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428 Cards in this Set

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Describe the blood cell origin/differentiation of RBCs.
Pluripotent hematopoietic stem cell --> proerythroblast --> reticulocyte -->erythrocyte
Describe the blood cell origin/differentiation of neutrophils, eosinophils, and basophils.
Pluripotent hematopoietic stem cell --> myeloid stem cell --> myeloblast --> promyelocyte --> myelocyte --> metamyelocyte --> stab (band) cell --> neutrophils/eosinophils/basophils
Describe the blood cell origin/differentiation of monocytes.
Pluripotent hematopoietic stem cell --> myeloid stem cell --> monoblast --> monocyte
Describe the blood cell origin/differentiation of platelets.
Pluripotent hematopoietic stem cell --> myeloid stem cell --> megakaryoblast --> megakaryoctye --> platelets
Describe the blood cell origin/differentiation of plasma cells.
Pluripotent hematopoietic stem cell --> lymphoid stem cell --> lymphoblast --> B cell --> plasma cell
Describe the origin/blood cell differentiation of active T cells.
Pluripotent hematopoietic stem cell --> lymphoblast --> T cell --> active T cell
What is the white blood cell differential from highest to lowest? (Mnemonic)
Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
("Neutrophils Like Making Everything Better")
How long do erythrocytes last survive?
120 days
What do RBCs have that allows them to transport CO2 from the periphery to the lungs for elimination?
Chloride-bicarbonate antiport. Important in the "physiologic chloride shift," which allows the RBC to transport CO2 to the lungs for elimination. When HCO3- exits a RBC (low CO2 levels, e.g. lungs), Cl- moves into the RBC to balance charges. When HCO3- enters a RBC (high CO2 levels), Cl- exits the RBC.
What does RBC anisocytosis mean?
varying sizes of RBCs
What does RBC poikilocytosis mean?
varying shapes of RBCs
What does erythrocytosis mean?
= polycythemia = increased number of red cells
What are the 2 major groups of leukocytes?
Granulocytes (basophils, eosinophils, neutrophils)
Mononuclear cells (lymphocytes, monocytes)
What type of cell is this, and what is its function?
Basophil. Mediates allergic reaction. Has a bilobate nucleus with densely basophilic granules containing heparin (anticoagulant), histamine (vasodilator) and other vasoactive amines, and leukotrienes (LTD-4). Found in blood.
What cell type is this and what is its function?
Mast cell. Mediates allergic reaction. Degranulation - histamine, heparin, and eosinophil chemotactic factors. Can bind IgE to membrane. Mast cells resemble basophils structurally and functionally but they are not the same cell type. Found in tissue.
What drug prevents mast cell degranulation?
Cromolyn sodium (prevents mast cell degranulation)
Mast cells are involved in what type of hypersensitivity reaction?
Type I
What is this cell type and what is its function?
Eosinophil. Defends against helminthic and protozoan infections (major basic protein). Highly phagocytic for antigen-antibody complexes. Bilobate nucleus. Packed with large eosinophilic granules of uniform size. Produces histaminase and arylsulfatase.
What are 5 causes of eosinophilia? (Mnemonic)
Neoplastic, Asthma, Allergic processes, Collagen vascular diseases, Parasites
("NAACP")
What cell type is this? What is its function?
Neutrophil. Acute inflammatory response cell. Phagocytic. Multilobed nucleus. Large, spherical, azurophilic granules (called lysosomes) contain hydrolytic enzymes, lysozyme, myeloperoxidase, and lactoferrin.
What cell type is this?
Monocyte. Large. Kidney-shaped nucleus. Extensive "frosted glass" cytoplasm. Differentiates into macrophages in tissue.
What is the cell in the middle? What is it's function.
Macrophage (One Plasma Cell (left), 1 Macrophage (center) and 3 lymphocytes). Phagocytoses bacteria, cell debris, and senscent red cells and scavenges damaged cells and tissues. Long life in tissue.
what type of cell is this? What is its function?
Dendritic cell. Professional APC. Expresses MHC II and Fc receptor (FcR) on surface. Main inducers of primary antibody respones. Called Langerhans cells on skin.
What type of cell is this? What is its function?
Lymphocyte. Round, densely staining nucleus. Small amount of pale cytoplasm. B lymphocytes produce antibodies. T lymphocytes manifest the cellular immune response as well as regulate B lympohocytes and macrophages.
Which parts of the lymphoid tissue and spleen are B lymphocytes found in?
Follicles of lymph nodes, white pulp of spleen
What type of cell is this and what is its function?
Plasma cell. Off-center nucleus, clock-face chromatin distribution, abundant RER and well-developed Golgi apparatus. B cells differentiated into plasma cells, which produce large amounts of antibody specific to a particular antigen.
What is one plasma cell neoplasm?
Multiple myeloma
The majority of circulating lymphocytes are what type of cell?
T cells (80%)
What are the vitamin K dependent coagulation factors?
II, VII, IX, X, protein C, protein S
What does protein C do in the coagulation cascade?
Thrombomodulin activates protein C (protein S is a cofactor in protein C activation). Activated protein C --> inactivation of Va and VIIIa
What is the function of antithrombin III? What drug activates it?
Antithrombin III inactivates thrombin (IIa), IXa, Xa, XIa. Activated by heparin.
What does tPA do?
Generates plasmin from plasminogen, which cleaves fibrin clots
1) What is the effect Kallikrein on the kinin cascade?
2) What is the effect of
3) Kallikrein on the fibrinolytic system?
What activates kallikrein?
1) Kallikrein activates bradykinin (HMWK --> bradykinin)
2) Kallikrein activates plasmin (plasminogen --> plasmin)
3) Factor XIIa activates Kallikrein (Prekallikrein --> Kallikrein)
What enzyme breaks up fibrin into fibrin split products (fibrinolysis)?
What is the effect of this enzyme on the complement cascade?
Plasmin breaks down fibrin into fibrin split products. Plasmin also converts C3 into C3a.
What are 3 actions of bradykinin? What enzyme activates bradykinin? What enzyme deactivates it?
Increases vasodilation, vessel permeability, and pain
Kallikrein activates bradykinin (HMWK --> bradykin) and ACE inactivates it
What does Factor V Leiden mutation cause?
Causes resistance to activated protein C (causes hypercoagulability)
What are the 3 steps in platelet plug formation?
1. Platelet adhesion to exposed basement membrane - requires vWF
2. Aggregate of platelets (TXA2 released by platelets increases aggregation, PGI2 and NO released by endothelial cells decreases aggregation)
3. Swelling - ADP and Ca++ release to strengthen plug --> fibrin deposition
What are 4 substances that activate factor XII in the coagulation cascade (XII --> XIIa)?
Collagen, basement membrane, activated platelets, HMWK
If you have blood group A, what antigen will you have on RBCs and what antibodies will you have in your plasma?
A antigen on RBC surface and B antibody in plasma
If you have blood group B, what antigen will you have on RBCs and what antibodies will you have in your plasma?
B antigen on RBC surface and A antibody in plasma
If you have blood group AB, what antigen will you have on RBCs and what antibodies will you have in your plasma?
A and B antigens on RBC surface, no antibodies in plasma ("universal recipient")
If you have blood group O, what antigen will you have on RBCs and what antibodies will you have in your plasma?
Neither A nor B antigen on RBC surface, both antibodies in plasma ("universal donor")
What form of RBC is this, and what are 2 diseases it can be present in?
Spherocyte. Can be found in hereditary spherocytosis and autoimmune hemolysis
What form of RBC is this and what disease can it indicate?
Elliptocyte. Can indicate hereditary elliptocytosis.
What form of RBC are the cells on the right (compared to normal RBCs on the left)? What are two diseases they are present in?
Macro-ovalocytes. Present in megaloblastic anemia (along with hypersegmented neutrophils), and bone marrow failure
What form of RBC is this? What does it indicate?
Helmet cell, indicates DIC or traumatic hemolysis. Schistocytes (irregular, jagged fragments of RBCs - see picture above) are also present in these conditions.
What is this form of RBC? What is it indicative of?
Bite cell. Indicative of G6PD deficiency.
What type of RBC is this? What is it indicative of?
Teardrop cell. Present in myeloid metaplasia with myelofibrosis.
What form of RBC is this? What disease is it found in?
Acanthocyte (spiny RBC). Found in abetalipoproteinemia.
What form of RBC is this? What are 4 diseases it is found in? (Mnemonic)
