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378 Cards in this Set

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3A intro and approaches to anemias
3A intro and approaches to anemias
WW causes of anemia?
iron deficiency- other nutritional deficits (vit A- B vit)- malaria- hookworm- HIV-AIDS- TB
what effects does anemia have on childrens' development
slower
what is anemia and what three things may be abnormal
reduced red cell mass lower Hb- lower Hct- or lower number of RBCs
what factors may influence the hematocrit?
dehydration may influence total volume. or leukemia may increase WBC proprtion
what two internal factors determine a rbc survival/what three external factors?
internal: maintain shape and osmotic integrity. external: antibodies- toxins- spleen- bleeding
would the hemoglobin binding curve be shifted left or right in a person adapted to live at high altitude?
it should be shifted RIGHT
why do red cells need active metabolism
they need it for glutathion/free radical reductase and to make hemoglobin
what is the methemoglobin raction? why do rbcs need a metabolism?
to put Fe in ferrous (+2) vs ferric (+3) state to bind o2
how long do normal rbcs last?
120 days
what organ produces the hormon for more rbcs and what is the stimulus/response?
kidney makes EPO to signal bone marrow to make more RBCs- stimulus is hypoxia OR anemia
what are four possible causes of anemia
kidney disorder- loss of EPO sensitivity in marrow- a decreased production/release of RBCs from marrow- or shorter than normal RBC survival (lost vs destroyed)
what are three classifications of anemia
decreased RBC production- hemolysis (RBC degradation)- or bleeding
what color do reticulocytes appear/how are they different from RBCs
reticulocytes are slightly bluish
what does the supervital stain do?
stains RNA dark in reticulocytes. special stain just for them
why do you not get iron def anemic with hemolytic anemia but you do with bleeding?
you are not iron deficient in hemolytic because the iron stays in your circ when the RBCs are destroyed- whereas when bleed it leaves
what's a normal reticulocyte count
0.5-2%
if a pt is anemic with low reticulocytes then they
have a marrow or erythropoietin disorder- eg low iron
if a pt is anemic with high reticulocytes then they
have a helathy marrow- trying to compensate for bleeding or hemolysis
why use a corrected reticulocyte count
(if marrow working high- could get uncorrected 10%- 20%) this is corrected for lowered number of RBCs in anemia. if the corrected number is below 2% the marrow has some degree of insufficiency
what are fundamental building blocks of hemoglobin needed in marrow
iron- folate b12
what might cause low EPO
kidney disease
what might cause deficiency of red cell precursors
low iron- folate- or b12. basically- if the marrow isn't working
what might cause a fatty marrow with low reticulocyte count- low WBC and platelets? what's this called and how do you treat it?
this is called aplastic marrow (low cellularity)/marrow hypoplasia. could give blood transfusion. could be caused by radiation. usu idiopathic although can react to drugs also
what are two location classifications of anemia?
intrinsic (lacking normal RBC- usu inherited eg sickle cell) or extrinsic (splenomegaly- prosthetic heart valve)
which are the most common causes of anemia?
iron deficiency- hemolysis- bleeding
what are words for smaller- bigger than normal RBCs?
microcytic- macrocytic
what are steps in workup of anemia
blood smear for RBC shape- reticulocyte count- histoy (Aids- bleeding family)- phys exam for underlying disease
what four things may anemia symptoms be attributed to?
low O2 to tissues- a cardiac/pulmonary response- hypovolemia of blood- or underlying dz
at what hb level do you experience symptoms with exercise? symptoms in daily living?
8-10 exercise- <8 dialy living
what results from low O2 delivery in anemia
pallor of skin nailbeds conjunctivae- fatigue- light headedness
what are cardiovascular symptoms
rapid pulse- dyspnea heart failure
what are 5 symptoms of hypovolemia (eg on a battlefield)- would you get these with an ulcer or GI bleed
pale- cold- rapid HR- low BP- dizziness. less likely with slow belld bc more time to compensate
with what type of anemia might you see jaundice and why?
hemolytic anemias due to breakdown of heme (bilirubin)
why might symptoms of acute anemia be unrelated to hemoglobin?
could be related to underlying cause eg blood in stool colon cancer or battlefield shock/hypovolemia due to loss of blood
3b morphology of anemia
3b morphology of anemia
what is a normal WBC
4k to 11k per ul
What's most practical way to classify anemias
by their size (MCV)
platelets normal value
150k to 400k per ul
red blood cell normal
3.8 to 5.3 mill Female 4.3 to 5.8 mill male
hemoglobin normal
11.8- 15.5 g female 13.5 - 17.5 g male
mcv normal
80-100 fl
hematocrit
36-46
where is the proper place to evaluate a wright blood smear
between the head and tail
what is polycythemia
when there are too many red blood cells?
what is RDW suggestive of?
