• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/198

Click to flip

198 Cards in this Set

  • Front
  • Back
  • 3rd side (hint)
What is the normal order of the WBC w/diff?
neutrophils
lymphos
monos
eos
basos
What is the vWF receptor?
Gp1b
What is the fibrinogen receptor?
GpIIb/IIIa
What cell type do platelets derive from?
megakaryocytes
What types of granules do platelets contain?
dense granules: ADP and Ca2+

alpha-granules: vWF, fibrinogen
In what condition do you see hypersegmented poly's?
B12/folate deficiency
What does a monocyte look like?
kidney shaped nucleus (one)

"frosted glass" cytoplasm
What do eosinophils look like?
bilobate nucleus

packed with large eosinophilic granules of uniform size
What do eosinophils contain?
major basic protein

histaminase

arylsulfatase (help limit rxn following mast cell degranulation)
What are the causes of eosinophilia?
NAACP:
neoplastic
asthma
allergies
collagen vascular disease
parasites (invasive only)
What do basophils contain?
heparin
histamine
vasoactive amines
leukotrienes (LTD-4)
similar to mast cells
What do mast cells contain?
histamine
heparin
eosinophil chemotactic factors
What are Landerhan's cells
dendritic cells in the skin
What does a plasma cell look like?
off-center nucleus
clock-face chromatin distribution
abundant RER
well-developed golgi
what is the difference between anit-AB antibodies and anti-Rh antibodies?
anti-AB are IgM so they can't cross the placenta while anti-Rh are IgG so they can.
what is thromboplastin?
tissue factor exposed in damaged endothelium that activated the extrinsic coagulation patheway by catalyzing factor VII conversion to VIIa
What does plasmin do?
activated complement cascade by converting C3 ==> C3a

helps degrade fibrin (anti-clotting factor)
What does Kallikrein do?
activates plasmin (clot buster)

activates bradykin (pro-inflam cascade)
What is the difference between Hemophilia A and B?
A - deficiency of factor VIII

B - deficiency of factor IX
Which factors does heparin-activated antithrombin (AT III) inhibit? What does it activate?
Inhibits:
intrinsic pathway (XIIa, XIa, Xa, IXa)
thrombin (IIa)
extrinsic pathway (VIIa)

Activates:
kallikrein
plasmin
What does tPA do?
activates plasminogen ==> plasmin which then cleaves fibrin mesh so it is a potent thrombolytic agent
What does Protein C do?
when activated, cleaves and inactivates factors Va and VIIIa
What is acanthocyte?
aka spur cell - spiny RBC found in liver disease and abetalipoproteinemia
In which conditions do you find basophilic stippling of RBCs?
Thalassemias
Anemia of chronic disease
Iron deficiency
Lead poisoning
What do "bite cells" indicate?
G6PD deficiency
In which conditions do you find schistocytes?
DIC
TTP/HUS
traumatic hemolysis
In which condition do you find tear drop cells?
bone marrow infiltration like myelofibrosis
In which conditions do you find target cells?
HALT:
HbC disease
Asplenia
Liver disease
Thalassemia
In which conditions do you find Heinz bodies?
alpha-thal
G6PD deficiency
In which conditions do you find Howell-Jolly bodies?
functional hyposplenia or asplenia (sickle cell, eg)
What is HbH and when is it found?
when Hg is made of four Beta-chains in alpha-thal

shows up differently on elecrophoresis

severe anemia but still compatible with life
What are the findings on electrophoresis for Beta-thalassemia?
no HbA
inc. HbA2 (two alpha, two delta)
inc. HbF (two alpha, two gamma)
How does lead poisoning cause anemia?
inhibits ferrochelatase and ALA dehydratase ==> dec. heme synthesis

Inhibits rRNA degradation ==>basophilic stippling
What causes sideroblastic anemia?
hereditary deficiency in delta-aminolevulinic acid sythase ==> defect in heme synthesis

also alcohol and lead
What is the tx for sideroblastic anemia?
give pyridoxine (B6) therapy
what do the iron studies in sideroblastic anemia show?
inc. iron
normal TIBC
inc. ferritin
What are the signs of lead poisoning?
Lead lines on gingivae and epiphyses of long bones
Encephalopathy
Basophilic stippling
Abdominal colic
sideroblastic anemia
Wrist and foot drop
What is the tx for lead poisoning?
EDTA and dimercaprol

