Heme-Onc

Front 1

What is the most common cause of an elevated homocysteine level?

Back 1

Folate deficiency

Front 2

What are some extopic sources of epo?

Back 2

renal cell carcinoma, hepatocellular carcinoma

Front 3

where is epo synthesized?

Back 3

the endothelial cells of the peritubular capillaries

Front 4

What is the retic count?

Back 4

measure of effective erythropoesis to compensate for anemia, hct/45%

more than 3% good, less than 3% not good

Front 5

Where does extra medullary hematopoesis most frequently occur?

Back 5

liver and spleen

occurs with myelofibrosis, or with accelerated destruction of RBCs (hemolytic anemia--> may expand the bone marrow)

Front 6

What is HbF, and what does it do to the oxygen binding curve?

Back 6

HbF is two alpha and two gamma chains, shifts the curve to the left (takes oxygen) -- this causes a release of epo

epo increases RBC, Hct and HGb

Front 7

Why are newborns jaundiced?

Back 7

the HgF is destroyed by splenic macrophages over the ensuing 6-9 months, the unconjugated bilirubin derived from the initial destruction is responsible for the physiologic jaundice

the HgF are replaced by HgA (97%), HgA2 (2.5%) and HbF (1)

Front 8

What are the changes in RBC counts with thalassemia?

Back 8

Decreased Hct and Hgb, Increased RBC count

Front 9

Hypochromasia

Back 9

Central Area of pallor on the Red Blood Cells, corresponds with a decreased Hg (microcytic anemia)

Front 10

Iron Deficiency Anemia

Back 10

increased RDW

decreased ferritin (diagnostic of iron deficiency), decreased percent saturation, INCREASED transferrin

Front 11

serum ferritin

Back 11

Diagnostic of Iron Deficiency (low levels)

ferritin is the primary soluble iron storage protein, seen in bone marrow macrophages

macrophages synthesis ferritin increases with inflammation due to IL-1 and TNF alpha

stored in bone marrow macrophages-- the serum levels of ferritin correlate with the level stored in

Front 12

What has increased serum ferritin levels?

Back 12

anemia of chronic disease and iron overload

Front 13

what is hemosiderin?

Back 13

insoluble degradation product of ferritin, the levels correlate with ferritin levels

Iron Deficiency: decreased ferritin, decreased hemosiderin

ACD and Iron Overload: increased ferritin, increased hemosiderin

Front 14

serum iron levels

Back 14

Iron bound to transferrin, the iron binding protein

transferrin is synthesized in the liver-- normal serum iron is 100ug/dL

Front 15

Decreased Serum Iron

Back 15

Seen in Iron Deficiency and ACD

Front 16

What is the relationship between ferritin and transferrin levels?

Back 16

decreased ferritin stores causes increased synthesis of transferrin

see increased transferrin levels in iron deficiency and anemia of chronic disease

Front 17

What is needed to make ALA?

Back 17

ALA synthase, Glycine and Vitamin B6

this occurs in the mitochondria

Front 18

What is needed to make heme?

Back 18

Iron plus protoporphyrin along with the enzyme ferrochetalase

this occurs in the mitochondria

Front 19

what does iron deficiency look like?

Back 19

decreased iron, decreased ferritin, decreased percent saturation, INCREASED transferrin level and RDW

Front 20

What would chronic alcholism do to a blood smear?

Back 20

Alcohol is a mitochondrial toxin, damamges heme biosynthesis pathways, causing sideroblastic anemia

Front 21

pyridoxine deficiency

Back 21

this is VB6; you need it as a cofactor to make ALA as a cofactor for ALA synthase, the rate limiting step in heme synthesis

Front 22

Thalassemia

Back 22

Autosomal Recessive

alpha thal- SE asians and blacks

beta thal: americans, greeks and italians

Front 23

what is the pathogenesis of alpha thal?

Back 23

gene deletions; there is a decrease in alpha golbin chain synthesis due to gene deletions of the 4 that control alpha globin synthesis

1 deletion: SILENT
2: alpha thal trait
mild anemia with increased RBC count, decreased HbA, HbA2, HbF (normal electrophoresis bc all Hg require alpha chains, proportion is the same) --> no treatment

3 deletions: HbH the four beta chain disease--> severe hemolytic anemia, electrophoresis detects HgH

4 deletion: Hb Barts-- no life

Front 24

what is the pathogenesis of beta thal?

Back 24

mild: it's a splicing defect
severe: stop codon

Front 25

release reaction

Back 25

when the platelet sticks, it releases chemicals (ADP and Thromboxane A2)

platelet is the ONLY cell that can make TXA2

Front 26

Functions of TXA2

Back 26

potent vasoconstrictor (what causes prinzemetal angina coronary spasm)
causes platelet sticking
bronchoconstrictor

Front 27

Mast Cells preformed chemicals

Back 27

histamine
esosinophilic chemotactic factor
serotonin


later on, releases prostaglandins and leukotrienes to enhance the inflammatory mediators

Front 28

thrombocytopenia

Back 28

less than 90,000 platelets

vWF (most common genetic AD--1 in 250) have it

taking aspirin causes prolonged BT

Front 29

Aspirin

Back 29

Endothelial cells have COX, but aspirin doesn't inhibit this. The platelet COX is a different compound

9 times greater inhibition of platelet COX than the endothelial COX

Front 30

Thrombin

Back 30

converts fibrinogen into fibrin

thrombin is generated by the coagulation pathway-- and will convert the unstable plug into something more stable

Front 31

plasminogen

Back 31

will break up the clot

Front 32

platelet abnormalities

Back 32

petechia, prolonged BT, ecchymosis, epistaxis (nose bleeds)

NONE of these occur in a coagulation deficiency

Front 33

Hemophilia

Back 33

has problems with LATE bleeding

after an appendectomy-- the platelet plugs are only temporary

if you don't have any problems after a wisdom tooth extraction, you've had no problems with coagulation

Front 34

bleeding time

Back 34

normal is about 7-9 minutes

cut vessel, release tissue thromboplastin (later activates extrinsic pathway)

expose collagen
activates (12, intrinsic)

endothelial cells and megakarocytes make vwF (a part of factor VIII) so platelets carry some glue with them, vwF is also made in the endothelial cells, damaged endothelial cells, vWF is exposed. vwF is exposed so that platelets can stick, and releases chemicals, ADP a POTENT aggregator, along with Thromboxane A2, which ends the bleeding time. clot formed

Front 35

ADP

Back 35

potent aggregator released by platelets

Front 36

Thromboxane Synthase

Back 36

only in platelets-- PGH2--> TXA2

TXA2 is a potent vasoconstrictor which helps platelets to stick. TXA2 causes the prinzmetal angina in coronary artery spasm. It's also a bronchoconstrictor.

Front 37

Platelet Plug

Back 37

temporary plug, held together by fibrinogen. Enough to prevent bleeding, but it's not stable

Front 38

Prolonged bleeding time

Back 38

Thrombocytopenia-- less than 90,000
Taking Aspirin (blocks platelet COX)
vwF deficiency: 1 in 250 people have this

Front 39

aspirin

Back 39

taking one, NONE of your platelets will work, no TXA2 around, no aggregating

bleeding time is around 15-20 minutes

Front 40

Who removes the platelet plug?

Back 40

plasminogen