19a - Hypoproliferative Anemias Flashcards
What are the three classifications of anemia?
Blood loss
Accelerated destruction
Decreased production
What three things can cause decreased RBC production?
Ineffective erythropoiesis
Decreases RBC precursors (marrow failure)
Anemia of chronic disease (anemia of inflammation)
What are two causes of hypoproliferative anemia that cause impaired proliferation/differentiation of stem cells?
Aplastic anemia
Myelodysplastic syndromes
What are five causes of hypoproliferative anemia that cause impaired proliferation/maturation of erythroid precursors (ineffective erythropoiesis)?
- Megaloblastic anemia
- Anemia of renal failure
- Anemia of chronic disease
- Pure red cell aplasia
- Myelodysplastic syndrome
What are three causes of hypoproliferative anemia that cause defective hemoglobin synthesis (ineffective erythropoiesis)?
- Iron deficiency anemia (heme)
- Sideroblastic anemia (heme)
- Thalassemias (globin)
What are four causes of hypoproliferative anemia that cause marrow replacement/infiltration (myelophthisic)?
- Hematopoietic tumors
- Metastatic tumors
- Granulomatous inflammation
- Storage disorders
What are two lab features of hypoproliferative anemias?
Anemia
Low reticulocyte count
What can cause hypocellular bone marrow (3 things)?
- Stem cell disorders
- Myelosuppression from drugs/treatments
- Infection
What two things can cause hypercellular bone marrows?
Marrow infiltration
Ineffective erythropoiesis
A 62 yo female has increasing fatigue, weakness, and epigastric pain. She also complains of neusea and loss of apetite. Her CBC and diff is attached. What is a likely diagnosis and why?
Myelodysplastic syndrome - because they have pancytopenia.
What are things that should be on your differential when you get a CBC with diff back showing pancytopenia?
What is stored in the spleen?
Estimated that 1/3 of platelets are stored in the spleen (more if the spleen is enlarged). Any and all lineaged can be sequestered there (just like any and all types of people can go to jail to be sequestered hehe).
What should be on your ddx in hypersplenism (a person with a large spleen)?
- Portal HTN
- Extramedullary hematopoiesis
- Leukemias/lymphomas
- Myeloproliferative neoplasms
- Storage disorders (Gauchers disease)
What is this cell type? What two diseases should you think of when you see it?
Hypersegmented neutrophil!
Two diseases to think of:
- B12 deficiency
- Folate deficiency
What is a common feature seen in people with B12 deficiency and people with Folate deficiency? (IE both types of decificies cause this NOT that the same person has both).
Decreased tetrahydrofolate
How do the folate pathway and SAM pathway interact?
They both use methionine synthase (an enzyme that requires B12) and tetrahydrofolate.
What are the functions of the folate pathway?
- Purine synthesis (A, G)
- Thymine synthesis (dUMP > dTMP)
- One carbon for SAM pathway
What is the function of the SAM pathway?
This is also called the mathylation pathway!
Methyl (CH3) donation for methyltransferases
What happens to folate acquired from the diet? What inhibits this process?
It has 3-9 polyglutamate tails that are removed by folate conjugase - This is inhibited by alcohol.
Dihydrofolate reductase converts folate into the active tetrahydrofolate (THF) - inhibited by methotrexate.
What are the three functions of folate?
- Purine synthesis (Adenine and guanine)
- Thymine synthesis: dUMP to dTMP for DNA synthesis
- Methionine synthesis for SAM pathway methylation reactions
Thymidylate synthetase (converts dUMP to dTMP) requires ______ and is inhibited by _______.
Requires THF
Inhibited by 5FU
What four things can cause megaloblastic anemia?
- Dihydrofolate reductase deficiency (methotrexate)
- Thymidylate synthetase deficiency (5FU)
- Folate deficiency
- VitB12 deficiency
What does the peripheral blood smear look like in megaloblastic anemia?
- Hypersegmented neutrophils (5 lobes or more)
- Macrocytic anemia with oral macrocytes
- Anisopoikilocytosis (Increased size and shape variation)
What is nuclear to cytoplasmic dyssynchrony (seen in megaloblastic anemia)?
When the nucleus is more immature than you would expect, or cytoplasmic maturation is less than the nucleus.
What are the functions of the cheif cells (CC) and parietal cells (PC) in the stomach?
Chief cells (CC): secrete pepsin
Parietal cells (PC): secrete intrinsic factor, acid
Vitamin B12 is bound to food. What happens next on it’s magical journey through our GI system in order to be metabolized?
(PS I’m sorry this is a long card but if there’s anyone that can do it, its you. YES YOU!)
PSS there are 5 steps.
- B12 is released from food in the stomach by HCL and pepsin
- Parietal cells secrete intrinsic factor (IF), and B12 binds mainly to R-protein but also to IF.
- In the duodenum, R-protein is degraded to release B12.
- B12 binds IF complex and binds IF receptor in ileum.
- B12 is transferred to transcobalamin in the blood.
What are some dietary and stomach causes of VitB12 deficiency?
B12 is only found in animal foods so vegans may be deficient.
Stomach:
- inadequate HCL or intrinsic factor
- Atrophic gastritis
- Pernicious anemia
- Long-term acid-reducing drugs
- Gastectomy/gastric bypass
Elevation in ______ is not specific to vitamin B12, but can occur.
Elecation in ________ is more specific and sensitive indicator of B12 status.
Elevated homocysteine is not specific to B12 deficiency but can occur.
Elevation in Methylmalonic acid is more specific to B12 status. This is because in B12 deficiency methionine synthase cannot work and methylmalonym CoA builds up.
What are clinical symptoms associated with Vitamin B12 deficiency?
Megaloblastic anemia: pernicious anemia
Subacute combined degeneration:
- Doral and lateral tract demyelintion
- Parasthesias
- Spastic paraparesis
- Sensory ataxia
