Anemias Flashcards
The who defines anemia for females as
Hct<4,000,000
The who defines anemia for woman as
Hct<4,000,000
Macrophages supply what?
supply Fe++ for Hgb production
what is the function of fibroblasts in maintaining homeostatic balance
support bone marrow integrity
what is the function of adipocytes in maintaining homeostasis?
store energy as fat
What is the function of osteoblasts and osteoclasts in maintaining homeostasis
support the boney trabeculae
what regulates erythropoiesis?
erythropoietin
where is erythropoietin secreted from
the kidney
what is the function of erythropoietin
governs day to day RBC production
what is the main stimulus for EPO
O2 availability
How should EPO levels change in relation to an anemia
they should increase in proportion to the severity of the anemia
what substrates are needed for RBC production
Iron,B12,Folate
what is the normal lifespan of an RBC
120days
what does hypoxia do to RBC’s
Increases RBC’s
Which types of people have relatively lower RBS mass?
African americans and older adults
there is an increased mortality with Hgb of what?
Hgb of <12g/dL
What would the plasma and erythrocytes look like in an athlete?
increase in both plasma and erythrocytes
what are examples of volume and anemia concept
Acute bleeding, When normal volume is restored, dehydration and pregnancy
what would a reticulocyte with an index<2.5 be classified as?
hypoproliferative
what would a reticulocyte index >2.5 be classified as?
hyperproliferative
what is a reticulocyte?
an immature RBS that is stained with methylene blue and reveals residual Ribosomal RNA as beads of tiny deep blue precipitates
what happens to the retic count with blood loss?
the marrow should be able to increase production by 3 to 4 times normal over a 10day period
Anemia symptoms
DOE, Fatigue, Palpitations, H/A, Tinnitus, Chest pain, Esophageal rings, Nail spooning, Picas, Neuropathies
Clinical signs of Anemia
Tachycardia, Orthostatic hypotension, Systolic ejection murmur, Pallor
GI signs of anemia
Jaundice, Positive stool guaiac, splenomeagly, hepatomegaly, Petechiae, glossitis, Koilonychia, neurologic, musculo-skeletal
what is the definition of microcytic and hypochromic anemia
MCV<80mm3
what are causes of microcytic anemia (TICS)
Thalassemia major/minor
Iron deficiency
Chronic dz/Inflammatory dz
Sideroblastic anemia and Pb poisoning
Iron deficiency anemia accounts for what % of anemias
50% of anemias worldwide
serum irons is measured how?
Iron bound to transferrin in the serum
norm 40-140uG/dL
total iron binding capacity
total transferrin in the serum
norm 200-400uG/dL
Fe/TIBC
is the % saturation of iron binding capacity
norm should be 25-50%
Serum ferritin
is a rough estimate of iron stored in the reticuloendothelial system
norm. 30-250ng/ml
what are causes of Iron deficiency anemia
GI bleeding Excessive Menstruation Malnutrition and Diet Insufficiency Malabsorption Increased demand (pregnancy&growth spurts) Blood donation,blood loss in dialysis
what are specific clinical manifestations of Iron Deficiency Anemia
Angular Cheilosis
PICA
Koilonychia
Plummer-Vinson Syndrome
How do you treat Iron Deficiency Anemia
6wks to correct anemia
6 months to replete bone marrow stores
Ferrous Sulfate 325mg 3x/day, avoid milk/dairy products/calcium simultaneously
-Can be given IV or IM
When should you give IV or IM iron treatment
intolerant to oral preparation If more rapid correction of Fe deficiency anemia is neded Patients can not absorb oral Iron Chronic blood loss Pt on Dialysis
what are causes for treatment failure
Unidentified blood loss
non-sdherence
Incorrect diagnosis
GI malabsorption
What would you want to educate your patient on with Fe++ side effects
Constipation, black stools, nausea, bloating, abdominal pain and diarrhea
-do not take with tetracyclines/fluoroquinolones and antacids/PPI’s and be careful with calcium supplements
Vitamin C
Where is alpha-thalassemia most prevalent?
Increase in malaria regions: Southeast Asia & China
where is beta-thalassemia most prevalent?
in mediterranean populations
Southern Italy, Greece and North Africa
What is the definition of Thalassemia
genetic d/o characterized by inadequate production of either alpha or beta globin chain of hemoglobin.
