Structure and Function of Hematopoietic and Immune Systems

Question 1

Components of Hematopoietic System

Answer 1

MOST BLOOD CELLS COME FROM BONE MARROW

• makes RBC, leukocytes (neutrophils, monocytes, lymphocytes), and megakaryocytes (cells that fragment to form platelets)
• 50% of the marrow space is adipocytes

Question 2

Stem Cell

• Reproduce itself indefinitely
• many types, exist in small numbers compared to other cell types

Answer 2

Bone-marrow derived cells (myeloid cells) descended from stem cells
-can differentiate into RBC, neutrophil, or megakaryocyte
-differentiate into immature cells called BLASTS, which are precursors for each cell type (RBC, neuts, megakaryocytic)
-this differentiation of blasts is controlled by proteins called growth factors; as they mature, they lose the ability to divide
-these matured blasts from differentiated stem cells (RBC, neuts, megakaryocytes) enter blood steam
Example of growth factor: ERYTHROPOIETIN- made by kidney which boosts RBC production
-Differentiation (blasts to mature blood cells), they divide rapidly, but as the approach maturity (RBC, neuts, megakaryocytes), they stop dividing

Question 3

Components of the blood ONE

Answer 3

Plasma
-Fluid portion containing water, proteins (made by liver), and nutrients
-Serum: plasma minus clotting proteins
FUNCTIONS: maintain homeostasis (fight infection, prevent bleeding-clotting proteins), transport nutrients and electrolytes to cells, transport waste products to kidneys, liver, lungs for excretion

Question 4

Components of blood TWO

Answer 4

Erythrocytes (RBC)
FUNCTION: carry oxygen and CO2
4-5.5 million cells/microliter of blood
Have a nuclei in bone marrow, do not in peripheral blood
40-45% blood volume occupied by RBC
Bags of hemoglobin; normal blood has 15 g hemoglobin/100 ml
Most predominant cell types in blood, next is platelets (1/10 that of RBC- 150-350 thousand/microliter)
Hematocrit: fraction of blood volume occupied by RBC (normal is 50%)
Biconcave disks that increase surface-volume ratio: important for proper gas exchange in lungs
Need iron, B12, and folic acid for proper RBC production

Question 5

Components of blood THREE

Answer 5

Leukocytes (WBC); least common cell in blood (1/1000 as many as RBC)
FUNCTION: fight infection
Several different types:
Neutrophils-phagocyte
Lymphocyte-makes antibodies, recognizes and kills foreign cells, regulates immune response
Monocyte-phagocyte, works with lymphocyte to control immune response
Eosinophil-allergic reactions, kills parasites
Basophil-allergic reactions

Question 6

Components of blood FOUR

Answer 6

Platelets
Small cell fragment (smallest formed elements in the blood)
FUNCTION: helps blood clot

Question 7

T LYMPHOCYTE

Answer 7

FUNCTION: regulation of the immune system; kill foreign or infected cells
-Cytotoxic: can kill infected cells directly, receive commands from helper T cells
-Helper: coordinate immune attack to foreign antigens by releasing cytokines; activate macrophages; cause inflammation, activate other T and B lymphocytes
-Regulatory: suppression of immune response
SOURCE: bone marrow, thymus, lymph nodes

Question 8

B LYMPHOCYTE

Answer 8

FUNCTION: antibody production
SOURCE: bone marrow, lymph nodes, spleen, lymph follicles in other tissues
Stimulation to make antibodies converts B cell into plasma cell: cell type that makes most antibodies

Question 9

NATURAL KILLER (NK) CELLS

Answer 9

FUNCTION: kills certain foreign/infected cells
SOURCE: BONE MARROW?

