RBC disorders Flashcards
what are the two parts of Anemia
Reduction of red cell mass
Impaired tissue oxygenation
how can reduction of RBC mass be shown
Red cell count
Hemoglobin/hematocrit
what are the signs of impaired tissue oxygenation
Shortness of breath
Weakness
Fatigue
Pallor
what do the normal levels of rbc’s depend on
Age
sex
geographic location
what is polycythemia
increase in red cell mass
what are the categories of Anemia
RBC loss (blood loss)
Decreased RBC survivial
Decreased RBC production
what causes RBC (blood) loss
Hemorrhage (acute)
Trauma (acute)
GI or GYN disease (acute or chronic, occult blood loss)
what causes decread RBC survival
HEMOLYSIS Mechanical trauma transfusion reaction Herediatry spherocytosis Hemoglobinopathies Thalassemias G6PD deficiency Erythroblastosis fetalis Malaria
what causes Decreased RBC production
Iron deficiency anemia Vitamin B12 deficinecy folate Deficiency Aplastic anemia Myelophthisic anemias
what does a CBC test for
RBC count Hemoglobin Hematocrit Mean cell volume, Hb, and Hb concentration WBC Platelts
what tests are done for anemia
Blood smear review
CBC
REticulocyte count
Iron indicies
what does an iron indice test for
Serum Fe, Iron-binding capacity
transferrin saturation
ferritin concentration
Vitamin B12 and Folate (also)
what is included in a hemolysis work-up
Dilirubin (direct and indirect) Haptoglobin LDH coomb's test Plasma hemoglobin Hemoglobin electrophoresis
how much blood loss can a young healthy indivudal tolerate with minimal symptoms
Up to 1000ml of rapid blood loss
what loss of blood results in shock
2000ml of rapid loss
what helps to re-expand vascular volume once blood loss in controle
Interstitial fluid redistribution
what are the symptoms of 500-1000ml of blood loss
vasovagal response
- sweating
- weakness
- nausea
- slow heart rate
- hypotension
what are the symptoms of 1000-1500ml of blood loss
Lightheadedness
orthostatic hypotension
what are the symotoms of 1500-2000ml of blood losss
thirst shortness of breath loss of consciousness sweating rapid pulse decreaed blood pressure clammy skin
what stimulates RBC production
erythropoietin
what is found in the blood at higher rates when lots of erythropoietin is made
lots of reticulocyte
when does chronic blood loss cause anemia
rate of loss exceeds capacity for RBC regeneration,
when iron reserves are depeleted
what are the important cuasese of iron deficiency
chronic GI hemorrhage due to ulcer or neoplasm GYN hemorrhage (menorrhagia)
what causes intravascular decrease in RBC survival
Destruction of RBC within circulation
what causes extravascular decrease in RBC survivial
Destruction of RBC within reticuloendothelial system
Tissue macrophages of the spleen and liver
what happens to hemoglobin released from RBC into circulation in intravascular hemolysis
bound to haptoglobin and cleared from ciculation by the liver
what is haptoglobin
binding protein for hemoglobin
what is a key feature of intravascular hemolysis
Decrease in serum haptoglobin
what happnes when plasma hemoglobin exceeeds haptoglobin
free hemoglobin is peded out (hemoglobinuria)
what is hemoglobin’s effect on the kidney
toxic due to iron accumulation in proximal tubular cells when the cells are shed
what is the shedding of cells lost when hemoglobin is peed out
Hemosiderinuria
what does conversion of heme to bilirubin lead to
Hyperbilirubinemia and jaundice
what determines the degree of jaundice
dependent on functional capacity of liver
rate of hemolysis
what are the immune causes of intravasvular hemolysis
Transfusion reaction
what are the non-immune causes of intravascular hemolysis
Mechanical trauma (defective heart valve
what all is affected in intravascular hemolysis
decreased: haptoglobin Hemoglobinemia Hemoglobinuria Hemosiderinuria Hyperbilirubinemia Reticulocytosis
what hapens to damaged or abnormal RBC’s
Removed in speen
what happens to hemoglobin in the spleen
Broken down intracellularily (not released directly into blood and urin)
what does breakdown of hemoglobin lead to an increase in the blood
hemoglobin breakdown products increase in the blood
what does the presence of hemoglobin breakdown products in the blood lesad to
hyperbilirubinemia
Jaundice
what organs are affected by extravascular hemolysis
Spleen and liver enlarrged
what does elevated levels of bilirubin lead to
Formation of gallstones
what are the intrisic defects that cause extravascular hemolysis
Non-immune
- RBC membrane defects
- Hemoglobinopathies
- metabolic fects
what kind of defect is hereditary spherocytosis
Membrane defect for extravascular hemolysis
what causes hereditary spherocytosis
less defomrability of the RBC so that they are sequested and destroyed in the spleen
what protein is affected in herditary spherocytosis
- is it quantitative or qualitative
quantitative or qualitative spectrin (structural protein)
how is hereditary spherocytosis transmitted
Autosomal dominant
when does hereditary Spherocytosis manifest it self
adult life
how does removal of spleen affect herediatry spherocytosis
