Anemia

Question 1

define anemia

Answer 1

• male Hb < 13.5 g/dL
• female Hb < 12 g/dL

Question 2

what are clinical consequences of anemia

Answer 2

• conjunctival pallor
• atrophic glossitis
• fatigue → lethary (depending on severity)
• bounding pulses, palpitations, chest pain
• high output congestive heart failure, MI (severe anemia)

Question 3

what are the essential building blocks in heme production and RBC maturation (hematopoeisis)

Renal ___ provides cytokine signaling for RBC maturation and release from bone marrow

Answer 3

dietary iron, folate, B12

Renal EPO provides cytokine signaling for RBC maturation and release from bone marrow

Question 4

1. dietary iron is absorbed in the ____

Answer 4

1. dietary iron is absorbed in the duodenum

Question 5

2. Fe 2+ may be stored in the ___ bound with apoferritin to produce the storage form ___

Answer 5

2. Fe 2+ may be stored in the enterocyte bound with apoferritin to produce the storage form ferritin

Question 6

3. Fe 2+ released from basolateral enterocyte surface via ____

Answer 6

3. Fe 2+ released from basolateral enterocyte surface via ferroportin 1

Question 7

4. Fe 2+ is oxidized to Fe 3+ by ___

Answer 7

4. Fe 2+ is oxidized to Fe 3+ by ferroxidase

Question 8

5. Fe3+ is bound and transported in the blood via ____ to sites of erythropoiesis: ____, and to the ___ where it binds to apoferritin for storage

Answer 8

5. Fe3+ is bound and transported in the blood via transferrin to sites of erythropoiesis: bone marrow, and to the liver where it binds to apoferritin for storage

Question 9

6. When ferritin is filled, hepatocytes produce ___ which feeds back on enteric iron absorption to ____ ferroportin 1 activity

Answer 9

6. When ferritin is filled, hepatocytes produce hepcidin which feeds back on enteric iron absorption to downregulate ferroportin 1 activity

Question 10

duodenal iron absorption: ___ mg/day

iron recycling in liver and spleen: ___ mg/day

Answer 10

duodenal iron absorption: 1 mg/day

iron recycling in liver and spleen: 30 mg/day

Question 11

in iron deficiency, what lab findings do you see?

transferrin saturation ?
ferritin ?
TIBC ?

Answer 11

• *decreased** transferrin saturation
• *decereased** ferritin
• *increased** TIBC

Question 12

___ route is preferred in iron therapy

Answer 12

oral route is preferred in iron therapy

Question 13

__ iron is best absorbed

Answer 13

ferrous (Fe2+) iron is best absorbed

Question 14

list the ferrous iron oral drugs and what is co-administered for optimal absorption?

Answer 14

• ferrous sulfate
• ferrous gluconate
• ferrous fumarate
• ascorbic acid for optimal absorption

Question 15

when do you give parenteral iron therapy?

Answer 15

chronic renal failure patients (high iron requirement)

hemodialysis patients (in combo with EPO)

Question 16

list the parenteral iron formulations

Answer 16

• iron dextran - highest risk for type 1 HSN
• sodium ferric gluconate complex
• iron sucrose

Question 17

list adverse affects of iron therapy

Answer 17

• black stool
• GI
  
  • nausea
  • epigastric discomfort
  • abdominal cramps
  • constipation
  • diarrhea

Question 18

what is the presentation of acute iron toxicity?

Answer 18

• history of iron ingestion by children
• direct GI irritation
  
  • acue vomiting
  • diarrhea
  • abdominal pain
  • mucosal ulceration and bleeding

Question 19

describe the pathogenesis for acute iron toxicity

Answer 19

• free iron disrupts critical cellular processes
  
  • metabolic acidosis
  • widespread organ toxicity → shock, coma, death
• abdominal radiographs showing radio-opaque pills in stomach

Question 20

how do you treat acute iron toxicity?

Answer 20

• activated charcoal is NOT effective (does not bind to iron)
• supportive care
• iron chelators:
  
  • Deferoxamine
  • Deferasirox

Question 21

contrast deferoxamine and deferasirox

Answer 21

• deferoxamine
  
  • given IV to bind system iron
  • promotes iron excretion (urine/feces)
  • moderate & severe iron toxicity
• deferasirox
  
  • oral
  • only effective at reducing iron absorption if given within 1 hour of ingestion
  • used for chronic iron toxicitiy → outpatient iron chelation in transfusion dependent individuals

Question 22

what can cause chronic iron toxicity?

