UWorld

Question 1

Streptozyme test?

Answer 1

Detects antibodies against group A streptococcus and can be used to retrospectively diagnose streptococcal infections (eg, when evaluating for post-streptococcal glomerulonephritis {PSGN}). Patients with PSGN have edema and hypertension, no hemolytic anemia.

Question 2

Hereditary angioedema?

Answer 2

A rare autosomal dominant disorder that is associated with painless episodes of swelling involving the face, lips, larynx, and extremities. It is caused by C1-inhibitor deficiency.

Question 3

Production and function of erythropoietin (EPO)?

Answer 3

A glycoprotein hormone produced by peritubular fibroblast cells in the renal cortex. EPO is released into the bloodstream in response to renal tissue hypoxia and subsequently acts on erythrocyte progenitor cells (erythroid colony - forming unit cells) in the bone marrow to reduce apoptosis and increase differentiation into mature red blood cells.

Question 4

Treatment of anemia in chronic kidney disease (CKD)?

Answer 4

These individuals are often treated with synthetic forms of EPO (eg, epoetin, darbepoetin) to supplement intrinsic EPO production and stimulate erythropoiesis. Because synthetic forms of EPO can rapidly deplete iron stores (due to increased red blood cell production), patients should be tested for iron deficiency prior to treatment with these agents.

Question 5

Warm autoimmune hemolytic anemia is characterized by …?

Answer 5

Antibodies against antigens on the red cell membrane that result in phagocytosis in the reticuloendothelial system (eg, spleen).

Question 6

Difference between coagulopathy and platelet defect?

Answer 6

Coagulopathies generally presents with deep-tissue bleeding into joints, muscles, and subcutaneous tissue. In contrast, platelet defects typically manifest with mucocutaneous bleeding (eg, epistaxis, petechiae).

Question 7

Age-related changes in bone marrow?

Answer 7

The bone marrow of older patients has a higher quantity of fat and a reduced overall mass, which limits the functional reserve of hematopoietic cells. In addition, hematopoietic progenitor cell diversity and the response to stimulatory cytokines (eg, stem-cell factor, granulocyte macrophage colony-stimulating factor) are also impaired, thereby limiting the generation of new cells in response to stress. Because of these changes, older individuals cannot rapidly generate new blood cells.

Question 8

The principal site of uric acid precipitation?

Answer 8

Uric acid (pKa = 5.4) is soluble at physiologic pH, bur precipitates in an acidic environment. The lowest pH along the nephron is found in the distal tubules and collecting ducts; so these are the segments of the nephron that become obstructed by uric acid crystals. Obstructive uropathy and acute renal failure follow.

Question 9

Splenic congestion?

Answer 9

Occurs during a splenic sequestration crisis (marked hemoglobin decrease, rapidly enlarging spleen), which develops due to vaso-occlusion within the cords of Billroth and splenic pooling of erythrocytes.

Question 10

Liver-associated macrocytosis?

Answer 10

Macrosistosis can occur in liver failure due to an increase in circulating phospholipids and cholesterol that adsorb onto erythrocytes, resulting in membrane expansion. However, liver-associated macrocytosis is generally mild (<110).

Question 11

BCR-ABL1 fusion gene?

Answer 11

Characteristic abnormality seen in chronic myeloid leukemia. The BCR-ABL1 protein is a constituvely active tyrosine kinase, which results in uncontrolled proliferation of granulocytes.

Question 12

Histopathological features of spleen in myelofibrosis?

Answer 12

The proliferation of erythroid, myeloid, and megakaryocytic progenitor cells in the spleen (large islands of hematopoietic progenitor cells) leads to a marked expansion of the splenic red pulp and usually results in dramatic splenomegaly.

Question 13

Diffuse neutrophilic infiltration and follicular necrosis of spleen?

Answer 13

Acute infections of the spleen (eg, septic emboli from infective endocarditis) are typically associated with diffuse neutrophilic infiltration. Follicular necrosis is also common if the infection is due to group A Streptococcus.

Question 14

Dilated sinusoids and fibrous nodules with hemosiderin of spleen.

Answer 14

Congestive splenomegaly due to portal hypertension (eg, from liver cirrhosis) is associated with dilated sinusoids, fibrosis of the red pulp, and hemosiderin-laden macrophages.

Question 15

Complication in polycythemia vera?

Answer 15

Include peptic ulcer disease (altered mucosal blood flow due to increased viscosity) and gouty arthritis (higher erythrocyte turnover).

Question 16

Erythropoietin functions?

