Serious complications are infrequent (<5%)Serious complications are infrequent (<5%) Splenic rupture is the most common cause of deathSplenic rupture is the most common cause of death

Lab values: >50% lymphocytes and at least Lab values: >50% lymphocytes and at least 10% atypical lymphocytes10% atypical lymphocytes

Diagnostic testDiagnostic test Monospot qualitative test for heterophilic antibodies Monospot qualitative test for heterophilic antibodies

Treatment: symptomaticTreatment: symptomatic


LeukemiasLeukemias Malignant disorder of the blood and blood-Malignant disorder of the blood and blood-

forming organsforming organs Uncontrolled proliferation of malignant Uncontrolled proliferation of malignant

leukocytesleukocytes Overcrowding of bone marrow Overcrowding of bone marrow Decreased production and function of normal Decreased production and function of normal

hematopoietic cellshematopoietic cells


LeukemiasLeukemias Acute leukemiaAcute leukemia

Presence of undifferentiated or immature cells, Presence of undifferentiated or immature cells, usually blast cellsusually blast cells

Rapid onset with short survivalRapid onset with short survival Chronic leukemiaChronic leukemia

Predominant cell is mature but does not function Predominant cell is mature but does not function normallynormally

Slow progressionSlow progression


LeukemiasLeukemias

Acute lymphocytic leukemia (ALL)Acute lymphocytic leukemia (ALL) Least common overall but most common childhood Least common overall but most common childhood

leukemia (80%)leukemia (80%) Acute myelogenous leukemia (AML)Acute myelogenous leukemia (AML)

Most common adult leukemia (mean age, 67)Most common adult leukemia (mean age, 67)


LeukemiasLeukemias Chronic myelogenous leukemia (CML)Chronic myelogenous leukemia (CML)

Usually diagnosed in adultsUsually diagnosed in adults Chronic lymphocytic leukemia (CLL)Chronic lymphocytic leukemia (CLL)

Common in adults (70% asymptomatic at diagnosis)Common in adults (70% asymptomatic at diagnosis)• LymphadenopathyLymphadenopathy

• Suppression of humoral immunity Suppression of humoral immunity

• Increased infection with encapsulated bacteriaIncreased infection with encapsulated bacteria


LeukemiasLeukemias

Signs and symptoms of leukemias Signs and symptoms of leukemias Anemia, bleeding purpura, petechiae, ecchymosis, Anemia, bleeding purpura, petechiae, ecchymosis,

thrombosis, hemorrhage, DIC, infection, weight loss, thrombosis, hemorrhage, DIC, infection, weight loss, bone pain, elevated uric acid, and liver, spleen, and bone pain, elevated uric acid, and liver, spleen, and lymph node enlargementlymph node enlargement

Clonal disorder in that a single progenitor cell Clonal disorder in that a single progenitor cell undergoes malignant transformationundergoes malignant transformation


LymphadenopathyLymphadenopathy Enlarged lymph nodes that become palpable Enlarged lymph nodes that become palpable

and tenderand tender Local lymphadenopathyLocal lymphadenopathy

Drainage of an inflammatory lesion located near Drainage of an inflammatory lesion located near the enlarged nodethe enlarged node

General lymphadenopathyGeneral lymphadenopathy Occurs in the presence of malignant or Occurs in the presence of malignant or

nonmalignant diseasenonmalignant disease


LymphadenopathyLymphadenopathy CausesCauses

Neoplastic diseaseNeoplastic disease Immunologic or inflammatory conditionsImmunologic or inflammatory conditions Endocrine disordersEndocrine disorders Lipid storage diseasesLipid storage diseases


LymphadenopathyLymphadenopathy


Malignant LymphomasMalignant Lymphomas

Malignant transformation of a lymphocyte and Malignant transformation of a lymphocyte and proliferation of lymphocytes, histiocytes, their proliferation of lymphocytes, histiocytes, their precursors, and derivatives in lymphoid tissues precursors, and derivatives in lymphoid tissues

Two major categoriesTwo major categories Hodgkin lymphomaHodgkin lymphoma

• Linked to EBVLinked to EBV Non-Hodgkin lymphomaNon-Hodgkin lymphoma

Lymphoblastic lymphomaLymphoblastic lymphoma


Hodgkin LymphomaHodgkin Lymphoma

Reed-Sternberg cells in the lymph nodesReed-Sternberg cells in the lymph nodes These cells necessary for diagnosis, but not specific These cells necessary for diagnosis, but not specific

to Hodgkin lymphomato Hodgkin lymphoma Classical Hodgkin lymphomaClassical Hodgkin lymphoma Nodular lymphocyte predominant Hodgkin Nodular lymphocyte predominant Hodgkin

lymphomalymphoma B cell in the germinal center that has not undergone B cell in the germinal center that has not undergone

successful immunoglobulin gene rearrangement but successful immunoglobulin gene rearrangement but has undergone apoptosishas undergone apoptosis



Physical findingsPhysical findings Adenopathy, mediastinal mass, splenomegaly, and Adenopathy, mediastinal mass, splenomegaly, and

abdominal massabdominal mass SymptomsSymptoms

FeverFever, , weightweight loss, nightloss, night sweatssweats, , prurituspruritus Laboratory findingsLaboratory findings