Answer 22

• hemochromatosis
  
  • cardiomyopathy
  • bronze diabetes
  • cirrhosis
• patients requiring frequent blood transfusions (thalassemia major)

Question 23

desribe B12 absorption

Answer 23

• consumed in animal products
• salivary R binders bind to free B12
• pancreatic enzymes break up the complex and binds of IF from parietal cells → duodenum
• IF-cobalamin complex absorbed in terminal ileum
• transported bound to glycoproteins as transcobalamin I, II, III

Question 24

The main storage site of B12 is in the ____ and takes ____ to develop B12 deficiency

Answer 24

The main storage site of B12 is in the liver and takes 5 years to develop B12 deficiency

Question 25

list causes of B12 deficiency

Answer 25

* **insufficient ingestion** (strict vegans) * defects in cobalamin absorption * autoimmune disease: **prenicious anemia** * surgery: **gastrectomy, ileal resection** * small bowel disease: **crohn's, celiac, fish tapeworm infection (diphyllobothrium latum)** * **Drugs**

Question 26

what drugs cause B12 deficiency?

Answer 26

* **metformin, neomycin:** alter gut flora * **nitrous oxide anethesia:** converts cob(I)alamin to inactive form cob(III)alamin * **proton pump inhibitors, histamine 2 receptor antagonists:** increase gastric pH

Question 27

describe the clinical presentaiton of vitamin B12 deficiency

Answer 27

* anemia * neurological symptoms * parethesias * **subacute combined degeneration** of spinal cord d/t abnormal myelination synthesis * prolonged deficiency = **irreversible nerve damage** * skeletal changes * suppressed osteoblast activity → osteoporosis

Question 28

what are the lab studies in B12 deficiency?

Answer 28

* megaloblastic macrocytic anemia * leukopenia and/or thrombocytopenia * decreased B12 * +/- antibodies agaist IF * increased homocysteine * **increased methylmalonate** * increased methylmalonyl-CoA

Question 29

explain B12 deficiency therapy and its adverse effects

Answer 29

* must be parenteral and continued for the duration of malabsorption * **hydroxycobalamin** * **​**preferred highly-protein bound form → stays in circulation longer * **cyanocobalamin** * **no adverse effects!**

Question 30

what is the most common nutrient deficiency in USA?

Answer 30

Folate deficiency

Question 31

describe folate absorption

Answer 31

1. polyglutamylated dietary folate cleaved to monoglutamate via brush border enzymes in the **jejunum** 2. enteres plasma via active and passive mechanisms 3. in peripheral tissue: polyglutamylated again so it cannot diffuse into the plasma 4. healthy individuals take 4-5 months for folate depletion (small hepatic store)

Question 32

list risk factors for folate deficiency

Answer 32

* advanced age * pregnancy * chronic hemolytic anemias eg. sickle cell anemia * alcohol abuse * drugs

Question 33

what drugs causes folate deficiency?

Answer 33

* inhibitors of DHF: * trimethoprim * pyrimethamine * methotrexate * phenytoin

Question 34

describe the presentation of folate deficiency

Answer 34

* **anemia** * no neurological sympytoms * **fetal neural tube defects** in 1st trimester of pregnany

Question 35

describe folate deficient lab study

Answer 35

* megaloblastic macrocytic anemia * decreased folate levels * increased homocysteine * **normal methylmalonic acid**

Question 36

describe folate therapy

Answer 36

* folic acid given orally for 1-4 months or until complete hematological recovery occurs * prophylactic supplements should be give for: * pregnant * alcohol dependent * hemolytic anemia * liver disease * exfoliative skin disease * renal dialysis

Question 37

list/describe erythrocytic growth factors

Answer 37

* **erythropoeitin & darbepoetin** * stimulates JAK/STAT receptors * Given parenterally in: * chronic renal failure * bone marrow suppression * AE: hypertension, thrombosis

Question 38

list/describe myeloid growth factors

Answer 38

* **Filgrastim (G-CSF)** * **Sargramostin (GM-CSF)** * stimulates JAK/STAT receptors * increases production/function of neutrophils * Sargramostin stimulates all myeloid pregenitor cells * given parenterally in: * ​cancer chemotherapy induced neutropenia * bone marrow suppresion * AE: bone pain, **filgrastim = better tolerated**

Question 39

Describe interleukin 11

Answer 39

* myeloid growth factor * acts via cell surface cytokine receptor * stimulates growth of primitive megakaryocuytic progenitors * increase platelets and neutrophils * reduces need for platelet transfusions in chemotherapy recipients with prior episodes of thrombocytopenia

Question 40

describe hydroxyurea

Answer 40

* **reduces vascular occlusion in SCD** * **increases HbF** (reduces sickling) * decreases expansion of neutrophil adhesion molecules * increases endothelial production of NO