Question 10

MONOCYTE/MACROPHAGE

Answer 10

FUNCTIONS: phagocytosis, digest foreign molecules and transfer pieces to T cells which then initiate specific immune response (tell B cells to make antibody), produce hormones (cytokines) that mediate inflammation and regulate growth of other cells
SOURCE: bone marrow
TWO FORMS: monocytes circulating in blood (monocyte 3-10% of blood leukocytes), macrophages in tissues

Question 11

Lymph Nodes

Answer 11

Collections of lymphoid cells scattered throughout the body, connected by small vessels through which lymph circulates
Lymphocytes enter immature on one end and mature as they get to middle of node, maturing before they exit
Lymphocytes become educated on antigens here-they exit to do their job
Lymphocytes undergo gene rearrangement to acquire ability to recognize and respond to specific antigens; can make a wade array of antibodies (when this goes wrong, can give rise to lymphomas and lymphoid leukemias)
Spleen is the largest lymphoid organ in the body: serves as a filter for the blood in addition to immune function

Question 12

Anemia

Answer 12

REDUCTION IN TOTAL CIRCULATING RED CELL MASS
-low hematocrit and hemoglobin levels in the blood OR total blood volume may be low with normal hematocrit/hemoglobin levels
SIGNS AND SYMPTOMS: fatigue, dyspnea (shortness of breath), cheat pain, tachycardia, pallor (pale skin)

Question 13

3 CAUSES OF ANEMIA

Answer 13

1. Decreased RBC production: Not enough stem cells due to bone marrow failure or bone marrow replacement by non-hematopoietic cells, stem cells present but do not mature properly due to genetic mutation
2. Rapid RBC destruction (hemolysis): autoimmune diseases, inherit abnormality that shortens its lifespan, abnormality of vessels that mechanically damage RBC
3. Blood loss

Question 14

RED CELLS SHAPE/SIZE: can give clues to underlying processes of how you became anemic

Answer 14

1. Macrocytic: larger than normal RBC
2. Normocytic: normal sized cells
3. Microcytic: smaller than normal cells (associated with hypochromia-pale cells due to decreased hemoglobin content)
4. Abnormal shapes: poikilocytosis

Question 15

APLASTIC ANEMIA

Answer 15

Decreased stem cell number –> problem producing ALL myeloid cells (RBC, neuts, megakaryocytes)=low WBC count, which predisposes to bleeding and infection
Macrocytic or normocytic
Bone marrow empty or partially empty of cells (all fat cells)
CAUSED BY: Agents that can damage or destroy stem cells
-cytotoxic chemicals (chemo)
-ionizing radiation in large doses
-viral infection
-idiopathic; often autoimmune disorder
TREATMENT: transfusion, marrow transplant, immunosuppression
Can be fatal

Question 16

ANEMIA OF INFLAMMATION

“ Anemia of chronic disease”

Answer 16

Iron is held in macrophages and not released to RBC precursors
Normocytic or microcytic
CAUSED BY: infection, rheumatoid arthritis, kidney failure, cancer, malnutrition (all associated with decreased stimulation of RBC production
NOTHING IS INTRINSICALLY WRONG WITH MARROW!
TREATMENT: treat causative condition, synthetic erythropoietin

Question 17

IRON DEFICIENCY

Most common cause of anemia worldwide

Answer 17

Iron is needed for hemoglobin synthesis, insufficient iron –> decreased hemoglobin production –> decreased RBC production, with microcytic hypochromic RBC
CAUSES: chronic blood loss, pregnancy, poor diet, menstreul bleeding in young women, cows milk in kids (contains little iron, elements bind iron that lead to the inability for absorption), bleeding rom GI tract in elderly, inability to absorb iron
TREATMENT: iron supplement or correct dietary deficiency, find and correct source of bleeding; iron normally recycled in a person

Question 18

VITAMIN B-12 DEFICIENCY (pernicious anemia)

Answer 18

B12 is needed for DNA synthesis during RBC production
Microcytic with abnormal/delayed maturation (megaloblastic); cells have more cytoplasm than usual
May also cause neurologic disease
CAUSES: Often due to stomach disorder caused decreased production of factor needed for B12 absorption (intrinsic factor) then due to poor diet
TREATMENT: B12 injections