Target cell. Found in:
HbC disease, Asplenia, Liver disease, Thalassemia ("HALT" said the hunter to his Target)
What are poikilocytes?
Nonuniform RBC shapes in TTP/HUS, microvascular damage, DIC
What form of RBC is this? What condition is it often found in?
Burr cell. Found in TPP/HUS
What is the description of these RBCs? What are 4 conditions it is associated with? (Mnemonic)
Basophilic stippling. Found in:
Thalassemias, Anemia of chronic disease, Iorn deficiency, Lead poisoning
("TAIL")
Thalassemias, Lead poisoning, and sideroblastic anemias all present with what type of anemia?
Microcytic, hypochromic anemia (MCV < 80)
What type of anemia is present in iron deficiency? What are the serum iron, TIBC, and ferritin levels like?
Microcytic, hypochromic anemia (MCV < 80)
Decreased serum iron, increased TIBC, and decreased ferritin (interacellular iron stores)
Drugs that block DNA syntesis (e.g. sulfa drugs, phenytoin, and AZT), vitamin B12/folate deficiency, and marked reticulocytosis all produce what type of anemia?
Macrocytic
(MCV>100)
What type of anemia is present in anemai of chronic disease? What are the TIBC and ferritin levels, as well as the amount of storage of iron in marrow macrophages?
Normocytic, normochromic anemia.
Decreased TIBC, increased ferritin, increased storage iron in marrow macrophages.
What are 2 blood markers of RBC hemolysis?
Decreased serum haptoglobin, increased serum LDH
What test can be used to distinguish between immune and non-immune mediated RBC hemolys?
Coombs test. Postive Coomb's test = immune mediated.
Hypersegmented neutrophils are associated with what problem?
Vitamin B12 and folate deficiencies
Total iron binding capacity (TIBC) is an indirect measure of what?
Transferrin
What are serum iron levels in:
1) Iron deficiency
2) Chronic disease
3) Pregnancy/OCP use
4) Hemochromatosis
1) Iron deficiency: Decreased (primary)
2) Chronic disease: Decreased
3) Pregnancy/OCP use: Normal
4) Hemochromatosis: Increased (primary)
What are transferrin levels in:
1) Iron deficiency
2) Chronic disease
3) Pregnancy/OCP use
4) Hemochromatosis
1) Iron deficiency: increased
2) Chronic disease: Decreased
3) Pregnancy/OCP use: Increased (primary)
4) Hemochromatosis: Decreased
What are ferritin levels in:
1) Iron deficiency
2) Chronic disease
3) Pregnancy/OCP use
4) Hemochromatosis
1) Iron deficiency: Decreased
2) Chronic disease: Increased (primary)
3) Pregnancy/OCP use (Normal)
4) Hemochromatosis (increased)
What are % transferrin saturation (serum Fe/TIBC) levels in:
1) Iron deficiency
2) Chronic disease
3) Pregnancy/OCP use
4) Hemochromatosis
1) Iron deficiency: Significantly decreased
2) Chronic disease: Normal
3) Pregnancy/OCP use: Decreased
4) Hemochromatosis: Significantly increased
Why are transferrin levels decreased in chronic disease?
Evolutionary reasoning - pathogen use circulating iron to thrive. The body has adapted a system in which iron is stored within the cells of the body and prevents pathogens from acquiring iron.
Pancytopenia characterized by severe anemia, neutropenia, and thrombocytopenia caused by failure or destruction of mulipotent myeloid stemm cells with, with inadequate production or release of differentiated cell lines is called...
Aplastic anemia
What are 3 viruses that can cause aplastic anemia?
Parvovirus B19, EBV, HIV. May also follow acute hepatitis.
What does this bone marrow biopsy show?
The bone marrow biopsy on the previous slide showed aplastic anemia. There are virtually no hematopoietic cells, and the marrow space consists of fat and stroma. The picture above shows what a normal bone marrow biopsy should look like. The overall cellularity is between 30 and 70 percent, with the remainder of the space being occupied by fat and stroma.
What are the treatments for aplastic anemia?
ithdrawl of offending agent, allogeneic bone marrow transplantation, RBC and platelet transfusion, G-CSF or GM-CSF
What mutation is present in sickle cell anemia?
HbS mutation is a single amino acid replacement in the beta chain (substitution of normal glutamic acid with valine).
What are some infectious disease that cause severe disease in sickle cell patients?
Parvovirus B19 --> aplastic anemia
Salmonella osteomyelitis
What is one drug that can be used in sickle cell anemia?
Hyroxyurea (increases the level of HbF)
What precipitates sickling in sickle cell?
Low O2 or dehydration
Sickle cell patients have an increased risk of disease from encapsulated organisms due to...
Autosplenectomy
What does the skull look like in x-rays of patients with sickle acell and thalassemia?
There can be bone marrow expansion that produces a "crew cut" appearnce on skull x-ray
Why are newborns with sickle cell initially asymptomatic?
Because of increased HbF and dereased HbS
What type of thalassemia is present in Asia an Africa?
Alpha thalassemia
What is the defect in alpha thalassemia?
The alpha-globin chain is underproduced. There are 4 alpha globin genes, and increased number of mutated genes is associated with increased severity of the disease.
What is HbH?
Tetramer of 4 beta globin chains. Caused by a mutation in 3 alpha globin genes.
What is Hb Barts?
Mutation in all 4 alpha globin genes. gamma-4 tetramers are present. Results in hydrops fetalis and intrauterine fetal death.
What is the difference between beta thalassemia minor and major?
Beta thalassemia minor (heterozygote): beta chain is underproduced
Beta thalassemia major (homozygote): The beta chain is absent.
What antibodies are produced in autoimmune anemia with warm agglutinins? What antibodies are produced when there are cold agglutinins? (Mnemonic)
Warm agglutinin = IgG
Cold agglutinin = IgM
"Warm wheather is GGGreat. Cold ice cream... MMMM"
What type of hemolysis is present in autoimmune anemia?
Mostly extravascular hemolysis (accelerated RBC destruction in liver Kupffer cells and spleen)
What are 2 causes of autoimmune anemia with cold agglutinins?
Mycoplasma pneumoniae, infectious mononucleosis (EBV)
What is the defect present in hereditary spherocytosis?
Spectrin or ankyrin defects
What are the dark blue dots and what do they indicate?
Howell-Jolly bodies. They are small fragments of DNA, and they are present after splenectomy.
What type of hemolysis is present in paroxysmal nocturnal hemoglobinuria? What is the defect?
There is intravascular hemolysis due to a deficiency of glycophosphatidylinositol (Gp I). Without Gp I, decay accelerating factor cannot anchor properly to the RBC membrane, and the RBCs are most susceptible to damage by complement.
What type of hemolysis is present in microangiopathic anemia (seen in DIC, TTP/HUS, SLE, or maligant hypertension)? What are some abnormal forms of cells you see?
Intravascular hemolysis. Schiztocytes/helmet cells can be found.
Activation of the coagulation cascade leading to microthrombi and global consumption of platelets, fibrin, and coagulation factors is called...
Disseminated intravascular coagulation (DIC)
What are 7 causes of DIC? (Mnemonic)
Sepsis (gram negative, Trauma, Obstetric complication, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion
("STOP Making New Thrombi")
What are the lab findings in DIC? What forms of RBCs are found?
Increased PT, PTT, fibrin split products (D-dimers),
Decreased platelet count.
Helmet cells and schistocytese present on blood smear.
Microhemorrhages are present in what bleeding disorders?
Platelet abnormalities. Increased bleeding time.
Macrohemorrhages are present in which bleeding disorders?
Coagulation factor defects. Increased PT and/or PTT.
What is the cause of idiopathic thrombocytopenic purpura (ITP)?
antiplatelet antibodies (against GpIIb:IIIa receptors (type II hypersensitivity reaction)
When does ITP usually occur?
Abrupt onset after an upper respiratory tract infection
What is the cause of thrombotic thrombocytopenic purpura (TTP)?
Acquired or genetic deficiency in vWF-cleaving metalloproteinase in endothelial cells. excess vWF increases platelet adheison to areas of endothelial injury at the arteriole-capillary junctions.
What is the clinical pentad of TTP?
Fever, thrombocytopenia, renal failure, microangiopathic hemolytic anemia with schistocytes, CNS deficits
Factor VIII deficiency is also known as...
Hemophilia A
Factor IX deficiency is also known as...
Hemophilia B
Deficiency of vWF leads to what?
Mild bleeding disorder. Leads to defect in platelet adhesion and decreased factor VIII survival.
What is Bernard-Soulier disease?
An autosomal recessive bleeding disorder where there is a deficiency of glycoprotein Ib (GpIb), the receptor for von Willebrand factor.

