Heme Flashcards
1
Q
Apt with chronic alcoholism presents with HA, chills, nausea, and dizziness and notes he has been home in his apartment a lot with a gas heater. What abn finding would be on his hgb dissociation curve?
A
Carbon monoxide poisoning
Decrease in oxygen carrying capacity of hgb
Tx - 100% Oxygen or hyperbaric therapy
2
Q
Pt presents with hemiparesis, recent history of gum bleeding, LUQ pain, Platelet count 900,000.
A
Essential thrombocytosis - platelet overproduction
Epistaxis, thrombosis, burising, bleeding, erythromelalgia (buring and redness in hands and fee)
Tx - hydroxyurea - inhibits ribonucleotide reductase preventing dNTP formation
3
Q
Hodgkin lymphoma is associated with which viral infection?
A
Epstein Barr (EBV) dsDNA linear
4
Q
INR increases when warfarin concentration is too
A
high.
High INR = hypocoaguable
IE when a CYP450 inhibitor is added to the pt regimen (isoniazid, cimetidine, quinidine, quinolones, spironolactone, macrolide, amiodarone, dapsone, ketoconazle
5
Q
A pt with G6PD deficiency has deficiency in which molecule after taking certain medications (primaquine, sulfonamides, nitrofurantoins) or fava beans?
A
NADPH (reduced by G6PD)
6
Q
Pt T cells have a multilobulated nucleus in “cloverleaf” cells. Skin lesions, hepatosplenomegaly, lymphadenopathy.
A
Adult T cell leukemia
Human T cell leukemia virus (HTLV-1) - rapidly progressive. Death in months
7
Q
Transplant recipient presents with itching over his palms and soles and recent diarrhea. Maculopapular rash over neck, shoulder, palms, and soles. Elevated ALT/AST alk phos
A
Acute graft vs host dz
Triad of dermatitis, hepatitis, gastroenteritis
Donor lymphocytes react against host MHC
Occurs weeks after transplantation
8
Q
In what order do organs begin hematopoiesis during development?
A
- Yolk sac (3-8 wks)
- Liver (6 wks - birth)
- Spleen (10-28 wks)
- Bone Marrow (~18 wks gestation)
9
Q
A pt with severe sepsis develops DIC. what changes will be seen in her RBCs?
A
microangiopathic hemolytic anemia
Schistocytes
10
Q
A 65 y/o pt has been experiencing pain exacerbation associated with OA for a week and has been brought to the ED with disorientation and lethargy. He is presenting with respiratory alkalosis and anion gap acidosis. What did he over dose on?
A
Aspiring (salicylate) tox
Would have ringing in the ears prior to disorientation
Combined resp alkalosis and anion gap acidosis
Other AEs = GI discomfort and bleeding
Tx - admin bicarb to alkalinize the urine and promote excretion
11
Q
What is the result of warfarin exposure in utero?
A
hemorrhage causing scaring of the organs (optic atrophy, Dandy-walker, developmental delay)
12
Q
A pt with iron deficiency anemia will have what finding on her labs for: Ferrittin, Iron-binding capacity, MCV
A
Low Ferrittin, MCV
High Iron binding capacity
13
Q
What is ferritin?
A
Binds free iron and stores it intracellularly. Count directly correlates with total body levels of iron
14
Q
What is give to a pt presenting acutely with a fib to protect from thrombosis? And what is given if they are over anti-coagulated?
A
Heparin (potentiates antithrombin)
Correct overdose with Protamine sulfate, a cationic molecule that binds the negatively charged heparin
15
Q
Which drug binds directly to IIb/IIIa on activated platelets to prevent aggregation?
A
Abciximab
Binds IIb/IIIa to prevent fibrinogen from binding and interfering with aggregation. Used in acute coronary syndrome and angioplasty
16
Q
Inheritance pattern for G6PD deficiency
A
X-linked
exposure to oxidant drug -> production of peroxides and free radicals -> GSH (glutathione) absorbs this radicals but fails to regenerate with G6PD is absent because NADPH becomes depleted
17
Q
In follicular lymphoma these is overexpression of bcl-2. What is its function?
A
antagonist of apoptosis by preventing cytochrome c from binding APAF
18
Q
Pt presents with chronic fatigue, pale conjunctivae, decreased cap refill, wide gait, mild parathsia, low hgb, low hct, high MCV, high platelet
A
Megaloblastic anemia due to B12 deficiency
smear would show macrocytic hypersegmented PMNs and large oval shaped erythrocytes
19
Q
How do you distinguish folate deficiency from B12?
A
Time of onset, folate occurs in months. B12 takes years
20
Q
Following a mono infection a college student presents with fatigue, scleral icterus, cervical lymphadenopathy and splenomegaly. Finger tips are purple. Low hgb, high reticulocyte, + heterophile testing. Dx?
A
IgM-mediated hemolytic anemia (cold agglutin)
Manifests shortly after EBV, acute HIV, mycoplasma, leukemia
heterophile test = sens and spec to cold agglutins
21
Q
pt presents with RLQ pain, diarrhea, fever x 10 years. Low hgb, large MCV. Hypersegmented PMNs and oval macrocytes on smear. Dx?
A
Crohn’s dz
Decreased abs of B12 causing megaloblastic anemia
Elevated methylmalonic acid level b/c B12 is an essential cofactor to convert it to succinyl-CoA
22
Q
Pt presents with anemia, jaundice, and splenomegaly with spheroids on smear
A
Hereditary spherocytosis
defect in cytoskeletal proteins (ankyrin, band 3, spectrin)
Tx - splenectomy
23
Q
A college student reports seeing blood in her urine but only first thing in the morning
A
Paroxysmal nocturnal hemoglobinuria (PNH)
abn PIG-A gene which produces the glycophosphatidylinositol (GPI) anchors on the cell surface
Without these anchors, MAC complexes attach to the RBC and cause hemolytic anemia
hematuria happens all day but most noticable in the morning because urine is concentrated
24
Q
When do you see the Taut form of hemoglobin?
A
It is the deoxygenated form, low oxygen affinity, favors offloading. See it in the venous system.
Relaxed form has greater oxygen affinity
25
What findings (demographic and labs) would be seen in Beta-Thalassemia?
hypochromic microcytic RBC
Elevated RBC count, nl to low hematocrit
Target cells
Mediterranean and North African descent
26
What hematologic changes may be found in a HCV pt that is taking ribavirin?
