Path Winter 2 Rbc I

Front 1

what is...

1. RBC count
2. MCV
3. Hct
4. Hgb

Back 1

1. RBC count: # RBC/Unit volume

2. MCV: mean corpusccular volume, measures the size

3. Hct: RBC x MCV

4. Hgb

Front 2

whats a band PMN

Back 2

immature PMN, means there is infection adn we are kicking them out!

Front 3

what are some general normal values

1. Hbg
2. Hct
3. reticulocyte
4. MCV

Back 3

12-15 Hgb
30-50 Hct
reticulocyte 1%
80-100

Front 4

what is:

1. Microcytosis
2. macrocytosis
3. hypochromic
4. polychromatophilia
5. hyperchromia

Back 4

1. Microcytosis: small RBC (MCV <80)
2. macrocytosis: large RBC (MCV >100)
3. hypochromic: decreased MCH, increased central pallor
4. polychromatophilia: means we get reticulocytes (early RBC) they arent quite mature and are a little blue
5. hyperchromia

Front 5

what is it called when there are lots of bluish early red cells

Back 5

reticulocytes, polychromatophilia

Front 6

whats a spherocyte
whats a sickle cell

Back 6

spherocyte: small, round dense, no central pallor

sickle: curved banana shape

Front 7

when do you get a Heinz body, what is it

Back 7

G6PD deficit

**precipitate of Hgb. blue dot around the membrane

Front 8

whats the progenitor line of blood cells

Back 8

1. Pluripotent: can be ANYTHING gives rise to myeloid and lymphoid

2. Multipotent: mydloid nad lymphoid

3. Lymphoid: Plasma, T, NK
4. Myeloid: all others: eosinophil, macrophage, granulocytes, platelets, RBC

Front 9

what are hte hematopoietic GF

Back 9

EPO
GM CSF
G CSF
thrombopoietin

**acts on pluripotent nad multipotent stem cells

Front 10

what is the normal fat to hematopoietic cells in BM

Back 10

1 to 1

shoudl be just as many fat cells as hematpoietic cells

**when we have hematopoies fat cells disappear

Front 11

what is the normal myeloid to erythoid ratio in the BM

Back 11

myeolid: erythroid= white: red
3:1

more white than red

Front 12

what lab vales define anemia

Back 12

decreased O2 capacity, low Hct and Hgb

can be:
blood loss, inpaired red cell production or increased destruciton

Front 13

what are common clinical features of ALL anemias

Back 13

1. pale, weak, fatigue
2. dyspnea on mild exertion
3. brittle concave nails
4. anoxia --> fatty change in liver, myocardium, kidney
5. acute blood loss/shock --> little pee
5. HA, faintness, dim vision

Front 14

what are 3 major groups of anemias as determined by underlying cause

Back 14

1. blood loss
2. increased destrucion
3. decreased production

Front 15

explain a bit of the pathogenesis of blood loss anemia

Back 15

sx can be from low volume rather than decreased Hgb

water shifts from interstitium to vessels to replace volume--> decreased HCT

decreased O2 to tissues --> EPO release --> Marrow responds and reticulocyte increases

Front 16

if you survive a gunshot wound, what changes do you expect in CBC 10 days after

Back 16

increased reticulocyte count

*body has decreased O2 so EPO is stim and we get more BM activity

Front 17

what can happen with chronic blood loss

Back 17

anemia

**Fe reserves can be depleted

Front 18

wht are the 3 major features of hemolytic anemia

Back 18

1. premature destruction of red cells (shorten life span) can be intravascular or extravascular

2. accumulation of Hgb catabolism products (seen in pee and serum)

3. increase in erythropoiesis within BM (reticulocyte count will increase)

Front 19

what are 5 features of intravascular hemolysis

Back 19

1. anemia
2. hemoglobinemia
3. hemoglobunuria
4. jaundice
5. hemosiderinuria
6. DECREASED serum haptoglobin

Front 20

what happens to the serum haptan levels with hemolytic anemia

Back 20

decreased

*the haptoglobin binds to hgb in plasma. its being tied up so levels decrease

Front 21

what are the 3 features of extravascular hemolysis, what is seen with extravascular but NOT intravascular hemolysis

Back 21

1. SPLENOMEGALY- not seen in intravascular (the RBC are weird shaped and so get trapped in the spleen)

2. anemia/jaundice

3. plasma haptoglobin is decreased (it is bound up to Hgb in plasma)

