pathology II final
clinical & genetic classification of α-thalassemia (-/α, α/α) (-/-, α/α ; asians) or (-/a, -/a ; blacks) (-/-, -/α) (-/-, -/-)
-/α, α/α silent carrier ; patient will be asymptomatic (-/-, α/α ; asians) or (-/a, -/a ; blacks) α-thalassemia trait ; asymptomatic ; akin to β-thalassemia minor -/-, -/α HbH disease ; severe ; resembles β-thalassemia intermedia -/-, -/- hydrops fetalis (Hb Barts) ; lethal in utero ; incompatible with life
hematopathology webpath A 30-year-old woman has had mild fatigue for many years. Physical examination reveals a palpable spleen tip. Laboratory studies show Hgb 11.1 g/dL, Hct 28.8%, MCV 77 fL, platelet count 229,000/microliter, and WBC count 7340/microliter. Her reticulocyte count is 3.9%. Examination of her peripheral blood smear shows small RBCs that lack central pallor. Which of the following patterns of inheritance is most likely present with her disease? A Autosomal dominant, European ancestry B Autosomal recessive, Asian ancestry C X-linked recessive, Middle Eastern ancestry D Autosomal recessive, West African ancestry E Sporadic occurrence
A Autosomal dominant, European ancestry the question stem is describing hereditary spherocytosis
hematopathology webpath A 51-year-old man has become increasingly fatigued for the past 10 months. On physical examination there are no abnormal findings. Laboratory studies show his Hgb is 9.2, Hct 27.9%, MCV 132 fL, platelet count 242,000/microliter, and WBC count 7590/microliter. Which of the following morphologic findings is most likely to be present on examination of his peripheral blood smear? A Hypersegmented neutrophils B Nucleated red blood cells C Blasts with Auer rods D Hypochromic, microcytic RBC's E Schistocytes
A Hypersegmented neutrophils increased MCV points to a macrocytic anemia such as a megaloblastic anemia that can also have hypersegmented PMN's
hematopathology webpath A 73-year-old woman has had increasing fatigue with a 3 kg weight loss over the past 7 months. Her hands become purple and painful upon exposure to cold. On physical examination she has a palpable spleen tip. Laboratory studies show Hgb 10.5 g/dL, Hct 31.7%, MCV 99 fL, platelet count 193,600/microliter, and WBC count 5390/microliter. The direct antiglobulin (Coombs) test is positive at 4°C and negative at 37°C. Which of the following underlying diseases is this woman most likely to have? A Non-Hodgkin lymphoma B Systemic lupus erythematosus C Pernicious anemia D Scleroderma E Thalassemia minor
A Non-Hodgkin lymphoma question stem is describing cold hemolytic anemia, which may be idiopathic or due to an infection, but a malignant lymphoma must be considered.
how are the clinical manifestations of clotting factor deficiency (ex. hemophilia A/B or von willebrand disease) different from those caused by platelet pathologies (ex. thrombocytopenia)?
bleeding disorders due to coagulation factor disorders (ex. hemophilia A/B, von willebrand disease) will present with ecchymoses/hematomas/large bruises along with prolonged bleeding post-laceration or surgical procedure (ex. bleeding for days after tooth extraction) bleeding disorders due to platelet abnormality (ex. thrombocytopenia) present with petechiae
what effect does idiopathic thrombocytopenic purpura (ITP) have on bleeding time, prothrombin time (PT) & partial prothrombin time (PTT), respectively?
bleeding time is prolonged PT is normal PTT is normal
the sole source of erythrocytes at birth is [...], primarily due to its ability to increase production (8-fold) if needed in instances such as anemia. however, in individuals that have an increased demand beyond this, a phenomenon known as [...] can occur in the [...] or [...].
bone marrow ; extramedullary hematopoiesis ; liver or spleen
intravascular hemolytic anemia & extravascular hemolytic anemia are similar in that they both cause [...] & [...], but differ in location of erythrocyte destruction, what they are caused by & the sequelae that each cause. explain.
both cause jaundice & decreased haptoglobin location intravascular: destruction within vessels (vascular compartment) extravascular: spleen or liver what they are caused by intravascular: mechanical injury (i.e. mechanical heart valve), complement, infection extravascular: RBCs are recognized as foreign (different shape than biconcave) or damaged sequelae they cause intravascular: hemoglobinemia, hemoglobinuria & hemosiderinuria extravascular: splenomegaly
tell me the causes of bleeding disorders (excessive bleeding) & the tests we can use to evaluate.
causes increased vascular fragility platelet deficiency coagulation defects tests bleeding time platelet count prothrombin time (PT) partial prothrombin time (PTT)
one cause of bleeding disorders is increased vascular fragility. tell me the causes of this, what cutaneous manifestations occur & describe the lab values seen.
causes infections (meningococcemia, rickettsia, infective endocarditis) drug reactions (immune complex deposition) poor vascular support (scurvy & Ehlers-danlos syndrome) henoch-schonlein purpura manifestations petechial & purpural hemorrhages lab values normal platelet count & coagulation time variable bleeding time
what are the causes of disseminated intravascular coagulation (DIC) & what are some of the clinical manifestations associated with this condition?
causes massive tissue injury neoplasms infection retained dead fetus placental complications (anything that causes endothelial injury, resulting in widespread release of factor III (tissue factor) clinical manifestations multi-system organ failure due to infarcts throughout the entire body microangiopathic hemolytic anemia respiratory abnormalities (dyspnea, cyanosis) neurologic abnormalities (coma, convulsions) acute renal failure circulatory failure/shock
what is the most common cause of iron deficiency anemia?
