heme/onc Flashcards

Question 1

Q

pt presents w -weight loss, night sweats, cough -CXR= apical granulomas w areas of central necrosis surrounded by large cells with abundant pale cyptoplasm most likely dx what are the large cells w pale cytoplasm? what cell marker are they most associated w

Answer

A

TB (apical granulomas = central caseous necrosis surrounded by Møs) macrophages = associated w CD14

Question 2

Q

pt w sickle cell comes in for fever, dyspnea, chest pain: prior hospitalizations for abd pain were trx w hydration and resolved low hct, high reticulocyte they die in the hospital spleen is found to be firm and brown what is the dx? explain the spleen findings

Answer

A

sx= Acute Chest Syndrome : a vaso-occlusive crises localized to the pulmonary vasculature that can occur in sickle cell patients = commonly precipitated by a previous lung infection -occurs in pts w homozygous HbS = repeated events of vaso-occlusion produce a spleen that is shrunken and fibrotic -spleen is brown bc of hemosiderosis secondary to years of extravascular hemolysis -this is the reason that most homozygous sickle cell patients have undergone “autosplenectomy” by the time they reach adulthood

Question 3

Q

tissue factor aka ____ plays a significant role in what ds

Answer

A

tissue factor aka thromboplastic associated w DIC: will cause excessive production of thrombin + widespread intravascular fibrin deposition and fibrinolysis –> consumption of clotting factors and platelets

Question 4

Q

most head and neck carcinomas will met/spread via what method

Answer

A

LYMPH (not direct extension) i.e. tonsils –> jugular LNs

Question 5

Q

chemo therapy w a cyclophosphomide (a _____-based chemo) has an increased risk of what AE in F patients how will it present how can it be prevented

Answer

A

chemo trx w a nitrogen-mustard based chemo i..e a cyclophosphamide –> HEMORRHAGIC CYSTITIS : inc frequency, dysuria, suprapubic pain, progressive hematuria –> prevent this w aggressive hydration and cotrx w MESNA (2-mercaptoethanesulfonate) that will bind the toxic metabolites of the drug in the urine

Question 6

Q

in sickle cell anemia, the hemoglobin of cells aggregates in response to what

Answer

A

“sickling” = aggregation of hemoglobin molecules in response to anoxic conditions

after polymerization, HbS forms a meshwork of fibrous polymers –> RBC distorts into the abn sickle shape

sickling is promoted by…

low O2 levels
inc acidity
low blood volume (dehydration)

(aka the conditions seen in the periphery –> inc sickling in the periphery –> impede BF–> microinfarcts all over the body–> vasoocclusive crises)

-organs that are predisposed to more sickling are

organs where blood moves more slowly –> low O2 and acidic conditions
- spleen and liver
organs w high metabolic demand = inc O2 unloading
- brain, M, placenta

Question 7

Q

compare and contrast the action of unfractioned heparin and LMWH on

factor Xa
thrombin

give an example of a LMWH

Answer

A

thrombin = factor I

LMWH= enoxaparin

Question 8

Q

what is porphyria cutanea tarda

etiology
presentation
*

Answer

A

is the MC disorder of porphyrin (heme) synthesis

(porphyria= deficiency in teh early steps of heme synthesis that result in inc of porphyrin-containing metabolites)

etiology: x uropophyrinogen decarboxylase
- any loss of enzyme after PBG conversion (aka late step dysunction) [see picture] wll result in PHOTOSENSITIVITY bc of the build up of UV LIGHT SENSITIVE PORPHORINS
presentation:
- acquired > inherited
- risk factors: inc alc intake, smoking, hep C, HIV
- photosensitivity= blisters and vesicle formation on sunexposed areas (i.e. dorsum of hand) : small itchy spots that will blister–> rupture–> heal with hyperpigmentation
- +edema, pruritis, erythema, pain

Question 9

Q

what is the difference in a heme synthesis defieciency and a porphyria

Answer

A

porphyria: an enzyme deficiency at specific points in the heme synthesis pathway that result in the build up of porphyrins that are UV light sensitive

late step deficiencies= any enzyme after PBG (PBG deaminase, UP III synthase, UP decarboxylase, CP oxidase
=photosensitivity= blistering in sunexposed areas + pruritis, hyperpigmentation, erythemia, and pain

heme synthesis deficiency is an xferrochetalase or ALA synthase

this just presents as a microcytic, hypochromic anemia

Question 10

Q

child presents w HA and gait ataxia

what is the most likely brain tumor

classic presentation?

differentiate this from the other common brain tumor in children

Answer

A

pilocytic astrocytomas are the most common brain tumor in children

HA and cerebellar sx
imaging shows well demarcated solid and cystic components
H&E = GFAP+ w hairlike processes and classic rosenthal fibers

VS MEDULLOBLASTOMA

=the most common malignant tumor in children
they are exclusively in the cerebellum
NOT cystic like pilocytic astrocytomas
imaging will show a solid mass in the cerebellum
the mass can compress on the v4th ventricle and lead to hydrocephalus (on imaging will look like a huge fluid build up in the superior ventricular system)
H&E: small cells with hypochromatic nuclei that form homer-wright rosettes

Question 11

Q

which drug class will inc PT+PTT but have NO effect on thrombin time
which drug class will have an effect on thrombin time
which pathway must be inhibited to effect PT time
which pathway must be inhbited to effect aPTT time

Answer

A

direct Xa inhibitors
direct thrombin inhibitors
extrinsic
intrinsic

Question 12

Q

what are CD3+ cells and what role do they play in the stem cell transplant process

Answer

A

CD3+ = CD4/CD8+ T cells

they are the cells in the donor BM that can cause graft-vs-host ds

(are often depleted from the graft before transplant)