High variation in size even if the mean cell volume is normal
spherocyte
suggests 2 dzs: spectrin dfect causing hereditary spherocytosis or autoimmune hemolytic anemia if older pt. have a LOT of hemoglobin in spherical cells
schistocyte
fragmented- helmet or wedge-shape
macroovalocyte
large and oval.
what are four causes of microcytic anemia
iron deficiency- chronic inflammatiory anemia- THALASSEMIA- sideroblastic anemia
what is basophilic stippling and what diseases does it suggest?
it is bluish pallor due to persistence of RNA- it suggests high reticulocyte production eg thalassemia vs. iron deficiency. iron deficiency are more hypochromatic
what is increased diameter of central pallor called?
hypochromasia- usua ssoc with iron deficiency
what is typical presentation of iron disease
microcytic hypochromic anemia
what are four causes of normocytic anemia
sickle cell- hemolytic anemia- blood loss anemia- chronic disease (also microcytic if severe) or very mild iron deficiency
what is the only RBC morphologic clue specific for certain disease
sickle cell but can't exclude just having TRAIT
how do polychromatic blood cells look compared to normal
sort of more blue- like a reticulocyte- stains RNA blue
what might you see in TTP and why?
microangiopathic hemolytic anemia
what are three causes of macrocytic anemia
B12 deficiency- folate deficiency- and myelodysplastic syndrome
what is a clue to macrocytic RBC presence
If they are bigger than nuclei of a lymphocyte
what are hypersegmented neutrophils indicative of?
b12/folate deficienct
what are hypo-lobated hypo-granulated neutrophils suggestive of?
myelodysplastic syndrome
What exactly is myelodysplastic syndrome
on the way to leukemia - abnormal cell maturation but not cancer yet
what is a leptocyte
an unusually flattened RBC
what is likely diagnosis with low RBC and hypochromasia- microcytic RBCs
iron deficiency anemia
what is likely diagnosis with low RBC- high MCV- progressive fatigue macrocytic- multisegment polynuclear-
b12 deficiency/folate
what is likely diagnosis for MCV 90- mean cell hematocrit 37- low RBC- abundance of reticulocytes? spherocytes- hyperchromatic-
autoimmune unless younger kid because hereditary spherocytosis
3C Iron flow- deficiency- and anemia of inflammation
3C Iron flow- deficiency- and anemia of inflammation
put these in order from most iron to least iron: transferrin/cytochrome- hemoglobin- ferritin/hemosiderin- myoglobin
hemoglobin- ferritin/hemosiderin- myoglobin- cytochromes/transferrin
what has highest Fe turnover
transferrin bound iron
where is most iron absorbed
duodenum (1mg/d)
what protein carries iron in the bloodstream and what three places can it go?
transferrin and it can go to the liver- bone marrow to make RBCs
what is DMT1
the iron entry protein - takes across the membrane
what is transferrin
the carrier protein (its receptor is located on the sirface of red cells
where are transferring receptors located?
on surface of rbcs
what is ferritin and what cells is it found in?
in enterocytes - storage form in the blood - binds Fe2+ then goes in circulation until it gets to cells where it bigns to receptor and is phagocytosed
what is the difference in stability between low iron and high iron regarding stability of the transferrin receptor mRNA
at low iron- the transferrin receptor mRNA is more stable based on iron regulatory proteins (IRP) while ferritin i degraded
why is pregnancy associated with anemia
baby needs iron
what groups should you consider for iron deficiency anemia
pregnant- young kid (too much milk)- picky eater; growing kid- menstruating woman. RAPID GROWTH=INCRESED DEMAND
what are the two types of iron sources named- which is better absorbed- what facilitates absorption
heme and iron of plants. 15% heme iron is better absorbed THAN 3%plant. Vit C enhances iron absorption
what three factors can cause decreased absorption of iron
tannins/bran/fiber/calcium - disrupted mucosa as in crohn's - or achlorhydia from PPIs- surgery
why might diverticuli or hemhorrhoids or NSAIDS be associated with anemia
these increase blood loss
what is angular stomatitis? koilonychia- what color are the sclerae?
koilonychia=spoon nails- sclearae are bluish- pallor of conjunctiva. angular stomatitis=rash at corner of mouth.
what are two signs of reduced iron store (early)
decreased marrow iron- decreased ferritin
what four signs of depleted iron stores
increased TIBC- low plasma iron- low transferrin sat- and elevated soluble transferrin receptor (IS THIS DUE TO mRNA stability?)
what stage would be associated with decreased Hb and decreased MCV>
true iron deficiency anemia
why is RDW elevated in iron deficiency anemia
new red cells are small and older are bigger. also might see higher platelets
would you expect to see normal- low or high reticulocytes in iron deficiency anemia
high reticulocytes bc lot of turnover due to EPO. also see high RDW and hypochromasia
what are the names for the diseases of decreased globin synthesis
the thalassemias
what shapes of RBCs are suggestive of decreased globin synthesis
pencil or teardrop shape common
what are five possiblities if you have microcytic anemia
iron deficiency- lead poisining- sideroblastic (problem putting iron into red cells) anemia- chronic inflammation- or thalassemia
how is iron deficiency usually treated
1)oral ferrous sulfate to replete stores (2mo past correction)- slow release form fewer Sfx but may have lower absorption. can also give parenteral iron or IV infusion.
