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Blood and Lymphatics > B&L Week 1 > Flashcards

B&L Week 1 Flashcards

1
Q

describe the shape of normal RBCs on blood smear

A
  • biconcave discs (increased surface area for gas exchange)
  • malleable (to squeeze through capillaries)
  • poikilocyte = an abnormally shaped RBC
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2
Q

describe the size of a normal RBC on blood smear

A

-7.5 um

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3
Q

what is anisocytosis

A

considerable variation in the size of RBCs seen on blood smear

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4
Q

what is macrocytosis

A

RBCs seen on blood smear that measure more than 9.0 um

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5
Q

what is microcytosis

A

RBCs seen on blood smear that measure less than 6 um

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6
Q

describe the normal number of RBCs seen on blood smear

A

4.5-5 x 10^12/L

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7
Q

what is polycythemia

A

an increase in the number of RBCs seen on blood smear

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8
Q

describe the content of RBCs normally seen on blood smear

A

Hb – 145 g/L

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9
Q

what is anemia

A

a decreased number of RBCs, decreased concentration of Hb or decreased volume of packed RBCs (i.e hematocrit)

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10
Q

what is the normal lifespan of healthy RBCs

A

120 days

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11
Q

what is a mnemonic for the order of normal differential count of WBCs on blood smear

A 
Never
Let
Monkeys
Eat 
Bananas 
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
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12
Q

what are the granular WBCs

A

neutrophils
eosinophils
basophils

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13
Q

what are the non-granular WBCs

A

lymphocytes

monocytes

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14
Q

what % of the normal count are…

  1. neutrophils
  2. lymphocytes
  3. monocytes
  4. eosinophils
  5. basophils
A
  1. 60-70%
  2. 20-40%
  3. 3-10%
  4. 1-4%
  5. 0-1%
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15
Q

how do the granules of neutrophils, eosinophils and basophils stain relative to one another

A

eosinophils have pink (eosinophilically) staining granules

neutrophils have more neutral staining granules

basophils stain blue/basophilic

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16
Q

what is the functional association of neutrophils

A

acute bacterial infection

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17
Q

what is the functional association of eosinophils

A

allergies and parasites

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18
Q

what is the function association of basophils

A

some inflammations
hypersensitivity reactions
leukemias

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19
Q

what is the lifespan of granular WBCs

A

short–hours to days

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20
Q

what % of lymphocytes are small? what % are medium-large?

A

90% are small (6-8 um)

rest are medium-large (15-18 um)

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21
Q

what are monocytes?

A

precursors of macrophages (become macrophages once migrate out of the circulation)

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22
Q

where does hematopoiesis occur?

A

in the bone marrow

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23
Q

what hormone regulates erythropoiesis and where is it produced

A

erythropoietin is produced in the kidney in the peritubular interstitial cells in response to oxygen levels in the blood

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24
Q

what are other hormones involved in the production of other hematopoietic cell lines?

A

GM-CSF–> granulocyte-monocyte colony stimulating factor

thrombopoietin–> for megakaryptes

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25
Q

how does the morphology of stem cells/progenitor cells/precursor cells/mature cells differ?

A

stem cells and progenitor cells–> not morphologically distinguishable, have the general aspect of lymphocytes

precursor cells show the beginning of morphological differentiation

mature cells show clear morphologic differentiation

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26
Q

how does the mitotic activity ofstem cells/progenitor cells/precursor cells/mature cells differ?

A

stem cells–> low mitotic activity; self renewing; scarce in bone marrow

progenitor cells–> high mitotic activity; self renewing; common in marrow and lymphoid organs; mono or bipotential

precursor cells–> high mitotic activity; NOT self renewing; common in marrow and lymphoid organs; MONO-potential

mature cells–> NO mitotic activity; abundant in blood and hematopoietic organs

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27
Q

what two types of cells can the hematopoietic stem cell give rise to?

A
  1. lymphoid multipotential cells (stem cells) that will migrate to the lymphoid organs
  2. myeloid multipotential cells (stem cells) that remain in the bone marrow
    * both are stem cells
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28
Q

what progenitor cell(s) arise(s) from the lymphoid multipotential cells in the lymphoid tissue?

A

lymphocyte-colony-forming cell (LCFC)

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29
Q

what do LCFCs develop into

A

LCFC are progenitor cells–> develop into lymphoblasts (precursor cells)

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30
Q

what do lymphoblast precursor cells develop into?

A

B and T lymphocytes

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31
Q

what are the 5 cell types (progenitor cells) that can arise from the myeloid multipotential cells in the bone marrow

A
  1. erythrocyte-colony-forming cell (ECFC)
  2. megakaryote-forming cell
  3. MGCFC (which splits into A. monocyte-colony forming cell/MCFC and granulocyte colony forming cell/GCFC)
  4. eosinophil colony forming cell (EoCFC)
  5. basophil colony forming cell (BCFC)
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32
Q

list the stages of cell development that lead to a erythrocyte

A

hematopoietic stem cell–> myeloid multipotential cell–> ECFC–> erythroblast–> erythrocyte

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33
Q

list the stages of cell development that lead to a megakaryocyte

A

hematopoietic stem cell–> myeloid multipotential cell–> megakaryocyte forming cell–> megakaryoblast–> megakaryocyte

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34
Q

list the stages of cell development that lead to a monocyte

A

hematopoietic stem cell–> myeloid multipotential cell–> MGCFC–>MCFC–> promonocyte–> monocyte

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35
Q

list the stages of cell development that lead to a neutrophilic granulocyte

A

hematopoietic stem cell–> myeloid multipotential cell–> MGCFC–> GCFC–> neutrophilic myelocyte–> neutrophilic granulocyte

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36
Q

list the stages of cell development that lead to a eosinophilic granulocyte

A

hematopoietic stem cell–> myeloid multipotential cell–> EoCFC (progenitor)–> eosinophilic myelocyte (precursor)-> eosinophilic granulocyte (mature)

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37
Q

list the stages of cell development that lead to a basophilic granulocyte

A

hematopoietic stem cell–> myeloid multipotential cell (stem)–> BCFC (progenitor)–> basophilic myelocyte (precursor)–> basophilic granulocyte (mature)

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38
Q

list the stages of development of an erythrocyte from the the erythroblast phase on to mature RBCs

A

proerythroblast–> basophilic erythroblast/early normoblast–> polychromic erythroblast/intermediate normoblast–> normoblast/late normoblast–> reticulocytes–> mature RBCs

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39
Q

what are some important changes that occur during the erythroblast stage–> mature stage that have functional consequences?

