CHAPTER: Heme Onc Flashcards by Logan Kolakowski

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

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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

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Fe def anemia

Where absorbed in GI
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

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Connect Plummer Vinson syndrome to Fe def anemia

PV triad:
Fe def anemia
Esophageal webs -> dysphagia

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Disease that produces HgH

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

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Disease that produced HgBarts

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

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Patho RBC seen in B thal minor

B/B+, ↑2 alpha, 2 delta (Hgb A2)

TARGET CELL

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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)

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Treat B thal major

Blood transfusions

SE: hemochromatosis

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2 enzymes blocked by lead poisoning

2 RBC findings of lead poisoning

ALAD - can’t get precursors out of mitochondria
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

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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)

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3 ways to treat lead poisoning

Dimercaprol
EDTA
Succimer to chelate kids

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Causes siderblastic anemia

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

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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)
Degen
1. Spinocerebellar = ataxia
2. Lat corticospinal
3. Dorsal column = X position + vibration sense
+ parasthesia (pins + needles)

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

Schilling
Diet: prolonged vegan
Malab: Crohn’s, diphyl latum, gastritis

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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
Alcoholism

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

AML

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

SICKLE CELL 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?

Work 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

``` Disease: Painful ab Port wine urine Polyneuropathy Psych changes Precipitated by drugs (P450 inducers) ```

Acute intermittent porphyria (PP syn => heme syn) AD X PB deaminase ↑ALA 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

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

``` AD 1. AIP 2. P cutaneous tarda 3. VWB disease 4. Spherocytosis (mom + whit) AR 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 NO Heparin like mol = ↑anti thrombin 3 tPA ↑s plasmin Thrombomodulin ↑protein C ```

RS cell markers

2 eyes x CD 15 = 30 | B cell origin