Ribavirin inhibits inosine monophosphate dehydrogenase (nucleotide formation)
Assoc with hemolytic anemia (low serum haptoglobin (b/c they are sopping up free hgb in the blood), high lactate dehydrogenase, indirect hyperbilirubinemia (intravascular hemolysis)
27
MOA of Cyclophosphamide?
Alkylating agent that covalently bonds DNA to guanine N-7
| Cell-cycle independent
28
MOA of vincristine?
Blocks polymerization of microtubules by binding tubulin and inhibits mitotic spindle formation. M-phase specific
29
A pt taking cyclophosphamide for non-Hodgkin's lymphoma. 2 months later she presents with a urinalysis finding: 1+ protein, 1+ leukocyte esterase, WBC, TMTC RBCs. This would have been prevented is she was also given which drug?
Mesna
AE's assoc with cyclophosphamide incl. myelosuppression and hemorrhagic cystitis
Mesna prevents hemorrhagic cystitis by binding cyclophosphamide metabolites in the urine and neutralizing them
30
When would you coadminister a treatment with diphenhydramine?
Along with a drug that may cause an allergic rxn (vanco) or alleviate dystonic rxns (haloperidol)
31
Pt presents with slow-onset, bizzare, paranoid behavior, jerky uncoordinated gait, weight loss. PE beefy red tongue, hyperreflexia, extensor plantar reflexes, + Romberg. What would be seen on smear?
Increased nuclear lobulations in PMNs, macrocytic RBC's
Dx = pernicious anemia. autoimmune Ab causing atrophic gastritis and IF deficiency which reduces B12 absorption
Tx - B12 injections
32
A pt with RA presents with fatigue and bruising. CBC shows decreased RBCs, WBCs, and platelets. He RA tx inhibits dihydrofolate reductase. Co-administration with what would have reduced these effects?
Pt is taking Methotrexate for R and it prevents thymidine synthesis.
Co-admin with leucovorin or folinic acid (tetrahydrofolate derivative) mitigates the myelosuppression
leucovorin rescue
33
pt presents with recurrent gum bleeding, severe menorrhagia. Notes her mom and gma had similar syx but not her dad. Labs:platelet 250,000, increased bleeding time, increased PTT, nl PT. Dx?
Von Willebrand dz (vWD)
AD
mucocutaneous bleeding and menorrhagia in women
Defect in platelet aggregation and factor VIII delivery (nl PT)
34
A pt with RA presents with fatigue, palpitations, and increased SOB. PE pallor and tachycardia. low hgb, low serum iron, high ferritin level, decreased TIBC. Smear shows decreased number of normal sized RBCs
Anemia of chronic dz
normochromic, hypoproliferative anemia, decreased Fe, decreased TIBC
Elevated ferritin demonstrates that Fe isn't so low that the stores are depleted
35
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A pt is treated for N. meningitides in Guatemala. 5 days post therapy her labs show:
WBC 2400
Hgb 5.3
Platelet 25,000
Ret 0.1%
What abx was she given?
```
Chloramphenicol
Causes aplastic anemia (pancytopenia, low Ret), gray baby syndrome
Rarely used in the US
36
Which type of transplant is the most effective and least likely to be rejected?
Autogenic (self-graft)
Skin, coronary a. bypass, cartilage
NO need for immunosuppresion
Option in Hodgkin lymphoma since stem cells are not affected and can be harvested
37
What is an allograft?
Graft from a genetically different member of the same species.
Require immunosuppresion to prevent T cell mediated organ rejection
Second line in Hodgkins if autogeneic graft fails
38
A pt with breast cancer was started on a chemo regimen and the masses have been shrinking. However, the masses have returned to their original size and have been found to have a mutation in beta tubulin. What drug was given?
Paclitaxel - prevents microtubule disassembly
| Vincristine, vinblastine - inhibit microtubule formation
39
What is the MOA of doxorubicin?
Generates free radicals and causes ds DNA breaks.
40
MOA of busulfan
DNA alkylating agent.
41
MOA of Ciplatin
DNA crosslinking agent
42
MOA of etoposide
inhibit type II topoisomerase.
43
A pt with sickle-cell may have what findings would be on their blood smear?
Normocytic RBCs, Sickle shaped RBCs, increased reticulocytes, and Howell-Jolly bodies
Also predisposed to calcium bilirubinate gallstones (radiopaque)
44
What does external validity mean in a study?
extent to which study results are applicable to a population outside of the study population. Randomization is one way to help ensure appropriate external validity
Measure of accuracy
45
A pt presents with dizziness, fatigue, megaloblastic anemia following abx use for UTI's. Which abx was used?
Trimethoprim-sulfamethoxazole
AE's of Bactrim = Stevens-Johnson syndrome, nausea, megaloblastic anemia, leukopenia, and granulocytopenia. These are reduced with a folinic acid supplement
46
When is Chloramphenicol given and what are it's AEs?
Used in bacterial meningitis
AE's = aplastic anemia, gray baby syndrome.
Can lead to death if unable to metabolize the drug
47
What should a pt with von Willebrand's dz (Increased PTT, Bleeding time) be given as a preventative prior to undergoing a procedure?
Desmopressin
| ADH analog, increases the release of vWF from storage sites and increase factor VIII activity
48
a pt with lead poisoning (fatigue, peripheral neuropathy) inhibits what enzyme?
Gamma-aminolevulinic acid
| Involved in heme synthesis
49
What lab findings are consistent with Iron deficiency anemia?
```
Decreased MCV (microcytic)
Low ferritin (hypochromic)
```
50
A pt with anemia symptoms and labs also have a positive direct coomb's test. Dx?
Autoimmune hemolytic anemia
| Idiopathic, viral induced, SLE-induced, lymphomas
51
Rank HCV, HBV, and HIV in order from highest infectability to lowest
HBV
HCV
HIV
52
What is the prominent protein in eosinophils?
Major basic protein
| They also produce histaminase and arylsulfatase which degrade histamine and slow-releasing substance of anaphylaxis
53
A vegan presents with macrocytic anemia and multilobed PMNs. What lab test will definitively determine the deficiency?
Methylmalonic acid level. Methylmalonyl CoA is converted to succinyl CoA with B12 as a cofactor. If B12 is deficient methylmalonic acid will accumulate
Don't want to measure B12 directly because most will be bound to a protein and won't tell you how much of the B12 content is bioactive
Folate deficiency will have normal methylmalonic acid levels
54
A pt has irregular bruising/bleeding and peripheral smear shows few platelets and large WBC's with azurophilic granular needles in the cytoplasm. Dx and Tx?
