lecture 4 diseases of leukocytes and erythrocytes

hematopoiesis

formation and development of blood cells

lineage from multipotential hematopoietic stem cell

becomes myeloid progenitor

- erythrocytes

- mast cells

- granulocytes (basophil, neutrophil, monocyte -> macrophage)

- thrombocyte (platelets)

becomes lymphoid progenitor

- natural killer cell

- t cell

- b cell

leukocyte vs lymphocyte

leukocyte - overall immune response (neutrophils, eosinophils)

lymphocyte - adaptive, specific immune response (natural killer cell, b cell, t cell)

2 types of white cell disorder

reactive - too much of these cells during an active infesion

neoplastic - ???

leukopenia

non neoplastic disorder, most common is neutropenia

causes include:

- decreased granulocyte production

- increased granulocyte destruction

lymphopenia

non neoplastic disorder, not enough b/t cells, less common than leukopenia

causes include:

- rare inherited immune disease

- HIV

- high corticosteroid treatment

reactive leukocytosis

non neoplastic disorder, too many WBCs, types include: polygamy morphonuclear leukocytosis, eosinophilic leukocytosis, monocytosis

polygamy morphonuclear leukocytosis

caused by acute bacterial infection or tissue necrosis

eosinophilic leukocytosis

seen with allergy disorders, parasitic infection, drug rxns

monocytosis

seen with chronic infection, lupus

reactive lymphadentitis

enlarged lymph node bc of foreign antigen, can have follicular hyperplasia or paracortical hyperplasia

follicular hyperplasia

enlarged secondary follicles bc of increased B cells (seen as regions)

paracortical hyperplasia

enlarged tissue on outside bc of active T cell response

neoplastic disorders

most common disorder of WBCs, malignant, occurs at any age/race, 150,000 new diagnosis, can be lymphoid neoplasm or myeloid neoplasm

leukemia vs lymphoma

leukemia = malignant w/ bone marrow involvement

lymphoma = lymphoid proliferations (lymph nodes)

** not distinguished sometimes can see one with the other

leukemia

cancerous cells that overpopulate marrow and replace normal cells

- pushes out RBCs and macrophages

-can infiltrate high vascularized tissues (liver, spleen. lymph nodes)

- can be acute or chronic

acute vs chronic leukemia

acute

- bone marrow is replaced by early lymphoid or myeloid progenitors -> loses ability to make RBCs

- cells are undifferentiated and nonfunctional

chronic

- well differentiated cells

- precursor to neutrophils, specified cells

lymphoma

- B and T cells

- swollen lymph nodes

- most common 15-24 yo

lymphoid neoplasms characterization

precursor B cell -> bone marrow

peripheral B cell -> in lymph nodes

precursor T cell -> bone marrow

peripheral T cell -> in lymph nodes

what causes lymphoma and leukemia

- environmental

- chromosomal translocation

- inherited

- viruses

- chronic inflammation -> leukocytes are constantly produced in bone marrow

- iatrogenic -> caused by medical treatment like chemotherapy

- smoking

lymphoid neoplasms

- B cell origin

- causes abnormal immunity (1 B cell overmultiplies and takes over other B cells present) -> leads to loss of protective immunity

- monoclonal origin -> specific B cell causes a problem

precursor lymphomas includes

acute lymphoblastic leukemia/lymphoma (ALL)

B cell acute lymphoblastic leukemia/lymphoma

acute lymphoblastic leukemia/lymphoma (ALL)

- transform hematopoietic cells w/o differentiation

- B cells or T cells (usually B)

- malignant B vs T can't be distinguished

- from chromosomal aberration -> affect function of TFs

B cell acute lymphoblastic leukemia/lymphoma

- most common in children

- more common in hispanics>whites>blacks

- clonal expansions of cells that aren't mature

- no immunoglobins on cell bodies

- suppresses normal hematopoiesis -> low RBCs, WBCs, platelets

- marrow has lots of lymphoblasts

- caused by chromosomal abnormalities -> Philadelphia chromosome (9+22 swap to create different promotor gene combo)

peripheral B cell neoplasms includes

chronic lymphocytic leukemia (CLL)

small lymphocytic lymphoma (SLL)

follicular lymphoma

plasma cell neoplasm

hodgkin lymphoma

chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) similarities

- morphologically same

- mature lymphocytes that can produe antibodies

- disrupt normal immune function

chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) differences

CLL

- bone marrow involvement

- most common in old adults

- mostly B cell

- shows positive CD5 markers of T cells on B cells

- smudge cells

SLL

- in lymph nodes

- invade lymph tissue and disrupt structure

follicular lymphoma

- non hodgkin

- non tender, enlarged lymph nodes

- resemble normal B cells

- caused by chromosomal translocation (14 + 18) -> causes overexpression of BCL2

- incurable (survival time 7-10 yrs)

plasma cell neoplasm

- clones 1 mature B cell

- multiple myeloma (uncontrollable growth)

- breaks down bone -> causes high Ca levels -> leads to hypercalcemia and renal failure

- on graph: end spike from increased B cells of 1 types

hodgkin lymphoma

- presence of Reed-Sternberg cells (owl looking)