A
  1. nucleus is extruded and so are other organelles–> makes cell smaller as development progresses
  2. cytoplasm color changes from basophilic to polychromatic to eosinophilic due to Hb accumulation
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40
Q

describe appearance of erythroblasts

A

large pale purple nucleus, sparse dark blue cytoplasm

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41
Q

describe appearance of basophilic erythroblast/early normoblast

A

intensely basophilic cytoplasm, reflects high polyribosome content

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42
Q

describe appearance of polychromatic erythroblast/intermediate normoblast

A

greyish cytoplasm (polychromatic–blue is RNA and red is hemoglobin)

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43
Q

describe the appearance of normoblasts

A

more eosinophilic cytoplasm due to higher Hb content–> nucleus is small and dark

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44
Q

describe the appearance of a reticulocyte

A

NO MORE NUCLEUS

has rRNA
released into BLOOD
mature into erythrocytes after 2-3 days in the blood

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45
Q

how do myelocytes (precursors to granculocytes) appear on blood smear?

A

pale, slightly basophilic, nucleus pushed to edge of cells and occupies 50% of cells area–> SPECIFIC GRANULES appear

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46
Q

how do metamyelocytes appear on blood smear

A

metamyelocytes develop from myelocytes and give rise to granulocytes

horsehoe-shaped nucleus, cytoplasm is less basophilic than myelocytes

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47
Q

how are platelets produced

A

megakaryocytes undergo emdomitosis–> a process whereby DNA is duplicated without cell division–> thus MKs become polyploid

platelets are simply bits of cytoplasm released from megakaryocytes

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48
Q

what is a megakaryocyte

A

A megakaryocyte (mega- + karyo- + -cyte, “large-nucleus cell”) is a large bone marrow cell with a lobulated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting

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49
Q

what are the physiological functions of the common lymphoid progenitor blood cell line?

A

develop into lymphocytes (B and T cells–> humoral and cellular immunity, respectively)

B cells differentiate into plasma cells when activated by antigen, and thus then synthesize and secrete more immunoglobulins

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50
Q

what are the three cell lines that arise from the common myeloid progenitor line of blood cells?

A
  1. granulocyte/monocyte progenitor line
  2. megakaryocyte progenitor line
  3. erythrocyte progenitor line
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51
Q

what are the physiological functions of the cells that arise from the granulocyte/monocyte progenitor line?

A
  1. neutrophils–> phagocytose bacteria
  2. eosinophils–> phagocytose Ag-Ab complexes and parasites; allergic responses
  3. basophils–> anticoagulation (platelet-activating chemotactic factors, heparin), increases vascular permeability (contain histamine), bind IgE in allergic reactions, anaphylaxis
  4. monocytes (are agranular)–> give rise to macrophages
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52
Q

what are the physiological functions of the cells that arise from the megakaryocyte progenitor line?

A

give rise to membranous cytoplasmic fragments–> platelets

blood clot and coagulation formation (produce von-Willebrand factor, thrombospondin, and platelet-derived growth factor)

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53
Q

what are the physiological functions of the cells that arise from the erythrocyte progenitor line?

A

transport Hb that binds O2 and CO2

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54
Q

how much body iron does the average adult male have?

how is this iron distributed in the body?

A

4g

65-70% hemoglobin (incorporated into porphyrin ring of heme)
10% myoglobin, iron-sulphur proteins
20-25% storage (reticuloendothelial cells, liver parenchyma)

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55
Q

how much body iron does the average adult female have?

how does iron distribution in the female differ than the male?

A

2-3 mg of body iron

smaller iron reserves than males
less hemoglobin iron

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56
Q

list iron containing proteins

A
  1. hemoglobin
  2. myoglobin
  3. transferrin
  4. ferritin
  5. hemosiderin
  6. enzymes–> catalase, peroxidases, cytochromes, iron-sulfur
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57
Q

function of hemoglobin

A

oxygen transport in the blood

2500 mg iron

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58
Q

function of myoglobin

A

oxygen storage in the muscle

300 mg iron

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59
Q

function of transferrin

A

iron transport

4 mg iron

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60
Q

function of ferritin and hemosiderin

A

iron storage

1000 mg iron

non-heme iron compounds

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61
Q

function of catalase

A

H2O2 decomposition

300 mg iron

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62
Q

function of peroxidases

A

oxidation

300 mg iron

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63
Q

function of cytochromes

A

electron transfer

300 mg iron

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64
Q

function of iron-sulfur enzymes

A

electron transfer

300 mg iron

*non-heme iron compounds**

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65
Q

state the iron requirements per day for the following populations:

  1. men and post-menopausal women
  2. women in their reproductive years
  3. pregnant or lactating women
A
  1. 1 mg/day
  2. 2 mg/day
  3. 3-4 mg/day
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66
Q

state the iron lost each day through:

  1. normal shedding (skin, GI, urinary epithelia)
  2. 1 menstrual cycle
  3. pregnancy + delivery + lactation
A
  1. 1 mg/day
  2. 20-40 mg
  3. 900 mg
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67
Q

what percentage of ingested iron is absorbed in the duodenum and upper small intestine?

A

5-10%

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68
Q

list three types of foods that increase Fe absorption by forming soluble iron chelates

A
  1. ascorbic acid
  2. sugars
  3. amino acids
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69
Q

list three types of foods that decrease iron absorption through forming insoluble iron complexes

A
  1. phosphates (dairy)
  2. oxalates and phytates (vegetables)
  3. tannates (tea)
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70
Q

in what form is most dietary iron? what is the significance of this?

A

most dietary iron is in the Fe3+ (FERRIC) form

this means that it must be converted to the FERROUS (Fe2+) form to be stored/absorbed by the body

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71
Q

how is dietary Fe3+ converted to the Fe2+ form that can be absorbed/stored by the body/cells of the GI?

A

dietary iron Fe3+ (ferric) is converted to the ferrous/useable form by FERRIC REDUCTASE on the BRUSH BORDER–> Fe2+ enters the cell via DIVALENT METAL TRANSPORTER (DMT1)

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72
Q

what happens to Fe2+ once it is incorporated inside the cell through the DMT1?

A

either:
1. incorporated into FERRITIN for storage (most lost via mucosal shedding)
or
2. transferred across the basolateral membrane into the plasma by the transmembrane protein FERROPORTIN

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73
Q

what is ferroportin?

A

the transmembrane protein found in the basolateral membrane of the intestinal cell that allows absorbed iron to transfer from the cell into the plasma

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74
Q

what happens to Fe2+ once it has exited the SI cell across the basolateral membrane and entered the plasma?

