Red Blood Cell Disorders Flashcards
What is the stimulation for EPO release
Hypoxemia
Anemia
Left shift of oxygen binding curve
it is released from Interstitial cells in peritubular capillaries of renal cortex
What 3 things cause left shift in oxygen binding curve
increased pH
decreased DPG
decreased temp
what 3 things cause a right shift in the oxygen binding curve
decreased pH
increased DPG
increased temperature
reticulocyte count
Recorded as a % of normal (normal 3> ineffective
extramedullary hematopoeisis
Naturally present in babies and young children - Liver and spleen
Compensatory response to anemia
-Hepatosplenomegaly
-Bone marrow expansion in active marrow
hemoglobin in newborns
Higher normal ranges than children and infants
Fetal hemoglobin – HbF (2α2γ) – shifts OBC to the left
Over 6-9 months, HbF cells are replaced by HbA (97%), HbA2 (2.5%), and HbF (<1%)
hemoglobin in children
lower than adults. Higher phosphorus levels increase synthesis of 2,3 DPG – leading to right shifted OBC
hemoglobin in adults
Men have higher Hb due to testosterone, and lack of cyclic bleeding
Anemia in adult male = Hb < 12.5 g/dL
PREGNANCY: lower normal ranges due to increased plasma volume (dilutional effect)
Anemia in pregnancy = Hb < 11g/dL
hemoglobin electrophoresis is used to…
detect hemaglobinopathies: Abnormal structure (sickle cell anemia) Abnormal synthesis (Thalassemias) HbA 2α2ß (97% in adults) HbA2 2α2δ (2.5% in adults) HbF 2α2γ (1% in adults)
clinical findings in anemia
Fatigue Dyspnea Concentration difficulties Dizziness Pallor Pulmonary flow murmur
what are the calculated RBC indices
MCV – mean corpuscular volume (Hct x 1000/RBC)
Useful for classifying anemias (see next slide)
-Microcytic = 100 um3
MCHC – Mean corpuscular Hemoglobin content
RDW – Red cell distribution width
MCV
MCV – mean corpuscular volume (Hct x 1000/RBC)
Useful for classifying anemias (see next slide)
Microcytic = 100 um3
MCHC – Mean corpuscular Hemoglobin content
average Hb concentration (Hb/Hct)
Low – implies defect in Hb synthesis: microcytic anemias
High - spherocytosis
RDW – Red cell distribution width
Reflects variation in size (anisocytosis)
Not very useful unless its increased
E.g. iron deficiency
mature RBC characteristics
Lack mitochondria
No TCA
No beta-ox
No ketone body synthesis
Rely on anaerobic glycolysis – cori cycle
Pentose phosphate pathway – synthesizes glutathione
Ferritin
Soluble iron binding storage protein
Serum levels correlate with ferritin stores in marrow macs
Synthesized by macs, driven by Il-1 and tnf-α
Decreased ferritin diagnostic of iron deficiency
Increased ferritin:
-Anemia of chronic disease
-Iron overload
Serum Iron
Serum iron represents iron bound to transferrin Synthesized in liver Normal iron ~100 ug/dL Decreased iron -Iron def -ACD Increased iron Iron over load (transfusions, sideroblastic, hemochromatosis)
Total Iron Binding Capacity
Correlates with [transferrin]
Normal ~300 ug/dL
iron saturation percentage
Percentage of iron binding sites on transferrin
=serum iron/TIBC x 100
Normal is ~33%
Ferritin storage and transferrin synthesis relationship
Decreased ferritin stores cause increased transferrin synthesis in the liver. Increased ferritin leads to decreased transferrin synthesis.
Microcytic Anemias
MCV<80
Iron deficiency
ACD
Thalassemia (α and ß)
Sideroblastic Anemia
Iron Deficiency Anemia
10% dietary iron resorbed in duodenum Oxidized form (ferric Fe+3) cannot be resorbed in the duodenum
Gastric acid frees elemental iron
Vitamin C reduces ferric iron
Most body iron is incorporated into hemoglobin
- Remainder is stored in marrow macs (~1,000 mg in men, ~400 mg in women)
- Myoglobin
- Enzyme cofactors
How common is iron deficiency anemia and who is at highest risk?
