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