A

once in the plasma, Fe2+ is converted back into Fe3+ by the membrane protein HEPHAESTIN and then bound to TRANSFERRIN (each transferrin has 2 binding sites for Fe3+) which transports iron in the blood

**free iron is toxic and insoluble, so it must be protein bound in blood and tissues–> the toxicity arises from the fact that interaction of free iron with molecular oxygen results in free radical production

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75
Q

what does transferrin do with the iron it is transporting?

A

transferrin delivers Fe3+ to cells that display a TRANSFERRIN RECEPTOR

transferrin receptors are membrane-bound dimeric proteins which bind two transferrin molecules (and thus 4 Fe3+)

the entire receptor-transferrin complex is endocytosed and formed into a vesicle

acidic pH of vesicle causes Fe to be released–> the receptor and the transferring is exocytosed and recycled

once inside the red blood cells, Fe can be either incorporated into heme or stored as ferritin

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76
Q

describe the process of RBC turnover as it relates to iron

A
  1. when RBCs turn over in the RE system (esp. in the spleen), macrophages destroy the heme porphyrin ring via HEME OXYGENASE, thus releasing iron and protoporphyrin
  2. macrophages then transfer the iron to PLASMA TRANSFERRIN to be carried to bone marrow for hemoglobin synthesis (recycle the iron)
  3. macrophages also maintain a storage pool of iron (which is adjustable depending on iron intake and RBC turnover, i.e production versus destruction)
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77
Q

in what two forms can iron be stored

A
  1. ferritin

2. hemosiderin

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78
Q

where are iron reserves located?

A
  1. liver (about 1/3 of body’s iron stores)
  2. bone marrow (about 1/3 of the body’s iron stores)
  3. remainder is in spleen and other tissues
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79
Q

describe the function of ferritin

A
  • ferritin is a multi-subunit protein shell, known as apoferritin, surrounding a core of up to 4500 iron atoms
  • it is present in most cells
  • it is an EASILY MOBILIZED storage form
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80
Q

describe the function of hemosiderin

A
  • an insoluble complex derived from ferritin, but that has lost some of its surface proteins and become aggregated
  • has higher concentration of iron than ferritin but releases iron MORE SLOWLY
81
Q

how is iron balance controlled?

A
  • iron loss is a continuous and unregulated process, and thus iron balance must be controlled by changes in ABSORPTION
  • absorption can increase 3-fold via stimulation by iron deficiency, pregnancy and erythropoiesis
  • central regulator is HEPCIDIN
  • high levels of hepcidin restrict flow of iron into the blood (i.e iron overload response)
  • low levels of hepcidin promote release of iron into circulation (iron deficiency response)
82
Q

what is hepcidin?

A

the central regulator of iron absorption (which is the only way to control iron content as iron loss is a continuous and unregulated process)

  • polypeptide hormone that is produced by the LIVER in response to Fe demands
  • it controls the flow of iron OUT OF intestinal cells, macrophages, reticuloendothelial cells and liver cells by binding to FERROPORTIN
  • the hepcidin-ferroportin complex is then taken up into the cell and degraded
83
Q

list 4 causes of vitamin B12 deficiency

A
  1. poor nutrition (i.e vegans)
  2. pernicious anemia
  3. total/partial gastrectomy
  4. intestinal disease
84
Q

describe vitamin B12 metabolism

A
  • it is release from food by gastric acid and enzymes
  • binds to R protein and then enters the duodenum–> released by enzymes–> binds to intrinsic factor (IF) released by gastric parietal cells
  • IF-B12 complex is specifically absorbed in the TERMINAL ILEUM
  • B12 circulates in the blood bound to a plasma protein called TRANSCOBALAMIN II
85
Q

what is the importance of vitamin B12

A

it is a cofactor for two important reactions

  1. homocysteine–> methionine
    - generates THF from methyl THF, which is the active form of folate inside cells and is needed for synthesis of DNA
  2. methylmalonyl CoA–> succinyl CoA
86
Q

describe folate metabolism

A
  • folate present in food is largely in the form of reduced polyglutamates
  • absorption requires transport and action of PTEROYLGLUTAMYL CARBOXYPEPTIDASE associated with mucosal cell membranes
  • mucosae of duodenum and upper jejunum are rich in DIHYDROFOLATE REDUCTASE and can methylate most or all of the reduced folate absorbed
  • once absorbed, folate is transported rapidly to tissues

*overall, dietary folate is converted to METHYL-THF

87
Q

why do we need the methyl-THF that is formed from dietary folate?

A

it is a cofactor in numerous biochem reactions

  1. transfers single carbon units bound to the N^5 or N^10 nitrogen atoms
  2. N^5, N^10 methylene THF is required to synthesize deoxythymidate (dTMP), which is a precursor in DNA SYNTHESIS
88
Q

list 4 causes of folate deficiency

A
  1. poor nutrition (i.e elderly, poverty, alcoholics)
  2. increased utilization of folate (i.e pregnancy and lactation, malignancy, inflammation, haemolytic anemia)
  3. intestinal disease
  4. drug induced
89
Q

what is the most common cause of megaloblastic anemia?

A

B12 and folate deficiency

90
Q

what is megaloblastic anemia

A

anemia in which the circulating RBCs are large and oval (macrocytic) with marked variation in size and shape

erythroblasts in the bone marrow show delayed maturation of the nucleus relative to the cytoplasm

some hypersegmented neutrophils

arises because DNA synthesis is defective usually due to B12/folate deficiency

91
Q

describe the structure of hemoglobin

A

64,500 kDaltons

consists of 4 globin chains and 4 haem groups

2 alpha globin and 2 beta globin chains

oxygen binds to the haem groups and thus each Hb molecule can bind to four oxygens

92
Q

where and how is haemoglobin synthesized

A

porphyrin synthesis starts int he mitochondria with the synthesis of DELTA-AMINOLEVULINIC ACID

protoporphyrin combines with iron in the mitochondria to form heme

globin is synthesized on polyribosomes and combines with heme in the cytoplasm of the cell

93
Q

how many globin genes do humans carry?

A

8 globin genes in two clusters

94
Q

on what chromosomes are the globin genes located? which ones are located on which chromosome?

A

Chromosome 16–> alpha 1, alpha 2 and zeta

chromosome 11–> beta, delta, epsilon, gammaA and gammaB

95
Q

what chains make up fetal hemoglobin

A

alpha and gamma

96
Q

what chains make up adult hemoglobin

A

HbA –> alpha and beta

HbA2 –> alpha and delta

97
Q

when are epsilon and zeta globin chains synthesized?

A

only syntehsized in the embryonic yolk sac and disappear in the first trimester

98
Q

what organs produce alpha globin chains

A

each erythropoietic organ produces alpha chains

99
Q

when do fetal gamma globin chains appear and disappear?

