Hematological Disorders Flashcards
What three components can blood be seperated into?
Plasma (55%), buffy coat (<1%), erythrocytes and RBCs (45%)
What does plasma contain?
Ions, proteins (albumin most abundant), lipids, dissolved oxygen and Co2
What does the buffy coat contain?
WBC/leukocytes, platelets, neutrophils (not normally in healthy tissue) and B and T cells
What are the cells found in blood?
Erythrocytes, neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets
What are the two alterations of RBCs?
Low number= anemia, excess= polycythemia
What is sickle cell anemia?
Alteration of RBCs, take on a sickle shape through amino acid substitution of beta chains that result in altered function, sickle cells less resilient to wear and tear= increased destruction/shorter lifespan
What are the alterations in WBCs?
Increased number= leukocytosis, decreased number= leukopenia
What are the alterations in numbers of platelets?
Low= thrombocytopenia, high= thrombocythemia
What is the composure of RBCs?
Lack nuclei, are small, primarily composed of hemoglobin
What is the function of hemoglobin?
Binds easily and reversibly to oxygen, made up of four globin proteins (each associated with iron containing heme group)
What do RBCs lack?
Mitochondria, need glycolysis to produce energy (mitochondria needs O2 to make ATP, prevents tug of war with hemoglobin)
What is erythropoiesis?
Process of RBC production
Which organ secretes erythropoietin (hormone)?
Secreted by the kidneys in response to hypoxia, goes to bone marrow and can increase number of RBCs being produced
What nutrients are needed for RBC production?
Iron, Vit B12, riboflavin, folate
What is hematocrit?
Proportion of whole blood sample occupied by intact RBCs
What is the erythrocyte count (ERCs)?
of erythrocytes in specific volume of blood
What is MCV?
Mean RBC volume
What is MCH?
Average amount of hemoglobin per RBC
What is MCHC?
Mean hemoglobin concentration per RBC
What is RDW?
RBC distribution width, estimation of variability in cell size
What are the two pathways of the coagulation cascade?
Intrinsic and extrinsic
What is required for clot to occur?
Coagulation enzymes must assemble on negative surface (ex: platelet membrane), calcium needed to bridge b/t y-carboxylated proteins and membrane surface, vit K required for y-carboxylation*
What is anemia?
Reduction in total circulating erythrocyte number or decrease in the quality/quantity of hemoglobin, results in decreased oxygen carrying capacity
What do the endings cytic and chromic refer to?
Cytic= cell size, chromic= hemoglobin content
How is anemia diagnosed?
With peripheral blood smear, able to assess size, colour, shape
What is macrocytic-normochromic anemia?
Increased RBC volume, and normal hemoglobin concentration, caused by impaired DNA synthesis and repair in RBC precursors. Inability of DNA to be synthesized, lack of cell division= megaloblasts
What is pernicious anemia?
Failure to absorb sufficient Vit B12, form of macrocytic-normochromic anemia
What is needed for effective DNA synthesis?
Vit B12 and folate important
How does Vit B12 absorption occur?
B12 freed from food via stomach acid. Parietal cells produce intrinsic factor which complexes with Vit B12, can be taken up in the ileum, dissociates and is stored in liver
What are some potential causes of pernicious anemia?
Impaired absorption (ex: chronic atrophic gastritis= autoimmune disorder that destroys parietal cells), ileostomies, etc.
What would labs show in someone with pernicious anemia?
Increase in MCV, decrease in hematocrit, normal MCHC, low Vit B12 levels
What would the bone marrow show in someone with pernicious anemia?
Increased number of megaloblasts
What is folate essential for?
Very important for DNA synthesis, needed for nucleotide synthesis
How does folate deficient anemia occur?
Lack of folate ingestion (found in leafy green veggies), chronic diarrhea, alcoholism (alcohol prevents activation of folate in the liver)
What would lab work show with someone who has folate defiency anemia?
Increased MCV, decreased hematocrit, low serum folate levels
What would the bone marrow biopsy show in someone with FDA?
Megaloblasts
What is microcytic-hypochromic anemia?
Smaller RBCs with less hemoglobin
What are two main causes of microcytic-hypochromic anemias?
Iron deficiency anemia and sideroblastic anemia
What is iron-deficiency anemia?
Need adequate amount of iron for hemoglobin production, obtained through diet in either non-heme or heme forms (preferred form)
Where is iron in the body?
75% in RBCs, some in liver attached to ferritin (a protein)
How can non-heme iron be converted to preferred heme form?
Vitamin C ingestion alongside it, allows conversion
How is iron absorbed?