There is an ineffective erythropoiesis and increase hemolysis
what happens when there is a defective alpha or beta globin chain production?
an imbalance of globin chains
The unaffected chain takes over-accumulates in the RBC interfering with normal maturation of the RBC
Leads to free radical production that induces hemolysis and anemia
what are heinz bodies
are precipitants of excess alpha chains in beta-thalassemia
are precipitants of excess beta chains in alpha thalassemia
-they impair DNA synthesis and decrease RBC production
-they damage RBC membrane and increase RBC destruction
what are the clinical features of thalassemia
positive family history
history of life-long hypochromic microcytic anemia not responsive to Fe++
From silent carrier statues to profound anemia
-depends on genetic defects
Beta-thalassemia minor contains how many gene mutations?
one gene mutation
results in mild anemia
beta-thalassemia major contains how many gene mutations?
two gene mutations
results in severe transfusion dependent anemia-Iron overload
If transfusions is delayed growth retardation ensues in children
What are complications of beta-thalassemia major (cooley’s anemia)
growth retardation Severe anemia abnormal facial structure pathologic fractures and osteopenia hepatosplenomegaly jaundice and bilirubin gall stones high out put CHF short life span <30yrs
what are the laboratory findings for thalassemia
Hg electrophoresis (confirms diagnosis) Inc Increase in fetal hemoglobin decrease in Hgb beta thal but increase in Hgb A2 HgbH in severe alpha thalassemia
what will thalassemia look like in a peripheral smear
small, pale RBC
target cells
nucleated erythroblasts
basophilic stippling
other laboratory findings in thalassemia
high serum iron and ferritin Hgb level 3-6g/dl Marked microcytosis Heinz bodies in beta-thalassemia increase retic count with hemolysis
what is the treatment for thalassemia?
transfusion + deferoxamine (to prevent iron overload)
Splenectomy
Experiment allogeneic hemtaopoietic stem cell transplantation in severe cases
avoid iron containing supplements
Transfusion complications
Iron overload -heart failure -liver failure pancreatic failure w/DM & malabsorption -Other endocrine abnormalities -skin pigmentation Tx iron overload with chelation
Thalassemia patient education
genetic counseling
testing of parents
prenatal diagnosis for severe forms of thalassemia
what is the definition of normochromic normocytic anemia
MCV 80-100
what are the causes of a normochromic normocytic anemia
anemia of chronic disease Early Fe deficiency Myelodysplasia or marrow failure Acute blood loss Anemia associated with renal failure
what is the pathophysiology of chronic/inflammatory disease
impaire iron utilization and metabolism -retic prod is low norm or incr. ferritin norm Fe/TIBC low transferrin and low serum iron Iron remain sequestered in RE system Controlled by hepcidin which is released by liver and controls Fe absorption
what is the most important hormone regulating the Fe release from cells
Hepcidin.
As hepcidin levels increase there is a decrease in iron availability.
what decreases the response to erythropoietin
IL-1, IL-6 & TNF
What is the treatment for anemia of chronic disease
treatment of the underlying condition is the most important
Fe++ supplement may or may not help
There is a decrease response to EPO
Anemia due to chronic renal failure is common and severe due to
EPO deficiency
Uremic toxins interfere with RBC production and survival
Hemodialysis
Responds well to EPO and Iron
What are intrinsic causes of hemolytic anemia (RBC defects)
G6PD deficiency
Sickle cel
Hereditary spherocytosis
what are the extrinsic causes?
immune hemolytic anemia Drug induced hemolytic anemia TTP hemolytic uremic syndrome DIC mechanical hemolysis d/t cardiac valve dysfunction hyperslpenism
what are general clinical features with hemolytic anemias
may be associated with jaundice
may have symptoms consistent with tissue hypoxia, similar to other anemia related syndrome: pallor, SOB, Tachycardia
what is sickle cell anemia
point mutation of the beta-globin chain of Hb-A molecule- with replacement of glutamine with valine-Hbs
short arm of chromosome 11 mutation
what is the pathophys of sickle cell anemia
HbS become sickled when doxygenated- producing structural cellular damage
sickle cell HgB can return to its normal configuration when reoxygentated
what is sickle cells disease defined as in terms of genetics
homozygous hemoglobin S
what is sickle cell trait defined as
heterozygous for Hgb A and HgbS
little tendency to sickle unless there is severe hypoxia usually asymptomatic
sickle cell demographics
affects .1-.2% african american
about 10% of african american carry sickle cell
positive fam. hx
symptoms of sickle cell anemia
due to deformed RBC’s causing hemolysis, splenic sequestration and microvascular occlusion
what happens during painful crisis with sickle cell anemia?
bone infarctions osteomyelitis part w/salmonella pneumococcal and other infx due to autoslpenectomy acute chest syndrome- pulmonary infarcts, hypoxia, fever slpenic sequestration crisis arthropathy renal papillary necrosis priapism-impotence retinal hemorrhage
what are complications of sickle cell?
infections d/t splenic infarction causes overwhelming infection by encapsulated organmism (strep, hemo,kleb,sal)
parvo B19 causing hemolysis
aplastic crisis due to viral infx.
transient arrest in Erythropoiesis with marked decreased in retic
how is sickle cell diagnosed
Hg electrophoresis -will detect HbS Smear -sickled cells, hemolysis, reduced RBC count -reticulocytes -nucleated RBC -Target Cells -Howell jolly bodies d/t autosplenectomy
what is the treatment for sickle cell anemia
prevent sickle cell crisis by monitoring condition that demand O2 from RBC’s
-infection
-exercise
-climate extremes
-dehydration during periods of physiologic/emotional distress
When patient with Hgb AS or SS presents with paint and distress this is a sickle cell crisis until proven otherwise
-Consider BM transplant
-hydroxyurea given PO chronically, this increases Hbf which decreases Hbs and painful crisis and acute chest syndrome
WBC and Retics which may worsen symptoms
how to treat sickle cell crisis
IV hydration, Supplemental O2, Analgesics-morphine, transfusion for Hct<30%
R/O occult infx, MI or PE
what are supportive cares treatments for sickle cell
folic acid
pneumococcal and H flu vac.