A

appear during first trimester, rises to peak in trimesters 2 and 3, falls off just prior to birth

major haemoglobin in the fetus and newborn is HbF

100
Q

when does the synthesis of beta globin chains begin

A

begins in the fetus and continues throughout life, the switch from producing mainly fetal to mainly adult occurs after birth

96-97% adult hemoglobin is HbA
2-3% of adult Hb is HbA2
1% of adult Hb is HbF

101
Q

List 3 hemoglobin abnormalities

A

porphyrias
thalassemias
structural haemoglobinopathies

102
Q

what are porphyrias

A

disorders of haem synthesis due to abnormal accumulation of porphyrin precursors or porphyrins in the bone marrow/liver

103
Q

what are thalassemias

A

inherited disorders characterized by reduced or absent synthesis of one or more globin chains (alpha or beta, variable number of chains affected)

104
Q

what are structural haemoglobinopathies

A

disorders caused by synthesis of abnormal globin chains (HbS)

105
Q

what types of anemia can be attributed to abnormal production of RBCs

A
  1. iron deficiency anemia
  2. pernicious anemia
  3. folate deficiency
  4. lead poisoning (usually in kids)
  5. thalassemia
  6. anemia of chronic disease
  7. aplastic anemia
106
Q

what types of anemia can be attributed to increased RBC destruction

A
  1. hereditary spherocytosis
  2. sickle cell anemia
  3. thalassemia (due to being malformed)
  4. autoimmune hemolytic anemia
  5. G6PD deficiency
107
Q

describe the pathophysiological process of iron deficiency anemia

A
  • iron is needed to produce properly functioning hemoglobin (and is incorporated into the heme ring with porphyrin)
  • extracorporeal blood loss is the most common cause of iron deficiency anemia in adults–> when RBCs are destroyed within the body, the reticuloendothelial system usually adequately recycles iron into the next generation of RBCs – poor iron uptake due either to poor nutrition or inadequate absorption is a less common cause of iron deficiency anemia in adults
  • by losing RBCs, their heme iron is depleted–iron stores become slowly used up in order to create new hemoglobin and thus eventually these stores will run dry
  • women develop iron deficiency more readily than men because of increased iron loss due to menstruation–pregnancy, lactation, and delivery additionally cost a woman an average of 1000 mg of iron for each pregnancy
  • in infancy, risk factors for iron deficiency are primarily dietary and include exclusive breast-feeding beyond 6 months without iron supplementation, prolonged bottle-feeding, and excessive cow’s milk consumption–> however, other risk factors for iron deficiency in childhood in canada include non-caucasian ethnicity, poverty and being overweight
108
Q

what is the age at which iron deficiency anemia usually presents

A

any age depending on demographic

most common anemia in the world

very common in children and menstruating women

109
Q

what is intrinsic factor?

A

a glycoprotein that binds cobalamin (B12) and is required for the effective absorption of cobalamin in the terminal ileum

110
Q

what are two underlying causes of pernicious anemia?

A

weakened stomach lining (atrophic gastritis) or an autoimmune process by which parietal cells or intrinsic factor itself is damaged

111
Q

what is the pathophysiology behind pernicious anemia?

A

basically, anything that interferes with intrinsic factor production (and thus the absorption of B12) or the lining that absorbs the B12 itself can cause pernicious anemia
(will focus on the autoimmune cause)

  1. gastric parietal cells are damaged by an autoimmune phenomenon that leads to two discrete effects: loss of gastric acid (achlorydria) and loss of IF
    - -> stomach acid is required for the release of cobalamin from foodstuffs and IF is needed for its absorption
  2. occurs when patients develop antibodies in the serum directed against the parietal cell membrane proteins
  3. major protein antigen appears to be the H+/K+ ATPase (the proton pump) which is responsible for the production of the stomach acid by pumping out H+
  4. moret han half of patients also have antibodies to IF itself or to the IF-cobalamin complex
  5. complete vitamin B12 deficiency develops slowly, even after total achlorydria and loss of IF occur as liver stores of B12 are adequate for several years
  6. in DNA synthesis, cobalamin, along with folic acid, is crucial as a cofactor in the synthesis of deoxythymidine from doxyuridine–> thus cobalamin deficiency impairs DNA synthesis due to lowered purine production
  7. a decreased rate of DNA synthesis results in fewer divisions but accumulation of protein products due to normal mRNA production–> this means cell gets larger but are fewer in number (less divisions)
  8. RBC precursors develop a characteristic morphology (MEGALOBLASTIC) with oval macrocytes and thus this is called megaloblastic anemia
  9. it is NOT ONLY RBCs which are affected by a systemic deficiency of B12 (or folate)–> every rapidly dividing tissue in the body is affected
112
Q

at what age does megaloblastic anemia usually present (due to autoimmune causes)

A

may present as late as the 3rd decade of life

113
Q

describe the pathophysiology behind folate deficiency anemia

A
  • because folate reserves are limited, deficiency develops rapidly in malnourished persons, typically the old, the poor and alcoholics
  • it only takes about 6-8 weeks to completely deplete the body’s folate stores (vs months to years of B12)
  • because folate is now supplemented in breads and cereals, it is rare to see nutritional folate deficiency in canada
  • if there is insufficient amount of folate within the body, the body cannot synthesize appropriate amounts of thymine (purine deficiency–> much like with B12 because they are both factors in the same synthesis pathway)
  • a decreased rate of DNA synthesis results in fewer divisions but accumulation of protein products due to normal mRNA production–> this means cell gets larger but are fewer in number (less divisions)
  • RBC precursors develop a characteristic morphology (MEGALOBLASTIC) with oval macrocytes and thus this is called megaloblastic anemia
  • it is NOT ONLY RBCs which are affected by a systemic deficiency of B12 (or folate)–> every rapidly dividing tissue in the body is affected
114
Q

at what age does folate deficiency anemia usually present

A

any age

115
Q

describe the pathophysiology behind lead poisoning anemia

A
  • lead interferes with the biosynthesis of HEME at several enzymatic steps
  • one of the largest threat to children is lead paint in homes (usually only older homes, less common now)
  • their smaller, growing bodies make them more susceptible to absorbing and retaining lead
  • specifically, lead may inhibit the enzymes delta-ALA and ferrochelatase, both of which are involved in the pathway to produce heme
  • lead has been speculated to be involved in some hemolytic processes as well (although this is controversial)
116
Q

what demographic does lead poisoning anemia usually affect?

A

children

117
Q

what is the primary underlying mechanism behind anemias due to thalassemia?

