hematological disorders Flashcards
what is blood
dilute saline with dissolved chemicals and suspended cells
what are four dissolved components of blood
nutrients (glucose, vitamins)
Electrolytes (Na, K, Cl, Ca)
Hormones (insulin, T3/T4)
Proteins (albumen, carriers)
T/F drugs are also found dissolved in blood
true
differentiate between blood, plasma, and serum
blood is all the dissolved and suspended components
plasma is blood with the suspended components removed
serum has all the cell and clotting factors removed
four functional factors of red blood cells
Hemoglobin
size, shape
flexibility
longevity
what is the protein structure of hemoglobin
a protein tetramer with alpha and beta or alpha and gamma polypeptide chains and one oxygen carrying heme group
what is the structural difference between adult and fetal hemoglobin
adult hemoglobin has 2 alpha and 2 beta chains
fetal hemoglobin has 2 alpha and 2 gamma chains
why do RBCs need to flexible?
why is this relevant?
RBCs neet to fit through small vessles
as people get older RBCs are less flexible and more likely to clot
what components of blood come from the myeloid line
erythrocytes
megakaryocytes (platelets)
granulocytes (N, B, E-phils) and monocytes
what cells come from the lymphoid line
NK cells
dendritic cells
T & B lymphoctyes
granular leukocytes
basophiles
neutrophils
eosinophils
agranular leukocytes (mononuclear)
monocytes
lymphocytes
why do some RBCs appear “speckled”
they are reticulocytes that have remains of the endoplasmic reticulum remaining
how long do RBCs last before being broken down
100-120 days
what cells break down RBCs
reticuloendothelial cells found in the spleen and liver
what is the main byproduct of hemoglobin breakdown
bilirubin
bilirubin is an indicator of what
liver function
what causes jaundice
high levels of bilirubin
T/F a small number of RBCs are lost through the GI, Urine, Skin
true
anemia
pathological deficiency of oxygen carrying capacity of blood caused by a decrease in the number or function of RBCs
what is a normal blood volume
4-8 liters
T/F gamma hemoglobin production is turned off in adults
true
white pulp of the spleen
lymph tissue
red pulp of the spleen
tortuous sinsoids that weed out old RBCs or RBCs with antigens to be broken down
where do RBCs come from
does all bone marrow produce RBCs
bone marrow
no, mostly in the hips, sternum, long bones
erythropoetin
cytokine that stimulates the production of erythrocytes
what triggets the production of EPO
decreased oxygen saturation in the blood
where is erythropoietin produce
the juxtapoglomerular cells of the kidneys
band cells
immature neutrophils that are indicative of rapid production of neutrophils
why is neutrophil count important in cancer treatment
chemo decreases bone marrow function
Do RBCs have a nucleus?
why is that important in transfusion
no
because we don;t have to match HLA-1 antigens just blood type
what are reticulocytes indictive of
rapid production of RBCs
destruction of RBCs
recyclining function of RE macrophages
amino acids and iron from hemoglobin is recycled into the bone marrow to make new RBCs
CBC
complete blood count (RBCs, WBCs, platelets, hemoglobin and hematocrit)
on a CBC the hematocrit is generally how much higher than hemoglobin
3x
when you spin out blood what is the “buffy coat”
white blood cells
what are the signs of hypervolemia based on the amount of blood lost
10-15% initial signs of vascular instability
greater than 30% orthostatic hypertension
greater than 40% hypovolemic shock
hemoglobin content is dependent on what two factors
production of Hgb - loss of Hgb
reduced hgb production is indicative of what?