Front 22

what happens in the BM and peripheral blood in cases of hemolytic anemia

Back 22

BM: reticulocytosis, decreased O2 --> increased EPO. more red to white (no longer a 3:1 W:R ratio)

Peripheral:

**increased bilirubin --> gallstone formation

Front 23

waht does increased bilirubin levels lead to, why might levels be high

Back 23

gallstone formation

**hemolytic anemia

Front 24

hemolytic anemias are broken into what classifications

Back 24

1. Intrinsic: problem with the RBC
-spherocytosis
- G6PD deficit
- SS
- thalasemmia
-PNH (acquired, all previous were genetic)

2. Extrinsic: not a problem with RBC

Front 25

what are the intrinsic hemolytic anemias

Back 25

1. GENETIC
-ss
-G6PD
-thalasemmia
-spherocytosis

2. Acquired
- PNH

Front 26

what causes heridetary spherocytosis

Back 26

intrinsic defect in the RBC, its inherited and is prevalent in Northern Europeans

**the membrane is defective bc of defective ankyrin in the cytoskeleton

Front 27

what protein is deficient in spherocytosis

Back 27

intrinsic genetic, hemolytic anemia
autosomal dominant

**ankyrin deficit makes the membrane bad

**cells get really round and will get stuck in teh spleen

Front 28

what does the molecular defect in HS (heriditary spherocytosis) lead to in the red cell

Back 28

the defect is in ankyrin, a protein in the cytoskeleton so the membrane of the RBC is bad. it gets round and then gets trapped in spleen.

Front 29

what is seen on the peripheral smear in spherocytosis

Back 29

small round red cells with no central pallor (microcytic)

big blue reticulocytes (polychromatophilia)
**spleen enlarges
**increased reticulocytes

Front 30

what happens to the spleen in spherocytosis

Back 30

gets big, the RBC with the bad membrane get small and round and cant squeeze through the spleen anymore

**splenectomy helps releive anemia but increases risk of infection with encapsulated organisms

Front 31

what are 3 clinical features of spherocytosis

Back 31

splenomegaly
reticulocytosis (polychromophilia)
haundice

can get gallstones from icnreased bilirubin
**common features of anemia: pallor, fatigue,

Front 32

what is the difference btwn aplastic and hemolytic crisis

Back 32

Aplastic: parvovirus. body stops making red cells

hemolytic crisis: RBC are lysed

**both can be seen in spherocytosis

Front 33

how is spherocytosis dx

Back 33

family hx (its an intrinsic genetic hemolytic anemia)
sphere shaped small RBC with no central pallor
osmotic fragility of RBC

**tx with splenectomy

Front 34

what procedure is beneficial to the patient with spherocytosis

Back 34

splenectomy

**the spherocytes can still carry O2 but they are being stuck in and destroyed by the spleen. this is bad news. if we take out the spleen we have less issues with anemia but increased risk for encapsulated organisms

Front 35

a 6 yo male presents with sore throat and mild scleral icterus. PE shows jaundice and splenomegaly. Hgb is 9 and HCT is 20%. Reticulocyte count is 14%. total biliruben is 4.5 and direct is 0.4. The pts uncle had a splenectomy

whats the dx, whats the significance of uncles splenectomy

Back 35

spherocytosis

**splenectomy helps releive anemia

Front 36

in hemolytic disease due to red cell enzyme defects what happens to the red cell which leads to hemolytic disease

Back 36

you get oxidative stress nad the cell cant protect itself from free radical damage

**its the hexose monophosphate shunt/glutathione reductase
**inherited

Front 37

what is the most important enzyme defecit in hemolytic disease 2 to enzyme defect

Back 37

G6PD

the normal is G6PD B
**abnormal is G6PD A and G6PD medeterranian

**these cells cant protect themselves from free radical oxidant damage

**midfolding of the protein
**inherited

Front 38

what 2 forms of G6PD result in hemolytic anemia? do these alterations have an upside

Back 38

G6PD B
G6PD medeterranian

**they are maintained alleles in the environment bc they protect against maleria

Front 39

most commonly with G6PD defecit we see hemolysis after what?