A
  • features of thalassemias are related to a PRIMARY IMBALANCE OF GLOBIN CHAIN SYNTHESIS
  • there is usually a mutation in the genes that encode for beta globin chains or alpha globin chains of hemoglobin, resulting in unbalanced globin chain synthesis (i.e beta thalassemias lead to a relative excess of alpha chains and vice versa)
  • the excess unpaired globin chains precipitate in the developing RBCs, causing HEMOLYSIS in the marrow or spleen
  • there is increased synthesis of RBCs in the marrow (because of increase EPO) but because the new RBCs are also abnormal, they also lyse
  • anemia causes decreased oxygen carrying capacity in the blood
118
Q

describe the specific pathophysiology of beta thalassemia

A
  • 3 major components
    1. inneffective erythropoiesis with intramedullary destruction of a variable proportion of the developing red cell precursors
    2. hemolysis resulting from destruction of mature RBCs containing alpha-chain inclusions
    3. hypochromic and microcytic red cells that result from the overall reduction in synthesis of normal hemoglobin
  • the degradation products of free alpha chains (globin, heme, hemin and free iron) also play a role in damaging red cell membranes
119
Q

describe the specific pathophysiology behind alpha thalassemia

A
  • essentially the same as in beta except the mutation occurs in the alpha chain
  • because alpha chains are shared by hemoglobins F, A and A2, there is no increase in HbF in the alpha thalassemias as there are in beta thalassemias to compensate for the defective alpha chains
  • the excess gamma/beta chains formed as a result of defective alpha chain production produce soluble homotetramers
  • because gamma4 and beta4 tetramers are soluble, they do not precipitate as much in the marrow RBCs and thus the alpha thalassemias are not charaacterized by severe ineffective erythropoiesis
  • however, beta4 tetramers precipitate as red cells age, with the formation of inclusion bodies, and thus the anemia of the more severe forms of alpha thalassemia in the adult results from a shortened survivial of red cells consequent to their damage in the microvasculature of the spleen as a result of the presence of the inclusions
120
Q

at what age do the thalassemias tend to manifest?

A

they are inherited

alpha manifests at birth

beta manifests around 6 months

121
Q

list 6 mechanisms by which chronic disease can cause anemia (“anemia of chronic disease”)

A
  1. increased erythrocyte destruction is caused by the activation of host factors such as macrophages that prematurely remove aging erythrocytes from the bloodstream
  2. some cytokines, chiefly tumor necrosis factor (TNF) alpha, IL-1 and the interferons, exert a suppressive effect on erythroid colony formation
  3. less EPO production than expected in other types of anemia
  4. inflammation seems to induce a state of relative resistance to EPO
  5. IL-6 is a potent and direct inducer of HEPCIDIN leading to trapping of iron in enterocytes and in reticuloendothelial cells (i.e macrophages in the marrow)–> total body iron stores are normal, but the iron is not available to the developing RBCs in the marrow (hepcidin sequesters iron)
  6. during inflammation, the release of iron from macrophages and probably also from liver stores is markedly inhibited
122
Q

what is the pathophysiology behind aplastic anemia?

A
  • condition of bone marrow failure that arises from injury to or abnormal expression of the hematopoietic stem cell–> bone marrow becomes hypoplastic and either anemia or pancytopenia develop
  • there are a number of causes
    1. direct hematopoietic stem cell injury may be caused by radiation, chemotherapy, toxins or pharmacologic agents
    2. systemic lupus erythematosus may rarely cause suppression of the hematopoietic stem cell by an IgG autoantibody directed against the stem cell
    3. however, the most common pathogenesis of aplastic anemia appears to be autoimmune suppression of hematopoiesis by a T cell mediated cellular mechanism
  • in some cases of idiopathic aplastic anemia, defects in the maintenance of the hematopoietic stem cell telomere length have been identified and are likely linked to both the initiation of bone marrow failure and the propensity to later progress to myelodysplasia, PNH or AML
123
Q

at what age does aplastic anemia usually manifest

A

any age

124
Q

describe the pathophysiology behind inherited spherocytosis

A
  • hereditary spherocytosis is the most common inherited defect of the RBC membrane
  • autosomal DOMINANT inheritance pattern in most cases
  • patients inherit one of a series of mutations of the structural proteins of the RBC membrane, i.e spectrin, ankyrin, paladin, and the Rh-associated glycoprotein
  • the resulting decreased membrane elasticity causes loss of the normal biconcave shape of the RBC–> small “blebs” of the RBC membrane develop in circulating RBCs and those blebs are removed in the spleen
  • thus the RBC gradually loses surface area while maintaining the same volume–> biconcave disc gradually evolves into a sphere as it passes through the spleen one or more times
  • eventually, the spherical RBCs will be detained and phagocytosed in the narrow fenestrations of the splenic cords–> they CANT DEFORM like normal biconcave disc RBCs and thus are prone to splenic phagocytosis (i.e extravascular hemolysis)
125
Q

at what age does inherited spherocytosis usually present?

A

born with the disorder… presents young

126
Q

describe the pathophysiology behind sickle cell anemia

A
  • a Glu–> Val substitution in the 6th animo acid of the BETA-globin gene
  • this change induces a conformational change in the hemoglobin tetramer that, in deoxygenated conditions, causes polymerization of the Hb molecule
  • the rod-like polymer bundles distort the red cell membrane into the characteristic sickle cell shape
  • likely that adhesion of the erythrocytes and leukocytes to endothelial receptors such as vascular cellular adhesion molecule-1 (VCAM-1) combines with physical rigidity and distortion (sickling) of the RBCs to OCCLUDE the miscovascular circulation
  • the resulting tissue ischemia-reperfusion drives tissue and organ injury, generalized inflammation, and ultimately produces tissue infarction (i.e splenic infarction leading to hyposplenism)
  • these pathophysiological events produce clinical and biochemical perturbations, such as fever and leukocytosis, which can mimic sepsis
  • some sickling is reversible–> these cells will “de-sickle” once they reoxygenate; some is irreversible and these cells hemolyze
127
Q

when does sickle cell anemia typically present?

