Impaired Production Anemias Flashcards
What is impaired production
anemias that are caused by impaired production of RBCs that results in a decreased production
Cause of Iron Deficiency Anemia
inadequate stores of Iron for Hgb
- decreased intake of iron - vegetarian, infancy, pregnancy
- increased need for iron - pregnancy, children
- increased loss of iron through blood loss - menstruation , chronic blood loss
Pathogenesis of Iron Deficiency Anemia
develops slowly as various iron compartments become depleted 3 stages: iron depletion iron deficient erythroipoiesis iron deficiency anemia
Stage 1 of IDA - Iron Depletion
body’s reserve is sufficient to maintain functions
iron stores are becoming depleted
decrease in serum ferritin
no anemia
Stage 2 of IDA - Iron Deficient Erythropoiesis
exhaustion of the storage pool of iron results in zinc complexes with protoporphyrin - ZPP RBCs become slightly microcytic Hgb will begin to drop Ferritin is still low serum iron is low TIBC of transferrin will rise % saturation will be low
Stage 3 of IDA - Iron Deficiency Anemia
Developing RBCs are unable to develop normally due to depleted iron stores & diminished iron transport show anemia symptoms MICROCYTIC, HYPOCHROMIC ferritin extremely low serum iron low TIBC of transferrin is high % saturation is low
Symptoms of IDA
Pica syndrome - crushed ice
sore tongue (glossitis)
cracks at corner of mouth
spooning of the fingernails
Screening for IDA
in the PB : increased RDW & microcytosis
hypochromic/microcytic
Hgb decreases
Diagnostic tests for IDA
ferritin decreased serum iron decreased TIBC increased % saturation decreased panel test for iron
Specialized testing for IDA
ZPP will be increased
BM will display iron deficiency - reveal an absence of hemosiderin
Anemia of Chronic Disease Pathogenesis
iron is abundant in the body serum iron is low (sideropenia) unable to recycle iron to BM normoblast Hepcidin is released in inflammation decreased EPO by cytokines suppression of RBC production by cytokines
Hepcidin in ACD
causes sideropenia
produced in response to inflammatory cytokines
blocks iron uptake in the duodenum & blocks the release of iron from Macrophages
Lab Diagnosis of ACD
mild anemia (Hgb 9-11) Normochromic/ Normocytic can be hypochromic/microcytic in long standing cases RDW -normal Retics - normal or decreased Ferritin - normal to increased serum iron - decreased TIBC -decreased % saturation - decreased ZPP - increased
Sideroblastic Anemia
anemia in which heme synthesis is impaired
iron is abundant
results from mutation that affects enzymatic steps of heme synthesis
2 Groups of Sideroblastic Anemias
inherited & acquired
Hereditary Sideroblastic Anemia
X-linked sideroblastic anemia
females are carriers & males are affected
very uncommon anemia
Acquired Sideroblastic Anemia
unknown cause or secondary to an underlying disease
most common causes :
1. heavy metals (lead)
2. alcohol
Lead Poisoning & children
eating lead based paint chips
leads to hyperactivity, low IQ, concentration disorders, hearing loss, impaired grown & development
Lead Poisoning and Sideroblastic Anemia
once ingested lead passes through the blood to the BM & accumulates in the mitochondria of erythroblasts & inhibits cellular enzymes involved in heme synthesis
Lab Diagnosis of Siderblastic Anemia
Normochromic Normocytic
can be microcytic/hypochromic with chronic exposure
can have a duel population of hypo & normo cells
Basophilic stippling
Pappenheimer bodies or siderotic granules (iron deposits)
poikilocytosis
in BM - ringed sideroblasts (excess of iron in mitochondria)
Porphyrias Definition
group of disorders that result in the build up of porphyrins
diseases characterized by impaired production of heme ( if any enzymatic step in heme synthesis is blocked)
RARE ANEMIAS
Symptoms of Porphyria Anemias
vary depending on type
abdominal pain
light sensitivity - rashes
problems with nervous system & muscles
Types of Porphyrias
2 types: Congenital erythropoietic porphyria (CEP) Erythropoietic protophyria (EPP)
Congenital Erythropoietic porphyria (CEP) Characteristics
autosomal recessive disease
missing enzyme: uroporphyrinogen III cosynthetase
creates a build up of : Uroporphyrin I & coproporphyrin I
EXTREME photosensitivity
RBC lifespan : 18 days
Erythropoietic protophyria(EPP) Characteristics