Question 19

FOLIC ACID DEFICIENCY

Answer 19

Folic acid is needed for DNA synthesis by RBC
Macrocytic and Megaloblastic
CAUSES: poor diet, alcohol abuse, use of certain drugs (anticonvulsants), malabsorption
TREATMENT: oral folic acid supplements

Question 20

THALASSEMIA

Answer 20

Inherited disorder of hemoglobin production
Microcytic, hypochromic
Alpha Thalassemia: decreased or absent production of alpha chain of hemoglobin
Beta Thalassemia: decreased or absent production of beta chain of hemoglobin
Thalassemia minor: hemoglobin production mildly or moderately decreased, anemia is mild or moderate
Thalassemia major: hemoglobin production nearly absent, anemia is very severe and need transfusion to survive (classification is mainly used for betaT)

Question 21

HEMOLYTIC ANEMIA

Answer 21

Increased rate of RBC production due to increased rate of RBC DESTRUCTION, increased numbers of RBC precursors in marrow, increased numbers of newly made RBC (reticulocytes-immature) in blood
High bilirubin level in blood, due to breakdown of hemoglobin, causes jaundice (intravascular hemolysis) and brain damage in infants
Extravascular hemolysis: RBC taken up by macrophages in spleen and liver and then destroyed
Intravascular hemolysis: RBC destroyed while still in blood
Low hematocrit (30%) and yellow plasma
RBC shistocytes indicate intra vascular hemolysis
TREATMENT: splenectomy may help

Question 22

SICKLE CELL ANEMIA

Answer 22

Inherited hemolytic anemia
DNA point mutation
Inherited structural abnormality of hemoglobin lead to polymerization of hemoglobin in absence of O2, damage to RBC membrane, and premature destruction of RBC
Repeated cycles of hemoglobin deoxygenation and oxygenation lead to cycles of hemoglobin polymerization, which causes RBC to become rigid and sickle and clog small vessels, causing tissue damage and death (infarction)
Recessive inheritance: parents of person with sickle cell anemia have trait
Mainly found in those of african, middle eastern descent

Question 23

AUTOIMMUNE HEMOLYTIC ANEMIA

Answer 23

Production of antibodies against one’s own RBC (mistake by immune system)
Antibodies coat RBC, which are eaten by macrophages in the spleen and destroyed
Antibody-coated red cells can be detected by Coombs test
TREATMENT: corticosteroids (suppress immune system) or other immunosuppressive drugs, splenectomy

Question 24

TRANSFUSION REACTION

Answer 24

Foreign RBC enter blood via transfusion
Immune system makes antibodies to antigens on these cells
Antibodies stick to transfused cells and cause their destruction
ABO-mismathced blood may cause immediate massive hemolysis and a severe or fatal immune reaction
Most other cases, cells are eaten and destroyed by macrophages and patient does not become acutely ill

Question 25

HEMOLYTIC DISEASE OF THE NEWBORN (erythroblastosis fetalis)

Answer 25

Mother previously exposed to an antigen (Rh antigen) on fetal cells and makes antibodies to it; exposure may occur during a prior pregnancy or via blood transfusion
If fetal blood cells bear the target antigen, maternal antibody can cross the placenta and destroy fetal RBC; infant liver is unable to properly metabolize hemoglobin breakdown products and are toxic
Most severe reactions occur when the mother has negative Rh and the fetus is Rh positive
TREATMENT: no good way to treat once this starts, need to prevent by giving anti Rh-serum to any Rh-negative mother at the time of delivery to destroy Rh-positive fetal cells that get into the mother’s circulation before they can sensitize the mother, she will not make antibody herself and subsequent child

Question 26

POLYCYTHEMIA

Answer 26

Too many RBC (opposite of anemia)
Blood is too thick (55% hematocrit): blush-red skin color
Polycythemia vera (primary)- pathologic; myelproliferative disorder, a low grade neoplasm- RBC progenitors proliferate independent of normal controls
Unregulated RBC production because the receptor for erythropoietin is to sensitive to erythropoietin- there is no negative feedback! Due to acquired mutation
TREATMENT: phlebotomy (removal of blood), antineoplastic drugs
Secondary polycythemia: Red cell progenitors proliferate
Feedforward mechanism prompt bone marrow to make more RBC
Decreased oxygen delivery to kidney –> increased production of erythropoietin by kidney –> increased red cell production
CAUSED: usually caused by chronically low blood oxygen level due to lung or cardiac disease, may be correctable y giving oxygen

