Anemia Flashcards
Hb < for anemia in males
Hb
Hb<13.5 males
Hb<12.5 in females
MCV for Microcytic, normocytic, macrocytic
MCV <80 microcytic
MCV=80-100 normocytic
MCV>100 macrocytic
Microcytosis seen in microcytic anemia is caused by a decrease in
Hemoglobin
Components of Hemoglobin?
Heme (Iron+protoporphyrin ring) and Globin chains
Anemia of chronic disease is caused when
iron is locked away in macrophages
Sideroblastic Anemia results in a deficient?
Protoporphyrin rin
Thalassemia is a deficiency or defect in the
globin component of Hgb
Most common nutritional deficiency in the world?
Iron deficiency anemia
Iron is absorbed in the
duodenum by the enterocyte
What cell in the duodenum regulates iron absorption?
Enterocyte in the duodenum
What transporter is used to move iron from the enterocyte to the blood?
Feroportin
How does the body regulate whether or not to allow iron into the blood?
Feroportin transporter in the enterocyte
In the blood, iron is transported by _______ to the liver and bone marrow macrophages
Transferritin
Once the iron is transported by transferritin, is it stored intracellularly bound to
Ferritin, this binding prevents iron from creating free radicals via the Fenton Reaction
What is the fenton reaction?
H202 + Fe2+ –> OH- + OH+ + Fe
Iron in the blood is measured via
iron in the blood
meausring the amount of trasnferrin molecules in the blood lab value?
TIBC
Iron deficiency in infants could be caused by
Breast feeding
Serum Ferritin measures
iron in the bone marrow and liver
Children w/ iron deficiency anemia
poor diet
Adult male w/ iron deficiency anemia?
Peptic Ulcer disease
Elderly w/ iron deficient anemia?
Colon polyps/carcinoma in the western world
Hookworm in the developing world
Necator and Ancylostoma both cause iron deficiency anemia because of
blood loss
Disease seen w/ HLA-DQ2, Dermatitis Herpetiformis on shoulder/elbows/knees, iron deficiency anemia from involvement of duodenum (villous blunting, patchy)
Celiacs
Fe2+ is more readily absorbed than Fe3+, and iron maintains Fe2+ state when in acidic or basic environment?
Acidic
Gastrectomy creates an environment that is less acidic which can lead to iron deficient anemia because the iron is mainly in Fe2+ or Fe3+ state?
Fe3+
what happens to TIBC when tranferrin goes down
it goes up
the very early stages of iron deficiency anemia because the bone marrow simply makes less red blood cells without adapting/compensating for less heme
Normocytic anemia
why would iron deficiency anemia ultimately lead to hypochromasia?
Less heme, so the central ring of pallor grows and also microcytic
Koilonychia is
spoon shaped nails
Red blood cell distribution width describes?
range of RBC size.
Why would the red blood cell distribution (RDW) increase in iron deficiency anemia?
At first the anemia is normocytic and then microcytic so wide range of sizes
Free erythrocyte protoporphyrin present with iron deficient anemia because?
there is no iron to make the ring and bind to form heme
Treatment of iron deficient anemia?
Ferrous Sulfate
Esophageal web (mucosal protrusion) and atrophic glossitis associated with
Plummer-Vinson syndrome
anemia, dysphagia, beefy-red tongue
Beefy-red tongue could be seen with esophageal web in
Plummer Vinson syndrome, seen with iron deficient anemia
Anemia of chronic disease is the most common anemia in
hospitalized patients, seen in cancer patients and chronic inflammation
Hepcidin is an acute phase reactant, its function?
sequesters iron in storage sites to keep iron from being transferred (prevents iron from macrophages to erythroid precursors)
Hepcidin is an acute phase reactant that prevents iron transfer from ______ to ______ ______ and it suppresses EPO production
macrophages to erythroid precursors
Giving exogenous EPO to patients w/ Anemia of chronic disease because hepcidin
hepcidin decreases EPO production
where does protoporphyrin synthesis occur?
mitochondria
HYRate limiting steps of Protoporphyrin synthesis?
Amino Lavulinic Acid Synthase (+B6) and ALAD
ALA —> porphobilinogen
ALAD
HYWhere does iron remain if protoporphyrin is deficient?
in the mitochondria, it will pile up and create a ring around the nucleus
When iron builds up in the mitochondria, what do we see histologically?
Ringed Sideroblasts seen with prussian blue stain
HYSideroblastic Anemia congenital defect associated with what rate limiting enzyme?
ALAS (Succinyl CoA—>Amino Lavalunic Acid)
Acquired Sideroblastic aneminina can be a result of
Chronic alcoholism Lead poisoning (ALAD and Ferrokolotase) Vitamin B6 deficiency (cofactor for ALAS)
Isoniazid therapy for TB can cause what sort of deficiency leading to Sideroblastic anemia?
Vitamin B6
Iron overloaded state lab findings?
Ferritin and TIBC
Serum Iron and %Saturation
Ferritin increased TIBC decreased
Serum Iron increased % Saturation increased
Iron overloaded lab findings in Sideroblastic anemia also look like
Hemochromatosis
thalessemia is not a defective globin chain, rather
decreased synthesis of globin chains
Thalessemia is protective against with species of malaria?
