Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

66 Cards in this Set

  • Front
  • Back
What is the cause of Megaloblastic Anemia?
Vitamin B12 or Folate deficiency
Describe why Vitamin B12 and Folate deficiencies cause Megaloblastic Anemia
Both are needed for DNA synthesis (Thymidine production) - without DNA Synthesis Erythroid precursor cells cannot replicate
Describe the Absorption of Vitamin B12
1. B12 is released from its protein-bound form by the action of pepsin and then binds to Salivary Vitamin B12 binding proteins = Cobalophilins or R-binders
2. R-Vitamin B12 complexes are broken down by Pancreatic Proteases in the Duodenum
3. Released B12 then attaches to Intrinsic Factor (from Parietal Cells)
4. IF/B12 attaches to receptor in the Ileum
5. Passed on to Transcobalamin II = plasma transport protein
What 3 processes is Vitamin B12 involved in?
1. Converts 5-methyl-THF to THF
2. converts Homocysteine to Methionine
3. Methylmalonyl CoA --> Succinyl CoA

**1&2 involve both B12 and Folate
What could be 3 general causes of Vitamin B12 deficiency?
1. Decreased intake = i.e. vegetarian
2. decreased Absorption
3. Increased requirement
What 6 things could cause decreased absorption of Vitamin B12?
1. Pernicious Anemia = IF deficiency
2. Gastrectomy = IF deficiency
3. Malabsorption (IBD)
4. Ileal resection
5. Bacterial overgrowth
6. Fish Tapeworm --> Diphyllobothrium latum
What 3 things could cause an increased need for Vitamin B12 and result in its deficiency?
1. Pregnancy
2. Hyperthyroidism
3. Cancer
What is the function of Folate?
Involved in 1-carbon transfers in producing Thymidine for DNA synthesis
What things are associated with decreased intake of Folic Acid?
Alcoholism and infancy
What 3 things would cause decreased absorption of Folate?
1. Malabsorption (Sprue)
2. Drugs = Anticonvulsants, Oral contraceptives
3. Intestinal disease (Lymphoma)
What would cause an increased loss of Folate?
What 4 things would cause an increased requirement for Folate and therefore cause deficiency?
1. Pregnancy
2. Infancy
3. Cancer
4. increased Hematopoiesis
What drug impairs the use of Folate
-Methotrexate = inhibits DHF Reductase-
-5-FU = inhibits Thymidylate Synthase
Describe the pathogenesis of Megaloblastic Anemia
1. B12 or Folate Deficiency
2. Decreased DNA synthesis
3. Impaired nuclear maturation
4. Megaloblastic anemia
Describe how Pernicious Anemia causes Megaloblastic Anemia
-Autoimmune disease in which Parietal Cells/IF is absent
-Lack of IF results in lack of absorption of Vitamin B12
Pernicious Anemia Antibody mechanism of action
I = block B12 binding to IF

II = block B12/IF binding to Ileal receptor

III = against gastric proton pump
What features can be seen on Blood Smear in Megaloblastic Anemia? (2)
1. Macro-ovalocytes = ↑ MCV

2. Hypersegmented Neutrophils
-have 7-10 lobes instead of 2-4
What Lab findings are consistent with Megaloblastic Anemia due to B12 deficiency? (3)
1. decreased SERUM B12

2. Increased Methylmalonic Acid

3. Increased serum Homocysteine
What lab finding is consistent with Megaloblastic Anemia due to Folate Deficiency?
Decreased *Red Cell* Folate

**Serum is not measured
Compare the length of time it takes to become deficient in B12 vs. Folate
B12 deficiency takes years to become deficient because it is stored in the LIVER

Folate deficiency can arise within months
Do Neurological problems occur in patients with B12 or Folate deficiency?
What are the 3 clinical features of B12 deficiency?
1. Megaloblastic anemia
2. Atrophic Glossitis = red & enlarged tongue
3. Neurologic abnormalities = ataxia, impaired proprioception and vibratory sensation
Type of anemia associated with Iron Deficiency?
Hypochromic Microcytic anemia
Which is absorbed more readily, Heme Iron or Non-heme iron?
Heme iron

**25% of Heme iron vs. 1-2% of non-heme iron is absorbable
What is the physiological storage form of Iron?

What is the transport protein for Iron?

Degraded Ferritin + Lysosomal debris = ?


What is the most important function of Transferrin?
to deliver Iron to cells, including Erythroid precursors, which require iron for Hemoglobin synthesis
What is the daily requirement of Iron?
1 mg absorbed or 10-20mg dietary
Globally, what is the most important cause of Iron deficiency?
Decreased Dietary Intake
In the US, what is the most important cause of Iron Deficiency?
Chronic blood loss
What would be possible causes of Chronic blood loss and Iron deficiency?
1. GI = peptic ulcers, hemorrhagic gastritis, gastric CA, Colon CA,)
2. GYN = menorrhagia, uterine cancer
3. GU = renal, pelvic, or bladder tumors
What are the abnormal Lab values in Iron Deficiency Anemia?
-Serum Iron
-Serum Ferritin
-Transferrin saturation

