chapter 24: disorder of white blood cells & lymphoid tissues

what are the two components of blood?

• cellular (45%) and plasma (55%)

• blood is 8% of body weight, w/ avg adult having ~4.6-6 liters

what consist of cellular components?

• erythrocytes (rbc)

• leukocytes (wbc)

  • neutrophils, eosinophils, basophila, monocytes, lymphocytes

• thrombocytes (platelets)

what consist of plasma?

• pale yellow fluid: ??

• 92% water + 8% proteins (albumin, fibrinogen, globulins)

blood transports:

• oxugen, carbon dioxide, hormones, nutrients, and metabolic waste products

blood regulates what and what does it carry?

• it regulates body temp and acid-base balance

• carries cells + antibodies that fight infection

centrifugation

• lab process that spins a blood sample at high speeds to separate it into its different parts (liquid, white cells, and red cells) based on their weight

• performed in lab before blood testing

white blood cells

• aka leukocytes, are also immune cells that protect body against infections, foreign substances and disease

• leukocytes classified as granular and agranular

granular (leukocyte classification)

• contains vesicles that appear when cells are stained

• neutrophils, eosinophils, basophils

agranular (leukocyte classification)

• contains no granules

• lymphocytes, monocytes

what are all the leukocytes?

neutrophils, eosinophils, basophils, monocytes, macrophages, t cells, b cells, nk cells

neutrophils (leukocyte)

• most abundant wbc

• destroy bacteria through phagocytosis

eosinophils (leukocyte)

• fight parasites

• involved in allergic reactions

basophils (leukocyte)

• release histamine and heparin

• participate in inflammation and allergic responses

monocytes (leukocyte)

circulates in bloodsteram

macrophages (leukocyte)

form when monocytes enter tissues, engulf pathogens (phagocytosis)

t cells (leukocyte)

coordinates immune response

b cells (leukocyte)

produces immunoglobulins

NK cells

part of innate immunity

hematopoiesis

formation and developing all types of blood cells in body

pluripotent stem cells give rise to what?

give rise to lymphoid stem cells and myeloid stem cells

leukopoiesis is the process of what?

• process of producing wbc (leukocytes) in bone marrow

• myeloid stem cells and lymphoid stem cells involved

in leukopoiesis, myeloid stem cells produce what?

granulocytes and monocytes

in leukopoiesis, lymphoid stem cells produce what?

produce t cells, b cells, and NK cells

hematopoietic growth factors is what?

• hormone-like regulatory molecules that help in survival, differentiation, and proliferation of progenitor cells

• functional activation of mature cells

lineage-specific growth factors stimulate what?

development of specific WBC types

granulocyte colony-stimulating factor (lineage-specific growth factors)

stimulates production of neutrophils

macrophage colony-stimulating factor (lineage-specific growth factors)

stimulates development of monocytes and macrophages

interleukin-5 (IL-5) (lineage-specific growth factors)

promotes growth and development of eosinophils

interleukin-7 (IL-7) (lineage-specific growth factors)

supports the dev of lymphocytes, especially b and t cells

differenctial WBC count measures what?

the percentage and absolute number of each type of leukocute in blood

shift to the left refers to what in diff WBC count?

• refers to increase in immature neutrophils (bands) in peripheral blood

• indicates that blood marrow releases neutrophils early in respones to increase demand

whats the normal neutrophil maturation?

myeloblast → promyelocyte → myelocyte → metamyelocyte → band neutrophil → segmented (mature) neutrophil

during a left shift, the bone marrow release more:

• band neutrophils (most common)

• occasionally metamyelocytes and myelocytes in severe cases

lymphatic system consist of:

• lymphatic vessels

• lymph nodes

• lymphoid tissues

• thymus

• spleen

four major functions of lymphatic system:

• defends body against pathogens

• produces and matures lymphocytes

• filters lymph and blood

• supports adaptive (specific) immunity

lymphoid tissues are categorized into:

primary and secondary

primary lymphoid tissues are:

• where lymphocytes become mature and immunocompetent

• bone marrow, thymus

bone marrow (primary lymphoid tissue)

site of dev of lymphocyte progenitor cells + maturation of immature b cells

thymus (primary lymphoid tissue)

trains and matures T-cells, which protect the body from viruses, bacteria, and infection + is the largest and most active during childhood and gradually shrinks and turns into fat after puberty

secondary lymphoid tissues are:

• where lymphocytes are activated by antigens

• lymph nodes, spleen, MALT

lymph nodes (secondary lymphoid tissue)

small, bean-shaped structures in your immune system that act as filters for your body's fluid??

spleen (secondary lymphoid tissue)

white pulp contains concentrated areas of b and t cells, whereas red pulp contains venous sinuses that filter blood by removing pathogens + senescent erythrocytes

