Red Blood Cell Disorders

Question 1

What is the stimulation for EPO release

Answer 1

Hypoxemia
Anemia
Left shift of oxygen binding curve

it is released from Interstitial cells in peritubular capillaries of renal cortex

Question 2

What 3 things cause left shift in oxygen binding curve

Answer 2

increased pH
decreased DPG
decreased temp

Question 3

what 3 things cause a right shift in the oxygen binding curve

Answer 3

decreased pH
increased DPG
increased temperature

Question 4

reticulocyte count

Answer 4

Recorded as a % of normal (normal 3> ineffective

Question 5

extramedullary hematopoeisis

Answer 5

Naturally present in babies and young children - Liver and spleen
Compensatory response to anemia
-Hepatosplenomegaly
-Bone marrow expansion in active marrow

Question 6

hemoglobin in newborns

Answer 6

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%)

Question 7

hemoglobin in children

Answer 7

lower than adults. Higher phosphorus levels increase synthesis of 2,3 DPG – leading to right shifted OBC

Question 8

hemoglobin in adults

Answer 8

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

Question 9

hemoglobin electrophoresis is used to…

Answer 9

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)

Question 10

clinical findings in anemia

Answer 10

Fatigue
Dyspnea
Concentration difficulties
Dizziness
Pallor
Pulmonary flow murmur

Question 11

what are the calculated RBC indices

Answer 11

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

Question 12

MCV

Answer 12

MCV – mean corpuscular volume (Hct x 1000/RBC)
Useful for classifying anemias (see next slide)
Microcytic = 100 um3

Question 13

MCHC – Mean corpuscular Hemoglobin content

Answer 13

average Hb concentration (Hb/Hct)
Low – implies defect in Hb synthesis: microcytic anemias
High - spherocytosis

Question 14

RDW – Red cell distribution width

Answer 14

Reflects variation in size (anisocytosis)
Not very useful unless its increased
E.g. iron deficiency

Question 15

mature RBC characteristics

Answer 15

Lack mitochondria
No TCA
No beta-ox
No ketone body synthesis
Rely on anaerobic glycolysis – cori cycle
Pentose phosphate pathway – synthesizes glutathione

Question 16

Ferritin

Answer 16

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

Question 17

Serum Iron

Answer 17

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)

Question 18

Total Iron Binding Capacity

Answer 18

Correlates with [transferrin]

Normal ~300 ug/dL

Question 19

iron saturation percentage

Answer 19

Percentage of iron binding sites on transferrin
=serum iron/TIBC x 100
Normal is ~33%

Question 20

Ferritin storage and transferrin synthesis relationship

Answer 20

Decreased ferritin stores cause increased transferrin synthesis in the liver. Increased ferritin leads to decreased transferrin synthesis.

Question 21

Microcytic Anemias

Answer 21

MCV<80

Iron deficiency
ACD
Thalassemia (α and ß)
Sideroblastic Anemia

Question 22

Iron Deficiency Anemia

Answer 22

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

Question 23

How common is iron deficiency anemia and who is at highest risk?

Answer 23

Most common anemia, and most common nutritional deficiency worldwide
Toddlers 1-2 years of age
Females 12-49 due to menstrual loss

Question 24

Three groups of causes for iron deficiency anemia

Answer 24

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

Question 25

Iron deficiency anemia clinical findings

Answer 25

``` Plummer-Vinson syndrome: esophageal web Achlohydria (decreased or absent stomach acid production) Glossitis koilonychia (spoon nails) ```

Question 26

lab findings with iron deficiency anemia

Answer 26

``` Decreased MCV Decreased serum iron, iron sat Decreased serum ferritin Increased TIBC, RDW Thrombocytosis – reactive ```

Question 27

Anemia of chronic disease

Answer 27

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)

Question 28

What is Hepcidin

Answer 28

secreted by liver in response to inflammation. it presents the release of iron to transferrin, keeping iron in macrophages

Question 29

Lab findings with ACD

Answer 29

Decreased MCV Decreased serum iron, TIBC, and iron sat Increased serum ferritin

Question 30

thalassemias

Answer 30

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)

Question 31

Beta thalassemia

Answer 31

``` 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

Question 32

beta thalassemia major

Answer 32

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

Question 33

alpha thalassemias

Answer 33

``` 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

Question 34

causes of sideroblastic anemia

Answer 34

``` Chronic alcoholism Pyridoxine deficiency (vit b6) Lead poisoning Iron overload Hereditary – x-linked recessive (rare) ```

Question 35

sideroblastic anemia in chronic alcoholics

Answer 35

Etoh is a mitochondrial toxin | 30% of hospitalized alcoholics will have sideroblastic anemia

Question 36

sideroblastic anemia in pyridoxine deficiency (vitamin B6)

Answer 36

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

Question 37

lead poisoning and sideroblastic anemia

Answer 37

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

Question 38

what critical enzymes does lead denature?

Answer 38

Ferrochelatase: therefore iron cannot bind with protoporphyrin ALA Dehydrase: causes increase in δ–ALA Ribonuclease: prevents the breakdown of ribosomes, causing basophilic stippling

Question 39

clinical finding with sideroblastic anemia

Answer 39

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)

Question 40

lab findings with sideroblastic anemia

Answer 40

Elevated lead levels (urine is the best test) Increased iron, iron sat, and ferritin Decreased MCV and TIBC Ringed-sideroblasts in marrow