A

born with disorder but may not present clinically until childhood

128
Q

what are the two types of autoimmune hemolytic anemia? (AIHA)

A

warm AIHA and cold AIHA

129
Q

what is the pathophysiology behind warm AIHA

A
  • in warm AIHA, the patients RBCs typically are coated with IgG autoantibodies with or without complement proteins
  • autoantibody coated RBCs are trapped by macrophages in the Billroth cords of the spleen, and, to a lesser extend, by Kupffer cells in the liver
  • macrophages phagocytose the portion of the RBC membrane with autoantibody on it, leading to gradual membrane loss and spherocytosis just like in hereditary spherocytosis
  • if amount of autoantibody on the cell is high, the whole cells is phagocytosed (hemolysis)
  • the macrophage has surface receptors for the Fc region of the IgG, with preference for the IgG1 and IgG3 subclasses and surface receptors for opsonic fragments of C3 (C3b and C3bi) and C4b
  • when present together on the RBC surface, IgG and C3b/C3bi appear to act cooperatively as opsonins to enhance trapping and phagocytosis
  • interaction of a trapped RBC with splenic macrophages may result in the phagocytosis of the entire cell–> more commonly, a type of partial phagocytosis results in spherocytes
  • spherical RBCs are more rigid and less deformable than normal, and thus these cells are eventually trapped and destroyed in future passages thru the spleen
  • most of damage doe to the RBC in the extravascular compartment
130
Q

describe the pathophysiology of cold AIHA

A
  • most cold agglutinins are unable to agglutinate RBCs at temps higher than 30 degrees celsius, so most are not clinically significant
  • the pathogenicity of a cold agglutinin depends upon its ability to bind host RBCs and to activate complement at body temperature–> “complement fixation”
  • complement fixation by cold agglutinins may effects RBC injury through 2 mechanisms–> 1. direct lysis and 2. opsonization for hepatic and splenic macrophages
  • patient may experience intravascular hemolysis leading to hemoglobinemia and hemoglobinuria
  • accordingly, RBCs heavily coated with C3b (and.or C3bi) may be removed from circulation by macrophages either in the liver or, to a lesser extent, the spleen
  • trapped RBCs may be ingested entirely or released back into circulation as spherocytes after losing plasma membrane
131
Q

describe the pathophysiology behind G6PD deficiency

A

-red blood cell enzyme deficiencies associated with hemolytic anemia may be classified into two groups–> deficiencies of enzymes involved in glycolytic pathways, such as pyruvate kinase (PK) deficiency, and deficiencies of enzymes needed to maintain a high ration of reduced to OXIDIZED GLUTATHIONE in the red blood cell (protecting it from oxidative damage), such as glucose-6-phosphate dehydrogenase (G6PD) deficiency
-most common red blood cell enzyme deficiency overall
-G6PD deficiency is an X-LINKED recessive hereditary disease characterized by abnormally low levels of G6PD–> a metabolic enzyme involved in the pentose phosphate pathway (especially important in RBC metabolism)
-G6PD converts glucose-6-phosphate into 6-phosphoglucono-delta-lactone and is the RATE LIMITING STEP of this metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme NICOTINAMIDE
ADENINE DINUCLEOTIDE PHOSPHATE (NADPH)
-the NADPH in turn maintains the supply of reduced glutathione in the cells that is used to reduce oxidized hemoglobin–> in the absence of NADPH (i.e absence of reduce glutathione) the oxidized hemoglobin accumulates and causes oxidative damage to the RBC
-the G6PD/NADPH pathway is the ONLY source of reduced glutathione in the RBCs
-people with G6PD deficiency are thus at increased risk of hemolytic anemia in states of oxidative stress
-oxidative stress can result from infection and from chemical exposure to medication and certain foods (i.e fava beans, which contain high levels of vicine, divicine, convicine and isouramil all of which are oxidants)
-exposure to fava beans causes oxidative hemolysis in patients with G6PD deficiency, a condition known as favism
-damaged RBCs are phagocytosed and sequestered in the spleen
-the RBCs rarely disintegrate in circulation so hemoglobin is rarely excreted directly in the kidney, but this can occur in severe cases, causing acute renal failure

132
Q

describe the red cell morphology associated with iron deficiency anemia

A
  • MICROCYTIC hypochromic anemia

- poikilocytosis-elliptocytes (aka PENCIL/CIGAR cells)

133
Q

describe the red cell morphology associated with anemia of chronic disease

A
  • MICROCYTIC or NORMOcytic anemia
  • differs from iron deficiency in that there are NO ELLIPTOCYTES and usually the microcytosis and hypochromasia are not as severe

-look at ferritin level (iron storage measure)–> it is increased in anemia of chronic disease and decreased in iron deficiency anemia

134
Q

how can ferritin levels be used to distinguish between iron deficiency anemia and anemia of chronic disease

A
  1. in anemia of chronic disease, iron stores are usually normal but more will be in storage than in circulation as ferritin is an acute phase reactant and thus goes up in inflammatory states and sequesters more iron
  2. ferritin is low in iron deficiency anemia because iron is overall low in this state
135
Q

describe the RBC morphology associated with pernicious anemia (b12 deficiency)

A
  • MACROCYTIC MEGALOBLASTIC anemia
  • OVAL macrocytes
  • neutrophil nuclear HYPERsegmentation
136
Q

describe the RBC morphology associated with folate deficiency anemia

A
  • MACROCYTIC MEGALOBLASTIC anemia
  • OVAL macrocytes
  • neutrophil nuclear HYPERsegmentation
137
Q

describe the RBC morphology associated with lead poisoning in children causing anemia

A
  • MICROCYTIC anemia –> lead poisoning is very rare but when it happens it usually presents with iron deficiency and thus shows up as a microcytic anemia because of iron deficiency
  • BASOPHILIC STIPPLING (aka punctate basophilia)
  • interferes with heme biosynthesis
138
Q

describe the RBC morphology associated with aplastic anemia

A
  • MACROCYTIC non-megaloblastic anemia

- low WBC and platelet counts

139
Q

describe the RBC morphology associated with G6PD deficiency

A
  • NORMOcytic anemia
  • BITE CELLS and BLISTER CELLS–> signs of oxidative damage (Hb is progressively more oxidized untl it precipitates–> spleen “fixes” cells by pitting out lumps of precipitated RBC)
  • can see other poikilocytes including spherocytes, schistocytes
140
Q

describe the RBC morphology associated with the thalassemias

A
  • MICROCYTIC anemia
  • poikilocytosis–> usually TARGET CELLS–> can see other shapes including schistocytes, elliptocytes, teardrop cells
  • basophilic stippling
141
Q

describe the RBC morphology associated with sickle cell anemia

A
  • NORMOCYTIC anemia
  • sickled RBCs (crescent/boat/holly leaves shapes)
  • Howell-Jolly body–> blue dot-like RBC inclusion representing DNA–> inclusions are normally removed by splenic macrophages–> patients with sickle cell are hyposplenic because of splenic infarction in childhood, so they have peripheral blood evidence of hyposplenism in the form of HJ bodies
142
Q

describe the RBC morphology of hereditary spherocytosis

A
  • NORMOcytic anemia (borderline macrocytic at times due to increased reticulocytes)
  • presence of SPHEROCYTES
  • occasional schistocytes
  • polychromasia

negative DAT test

143
Q

what are schistocytes

A

fragmented RBCs

144
Q

describe the RBC morphology associated with AIHA

A
  • NORMOcytic anemia (borderline macrocytic at times due to increased reticulocytes)
  • presence of SPHEROCYTES
  • occasional schistocytes
  • polychromasia

positive DAT test

145
Q

how do you distinguish between hereditary spherocytosis and AIHA?

