Anemias of Blood Loss & Decreased Production Flashcards
What is the unifying feature of hypoproliferative anemias? Classify them by pathophysiology.
low reticulocyte
- Extrinsic cause
- nutritional deficiencies
- renal failure
- chronic disease
- Intrinsic cause (bone marrow failure)
- infiltrative processes
- aplastic anemia
- hematopoietic neoplasms
What diseases are associated with microcytic anemia?
iron deficiency
chronic disease
sidroblastic anemia
thalassemia
What diseases are associated with Normochromic normocytic anemia?
chronic disease
What diseases are associated with macrocytic anemia?
Vitamin B12 or folate deficiency
medication/toxin effect
infections
neoplasms
What are the defects seen in microcytic hypochromic anemias?
decreased RBC hemoglobin production
cytoplasmic maturation defect
What is the most common cause of anemia world-wide?
iron deficiency
What are the common causes of iron deficiency anemia?
dietary deficiency
impaired absorption
increased requirement
chronic blood loss
What is the cause of iron deficiency in post-menopausal women & adults without uteruses?
chronic blood loss (cancer, etc.) until proven otherwise
Where is iron absorbed & in what form?
duodenum
most in the form of heme iron
How are we able to control the amount of iron stores in the body?
by controlling the absorption
we do not have good ways of getting rid of iron once it is absorbed
Free iron is bound to what carrier protein? Why?
transferrin
because free iron is toxic to cells
Iron is transferred from the duodenum to what main locations?
- bone marrow
- production of erythroid precursors
- liver
- storage
- production of some enzymes
The storage of iron in the liver triggers the production/secretion of what protein? What does it do?
Hephaestin
induce the degradation of ferroportin (iron membrane transporter), therefore decreasing the amount of iron absorbed
What are the general physical signs of anemia?
- Pale nail beds
- Pallor
- tachycardia (palpitations)
- fatigue
What is koilonychia & what pathology does it indicate?
“spooning” of the fingernails
long-standing severe iron deficiency anemia
Glossitis is a sign indicative of what types of anemia?
inflammation of the tongue
iron or B12/folate deficiency
What are the features of Plummer-Vinson syndrome?
iron-deficiency anemia,
postcricoid dysphagia,
upper esophageal webs.
What are the classic findings in peripheral blood associated with iron deficiency?
- Microcytic hypochromic cells
- small cells w/ large area of central pallor
- anisocytosis
- poikilocytosis (elliptocytes, mainly with “pencil cells”
- decreased reticulocyte count
- mild thrombocytosis
A trick for estimating red blood cell size: a normal red blood cell should be about the same size as what other cell?
lymphocyte
Why do you commonly see mild thrombocytosis with iron deficiency anemia?
because have erythropoietin stimulating erythroid precursors in the bone marrow to start proliferating & maturing into RBC
it also stimulates the megakaryocytes
What type of bone marrow biopsy is shown in the provided image?
normal
iron is stained blue- the high power image is an example of an iron granule in a normal erythroid-precursor
What type of bone marrow biopsy is shown in the provided image?
iron deficiency anemia
(negative iron stain) – looking for blue
What tests should be performed to diagnose iron deficiency?
serum iron (measuring bound iron)
total iron-binding (equivalent to plasma transferrin)
serum ferritin quantitation (estimation of bone marrow iron store)
serum soluble transferrin receptor (soluble protein in the plasma that helps RBC accept iron form transferrin, gives good estimation of what is going on with transferrin receptors on RBC)
What condition could cause elevated levels of serum ferritin quantitation?
chronic inflammatory states - it is an acute phase reactant
(serum soluble transferrin receptor measure developed to assess individuals with severe chronic inflammatory diseases)
What is the relationship between iron stores and serum soluble transferrin receptor levels?
inversely proportional
-don’t memorize, but check out these relationships if it helps you-
Fill out the provided table
What is the second most common cause of microcytic hypochromic anemia world-wide?
Anemia of chronic disease
Anemia of chronic disease is general what type?
microcytic hypochromic
normocytic normochromic
How quickly after onset of chronic disease is anemia usually detcted?
1-2 months
How quickly after onset of chronic disease is anemia usually detcted?
1-2 months
What are the 3 effects of chronic disease that lead to anemia?
failure of erythropoiesis
lack of iron for hemoglobin synthesis
decreased RBC survival
all cytokine mediated
What are the characteristic morphologic features of a peripheral blood smear from a patient with anemia of chronic disease?
