Anemia, Nutritional ASPHO Flashcards
1
Q
Describe fetal erythropoeisis
A
- Yolk Sac first
- Liver starts to contribute at 1.5-2 months
- at 3 months, spleen also continues
- 4 months: starts in marrow (and continues to increase until time of birth)
2
Q
what happens to tissue O2 level at birth?
A
Increases, and causes decrease in Epo
3
Q
When does hgb production decrease for a neonate?
A
at birth, due to decreased epo. synthesis at minimum as of 2nd week of life–> phgy nadir….later, epo stimulated again and get max hb production at age 3 months
4
Q
For an RBC, central pallor should be about how much of the diameter of the cell?
A
1/3 (if more, hypochromic)
5
Q
how do RBCs in neonates compare to those of adults (2)
A
- neonatal RBCs have larger volume
- neonatal RBCs have lower hb concentration
6
Q
Describe RBC life cycle.
A
- Made in marrow
- Retic is released (takes a few days to mature into mature RBC)
- Mature RBC lasts 120 days
- old RBC gets engulfed by reticuloendothelial macrophage, which breaks down heme into iron and bilirubin…heme oxygenase releases ferritin
- iron (ferritin) is exported via ferroportin, bound by transferrin and taken back to marrow to make new RBCs
7
Q
lifespan of RBCs in adults vs. infants vs. prems?
A
adults: 120
term infant: 60-70 days
premat infant: 35-50 days
8
Q
Define anemia
A
reduction of RBC mass (hct) or hemoglobin; hb >2 SD below the mean for age, sex, and race
alternative pghy definition: hb is too low to meet cellular oxygen demands
9
Q
hb affected by? (5)
A
HEATS heredity ethnicity age Tanner stage Sex Also: altitude
10
Q
Two major things to consider in approach to anemia
A
Pathophys (production, hemolysis, blood loss)
vs. size
11
Q
If anemia and appropraite increase in retics, two major categories?
A
hemolysis blood loss (>48 hours since bleeding)
12
Q
normal/decreased retic count in setting of anemia…give a differential based on size of RBC (3 each)
A
Micro: IDA, thal, ACD (late), sideroblastic
Normo: TEC, hypoT4, BM invasion
Macro: B12/folate def, meds, BM aplasia
13
Q
two major categories of hemolysis?
A
Extrinsic= immune, non-immune
Intrinisc to RBC= membrane, Hb, enzyme problems
14
Q
3 major things you need when evaluating anemia cause
A
clinical hx, cbc + retics, peripheral smear
15
Q
Explain how newborns acquire iron stores
A
- Iron endowment from mom occurs in 3rd trimester, even if mom is deficient
- Term babies have enough iron to last 6 months
- Prems have enough to last 3-4 months or sooner
16
Q
iron requirements per day?
A
1-2 mg…but higher in kids and anyone losing blood
17
Q
where is iron found in the body?
A
- most in RBCs + bone marrow
- also stored in liver
- 0.1% is circulating in body bound to transferrin
18
Q
How does Fe get absorbed?
A
- Fe+3 gets reduced to Fe+2 via ferrireductase on mucosal surface
- Ferritin enters cell via DMT1; either stored in cell, or enters blood stream via ferroportin and oxidized by hephaestin or cerruloplasmin and attaches to transferrin to be delivered to the tissues
19
Q
Explain role of hepcidin
A
-acts at ferroportin to cause its internalization and degraduation to prevent release of iron into the bloodstream; in this case, iron does not get absorbed and gets lost in GI tract
20
Q
3 things that increase hepcidin production?
A
- hepcidin is increased by iron load (iron rich meal–> increases hepcidin)
- iron sufficent state, hepciidn production up
- in inflammation, cytokines–>increase hepcidin to limit iron availability to pathogens
21
Q
3 things that regulate iron homeostasis?
A
- erythropoieitic demand
- hypoxia
- total body iron
22
Q
2 microscopic problems secondary to iron overload?
A
- free radical generation
- oxidant injury to cells
23
Q
How does body prevent IDA? 2
A
- Minimizes iron loss (no active iron excretion from body)
- Enhances iron absoprtion when iron deficient
24
Q
How does body prevent iron overload?
A
- Minimize absorption when sufficient iron (via hepcidin)
- Iron in cells/plasma tightly bound to proteins to prevent general of free radicals
25
3 general reasons for IDA?
- Increase iron demands (rapid growth)
- Insufficient iron intake
- Excessive iron losses
26
2 general reasons for iron overload?
