HEME Flashcards
acanthocyte
spur cell
degmacyte
bite cell
Echinocyte
burr cell
erythrocyte
RBC
Heinz body
oxidized hgb
Howell- Jolly body
nuclear remnant in patients with asplenia
Reticulocyte
immature RBC
Schistocyte
fragmented RBC
Spherocyte
spherical RBC
young liver synthesizes blood
Yolk sac (3-8 weeks) Liver (6wks- birth) Spleen (10-28wks)- most important site of hematopoesis throughout fetal development Bone marrow (18 wks to adult)
infancy/childhood: long/flat bones
sternum, pelvis, ribs, cranial bones, vertebrae, long bones of leg
adult: axial
vertebrae, sternum, ribs, pelvis
cytoplasmic ENZYME that is deficient in acute intermittent porphyria
uroporphyrinogen-1-synthase
aka porphobilinogen deaminase
which converts porphobilinogen to hydroxymethylbilane
Acute intermittent porphyria presentation
uroporphyrinogen-1-synthase
aka porphobilinogen deaminase
abdominal pain "port wine" urine polyneuropathy psychological disturbances precipitated by drugs
- barbiturates
- seizure drugs
- rifampin
- metoclopramide
Treat with glucose and heme, which inhibit delta- aminolevulinic acid synthase
delta- aminolevulinic acid synthase
rate limiting mitochondrial enzyme in heme synthesis
inhibited by glucose and heme
porphyria cutanea tarda
most common form of porphyria
primarily a skin problem
most common porphyria
presentation: blistering of skin photosensitivity tea- colored urine hypertrichosis facial hyperpigmentation associated with hep C and alcoholism
cytoplasmic enzyme: uroporphyrinogen decarboxylase
increased LFTs
mitochondrial enzyme inhibited in lead poisonint
ferrochelatase
ALA dehydratase
enzymes
protoporphytin and D-ALA accumulate in the blood
microcytic anemia (basophilic stippling), GI, colicky abdominal pain HA, neurologic issues
encephalopathy
memory loss
delirium
mental deterioration
foot/wrist drop
lead lines (blue/black lines on the gums)
hyperlucent lines on metaphasis (of children)
renal failure
Tx: EDTA, succimer
dimercaprol instead of succimer if severe in a child
polycythemia (relative and absolute causes of erythrocytosis)
relative= volume decreased absolute= too many RBCs
Absolute can be appropriate (hypoxia) or inappropriate (ectopic epo or cancer)
polycythemia vera- monoclonal proliferation of RBCs
Chronic hypoxia polymonary disease sleep apnea cyanotic heart disease high altitudes
inappropriate increase in EPO
EPO- inducing tumor
EPO- producing tumors:
Potentially Really High HCT
Pheochromocytoma RCC HCC Hemangioblastoma many trisomy 21 babies have polycythemia at birth
conditions that yield target cells
thalassemia
Hgb C disease
asplenia
liver disease
sideroblastic anemia
defective heme synthesis
ringed sideroblasts on bone marrow
causes:
hereditary form
chronic alcohol use
drugs (seizure drugs, isoniazid, chloramphenicol)
labs show increased iron and ferritin
Treat with B6
symptoms of folate deficiency
glossitis
increased homocysteine
normal MMA
NO Neurological deficits
symptoms of B12 deficiency
glossitis
neurologic deficits
increased homocysteine
increased MMA
microcytic anemia
swallowing difficulty
glossitis
Plummer-Vinson syndrome
microcytic anemia + >3.5% HbA2
beta thalassemia minor
megaloblastic anemia not correctable by B12 or folate
orotic aciduria
megaloblastic anemia plus peripheral neuropathy
B12 deficiency
microcytic anemia + basophlic stippling
lead poisoning
microcytic anemia reversible with B6
sideroblastic anemia. p.391
B6 is a cofactor for d-ALA synthase
HIV- positive patient with macrocytic anemia
zidovudine
drugs that cause sideroblastic anemia
seizure drugs
INH
chloramphenicol
drugs that cause nonmegaloblastic macrocytic anemia
5-FU
zidovudine
hydroxyurea
normocytic anemia with elevated creatinine
chronic kidney disease
uses for epo
cancer patients, ESRD, HIV infections
haptoglobin
binds free hgb in the blood (decreased in intravascular hemolysis). since haptoglobin does not bind up bilirubin with extravascular hemolysis you see unconjugated (indirect) bilirubin in extravascular hemolysis
warm agglutinins
extrinsic hemolytic normocytic anemia antibodies that react against RBC protein antigens at body temperature IgG seen in: 1. EBV (warm or cold), HIV 2. lupus 3. malignancies including CLL 4. congenital immune abnormalities
cold agglutinins
extrinsic hemolytic normocytic anemia
Cold weather is MMMiserable?
igM
Mycoplasma pneumonia infection
infectious mononucleosis (EBV)
CLL
Coombs test- direct
red cell agglutination with addition of antihuman ab
because RBCs are coated with immunoglobulin or complement proteins
positive in autoimmune hemolytic anemia
- hemolytic disease of the newborn
- drug- induced autoimmune hemolytic anemia
- hemolytic transfusion reactions
Coombs test- indirect
red cell agglutination with addition of patient’s serum to normal RBCs. This indicates that the serum contains anti-RBC surface Ig; RBCs agglutinate when Coombs reagent (antihuman abs) is added.
positive in autoimmune hemolytic anemia
- screen blood before transfusion
- screen maternal blood for anti-RBC fetal antibodies
Ham’s test
paroxysmal nocturnal hemoglobinuria
Heinz bodies
G6PD deficiency
vWF
several subunits linked by disulfide bonds
synthesized by endothelial cells and megakaryocytes
major functions:
-complexes with and stabilizes factor VIII (deficiency leads to increased PTT)
-PLT adhesion to vessel wall, and other PLC (defect leads to increased bleeding time)
lifespan of a PLT
8-10 days
What surface receptor is expressed after ADP is released from PLT, and is responsible for PLT aggregation
glycoprotein IIb/IIIa
NSAIDs prevent which platelet enzyme?