what developmental effect of iron deficiency
development and behavior changes- lower immunity- work performance- developmental effects
with what chronci diseases is anemia associated?
chronic infection- lupus- cancer- trauma- ulcerative colitis- regional enteritis
what process is defective in anemia associated with chronic dz?
transfer of iron from reiculoendothelial macrophages to transferrin is broken. so the STORAGE iron is GREATER. Ferritin is ELEVATED unlike in deficiency anemia. also reducied EPO and shorter RBC lifespan
what is hepcidin
a protein made in liver- antimicrobial activity- increased in inflammation and with high iron levels. it's like an antiiron protein which binds ferroportin- degrades it- preventing iron's door from the gut form opening
what does inflammation do to hepcidin levels and why?
it increases them because it's antimicrobial. any acute infection may cause anemia
Diff btwn iron def and anemia of chronic infect
TIBC high in iron def- ferritin/bone marrow Fe low. Whereas TIBC maybe low in ica- ferritin/bone marrow iron HIGH.
3D B12 and folate deficiency
3D B12 and folate deficiency
what are morphologic characteristics of megaloblastic anemia
increased N/C ratio and increased hypersegmentation of neutrophils. immature nuclei in RBCs
describe N/C ratio
it decreases as cells mature. if you're B12 deficient- the nucelus gets bigger
what are five causes of megaloblastic anemia
folate deficiency- cobalamin- acute megaloblastic anemia- drugs- inborn error. all lead to imbalance in nucleus to cytoplasm
How are b12 and folate dificencies related in megaloblastic anemia
they both result in decreased DNA synthesis- causing rapid cytoplasm maturation and slow nuc maturation and effect eryhtrocytes
what is vit b12 bound to in the body
intrinsic factor or Rbinders (temp) OR transcobalamin II (uptake in cells)
why is vitamin B12 necessary for DNA synthesis
it's a cofactor for mTHF to THF rxn which is requred to convert dUMP to dTMP nucleotide. basically it converts RNA precursor into DNA precursor. protein synthesis is OK
what do R proteins/binders do
may dispose of B12 analogs. compete with IF
how do you get b12
it lives in dirt- synth by a bacteria- cows wat and as we eat them we get b12. we can also get it from eatting dirt. usu NOT nutritional deficiency
what is cobalamin
vit b12
how do you absorb b12
parietal cells make intrinsic factor (along with stomach acid)- helping transport through bowel system. IF competes with R-binders- not as good at binding in the stomach's acidity but better at end of digestive sys because proteases cause its release from R-binders in the small bowel. essentially: two chances for IF to bind B12
what might pernicious anemia- a gasterectomy- zollinger-ellison syndrome-
these are all gastric causes of cobalamin deficiency. ZE is a type of cancer where you generate too much stomach acid and you never neutralize Rbinders.
what causes pernicious anemia
autoimmune against parietal cells- lack of intrinsic factor causes b12 deficit- pernicious anemia
what are intestinal causes of cobalamin deficit
ileal resection (crohn's)- blind loop syndrome- fish tapeworm. vegetarianism a MINOR cause
what are key proteins in B12 transsport
IF- pancreatic enxymes destroy R binders- transcobalamine II transporter- liver storage
what is the schllings test
basically- this test asks- at what level can you correct their defect - eg give radioactive B12 and IF- see if corrects- if so- IF deficit
what is pernicious anemia and what types of pts may be comorbid with it?
An IF deficit. diabetes- thyroid- hypotparathyroid- ulcerative colitis- vitiligo- OR autoantibodies may cause this
what are signs of megaloblastic anemia
tired- CHF (due to increased output demand)- pallor- jaundice- epithelial lesions (tongue!!) think rapidly dividing cells
ethnic groups prone to pernicious anemia
northern europeans and african americans
what is combined systems disease
sensory/proprioceptive defect and unable to walk bc can't feel feet
why are there neurologic symptoms associated with cobalamin deficiency
demyelination causes combined systems disease (irev) can't feel feet- paresthesias
how do you treat cobalamin deficiency (what should you NOT do)
DON't transfuse. Instead treat with B12. you CAN give folate- but WON'T solve neurologic deficit. Folate solves anemia ONLY.
