L30: Anemias, Pt. 1 Flashcards
What is anemia? What is it due to?
Anemia is a decrease in O2 carrying capacity of blood
Due to a decrease in absolute # of RBCs or decrease in hemoglobin or its ability to carry oxygen
At what hemoglobin levels is anemia classified in males and females?
Less than the following levels
Male: 13.0 - 13.5 g/dL
Female (non-pregnant): 12 g/dL
Female (pregnant): 10.5 - 11 g/dL
What can persistent, severe anemia lead to?
Arrhythmias and/or heart failure
What is observed in initial assessment of anemia?
General symptoms: fatigue, dyspnea, vertigo
History: age, diet, mediations, family history, travel, etc.
Physical exam: pallor, jaundice, cardiac arrhythmias, evidence of bleeding, hepato- or splenomegaly, lymphadenopathy, neurologic manifestations
What information does reticulocyte count provide?
Increased means BM is responding to anemia
Decreased means BM is not resonding to anemia
What would peripheral blood smear examination show in initial assessment of anemia?
Abnormal RBC morphology (volume, shape, hemoglobin content)
Immature forms: nucleated RBCs
Abnormalities in #, maturity, or morphology of WBCs and PLTs
What information does serum ferritin provide in microcytic anemias?
Low serum ferritin: iron deficiency anemia
High or normal serum ferritin: anemia of chronic disease, sideroblastic anemia, thalassemias (or Hb E disease/trait)
What are the causes for the types of microcytic anemias?
Iron deficiency anemia: quantitative iron deficiency
Anemia of chronic disease: iron sequestration and decreased iron availability
Sideroblastic anemias: deficiency or inhibition of enzymes for synthesis
Thalassemas, Hb E disease or trait: absence or inhibition of synthesis
What are the causes of iron deficiency anemia (IDA)?
Inadequate intake - dietary deficiency: malnutrition, dieting
Increased iron requirements: pregnancy, lactaton, infancy, toddlers, adolescent growth periods
Decreased absorption: celiac disease, gastrectomy, bariatric surgery
Excessive loss - chronic bleeding: gastrointestinal blood loss (colon cancer, gastritis, Chron’s disease, ulcer, etc.), genitourinary blood loss, miscellaneous
What are some symptoms of IDA?
Fatigue, lethargy, shortness of breath, pallor, dizzness, poor exercise tolerance
Pica (severe IDA): craving for and consumption of unusual substances (dirt, clay, glass)
Epithelial cell changes (stomatitis, glossitis)
Gastritis
Spoon shaped nails (koilonychia) rare; brittle or ridged nails
Plummer-Vinson syndrome
Triad of IDA, esophageal webs, glossitis
Dysphagia
How is iron deficiency diagnosed?
Serum ferritin: reflects iron storage in bone marrow; early indicator of iron deficiency when ↓; acute phase reactant - will ↑
in inflammation due to ↑ hepcidin
Serum iron: ↓ only after storage iron is depleted; ↓ in infection, inflammation, neoplasms; recent ingestion of iron supplements falsely increases serum levels
Total iron binding capacity (TIBC): a measure of the amount of transferrin; ↑ in iron deficiency (upregulated to transport more iron); ↓ in inflammation, infections, malignancies and liver disease (site of transferrin synthesis)
% Transferrin saturation: normally 1/3 saturated; IDA < 16 - 20%
What is the treatment for iron deficiency anemia?
Determine and treat underlying disorder
Oral iron therapy, ↑ retics ~1 week post-therapy
Oral iron not effective if deficiency due to malabsorption; intravenous iron needed
What occurs in anemia of chronic disease/inflammation?
Iron maldistribution
↑Hepcidin: traps iron in enterocytes and macrophages and inhibits iron absorption
How can IDA and ACD be differentiated? Why is it important to differentiate them?
In IDA, would have severe decreases in hemoglobin whereas in ACD the decrease is mild to moderate
TIBC is ↑ in IDA and normal or ↓ in ACD
Serum ferrtin is ↓ in IDA and normal or ↑ in ACD
It is important to differentiate them bc the treatments are different; iron therapy for IDA and EPO for ACD
What occurs in sideroblastic anemia?