Acute DIC due to Acute promyelocytic leukemia (auer rod, t(15;17))
Tx - all-trans retinoic acid which promotes the differentiation of immature tumor cells
55
A pt with a hx of weakness of weightloss has hepatosplenomegaly and general lymphadenopathy. Peripheral smear shows lymphocytes that are destroyed during slide preperation. This dz involves clonal expansion of which cell type?
B lymphocyte
This is chronic lymphocyte leukemia (CLL)
Smudge cells are seen on the smear which are clonal B lymphocytes arrested in the B cell differentiation pathway between pre-B cells and mature B cells
56
4 y/o presents with fatigue, loss of appetite, and bruising. Smear shows abundant lymphoblasts. Dx?
Acute lymphocytic leukemia (ALL)
Neoplasm from a single B or T progenitor cell. Blast accumulates in the marrow crowding out the other cells lines and suppressing hematopoiesis.
Syx = anemia, thrombocytopenia, neutropenia
57
Following a UTI a pt has an elevated INR. Why?
Loss of gut bacteria (bit K deficiency)
58
A child has jaundice following a viral infection. Peripheral smear and osmotic fragility test are diagnostic. Dx?
```
Hereditary spherocytosis (defect in spectrin, ankyrin)
Spherocytes are fragile and pt is more prone to heolysis with stress. Difficult for spherocytes to filter through spleen and splenectomy ameliorates the condition
```
59
What is heaprin-induced thrombocytopenia (HIT)?
Low platelet state 5-14 days post heparin therapy
Ab form against heparin-platelet factor 4 complex causing stroke, MI, DVT etc. Occurs when platelets fall to 50% and more common in pts that have received heparin before
60
A teenager has a nosebleed lasting 1 hr after a URI. PE shows small nonblanching petechiae on the legs. Labs: 25,000 platelet, aPTT and PT are WNL. Dx and additional lab findings?
Idiopathic thrombocytopenic purpura (ITP)
autoimmune dz triggered by viral infection
dx of exclusion
Ab against GPIIb/IIIa
80% of childhood cases are self limiting
Adults - tx with steroids, IVIG, plasmapheresis, rituximab
61
A newborn (3 days) presents with an umbilical stump oozing blood and black malodorous stool. Dx and lab findings?
Vitamin K deficiency
NL platelet count, bleeding time, d-dimer
Elevated PT and PTT
62
Pt presents with B symptoms, nontender cervical and supraclavicular lymphadenopathy. Bx = large cells with lobed nuclei and prominent eosinophilic inclusion like nucleoli. Dx?
Hodgkin's lymphoma
Bx describes a reed-sternberg cell. These cells are CD15/CD30 +
RF's 15-40 y/o male and 55+ y/o male, EBV infection, immunodeficiency, prolonged HGH use
63
What molecule does fetal Hgb have lower affinity for and contributes to the left shift seen on the oxygen-hgb dissociation curve?
2,3-bisphosphoglycerate
| Lower 2,3-BP affinity = higher oxygen affinity = left shift
64
After a long flight a pt has a DVT and then experiences a PE in the middle of the night. Dx?
Factor V Leiden
Most common inherited hypercoagulability.
Arg to glut substitution in residue 506 of Factor V makes the protein resistant to cleavage by protein C
65
A cancer pt is presenting with aplastic anemia (anemia, neutropenia, thrombocytopenia). What drug could have prevented this and what is its MOA?
G-CSF is given during chemo to prevent neutropenic fever
It binds a transmembrane receptor to stimulate immature PMN differentiation in the marrow
Can also use bone marrow transplant and transfusion but these are infrequently used
66
What is neutropenic fever?
PMN count 38 for at least an hour or one temp at >38.3
| Assumed to have an infection and initiate broad spectrum abx
67
Translocation of 15;17. Dx and tx?
Acute promyelocytic leukemia (APL)
Tx - all-trans retinoic acid (vit A derivative, bind nuclear receptors to upregulate genes to allow maturation of myeloid cells)
Auer rods = pathognomonic
68
A child presents with B symptoms x 1 week. Lymphoblasts are seen on smear are seen on smear. Dx?
Acute lymphocyte leukemia
| Presents with sudden onset of syx associated with bone marrow suppression.
69
How do you distinguish lymphoblasts from myeloblasts?
Lymphoblast - large blue cell
| Myeloblast - more nucleoli, more granules, auer rods
70
A child presents with jaundice. Labs: anemia, increased ret count, + warm agglutinin test
Warm-reactive autoimmune hemolytic anemia (AIHA)
Tx - corticosteroids
Corticosteroids inhibit the Fc receptor mediated clearance of sensitized RBCs
71
How does the diptheria vaccine work?
Cross-reactivity of toxoid
Toxoid = toxin that has been modified so that it is no longer toxic but antigenicly similar
Toxid cross-reacts with the toxin.
72
A 12 y/o develops hemorrhagic cystitis following use of cyclophosphamid for juvenile RA. She also develops petechiae. What is likely to manifest with these symptoms?
Fanconi's anemia
ar, marrow hypofunction and eventual pancytopenia
Presents early in life
Hallmark = increased chromosolmal breakage in response to DNA-damagin agents due to a defect in homologous recombination repair.
More sensitve to cyclophosphamide and other chemo's
73
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A pt with colon cancer is have dark colored stools
WBC - 10,200
Hgb 8.8
HCT 26.5%
Platelet 231,000
```
Microcytic anemia
| Blood loss = Fe loss = hypochromic microcytic anemia
74
What is the MOA of mesna?
free thiol compound that reacts with urotoxic products of cyclophasphamide. Prevents hemorrhagic cystitis associated with cyclophosphamide usage
75
A pt presents with a single (painless) large mass. Bx shows many large cells resemblind lymphocytes. B symptoms
Diffuse large B-cell lymphoma (DLBCL), most common type of Non-Hodgkin lymphoma
RF's immunosuppresion (esp HIV, HH8). Increasing age
76
A pt presents with megaloblastic anemia due to folate deficiency. What process will the pt have a defect in?
One-Carbon unit transfers
Tetrahydrofolate is an intermediate that transfers 1 unit of C in purine synthesis.
NO neuro symptoms
77
A dz is characterized by lytic bone lesions, hypercalcemia, renal insufficiency, anemia, susceptibility to infection. Monoclonal spike on protein electrophoresis.
Multiple myeloma
Proliferation of plasma cells
Spike = monoclonal M
Produces great quantities of Bence Jones proteins (Ab light chains)
Renal insufficiency due to production of large, tubular casts obstructing the tubular lumina
78
How do you treat hemochromatosis?