Taken up by intestinal epithelial cells in duodenum, needs acidic PH, transported into blood where it complexes with transferrin and allows it to be taken up
Is iron easily lost?
No-body is good at recycling it. Macrophages break down old RBCs, produce bilirubin (excreted in bile), iron sent back to bone marrow and re-used
What are some potential causes of iron deficiency anemia?
Blood loss, parasites, cancer, decreased stomach acidity, decreased intestinal transit time, malnutrition
What is the pathophysiological process of iron deficient anemia?
Lack of sufficient iron supply in bone marrow causes release of stored iron from liver, erythropoiesis impaired, production of microcytic-hypochromic RBCs
What would lab samples show in iron deficient anemia?
Decreased MCV, decreased hematocrit, increased RDW, decreased MCH/MCHC, decreased ferritin and transferrin, decreased serum iron
What is sideroblastic anemia?
Can be acquired or congenital, characterized by ring sideroblasts (normoblasts surrounded by granules of iron) due to the iron not being encorporated into the heme
What causes sideroblastic anemia?
Defects in enzymes and transporters involved in heme synthesis, impaired synthesis= hypochromic RBCs with abnormal shape
What are some symptoms of sideroblastic anemia?
Can see enlargement of liver and spleen d/t iron accumulation
What is normocytic-normochromic anemia?
Normal RBC size and hemoglobin content, decreased overall number of RBCs
What are some causes of normocytic-normochromic anemia?
Aplastic anemia, posthemorrhagic anemia, hemolytic anemia, anemia of chronic inflammation
What is aplastic anemia?
Problem with hemocytoblasts of stem cells, part of pancytopenia, caused by autoimmune disorder (75%) or secondary causes (15%)
What is posthemorrhagic anemia?
Acute blood loss results in decreased blood volume, reduction in total number of cells. Hematocrit would be normal b/c equal loss of components
What happens in severe blood loss?
Initially hematocrit normal, but after 24 hours, replacement of RBCs takes longer and hematocrit would decrease (you’d see anemia symptoms now). Would need PRBCs
What is hemolytic anemia?
Breakdown of old RBCs (phagocytosed by macrophages) occurs at accelerated rate, hematopoiesis cannot keep up. Can be congenital or acquired
What would be an example of congenital hemolytic anemia?
Sickle cell anemia, thalessemia. Defects make RBCs more susceptible to rupture and phagocytosis
What would be a cause of acquired hemolytic anemia?
Drug-induced hemolytic anemia
What would lab samples show in hemolytic anemia?
Decreased hematocrit, hemoglobin, normal MCV/MCH/MCHC/RDW, increased % of reticulocytes, elevated bilirubin
What is anemia of chronic disease?
Decreased erythropoiesis response to chronic systemic disease/inflammation (AIDs, rheumatoid arthritis, hepatitis, renal failure), can occur in elderly (aging of hematopoietic system and increased cytokines)
What occurs during anemia of chronic disease?
Lactoferrin and iron-binding anti inflammatory glycoprotein released by neutrophils to bind iron and reduce availability for bacteria, creates unavailability for erythropoiesis and complexes that can deposit in kidneys
What are dysfunctions of WBCs?
Lymphomas and leukemias
What is a lymphoma?
Cancer stemming from lymphocytes (B or T-cells)
Where are lymphocytes housed?
Found within lymph nodes and other lymphatic tissue (spleen)
What is lymphadenopathy?
Enlargement of lymph node (if close to skin, can be palpated)
When do we worry about lymphadenopathy?
When generalized and painless. When localized and tender, usually means body fighting infection/reacting to allergen
What are two types of malignant lymphoma?
Non-Hodgkin’s Lymphoma (NHL) and Hodgkin’s Lymphoma (HL)
What characterizes hodgkin’s lymphoma?
Malignant proliferation of B-cells, presence of Reed- Sternberg cells and localized painless lymphadenopathy
What are Reed-Sternberg cells?
B cells that don’t divide properly when proliferating, develop 2 nuclei and are large
What happens to B-cells in HL?
Mutations occur to genes encoding antibodies secreted by B cells, mutant cells lose B cell characteristics, proliferate uncontrollably through clonal expansion, do not divide properly (RS cells). Happens in lymph nodes, metastasize to other areas
What can malignant B-cells do in HL?
Secrete cytokines that help with proliferation/survival, secrete anti-inflammatory cytokines (IL-10) to prevent CD8+ T cells from attacking
How does staging occur in HL?
Determined by number and location of lymph nodes affected, spread
Is HL highly curable?
Yes, often relapse though
What is the cause of HL?