MALT (secondary lymphoid tissue)

non-capsulated lymphoid tissue in GI tract, respiratory tract, and genitourinary system

non-neoplastic disorders

non-malignant disorders of WBCs are more common than malignant disorders

some disorders (neo-plastic) affect count of single type of WBC, whereas others affect:

counts of multiple or all five types of WBCs

common neoplastic disorders involve changes in:

• neutrophil or lymphocyte count

• -penia = deficiency, lack, or abnormal reduction in the number of something within the body

• -cytosis = an abnormal increase or elevated condition in the number of cells, typically blood cells

absolute neutrophil count (ANC)

• actual number of neutrophils circulating in blood

• WBC = total wbc count

• segs = % mature neutrophils

• bands = % immature neutrophils

• ex: Total WBC count = 10,000 cells/μL, Segs = 60%,

  Bands = 5% : ANC=10,000×60+5/100

  • ANC = 6,500 cells/μL

leukopenia

• decrease in total number of wbc in blood

• most commonly involves neutrophils, leading to neutropenia

neutropenia

• a condition where you have an abnormally low number of neutrophils

• ANC <1000 cells/μL

• normal range: 2000-7000/μL

• increased risk for infection

agranulocytosis

• nearly complete absence of neutrophils

• extremely high risk of life-threatening infection

types of neutropenia

congenital and acquired

congenital neutropenia

present at birth due to: genetic disorders affecting neutrophil production

acquired neutropenia

develops later in life due to: chemotherapy, viral infections, autoimmune diseases, bone marrow diseases

patients become prone to recurrent infections:

bacterial/fungal, immunosuppressed

common features of neutropenia:

• frequent or recurrent infections

• fever: may be only sign

treatment of neutropenia:

• antimicrobial agents

• specific hematopoietic growth factors

  • ex: GM-CSF

neutrophilic leukocytosis (granulocytosis):

• abnormally increased total WBC count caused mainly by an increase in neutrophils

• more than: 7500/μL

• normal range: 2000-7000/μL

most common cause of neutrophilic leukocytosis:

• acute bacterial infection

• evident in first stages of infection or inflammation

other causes of neutrophilic leukocytosis:

• inflammation, corticosteroid use, certain blood cancers, such as leukemia

• if need for neutrophils increases beyond supply, then immature neutrophils are released into blood

• premature release of immature leukocytes is termed a shift-to-the-left

lymphocytopenia (lymphopenia):

• an abnormally low number of lymphocytes in blood

• less than: 1000/μL

• normal: 1000-4500/μL

common causes of lymphocytopenia (lymphopenia):

• inherited genetic disorders

• chemotherapy and radiation therapy

• viral infections

patients become prone to recurrent infections from lymphocytopenia:

initial infections may not be fully eliminated, allowing pathogens to persist and cause repeated infections

treatment for lymphocytopenia (lymphopenia)

• antimicrobial agents

• IV immunoglobulins

lymphocytic leukocytosis

• increased total WBC count caused mainly by increase in lymphocytes

• more than: 4500/μL

• normal range: 1000-4500/μL

common causes of lymphocytic leukocytosis

• infectious mononucleosis: contagious viral illness known as Epstein-Barr virus that spreads through saliva and causes extreme fatigue, a severe sore throat, fever, and swollen lymph nodes

• chronic immune mediated inflammation (ex: RA)

• chronic lymphocytic leukemia (CLL)

treatment of lymphocytic leukocytosis:

focus on underlying cause

malignant lymphomas

• solid malignant tumors originating in peripheral lymphoid tissues (typically lymph nodes)

• two main categories: hodgkin’s lymphomas (HLs), non-hodgkin’s lymphomas

hodgkin’s lymphomas (HLs)

• originate in single lymph node or a group of adjacent lymph nodes

• neck, chest pits

non-hodgkin’s lymphomas (HLs)

• originate in multiple lymph nodes or multiple groups of lymph nodes

• chest, pits, abdomen, groin

non-hodgkin lymphomas are a heterogeneous:

group of cancers affecting lymphocytes at different stages of development

disruption of normal lymphocyte maturation can result in:

• various NHL subtypes

• exact cause remains unknown

• associated infectious agents include:

  • epstein-barr virus (EBV)

  • human t-lymphotropic virus type 1 (HTLV-1)

mature b-cell lymphomas originate from:

• germinal center of b cells or activated b cells that have exited the germinal center

• most common subtype of non-hodgkin lymphoma (NHL)

common b-cell lymphoma subtypes include:

