CHAPTER: Heme Onc Flashcards Preview

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Flashcards in CHAPTER: Heme Onc Deck (38):

What is the difference between ornithine transcarbamylase def vs UMP synthase defect?

Orotic aciduria = UMP synthase problem
- AR
- Kid who presents with megaloblastic anemia that doesn't respond to B12 (cobal) or B9 (folate) supplements - WHY? because these are the 2 things you think of causing this problem, but the issue generating pyrimidines is actually converting orotic acid -> UMP
Difference = NO hyperammonemia
Treat: + UMP
OTD - orotic acid AND ammonia high in urine


What is Diamond Blackfan anemia

Defective erythoid precursor cells -> anemia before 1 yo
Normocytic `anemia - aka low total Hgb but of that, higher percentage HgF (2a, 2g) than expected
Short stature
Craniofacial abnormalities
UE deform = 3 joints in the thumb


Fe def anemia
1. Where absorbed in GI
2. Symptoms

@ duodenum - unlikely you'd lose your duodenum in surg - instead think GASTRECTOMY b/c less acid ↑Fe 3>2 (less absorbed)
Fatigue + pallor
**PICA, spoon nails


Connect Plummer Vinson syndrome to Fe def anemia

PV triad:
Fe def anemia
Esophageal webs -> dysphagia


Disease that produces HgH

3 mutated alpha alleles (chr 16)
Tetramers of beta form = HgH
Severe alpha thal anemia (RBC damage)


Disease that produced HgBarts

4 mutated alpha alleles (chr 16)
Tetramers of gamma
Fetal hydrops


Patho RBC seen in B thal minor

B/B+, ↑2 alpha, 2 delta (Hgb A2)


You know that B thal major means no B globin. Therefore, get tetramers of alpha once babies lose gamma globin. SO what does this mean for clinical picture

A2A2 causes RBC damage - don't all make it out of bone marrow
Body sees ANEMIA -> ↑EPO = bone marrow hyperplasoa
1. Crew cut skill XR, large facial bones
2. ↑spleen + liver size (↑risk parvo b19 infection)


Treat B thal major

Blood transfusions
SE: hemochromatosis


2 enzymes blocked by lead poisoning
2 RBC findings of lead poisoning

1. ALAD - can't get precursors out of mitochondria
2. Ferrocheletase - can't join PP + Fe to make heme
Fe builds up in mitochondria (where would be joined) *ringed sideroblasts*
Fe overloaded state explains the lab findings:
↑ferattin, ↓TIBC, ↑serum Fe ↑% sat
Can't breakdown rRNA - basophilic stipling


LEAD of lead poisoning

Lead lines - gums + bones (blue-ish)
Encephalopathy (headaches, memory loss)
Ab pain // constipation
Drops - wrist and foot (b/c peripheral demyelin)


3 ways to treat lead poisoning

Succimer to chelate kids


Causes siderblastic anemia

1. ALAS defect - X linked - 1st step PP synthesis
2. Myelodysplastic syndromes
3. Alc = mitochondrial poison, mito steps don't work
4. B6 def
5. Isoniazid - why you give B6 with iso to prevent complication


Name the difference in the labs + presentation of B9 vs B12 def causing megaloblastic anemia

B9: ↑homocysteine only (THF regen), no neuro
B12: ↑homocysteine + methylmalonic acid (FA breakdown)
1. Spinocerebellar = ataxia
2. Lat corticospinal
3. Dorsal column = X position + vibration sense
+ parasthesia (pins + needles)


Dx cause of B12 def as malab vs diet insuff with what test?

Diet: prolonged vegan
Malab: Crohn's, diphyl latum, gastritis


Disease: megaloblastic anemia w/ orotic acid crystals in urine
Presents as kid w/ growth delay, weakness

Orotic aciduria
HUGE clue is orotic acid in urine
UMP synthase problem -> can't make UMP (pyrimidine)
Supplement: uridine + cytidine (U/T + C = pyrimidines)


What are you thinking if the macrocytic anemia is isolated aka not megaloblastic with normally segmented neutrophils

It's not a problem with DNA synthesis
Liver disease


Name what gets absorbed at all 3 parts SI

Duodenum - iron - iron def anemia
Jejunum - fat + folate - fat sol vitamin def + megaloblastic macrocytic anemia
Ileum - B12 - megalo macro