Plasmodium Falciparum
3 normal types of hemoglobin:
HbF (alpha2gamma2)
HbA (alpha2beta2)
HbA2 (alpha2gamma2)
alpha chain is incredibly important and usually has ____ alleles and are present on chromosome ____
alpha chain: 4 alleles, on chromosome 16
alpha thalessemia is usually due to
gene deletion
1 alpha gene deletion of the globin chain is asymptomatic, 2 alpha genes deleted can be cis (on the same chromosome) or trans, which is worse and associated with increased risk of what in offspring?
Cis alpha deletion associated with increased risk of severe thalessemia in offspring and associated with spontaneous abortion in asians.
Trans deletion not as severe and seen in Africa
3 alpha globin chain deletions seen in alpha thalassemia will result in damage to the RBCs because the beta chains form _____
tetramers known as HbH
Tetramers of beta globin chains are known as HbH which can be seen on
electrophoresis
4 alpha genes deleted in alpha thalassemia would lead to a gamma chain tetramer formation known as Hb Barts which will do what to a baby in utero?
hydrops fetalis, this is a lethal gene deletion
What’s a significant difference between the genetic nature of alpha thalassemias versus beta thalassemias?
alpha thalassemias due to gene deletions
beta thalassemia due to gene mutations
B-thalassemia: 2 beta genes on which chromosome?
Chromosome 11
B-thalassemia: least severe form=
Normal Beta and B+
Target cells seen with
Beta thalassemia minor
Beta-thalassemia seen with
isolated increased HbA2 (5%)
B-thalassemia major: both beta chains knocked out doesn’t affect the fetus because
fetus uses a gamma chain not a beta
Severe anemia in neonate a few months after birth could be
Beta-thalassemia because baby starts switching to AB hemoglobin chains from HbF
in B-thalassemia major alpha chains form tetramers which damages the RBCs while being made, but if the RBC is able to escape, what will happen?
the spleen will destroy the RBC
The severe anemia seen in B-thalassemia will cause
massive erythroid hyperplasia
Expansion of hematopoesis into the marrow of the skull and facial bones seen in B-thalassemia will present with what radiological findings? and what will happen to the face?
Crewcut appearance of the skull (massive expansion of hematopoeisis) and chipmunk face
chronic transfusions seen in patients with b-thalassemia major can lead to
hemochromatosis
no HbA seen in
b-thalassemia major
2 most common cause of megaloblastic anemia (macrocytic anemia)
Folate or Vitamin B12 deficiency
folate enters the body as methylated-THF, to enter the body it THF needs to be demethylated which Vit B12 takes off the THF. methylated Vitamin B12 passes off the methyl group to _______ which turns into _____
Homocysteine turns into methionine (these are needed for DNA synthesis)
there is a different between macrocytic and megaloblastic anemias
Macrocytic due to another cause that isn’t vitamin deficiency then that is simply called macrocytic anemia and not megaloblastic.
Causes of macrocytic anemias:
Alcoholism
Liver Disease
Drugs (5-FU)
Findings in neutrophils w/ megaloblastic anemia due to folate or vit b12 deficiency
hypersegmented neuts (also will show really large RBCs)
Macrocytic Anemia won’t present with what findings as compared to Megaloblastic anemias?
Macrocytic won’t present w/ hypersegmented neutrophils or megaloblastic cells in rapidly dividing cells. RBCs will still have MCV>100 though
Where is Folate absorbed?
Jejunum
Causes of Folate Deficiency?
Poor diet (EtOH, elderly) Increased demand (pregnant, cancer, hemolytic anemia) Folate Antagonists (methotrexate)
Methotrexate can lead to folate deficiency which can lead to Megaloblastic Anemia because it is inhibits ________
Dihydrofolate reductase
HY Why is there an increase in serum homocysteine with folate deficiency?
there isn’t enough THF for Vit b12 to demethylate and then pass on to Homocysteine so homocysteine piles up
Methylmalonic acid gets converted to Succinyl CoA by Vitamin B12 and is normal in ______ deficiency which helps distinguish from a similar clinical presentation of Vitamin B12 deficiency.
Folate deficiency
Salivary gland produces what binding protein that attaches to Vitamin B12
Haptocorrin (R-Factor) which is cleaved and in the intestine it is bound to intrinsic factor that is produced in the body of the stomach by parietal cells
Parietal cells of the stomach are important because they produce ______ which bind to Vitamin B12 after Vitamin B12 has been cleaved from Haptocorrin
Intrinsic factor.
The Intrinsic Factor + Vit B12 complex is absorbed in the
Ileum
Most common cause of Vitamin B12 deficiency?
Pernicious Anemia
Pernicious Anemia is the autoimmune destruction of the parietal cells in the stomach which is an issue for Vitamin B12 because
Vitamin B12 needs to bind to IF before being absorbed in the ileum
The P’s of Parietal Cells
Pernicious Anemia
Proton Pumps: make acid
Pink
Other than Pernicious anemia, other causes of Vitamin B12 deficiency?