succimer for kids
What are the neurological sx in B12 deficiency?
peripheral neuropathy
posterior column degeneration (de. vibration/proprioception)
Later corticospinal tract degeneration (spasticity)
Dementia
What are the causes of non-megaloblastic macrocytic anemia?
Liver disease
Alcoholism
reticulocytosis
Congenital deficiencies of purine/pyrimidine synthesis
Drugs: 5-FU, AZT, hydroxyurea
What is the pathophys of anemia of chronic disease?
inflammation ==> inc. hepcidin ==> dec. release of iron from macrophages
What are the pathologic features of aplastic anemia?
pancytopenia (anemia, neutropenia, thrombocytopenia)
normal cell morpho
hypocellular bone marrow with fatty inflitration
What causes aplastic anemia?
radiation and drugs
viral agents (B19, EBV, HIV, HCV)
fanconi's anemia (inheritied defect in DNA repair)
idiopathic (immune-mediated or primary stem cell defetc, may follow acute hep)
Which drugs cause aplastic anemia?
benzene
chloramphenicol
alkylating agents
antimetabolites
Aplastic anemia sx
faituge
malaise
pallor
purpura
mucosal bleeding
petechiae
infection
Aplastic anemia tx
allogeneic bone marrow transplantation
RBC and platelet transfusion
G-CSF or GM-CSF
Hereditary spherocytosis findings:
splenomegaly
aplastic crisis (B19 infection)
howell-jolly bodies (if splenectomy)
small, round RBCs with no central pallor
Hereditary spherocytosis labs:
positive membrane fragility test
Hereditary spherocytosis tx
splenectomy (cuz they are usually removed prematurely by spleen even though they are functioning properly)
What is the pathophys of anemia in G6PD deficiency?
hereditary defect in G6PD ==? dec. glutathione ==> inc. RBC susceptibility to oxidant stress
G6PD deficiency findings
hemolytic anemia following oxidant stress (e.g. sulfa drugs, infections, fava beans)

back pain

hemoglobinuria a few days after stress
G6PD deficiency labs
blood smear shows RBCs with Heinz bodies and bite cells
Pyruvate kinase defiency causes:
heymolytic anemia of newborn

can't make enough ATP via the anaerobic pathway so RBC's die
Where is the mutation in sickle cell anemia?
point mutation at position 6 of the beta chain (Glu ==> Val)
Sickle cell tx
hydroxyurea (inc. HbF)

bone marrow transplant
Paroxysmal nocturnal hemoglobinuria pathophys
defect in decay-accelerating factor makes RBCs more vulnerable to complement activation and subsequent destruction.
PNH findings
red pee in the morning

inc. urine hemosiderin
what is the difference between direct and indirect Coomb's test?
in direct, you are adding anti-Ig antibody to the patient's RBCs

in indirect you are adding patient's serum to normal RBC's
Warm agglutinin hemolytic anemia is caused by/associated with?
anti-IgG

SLE
CLL
alpha-methyldopa
Cold agglutinin hemolytic anemia is caused by/associated with?
anit-IgM

CLL
M. pneumo
mono
What causes microangiopathic anemia?
DIC
TTP-HUS
SLE
malignant HTN
What causes macroangiopathic anemia?
prosthetic heart valves
aortic stenosis
malaria
babesia
What is transferrin?
molecule that transports iron in the blood
What is ferritin?
Molecule that stores iron
What is TIBC?
indirect measure of transferring
What is %transferrin saturation?
Fe/TIBC
Acute intermittent porphyria pathophys
deficient in porphobilinogen deaminase so porphobilinogen, delta-ALA and uroporphyrin accumulate
Acute intermittent porphyria sx
painful abdomen
red wine-colored urine
polyneuropathy
psych disturbances
*often precipitated by druge
Porphyria cutanea tarda pathophys
deficiency in uroporphyrinogen decarboxylase so uroporphyrin accumulates
Porphyria cutanea tarda tx
tea-colored urine
blistering cutaneous photosensitivity
most common porphyria
What does PT test?
function of extrinsic pathway - factors I, II, V, VII and X
What does PTT test?
function of all factors except VII and XIII (intrinsic pathway)
What kind of coagulation pathway defect is Hemophilia?
intrinsic pathway so inc. PTT
What is Bernard-Soulier disease?
defect in platelet plug formation

dec. Gp1b which binds to vWF

lower platelet count
inc. bleeding time
What is Glanzmann's thrombasthenia
defect in platelet plug formation

