anemia Flashcards
Pyrroles is synthesized from
succinyl coA and glycine
Synthesis of hemoglobin begins with and ends with
Synthesis of hemoglobin begins in the proerythroblasts and continues even into the reticulocyte stage of the RBCs.
when reticulocytes leave the bone marrow and pass into the blood stream they continue to form hemoglobin for another day or to until they become mature erythrocytes
protoporphyrin IX is synthesized from
b. 4 pyrroles
of iron forms from
Heme and protoporphyrin IX
hemoglobin chain (alpha or beta)
formed from polypeptide and heme
what is hemoglobin A synthesized form
2 alpha chains 2 beta chains
4 subunits
anemia define
Abnormally low number of circulating red blood cells or level of hemoglobin, or both, resulting in diminished oxygen-carrying capacity.”
sign nOT dz
major function of RBC
also known as erythtrocytes is to transport hemoglobin which carries oxygen form the lungs to the tissues
functions of the RBC
transport hemoglobin so it doesn’t leak through capillary membranes
contain carbonic anhydrase whihc catalyzes the reaction betwen CO2 and water –>carbonic acid
H2CO3
hemoglobin also serves as a acid base buffer and therefore RBC at large are great for acid base buffering
role of carbonic anhydrase
makes it possible for the water of the blood to transport enormous quantities of CO2 in the form of bicarbonate ion (HCO3−)
three “dz” that are very similar
Thyroid, Depression, Anemia present VERY similarly
reduced oxygen capacity could be caused by
imparied oxygen transport (i.e. hemoglobin)
or reduced red cells
Condition typically results from red cell loss (hemolysis/hemorrhage), deficient erythropoiesis, or deficient hemoglobin production
physical effects of hypoxia and sxs assoicated with anemia
i. Fatigue
ii. Weakness
iii. Dyspnea
iv. Angina
v. HA, faintness, dim vision
skin effects of hypoxia
Pallor of skin, mucus membranes, conjunctiva, nails
what could blue mucus membranes in the nose indicate
allergies or anemia
Normocytic
normal-sized rbc but ↓ amount í MCV 80-100 fl
Macrocytic
presence of large rbc in peripheral smear í MCV>100 fl
Microcytic
presence of small, often hypochromic, rbc in peripheral blood smear í MCV<80 fl
anemia usually characterized by a low MCV
Microcytic
etiologies of microcytic anemia
” IDA: Iron Deficiency Anemia
“ Thalassemia
etiologies of normocytic anemia
” ACD: anemia of chronic disease (or anemia of inflammation)
etiologies of Macrocytic anemia
” B12/Folate deficiency
“ w/ ↑ reticulocyte: hemolysis
diagnostic that tells you O2 carrying capactiy
Hgb
Hct tells you
% of intact RBCs and RBC count
Any time you have an increased reticulocyte count, you need to think
why is the person working so hard to push RBCs into the blood before they are ready?
What are they replacing? What are they trying to adapt to?
this is seen with hemolytic anemia
Possible jaundice think
might be producing more bilirubin than they can handle
Hgb content can refer to
normochromic-normal hemoglobin
hypochromic- less hemoglobin
Typically don’t see hyperchromic anemias
Iron deficiency
can’t make heme and so red cells are smaller (microcytic)
If acute blood loss, and anemic tend to see what in terms of cell morphology
- tend to have normal cell morphology (normal cell size and normal Hgb content)
If you lose blood over long period of time - you become
iron deficient and get small cells
acute blood loss think
think hypovolemia/shock
sxs associated with acute blood loss
Will feel symptoms consistent w/ anemia at relatively high hemoglobin levels - don’t usually get as low as you will with chronic loss
could feel this at 9 or 10
Fluid enter compartment, dilutes blood, Hgb/Hct fall with normal cell morphology
iv. Chronic loss leads to iron
chronic blood loss leads to
Chronic loss leads to iron deficiency anemia over time, NO volume depletion (microcytic anemia)
Your body adapts to that blood loss so your hemoglobin can be down to 6
usually
13.5 to 17.5 grams men
For women, 12.0 to 15.5
what labs are important when assessing anemia
red cell indicies/Hgb is usually ordered as part of a cbc
used to diagnose the cause
Average red blood cell size (MCV)
Hemoglobin amount per red blood cell (MCH)
The amount of hemoglobin relative to the size of the cell (hemoglobin concentration) per red blood cell (MCHC
chronic kidney disease anemia
secondary to loss of erythropoietin
why is tachycardia seen as a sx of anemia
cycling the RBC you have faster for quicker oxygenation
might also increase your ventilation rate
in the developed world iron deficiency anemia is related to
diet
in the developed world iron deficiency anemia is related to
bleeding
pathophys of hereditary spherocytosis
Deficiency of red cell membrane proteins (spectrin, ankyrin) that helps maintain the disc shape
get a little beach ball
loss of surface area
loss of disc results in the impeded ability to travel through small spaces and the result is damage
what happens to the body in hereditary spherocytosis
Signs include jaundice- bilirubin accumulation from distruction
splenomegaly- destruction occurs in the spleen
bilirubin stones
tx for hereditary spherocytosis
take out the spleen where most of the hemolysis is happening
keep red cells a little bit longer and stave off destruction to the bone marrow
why would we see a aplastic crisis with hereditary spherocytosis
g. Aplastic crisis when red cell production disrupted as by virus
what can put a sickle cell pt into crisis
exertion cold stress altitude stress dehydration acidosis
Low oxygen tension leads to sickling
can all result in a lot of occlusive damage to the vasculature with the cells get caught
Sickle Cell Anemia
Point mutation in beta chain of hemoglobin, abnormal substitution
transmitted in by recessive pattern
what % of pts present with heterozygotic sickling
40% sickling with heterozygotic trait
Thalassemias
seen in (MEDITERRANEAN population
Thalassemias
Alpha: result of deletion of alpha subunit on Chromosome 16
severe disease Hgb H formed
Beta: usually caused by point mutations in b subunit. Relative increases in Hgb A2 and F.
