Bugs & Drugs
This group of Gram-positive cocci is catalase negative, beta hemolytic, and is the primary cause of neonatal meningitis.
What is group B strep (strep agalactiae)?
A bone marrow cell expresses CD34 and CD117 and can self-renew while giving rise to both myeloid and lymphoid progenitors. Identify the cell and the cytokine that promotes its dormancy.
What is a hematopoietic stem cell? What is TGF-B?
A patient with hyperbilirubinemia is given a therapy that involves sitting under a blue light for hours. The therapy is called this and does this to bilirubin.
What is phototherapy? What is a change in conformation from Z,Z-bilirubin (insoluble) to E,E-bilirubin (soluble)?
A patient on Warfarin therapy could potentially have a significant decrease in these coagulant factors and protein inhibitors.
What are factors 2, 7, 9, and 10 and proteins C and S?
Burkett lymphoma is identifiable by this chromosomal translocation and is associated with this viral infection in endemic countries.
What is t(8;14) and EBV?
This component of Gram-negative bacterial LPS is responsible for endotoxin activity and can trigger a major inflammatory response.
What is lipid A?
A patient has chronic inflammation, anemia, elevated ferritin, low serum iron, and low TIBC. Explain the cytokine - hormone - transporter pathway that causes iron to become less available for erythropoiesis.
IL-6 is increased, leading to an increase in hepcidin release which breaks down ferroportin and prevents iron release to the serum.
A patient comes in with a gunshot wound to the abdomen. They require a blood transfusion and the attending physician orders a forward and reverse type because we have oh so much time! Using the agglutination scale (0 and 4) what blood type must this patient be based on the following results:
AB positive
This type of von Willebrand disease causes faulty Binding of vWF to factor VIII and has this kind of inheritance pattern.
What is type 2N and what is autosomal recessive?
These symptoms are indicative of end-organ damage in myeloma patients and have a useful acronym to remember them by.
What is CRAB? (HyperCalcemia, Renal insufficiency, Anemia, Bone lesions)
A patient has a UTI. The isolate is a non-lactose fermenting Gram negative bacillus that produces urease and swarms on culture. It is associated with struvite stones.
bonus points: after getting a negative oxidase test, what would be the next step in distinguishing this organism?
What is Proteus Mirabilis?
bonus: what is H2S production?
A patient develops carbon monoxide poisoning. Even if some heme sites remain available to bind oxygen, explain why the hemoglobin-oxygen dissociation curve shifts left and why tissue oxygen delivery falls.
CO binds hemoglobin with much higher affinity than oxygen and stabilizes a higher-affinity state at remaining oxygen-binding sites. Left shift impairs oxygen unloading.
A lack of this enzyme can cause neonatal jaundice, Gilbert syndrome and Crigler-Najjar.
What is UDP-glucuronosyl transferase?
A patient with hemophilia A develops an inadequate response to factor VIII replacement. A newly administered medication is a bispecific monoclonal antibody that binds factor IXa and factor X, bringing them together to perform a function normally facilitated by factor VIII. Name the medication and explain its mechanism.
What is emicizumab?
Emicizumab bridges factor IXa and factor X, mimicking factor VIII's cofactor function in the coagulation cascade. It can be used for prophylaxis in hemophilia A, including patients with factor VIII inhibitors.
Th plasma cell disorder has a serum M-protein under 3 g/dL, fewer than 10% clonal plasma cells in the bone marrow and no myeloma-defining events (no CRAB). It needs no treatment, just life long monitoring.
What is MGUS? (Monoclonal Gammopathy of Undetermined Significance)
A hospitalized patient with a severe gram-negative infection is treated with an antibiotic that inhibits bacterial protein synthesis. The drug exhibits concentration-dependent killing, and its efficacy correlates with the ratio of peak serum concentration to MIC. After several days, the patient develops acute kidney injury and difficult hearing due to this antibiotic.
What is an aminoglycoside? (Remember, these have ADRs of nephrotoxicity, ototoxicity and neuromuscular effects)
A patient with severe malaria is given an antimalarial. Soon afterward they develop acute hemolytic anemia. Their erythrocytes cannot adequately regenerate reduce glutathione because they have impaired NADPH production. Identify the drug, the enzyme deficiency and the biochemical link between them.
What is primaquine? What is G6PD deficiency?
G6PD in the PPP regenerates NADPH which is needed to regenerate reduced glutathione from GSSG.
Name and describe the four types of hypersensitivity reactions.
Type 1 - IgE mediated, immediate
Type 2 - IgG/IgM mediated
Type 3 - immune complex mediated (involves IgG/IgM responding to soluble antigens that get deposited in distant vessels/tissues)
Type 4 - delayed, T-cell mediated
HUS can be caused by these two bacteria, and can progress into this type of hemolytic anemia that presents schistocytes on a peripheral blood smear.
What are E. coli and Shigella? What is MAHA?
A 72 year old patient presents with pancytopenia despite hypercellular bone marrow. Peripheral smear shows hypo segmented neutrophils and abnormal RBC morphology. Bone marrow biopsy reveals 14% myeloblasts without AML-defining genetic abnormalities. This clonal disorder is characterized by ineffective hematopoiesis and an increased risk of progression to acute leukemia.
What is MDS? (Myelodysplastic Syndrome)
A patient with a serious gram-positive infection is treated with an antibiotic that binds the 50S ribosomal subunit and inhibits protein synthesis by preventing formation of the initiation complex. The drug is also active against certain resistant gram-positive organisms. Several days later, the patient develops thrombocytopenia and reports visual disturbances.
Name the antibiotic, its specific mechanism of action, and what famous drug-drug interaction exists.
What is linezolid? What is blocking the 50S subunit, preventing transcription? What are SSRIs?
A patient returns from a region where Plasmodium vivax is endemic. They initially improve after a treatment that kills blood-stage parasites, but months later develop another episode of malaria. A follow-up regimen is planned to eradicate the hypnozoites in the liver. Name the drug needed for the dormant liver stage and the critical safety test required before giving this follow up drug.
What is primaquine? What is G6PD deficiency?
Clinical picture: Woman with history of aplastic anemia presents with worsening fatigue, dark urine and abdominal pain.
Labs: elevated LDH, decreased haptoglobin, elevated reticulocyte counts with leukopenia and thrombocytopenia. Negative DAT.
Histology: RBCs are CD55 & CD59 negative
what is the diagnosis? what is its MOA?
Paroxysmal Nocturnal Hemoglobinuria (PNH)
the only acquired intrinsic hemolytic anemia
due to an acquired mutation which causes loss of GPI (responsible for tethering antigens to RBCs). Destroyed by complement.
Dipyrimadole is this type of drug. Its MOA is An accumulation of intracellular cAMP and eventual inhibition of platelet activation.
What is a phosphodiesterase 3 (PDE3) inhibitor?
A growing lump near the jaw is concerning, history with a Sjögren’s syndrome might cause a murder, this infection could be the killer but I haven’t a clue.
What is MALT lymphoma: H. pylori?