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191 Cards in this Set
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- Back
types of WBC
|
Neutrophils
Lymphocytes Monocytes Eosinophils Basophils |
|
amount of blood in body
|
5 L
|
|
functions of plasma
|
H2O/fluid reservoir- can release H2O to tissue that needs it or absorb XS
prevents vessel collapse helps regulate BP helps regulate body temp - carries heat from core to extremities |
|
major components to blood volume
|
>1/2 is plasma
~ 40% RBC |
|
leukopenia
|
number of WBC too low
increased chance of infection |
|
leukocytosis
|
high number of WBC than normal
may not cause symptoms can be indication of disease or infection or leukemia |
|
thrombocytes
|
aka platelets
1:20 RBC normal 150x10^9/L - 400 x 10^9/L |
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thrombocytopenia
|
number of platelets too low
<150 x 10^9/L bruising and abnormal bleeding bleeding when <50 <10 frequently fatal |
|
thrombocythemia
thrombocytosis |
number of platelets too high
>500 x 10^9/L blood may clot excessively, cause stroke or heart attack |
|
normal life spans of blood cells
|
WBC: hours to days
platelets: 10 days RBC: 120 days |
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erythropoietin
|
hormone produced and released by kidneys (90%, rest in liver) to stimulate bone marrow to produce more RBC
HIF-1 binds hypoxia response element in erythropoietin gene = transcription |
|
effects of aging on blood
|
bone marrow more fat than cell-producing marrow
usually not a problem but if body experiences higher demand for RBC, marrow may not be able to meet typically anemia results |
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general symptoms of thickened/viscous blood
|
dyspnea
headaches dizziness confusion may be from polycythemia, too many WBC, or immune-related proteins (multiple myeloma) |
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Complete Blood Count test
|
most common
evaluation of all components < 1min on automated machine, may be supplemented by microscope Hgb Hct MCV MCHgb WBC count platelet count |
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CBC Hemaglobin
|
Amount of this oxygen-carrying protein within red blood cells
Men: 12.7 to 13.7 grams per deciliter Women: 11.5 to 12.2 grams per deciliter below 8 definitely should be seeing symptoms around 5, should have trouble getting out of chair, below HF signs therefore when treating, once rise above 8 getting better symptomatically |
|
CBC Hematocrit
|
Proportion of total blood volume made up of red blood cells
Men: 42 to 50% Women: 36 to 45% |
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Mean corpuscular volume
|
Average volume of individual red blood cells
86 to 98 femtoliters |
|
Mean corpuscular hemoglobin concentration
|
Average concentration of hemoglobin within red blood cells
33.4 to 35.5 grams per deciliter |
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White blood cell count
|
Number of white blood cells in a specified volume of blood
4,500 to 10,500 per microliter 4.5 - 10.5x10^9/L |
|
Differential white blood cell count
|
Percentages of the different types of white blood cells
Segmented neutrophils: 34 to 75% Band neutrophils: 0 to 8% Lymphocytes: 12 to 50% Monocytes: 2 to 9% Eosinophils: 0 to 5% Basophils: 0 to 3% |
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CBC Platelet count
|
Number of platelets in a specified volume of blood
140,000 to 450,000 per microliter 140-450x10^9/L |
|
Reticulocyte Count
|
measures the number of newly formed (young) red blood cells (reticulocytes) in a specified volume of blood.
~1% of the total RBC measure of the capacity of the bone marrow to make new RBC - useful in evaluating the pathogenesis of anemia by distinguishing inadequate production from accelerated destruction *should ^ w decrease in RBC * normal count in anemia = sign of decreased production! |
|
bone marrow samples
|
either:
aspirate core biopsy usually from iliac crest, sometimes aspirate from sternum young children from tibia |
|
major mechanisms causing anemia
|
Blood loss (excessive bleeding)
Inadequate production of red blood cells Excessive destruction of red blood cells |
|
most critical nutrients for RBC production
|
iron
vit B12 folate also trace amts vit C riboflavin copper vit E vitB6 and proper balance of hormones... androgen thyroxine |
|
causes of chronic excessive bleeding
|
Bladder tumors
Cancer in the digestive tract Heavy menstrual bleeding Hemorrhoids Kidney tumors Nosebleeds Polyps in the digestive tract Ulcers in the stomach or small intestine |
|
marrow cellularity
|
percentage of marrow space occupied by hematopoietic cells as opposed to fatty and nonhematopoietic tissue
decreases with age 80% children 50% by 30 y/o |
|
erythroblasts
|
Cells in the erythroid series
cytoplasm gradually loses the bluish color imparted by RNA, which is replaced by the pink-staining hemoglobin |
|
HIFs
|
hypoxia-inducible factors (HIF), HIF-1 and HIF-2
principal regulators of the response to hypoxia modulate erythropoiesis by regulation of EPO production and iron metabolism bind hypoxia response element in erythropoietin gene = transcription mRNA |