chronic blood loss women with gynecological disturbances (uterine bleeding) elderly individuals with colon cancer or bladder cancer
which extracorpuscular hemolytic anemia is considered intravascular?
cold immunohemolytic anemia this anemia is considered intravascular because as IgM antibodies bind to RBCs in peripheral tissues where temperatures are cooler, complement is activated, resulting in hemolysis on the spot
von willebrand disease common or rare? how does it present? how does this pathology affect factor VIII? what are the two categories of this disease? how is bleeding time, PT & PTT affected?
common or rare? extremely common how does it present? spontaneous bleeding from mucous membranes, excessive bleeding from wounds & menorrhagia how does this pathology affect factor VIII? factor VIII will be reduced because von willebrand factor stabilizes it in systemic circulation categories reduced quantity of vWF (type I & III) ; qualitative defect ; vWF levels are normal, but it is mutated (type II) how is bleeding time, PT & PTT affected? bleeding time is prolonged in presence of normal platelet count PT is normal PTT is slightly prolonged "patient has petechiae, they can't stop bleeding after a minor surgery, but their blood levels show a normal platelet count & a slightly prolonged PTT. what do they have? von willebrand disease"
ineffective erythropoiesis, a common cause of anemia, can be due to disturbance of proliferation of erythroblasts. one of the mechanisms that can cause this to occur is deficiency of [...] or [...], resulting in defective DNA synthesis. other mechanisms that can cause this to occur is [...] or [...], both of which resulting in defective hemoglobin synthesis.
defective DNA synthesis: vitamin B12 or folate deficiency defective hemoglobin synthesis: iron deficiency or thalassemia
commonly EC'd question histological hallmark of sickle cell?
denatured hemoglobin
name the intracorpuscular hemolytic anemias. then tell me which is caused by enzyme deficiency, which is caused by cell membrane disorder & which are caused by hemoglobin synthesis.
enzyme deficiency G6PD deficiency cell membrane disorders spherocytosis hemoglobin synthesis disorders thalassemia or sickle cell anemia
thalassemias are a group of inherited disorders caused by genetic lesions, resulting in decreased synthesis of either the α-globin chain of HbA (α-thalassemia) or the β-globin chain of HbA (β-thalassemia). in each of these conditions, absence of one globin chain allows for excess of the normal globin chain. what effect does this have on these individual's erythrocytes?
excess of one globin chain can result in premature destruction of maturing erythroblasts in the bone marrow & lysis of mature RBCs in the spleen
immunohemolytic anemias are [intracorpuscular/extracorpuscular], are classified based on [...] & are diagnosed via what laboratory test?
extracorpuscular ; antibody involved (ex. IgG, IgM) ; Coombs antiglobulin test (direct detects antibodies in patient's RBCs, indirect detects antibodies in patient's serum)
factor VIII is synthesized in the [...] & [...] while von willebrand factor is synthesized in [...] & [...]. these two associate to form a complex in the systemic circulation & each have a respective function in response to endothelial injury. tell me their respective functions.
factor VIII: synthesized in liver & kidney ; takes part of coagulation cascade & acts as cofactor for activation of factor X von willebrand factor: synthesized in endothelial cells & megakaryocytes ; stimulates adhesion of platelets
folate deficiency is associated with a [...] diet while a vitamin B12 deficiency is associated with consumption of [...] diet. both of these vitamins are needed for [...] & deficiency in either results in [...], so how can you differentiate which vitamin is deficient?
folate deficiency: carnivore diet (no vegetables) vitamin B12 deficiency: vegetarian diet (no meat) DNA synthesis ; megaloblastic anemia folate deficiency is also associated with neural tube defects while vitamin B12 deficiency is also associated with myelin degeneration
there are two patterns of chronic nonspecific lymphadenitis depending on what is causing expansion of one's nodes. describe each pattern & tell me the causes of each.
follicular hyperplasia expansion of germinal centers & B cells causes: rheumatoid arthritis, toxoplasmosis, early HIV, follicular lymphoma paracortical hyperplasia expansion of T cells causes: acute viral infection, drug reactions, post-vaccination responses.
what is the most common instance in which you see an individual with neutropenia?
following a bone marrow transplant patients that receive BM transplant are at high risk of sepsis/dying from infection due to lack of neutrophils
what are schistocytes & which condition will they be linked to for this exam?
fragmented RBCs ; linked to DIC or TTP
the histological hallmarks associated with G6PD-deficiency hemolytic anemia are [...] & [...]. describe each.
heinz bodies & bite cells heinz bodies are just accumulations of denatured hemoglobin in the form of inclusions (them being in this form predisposes them to phagocytic activity in the spleen) bite cells are these same inclusions that have had a bite taken out of them by splenic phagocytes
[intravascular/extravascular] presents with hemoglobinemia, hemoglobinuria & hemosiderinuria while [intravascular/extravascular] hemolytic anemia presents with splenomegaly.
hemoglobinemia, hemoglobinuria & hemosiderinuria: intravascular splenomegaly: extravascular
what is the only difference between hemophilia A & hemophilia B?
