Blood Components, Leukocytes, and Lymphoid Tissues

Blood makes up __% of the total body weight

8

Average adult has ~____liters of blood

4.5-6

Blood =

cellular components + plasma components

Cellular components percentage

45

Plasma components percentage

55

Cellular components in blood

erythrocytes (red blood cells), leukocytes (white blood cells), thrombocytes (platelets)

Types of leukocytes (WBCs)

neutrophils, eosinophils, basophils, monocytes, lymphocytes

Plasma contains

92% water + 8% proteins (albumin, fibrinogen, globulin)

Functions of blood

• transport oxygen, co2, hormones, nutrients, and metabolic waste products

• regulate blood temperature and acid-base balance

• carry cells and antibodies that fight infection

Centrifugation

process of separating blood into its component parts (before blood testing)

Layers of blood components

plasma 55% least dense component

buffy coat <1% with leukocytes and platelets

Erythrocytes 45% of whole blood and most dense

White blood cells (leukocytes) are

immune cells that protect the body against infections, foreign substances, and disease

Granular leukocytes

contains vesicles that appear when the cells are stained - neutrophils, eosinophils, basophils

Agranular leukocytes

no granules - lymphocytes, monocytes

Neutrophils

most abundance WBC, destroy bacteria through phagocytosis

Eosinophils

fight parasites, involved in allergic reactions

Basophils

release histamine and heparin, participate in inflammation and allergic responses

Monocytes

circulate in the bloodstream

Macrophages

form when monocytes enter tissues, engulf pathogens (phagocytosis)

T cells

coordinate the immune response

B cells

produce immunoglobulins

NK cells

part of innate immunity

Hematopoiesis

formation and developing all types of blood cells in the body

Pluripotent stem cells

give rise to lymphoid stem cells and myeloid stem cells

Leukopoiesis

process of producing white blood cells (leukocytes) in the bone marrow

Myeloid stem cells

produce granulocytes and monocytes

Lympoid stem cells

produce T cells, B cells, and NK cells

Hormone-like regulatory molecules help in

survival, differentiation, and proliferation of progenitor cells, as well as the functional activation of mature cells

Grandulocyte colony-stimulating factor

stimulates the production of neutrophils

Macrophage colony-stimulating factor

stimulates the development of monocytes and macrophages

Interleukin-5 (IL-5)

promotes the growth and development of eosinophils

Interleukin-7 (IL-7)

supports the development of lymphocytes, especially B and T cells

Differential WBC

count measures the percentage and absolute number of each type of leukocyte in the blood

Shift to the left refers to

an increase in immature neutrophil (bands) in the peripheral blood

Shift to the left indiciates

bone marrow is releasing neutrophils early in response to increased demand

Normal neutrophil maturation

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

During a left shift, the bone marrow releases more:

• band neutrophils (most common)

  • occasionally metamyelocytes and myelocytes in severe cases

The lymphatic system consists of:

lymphatic vessels, lymph nodes, lymphoid tissues, thymus, spleen

Lymphatic system major function

defends the body against pathogens, produces and matures lymphocytes, filters lymph and blood, supports adaptive immunity

Primary where the lymphocytes becomes mature and immunocompetent

bone marrow & thymus

Bone marrow

site of development of lymphocyte progenitor cells and maturation of immature B cells

Thymus

site of maturation of immature t cells

Secondary where the lymphocytes are activated by antigens

lymph nodes, spleen, MALT

Lymph nodes

sites of filtration of lymph

Spleen

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

MALT

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

White pulp

contains concentrated areas of B cells and T cells

Red pulp

contains venous sinuses that filter blood by removing pathogens and senescent erythrocytes

Non-malignant disorders of the WBCs are ____ common than malignant disorders

more

-penia

decreased number of cells

-cytosis

increased number of cells

Aboslute neutrophil count (ANC) is

actual number of neutrophils ciruclating in the blood

ANC equation

(bands x WBC + segs) / 100

ANC components

WBC = total white blood cell count

segs = % mature neutrophils

bands = % immature neutrophils

Leukopenia

decrease in the total number of white blood cells in the blood

Neutropenia

abnormally low number of neutrophils in the blood

ANC <1000 cells/uL; increased risk of infection

can lead to neutropenia

Agranulocytosis

nearly complete absence of neutrophils, extremely high risk of life-threatening infection

Types of neutropenia

congenital & acquired

Congential

present at birth due to genetic disorders affecting neutrophil production

Acquired develops

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

Features of patients become prone to recurrent

frequent or recurrent infections, fevers that may be the only sign

Treatment of prone to recurrent infections

antimicrobial agents, specific hematopoietic growth factors (eg GM-CSF)

