RBC Pathology 2 Flashcards
(T/F) Humans are totally dependent on dietary Vitamin B12
True
Vitamin B12 is absorbed in what part of the small intestine?
Ileum
Intrinsic factor is secreted by parietal cells in the _______ muscosa of the stomach
Fundic
Vitamin B12 takes the _____ group from methyltetrahydrofolate and transfers a carbon to homocysteine to form __________
Methyl; methionine
___________ delivers vitamin B12 to the liver and other cells of the body
Transcobalamin II
2 pathways where vitamin B12 is used
1) Conversion of homocysteine to methionine
2) Isomerization of methylmalonyl CoA to Succinyl CoA
In ________ deficiency, both homocysteine and methylmalonic acid are elevated while in ________ deficiency, only homocysteine levels are increased
B12; Folic acid
In Vitamin B12 deficiency, accumulation of methylmalonic acid causes demyelination of the _________ and ________ tract of the spinal cord
dorsal and lateral
In Vitamin B12 deficiency, provision of folate will improve s/s of _________ but not _______
anemia; neurologic symptoms
Enumerate anemias d/t diminished erythropoesis
Megaloblastic anemia, pernicious anemia, iron deficiency anemia
Why does folic acid and B12 deficiency cause megaloblastic anemia?
B12 and folic acid are needed in nuclear maturation and DNA synthesis causeing nuclear-cytoplasmic asynchrony
Enumerate the common causes of megaloblastic anemia
1) Decreased intake (vegan diet, alcoholics)
2) Impaired absorption
3) Fish tapeworm (competitive uptake)
4) Increased requirements (pregnancy, thyrotoxicosis, cancer, infants)
5) Medication: folic acid antagonists like methotrexate
6) Increased losses (hemodialysis)
In PBS of megaloblastic anemia what type of RBC is seen? Which cells are affected?
Macrocytic, hyperchromic RBCs; RBCs, Platelets, WBCs
In PBS of megaloblastic anemia what type of neutrophils are seen?
hypersegmented (macropolys)
The reticulocyte count is _________ in megaloblastic anemia. What is seen 5 days after IV administration of B12 / folic acid
decreased; striking reticulocytosis
In megaloblastic anemia there is bone marrow ___________ that is hypercellular
hyperplasia
In the BM of megaloblastic anemia, what is the erythroid:myeloid ratio?
1:1
In megaloblastic anemia, MCHC is always elevated (T/F)
false, may be normal to elevated
In pernicious anemia, there are autoantibodies against?
Intrinsic factor and/or parietal cells
Describe Type I of autoantibodies to intrinsic factor-type of pernicious anemia
Blocks attachment of B12 to IF
Describe Type II of autoantibodies to intrinsic factor-type of pernicious anemia
Blocks attachment of B12-IF complex to ileal receptors
Describe Type III of autoantibodies to intrinsic factor-type of pernicious anemia
Antibodies recognize the alpha and beta subunits of the gastric proton pump
Autoantibodies to gastric parietal cells leads to _____ and __________
Chronic atrophic gastritis; gastric atrophy
Enumerate the changes seen in pernicious anemia NOT seen in megaloblastic anemia
1) Achlorhydria
2) Serum antibodies
3) Atrophy of the stomach
4) Beefy red tongue (atrophy of the tongue)
Most common nutritional disorder in developing countries
Iron deficiency anemia (IDA)
Causes of IDA
1) Low dietary intake (elderly, infants and the mamamayan who cant afford meat =P)
2) Poor absorption
3) Increased demand (pregnancy, children)
4) Chronic blood loss
Which type of heme is more well-absorbed?
Heme iron
What are the functional forms of iron?
Heme, myoglobin, catalase
What is the storage form of iron? Where are they stored?
Ferritin; bone marrow & macrophages (RES)
(T/F) Free iron is highly toxic
True
What is ferritin? Where is it found? Where is it MAINLY found?
Iron-protein complex; liver, spleen, BM, skeletal muscle; Macrophages
Where is the storage form of iron in macrophages derived from?
breakdown of RBCs
Where is hepatocyte iron derived from?
plasma transferrin
(T/F) Iron is actively excreted
False, there is very limited iron excretion
What is the only way that iron can be removed from the body?
Chelation
Protein that ihibits absorption of iron in the gut
Hepcidin
Hepcidin is increased in these situations
Anemia of chronic disease
Untreated infections
PBS in IDA shows _______ ________ RBCs
hypochromic, microcytic
If you see hypochromic, microcytic anemia in adults, what do you check for? In children?