Thrombocytosis, leukocytosis, eosinophilia,Thrombocytosis, leukocytosis, eosinophilia, elevatedelevated erythrocyte sedimentation rate (ESR), elevatederythrocyte sedimentation rate (ESR), elevated alkalinealkaline phosphatasephosphatase

Paraneoplastic syndromesParaneoplastic syndromes


Non-Hodgkin LymphomaNon-Hodgkin Lymphoma Generic term for diverse group of Generic term for diverse group of

lymphomaslymphomas The lymphomas can be differentiated based The lymphomas can be differentiated based

onon etiology, unique features, and response etiology, unique features, and response to therapiesto therapies

Non-Hodgkin lymphomas are linked toNon-Hodgkin lymphomas are linked to chromosome translocations, viral and chromosome translocations, viral and bacterial infections, environmental agents, bacterial infections, environmental agents, immunodeficiencies, and autoimmune immunodeficiencies, and autoimmune disordersdisorders


Non-Hodgkin LymphomaNon-Hodgkin Lymphoma Clonal expansion of B cells (85%), T cells, Clonal expansion of B cells (85%), T cells,

and/or NK cellsand/or NK cells Changes in proto-oncogenes and tumor-Changes in proto-oncogenes and tumor-

suppressor genes contribute to cell suppressor genes contribute to cell immortality and thus an increase in immortality and thus an increase in malignant cells malignant cells


Burkitt LymphomaBurkitt Lymphoma Most common type of non-Hodgkin Most common type of non-Hodgkin

lymphoma in childrenlymphoma in children A very fast-growing tumor of the jaw and A very fast-growing tumor of the jaw and

facial bonesfacial bones Epstein-Barr virus is found in nasopharyngeal Epstein-Barr virus is found in nasopharyngeal

secretions of individualssecretions of individuals


Burkitt LymphomaBurkitt Lymphoma


Plasma Cell MalignanciesPlasma Cell Malignancies Multiple MyelomaMultiple Myeloma WaldenstrWaldenströömm


Multiple MyelomaMultiple Myeloma

Proliferation of plasma cellsProliferation of plasma cells The tumor may be solitary or multifocal The tumor may be solitary or multifocal

(multiple myeloma)(multiple myeloma) The malignant plasma cells produce The malignant plasma cells produce

abnormally large amounts of one class of abnormally large amounts of one class of immunoglobulin or incomplete immunoglobulinimmunoglobulin or incomplete immunoglobulin The unattached light chains of the immunoglobulins The unattached light chains of the immunoglobulins

(Bence Jones proteins) can pass through the (Bence Jones proteins) can pass through the glomerulus and damage the renal tubular cellsglomerulus and damage the renal tubular cells


Multiple MyelomaMultiple Myeloma Increased osteoclastic bone destructionIncreased osteoclastic bone destruction Hypercalcemia (13%), renal failure (19%), Hypercalcemia (13%), renal failure (19%),

anemia (72%), bone lesions (80%)anemia (72%), bone lesions (80%) Clinical manifestationsClinical manifestations

Cortical and medullary bone lossCortical and medullary bone loss Skeletal painSkeletal pain Recurring infections due to loss of the humoral Recurring infections due to loss of the humoral

immune responseimmune response


Alterations in Splenic FunctionAlterations in Splenic Function

SplenomegalySplenomegaly Hypersplenism Hypersplenism Congestive splenomegalyCongestive splenomegaly Infiltrative splenomegalyInfiltrative splenomegaly Removal of the spleenRemoval of the spleen

Increased WBCs and plateletsIncreased WBCs and platelets RBC abnormalitiesRBC abnormalities


Disorders of PlateletsDisorders of Platelets ThrombocytopeniaThrombocytopenia

Platelet count <100,000/mmPlatelet count <100,000/mm33

• <50,000/mm<50,000/mm33—hemorrhage from minor trauma—hemorrhage from minor trauma

• <15,000/mm<15,000/mm33—spontaneous bleeding—spontaneous bleeding

• <10,000/mm<10,000/mm33—severe bleeding—severe bleeding

Causes:Causes:• Hypersplenism, autoimmune disease, hypothermia, and Hypersplenism, autoimmune disease, hypothermia, and

viral or bacterial infections that cause DICviral or bacterial infections that cause DIC


Disorders of PlateletsDisorders of Platelets

Immune thrombocytopenic purpura (ITP)Immune thrombocytopenic purpura (ITP) IgG antibody targets platelet glycoproteinsIgG antibody targets platelet glycoproteins Antibody-coated platelets are sequestered and Antibody-coated platelets are sequestered and

removed from the circulationremoved from the circulation Acute form develops after viral infectionsAcute form develops after viral infections

• One of the most common childhood bleeding disordersOne of the most common childhood bleeding disorders ManifestationsManifestations

• Petechiae and purpura, progressing to major hemorrhagePetechiae and purpura, progressing to major hemorrhage