Neutrophilic leukocytosis (granulocytosis)

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

more than 7,500/uL

normal range: 2000-7000/uL

Most common cause of neutrophilic leukocytosis (granulocytosis)

inflammation, corticosteroid use, certain blood cancers (leukemia)

If need for neutrophils increases beyond supply, then _________ are released

immature neutrophils

Lymphocytopenia (lymphopenia)

abnormally low number of lymphocytes in the blood

less than 1000/uL

normal range 1000-4500/uL

Lymphopenia causes

inherited genetic disorders, chemotherapy and radiation therapy, viral infections (HIV destroys CD4 cells)

Lymphopenia recurrent infections

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

Treatment of lymphopenia

antimicrobial agents, IV immunoglobulins

Lymphocytic leukocytosis

an increased total WBC count caused mainly by an increase in lymphocytes

More than 4500/uL

Normal range: 1000-4500/uL

Common causes of lymphocytic leukocytosis

infectious mononucleosis (most common), chronic immune mediated inflammation, chronic lymphocytic leukemia (CLL)

Treatment of lymphocytic leukocytosis

focus on the underlying cause

Malignant Lymphomas

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

Hodgkin’s lymphomas (HLs)

originate in a single lymph node or a group of adjacent lymph nodes (neck, chest, armpits)

Non-Hodgkin’s lymphoma (NHLs)

originate in multiple lymph nodes or multiple groups of lymph nodes (armpits, chest, abdomen, groin)

Non-Hodgkin lymphomas are a ________ group of cancers affecting lymphocytes

heterogenous

Disruption of normal lymphocyte maturation can result in various

NHL subtypes

Associated infectious agents of non-hodgkin lymphomas

Epstein-Barr virus (EBV), human t-lymphotropic virus type 1 (NTLV-1)

Mature B-Cell lymphomas

most common subtype of non-hodgkin lymphoma

originate from germinal center of B cells or activated B cells that have exited the germinal center

Common B-cell lymphoma subtypes

Follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma

Follicular lymphoma

indolent (slow-growing); typically doesn’t respond as well to treatment; normal lymph node architecture is replaced by malignant lymphoid follicles in a back-to-back pattern

Diffuse large B-cell lymphoma (DLBCL)

aggressive, fast-growing, most common between 60 and 70 years

Mantle cell lymphoma

aggressive, characterized by rapid disease progression and poor prognosis

Burkitt Lymphoma

highly aggressive B-cell non-Hodgkin lymphoma; fast-growing tumor of the jaw and facial bones

Endemic Brukitt Lymphoma

primarily affects children, commonly in equatorial Africa

closely associated with EBV infection (100% show evidence of previous EBV infection)

Sporadic Burkitt Lymphoma

Occurs worldwide; less frequently associated with EBV

Clinical manifestations of Non-Hodgkin Lymphoma

• localized or generalized painless lymphadenopathy

• nodal enlargement and transformation over months or years

• retroperitoneal and abdominal masses with symptoms of abdominal fullness and back pain

• ascites (fluid in the peritoneal cavity) and leg swelling

Diagnostic tests with NHL

biopsy is the primary means

Hodgkin lymphoma (HL) is distinguished by the presence of an abnormal _______________

Reed-Sternberg cell

HL commonly occurs in two groups

young adults - 15-40 years

older adults - 55 and above

Clinical manifestations of Hodgkin Lymphoma

• enlarged painless neck lymph nodes

• lymphadenopathy, causing pressure or obstruction

• mediastinal mass

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

Classic Reed-Sternberg cell

Owl’s Eye two large nuclear lobes, each with a prominent red nucleolus surrounded by a clear halo

Stage 1 of Hodgkin Lymphoma

Cancer is found in one lymph node region or one lymphoid organ

Stage 2 of Hodgkin Lymphoma

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

Stage 3 of Hodgkin Lymphoma

Cancer is present in lymph node regions on both sides of the diaphragm (could involve spleen or nearby extranodal organs)

Stage 4 of Hodgkin Lymphoma

Cancer has spread widely to one or more extranodal organs (bone marrow, live, lungs, bones)

Leukemia

malignant neoplasms of hematopoietic precursor cells that are characterized by uncontrolled growth of immature white blood cells affecting blood cell production

Leukemia (simple)

the abnormal increase in white blood cells compared with red blood cells

Approximately ___________ new cases of leukemias are diagnosed annually

60,000-62,000

Leukemia is the most common cancer in

children and adolescents (29% of childhood cancers)