Pathoma 5 Flashcards
1
Q
heme = ?
A
iron + protoporhyrin
2
Q
ddx microcytic anemia
A
- iron deficiency
- ACD
- sideroblastic
- thalassemia
3
Q
Iron absorption occurs?
A
duodenum
4
Q
Iron from duodenum into enterocyte through?
A
DMT1
5
Q
iron from enterocyte to blood through
A
ferroportin
6
Q
iron transporter in blood
A
transferrin
7
Q
places where iron is stored
A
liver and BM macrophages
8
Q
stored intracellular iron is bound to?
A
ferritin
9
Q
normal iron % saturation
A
33% transferrin bound by iron
10
Q
microcytic hypochromic RBCs with inc RDW Dec ferritin Inc TIBC Dec serum iron Dec % saturation
A
iron-deficiency labs
11
Q
anemia + dysphagia + beefy red tongue
A
Plummer Vinson Syndrome (iron deficiency + esophageal web + atrophic glossitis)
12
Q
Hepcidin sequesters iron in storage sites by
A
- limiting iron transfer from macrophages to erythroid precursor
- suppressing EPO
13
Q
Inc ferritin Dec TIBC Dec serum iron Dec iron sat Inc FEP
A
Lab findings ACD
14
Q
what causes sideroblastic anemia?
A
defective protoporhyrin synthesis
15
Q
rate limiting step in protoporphyrin synthesis
A
ALAS-catalyzed S CoA –> ALA using vB6 as cofactor
16
Q
enzymes in protoporphyrin synthesis
A
ALAS (B6) + ALAD (and others)
17
Q
where is the iron in sideroblastic anemia
A
stuck in the macrophages (seen w/ prussian blue stain)
18
Q
congenital sideroblastic anemia
A
usually ALAS defect
19
Q
acquired sideroblastic anemia
A
- alcoholism
- lead poisoning (inhibits ALAD + ferochelatase)
- vB6 deficiency (isoniazid side effect)
20
Q
inc ferritin
dec TIBC
inc serum iron
inc % sat
A
sideroblastic labs
21
Q
HbF =
A
alpha2gamma2
22
Q
HbA =
A
alpha2beta2
23
Q
HbA2 =
A
alpha2delta2
24
Q
how many alpha genes present on chromosome 16
A
four total
25
cis deletion (--> mild anemia w/ inc RBC count) in what population
Asian
26
trans deletion (--> mild anemia w/ inc RBC count) in what population
African
27
HbH =
beta4
28
What happens with three deleted alpha hemoglobin chains?
severe anemia; HbF seen on electrophoresis
29
What happens with four deleted alpha hemoglobin chains?
hydrops fetalis; Hb Barts = gamma4
30
beta thal in what populations
Mediterranean + African
31
alpha hemoglobin gene is on what chromosome?
16
32
beta hemoglobin gene is on what chromosome?
11
33
microcytic hypochromic RBCs and target cells
beta thal minor on smear
34
beta thal minor electrophoresis
slightly decreased HbA, increased HbA2 + HbF
35
beta thal major cause of damage
alpha tetramers --> ineffective erythropoiesis + extravascular hemolysis
36
what ID is really bad if you have beta thal major?
parvovirus B19
37
severe anemia a few months after birth; massive erythroid hyperplasia; extra medullary hematopoiesis w/ HSM
beta thal major symptoms
38
microcytic, hypochromic RBCs w/ target cells + nucleated RBCs
beta thal major smear
39
beta thal electrophoresis
HbA2 + HbF + little or no HBA
40
macrocytic anemia w/ megaloblastic change ddx
folate or B12 deficiency
41
macrocytic anemia w/o megaloblastic change ddx
alcoholism, liver dz, drugs (5-FU)
42
where is folate absorbed?
jejunum
43
causes of folate deficiency
1. poor diet
2. increased demand (pregnancy, cancer, hemolytic anemia)
3. folate antagonists (methotrexate)
44
macrocytic RBCs and hypersegmented neutrophils
folate or B12 deficiency on smear
45
dec serum folate
inc homocysteine (inc risk for thrombosis)
nl methylmalonic acid
folate deficiency labs
46
how to differentiate folate/b12 def?
methylmalonic acid
47
where is B12 absorbed?
ileum (complexed w/ IF)
48
absorption of iron, folate, b12
duodenum, jejunum, ileum
49
how does b12 get through the stomach?