Pancreatic Insufficiency
Damage to terminal ileum from Crohn disease or Diphyllobothrium latum
Dietary deficiency is rare except in vegans
Iron deficiency seen in _________ disease whereas Crohn’s disease presents w/ _______ deficiency
Iron deficiency seen in Celiacs
Vitamin B12 deficiency seen in Crohn’s (because of terminal ileum involvement)
Why could Pancreatic insufficiency cause a vitamin B12 deficiency?
B12 from diet + Haptocorrin from saliva—Proteases from pancreas–>cleaved free B12 in small bowel + Intrinsic factor from parietal cells—-> terminal ileum–>absorbed
So the R-binder and Vitamin B12 complex aren’t cleaved
Why could Pancreatic insufficiency cause a vitamin B12 deficiency?
B12 from diet + Haptocorrin from saliva—Proteases from pancreas–>cleaved free B12 in small bowel + Intrinsic factor from parietal cells—-> terminal ileum–>absorbed
So the R-binder and Vitamin B12 complex aren’t cleaved
Inherited hereditary spherocytosis is autosomal
dominant
Hereditary spherocytosis is a defect causing blebs of the membrane jutting out because of a defect in what protein?
tethering proteins commonly spectrin, ankyrin, band 3.1.
Hereditary Spherocytosis will present with what on peripheral smear?
loss of central pallor, round, wide range of sizes
An increase in MCHC is seen in along w/jaundice with unconjugated bilirubin and and increased risk for bilirubin gallstones
Hereditary Spherocytosis (also in autoimmune anemia you see the increased MCHC)
What virus affects the erythroid precursors and those w hereditary spherocytosis are particularly susceptible to infection
Parvovirus B19
Diagnosis of Hereditary spherocytosis
osmotic fragility test (increased fragility in hypotonic solution)
Splenectomy is recommended to alleviate associated anemia in the treatment of
Hereditary Spherocytosis. Will still present w/ spherocytes and will present w/ Howell-Jolly bodies because of splenectomy.
Autosomal recessive mutation in the Beta chain of the Hgb in which the normal ________ acid which is hydophilic is replaced w/ _____ which is hydrophobic
Normal hydrophilic glutamic acid replaced w/ valine which is hydrophobic
what do HbS chains form?
polymers causing sickling of the RBCs, they sickle when oxygen is removed and desickle while passing through circulation leading to membrane damage of the RBC
Increased risk of polymerization of HbS includes
Hypoxemia
Dehydration
Acidosis
Protective against sickling?
HbF. which is why people with sickle cell disease won’t present until 6months in neonate.
Why would treatment w/ hydroxyurea prevent sickling?
Hydroxyurea increases the levels of HbF (for unknown reasons)
the membrane damage that occurs via the sickling and desickling of HbS leads to extravascular hemolysis as the spleen removes these damaged cells from the circulation. this presents as
Anemia
Jaundice w/ unconjugated hyperbilirubinemia
Increase risk for bilirubin gallstones
Target cells in blood smear
There is some intravascular hemolysis w/ HbS. This presents with a decrease in the scavenger molecule that tries to save the hemoglobin?
Haptoglobin
Extramedullary hematopoeisis can lead to what on xray and what facial appearance?
Crew cut on xray
Chipmunk facies
Irreversible sickling can lead to vasoocclusion which will present as swollen hand and feet due to vaso-occlusive infarcts of bones. A 6 months old black baby’s hands shown that are swollen?
Dactylitis from irreversible sickling leading to vaso-occlusion
Why would a kid w/ sickle cell disease be at an increased risk of encapsulated organisms?
Because of autosplenectomy as complication, so you’d see howell-jolly bodies on blood smear
Osteomyelitis is most commonly caused by Staph Aureus, however in those with sickle cell anemia, what gram-negative motile rod is more commonly implicated in osteomyelitis in those w/ SCA
Salmonella paratyphi
Most common cause of death in those w/ sickle cell anemia for
kids
adults
Kids: infection by encapsulated organisms
Adults: Acute Chest syndrome (vaso-occlusion in pulmonary microcirculation often precipitation by pneumonia)
Vaso-occlusive crisis complications in those with sickle cell anemia
Acute Chest Syndrome: occlusion in pulmonary microcirculation usually after pneumonia, most common cause of death in adults w/ SCA (presenting w/ dactylitis)
Pain crisis
Renal papillary necrosis: gross hematuria and prorteinuria
how much HbS do you need to actually sickle and get the symptoms?
45%
if you have less than 45% HbS, you will asymptomatic but because of the hypoxia and hypertonicity of the renal medulla, the low amount of HbS will still cause sickling. What is the classic findings from microinfarctions in the renal medulla in someone w/ sickle cell trait
Microscopic Hematuria and a decreased ability to concentrate urine
What screen identifies HbS in any cell (so sickle cell trait and disease)
Metabisulfite screen
Can also do Hb Electrophoresis to confirm presence and amount of HbS
In Sickle Cell disease, Glutamic acid is replaced by valine. In hemoglobin C, what is glutamic acid replaced w/?
Lysine
You’ll see Hgb C on PBS