hemophilia A is caused by deficiency of factor VIII hemophilia B is caused by deficiency of factor IX
hematopathology webpath A 47-year-old man has been chronically fatigued for the past year. A physical examination yields no abnormal findings. A CBC shows: Hgb 10.8 g/dL, Hct 33.1%, MCV 105 fL, platelet count 239,000/microliter, and WBC count 7720/microliter. His peripheral blood smear shows normal WBC morphology and RBCs with mild poikilocytosis and a few target cells. His serum vitamin B12 and methylmalonic acid assays are normal. His serum haptoglobin is 151 mg/dL. Direct and indirect antiglobulin (Coombs) tests are negative. Which of the following underlying conditions is most likely to explain his findings? A Chronic lymphocytic leukemia B Peptic ulcer disease C Lead poisoning D Chronic alcohol abuse E Hereditary spherocytosis
D Chronic alcohol abuse There is mild macrocytosis with normal B12 (and methlymalonic acid is a more sensitive test for B12 deficiency), without evidence for significant hemolysis.
hematopathology webpath A study is conducted to determine what changes in the size of the spleen take place with hematologic disorders. The spleen sizes are estimated from CT scans for adult patients who developed complications of their hematologic disease. For which of the following diseases is the spleen most likely to remain normal in size? A Autoimmune hemolytic anemia B Chronic ethanol abuse C Myeloproliferative disorder D Immune thrombocytopenic purpura E Sickle cell anemia
D Immune thrombocytopenic purpura splenomegaly is not seen with ITP
hemathopathology webpath A 12-year-old girl has the sudden onset of severe abdominal pain and back pain. On physical examination her abdomen is diffusely tender, but there are no masses. She is afebrile. A CBC shows Hgb 6.5 g/dL, Hct 19.0%, MCV 99 fL, platelet count 149,000/microliter, and WBC count 11,200/microliter. Examination of her peripheral blood smear shows nucleated RBCs and sickled RBCs. Which of the following types of gene mutation is she most likely to have? A Deletion B Duplication C Insertion D Missense E Nonsense F Splice site G Tandem repeat
D Missense this girl has sickle cell anemia, which is caused by glutamic acid being replaced by valine
hematopathology webpath A 42-year-old man has had multiple episodes of painful red nodules on his skin from dermal venous thrombosis, as well as abdominal pain from mesenteric vein thrombosis over the past year. He notes passing darker urine. Laboratory studies show Hgb 9.4 g/dL, Hct 29.2%, MCV 100 fL, platelet count 215,000/microliter, and WBC count of 8800/microliter. His RBCs show increased sensitivity to complement lysis. Flow cytometry show reduction in the CD55 marker on his RBCs. Which of the following conditions is he most likely to have? A HIV infection B Chronic lymphocytic leukemia C Acute myelogenous leukemia D Paryoxysmal nocturnal hemoglobinuria E Langerhans cell histiocytosis
D Paryoxysmal nocturnal hemoglobinuria The RBC markers CD55 and CD59 are reduced with PNH. buzzword is darker urine
what laboratory test should be utilized to confirm disseminated intravascular coagulopathy (DIC)?
D-dimer
an intracorpuscular hemolytic anemia caused by disorder in the cell membrane is [...]. is this condition inherited & in what manner? which cytoskeleton protein is deficient? what effect does this have on the cells? which viral infection is dangerous to these patients & why? what are the characteristic clinical features? how is this treated?
hereditary spherocytosis is this condition inherited & in what manner? inherited ; autosomal dominant which cytoskeleton protein is deficient? spectrin what effect does this have on the cells? spheroidal in shape, less deformable & vulnerable to splenic sequestration which viral infection is dangerous to these patients & why? parvovirus what are the characteristic clinical features? jaundice, spenomegaly & anemia how is this treated? splenectomy
extracorpuscular hemolytic anemia can result from mechanical trauma, infections, chemical injury or be a result of antibody-mediated damage. provide examples of each.
mechanical trauma microangiopathic hemolytic anemias: thrombotic thrombocytopenia purpura (TTP) or disseminated intravascular coagulation (DIC) infections malaria or hookworm chemical injury lead poisoning antibody-mediated damage erythroblastosis fetalis ; individuals can also develop autoantibodies that go on to destroy RBCs (drug associated, SLE, malignant neoplasms, mycoplasmal infection)
warm immunohemolytic anemia vs. cold immunohemolytic anemia mediated by which antibody? associated with splenomegaly? which causes Raynaud's phenomenon? which causes extravascular hemolysis? which causes intravascular hemolysis?
mediated by which antibody? warm: IgG cold: IgM associated with splenomegaly? warm: yes cold: no which causes Raynaud's phenomenon? cold which causes extravascular hemolysis? warm which causes intravascular hemolysis? cold
certain infections can cause increased vascular fragility, leading to bleeding disorders. name the infections & explain the mechanism behind this.
meningococcemia (neisseria meningitidis) infective endocarditis rickettsia these infections cause damage to microvasculature, resulting in vasculitis or DIC
those with β-thalassemia will have [...] as a result of bone marrow expansion caused by entrapped erythrocytes, [...] as a result of extramedullary hematopoiesis, [...] as a result of excessive hemolysis & red blood cells that can be described as [...] & [...]. another histological feature of this condition are the presence of [...]. what are some clinical presentations associated with this disease?
skeletal deformities ; splenomegaly/hepatomegaly ; severe hemosiderosis ; microcytic & hypochromic RBCs ; target cells ; frontal bossing & splenomegaly
hematopathology webpath A 38-year-old woman has become increasingly fatigued for the past 3 months. During the past week she has noted purple blotches on her skin. On physical examination there are purpuric areas of skin on her trunk and extremities. She has no hepatosplenomegaly and no lymphadenopathy. Laboratory studies show Hgb 6.8 g/dL, Hct 20.7%, MCV 91 fL, platelet count 28,760/microliter, and WBC count 1940/microliter. Which of the following is the most likely diagnosis? A Aplastic anemia B Myeloproliferative disorder C Immune thrombocytopenic purpura D Large B cell lymphoma E Hereditary spherocytosis
A Aplastic anemia marked hypocellularity of the bone marrow with aplastic anemia. The spleen is of normal size with aplastic anemia. The 'aplasia' here refers to the three major cell lines
neutropenia is defined as a [...]. this condition can result from either [...] (list the ways this can occur) or [...] (list the ways this can occur). then tell me the primary clinical consequence of this pathology & describe the morphology of one's blood with this pathology.
