hypoproliferative Flashcards
erythropoiesis in bone marrow does not match the demand for oxygen-carrying capacity (red cells) in the peripheral blood circulation
anemia
in the most simplest term anemia is when there is
inadequate delivery of O2 to tissues
of red cells in a ul of blood
RBC count
measures the size of the red cell
Hct/RBC
MCV
measures hemoglobin concentration within a single red cell
Hb/RBC
MCH
hemoglobin concentration in a given volume of red cells
Hb/Hct
MCHC
measures red cell size distribution
RDW
orthostatic hypotension
decreased blood pressure upon standing
youngest normal RBC entering circulation from the bone marrow
reticulocyte
how does a reticulocyte looks like
large purplish cell in standard peripheral blood smear
reticulocytes contains ____ remnants and ____ machinery precipitated and visualized with supravital stains
contains RNA remnants and ribosomal machinery
wright stain
large purplish cells with no central pallor- reticulocytes
normal reticulocyte count
1%
absolute reticulocyte count
absolute number of red cells that are reticulocytes
reticulocyte index
correct the measured retic count for the degree of anemia
retic. count (%) x patient’s Hct/ 40
if the retic. index is <2 and/or if the absolute retic. count is less than normal
hypoproliferative anemia
if the retic. index is elevated and/or is the absolute reticulocyte is increased in a patient with anemia
hyper-proliferative anemia
microcytic
red cell size is smaller
normocytic
red cell size is within normal
macrocytic
red cell size is larger
Fatigue, pallor, dyspnea (common to all anemias)
Hair loss
Pica
Restless legs
Spoon shaped nails (koilonychia)
Angular cheilitis
Swollen and sore tongue
symptoms for iron deficiency
iron homeostasis is highly regulated
yep
total body iron
4 grams
iron is reduced to ferrous state by
duodenal cytochromeb – DCYtb
how is iron tranported into the cell
divalent metal transporter 1 (DMT1)
a ferrioxidase that re-oxidazes iron for release from enterocyte to plasma transferrin
hephaestin
key transport protein in the exchange of FE from enterocyte ti transferrin
ferroportin
iron transport protein in plasma circulation
transferrin
key iron regulator and blocks iron transport at multiple sites, including intestinal epithelium and macrophages.
hepcidin
Hepcidin is a protein synthesized in the _____ and forms a high affinity bond with TfR; which is capable of sensing the level of _______saturation.
Hepcidin is a protein synthesized in the liver and forms a high affinity bond with TfR; which is capable of sensing the level of transferrin saturation.
Hepcidin synthesis is ________ in inflammation and secondary iron overload, and _________ in iron deficiency and hypoxia.
Hepcidin synthesis is increased in inflammation and secondary iron overload, and decreased in iron deficiency and hypoxia.
as we know hepcidin is a central regulator of iron metabolism it binds to
ferroportin and down-regulates efflux of iron
how does hepcidin regulates efflux of iron? (3)
- decrease of iron absorption by enterocyte
- decrease of ferroportin-mediated export from enterocyte into blood
- decrease of iron from macrophages of RES
iron storage forms (2)
which is the main one?
- ferritin– main storage of iron in cells
2. hemosiderin- insoluble form of iron that is no longer available for chemical rxn
CBC in iron deficiency:
- MCV
- MCH
- red blood count
- retic. count
- low MCV- microcytosis
- low MCH- hypochromia
- decreased red blood count
- low retic. count
diagnosis of Fe deficiency studies :
- serum Fe
- TIBC
- Ferritin
- Transferrin Sat
- serum Fe is low
- TIBC is high
- ferritin is low
- transferrin Sat is low
treatment of Fe deficiency
- oral
- IV
- transfusion
Pb inhibits the _____ and also inhibits the breakdown of ____. this causes____
final steps in heme synthesis and also inhibits the breakdown of RNA. this causes RNA aggregates in RBC- basophilic stippling
lead toxicity is what type of anemia?
microcytic hypoproliferative anemia
- low MCV
Symptoms: abdominal pain, anemia,
neurological symptoms, fatigue, malaise,
irritability
what type of diagnostic test should we do?