|
principle transcription factors and cytokines of erythropoiesis
|
GATA-1 in erythro and megakaryocyte differentiation
EPO (erythropoietin) |
|
stages erythropoiesis
|
1) commitment of pluripotential hematopoietic progenitors to committed erythroid precursor
2) expansion of erythroid progenitors that is largely regulated by EPO 3) enucleation and removal of remnants of organelles and nucleotides that may be toxic to mature circulating erythrocytes |
|
principle regulator of erythropoiesis
|
hypoxia
controlled by hypoxia-inducible factors (HIF) transcriptional factors |
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Hgb in RBC
|
maxed out normally, metabolic limit
34g/100mL of cells with deficient Hgb formation, this falls and see smaller cell volume bc less Hgb inside to fill it up each gram of Hgb can combine with 1.34mL of O2 |
|
growth inducers in hematopoiesis
|
promote growth, not differentiation (differentiation inducers do that)
4 major types * IL-3: promotes growth and repro of all types of committed stem cells |
|
proerythroblast
|
first cell that can be identified as belonging to the RBC series, from CFU-E stem cells
|
|
basophil erythroblast
|
first-generation from proerythroblast
still stain basic v little Hgb |
|
stages of RBC genesis
|
proerythroblast
basophil erythroblast polychromatophil erythroblast orthochromatic erythroblast reticulocyte erythrocyte |
|
diapedesis
|
squeezing thru pores of capillary membrane
RBC move from bone marrow into blood capillaries via this |
|
reticulocyte
|
final stage before mature
1-2 days in blood b4 erythrocyte no nucleus small amt basophilic material - remenants of Golgi, mitochondria, etc less than 1% in blood normally |
|
factors decreasing oxygenation
|
1) low blood volume
2) anemia 3) low Hgb 4) poor blood flow 5) pulmonary disease = decrease in tissue oxygenation = increase RBC production |
|
erythropoietin in low O2
|
get increase formation within minutes to hours
BUT no new RBC until about 5 days later b/c acts on HSC to produce proerythrocytes, takes time to form, but also speeds up process |
|
consequences of lack of vit B12 or folic acid
|
maturation failure:
causes abnormal and diminished DNA - failure of nuclear maturation and cell division - produce larger than normal RBC = macrocytes - flimsy membrane, irregular, large, oval (normally biconcave) = fragile, 1/2-1/3 normal life span |
|
pernicious anemia
|
failure of B12 absorption from GI tract
- atrophic gastric mucosa - fails to produce normal gastric secretions, lack of intrinsic factor |
|
intrinsic factor
|
secreted by parietal cells of gastric glands
- combines w B12 in food to make available for absorption: 1) binds to B12 tightly, protects from digestion 2) binds to R on brush border in ileum 3) transported into blood via pinocytosis |
|
B12 storage in body
|
1000 times what need a day stored in liver etc
(need 1-3 micrograms daily) therefore 3-4 years of defective absorption to cause maturation failure anemia |
|
components of heme
|
protoporphyrin IX and Fe++
combines with polypeptide to become a Hgb chain (alpha or beta) |
|
Hgb chain types
|
alpha
beta gamma delta * chain type determines binding affinity for O2 |
|
O2 binding in Hgb
|
each iron molec in prosthetic group can bind one molec of O2
therefore 4 O2s per Hgb binds via coordination bonds with Fe++ (not with ++) which creates loose bond = easily reversible |
|
Fe++ in body
|
4-5 grams total
65% Hgb 4% myoglobin 1% various heme compounds promoting intracell oxidation 0.1% transferrin bound in blood 15-30% stored for later use - ferritin = reticuloendothelial system bone marrow = liver parenchymal cells |
|
transferrin
|
transported in plasma
formed when iron from intestine binds with apotransferrin - loosely bound |
|
Fe lost in menses
|
0.7mg daily
|
|
ferritin
|
iron bound to apoferritin in cell cytoplasm
|
|
storage iron
|
iron bound with apoferritin in cell cytoplasm (ferritin form)
|
|
hemosiderin
|
small quantity of iron stored in exremely insoluble form, especially when too much for apoferritin
collects in cells in large cluster that can be seen microscopically mainly in macrophage-monocyte system |
|
hypochromic anemia
|
RBC contain much less Hgb than normal
occurs when have inadequate quantity of transferrin in blood, so little iron transported to bone marrow to R on erythroblasts (usually transferred into mito when heme made) |
|
daily excretion Fe
|
0.6mg, mainly into feces
also hair, nails, skin, urine |
|
iron absorption from food
|
very slow, only few mg per day; rate changes as stores (apoferritin) fill/deplete
apotransferrin secreted by liver into bile - into duodenum binds w free iron and iron in compounds like Hgb and myoglobin from meat |
|
function of enzymes in RBC
|
1) metabolize glucose, form small amts ATP
2) maintain pliability of cell membrane 3) keep iron in ferrous form 4) prevent oxidation of proteins |
|
destruction of Hgb when cell dies
|
- phagocytized by macrophages