Disorders of PlateletsDisorders of Platelets Thrombotic thrombocytopenic purpura (TTP)Thrombotic thrombocytopenic purpura (TTP)

A thrombotic microangiopathyA thrombotic microangiopathy• Platelets aggregate, form microthrombi, and cause Platelets aggregate, form microthrombi, and cause

occlusion of arterioles and capillariesocclusion of arterioles and capillaries

Chronic relapsing TTPChronic relapsing TTP Acute idiopathic TTPAcute idiopathic TTP


Disorders of PlateletsDisorders of Platelets Essential (primary) thrombocythemiaEssential (primary) thrombocythemia

Thrombocythemia is characterized by platelet Thrombocythemia is characterized by platelet counts >600,000/mmcounts >600,000/mm33

Myeloproliferative disorder of platelet precursor Myeloproliferative disorder of platelet precursor cells cells • Megakaryocytes in the bone marrow are produced in Megakaryocytes in the bone marrow are produced in

excessexcess

Microvasculature thrombosis occursMicrovasculature thrombosis occurs


Alterations of Platelet FunctionAlterations of Platelet Function

Qualitative alterations demonstrate an Qualitative alterations demonstrate an increased bleeding time in the presence of a increased bleeding time in the presence of a normal platelet countnormal platelet count

Disorders result from platelet membrane Disorders result from platelet membrane glycoprotein and von Willebrand factor glycoprotein and von Willebrand factor deficienciesdeficiencies

ManifestationsManifestations Petechiae, purpura, mucosal bleeding, gingival Petechiae, purpura, mucosal bleeding, gingival

bleeding, and spontaneous bruisingbleeding, and spontaneous bruising Disorders can be congenital or acquiredDisorders can be congenital or acquired


Alterations of CoagulationAlterations of Coagulation Vitamin K deficiencyVitamin K deficiency

Vitamin K is necessary for synthesis and regulation of Vitamin K is necessary for synthesis and regulation of prothrombin, the prothrombin factors (II, VII, XI, X), and prothrombin, the prothrombin factors (II, VII, XI, X), and proteins C and S (anticoagulants)proteins C and S (anticoagulants)

Liver diseaseLiver disease Causes broad range of hemostasis disordersCauses broad range of hemostasis disorders

• Defects in coagulation, fibrinolysis, and platelet number and Defects in coagulation, fibrinolysis, and platelet number and functionfunction


Disseminated Intravascular Disseminated Intravascular Coagulation (DIC)Coagulation (DIC)

Complex, acquired disorder: clotting and Complex, acquired disorder: clotting and hemorrhage simultaneously occurhemorrhage simultaneously occur Sepsis, cancer, trauma, blood transfusionSepsis, cancer, trauma, blood transfusion

Result of increased protease activity in the Result of increased protease activity in the blood caused by unregulated release of blood caused by unregulated release of thrombin with subsequent fibrin formation and thrombin with subsequent fibrin formation and accelerated fibrinolysisaccelerated fibrinolysis

Endothelial damage is primary initiatorEndothelial damage is primary initiator



Blockage of blood flow to organs, resulting in Blockage of blood flow to organs, resulting in multiple organ failuremultiple organ failure

Magnitude of clotting may result in consumption Magnitude of clotting may result in consumption of platelets and clotting factors, leading to of platelets and clotting factors, leading to severe bleedingsevere bleeding



The amount of activated thrombin exceeds The amount of activated thrombin exceeds the body’s antithrombins and the thrombin the body’s antithrombins and the thrombin does not remain localizeddoes not remain localized

The widespread thromboses created cause The widespread thromboses created cause widespread ischemia, infarction, and organ widespread ischemia, infarction, and organ hypoperfusionhypoperfusion



By activating the fibrinolytic system (plasmin), By activating the fibrinolytic system (plasmin), person’s fibrin degradation product and person’s fibrin degradation product and DD-dimer -dimer levels increaselevels increase

Due to the person’s clinical state, the disorder Due to the person’s clinical state, the disorder has a high mortality rate has a high mortality rate

Treatment is to remove the stimulusTreatment is to remove the stimulus



Clinical signs and symptoms demonstrate Clinical signs and symptoms demonstrate wide variabilitywide variability Bleeding from venipuncture sitesBleeding from venipuncture sites Bleeding from arterial linesBleeding from arterial lines Purpura, petechiae, and hematomasPurpura, petechiae, and hematomas Symmetric cyanosis of the fingers and toesSymmetric cyanosis of the fingers and toes


Thromboembolic DiseaseThromboembolic Disease Arterial thrombiArterial thrombi

Defects in proteins involved in hemostasisDefects in proteins involved in hemostasis Venous thrombiVenous thrombi

Variety of clinical disorders or conditionsVariety of clinical disorders or conditions Hypercoagulabilty (thrombophilia)Hypercoagulabilty (thrombophilia)

AcquiredAcquired Mutations in coagulation proteins, fibrinolytic Mutations in coagulation proteins, fibrinolytic

proteins, platelet receptorsproteins, platelet receptors Triad of VirchowTriad of Virchow

alterations of leukocyte, lymphoid, and hemostatic function chapter 27 mosby items and derived items...

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