Back 39

oxidative stress. the protein G6PD is milfolded and so loss of function

drugs: primaquine, chloroquine, sulfonamides, nitrofurantoins
infection
Fava Beans

Front 40

what is a heinz body

Back 40

seen in G6PD defecit

**oxidant damage leads to hemolysis when the enzyme G6PD is misfolded
**the denatured Hgb forms PPT on teh cell membrane and can lead to intravascular hemolysis (different than spherocytosis which is an intrinsic defect with the membrane)

Front 41

what 3 clinical features are seen 2-3 days after an individual with G6PDA or G6PD medetrerranian is exposed to oxidant stress

Back 41

1. Hemoglobinemia, hemoglobinuria and decreased
hematocrit

2. old cells killed

3. hemolysis stops when there are only young cells left

Front 42

what is the course of hemolysis in G6PD defecit

Back 42

self limited

**its an issue with folding of G6PD B/medeterranian
**young reticulocytes are ok so only the old cells are lysed after all of that hemolysis of the old cells happens its ok

Front 43

how is recovery ID in an individual with G6PD defecit

Back 43

reticulocytosis, more RBC being made to replace the lost ones

Front 44

is G6PD...

1. hemolytic, blood loss, impaired production

2. intrinsic or extrinsic

3. genetic or acquired

Back 44

intrinsic genetic hemolytic disease

always a self limited disease bc young cells arent lysed

Front 45

if you have a person who takes a sulfa drugs and then becomes anemic for a short time what is goind on

Back 45

G6PD defecit

Oxidant damage 2 to:
1. Drugs: "quines" & sulfa
2. infections
3. fava beans

initiate hemolysis of OLDER RBC

Front 46

what is the disease that is an inherent problem with the RBC membrane

what is the disease where you get build up on the membrane which leads to damage

Back 46

spherocytosis

G6PD- heinz bodies form as an accumulation og Hgb breakdown

Front 47

in G6PD do we have intra or extravascular hemolysis

Back 47

BOTH

Intravascualr: heinz bodies on RBC membrane

Extravascualr: spleen picks out the bad parts of the RBC membrane

Front 48

what is the fundamental defect in SS anemia

Back 48

inherited intrinsic hemolytic disease

**Hgb is structurally abnormal in b globin chain and is called HbS (HbA is normal)

Front 49

what globin chain is affected in SS

Back 49

beta --> HbS (HbA is normal)
*single point muitation in 6th posistion

Front 50

what does HbS do when deoxygenated. is this reversible

Back 50

they aggregate and polymerize

**this sickling is initially reversible, when it reoxygenates the HbS depolymerizes and the normal shape returns

**after repeate episodes the sickling is irreversible

Front 51

what affect the rate of sickling? what can decrease the rate of sickling

Back 51

**the amt of HbS determines the amt of sickling!!!

**HbF can inhibit the polymerization of HbS. this is why kids present at about 2 yo

Front 52

what happens due to vascular occlusion in SS disease

Back 52

infarct of tissue

Front 53

a 15 yo black male is in ER with bone pain. Recurrent episodes since 2 years old. pts bro adn father have sickle gene.Father has simliar pain. Pts Hgb is 8

whats the deal

Back 53

SS disease

**HbF protects inflants. it inhibits polymerization of HbS

Front 54

what protects against maleria

Back 54

G6PD b/medeterrainian
HbS (Sickle cell)

Front 55

what is sort of the pathogenesis of SS

Back 55

well a cell has a point mutation at position 6. when the RBC deoxygenates it polyperizes and aggregates. Initialyl after it gets more oxygen the shape comes back but after repeated episodes of this there is permanent damage.

When HbS precipitates there is oxidative damage to the sickled AND normal cells, this creates STICKY cells that can cause microocclusions

Front 56

what happens to bone in SS
what happens to BM
what happens to the spleen, early and late

Back 56

BONE: new bone growth

BM: active and hyperplastic. lots of red cell precursors

Spleen: early enlarges then late it infarcts and shrivels up

Front 57

what 3 things cause the anatomic alterations seen in SS

Back 57

1. chronic hemolysis (intra and extravascular) this leads to hyperplastic BM and increased bone growth

2. Increased release of Hgb so increased biliruben so risk of GALLSTONES

3. Capillary stasis and thrombosis: infacts in bone, brain, kidney, liver, retina etc. Leg ulcers

Front 58

what are the 2 major consequences of HbS

Back 58

1 chronic hemolytic anemia
2. vasoocclusions --> ischemic tissue damage

Front 59

how does the presenence of HbS lead to chronic amemia

Back 59

well its intravascular hemolysis bc of mechanical fragility

extravascular hemolysis bc the cells are weird shaped and so are sequestered by the slpeen

