Red Blood Cell Disorders Flashcards
What part of the body can be easily identifiable during anemia?
pale conjuctiva
What is the definition for anemia in men? Women?
men =
What is the definition for macrocytic anemia? Microcytic?
macro = > 100
micro =
What is the single contributing factor for a microcytic anemia?
deficient hemoglobin production
Why does microcytosis occur?
to keep Hb concentration in cells adequate
Where in the GI tract does absorption of iron occur?
Duodenum
What protein transports heme from Gi enterocytes into the blood?
Ferroportin
What protein transfers iron in the blood?
transferrin
What protein stores iron in cells?
ferritin
Which rxn describes how iron can generate free radicals?
Fenton
What two locations in the body is iron stored by ferritin?
liver and macrophages
What two diseases should always be ruled out when an elderly person presents with iron deficient anemia?
colonic polyps and gastric carcinoma
What two genus and species of worms can cause an iron deficiency anemia?
Necatur americanus
Ancylostoma duodenale
What type of surgery can cause iron deficient anemia?
gastrectomy
What two markers of iron are almost always in opposite to each other?
ferritin and TIBC
Pica is indicative of what deficiency?
iron
Koilonychia is indicative of deficiency of what mineral?
iron
What two metals can increase Free Erythrocyte Protoporphyrin?
lead or zinc
What causes Plummer-Vinson Syndrome?
Iron deficient anemia
What is the triad of Plummer-Vinson Syndrome?
iron deficient anemia, atrophic glossitis and esophageal webs
What cytokine mediates Anemia of Chronic Disease?
hepcidin
What two MOAs does hepcidin use to sequester iron?
- limiting iron release from macrophages
2. limiting producion of EPO
What molecule is deficient in sideroblastic anemia?
Protoporphyrin
ALA synthase works on what two products? What is needed as a cofactor for ALA Synthase
glycine and Succinyl-CoA
B6
What rxn is catalyzed by ALA dehydratase?
ALA to Porphobilinogen
What molecule does ferrochelatase attach iron to?
protoporphyrin
Where in the cell is heme synthesized?
mitochondria
If protoporphyrin is deficient, where does iron get trapped? Why?
mitochondria
Protoporphyrin is attached to iron in the mitochondria
Where in the cell do ringed sideroblasts accumulate?
around the nucleus
Sideroblastic anemia almost always involves what enzyme?
ALA synthase
What organelle does alchocol destroy? Can this lead to sideroblastic anemia?
mitochondria
What two enzymes of heme synthesis does lead impair?
ALA dehydratase and ferrochelatase
What cofactor is required for heme synthesis? What drug can deplete this cofactor?
B6
isoniazid
During sideroblastic anemia, would ferritin increase or decrease? Why?
increase
iron cant leave mitochondria/cell
Carriers of the gene for thalassemia are protected agaist what exact species?
Plasmodium falciparum
What globin chains are present in HbF?
two alpha
two gamma
What globin chains are present in HbA?
two alpha
two beta
What globin chains are present in HbA2?
two alpha
two delta
α-Thalassemia is usually caused by what type of mutation?
deletion
What chromosome are the genes for α-globin located?
16
What mutation is worse for offspring, cis or trans?
cis
What is a cis-deletion?
when both deletions occur on same chromosome
What population is cis-deletion seen?
Asians
What population is trans-deletion seen?
african
What is a trans deletion?
one deletion occurs on each chromosome
What form of hemoglobin is seen when three deletions occur? What chain would hemoglobin be primarily compsoed of in this situation?
HbH
β-chain tetramers
What form of Hb is seen when four genes are deleted? What form of Hb is seen?
Hb Barts
gamma-chain tetramers
What type of mutation gives rise to β-thalassemia?
point mutation
In what two populations is β-thalassemia seen?
africans and mediterranean descent
On what chromosome are β-globin present?
16
What type of RBCs would a β-thalassemia minor produce?
target cells
Why does β-thalassemia major damage RBCs?
α-globin chains precipitate and destroy RBCs
β-thalassemia major will produce what types of changes on X-ray?
crew-cut skull
abnormal facial bones
What virus do individuals with β-thalassemia major have a greater risk of being infected with?
Parvovirus B19
Lack of what two nutrients can cause a megaloblastic anemia?
folate or B12
What does THF transfer to cobalamin?
methyl group
Other than RBCs and neutrophils, what other cell type can become hypersegmented?
rapidly dividing epithelial cells (intestine)
Where in the GI tract is folate absorbed?
jejunum
What protein from the salivary gland binds B12?