- upregulated iron absorption (hereditary hemochormatosis)
| - iron loading (transfusions)
27
Two peds patient populations at highest risk for IDA? Rate? Why?
- Age 0-4; 2-3% (diet, excessive cow milk, breastfeeding)
| - Adolescent females, 9-16%; menstrual blood loss
28
in kids 5-10 and boys 10-18, rate of IDA? primary cause?
<1%; GI blood loss
29
3 disordres in which PICA is seen?
IDA
SCD
Neurodevelopmental d/o's
30
Non-CBC labs associated with IDA? 6
```
Low ferritin= most imp
Low serum iron
High Total iron binding capacity
Low transferrin saturation (=Fe/TIBC)
High soluble transferrin receptor
Low hepcidin
```
31
CBC labs associated with IDA? Hb happens last and first to correct
Low hb
Low MCV
High RDW
Low retic Hb (also low in thal trait)
32
3 things you will see on smear in IDA
hypochromia
microcytosis
thrombocytosis
33
5 reasons for persistent IDA
- incorrect dx
- persistent etiology (low fe diet, blood loss)
- insufficent iron dose
- non-adherence
- malabs..also IRIDA= genetic
34
besides prescribing iron, 2 prong approach for tx'ing IDA
- Iron-rich diet: meat, liver, beans...limit tannins (tea), milk
- minimize blood loss (hormonal therpay for menses, tx of underlying GI disease)
35
Prescribe what for IDA?
Ferrous sulfate once daily, minimum of 3 months
36
Describe follow up for IDA
- 1 week for severe pts only: to assess retics
- 1 month to assess hg increase (ideally, anemia resolved); check CBC +/- retics
- 3 months: to assess if can stop therapy: CBC, retic, ferritin
37
Iron refractory iron deficiency anemia: name the gene involved. heredity?
-TMPRSS6 (mnemonic= TeMPeRS in age "Sous" 6...AR
38
What does TMPRSS6 do?
upregulates hepcidin--> won't absorb iron
39
5 features of IRIDA?
CSACI
"Congen iron anemia challenges some"
-persistent moderate IDA with Congenital onset
-Severe microcytosis (MCV 5-60 fL)
-poor PO Absorption--> not responsive to oral Fe
-"Fail" oral iron Challenge
-blunted response to IV iron, though may be overcome by high doses
40
Describe the oral iron challenge test
- pt comes in am, fasting
- give dose of oral iron
- check serial serum iron levels after that
- if NOT deficient, slight increase in iron after...if IDA, baselien iron low--> increase serum iron >200 by 1 hour = able to absrob...if blunted resposne, poor absorption
41
4 indications for IV iron
- CKD
- intolerance to oral Fe
- concomitant IDA and anemia of inflammation
- confirmed IRIDA
42
what is the ganzoni formula?
Weight {kg} x (Target Hb – Actual Hb) {g/l} x 2.4 + Iron stores {mg}
43
name 3 iv iron formulations used in kids
- Ferric gluconate
- Iron sucrose
- LMW Iron dextran
44
explain the pathophys of anemia of inflammation
body increases hepcidin production as an immunoprotective mechanism to prevent infectoius organisms from having iron to use...it also acts on ferroportin within macrophage to keep iron from being released into bloodstream after RBC dies
45
anemia of inflammation: MCV?
| ferritin is? TIBC?
- normal MCV-> low later
- ferritin is normal or high
- TIBC low
46
manage anemia of inflamm?
- tx underlying cause
| - if severe/prolonged, assess for iron def; tx with iv iron, if needed
47
3 most common causes of low MCV?
IDA, thal trait, anemia of inflamm or chronic disease
48
ways clinical hx can help you distinguish IDA vs thal trait vs anemia of inflamm/chronci disease?
IDA: low iron diet, blood loss
Thal trait: ethnicity, fam hx
Anemia of inflamm/chronic disease: recent acute and/or chronic illness; inflamm; tissue injury
49
ways lab can help you distinguish between IDA vs thal trait vs anemia of inflamm/chronci disease?
IDA: high RDW, low serum ferritin or TSAT
THal trait: normal iron panel + Hgb Barts on NBS (alpha); elebated hb A2 on hb analysis (beta)
Anemia of inflamm/chronic disease: MCV normal or low; ferritin normal or high; transferring/TIBC may be low; sTfR/log10ferritin index low
50
distinguishing features between IDA, thal trait, anemia of inflamm or chronic disease?
