ch. 24: disorders of WBCs and lymphoid tissues -

what % of body weight is made up of blood?

8%

how many L of blood does the average adult have?

4.6-6L

what % of blood is made of cellular components and what % is made of plasma?

• 45% cellular components

• 55% plasma

what are the cellular components of blood?

• erythrocytes (RBCs)

• leukocytes (WBCs)

• thrombocytes (platelets)

what are the 5 different kinds of leukocytes?

• neutrophils

• basophils

• eosinophils

• monocytes

• lymphocytes

what % of plasma is water and what % is protein?

• 92% water

• 8% protein

what are the proteins found in plasma and what do they do?

• albumin

  • most abundant

  • 60% of protein in plasma

  • regulate osmotic pressure

• fibrinogen

  • clotting factor

• globulin

  • makes up IGs

what is centrifugation?

separating blood by components

granular vs. agranular WBCs

• granular contain vesicles that appear when stained

• agranular do not contain visible vesicles

what do neutrophils do?

• most abundant WBC

• destroy bacteria through phagocytosis

what do eosinophils do?

• fight parasites

• involved in allergic reactions

what do basophils do?

• release histamine and heparin

• participate in inflammation and allergic responses

what do monocytes do?

circulate in bloodstream

what do macrophages do?

• form when monocytes enter tissues

• engulf pathogens

what do T cells do?

• ID and attack pathogens

what do B cells do?

• produce antibodies

what is leukopoiesis?

process of making WBCs in bone marrow

what is hematopoiesis?

making the components of blood from pluripotent stem cells

what is the original stem cell that all cellular blood components come from?

pluripotent stem cells

pluripotent stem cells can split into myeloid stem cells, which then create what?

granulocytes, monocytes, megakaryocytes, and erythrocytes

pluripotent stem cells can split into lymphoid stem cells, which then create what?

T cells, B cells, and NK cells

after a pluripotent stem cells becomes a myeloid stem cell, and then a granulocyte, what is created next?

• eosinophils

• neutrophils

• basophils

what do granulocyte colony-stimulating factors do?

stims neutrophil production

what do macrophage colony-stimulating factors do?

stims monocyte and macrophage development

what does interleukin-5 do?

promotes growth and development of eosinophils

what does interleukin-7 do?

supports the development of lymphocytes, especially B and T cells

what is a differential WBC count?

% and number of each WBC in blood

what is a left-shift WBC count?

indicates an increase in immature neutrophils (called bands) in blood

what does a left-shift WBC count signify in terms of what is happening in the bone marrow?

• the bone marrow is releasing neutrophils early because there is an increased demands

  • metamyelocyte & myelocytes are also released in extreme cases

what is the normal pathway of neutrophil maturation?

myeloblast —> promyelocyte —> myelocyte —> metamyelocyte —> band neutrophil —> segmented (mature) neutrophil

what does primary lymphoid tissue mean? what are primary lymphoid tissue sites?

• site where lymphocytes become mature

• bone marrow: lymphocyte progenitor cells & immature B cells OG here

• thymus: where T cells mature

what does secondary lymphoid tissue mean? what are primary lymphoid tissue sites?

• where lymphocytes are activated by antigens

• lymph noodes: lymph filtration system

• spleen: the white pulp contains B and T cells, where the red pulp contains venous sinuses that filter blood through removing pathogens old RBCs

• MALT: non-encapsulated lymphoid tissue in the GI, resp, and GU tracts

what are common non-neoplastic disorders of WBCs?

neutrophil and lymphocyte count changes

what does -penia mean?

lack of

what does -cytosis mean?

increase

what is leukopenia?

decrease in WBC count in blood

what is neutropenia?

lack of neutrophils

what is the indication value for neutropenia?

< 1000 cells/mL

what is a normal neutrophil range?

2,000 - 7,000/mL

what is a complication of neutropenia?

• increased risk of infection

• prone to recurrent infections

  • especially bacterial & fungal

what is agranulocytosis?

• nearly complete absence of neutrophils

• extremely high risk of life threatening infection

what are the 2 types of neutropenia?

• congenital

  • present at birth because of genetic disorders affecting neutrophil production

• acquired

  • develops later in life because of chemo, viral infections, autoimmune disease, bone marrow disorders

what are common features of neutropenia?

• frequent/recurring infections

• unexplained fever

  • may be only sign

treatment for neutropenia?

• antimicrobial agents

• specific hematopoietic growth factors (GM-CSF)

  • granulocyte colony-stimulating factors

what is neutrophilia?

increase in neutrophil count

what is the value for neutrophilia?

>7500/mL

what causes neutrophilia?

• bacterial infections

• inflammation

• corticosteroids

• blood cancer

  • leukemia

what is lymphocytopenia?

drop in lymphocytes

what is the value for lymphocytopenia?

<1000/mL

what is the normal lymphocyte range?

1000 - 4500/mL

what causes lymphocytopenia?

• inherited disorders

• chemotherapy

• radiation therapy

• viral infections

true or false: pts with lymphocytopenia are prone to repeated infections?

true

lymphocytopenia treatment?

• antimicrobials

• IGs through IV

what is lymphocytic leukocytosis?

increase lymphocyte count

what is the value for lymphocytic leukocytosis?

>4500/mL

what are causes of lymphocytic leukocytosis?