It is a Giant Platelet Syndrome that is characterized by abnormally large platelets.
What is Glanzman's thrombasthenia?
Platelets lack glycoprotein IIb/IIIa, leading to increased bleeding time.
What is the defenition of thrombocytopenia?
At what level does generalized bleeding occur?
Thrombocytopenia: < 100,000 platelets/mm^3
Generalized bleeding: <15,000-20,000 platelets/mm^3
What are the coagulation factors in the extrinsic (PT) pathway?
Factors II, V, VII, and X
What are the coagulation factors in the intrinsic (PTT) pathway?
All factors except VII and XIII
What type of cells are these and what type of cancer are they often seen in?
Reed-Sternberg cells. Distinctive tumor giant cell seen in Hodgkin's disease. Binucleate or bilobed with the 2 halves as mirror images ("owls eyes"). Necessary but not sufficient for a diagnosis of Hodgkin's disease. Variants include lacunar cells in nodular sclerosis variant.
What CD's are present on Reed Sternberg cells in Hodgkin's lymphoma?
CD30+, CD15+. B cell origins
How does Hodgkin's lymphoma spread?
Localized spread, single group of lymph nodes are involved. Extranodal involvement rare. Contiguous spread.
What sort of symptoms are present in Hodgkin's lymphoma?
Constitutional ("B") signs/symptoms: low grade fever, night sweats, weight loss
50% of Hodgkin's lymphoma are associated with what?
EBV
What age groups are affected by Hodgkin's lymphoma?
Bimodal distribution: Young and old. More common in men, except for nodular sclerosing type.
Increased lymphocytes and decreased Reed-Sternberg cells indicate ____ prognosis in Hodgkin's lymphoma.
Good
Non-Hodgkin's lymphoma are associated with what conditions?
HIV and immunosuppression.
How does non-Hodgkin's lymphoma spread?
Multiple, peripheral nodes; extranodal involvement common; noncontiguous spread.
What type of cells are involved in non-Hodgkin's lymphoma?
Majority involve B cells, except those of lymphoblastic T cell origin
Do you get constitutional signs and symptoms in non-Hodgkin's lymphoma?
Fewer than in Hodgkin's lymphoma
What age group has peak incidence of non-Hodgkin's lymphoma?
20-40 years of age
List 4 types of Hodgkin's lymphoma from most common to least common.
Nodular sclerosing > Mixed cellularity > Lymphocyte predominant > Lymphocyte depleted (rare).
What are 2 types of Hodgkin's lymphoma with the best prognosis?
Nodular sclerosing, Lymphocyte predominant (these two types also have the most lymphocytes)
What type of Hodgkin's lymphoma has the worst prognosis?
Lymphocyte depleted
Which type of Hodgkin's lymphoma has the most numerous RS cells?
Mixed cellularity
What type of cancer is this?
Multiple myeloma. These are monoclonal plasma cells with a "fried-egg" appearance.
What is the apearance of bone x-rays in someone with multiple myeloma?
Punched out lesions. Destructive bone lesions leads to hypercalcemia.
What would a blood smear show in multiple myeloma?
Rouleaux formation (stacks of RBCs)
What does serum protein electrophoresis show in multiple myeloma?
Monoclonal immunoglobulin spike (M protein)
What is found in the urine in multiple myeloma?
Ig light chains (Bence Jones protein)
Most non-Hodgkin's lymphomas are derived from what cell type?
Most are derived from B cells (e.g. small lymphocytic lymphoma, follicular lympohoma, 80% of diffuse large cell lymphoma, mantle cell lymphoma, and Burkitt's lymphoma)
What are the only 2 non-Hodgkin's lymphomas derived from T cells?
Diffuse large cell lymphoma (20% are derived from T cells),
Lymphoblastic lymphoma
What non-Hodgkin lymphoma is most common in children? What cancer does it commonly present with?
Lymphoblatic lymphoma (T cell origin). Commonly presents with ALL and mediastinal mass; very aggressive T-cell lymphoma.
What is the most common non-Hodgkin lymphoma in adults?
Diffuse large cell lymphoma
What are the 3 non-Hodgkin's lymphomas that affect mostly children?
Lymphoblastic lymphoma (most common in children - T cell origin), Burkitt's lymphoma, Diffuse large B cell lymphoma (20% occur in children)
t(9;22) is associated with...
CML. t(9;22) is the Philadelphia chromosome
t(8;14) is associated with...
Burkitt's lymphoma (c-myc activation. c-myc gene moves next to heavy-chain Ig gene on chromosome 14.)
t(14;18) is associatd with...
Follicular lymphomas (bcl-2 activation)
t(15;17) is associated with...
M3 type of AML (responsive to all-trans-retinoic acid)
t(11;22) is associated with...
Ewing's sarcoma
t(11;14) is associated with...
Mantle cell lymphoma
What cancer is this?
Burkitt's lymphoma. Shows sheets of small, undifferentiated cells with interspersed tingible-body macrophages
What is a leukemoid reaction?
A benign, exagerratd leukocyte response to infection. There is a left shift (80% bands) and an increase in leukocyte alkaline phosphatase.
What non-Hodgkin's lymphoma is CD5+?
Mantle cell lymphoma.
What type of leukemia is TdT+?
ALL (TdT is a marker of pre-T and pre-B cells)
What type of cancer is this?
AML. Auer rods are present in the cytoplasm. Auer rods are peroxidase-positive cytoplasmic inclusion in granulocytes and myeloblasts. Primarily seen in acute promyelocytic leukemia (M3). Treatment of AML M3 can release Auer rods --> DIC.
What are 3 characteristics of acute leukemias?
Blasts predominate,
Occurs in children or elderly, Short and drastic course
What are 3 characteristics of chronic leukemias?
More mature cells,
Midlife age range,
Longer, less devastating course
Which leukemias are found in the following age ranges:
1) <15
2) 15-39
3) 40-60
4) >60
1) <15: ALL
2) 15-39: AML
3) 4-60: CML
4) >60: CLL
What type of leukemia is the most responsive type and may also spread to the CNS and testes?
ALL
Which leukemia is defined by the Philadelphia chromosome?
CML t(9:22), bcr-abl
Which leukemia stains TRAP (tartrate-resistant acid phosphatase) positive?
Hairy cell leukemia
What disease is this found in?
Histiocytosis X. Caused by Langerhan's cells from the monocyte lineage that infiltrate the lung. Birbeck granules ("tennis rackets" on EM). Primarily affects young adults. Worse with smoking.
Does Warfarin affect PT or PTT? (Mnemonic)
Affects the Extrinsic pathway and increases PT
("The EX-PaTriot went to WAR(farin)")
What are 3 stimuli for EPO release?
Hypoxemia, left-sided OBC, high altitude
Where is EPO synthesized?
The endothelial cells of the peritubular capillaries in the kidneys
This blood smear was stained with supravital stain. What are the threadlike filaments in the cytoplasm?
These are reticulocytes. The supravital stain detects thread-like RNA filaments. In 24 hours they become mature RBCs.
What is the reticulocyte count a measure of?
Reticulocyte count is a measure of effective erythropoiesis. It needs to be corrected for the degree of anemia.
How do you calculate a corrected reticulocyte count?
Corrected retic count = (actual Hct/45) x reticulocyte count, where 45 represents the normal hematocrit.
In a corrected reticulocyte count, what represents effective and ineffective erythropoiesis?
Corrected retic count:
<3% is ineffective erythropoiesis
> or = 3% is effective erythropoiesis
What are the 2 most common sites of extramedullary hematopoiesis?
Liver, spleen
Where does hematopoiesis take place in the fetus?
RBC formation begins in the yolk sac and subsequently moves to the liver and finally the bone marrow by the fifth to sixth months of life
What globin chains are present in HbF? What does HbF do to the OBC?
2alpha/2gamma chains. HbF shifts the OBC to the left (compared to HbA), causing an increase in Hb
What causes physiologic jaundice of the newborn?
Fetal RBCs containing HbF are destroyed by splenic macrophages. The unconjugated bilirubin derived from the initial destruction of the fetal RBCs is responsibele for physiologic jaundice of the newborn, which occurs around 3 days from birth.
Why do men have higher hematocrits?
Due to increased testosterone (stimulates erythropoiesis) and lack of cyclic bleeding.
How pregnancy affect RBC production and plasma volume?
During pregnancy, there is a 2 times greater increase in plasma volume than RBC mass (but both are increased)
What is the definition of anemia? How are O2 saturation and PO2?
Anemia is a decrease in Hb, Hct, or RBC concentration. O2 saturation and PO2 are normal.
Define microcytic, normoctyic and macrocytic anemia.
MCV is useful for classification of anemias.
Microcytic (<80 Micrometers^3),
Normocytic (80-100 micrometers^3),
Macrocytic (>100 micrometers^3)
If a patient has blood loss, how long before you would expect the corrected reticulocyte to increase above 3%?
1 week
What is the mean corpuscular hemoglobin concentration (MCHC) and indication of?
Average Hb concentration in RBCs.
When is MCHC decreased, and when is it increased?
MCHC is decreased in microcytic anemais and increased in hereditary spherocytosis (increased MCHC correlates with the presence of spherical RBCs)
What does RDW refelect?
RDW reflects variation in the size of RBCs in peripheral blood (anisocytosis). Increased if RBCs are not uniformly the same size.
What is the only microcytic anemia with an increased RDW?
Iron deficiency anemia, due to a mixture of normoctyic and microcytic RBCs.
What is the only source of energy for mature RBCs?
Anaerobic glycoysis. Lactic acid is the main end product of RBC metabolism.
What is methemoglobin?
Heme iron that is oxidized (Fe 3+). MetHb cannot bind O2.
What substance is required to right-shift the OBC of RBCs (i.e., increase release of O2 into tissues)?
2,3-bisphosphoglycerate
What happens to senescent RBCs? What is the end product of heme degredation?
Senescent RBCs are removed by splenic macrophages. The end product of heme degredation in macrophages is uncojugated bilirubin.
What is the arrow pointing to?
A platelet. Derived from the cytoplasmic budding of megakaryocytes.
What is the primary soluble iron storage protein in the body? Where is the iron/protein complex stored?
Ferritin. The ferritin/iron complex is stored in bone marrow macrophages.
Serum ferritin levels correlate with what?
Ferritin stores in macrophages
What happens to ferritin levels during inflammation?
Synthesis of ferritin increases in inflammation due to release of interleukins and TNFalpha. This sequesters iron away from potential pathogens.
Decreased serum ferritin is diagnostic of what condition?
What are 2 conditions with increased serum ferritin?
Decreased: Iron deficiency
Increased: Anemia of chronic disease, iron overload disease
What is serum iron?
Represents iron bound to transferrin. Transferrin is synthesized in the liver
When do you have decreased serum iron? When do you have increased serum iron?
Decreased: Iron deficiency, anemia of chronic disease
Increased: Iron overload disorders
What is serum total iron binding capacity (TIBC)?
Serum TIBC correlates with the concentration of transferrin.
Increased TIBC = Increased transferrin
Decreased TIBC = Decreased transferrin
What is the relationship between transferrin synthesis and ferritin stores in macrophages?
Decreased ferritin stores causes increasaed synthesis of transferrin
What are the levels of ferritin and TIBC in iron deficiency, anemia of chronic disease, and iron overload?
Decreased ferritin --> increased TIBC: Iron deficiency