Regular phlebotolmy
| Iron-chelating agent (deferoxamine)
79
Following a blood transfusion pt develops fever, tachycardia, dyspneanausea, tight chest, flank pain and diffuse ECG changes. What is the mechanism of the rxn?
Type II HS (complement mediated cytotoxic) due to ABO incompatibility
Massive hemolysis leads to hyperkalemia (spiked T waves on ECG)
80
Vinca alkaloids and paclitaxel have what common feature?
Specific mitotic phase inhibitors of the cell cycle (microtuble assembly and disassembly)
Vinca alkaloids = vincristin and vinblastine, inhibit spindle formation
Paclitaxel = hyperstabilizes microtubules, prevents spindle breakdown
81
A pt presents with tingling that has progressed over months. No travel hx. Mildly jaundiced, tongue is glazed in appearance, decreased vibration sense and muscle strength in lower extremities. Hypersegmented PMNs on smear
Pernicious anemia
Syx resemble B12 deficiency (pallow, jaundice, low RBC, fissures at the cornors of the mouth, glossitis, motor and sensory loss (abn myelin))
Pernicious anemia = most common cause of B12 deficiency. Ab against IF decreases B12 absorption despite normal intake
82
A pt presents with labs showing abn monoclonal serum Ig levels. Bone scan, abd CT, 24 hr urine collection are all normal. What is the next step?
Repeat labs in 6 mo
| pt likely has monoclonal gammopathy of undetermined significance (MGUS). Premalignant dysproteinemia
83
A pt with frequent bruising presents with prolonged PTT and reduced ristocetin-induced platelet aggregation
Von Willebrand's dz
NL function
1. Platelet adhesion to collagen via glycoproteins
2. Carries factor VIII
vWD complain of nose bleeds, menorrhagia, prolonged bleed after procedures
Hemopheliacs have appropriate hemostasis following a procedure but will have hemorrhages
84
Pt presents with anemia and tingling. Labs: elevated homocysteine and methylmalonic acid, and mild thrombocytopenia. Hypersegmented PMN on smear. Dx?
Pernicious anemia
2 possible Ab:
1. Ab against parietal cells (secrete protons and IF)
2. Ab against IF directly
85
What is the active form of prednisone?
Prednisolone
| Converted to active form by 11-B-hydroxysteroid dehydrogenase
86
t(8;14)
Burkitt's lymphoma
Starry sky appearance
c-myc on chr 8 onto IG heavy choin on chr 14
Assoc with EBV
Common cause of tumors of the maxilla or mandible in African pts. Americans tend to have abdominal tumors
87
10 y/o boy presents with recurrent bacterial infections, eczema, nosebleeds. Platelet 60,000
Wiskott-Aldrich syndrome
X-linked
recurrent pyogenic infections, thrombocytopenia, purpura, eczema
Low IgM but high IgE
88
#1 RF for DVT?
Smoking
89
shortly after receiving 5U of blood a pt presents with tingling around his mouth and muscle cramps. What other finding would you expect
Tapping the pt's cheek just anterior to the ear elicits ipsilateral facial muscle contraction
Hypocalcemia is a common AE when administering large quantities of blood. usually coadmin with citrate
90
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A teenager presents with 2 weeks hx of B symptoms, fever, petechiae, lymphadenopathy, widened mediastinum
WBC - 18,000
Hgb - 11.5
Platelet - 120,000
Dx and Bx?
```
Acute Lymphoblastic Leukemia/lymphoma (ALL)
Bx - Pre-T cells, terminal deoxynucleotidyl transferase positive
All can be B-ALL (young kids) or T-ALL (teens, adults)
Wide mediastinum = thymic mass
91
Memory B cells, tartrate resistant acid phosphatase positive on bx?
Hairy cell leukemia
| Older men with an indolent cours
92
Female pt presents with bruises on her legs and petechiae and thrombocytopenia. Pts symptoms resolve 3 weeks a later.
Immune thrombocytopenic purpura (ITP)
Dx of exclusion
Tx - steroids
93
50 y/o male presents with weight loss, fatigue, night sweats, easy bruising, nosebleeds, pain near the first metotarsophalangeal joint in the left foot, heptosplenomegaly
WBCs = 50,000 and spectrum of myeloid cells on smear. Genetic translocation is found
Chronic myelogenous leukemia
t (9;22), Philadelphia chromosome, BCR-Abl
Bcr-Abl becomes constiutively active tyrosine kinase, promoting unregulated cell growth
Can have gout due to overproduction and death of leukemic cells.
Tx - Imatinib (inhibits tyrosine kinase)
94
A man with an acute stroke/TIA and a fibrinolytic enzyme is given. 2 hours later he bleeds from his gums and has several large subcutaneous ecchymoses. What should be given?
Aminocaproic acid
| Blocks conversion of plasminogen to plasmin
95
A breast cancer pt has struggled to complete a round of chemo due to fever. She is given a factor to assist in mobolizing hematopoietic progenitor and stem cells from the BM into the blood. What was she given and what does it bind to?
G-CSF
Stimulates WBC production CD34+ is a marker found on pluripotent stem cells
CD34 + cells can differentiate into erythroblasts or myeloblasts by using GCSF
96
A pt presents with LUQ pain and chronic fatigue. Smear shows increased WBC at all stages of maturation (granulocytes, metamyelocytes, myelocytes). Dx and Tx?
Chronic Myelogenous Leukemia (CML)
Imatinib mesylate = inhibits the constitutively active tyrosine kinase that enables the unchecked proliferation of granulocytes in CML
97
Which cell type is most common neoplasm in pts with non-Hodgkins lymphoma
```
B lymphocytes (90%)
Exceptions: Lymphoblastic lymphoma (T lymphocytes)
```
98
In pts with sickle cell dz, hat is the clinical benefit of hydroxyurea?
Increase fetal Hgb in the circulation in place of HgbS
99
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A pt with fever, scleral icterus, mental status changes
Total bili - 3.6
Hct 28%
Lactate DH - 650
Pt and PTT - WNL
Schistocytes on smear
```
Thombotic thrombocytopenic purpura (TTP)
Deficiency of vWF factor metalloprotease (ADAMTS13) that degrades vWF.
See unregulated platelet adhesion
RF's = meds, HIV, pregnancy, familiar, idiopathic
Classic pentad: Neuro, fever, thrombocytopenia, renal insuficiency (elevated creatinine)
100
A pt presents with DVT and a PE. Dx?
