Anemias Flashcards
1
Q
MVC
A
mean cell volume
80-100
2
Q
mean cell hemoglobin
A
27-33
3
Q
mean cell hemoglobin concentration
A
33-37
4
Q
hemoglobin
A
M- 13.6-17.2
F- 12-15
5
Q
hematocrit
A
M- 39-49
F- 33-43
6
Q
red cell count
A
M- 4.3-5.9
F- 3.5-5
7
Q
reticulocyte count
A
.5-1.5
8
Q
RDW
A
11.5-14.5
9
Q
general changes of anemia
A
pale, weak, malasie, easy fatiguability
dyspnea on mild exertion
Hypoxia -> fatty changes of liver, myocardium, and kidney -> severe cardiac failure -> worse hypoxia
10
Q
acute blood loss
A
low hematocrit b/c diluted w/interstitial fluid
increased erythropoietin -> 5 days for increased retic
leukocytosis due to adrenergic compensatory response
initially normocytic, normochromic -> macrocytic, chromatophilic
early recovery thrombocytosis
11
Q
hemolytic anemia general characteristics
A
life span <120
elevated erythropoietin and increase in erythropoiesis
accumulation of hemoglobin degredation products
12
Q
types of hemolytic anemias
A
hereditary spherocytosis G6PD deficiency thalassemias sickle cell paroxysmal noctural hemoglobinuria hemolytic disease of newborn transfusion reactions drug induced autoimmune HUS DIC TTP malaria, babeosis hypersplenism
13
Q
extravascular hemolysis
A
anemia splenomegaly jaundice (unconjugated) -> gallstones decreased haptoglobin often benefit from splenectomy
14
Q
intravascular hemolysis causes
A
less common mechanical injury (prosthetic valves, repetitive physical injury) C' fixation intracellular parasites (malaria) exogenous toxins (clostridial sepsis)
15
Q
intravascular hemolysis clinical
A
anemia hemoglobinemia hemoglobinuria hemosideriuria jaundice (unconjugated) -> gallstones decreased haptoglobin increased methemoglobin -> red brown urine renal hemosiderosis no splenomegaly
16
Q
HS
A
hereditary spherocytosis red cells are spheroid highest in northern Europe autosomal dominant 75% 25% of compound heterozygosity -> more severe present at birth
17
Q
HS spectrin
A
normal RBC skeleton made of spectrin
HS caused by frameshift mutations in: ankyrin, spectrin, Band 3, Band 4.2
life span 10-20 days
18
Q
HS morphology
A
spherocytosis- small hyperchromic red cells marrow marrow erythroid hyperplasia hemosiderosis mild jaundince cholelithiasis moderate splenomegaly
19
Q
HS clinical
A
abnormally sensitive to osmotic lysis
increased MCHC
anemia, splenomegaly, jaundice
20-30 asymptomatic
20
Q
HS aplastic crises
A
usually triggered by parvovirus
transfusions may be necessary
21
Q
HS hemolytic crises
A
infectious mono
22
Q
HS Tx
A
splenectomy
23
Q
G6PD deficiency
A
recessive X-linked (males higher risk) G6PD- and mediterranean subtypes protective against malaria episodic episodes of hemolysis due to oxidant stress (self limited b/c only older cells at risk) intra and extravascular hemolysis
24
Q
sources of oxidant stress
A
infectious most common (hep, pneumonia, typhoid)
Drugs (antimalarials, sulfonamides, nitrofurantoins)
fava beans
25
G6PD morphology
heinz bodies - dark inclusions on crystal violet stain
| bite cells/spherocytes
26
sickle cell disease
point mutation in beta hemoglobin (glu -> val) -> polymerization of deoxygenated hemoglobin -> sickling -> hemolysis and microvascular obstruction
27
sickle cell protection against malaria
increased extravascular hemolysis -> clears infection
| intravascular- due to impaired formation of membrane knobs containing viral PfEMP-1 protein (cerebral malaria)
28
HbF and sickle cell
inhibits polymerization of HbS, therefore infants not symptomatic until 5-6months
people with hereditary persistence of HbF less severe disease
29
HbSC disease
heterozygotes for HbC/HbS
HbC common in Africa
increased sickling
30
factors that affect sickling
MCHC- decreased MCHC less sickling therefore patients w/coexisting thalassemias have less sever disease
intracellular pH- decreased pH worse sickling
transit time- slower more obstruction
31
microvascular occlusion in sickle cell
dependent on red cell membrane damage, not number o sickled cells
also attributed to depleted NO
32
morphology of sickle cell
target cells
howell-jolly bodies