Question 27

NEUTROPENIA

Answer 27

Decreased neutrophils
CAUSES: decreased neutrophil production (aplastic anemia or other forms of marrow failure, temporary drop in production due to marrow suppression by cancer chem-decreases number of neuts produced), increased neutrophil consumption (autoimmune, severe infection, enlargement of spleen-acts like a sponge)
INCREASED RISK FOR BACTERIAL OR FUNGAL INFECTION

Question 28

NEUTROPHILIA

Answer 28

Increased production of neutrophils by marrow in response to physiologic stimuli (infection) or neoplastic conditions
Doly body seen in peripheral smear indicates infection, not cancer as the cause

Question 29

Lymphadenopathy

Answer 29

Enlarged lymph nodes due to local or systemic infection or other inflammation OR cancer (metastatic carcinoma or lymph cancer-leukemia or lymphoma)

Question 30

Splenomegaly

Answer 30

Enlarged spleen
CAUSES: infections, lymphomas and leukemias, liver disease, inflammatory disorders
May cause low WBC and platelet counts because spleen soaks up these cells (hypersplenism)

Question 31

Asplenia

Answer 31

absence of spleen
CAUSES: surgical removal, certain blood diseases (sickle cell-no longer have functional spleen because of repeated infarction)
Lower resistance to certain bacterial infections because spleen can act as filter and remove infections from blood

Question 32

Thrombocytopenia

Answer 32

Low platelet count

Question 33

Qualitative platelet disorders

Answer 33

platelet number may be normal, but platelet function is abnormal

Question 34

LEUKEMIA

Answer 34

Cancerous proliferation of WBC precursors (blasts) or WBC themselves-they replace normal marrow and spread via blood to other tissues
CAUSES: alteration in genes that regulate cell growth and division caused by exposure to radiation, mutagenic chemicals or drugs, viral infections, needs to accumulate many mutations before it can overcome the normal safeguards

Question 35

Acute vs Chronic Leukemia

Answer 35

Acute: proliferation of blasts that have lost he ability to differentiate; these immature cells never stop dividing, accumulate rapidly and disease is usually fatal within months if not treated.
Chronic: proliferation of WBD precursors that have retained their ability to differentiate-cells stop dividing as they differentiate, so these progress more slowly; more mature cells

Question 36

MANIFESTATIONS OF LEUKEMIA (generally more severe in acute then chronic leukemias)
Hematocrit tube 5-10% buffy coat- usually not visible

Answer 36

1. Accumulation of leukemic cells in bone marrow (no room for normal hematopoiesis to take place)
   - Marrow failure (anemia, leukopenia-increased susceptibility for infection, thrombocytopenia-bleeding)
   - Bone Pain
2. Accumulation of leukemic cells in blood
   - Circulatory disturbance occurs at very high blast count
3. Accumulation of leukemic cells in other tissues
   - Enlargement of spleen and/or lymph nodes
   - Skin infiltration
   - Brain infiltration
4. Release toxic substances from leukemic cells
   - Enzymes activating coagulation or fibrinolysis
   - Uric acid

Question 37

ACUTE LYMPHOCYTIC LEUKEMIA (ALL)

Answer 37

Most common form of leukemia in children
Cell or origin: B or T cell precursor (blast cell)
CAUSE: unknown
Rapidly progressive, fatal if not treated
Often curable, particularly in children with chem and/or marrow transplant
-White cells depositing in soft tissues of gums

Question 38

ACUTE MYELOGENOUS LEUKEMIA (AML)