- esp in Kupffer cells liver, spleen, bone marrow - iron released into blood - porphyrin converted into bile pigment bilirubin: heme -(heme oxygenase)-> biliverdin -(biliverdin reductase)-> bilirubin |
|
blood loss anemia
|
fluid portion of plasma replaced by body in 1-3 days but low [RBC]
usually back to normal 3-6 weeks |
|
microcytic, hypochromic anemia
|
chronic blood loss
can't absorb enough Fe from intestines to form Hgb as rapidly as it is lost cells are smaller and low Hgb |
|
bone marrow aplasia
|
lack of functioning bone marrow
leads to aplastic anemia eg due to chemo or radiation, high doses certain chemicals (benzene, insecticides), autoimmune destruction (lupus) |
|
idiopathic aplastic anemia
|
cause of aplastic anemia unknown
|
|
severe aplastic anemia tx
|
blood transfusions
bone marrow transplant or die |
|
megaloblastic anemia
|
improper formation of RBC leads to megaloblast formation
cells rupture easily low folic acid, B12, intrinsic factor, intestinal sprue |
|
hemolytic anemia
|
various abnormalities of RBC (some hereditary) make cells fragile = rupture easily, esp in spleen
even tho production pace normal, can't make RBC fast enough to replace short lifespans eg hereditary spherocytosis sickle cell anemia erythroblastosis fetalis |
|
hereditary spherocytosis
|
RBC small and spherical
can't withstand compression forces, easily ruptured |
|
sickle cell anemia
|
abnormal Hgb (S) (Glu->Val substitution)
faulty beta chains deoxy HbS polymerizes -> precipitates into long crystals when exposed to low pO2 (dehydration, pain, infection; exercise) - aggrecated by acidemia, ^CO2, ^2,3-DPG, ^temp, osmolality heterozygotes pO2 40mmHg = sickling homozygotes pO2 80mmHg damages membrane, fragile can present like PE |
|
erythroblastosis fetalis
|
Rh-positive RBC in fetus attacked by Ab from Rh-negative mother
born w serious anemia |
|
normal blood viscosity
|
3 times that of water
anemia as low as 1.5X = ^CO |
|
anemia and exercise
|
heart already pumping at high CO, can't pump more
extreme tissue hypoxia results acute cardiac failure may ensue |
|
anemia effects on heart
|
increased CO
increased pumping workload on heart partly offsets reduced O2 low blood viscosity = decrease in resistance in peripheral bv = ^CO hypoxia from decreased O2 transport = vasodilation or peripheral bv = even higher CO up to 3-4X normal CO |
|
secondary polycythemia
|
30% above normal RBC as a result of tissue hypoxia (altitude or HF)
|
|
physiologic polycythemia
|
occurs in natives of altitudes 14,000-17,000 feet
6-7 mill RBC/mm^3 |
|
polycythemia vera
|
high RBC count (7-8 mill/mm^3)
high Hct (60-70%) increase total blood volume (2X normal) increase viscosity 10X water genetic aberration of hemocytoblastic cells producing blood cells - don't stop producing |
|
effect of polycythemia on CO
|
CO remains normal
increased viscosity decreases venous return (decrease CO) BUT increase in blood volume (increase CO) |
|
cyanosis
|
apparent when arterial blood contains more than 5g deoxy Hgb in each 100 mL blood
almost never see in anemia b/c not enough Hgb for 5g to be deoxy in 100mL blood! yet frequent cyanosis in polycythemia vera bc XS Hgb |
|
plethora
plethoric |
bodily condition characterized by an excess of blood and marked by turgescence and a reddish complexion
|
|
persistantely raised venous Hct
|
>0.52 males, >0.48 females for >2 months
= investigated by measurement of their red cell mass (RCM) RCM >25% predicted = absolute erythrocytosis (otherwise relative erythrocytosis=dehydration) >0.60 males >0.56 females =assumed to have absolute erythrocytosis |
|
congential causes polycythemia
|
High oxygen-affinity haemoglobin
2,3-Biphosphoglycerate mutase deficiency Erythropoeitin receptor-mediated Chuvash erythrocytosis (VHL mutation) |
|
Aquired 2ndary polycythemia
|
EPO-mediated:
- Hypoxia driven - Local renal hypoxia Pathologic EPO production - Tumors Exogenous EPO - Drug associated (androgen preparations; postrenal transplant) |
|
Causes of local renal hypoxia
|
Renal artery stenosis
End-stage renal disease Hydronephrosis Renal cysts (polycystic kidney disease) |
|
Causes of central hypoxic process
|
Chronic lung disease
Right-to-left cardiopulmonary vascular shunts Carbon monoxide poisoning Smoker’s erythrocytosis Hypoventilation syndromes including sleep apnea (high-altitude habitat) |
|
diagnostic criteria for polycythemia vera
|
Major:
*1) Raised RCM (>25% predicted) or Hct (>0.60 m, >0.56 f) *2) no 2ndary cause of polycythemia (dual path?) 3) palpable splenomegaly 4) Clonality marker Minor 1)Thrombocytosis (Plt >400x10^9/L) 2) Neutrophil leukocytosis (>10x10^9/L nonsmokers, >12.5x10^9/L smokers) 3) Splenomegaly U/S 4) BFU-E growth or reduced serum EPO |
|
cyanotic congenital heart disease and polycythemia
|
compensatory erythrocytosis develops to maintain
tissue oxygen delivery 2 categories heart defects: 1) absent or poorly developed central pulmonary arteries with pulmonary blood flow via collateral arteries from the aorta or branches and a large right to left shunt 2) pulmonary vascular disease where the intrapulmonary arterioles and capillaries have undergone obliterative changes secondary to high pressure and high flow shunts |