autosomal dominant disease missing enzyme: ferrocheletase build up of : protoporphyrin less severe photosensitivity no hemolytic anemia
Causes of Megalobastic Anemia
- deficiency of vitamin B12 (cobalamin)
2. deficiency of folic acid (folate)
Pathogenesis of Megaloblastic Anemia
v B12 & folic acid are necessary as coenzymes for nucleic acid synthesis = DNA synthesis will be impaired
results in the demyelinization of nerves
Causes of Vitamin B12 Deficiency
- dietary deficiency - vegans etc
- increased need during pregnancy/lactation & growth
- impaired absorption of v B12
Vitamin B12 Absorption
V. B12 is bound to haptocorrin & is released from haptocorrin by trypsin in the small intestine
V. B12 then binds to Intrinsic factor (IF) produced by gastric cells
Ways of Impaired absorption of Vitamin B12
- failure to separate VB12 from haptocorrin
- Lack of IF - most common cause
- malabsorption caused by conditions (inflammatory bowel disease)
- competition for available VB12- tapeworm etc
Symptoms of Vitamin B12 deficiency
memory loss numbness loss of balance 'megaloblastic madness' all symptoms derived from demylination of the nerves
Causes of Folic Acid Deficiency
- dietary deficiency
- increased need w/ pregnancy & growth
- impaired absorption -usually due to intestinal disease
- impaired utilization due to drugs - anti-epileptic drugs
- excessive loss w/ renal dialysis
Symptoms of Folic Acid Deficiency
depression/ psychosis
fetus can be effected - spina bifida
all neurological symptoms
in addition to generic anemia symptoms
Wintrobe Classification of Megaloblastic Anemia
Normochromic, Macrocytic anemia MCV > 120 fL pancytopenia elevated RDW oval macrocytes HYPERSEGMENTED NEUTROPHILS poikilocytosis low retic count
Bone Marrow Diagnosis for Megaloblastic Anemias
confirm megaloblastic appearance of cells
nuclear-cytoplasm asynchrony = nucleus appears younger than expected in relation to the cytoplasm
WBCs appear larger/giant
Chemistry tests for Megalobastic Anemias
Vitamin B12 levels
serum folate or red cell folate
intermediate tests:
methylmalonic acid (MMA) - normal in folate def. & increased in vB12 def.
homocysteine levels - elevated in both vB12 & folate def.
Pernicious Anemia (PA)
form of megaloblastic anemia - most common form
due to vitamin B12 deficiency- autoimmune destruction of IF secreting gastric cells
produce antibodies to IF that can be assayed
Determining the Cause of Megaloblastic Anemia
- assay the amount of folate or vitamin B12 in the body
2. if vitamin B12 is decreased, determine whether if it is due to IF deficiency (schilling test/ assays)
Schilling Test Principle
once absorbed, a portion of any oral dose of v. B12 hat is not used by the body will be excreted in the urine
if vB12 is nto detected in the urine then malabsorption is confirmed
2 phase test
Why is the Schilling Test not used any longer
because of the use of radio-labeled vitamin B12
Macrocytic Anemia w/o Megaloblastosis
macrocytes (not as pronounced)
no hyper-segmented neutrophils
WBC & Plts are normal
other symptoms of megaloblastosis are not present
Two most common causes of Macrocytic Anemia w/o Megaloblastosis
Alcoholism - usually no alcohol
Liver Disease- anemia is present
Causes of Aplastic Anemia
acquired : Fanconi’s Anemia & Dyskeratosis Congenita
inherited - ~ 70% of cases have unknown causes secondary to toxic chemicals (benzene), radiation, drugs, etc
Pathogenesis of Aplastic Anemia
Bone marrow failure due to depletion of BM & replacement of BM with fat
results in pancytopenia
Lab Diagnosis of Aplastic Anemia
normochromic, normocytic anemia
panctyopenia
normal RDW
Causes of Myelophthisic Anemia
Tumors & malignant diseases (prostate, breast, stomach cancer) nonmalignant diseases (TB)
Pathogensis of Myelophthisic Anemia
normal BM is replaced with or infiltrated by fibrotic or neoplastic (cancerous) cells and leads to BM failure
Lab Diagnosis of Myelophthisic Anemia
normochromic, normocytic anemia
pancytopenia
moderate-marked poikilocytosis - often decryocytes
Anemia Associated with Renal Disease
caused by renal disease
Hgb < 11 g/dL
deficiency of EPO production by the kidneys
Lab Diagnosis of Anemia Associated with Renal Disease
normochromic, normocytic anemia
normal RDW
poikilocytosis
retics - normal or decreased