bone marrow hyperplastic -> bone resporption and reformation -> crewcut skull
splenomegaly as child -> autosplenectomy as adult
33
sickle cell morphology
hematocrit 18-30%
reticulocytosis, hyperbilirubinemia, sickled cells
vaso-occlusive/pain crises
acute chest syndrome
priapism
stroke and retinopathy (depletion of NO)
occlusions most common cause of morbidity and mortality
34
vaso-occlusive/pain crises in sickle cell
infection, dehydration, and acidosis can trigger, but most have no predisposing cause
bone, lungs, liver, brain, spleen, penis
bone most common in kids -> hand-foot syndrome/dactylitis
35
acute chest syndrome
particularly dangerous involving the lungs, present w/fever, cough, chest pain, and pulmonary rales
usually when infections slow blood flow
36
other occlusive effects of sickle cell
priapism
stroke and retinopathy (depletion of NO)
occlusions common cause of morbidity and mortality
general chronic tissue hypoxia
generalized impairment of growth and development and organ damage
37
sequestration crises
kids w/intact spleen
rapid splenic enlargement, hypovolemia, and sometimes shock
may be fatal
38
aplastic crises
infection of red cells w/parvovirus B19
39
sickle cell infections
increased risk to capsulated organisms due to decreased splenic fnx, defects in alternative C'
S. pneumoniae, H. influenza, meningitis
40
Dx of sickle cell
culture cells w/metabisulfite which consumes oxygen
41
Tx of sickle cell
hydroxyurea
| HSC transplant
42
alpha chain
on chrom 15
43
beta chain
on chrom 11
44
thalassemias endemic in
mediterranean basin, middle east, tropical aftrica, india, and asia
45
beta mutations
B0- absent beta synthesis
B+- reduced beta globin synthesis
100 different mutations, mostly point
46
mechanisms of anemia in beta thalassemia
1) deficit in HbA synthesis -> underhemoglobinized, hypochromic, microcytic red cells -> submornal O2 delivery
2) diminished survival of red cells:
- unpaired alpha chains precipitate in red cell precursors -> insoluble inclusions -> membrane damage -> apoptosis -> this happens to 80% of red cell precursors
- red cells which are released still have inclusions and damage and cleared by spleen
- massive erythroid hyperplasia in bone marrow -> impairs bone growth -> crew cut
- extramedullary hematopoiesis creates higher O2 demand for already oxygen starved tissues
47
beta thalassemia major
```
severe, transfusion depended anemia
have 2 mutated Beta alleles
anemic by 6-9months
hemoglobin levels 3-6
elevated HbF
HbA2 sometimes high
```
48
beta thalassemia minor
only 1 allele
| mild asymptomatic microcytic anemia
49
beta thalassemia major morphology
```
microcytosis and hypochromic red cells
target cells, basophilic stippling, and fragmented cells
inclusions of aggregated alpha chains efficiently removed by spleen so usually NOT seen
retics elevated
expansion of active marrow
crew cut appearance on xray
splenomegaly
Fe overload
```
50
beta thalassemia major clinical
course is short if untreated
suffer from growth retardation and die at early age
hepatosplenomegaly
crewcut
cardiac disease due to Fe overload common COD
HSC transplant only cure
51
beta thalassemia minor
usually asymptomatic
anemia if present mild
hypochromic, microcytic, basophilic stippling, and target cells
mild erythroid hyperplasia in bone marrow
increased HbA2
HbF normal, slightly increased
exclude Fe deficiency anemia
52
alpha thalassemias
newborns excess gamma from tetramers -> hemoglobin Barts
older children and adults have HbH
free beta and gamma chains more soluble and from stable tetramers hemolysis and ineffective erythropoiesis less severe then in beta thalassemias
deletion mutations most common cause
53
four types of alpha thalassemia
silent carrier disease
alpha-thalassemia trait
hemoglobin H disease
hydrops fetalis
54
silent carrier disease
only 1 mutated alpha alelle
| completely asymptomatic
55
alpha thalassemia trait
2 alleles mutated
| asymptomatic
56
hemogloin H disease
deletion of 3 genes
HbH tetramers -> extremely high affinity for O2 don't deliver it