Increased ferritin --> decreased TIBC: Anemia of chronic disease, iron overload
What is iron saturation (%)? What is the formula used to calculate it?
Represents the percentage of binding sites on transferrin occupied by iron.

Iron saturation (%) = serum iron/TIBC x 100
When do you have decreased % iron saturation, and when do you have increased % iron saturation?
Decreased: iron deficiency, anemia of chronic disease

Increased: iron overload disease
What is hepcidin?
Hepcidin is a peptide hormone produced by the liver that directly inhibits ferroportin, a protein that transports iron out of macrophages and enterocytes. By inhibiting ferroportin, hepcidin prevents macrophages from secreting stored iron into the blood, and prevents iron absorption by blocking iron release into the blood by enterocytes. In anemia of chronic disease hepcidin is released to prevent release of stored iron and to increase synthesis of ferritin.
What globin chains make up HbA?
HbA2?
HbF?
HbA: 2alpha/2beta (97% in adults)
HbA2: 2alpha/2delta (2% in adults)
HbF: 2alpha/2gamma (1% in adults)
What is the pathogenesis of microcytic anemias?
Defects in the synthesis of Hb (heme + globin chains)
What is the most common anemia, and what is the most common cause of it?
Mot common anemia: Iron deficiency (most commonly caused by bleeding)
What is Plummer Vinson syndrome?
Triad of dysphagia (due to esophageal webs), glossitis, and iron deficiency anemia (also have achlorhydria, and spoon nails - koilonychia)
How are iron % saturation, ferritin, TIBC, and RDW in iron deficiency?
Decreased iron % saturation and ferritin
Increased TIBC and RDW
What is the most common cause of iron deficiency in young children?
Inadequate intake
What is the most common anemia in hospitalized patients?
Anemia of chronic disease
What is the effect of hepcidin on macrophage iron stores?
Increases them (decreased release, increased ferritin synthesis)
What type of thalassemias are common in black American, Greeks, and Italians?
Beta-Thal.
What are the 4 levels of alpha-Thalassemia?
4 alpha chain genes:
1 gene deletion --> silent carrier with no associated anemia,
2 gene deletions -->alpha-thal trait with mild anemia and increased RBC count
3 gene deletions -->HbH (four beta chains). Severe hemolytic anemia.
4 gene deletions --> HbBarts (four gamma chains). Incompathible with life.
What are the levels of HbA, HbA2, and HbF in alpha-Thal trait?
Decreased HbA, HbA2, and HbF, but normal electrophoresis because all normal Hb types require alpha-globin chains. Increased RBC count.
What defects lead to beta-Thalassemia?
There is a decrease in beta-globin chain synthesis due to a DNA splicing defect (produces mild anemia) or due to a nonsense mutation with formation of a stop codon (produces severe anemia).
What does beta-thal minor look like on Hb electrophoresis?
Decreased HbA (2alpha/2beta)
Increased HbA2 (2alpha/2delta) and HbF (2alpha/2gamma)
What is the difference in symptoms between beta-Thal major and minor?
Major = severe hemolytic anema
Minor =mild hemolytic anemai
In beta-Thal major, what sort of inclusions do patients develop in their RBCs, and what does this causes?
They develop alpha chain inclusions. RBCs with alpha-chain inclusions undergo apoptosis in teh bone marrow
What does beta-thal major look like on Hb electrophoresis?
No HbA (because no beta chains are being made, increased HbA2 and HBF
What are causes of sideroblastic anemia? Which is most common?
Chronic alcoholism (most common), pyridoxine (B6) deficiency, Lead poisoning
What is this and what is the pathogenesis?
Ringed sideroblasts. Dark blue iron granules around the nucleus of developing normoblasts represent iron trapped within mitochondria and indicate a defect in heme synthesis.
Why does pyridoxine deficiency cause sideroblastic anemia? What is the most common cause of pyridoxine deficiency?
Vitamin B6 is a cofactor in delta-aminolevulinic acid synthetase (rate limiting reaction of heme synthesis). Deficiency of B6 leads to defective heme synthesis.
Isoniazid (INH) therapy (used to treat TB) is the most common cause of deficiency of Vitamin B6
What are 2 common sources of lead poisoning?
Paint (old paint chips, or paint used for decorating pottery), batteries
What causes basophilic stippling in RBCs?
Lead poisoning. The dots in basophilic stippling represent ribosomes. Lead denatures ribonuclease, causing the ribosomes to persist in the cytoplasm.
What are 3 enzymes that are denatured in lead poisoning?
Ferrochetalase (last enzyme in heme synthesis), Aminolevulenic acid (ALA) dehydrase (earlier step in heme synthesis), and Ribonuclease (degrades old ribosomes).
What are 3 symptoms of lead poisoning?
Abdominal colic with diarrhea, encephalopathy in children / peripheral neuropathy in adults, growth retardation in children
Where in the bones does lead deposit in growing children?
Epiphyses.
What is Fanconi's syndrome and how does it relate to lead poisoning?
Lead poisoning can cause tubular damage that produces Fanconi's syndrome. Fanconi's syndrome is a disorder in which is a disorder in which the proximal tubular function of the kidney is impaired. The syndrome includes proximal renal tubular acidosis (loss of bicarbonate in the urine), aminoaciduria, phosphaturia, and glucosuria.
What is the best screen and confirmatory test for lead poisoning?
Checking for increased whole blood and urine lead levels.
Where does B12 come from in the diet?
Animal products
What does vitamin B12 need to be bound to to be absorped by the terminal ileum? Where is this synthesized? What binds to B12 before it is secreted into the plasma?
Needs intrinsic factor (IF), made in the parietal cells of the stomach.
After absorption, B12 binds to transcobalamin II and is secreted into the plasma.
What is the most common cause of vitamin B12 deficiency?
Pernicious anemia (no intrinsic factor is produced due to autoimmune destruction of parietal cells)
How does phenytoin inhibit folate absorption?
Phenytoin inhibits intestinal conjugase, which is necessary to convert the form of folate found in the diet (polyglutamates) to the form that can be absorbed by the jejunum.