Question 13

Q

what is the MOA of hydroxyurea

what is its use in sickle cell ds

Answer

A

hydroxyurea
- has myelosuppressive effects by arresting cell cycle in rapidly dividing hematopoetic cells
- will inc the HbF levels
effects
- improve O2 delivery
- reduce vasoocclusive crises
- lessen need for transfusions

Question 14

Q

acute intermittant porphyria

etiology
presentation
trx

Answer

A

=PBG deaminase deficiency
hx of abd pain&gen GI sx + neuro sx (change in sleep/concentration, anxiety, numbness+tingling)
- +change in urine (port wine color)
trx= ALA synthase inhibition
- long term management w glucose or heme will also inhibit ALA

Question 15

Q

how does HPV associated CA present

what gene mutation does HPV cause

Answer

A

HPV related CA– sore throat, enlarged/ulcerated tonsil, with a neck mass (often firm and immobile bc malignant)
HPV is associated w HEAD AND NECK CA
HPV release E6 and E7 proteins
- E6 protein of HPV degrades p53 from the TP53 gene
- E7== x Rb protein tumor suppressor) from the RB gene

Question 16

Q

what is the similarity between RET and BRAF

what tumors are they associated with

Answer

A

both are protooncogenes that require GOF mutations to become oncogenes

BRAF

code fore Ser/Thr specific protein kinase
melanoma, NHL, papillary thyroid CA

RET

code for an RTK
MEN 2A and MEN 2B, papillary thyroid CA

Question 17

Q

inc 5-HIAA in the urine represents what

Answer

A

the presence of carcinoid tumor

Question 18

Q

why does warfarin need a bridge therapy w heparin till the INR levels out

having a heparin bridge lowers the risk of what AE

Answer

A

bc warfarin inhibits carboxylaton of NEW k-dependent clotting factors, your body first needs to use up all the pre-existing clotting factors in the plasma

only once those are all gone will the INR reach therapeutic activity

a bridge will lower the risk of skin necrosis due to the loss of Protein C before anything else (short half life)

Question 19

Q

compare the change in PT, PTT, platelets, and bleeding time in…

hemophilia
vWF deficiency
DIC
uremic platelet dysfunction
heparin use
warfarin use
immune thrombocytopenia

Question 20

Q

what are the pathologic cells seen in this histo pic

what is the dx?

clinical presentation

Answer

A

spherocytes

2/3 the diameter of a normal RBC
more densely hemoglobinized around the periphery
no central zone of pallor
hereditary spherocytosis = x ankyrin and spectrin –> inc sequestration and destruction in the spleen
inc extravascular hemolysis = jaundice, splenomegaly, inc INDIRECT bilirubin
- often young age
- infection can lead to an acute hemolytic crisis –> acute worsening of pallow, scleral icterus, fatigue, and splenomegaly

Question 21

Q

describe what an osteoblastic vs osteolytic bone lesion would look like

which metastatic CAs to the bone result in which

Answer

A

osteoblastic = SCLEROTIC = usually more indolent

osteolytic = LUCENT = tend to be from more aggressive CAs

Question 22

Q

what are the bone changes seen w age

BE SPECIFIC

Answer

A

inc quantity of fat

dec overall mass

Question 23

Q

desscribe the cause of abn bleeding in patients with uremia

how is this treated

Answer

A

pts w uremia (often ESRD, need dialyses) have abn platelets (qualitatively)

this results in n PT/PTT/platelet count but an abn bleeding time bc platelets are non-functional

treat w dialysis to remove the uremic toxins and allow the partial reversal of the abn

Question 24

Q

what are the 5 features of anaplastic tumors

Answer

A

poorly differentiated
sign variation in size and shape of cells
abnormally large, hyperchromiatic nuclei
lots of mitotic figures
giant, multinucleated tumor cells

Question 25

Q

rapidly growing tumor of the mandible/jaw with palpable regional lymphadenopathy

often an immigrant from the middle east

dx
histo findings
genetic mutations and associated causes
prognosis

Answer

A

burkitt lymphoma
lymphocytes a basophilic cytoplasm, high mitotic index, diffuse distribution of tingible body macrophages (macrophages that phagocytose the cell debris) surrounded by clear space –> starry sky appearance
assocated a c-Myc oncogene overexpression
v aggressive, but respond well to chemo

Question 26

Q

differentiate the mechanism of anemia causing disease in an M. pneumonia infection vs SLE

by what mechanism does treatment relieve the anemia?

Answer

A

M. pnuemonia

cold agglutin
M. pnuemonia attacks respiratory epithelium with the I Ag –> the body create IgM Abs, that also happen to be cross reactive in cold Temps–> cause agglutination of RBCs–> set off complement–> intravascular hemolysis
trx–> fall in IgM Ab creation will stop the cascade leading to hemolysis

SLE

warm agglutination
IgG Ab bind to RBC membranes, causing them to be extravascularly hemolysed in the spleen
immune suppression will dec the IgG Ab creation

Question 27

Q

drugs that alter warfarin therapeutic levels (INR) in the body can do so by 3 mechanisms: (which drugs are in each category and what is the effect on INR/warfarin levels)

disruption to gut flora
activate CYP450
inactivate CY450

Answer

A

disruption to gut flora
- G (-) gut flora make Vit K during their metabolism so abx that reduce Vit K producing gut flora will –> supratherapeutic INR (too much warfarin activity)
- abx that target G- bac= metronidazole, macrolides (azithryo, clarythro, erythro-mycin), flouriquinolones (floxacins)
activate CYP450
- –> make the CYP450 metabolize warfarin faster –> subtherapeutic warfarin levels
- phenytoin, carbamezapine, rifampin
inactivate CY450
- –> slow down the metabolism of warfarin–> supratherapeutic INR/warfarin levels
- metronidazole, fluconazole, amiodarone