Factor V Leiden
AD condition preventing protein C from degrading Factor V
Va is resistant to cleavage
elevated D-dimer, fibrin split products
101
t (9;22)
Chronic Myelogenous Leukemia
bcr-abl = constitutively active tyrosine kinase
Tx - Imatinib
102
After a splenectomy the pt is at increased risk of what? And what cells would be seen on smear?
Risk of infection with encapsulated organisms
| Target cells and Howell-Jolly bodies on smear
103
Aeur rods are found in?
Acute myelogenous leukemia (AML)
variant M3, assoc with DIC
Aeur rods = fused lysosomal granules
104
A woman with sepsis develops DIC, Low WBC, Low platelet, high Cr, high PT and PTT, high D-dimers. Schistocytes on smear. What is the underlying pathology?
Widespread activation of the coagulation cascade
105
What do fetuses do in order to compensate for RBC loss in erythroblastosis fetalis?
```
Extramedullary hematopoiesis (liver, spleen)
Rh - mother produces IgG Ab against fetal Rh +
```
106
Why does vWF dz increase bleeding time and PTT?
Increased bleeding time - defect in platelet adhesion
Increased PTT - reduction in VIII
Syx similar to hemophilia but no joint bleeds
107
Which Interleukins are involved in acute-phase reactions?
IL-6 = pro-inflammatory cytokine; "acute-phase protein synthesis"
Secreted from Th2 and macrophages
Other acute-phase proteins = IL-1, IL-8, TNF alpha
108
What is the MOA of thrombolytics (ie tPA)
Promotes the conversion of plaminogen to plasmin (directly or indirectly) thereby breaking existing blockages
tPA acts on fibrin-bound plasminogen
109
What is the MOA of chloramphenicol?
Bind and inhibits 50S subunit
110
Which class of abx inhibit DNA gyrase?
Ciprofloxacin (fluoroquinolones)
| Assoc with tendonitis, tendon rupture
111
Which complication is associated with pts that have sickle cell trait?
Episodic hematuria, Impaired ability to concentrate urine due to microscopic thromboembolic events in the renal medulla
Autosplenectomy at high altitudes
PM in Beta globin chain
112
What lab findings are associated with hereditary spherocytosis
Increased mean corpuscular hemoglobin
| AD
113
A 7 y/o presents with 3 week hx of fever and weakness. PE - diffuse petechiae on the trunk and upper limbs. Smear = many lymphoblasts. BM bx = 30% of cells show a homogenous population of lymphoblasts. What is this associated with?
Trisomy 21
Pt has Acute lymphocytic leukemia (ALL). Rapid onset of bone marrow suppresion (anemia, thrombocytopetia, susceptible to infection)
On bx at least 25% lymphoblasts from a homogenous population
ALL is associated with down syndrome
114
How does CO poisoning affect the hemoglobin dissociation curve?
Left shift. Like increased pH
| Looks like increased Oxygen affinity
115
Which part of the spleen is responsible for generating T cells?
Periarterial lymphoid sheath (PALS)
Sheet of lymphoid tissue that surrounds the central arteries of the spleen.
Allows T cells to be in close contact with Ag in the blood
116
Bactrim is contraindicated in pregnancy because it binds albumin and displaces which heme degredation product?
Indirect bilirubin
| Will cause cerebal toxicity in the fetus
117
How is heme broken down?
By phagocytic cells in the periphery. Heme oxygenase will break heme into biliverdin and then biliverden reductase will form indirect bilirubin. Unconj bili is carried to the liver by albumin where it is processed into water-soluble bilirubin glucuronide. Excreted into the colon
Sulfa abx, warfarin, and contrast can displace albumin
118
A cancer pt presents with a leg that has become red and tender. Nodular warm cord is palpable along her inner thigh and minor bleeding at her mouth and puncture sites. Schistocytes on smear
Chronic DIC
Elevated PT, PTT, and D-dimer
thrombosis can cause superficial and deep thrombophlebitis, can cause PE
Warm cord = phlebitis
119
What lab findings would be expected in a SLE pt that has developed antiphospholipid Ab syndrome (APA)
Prolonged PTT, not corrected by mixing 1:1 with FFP
APA can be primary or secondary SLE
Predisposes to arterial and venous thromboses and recurrent fetal loss during pregnancy
SLE APA is associated with a SLE anticoagulant so it cannot be corrected with FFP
120
An SLE pt presenting with low Hgb, Low serum Fe, elevated ferritin, and Low TIBC should be given what anemia treatment after her SLE is managed?
Erythropoietin
Anemia of Chronic dz
In SLE Hepcidin impairs the transfer of iron from macrophages to erythroid precursors
121
Pt presents with abdominal fullness, fatigue, weight loss, splenomegaly, pancytopenia. Smear shows a ruffled appearing leukocyte
Hairy cell leukemia
B cell malignancy with varying numbers of projections from the cytoplasm
Confirm Dx with elevated tartrate-resistant acid phosphatase (TRAP) in B lymphocytes in the bone marrow.
"TRAP the Hairy"
122
Decreased ristocetin-induced plately aggregation is diagnositc for?
Von Willibrand dz
123
On lymph node bx = malignant neoplasm containing a large number of cells with dark staining nuclei and little cytoplasm, as well as a few binucleate giant cells with eosinophilic inclusion-like nucleoli. Lacks collagen banding and lacunar cells. Dx?
```
Lymphocyte-rich Hodgkin lymphoma
B syx + pruritius, diaphoresis
RS cells are CD15/CD30 +
young males
Nodular banding and lacunar cells would suggest nodular sclerosing Hodgkins
Assoc with EBV
Good prognosis
```
124
Which immunosuppresant therapy will inhibit guanine and adenine synthesis?
6-mercaptopurine
Derivative of azathioprine
Use in kidney transplant and autoimmune disorders
Inhibits purine synthesis and DNA synthesis/repair
125
Which other drug should be avoided when a pt is taking amphotericin due to synergistic renal toxicity?
Cyclosporine
| This is an immunosuppresent that inhibits IL-2 transcription, commonly used in graft vs. host dz
126
A Schilling's test shows low radiolabeled B12 in a pts urine. A repeat radiolabeled B12 dose is given with UF and the pt has high levels of urinary B12. Dx?
Pernicious anemia with Ab against parietal cells
| Failure to absorb cobalamin from the diet
127
Heparin is given to a pt to prevent DVT and PE. What lab finding would you expect to have the most drastic change?
Increased activated PTT time
Acts on intrinsic pathway by accelerating the action of antithrombin III -> inactivates thrombin and factors IX, X, XI, XII
NO effect on PT or INR
128
What would be seen in concurrent use of erythromycin and cyclosporine?
