Anemia and Red Cell Disorders-Usera Flashcards
What is the production of RBCs in bone marrow?
erythropoiesis
Erythropoiesis is stimulated by (blank) release by interstitial cells in peritubular capillaries of renal cortex
EPO
What is the stimuli for EPO release?
Hypoexemia
Anemia
Left shift of oxygen binding curve
How can you increase (left shift binding curve) oxygen binding affinity?
Increased pH
decreased DPG
decreased Temp
How do you right shift the oxygen binding curve (i.e get rid of oxygen easily)?
decrease pH
increase DPG
increase temp
What are reticulocytes a sign of?
active erythropoiesis
Thread-like RNA filaments become mature RBC in (blank) hours
24 hours
How is reticulocyte count recorded?
as a % of normal (normal less than 3%)
What is falsely increased in anemic states?
reticulocyte count (must be corrrected for)
How do you correct for reticulocyte count in anemic states?
Corrected Count = (actual Hct/45) x Retic count
(blank) requires additional correction beyond this Corrected Count = (actual Hct/45) x Retic count
…. what is it?
Polychromasia
you divide corrected count by 2
Extramedullary hemaotpoiesis (EMH) is naturally present in (Blank) and (Blank) -liver and spleen
babies and young children
What is the compensatory response to anemia?
- hepatosplenomegaly
- bone marrow expansion in active marrow
If you see accelerated erythropoiesis what should you be thinking about?
polycytotheia vera, anemia
If you have hyperstimulation of bone marrow how will this present in children?
How about in adults?
hepatosplenomegaly
In their bones
If you order a CBC and there is no comment on morphology what does this mean?
this means there is nothing wrong
What are the measured variables provided by a CBC?
Hemoglobin, Hct, RBC count
What is a calculated variable provided by a CBC?
RBC indices
WHat else will a CBC provide that is not measured nor calculated?
WBC count with diff
Platelet count
morphology
Newbons have (lower/higher) ranges of hemogloin thatn children and infants
higher
What is this
HbF (2a2y)-shifts OBC to the left
fetal hemoglobin
Over (blank) months, fetal hemoglobin cels are replaces by HbA (97%), HbA2 (2.5%) and HbF (less than 1%)
6-9
Why can you get physiologic jaundice of newborn?
Fetal RBC with HbF are destroyed by splenic macrophages. This leads to elevations of unconjugated bilirubin.
Children have (higher/lower) hemoglobin than adults…. why?
lower
Cuz they have higher phosphors levels that increase synthesis of 2,3 DPG leading to righ shifted OBC
Why do men have higher Hb?
due to testosterone and lack of cyclic bleeding
What constitutes anemia in adult male?
Hb less than 13.5 g/dL
What consitutes anemia in nonpregnant female?
Hb less than 12.5 g/dL
Why do you have lower normal levels of hemoglobin?
due to increased plasma volume resulting in dilution of hemoglobin
What constitutes anemia in pregnant female?
less than 11
What is hemoglobin electrophoresis for?
used to detect hemoglobinopathies
If you see abnormal structure in a hemoglobin electrophoresis what does this mean?
sickle cell anemia
If you see abnormal synthesis in a hemoglobin electrophoresis what does this mean?
thalassemias
What is the make up adult hemoglobin?
HbA 2α2ß (97% in adults)
HbA2 2α2δ (2.5% in adults)
HbF 2α2γ (1% in adults)
(blank) is usually a sign of an underlying disease
Anemia
What are the clinical findings in anemia?
fatigue dyspnea concentration difficulties dizziness pallor pulmonary flow murmur
How do you find the MCV?
HCT X 1000/ RBC
What is MCV helpful for?
classifying anemia
What is considered microcytic?
less than 80
What is considered normocytic?
80-100
What is considered macrocytic?
greater than 100
What does MCHC stand for?
mean corpuscular hemoglobin content
What exactly does MCHC tell us?
what the concentration of hemoglobin is within the RBC
What does a bone marrow reticulocyte count less than three mean?
problems with bone marrow (cant response or hasnt responded yet)
A corrected reticulocyte count greater than 3 can be indicative of what?
an intrinsic RBC defect and extrinisic RBC defect
A reticulocyte less than three is due to what?
- Blood loss less than a week
- early-stage iron deficiency
- early-stage anemia chronic disease
- aplastic anemia
- renal disease
- malignancy
How do you get the MCHC (average hemoglobin concentration)?
Hb/Hct
What does low MCHC tell us?
implies defect in Hb synthesis; microcytic anemias
What does high MCHC tell us?
spherocytosis
(blank) is a condition that causes an abnormality in the red blood cell membrane. While healthy blood cells are shaped like flattened, indented disks, these abnormal membranes lead to sphere-shaped red blood cells, and the premature breakdown of those cells, these cells are packed with hemoglobin.
spherocytosis
A lot of White in the center of a RBC indicates what?
lack of hemoglobin
What is the red cell distribution width (RDW)?