Thalassemias tests
Diagnosis – Electrophoresis í get a hemoglobin electrophoresis and it tells you different proportions of different hemoglobin
i. Normal pt’s don’t Hgb H
Microcytosis out of proportion to the degree of anemia
Thalassemias
MCC worldwide
(dietary deficiency or bleeding)
IDA
microcytic hypochromic anemia
Anisocytosis
red cells are all different sizes, they are not similar to each other
seen in IDA because of increased production to make up for low hemoglobin
Poikilocytosis
abnormally shaped red blood cells
seen in IDA because of increased production to make up for low hemoglobin
this type of anemia results from impaired nucleic acid synthesis when the cells are turning over
Megaloblastic Anemias
not till the very end that the precursor cell losses the nucleus
MCC of megaloblastic Anemias
MCC: B12 or folate deficiency
can’t turnover the DNA as fast as you normally would
cell is getting bigger and bigger as it’s waiting for nucleus to turn over DNA
generating more and more cytoplasm but doesn’t’ have the cofactors it needs to turnover the DNA
offspring are bigger
B12 is absorbed and stored where
a. Bound to intrinsic factor in stomach
b. Absorbed at terminal ileum
c. Stored in liver (sufficient for 3 years without intake)
Microcytic Anemia (MCV <80fL)
MC and 2nd MC
IDA MC
2nd: thalassemia
AKA bone marrow depression
Aplastic Anemia
Fatty replacement of bone marrow - loss of all 3 stem cell lines
results in loss of all products
pancytopenia
pancytopenia
reduction in all blood cell numbers seen with bone marrow depression (aplastic anemia)
sxs with aplastic anemia
e. Petechiae and bruising from loss of platelets, and infections from WBC loss
causes of aplastic anemia
Often caused by exposures (radiation, chemicals, Felbamate & tegretol [AED])
and chronic liver disease (where clottng factors are made)
tx of aplastic anemia
May require BMT (bone marrow transplant)
ACD: Chronic Disease theory
a. Common result of chronic infections (eg AIDS, RA, SLE, Hodgkin’s)
Theory focuses on macrophage and lymphocyte role in sequestering iron, destroying red cells, chemical suppression of EPO response, inhibited precursor cells, reduced Fe transport
Similar to IDA (microcytic/hypochromic) - separate from CRF (normocytic/normochromic)
the capacity of a red cell is about ____ hbg
1/3
MCHC (mean corpuscular hmg content) should always be around 33%)
RDW
reticulocyte distribution width aka variability in size
standard deviation of red cell size
when this is high it means that you have a lot of different size red cells
(Reticulocytes and epo are high trying to repair)
1. Reference range = 11-14.5
measure aka variability in size
reticulocyte distribution width (RDW)
average volume of RBC
v. MCV
if I say MCV you say
cell size
MCV If low = then microcytic
- If low = then microcytic
mcv If high
= then macrocytic
MCV if normal
If normal = normocytic
vi. MCH
= Mean corpuscular hemoglobin
how to tell if you have a good sample of blood
with rule of 3’r
(red count, Hgb content and Hematocrit should be roughly mupltiples of 3)
if it fits= good specimen
Evaluate anemia
good specimen= rule of 3’s
i. Hgb/Hct
1. 14-18 men
2. 12-16 women
ii. Check MCV and classify
iii. Check RBC count
if you see microcytic hpochromic anemia
what should you suspect and hwta labs would you get
IDA
iron studies
Total iron binding capacity (TIBC)
Ferritin
Ferritin
how we store iron (MOST important one)
- Below 15 is diagnostic of iron deficiency anemia even if we don’t see anything else
- Last thing she restores is the
if iron level is low
if iron level is low, binding capacity is high
with macrocytic anemia order
i. Get a B12 level
ii. Get a folate level
iii. Iron studies are NOT indicated but do it anyway to r/o
1. Since it is macrocytic there is not reason for them to Iron deficient
hallmark of Thalassemia
hallmark if microcystosis out of proportion to the presentation
MCV will be super low without fatigue
Thalassemia dx test
Hemoglobin Electrophoresis
the goal with IDA
to repair ferritin level
who gets macrocytic anemia due to B12 deficiency
” Pernicious anemia (MC); gastrectomy = ↓production of intrinsic factor (can’t absorb B12)
“ H. Pylori infxn
“ Competition for Vit B12 in gut
“ Pancreatic insufficiency
“ Decr ileal absorption of B12 = surgical resection, Crohn’s MC
“ Dietary & transcobalamin II deficiencies = RARE cause