How do alcohol and oral contraceptivees inhibit folate absorption?
Alcohol and oral contraceptives block monoglutamate reabsorption
What is the most common cause of folate deficiency?
Alcoholism (alcoholics don't have good diets)
How does folate and B12 deficiency cause macrocytic anemia?
Folate and B12 deficiency cause impaired DNA synthesis. Cell division is delayed while the cytoplasmic volume continues to grow --> cells with extra cytoplasm.
What builds up in the blood in people who are folate or B12 deficient?
Homocysteine.
What is the most specific test for pernicious anemia?
Checking for antibodies that block binding of B12 to IF.
What type of cancer is pernicious anemia a risk factor for?
Pernicious anemia is a risk factor for gastric adenocarcinoma
Macrocytic anemia + neurologic disease = ?
Vitamin B12 deficiency
What's the most sensitive test for vitamin B12 deficiency?
Checking for increased methylmalonic acid in the urine (vitamin B12 is a cofactor for methylmalonyl CoA mutase, one of the steps in odd-chain fatty acid metabolism). Occurs in 95% of cases.
What test can be used to determine the cause of B12 deficiency?
Schilling test: Give radioactive B12 alone (dietary defiency), with IF (pernicious anemia), with antibiotics (bacterial overgrowth), or with pancreatic enzymes (chronic pancreatitis - can't cleave off R-binders) and see if there is absorption of the radioactive B12
Decreased maternal intake of folate is an increased risk for what?
Open neural tube defect in the newborn
What test is the best indicator of folate stores in the body?
Checking RBC folate levels
Decreased blood pressure and increased pulse are indications of what?
Volume depletion
How does the MCV of red blood cells change in iron deficiency or anemia of chronic disease?
It is normocytic before it becomes microcytic.
What is the most common cause of aplastic anemia?
Most cases are idiopathic (50-70%). Drugs are the most common known cause.
What is the most common infection that causes aplastic anemia?
Hep B
What is the most common cause of anemia in acute renal failure?
Decreased production of EPO
Increases in serum lactate dehydrogenase and uncojugated bilirubin are associated with...
Extravascular hemolysis (e.g. RBC phagocytosis by macrophages in the spleen). Uncojugated bilirubin is the end product of macrophage degredation of Hb. Hemolyzed RBCs release LDH.
What is haptoglobin, and what does decreased haptoglobin indicate?
Haptoglobin is an acute phase reactant that combines with free Hb to form a complex that is degraded in the spleen. Haptoglobin levels are decreased in intravascular hemolysis. The amount of Hb in the complexes is so small that unconjugated bilirubin is not significantly increased.
Decreased serum haptoglobin and hemoglobinuria indicate...
Intravascular hemolysis
What is the most common mutation in hereditary spherocytosis?
Ankyrin. Mutations in band 2, spectrin, or band 3 accoutn for other defects.
What sorts of RBCs are phagocytosed by macrophages in the spleen (extravascular hemolysis)?
RBCs coated with complement or C3b, or abnormally shaped RBCs (e.g. spherocytes, sickle cells)
Increased RBC osmotic fragility is associated with...
Hereditary spherocytosis (and hereditary elliptocytosis)
What is the treatment for hereditary spherocytosis?
Splenectomy, so that spherocytes don't get cleared by the spleen
Aplastic crisis in a hereditary spherocytosis patient is associated with what?
Parvovirus
What are the mutations in hereditary elliptocytosis?
Defective spectrin and band 4.1
Loss of anchor for decary accelerating factor (DAF) is associated with...
Paroxysmal nocturnal hemoglobinuria (PNH)
What is the best screening test for PNH? What is the confirmatory test?
Screening test is sucrose hemolysis test (sucrose enhanes complement destruction of RBCs). Confirm with acidified serum test (acidified serum activates the alternative pathway causing hemolysis).
What is the most common hemoglobinopathy in African Americans?
Sickle cell anemia
How is sickle cell disorder inherited?
Autosomal recessive. Heterozygous condition (sickle cell trait, HbAS) has no anemia. Homozygous condition (HbSS) produces anemia.
What is the mutation in sickle cell? What type of hemolysis occurs?
Sustitution of valine for glutamic acid at the sixth position of the beta globin chain. Mostly extravascular hemolysis.
What is the most important factor for sickling in sickle cell?
> 60% HbS concentration
Besides increased HbS concentration, what is another risk for sickling in sickle cell?
Increased concentration of deoxyhemoglobin. Can be caused by acidosis (causes O2 to be released from RBCs), volume depletion (intracellular dehydration causes increased concentration of deoxyhemoglobin), and hypoxemia
What causes microvascular occlusions in sickle cell?
Initial sickling is reversible. Recurrent sickling causes irreversible sickling. Irreversibly sickled cells have icnreased adherence to endothelial cells in the microcirculation.
What is the most common presentation of sickle cell disease in infants?
Dactylitis - painful swelling of hands and feet in infants (usually 6-9 months old). It is due to bone infarcts.
What is the most common cause of death in adults with sickle cell disease?
Acute chest syndrome: vaso-occlusion of pulmonary capillaries, chest pain, lung infiltrates, hypoxemia
What is the most common cause of death in children with sickle cell disease?
Strep pneumo sepsis. The spleen is dysfunctional by two years of age in sickle cell patients, which leaves them at risk for encapsulated bacteria
What is the most common cause of osteomyelitis in sickle cell patients?
Salmonella paratyphi
How does chronic hemolysis increase the risk of gallstones?
There is increased conjugated bilirubin in the bile, increasing risk for calcium bilirubinate gallstones
What are the symptoms of people with sickle cell trait?
No anemia, microhematuria
What are the levels of HbA and HbS in sickle cell trait vs. sickle cell disease?
Sickle cell trait (HbAS): HbA (55-60%), HbS (40-45%)