Reflects variation in size (anisocytosis)
When is RDW useful?
only if it is increasd because it will indicate iron deficiency
What processes do RBC not do because they lack mitochondria?
No TCA
No Beta-ox
No ketone body synethesis
What do mature RBCs rely on for energy?
anaerobic glycolysis-cori cycle
AND
pentose phosphate pathway-synthesize glutatione
(blank) is a soluble iron binding storage protein
ferritin
serum levels of iron correlate with ferritin stores in marrow (blank)
macrophages
How do you get ferritin?
synthesized by macrophages and driven by IL-1 and tnf-alpha
(blank) ferritin is diagnostic of iron deficiency
decreased
Increased ferritin are signs of what?
- anemia of chronic disease
- iron overload
When do you see a lot of iron often?
in people who have undergone a lot of transfusions
Serum iron represents iron bound to (blank)
transferrin
Where is transferrin synthesized?
liver
What is normal iron levels?
100
What are causes for decreased iron?
iron deficiency
anemia chronic disease
What are causes of increased iron?
iron overload (transfusions, sideroblatic anemia, hemochromatosis)
What does TIBC stand for?
total iron-binding capacity (TIBC)
it is the fraction of iron bound to transferrin
What does TIBC correlate with?
transferrin
What is the normal TIBC?
300
What is iron saturation percent?
- percentage of iron binding sites on transferrin
- normal is 33%
How do you calculate iron saturation percent?
-serum iron/ TIBC x 100
If you are iron deficient your body wil upregulate (Blank) to try and increase iron serum levels and will decrease (blank) levels to keep from storing iron.
transferrin
ferritin
What will you see in anemia chronic disease?
decreased transferrin
increased ferritin
increase hepcidin
Why do you see the levels of ferritin, transferrin and hepcidin that you do in anemia chronic disease?
you have chronic inflammation which will increase cytokines such as IL-1 and TNF alpha which will stimulate liver to release hepcidin and macrophages to release ferritin which tells the body you have enough iron so you decrease transferrin but since you have hepcidin you cant get the iron from ferritin to periperal blood, hence you are anemic.
What are the 4 microcytic anemias (less than 80)?
- iron deficiency
- anemic chronic disease
- thalassemia (a and b)
- sideroblastic anemia
(blank) percent of dietary iron is resorbed in duodenum
10
Can the oxidized (ferric Fe+) form of iron be resorbed in the duodenum?
no
(blank) frees elemental iron?
gastric acid
(blank) reduces ferric iron
Vit C
Most body iron is incorporated into (blank) and the remainder is stored where?
hemoglobin
marrow macrophages, myoglobin, enzyme factors
Iron is absorbed in the (blank)
Folate is absorbed in the (Blank)
B12 is absorbed in the (blank)
duodenum
jejunum
colon
How much iron is stored in mens macrophages? Womens?
1000
400
What is the most common anemia and most common nutritional deficiency worldwide?
iron deficiency anemia
Toddles typically get iron defiency anemia at what age?
1-2
Females age (blank) tend to get iron deficiency anemia due to menstrual loss?
12-49
(blank) is common in nursing homes
iron deficiency anemia
What are some reasons that you get iron deficiency anemia due to blood loss?
GI bleed Peptic Ulcer Disease Hookworm infection NSAIDs/Ulcers Meckels menorrhagia
What are some reasons that you get iron deficiency anemia due to inadequacy?
prematurity
restricted diets
malabsorption (e.g celiac)
What are some other reasons for iron deficiency anemi?
overutilization (pregnacy/lactation)
Desctruction; (hemolytic anemia, PNH)
(blank) is a disease of the duodenum
celicas
What occurs in people with long term iron deficinecy anemia and what are the clinical symptoms of this?
Plummer-Vinson syndrome:
- esophageal web
- Achlohydria
- Glossitis
- koilonychia
What is this: fibrous constrictive ring that grows in Gi lumen and has dysphagia for solids
Esophageal web
What is this:
causes red ulcers on side of mouth?
angular stomatitis
What is indicative of B12 deficiency?
glossitis
(blank) AKA spoon nailing is not specific for iron deficiency anemia but a clinical finding
Koilonychia
What will the following be like in iron deficiency anemia: MCV? Serum iron, iron sat? Serum ferritin? TIBC, RDW?
decreased decreased decreased increased (cuz transferrin will be high) (with reactive thrombocytisis)
What is the most common anemia in hospital setting?
anemia of chronic disease (ACD)
What are the symptoms of ACD?