|
Symptoms of hyperviscosity in Cyanotic Congenital Heart Disease with erythrocytosis
|
Chest and abdominal pain
Myalgia and weakness Fatigue Headache Blurred vision or symptoms to suggest amaurosis fugax Paraesthesiae Slow mentation, sense of depersonalisation |
|
amaurosis fugax
|
temporary partial or complete loss of sight especially from the effects of excessive acceleration (as in flight)
|
|
par·es·the·sia
|
sensation of pricking, tingling, or creeping on the skin having no objective cause and usually associated with injury or irritation of a sensory nerve or nerve root
|
|
tx for cyanotic congenital heart disease with polycythemia
|
IF SYMPTOMATIC:
venesection if Hct>0.65, and has adequate iron stores also improves peripheral vascular resistance, ^ SV, CO, systemic blood flow |
|
Hypoxic pulmonary disease and polycythemia
|
causes increased risk of cor pulmonale
long term O2 therapy improves survival and reduces Hct could also do venesection if Hct >0.56 (to get range 0.50 - 0.52) limited evidence that ACE inhibitors or ARBs may help |
|
physiologic adaptations to High O2 Affinity Hgb
|
increase Hct (modest)
increase CO |
|
apparent erythrocytosis
|
not absolute yet
Hct >0.52 male, >0.48 female increase risk of thrombotic events and CV mortality advise reduction/elim contributing factors: smoking, EtOH, HTN venesection if recent hx thrombosis, high risk, Hct>0.54 (target Hct <0.45) monitor for further rise/shift to absolute |
|
neutrophils and smokers
|
smokers have higher neutrophil counts than non smokers
high end of normal is 10x10^9/L in non smokers 12.5x10^9 in smokers |
|
Tests for polycythemia
|
all pts:
EPO levels Blood gas measurements Stage 1: Full blood count/film Ferritin level Renal/liver f'n tests Abdominal U/S chest xray Stage 2: Bone marrow aspiration/biopsy cytogenetics ODC - p50 measurement sleep study lung f'n tests EPO R gene analysis |
|
causes of misleading SaO2
|
CO posioning
high O2 affinity Hgb (measure p50) sleep apnea - normalizes during day (DDx for idiopathic erythrocytosis) |
|
Hypoproliferative Anemias
|
inability to produce an adequate number of erythrocytes in response to the appropriate stimulus
Nutritional deficiencies are the most common causes |
|
Common Causes of Newly Diagnosed Anemia
|
Iron deficiency
Acute or chronic inflammation Renal disease Folate or vitamin B12 deficiency α- or β-thalassemia syndromes Sickle cell disease Enzymopathies (G6PD, others) Hereditary spherocytosis Autoimmune hemolytic anemia Myelodysplastic syndromes Myelophthisic processes Leukemia Congenital or acquired red cell aplasia |
|
hemolytic anemias
|
consequence of the premature destruction of erythrocytes and are due to a broad array of disorders that may be congenital or acquired
may lead to severe problems in early childhood (eg, β-thalassemia major, sickle cell anemia), or may remain silent until a stressor is encountered later in life |
|
angular cheilitis
|
cracking at the edges of the lips
may accompany iron deficiency anemia |
|
koilonychia
|
spooning of the nails
may accompany iron deficiency anemia |
|
red blood cell distribution width (RDW)
|
dimensionless quantity (actually the standard deviation of red blood cell volume divided by the mean volume) that reflects the variation in cell size in the population of red blood cells
used to distinguish the etiologies of microcytosis Fe deficiency = ^ RDW Thalassemia minor = normal RDW how quickly bone marrow producing cells and how quickly maturing (won't tell how long problem persisting) - constantly being stimulated to produce more RBCs = wider |
|
neutrophil
|
granulocyte integral in innate immunity
main cell in acute inflammation |
|
eosinophil
|
involved in response to parasites (especially helminths) and allergic response
|
|
basophil
|
granulocyte mainly involved in allergy and parasitic infection
|
|
monocyte
|
involved in innated immunity
can differentiate into macrophage or dendritic cell |
|
serum
|
equivalent to plasma minus clotting factors and fibrinogen
|
|
granulocytes and agranulocytes
|
Basophil
Eosinophil Neutrophil lymphocytes monocytes |
|
anisocytosis
|
increased variability in size of RBC (increased RDW)
- see in iron deficiency anemia, thalassemia major, myelofibrosis |
|
MCV ranges
|
microcytic: MCV <80 microm^3
normocytic: MCV 80 - 100 macrocytic: MCV >100 |
|
conditions when see hypochromic RBCs
|
normal is less than 1/3 RBC diameter
- iron deficiency anemia - anemia of chronic disease - hemolytic anemias - sideroblastic anemia |
|
polychromasias
|
increased reticulocytes
(polychroma bc pinkish-blue cells) indicates increased RBC production by bone marrow |
|
poikilocytosis
|
increased proportion of RBCs with abnormal shape
see in: iron deficiency anemia myelofibrosis |
|
symptoms of anemia
|
fatigue
malaise weakness dyspnea decreased exercise tolerance palpitations headache dizziness tinnitus syncope |
|
level of Hb when see pallor of mucous membranes and conjunctiva
|
Hb <90 g/L
|
|
cardiac signs of anemia
|
tachycardia
orthostatic hypotension (w hypovolemia) systolic flow murmur wide pulse pressure signs of CHF |
|