Sickle cell disease (HbSS): No HbA, HbS (90-95%), HbF (5-10%)
What is the most common enzyme deficiency causing hemolysis?
G6PD Deficiency
How is G6PD deficiency inherited? What type of hemolysis is there?
X-linked recessive. Primarily intravascular hemolysis.
What are Heinz bodies?
In G6PD deficiency, there is not enough GSH (glutathione) to neutralize hydrogen peroxide, an oxidant product of RBC metabolism. Peroxide oxidizes Hb, which precipitates in the form of Heinz bodies. Heinz bodies damage the RBC membranes causing intravascular hemolysis. Bite cells are produced when splenic macrophages remove Heinz bodies.
Increased 2,3-BPG and right-shifts in the OBC are signs of which RBC enzyme deficiency? What other lab findings are there?
Pyruvate kinase deficiency. There is an increase in 2,3-BPG synthesis proximal to the enzyme block, which causes a right shift in the OBC. Other lab findings include normocytic anemia, and RBCs with throny projections.
What is the most common type of immune hemolytic anemia?
Warm type (IgG) - 70% of autoimmune hemolytic anemias. The cold type (IgM) makes up the other 30%.
What are examples drug induced autoimmune hemolytic anemias caused by:
Drug adsorption, Immunocomplex, and autoantibodies
Drug adsorption: Penicillin, Immunocomplex: Quinidine, Autoantibodies: Methyldopa
What type of hemolysis is produced in IgG-mediated hemolysis?
Extravascular - RBCs are phagocytosed by splenic macrophages. Spherocytes are produced if a small portion of the membrane is removed.
What type of hemolysis is there in IgM-mediated hemolysis?
May be extravascular or intravascular depending on the degree of complement activation.
What type of hemolysis is there in complement-mediated hemolysis?
Intravascular (if RBCs are lysed by MAC complexes), extravascular if they are coated by C3b
What type of antibodies are produced in autoimmune hemolysis caused by SLE? How about by Mycoplasma pneumoniae or infectious mononucleosis?
SLE: IgG (warm antibodies)

Mycoplasma pneumoniae or infectious mononucleosis: IgM (cold antibodies)
What type of hemolysis produces jaundice?
Extravascular hemolysis, due to unconjugated hyperbilirubinemia
What are 2 tests for immune hemolytic anemia?
Direct antihuman globulin test (DAT - aka Coomb's test): Detects RBCs sensitized with IgG and/or C3b

Indirect antihuman globulin test (indirect-Coombs' test): Detects antibodies in teh serum
What is the most common cause of macroangiopathic hemolytic anemia?
Aortic stenosis
What is the most lethal type of malaria?
What are the fever patterns of:
Plasmodium vivax
Plasmodium falciparum
Plasmodium malariae
Plasmodium falciparum

Plasmodium vivax: Every 48 hours
Plasmodium falciparum: Daily fever with no pattern
Plasmodium malariae: Every 72 hours
When do you screen for Heinz bodies in G6PD deficiency? When do you do an enzyme assay?
Heinz body prep: screen during active hemolysis
Ezyme assay: confirmatory test when hemolysis subsides
"Cold" soft tissue abscesses, chronic eczema, and increased IgE (hyperimmune E syndrome) are all associated with...
Job's syndrome. An autosomal recessive disorder of neutrophils, characterized by abnormal chemotaxis. Patients have red hair and a leonine face.
How do you calculate absolute leukocyte count?
Absolute count = % leukocytes x total WBC count
A benign, exaggerated leukocyte response is called...
Leukomoid reaction
What is a leukoerythroblastic reaction?
Immature bone marrow cells enter into the peripheral blood stream. Indicates bone marrow infiltrative disease (e.g. fibrosis, metastatic breast cancer)
A leukoerythroblastic reaction in a woman over 50 years of age usually indicates what?
Metastatic breast cancer
What is the cause of neutrophil leukocytosis due to corticosteroids, catecholamines, and lithium?
Decreased activation of neutrophil adhesion molecules (normally hold neutrophils to the endotheilal wall), so more neutrophils end up in a blood sample
Type I hypersensitivity, invasive helminths, and hypocortisolism are all associated with...
Eosinophilia
Note: Corticostoeroids and cortisol cause sequestration of eosinophil in the lymph nodes
EBV binds to what site on B cells?
CD21
What are atypical lymphocytes (see above)?
Antigenically stimulated T cells
What are heterophile antibodies?
IgM antibodies directed against horse, sheep, and bovine RBCs. Present in infectious mononucleosis casued by EBV.
Neutrophilic leukocytosis, eosinopenia, and lymphopenia are all associated with what type of drugs?
Corticosteroids
What type of cells proliferate in response to chronic inflammation or malignancy?
Monocytes (develop monocytosis)
What is the most common overall type of leukemia?
Chronic lymphocytic leukemia (CLL)
What is the most important test for diagnosing leukemia?
Bone marrow exam
What is the only type of leukemia that doesn't always cause thrombocytopenia?
CML - causes thrombocytosis in 40% of cases
What are typical percentages of blasts in bone marrow biopsies in chronic and acute leukemias?
Chronic: <10% blasts
Acute: >20% blasts
(both will cause hypercellular bone marrow)
What are myeloid disorders?
Neoplastic stem cell disorders
Splenomegaly, propensity for reactive bone marrow fibrosis ("spent phase") and propensity for transformation to acute leukemia are all characteristics of...
Chronic myeloproliferative disorders
Increased Hb, Hct, and RBC count are all signs of ...
Polycythemia
What is the formula for RBC count?
RBC count =
RBC mass/(Plasma volume)
What is RBC mass?
Total number of RBCs in the body in mL/Kg
What is the difference between relative and absolute polycythemia?
Relative polycythemia: Increased RBC count due to a decrease in plasma volume (increased RBC count, decreased PV, normal RBC mass)

Absolute polycythemia: Increased BM production of RBCs (inreased RBC count, RBC mass)
When is absolute polycythemia appropriate and when is it inappropriate?
Appropriate: If there is a hypoxic stimulus for EPO release (increased RBC mass, increased EPO, normal PV, decreased SaO2)

Inappropriate absolute polycythemia: Ectopic secretion of EPO (increased RBC mass, increased EPO, mormal PV, normal SaO2)
What cells are increased in polycythemia vera?
Everything except the lymphocytes.
A ruddy face, pruritis after bathing, and peptic ulcer disease or all signs of ...
Increased histamine release (released from mast cells in the skin)
What is the only type of polycythemia with increased plasma volume and decreased EPO?
Polycythemia vera
What is the only polycythemia with decreased SaO2?
Appropriate polycythemia
Is the Philadelphia chromosome specific for CML?
No. It is also not lost during therapy unless alpha-interferon is used.
What is the most sensitive and specific test for CML?
Presence or absence of BCR-ABL fusion gene (100% of cases)
Myelofibrosis and myeloid metaplasia both have what two characteristics?
Marrow fibrosis, extramedullary hematopoiesis
Why is bleeding one of the findings in essential thrombocythemia?
There are increased numbers of platelets, but they are non-functional
What syndrome usually occurs in ment between 50 - 80 years old, has severe pancytopenia, and often progresses to AML (it is often called "preleukemia")?
Myelodysplastic syndrome
t(15;17) translocation is present in what leukemia?
Acute myelogenous leukemia (AML) - M3 (acute promyelocytic anemia)
What cytological structures are present in AML?
Auer rods
What is a common clinical finding in AML, especially in M3? What is commonly found in M5? Which one is common in Down syndrome?
M3: DIC
M5: Gum infiltration
M7 is common in Down syndrome
What's the most common leukemia in children?
ALL
What type of ALL is CD10 and TdT positive?
What type of ALL is CD10 negative and TdT positive?
CD10 and TdT positive: Early pre-B cell ALL