normal RBC survival
does not give normal RBC morphology
what kind of problem is sickle cell anemai
Abronal hemoglobin extravascular hemolysis
(hemoglobinopathies)
how is sickle cell anemia transported
Autosomal codominant
what causes sickle cell anemia
the strucutre of globin chain causes hemoglobin to gel upon deoxygenation
what is the mutation that causes sickle cell anemia
one single base pair substitaion at position 6 (valine for gluatmic acid)
what happens in sickle cell anemia in low O2 conditions
abnormal hemoglobin polymerizes causing RBC to create a sickle shape
problem with sickle cell shape
Rigid and vulberable to splenic sequestation (decreased survival)
block microciuluation
- ischemia and or infarcause
how many alleles do you ned for sickle cell disease
homozygous
characteristics of homozygous sickle cell disease
severe anemia
Vaso-occlusive crises
- acute chest syndrome
- stroke
what are the complication of homozygous sickle cell disease
autospenectormy
painful crises
leg ulcers
retinal and renal thrombosis
what are the odds of having at least one sickle cell genee
8% of blacks
blood effect of sickle cell anemai
Moderate to severe anemia
Hyperbilirubinemia
Reticulocytosis
what is the type of anemia that is thalassemia
extravascular hemolysis due to lack of globin chains
how is thalassemia transmitted
Autosomal codominant
what causes thalassemia
Diminished or absent synth of alpha or beta globin chains of hemoglobin
what happens to the gene in thalassemia
whole or partial gene deletion
mutation of coding sequence/promoter
mRNA instability
what does decreased globin from thalassemia lead to
Decreased hemoglobin prudction with anemia
what does the production of excess of other globulin chains in Thalassemia lad to
membrane damage and premature destruction of RBC precursors in the marrow and sleen
what are the clinical manifestations of Thalassemia
Varibale anema (asymptomatic to severe) moderate to marked microcytosis with target cells and basophilic stipping of the REd cells present in a blood smear
where is Thalassemia common
mediterranean
african
southeast asia
what kind of defect is Glucos-6-phosphate dehydrogenase deficiency
Metabolic Defect
how is G6PD transmitted
X linked inheritance
what ahppens to red cells susceptible to oxidance injury
usually precipiated by drugs/toxins or infections
what happens to oxidized hemoglobin from G6PD
precipitates within the cell and attaches to the RBC membrane
- reduced membrane flexibility
what does reduced membrane flexibility lead to in glucose-6-phosphate dehydrogenase Deficiency
Extravascular hemolysis in the sleen
what is needed to make Glucose-6-phosphate Dehydrogenase symptomatic
Oxidant is present
what is the cytomorphologic halmmark of glucose-6-phasophate
Bite cells
what extrinisic defect is the hemolytic disease type of the newborn
Autoimmune
what type of hemolysis is Erythroblastosis fetalis
Immune destruction extravascular hemolysis
what causese erythroblastosis featlis
blood group incompatibility between mom and fetus
when does erythroblosis featilis occur
in utero when fetus has antigens from dad that the mom does not have
what cause sensitization in the mother in erythroblosis featalis
Fetal RBC during 3rd trimester during pregnancy or childbirth entering materal circulation leads t
when do the full effects of Erythroblosis featalis affect featus
second pregnancy antibodies go into the featus leading to extravascular hemolysis
what antigens are the most important for erythroblosis featalis
ABO and Rh antigens
what is done in Rh mothers to prevent Erythroblastosis fetalis
given anti-D within 72 hours of delivery of Rh-positive featus
what is the action of Anti-D in preventing Erythroblastosis
binds to Rh-positive fetal cells and removes them from circulation before antibodies can form and mom becomes sensitized
when does ABO hymolytic disease occur
In A or B infants with O moms
why is lysis of featl RBC miniminal during ABO hymolytic disase
Fetal cells Present some A weakly
other cells express A and B antigens and soak up the antibody
what kind of RBC disorder is Hemolytic Tranfusion reaction
Intravascular hemolysis autoimmune
what happens in hemolytic transfusion reaction
incompatable RBC into a sensitized patient causes antibody binding to antigen
- activates complement
- immediate intravascular hemolysis
what are the problems with hemolytic transfusion reaction
Bleeding
renal failure
Shock
Death
what antigens are important for hemolytic transfuction reactions
ABO (others can cause problems through)
what kind of problem is Autoimmune hemolysis
extravascular hemolysis
what causes autoimmune hemolysis
Patient makes antibodies to own RBC
what does autoimmune hemolysis lead to
- anitbody coated cells are lysed(complemt) or removed by retriculoendo system
phargocytic removal of RBC from autoimmune hemolysis leads to
partial loss of red cell membrane (Spherocytes)
- sequester in spleen (anemia)
what kind of disorder can be cause by caridac valve prosthesis
Intravscular hemolsys