ANC <1000 inadequate granulopoiesis suppression of myeloid stem cells (ex. aplastic anemia) drug exposure (ex. chemotherapy) megaloblastic anemias accelerated destruction of neutrophils immunologic disorders (ex. SLE) splenic sequestration increased peripheral utilization (ex. fighting infections) clinical consequences inability to fight infection, making one susceptible to sepsis morphology neutropenia caused by suppressed granulopoiesis (ex. leukemia, lymphoma, chemotherapy): marrow hypocellularity neutropenia caused by increased destruction of neutrophils: marrow hypercellularity with increase in granulocytic precursors
hematopathology webpath A 19-year-old primigravida of Southeast Asian ancestry gives birth at 35 weeks gestation a male infant. On physical examination the infant is markedly hydropic. Laboratory studies show his hematocrit is 17% and the peripheral blood smear reveals numerous nucleated red blood cells and even a few erythroblasts. The red blood cells display marked anisocytosis and poikilocytosis. Which of the following diseases is most likely to be present in this infant? A Sickle cell anemia B Alpha-thalassemia C Hemoglobin E disease D G6PD deficiency E Hereditary elliptocytosis
B Alpha-thalassemia The form of alpha-thalassemia seen in Southeast Asia has two abnormal alpha globin genes on the same chromosome
hematopathology webpath A 68-year-old man has had malaise for the past year. On physical examination, there are no abnormal findings. His Hgb is 10.5 g/dL, Hct 31.5%, MCV 88 fL, platelet count 211,000/microliter, and WBC count 6980/microliter. His total serum iron is 130 microgm/dL total iron binding capacity (TIBC) 230 microgm/dL, and soluble serum transferrin receptor is normal. A bone marrow biopsy is performed and microscopic examination shows that maturation is occurring in all cell lines and there are no abnormal cells seen. Stainable iron in the bone marrow is increased. Which of the following underlying diseases is he most likely to have? A Diverticulosis B Hepatitis C infection C Systemic lupus erythematosus D Atrophic gastritis E Fanconi anemia
B Hepatitis C infection the question stem is describing anemia with chronic disease (ACD)
hematopathology webpath A 29-year-old woman has the sudden onset of fever, abdominal pain, tachycardia, and nausea. On physical examination her vital signs include T 37.6°C, P 90/minute, RR 18/minute, and BP 100/60 mm Hg. Her conjunctivae are icteric. The spleen tip is palpable. Laboratory studies shows Hgb 9.0 g/dL, Hct 27.3%, MCV 99 fL, platelet count 209,500/microliter, and WBC count 6840/microliter. Her reticulocyte count is 0.1%. On microscopic examination of her peripheral blood smear, the RBC's are small and lack central pallor. Which of the following most likely initiated this woman's acute illness? A Quinacrine use B Parvovirus infection C Decreased oxygen tension D Exposure to cold E Transfusion therapy
B Parvovirus infection the findings in the question stem point to hereditary spherocytosis
hematopathology webpath A 28-year-old woman has had worsening fatigue for the past 2 months. On physical examination she has an erythematous macular rash on her upper chest, forearms, and face. Laboratory studies show Hgb 9.2 g/dL, Hct 27.9%, MCV 101 fL, platelet count 179,000/microliter, and WBC count 5850/microliter. The red blood cell distribution width is markedly increased. Her peripheral blood smear shows polychromasia. Her reticulocyte count is 4.2%. The serum haptoglobin is 3 mg/dL. Serum chemistries show total protein 7.9 g/dL, albumin 3.8 g/dL, alkaline phosphatase 49 U/L, AST 81 U/L, ALT 27 U/L, total bilirubin 3.3 mg/dL, and direct bilirubin 0.8 mg/dL. Hemoglobinuria is detected on urinalysis. Which of the following underlying conditions is she most likely to have? A Multiple myeloma B Systemic lupus erythematosus C Hepatitis C infection D Hereditary spherocytosis E Vitamin B12 deficiency
B Systemic lupus erythematosus question stem is indicating intravascular hemolysis, which is seen in warm autoimmune hemolytic anemia, which is associated with SLE
lymph node review B cells reside in the [...] of lymph nodes, T cells reside in the [...] of lymph nodes & macrophages/plasma cells reside in the [...] of lymph nodes.
B cells: cortex T cells: paracortex macrophages/plasma cells: medullary cord
a majority of lymphoid neoplasms are of [B/T]-cell origin & it is important to remember that all are [...]. we must remember that because these are tumors of the [...], they tend to cause [...]