Thromboxane A2
what is the mechanism of streptokinase
converts plasminogen to plasmin
cleaves fibrin and breaks down clots
aspirin- mechanism
irreversibly inhibits COX-1
clopidogrel
blocks PLT ADP receptors
abciximab
monoclonal ab
binds glycoprotein IIb/IIIa on platelets
tirofiban
inhibits glycoprotein IIb/IIIa
ticlopidine
blocks ADP receptors
enoxaparin
LMWH, inhibits factor Xa
eptifibatide
glycoprotein IIb/IIIa inhibitor
HUNT for The Toilet Paper
TTP
Hemolysis Uremia Neurological symptoms Thrombocytopenia Fever TTP
Nasty Fever Torched His Kidneys
TTP
Neurological symptoms Fever Thrombocytopenia Hemolysis Kidney failure
HUS
hemolysis
renal insufficiency
thrombocytopenia
O157:H7 in children
anti GPIIB/IIIa ab
ITP. this is a chronic disease
ADAMTS-13 deficiency
TTP-HUS acute disease
GP2b/3a defect
Glanzmann’s thrombasthenia chronic
vWF defect
vWF disease chronic
widespread activation of PLT and coag cascade
DIC acute
gp1b defect
Bernard-Soulier syndrome
chronic
causes of DIC
sepsis trauma obstetric complications acute pancreatitis malignancy nephrotic syndrome transfusions (STOP Making New Thrombi)
where does leukemia come from
bone marrow
where does lymphoma come from
lymph nodes
compare the age distribution of Hodgkin lymphoma to non-Hodgkin lymphoma
Hodgkin has a bimodal distribution
peak age: 20
peak age: 65
NHL has a variable age distrubution
MC lymphoma in adults
diffuse large B cell lymphoma
MC lymphoma in children
lymphoblastic lymphoma
MC lymphoma in the US
diffuse large B cell lymphoma
Reed sternberg cells
Hodgkin lymphoma
particularly associated with EBV
Burkitt lymphoma, hodgkin lymphoma
associated with longterm celiac disease
intestinal T cell lymphoma
lymphoma equivalent of CLL
small lymphocytic lymphoma
starry sky pattern due to phagocytosis of apoptotic tumor cells
Burkitt lymphoma
associated with sjogren syndrome, hashimoto thyroiditis, h.pylori
NHL
marginal cell lymphoma -MALTOMA, an intestinal lymphoma
t(8;14)
Burkitt lymphoma
t(15;17)
M3 type of AML, treated with all- trans retinoic acid
t(14;18)
follicular lymphoma (BCL2 activation) always seen in CML
Philadelphia CreaML cheese
t(9;22)
Philadelphia chromosome (Bcr-Abl constitutively active TKR oncogene) responds to imatinib
t(11;14)
Mantle cell lymphoma (cyclin D1 activation)
t(8;21)
AML
This is why Down syndrome patients have a higher incidence of AML
gene mutation commonly implicated in myeloproliferative disorders
JAK2 (Janus kinase 2- growth factor signaling, constitutive due to mutation).
plethora
pruritis after hot bath or shower
monoclonal proliferation of mature myeloid cells (may be one or several cell types)
Polycythemia vera
increased RBC synthesis with low EPO (consider JAK2 mutation) this is a myeloproliferative disorder plethora pruritis after hot bath or shower splenomegaly hyperviscosity of blood HA erythromelalgia
Essential thrombocytosis
increased platelets with low thrombopoietin (consider JAK2 mutation) this is a myeloproliferative disorder)
thrombosis (too many platelets)
bleeding (the platelets the person has don’t work correctly)
myelofibrosis
fibrosis and obliteration of marrow space
causes tear drop shaped RBCs
note that this is different from aplastic anemia (adipocytes fill the marrow space)
multiple myeloma versus Waldenstrom
MM- IgG
Waldenstrom- IgM, no hypercalcemia, no renal involvement, no anemia, no lytic bone lesions, no back pain
Plasmacytoma
solid tumor of plasma cells
- solitary plasmacytoma of bone
- extramedullary plasmacytoma
do not cause lytic bone lesions
Monoclonal gammopathy of undetermined significance (MGUS)
monoclinal proliferation of plasma cells
asx
may lead to MM (1% per year)
no hypercalcemia, no renal involvement, no anemia, no lytic bone lesions or back pain
more than 20% blasts in marrow
acute leukemia
leukemia with more mature cells and
chronic leukemia
TdT(+) acute leukemia
ALL
commonly presents with bone pain
ALL
numerous basophils, splenomegaly, negative for leukocyte alkaline phosphatase (LAP)
CML
always positive for Philadelphia chromosome t(9;22)
CML
acute leukemia positive for peroxidase
AML (Auer rods)
solid sheets of lymphoblasts in marrow
ALL
Always associated with BCR- ABl gene
CML