A

DAT test

negative in HS
positive in AIHA

146
Q

what anemia is characterized by:

macrocytic
oval macrocytes
neutrophil nuclear hypersegmentation

A

pernicious (b12) and/or folate deficiency

147
Q

what anemia is characterized by:

microcytic anemia
poikilocytosis–usually target cells + others
basophilic stippling

A

thalassemia

148
Q

what anemia is characterized by:

macrocytic
low WBC and platelets

A

aplatic anemia

149
Q

what anemia is characterized by:

normocytic
bite cells/blister cells
other poikilocytes

A

G6PD deficiency

150
Q

what anemia is characterized by:

normocytic
sickled RBCs
Howell-Jolly bodies

A

sickle cell anemia

151
Q

what anemia is characterized by:

normocytic
presence of spherocytes
occasional schistocytes
polychromasia

A

either hereditary spherocytosis or AIHA depending on results of DAT test

152
Q

what anemia is characterized by:

microcytic hypochromic
poikilocytosis (ellipsocytes–> pencil/cigar shaped cells)

A

iron deficiency anemia

153
Q

what anemia is characterized by:

micro or normocytic
no elliptocytes

A

anemia of chronic disease

154
Q

should blood products ever be used for volume replacement?

A

NO

155
Q

what are the two indications for transfusion of pRBC?

A
  1. increase O2 carrying capacity

2. dilute sickled red cells

156
Q

what are the three indications for transfusion of platelets

A
  1. severely decreased platelet counts PLUS bleeding/bruising
  2. prophylaxis prior to surgery if platelets are severely low
  3. dysfunctional platelets PLUS bleeding/bruising
157
Q

what are two relative contraindications for transfusion of platelets?

A
  1. immune thrombocytopenic purpura (ITP)

2. hypersplenism (will simply sequester the infused red cells)

158
Q

what are the two absolute contraindications for transfusion of platelets

A
  1. thrombotic thrombocytopenic purpura (TTP)

2. HEPARIN-induced thrombocytopenia and thrombosis (HITT)

159
Q

what are the indications for transfusion of fresh frozen plasma

A
  1. multi-factor deficiency PLUS bleeding/bruising (i.e excess coumadin, vitamin K deficiency, DIC, liver disease)
  2. prophylaxis (pre-op if clinical evidence of multifactor deficiency)
160
Q

what are the indications for transfusion of albumin

A 
burns
erythroblastosis fetalis
hyperbilirubinemia
hypoproteinemia
hypovolemia
nephritic syndrome
161
Q

what are the contraindications for transfusion of albumin

A 
hypersensitivity
anemia
heart failure
hypernatremia
hypertension
infection
pregnancy
breast feeding
renal disease
viral infection
162
Q

what are potential immune complications of transfusion?

A 
ABO incompatability
IgG antibody incited
febrile
allergic
anaphylactic
163
Q

what are potential infectious complications of transfusion

A

viruses
bacteria
parasites
prions

164
Q

what are some fluid complications of transfusion

A

overload

hypothermia

165
Q

what are some electrolyte complications of transfusion

A

hyperkalemia
hypocalcemia
increased iron

166
Q

what are the symptoms of anemia

A

fatigue
dyspnea
palpitations (particularly after exercise)

if Hb falls below 7.5 g/dL, resting cardiac output is likely to rise (increasing SV and HR)–> patients complain of rapid, pounding sensation in precordium; if have compromised myocardial reserve, may complain of signs of cardiac failure or ischemia

more severe anemia–> dizziness, headache, syncope, tinnitus, vertigo, irritability, difficulty sleeping, concentration difficulties + GI symptoms (indigestion, anorexia, nausea–> shunt blood away from splanchnic bed); in males can get impotence and loss of libido

167
Q

what are the physical findings associated with anemia

A

pallor–> shunt blood to vital organs and away from skin and peripheral tissue

tachycardia
wide pulse pressure
hyperdynamic precordium
systolic ejection murmur (especially in pulmonic area)

168
Q

what is one classification method for anemias?

A

failure of red cell production, blood loss, or increased red cell destruction

169
Q

list 7 anemias attributed to inadequate production of RBCs

A
  1. iron/B12/folate deficiency
  2. EPO deficiency secondary to renal disease
  3. endocrinopathy
  4. myelodysplastic syndrome (MDS) or marrow abnormality
  5. anemia of chronic disease
  6. liver disease (essentially a special example of anemia of chronic disease)
  7. chemotherapy or other drug induced marrow suppression (aplastic anemia)
170
Q

list anemias associated with excess destruction of RBCs after they leave the marrow

A
  1. hemolytic anemia
    - intrinsic defects in RBC: A. membrane (hereditary spherocytosis), B. enzyme (G6PD), C. hemoglobin (thalassemia, sickle cell)
    - extrinsic: A. immune mediated (AIHA), B. infectious (clostridial sepsis), C. prosthetic valves (causing mechanical trauma to RBCs), D. microangiopathic hemolytic anemia (MAHA–> HUS, DIC, TTP)
  2. loss of RBCs due to acute hemorrhage
171
Q

how does iron deficiency anemia appear in lab tests?

A 
1. LOW: 
Hb
MCV
RBCs
reticulocytes
serum iron (very low)
transferrin saturation (very low)
ferritin
  1. HIGH:
    RDW
    TIBC
172
Q

how does thalassemia appear on lab tests?

A
  1. LOW:
    Hb
    MCV (very low)
    TIBC (or normal)
2. HIGH:
RBCs
reticulocytes (or normal)
serum Fe (or normal)
transferrin saturation (or normal)
  1. NORMAL:
    RDW
    ferritin
173
Q

how does anemia of chronic disease appear on lab tests?

A 
1. LOW:
Hb
MCV (or normal)
RBCs
reticulocytes
serum Fe (very low)
TIBC (or normal)
transferrin saturation (or normal)
  1. HIGH:
    ferritin
  2. NORMAL:
    RDW
174
Q

how does anemia due to acute hemorrhage present on lab tests

A
  1. LOW:
    Hb
    RBC
  2. HIGH:
    reticulocytes
  3. NORMAL:
    RDW
    MCV
175
Q

how does AIHA present on lab tests?