Answer 38

Malignant proliferation of immature granulocyte (or occasionally erythroid or megakaryocytic) blast cells, leading to accumulation in blood, bone marrow, and other tissues. Proliferation more rapid than in CML because blast cells divide faster than stem cells
CAUSES: most cases not known, genetic mutations caused by chemo, radiation, benzene, viruses in animals, not humans
Most common adult leukemia
TREATMENT: treatable, occasionally curable with aggressive chem and/or bone marrow transplant
some cases preceded by myelodysplastic syndrome (pre leukemia)

Question 39

CHRONIC MYEOLGENOUS LEUKEMIA (CML)

Answer 39

malignant proliferation of myeloid stem cell, with overproduction of WBC and often platelets
Causes enlarged spleen, fever, fatigue, weight loss, occasionally circulatory problems if WBC/platelet count very high
TREATABLE: can transform into fatal acute leukemia, can be cured by marrow or marrow stem cell transplant
Rare in children, but may occur throughout adult years; drugs that block this protein synthesis, many patients are successful without marrow transplant
CAUSED BY: specific chromosome mutation on Philadelphia chromosome so that part of 2 different chromosomes stick together and create new gene that produces a protein that causes uncontrolled growth of myeloid cells

Question 40

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

Answer 40

Cell of origin: B cell and slowly growing; mature appearing cells that may take years to accumulate to the point that they cause symptoms
Primarily effects older people; very rare under age 40
CAUSES: unknown
Clinical manifestation: asymptomatic for years, enlarged lymph nodes (leukemic cells travel to nodes) and spleen, as they accumulate in marrow they cause decrease marrow function, impaired immune function (decreased antibody production)
TREATMENT: NOT CURABLE, with chemo, radiation

Question 41

LYMPHOMAS

Answer 41

Cancerous proliferation of lymphocytes and their precursors
T vs B cell, immature vs almost fully differentiated, rapidly dividing vs slowly dividing, Hodgkins vs non-hodgkin
Generall solid tumors- cells mostly found in lymph nodes, marrow, spleen, other internal organs, sometimes blood)

Question 42

LYMPHOMAS OTHER THAN HODGKIN DISEASE

Answer 42

Derived from lymphoid cells of various types and at various stages of maturation
TWO GROUPS:
Low grade: slow growing, mature appearing cells; usually effects older people
Bad news=often improves with treatment but INCURABLE
Good news=patients often survive with disease for many years (ex: small lymphocytic lymphoma- same as CLL)
High grade: fast growing, less mature appearing cells, most aggressive forms similar to ALL (Burkitt lymphoma); some cases effect children
Good news=potentially curable with chemo
Bad news=patients who are not cured usually die within months to years
Enlargement of lymph nodes, spleen, often infiltrate marrow; some types cause leukemia (cells show up in blood also)
Most types are treatable with chemo and radiotherapy, some can be cured

Question 43

HODGKIN DISEASE

Answer 43

Reed-sternberg cells; large multinucleated cells
cell of origin probably a lymphocyte
CAUSE: unknown
One of more common cancers in adolescents and young adults
Almost always originates in lymph nodes; spreads to spleen, marrow, liver, and others
Moderate growth rate; causes inflammatory response with fever, weight loss, other symptoms
Prognosis and treatments vary on stage:
Stage 1: disease confined to single lymph node or group of nodes; can be cured with treatment, can be treated with radiation alone
Stage 2: disease in 2 or more lymph node groups on same side of diaphragm
Stage 3: disease in lymph nodes on both sides of diaphragm
Stage 4: spread outside lymph nodes

Question 44

MULTIPLE MYELOMA

Answer 44

Cell of origin: plasma cell; neoplastic cells often secrete antibody-like protein
Almost all patients >40 yrs old
CAUSE: uncertain
Secreted protein has uniform structure termed monoclonal immunoglobulin-may be found in blood or secreted by kidneys into urine, RBC stuck together by abnormal protein
Clinical findings: bone destruction (holes in bones), monoclonal immunoglobulin may damage kidneys, may cause circulatory problems due to increased blood thickness, predispose to infection because defective production of normal antibody, marrow infiltration –> anemia
TREATABLE: chemo, radiation, BUT NOT CURABLE with avg survival 3-4 yrs.