R-binder
50
what detaches b12 and R-binder?
pancreatic proteases in duodenum
51
what makes IF
gastric parietal cells
52
b12 deficiency takes a long time to develop bc?
there are large hepatic stores
53
5 causes of b12 deficiency
1. pernicious anemia (AI destruction of parietal cells)
2. pancreatic insufficiency
3. Crohn dz
4. D latum
5. veganism
54
what does vB12 do in the body normally?
cofactor for conversion of methylmalonic acid to succinyl Coa (important in fatty acid metabolism)
55
B12 def --> inc methylmalonic acid --> impaired myelinization -->
subacute combined neurodegeneration (damage to posterior column and lateral corticospinal tract)
56
anemia w/ splenomegaly,
jaundice due to unconjugated bilirubin,
increased risk for bilirubin gallstones (pigmented);
marrow hyperplasia w/ high corrected retic count
clinical + lab findings w/ normocytic anemia w/ extravascular hemolysis
57
hemoglobinemia,
hemoglobinuria,
hemosiderinuria,
decreased serum haptoglobin
clinical + lab findings w/ normocytic anemia w/ intravascular hemolysis
58
normocytic anemias w/ predominant extravascular hemolysis
1. hereditary spherocytosis
2. sickle cell anemia
3. Hemoglobin C
59
normocytic anemias w/ predominant intravascular hemolytis
1. PNH
2. G6PD deficiency
3. immune hemolytic anemia
4. microangiopathic hemolytic anemia (TTP, HUS, DIC, HELLP, mechanical trauma)
60
Inherited defect of RBC cytoskeleton-membrane tethering proteins (ankyrin, spectrin, band 3)
hereditary spherocytosis
61
increased MCHC
hereditary spherocytosis
62
labs with hereditary spherocytosis
increased RDW and MCHC
63
smear with hereditary spherocytosis
spherocytes w/ loss of central pallor
64
clinical symptoms of hereditary spherocytosis
1. splenomegaly, jaundice w/ UCB, inc risk for bilirubin gallstones
2. increased risk for aplastic crisis w/ parvovirus B19
65
Diagnosis for hereditary spherocytosis
osmotic fragility test (RBCs break in hypotonic solution)
66
treatment of hereditary spherocytosis
splenectomy (then you'll see howell-jolly bodies!)
67
what causes sickle cell anemia?
single AA chain from glutamic acid (hydrophilic) to valine (hydrophobic) in beta chain of hemoglobin
68
treatment for sickle cell anemia?
hydroxyurea increases HbF
69
why do sickle cell pts have extravascular hemolysis
reticuloendothelial system removes RBCs with damaged membranes
70
why do sickle cell pts have intravascular hemolysis?
RBCs w/ damaged membranes dehydrate --> hemolysis
71
irreversible sickling in sickle cell anemia leads to vaso-occlusion, wh/ presents in five ways
1. Dactylitis
2. Autosplenectomy
3. Acute chest syndrome
4. Pain crisis
5. Renal papillary necrosis
72
consequences of autosplenectomy
1. inc risk of enc org infxn (S pneumo + H flu)
2. inc risk of salmonella paratyphoid osteomyelitis
2. Howell-Jolly bodies on smear
73
most common cause of death in adult sickle cell pts
acute chest syndrome
74
symptoms of renal papillary necrosis
gross hematuria and proteinuria
75
RBCs in sickle cell trait do not sickle except where?
