Heme Flashcards
If on blood smear, you see round RBCs that lack the normal biconcave shape and the normal central pallor, what should you suspect?
Spherocytosis - defect in structural proteins (usually spectrin or ankyrin)
What is the difference between FDP (fibrin degradation products) and d-dimer?
FDP - can be generated from the degradation of fibrin or fibrinogen
D-dimer - derived exclusively from fibrin, making d dimer a more informative test for diagnosing clots/DIC
When treating jaundice with phototherapy, what vitamin do you need to supplement?
Riboflavin (B2) because it breaks down when it absorbs light
Which enzymes can be inhibited in lead poisoning?
Aminolevulinate dehydratase (ALAD) and ferrochelatase
What lab values are affected by fibrinolytics? Why?
PT and PTT because tPA lead to degradation of both fibrinogen and fibrin. By breaking down fibrinogen, the common pathway will be partially inhibited (increasing both PT and PTT)
Platelet count is unaffected
How does uterine leiomyoma lead to anemia?
Increased blood loss during menstruation –> iron deficiency –> microcytic anemia
How does ketoconazole interact with warfarin?
Ketoconazole potentiates warfarin’s effects because it inhibits cytochrome P450 (thus decreasing the metabolism of warfarin)
Describe what a Reed-Sternberg cell looks like.
Large binucleate eosinophilic cells
Why is TIBC low in anemia of chronic disease?
TIBC measures blood’s capacity to bind iron with transferrin. Transferrin and relatedly TIBC are low in ACD because even though the serum Fe levels are low, the body senses high iron in its intracellular stores (ferritin) because it’s storing iron there.
What five cancers should you suspect when you see polycythemia (i.e. to see if it’s a paraneoplastic syndrome).
- Hepatocellular carcinoma
- Renal cell carcinoma
- Hemangioblastoma
- Pheochromocytoma
- Uterine myomata
Describe the characteristic histologic findings in a benign reactive lymphadenitis.
- Tingible body macrophages (macrophages that have ingested lymphocytes - filled with debris)
- Multiple large germinal centers
- Frequent mitoses
- Recognizable light and dark zones
Does warfarin affect PT, PTT, or both? Compare normal therapeutic doses vs. overdose.
In normal therapeutic dose - just PT (because it’s mainly the effect of Factor VII)
In overdose - both (because of the effects of all the factors in the common pathway)
What cranial X ray finding is typical of sickle cell anemia?
Sickle cell anemia
Why would a sickle cell patient have shortened digits?
Result of past crises damaging bone growth
What cells are classically found in EBV mononucleosis?
Downey cells - atypical reactive CD8+ lymphocytes
What are two side effects of chloroquine?
- Worsen psoriasis
2. Retinopathy
What should you give with ALL chemo to prevent uric acid stones?
Xanthine oxidase inhibitor - e.g. febuxostat, allopurinol
How do macrolides interact with warfarin?
Potentiate the effects of warfarin - macrolides inhibit CYP450 so they inhibit the metabolism of warfarin
What are Heinz bodies composed of?
Denatured hemoglobin
What lab test is used to monitor the effects of heparin?
PTT
Lymph node biopsy shows “follicle formation with predominantly small lymphocytes containing scanty cytoplasm and irregular, twisted, and indented nuclei”. What is the likely diagnosis and what genetic translocation is associated with it.
Follicular lymphoma
t(14:18)
immunoglobulin heavy chain and bcl-2
Which cells found in small number on skin are perivascular, have darkly stained ovoid nuclei on H&E, and demonstrate metachromasia of cytoplasm when stained with Giemsa?
Mast cells
What drug, commonly given with aspirin to lower risk for MI after stent placement, has a potential toxicity of neutropenia? How does this drug work?
Ticlopidine - irreversibly blocks ADP from binding platelets
Why does placental abruption increase risk of DIC?
The placenta contains massive amounts of tissue factor, which is the primary initiator of the clotting cascade (found in subendothelial tissue) through thrombin generation
What cancers are associated with EBV?
Nasopharyngeal carcinoma, Burkitt’s lymphoma, B-cell lymphoma
Which thalassemia is associated with increased levels of A2?
Beta thalassemia
What are Russell bodies in multiple myeloma patients?
Plasma cells with accumulated immunoglobulins
What is a Schuffner dot and which malarial types is it found in?
Schuffner dot - brick red dots (morphologic changes) in infected erythrocytes
Found in both plasmodium vivax and ovale
What translocation is associated with nodular lymphomas?
Derived from B-cell line
Associated with t(14, 18) - bcl2 activation
What is seen microscopically in cat scratch disease?
Stellate granulomas with central necrosis and organisms
What is the chance that someone with alpha thalassemia will pass the disease on to his offspring?