IDA: improves iwth oral iron; smear
thal trait: minimal to no change with oral iron; smear
anemia of inflamm/chronic disease: improves as inflammation decreases; may benefit from IV iron
51
3 ddx for normocytic anemia?
inflamm, hypoT4, renal disease
52
clinical hx needed to for normocytic anemia? 2
growth charts, history of recent/recurrent infections, inflamm
53
8 tests for normocytic anemia?
```
CBC
retics
smear
CRP
BUN
creat
TSH
fT4
```
54
Smear in TEC?
Normal
55
What is statistical anemia?
patients whose normal hb falls <2 SDs below normal; just need annual follow up with PCP
56
Iron overload- 2 main categories for etiology?
increased intestinal iron absorption and chronic transfusions
57
2 egs of increased intestinal iron absoprtion?
Hereditary hemochromatosis and ineffective erythropoiesis (eg: thal)
58
Pathophys of hereditary hemochromatosis?
HFE mutation downregulates hepcidin--> increased iron absorprtion...as iron stores increase, transferrin becomes saturated--> get non-transferring bound iron (NTBI) accumulation--> accumuolates in organ--> the longer NTBI is presenst, the more damage occurs
59
give 6 clinical manifestations of iron overload
Don't give children too much hemoglobin chronically
```
Cirrhosis
liver failure
hepatocellular Ca
diabetes Mellitus
hypoGonadism
hypoThyroidism
Heart failure
Dysrhythmias
sudden death
```
60
mutations that can cause hereditary hemochormatosis?
Mnemonic:
Hemochromatosis: the JV team HAMPers the varsity team from TransFeRing 2 Fancier Parks Nov 1. Have Fun Everyone.
```
HFE
HJV= hemojuvelin
HAMP= hepcidin gene
TFR2= transferrin receptor 2
FPN1= ferroportin
```
61
Which hereditary hemochromatosis mutations are AR?
HJV
HAMP
TFR2
HFE
62
Which hereditary hemochormatosis mutation is AD?
FPN1
63
Which hereditary hemochromatosis mutations present in adulthood?
TFR2 and FPN1 and HFE... (think back to mnemonic: the JV team HAMPers the varsity team from TransFeRing 2 Fancier Parks Nov 1)...HJV and HAMP come first and present in childhood...there's also a separate dx called neonatal hemochormatosis
64
2 most common Hereditary hemochromatosis mutations?
HFE C282Y>H63D
65
How to dx HH?
Determine HFE genotype of index case.
Test both of child's parents to determiene genotype. Unless BOTH parents have an HFE mutation, the child's risk is NEGLIGIBLE and no further testing needed. I If both parenst have mutation, determine gentoype of child. If kid is homozygous, he/she is at risk for HH but no definitive due to variable clinical presentation
66
How to manage well kid with homozygous HFE mutation?
monitor iron markers q1-2 yrs
67
transfusions: 1 ml of pRBCs contains about how much iron?
1 mg
68
after how many pRBC transfusions should you start screening pts for iron overload?
10+...check if ferritin >1000
69
ferritin concerning at what level for iron overload?
1000
70
further eval for iron overload if ferritin >1000?
full iron panel including transferrin saturation, MRI liver, cardiac MRI
71
what is normal iron content on liver MRI
<1.8 g Fe/mg dry weight
72
when should you do cardiac MRI for iron overload? 3
LIC= liver iron content >15 or evidence of pancreatic iron on MRI of abdomen; also consider in patients with cardiotox
73
what are you looking for on cardiac mri for iron overload?
decrease in LVEF
74
how do you manage iron overload?
therapeutic phlebotomy (if no longer needing transfuions)
75
folate is found where?
fruits and veg
76
where is folate absorbed?
jejunum, duodenum
77
where is folate stored?
liver
78
megaloblastic anemia: missing what?
b12, folate
79
b12 is found where?
animal origin foods
80
where is b12 stored?
liver
81
how is b12 abosrbed?
binds intrinsic factor (made by gastric parietal cells); intrinsic factor-b12 complex binds to cubulin in the terminal ileum, where it gets absorbed
82
vit b12 and folate are important for what process?
DNA synthesis...def --> reduced DNA replication--> megaloblastic anemia
83
2 findings seen in megaloblastic anemia
- Large marrow progenitors
- Nuclear-cytoplasmic dysynchrony....might also see hypersegmented neurophils, macrocytosis with marked variation in RBCs, occ pancyopenia
84
if you have megaloblastic anemia, in addition to dective dna synthesis, can have ___ ___ ___ which leads to increase in ____ and
- bone marrow lysis
- LDH
- Bilirubin
85
4 ddx or high mcv, not including megaloblastic anemia.
| general MCV range?