Defect in heme biosynthesis
Hereditary X-linked sideroblastic anemia
Mutation in ALAS-2 (enzyme needed for the first step of protopophyrin synthesis)
Treated w/ pyridoxine (vitamin B6), a cofactor for ALAS
Acquired sideroblastic anemia
Idopathic: refractory anemia w/ ring sideroblasts (type of MDS)
Secondary due to drugs/toxins (reversible): lead, alcohol, isoniazd, chloramphenicol
How does lead poisoning lead to microcytic anemia?
Inhibition of ALA dehydrase and ferrochetalase in protoporphyrin synthesis
Inhibits rRNA degradation (caorse basophilic stippling)
What is the etiology, findings, labs and treatment for lead poisoning?
Etiology: infants and children exposed to lead-based chipped pain; adults with occupational exposure
Findings: anemia, neuropathy, memory and motor problems, abdominal colic, kidney damage, wrist and foot drop, Burton’s lines on gingivae
Lab: ↑ in serum δ-amino levulinic acid (ALA) and ↑ in blood lead levels
Treatment: EDTA, dimercaprol (chelation therapy; binds with lead; excreted in urine)
What are some findings of sideroblastic anemia?
↑ serum ferritin and bone marrow iron
Ring sideroblasts in bone marrow (non-heme iron granules in RBC precursors)
Basophilic stippling (abnormal rRNA aggregates in RBCs; may be very coarse)
Pappenheimer bodies (non-heme iron aggregates in RBCs)
Iron deposits in other organs
How can microcytic anemias be differentiated?
By looking at serum ferritin and TIBC
What are porphyrias causes by?
Due to mutation or inhibition of an enzyme in heme synthesis
Accumulation of heme precursors damage cells
What are the most common porphyrias? What are their features?
Prophyria cutanea tarda (PCT): chronic, blistering photosensitivity, red/brown “tea-colored” urine, most are acquired & in adults
Acute intermittent porphyria (AIP): acute, polyneuropathy, abdominal pain, psychological symptoms, red urine
Erythropoietic protoporphyria (EPP): acute, non-blistering, photosensitivity, mainly affects RBC precursors, mild anemia
What is hemochromatosis caused by?
Iron overload
↑ transferrin saturation
↑ ferritin
No effective mechanism for excretion of iron
Free iron accumulates and damages parenchymal cells mainly of: liver (cirrhosis), heart (cardiomyopathy, heart failure), skin (brown color)
What are the types of hemochromatosis?
Acquired (also caused transfusion-related hemosiderosis) due to repeated transfusions to treat severe, chronic anemias such as thalassemia major
Hereditary hemochromatosis: due to mutations in proteins involved in iron metabolism; proteins with mutations that ↓
hepcidin production include hereditary hemochromatosis protein (HFE), hemojuvelin; mutations in other iron regulatory proteins also occur; without sufficient hepcidin, intestinal iron absorption continues despite ↑↑↑ iron stores
What does iron accumulation in liver in hemochromatosis increase risk for?
Increases risk of hepatocellular carcinoma
What is the treatment for herditary hemochromatosis?
Therapeutic phlebotomy to periodically remove RBCs containing iron
Patients must also avoid iron supplements and large oral doses of vitamin C
What do patients with herediatry hemochromatosis have to avoid?
Pts have to avoid iron supplements and large oral doses of vitamin C
What are megaloblastic characteristics?
Oval macrocytes
Hypersegmented neutrophils
Pancytopenia
What are the common causes of megaloblastic anemia?
Vitamin B12 deficiency
Folate deficiency
No deficiency: myelodysplasic syndrome, orotic aciduria, drugs
How do vitamin B12 and folate deficiencies lead to megaloblastic anemia?
Deficiency → results in impaired DNA synthesis in nucleus → ineffective hematopoiesis (apoptosis of hematopoietic cells) → megaloblastic anemia
What are the findings in the bone marrow and the peripheral blood of megaloblastic anemia?