investigations for anemia
|
1) rule out dilutional anemia
2) CBC w differential (note MCV, RDW) 3) reticulocyte count 4) blood film 5) rule out GI disease in iron deficiency anemia 6) additional lab investigations as indicated for diff anemias |
|
measures defining anemia
|
males:
Hb <135g/L or Hct <41% females Hb <120g/L or Hct <36% 2y to puberty Hb <110g/L birth <140g/L |
|
measures defining polycythemia
|
males:
Hb >185g/L or Hct >52% females or African males: Hb >165g/L or Hct >47% |
|
causes or relative erythrocytosis
|
decreased plasma volume
- diuretics - severe dehydration - burns - "stress" |
|
clinical features of polycythemia
|
due to high RBC mass and hyperviscosity:
- headache - dizziness - tinnitus - visual distrubances - symptoms of angina, CHF - thrombosis or bleeding (abnormal platelet fn) - hepatomegaly - plethora face and or palms |
|
pancytopenia
|
decrease in all hematopoietic cell lines
|
|
causes of microcytic anemia
|
TAILS
Thalassemia Anemia of chronic disease Iron deficiency Lead poisoning Sideroblastic anemia |
|
avg North American iron intake per day
|
10-20mg in diet
5-10% absorbed = 0.5 - 2mg |
|
enhancement of iron absorption
|
citric acid
ascorbic acid (vit C) |
|
reductors of iron absorption
|
polyphenols (tea)
phytate dietary calcium soy protein |
|
iron indicies
|
1) bone marrow aspirate (gold standard)
2) serum ferritin (most imp blood test) 3) serum Fe 4) total iron binding capacity (TIBC) 5) saturation (3/4) 6) soluble transferring receptor (sTfR) |
|
sTfR
|
reflects availability of Fe at tissue level
- TfR norm expressed on surface erythroblasts - some cleaved off = sTfR in circulation - iron deficient = ^TfR on erythroblasts (and more cleaved in circ) - lower levels in reduced erythropoiesis or iron overload |
|
etiology iron deficiency anemia
|
1) increased demand
- pregnancy 2) decreased supply - infants and cows milk - elderly tea and toast diet - absorption imbalances - post-gastrectomy - malabsorption 3) increased losses: - hemorrhage - intravascular hemolysis - vit C deficiency |
|
symptoms of iron deficiency anemia
|
1) may be fatigue b4 anemia
2) anemia 3) brittle hair, nail changes 4) dysphagia 5) pallor 6) glossitis 7) angular stomatitis 8) pica |
|
symptoms of anemia in iron deficiency anemia
|
weakness,
irritability, exercise intolerance, syncope, dyspnea, headache, palpitations, postural dizziness, tinnitus, feeling cold, confusion/ LOC |
|
lab investigations for iron deficiency anemia
|
1) iron indicies:
- ferritin (<45microg/L) diagnostic - ferritin 46-99 a) TIBC, serum Fe, sat b) sTfR 2) peripheral blood film: - hypochromic microcytosis - anisocytosis, but not marked 3) bone marrow (gold std but not commonly done) |
|
oral tx iron deficiency
|
ferrous sulphate:
- 325mg tid ferrous gluconate: - 300 mg tid ferrous fumarate: - 300 mg tid until anemia corrects, additional 3+ months until serum ferritin normalizes **take with citrus juice to enhance absorption! take empty stomach before meals unless having hard time tolerating NOT with milk, Ca2+, Coffee, Tea, eggs, whole grains, |
|
indications iron-deficiency anemia co-existing with ACD
|
1) serum ferritin <100microg/L in setting of chronic inflam
2) elevation sTfR 3) absence of stainable iron in bone marrow aspiration/biopsy 4) response to tx trial of oral iron |
|
causes normocytic anemia
|
ABCD
Acute blood loss Bone marrow failure Chronic Disease Destruction (hemolysis) |
|
sites of hematopoiesis w age variance
|
fetus:
0-2 m: yolk sac 2-7 m: liver, spleen 5-9 m: bone marrow infants: bone marrow of practically all bones adults: vertebrae ribs sternum skull sacrum pelvis proximal ends femur |
|
EPO as therapy
|
IV or subcutaneous
main indication: end-stage renal disease other: pre-autologous blood trans ACD (RhA, CA) some myelodysplasia or myeloma AIDS anemia of prematurity often need oral or parenteral iron to max response |
|
Methaemoglobinaemia
|
circulating Hgb is present with Fe3+ (oxidized state) instead of usual Fe2+
may be hereditary or toxic - drug or other toxic substance oxidizes Fe pt likely to show cyanosis *normally 3% Hgb transformed to methemaglobin each day but reduced with enzyme methemaglobin reductase and NADH |
|
anemic changes in ODC
|
anemia causes ^ 2,3-DPG
= right shift ODC particularly marked in anemias affecting RBC metabolism directly or associated with low-affinity Hgb (HgbS) |
|
common phsysiological situations where MCV is outside normal ranges but not patho
|
Birth/infancy:
high for few weeks as newborn low in infancy rises slowly thruout childhood to normal adult size pregnancy: often large even w/o other causes macrocytosis |
|
RBC dimorphic appearance in blood film
|
causes of both micro and macrocytosis present
(ie Fe deficiency and B12 deficiency) = dual population of large well-Hgb cells and small hypochromic cells) also early sign of iron deficiency anemia from hemorrhage: see normocytic cells from before blood loss and microcytic cells from iron deficient replacement - increased RDW |
|
hepcidin
|
protein produced by liver