dec. GpIIb/IIIa ---> platelets don't stick to each other

inc. bleeding time but platelet count is normal
Idiopathic thrombocytopenic purpura pathophys
dec. platelet survival due to anti0GpIIb/IIIa antibodies causing peripheral platelet destruction
Idiopathic thrombocytopenic purpura findings
inc. megakaryocytes
dec. platelet count
inc. bleeding time
Thrombotic thrombocytopenic purpura
pathophys
dec. platelet survival due to deficiency of ADAMTS13 ==> dec. degradation of vWF multimers ==> inc. platelet aggregation and thrombosis
Thrombotic thrombocytopenic purpura symptoms
neurologic and renal symptoms
fever
thrombocytopenia
microangiopathic hemolytic anemia
vonWillebrand's disease tx
DDAVP (desmopressin) rleases vWF stored in endothelium
vonWillebrand's disease pathophys
coagulation defect: vWF carries factor VII so inc. PTT (intrinsic pathway)

platelet plug defect: dec. vWF means platelets can't stick to endothelium (inc. BT)
What are the coagulation disorders?
Hemophilia A/B

Vit. K deficiency
What are the platelet disorders?
Bernard-Soulier disease
Glanzmann's thrombasthenia
ITP
TTP
What are the hereditary thrombosis (hypercoagubility) syndromes?
Factor V Leiden
Prothrombin gene mutation
ATIII deficiency
Protein C or S deficiency
What is Factor V Leiden disease?
production of mutant factor V that cannot be degraded by protein C --> hereditary hypercoagulability
What is Protein C or S deficiency?
dec. ability to inactivate factors V and VII ==> hypercoagulable

inc risk of skin necrosis with hemorrhage following administration of warfarin
What is a Reed-Sternberg cell?
distinctive tumor giant cell seen in hodgkin's disease

binucleate or bilobes with 2 halves as mirror images (owl eyes)

CD30+ and CD15+ B cell origin
What determines a good prognosis in Hodgkin's lymphoma?
inc. lymphocyte-to-RS ratio

more reed-steinberg relative to lympohcytes = worse disease

(usually found in older males with disseminated disease)
Who gets Burkitt's lymphoma?
young adults and adolescents

it is a non-hodgkin's lyphoma
What is the genetic defect in Burkitt's lympoma?
t(8;14) c-myc gene mext to heavy chain Ig gene (14)
Burkitt's histology
"starry-sky" appearance of sheets of lymphocytes with interspersed macrophages
Which is the most common adult non-Hodgkin lymphoma?
Diffuse large B-cell lymphoma
What is Mantle cell lymphoma?
A CD5+ non-Hodgkin's lymphoma with a poor prognosis found in older males
What is the genetic defect in Mantle cell lymphoma?
t(11;14)
What is follicular lymphoma?
It is a type of non-hodgkin's lymphoma found in adults that has an indolent course and is difficult to cure
What is the genetic defect in follicular lymphoma?
t(14;18) bcl-2 gene (inhibits apoptosis)
What is Adult T-cell lymphoma?
An aggressive type of non-hodgkins lymphoma found in adults in Japan, West Africa and the Carribean that is caused by HTLV-1
What is mycosis fungoides/sezary syndrome?
a type of indolent non-hodgkin's lymphoma found in adults presenting with cutaneous patches/nodules
What are Bence Jones proteins?
Ig light chains in urine of multiple myeloma patients
Where do you see rouleaux formation?
RBC's stacked like poker chips found in multiple myeloma
When do you get an M spike on electrophoresis
Too many monoclonal IgM due to multiple myeloma
What are the sx/findings in multiple myeloma?
hypercalcemia
renal insufficiency
anemia
bone lytic lesions (punched out)
What other condition is multiple myeloma associated with?
primary amyloidosis
Who gets ALL?
kids
How does ALL present?
bone marrow involvement in childhood or mediastinal mass in adolescent males
What are the markers of ALL?
TdT+ (marker on pre-B and T cells)

CALLA+
What is the translocation in ALL?
t(12;21)
Who gets CLL?
adults >60
What are the findings in CLL?
often asymptomatic

smudge cells on PBS

warm antibody autoimmune hemolytic anemia
Who gets Hairy cell leukemia?
the elderly
What are the findings in hairy cell leukemia?
mature b-cell tumor

cells have filamentous hair-like projections

stain TRAP+
What are the findings in AML?
auer rods

tons of circulating myeloblasts on PBS
AML tx
all-trans retinoic acid (vitamin A) induces differentioation of myeloblasts
What is the translocation in CML?
philadelphia chromosome

t(9;22) bcr-abl
What are the findings in CML/how does it present?
myeloid stem cell proliferation
inc. neutrophils, basophils, metamyelocytes
splenomegaly
blast crisis (AML/ALL progression)
very low leukocyte alkphos
CML tx
imatinib (anti-bcr-abl antibody)
Age ranges for the leukemias (ALL, AML, CML, CLL)
ALL = <15
AML = >60
CML = 30-60
CLL = >60
What are Auer bodies?
peroxidase-positive cytoplasmic inclusion in granulocytes and myeloblasts commonly seen in the M3 type of AML (release of them during tx could cause DIC)
What is Langerhans cell histocytosis?
proliferative disorders of dendritic (langerhans) cells.
what are lab/microscopic findings in Langerhans cell histocytosis?
defective cells express S-100 and CD1a.

