RBC I, Anemias of diminished Erythropoiesis Putthoff Flashcards
what are anemias from underproduction caused by
nutritional deficiencies, renal failure and chronic inflammation
What causes megaloblastic anemia
impairment of DNA synthesis
Vit B12 and folic acid are needed for what
synthesis of thymidine
what do neutrophils look like in megaloblastic anemias
larger and with hypersegmentation
Pernicious anemia is caused by what
autoimmune gastritis that impairs production of IF
where is IF secreted
parietal cells of fundic mucosa
Vit B12 binds to what in stomach
haptocorrin
where does Vit B12 join IF
jejunum after pancreatic proteases released
Where is B12 absorbed
distal ileum
Absence of VitB12 leads to what
increased homocysteine and methyl-tetrahydrofolate
What is proximate cause of anemia in B12 deficiency
lack of folate
What Sx of B12 deficiency are not resolved by folic acid replacement
neurologic complications
What are the neurologic signs of B12 deficiency
spastic paraparesis, sensory ataxia, severe parathesias of lower limbs
what population is most affected by pernicious anemia
Scandinavian and other Caucasian populations
also blacks hispanics
60 y.o
What Ab are found in patients with pernicious anemia
type I Ab that blocks VitB12-IF binding
Type II Ab that prevent IF-B12 complex binding to ileal R
Type III Ab that recognize alpha and beta subunits of gastric H+ pump
Dx pernicious anemia is based on what criteria
moderate to severe megaloblastic anemia
leukopenia with hypersegmented granulocytes
low serum B12
elevated serum levels homocystein and methymalonic acid
increased homocystein is assoc with what other condition
accelerated athersclerosis
pernicious anemia is asso with what other conditions
autoimmune disorders
after parenteral administration of B12 when will Hct increase and reticulocytosis be notable
5 days
what are the Dx utility in pernicious anemia
autoantibodies
What is postulated to be the primary cause of gastric pathology in pernicious anemia
autoreactive T cell resoponse that inflicts gastric injury and triggers formation autoAb
What is acholorhydria and how does it lead to B12 deficiency
loss pepsin secretion, so B12 not readily released from foods
how does gastrectomy lead to B12 deficiency
IF not available
if pancreas is affected what could happen to B12 levels
B12 cannot be released from haptocorrin B12 complex
Ileal resection leads to what
megaloblastic anemia form def B12
patient has Hx of eating raw fish and is presenting with megaloblastic anemia
tapeworm competes for B12
What are some metabolic states that have increased demand B12
pregnancy, hyperthyroidism, disseminated cancer, chronic infection
patient has shiny beefy tongue, sign of what
megaloblastic anemia
atrophic glossitis
what are the CNS morphological changes in pernicious anemia
demyelination of dorsal and lateral spinal tracts
pernicious anemia patients are at increased risk in developing what
gastric carcinoma
what is folic acid needed for
purien synthesis, conversion of homocystein to methionine and dTMP synthesis (needed for DNA synthesis)
Folic-acid rich foods
green vegetables
What are the 3 major causes of folic acid deficiency
decreased intake
icnreased requirements
impaired utilization
In the US what population is more prone to Fe deficiency
adolescent girls, women of child bearing age and toddlers
alcoholics
sprue can lead to what
Fe deficiency microcytic anemia
what drugs can lead to folic acid deficiency
anticonvulsant phenytoin and oral contraceptives that affect absorption
what are folic acid antagonists
methotrexate
how can you differentiate B12 def from folic acid
look at folate levels
also methymalonate will be normal in folic acid.