- hemolysis/high retics
- marrow hypo/aplasia
- liver disease
- drugs/toxins
- MCV<105
86
megaloblastic anemia= DEFECTIVE DNA SYNTHESIS and includes what 4 causes? generally mcv range?
```
folate def
vit b12 def
inherited metab disease
drugs/toxins
MCV>110
```
87
6 ddx for high MCV
- normal newborn
- T21
- Brisk reticulocytosis
- marrow failure
- meds, including anti-epileptic drugs
- hypoT4, liver disease
- megaloblastic anemia (b12, folate def)
88
5 clinical findings associated with megaloblastic anemia
- non-specific signs/sx of anemia
- jaundice due to ineffective erythropoieiss
- neuro findings (b12 def only)...due to degen of the posterior columns of the spinal cord...get proripceptive and fine motor defs, ataxia, psychomotor retardation, sz, depression, pyschosis...if this is hte case, folate supp may correct heme findings but won't fix these neuro problems!
89
what does b12 do? 2
-co-enzyme for methylmalonyl mutase (if not there, increase in methylmalonic acid)...also coenzyme for methionine synthase (if don't have b12 or don't have folate, get increase in homocysteine)
90
in folate def, what are the expected effects on the following labs?? folate, RBC folate, serum b12, methylmalonic acid (MMA), homocysteine
```
Folate low
RBC folate low
B12 normal or low
MMA normal
Homocysteine high
```
91
in b12 def, what are the expected effects on teh following labs?
folate, rbc folate, b12, MMA, homocystiene
```
Folate normal to high
rbc folate normal to high
serum b12 low
MMA high
homocyseteine high
```
92
Etiologies of Vit b12 def? 5 and 2 egs
ICORN
- Nutritional (vegans, breastfed infants of vegan mom)
- IF deficiency (gastrectomy, autoimmune gastritis= pernicious anemia)
- Competition (fish tapeworm, intestinal blind loop)
- Receptor deficiency (ileal resection, crohn's Imerslund-Grasbeck syndrome)
- Other = nitric oxide, transcobalamin II deficiency
93
Etiolgoies of folate def?
- Nutritional (malnutrition, increased demand, like hemolytic anemias)
- Malabs (gluten-sensitive eneteropathy, tropical sprue, jejunal resection, severe crohn's, intestinal failure= short gut syndrome, sulfasalazine)
- Other (methotrexate, alcohol)
94
other name for vit b12?
Cobalamin
95
how to tx vit b12 def?
IM or PO vitamin b12
96
pernicious anemia: cause in adulthood? tx?
- acquired due to autoimmune conditions; reduced IF production due to autoantibodies
- tx with IM b12
97
inheritance of juvenile pernicious anemia= vit b12 def?
AR
98
mutation in what gene --> juvenile pernicious anemia?
intrinsic factor gene
99
diagnose juvenile perncious anemia how? 2
- Low b12
| - abnormal Schilling test, corrected by IF
100
tx juvenile pernicious anemia how?
IM b12
101
2 causes of autosominal recessive b12 def?
Imerslude-Gräsebeck syndrome and Transcobalamin II Deficiency
102
give 5 features of Imerslude-Gräsbeck syndrome
- AR
- mutations in cubilin or amnionless genes
- malabs of b12 due to inability of IF/B12 to bind in terminal ileum
- Abnormal schilling test, NOT corrected by IF
- associated proteinuria
103
5 features fo Transcobalamin II def?
- AR
- pancytopenia
- Diarrhea
- FTT
- normal b12 and folate levels
- marrow floridly megaloblastic
- low or absent TC-II levels in serum
104
what's more common-folate or b12 def?
b12
105
2 things on hx you might find in folate def?
- drinking goat's milk
| - impaired absorption (crohn's, celiac)
106
do you get neuro side effects in folate def?
No (not post-natally)
107
tx folate def how?
PO folate
108
4 causes of megalblastic anemia other than b12 and folate def
- thiamine= b1 responsive megalobastlic anemia (TRMA)
- hereditary orotic aciduria
- congential dyerythropoietic anemia
- myelodysplasia; M6 AML
109
in megaloblastic anemia, expect retics when? anemia to be fixed when? normal mcv when?