Increased serum concentration of cyclosporine
| Ezythromycin = CYP450 inhibitor
129
What is the tx regimen for Hodgkins Lymphoma?
```
ABVD protocol
Adriamycin (Doxorubicin)
Bleomycin
Vinblastine
Dacarbazine
```
130
Pt presents with microangiopathic hemolytic anemia, fever, purpura, renal failure, and neurological abnormalaties
Thrombotic thrombocytopenic purpura
Deficient in the metalloprotease that breaks down vWF multimers (ADMTS13).
As RBC's pass through the narrowed vessels they become hemolyized or form schistocytes
131
```
A child presents with:
HCT 31.2%
MCV 76.5
Smear reveals target cells
Fam Hx significant for sibling that died from hydrops fetalis
```
alpha-thalassemia
| Hydrops fetalis suggests alpha as mutations in all 4 genes are incompatible with life
132
What mnemonic helps with dx'ing target cells on a smear?
```
HALT
Hemoglobin C dz
Asplenia
Liver dz
Thalassemia
```
133
During aerobic exercise, what is the most important mechanism for transporting the carbon dioxide produced in her muscles to her lungs?
Carbon dioxides is converted to bicarbonate in RBC's
| CO2 is poorly soluble in blood, so carbonic anhydrase converts CO2
134
DiGeorge syndrome is due to hypoplasia of the thymus. From which embryonic structure is the thymus derived?
Third pharyngeal pouch
DiGeorge causes lack of development of the thrid and fourth branchial pouches
Defect in 3rd = T cell deficiency (thymus)
Defect in 4th = hypocalcemia (parathyroid)
135
Why do Cox-2 inhibitors improve the symptoms associated with Osteoarthritis?
Decreases prostaglandins, prostacyclins
136
Which anti-platelet medication decreases further clot propagation by binding the same receptor normally bound by fibrinogen?
Abciximab
| Blocks fibrinogen binding to GIIb/IIIa and prevents platelet aggregation
137
An 8 year old presents with hemolytic anemia, hepatosplenomegaly, and chipmunk facies. On gel electrophoresis has elevated HbF, HbA2, and no HbA1
Beta-Thalassemia major (Cooley's anemia)
| COD = cardiac failure secondary to cardiac failure
138
What globulin chains make up:
HbF
HbA2
HbA1
```
HbF = a2g2
HbA2 = a2d2
HbA1 = a2b2 (adult hemoglobin)
```
139
What complications are associated with CLL?
```
CLL = lymphoproliferative disorder of B cells in pts 60+ Smudge cells, BM failure, lymphadenopthy, hepatosplenomegaly
Complications = Warm or cold autoimmune hemolytic anemia, hypogammaglobulinemia
COD = infection
```
140
What would be seen on smear in a pt with immune thrombocytopenic purpura?
Few platelets with normal morphology
141
An unresponsive pt is brought to the ED. 80/50, 120/min, 26/min, leukocytosis and elevated lactate. BP does not improve with fluid administration. Dx and how does this affect:
PVR, CO, PCWP?
Dx = septic shock
PVR, PCWP = lowered
CO = increased
CO increases to maintain bp and overcome the low PVR (vasodilation due to endotoxin)
142
A pt presents with prolonged bleeding and lumps in his axilla and groin. Increased BUN, total protein, and immunofixation shows high levels of IgM. BM bx = predominance of plasma cells
Waldenstrom macroglobulinemia
| B cell lymphoproliferative disorder resulting in blood hyperviscosity secondary to increased IgM
143
What lab finding would be seen in a pt with drug-induced autoimmune hemolysis
Increased indirect bilirubin
144
Which medication can be used in ischemic stroke to that works by irreversible blocking adenosine diphosphate receptors.
Clopidogrel (also ticlopidine)
irreversibly block adenosine diphosphate receptors and inhibit platelet aggregation.
Clopi is used in acute coronary syndrome without ST elevation
145
Following abx use a pt has a peripheral smear with supravital staining reveals dark inclusion bodies in RBCs
G6P DH deficiency
Reduced NADPH
Triggered by sulfonamides, anti-malarials, and isonizaid
Dark inclusion = Heinz bodies, represents oxidation and precipitation of globin chains
146
In a pt with thalassemia major, what would be expected on:
| Hgb, Ret count, MCH, MCV, Iron
hypochromic microcytic anemia
Low - Hgb, MCH, MCV
High - Ret
Nl - serum iron
147
Following a surgery a pt is put on heparin therapy. 10 days later they develop bilateral occlusion of the popliteal v. Now what?
D/c heparin and start a direct thrombin inhibitor (argatroban, lepirudin)
Pt has heparin-induced thrombocytopenia (HIT) (Ab againsst heparin platelet complex)
148
Rouleaux formation is associated with?
Multiple myeloma
M spike in gamma globulin faction
Excesive Ig produced by these cells are excreted in the urine (Bence Jones proteins)
149
On smear small BCs, lack central pallor, abundant reticulocytes. (rets have a purplish appearance)
Hereditary sphercytosis
| See increased ret in hemolytic anemias (incl. hereditary spherocytosis)
150
A pt presents with RBC aplasia and Myasthenia gravis?
Thymoma (assoc with paraneoplastic syndromes: MG, pure RBC aplasia, and hypogammaglobulinemia)
RBC aplasia = autoimmune hypoproliferation of RBC precursors in the BM
151
Pt presents with fever, night sweats, dysuria, flank pain x 2 days. Dad died of CML. 38.5C, 100/60, 112/min, 14/min
WBC - 15,000
Segmented PMN 70%
Dx?
This is a case of bacterial sepsis, as demonstrated by symptoms and elevated band PMNs
Needs immediate fluids and abx
152
What are the SIRS criteria?
WBC 12000
HR > 90/min
Respiratory rate > 20/min or pp of CO2 38C
153
A pt with pancytopenia and t15;17 will have which protein abnormality in hematopoietic cells
Retinoic acid receptor
Acute promyelocytic leukemia
Promyelocytic leukemia (chr 15) fusion with retinoic acid receptor alpha (RARA) (chr 17)
PML/RARA fusion - inhibits differentiation of myeloblasts and triggers APML
154
Why do pts develop parathesia and hypocalcemia following a blood transfusion?
Calcium chelation by a substance in the transfused blood
Whole and packed blood is prepared with citrate to prevent anticoagulation. Citrate can chelate calcium following massive transfusions (5+L) over 24 hrs
Also chelates magnesium
155
A 1 y/o AA boy presents with severe sweling and tenderness of his hands and feet. Brother died of pneumococcal sepsis. What is abn in this pt?