acute phase protein major hormonal regulator of iron homeostasis decreased production in iron deficiency, hypoxia, ineffective erythropoiesis usually inhibits Fe release from macrophages, intestinal epithelial cells by interacting w transmembrane iron exporter ferroportin |
|
regulation of hepcidin synthesis
|
transferrin receptor 2
high saturation of transferrin stim hepcidin low sat levels = reduction hepcidin synthesis restricted to erythoid cells, duodenal crypt cells, liver cells |
|
iron deficiency in children
|
irratibility
poor cognitive funciton decline in psychomotor development lower intelligence quotient (IQ), a diminished capability to learn, a suboptimal growth rate |
|
increased iron need in pregnancy for:
|
- increased maternal blood cell mass (35%)
- transfer 300 mg to fetus - blood loss at delivery iron therapy if Hb below 100g/L or MCV below 82fl in 3rd trimester |
|
menorrhagia
|
a loss of 80 mL or more of blood at each cycle
difficult to assess clinically |
|
RBC indicies and film results in iron deficiency anemia
|
-hypochromic microcytic RBC
- target cells - pencil shaped poikilocytes - reticulocyte count low for degree of anemia - dimorphic if coexisting B12 or folate deficiency |
|
serum ferritin
|
small fraction of body ferritin circulates in the
serum - the concentration being related to tissue, particularly reticuloendothelial, iron stores -iron deficiency anaemia the serum ferritin is very low while a raised serum ferritin indicates iron overload or excess release of ferritin from damaged tissues or an acute phase response |
|
parenteral iron
|
ferric hydroxide-sucrose
= Venofer slow IV injection or infusion 200mg/infusion stores replenished faster, but same hematologic response higher chance of anaphylaxis only if Hb<100g/L, oral didn't work proven |
|
reasons for failure of response to oral iron therapy
|
1) continuing hemorrhage
2) failure to take tablets 3) wrong diagnosis (thalassemia, sideroblastic) 4) mixed deficiency (B12 or folate as well) 5) another cause for anemia (ACD) 6) malabsorption 7) use of slow-release preparation |
|
characteristic features of anemia of chronic disease
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1 Normochromic, normocytic or mildly hypochromic
(MCV rarely <75 fL) indices and red cell morphology. 2 Mild and non-progressive anaemia (Hgb rarely <9.0 g/dL)-the severity being related to the severity of the disease. 3 Both the serum iron and TIBC are reduced; sTfR levels are normal. 4 The serum ferritin is normal or raised. 5 Bone marrow storage (reticuloendothelial) iron is normal but erytlroblast iron is reduced |
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pathogenesis of ACD
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may be:
1) decreased release Fe from macrophages to plasma (hepcidin release in response to inflammation) 2) reduced rBC lifespan 3)inadequate EPO response to anemia via IL-1 and TNF negative effects on erythropoiesis |
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causes of anemia of chronic disorders
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chronic inflammatory diseases:
- infections (pulm abscess, Tb, osteomyelitis, pneumonia, bacterial endocarditis) - non-infectious (rheumatoid arthritis, lupus, CT diseases, sarcoidosis, Crohn's) Malignant: Carcinoma Lymphoma Sarcoma |
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sideroblastic anemia
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- defect in heme synthesis
- characterized by hypochromic and microcytic RBC - see ring of iron granules around nucleus ("ring sideroblasts") in marrow (>15% marrow erythroblasts are ring sideroblasts) |
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lead effects
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inhibits heme and globin synthesis at multiple levels
- also see basophilic stippling = accumulation of denatured RNA (inhibition of its normal breakdown) may get hypochromic or hemolytic anemia ring sideroblasts in bone marrow |
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iron deficiency anemia prognosis
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easily treated,, excellent outcome
UNLESS underlying condition has poor prognosis (ie CA) or co-morbid, or aggrevates underlying cardio/resp probs from hypoxia mostly debilitating from fatigue and muscular dysfunction more negative outcomes in children |
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pagophagia
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compulsive eating of ice that is a common symptom of a lack of iron
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esophageal web
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hin (2-3 mm), eccentric, smooth extension of normal esophageal tissue consisting of mucosa and submucosa that can occur anywhere along the length of the esophagus but is typically located in the anterior postcricoid area of the proximal esophagus
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glossitis
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inflammation of the tongue
can be seen in iron-deficiency anemia |
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Plummer-Vinson syndrome