renal medulla --> microinfarction --> microscopic hematuria + decreased ability to concentrate urine
76
screen for sickle cell
metabisulfite
77
90% HbS,
8% HbF,
2% HbA2
(no HbA)
labs in sickle cell dz
78
55% HbA,
43% HbS,
2% HbA2
labs in sickle cell trait
79
glutamic acid replaced by lysine in beta globin
HbC
80
symptoms of HbC
mild anemia due to extravascular hemolysis
81
Acquired defect in myeloid stem cells resulting in absent GPI --> cells susceptible to destruction by complement
PNH (NB: deficiency of CD55 + CD59 = PNH!!)
82
DAF (CD55) normally protects RBCs from complement by
inhibiting C3 convertase
83
what secures DAF to RBC?
GPI (so in PNH, no GPI --> no DAF)
84
PNH screening
sucrose test; confirmatory test is acidified serum or flow cytometry for DAF
85
cause of death in PNH
thrombosis of hepatic, portal, or cerebral veins (bc lysed platelets release their contents)
86
complications of PNH
iron deficiency anemia + AML
87
x linked recessive disorder that renders cells susceptible to oxidative stress
G6PD deficiency
88
pathophys of G6PD deficiency
dec G6PD --> dec NADPH --> dec GLUTATHIONE --> oxidative injury of H2O2 --> intravascular hemolysis
89
there are two variants of G6PD - what are they and which is worse?
Mediterranean variant is more severe than African variant
90
dark inclusions in RBCs when stained by crystal violet
Heinz bodies (oxidative stress precipitates Hb)
91
causes of oxidative stress in G6PD deficiency
1. infections
2. drugs (primaquine, sulfa drugs, dapsone)
3. fava beans
92
hemoglobinuria and back pain hours after exposure to oxidative stress
presenting symptoms of G6PD deficiency
93
bite cells! (splenic macrophages remove heinz bodies)
smear w/ G6PD
94
IgG mediated destruction of RBCs
warm agglutinin (immune hemolytic anemia), primarily extravascular hemolysis
95
causes of IgG-mediated IHA
SLE, CLL, drugs (penicillin + cephalosporin)
96
treatment of IgG-mediated IHA
1. remove the offending drug
2. steroids
3. IVIG
4. splenectomy
97
IgM mediated destruction of RBCS
cold agglutinin, primarily intravascular hemolysis
98
causes of IgM-mediated IHA
mycoplasma pneumonia + infectious mono
99
direct coombs test confirms presence of antibodies where?
On the RBCs
100
indirect coombs test confirms presence of antibodies where?
in the plasma
101
what are you mixing if you do a direct coombs test?
Anti-IgG + patients RBCs
102
what is mixed in indirect coombs test?
Anti-IgG + test RBCs + patients serum
103
causes of microangiopathic hemolytic anemia (schistocytes!)
TTP, HUS, DIC, HELLP, prosthetic heart valves, aortic stenosis
104
how is malaria transmitted?
female anopheles mosquito
105
what produces EPO?
peritubular interstitial cells in the kidney
106
Infects progenitor red cells and temporarily halts erythropoiesis; significant anemia in setting of preexisting marrow stress (sickle cell)
Parvovirus B19
107
what type of virus is parvovirus B19? (i.e. RNA vs DNA, ss vs ds, env vs nonenv)
Non-enveloped ssDNA
108
anemia + thrombocytopenia + leukopenia + low retic count
pancytopenia
109
possible treatments for aplastic anemia?
```
EPO,
GM-CSF,
G-CSF,
immunosuppression,
BMT
```
110
pathologic process (e.g. metastatic cancer) that replaces bone marrow --> impaired hemopoiesis --> pancytopenia
myelophthisic process
111
deficiency of CD55 + CD59 =
PNH!!
112
what sequesters iron in storage sites?
hepcidin