Question 28

Q

this person has hemolytic anemia

what three types of erythrocytes are seen in this pic and what are the sign of each

Answer

A

polychromatic RBCs
- =reticulocytes that are bigger than normal RBCs, slighly bluish, and lack a central pallor
- indicate BM response to anemia
spherocytes
- erythrocytes w reduced cell membrane
- associated w immune mediated anemia
nucleated erythrocytes
- are v immature RBCs
- indicates a strong BM response to anemia
  *

Question 29

Q

what is the effective trx for an overdose in warfarin vs heparin

Answer

A

warfarin

immediate= FFP
over time: Vit K replenish

heparin

protamine sulfate= a direct antagonist

Question 30

Q

what is primary myelofibrosis

etiology
presentation + findings

Answer

A

primary myelofibrosis = a hematopoeitic stem cell malignancy in the BM that is associated w the expansion of megakaryocytes

neoplastic megakaryocytes will secrete TGF-beta–> stimulate BM fibroblasts to fill the medullary space w collagen –> bone marrow fibrosis
this results in (exramedullary hematopoeisis) and dacrocytes on peripheral blood smear
present
- splenomegaiy and hepatomegaly
- anemia / pancytopenia secondary to EMH not being as efficienct as hematopoeisis in the BM
- tear drop cells and nucleated RBCs will appear in periphery as RBCs have to squeeze out of fibrotic BM/congested spleens
- dry tap on BM: no marrow is yielded on BM aspiration due to all the fibrosis
- old person, fatigue, unintensional weight loss, etc

Question 31

Q

what is the MOST important prognostic factor in urothelial (transitional cell) carcinoma

Answer

A

TUMOR DEPTH OF INVASION

(even more than atypia or grade of the lesion i.e. an in situ lesion can have high grade)

show in picture is an atypical mitotic figures (not the most important factor in prognosis, but def a prognostic factor)

Question 32

Q

alcoholism that develops over the course of WEEKS can cause an anemia by depleting what vitamin

presentation
etiology

what other big Vit can be depleted by alcoholism and this cause anemia

how long would that take
what are other causes of deficiency
presentation

Answer

A

FOLATE: def develop over weeks

etiology: x nucleoside synthesis –>x DNA production in blood cell precursors–> abn cell division –> megaloblastic hyperplasia of the BM (v big RBCs)
- ***normally it would take months to become folate deficienct bc of body stores but an ALCOHOLIC can become folate deficient in weeks***
peripheral blood smear shows pancytopenia and hypersegmented neutrophils (picture attached)
- RBC abnormalities= ovalocytosis (elipses shape) and macrocytosis (iMCV>100)

vs Vit B12 (cobalamin) deficiency

this would take YEARS, even in an alcoholic
associated w pernicious anemia, chronic gastritis, certain meds, and fish tapeworm
presents w neuro sx (subacute combined degeneration w parasthesias ataxia, loss of proprioception)

Question 33

Q

differentiate between the two types of heparin induced thrombocytopenia (HIT)

Answer

A

HIT Type 1
- a NON-IMMUNE mediated condition caused by platelet clumping
- presents aruond 2 days after starting therapy
- thrombocytopenia is only minimal (nadir of about 100k)
- does NOT cause thrombosis (i.e. DVT/PE), so essentially nbd and can continue heparin
HIT Type 2
- Ab aggregation on the RBCs secondary to IgG Abs created against an heparin induced neoangtigen (heparin platelet factor 4)
- manifests around 5-10 days after starting therapy
- splenic Mø removal of Ab-marked RBCs results in significant thrombcytopenia
  - Ab-aggregation also results in widespread platelet aggregation–> thrombocytopenia worsens –> inc risk of thrombosis (venous or arterial)
- pt may present with DVT/PE and thrombocytopenia shortly after beginning heparin therapy
- NEED TO STOP HEPARIN IMMEDIATELY and switch to a different anticoag (i.e. argatroban)

Question 34

Q

what is a biologic response modifier?

what are the MOA of the following BRMs and when are they used?

Rituximab
trastuzumab (aka herceptin)
infliximab
interleukin 2
imatinib
abciximab

Answer

A

BRMs= treatments that are meant to boost the host immune response to better fight off a ds

Rituximab
- a mab that targets the CD20 surface Ig
- used in lymphoma immunotherapy
trastuzumab (aka herceptin)
- anti-HER2-R mab
- breast CA
infliximab
- in IgG1 Ab against TNF-alpha
- trx RA, ankylosing spondylitis, and fistulizing Crohns ds
interleukin 2
- a cytokine that regulates the differentiation of T cells to aid in tumor destruction
- RCC and melanoma
imatinib
- a potent inhibitor of the BCR/ABL protein tyrosine kinase found on the philidelphia chromosome, without causing cell apoptosis
- trx CML
abciximab
- mab against platelet GpIIb/IIIa receptor: blocks the final step in platelt aggregation
- often administered during angioplasty in patients w ACS

Question 35

Q

multiple myeloma should be suspected with what patient presentation

what is the etiology of renal ds in pts with MM and how will be detected

Answer

A

suspect MM in an elderly patient with

some combination of osteolytic lesions, anemia, hypercalcemia, or acute kidney injury
AKI is caused by the deposition of lambda light chains of Igs in the PT of the kidney at levels that oversaturate the kidney’s ability to reabsorb them
- this results in them to combine, form obstructive casts –> tubular rupture and kidney injury
monoclonal Abs will not be found on dipstick (bc they’re not albumin) but they will show elevated protein on 24 hour urine