HbH prone to oxidation -> precipitate and form intracellular inclusions -> red cell sequestration by spleen
57
hydrops fetalis
most severe form, deletion of all 4 alleles
hemoglobin barts in fetus have very high affinity for O2
fatal in utero w/o transfusions
HSC transplant only cure
58
PNH
paroxysmal nocturnal hemoglobinuria
acquired mutations in PIGA, an enzyme essential for synthesis of membrane associated C' regulatory proteins
rare
only hemolytic anemia caused by acquired genetic defect
x-linked and subject to lyonization (mixed normal and abnormal red cells in female)
correlated w/aplasitc anemia b/c expressed when autoimmune reactions against GPI-linked Ags occurs
59
PNH mutations
CD55
CD59- most important
C8 binding protein
all regulate C'
60
lysis in PNH
intravascular due to MAC
| only nocturnal in 25%, maybe due to decreased pH -> more active C'
61
PNH clinical
Fe deficient due to hemolysis
venous thrombosis is leading COD
10% develop AML or MDS
62
PNH Dx
flow cytometry to detect cells deficient in CD59 and others
63
Tx PNH
eculizumab blocks conversion of C5-C5a
| only cure HSC transplant
64
direct coombs test
patients red cells mixed w/sera w/Abs
65
indirect coombs test
patients serum mixed w/red cells expressing specific Ags
66
immunohemolytic anemias
aka autoimmune hemolytic anemias
| Dx requires detection of Abs or C' on red cells via direct coombs test -> agglutination
67
immunohemolytic anemia types
warm body Ab type
cold agglutinin type
cold hemolysin type
68
warm body Ab type
```
most common
50% idiopathic
IgG (can be IgA)
extravascular hemolysis
moserate splenomegaly
many Abs against Rh
```
69
drug induced warm Ab type
antigenic drugs: penicillin and cephalosporins
tolerance breaking drugs: antiHTN alpha-methyldopa
1-2 weeks post exposure to IV drug infusion
70
cold agglutinin type
IgM that binds red cells at low temp
sometimes post infection w/M. pneumoniae, EBV, CMV, influenza virus, HIV, or mycoplams
self limited
chronic occurs in certain B-cell neoplasms or as an idiopathic condition
71
cold hemolysin type
```
IgG bind P blood grp Ags
paroxysmal cold hemoglobinuria
rare, sometimes fatal
seen in kids post viral infections
transient most recover w/in 1 month
```
72
hemolytic anemia due to trauma
cardiac valve prosthetics
microangiopathic hemolytic anemia most often seen w/DIC, but also occurs in TTP, HUS, maligant HTN, SLE, and disseminated CA
Red cell fragments -> schistocytes
burr cells, helmet cells, triangle cells
73
megaloblastic anemia
lack central palor and are hyperchromic, but MCHS is not elevated
neutrophils also large then normal w/hypesegmentation of nucleus
74
pernicious anemia
autoimmune gastritis that impairs production of IF
more prevalent in scandinavian and other caucasian populations
median age 60, rare <30
75
Vit B deficiency
impairs DNA synthesis due to reduced availabiltiy of FH4
76
Abs in pernicious anemia
Type I- blocks binding of vit B to IF
type II- prevent binding of IF to IFR
type III- most common, recognize alpha and beta subunits of gastric proton pump
77
other disorders associated w/B12 deficiency
```
achlorhydria and loss of pesin
gastrectomy
loss of exocrine fnx
Ileal resection or diffuse ileal disease
tapeworms
pregnancy, hyperthyroidism, disseminated CA, chronic infection all increase demand
```
78
vit B12 deficiency morphology
intestinlization of stomach
atrophic glosstitis
CNS changes -> demylinating of dorsal spinal tracts
79
vit B12 deficiency clinical
moderate to sever megaloblastic anemia
leujopenia w/hypersegmented granuocytes
low serum B12
elevated serum homocysteine and methmylmalonic acid
rise in hematocrit 5 days post parenteral B12
serum Abs to IF
elevated homocysteine -> cardiac risk factor
80
anemia of folate deficiency
megaloblastic appears same as B12
| humans entirely dependent on dietary source
81
reactions dependent on folic acid
purine synthesis
conversion of homocysteine to methionine
dTMP synthesis (can be inhibited by drugs) required for DNA synthesis
82
risks for folate deficeincy
```
chronic alcoholics (also trapped in chirrhotic liver)