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webbing of the mucosa at the junction of the hypopharynx and the esophagus
can cause dysphagia |
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approach to dx of iron deficiency anemia
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1) hx: veg, pica, hemorrhage
2) PE 3) CBC, peripheral smear 4) serum Fe, TIBC, serum ferritin 5) eval for hemosiderinuria, hemoglobinuria, pulm hemosiderosis 6) Hgb electrophoresis, A2 and F 7) reticulocyte hgb count 8) others to determine etiology: stool, lead, bone marrow |
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hemoglobinuria
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hemoglobin is found in abnormally high concentrations in the urine
suspect if freshly obtained urine sample appears bloody but no RBC in it classically is ascribed to paroxysmal nocturnal hemoglobinuria, but it can occur with any brisk intravascular hemolytic anemia |
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pulmonary hemosiderosis
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hemorrhage into the lungs leads to abnormal accumulation of iron, causes anemia and lung damage
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pathognomonic
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characteristic for a particular disease. A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doubt
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NSAIDS and GI
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complications in gastroduodenum and, more recently recognized, colon
ulcers bleeding perforation protein-losing enteropathy diaphragm-like strictures, particularly in ileum |
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presentation of NSAID colopathy
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iron-deficiency anemia
fecal occult blood-positive stools crampy abdominal pain weight loss alteration in bowel habit pain - stricture? long term NSAID use, often for joint pain |
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common causes of anemia in elderly
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- ** chronic disease
- ** iron deficiency - Vit B12 deficiency - folate deficiency - GI bleeding - myelodysplastic syndrome serum ferritin most useful test to differentiate iron deficiency anemia from ACD serum methylmalonic acid for dx B12 deficiency |
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anemia in elderly
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female <12g/dL
male <13g/dL prevalence 8-44% highest prevalence men >85 onset of signs and symptoms often insiduous; activity adjustment *conjunctival pallor reliable sign frequently get worsening of other condition due to anemia (ie worsening CHF) *algorithms of based on MCV may not be helpful bc doesnt change much |
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acute phase reactant
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proteins whose serum concentrations increase or decrease by at least 25 percent during inflammatory states
positive APR include fibrinogen, alpha-1 antitrypsin, haptoglobin, interleukin (IL)-1 receptor antagonist, hepcidin, ferritin Negative APR include albumin, transferrin, and transthyretin rythrocyte sedimentation rate (ESR), a nonprotein APR, reflects plasma viscosity and the presence of acute phase proteins |
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TIBC iron deficiency anemia vs ACD
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classic iron deficiency anemia, the TIBC is higher than 400 (mu)g per dL
anemia of chronic disease, the TIBC is usually below normal, not only because the iron stores are elevated but also because, as an acute-phase reactant, transferrin is reduced in the presence of acute and chronic stress |
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serum ferritin
iron deficiency anemia vs ACD |
most useful test, differentiating anemia of chronic disease from iron deficiency anemia in 70% of patients
Ferritin can also be an acute-phase reactant in liver injury and in some types of tumor, raising the serum ferritin to normal levels even in the presence of iron deficiency |
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EPO as tx
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50 to 100 U per kg 3 times per week
up to 150 U if response to lower dose inadequate may be helpful in ACD |
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Myelodysplastic syndrome
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relatively uncommon cause of anemia
more common cause in the elderly than in younger patients defect in the development of one of the marrow cell lines, limiting the release of functioning cells diagnostic consideration when white cell or platelet abnormalities accompany the anemia dx usually made by bone marrow biopsy |
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factors favouring absorption of iron
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Heme iron