CD10 negative and TdT positive: T-cell ALL
Where do the B cell and T cell types of ALL commonly metastasize?
B cell: CNS and testicles
T cell: Anterior mediastinum
Adult T-cell leukemia is associated with what virus? What is the pathogenesis?
Human T-cell Leukemia Virus (HTLV-1). Activates TAX gene inhibits TP53 supressor gene --> monoclonal proliferation of T cells
What is a common finding in T cell malignancies?
Skin infiltration
What markers are present in adult T cell leukemia?
CD4+, TdT -
What is the most common cause of generalized lymphadenopathy in individuals over 60?
Chronic lymphocytic leukemia (CLL)
What is the most common overall leukemia? What is its pathogenesis?
CLL. Neoplastic disorder of virgin B cells (B cells that cannot differentiate into plasma cells)
CLL has increased incidence of what finding?
Immune hemolytic anemia - both warm (IgG) and cold (IgM) types
What characteristic type of cells are visible in CML?
Smudge cells or basket cells - Leukocytes that have been damaged during preparation of the peripheral blood smear
t(12;21) offers a good prognosis in what leukemia?
ALL
Hypogammaglobulinemia is associated with what leukemia?
CLL
What leukemia is associated with lytic bone lesions?
Adult T cell leukemia
What leukemia is TRAP stain positive and shows a dramatic response to purine nucleosides?
Hairy cell leukemia
What's the only leukemia without lymphadenopathy?
Hairy cell leukemia
Which parts of the lymph nodes are the following found:
B cells
T cells
Histiocytes
B cells: germinal follicles
T cells: paracortex
Histiocytes: sinuses
Where do metastastases spread in the lymph node?
Sinuses
Nodal enlargement is more often malignant above this age than below it.
30: Below 30 years of age, nodal enlargement is usually benign (80%). Above 30, nodal enlargement is usually malignant (60%)
Painful lymph nodes imply...
Inflammation (e.g. infection)
Painless lymph nodes imply...
malignancy, either metastasis or primary malignant lymphoma
What is an example of a lymphoma that creates localized lymphadenopathy? What is an example that creates genralized lymphadenopathy?
Localized: Hodgkins
Generalized: Follicular B-cell lymphoma
Left sided supraclavicular node metastasis is most often...
Stomach or pancreatic carcinoma (Virchow's nodes)
Mixed B and T cell hyperplasia in the lymph nodes is common in what infection?
Cat-scratch disease (due to Bartonella henselae)
What's the most common type of malignant lymphoma?
Non-Hodgkin's lymphoma
H. pylori is associated with what lymphoma?
Malignant lymphoma of the stomach - derives from mucosa-associated lymphoid tissue (MALT) in the stomach
What areas are involved in American type and African type Burkitt's lymphoma?
American type: GI tract, para-aortic lymph nodes
African type: Jaw
What is mycosis fungoides?
Neoplasm of CD4 Th cells with skin involvement. Begins in skin and prgoresses to lymph nodes, lung, liver, spleen
Mycosis fungoides with a leukemic phase is called...
Sezary syndrome (circulating cells are called Sezary cells and have a prominent nuclear cleft)
EBV is associated with what type of Hodgkin's lymphoma?
Mixed cellularity Hodgkin's lymphoma (the ones with Reed Sternberg cells)
What's the most common type of Hodgkin's lymphoma?
Nodular sclerosing - also the only type that affects more women than men
Associate CD15, CD30 with...
Reed-Sternberg cells
What is a Reed-Sternberg variant fonud in Lymphocyte predominant Hodgkin's lymphoma?
"Popcorn cells" - Large, pale staining, multilobed nucleus
What RS cell variant is found in Nodular sclerosing Hodgkin's lymphoma?
Lacunar cells. Pale cells with multilobed nucleus containing many small nucleoli. Cell lies within a clear space in formalin-fixed tissue.
How is Hodgkin's lymphoma different than NHL in terms of location?
Hodgkin's lymphoma less commonly involves Waldeyer's ring (lymphoid tissue ring located in the pharynx and to the back of the oral cavity), mesenteric nodes, and extranodal sites
Hodgkin's lymphoma increases the risk of what other cancers?
AML or NHL
Nodular sclerosing Hodgkin's lymphoma normally presents in which part of the body?
Anterior mediastinal mass + single group of nodes above the diaphragm
CD1 positive with tennis racket shaped structures on EM = ?
Langerhans cell histiocytosis (Histiocytosis X)
In what age group does Histiocytosis X usually occur in?
Children and young adults
The triad of cystic skull defects, diabetes insipidus due to invasion of the posterior pituitary, and exopthalmos from infiltration of the orbit is associated with...
Hand-Schuller-Christian disease, a type of Langerhans Cell Histiocytosis. Intermediate prognosis.
What is the most benign form of histiocytosis?
Eosinophilic granuloma - benign histiocytosis that presents with pathaologic fractures
What is the most rapidly fatal histiocytosis?
Letterer-Siwe disease. Prsents with diffuse eczematous rash, multiple organ involvement, cystic defects in skull, pelvis, and long bones
Involvement of which area is common in the malignant histiocytoses?
Skin
Pruritis, swelling, and hyperpigmentation are all signs of what disease?
Mast cell disease. The skin lesions in the previous picture are called urticaria pigmentosa (multiple oval, red-brown , nonscaling macules or papules. Lesions remain hyperpigmented when they regress).
What is a plasma cell dyscrasia?
A monoclonal B cell disorder that creates a monoclonal spike (M component) on serum protein electrophoresis. Bence Jones proteins are light chains excreted in the urine.
Lytic lesions, pathologic fractures, and hypercalcemia are all associated with which plasma cell dyscrasia?
Multiple myeloma
What is the most common cause of acute renal failure in multiple myeloma?
Nephrocalcinosis - metastatic calcification of tubular basement membranes in the collceting ducts
What are characteristics of Bence Jones renal disease?
Proteinaceous casts with multinucleated giant cell reaction. BJ proteins damage the tubular epithelium causing a intratubular multinucleated giant cell reaction.
What is the most common monoclonal gammopathy?
Monoclonal gammopathy of undetermined significance (MGUS)
What is the most common cause of death in multiple myeloma?
Recurrent infections. Median survival is 6 months without treatment.
What type of pulmonary embolus can cause sudden death?
Saddle embolus occluding the major pulmonary artery branches
Abrupt onset dyspnea, hypotension, and bleeding (DIC) in a woman during labor or peripartum shuold make you think of...
Amniotic fluid embolism (60-80% mortality)
What's the most common cause of splenomegaly in deveoping countries?
Malaria
What cells do the white and red pulp of the spleen contain?
Red - contains fixed macrophages
White - B and T cells
What is hypersplenism?
Exaggeration of normal splenic function - destruction of hematopoietic cells