Autosomal recessive disease (each parent has 2 alpha alleles) so 1 in 2 chance since typically someone with the disease has 2 alleles
For Asians, it’s more often in a cis configuration so inherited together
Is phenytoin a CYP 450 inducer or inhibitor?
Inducer
95% of all observations lie within how many standard deviations of the mean?
2
How does CO poisoning affect PaO2, carboxyhemoglobin, and methemoglobin levels?
Raises carboxyhemoglobin (hemoglobin bound to CO)
Does not change PaO2 or methemoglobin levels
Where in the body does parvovirus primarily replicate?
Bone marrow
What are the atypical lymphocytes observed in the blood smear of patients with mono?
activated CD8+ cells
What type of anemia does disfigured fingernail (spoon nails or koilonychia) suggest?
Iron deficiency anemia
What is the relationship between vWF and Factor VIII?
vWF carries and stabilizes Factor VIII meaning if you have a vWF defect, you will affect both vWF (bleeding time) and Factor VIII (PTT).
If you have a Factor VIII problem like hemophilia A, you will only affect PTT NOT bleeding time.
What is the only vitamin deficiency that can take years to develop?
B12 (cobalamin)
What is the Kozak sequence?
An adenine or guanine in a _CC sequence upstream of an AUG codon that plays a role in the initiation of translation (synthesis of the protein)
Hemolysis induced by TMP-SMX can be indicative or what condition?
G6PD deficiency
Describe the difference in energy utilization in the liver’s handling of conjugated vs. unconjugated bilirubin.
Taking up unconjugated (indirect) bilirubin - passive
Secreting conjugated (direct) bilirubin into the biliary system - active so if this step is impaired then you get a conjugated bilirubinemia which leads to increased excretion of conjugated bilirubin in the urine
What is typically the problem caused by the mutation in beta thalassemia?
Aberrant splicing of precursor mRNA or premature chain termination during mRNA translation
How can you distinguish between CML and leukemoid reaction?
Neutrophil alkaline phosphatase is normal or elevated in leukemoid reaction vs. decreased in CML
What happens when you add thrombin to the blood of a hemophilia patient?
Clots because thrombin is in the common pathway; makes up for the deficit of Factor VIII
What are 3 common non-nucleoside reverse transcriptase inhibitors?
Nevirapine, efavirenz, delavirdine
What drug, commonly given with aspirin to lower risk for MI after stent placement, has a potential toxicity of neutropenia? How does this drug work?
Ticlopidine - irreversibly blocks ADP from binding platelets
What should you give with ALL chemo to prevent uric acid stones?
Xanthine oxidase inhibitor - e.g. febuxostat, allopurinol
When treating jaundice with phototherapy, what vitamin do you need to supplement?
Riboflavin (B2) because it breaks down when it absorbs light
What do we use to treat HIT (heparin induced thrombocytopenia)?
Recombinant hirudins like lepirudin
What pain medication is preferable in patients who are at increased risk of GI and cardiotoxicity?
Acetaminophen
Which plasmodium species occurs in the Western hemisphere?
Vivax
What complication do you need to watch out for in lysing tumor cells with Auer rods?
DIC - the rods are composed of enzymes found in azurophilic granules
How is Rh inherited?
Rh+ is dominant to Rh-; one allele from each parent
What translocation is Burkitt’s lymphoma associated with?
t(8,14) - c myc activation
What is a “large cell with prominent nucleoli” referring to in the context of cervical lymphadenopathy, night sweats, pruritus?
Reed Sternberg cell (Hodgkin’s lymphoma)
What are Heinz bodies made of?
Denatured hemoglobin
Presentation: 4 month old boy with low-set ears, hypertelorism (increased space between eyes), short philtrum (groove in the middle area of the upper lip)
Diagnosis?
DiGeorge Syndrome
Why are patients with DiGeorge Syndrome at increased risk of infection and lack type IV hypersensitivity?
Absence of the thymus - increased risk of infection
Also leads to absence of T cell dependent immunity meaning lack of type IV hypersensitivity
What hematologic cancer is found in older adults and presents histologically with lymphocytosis and smudge cells?
CLL - chronic lymphocytic leukemia
What substances does aspirin inhibit the formation of?
Prostaglandins and thromboxane A2
It irreversibly inhibits cyclooxygenase activity but does not inhibit its formation
How does aspirin decrease platelet aggregation?
Inhibits thromboxane A2
What disorders are closely related to polycythemia vera?
Myeloproliferative disorders including:
- Chronic myeloid leukemia
- Myeloid metaplasia with myelofibrosis
- Essential thrombocythemia
In multiple myeloma, what are the inclusions found within plasma cells?