B-cell origin ; all are monoclonal ; tumors of immune system ; cause immune abnormalities the immunosuppression caused by lymphomas/leukemias is a leading cause of death ; these malignancies can also cause autoimmune diseases
hematopathology webpath A 72-year-old man has been feeling tired for the past 8 months. On physical examination there are no abnormal findings. Laboratory studies show Hgb 10.4 g/dL, Hct 30.3%, MCV 72 fL, platelet count 239,000/uL, and WBC count 7500/uL with automated differential count of 70.1% grans, 18.8% lymphs, and 11.1% monos. His total bilirubin is 1.0 mg/dL. Which of the following morphologic findings is most likely to be seen on his peripheral blood smear? A Fragmentation B Many nucleated forms C Hypochromasia D Spherocytosis E Howell-Jolly bodies
C Hypochromasia The most probable cause of a hypochromic, microcytic anemia in an older man is iron deficiency anemia.
tell me which cells the following antigens correspond to: CD1 CD3 CD4 CD8 CD20 CD79a CD68 CD56 CD34 CD45 CD30
CD1: langerhans cells CD3: all T cells CD4: helper T cells CD8: cytotoxic T cells CD20: all B cells CD79a: all B cells CD68: macrophage marker CD56: NK cells CD34: pluripotent stem cells CD45: all leukocytes ; also known as leukocyte antigen (LCA) CD30: activation marker ; seen in conditions such Hodgkin lymphoma
hematopathology webpath A 78-year-old woman has developed increasing dyspnea for the past 2 weeks. On physical examination she has diffuse rales in all lung fields. Scleral icterus is noted. A CBC shows Hgb 7.1, Hct 22.2, MCV 93 fL, platelet count 205,000/microliter, and WBC count 6500/microliter with differential count of 60 segs, 4 bands, 25 lymphs, 9 monos, and 2 eos with 10 nucleated RBCs/100 WBCs. Which of the following is the most likely diagnosis? A Iron deficiency anemia B Pernicious anemia C Anemia of chronic disease D Sickle cell anemia E Hemolytic anemia
E Hemolytic anemia She may have an autoimmune hemolytic anemia, and may have an underlying malignancy such as lymphoma. The icterus is consistent with hyperbilirubinemia from hemolysis. Nucleated RBCs are consistent with high marrow output of erythroid cells. The marked anemia has led to high output congestive heart failure with pulmonary edema.
an intracorpuscular hemolytic anemia caused by enzyme deficiency is [...], which is primarily seen in [...]. tell me what we are to remember regarding when symptoms are seen in the absence of this enzyme. explain the pathogenesis behind this condition & tell me the histological hallmarks associated. finally, tell me if this condition is associated splenomegaly & explain why or why not.
G6PD-deficient hemolytic anemia ; african-americans this disorder does not cause symptoms unless RBCs are subjected to oxidant injury by exposure to certain drugs (ex. antimalarials, sulfonamides, aspirin, phenacetin), toxins or infections pathogenesis normally, RBCs have this enzyme present to inactivate oxidants acting upon them. however, in the absence of this enzyme, they are vulnerable to oxidative stress & are not able to protect themselves, resulting in injury & hemolysis histological hallmarks Heinz bodies & bite cells splenomegaly? no ; the hemolytic episodes associated with this condition are self-limited & intermittent, so splenomegaly is absent
warm immunohemolytic anemia is primarily mediated by [...]. explain what happens in this pathology.
IgG RBCs become coated in IgG antibodies & are subsequently sequestered to the spleen here, they bind to receptors present on splenic macrophages resulting in partial phagocytosis & loss of cell membrane this loss of membrane converts RBCs to spherocytes, allowing for their removal via extravascular hemolysis this results in splenomegaly
cold immunohemoytic anemia is mediated by [...]. because this antibody isotype tends to adhere to erythrocytes & activate complement in peripheral tissues where temperature is cooler than the core, [...] is a common presentation. acute cases of this anemia are often a complication of [...] or [...] infection whereas chronic cases of this anemia condition are associated with [...]. we must remember that this type of anemia is not associated with [...], primarily because phagocytosis of the damaged erythrocytes is performed by [...].
IgM ; raynaud's phenomenon acute: EBV or mycoplasma pneumoniae infection chronic: lymphoid neoplasm not associated with splenomegaly ; this is because phagocytosis occurs in kupffer cells in the liver
prothrombin time (PT) measures [...] while partial prothrombin time (PTT) measures [...].
PT measures extrinsic coagulation pathway (fibrin polymerization) PTT measures intrinsic coagulation pathway
the most common cause of vitamin B12 deficiency is [...]. explain the pathogenesis behind this & tell me the consequence.
atrophic (autoimmune) gastritis autoantibodies destroy parietal cells in stomach, which are responsible for making intrinsic factor, the substance needed to absorb vitamin B12 this results in pernicious anemia (chronic atrophic gastritis can result in a permanent loss of parietal cells)
pure red cell aplasia is defined as an [...]. while this pathology can be seen in certain autoimmune conditions, it is commonly secondary to a [...].
absence of erythroid precursors ; secondary to thymoma
external blood loss can be acute or chronic. explain what can occur in each scenario & how each are compensated for.
acute external blood loss can lead to CV collapse, shock & death compensated by bone marrow increasing amount of reticulocytes (reticulocytosis) chronic external blood loss iron stores can be depleted, resulting in iron deficiency anemia compensated by iron supplementation ; as soon as iron is available, an increase in erythropoiesis is seen
what is anemia of chronic disease, what type of anemia is this & what is true of the lab values seen in this pathology?