Question 36

Q

what is the genotypic change seen in sickle cell ds, (AA change and the codon change)

Answer

A

glutamic acid –> valine

GAG–> GTG

Question 37

Q

explain how each of the results of sickle cell ds will present

hemolysis (labs)
vasoocclusive sx
- children vs adults
infections

Answer

A

hemolysis (labs)
- =intra and extravascular –> ↑INDIRECT bili, ↑ LDH, ↓ haptoglobin
- (on change in the complement factor levels)
vasoocclusive sx
- pain w hypoxic injury and ischemia: typically of BM, periosteum, and deep Ms
- in children, oft present as hand-foot syndrome: dactylitis 2° infarctions of the bones in the extremities–> swelling, edema, tenderness of the hands, feet
- in adults: the small bones no longer contain hematopoeitic cells so they present with acute chest syndrome, pain crises, leg ulceration, priapism, autosplenectomy, and stroke
infections
- w encapsulated organisms secondary to autosplenectomy
- i..e S. pneumoniae

Question 38

Q

young boy with hx of bone CA presents w lung mass with the following histology

dx?

Answer

A

ewing sarcoma

common in young children
mets to the lung and other bones EARLY ON
histo shows: vascular fibrous septae, with areas of hemorrhage and an abrupt transition from viable to necrotic cells
- arise from MESENCHYMAL CELLS

Question 39

Q

at what point of the cell cycle do the following chemo drugs cause arrest

vinca alakloids
taxanes
antimetabolites
bleomycin
doxorubicin
mitomycin
platinum analogs
procarbazapine
classic alkylating agents

Answer

A

vinca alakloids
- vinblastin, vincristine, vinorelbine= M phase
taxanes
- piclataxel, docetaxel, cabataxel, ixabepilone, eribulin = M phase
antimetabolites
- MTX, pemetrexed, pralatrexate, = S phase
- 5-FU, cepecitiabine, cytarabine, gematabine = S phase
- 6-MP, 6-TP, fludarabine, cladribine = S phase
bleomycin
- (an abx) = G2
doxorubicin
- (an abx) = G2
mitomycin
- (an abx) = all phases
platinum analogs
- cisplatin, carboplatin, oxaliplatin = every stage
procarbazapine
- (a non-classic alkylating agent)= all phases
classic alkylating agents
- cyclophosphamide, mechlorethamine, melphalan, chlorambucil, thiotepa, carmustine, streptozocin, busulfan, = late G1/early S phase

Question 40

Q

older adults taking antacids for GERD may present with what kind of anemia due to what etiology

histo will show?

Answer

A

older adults taking antacids for GERD may present with megaloblastic anemia secondary to cobalamin deficiency (b12)

histo= macrocytosis w segmented neutrophils

Question 41

Q

what is the etiology by which a G6PD deficiency leads to anemia

–how does it present

what are the hallmark histo signs
deficiency of what other enzyme can lead to a clin presentation similar to G6PD

Answer

A

G6PD

an X-linked Recessive hemolytic anemia that presents w sx following oxidative stress on the body
mostly affects males of asian/african/mediterranean (greek) descent: can often be uncovered by hemolysis that presents after the pt starts taking TMP/SMX
this is bc G6PD is an enzyme in the PPP that will reduces (creates) NADPH–> NADPH is needed to detoxifying hydrogen peroxide in RBCs
w/o NADPH, glutathione remains oxidized –> RBCs are susceptible to oxidative damage

hallmark histo

heinz bodies
bite cells (caused by splenic macrophages)

similar presentation w

x glutathione reductase: which does the actual reducing of glutathione using the NADPH

Question 42

Q

which transcribing enzyme works solely in the nucleolus

where on this histo pic is the nucleolus (note, these are malignant cells)

Answer

A

RNA polymerase I = transcribe 45 s rRNA (ribosomal RNA) into mature rRNAs

works in the nucleolus

nucleolus= the prominant, round, basophilic bodies in the (large) nucelei of these cells

Question 43

Q

the most common causes of drug induced hemolysis are what

-etiology?

Answer

A

antiinflammatory meds, penicillins, and cephalosporins (i.e. ceftriazone)

-bind to the RBC and create a hapten for IgG attachment –> extravascular hemolysis

Question 44

Q

patient comes in w meningitis caused by a G- dipplococci: in the ED their BP plummets and they start bleeding from the venous access site

dx? etiology? what will be seen on histo and labs?

Answer

A

meningococccal meningitits that develops into shock (sudden, severe hypotension)

the bleeding from the access sites suggests DIC (oft associated w sepsis)

etiology of DIC 2° to G-sepsis:

bacterial endotoxins activate the coagulation cascade –> widespread fibrin deposition and the consupmtion of platelets and coag factors .

this will present as

oozing from the site with dec PT/PTT
dec platelet count
inc bleeding time
schistocytes on histo (As they shear past the microthrombi)
as fibrinolysis inc (from all the microthrombi) the D-dimer will inc too

Question 45

Q

what are Howell Jolly bodies and when are they seen

Answer

A

=round, dark purple/red inclusions in RBCs

they are the nuclear fragments that typically would have been removed by the spleen
they appear in the periphery in the setting of autosplenectomy or post splenectomy
- associated w sickle cell ds

Question 46

Q

what are integrins and what are their role in malignancies

Answer

A

integrins= cell adhesion proteins that are transmembrane receptors that react with the ECM

they bind fibronectin (produced by fibroblasts and some epithelial cells) to mediate cell adhesion and migration
differential expression of integrins affects adhsion and correlates with malignant potential of certain CAs, i.e. melanoma
*

