Week 3 Anemia of Chronic Inflammation Flashcards
What are the anemias of INSUFFICEINT vs INEFFECTIVE erythropoiesis
INSUFFICEINT
-IDA : diminished heme synthesis
-Anemia of Chronic Inflammation : Iron sequestering
INEFFECTIVE
-Sideroblastic anemia and Lead poisoning - defective protoporphyrin synthesis
-Thalassemia - Defective globin chain synthesis
what are examples of micro cytice anemia
IDA- most common cause of microcytic anemia
Anemia of chronic inflammation
Sideroblastic anemia and lead Poisoning
Thalassemia
what is anemia of chronic inflammation
-chronic inflammation common in hospital pts
-associated with chronic infections like TB, HIV, RA, Renal disease, Hodgkins
Other names
Iron reutilization anemia
Anemia of chronic infection
Anemia of chronic disease
What are the symptoms of ACI and what would you see in a smear
-patients with system diseases
-normo/normo or micro//hypo
-when you have decreased serum iron levels but with many iron stores
Symptoms
Weakness, pallor, shortness of breath
What causes ACI
increased inflammation activates macrophages that secrete cytokines which produce Acute Phase Reactants that have a negative impact on iron levels, RBC production and life
APRs- Hepcidin, Lactoferrin, Ferritin
They cause impaired ferrokinetics causing iron restricted erythropoiesis which lessens RBC life span
What is hepcidin
-helps to maintain the bodys’ iron status
-systemic iron regulatory hormone
-produced by the liver
-binds to ferroportin
-regulates intestinal iron absorption
-regulates plasma iron concentrations
-regulates tissue iron distribution
how does Hepcidin act when body iron levels increase
heptaocytes increase hepcidin production
enterocytes release LESS iron into plasma
macrophages and heptocytes retain more iron
hepcidin levels increase during inflammation regardless of body iron levels
a non specific defense against bacterial infection to ensure iron is not made available to bacteria
how does Hepcidin act when body iron levels decrease
-hepatocytes produce less hepcidin
-enterocytes release more iron into plasma
-macrophages and hepatocytes release more iron into plasma
when there is inflammation in the body what will we see with hepcidin levels
-hepcidin synthesis increased with IL acting on the liver
-iron absorption from intestine is decreased
-iron release from macrophages and hepatocytes also decrease
-now iron is not available for developing RBCs
what is lactoferrin
-part of transferrin family an iron binding glycoprotein
-found in 2ndry neut granules
-prevent bacteria from using phagocytized iron
-protects from oxidized iron during phagocytosis
-contributes to ACI but less than hepcidin acting as an APR
how does lactoferrin act as an APR
-released in plasma during inflammation as neuts die
-scavenges iron and binds it -oxidized iron is bad
-higher affinity for Iron than Transferrin
-increased hepcidin means iron cant be taken up by macrophages or hepatocytes because ferropotin is blocking it
-RBC progenitors dont have receptors for lactoferrin
-iron cannot be incorporated into developing RBC
What action does increased Ferritin have in inflammation
another APR
-primary non specific response to inflammation
-in high ferritin levels it binds functional iron
-developing RBCs dont have a ferritin receptor like lactoferrin
-iron cannot be brought into the hemoglobin
-reduced tissue release
also sequesters iron by making it unavailable to developing RBCs
How does impaired erythropoiesis contribute for anemia
-macrophages produce inflammatory cytokines that act on BM and kidney to
-impair proliferation of erythroid progenitor cells
-decrease EPO production
-reduce erythroid progenitor response to EPO
-reduce RBC lifespan with increased production of macrophages due to increased inflammation
EPO binds RBC precursors allows early release of RBC from bone marrow , prevents apoptosis, reduced BM transit time
what are the expected CBC results of ACI
HGB - normal or SD
HCT - normal or SD
MCV - Normal due to duel pop with micro (2 peaks on histo)
Ret- decreased (because erythropoiesis decreases)
starts as normo/normo but can turn into micro/hypo over time on PBF
What would be the results of iron studies with ACI
Serum iron - N or D
TIBC - N or D - reflects iron store in hepatocytes
FER - N or I
% SAT - N or D
what does it mean
if you have decrease iron with lots of iron stores - Functional Iron Def
in BM biopsy BM macrophages are stained positive for PPB and RBC precursors are more pale
how is ACI treated
EPO therapeutic administration
comparison between IDA and ACI
why is HCT and HGB decreased in IDA but normal in ACI
IDA has stores that are becoming depleted and functional iron is reducing. This leaves no iron to be incorporated into heme that is why for IDA we see decreases in HCT, RBC
Whereas in ACI the stores in the macrophages are abundant but will decrease over time but you wont see the same decreases
what is sideroblastic anemia and its symptoms
-when the enzyme that synthesizes or incorporates iron into protoporphyrin ring is impaired
Acquired
- primary SA refractory
-secondary caused by drugs and bone marrow toxins , metal poisoning, chloramphenicol or chemo
Inherited
-porphyria’s - X linked
Autosomal recessive
symptoms
fatigue, SOB, hepatomegaly, splenomegaly
if incorporation of iron into protoporphyrin ring is blocked what happens
- iron builds up in the BM
-specifically in the mitochondria of developing erythroblasts- waiting to be taken into as heme
-therefore when you do a BM biopsy and stain with PPB you see Ringed sideroblasts (hemosiderin deposits) which is a hallmark of sideroblastic anemia
how does IDA result from VS SA
IDA comes from inadequate supplies of iron for hem production or lack of raw materials to product hem, RBC precursors are not defective
SA come from inadequate amounts of protoporphyrin , RBC precursors are defective but there is enough iron
unlike IDA iron is abundant in BM in SA.
what would we see in SA with a CBC, PBF and BM
HGB - low
HCT- lot
MCV - N or D
Morph - dual pop with PPHB
BM biopsy
ringed sideroblast present
positive staining with PPB erythroblasts have mitochondria that is loaded with iron
what would iron studies in SA show
Serum iron - N or I- abundant iron stores occur
TIBC - N or D - all spots on transferrin are occupied by iron
FER - N or I
% SAT - N or I
How does lead poisoning cause SA
acute vs chronic
Heavy metal poisoning is most common cause of SA
- lead interferes with porphyrin synthesis (enzyme impairment and iron incorporation)
-affects nervous system
-anemia especially in kids
Acute exposure
normo/normo but increased RET and poly because of RBC hemolysis
Chronic exposure
Micro/hypo
-decreased RET
-Basophilic stippling
-stomatocytes
the iron studies will show abundant iron storage but the iron is not available to developing erythroblasts
how to treat SA if inheritied vs acquired
Inherited
pyridoxine B6 - first step in porphyrin synthesis
Acquired
Calcium Disodium edetate or dimercaprol are used because they chelate the lead in the body so it can be excreted in the urine
What is iron overload Primary and Secondary
Access Iron accumulation
Primary
inherited conditions causing too much iron to be absorbed and stored - Hereditary Hemochromatosis (where there are genes for proteins controlling iron kinetics)
Secondary
-when iron accumulates because of chronic anemias like Sickle or Thalassemia Major and the treatment of repeat transfusions
either way acquisition is greater than loss because the body conserves as much as possible
how is excess iron stored
Ferritin and then hemosiderin within cells
-when the stores becomes saturated ferrous iron or free iron builds up intracellularly and forms free radicals. this causes damage to neighboring cells , pancrease, heart and skin can cause mutations
what will iron studies show you in iron over load
Serum iron - variable
TIBC - N
FER - I - increased because because there is no way to excrete the increasing iron
% SAT - I