why DON't give transfusion
their anemia occurred REALLY slowly- their heart is pumping a TON- and then you give MORE blood- you may trigger acute heart failure. SO MUST CHECK B12 in megaloblastic anemia
what are only two things you should give RBCs for
active bleeding and low hemoglobin- OR iron deficiency anemia without too much volume
what symptoms are not adequately treated by high dose folate
neurologic aren't treated
how are vit b12 and folate associated
b12 catalyzes activation of THF (folate)
what could you be concerned about in old age- poverty- alcoholism- hemodialysis- preemies- or goat's milk anemia- pregnancy
FOLATE deficiency
what dz is nontropical and tropical sprue assoc with
folate deficiency
what drugs might cause folate deficiency
methotrexate- 5FU- hydroxyurea- anticonvulsants- OCs. ALL impair DNA maturation
what are inborn errors of cobalamin
imerslund grasbeck- congenital IF deficit-
what are inborn errors of folate metabolism
congeinital folate malabsorption DHF reductase deficit- homocysteine
what is the RBC count in megaloblastic anemia?
depressed- because they are rapidly dividing.
ileal reseaction- blind loop syndrome- or a fish tapewrom result in
pernicious anemia
3I Neoplasia 3
3I Neoplasia 3
what type of gene results in growth stimulation subsequent to a loss of function
tumor suppressor
what's an oncogene
requires only 1 hit to turn on tumor
what is Ras an example of?
It's a cytosolic protein that carries downstream signals from the EFGR tyr kinase- and if mutant can cause cell proliferation
How can FISH be used to demonstrate oncogenic activity of a Ras translocation?
HSR 9homologous staining region
region of gene amplification
**What is the EGFR gene product duplicated and what ELSE must be mutant to cause cell proliferation
Would a Ras mutation causing cancer be expected to increase or decrease GTPase activity?
DECREASE bc active form is GTP bound
What's the active form of Ras
Ras-GDP
What does Myc do and would it be expected to be over or underactivated in cancer?
oncogene. overactive. normally it makes repressors of the cell cycle, so no block in the G to S transition.
what is myc
a protein that activates the cell cycle and represses cell cycle repressors- when it's active it's an oncogene. Ras phosphorylates and activates myc
Describe the mechanism of Burkitt's lymphoma from the myc gene
Basically chromosomal translocation changing regulator of myc causing increased expression of c-myc and speeds cell cycle- less differentiation- more telomerase- less adhesion
what type of genes are associated with point mutations- amplifications and translocations
oncogenes
what type of genes are associated with methylation and why?
tumor suppressor
what is the inheritance pattern for hereditary retinoblastoma?
autosomal dominant
is hereditary more likely to be uni- or bilateral and why?
bilateral (hit earlier in life)
is the RB1 gene likely to be a tumor suppressor or oncogene?
Tumor suppressor because require two hits to one cell to develop cancer - even in hereditary form
What two ways might the RB1 protein be mutatn
Most are due to erroneous transcript production- but 10% of sporadic may be due to hypermethylation and thus inactivation of DNA
what does methylating do to DNA
it inactivates it
what do CpG islands mean for DNA and would they have greater effect on tumor promoters or suppressors
these are locations for methylation of DNA and they should have a greater effect on suppressors
What other strategy might turn off a perfectly functional RB1 gene?
cdks phosphorylate to inactivate
what do cyclins (cdks) do to rb
they phosphorylate it- removing the rb block on the G to S transition
are cyclins and cdk4s oncogenes or tumor suppressors?
they are oncogenes if broken in phosphoyrylate on
What are 3 DNA tumorviruses
adenomvirus- polyomavirus- and papillomavirus
How are tumorviruses associated with cancer?
their oncoproteins bind to Rb OR p53 and inhibit them (mimic cyclin or cdk4)
What does the RB1 protein normally do?
It represses transcription factors that tend normally to move through the cell cycle
3J Hemoglobinopathies
3J Hemoglobinopathies
How many O2 can one heme subunit bind? How many can one hemoglobin molecule then bind?
1..4
Is the curve higher affinity if shifted right or left?
left
What allosteric modifiers shift the curve right to give the molecule less affinity
heat acidity, 2,3 BPG which a product of glycolsis
What does 2-3 BPG do to O2 affinity of hemoglobin and why?
It should decrease it. A byproduct of glycolysis??
What type of mutation are hemoglobinopathies caused by?
null product so deletional or nondeletional but prevent expression
What type of mutations are thalassemias
nondeletional - just misformed product
are deletional mutations more common in a or B genes?
deletional more common in alpha genes but of course there are two genes, not one like B
describe some ways in which B genes can be modified
can be Bo or B+, if B+ has some level of transcript present
What three steps in mRNA processing might lead to defective B globin?
splicing and polyadenylation and the 3'UTR must mediate stability
why is HbA2 important?
If it's elevated above 3 then likely to have some kind of thalassemia - it's the
Any significant phenotype with a thal (hint: B4)
HbH is a disease due to 4Bs associating soluble, but are destroyed at a greater rate than normal
3M hemoglobinopathies and thalassemias
3M hemoglobinopathies and thalassemias
Look closely at the Hb electrophoresis and make sure oyu understand
What is a thalassemia
What characterizes thalassemia and what predicts their severity
what type of anemia si produced in thalassemia
where are hotspots for thalassemia? assoc with what dz?