R-binder
What enzyme detaches B12 from R-binder?
PANCREATIC proteases
What organism can cause B12 deficiency? In what food is this organism found?
Diphyllobothrium latum
fish
What molecule impairs myelin synthesis?
methylmalonic acid
During anemia, what will the reticulocyte count rise to?
> 3%
What equation is used to correct reticulocyte count?
(Hct/45)(reticulocyte count)
What does a reticulocyte count greater than 3% indicate? What does this suggest?
good marrow response
peripheral destruction
What does a reticulocyte count lower than 3% indicate? What does this suggest?
poor marrow reponse
underproduction of RBCs
Where does extravascular hemolysis occur?
Reticuloendothelial system
What is heme broken down into by the RES?
iron and protoporphyrin
Where does intravascular hemolysis occur?
vessels
During hemoglobinemia, how does iron accumulate in the kidney?
Hemosiderin
What does hemosidinuria happen?
renal tubular cells with hemosiderin are shed
What three major proteins are defective resulting in hereditary spherocytosis?
ankyrin, spectrin and band 3
What type of cell is seen during hereditary spherocytosis?
spherocytes
Why does splenomegaly result during hereditary spherocytosis?
spherocytes get trapped in splenic sinusoids
What is lost in spherocytes?
central pallor
Does RDW increase or decrease during hereditary spherocytosis?
increase
Does MCHC increase or decrease during hereditary spherocytosis? Why?
increase
spherocytes shrink and [Hb] increases
What is the treatment for hereditary spherocytosis?
splenectomy
Does Sickle Cell Anemia affect the α or β chain of Hb? What amino acid substitution takes place?
β-chain
glutamate to valine
Sickle Cell Anemia protects against what species of bug that can cause malaria?
Plasmodium falciparum
What three driving factors can cause sickling?
hypoxemia, acidosis, dehydration
What form of Hb is protective against HbS? When do sickle cell patients usually present?
HbF
6 months
What is the treatment of SSA? Why?
hydroxyurea
increases HbF
What is a common presenting sign in infants with sickle cell anemia? Why?
Dactylitis
vaso-occlusive infarct in bone
Patients with SSA are at an increased risk of developing an infection caused by what? Why?
encapsulated organisms
Osteomyelitis in patients with SSA is caused by what organism primarily?
Salmonella paratyhphi
What is the most common cause of death in adults with sickle cell anemia? What often precipitates this disease?
acute chest syndrome
pneumonia
What specific type of kidney damage occurs in SSA?
renal papillary necrosis
What type of genetic anomaly occurs in Sickle Cell Trait?
one mutated chain
one normal chain
Where in the body do RBCs with sickle cell trait actually sickle? Why does this happen? What two things can this lead to?
renal medulla
severe hypoxia of renal medulla
inability to concentrate urine and microscopic hematuria
What drug is used to screen sickle cell trait? What does this drug cause?
Metabisulfite
HbS to sickle
What amino acid substitute is present HbC?
Glutamate to Lysine
What type of Hb can produce crystals in the blood?
HbC
What protein is missing during PNH? This makes RBCs particularly susceptible to destruction by what?
GPI anchor
complement
What protein attached to GPI is missing during PNH? What is the normal function of this protein?
DAF
inhibits C3 convertase
Why does PNH happen at night?
acidosis = activate complement
What two tests can be used to screen for PNH?
sucrose test
acidify serum
The main cause of death of PNH is what? What three locations?
massive thrombus
hepatic, portal or cerebral
What leukemia can PNH lead to? Why?
AML
mutations in myeloid stem cell
What causes the thrombus in PNH?
lysed platelets
What two diseases can arise due to PNH?
iron deficient anemia
AML
What is the inheritance pattern of G6PDase deficiency?
X-linked recessive
G6PDase deficiency can be protective against what?
Plasmodium falciparum
Is the african variant of G6PDase deficiency mild or severe?
african = mild
Is the mediterranean variant of G6PDase deficiency mild or severe?
severe
How does Hb precipitate during G6PDase? How does this manifest in RBCs?
Heinz bodies
bite cells
What group of antibacterials can cause RBC oxidative stress?
Sulfa drugs
What are the two classic presentations G6PDase will present with? Why?
back pain and hemoglobinuria
Hb is nephrotoxic
What isotype of Ab is present in the warm agglutinin test? What type of RBC is produced?
IgG
Spherocytes
What two diseases can cause a positive warm-agglutinin test?