anemia seen in patients with chronic microbial infections, immunologic disorders or neoplasms normocytic/normochromic or microcytic/hypochromic low iron binding capacity (TIBC) normal/high ferritin levels (iron binding capacity (TIBC) is low because all of the transferrin is already carrying iron/ferritin, but it is not being transported to RBCs)
ineffective erythropoiesis, a common cause of anemia, can be due to disturbance of proliferation of stem cells & present in the form of [...], [...], [...] or [...].
aplastic anemia pure red cell aplasia anemia of renal failure anemia of endocrine disorders
the biggest risk in those with hereditary spherocytosis is [...], which is triggered by [...].
aplastic crisis ; parvovirus infection this virus specifically targets erythroid stem cells within the bone marrow & shuts off erythropoiesis
some individuals with sickle cell anemia can develop an increased susceptibility to infections caused by encapsulated organisms, such as streptococcus pneumoniae. explain why.
as we know, the spleen is responsible for storing B-lymphocytes & maintaining humoral immunity in those with sickle cell, the spleen can get overwhelmed to the point where it spontaneously infarcts (autosplenectomy)
what are the two categories of leukocyte proliferation?
lymphoid neoplasms tumors of B-cell/T-cell/NK-cell origin myeloid neoplasms tumors that originate from transformed hematopoietic stem cells which give rise to myeloid cells
leukocytosis is defined as an [...] & is a common reaction to [...]. what is the cause of neutrophilic leukocytosis? what is the cause of eosinophilic leukocytosis? what is the cause of basophilic leukocytosis? what is the cause of monocytosis? what is the cause of lymphocytosis?
increase in blood leukocytes ; inflammatory states what is the cause of neutrophilic leukocytosis? acute bacterial infections what is the cause of eosinophilic leukocytosis? allergic disorders (i.e. asthma, hay fever, dermatitis), parasitic infestations or drug reactions what is the cause of basophilic leukocytosis? myeloproliferative disease what is the cause of monocytosis? chronic infections (i.e. tuberculosis), bacterial endocarditis, SLE, malaria, inflammatory bowel disease what is the cause of lymphocytosis? viral infections ; often accompanies monocytosis
what is reticulocytosis, in what setting is it seen & how does it present in a patient's blood smear?
increased population of reticulocytes (immature erythrocytes) seen in cases of acute external blood loss such as a hemorrhage patents erythrocytes will have remnants of nuclei
what is a frequent cause of hemolytic uremic syndrome (HUS)?
infectious gastoenteritis by way of E. coli
the most common pathologies that cause deficiency of clotting factors are [...]/[...] & [...], which are inherited & [...], which is acquired.
inherited hemophilia A/B & von willebrand disease acquired vitamin K deficiency
hemolytic anemia can be due to either [...] defects or [...] defects within red blood cells
intracorpuscular (intrinsic) defects (abnormal shape, size or enzyme) ; extracorpuscular (external damage via antibodies or complement)
sickle cell anemia is an [intracorpuscular/extracorpuscular] hemolytic anemia caused by a disorder of hemoglobin synthesis & is typically seen in [...]. this condition is a result of a point mutation in the β-globin gene, causing [AA] to replace [AA], resulting in a [...] genotype. explain the pathogenesis of this condition, the three consequences of this condition & the evolutionary benefit that keeping this mutation in the gene pool yields.
intracorpuscular ; african-americans ; valine replaces glutamic acid ; HbS pathogenesis when deoxygenated, HbS molecules undergo aggregation & polymerization, eventually leading to an irreversible sickled shape of erythrocytes consequences 1. chronic hemolysis results in severe anemia 2. microvascular occlusions results in ischemic organ damage 3. increased susceptibility to infection by encapsulated organisms evolutionary benefit heterozygous for HbS makes one resistant to malaria because mosquitoes stay away
hemolytic anemia is either classified as [...], meaning erythrocytes are destroyed in the [...] or classified as [...], meaning erythrocytes are destroyed in the [...]/[...]. tell me the characterizations of this pathology.
intravascular: RBCs destroyed within vessels extravascular: RBCs destroyed in spleen/liver intracorpuscular (intrinsic) defects (abnormal shape, size or enzyme) ; extracorpuscular (external damage via antibodies or complement) characterizations premature destruction of RBCs accumulation of bilirubin elevated erythropoietin levels & increased erythropoiesis in bone marrow
the most common nutritional disorder in the world is a deficiency of [...]. [...]% of this mineral in our body is in active use & is found within [...] while the remaining percentage is in its storage forms [...] & [...]. which of these forms is accessible?
iron ; 80% within hemoglobin ; storage forms: hemosiderin & ferritin ferritin is accessible stored iron, hemosiderin is just random lost scattered iron
compare the lab values of total iron binding capacity (TIBC) & ferritin in iron deficiency anemia versus anemia of chronic disease.
iron deficiency anemia: high iron binding capacity (TIBC) & low ferritin anemia of chronic disease: low iron binding capacity (TIBC) & high/normal ferritin
explain the mechanism behind anemia of chronic disease.
iron levels are normal (neither in excess or deficient), but the iron is not being transferred to RBCs by transferrin can also be due to inability to free iron from macrophages
name the three types of lymphoid neoplasms & describe each.
leukemias leukocytic malignancy that originates in one's bone marrow & reaches one's peripheral blood lymphomas leukocytic proliferation arising as discrete tissue masses within lymph nodes, spleen or peyer's patches two categories: Hodgkin lymphoma & non-hodgkin lymphoma plasma cell neoplasms tumors composed of terminally differentiated B cells
leukemias originate from [...] while lymphomas originate in [...].