Unknown, EBV found in 40% of those- causes malignant B cells to change their phenotype and allows for survival/proliferation
What are some clinical manifestations of HL?
Enlarged cervical, axillary, inguinal, and/or retroperitoneal lymph nodes, weight loss, fever, night sweats, can have masses that result in superior vena cava syndrome and other clinical manifestations
What is NHL?
Cancer cells derived from B cells, T cells, or NK cells
Which malignant lymphoma is more common?
NHL
What is the cell type most commonly affected in NHL?
Diffuse large B-cells
What are the two classifications of NHL?
Indolent or aggressive
What are potential causes of NHL?
Chromosomal translocation, toxins, infections, chronic inflammation, environmental factor, immunodeficiency, some autoimmune disorders (increases risk)
What are some clinical manifestations of NHL?
Generalized, painless lymphadenopathy (cervical, axillary, inguinal, femoral), extranodal involvement likely
What is the cure rate of NHL?
68%, less than HL, 50% will relapse
What is different about NHL in children?
B and T-cell etiology equally likely, disease more aggressive but treatment MORE successful
What is leukemia?
Malignant disorder of leukocytes in the blood and bone marrow, usually characterized by uncontrolled proliferation and decreased apoptosis
What are the four types of leukemia?
Acute lymphocytic, acute myelogenous, chronic lymphocytic, and chronic myelogenous
What is typical of acute forms of leukemia?
Cells less differentiated, onset of symptoms more rapid
What occurs in AML?
Involves WBC that are not lymphocytes, cells of myelogenous lineage unable to differentiate into more mature forms and remain in blast stage (few effector cells in circulation),
What are some clinical manifestations of AML?
Ineffective erythropoiesis, bone marrow failure due to crowding (WBC, RBC, and platelet production compromised), cancer cells invade blood and affect other cells (lymphadenopathy, enlargement of spleen/liver), bone pain/increased fracture risk (overcrowding= marrow cavity enlargement, disruption of trabecular bone that provides support), systemic effects
What is CML?
Affects cells of myeloid lineage, develops slowly
What chromosome is present in CML?
Philadelphia chromosome which is the fusion of BCR/ABL1 d/t translocation
How does CML progress?
Slowly, patients often asymptomatic, progression occurs in three stages (chronic, accelerated, blast)
What is ALL?
Most common form of leukemia in children, least common in adults. Uncontrolled proliferation of abnormal, immature lymphocytes and their progenitors= overcrowding in bone marrow and lymphoid organs
What is the most common cause of ALL in children?
B-cell progenitor, equal between B and T cell progenitor in adults
What is CLL?
Indolent malignancy characterized by increased production of mature but dysfunctional B lymphocytes, common leukemia in those over 65
What is characteristic of CLL?
Does not result in overcrowding of the bone marrow because most mature B lymphocytes reside in the lymph nodes/nodules
What leukemias are the Philadelphia chromosome present in?
ALL, CML
What protein is not a normal component of plasma?
Collagen (albumin, clotting factors, globulins are)
What secondary lymphoid organ can release blood into circulation to restore blood volume?
Spleen
In adults, where does erythropoiesis occur?
Vertebrae, ribs, pelvic bones, sternum
How is iron stored in tissues?
As myoglobin in muscles, as ferritin and hemosiderin in liver and bone marrow
Where does destruction of aged erythrocytes occur?
Spleen
Which WBC does not circulate in the plasma?
Mast cells
What is a megakarocyte?
Large cells responsible for production of platelets
What are potential causes of thrombocytopenia?
Decreased platelet production (secondary to infection, drugs, deficiencies, renal failure, radiation, cancer in bone marrow) , increased consumption (heparin-induced, ITP, TTP) , or both
What is HIT (heparin-induced thrombocytopenia?)
Immune mediated, adverse drug reaction caused by IgG antibodies against heparin-platelet factor 4 complex= increased consumption, decrease in counts
What is ITP (immune thrombocytopenic purpura)?
Secondary to infections, large amount of antigen in blood and immune complexes bind to receptors on platelets= destruction, common in children
What is thrombopoietin?
Glycoprotein produced by liver and kidney, regulates production of platelets (stimulates production/differentiation of megakarocytes)
What is Vit K?
Fat-soluble vitamin, needed for synthesis and regulation of prothrombin and procoagulant factors, found in leafy green veggies, also synthesized by intestinal flora
What are some potential causes of a clotting disorder?
Vit K deficiency, liver disease (b/c hepatic cells produce factors involved in hemostasis)
What is DIC?
Widespread activation of coagulation resulting in formation of fibrin clots in medium and small vessels throughout body, can result in multisystem organ failure, may result in increased consumption of platelets