SLE and CLL
What two drugs can cause a positive warm-agglutinin test?
penicillin and cephalosporin
What drug may bind directly to the RBC cell membrane and produce a cold agglutinin test?
penicillin
What drug may cause the body to produce autoantibodies that can give a positive cold agglutinin test?
methyldopa
What molecule serves as an opsonin in the spleen during Immune hemolytic anemia?
C3b
What two infectious agents can cause a positive cold-agglutinin test?
Mycoplasma pneumoniae
Mononucleosis
What does direct Coombs test detect? What two antibodies added to the reaction?
antibodies against RBCs
anti-IgG or anti-complement
What four disease states can cause microangiopathic hemolytis anemia?
TTP, HUS, DIC, HELLP
What is HELLP?
Hemolysis Elevated Liver Enzymes & Low Platelets
What type of RBC is produced during microangiopathic hemolytic anemia?
Schistocytes
Aortic stenosis can cause what sort of RBC to form? What disease does this happening fall under the umbrella of?
schistocytes
Microangiopathic Hemolytic Anemia
What two systems get infected by malaria?
RBCs and liver
What genus of mosquitos transmits malaria?
Anopheles
What species produces fever every other day?
vivax and ovale
What species produces fever every day?
falciparum
What cells of the kidneys produce EPO?
peritubular interstitial cells
What virus can produce anemia? Why?
Parvovirus B19
infects erythroid precursors
What three cell types are deficient during aplastic anemia?
anemia, thrombocytopenia and leukopenia
What invades the bone marrow during aplastic anemia?
fatty infiltrate
What are the three treatments of aplastic anemia?
EPO, G-CSG and GM-CSF
What does myelophthistic mean?
displacement of bone marrow
What two tissues store iron? What protein?
liver and bone marrow macrophages
ferritin
What fraction of transferritin is bound to iron?
1/3
TIBC measures what iron carrying protein?
transferrin
Why can gastrectomy cause iron deficient anemia?
loss of acid producing cells
acids maintains iron in Fe2+
Fe3+ is not absorbed
What is the first mechanism the body employs to generate iron in an iron deficient anemia?
release iron stores
What is the second mechanism the body employs to generate iron in an iron deficient anemia?
serum iron is used
What is the third mechanism the body employs to generate iron in an iron deficient anemia?
normocytic anemia (fewer RBCs)
What is the fourth mechanism the body employs to generate iron in an iron deficient anemia?
microcytic anemia
Does a microcytic anemia have an increased RDW?
yes
What does low ferritin cause higher TIBC?
liver senses low ferritin and increases production of transferrin
What a microcytic anemia have an increased or dcreased FEP?
increased
What drug is used to treat iron deficiency anemia?
ferrous sulfate
What three symptoms does a patient with Plummer Vinson Syndrome present with?
anemia, dysphagia and beefy red tongue
What are the two causes of ACD?
inflammation and cancer
Why does ACD cause TIBC to go down?
liver senses high ferritin and inhibits production of transferrin
Would ACD cause increased or decreased FEP?
increased
What cell do bone marrow macrophages hand iron off to?
erythroblasts
What is a good treatment of ACD in cancer pt’s?
EPO
What happens if one alpha-chain allele is deleted?
nothing
How many alleles are deleted during a cis or trans alpha-thalessemia?
two
Which is worse, cis or trans? Why?
cis
passing of severe thalassemia to offspring
How many genes are deleted if alpha-thalassemia is detected in the fetus?
all four
What chromosome is β-globin on?
eleven
What is the key isolated finding in β-thalassemia minor?
isolated increase in HbA2
Does β-thalassemia major produce symptoms in the fetus? Why?
no
HbF predominates
What type of globin tetramer is present during β-thalassemia major?
alpha tetramer
What four locations will undergo hematopoiesis during β-thalassemia major?
skull
facial bones
spleen
liver
What type of cell does B19 infect?
erythroid progenitors
How does folate enter the body?
THF
What develops faster, folate or B12 deficiency?
folate
Where is R-binder produced?
salivary gland
Where is B12 found?
animal proteins
What could produce a B12 deficiency, Crohns or U.C.?
Crohn’s
What color are parietal cells?
pink
Where in the GI tract does Diphyllobothrium latum damage?
distal ileum
What are the three presentations of B12 deficiency?
Macrocytic anemia
Subacute combined degeneration
glossitis
What B12 related substance damages the spinal cord? What structure is disturbed?
methylmalonic acid
myelin
What color is the nucleus of reticulocytes? Why?
blue-ish
residual RNA
What are the two etiologies of normocytic anemia?
peripheral destruction or underproduction
What is the normal reticulocyte count?
1-2%
What is the formula for correcting reticulocyte count?