• infectious mononucleosis: RBV/mono

• chronic immune-mediated inflammation (like RA)

• chronic lymphocytic leukemia (aka CLL)

what is the treatment for lymphocytic leukocytosis?

treat the underlying cause

what is a malignant lymphoma?

solid tumors that originate in lymph tissues (usually lymph nodes)

what is hodgkins lymphoma? where is it common?

lymphoma that originates in a single node or in a group of adjacent nodes

• common in the neck, chest, arm pits

what is non-hodgkins lymphoma? where is it common?

• originates in multiple nodes/groups

  • common in chest, armpits, abdomen, groin

what causes NHL?

unknown

what’s associated with NHL?

• EBV (for burkitt lymphoma)

• T-lymphotropic virus type 1 (HTLV-1)

  • for T-cell lymphomas

what is a mature B-cell lymphoma & what causes one?

• the most common subtype of NHL

• originates from germinal center of B cells, or activated B cells outside of the germinal

what are 3 common B-cell lymphoma subtypes?

• follicular lymphoma: an indolent, slow-growing form

• diffuse large B-cell lymphoma (DLBCL): aggressive, fast-growing form, most common between 60 and 70 years

  • most aggressive form

• mantle cell lymphoma: aggressive, rapid disease progression, poor prognosis

for B-cell lymphomas, do indolent or aggressive forms respond better to treatment?

aggressive

what is burkitt lymphoma?

• highly aggressive B-cell NHL

• fast growing tumor of the jaw & facial bones

• common children

what is endemic african burkitt lymphoma?

• kind of lymphoma that primarily affects children in equatorial africa

• closely related with EBV

  • 100% of patients with endemic african burkitt lymphoma show evidence of previous EBV infection

what is sporadic burkitt lymphoma?

• occurs worldwide

• less associated with EBV

manifestations of NHL?

• localized or generalized painless lymphadenopathy

• nodal enlargement & transformation over months/years

• retroperitoneal & abdominal masses w/ symptoms of abdominal fullness & back pain

• ascites and leg swelling

what is the diagnostic method for NHL?

biopsy

what is hodgkins lymphoma distinguished by?

the presence of a reed-sternberg cell

what are the 2 common occurrence age groups for HL?

• young adults: 15-40 yrs

• older adults: +55 yrs

manifestations of HL?

• painless lymphodenopathy

  • causing pressure & obstruction

• mediastinal masses

• fever, weight loss, night sweats, pruritus (itchy skin)

what is leukemia?

malignant neoplasms of hematopoietic precursor cells

what causes leukemia?

• uncontrolled WBC growth of immune cells

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

for which pop is leukemia most common?

• most common CA in children

• accounts for 29% of childhood cancers

what is lymphocytic leukemia?

leukemia caused by abnormal lymphoid cells

what is myelogenous leukemia?

leukemia caused by abnormal myelogenous cells

what is stage 1 HL?

• cancer found in one lymph node region or one lymphoid organ (spleen or thymus)

• nodes above diaphragm

what is stage 2 HL?

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

what is stage 3 HL?

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

  • can also involve spleen or extranodal organ nearby

what is stage 5 HL?

• cancer spread widely to one or more extranodal organs

  • bone marrow

  • liver

  • lungs

  • bones

what is acute leukemia?

• rapid onset

• without treatment, death in 6 mo

• common in children

what is chronic leukemia?

• slow progression

• common in elders

• can become acute in terminal stages

can acute leukemia ever become chronic?

no, but chronic can become acute in terminal stages

what are the 4 types of leukemia according to the French-American-British (FAB)?

➢ ALL: Acute Lymphocytic (Lymphoblastic) Leukemia

➢ CLL: Chronic Lymphocytic Leukemia

➢ AML: Acute Myelogenous (Myeloblastic) Leukemia

➢ CML: Chronic Myelogenous Leukemia

what are characteristics of acute leukemia?

• presence of undifferentiated/immature cells, usually blast cells

• sudden onset, rapid progression, short survival

• severe and quick symptoms

what are characteristics of chronic leukemia?

• predominant cell is mature but does not function normally

• slow, gradual onset

• slow progression

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

what is the cause of leukemia?

unknown

what occurs at the molecular level in the etiology of leukemia?

• disruption of genes, chromosomal abnormalities that control blood cell development, causing uncontrolled production of abnormal blood cells

origin of lymphocytic leukemias

immature lymphocytes & their precursors in the bone marrow

origin of myelogenous leukemias

pluripotent myeloid stem cells in bone marrow

common sites of infiltration for lymphocytic leukemias

• spleen

• lymph nodes

• CNS

clinical consequences of lymphocytic leukemias

impaired immune function & lymphocyte production

myelogenous leukemias interfere with the maturation of…

• granulocytes

• erythrocytes

• thrombocytes

clinical consequences of myelogenous leukemias

• increased infection risk

• anemia

• bleeding

characteristics of acute lymphocytic leukemia (ALL)

• most common childhood leukemia

• greater than 30% of lymphoblasts in bone marrow and blood

characteristics of acute myelogenous leukemia (AML)

• most common adult leukemia

• greater than 20% myeloblasts in blood marrow or blood

predisposing factors for ALL

• radiation exposure

• previous chemo

• genetic disorders

  • down syndrome

• age

  • 2-5 years old

predisposing factors for AML

• radiation exposure

• benzene exposure

• chemo