birbeck granules
"tennis rackets" on EM
What is polycythemia vera?
chronic myeloproliferative disorder in which RBCs, WBCs and platelets are all increased due to a JAK2 mutation
What is essential thrombocytosis?
chronic myeloproliferative disorder in which platelets are all increased due to a JAK2 mutation
What is myelofibrosis?
chronic myeloproliferative disorder in which RBC's are decreased due to fibrotic obliteration of bone marrow
What is JAK2 and what is it associated with?
JAK2 is involved in hematopoietic growth factor signaling.

mutatons are implicated in myeloproliferative disorders other than CML
What is appropriate absolute polycythemia?
inc. in RBC mass due to lung disease, congenital heart disease or high altitude (epo is inc.)

O2 sat. is dec.
What is inappropriate absolute polycythemia?
inc. RBC mass due to ectopic epo production
what is polycythemia vera?
inc. RBC mass due to RCC, wilms' tumor, cyst, HCC or hydronephrosis

(epo will be dec due to neg. feedback)
Lepirudin, bivalirudin MOA/uses
hirudin derivatives that directly inhibit thrombin

used as an alternative to heparin in patients with HIT
What does aminocaproic acid do?
inhibits the conversion of plasminogen to plasmin

used in tPA/streptokinase overdose
What do tPA/streptokinase do to PTT, PT, and bleeding time?
inc. PT
inc. PTT
no effect on bleeding time
What does aspirin do to PTT, PT, and bleeding time?
inc. bleeding time
no effect on PT or PTT
Aspirin MOA
acetylates and irreversibly inhibits COX-1/2 thereby preventing the conversion of arachadonic acid to TXA2
dec. TXA2 means less platelet aggregation
Clopidogrel, ticlopidine MOA
inhibit platelet aggregation by irreversibly blocking ADP receptor. inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa expression
Ticlopidine toxicity
neutropenia
Clopidogrel, ticlopidine clinical uses
acute coronary syndrome
coronary stenting
to dec. the incidence or recurrence of thrombotic stroke
Abciximab MOA
monoclonal antibody that binds to the glycoprotein receptor IIB/IIIA on activated platelets, preventing aggregation
Methotrexate MOA
folic acid analog that inhibits dihydrofolate reductase ==> dTMP ==> dec. DNA and protein syn
Methotrexate clinical use
cancers: leukemias, lymphomas, choriocarcinoma sarcomas

abortion, ectopic preg. RA, psoriasis
Methotrexate toxicity
myelosuppression (reversible with leucovorin)
macrovesicular fatty change in liver
mucositis
teratogenic
5-FU MOA
pyrimidine analog bioactivated to 5F-dUMP which covalently complexes with folic acid, inhbiting tymidylate synthase ==> dec. dTMP => dec. DNa and protein syn
5-FU clinical use
colon cancer and other solid tumors
basel cell carcinoma (topical)
synergy with MTX
5-FU toxicity
myelosuppresion which is NOT reversible with leucovorin ("rescue" is with thymidine)

photosensitivity
6-MP MOA
purine analog ==> dec. de novo purine synthesis

activated by HGPRTase
6-MP clinical use
leukemias, lymphomas (not CLL or hodgkin's)
6-MP toxicity
bone marrow, GI, liver
metabolized by xanthine oxidase so worse with allopurinol
6-TG MOA
same as 6-MP (dec. de novo purine synthesis)
6-TG clinical use
acute lymphoid leukemia
6-TG toxicity
bone marrow depression, liver
can be given with allopurinol
Cytarabine (ara-C) MOA
pyrimidine antagonist ==> inhibition of DNA polymerase
Cytarabine (ara-C) clinical use
AML
ALL
high-grade non-Hodgkin's lymphoma
Cytarabine (ara-C) toxicity
leukopenia
thrombocytopenia
megaloblastic anemia
Dactinomycin MOA
intercalates in DNA
Dactinomycin clinical use
Wilm's tumor
Ewing's sarcoma
rhabdomyosarcoma

