L30: Anemias, Pt. 1 Flashcards Preview

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Flashcards in L30: Anemias, Pt. 1 Deck (49)
1

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

2

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

3

What can persistent, severe anemia lead to?

Arrhythmias and/or heart failure

4

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

5

What information does reticulocyte count provide?

Increased means BM is responding to anemia

Decreased means BM is not resonding to anemia

6

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

7

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)

8

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

9

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

10

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

11

Plummer-Vinson syndrome

Triad of IDA, esophageal webs, glossitis

Dysphagia

12

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%

13

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

14

What occurs in anemia of chronic disease/inflammation?

Iron maldistribution

↑Hepcidin: traps iron in enterocytes and macrophages and inhibits iron absorption

15

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

16

What occurs in sideroblastic anemia?

Defect in heme biosynthesis

17

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

18

Acquired sideroblastic anemia

Idopathic: refractory anemia w/ ring sideroblasts (type of MDS)

Secondary due to drugs/toxins (reversible): lead, alcohol, isoniazd, chloramphenicol

19

How does lead poisoning lead to microcytic anemia?

Inhibition of ALA dehydrase and ferrochetalase in protoporphyrin synthesis

Inhibits rRNA degradation (caorse basophilic stippling)

20

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)

21

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

22

How can microcytic anemias be differentiated?

By looking at serum ferritin and TIBC

23

What are porphyrias causes by?

Due to mutation or inhibition of an enzyme in heme synthesis

Accumulation of heme precursors damage cells

24

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

25

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)

26

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

27

What does iron accumulation in liver in hemochromatosis increase risk for?

Increases risk of hepatocellular carcinoma

28

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

29

What do patients with herediatry hemochromatosis have to avoid?

Pts have to avoid iron supplements and large oral doses of vitamin C

30

What are megaloblastic characteristics?

Oval macrocytes

Hypersegmented neutrophils

Pancytopenia

31

What are the common causes of megaloblastic anemia?

Vitamin B12 deficiency

Folate deficiency

No deficiency: myelodysplasic syndrome, orotic aciduria, drugs

32

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

33

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)

34

Where does folate absorption take place?

Jejunem

Folate uptake by RBCs requires vitamin B12

35

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

36

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)

37

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

38

What is vitamin B12 required for?

DNA and amino acid biosynthesis

Myelin formation

Folate interconversions

39

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

40

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

41

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

42

What are causes of vitamin B12 deficiency?

Inadequate intake: strict vegans

Increased requirement: rapid cell proliferation (e.g. cancers, leukemia), pregnancy

Impaired absorption

43

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

44

Pernicious anemia

Autoimmune disease

Usually occurs >50 years

Gastritis and parietal cell atrophy

Antibodies to intrinsic factor and parietal cells commonly present in serum

45

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

46

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

47

What is the Schilling test result in pernicious anemia?

Absorption increased with addition of iF

48

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

49

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