Serum haptoglobin
Pt is presenting with dactylitis (painful swelling of hands and feet) which is a common presentation in sickle cell dz in young children due to vasocclusion.
Sickling -> hemolysis -> increased indirect bilirubin and lactate dehydrogenase but decreased haptoglobin
156
What is the function of haptoglobin?
Binds free hemoglobin in the circulation and reduces renal excretion. Saves Fe and prevents tubular injury
157
A pt is treated for cancer and weeks later his tumors are decreased in size and bx shows shrunken eos cells within the tumor. Which substance released from the mitochondria most likely triggered this change?
Cytochrome c
Activates caspases and indirectly brings about cell death through intrinsic pathway apoptosis
Anti-apoptotic proteins (Bcl-2, Bcl-x) are replaced by pro-apoptotic proteins (Bak, Bax, and Bim). Allows the mito's to be more permeable and relase cytochrome c
Cells are phagocytized so NO inflammation
158
If a malignant cell loses integrin expression, the cell will have poor adhesion to which component of the extracellular matrix?
Fibronectin
Cell adhesion involevlves integrin mediated binding to fibronectin, collagen, and laminin
Loss of cell adhesion correlates with malignant behavior
Fibronectins mediate b/w ctransmembrane protein and ECM
Other adhesion molecules: cadherins, selecting, and Ig superfamily
159
How does CO poisoning affect levels of carboxyhemoglobin, partial pressure of oxygen, and methemoglobinemia?
```
Increases Carboxyhemogloben
PaO2, Methemoglobin - WNL
carboxyhemoglobin = CO + hemeoglobin
Decreases the amount of Oxygen bound to hemoglobin but has no effect on the amount of oxygen dissolved in the plasma (PaO2)
Left shift
```
160
A pt with boob implants presents with a red rough rash on her chest x 2 months. PE - induration and swelling of the right breast, right axillary lymphadenopathy without breast masses. Left breast = normal. Dx?
Lymphatic obstruction
Peau d'orange = erythematous itchy breast rash with skin texture changes similar to an orange peel. Key derm presentation of inflammatory breast cancer caused by cancerous cells obstructing lymphatic drainage due to spread to dermal lymphatic spaces
161
A pt on LMWheparin becomes unconscious because he is bleeding into his cranial tumor. After d/c'ing heparin, what should be used for anticoagulant reversal?
Protamine
| It helps in LMWH toxicity, but it does not completely reverse the anti-XA activity of LMWH
162
Thymus cell that is CD4/CD8 double positive?
Immature cortical T lymphocyte
Pro-T cells arrive to the thymus double negative but through TCR rearrangement of the b chain there is stimulation of both CD4/CD8. Now positive selection in the thymic cortex and negative in the thymic medulla, and then the lymphocyte will lose either Cd4 or CD8
163
What is the normal function of BRCA1 and BRCA2?
Tumor suppressor genes involved in DNA repair. Mutation results in LOF and increases risk of breast and ovarian cancer
164
Heparin and LMWH bind to?
Antithrombin III which becomes active and decreases Factor X activity
Heparin also decreases Factor II (thrombin) activity
165
What happens when retinoblastoma is phosphorylated?
Rb is inactive when phosphorylated and allows cells to transition from G1 to S
Cyclin D and CDK phosphorylate Rb
Hyperphosphorylated Rb releases E2F allowing it to participate in transcription
Rb inhibits the cell cycle by sequestering E2F until Rb is phosphorylated by the cyclin/CDK complex
166
Following delivery to a A- baby, a B- mom has high levels anti-A Ab in her blood. Why did hemolysis not occur in the baby?
The mom's antiA Ab are likely to be IgM because they can't cross the placenta
However, a type O mom would have predominantly IgG ab and would cause erythroblastosis fetalis in a non O baby.
167
A kid with hereditary spherocytosis is likely to have which lab findings?
Increased mean corpuscular hemoglobin concentration due to mild dehydration of the RBC. Also other markers of hemolysis: elevated lactate dehydrogenase, reticulocytosis, decreased haptoglobin
168
Pt presents with dizziness, HA, and pruritus after showering. Ruddy complexion and splenomegaly on PE. Labs show elevated RBCs, platelets, and leukocytes. Dx?
Polycythemia vera
JAK2 V617F
Mutation increases bone marrow sensitivity to growth factors and allows for clonal myeloproliferative dz of pluripotent hematopoietic stem cells
Increased RBC mass, increased plasma voume, and low epo.
169
A pt with diffuse large B cell lymphoma presents with symmetric distal neuropathy in "stcking and glove" distribution. Which chemo drug caused this?
Vincristine
| Neurotoxicity limits the dose
170
What is the initial step in the pathogenesis of beta thalasemia?
mRNA formation
| Because it is encoded in the DNA
171
A pt presents with cholecystitis and pigmented gallstones. What predisposed her to this?
Chronic hemolysis
Pigment stones come from conditions that increase unconjugated bilirubin in bile which protes precipitation of calcium bilirubinate
Occurs in chronic hemolysis and increased enterohepatic cycling of bilirubin (ileal dz)
172
MOA of rivaroxaban?
Inhibits Factor Xa
Used in venous thromboembolism (DVT) and a fib
Factor Xa inhibitors = Xaban (Foxaban, ban the fox)
173
Which enzyme inactivates 6-mercaptopurine?
Degraded by Xanthine oxidase in the liver
Allopurinal can increased 6-MP concentration by inhibiting XO.
6-MP and 6-thioguanine are prodrugs that require activation of HGPRT (so don't use 6-MP is lesch Nyan..?)
174
Following episodes of bloody diarrhea a 7 y/o presents for F/U. Labs reveal acute renal failure. CBC - anemia, thrombocytopenia but coag studies WNL. Schistocytes on smear. What is the cause of his anemia?
Micrangiopathic hemolytic anemia
Hemolytic uremic syndrome!
HUS is often preceded by bloody diarrhea.
175
Presence of schistocytes should suggest?
Microangiopathic hemolytic anemia (HUS, thrombotic thrombocytopenic purpura (TTP), DIC), mechanical damage
Coag studies are WNL in HUS and TTP but abn in DIC.
176
Differential for bacteremia in a sickle cell pt?
Strep pneumo
H. flu
Asplenic pts should receive penicillin prophylaxis and pneumococcal vax
177
How is dysplastic different from carcinoma
dysplastic = reversibility of the changes
Epithelial malignancies progress through the sequence of low-grade dysplasia -> high-grade dysplasia/carcinoma in situ -> invasive carcinoma
Once the dysplastic cells have breached the asement membrane (ie invasive carcinoma), the process is no longer reversible
178
43 y/o female on Fe supplementation for anemia has a smear with numerous enlarged red blood cells that appear blue on Wright-Giemsa stain. Why is it blue?