(childhood tumors)
Dactinomycin toxicity
myelosuppression
Doxorubicin (adriamycin), daunorubicin MOA
generate free radicals
noncovalently intercala in DNA ==> breaks DNA ==> dec. replication
Doxorubicin (adriamycin), daunorubicin clinical use
Hodgkin's lymphomas
myelomas
sarcomas
solid tumors (ovary, breast, lung)
Doxorubicin (adriamycin), daunorubicin toxicity
cardiotoxicity
myelosuppression
alopecia
toxic to tissues with extravasation
Bleomycin MOA
induces free radical formation, which causes breaks in DNA strands
Bleomycin clinical use
tisticular cancer
hodgkin's lymphoma
Bleomycin toxicity
pulmonary fibrosis
skin changes
minimal myelosuppression
Etoposide (VP-16), teniposide MOA
inhibits topoisomerase II ==> inc. DNA degradation
Etoposide (VP-16), teniposide clinical use
small cell lung cancer
prostate cancer
testicular cancer
Etoposide (VP-16), teniposide toxicity
myelosuppression
GI irritation
alopeica
Cyclophosphamide MOA
covalently cross-links DNA at guanin N-7

*requires bioactivation by liver
Cyclophosphamide clinical use
Non-hodgkin's lymphoma
breast and ovarian carcinomas

(also immunosppressants for anti-rejection)
Cyclophosphamide toxicity
myelosuppression
hemorrhagic cystitis (partially prevented with mesna)
Nitrosoureas (carmustine, lomustine, semustine, sretozocin) MOA
require bioactivation

cross BBB ==> CNS
Nitrosoureas (carmustine, lomustine, semustine, sretozocin) clinical use
brain tumors (including glioblastoma multiforme)
Nitrosoureas (carmustine, lomustine, semustine, sretozocin) toxicity
CNS toxic - dizziness, ataxia
Busulfan MOA
alkylates DNA
Busulfan clinical use
CML

also used to ablate patient's bone marrow before transplant
Busulfan toxicity
pulmonary fibrosis
hyperpigmentation
Vincristine, vinblastine MOA
alkaloids that bind tubulin in M-phase and block polymerization of microtubules so that mitotic spindle cannot form
Vincristine, vinblastine clinical use
Hodgkin's lymphoma
Wilm's tumor
choriocarcinoma
Vincristine, vinblastine toxicity
neurotoxicity (areflexia, peripheral neuritis)
paralytic ileus
bone marrow suppression (vinblastine)
Paclitaxel MOA
hyperstabilize polymerized microtubules in M-phase so that mitotic spindle can not break down (anaphase can't occur)
Paclitaxel clinical use
breast and ovarian cancers
Paclitaxel toxicity
myelosuppression

hypersensitivity
Cisplatin, carboplatin MOA
cross-link DNA
Cisplatin, carboplatin clinical use
testicular
bladder
ovary
lung
Cisplatin, carboplatin toxicity
nephrotoxicity
acoustic nerve damage
Hydroxyurea MOA
inhibits ribonucleotide reductase ==> dec. DNA synthesis (S-phase specific)
Hydroxyurea clinical use
melanoma
CML
sickle cell disease (inc. HbF)
Hydroxyurea toxicity
bone marrow suppression
GI upset
Prednisone MOA (in cancer)
may trigger apoptosis, may even work on nondividing cells
Prednisone clinical use (in cancer)
CLL
Hodgkin's lymphomas (mart of MOPP)
auto-immune diseases
Prednisone toxicity
Cushingoid
immunosuppression
cataracts
acne
osteoporosis
HTN
peptic ulcers
hyperglycemia
psychosis
Tamoxifen, raloxifene MOA
SERMs - receptor antagonists in breast and agonists in bone. block the binding of estrogen to estrogen receptor-positive cells
Tamoxifen, raloxifene clinical use
breast cancer
prevention of osteoporosis
Tamoxifen, raloxifene toxicity
tamoxifen = inc. risk of endometrial carcinoma via partial agonist effects. also "hot flashes"

raloxifene does not have this effect
Trastuzumab MOA
aka Herceptin
monoclonal antibody against HER-2 (erb-B2). helps kills breast cancer cells that express HER-2 through antibody mediated cytotoxicity
Trastuzumab clinical use
metastatic breast cancer
Trastuzumab toxicity
cardiotoxicity
Imatinib MOA
aka Gleevec
philadelphia chromosome bcr-able tyrosine kinase inhibitor
Imatinib clinical use
CML

GI stromal tumors
Imatinib toxicity
fluid retention
Rituximab MOA
monoclonal antibody again CD20, which is found on most B-cell neoplasms
Rituximab clinical use
non-hodgkins lymphomas
RA (w/MTX too)