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Pathology > Anemias of Diminished Erythropoesis > Flashcards

Anemias of Diminished Erythropoesis Flashcards

1
Q

Diminished Erythropoiesis

A

Inadequate supply of substances needed for hematopoiesis
-Iron, folic acid, vitamin B12
Bone marrow failure
Bone marrow replacement

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2
Q

Iron Metabolism

Total body iron content

A 
2 gm for women, up to 6 gm for men
80% functional iron, 20% storage pool
-Functional iron
*80% hemoglobin
*20% myoglobin and other iron containing proteins (catalase, cytochromes)
-Storage pool
*Hemosiderin and ferritin
*Stored iron mainly in liver, spleen, marrow, skeletal muscle
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3
Q

Iron laboratory tests

A

Serum ferritin
-Assesses body iron stores
-Stainable iron in marrow can also be used
Serum iron levels (nl: 100 µg/dL)
Total iron binding capacity (TIBC) (nl: 300 µg/dL)
-Measure of transferrin levels
% saturation or transferrin % saturation (nl: 33%)
-Serum iron/TIBC

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4
Q

Iron Metabolism

A

Metabolic pathways are strongly biased toward iron retention
No regulated pathway for iron excretion
-Normal losses are 1-2 mg/day
Iron balance is maintained by regulating iron absorption

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5
Q

Iron Dietary forms

A

Heme iron from animal products
-About 20% is absorbable
Inorganic iron in vegetables
-1-2% is absorbable

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6
Q

Iron absorbtion

A

Iron is absorbed in the duodenum

Iron passes through the apical membrane then the basolateral membrane of enterocytes

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7
Q

Nonheme iron

A

Apical membrane
-Ferric reductase reduces iron
-Divalent metal transporter (DMT1) transports across apical membrane to cytoplasm
Basolateral transfer of iron to transferrin in plasma
-Ferroportin transport protein
-Hephaestin oxidizes iron
Iron not transported to plasma is stored as ferritin and lost though exfoliation of mucosal cells

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8
Q

hepcidin

A

Iron balance is regulated by a small hepatic peptide, hepcidin

  • Hepcidin binds to ferroportin and causes it to be internalized and degraded
  • High hepcidin results in reduced iron absorption
  • Low hepcidin results in higher iron absorption
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9
Q

Iron Deficiency Anemia Causes

A

Most common type of anemia
Causes
Low dietary intake
-Rarely cause in US where average iron intake is 10-20 mg/day
-Important cause in other parts of world where low intake is combined with poor bioavailability of predominantly vegetarian diet
Malabsorption
-Sprue, celiac disease, gastrectomy
Increased demands
-Pregnancy, infancy
Chronic blood loss
-Most important cause in Western world
-GI tract (e.g., ulcers, colon cancer, hemorrhoids, hookworm)
-Female genital tract (e.g., menorrhagia, cancers)

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10
Q

Iron deficiency develops insidiously

A

Iron stores depleted
Decline in serum ferritin; loss of stainable iron in marrow
Decrease in serum iron and rise in TIBC
Ability to synthesize iron containing proteins diminished

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11
Q

Iron Deficiency Anemia morphology

A

Anemia is generally mild
Microcytic and hypochromic (↓MCV and ↓MCHC)
Increased platelet count

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12
Q

Iron Deficiency Anemia clinical

A

Mostly asymptomatic or non-specific
-Weakness, listlessness
In severe cases
-Pallor, koilonychia (nail spooning), alopecia, atrophy of tongue and gastric mucosa, intestinal malabsorption
-Pica, consuming non-foodstuffs like dirt or clay
In well-nourished persons, iron deficiency anemia is not a disease but a symptom of an underlying disorder

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13
Q

Anemia of Chronic Disease

A

Most common form of anemia in hospitalized patients
Resembles iron deficiency anemia, but is caused by inflammation-induced iron sequestration within the mononuclear phagocyte system