-Total Iron Binding capacity (TIBC)
-Transferrin receptor
-Free Erythrocyte Protoporphyrin
What are the Blood Smear findings of Iron Deficiency Anemia?
1. Hypochromic microcytic anemia

What are the clinical features of Iron Deficiency Anemia
1. Hypochromic, microcytic anemia
2. Atrophic glossitis
3. Koilonychia = spoon nails with abnormal splitting
4. Plummer-Vinson Syndrome = Esophageal Webs, Glossitis, Iron Deficiency
What is Plummer-Vinson Syndrome?
1. Esophageal Webs
2. Glossitis
3. Iron Deficiency

**increased risk for developing Esophageal Cancer
What is the treatment for Iron Deficiency?
1. Iron supplementation

2. Investigation and treatment of the underlying disease
Describe the pathogenesis of Anemia of Chronic Disease
Most common cause of anemia among hospitalized patients in the U.S.
Anemia of Chronic Disease
What are the possible underlying disease causing Anemia of Chronic Disease?
1. Chronic microbial infections
2. Chronic Immune Disorders = Rheumatoid arthritis
3. Neoplasms = Hodgkin's and Lung/Breast CAs
How do cytokines and inflammatory modulators cause anemia of chronic disease?
Lead to decreased Renal EPO secretion
What are the 2 ways in which anemia is caused in chronic disease?
1. Cytokines cause decreased renal EPO secretion

2. Impaired Iron Utilization -> IL-1 causes increased Lactoferrin, which in turn traps iron in BM macrophages

**Lactoferrin is an antimicrobial protein that has a high affinity for Iron
What are the lab findings in Anemia of Chronic Disease?
1. Low serum Iron
2. Low Total Iron Binding Capacity (TIBC)
3. High Serum Ferritin

*normal serum transferrin receptor
How do you differentiate between Iron deficiency anemia and Anemia of Chronic Disease?
Iron deficiency = low serum ferritin and high TIBC

Anemia of Chronic Disease = high serum ferritin and low TIBC
What is the treatment for Anemia of Chronic Disease?
1. treatment of underlying disorder
2. Recombinant EPO
Define Aplastic Anemia
Hypocellular Bone Marrow with almost total loss of hematopoietic cells, including Erythroid and Myeloid precursor cells
What are 65% of the causes of Aplastic Anemia?
-Stem Cell defect
-autoimmune dysfunction of cytotoxic T cells
What chemicals can cause Aplastic Anemia?
1. Alkylating agents
2. Benzene
3. Chloramphenicol
4. Insecticides
5. Antimetabolites (5-FU, Methotrexate
6. Arsenicals
What viral infections can typically cause Aplastic Anemia?
1. Parvovirus B19
2. EBV
3. CMV
4. HIV
5. Herpes VZV
6. HCV
T or F: Radiation can cause Aplastic Anemia
In about 50% of cases, what response removes Hematopoietic cells from the BM and causes Aplastic Anemia?
T-cell response
What is the inherited form of Aplastic Anemia?
Fanconi anemia
What are the lab findings of Aplastic Anemia?
1. Anemia = fatigue
2. Neutropenia = recurrent infections
3. Thrombocytopenia = bleeding and petechiae
Describe the pathogenesis of Aplastic Anemia
Hypocellular Bone Marrow in Aplastic Anemia
What is this showing?
What is the treatment for Aplastic Anemia (2)
1. Immunosuppression -> Antithymocyte globulin

2. Bone Marrow Transplantation
What is Pure Red Cell Aplasia associated with?
Thymoma = tumor of the thymus
What is Myelophthisic Anemia?
Anemia caused by Bone Marrow replacement, most often by a malignant neoplasm

**can also be due to Marrow Fibrosis
How could Chronic Renal Failure lead to anemia?
decreased synthesis of EPO
What is Polycythemia?
increased concentration of RBC's, usually with a corresponding increase in Hb levels
What is the cause of Relative Polycythemia?
Any kind of dehydration that causes increased concentration of RBC's
What is Absolute Polycythemia?
An actual increase in the # of RED CELL MASS
What is Primary Absolute Polycythemia?
Caused by an intrinsic abnormality of Myeloid Stem Cells
-clonal proliferation (polycythemia vera)
-increased responsiveness to EPO due to mutation in the EPO receptor
What is Secondary Absolute Polycythemia?
Presents with normal Red Cell Progenitors but an increased amount of EPO, which causes proliferation of Erythrocytes
What are some Appropriate causes of Secondary Absolute Polycythemia?
1. Lung disease
2. Cyanotic heart disease
3. High altitude
What are some Inappropriate causes of Secondary Absolute Polycythemia?
EPO-secreting tumors
Megaloblastic Anemia

Macro-ovalocytes and Hypersegmented Neutrophils

B12 or Folate deficiency
What is this picture showing?
How do you know?
What is the cause?
1. Iron deficiency

2. Hypochromic microcytic anemia (low MCV)

3. Thalassemias = low Hb / Anemia of Chronic Disease = iron is trapped in BM macrophages
1. What deficiency is this due to?
2. What type of anemia is it?
3. What other 2 diseases could cause it?