very old
sprue and diffuse disease of small intestines (lymphoma)
```
83
drugs associated w/folate deficiency
phenytoin
| oral contraceptives
84
relative folate defiencies
pregnancy
infancy
hyperactive hematopoiesis
disseminated CA
85
folic acid anatgonits
methotrexate
86
folic acid clinical
serum homocysteine increased
methymalonate concetrations normal
no neuro changes
87
Fe deficiency
in US most common in toddlers, adolescent girls, and women of childbearing age
88
normal Fe absorption
Ferric(3) -> ferrous (2) via ferrireductase
transported across apical membrane via DMTA
basolateral membrane via ferroportin-> ferrous -> ferric binds tranferrin (usually 2/3 saturated)
89
hepcidin
regulates Fe absorption by blocking ferroportin
| small circulating peptide from liver
90
Fe absorption inhibited by
tannates, carbonate, oxalates, and phosphates
91
morphology of Fe deficeincy
microcytic, hypochromic
| disappearance of stainable Fe from macros in boen marrow Pencil cells
92
Fe deficiency clinical
kolionychia
alopencai
atrophic changes in tounge and gastric mucosa
PICA
93
plummer vinson syndrome
esophageal webs
microcytic hypochromic anemia
atrophic glossitis
94
Dx of Fe deficeincy
```
HCT, Hgb decreased
serum Fe decreased
serum ferritin decreased
TIBC increased
hepcidin decreased
```
95
anemia of chronic disease
due to systemic inflammation
| most common anemia in US hospitals
96
categories of anemia of chronic disease
chronic microbial infections- osteomyelitis, endocarditis, lung abscesses
chronic immune disorders- RA
neoplasms- carcinomas of lung, breast and HL
97
anemia of chronic disease morphology
low serum Fe, reduced TIBC, abundant Fe stored in tissue macros
red cells usually normocytic, normochormic, if progresses can becoome hypochromic and microcytic
98
anemia of chronic disease pathology
IL6 -> stimulates increase in hepcidin
| low erythropoietin which may be due to hepcidin
99
anemia of chronic disease clinical
anemia mild, which major symptoms being of the underlying disease
100
aplastic anemia
syndrome of chronic primary hematopoietic failure and pancytopenia
majority of patients autoimmune mechanisms suspected
most cases of known etiology are due to drugs
can also be post viral or due to radiation
65% idiopathic
101
drugs that cause aplastic anemia
chemo and organic benzene
chloramphenicol
gold salts
102
inherited causes of aplastic anemia
fanconi anemia
| telomerase defects
103
fanconi anemia
rare autosomal recessive disorder due to defects in multiprotein complex necessary for DNA repair
marrow hypoplasia early in life often w/hypoplasia of kidney, spleen, and bones (thumbs and radii)
104
morphology of aplastic anemia
markedly hypercellular bone marrow mostly fat and stroma and scattered lymphocytes
dry tap
granulocytopnia, thrombocytopenia
infections, bleeding
105
aplastic anemia clinical
```
any age, either sex
insidious
Tx- multiple transfusions, bone marrow transplant
pancytopenia
splenomegaly absent
slight macrocytic and normochromic cells
reticulocytopenia
```
106
pure red cell anemia
```
neoplasm (thyoma, large granular lymphocytic leukemia)
drugs
autoimmune disorders
parvovirus
immunosupressive tx usually beneficial
plasmapharesis if autoAbs
```
107
meylophthisic anemia
space-occupying lesions replace normal marrow elements
most common cause is metastatic CA (breast, lung, prostate)
any infiltrative process-> granulomatous disease (TB, sarcoidosis, fungal)
spent phase of MPDs
leukoerythroblastosis and tear drop shaped red cells
108
chronic renal failure
almost invarialby associated w/anemia proportional to severity of uremia
diminished synthesis of erythropoietin
extracorpuscular defect that reduces red cell life span and Fe deficiency due to platelet dysfunction and incereased bleeding
109
hepatocellular liver disease
toxic, infectious, or cirrhotic
decreased marrow fnx
folate and Fe deficiencies
erythroid progenitors preferentially affected
slightly macrocytic due to lipid abnormalities
110
endocrine anemina
hypothyroidism
| mild normochromic, normocytic anemia