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14
Q

Anemia of Chronic Disease

Seen in chronic inflammatory disorders

A

Chronic microbial infections
-Osteomyelitis, bacterial endocarditis, lung abscess
Chronic immune disorders
-Rheumatoid arthritis, regional enteritis
Neoplasms
-Carcinoma of lung and breast, Hodgkin lymphoma

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15
Q

Anemia of Chronic Disease anemia

A

Normocytic/normochromic most commonly

Microcytic/hypochromic

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16
Q

Anemia of Chronic Disease labs

A

Low serum iron
High serum ferritin or marrow iron
Low TIBC
These R/O iron deficiency

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17
Q

Anemia of Chronic Disease

A

Findings due to high levels of hepcidin
Elevated hepcidin caused by proinflammatory cytokines
Inflammation also blunts erythropoietin response
Only effective treatment of the underlying disease is curative
-Iron and epo treatment may improve anemia

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18
Q

Megaloblastic Anemia causes

A

Folic acid deficiency and vitamin B12 deficiency

Caused by impaired DNA synthesis

19
Q

Megaloblastic Anemia CBC

A

Macrocytic anemia
-↑MCV often >110 fl
Granulocytopenia
Thrombocytopenia

20
Q

Megaloblastic Anemia Peripheral blood morphology

A 
Abnormally large red cells (macrocytes or ovalomacrocytes)
Hypersegmented neutrophils (seen before anemia develops)
21
Q

Megaloblastic Anemia marrow morphology

A

Enlarged erythroid precursors (megaloblasts)
Enlarged granulocytic precursors (giant metamyelocytes)
Megakaryocytes may be enlarged with abnormal nuclei

22
Q

Megaloblastic Anemia

A

Impaired DNA synthesis results in delayed nuclear maturation and cell division
Synthesis of RNA and cytoplasmic elements proceeds at normal rate
Cells show nuclear-cytoplasmic asynchrony

23
Q

Megaloblastic Anemia contin

A

Impaired DNA synthesis causes anemia
-Some megaloblasts undergo apoptosis due to the DNA synthesis defect (ineffective hematopoiesis)
-Other cells mature but with fewer cell divisions
*Lower total output of cells from a precursor cell
Granulocyte and platelet lineages are similarly affected
Pancytopenia rather than isolated anemia

24
Q

Folic Acid Deficiency Anemia Risk factors

A 
Marginal folate stores are fairly common
Poor diet
Increased needs
-Pregnancy, chronic hemolysis
Poor absorption (upper third of small intestine)
-Phenytoin, oral contraceptives
-Malabsorptive disorders
Inhibitors of folate metabolism (methotrexate)
25
Q

Folic Acid Deficiency Anemia Clinical

A

Onset is insidious
May be complicated by other coexisting vitamin deficiencies
GI tract symptoms
-Sore tongue, cheilosis

26
Q

Folic Acid Deficiency Anemia Diagnosis

A

Peripheral blood and bone marrow examination
Serum and red cell folate levels
Vitamin B12 level

27
Q

Vitamin B12 (Cobalamin) Deficiency Anemia

A

Causes a megaloblastic macrocytic anemia similar to folate deficiency
Causes a demyelinating disorder involving the spinal cord
Many causes of vitamin B12 deficiency
-Long-standing malabsorption is the most common and important
-Liver stores are normally last more than 5 years

28
Q

Vitamin B12 (Cobalamin) Deficiency Anemia Pernicious anemia

A

Presumed cause of vitamin B12 deficiency until proven otherwise in the western world
Autoimmune reaction against parietal cells and intrinsic factor
Antibodies present in the serum and gastric juice of most patients
-Parietal canalicular antibodies
-Blocking antibodies prevent B12-IF binding
-Binding antibodies prevent binding to ileal receptor
Association with other autoimmune diseases
-Hashimoto thyroiditis, Addison disease, type I diabetes