Portal hypertension associated with cirrhosis is the most common cause
What is the mechanism of action of heparin?
Enhances ATIII - neutralizes factors XII, XI, IX and X, as well as prothrombin (factor II) and thrombin
What do proteins C and S do?
Inactivate factors V and VIII, enhance fibrolysis. Vit K dependent factors
What does tPA do?
Activates plasminogen to relase plasmin
What cells synthesize vWF?
Endothelial cells. Platelets carry vWF in their alpha granules.
What is the function of vWF?
Platelet adhesion. Prevents degredation of VIII:C
What does tissue thromboplastin do?
ACtivates factor VII in extrinsic coagulation system
What platelet receptor binds to vWF, and which binds to fibrinogen?
GpIb binds to vWF
GpIIb/IIIa (binds to fibrinogen)
What are 2 important proteins stored in alpha granules of platelets?
vWF, fibrinogen
What does platelet-derived growth factor do?
Stimulates smooth muscle hyperplasia - important in the pathogenesis of atherosclerosis
What does Factor XIII do?
Cross-links insoluble fibrin monomers
Vitamin K is activated in the liver by what enzyme? What does vitamin K do after it is activated?
Epoxide reductase. Activated vitamin K gamma-carboxylases vitamin K dependent factors so that they will bind calcium
What drug inhibits epoxide reductase?
Warfarin
What does aminocaproic acid do?
Competetively blocks plasminogen activation, thereby inhibiting fibrinolysis
Fragments of cross-linked insoluble fibrin monomers (after plasmin has cleave fibrin) are called...
D-Dimers
What is the sequence of actions when platelets bind to a wound?
Adhesion (Gp1b binds vWF in damaged endothelial cells)
Release of ADP (causes platelet aggregation)
Synthesis of TXA2, temporary plug is formed
Bleeding time is a test of...
Platelet function to formation of temporary plug
What is a test of vWF function?
Ristocetin cofactor assay - abnormal assoay indicates vWF deficiency or Bernard-Soulier disease (absent GpIb receptor)
Prothrombin time evaluates...
Extrinsic system down to formation fo the fibrin clot (factors VII, X, V, II, and I)
Partial thromboplastin time (PTT) evaluates...
Intrinsic system down to formation of a fibrin clot (factors XI, XI, VIII, X, V, II, I)
What tests do you use to follow heparin and warfarin therapy?
PTT - follow heparin therapy
PT- follow warfarin therapy
(but with both heparin and warfarin, both PT and PTT will icnrease)
Fibrin(ogen) degredation products are increased when?
with lysis of fibrinogen or fibrin in fibrin thrombi
What is a test that only detects corss-linked insoluble fibrin monomers in a fibrin clot (not fibrinogen degredation products that are not crosslinked)
D-dimer assay
What is thrombocytopenia?
Decreased number of platelets due to decreased production (e.g. aplastic anemia), increased destruction (e.g. ITP, TTP), or sequestration in the spleen (hypersplenism in portal hypertension)
What's the most common cause of thrombocytopenia in children?
Acute ITP
What's the most common cause of a qualititative platelet defect?
Aspirin
What's the most common symptom associated with platelet dysfunction?
Nosebleed
What's the cause of idiopathic thrombocytopenic purpura and when does it occur?
IgG antibodies directed against GpIIb:IIIa receptors (type II hypersensitivity) - abrupt onset after an upper respiratory tract infection
What is the pathogenesis of heparin-induced thrombocytopenia (type II variant)?
Macrophage removal of platelets surfaced by IgG antibody directed against heparin attached to PF4 (type II hypersensitivity)
abnormality in HIV?
HIV thrombocytopenia (similar to ITP)
What is the cause of thrombotic thrombocytopenic purpura?
Acquired or genetic deficiency in vWF-cleaving metalloproteinase in endothelial cells - occurs in adult females
Most coagulation disorders are due to...
a decreased production of a coagulation factor (e.g. hemophilia A, cirrhosis)
What is the pathogenesis of hemophilias A and B?
Hemophilia A: Decreased factor VIII (increased PTT)

Hemophilia B: deficiency of factor IX. Clinically indistinguishable from hemophilia A.
What's the most common hereditary coagulation disorder? How is it inherited?
von willebrand disease (vWD) - autosomal dominant. Combined platelet and coagulation factor disorder (decreased vWF and factor VIII:C)
How are bleeding time, PTT, and PT affected in vWD?
Increased bleeding time and PTT
Normal PT
What is a drug that can treat both vWD and mild hemophilia A?
Desmopressin acetate (increases vWF and VIII activity)
What do mixing studies show?
Normal plasma is mixed with patient plasma in a test tube.
No correction of PT and/or PTT indicates immune destruction of coagulation factors
Correction of PT and/or PTT indicates decreased production
Most common cause of Vit K deficiency in hospitalized patient?
Antibiotics - sterilize bowel causing decreased production of vitamin K by bacteria
What is the effect of cirrhosis on vit K?
Decreased activation of vitamin K, decreased synthesis of vitamin K dependent factors
What's the most common cause of DIC?
Sepsis
What's the best screen for DIC?
D-Dimers
How does estrogen act as a procoagulant?
increases synthesis of coagulation factors and decreases ATIII
What's the most common hereditary thrombosis syndrome?
Factor V Leiden - mutant form of factor V cannot be degraded by protein C and S
Hemorrhagic skin necrosis is associated with what deficiency?
Protein C deficiency - remaining protein C activity falls to zero, causing a hypercoagulable state due to increased activity of factors V and VII --> cutaneous vessel thrombosis and skin necrosis
What's the most common blood group?
Blood group O
What's the least common blood group?
AB
What do forward and backward typing of blood group determine?
Forward typing: identifies blood group antigen
Backward typing: identifies natural antibodies
What are the five Rh antigens?
D, C, c, E, and e
An individual who is Rh positive is ____ antigen positive
D antigen
What is alloimmunization?
Production of antibodies against foreign antigens not present on an individuals RBCs.
What type of blood must an individual with atypical antibodies receive?
Must receive blood lacking the antigen
______ antigen negative RBCs provide protection against P. vivax malaria
Fy (because Fy antigens are the binding site for infestation of RBCs by P. vivax)
I and i are clinically important non-Rh antigens. Anti-i hemolytic anemai may occur in 1.____________, while anti-I hemolytic anemia may occur in 2.___________ infections
1. Infectious mononucleosis
2. Mycoplasma pneumoniae
What's the safest type of blood transfusion?
Autologous transfusion
What's the most common pathogen transmitted by blood transfusion?
CMV
Each unit of packed RBCs should raise the Hb by________ g/dL and teh Hct by ____%
Increased Hb by 1 g/dL
Increased Hct by 3%
What's the msot common contaminant of stored blood?
Yersinia enterocolitica, a pathogen that thrives on iron
Each unit of platelets should raise the platelet count by how much?
5000-10,000 cells/microliter
Before blood is transfused into newborns or patients with T-cell deficiencies, what must be done to it?
Must be irradiated to kill donor lymphocytes. This prevents patient from developing graft-versus-host reaction or a CMV infection
What's the most common transfusion reaction?
Allergic transfusion reaction: IgE mediated
What is the cause of febrile transfusion reactions?
anti-HLA antibodies against donor leukocytes
What is the cause of acute hemolytic transfusion reactions?
Blood group incompatibility or presence of atypical antibody
What's the most common hemolytic disease of the newborn?
ABO HDN: Mother group O, fetus blood group A or B
What do the direct and indirect Coomb's tests indicate?
+ Direct coomb's = Antibodies present on RBCs

+ indirect coomb's = Antibodies present in plasma
How do you prevent Rh hemolytic disease of the newborn?
Rh negative mothers without anti-D are given Rh immune globulin (anti-D globulin) during the 28th week of pregnancy. Does not cross the placenta and protects the mother from sensitization to fetal Rh positive cells that may enter her circulation during the last trimester
What is kernicterus?
Free unconjugated bilirubin deposits in the basal ganglia. Bilirubin damages neurons in teh brain, causing severe dysfunction
How does ABO compatibility affect Rh sensitiziation in a Rh negative mother with a Rh positive fetus?
ABO incompatibility protects mother from Rh sensitization (which causes more severe HDN) because premade antibodies in mother (against ABO antigens) will kill fetal RBCs that enter her circulation.
How is jaundice in the newborn treated?
Blue fluorescent light. converts bilirubin in skin to water-soluble dipyyrole