Answer 16

EPO travels from the kidneys through the bloodstream to the bone marrow, where it binds to a surface receptor on erythrocyte colony-forming unit cells (ie, erythrocyte precursors). Binding activates the Janus kinase 2/signal transducer and activator of transcription (JAK/STAT) signaling pathway, which induces the transcription of proteins that inhibit erythrocyte precursor apoptosis and promote survival. Binding also activates signals that increase the differentiation of erythrocyte precursors into mature erythrocytes. Together, these effects accelerate the production of erythrocytes and increase curculating red blood cell counts.

Question 17

Paradoxical PTT prolongation and false-positive RPR/VDRL results in antiphospholipid syndrome?

Answer 17

Antiphospholipid antibodies interfere with common serologic tests: lupus anticoagulant (LA) cross-reacts with phospholipid reagents in the activated PTT test, and anticardiolipin antibody (aCL) binds cardiolipin, the predominant antigen used in the rapid plasma reagin (RPR) and VDRL tests. Therefore, patients with circulating antiphospholipid antibodies have paradoxical PTT prolongation and false-positive RPR/VDRL results. Bleeding time and PT, which are coagulation tests unaffected by antiphospholipid antibodies, are normal.

Question 18

Rhabdomyolysis?

Answer 18

Typically presents with muscle pain, red urine (ie, myoglobinuria), and elevated creatine kinase. Release of intracellular phosphate from muscel cells can precipitate calcium salts in damaged muscle and lead to hypocalcemia, but this is typically a delayed finding (24-72 hours after trauma).

Question 19

Intrinsic platelet dysfunction in cirrhosis?

Answer 19

Cirrhosis is associated with intrinsic platelet dysfunction and thrombocytopenia due to decreased hepatic synthesis of thrombopoietin and increased splenic platelet sequestration (secondary to hypersplenism). Platelet dysfunction and significant thrombocytopenia (eg, platelets <50000/mm3) lead to mucocutaneous bleeding/petechiae and prolonged bleeding time.

Question 20

DIC in exertional heat stroke?

Answer 20

Exertional heat stroke is a life-threatening multisystem disorder caused by inadequate body heat dissipation. Severe hyperthermia increases tissue oxygen demand and metabolic rate and shunts blood away from the central organs (eg, brain, kidneys, liver, GI tract) to the skin to dissipate heat. This can lead to tissue ischemia/necrosis and the release of procoagulant proteins (eg, tissue factor), which can trigger disseminated intravascular coagulation (DIC).

Question 21

DIC due to gram-negative sepsis?

Answer 21

DIC is a common complication of sepsis (particularly with gram-negative organisms) because lipopolysaccharide is a procoagulant that triggers the coagulation cascade. This leads to the formation of fibrin- and platelet-rich thrombi in the vasculature, which consumes platelets (thrombocytopenia), coagulation factors (prolonged PT/PTT), and fibrinogen. Fibrinolysis is then triggered to degrade the clots, which elevates D-dimer (a fibrin degradation product) and depletes protein C, protein S, and antithrombin. The thrombi also often shear red blood cells, leading to microangiopathic hemolytic anemia (MAHA).

Question 22

Factor XIII deficiency?

Answer 22

An extremely rare autosomal recessive disorder that causes clot instability. Affected patients often have delayed, recurrent bleeding after trauma or surgery. Hemophilia-like bleeding (eg, deep-tissue bleeding) is seen in factor XIII deficiency.

Question 23

Difference between von Willebrand disease and Immune thrombocytopenia?

Answer 23

Patients with vWD experience easy bleeding from skin and mucosal sites, including the gingivae, nasal mucosa, gastrointestinal tract, and endometrium.
Immune thrombocytopenia produces isolated thrombocytopenia with episodic bleeding that is typically mucocutaneous (eg, petechiae, purpura, epistaxis).

Question 24

Terminal deoxynucleotidyl transferase (TdT)?

Answer 24

Responsible for adding nucleotides to the V,D and J regions of the antibody gene for antibody diversity. It is a marker of immature lymphocytes, both B and T cells. Neoplastic cells in acute lymphoblastic leukemia (ALL) are TdT positive. ALL mainly affects children.

Question 25

The atypical cells seen in infectious mononucleosis (IM)?

Answer 25

After entering the bloodstream through the pharyngeal mucosa and tonsillar crypts, the Epstein-Barr virus (EBV) preferentially infects B lymphocytes by binding to CD21 cell surface receptors. EBV-infected B lymphocytes then activate cytotoxic T lymphocytes (CD8+) through the presentation of viral antigens on MHC I molecules. These reactive (atypical) CD8+ T lymphocytes are the primary immune response to EBV and clonally expand to destroy virus-infected cells.