• follicular lymphoma

• diffuse large b-cell lymphoa

• mantle cell lymphoma

follicular lymphoma (common b-cell lymphoma)

indolent (slow-growing)

diffuse large b-cell lymphoma (DLBCL) (common b-cell lymphoma)

aggressive, fast growing, most common btwn 60-70 years

mantle cell lymphoma

aggressive, characterized by rapid disease progression and poor prognosis

follicular lymphoma

normal lymph node architecture is replaced by malignant lymphoid follicles in a back-to-back pattern

burkitt lymphoma

• highly aggressive b-cell non-hodgkin lymphoma

• fast-growing tumor of jaw and facial bones = tumor of jaw distorts a child’s face

• classified based on geographic distribution = endemic (african), sporadic

endemic (african) burkitt lymphoma

• a fast-growing type of non-hodgkin b-cell cancer that primarily affects children in equatorial africa

• closely associated w/ EBV infection (100% of patients w/ endemic african burkitt lymphoma show evidence of prev EBV infection)

sporadic burkitt lymphoma

• fast-growing, rare subtype of b-cell non-hodgkin lymphoma that occurs worldwide

• less frequently associated w/ EBV

NHL clinical manifestations:

• localized or generalized painless lymphadenopathy

• nodal enlargement + transformation over months or yrs

• retroperitoneal + abdominal masses w/ symptoms of abdominal fullness and back pain

• ascites (fluid in peritoneal cavity) + leg swelling

NHL diagnostic tests:

biopsy is primary means of diagnosis

hodgkin lymphoma (HL) is distinguished by:

presence of abnormal Reed-Sternberg cell

HL commonly occurs in two age groups:

• young adults: most commonly affects adolescents and young adults aged 15–35 (or roughly 20–40 depending on the exact source), making it the most frequent cancer diagnosed in teenagers aged 15–19

• older adults: occurs again later in life, typically in adults aged 55 and older

HL clinical manifestations:

• enlarged painless neck lymph nodes

  • usually begins in simple lymph nodes or chain of nodes

• lymphadenopathy, causing pressure or obstruction

• mediastinal mass

• fever, weight loss, night sweats, pruritus, fatigue

description of hodgkin lymphoma

• classic reed—sternberg cell, mirror-image nuclei

• “owl’s eye” two large nuclear lobes, each w/ prominent red nucleolus surrounded by clear halo

stage 1 of hodgkin lymphoma

• cancer found in one lymph node region or one lymphoid organ

• ex: spleen or thymus

stage 2 of hodgkin lymphoma

• cancer involves two or more lymph node regions on same side of diaphragm (either above or below)

• may also involve nearby extranodal site

stage 3 hodgkin lymphoma

• cancer present in lymph node regions on both sides of diaphragm

• may also involve spleen or nearby extranodal organ

stage 4 of hodgkin lymphoma

cancer spread widely to one or more extranodal organs, such as: bone marrow, live, lungs, bones

leukemia

• malignant neoplasms of hematopoietic precursor cells

• characterized by uncontrolled growth of immature wbc

• these abnormal cells replace normal bone marrow cells, affecting blood cell production

• approx 60k-62k new cases diagnosed annually

  • most common cancer in children + adolescents

  • accounts for approx 29% childhood cancers

leukemia means white blood, first used by rudolf virchow, which described:

the abnormal increase in wbc compared w/ rbc

leukemias are classified based on:

• predominant cell type

  • lymphocytic (lymphoid)

  • myelogenous (myeloid)

• disease progression

  • acute

  • chronic

• french-american-british (FAB) classification identifies 4:

  • ALL: acute lymphocytic (lymphoblastic) leukemia

  • CLL: chronic lymphocytic leukemia

  • AML: acute myelogenous (myeloblastic) leukemia

  • CML: chronic myelogenous leukmeia

acute leukemia:

• presence of undiff or immature cells, usually blast cells

• sudden onset, rapid progression w/ short survival

  • symptoms severe + dev quickly

chronic leukemia

• predominant cell mature but not function normally

• slow, gradual onset w/ slow progression

• symptoms mild or absent initially, dev over months or years

lymphocytic leukemias: origin, common sites of infiltration, and clinical consequences

• origin: dev from immature lymphocytes + precusor cells in bone marrow

• csoi: spleen, lymph nodes, cns

• cc: impairs normal immune function + lymphocyte production

myelogenous leukemias: origin, interferes w/ maturation of, and clinical consequences

• origin: arise from pluripotent myeloid stem cells in bone marrow

• iwmo: granulocytes, erythrocytes, thrombocytes

• cc: increase risk of infections, anemia, bleeding tendencies

exact cause of leukemia:

• largely unknown

• develops due to genetic + environmental factors

molecular basis for leukemia:

• develops due to disruption of genes + chromosomal abnormalities controlling blood cell dev, growth, and survival

• leads to uncontrolled prod of abnorm blood cells

molecular has improved w/:

• diagnosis + classification into specific subtypes

• targeted treatment selection

• monitoring of treatment response + disease progression