- starts in 1 lymph node and spreads to spleen + liver

- peaks in 20s and 50+

- treat w radiation and chemotherapy (if caught early enough can remove single lymph node)

myeloid neoplasm

- derived from hematopoietic progenitor cells in marrow

- progenitor cell for RBCs, granulocyte, monocytes, platelets

acute myeloblastic leukemia (AML)

- caused by mutation that affects differentiation

- blast cells replicate w/o differentiating

- affects committed myeloid progenitor (younger pts), pluripotent stem cell (older pts)

- peaks in 60s

- presence of Auer rod after staining

- causes anemia, neutropenia, thrombocytopenia

chronic myeloproliferative disease

- 90% have Philadelphia chromosome (9+22)

- mutant cells continue to mature -> shows inc granulocyte precursors in blood

- has 3 stages

- caused by having too much myeloid stem cell

3 stages of chronic myeloproliferative disease

1. initial stable phase (2-8 yrs)

2. accelerated phase (6-12 months) - fail to respond to treatment, inc anemia and thrombocytopenia

3. blast crisis - similar to acute leukemia

- lose adaptive immunity -> production of myeloblasts

- produce lymphoblasts

- don't repond to treatment

- fatal quickly

erythropoiesis process

produced in kidney then into bone marrow, entire process is about 1 week

Day 1: proerythroblast (committed stem cell)

Day 4: normoblast -> eject nucleus

Days 5-7: reticulocyte -> dark staining bc extra RNA to maintain hemoglobin protein, not as oxygen binding as a mature RBC

erythropoietin

hormone (signal molecule of stem cell precursor)

- regulates development of erythroid cells

- produced in kidney

- promotes growth of erythroid progenitor cells (associated w cytokines)

- stimulate release of reticulocytes from bone marrow

response to stress in bone marrow

- inc number of erythroid stem cells differentiating into erythrocytes (~1 week)

- dec maturation (1 week -> couple days)

- release reticulocytes into bloodstream earlier

OVERALL: needs more blood to carry 02

polycythemia

primary - clonal stem cell disorder, not dependent on erythropoietin levels, caused by mutation/inherited

secondary - from erythropoietin stimulation, physiologic response to low O2

anemia description

caused when the bone marrow cannot compensate for lack of O2 in the body

levels of hemoglobin and hematocrit for anemia

males

hemoglobin: < 13 gm/dL

hematocrit: < 39%

females

hemoglobin: < 12 gm/dL

hematocrit: < 36%

** difference in male and female due to muscle mass

4 compensatory mechanisms for anemia

1. decrease hemoglobin-oxygen affinity -> dec presence of 2,3 BPG (usually binds to hemoglobin to release O2)

2. increased tissue perfusion (decreases tissue perfusion to skin to send it to organs like heart and brain)

3. increased cardiac output

4. increased RBC production

clinical features of anemia

- pallor

- weakness, fatigue

- dyspnea (short breath)

- cardiac failure

ocular manifestations of anemia

- retinal hemorrhage -> leaky RBCs produced

- cotton wool spots -> portions that die off due to no vascularization

- vessel tortuosity -> squiggly vessels

- conjunctival pallor -> white under eyes

2 ways to classify anemia

underlying mechanism

- impaired erythrocyte production

- increased rate of destruction

- blood loss

appearance of RBCs:

- size (normocytic, microcytic, macrocytic)

- color/hemoglobin content (normochronic, hypochronic)

- shape (round, sickle)

anemia caused by impaired erythrocyte production

- aplastic anemia (bone marrow failure)

- megaloblastic anemia (maturation failure) -> pernicious, folate deficiency anemia

- iron deficiency anemia

anemia caused by increased rate of destruction

- hemolytic anemia (intravascular + extravascular)

- sickle cell anemia (intravascular)

aplastic anemia

impaired erythrocyte production -> disturb stem cell differentiation

- hypocellular

- creates empty marrow spaces -> filled by fat cells and fibrous stroma

- pancytopenia -> reduction of RBCs, platelets, WBCs

megaloblastic anemia

impaired erythrocyte production -> disturb maturation of erythroblasts

- caused by impaired DNA + defective nuclear maturation

- cytoplasmic maturation not in sync w nuclear maturation

- defective cell maturation + division

- major types: vitamin B12 deficiency, folic acid deficiency (both coenzymes for DNA synthesis)

pernicious anemia description

caused by vitamin B12 deficiency

- macrocytic

- mean cell volume greater than 100

- hypersegmented neutrophils (4+ lobes)

- causes neurologic change: posterolateral spinal tract

- folate can improve hematologic signs but not neurologic ones

pernicious anemia ocular findings

- gradual vision loss

- can be cecocentral scotoma (skewed to side)

- pallor of optic disc

- dec color vision

folate deficiency anemia

caused by dec intake, increased requirements (pregnancy), malabsorption

- NO neurologic changes

- macrocytic

- normal serum vitamin B12

iron deficiency anemia

most common; caused by dietary lack, impaired absorption, increased requirements, chronic blood loss

- microcytic, hypochromic

pathway of iron deficiency anemia

1. initial blood loss/deficiency

2. ferrtin and transferrin (storage forms) loss in bloodstream

3. ferritin and transferrin lose ability to make Hgb

4. low serum iron

** progressive deficiency

hemolytic anemia

premature destruction

- short survival of RBCs

- accumulate hemoglobin breakdown products

- see inc erythropoiesis in bone marrow

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