What is deficient in a thalassemia and what stocks up as a result
what is HbH? what is the a genotype?
What is deficient in B thalassemia and how is the resultant product DIFFERENT from in a-chain
SO you can't get a+ but you can get B+? weird
what is cooley's anemia?
Bo/Bo
When you measure the weird hemoglobins- do you use the same measurement tests?
What is notable about the spectrum of thalassemias
What do splenomegaly- microcytic yet hypochromatic RBCs- normal iron but elevated bilirubin- poor growth and endemic area suggest
woop woop severe B thalassemia
Why does a chain preciptiation lead to prodound anemia? what can you say about blood iron levels?
How does hepatosplenomegaly result in B thalassemia
what causes cardiac- hepatic- endocrine tissue damage?
iron overload due to ineffective erythroid progenitors
what cell shapes are specifically associated with B thalassemia
what does anisocytosis mean
variation in cell sized
what characteristic morphology of b-thalassemia trait
microcytic hypochromic
DOES THE a TRAIT LOOK DIFFERENT?
What two causes of low MCV will you see commonly>
Iron deficiency anemia and thalassemia
What allows you to distinguish B thalassemia form iron deficiency
What is the HbA2 level in thalassemia? In iron deficiency?
High in thalassemia and low in iron def.
would you expect thalassemia to have higher or lower retics?
What's the difference between major and minor B thalassemias?
What is standard of care for B thalassemia
what does desferal do?
3L hematopathology Lymphoma Overview
3L hematopathology Lymphoma Overview
What is the difference between reactive disorders and neoplastic disorders
neoplastic are clonal
what's the difference between leukemia and lymphoma
leukemia is disseminated in blood whereas lymphoma is solid masses in organs but this distinction not definite
what difference between acute vs chronic leukemia/lymphoma
acute=blast cells, chronic=mature lymphocytes. may somewhat correlate with speed of disease
what is a lymphoma
a nodular tumor of one of the lymhoid organs eg speeln, thymus lymph node
describe where lymphocytes and plasma cells are found in the normal lymph node
medulla=plasma, cortex=lymphocytes,
what is a secondary lymph node
one where the germinal center has been activated and B cells are proliefarting
what is the difference between hodgkin and nonhodgkin lymopha
hl is a different type of lymphoma which spreads from node to node. NHL is mostly Bcell tumors but some T cell tumors and plasma
how do you distinguish size of lymphocytes
small cell are size of normal lymphocytes while large cell are size of histiocyte nuclei
what is the immunophenotype and why is it used?
it's the molecules expresse don the surface of the cell and it tells you what type of progenitor cell population your B cell came from
how can immunophenotype distinguish bening and neoplastic?
on an immunoplot there are all molecules of one type (eg all with k chain, eg)
what molecule marks immature B cells
Tdt (and cd19)
what marks mature B cells
CD20 (and cd19)
what do CD10 and BCL6 identify? what is NOT expressed by these cells?
germinal center cells. BCL2 should NOT be expressed in these cells unless there has been a translocation
What cell type is CD3 specific for?
immature T cells
What call type is CD19 specific for?
B cells
What does surface Ig say about a cell?
it can tell you whether the cell population is clonal or not
would you be concerned about B cells expressing CD5?
CD5 is normally on T cells. B cells expressing CD5 likely malignant
What information does a genotype of a lymphoma give you?
tells you about its mechanism of disease
why are mature B cells more prone to neoplasm than T cells?
they undergo two additional rearrangements that T cells do not
what is a normal cell counterpart in the context of a lymphoma?
normal cell counterparts are identified based on morphologic characteristics, geno
what are type B symptoms of a lymphoma?
fever chills night sweats
What are kappa and lambda chains
they are part of the immunoglobulin chain and may indicate clonality of a cancer type
what does it say if cancer found in bone marrow
bad sign since normally there is not hematopoeisis in the bone marrow
What are two causes of microcytic anemia
iron deficiency or B thalessemia
How can you tell the difference between Iron deficiency and B thalessemia
Iron level diagnostic Higher retics and higher A2 in B thal
How can you tell between Bo and ao
Look and see if she has any A2 hemoglobin. If yes, then B major (Bo) if no then a thalessemia
treatment
chelator of excess iron and packed RBCs
What are three forms of B thal
minor (trait), intermedia (above 50%) major - Bo/Bo
What is different between sickle cell trait and sickle cell disease
they nly have one abnormal B globin gene an dit's benign
What is the mutation in sickle cell disease
missense resulting in a Glu to val subsitution
Why do you see problems if HbS is a normal O2 transporter?
when HbS is deoxy, it forms polymers which can disrupt cell shape
Describe what causes aggregation of HbS
the change of acidic acid to a nonpolar Val, causing trend toward aggregation
What is the log jam model of SCD? What is added currently?
that the sickled cells can't get through small vessels, ADDED=rheology-flow, rbc dehydration, cell adhesion
How does delay time affect HbS formation? What affects delay time?