leukemias: bone-marrow (then travel through blood) lymphomas: lymph nodes, spleen or peyer's patches
acute nonspecific lymphadenitis can be [...] or [...]. tell me what each type is caused by & how one's lymph nodes will present with this condition.
localized or systemic localized commonly caused by direct microbiologic drainage systemic characteristic of viral infections & bacteremia lymph nodes will be swollen & engorged, with large germinal centers containing many mitotic figures "patient will have large & painful lymph nodes"
what type of anemia is iron deficiency anemia?
microcytic & hypochromic he has asked this before, might ask it again
how will a peripheral blood smear present in a patient with β-thalassemia?
microcytic & hypochromic RBCs
besides megaloblastic anemia, what is a common side effect of vitamin B12 deficiency?
myelin degeneration patient's will present with peripheral neuropathy
the organs & tissues involved in hematopoiesis have been divided into myeloid tissue & lymphoid tissue. tell where each are derived from/reside in & what cells they produce.
myeloid tissue derived from bone marrow produce erythrocytes, platelets, granulocytes & monocytes lymphoid tissue reside in thymus, lymph nodes & spleen produce lymphocytes, plasma cells & NK cells
besides megaloblastic anemia, what is a common side effect of folate deficiency?
neural tube defects
in a patient that is at an advanced stage, is it possible to differentiate if they have leukemia or if they have a lymphoma?
no a leukemia could start at the bone marrow, travel through the blood & reach one's lymph nodes, resulting in secondary lymphoma & vice versa ; a lymphoma could start in the lymph nodes, travel through the blood & reach one's bone marrow, resulting in secondary leukemia
describe the morphology of one's blood that has megaloblastic anemia.
pancytopenia (decrease of all cells) macrocytic (abnormally large) RBCs large hypersegmented neutrophils markedly hypercellular bone marrow patient will have high MCV value
the only intracorpuscular hemolytic anemia that is not inherited, but rather acquired is [...]. explain the pathogenesis behind this condition & the clinical manifestations associated.
paroxysmal nocturnal hemoglobinuria due to an unknown etiology, RBCs will have an absence of cell membrane proteins needed to protect them from being attacked by complement, resulting in increased complement-mediated hemolysis clinical manifestations increased risk of thrombosis increased risk of developing AML hemosiderinuria episodic venous thrombosis
a phenomena known as vaso-occlusive crisis can occur in those with sickle-cell anemia. explain the pathology behind this.
sickled RBCs can aggregate & form microthrombi, which block vessels & cause ischemic organ damage, resulting in microinfarcts this is extremely painful ; can also put patient at risk of a DIC event
what is a hallmark presentation of intravascular hemolytic anemia?
pepsi-cola urine patient's urine will be dark brown due to hemoglobin & hemosiderin present
macroovalocytes are commonly seen in which condition?
pernicious anemia or megaloblastic anemia
the most commonly utilized schemes for classifying lymphoid neoplasms are WHO & REAL, both of which sort these pathologies into four categories. what are those categories?
precursor B-cell neoplasms peripheral B-cell neoplasms precursor T-cell neoplasms peripheral T-cell & NK-cell neoplasms
one cause of increased vascular fragility is henoch-schonlein purpura, which is a type of vasculitis. how does a patient with this condition present?
purpuric rash colicky abdominal pain polyarthralgia acute glomerulonephritis
define anemia & tell me the three mechanisms in which it occurs.
reduction in the oxygen transport capacity of blood internal blood loss (acute trauma, chronic bleeding of GI, gynecologic disturbances) external blood loss (increased RBC destruction ; ex. hemolytic anemia) ineffective hematopoiesis (vitamin B12 or folate deficiency)
what are the two main functions of the spleen?
removal of old/damaged RBCs & storing B-lymphocytes, which preserves humoral immunity
[...] & [...] are two related disorders within the spectrum of thrombotic microangiopathies. both of these pathologies are caused by a mutation in [...], which results in an elevated [...]. these conditions are similar in that they both cause [...] & [...], but differ in that the former occurs in [...] & causes [...] while the latter occurs in [...] & causes [...]. what is the underlying defect that causes these pathologies & what effect do these pathologies have on one's bleeding time, prothrombin time (PT) & partial prothrombin time (PTT)?
thrombotic thrombocytopenic purpura (TTP) & hemolytic uremic syndrome (HUS) ; ADAMTS ; elevated von-willebrand factor ; both cause thrombocytopenia & microangiopathic hemolytic anemia (remember that they both cause widespread microthrombi) TTP: seen in adults & causes transient neurologic defects (mental confusion) HUS: seen in children & causes acute renal failure underlying defect is endothelial injury, which results in platelet activation & aggression bleeding time: prolonged PT: normal PTT: normal
adult hemoglobin (HbA) contains [...] α-chains, which are coded for by [...] α-globin genes present on chromosome [...] & [...] β-chains, which are coded for by [...] β-globin genes present on chromosome [...].
two α-chains, 4 α-globin genes, chromosome 16 two β-chains, 2 β-globin genes, chromosome 11
iron deficiency anemia what are the causes? what are the morphologic features? what are the lab values seen with this condition? how is this treated?
what are the causes? chronic blood loss (most common) dietary lack (vegetarians) impaired absorption (celiac sprue or chronic diarrhea) increased demand (pregnant women or growing infants) what are the morphologic features? decreased erythrocyte count microcytic & hypochromic cells what are the lab values seen with this condition? low hemoglobin & hematocrit low serum iron & ferritin high iron binding capacity (TIBC) how is this treated? oral iron
aplastic anemia what is it caused by? what is the most common etiology? what does this pathology result in? describe the morphology of bone marrow in this pathology. is splenomegaly seen?