Ferrous form 2+ Acids (HCl, vit C) Solubilizing agents iron deficiency ineffective erythropoiesis pregnancy herediatary hemochromatosis |
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developmental hematopoiesis cell type proportions
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embryo - 1-8 wks: nucleated RBC only
fetus: 9 weeks to birth: 50% erythropoiesis in liver, 50% WBC (mostly naive lymphocytes) and platelets (bone marrow) neonate: normalize to adult values, Ig production by 6m |
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thymus changes over lifespan
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t cell production areas get progressively exchanged with fat
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developmental stages
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embryo: 1-8 weeks
fetus: 9 weeks to birth neonate: birth developmental not gestational! (gestational is 2 weeks added on to these - starts counting from last period) |
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types of HbE
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z2e2 = Gower 1
a2e2 = Gower 2 z2g2 = Portland |
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approach to anemia
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determine acute vs chronic:
1) hemodynamic stability (HR,BP) 2) Previous CBC 3) Overt blood loss 4) Reticulocytes Chronic: 1) what is MCV? 2) hemolytic? (signs of ^ RBC production and ^ RBC destruction) |
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acute causes of anemia
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acute hemolysis
bleeding ** check reticulocytes - going to be cranked out by bone marrow, >100 x10^9/L |
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symptoms from anemia depend on:
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- decreased O2 carrying capacity (fatigue)
- rate of development of anemia - change in blood volume - CV and resp capacity (young healthy can tolerate anemia better) - associated symptoms of underlying disease (what is causing anemia) |
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Direct Antiglobulin Test
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DAT
positive = autoimmune hemolytic anemia measure of Ab attached to RBC - immune system is attacking own RBCs |
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determining iron deficiency vs thalassemia
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1) ethnic background
2) family hx 3) Hb vs MCV: Thal Hb norm, slightly low; MCV 65 Fe def = Hb <80, MCV 65 but variable - as Hb decreases, MCV decreases 4) RDW (Fe ^, Thal normal) 5) Peripheral smear |
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determination if hemolytic anemia
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1) increased RBC production
- ^ reticulocytes - bone marrow erythroid hyperplasia 2) increased RBC destruction: - ^ indirect bilirubin - ^ LDH - dec haptoglobin - free Hgb - maybe hemoglobinuria or positive DAT |
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causes of hemolytic anemia
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Congenital:
- membrane disorder - hemoglobinopathies - enzyme issues Acquired: - Immune (drugs, autoimmune, alloimmune) - Nonimmune |
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alloimmune hemolytic anemia
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only seen in patients who have received blood transfusion or fetal/mother issues
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investigations for hemolytic anemia
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1) peripheral blood smear
2) DAT |
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definition of anemia
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Blood hemoglobin concentration
(or hematocrit) that is below the appropriate reference range for the patient |
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Ddx microcytic anemia
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Iron deficiency
l Thalassemia trait l Anemia of chronic disease l Sideroblastic anemia l Lead poisoning usually result from defective hemoglobin synthesis |
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Ddx normocytic anemia
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- Acute blood loss
- Hemolysis (acute or chronic) - Anemia of chronic disease: - Anemia of renal failure - Liver failure - Endocrinopathies (Addison’s, Hypothyroidism, Hypogonadotropic states) - Early iron deficiency - Pregnancy - Bone marrow disorders |
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Ddx macrocytic anemia
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- Megaloblastic – MCV may be as high as >120
(= B12 deficiency = Folate deficiency = Medications (e.g. hydroxyurea, zidovudine)) - Alcohol abuse - Liver disease - Hypothyroidism - Myelodysplastic syndrome (MDS) - Other anemia with high reticulocyte count |
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anemia levels
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mild: no-symptoms, Hgb>100
symptoms below that, but varies with patients |