How does ↑ferroportin cause anemia in chronic disease

Binds ferroportin - can't bring any in @ SI
Anemia starts normo -> micro (b/c ↓Fe)


Anemia caused by pyruvate kinase def

RBC only tissue affected b/c ONLY use glucose for E (no mito)
PEP -> pyruvate nets 1 ATP in glycolysis
↓ATP -> rigid RBCs = extravas hemolysis = normocytic anemia


Which disease has target cells w/ Hgb crystals next to it

HbC disease
Crystals look like RBC turned on side - all red
B globin mutation (therefore also chr 11)
Glutamic acid -> lyCine
Target cells -> extravas hemolysis


If RBCs don't have CD 55, what disease will they have?

*Acquired* no GPI to anchor DAG/MIRL (CD 55/59)
Can't resist complement
Coombs test is negative b/c no Abs
Night time - breathe less - ↑CO2 = resp acidosis = activates complement


High risk complication for PNH

GPI mutation is in the stem cell - 1 mutation increases likelihood of another


What is the sickle cell mutation and why does it make RBCs sickle

B chain: valine instead of glutamic acid
Allows hydrophobic interaction so Hgb precipitates -> sickling


Howell Jolly bodies + +/- target cells + renal papillary necrosis makes you think of what disease

HJ bodies: nuclear remnants (asplenia)
Target cells if progressed to asplenia (repeated infarcts)
Renal pap necrosis b/c ↓O2 to papilla
Blood in urine b/c kidney medulla infarcts


Is the change to the spleen in hereditary spherocytosis hyperplasia or hypertrophy?

Make more cells to deal with massive extravasc hemolysis


Is sickle cell intravasc or extravasc hemolysis

EXTRA - the body trying to remove sickled RBC
A sickle crisis intravasc isn't about bleeding at all -> infarct
↓Haptoglobin tho b/c small amt intravasc hemolysis


Whats coombs direct vs indirect

DIRECT: RBCs already coated with Ig, bind the Ab vs Ig you add
INDIRECT: add RBC to serum to see if anti-RBC Ab is present


Cold vs warm agglutanins - what are they, disease that cause them - what kind of anemia do these diseases have

Abs vs RBC - will show + Coombs
Ab + RBC complex goes to spleen = extravasc hemolysis
Cold = IgM = mycoplasma, infectious mono (EBV = + monospot, CMV = - monospot)
Warm = IgG causing chronic anemia in SLE + CLL


What is TTP

Ab vs ADAMS T12
Can't breakdown VWF
Causes microangiopathic hemolytic anemia (same idea as HUS)
Abnormal thrombus (drop platelets) -> shistocyte RBCs
Intravasc hemolysis + clotting at same time


Painful ab
Port wine urine
Psych changes
Precipitated by drugs (P450 inducers)

Acute intermittent porphyria (PP syn => heme syn)
AD X PB deaminase
Treat: glucose + heme


Tea colored urine + photosensitivity aka blistering skin rash

Porphyria cutanea tarda
AD X URO decarbox - ↓heme
↑porphyrin (just didn't get all way down to step to make protoP) -> deposits in skin = free rad damage = photosense


What is the difference between Glanzmann thrombasthenia + immune TCP

Glanz = X GP 2b3a = normal platelet count, quality problem
Immune TCP = Ab vs GP 2b3a - causes destruction of platelets = ↓ platelet count
Both ↑bleeding time


Why does PTT rise in VWB disease

VWF stabilizes F8 - without, ↓F8 = ↑PTT


Acute intermit porphyria
Porphyria cutaneous tarda
VWB disease
Hereditary spherocytosis
Pyruvate kinase def
G6PD def
Orotic aciduria

1. AIP
2. P cutaneous tarda
3. VWB disease
4. Spherocytosis (mom + whit)
1. Pyruvate kinase
2. Orotic aciduria
X recessive = G6PD


Why do you bridge coumadin patients with heparin

Prevent skin necrosis = result of hypercoag state after lose C + S first


Name 5 substances secreted by endothelium to stop clotting normally

PGI2 Xs platelet agg
Heparin like mol = ↑anti thrombin 3
tPA ↑s plasmin
Thrombomodulin ↑protein C


RS cell markers

2 eyes x CD 15 = 30
B cell origin