A
  1. LOW:
    Hb
    RBC
    haptoglobin
2. HIGH:
MCV (or normal)
reticulocytes 
RDW
bilirubin 
LDH (lactate dehydrogenase)

positive DAT test

176
Q

how does hereditary spherocytosis appear on lab tests?

A
  1. LOW:
    Hb
    RBC
  2. HIGH:
    reticulocytes (very high)
    RDW
    bilirubin (very high)
  3. NORMAL:
    MCV
177
Q

how does anemia due to liver disease present in lab tests?

A
  1. LOW:
    Hb
    RBC
    reticulocytes
  2. HIGH:
    MCV
  3. NORMAL:
    RDW

**round macrocytes and target cells on blood smear

178
Q

how does hemolytic uremic syndrome present on lab tests?

A
  1. LOW:
    Hb
    RBC
    platelets (very low)
  2. HIGH:
    MCV (or normal)
    reticulocytes (very high)
    RDW

**schistocytes, polychromatic RBCs due to reticulocytosis, and severe thrombocytopenia on blood smear

179
Q

how does myelodysplastic syndrome appear on lab tests?

A
  1. LOW:
    Hb
    RBC
    reticulocytes
  2. HIGH:
    MCV
    RDW

**round or oval macrocytes

180
Q

how does megaloblastic anemia (B12/folate deficiency) appear on lab tests?

A
  1. LOW:
    Hb
    RBC
    reticulocytes
  2. HIGH:
    MCV
181
Q

how does anemia due to chronic blood loss present on lab tests?

A 
1. LOW:
Hb
MCV
RBC
reticulocytes
  1. HIGH:
    RDW

**hypochromic microcytes, pencil cells–> same thing as iron deficiency because eventually chronic blood loss causes low iron

182
Q

what are some complications of anemia?

A
  1. fatigue
  2. diminished physical capacity
  3. reduced endurance
  4. secondary organ dysfunction–> damage due to low O2 carrying capacity of blood
  5. arrhythmias, heart failure, cardiac ischemia
  6. flow murmurs
  7. in children and adolescents, growth impairment and mental development delay, decreased attention span, decreased alertness
  8. B12 anemia can cause neurologic damage which can be irreversible (“subacute combined degeneration”)
  9. frequent blood transfusions can cause iron overload
183
Q

what is the first line treatment for AIHA?

A

corticosteroids

  • warm type AIHA is initially treated with oral PREDNISONE
  • improvement usually noted within 1 week, and 70-80% of patients are improved within 3 weeks
  • once the patient’s hemoglobin levels stabilize, the steroids can be tapered
  • complete remission is achieved in 15-20% of new-onset cases of warm type AIHA, but half of patients will need low dose prednisone for several months
184
Q

what is the second step treatment if steroids fail in AIHA treatment?

A
  • between 10-20% of steroid-treated patients will fail to respond adequately or will require unacceptably high doses to maintain desired response
  • such patients are then treated with either splenectomy or cytotoxic (immunosuppressant) drugs
  • splenectomy removes both the main site of extravascular hemolysis and a major site of general autoantibody production–> produces a 65-70% response rate and has the potential for a LONG TERM remission or a COMPLETE CURE
185
Q

how do you treat AIHA is splenectomy fails

A
  • cytotoxic drugs produce a 40-60% response rate and have been used for patients who have not responded to steroids or splenectomy
  • severe hemolysis in cases of warm type AIHA may be treated with plasmapheresis as a transient stabilizing measure while waiting for steroids or cytotoxic agents to take effect
  • it is impossible to plasmapherese all of the autoantibody away–the patients lymphocytes will always be able to make more
186
Q

what are important aspects of a patients history with regard to evaluating anemia?

A
  1. blood loss (GI, menstruation, urinary)
  2. dietary inadequacies
  3. previous/family Hx of blood disorders (genetic etc…)
  4. medication
  5. constitutional Sx (fever, weight loss, loss of appetite)
  6. associated/comorbid conditions (renal failure)
187
Q

what are some findings suggestive of anemia

A 
pallor
tachycardia
flow murmur
fatigue
SOB on exertion
188
Q

what do the follow findings point to in terms of etiology for an anemia?

  1. scleral icterus and hepatosplenomegaly
  2. lymphadenopathy
  3. bruising/petechiae
  4. neurological changes
  5. rectal bleeding
  6. kolionychia (spoon nails)
  7. pica (abnormal appetite for non-foodstuffs)
  8. glossitis and angular stomatitis
A
  1. scleral icterus and hepatosplenomegaly–> hemolytic anemia
  2. lymphadenopathy–> infection
  3. bruising/petechiae–> microangiopathic hemolytic anemia (DIC, TTP)
  4. neurological changes–> B12 deficiency
  5. rectal bleeding–> UC or crohns or GI malignancy (chronic bleed)
  6. kolionychia (spoon nails)–> iron deficiency
  7. pica (abnormal appetite for non-foodstuffs)–> lead poisoning
  8. glossitis and angular stomatitis–> iron or vitamin B12 deficiency
189
Q

lists tests that apply to anemia (lab tests)

A
  1. complete blood count–> Hb and/or hematocrit, MCV (classify into micro, normo or macrocytic anemia), WBC and platelet count (indicate pancytopenias)
  2. reticulocyte count
  3. peripheral blood smears
190
Q

what is the significance of the reticulocyte count in the etiological determination of an anemia?

A

reflect bone marrow response

increased reticulocyte counts indicate adequate marrow response (i.e to hemorrhage or hemolysis)

decreased reticulocyte counts indicate poor marrow response (i.e because of inadequate stores of iron, B12, folate etc/// or other marrow abnormalities)

191
Q

in what conditions might you see:

target cells

A

thalassemia

liver disease

192
Q

in what conditions might you see:

round macrocytes

A

non megaloblastic anemias (ie liver/alcohol disease, aplastic anemia, MDS)

193
Q

in what conditions might you see:

oval macrocytes

A

megaloblastic anemias

194
Q

in what conditions might you see:

neutrophil hypersegmentation (>6 lobes)

A

vit B12, folate deficiency

195
Q

in what conditions might you see:

hypolobated neutrophils (

A

myelodysplastic syndromes

196
Q

how big should the central zone of pallor normally be?

A

no more than 1/3 of the diameter of the RBC

197
Q

what is a mnemonic for microcytic anemias?

A

TAILS

thalassemia
anemia of chronic disease
iron deficiency
lead poisoning
sideroblastic anemia (rare)
198
Q

what are some causes of normocytic anemia?

A

ASHAA

acute blood loss
sickle cell anemia
hemolysis (including several causes)
aplastic anemia
anemia of chronic disease

Blood and Lymphatics (2 decks)

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