Bone marrow: nuclear-cytoplasmic asynchrony (nucleus matures slower than cytoplasm); large, abnormal RBC precursors (megaloblasts)
Peripheral blood: pancytopenia, oval macrocytes (↑ MCV), hypersegmented neutrophils, ↓ retics (↑ erythropoiesis but ineffective), RBC inclusions (basophilic stippling, Howell-Holly bodies)
Where does folate absorption take place?
Jejunem
Folate uptake by RBCs requires vitamin B12
What are some symptoms of folate deficiency?
Weakness, pallor, shortness of breath, dizziness
Jaundice (↑ indirect bilirubin due to intramedullary hemolysis)
Glossitis (loss of epithelial cells)
Gastritis (loss of GI epithelium)
Neural tube defects in developing fetus
Whare are causes of folate deficiency?
Inadequate intake: malnutrition (alcoholics, elderly, impoverished)
Increased requirement: pregnancy, lactation, infancy, rapid cell proliferation (erythroid hyperplasia in hemolytic anemia, cancers, leukemia)
Impaired absorption: celiac disease, inflammatory bowel disease
Excessive loss through renal dialysis
Antifolate drugs (methotrexate, trimethoprin, phenytoin, 5-fluorouracil, others)
In absence of dietary folate, how long does it take to develop a deficiency?
Only a few months since don’t have much folate stored in the body
What is vitamin B12 required for?
DNA and amino acid biosynthesis
Myelin formation
Folate interconversions
With malabsorption of B12, how long does it take to develop a deficiency?
3 - 4 years to develop a deficiency since have lots of stores in the body
Describe vitamin B12 absorption
Vitamin B12 is attached to food proteins → broken off from food proteins by pepsin and HCl (secreted by gastric parietal cells) → bound by haptocorrin from saliva → B12 is broken off from haptocorrin by pancreatic proteases in duodenum → B12 binds to IF (secreted from gastric parietal cells) → is then absorbed in enterocytes in ileum
What are symptoms of vitamin B12 deficiency?
Prolonged onset of weakness, pallor, shortness of breath, dizziness
Jaundice (due to ↑ indirect bilirubin due to intramedullary hemolysis)
Glossitis (loss of epithelial cells)
Gastritis (loss of GI epithelium)
Neuropsychiatric disorders (depression, dementia, irritability)
Demyelinating neuropathies (peripheral neuropathy, loss of balance)
Vitamin B12 needed for fatty acid metabolism and myelination of the spinal cord and peripheral nerves
What are causes of vitamin B12 deficiency?
Inadequate intake: strict vegans
Increased requirement: rapid cell proliferation (e.g. cancers, leukemia), pregnancy
Impaired absorption
How can impaired B12 absorption due to lack of intrinsic factor occur?
Lack of parietal cells
Gastrectomy, gastric bypass, gastric atrophy, gastric lesions
H. pylori infection
Pernicious anemia
Autoimmune disease
Usually occurs >50 years
Gastritis and parietal cell atrophy
Antibodies to intrinsic factor and parietal cells commonly present in serum
How are vitamin B12 and folate deficiencies diagnosed?
Measure serum vitamin B12 and folate levels
Serum homocysteine will be increased in both since they are needed to break down homocysteine
Increased methylmalonic acid in B12 deficiency
Schilling test
Describe how the Schilling test is done
Stage 1: Oral dose of vitamin B12 labelled with 57-Co → flushing injection of vitamin B12 → measure 57-Co in 24 hour urine → normal is > 8% of oral dose excreted in urine
Stage 2: Oral dose of vitamin B12 labeled with 57-Co and intrinsic factor → flushing injection of vitamin B12 → measure 57-Co in 24 hour urine
What is the Schilling test result in pernicious anemia?
Absorption increased with addition of iF
What are other causes of megaloblastic anemia (not responsive to folate or vitamin B12 therapy)?
Malignancies (mutations affect DNA synthesis) such as myelodysplastic syndrome
Orotic aciduria
Certain antimetabolite drugs
Why must both vitamin B12 and folate therapy be given if vitamin B12 deficiency has not been definitively ruled out?
Folate therapy in a pt with vitamin B12 deficiency may correct the anemia, but willnot halt or correct the neurological damage