Question 47

Q

what is the role of cell surface proteins CD55, CD59?

their absence on an RBC membrane suggests what pathology?

etiology
manifestations

Answer

A

CD55= decay accelerating factor

CD59= MAC inhibitor protein

both are cell surface markers on RBC that inhibit complement mediated cell lysis via inactivation of the complement system

lack of CD55/CD59 suggests…

paroxysmal nocturnal hemoglobinuria (PNH)

this ds is due to x PIGA gene –> x GPI protein
the CD55/CD59 markers need the GP1 protein on the cell surface in order to bind
without CD55/CD59 bound to the cell membrane, the RBC is open to completement mediated intravascular hemolysis

manifestations of PNH

hemolytic anemia –> fatigue, jaundice, ↑bili+LDH, ↓haptoglobin
hemoglobinuria (more at night)
thrombosis at atypical sites as lysed cells release prothrombin factors at random places
pancytopenia secondary to stem cell injury
hemosiderosis= iron dep in the kidneys with the inc in intravascular hemolysis releasing the iron from RBCs
- PT damage –> interstitial scarring and cortical infarcts

Question 48

Q

what is the typical presentation of hodgkin lymphoma

DESCRIBE the diagnostic biopsy finding
what are the CBC and peripheral blood smear findings

Answer

A

hodgkin lymphoma

bimodal in age= 20s or 60s
typically with either nontender lymphadenopathy (i.e. cervical), or incidentally found lymphadenopathy on CXR
present w B symptoms: fever, night sweats, and weight loss
CBC and peripheral blood smear are UNREMARKABLE
diagnostic LN biopsy finding is the REED-STERNBERG CELL
- = big cells w plenty of cytoplasm and a bi-lobed/double-nuclei and inclusion eosinophilic nucleoli (purple dots in the nuclei)
- surrounded by a bunch of other immune cells

Question 49

Q

hair cell leukemia

clinical presentation
etiology
common signs and sx
diagnostic findings

Answer

A

hair cell leukemia

clinical presentation
- =indolent (slow and mild)
- presents in midde aged males (40s&50s)
etiology
- a leukemia that will invade the bone marrow and reticuloendothelial system
- causes bone marrow fibrosis and failure
common signs and sx
- massive splenomegaly: “cross the midline”, “extend into LLQ”
- common: LUQ pain/fullness, early satiety, fatigue, wknss, fever, recurrent infections, abd distension, pallor
diagnostic findings
- splenic RED pulp infiltration causing splenomegaly
- hair cells: lymphocytes w cytoplasmic projections (shown in pic)
- dry tap on BM (due to fibrosis)
- flow cytometry done

Question 50

Q

what are ringed sideroblasts and when will you see them

Answer

A

ringed sideroblasts: abn erythrocyte precursors where the mitochrondrial iron surrounds the nucleus

seen in patients with MYELODYSPLASTIC SYNDROMES

NOT the same as myeloproliferative (pcv, etc)
myelodysplastic syndromes present with petechiae, weakness, and recurrent infections

Question 51

Q

describe the splenic changes seen in acute sickle crises vs chronic changes over years of ds

what type of anemia is associated with sickle

etiology?

Answer

A

acute crises ∝ congested spleen

chronic sickle cell ds ∝ autosplenectomy = fibrosis and atrophy

sickle cell pts have higher folate requirements (∝ inc erythrocyte turnover) so they tend to develop folate deficiency –> megaloblastic anemia (MCV>110)

Question 52

Q

RBCs use more 2,3 BPG during what conditions

what does this allow for, and what does it sacrifice?

Answer

A

more 2,3 BPG in times of anoxiea/hypoxia or acidemia

allow for the Hgb to have a lower affinity for O2 so that it will release it into the peripheral tissue with more ease
sacrifice ATP production bc 2,3 BPG must be made from 1,3 BPG (a step in glycolysis –> less glyoclysis–> less ATP made)

Question 53

Q

signs of hemolysis that show up after staring TMP/SMX (bactrim) trx is caused by what etiology

Answer

A

this is a common way for G6PD deficiency to first present

=a heriditary erythrocyte enzyme deficiency

Question 54

Q

etiology of anemia of chronic ds

Answer

A

the high levels of circulating inflammatory mediators result in abn utilization of iron

the biggest mediator of this ds is hepcidin

binds and inhibits iron channels on enterocytes and reticuloendothelial macrophages –> reduced iron reabsorption in the cut and reduced iron recycling –> sign reduce iron circulating in the system –> less iron available for erythropoeisis

results in normocytic or slightly microcytc anemia w a dec TIBC (via transferrin suppression by cytokines)

Question 55

Q

presence of myelocytes and metamyelocytes on leukocyte differentiation suggests what

etiology
histo findings

how is this different than than the presence of promyelocytes and myeloblasts

Answer

A

=leukemoid reaction

benign leukocytosis that occurs in reaction to an underlying ds
i.e. in response to severe infection/hemorrhage, solid tumor, or hemolysis
the BM responds to the underlying disease state by increased bands and early mature neutrophil precursors
histo=
- Dohle bodies= basophilic oval inclusions in mature neutrophils
- and toxic granulations (granulations in the neutrophils)
- left shift (inc neutrophils)
- cytoplasmic vacuoles in the neutrophils

vs: acute leukema
- w the release of immature neutrophil precursors = promyelocytes and myeloblasts

Question 56

Q

what is the etiology of polycythemia vera

sx
associated conditions
labs

Answer

A

polycythemia vera = myeloproliferative disorder with uncontrolled erythrocyte production

caused by a mutation in the intracytoplasmic JAK2 tyrosine kinase that connect to the EPO-receptor on the membrane
constituituve activation of JAK2–> abn signal transduction for erythropoesisn –> clonal proliferation of myeloid cells

sx

nonspecific- HA, wknss, diaphoresis
aquagenic pruritis: contact w water causes itching
facial plethora = reddish complexion
splenomegaly

associated conditions=

peptic ulcer ds : inc blood viscosity will alter mucosal blood flow
gouty arthritis : higher red cell turnover

labs

inc number erythrocytes- high Hgb and Hct
thrombocytosis
leukocytosis
low EPO levels
*

Question 57

Q

what is the specific MOA of the following atni-platelet drugs

aspirin
clopidegrel, prasugrel, ticlopidine
abciximab, eptifibatide, tirofiban

what is the purpose of giving a patient ristocetin?