Question 26

Effect of hypoxia to the brain?

Answer 26

Severe cerebral hypoxia drives increased sympathetic tone, increasing respiration, cerebral perfusion pressure, and oxygen delivery.

Question 27

Site of neutrophils storage?

Answer 27

Although neutrophils are normally the most prevalent leukocyte in the blood, the vast majority of mature neutrophils are held in reserve in the bone marrow or are reversibly attached to the endothelial wall (marginated pool).

Question 28

Acute myelogenous leukemia (AML) characterized by …?

Answer 28

Failure of immature myeloid precursors (myeloblasts) to differentiate into mature granulocytes, is divided into 8 types (M0 through M7).

Question 29

Association of Epstein-Barr virus (EBV) with lymphoma?

Answer 29

Lymphoma is frequently associated with Epstein-Barr virus (EBV), a ubiquitous herpesvirus that primarily infects B lymphocytes and causes persistent latent infections. Although viral reactivation is uncommon, the latent EBV genome still transcribes viral gene products that can result in malignant transformation of infected cells. EBV is particularly associated with nasopharyngeal carcinoma, Hodgkin lymphoma, and some forms of non-Hodgkin lymphoma (NHL; eg Burkitt lymphoma).

Question 30

Intracellular dehydration?

Answer 30

Occurs during the pathogenesis of sickle cell anemia and spherocytosis.

Question 31

Anemia in pyruvate kinase deficiency?

Answer 31

Most of the ATP produced is used for transport of cations against a concentration gradient in the RBC membrane. Therefore, pyruvate kinase deficiency, which results in insufficient ATP production, disrupts this gradient, leading to water and potassium loss, defective maintenance of membrane architecture (echinocyte formation), and hemolysis.

Question 32

Splenomegaly in pyruvate kinase deficiency?

Answer 32

As reticuloendothelial cells in the splenic red pulp are involved in removal of damaged RBCs, their increased activity in the setting of pyruvate knase deficiency causes them to undergo hyperplasia, resulting in splenomegaly.

Question 33

Characteristic histopathologic feature of follicular lymphoma?

Answer 33

At low magnification, the characteristic histopathologic feature of follicular lymphoma is the presence of nodular follicles that obscure the normal lymph node architecture. In contrast to normal reactive lymph nodes, the neoplastic follicles are closely packed and similar in size. Instead of being polarized into dark and light zones, they consist of a mixture of centrocytes (smal, cleaved cells) and centroblasts (larger, noncleaved cells).

Question 34

Histologic features of Reed-Sternberg cells?

Answer 34

RS cells have ample cytoplasm, a multilobed nucleus or multiple nuclei, and inclusion-like nucleoli.

Question 35

Idiopathic aplastic anemia?

Answer 35

Although aplastic anemia is linked to certain medications, infections, toxins, or radiation, most cases are idiopathic and thought to be caused by autoimmune-induced loss of multipotent hematologic stem cells. In idopathic AA, an underlying insult (eg, mutation, virus) causes alteration of surface antigens on multipotent stem cells, making them appear foreign and triggering a cytotoxic T-cell response. Cytokine released by T-helper cells (type 1 cytokine) also contribute to the pathogenesis, most notably IFN-gamma, which triggers apoptotic cell death due to the stimulation of a destructive cytokine cascade and the increased expression of the Fas receptor on the hematologic stem cell surface.

Question 36

Diffuse large B-cell lymphoma?

Answer 36

Typically presents with a rapidly enlarging nodal (neck, abdomen, mediastinum) or extranodal symptomatic mass. The Waldeyer’s ring (oropharyngeal lymphoid tissue) and gastrointestinal tract are commonly involved, and systemic “B” symptoms (fever, weight loss, drenching night sweats) can also be seen.

Question 37

The mechanism of HIT type 2?

Answer 37

Platelet factor 4 (PF4) is a protein released from the alpha granules of platelets that plays a role in platelet aggregation. It also binds heparin and helps inactivate the molecule. The mechanism of HITT involves the generation of IgG antibodies to these complexes of heparin and PF4. The Fc component of the activated IgG antibodies then binds to additional platelets, resulting in further PF4 release and widespread platelet activation. This leads to a prothrombotic state that places patients at high risk for both arterial and venous thrombosis.

Question 38

Prolonges bleeding in hemophilia?

Answer 38

Patients with hemophilia have normal platelet function and can form a platelet plug, so bleeding after procedures can be delayed rather than immediate, in contrast to patients with platelet disorders.