Front 60

ok so we know vasoocclusive crisis in SS leads ultimatly to tissue ischemia but what else

Back 60

abnormal cell membranes (also seen in G6PD with heinz bodies)
increased adhesion molecules- STICKY
microvasculature narrows
SS cells trapped


**NO and decreased due to binding and inactivation by released Hgb from Sickled cells

Front 61

when might you see a crew cut on x ray

Back 61

when pt has SS

**there is destruction of RBC so BM is ACTIVE! new bone formation. BM is hyperplastic

Front 62

what does peripheral smear of SS look like

Back 62

there will be a sickled cell

b globin is messed up so we get HbS

Front 63

in what disease is autosplenectomy common

Back 63

SS

**the spleen will be enlarged in kids but then we get lots of infarcts which is damaging and the spleen self kills and gets little and small

Front 64

if you have a 3 yo black male with a bulging fontanelle and TONS of joint pain whats the deal

Back 64

SS

**the BM becomes realyl active and thats why the skull bulges. its a "crew cut" on x ray

**also see expanded marrow in thalassemmia

Front 65

what are 4 features of SS disease lead to problems in the patient

Back 65

1. anemia
2. vaco-occlusive prblms
3. increased bilirubin --> gallstones
4. increased susceptibility to infections (esp encapsulated bacteria bc spleen isnt working ex pneumococci adn H influenza)

Front 66

what is a vasoocclusive crisis (pain crisis)

where is a common site

Back 66

specific to SS

**episode of hypoxia/infarct
**not ppt by anything in particular
**common in bone, lung, liver, brain, spleen, penis

Front 67

what is sequestration crisis and in whom does it occur

Back 67

seen in SS (contrast to an aplastic crisis which is seen in SS as well as spherocytosis)

**kids with large spleen there can be a MASSIVE sequestration of deformed red cells that leads to hypovolumia and shock

Front 68

how is SS dx

Back 68

HCT 18-30%
reticulocytosis
sickled cells on smear

Hgb electrophoresis shows HbS

Front 69

what are the treatment options for SS

Back 69

hydroxyurea to increase conc of HgF. HgF- prevents HbS polymerazation

Hydroxyurea also:
anti inflammatory
increases MVC--> decreased [HbS]
increased NO

Front 70

who is susceptible to H influenzea and pneunococci

Back 70

ppl w/o spleen

**SS- autosplenectomy
**spherocytosis

Front 71

if you think a kid is having vasoocclusive crisis what must you rule out

Back 71

osteomylitis, pts with SS are prone to infection (i think salmonella causes osteomylitis in ss pts)

Front 72

what does this describe and in what disease is it seen

**kid with splenomegaly has a massive sequestration of red cells and gets hypovolumic nad shocky

describe another type of crisis

Back 72

sequestration crisis, unique to SS

**contrast to an aplastic crisis when there is TEMPORARY stop in BM activity. usually caused by pavovirus. causes a rapid worsening of anemia nad stop in reticuocytosis

Front 73

the following can ppt what kind of crisis

1. Primaquine, chloroquine
2. parvovirus
3. decerased O2 tension
4. exposure to cold
5. transfusion

Back 73

1. Primaquine, chloroquine- G6PD
2. parvovirus- aplastic crisis. spherocytosis, SS (contrast to sequestration crisis which is SS)
3. decerased O2 tension- SS
4. exposure to cold
5. transfusion

Front 74

what things affect degree of sickling?

Back 74

1. amt of HgS
2, Hg conc in cell (MCHC)
3. decrease pH (decreased O2 affinity to Hgb
4. decreased O2 tension

Front 75

describe the coombs (DAT) test. what does a + result look like

Back 75

1. human serum injected in rabbits
2. rabbit makes Anti human Ig, anti human complement (whatever you put in the serum) this is the coombs serum
3. you then add the coombs reagent that is anti human with pts RBC that has AG on it
4. Agglutination occurs when the RBC AG are the same as the antihuman junk. POSITIVE TEST

**+ when AB coat cells in vivo (body)

Front 76

what is this...

1. antihuman globin is added to patients cells
2. agglutination occurs bc pts cells were coated with AB IN VIVO (in the body)
3.