Answer

A

aspirin
- irreverisble inhibition of COX–> xTXA2 synthesis –> inhbitory effect on platelet aggregation
clopidegrel, prasugrel, ticlopidine
- irreversibly block P2Y12-receptor on platelets = inhibit expression of GpIIb/IIIa on platelets
- no GpIIb/IIIa means that the plt can’t bind fibrin = inhibit aggregation
abciximab, eptifibatide, tirofiban
- inhibit GpIIb/IIIa on platelets directly –> block fibrin binding –> block aggregation

ristocetin : activaties vWF to bind GpIb

failure of aggregation indicates the pt may have vWF ds or Bernard-Soulier syndrome

Question 58

Q

PT tests which pathway and factors?

PTT tests which pathway and factors?

-how are coagulation disorders caused by factor deficiency differentiated from a factor inhibition?

Answer

A

PT= common and extrinsic pathways
- 1, 2, 5, 7, 10
PTT= common and intrinsic pathway
- I, II, IX, X, XI, and XII
mixed studies where you add normal plasma to the pt’s plasma
- deficiency will be fixed, secondary to inhibition will not
  *

Question 59

Q

what is the etiology of hemophilia

how will it present
difference between types A, B, and C
trx for dif types

Answer

A

= x intrinsic pathway coag defect = (n PT, inc PTT)

present with hemorrhages: hemarthroses, easy bruising, bleeding after trauma or surgery…
type A= deficiency factor 8 XR
- trx= desmopression and F8 concentrate
type B= deficient factor 9 XR
- trx= factor 9 concentrate
type C= deficient factor 11 AR
- trx= factor 11 concentrate

Question 60

Q

which coag factors are dependent on Vit K

what coagulation lab changes will be seen with vitamin K deficiency

Answer

A

Vit K–> need for Factors 2, 7, 9, 10 and protein C+S
result in inc PT and PTT, with NORMAL bleeding time

Question 61

Q

Acute intermittant porphyria

etiology
presentation
- what is the pathognomic finding
what things exacerbate sx
appr trx?

Answer

A

etiology
- prophobilinogen deaminase, an enzyme used in Hgb production
- without PB-deaminase working, the levels of ALA will build up bc ALA synthase is still working and breaking down glycine and succinyl CoA
presentation
- can be a young person (inherited)
- inc prophobilinogen levels in urine= pathognomonic ; urine darkens when it is exposed to air and light
- neuropath: can look like hyporeflexia, gen wknss… depression and insomnia
- attacks of abd pain secondary to build up of ALA
what things exacerbate sx
- “attacks” of sx= when inc ALA synthase activity
- associated w endogenous or exogenous inc in gonadal steroids
- use of sulfonamides, antiepileptics
- alcohol
- dec calorie diets
- stress
appr trx?
- give IB heme –> repress ALA synthase and help control sx
- IV dextrose and carb loading will also help to abate attacks
- mostly monitor for and trx for any neuro and respiratory complications

Question 62

Q

Acute lymphoblastic leukemia

associated populations, markers, genetics
lab findings and histo
common presenting sx and the associated etiologies with them
trx

Answer

A

associated populations, markers, genetics
- often YOUNG&children (L for little)
- (when it is adults, they have a worse prognosis)
- associaed w Downs Syndrome
- (+)TdT, (for T and B cell precursors)
- (+) CD10
lab findings and histo
- inc peripheral lymhoblasts on peripheral smear: “inc IMMATURE white cells w CONDENSED chromatin, absent nucleoli, and SCANT AGRANULAR cytoplasm)
- anemia, thrombocytopenia, w inc WBC count (lymphoblastic means T and B cell precursors)
- inc LDH 2° to inc cell turnover
common presenting sx and the associated etiologies with them
- sx are often secondary to leukemic expansion –> crowds out the BM
- MC sign= fever (inc cytokine release)
- fatigue&lethargy/weakness 2° to anemia
- bone&joint pain 2° to periosteal invasion
- painless enlarged scrotum/CNS may occur 2° to extramedullary invasion
- hepatomegaly
- scattered petechiae and bruising
trx & prognosis
- complex chemo
- cyclophosphamides + doxorubicin + vincristin +dexamethasone/prednisone
- ± MTX ± asparagnese ± cytarabia

Question 63

Q

Acute myelogenous Leukemia

typical population
etiology
sx and presentation
histo, labs, BM biopsy
risks and associations
dx and trx