slight changes in conc of hemoglobin has a huge impact in how fast RBCs sickle so if they're more dehydrated they sickle faster
What is relationship between NO and HbS
Burst cells allow their hemoglobin to scavenge NO which can no longer relax vessels
Explain some organ consequences of sickle vasoocclusion
skin ulcers, neuro=stroke, pulm hypertension, MI, immunologic problems because spleen infarcts
What are four SCD crises?
acute chest (fat emboli); splenic sequestration=fatal anemia; aplastic crisis secondary to parvovirus=anemia, vasoocclusive crisis
What are treatments
underlying cause eg infection, oxygen, last resort RBC transfusion
Why might inducing fetal y globin be a good treatment
hydroxyurea increrases Y glbon because it makes sure that the hemoglobin is excluded from polymer
what's important for chronic SCD re: prevention
folate; vaccination, penicillin
What are Hb, MCHB, MCV in SCD?
anemic mild but normal other two. Weird cell morphology only
What type of Hb might be elevated in SS
HbS
What are key differences in HbA levels between sickle cell trait and scd?
SS can't produce hemoglobin A. AS can make 60% HbA and 40%HbS. If not this split, there's something else going on!!!
3N Hemolytic anemias
bilirubin
What 3 factors to consider a hemolytic anemia
stable/dropping Hb despite more RBC production and no bleed
How can reticulocytes be used to monitor hemolytic anemia?
if theyre hight be hemolytic anemia
What forms bilirubin?
Bilirubin is formed from heme breakdown
What binds free heme and what two organs may be involved in its disposal (hint the second one is if there are no blood binders)
haptoglobin and hemoplexin. Albumin binds ferri heme. These three are processed in the liver, but if binding capacity exceeded, start excreting in urine
Why is decreased serum haptoglobin and increased bilirubin suggestive of hemolytic anemia
these are breakdown and transport proteins for heme. Also increase retics
What are five non-immune mediators of hemolyisis?
microangiopathy, hypersplenism, infection, toxins, and venoms
What type of RBCs show up in hemolytic anemias
schistocytes=fragmented red cells
How does the Coombs (DAT) test work?
BOUND antibodies are tested by this by adding antisera which would measure these antibodies and clump
What's the difference between indirect and direct Coombs test?
indirect is for circulating antibodies if all of your RBCs have been destroyed, you can still find the Ab in the serum
Where do spherocytes come from?
Spherocytes CAN come from phagocytic cells chomping off bits of the membrane, OR due to internal protein defects
What is autoimmune hemolytic anemia a common sequelae of?
cold, illness
List four symptoms of autoimmune heolytic anemia
jaundice, anemia, splenomegaly, reticulocytosis
what's an appropriate treatment for autoimmune hem anemia
In whom are cold reactive anti-red cell antibodies found?
IgM antibodies are produced which can cause mild to moderate hemolysis by fixing complement to RBC surface The Coombs test will be positive for complement.
What is heriditary spherocytosis a disease of?
normally spectrin and ankyrin give its shape, but can have mutations, get trapped in spleen and destroyedcomplications gallstone from bilirubin, red cell aplasia, leg ulcers
Why is splenectomy treatment for spherocytosis?
because then you remove the thing that's destroying the RBCs
what is g6pD? Why do certain drugs given to G6PD patients induce hemolysis?
Sex-linked Enzymoptahy that causes hemolysis in response to infection OR drugs. Primaqine (fava beans) antimalarial caused soldiers to hemolyze. RBCs with Heinz bodies are destroyed in the spleen.
3N Nonhodgkin's Lymphoma
What is the progenitor cell of small B cell NHL?
What is the most common NHL
Follicular lymphoma 45%
What are clinical features of FL? (eg, how fast, involvement?)
cervical lymphadenopathy, BM involvement hematogenous spread stage IV disease, indolent, liver and spleen involvement
How is the spleen affected in follicular lymphoma?
Painless diffuse splenomegaly (manifest as early satiety) in contrast to aggressive lesions which form masses
What peripheral blood features are seen in 10% of patients?
small celaved cells (centrocyte) and
What is the prognosis for FL? What potential problem?
indolent slow-growing so hard to eradicate but may transform
Where do FL come from (what were they doing before?)
They were in the GC
Describe a neoplastic FL lymh node
It can be nodular or
What cell morphologies are predictive of aggressive behavior?
centroblasts and diffuse nodules
What characteristic bone marrow growth pattern is diagnostic of FL?
paratrabecular groth rather than just rampaging through the whole bone
What is different about immunophenotype on B cells in FL?
They express BCL2+ and are kappa or alambda restricted
How do FL cells behave diferently in germinal centers than normal B cells
they don't grow fast but they don’t die due to persistence of BCL2
What's a cytogenetic hallmark of FL?
t14 -t18
What are clinical features of CLL/SLL (Blood symp, BM involvement, immune dysregulation?)
frequent blood involvement common cause of adult leukemia, indolent to aggressive, interstitial bone marrow involvement, TWO TYPES (1 and 2)
How swiftly does it progress/transform?