Back 76

direct coombs test

seen in:
‐ Autoimmune hemolytic anemia;
cold agglutinin disease
‐ Hemolytic transfusion reaction
‐ Hemolytic disease of newborn

Front 77

what is indirect coombs test

Back 77

1. pt serum- IgG, blood group antibodies is added to RBC with KNOWN AG. this makes in vitro sensitized RBC (the RBC gets AB in the tube)

2. in vitro sensitized RBC added to antihuman IgG

3. agglutination

**used for AB screen, + means atypical AB are present

**pt serum is incubated with reagent cells with known AG

Front 78

what test uses RBC sensitized in vitro

Back 78

indirect coombs

Front 79

what is the only acquired intrinsic hemolytic anemia

Back 79

PNH

Front 80

the synthesis of what is decreased in thalasemmia

Back 80

a or b globulin chain of HbA

**diff than sickle, in SS its abnormal globin. thal is a decrease in it

Front 81

what are hte 2 types of thalasemmia

Back 81

alpha- deletion

beta- point mutaion. decreased b globulin, excess a globulin chains

Front 82

what things happen to the red cell that causes problems in thalasemmia

Back 82

low intracellular Hgb
relative excess of unpaired chain (remember HbA- normal is 2a and 2b, so if we are mission one of these the other builds up)

Front 83

what is reduced and what is in excess in b thal erythroblast

Back 83

decreased b globin

excess a globin chain

Front 84

what is ineffective erythropoiesis, what disease is it associated with

Back 84

when BM doest work!! cant compensate

**apoptotic death of red cell precursors in BM

Front 85

what happens to red cells that escape the BM in thalasemmia

Back 85

they have a globin aggregates in them and hte spleen degrades them

Front 86

what does increased EPO levels in thalassemia cause

Back 86

the marrow expands and we get skeletal deformities

Front 87

what is abs in excess in thalassemia

Back 87

Fe

Front 88

paired b globin synthesis contributes to anemia in b thal in what ways

Back 88

1. no HbA formation, pale cells

2. decreased survival bc of a/b chain mismatch

Front 89

in what thal are there a globin ppts that damage the cell membrane and creates aggregates that leads to their destruction by the spleen

Back 89

beta

Front 90

at are the 3 tpyes of thalasemmia and what are their classifications based on

Back 90

Major
Intermedia
Minor

**based on genetic defect and gene dosage

Front 91

b thal major manifests at what age, why

Back 91

6-9 months bc this is when we switch from HgF to HbA

**in b thal we cant make b chain
*Hbg is like 3-6 LOW
**reticulocyte count is elevated but there is ineffective erythropoiesis

Front 92

what is seen on the peripheral smear of b thal

Back 92

small pale cells

microcytic, hypochromic

Front 93

what is the morph of b thal

Back 93

1. BM expands bc EPO is high

2. spleen is large (unlike SS it stays big, in ss it infarcts nad dies)

3. excess Fe that damages heart, liver, pancreas (hemosideroisis, 2nd hemachromatosis)

Front 94

what is the clinical course of b thal when no tx is provided

Back 94

die bc of growth retardation

**NEED transfusions

Front 95

what is the tx for b thal

Back 95

transfusion, but we are already getting tons of Fe so we also need chelators

**cure with BM transplant

**face gets big, liver/spleen enlarge

Front 96

why is it important to recognize b thal minor

Back 96

trait offers protection against maleria (same as ss adn other)

**need to recognize the trait so you can distinguish it from Fe deficit

Front 97

what are hte 4 clinical syndromes of a thal

Back 97

silent carrier
a thal trait
HbH disease
Hydrops fetalis

**classified according to the number of a glubin genes deleted

Front 98

what does hte severity of a thal depend on

Back 98

how many a globin chains are affected (deletion, b thal is point mutation)

**anemoa from lack of adequate Hgb and from effects of unpaired NON a CHains (in b we had unpared a but in a thal we have more than just unpaired b)

Front 99

what are the non a chains in infants and adults (excess unpaired chains)

Back 99

infants: barts Hgb

Adults: HbH

Front 100

describe the diseases for a thal- range from silent carrier to HbH to hydrops fetalis.

lets talk HbH

Back 100

HbH is the excess unpaired glibin chains in adults

it has a really high O2 affinity so is no good for exchange

**older red cells with PPT of HbH are removed by the spleen

Front 101

what are hte non a chaings in a thal

Back 101

1. infants: barts Hgb. gamma globulin tetramer

2. Adults: HbH


**more soluble than unpaired b chains so a thal is less severe than bets

**DELETION

Front 102

what is hydrops fetalis with a thal

Back 102

deletion of ALL 4 a globin genes

fetus is pale and edematous