Serum Pb level to check for Pb toxicity
This form of anemia develops because there is functional rather than absolute iron deficiency. That is, the lack of iron in the circulation is not due to deficient dietary intake, but instead dysregulation of iron transport.
anemia of chronic disease
anemia of chronic disease
- associated with
- ______ induces hepcidin expression leading to dysregulation of iron transport, utilization and storage
- Fe release from enterocytes and macrophages is
- decrease plasma Fe but normal
- associated with inflammatory disorders
- inflammatory cytokines induce hepcidin expression leading to dysregulation of iron transport, utilization and storage
- Fe release from enterocytes and macrophages is inhibited
- decreased plasma Fe but normal bone marrow iron stores
anemia of chronic disease lab results:
- Serum iron
- TIBC
- transferrin saturation
- ferritin
- MCV
- low serum iron
- decreased TIBC
- normal transferrin saturation
- increased or normal ferritin
- normal or low MCV
treatment of chronic disease of anemia
treat he underlying disorder
megaloblastic anemia (2)
- folate deficiency
2. B12 deficiency
megaloblastic anemia is what type of anemia
hypoproliferative macrocytic anemia
___ is a water-soluble vitamin. Under normal conditions _____is absorbed throughout the proximal half of the small intestine, like most vitamins and minerals (with the notable exception of vitamin B12). _____ is a carrier of 1-carbon fragments (methyl groups) and is required for synthesis of purines, pyrimidines, and methionine. ____exists in various methylated forms, of which tetrahydrofolate (THF) is the biologically active form. ______ is conjugated with a series of glutamic acid residues, which controls its ability to be retained within cells.
Folate
causes of folate deficiency (5)
- dietary
- malabsorption
- increased demands such as pregnancy
- drugs such as methotrexate
- liver disease
______absorption is more complex than folate absorption. Cobalamin ________ is bound by a series of transport (R-binder) proteins until it reaches the duodenum. After digestion of the B12-R binder complex by pancreatic enzymes in the duodenum (alkaline pH), free cobalamin is bound to Intrinsic Factor (IF), which is secreted by parietal cells of the stomach (acid pH). _____-IF complexes traverse the small intestine and are internalized at the terminal ileum through a specialized receptor.
Cobalamin is a coenzyme for 2 enzymatic pathways: one is involved in amino acid metabolism and the other in the formation of methionine and the conversion of methyltetrahydrofolate to tetrahydrofolate. Thus adequate ____stores are required for adequate synthesis of biologically active folate.
vitamin B-12
causes of vit. B-12 deficiency (5)
- malabsorption- lack of intrinsic factor
- gastrointestinal- ileal resection
- transcobalamin II deficiency
- NO toxicity
- meds- metformin, proton pump inhibitors
giant hypersegmented neutrophils
seen in folate and B-12 deficiency
feared complication of B-12 deficiency
neuropathy and neural column degeneration
Folate and Vit B12 deficiencies predispose to ________ defects in the fetus
neural tube
labs in B-12 deficiency
- Serum B-12
- RBC folate
- serum folate
- serum B12 low
- RBC folate normal/low
- serum folate normal/high
labs in folate deficiencies
- Serum B-12
- RBC folate
- serum folate
- Serum B-12 normal
- RBC folate low
- serum folate low
evaluation of B12 deficiency (3)
- increased homocysteine and methylmalonic acid levels in blood
- endoscopy to evaluate for atropic gastritis
- blood for parietal cell antibodies
treatment for B-12 deficiency
administer both B12 and folate (large doses of folate will correct the hematologic picture bit not neuropathy)
spinal cord damage is irreversible in B-12 deficient pt.
yep
When the fine balance of iron uptake and iron loss is disturbed iron overload can occur, leading to disease. Transfusion is a common cause of iron overload.
yep
hereditary hemochromatosis
- mutation in
- inheritance
- allele prevalence
- what happens
- increased levels of
- iron deposition
- presentation
- mutation in HFE gene chromosome 6
- autosomal recessive
- 1:300
- excessive absorption of FE from GI tract- iron overload
- increased transferrin saturation and ferritin
- iron deposition in liver, heart and endocrine organs
- presentation usually in adults