Most common anemia, and most common nutritional deficiency worldwide
Toddlers 1-2 years of age
Females 12-49 due to menstrual loss
Three groups of causes for iron deficiency anemia
BLOOD LOSS GI bleed PUD Hookworm infection NSAIDS/Ulcers Meckels Menorrhagia
INADEQUACY Prematurity Restricted diets Malabsorption (e.g. celiac)
OTHER
Overutilization: Pregnancy/lactation
Destruction:
- Hemolytic anemias
- PNH
Iron deficiency anemia clinical findings
Plummer-Vinson syndrome: esophageal web Achlohydria (decreased or absent stomach acid production) Glossitis koilonychia (spoon nails)
lab findings with iron deficiency anemia
Decreased MCV Decreased serum iron, iron sat Decreased serum ferritin Increased TIBC, RDW Thrombocytosis – reactive
Anemia of chronic disease
Most common anemia in hospital setting
–Chronic inflammation (e.g. arthritis, infections, malignancy, alcoholism)
Decreased synthesis of heme
Inadequate renal secretion of EPO
Hepcidin secretion by liver – response to inflammation
–Prevents the release of iron to transferrin (iron is in Macs, just can’t get out)
What is Hepcidin
secreted by liver in response to inflammation. it presents the release of iron to transferrin, keeping iron in macrophages
Lab findings with ACD
Decreased MCV
Decreased serum iron, TIBC, and iron sat
Increased serum ferritin
thalassemias
Autosomal recessive traits
Quantitative abnormality of normal globin chains
Most common in Mediterranean, Africa and southeast Asia . . .
One copy of ß gene on each chromosome 11 (2 total loci)
2 copies of α gene on each chromosome 16 (4 total loci)
Beta thalassemia
DEFECTIVE UPSTREAM PROMOTER REGION OF ß GLOBIN GENE Mild microcytic anemia Decreased MCV, Hemoglobin and hct Increased RBC count Normal RDW and ferritin --Decreased HbA 2α2ß --Increased HbA2 2α2δ and HbF 2α2γ
DO NOT TREAT
beta thalassemia major
Aka cooley’s anemia ß0ß0
Severe hemolytic anemia Rbc’s accumulate α chain inclusion, and are removed by splenic macrophages Increased RDW and reticulocytes ZERO HbA 2α2ß Increased HbA2 2α2δ and HbF 2α2γ
REQUIRES LONG TERM TRANSFUSION
alpha thalassemias
GENE DELETION ONE DELETION DOES NOT CAUSE ANEMIA 2 GENE DELETION IS α–THAL TRAIT Blacks (α/- α/-) – mild anemia Asians (-/- α/α) – increased risk for more serious forms
Decreased MCV, Hb, Hct
Increased RBC count
Normal RDW, ferritin
causes of sideroblastic anemia
Chronic alcoholism Pyridoxine deficiency (vit b6) Lead poisoning Iron overload Hereditary – x-linked recessive (rare)
sideroblastic anemia in chronic alcoholics
Etoh is a mitochondrial toxin
30% of hospitalized alcoholics will have sideroblastic anemia
sideroblastic anemia in pyridoxine deficiency (vitamin B6)
Co-factor for δ–aminolevulinic acid synthase (δ–ALA)
Rate-limiting step in heme synthesis
Deficiency see in alcoholics and Isoniazid (INH) therapy
INH used to treat Tuberculosis, complexes with pyridoxine
lead poisoning and sideroblastic anemia
Most common cause in little dudes 1-5 years of age
Eating lead-based paint
Battery and ammunition factories
Lead denatures critical enzymes:
Ferrochelatase: therefore iron cannot bind with protoporphyrin
ALA Dehydrase: causes increase in δ–ALA
Ribonuclease: prevents the breakdown of ribosomes, causing basophilic stippling
what critical enzymes does lead denature?
Ferrochelatase: therefore iron cannot bind with protoporphyrin
ALA Dehydrase: causes increase in δ–ALA
Ribonuclease: prevents the breakdown of ribosomes, causing basophilic stippling
clinical finding with sideroblastic anemia
Abdominal colic
Encephalopathy (due to increased δ–ALA)
growth retardation (maybe not in Tommy boy’s case though)
Peripheral neuropathy
Nephrotoxicity
Burton’s line (blue lining of gums at base of teeth)
lab findings with sideroblastic anemia
Elevated lead levels (urine is the best test)
Increased iron, iron sat, and ferritin
Decreased MCV and TIBC
Ringed-sideroblasts in marrow