Chronic blood loss; thalassemia or IDA
BM in IDA shows __________ sideroblasts
decreased
In IDA, serum ____ and _____ are decreased and ______ is increased
Fe and ferritin; TIBC
What is the response to treatment in IDA
Reticulocytosis in 3 days
Give s/s of IDA
koilonychia, pica, alopecia, atrophic glossitis, atrophic gastritis
What constitutes the Plummer Vinson Syndrome?
Esophageal webs + atrophic gastritis + IDA with depressed Hb, Hct, MCV, serum Fe, ferritin
Anemias d/t BM failure
aplastic anemia
Aplastic anemia is a syndrome of?
chronic primary hematopoetic failure and attendant pancytopenia
In the diagnosis of aplastic anemia, the BM shows? PBS shows? and the reticulocyte count is (decreased / increased)?
hypocellular with fat and no hematopoetic elements; Pancytopenia; Decreased
2 treatments for aplastic anemia
transplant, immunosuppressive therapy
Causes of aplastic anemia
hereditary (Fanconi’s anemia)
Idiopathic (Stem cell defects)
Acquired
Give some acquired causes of aplastic anemia
Drugs (chloramphenicol, phenytoin, carbamazapine), Chemicals, infections (CMV, parvovirus, etc), Whole body irradiation
The normal histology of the bone marrow shows ___ % fat and ___% hematopoetic cells
50%; 50%
How do you histologically differentiate tumoral BM vs BM in aplastic anemia?
Tumoral is hypocellular with no fat while Aplastic anemia is hypocellular with more fat (than hematopoetic cells)
Enumerate the clinical features of aplastic anemia
1) Pancytopenia
2) Progressive weakness, pallor, dyspnea
3) Thrombocytopenia
4) Splenomegaly
5) RBCs are slightly macrocytic, normochromic
What is a primary BM disorder wherein only the erythroid progenitors are suppressed? What is it usually associated with?
Pure red cell aplasia; neoplasms, thymoma, large granular lymphocytic leukemia
Give other causes of anemia
Myelophtisic anemia, chronic renal failure, diffuse liver disease, neoplasia, hypithyroid disease
What type of RBC is diagnostic of myelophthisic anemia
teardrop shaped RBC
Give the anemias associated with decreased MCHC, MCV and MCH
IDA, thalassemia, Anemia of chornic inflammation
Give the anemias associated with increased MCHC, MCV and MCH
Pernicious anemia, B12 deficiency, Folate deficiency
Give the anemias associated with normal MCHC, MCV and MCH
Hemolytic anemia, aplastic anemia, Polycythemia
Which anemia has an increase in color (MCHC) but a decrease in size (MCV)?
Spherocytosis
Polycythemia is an increase in _____ with a corresponding increase in ______
RBCs; Hemoglobin
What are the 3 types of polycythemia? What is the difference between them?
Relative ( Volume is decreased but RBC not actually increased); Absolute (increase in total RBC); Stress polycythemia (individuals are usually hypertensive, obese & anxious)
Primary absolute polycythemia results from?
An intrinsic abnormality oh hematopoetic precursors, neoplastic condition
Secondary absolute polycythemia results from?
Increased erythropoetin secretion that may be compensatory or pathologic
Give some tumors that produce erythropoetin
renal cell CA, hepatocellular CA, cerebellar hemangioblastoma
How do you differentiate between primary and secondary absolute polycythemia?
Primary has decreased erythropoetin which is increased in secondary
Type of polycythemia where there is an increase in marrow production of myeloid progenitors but lymphocytes are not increased
Polycythemia vera
Polycythemia vera is d/t a mutation of ______ causing erythropoetin receptors to become ______
JAK2 tyrosine kinase; hypersensitive
In the laboratory diagnosis of polycythemia vera, what are the values of: RBC, WBC, Platelets, Hct; What is seen in the PBS?
RBC (6M); WBC (12000 - 50000); Platelets (=/> 500000); Hct (=/> 60%); PBS shows Panmyelosis
Incidence of polycythemia vera is higher in?
Males, middle aged to elderly
S/S of polycythemia vera
Cyanosis, pruritus, peptic ulcer, plethoric headache, dizzines, hypertension
Complications of polycythemia vera
Thrombosis, Bleeding, Hyperuricemia, Myelofibrosis
Treatment for polycythemia vera
Regular phlebotomy