- retics in 1 week
- anemia fixed in 2-4 weeks
- MCV normal in 1-2 months
110
if neuro sx in b12 def reversible, takes how long to fix?
within weeks
111
how shoudl you think of polycytheemia?
appropriate (in response to hypoxia) vs inappropraite (no hypoxia)
112
2 egs of appropraite polycythemia
- right to left shunt
- high altitude
- hb mutation with high oxygen affinity
113
2 egs of inappropraite polycyhtemia
- high EPO level (caused by tumour)
- myeloprolif disease with JAK 2 mutation
- Epo receptor mutation
114
explain what drive erythropoiesis
kidney senses low O2 due to decreased O2 carrying capacity--> epo synthesis--> increase in plasma epo--> erythropoeisis--> increased red cell mass--> increased O2 carrying capacity
115
what is allosteric cooperativity?
oxygen affinity of Hb is proportional to quantitiy of oxygen bound at a given time
116
what happens as hb travels from lungs to the tissues? 3
- decrease in pH (increase in protons)
- increase in pCO2
- leading to Hb to have LOWER o2 affinity, therefore releasing O2 into the tissues
117
how would you draw the oxyhemoglobin dissocation curve?
x axis is oxygen partial pressure (mmHg)
y axis is Hb oxygen saturation (%)
curve looks like an S
118
what makes the oxyhemoglobin dissociation curve shift to the left= INCREASED affinity for O2? 4
```
lower temp
lower 2,3-DPG
lower pCO2
lower H+
Hb A
```
119
what makes the oxyhemoglobin curve shift to the right= DECREASED affinity for O2? 4
```
increased temp
increased 2,3 DPG
increased pCO2
increased H+
Hb F
```
120
what is 2,3-DPG and what does it do?
2,3 di-phosphoglycerate is abundant in the RBC. it binds to and stabilizes the deoxy form of H, resulting in lower O2 affinity. this is an adaptive response, requiring several days (like in high altitude)
121
what is a P50? when should you send it?
p50= test that measures partial pressure of oxygen when 50% of hb is saturated with O2...send it in cases of polycythemia...as teh p50 goes down, teh o2 affinity goes UP
122
what are the relative p50s of Hb A, F, S?
F less than A less than S
123
5 causes of neonatal eyrhtocytosis (hct>65%)
- diabetic mother
- IUGR
- delayed cord clamping
- maternal-fetal transfusion
- twin to twin transfusion
- T21
124
Ohter than high hb and hct, what are 3 other lab findings in neonatal polycythemia?
Low plts
high bili
hypoglycemia
125
3 clinical manifestations of polycythemia= erythrocytoiss in neonates?
plethora
tachypnea
seizures
126
tx for polycythemia? goal hct?
partial exchange; 55%
127
Outside of the neonatal period, describe yoru approach to polycythemia
- is the patient hypoxic? if yes, this is appropriate. determine if congential or acquired hypoxia.
- If not hypoxic, determine their EPO level. if it's low, this is primary erythocytosis. if it's high, this is SECONDARY erythrocytosis. if high EPO, look into congential (altered O2 sensing, HIF mutations) vs acquired causes
128
what are congen causes of appropriate polycytehmia?
- high affin hb
- aberrant 2, 3 DPG synthesiss
- methemoglobinemia
129
what are acquired causes of appropriate polycythemia?
- R to L shunt
- OSA
- pulmonary disease
- CO poisoning, smoking (carboxyhb)
- renovascular disease
- drugs (NO)
- toxins
130
if inappropriate polycythemia with low epo (primary erythrocytosis): give 2 ddx
- epo receptor mutation
| - myeloproliferative disorder
131
congenital causes of secondary erythrocytosis in the absence of hypoxia? 3
- Chuvash polycythemia (AR)
- PHD2 erythrocytoiss (AD)
- HIF2alpha ertyrhocytosis (AD)
132
acquired causes of secondary erythrocytosis (high epo) in absence of hypoxia? 3
- hydronephrosis
- renal cysts
- epo-secreting tumour (renal, posteiror fossa)
- performance enhancing drugs (exogenous epo, anabolic steroids)
133
other than hx and physical and looking at CBC check what for eval of polycthemia?
- O2 sat
- serum epo level
- O2 hb dissoc curve (p50)
- Imaging studies (renal, posterior fossa)
134
- polycytehmia tx based on?
- do therapeutic phleb when?
- also consider what?
- symptom management
- non-sepcific signs and sx of hyperviscosity (plethora, fatigue)
- thrombosis risk (individual)