Richter's transformation possible with poor prognosis, some indolent some rapid, hard to tell who's who?
What are morphologic characteristics of CLL/SLL
not known origins, but has smudge cells which are in peripheral smear
What cells are characteristic of CLL/SLL
erase normal architecture of follicels, bu has pseudoproliferation centers vs follicles, can have diffuse marrow growth unlike FL
What is unique about the immunophenotype of CLL/SLL
They are B cells but they express Cd5+ which is a T cell marker
What may act as tumor suppressor in CLL/SLL (better progrnosis)
there may be miRNAs which act as tumor suppressors (13q)
Which form of CLL/SLL does better? Why?
Distinguish btwn group 1 (unmutated grIgV, less mature) VS group 2 hypermutated Zap70-, have traversed germinal center, have hypermutated IgV. Group 2 are LESS AGGRESSIVE
What are three types of marginal zone lymphomas?
Nodal, extranodal (MALT), or splenic. From B cells that have TRAVERSED the germinal center
What can MALT be associated with
Assoc with chronic infection-helico, campylo, skin borrelia, orbit chlamydia. The spleen MAY be assoc with hep C
What's MALT prognosis?
indolent slow-growing so hard to eradicate but may transform
What are two histologic features of MALT
Larger than normal marginal zones with a tropism for invading/destroying epithelial structures
Immunophenotype of MALT?
Nothing significant but they are Cd10-, BCL6-, BCL2+
Two key factors of MALT biology (antigen, spread)
first clonal expansion due to inflammatory stimulus, then can become stimulus independent by translocation
What translocation in MALT?
Normally upregulation of NFKB which causes accum of B cells in MALT lymphoma. t11.18 Cells grow too much and don't die.
How to treat MALT? 1st and 2nd
1st treat underlying infection (cut off chronic inflmmation). ANTIBIOTICS. OR 2nd can treat spread from mucosa to mucosa (tumor spread) readiation chemo
what is characteristic MALT spread pattern
mucosa to mucosa infrequent marrow involvement
3S Multiple myeloma
What cells is multiple myeloma from?
MM comes from plasma cells and is associated with the bone marrow
What is unique about the epidemiology of multiple meloma?
Most common in AA and increasing
Immunophenotype of MM (remember this is different from other B cells and is not technically a lymphoma)
CD138 syndecam as well as NCAM to stick to marrow
Where do you find MM?
bone marrow and also lymph nodes
pathology of MM
Flame cells (express IgA) and Mott cells (large glops of fat like a pearl necklace around the cell)
What are clinical features of MM?
MM cause extensive bone remodeling and anemia due to marrow replacement. Osteopenia/hypercalcemia. lytic bone lesions in axial skeleton! Painful. Anemia due to marrow replacement
what chromosomal activating mechanism for MM?
deletions of 13q
What is paraprotein and how does it have its effects?
aka M (for monoclonal) protein, oversecreted antibody by the cancerous cell, usually these are IgG or IgA, cause renal failure due to cast nephropathy, anemia, immunodeficiency bc only make one kind of Ig
amyloidosis
when the paraproteins bind together in plaques and settle out in some organs
How does MM have its effects?
Light chains can pass through the urine alone (called Bence Jones protein, measure of disease severity). Can block renal tubules in "tubular casts" also die of immunodef
what is bence jones protein
light chain in urine and marker of MM progress/recurrence
Describe what's unique about two pathogetic mechanisms of DLBCL
two ways: either progression of another lesion or de novo
What two lymphomas are aggressive type
Burkitt's and DLBCL
What is typical presentation of DBLCLs and how does this affect their grading?
They tend to present at a single site, quick growth, so pain. Better prognosis
What lymphomas is associated with fish flesh (discuss architecture)
DLBCL is fishflesh, cells not set up to organize
which type of DLBCL does better
the germinal center B cells (GCB) do better than activated B cells (ABC)
Describe the malignancy of Burkitt's lymphoma, is it curable?
it is very rapidly malignant and curable bc of this
Where is Burkitt's lymphoma (nodal or extranodal)
i think both, wherever
Describe each of the three variants of Burkitt's lymphoma
endmeic, sporadic, immundeficiency
What is link between EBV and Burkitt
the endemic forms usually have EBV in them - EBV drives B cell proliferation always found in african variants. other two have lower association with EBV
What disease may develop with ct14:18 and what gene is activated?
Burkitt. c-myc is activated causing cyclin activation
what are the main differences between endemic, sporadic, and immunodeficient burkitt's?
endemic is in africa facial, viral associated, sporadic may be associated abdominal masses more common, immunodeficient=HIV assoc
why is burkitt's both an emergency and rapidly responsive to treatment?
it doubles quickly but this also means it's very responsive to therapeutic agents
What cells produce the histologic pattern seen in BL and what's the pattern called?
starry sky pattern and they are called tingible body macrophages
What tumor might have hgih Ki67 and why?