bone marrow issue
increasd hgb loss means
accelerated destruction or loss from vasculature
three questions to ask when considering bone marrow deficiency in anemia
enough stem cells
enough nutrients to make RBCs (iron, folate)
enough stimulation (EPO)
three systems that patients will often loss RBCs through (example of disoder)
GYN (heavy period)
GI (cancer, ulcer)
GU (cancer)
four problems that would lead to decreased erythropoesis in the RBCs
nutritional deficiencies
loss of stimulation
toxicity
neoplasm
two general nutrition deficiency that cause anemia
anemia of chronic disease
starvation
three specifict nutrient deficiencies that will cause anemia
folate
b12
Iron
four dietary sources of iron
meat, seafood, beans, spinach
two histological descriptors of iron deficient anemia
microcytic (small)
hypochromic (pale colored)
T/F pregnancy and lactation can caused anemia through loss of RBCs
false, they cause increased demand
four steps to treat iron deficiecy
stop blood loss if there is any
improve diet
oral iron
parenteral iron
what is the complication with oral iron supplements
compliance issues due to GI side effects
what is the histological sign of B-12 and folate deficency
megaloblastic anemia
megaloblastic anemia
Large RBCs, hypersegmented neutrophils caused by impaired DNA synthesis
cobalamin
B 12
B12 is important to the synthesis of what
nucleic acid synthesis
where is B12 found
tightly bound to protein in meat
what is needed to extract dietary b12
low gastric pH and intrinsic factor
causes of b12 deficiency
dietary (strict vegan)
gastric dysfunction
GI malabsorption (ileal disease)
three ways gastric disfunction can cause b12 deficiency
pernicious anemia
gastric atrophy
gastric surgery
what causes pernicious anemia
auto antibodies against intrinsic factor
what will be two signs of pernicious anemia
megaloblastic anemia and progressive neurological deterioration
why is it dangerous to give folate to treat pernicious anemia
folate will correct the anemia but not the neurlogical damage
treatment for b12 deficiency
large oral doses of B12
intramuscular B12
folic acid is an essential cofactor in what
amino acid and DNA synthesis
what is the effect of folic acid on fetal development
assist in neural tube development and decreases ther risk of anencephaly or spina bifida
causes of folate deficincy
not enough fruits and veggies
increased demand (pregnancy, hemolytic anemia)
malabsorption of folate
folate deficiency treatment
daily folic acid tablets
if there is a coexisting B12 deficiency what will folate treatment do
correct anemia but not neurodegeneration
how do chronic renal failure cause anemia
loss of EPO resulting in moderate anemia
three causes of bone marrow toxicity
pharmacological
environmental
immunologic
three environmental sources of bone marrow toxic substances
solvents
pesticides
radiation
aplastic anemia
an autoimmune disorder that causes the loss of hemopoietic cells
what are the three clinical manifestations of aplastic anemia
anemia
leukocytopenia (chronic infection)
thrombocytopenia (no clotting factors0
treatment of aplastic anemia
immunosuppresion
bone marrow transplant
what is the immunosuppressive treatment of aplastic anemia
how often is it successful
antilymphocyte or antithymocyte globulin
50-70%
why is a good HLA match needed for bone marrow transplant
a poor match will produce graft versus host disease as the graft produces lymphocytes that react to antigens
myeloproliferative disorders
cancers that will displace normal bone marrow
types of myeloproliferative disorders
leukemia
lymphoma
multiple myeloma
polycythemia
thromocythemia
two types of leukemia
myeloid (acute or chronic)
lymphoid (acute or chronic)
two types of lymphoma
hodgkins
non-hodgkins
what is the diffence between hodgkins and non-hodgkins
polycythemia
overly productive bone marrow that produces too many blood cells
risk of thrombocythemia
increased clotting
classic GI causes of chronic bleeding
peptic ulcer or cancer
classic cause of anemia from gyn
uterine (heavy period, leiomyoma
classic urinary causes of anemia
renal cell carcinoma
bladder carcinoma
causes of hemolysis
defect in RBC size shape or function
outside destructrion of normal RBCs
hemoglobinopathy
two types
change in Hgb structure and function
sickle cell anemia
thalassemia
what causes sickle cell anemia
autosomal recessive mutation of Hgb A
what causes sickle cell disease
homozygous vs heterozygous Hgb A mutation
T/F heterozygous Hgb is usually asymptomatic
true
are the risks associated with sickle cell anemia
chromic hemolytic anemia
microinfarction due to clottin
what will microinfarctions from sickle cell cause
leg ulcers
functional splenomegaly
shortened life span
thalassemia
genetic defect in globin biosynthesis
classified as alpha or beta thalassiema
describe the genetic characteristics of thalassemia
autosomal recessive
differniate between homozygous and heterozygous thalassemia
homozygotes have signifcant disease (major)
heterozygotes are mildly anemia or asymptomatic
what are the risks of major thalassemia
severe anemia
hepatosplenomegaly
growth abnormalities
what is the treatment for severe anemia for major thalassemia
what is the risk
repeat transfusions
iron overload (hemosiderosis)
what is the treatment for hepatosplenomegaly caused by thalassemia
eventually splenectomy, which will increase risk of infection
why are growth abnormalities present in beta thalassemia
there is an overgrowth of bone marrow that can cause pathologic fractures or “chipmunk facies”
two RBC enzyme deficiencies
G6pD
PKD
T/F G6PD and PKD defiency are both autosomal dominant
false, they are autosomal recessive
what is the evolutionary benefit to G6PD deficieny
heterozygotes have increase survival rate with malaria infection
G6PD homozygotes are at risk for hemolysis triggered by what three factors
certain diseases (infection, diabetes)
certain foods (fava beans)
certain drugs (sulfa, aspirin)
four other causes of hemolysis that arent sickle cell or
important questions to ask in anemai
diet
menstruation
GI distress
medication
normochromic, normocytic RBCs with normal reticulocytes, iron
but
pancytopenia
three things that top the DDx
aplastic anemia
bone marrow dysfunction
drug reaction
DDx for
megaloblastic anemia
low reticulocytes
normal iron studies
folate deficiency
B12 deficiency
metformin
GI symptoms
DDx for
Normal indices (red blood cell size)
Reticulocyte count high
Iron studies normal
Bilirubin level elevated
Hemolysis
Inheritied hemoglobin disorderd (thalassemia or sickle cell)
Autoimmune disorders (lupus)
G6PD
Pyruvate kinase deficiency