Russell bodies - accumulation of immunoglobulin
What translocation is associated with follicular lymphoma?
t(14,18) - immunoglobulin heavy chain with bcl-2
Why are antimalarial drugs contraindicated in a patient with G6PD deficiency?
Added oxidative stressors
Between heparin and warfarin, which one is used to treat acute PE/DVT and which one is used to prevent future PE/DVT?
Heparin - acute
Warfarin - long term prevention
What is the inheritance pattern for Hemophilia A/B?
X linked recessive
Inoculation of candida in serum for 3 hours at body temperature shows what?
Germ tube test - the yeast show the beginnings of true hyphae (like tubes extending out from the yeast)
Describe the morphologic characteristics of parvovirus.
Single stranded DNA without an envelope
Presentation: infant with eczema, thrombocytopenia, and history of recurrent infections (combined B and T lymphocyte deficiency)
Diagnosis?
Wiscott-Aldrich syndrome - X linked disorder
T cells binding to MHC with high affinity - positive or negative selection?
Negative selection - wanting to get rid of those that are potentially autoimmune reactive
How do we give B12 to patients who are deficient?
Parenteral
What are the most common causes of B12 deficiency?
Gastric atrophy, intrinsic factor deficiency, terminal ileal disease
What should you think of in elderly patient with chronic anemia and no clear identifiable underlying source?
B12 malabsorption
Why do erythrocytes have an alternate glycolytic pathway using bisphosphoglycerate mutase even though they are not producing any ATP with this alternate pathway?
They are producing 2,3-bisphosphoglycerate (2,3-BPG) which decreases hemoglobin’s affinity for oxygen thus allowing increased delivery of oxygen to the peripheral tissues
Presentation: Anemia, jaundice and splenomegaly.
Diagnosis?
Hereditary spherocytosis
Which group of hematologic disorders results from constitutively active tyrosine phosphorylation activity?
Myelofibrosis - have mutations in JAK/STAT pathway which is a tyrosine kinase
Histology: diffuse medium sized lymphocytes with high Ki-67 (cell proliferation) fraction
Diagnosis?
Burkitt’s lymphoma
What infectious agent is most often associated with Burkitt’s lymphoma?
EBV
The binding of oxygen to hemoglobin drives the release of what 2 things from hemoglobin?
CO2 and H+
Why might a sickle cell patient get megaloblastic anemia?
Predisposed to folate deficiency because of increased erythrocyte turnover
(same is true in other chronic hemolytic anemias)
Why would a patient who receives blood transfusion have lowered calcium levels?
Blood transfusion –> elevated levels of citrate (added to blood) –> citrate chelates calcium and magnesium and may reduce their levels
What would happen to the oxygen binding curve of hemoglobin if you instead broke it up into its individual subunits?
Becomes like myoglobin which is monomeric - hyperbolic curve
What is the role of PECAM-1 (platelet endothelial cell adhesion molecule)?
Transmigration - neutrophils migrate out of the vasculature via integrin attachments and adherence to PECAM-1
What is JAK2?
A non-receptor tyrosine kinase associated with the erythropoietin receptor (commonly involved in myeloproliferative diseses)
What is Akt (protein kinase B) and what does it do?
Serine/threonine specific protein kinase that activates mTOR which translocates to the nucleus to induce genes involved in cell survival, anti-apoptosis, and angiogenesis
How does folate deficiency limit DNA synthesis?
Inhibits the formation of deoxythymidine monophosphate (dTMP) since dUMP –> dTMP requires the conversion of tetrahydrofolate to dihydrofolate
Why would you see pigmented gallstones in hereditary spherocytosis?
Chronic hemolysis - increased bilirubin from lysed RBC’s precipitates as calcium bilirubinate, bilirubin polymers, calcium salts
If platelets aggregate normally in response to ADP but poorly in response to ristocetin, what does this suggest?
vWF deficiency - ristocetin activates gp1b receptors on platelets and makes them available for binding by vWF so if there is no response then that suggest vWF deficiency
What reaction is catalyzed by G6PD?
Glucose-6-phosphate –> 6-phosphogluconate
Part of the HMP shunt to generate large amounts of NADPH to maintain glutathione in a reduced state
Does antiphospholipid syndrome lead to a hypercoagulable or hypocoagulable state?
Hypercoagulable
Presentation: Lifelong history of gingival bleeding, epistaxis, mucosal bleeding, and/or menorrhagia
Diagnosis?
von Willebrand disease
Describe the cause of most cases of polycythemia vera.
JAK2 mutation that renders hematopoietic stem cells more sensitive to growth factors
Describe the difference in lymph node architecture between DiGeorge syndrome vs. agammaglobulinemia.
DiGeorge - deficiency in number of mature T lymphocytes leading to poor development of lymph node paracortex
Agammaglobulinemia - FINISH THIS