- decreased synthesis of heme
- inadequate renal secretion of EPO
- hepcidin secretion by liver-response to inflammation
What prevents the release of iron to transferrin?
Hepcidin
How can chronic renal failure cause ACD?
EPO deficiency and diabetes
What are the lab findings for ACD:
MCV?
Serum Iron, TIBC, Iron sat?
Serum ferritin?
decreased
decreased
increased
What is this:
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)
Thalassemias
So is something wrong with your hemoglobin with thalassemias?
no, your just not making enough of it
Where do you commonly see thalasseias?
Mediterranean, africa, and southeast asia
What is the problem in beta-thalassemia?
defective upstream promotor region of beta globin gene
Is beta thalassemia minor macrocytic or microcytic?
microcytic
What do the lab values look like in beta thalassemia minor?
decreased MCV, hemoglobin and Hct
Increased RBC count
normal RDW and ferritin
In beta thalassemia minor you have:
(Increased/Decreased) HbA 2α2ß
(Increased/Decreased) HbA2 2α2δ and HbF 2α2γ (compensatory responses)
Decreased
Increased
What is another name for beta thalassemia major?
Cooleys anemia
What happens in beta thalassemia major?
severe hemolytic anemia
- RBCs accumulate alpha chain inclusion, and are removed by splenic macrophages
- increased RDW and reticulocytes
What are the hemoglobin chains like in beta thalassemia major?
ZERO HbA 2α2ß
Increased HbA2 2α2δ and HbF 2α2γ
What does beta-thalassemia major require?
long term transfusion
Why do you get a lot of hemolysis in beta thalassemia major?
Since your not making beta chains, you have increased alpha chaisn that fold into each other retardly and macrophages get rid of them and you have broken down RBCS so hemolytic.
What is the cause of alpha thalassemia?
gene deletion (one deletion does not cause anemia, its a two deletion sort of thing)
2 gene deletion is (blank) trait
alpha thal
Blacks often get what form of alpha thal? What about asians?
Blacks (α/- α/-) – mild anemia
Asians (-/- α/α) – increased risk for more serious forms
What are the lab values of alph thal?
decreased MCV, Hb, Hct
Increased RBC count
Normal RDW, ferritin
What type of alpha thal is incompatible with life?
hydrops fetalis
What type of alpha thal is this:
symptomatic, hemolytic and microcytic anemia, splenomegaly
Hb H
What are causes of sideroblastic anemia?
Chronic alcoholism Pyridoxine deficiency (vit b6)-> common in alcoholics Lead poisoning Iron overload Hereditary – x-linked recessive (rare)
What is the rate limiting step in heme formation?
delta-aminolevulinic acid
What is the pathogenesis of sideroblastic anemia?
-defect in heme synthesis within mitochondria,
OR
iron cannot be incorporated into heme
How come chronic alcoholism can cause sideroblastic anemia?
cuz ETOH is a mitochondrial toxin
(blank) percent of hospitalized alcohlics will have sideroblastic anemia
30
ALchol effects all the steps of (blank)
heme synthesis
What is another word for pyridoxine deficiency?
vit B6 deficiency
What do you use vit b6 for and if you dont have it what wil it cause?
co-factor for δ–aminolevulinic acid synthase (δ–ALA)
the Rate-limiting step in heme synthesis, therefore causes sideroblastic anemia
In whom do you often see sideroblastic anemia in?
alcoholics and in isoniazid (INH) therapy
What do you use INH for?
TB, complexes with pyridoxine
Lead poisoning is the most common cause of sideroblastic anemia in whom?
little dudes 1-5 years of age cuz they eat paint AND
battery and ammunition factory workers
Lead denatures critical enzymes such as ….?
ferrochelatase
ala dehydrase
ribonuclease
If you mess up ferrochelatase what happens?
iron cannot bind with protoporphyrin
What happens if you have messed up ala dehydrase?
causes increase in delta-ala
What happens if you have messed up ribonuclease?
prevents the breakdown of ribosomes, causing basophlic stippling
What are the clinical findings of sideroblastic anemia in lead poisoning?
Abdominal colic Encephalopathy (due to increased δ–ALA) growth retardation (maybe not in Tommy boy’s case though) Peripheral neuropathy Nephrotoxicity Burton’s line
(blank) is toxic to neurons, causes vascular permeability and edema and demyelination
δ–ALA
What can you see on x rays in lead posioning?
lead deposition
Why do you see growth retardation in sideroblastic anemia?
lead deposits on epiphyseal plates so poor bone growth
What is burtons line and where do you see it?
blue line on the gingiva indicative of sideroblastic anemia
What are the lab findings of lead posoining (sideroblastic anemia)
Elevated lead levels (urine is the best test)
Increased iron, iron sat, and ferritin
Decreased MCV and TIBC
Ringed-sideroblasts in marrow