what happens in cardiac valve prosthesis hemolysis
RBC disrupted by phsycial trauma as pass through turbulance and abnormal pressure
how can DIC lead to RBC disorders
RBC’s lysed as they pass through fibrin clots and strands and produce schistrocytes
what kind of Disorder does Malaria cuase
Intravascular hemolysis
what does Malaria fur
Infect RBC to cause lysis of RBC during maturation
what is the hallmark of autoimmune hemolytic anemai
Spherocytes
what test is done for Autoimmune hemolysis
Positive direct Coomb’s test
what does the presence of schistocytes show
Indicuate hemolysis due to mech trauma
what can causes a nutrition decrease in RBC production
IRon deficincy
B12 an dFolate deficiency (megaloblastic anemia)
what is the most common basis of anemia world wide
Iron deficicy
how does IRon deficiency anemia usually develop
Insidiously
how tends to suffer from inadequate intake of iron
Infants
who has icnreased demand for iron
Pregnancy
Adelescencts
what can cause an increased loss of iron
Bleeding
does an iron deficincy often stand a lone
No, may be related to a more serious condition
what happens to the RBC in lab during iron deficincy
Microcytic (low MCV)- smaller)
Hypochromic (low MCHC) - less hemoglobin
what is lost in the serium during a iron deficincy
Less serum ferritin
more serum iron binding capcaicty
less serum iron
how does the reticulocyte respond in rion defiincy anemai
Absent reticulocyte response
what is rion used for
Hemoglobin
Myoglobin
enzymes
what is usually done to test anemia
Lab work
what causes MEgaloblasti anemia
Folate and B12 deficiency
what synthesis does Megaloblastic Anemia involve
Synthesis of Thymidine
how does Impaired DNA synth affect mitotic division
delays it
what does megaloblastic anemia do to the nucleus and cytoplasm
Nuc Does not matuer appropriately
Cytoplasm does normal
how does Megalblastic Anemia change cells
Large red and white cells precursors (increased MCV)
what does Megalblastic Anemia do to the neutrophils
Hypersegmented
how does MEgaloblastic Anemia affect mature RBC production
Decreased due to absent reticulocyte reponse
what may severe megaloblastic anemia do
White cell and platelet production affected
how does Megaloblastic anemia cause annemia
megaloblast Accumulate in the bone marrow, not enought RBC released
what happens to the megaloblasts in the marrow
Autohemolysis or destroyed by phagocytic cells in the marrow
what other cells can be affected by Megaloblastic anemia
All regularily deviding cells
where is Folate found
Fesh veg
how much folate does the body store
Small amounts
what causes an increased need in Folate
Pregnancy
Hemolytic anemia
hell cell turnover state
what may cause a folate deficiency
Increased need
Decreased dietary intake or Malabsorption
where is B12 found
Animal foods
how much B12 does your body store
Lots
what causes a B12 deficiency
Increased need
Decreased intake/malabsorption
what all can B12 deficiency affect besides Hematologic abrnormalities
Neurologic symptoms
what is needed to absorb Vit B12
Intrisic factor
where is intrisic factor found
Produced by parietal cells of the gastric mucosa
what happens when Vit B12 binds to Intrinsic factor
passes to distal ileum to attach to receptors to absorb
what does Absorbed B12 do
Binds to TRanscobalamins in plasma to deliver to liver and other cells via blood
where is folate abosrbed
In proximal small intestine
what causes Pernicious Anemia
Autoanitbodies to parietal cells and intrinsic factor
what is a B12 deficiency associated with
Atrophic gastritis(loss of gastric parietal cells)
achloyhydria
Deficiency IF
types of Decreased RBC production
Aplasitic anemia
Myelophthisic processes
what dose a decrease in cellular elements of blood cause
Aplastic Anemia
do we know the cause of more aplastic anemia s
no, 1/2 are idiopathic
what causes aplastic anemia
Drugs (Chloramphenicol)
Toxins (benzene)
Viral hep
what casues Aplastic Anemia
- An acquired stem cell defect with decreased production of types of Blood cells
- suppresssion of stem cells via T lymphocytes
what surpresses stem cells in Aplastic Anemia
T lymphocytes
how to treat Aplastic Anemai
Bone marrow transplant (less than 40 year old patients)
what causes Myelopohthisic anemia
decreased production of red cells due to replacement of marrow elements
what happens in Myelophthisic anemia
Normal hematopoietic cells in marrow are crowded out by tumor or fibosis
what happens to cell shapre in myelophthisic Anemia
misshapen RBCs resembling teardrops on blood smear
what else besides RBC are affected in myelophthisic anemia
Platelets are decreased
what in an increase in Red Cell mass
Polycythemia
what causes Relative polycythemia
Dehydration
Diarrhea
what causes primary Absolute polycythemia
Neoplastic proliferation of Red ells
what causes secondary absolute polycythemia
Icnreased Erythopoieticin fruction
what causes an increase in erythorpoietin
Cyanotic heart disease
Pulmonary disease
High altitude
Erythropoietin producting tumors
neoplastic growth of RBC and Myeloid cells
Polycythemia veria