```
ribosomal RNA (indicative of reticulocytes)
Increased Bone marrow erythropoiesis results in an accelerated release of immature RBCs (rets) into the blood stream. Rets contain blusih cytoplasm and reticular precipitates of residual ribosomal RNA
```
179
What is the MOA of gardos channel blockers for sickle cell treatment?
hinder efflux of K+ and water from the cell, preventing dehydrationof erythrocytes and reduce polymerization of HbS
180
Side effect of treating CMV with Ganciclovir + Bactrim?
Neutropenia
Neutropenia is a significant AE of ganciclovir therapy and its incidence is increased with co-administration of zidovudine or Bactrim
181
Major side effects of ganciclovir monotherapy?
```
Neutropenia
Anemia
Thrmbocytopenia
Impaired renal fxn
Adding bactrim or zidovudine can lead to bone marrow suppression
```
182
Inheritance pattern for herediatry spherocytosis?
AD
183
Auer rods
```
APL
t (15;17)
Persistant infection, coagulopathy (DIC), hemrrhagic signs. BM bx = promyelocytes with Auer rods)
PML and retinoic acid receptor
tx - trans retinoic acid
```
184
What finding would be a strong suggestion of malignancy on lymph node bx?
Monoclonal lymphocytic proliferation
| Reactive lymphadenopathy is polyclonal with proliferation of many different cell types
185
bcl-2 inhibits?
apoptosis
| Overexpressed in follicular lymphoma t(14/18)
186
When cytotoxic T cells stimulate apoptois, which proteins acts as an effector for the response?
Caspases
Extrinsic (receptor initiated) and intrinsic (mitochondria-mediated) pathways both activate caspases
Caspases are proteolytic enzymes that cleave cellular proteins
187
Despite being very healthy, a pt is dx'd with T2DM. What explains this abnormality?
Beta thalassemia trait
These pts have HbA2 but A1C levels are based off of HbA levels
Use A1c levels with cautions in pts that have alerations in RBC turnover time
188
When using a EGFR inhibitor, and activating mutation in which enzyme would render the tx uneffective?
KRAS
Activating mutation of KRAS leads to constiutive activation of the epidermal growth factor receptor (EGFR) pathway, promoting increased cell proliferation and growth. Tumors harboring these mutations are resistant to chemo with anti-EGFR drug (cetuximab, panitumumab)
189
If a pt has constant bone pain that is worse at night but not responsive to position changes, think?
Metastasis
worse at night *
Not alleviated by moving around *
190
If you see schistocytes think
Mechanical trauma to RBCs traveling through narrowed vessels (prosthetic valves, HUS, or TTP)
191
If a pt has a Point Mutation just one codon upstream of the start codon on a strand of mRNA, what cellular process is likely to be defective?
Initiation of translation
| Kozak consensus sequence occurs only in eukaryotic mRNA. Helps to intiate translation at the met start codon AUG
192
Pt presents with maxillary sinus tenderness, pharyngeal erythema, and tender anterior cervical lymphadenopathy, elevated myelocytes. Leukocyte alkaline phosphatase score is low. Dx?
CML
t (9;22) BCR-ABL
If leukocyte (PMN) alk phos was WNL dx would have been leukemoid rxn (over-exuberant WBC response associated with bacterial infection or malignancy
193
Pt presents with breast lump. She has a limb amputation at 17 due to osteosarcoma. Mom died of an adrenal tumore, younger sister died of leukemia. Etiology?
Li-Fraumeni syndrome
TP53
Sarcomas, breast cancer, brain tumors, adrenocortical carcinoma, leukemia
AD, inactivates p53 two hit hypothesis required for malignant transformation
194
Smear finding in DIC?
Schistocytes
Common complication in Gram negative sepsis
Bacterial endotoxins activate coagulation cascade
195
How do you treat a kid in the ED following a dental procedures that won't clot. History suspicious for hemophilia.
Thrombin
| Decreased factor VIII and IX leading to failure to convert prothrombin to thrombin
196
Most carcinogens enter the body as procarcinogens. Which enzyme activates these molecules?
cytochrome P450
ie microsomal monoxygenase
NOT mitochondrial cytochrome oxidase which is in the ETC
197
MOA of argatroban?
Binds to thrombin active site
Direct thrombin inhibitors = hirudin, lepirudin, argatroban
Use these in pts with HIT
198
von Willebrand factor normally binds to?
Collagen
Promotes platelet adhesion and sites of vascular injury by binding platelet glycoproteins to subendothelial collagen. Also carries factor VIII
199
In the setting of folate deficiency, supplementation with what would prevent erythroid precursor apoptosis?
thymidine
| Moderately increases dTMP levels to reduce erythroid precursor cell apoptosis
200
CD 14 is a marker for?
Monocytes
| Macrophages
201
Methotrexate is administered for an atopic pregnancy. What substance will accumulate in the embryonic tissue?
Dihydrofolate polyglutamate
Normally folic acid -> dihydrofolate -> tetrahydrofolate which is an integral precursor for DNA synthesis
Methotrexate inhibits Dihydrofolate reductase which leads to accumulation of the intermediate dihydrofolate
202
After starting chemo a pt presents with hemturia. What should have been coadministered?
Mesna
hemorrhagic cystitis = progressive hematuria + suprpubic tenderness
Chemo drug = cyclophosphamide
203
Binding of which T cell receptor will downregulate the immune response against tumor cells by inhibiting cytotoxic T cells.
Programmed death receptor 1 (PD-1) ligand
Cancers evade the immune system by increasing expression of PD-L1 (the ligand for PD-1).
mAb blocking PD-1 prevents T cell inhibition to promote apoptosis of tumor cells
204
Pt is still having post chemo emesis despite ondansetron tx. Additional therapy blocking which receptor would be most helpful to this pt?
Neurokinin 1 antagonists (prevent substance P release; aprepitant, fosaprepitant)
5HT3 (ondansetron's target) and NK1 antagonist are the most useful in post chemo n/v
Others: M1, D2 (metoclopramide), H1
205
Impaired gamma carboxylation is?
Vit K deficiency
| Coag factors II, VII, IX, X (diSCo 1972)
206
Most common cancers in women (incidence and mortality)
Incidence: breast > lung > colon
Mortality: Lung> breast > colon