Answer

A

AML

typical population
- older people, mean= 65 yo (aMl= mature)
etiology
- myeloblasts= immature neutrophils, basophils, eosinophils
- associated w t(15;17) translocation = M3 variant of APL gene –> (see trx)
- appear on smears as inc in granulocyte precurosrs, monocytes, megakarycytes, and erythroblasts
sx and presentation
- epistaxs, skin rash, petechiae
- bone pin, SOB
- gingival hyerplasia (2° to leukemic invasion)
- leukemia cells (skin infiltrate)
- neuro deficits
- v common to have DIC (esp w ACUTE PROMYELOBLASTIC LEUKEMIA VARIANT)
histo, labs, BM biopsy
- inc circulating myeloblasts in the periphery
- =inc WBC count, w ↑↑ blastocytes >> lymphocytes
- BM will show proliferation of myeloblasts w characteristics of eosinophils
- Auer Rods= pathognomonic= needle like cytoplasmic inclusions seen on BM
risks and associations
- previous alkylating chemo/radation exposure
- myeloproliferative ds (i.e. polycythemia vera…)
- Downs Syndrome
- hx of acute promyelocytic leukemia
- associated with cellulitis because neutropenia 2° to the leukemia will ==> inc susceptibility to skin infections
dx and trx
- acute promyelocytic leukemia variant will respond well to Vit A retinoic acid variants and arsenic
- those w t(15;17) can specifically be treated w ALL trans-retinoic acid –> incudec apoptosis of promyelocytes –> inc remission and cure

Question 64

Q

aplastic anemia

sx and labs
etiology
diagnostic test
trx

Answer

A

sx and labs
- low WBC, RBC, and plt
- show with purpura and petechiae, malaise and wknss, repeated + easily infections
etiology
- = BM failure–> pancytopenia
- most are idiopathy (autoimmune) causes of BM failure
- but can also be caused by
  - viruses: EBV, HIV, parvovirus B19, herpes viruses
  - genetic abn = fanconi, SLE
  - drugs/chemicals: alkylating agents or antimetabolites, chloramphenicol, arsenic, insecticide, benzene
diagnostic test
- BM biopsy = hypercellular BM (>30%) with fatty infiltrate
trx
- 1. withdraw any possible toxic agent
- supportive care (abx for any infection, blood transfusions…) –> SCC transplant/mmunosupp

Answer 64

A

= low MCV, low Hgb

=iron deficiency anemia OR thalassemia

Answer 65

A

beta thalassemia= only has one gene ( 2 alleles) : mutations result in either decreased or no B globin chains

mediterranian populations (greece)

alpha thalassemia: has 2 genes (4 alleles): disease state depends on the number of alleles that have been deleted 2° to unequal meitoic crossover

southeast asians (associated w more severe ds) + blacks

Answer 66

A

ALPHA THALASSEMIAS

aT-minima

(αα/α-)
silent carrier

aT- minor

(α-/α-) OR (αα/–)
mild, microcytic hypochromic anemia
SE asians are more associated w the homozygous version = more likely to pass on to offspring : AA are more associated w the heterozygous condition

HbH Ds

(–/-α)
mod-severe microcytic, hypochromic anemia
exces beta globin relatively –> form beta-4 tetramers

Hgb Barts Ds

(- -/- -)
HYDROPS FETALIS= incompatible w life
excess gamma chain relatively –> gamma-4 tetramers form

BETA THALASSEMIAS

=point putations in splice sites/promoter sequences

β-T minor:

w+/b
usually asx
dec beta globin production, dx via inc levels of HbA on electrophoreseis

β-T major:

(b/b)
severe anemia due to absent beta chain = target cells, inc anisospoikilocytes (dif sized RBCs),
- sx frst appear ~ 6months of age, at which point y-Hgb alls without the increased in b-Hgb: early sx= pallor, growth retardation, hepatosplenomegaly, and jaundice
- x-ray: crew cut skull + chipmunk face deformity = marrow expansion
- inc extramedullary hematopoeisis –> hepatomegaliy
- parvovirus B19 infection–> aplastic crisis
regular blood transfusions needed = inc risk of hemachromatosis
- inc HbF&HbA levels
- (b/s) heterozygote would have mild to mod sickle cell ds depending on the amount of beta globulin production

DIAGNOSES= gel electrophoresis to distringuish type o hg_ present

TRX= HbF induction,

FOR beta-MAJOR: repeated transfusions, and splenectomy

Answer 67

A

warm agglutinin

= positive direct coombs test = Abs against RBCs are directly detected on the RBCs themselves
causes: MC= idiopathic
- second MC= autoimmune (i.e. SLE)
- also- meds (methyldopa), lymphomas/leukeias
etiology: IgG coated RBCs are phagocytosed in the spleen by the møs
- if caused by a drug: the RBC-bound drugs are recognized by Abs and targeted for destruction
sx=fatigue, lethargy, hepatomegaly, spherocytes and reticulocytes, low Hgb

cold agglutinin:

indirect Coombs test= Abs against RBCs are detected in the serum, not on the RBCs themselves
causes: certain infections (mono [EBV], mycoplasma)
usually self limited, sx caused by vascular obstruction in the periphery from complement deposition 2° to IgM molecules clumping together in the cooler periphery
- pallor + cyanosis of distal extremities that is transient

Answer 68

A

MC = sporadic (rather than a HER2/ER/PR/BRCA1/2 mutation)

often present w: LATE age of onset : early menarche and late menopause : obesity

inc risk

F
alc intake
inc breast density
inc estrogen exposure (HRT, nuliparity/late first pregnancy, obesity)
inc age
FH
prior biopsy, esp fr atypia
radiation exposure to the chest

Answer 69

A

75-80% carcinoid tumrs are in the small intestine
only 10% will become carcnoid syndrome: most of the time, the syndrome only develops once the tumor mets to the liver
- syndrome= tumor + sx (diarrhea, flushing, pain, asthma/wheezing, pallegra)
- sx develop when the secreted substances reach the general circulation = gastrin, somatostatin, substance , VIP, pancreatic polypeptide, histamine, chromogranin A, serotonin
flushing+ inc 5-HIAA in the urine = diagnostic
carcinoid syndrome ∝ tricuspid (>pulm) valve involvement
- associated w serotonin mediated fibrosis in the endocardium
trx= surgival resectin + octeotride (somatostatin analog)