BL because it's very proliferative
what's the difference between follicular lymphoma a Burkitt's in terms of proliferative drive?
FL has low proliferative drive but has BCL2+ which means it's lost ability to apoptose, whereas BL has high proliferative drive due to myc translocation
how does overexpression of cMYC happen and what cancer is this specially associated with?
BL is associated with cMYC translocation in fron to fthe light an dheavy chain loci
3T Hodgkin lymphoma
What are key differences in lymphoma and leukemia
lymphomas tend to have focal masses and staging. leukemias present with bone marrow failure. diagnostic difference-lnode bipsy vs bone marrow aspirate
What are two similarities between HL and NHL
painless lymphadenopathy, constitutional symptoms BUT different prognoss, spread pattern, prognosis much better for HL
what's diff btwn acute and chronic
depends if neoplastic block comes before blast or after
what' s unique about age spread in Hodgkin
bimodal (15-30) and greater than 50. mostly a disease of young adults
what are diagnostic features of HL
orderly spread, unifocal, reed sternberg owl cells, effaced architecture of LNs, pleomorphic infiltrate,
where do reed sternberg cells come from
B cells
cytokine soup
Reed Sternberg cells secrete cytokine soup to cause the other cells to come in night sweat symptoms predispose to constitutional symptoms
what two classifications of HL and describe the more common
Classical 95%, with four subtypes: nodular sclerosis, lymphocyte rich or poor, or mixed cellularity
which HL classification has diffuse or nodular growth, rs cells, mononuclear/lacunar CD45-, static IgH genes
classical HL. (nodular lymphocyte predominant HL)
which subtype of classical HL is strongly associated with fibrosis
nodular sclerosis
Which type of HL is most common in young? second most common?
young is 70% - and nodular sclerosis, good survival. females, mediastinal.
Describe the pathology of HL
fish flesh appearance (custanrd, eg yolk), with a lot of fibrosis, also look for reed sternberg cells
What determines staging of disease
how many regions in the body and whether they are on the same or different sides of the diaphragm
What is early stage treatment
radiation OR chemo alone, combo.
what are chemos used for HL
MOPP or ABVD but toxicity includes 2ndary AML, pulmonary fibrosis. sterility. more often ABVD
what late stage treatment
chemo ALWAYS very bulk
3V Bone Marrow Overview
3V bone marrow overview
What are anemia polycythemia
anemia too few RBCs, polycythemia too many
what is the difference between thrombocytosis/thrombocytopenia
cytosis too many platelets, penia too few
what's the difference between leukocytosis/ leukoopenia
cytoisis=toomany, penia too few
how is bone marrow used in cancer
as a measure of disease progress (stage IV)
where do you withdraw bone marrow/complications
posterior superior iliac spine
what marrow is associated with cellular trabeculae
cancer of follicular lymphomas
describe organization of bone marrow normally
normally the myeloid cells are clumped close to the trabeculae and the erythroid and megakaryocytes are closer to the center
why might you be unable to identify FL or HL fmor a bone maarrow smear
FL: lose paratrabecular organization of cancers, HL can't see the fibrotic regions because they don't aspirate
Describe patterns of chromatin transition and granules within the cytoplasm
chromatin goes from tiny spots to circles or lines, while the NC ratio increases
What cells can be confused with megakaryocytes and how to tell difference
osteoclasts - but these are true multinucleate
what can be confused with lymphocyte
osteoblasts - but can tell apart byprotrusional nuclei and polygonl cytoplasm
what are 2 different categories of bone marrow failure anemia
pancytopenia/isolated OR inherited/acquired
what can ethanol toxicity result in
acquired decreased erythropoeisis
what does bone marrow look like in failure
marked hypocellular marrow (lots of fat) in aplastic anemia
why wouldn't you expect to see increased lymphopoeisis in bone marrow
normally reactve lymphopoeisis occurs only in peripheral blood
if you see a neutrophil with a Dohle body, what's in it and what can you condlude about origins of neutrophilia
Dohle body is proteins, vacuoles, and RNA and these usually arise from sickness
what is MPD
myeloproliferative disorder, espansion of all cells or just a few eg (polycythemia vera RBC expansion)
what is the diagnosis if you have 20% of more blasts in your blood
AML/ALL which cause clonal expansion of different cell lines
Difference between Myeloproliferative disease, leukemia,
MPD is clonal expansion of hematopoeitic stem cell lines (1 or more) including differentiationwhereas leukemia is block in differation and decrease in apoptosis leading to oncrease of progenitor cells in blood and LOW regular cells in blood
What type of lymphocyte do you see in EBV
wedge shaped downey cells - they're NK cells or monocytes
what infiltrate in cml
neutrophils
basophilic stippling=dohle body