what is it caused by? failure or suppression of myeloid stem cells what is the most common etiology? chemotherapy or other myelotoxic drugs/chemicals (benzene, alkylating agents, antimetabolites, chloramphenicol) what does this pathology result in? pancytopenia (anemia, neutropenia, thrombocytopenia) describe the morphology of bone marrow in this pathology. hypocellular marrow ; bone marrow will be empty because there are no cells being produced is splenomegaly seen? no
idiopathic thrombocytopenic purpura (ITP) what is this condition? does the patient present with petechiae or purpura? what is the mechanism behind this condition? in what individuals is acute ITP seen & how does it present? in what individuals is chronic ITP seen & how does it present? does this condition cause splenomegaly? what effect does this condition have on bleeding time, prothrombin time (PT) & partial prothrombin time (PTT)?
what is this condition? decrease in platelets to less than 100k (normal is 150k-300k) does the patient present with petechiae or purpura? presents with widespread systemic petechiae ; "patient presents with widespread diffuse petechiae. what is wrong? thrombocytopenia" what is the mechanism behind this condition? autoantibodies bind to platelets & cause destruction in what individuals is acute ITP seen & how does it present? children that are post viral infection (rubella, CMV, viral hepatitis) ; presentation is mild in what individuals is chronic ITP seen & how does it present? adults, particularly women of child-bearing age ; presents with minor splenomegaly (due to antibodies binding to platelets, causing splenic sequestration), easy bruising & constant nosebleeds does this condition cause splenomegaly? spleen will essentially be normal, slightly enlarged in some cases what effect does this condition have on bleeding time, prothrombin time (PT) & partial prothrombin time (PTT)? bleeding time is pronged PT is normal PTT is normal
disseminated intravascular coagulation (DIC) what is this pathology characterized by? what is the mechanism behind this pathology? why is this pathology considered a "consumptive coagulopathy"? how does this pathology present? what are the two ways in which this pathology can be triggered? what effect does this pathology have on PT & PTT?
what is this pathology characterized by? formation of microthrombi throughout the entire circulation what is the mechanism behind this pathology? endothelial injury results in release of factor III (tissue factor) & fibrin polymerization ; both of these cause occlusion of vessels, leading to microthrombi formation why is this pathology considered a "consumptive coagulopathy"? patient will consume their platelets, fibrin & coagulation factors all at the same time (secondarily, a fibrinolytic mechanism will be activated to combat the fibrin polymerization) how does this pathology present? symptoms relating to infarction in the heart, brain or other organs (patient will die from massive hemorrhage due to all their coagulation factors & platelets being consumed) what are the two ways in which this pathology can be triggered? widespread injury to endothelial cells release of tissue factor or thromboplastic substances into the circulation what effect does this pathology have on PT & PTT? both are prolonged ; other lab values: increased fibrin split products, low platelets (thrombocytopenia) & low fibrinogen
extravascular hemolytic anemia where are erythrocytes destroyed? why are erythrocytes destroyed? does it present with hemoglobinuria, hemoglobinemia & hemosiderinuria? does it present with hepatomegaly? does it cause jaundice & decreased haptoglobin?
where are erythrocytes destroyed? spleen or liver why are erythrocytes destroyed? recognized as foreign (different shape than biconcave) or damaged does it present with hemoglobinemia, hemoglobinuria & hemosiderinuria? no does it present with hepatomegaly? yes does it cause jaundice & decreased haptoglobin? yes
intravascular hemolytic anemia where are erythrocytes destroyed? why are erythrocytes destroyed? does it present with hemoglobinuria, hemoglobinemia & hemosiderinuria? does it present with hepatomegaly? does it cause jaundice & decreased haptoglobin?
where are erythrocytes destroyed? within vessels (vascular compartment) why are erythrocytes destroyed? mechanical injury (i.e mechanical heart valve), complement, infection does it present with hemoglobinemia, hemoglobinuria & hemosiderinuria? yes does it present with hepatomegaly? no does it cause jaundice & decreased haptoglobin? yes
hemophilia A is an [...] disorder that is characterized by deficiency of [...]. individuals with this condition will present with [...] & [...]. we must remember that they [will/will not] present with petechiae. this pathology is associated with a [...] bleeding time, [...] prothrombin time & a [...] partial prothrombin time. how do we treat this condition?
x-linked ; deficiency of factor VIII present with massive hemorrhage after trauma/surgery & spontaneous bleeding into joints will not present with petechiae bleeding time: normal PT: normal PTT: prolonged (bleeding time & PT are normal because platelet function is normal & so is the extrinsic coagulation pathway) treatment: factor VIII infusions
β-thalassemia is most prevalent in [...] while α-thalassemia is most prevalent in [...].
β-thalassemia I: mediterranean populations α-thalassemia: asians
as we know, β-thalassemias are caused by diminished synthesis of structurally normal β-globin chains. β° thalassemia is characterized as [...] while β+ thalassemia is characterized as [...]. tell me the two factors that contribute to the anemia seen in this condition.
β° thalassemia: complete absence of β-globin chain β+ thalassemia: reduced but detectable β-globin synthesis 1. reduced synthesis of β-globin leads to inadequate adult hemoglobin (HbA) formation ; this results in cells that appear hypochromatic 2. free α-chains will form insoluble aggregates that reside within erythrocytes & damage their cell membranes, making them susceptible to phagocytosis