Penicillin prophylaxis
Opthalmological monitoring against retinopathy
Orthopedic care
careful monitoring of renal,pulm and cardiac function
paint management
what is the definition of autoimmune hemolytic anemias
acquired antibody mediated toward RBC membrane antigens, mostly non-specific but occasionally against Rh
Types IgM or IgG
what is warn AIHA
IgG mediated
more common than cold AIHA
IgG binds to RBC at >37C
results in extravascular hemolysis- especially in spleen and liver
what are the causes of warm AIHA
primary or Idopathic
Secondary to lymphoid malignancies, collagen vascular dz, viral infx or drugs
cold AIHA
IgM mediated
IgM binds to RBC in temp <37C
produces complement fixation and activation leading to intravascular hemolysis within blood vessels
what causes cold AIHA
Idiopathic
lymphoproliferative dz
mycoplasma pneumonia
Infectious mono EBV
what are clinical signs of autoimmune hemolytic anemia
jaundice
splenomegaly
fatigue
pallor
what are the lab findings like for AIHA
sine qua non: positive direct coombs test elevated retic count blood smear shows immature RBC free serum hemoglobin and hemoglobinuria high unconjugated bilirubin elevated LDH low or absent haptoglobin
Tx of AIHA
treat underlying disease -Lymphoma, Mycoplasma pneumonia, EBV Immunosuppressive meds RBC transfusions Folate splenectomy-to reduce hemolysis and destruction/sequestration
What is a macrocytic anemia
MCV>100
what is the cause of a B12 macrocytic anemia
most common cause if of B12 is impaired GI absorption due to lack of intrinsic factor produced by gastric parietal cells
what is a pernicious anemia
is a lack of intrinsic factor due to auto-antibody destruction of gastric parietal cells
what are causes of B12deficiency
Bariatric Surgery Gastrectomy Poor diet-alcoholic Vegetarians Terminal ileal resection Crohns celiac competing organism -tape worm, GI or fungal growth
what is the clinical presentation of B12 deficiency?
can take >3yrs to show up
Macrocytic hypoproliferative anemia
Weakness, faintness, pallor of skin and mucous membranes
Dyspnea after slight exertion
Atrophic glossitis and stomatitis
Neuropathy-distinguishes between B12 and Folate
Important causes of dementia
what are the lab findings in B12 deficiency
blood smear shows marked macrocytosis >100mm
low serum B12<250pg/ml
high methylmalonic acid (high only in B12)
high homocysteine (elevated in both B12 and folate)
macro ovalocytes and hypersegmented PMN
low retic count
elevated LDH and Indirect bilirubin
what are the co-factors for DNA synthesis
B12 and folate
what happens with there is a deficiency in erythropoiesis
Ineffective RBC production
defective and fragile RBC
Asynchronous maturation between cytoplasm
What is the importance of B12 in terms of neurons
B12 maintains neuronal myelin integrity
deficiency predisposes to myelin breakdown with resulting neurological symptoms=peripheral neuropathy
what is the treatment for B12 deficiency anemia
1mg B12 (cyanocobalamin) IM/PO x7days then q wkx 4-8 wks (IM for pernicious anemia)
If tx is delayed >6mths neurological prob may not respond to tx
Folate can reverse hematologic abnormalities of B12 but not neurologic symptoms
IT IS ESSENTIAL TO GET B12 & FOLATE in MACROCYTIC ANEMIA
what is the pathophys for folate deficiency
body stores sufficient 2-3 months
decrease folic acid causes impaired RBC maturation and early destruction
what are the causes for folate deficiency
inadequate folate intake alcoholics anorectic persons elderly diet low in meat, fruit, and vegetables(leafy green veggies)
what are reasons for increased requirement of folate
pregnancy chronic hemolytic anemias malignancy dialysis infants and children defective absorption Celiac sprue
meds that can cause folate deficiency
methotrexate
trimethoprim
anticonvulsants
what are clinical presentations of folate deficiency
symptoms from dietary deficiency can be seen in a few months-quicker than B12
atrophic glossitis and angular chelosis
anemia symptoms
what are the lab findings for folate deficiency
macro-ovalocytes
hypersegmented PMNs
B12 levels are normal
low levels of serum folate
what is the Tx for folate
1-5mg/day folic acid PO
avoid alcohol and folic acid antagonist
treat malabsorption
rule out B12 deficiency