where is Fe from in normal diet
heme from animal products and inorganic iron in vegetables
80% functional Fe found where
in hemoglobin and myoglobin
Major sites of Fe storage
liver and mononuclear phagocytes
how do you measure storage pool of Fe
plasma ferritin levels
Iron absorption is regulated how
hepcidin made in liver
where does absorption of Fe occur
duodenum proximally
What disorders have increased hepcidin levels
anemia of chronic disease
familial diseases with inability to absorb iron
when do you see low hepcidin levels
primary and secondary hemochromatosis
most common cause of Fe deficiency in the western worl
chronic blood loss
patient has microcytic anemia and mutation in TMPRSS6
will they respond to Fe therapy
no because have high levels hepcidin
how come primary and secondary hemochromatosis ahve low levels hepcidin
because ineffective erythropoeisis somehow suppresses hepcidin production
melena in anemic patient is indicative of what
GI bleed somwhere
chronic anemia
what is morphology of Fe deficiency anemia
microcytic hypochromic anemia with poikilocytosis
Causes of Fe deficiency
dietary lack, impaired absorption, increased requirement or chronic blood loss
what increases absorption of inorganic iron
ascorbic acid, citric acid, amino acids and sugars in diet
and inhibited by tannates (found in tea)
criteria for Dx Fe deficiency anemia
Hct and Hb decreased
low serum Fe and ferritin
High TIBC
low serum hepcidin
how can gastrectomy lead to Fe deficiency
impairs acidity in proximal duodenum
good way to Dx Fe deficiency based on morphology
no stainable Fe in macrophages in BM with Prussian blue stains
increased zone of pallor in center of RBC
elongated RBC called pencil cells are characteristic
what type of physical changes do you get with Fe deficiency
kiolonychia, alopecia, atrophic changes in tongue, gastric mcosa and intestinal malabsorption
PICA (eating dirt)
Triad plummer vinson syndrome
esophageal webs with microcytic hypochromic anemia and atrophic glossitis
Most common type anemia in hospitalized patients in the US
anemia of chronic disease
impaired RBC production assoc with chronic disease
3 major categories of diseases that cause chronic anemia
chronic infection
chronic autoimmune disorders
Neoplasms: bronchogenic carcinoma, hodgkin lymphoma
what happens in anemia of chronic disease
persistent inflammation and cytokines and medioatros suppress erythropoiesis
stimulate hepcidin
low WPO levels
Dx anemia of chronic disease based on CBC
serum ferritin is high
TIBC low!!
Which inflammatory mediator is most assoc with anemia of chronic disease because it stimulates hepcidin
IL-6
Tx anemia of chronic disease
Tx underlying disease
Aplastic anemia is what
syndrome of chronic primary hematopoietic failure and pancytopenia
what are major causes of aplastic anemia
acquired, chemical agents, physical agents, inherited
persistent marrow aplasia can appear after what viral infections
non-A non-B non-C non-G type viral hepatitis
What is Fanconi anemia
rare autosomal recessive
defects in complex needed for DNA repair
accompanied by congenital anomalies (hypoplasia)
Adult onset inherited aplastic anemia is assoc with what
defects in telomerases or just abnormally short telomeres
What are types of acquired aplastic anemias
idiopathic, stem cell defects, immune mediated
what type of chemical agents have dose related causes of aplastic anemia
alkyating agents antimetabolites benzene chloramphenicol Inorganic arsenicals
What chemical agents are idiosyncratic in causing aplastic anemia
chloramphenicol phenylbutazone organic arsenicals methylphenylethylhydantoin carbamazepine penicillamine gold salts
Majority aplastic anemia are considered what cause
idiopathic
how to Dx aplastic anemia
BM biopsy
Wat physical agents can cause aplastic anemia
irradiation
viral infections
CMV, EBC Herpes Zoster
what 2 major mech are thought to be involved with aplastic anemia
intrinsic stem cell abnormality
extrinsic immune mediated suppression of marrow precursors
what can aplastic anemia transofrm into
myeloid neoplasia like myelodysplasia or AML
what does BM aspirate look like in aplastic anemia
devoid of hematopoietic cells and lots of fat cells and fibrous stroma
scattered lymphocytes and plasma cells
Sx aplastic anemia
panctyopenia cause weakness, pallor, dyspneam petichae, ecchymosis, minor infections that are persistent
chills, fever and prostration
NOT splenomegaly!!!
what do TBC look like in aplastic anemia
macrocytic and normochromic
reticulocytopenia!
Tx choice for aplastic anemia
bone marrow transplantation
What is the primary marrow disorder that only afects erythroid progenitors
pure red cell aplasia
what can cause pure red cell aplasia
thymoma, large granular lymphocytic leukemia
certain drugs, autoimmune disorders
parvovirus B19 infection (immunocompromised)
Tx of pure red cell aplasia with patient who has thymoma
resection = improvement
What are myelophthisic anemias
space occupying lesions like metastatic breast lung prostate carcinomas that replace normal marrow
myelophthisic anemia is a feature of what disorder
myeloproliferative disorders
tear drop cells
hwo does chronic renal failure lead to anemia
diminished syntehsis of EPO by dmaged kidneys
How does hepatocellualr liver failure lead to anemia
decreased marrow function
hypothyroidism is assoc with what type anemia
mild n/n anemia
What is polycythemia
abnormal high RBC and increase Hb
what can cause relative polycythemia
dehydration, prolonged vomiting diarrhea or diuretics
or stress polycythemia- obese HTN patients
what can cause absolute primary polycythemia
intrinsic abnormalitiy of hematopoietic precursors
what can cause secondary absolute polycythemia
RBC progenitors respond to increased EPO
most common cause primary polycythemia
Polycythemia Vera
myeloproliferative disorder with mutations with EPO independent growth
What can cause secondary polycythemia
EPO secreting tumors
inherited defects that stabilize HIF-1alpha that stimulates transcription EPO gene