NO characteristic morphologic feature
What would you expect from the RDW & reticulocyte count in patients with anemia of chronic disease?
normal RDW
low reticulocyte count
Fill out the provided table
Why do you see an increase in bone marrow iron with anemia caused by chronic disease?
reticularendothelial cells are not releasing the iron, leading to a buildup of iron in the marrow
What happens in sideroblastic anemias?
abnormal iron metabolism within the RBC itself
iron is sequestered in the developing erythroblast mitochondria & is unavailable for heme synthesis
What are the characteristic morphological findings seen in a peripheral blood smear from a patient with sideroblastic anemia?
blood appearance varies with cause
What type of anemia is shown in the provided bone marrow stains?
Sideroblastic anemia
the stain on the right had a counterstain performed to make the nuclei more visible, which helps to identify the ringed sideroblasts (arrows)
left hand side shows an increase in iron stores (blue)
Fill out the provided table
What is the most common cause of megaloblastic anemia?
Vitamin B12 deficiency or folate deficiency
What are the most common
reduced intake
impaired absorption
increased requirement
drug effect
What cofactor is necessary for absorption of Vitamin B12?
intrinsic factor
(produced by parietal cells in gastric mucosa)
Describe the pathophysiology associated with how the disease depicted in the slides causes anemia?
autoimmune destruction of gastric mucosa – destruction of the parietal cells
parietal cells are unable to produce intrinsic factor
the body is unable to absorb vitamin B12
What is a unique feature of megaloblastic anemia?
jaundice
What features of the provided peripheral blood smear are indicative of megaloblastic anemia?
jaundice
Describe the pathophysiology associated with Vitamin B12 and Folate Deficiency megaloblastic anemia.
Vitamin B12 7 folate are required for DNA synthesis - Cells divide more slowly in deficiency
However, RNA synthesis continues normally, which leads to enlarged precursor cells with immature nuclei as compared to the cytoplasm
How would you describe the bone marrow in the provided image?
normal erythroblasts
How would you describe the bone marrow in the provided image?
Megaloblastic Anemia
large erythroid precursors
large bands
nucleus is larger & less mature for the amount of cytoplasm
Severe megaloblastic anemia bone marrow biopsy can mimic what other condition?
leukemia
immature nuclei causes cells to be mistaken for blasts
Why do you see hypercellular marrow in severe megaloblastic anemia?
erythroid & granulocytic hyperplasia because of ineffective hematopoiesis
Fill out the provided table
Are folate or Vitamin B12 deficiencies more common?
folate – can become deficient within months
Vitamin B12 will take about 5 years to develop symptoms of deficiency
What are the clinical features seen in apalstic anemia?
any age / sex
insidious onset
- Pancytopenia
- anemia: weakness, pallor, dyspnea, tachycardia
- thrombocytopenia: ecchymoses, petechiae
- neutropenia
- frequent persistent minor infections
- acute serous infections with fever, chills, etc.
- risk for disseminated fungal infections
What type of anemia is Fanconi Anemia?
What is its cause?
Clinical features?
Constitutional Aplastic Anemia
defect in DNA repair - autosomal recessive
usually die of marrow failure - risk of leukemia / malignancies
What features of the provided slides are consistent with Fanconi Anemia?
What features of the provided slides are consistent with Fanconi Anemia?
What is the cause of pure red cell aplasia?
only erythroid progenitors are suppressed
Thymomas as associatd with what type of anemia?
pure red cell aplasia
& Myasthenia Gravis
Large glandular lymphocytic leukemia is associated with what type of anemia?
pure red cell aplasia
The provided condition shown in the slide is associated with what condition?
giant erythroblasts - nuclear inclusions composed of viruses
Pure Red Cell Aplasia Associated with Parvovirus B19
What types of hematopoiesis is affected in Parvo B19 virus?
erythropoiesis is messed up
granulopoiesis & megakaryopoiesis is normal
What is the cause of Blackfan-Diamond Anemia?
It is what type of condition?
Clinical associations?
Defect in generation of ribosome in RBC precursors (pure red cell aplasia)
Autosomal dominant
short stature, craniofacia, thumb, skeletal
How can you differentiate Inherited Red Cell Aplasia from Parvo B19 associated Red Cell Aplasia?
No giant erythroblasts in inherited Red Cell Aplasia?
What is the cause of Myelophthisic Anemia?
Metastatic Carcinoma