Answer 70

A

hereditary angioedema

random episodes of edema
- usually= swelling of face, lips, tongue … but can also be of internal organs
- i.e. abd angioedema –>random bouts of abd pain w V/D
- i.e. resp tract angioedema –> episodes of diff breathing
- self limited events
no C1 esterase inhibitor = inc kallikrein(–>plasmin* and *bradykinin) + inc activated C1 –> inappropriate angioedema
ACE inhibitors are contra-indicated bc they increase bradykinin –> can trigger an episode

Answer 71

A

beta blockers
- ↓renin : ↓AGI : ↓AGII : ↓ALD : n bradykinin
direct renin inhibitors
- ↑ renin : ↓AGI : ↓AGII : ↓ALD : n bradykinin
ace-i
- ↑ renin : ↑ AGI : ↓AGII : ↓ALD : ↑ bradykinin
ARBs
- ↑renin : ↑AGI : ↑AGII : ↓ALD : n bradykinin
ALD- antagonist
- ↑renin : ↑AGI : ↑AGII : ↑ALD : n bradykinin

Answer 72

A

abciximab = anti-PLT = inhibit GpIIb/IIIa on plts so that it can’t bind fibrin

used in: unstable angina, acute coronary syndrome, and in pts undergoing percutaneous coronary intervention

Glansman thrombasthenia = AR ds caused by deficient/defective GpIIb/IIIa
- presents in childhood w mucocutaneous bleeding w no platelet clumping on peripheral smear (in important diagnostic clue)

Answer 73

A

HEPARIN

partial thromboplastin time = inc
prothrombin time = n/a
Xa activity = dec
thrombin time = inc
reptilase time = norm
drVVT = n/a

WARFARIN

partial thromboplastin time = n/a
prothrombin time = inc
Xa activity= inc
thrombin time=n
reptilase time= n/a
drVVT=n/a

LUPUS ANTICOAG (antiphospholipid ab syndrome)

partial thromboplastin time= inc
prothrombin time = inc
Xa activity = n/a
thrombin time = inc
reptilase time =inc
drVVT =inc
*fail to correct w mixing, corrects when you add phosphilips (oversaturate the Ab)

Answer 74

A

setting:

-acute flare of an immune ds i.e. sarcoidosis

AE=

glucose intolerance (high glucose levels for a bit)
dec L-selected expression on neutrophils –> impaired neutrophil migration, extravasation
x IL-8 production –> impaired neutrophil migration –> neutrophilia bc all the neutrophils are stuck in the circulation

change in immune cells

dec neutrophil apoptosis
inc apoptosis of neutropils, eosinophils, monocytes
dec Mø activation
inhibit PLA2 –> dec production of prostaglands and leukotrienes

Answer 75

A

CDK 4/6 inhibitors (i.e. pablociclib) = inhibit G1->S phase

used in CA trx
dose limiting AE= bone marrow suppression

Answer 76

A

mild ds w no systemic inflammation
- glucocorticoid: give budesonide= less systemic AE due to high first pass metabolism
- inhibit proinflammatory genes = x NFKB
to reduce inflammation in mod-severe ds
- azaothioprine & mycophenolate= inhibit de novo purine synthesis
to induce remission
- infliximab= mab that inhibits effects of TNF-alpha

Answer 77

A

STATINS

inhib HMG-CoA reductase ; dec cholesterol synthesis

cholestyramine

inc HMG CoA reductase activity ; inc chol synthesis
(bind bile acid in GI tract —> interrupt enteric-hepatic circulation –> inc bile acid secretion –> inc hepatic production of bile acids –> inc hepatic LDL intake in order to get th ebuilding blocks to make bile acid –> inc chol break down–> inc HMG CoA reductase acitivty)

Answer 78

A

porphyria cutanea tarda

x uroporphyrinogen decarboxylase –> accumulate uroporphyrin
uroporphyrin is excited by visible light.. so sx =
- blistering, cutaneous photosensitivity and hyperpigmentation
can be exacerbated by alc; can be familial in origin or caused by hepatitis C
trx= phlebotomy, avoid the sun, hydroxychloroquine (an anti-malarial)

Answer 79

A

vitamin E deficiency (x DCML)

Answer 80

A

target cells = beta thalassemia

(+ hypochromic, poikolycytes) (also microcytic, though you know that from the low MCV)

Answer 81

A

round nuclei with basophilic cytoplasm with prominent lipid vacuoles

Answer 82

A

CML

leukocytosis and many immature myelocytes

Answer 83

A

childhood B-cell Acute lymphocytic leukema

anemia, thrombocytopenia, and lymphoblasts

Answer 84

A

follicular lymphoma

-notches/clefts = centrocytes

Answer 85

A

major basic protein
- in eosinophil granules - defend against parasites
myeloperoxidase
- in myeloblasts: the Auer rods will stain MPO+
- associated with APL (variant of AML) - immature myeloid lineage cels cannot differentiate so they proliferate in the BM and suppress the growth of other hematopoeitc cells= marrow replacements
- present = thrombocytopenia, fever+infections (neutropenia), in adults
platelet-derived growth factor
- GI stromal tumors - PDGF-R mutations
tartrate resistant acid phosphatase (TRAP)
- on the neoplastic cells of Hairy Cell Leukemia (“long hair is a trap!”)
- present = splenomegaly, fatigue, pancytopenia
Terminal deoxynucleotideyl transferase (TdT)
- marker of immature lymphocytes, T&B cells
- in ALL, (acute lymphoblastic leukemia), in children