29
Q

Vitamin B12 (Cobalamin) Deficiency Anemia Subacute combined degeneration

A

Demyelination of the posterior and lateral columns of the spinal cord
Severity of neurological problems not related to degree of anemia
Can see neurological disease in absence of anemia

30
Q

Vitamin B12 (Cobalamin) Deficiency Anemia Clinical

A

Non-specific anemia symptoms
GI symptoms similar to folate deficiency
Spinal cord disease
-Symmetric numbness, tingling, and burning in hands or feet
-Unsteady gait
-Loss of position sense, especially in toes
Increased risk of gastric carcinoma with pernicious anemia

31
Q 
Vitamin B12 (Cobalamin) Deficiency Diagnostic features of pernicious anemia
Anemia
A

Low serum vitamin B12 levels
Normal or elevated folate levels
Serum antibodies to intrinsic factor
Moderate to severe megaloblastic anemia
Leukopenia with hypersegmented neutrophils
Dramatic reticulocyte response (in 2-3 days) to parenteral vitamin B12

32
Q

Warning

A

Vitamin B12 deficiency anemia will respond to folate therapy! This will only fix the anemia; the neurological problems will persist and progress

33
Q

Aplastic Anemia

A

Multipotential myeloid stem cells are suppressed leading to marrow failure and pancytopenia
Idiopathic >50% of the time
Exposure to myelotoxic agents in remainder
-Can group the exposures
*Damage is predictable, dose related, and usually reversible
Antineoplastic drugs, benzene, chloramphenicol
*Idiosyncratic or hypersensitivity reactions to small doses
Known toxic: Chloramphenicol
Not toxic: Sulfonamides

34
Q

Aplastic Anemia

Some cases arise after certain viral infections

A

Community-acquired viral hepatitis

  • Non-A, non-B, non-C virus
  • Aplasia develops several months after hepatitis resolves
35
Q

Aplastic Anemia Idiopathic

A

Autoreactive T cells may play a role
-70-80% respond to immunosuppressive therapy aimed at T cells
-Association with Paroxysmal Nocturnal Hemoglobinuria
*Is PGI anchor the target of the T cells?
Telomerase defects in small fraction

36
Q

Aplastic Anemia Morphology

A 
Hypocellular marrow (<10% cellularity)
Only lymphocytes and plasma cells present
“Dry tap”
Pancytopenia
-Normocytic/normochromic anemia
-Decreased reticulocytes
37
Q

Aplastic Anemia Clinical

A

Anemia: weakness, listless, pallor, dyspnea
Thrombocytopenia: petechiae, ecchymoses
Granulocytopenia: infections
Splenomegaly is absent

38
Q

Aplastic Anemia

Idiopathic form has poor prognosis if untreated

A

Bone marrow transplant
-Young, non-transfused patients
Immunosuppressive therapy

39
Q

Myelophthisic Anemia

A

Extensive replacement of the bone marrow by tumors or other lesions
Metastatic breast, lung, or prostate cancer
Other cancers
Advanced tuberculosis
Lipid storage disorders
Osteosclerosis

40
Q

Myelophthisic Anemia Morphology

A

Anemia and thrombocytopenia principally
-White cells less effected
Misshapen red cells (esp. teardrops)
Immature granulocytic and erythroid precursors (leukoerythroblastosis)
Treatment is to manage underlying condition

41
Q

Polycythemia

A

Polycythemia or erythrocytosis is the increase in the blood concentration of red cells
Usually correlates with an increased hemoglobin concentration

42
Q

Relative Polycythemia

A

Hemoconcentration due to decreased plasma volume

  • Any cause of dehydration
  • Water deprivation, prolonged vomiting, diarrhea, excessive use of diuretics
43
Q

Absolute Polycythemia

A 
Increase in total red cell mass
Primary
-Autonomous proliferation of myeloid stem cells
Secondary
-Response to increased erythropoietin
-Appropriate
*Lung disease, high-altitude living, cyanotic heart disease
-Inappropriate
*Erythropoietin-secreting tumors, doping

Pathology (16 decks)

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