(RC Count) (Hct/45)
What three organs compose the RES?
macrophages of spleen, liver and lymph nodes
What is globin broken into ?
amino acids
The levels of what will drop during intravascular hemolysis?
Haptoglobin
What starts appearing in RBC during splenectomy? What are these made of? Why?
howell-jolly bodies
fragments of remnant RBC nuclear material
spleen
When RBCs sickle, what chemical change is this called?
polymerization
Why can SSA result in extra-vascular hemolysis?
spleen removes deformed cells
Why can SSA lead to intravascular hemolysis?
sickled RBCs can lyse
Does sickle cell trait possess target cells?
no
Does PNH result as an acquired mutation or congenital mutation?
acquired
A mutation in what type of stem cell gives rise to PNH? What cell types are depleted during PNH?
myeloid
RBCs, WBCs and platelets
What is the Tx for Autoimmune Hemolytic Anemia? Why does this work?
IV immunogloblin
splenic macrophages eat Ig instead of coated RBCs
What surgery is used for Autoimmune Hemolytic Anemia?
splenectomy
Does IgG mediated hemolytic anemia involve intravascular or extravascular hemolysis? Why?
Extravascular
IgG binds RBCs in relatively warm central body regions
Does IgM mediated hemolytic anemia involve intravascular or extravascular hemolysis? Why?
intravascular
IgM binds RBCs in the relatively cool areas of the extremities
What protein binds to an IgM coated RBC? What does this protein serve to do in the spleen?
fixes complement
acts as opsonin for splenic macrophages
What does the Indirect Coombs test detect?
presence of auto-antibodies
What is the first stage of Iron deficient anemia? What are the lab values?
storage iron is depleted
↓ ferritin and ↑ TIBC
What is the second stage of Iron deficient anemia?
serum iron is depleted
What is the third stage of Iron deficient anemia?
normocytic anemia
What is the fourth stage of Iron deficient anemia?
microcytic anemia
In what two locations are β-thalassemia mutations prevalent?
promoter and splice site
What does β+ mean during a β-thalassemia?
decreased production
When does β-thalassemia major arise? Why?
a few months after birth
depletion of HbF
How many lobes must a hypersegmented neutrophil have?
five or more
What drug can cause a macrocytic anemia?
5-FU
During a folate deficiency, what are the levels of homocysteine? MMA?
high homocysteine
normal MMA
Where in the GI tract does B12 bind intrinsic factor?
small bowel
What part of the GI tract is most often damaged during Crohn’s disease?
ileum
What is the serum marker for extravascular hemolysis?
Unconjugated bilirubin
What is the serum marker for intravascular hemolysis?
hemoglobin
Howell-Jolly boides are indicative of what procedure?
Splenectomy
Is HbS an extravascular or intravascular hemolysis?
extra
Other than sickled cells, what would be present on a blood smear in a patient with sickle cell anemia? Why?
Howell-Jolly bodies
autosplenectomy b/c of sickled cell damage
What is the mode of inheritance of HbC?
autosomal recessive
Paroxysmal Nocturnal Hemoglobinuria is a defect in what cell type?
Myeloid
Does PNH result in intravascular or extravascular hemolysis?
intravascular
Why can PNH cause a massive fibrosis?
lysed plateletes release contents into blood
During Immune Hemolytic Anemia, does IgM or IgG fix complement? Cold or Warm?
IgM
cold
Is heme or non-heme iron more easily absorbed?
heme
TIBC indirectly measures what protein?
transferrin
Which two enzymes of heme synthesis are housed in the mitochondria?
ALA synthase
Ferrochelatase
What is Methylmalonic Acid converted into?
Succinyl-CoA
Does Sickle Cell Trait have any HbF on electrophoresis?
no
Does Sickle Cell Disease have any HbA on electrophoresis?
no
What happens to the kidneys during PNH?
hemosiderin accumulation
What is a Myelophthisic Process?
process that replaces bone marrow
What can anemia do to ones heart especially in the presence of pre-existing heart disease?
angina
What two groups of people are more likely to develop a folate deficiency?
alcoholics and elderly
Is glossitis due to folate or B12 deficiency?
folate
What is the inheritance pattern of SSA?
AR
What swells during Dactylitis? How old?
hands and feet
six months
What CD molecule is DAF?
CD55
What particular oxidative molecule are RBCs exposed to?
H2O2
What is reduced during G6PDase Deficiency?
G6PD half life
What would be seen on blood smear during Autoimmune Hemolytic Anemia?
spherocytes
What does the fever during malaria correlate with?
RBC lysis
