Structure and Function/ Hematopoiesis Flashcards
eosinophil
< 5% of leukocytes
increase in allergic reactions and parasite infections
basophil
< 1% of leukocytes
degranulates in allergic reaction and only rarely increased in non-neoplastic conditions
monocyte
3-8% of blood leukocytes
APC and phagocytes
increased numbers in inflammation
macrophages
derived from monocyte
lymphocyte
20-30% of blood leukocytes
increase in viral syndrome or neoplastic process
predominantly T-cells, then B and NK cells
reactive lymphocytes
increase in viral syndromes
neutrophils
40-70% of leukocytes
phagocytosis, degranulation (lysozyme), NETs (neutrophil extracellular traps made of chromatin) in bacterial infection
rapid turnover
IL-8
attracts neutrophils
CD11a/CD18 complex
integrins: grab and hold neutrophils
Leukocyte adhesion defect
CD18 defect
Wiskott-Aldrich Syndrome
cytoskeleton dysfunction of T cells (some neutrophil dysfunction)
How do neutrophils recognize pathogens?
- TLR
- Complement receptors
- Fc receptors
Chemokines secreted by neutrophils
- CXCL2
- IL-8
- TNF
chronic granulmatous disease
myeloperoxidase deficiency
neutrophils can’t make hypochlorite
left shift
lots of new granulocytes due to bacterial infection: bands, metamyelocytes, myelocytes
toxic granulation
neutrophils have primary granules suggesting infection
primary granules
blue granules
usually only seen in early myeloid precursors in bone marrow
secondary granules
salmon pink granules seen in mature neutrophils
platelets
concentrations 100x that of white cells
9-10 day lifespan
Function:
1. primary hemostatic plug (adherence/activation/aggregation)
2. stimulate coagulation cascade (fibrin formation/clot retraction)
3. stimulate wound healing (fibroblast growth/migration)
4. immune function (including antigen presentation and pathogen activation)
What happens to platelets in iron deficient patients?
increases
PF4
platelet factor 4 (platelet cytokine)
kills malaria pathogen
What causes reduced production of all coagulation factors?
liver disease (liver makes all the factors)
What causes reduction of coagulation factors (and often platelets)?
excessive activation platelets and cascade
giant platelets
occurs when platelet production is ramped up or in abnormal production due to disease that effect bone marrow
What happens when RBC hemoglobin precipitates?
obstruct vessels, rupture RBC
ankyrin
attaches RBC integral membrane protein to spectrin
spectrin
links the RBC plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles
What is the most important micro-organism that thrives on hemoglobin?
Plasmodium (protozoa that causes malaria)
What happens if RBCs have impaired ATP production?
Na/K ATPase fails
RBC swell and burst
What happens when RBC antioxidant system fails?
- oxidized-SH groups on hemoglobin crosslink: Hgb denaturation/precipitation
- oxide iron (Fe3+++) can’t carry O2: hemoglobin containing Fe3+++ (methemoglobin) and patient is hypoxic
glutathione (GSH)
eliminates peroxide
req. NADPH
cytochrome b5 reductase
reduces methemoglobin back to hemoglobin
req. NADH
precipitated hemoglobin
Can be due to hemoglobinopathy or oxidized hemoglobin
can result in hemolytic anemia
can see heinz bodies, sickle cells, and bite cells
hemolytic anemia
excess RBC lysis
bite cells
macrophages take hemoglobin clumps our of RBCs in big bites resulting in deformed RBCs
How do RBCs make energy?
- glycolysis: ATP and NADH
2. pentose shunt: NADPH
Glucose 6 phosphate dehydrogenase deficiency
first failure point in pentose shunt pathway
see bite cells
DAF
slows down complement fixation
hypochromia
lack of color
anisocytosis
abnormal distribution of RBC sizes
poikilocytosis
abnormal RBC shape
morphology of RBC that don’t have enough hemoglobin
hypochromic and/or microcytic
polychromasia
blue: seen in accelerated production due to residual mRNA
due to rapid RBC loss
methylene blue
binds negative (nucleic acids)
eiosin
red binds positive (ex: some proteins)
reticulocyte
immature RBC: lots is polychromes
Heinz bodies
clumps of oxidized hemoglobin
hemoglobinopathy
genetic defect in hemoglobin structure
Diseases selected for by providing heterozygotes from malaria
- sickle cell anemia
2. G6PD
schistocytes
red cell fragments due to mechanical lysis or microangiopathic process
hemoglobin: hematocrit ratio
1: 3
What does a turbid blood specimen indicate?
fatty meal: increases scatter
looks like you have more hemoglobin
hematocrit
RBC/blood volume
What will clumping of RBC look like on blood count?
red cells counted as one cell
- artificially increased MCV
- artificially reduced red cell count
- reduced hematocrit
What will a hematology analyzer count bands as?
neutrophils
What will a hematology analyzer count blasts as?
lymphocytes or monocytes
What will a hematology analyzer count red cell fragments as?
platelets
What will a hematology analyzer count platelet clumps as?
lab artifact (EDTA can expose antigens and cause clumping due to Ab): not always detected: can resolution an artificial thrombocytopenia use citrate instead for these cases
Iron deficiency
- morphology
- labs
- causes
- microcytic, hypochromia, anisocytosis, poikilocytosis
- reduced ferritin, reduced transferrin saturation, increased TIBC, iron reduced, (reduced RBC)
- chronic blood loss or deficient diet
RDW
red cell distribution width
correlates with anisocytosis
transferrin
binds Fe3+ and transports it
ascorbate
cofactor for duodenal reductase (ferrireductase)
ferrireductase
Fe3+ -> Fe2+
conversion needed to absorb iron in intestines
DMT-1
active transport of iron from GI tract into intestinal cells
regulation: iron dependent
ferritin
binds iron (Fe2+) for storage
ferroportin
transport iron out of intestinal cell into plasma
export of iron from iron storage pool
increases in response to low iron
hephaestin
ferioxidase: Fe2+ -> Fe3+
need oxidized to transport in plasma (keep away from bacteria)
iron reservoir in body
macrophages in bone marrow, liver, spleen
hepcidin
increased by: increased levels of transferrin-bound iron and inflammation
decreased in low iron;
action: decreases ferroportin expression in macrophages and enterocytes (internalize and degrades it)
serum iron
direct measure of transferrin-bound iron
total iron binding capacity (TBIC)
total amount of transferrin in circulation
transferrin saturation
serum iron/total transferrin
serum ferritin
direct measurement of storage pool iron
soluble transferrin receptor
second line measurement of storage pool iron
increases on macrophages in iron starved state
High hepcidin levels
results in anemia
Low hepcidin levels
get too much iron stored: liver disease, cardiomyopathy, diabetes
Beta thalassemia
- morphology
- lab
- confirmation
- very microcytic, hypochromia, target cells
- normal or increased RBC, low MCV
- hemoglobin electrophoresis: hemoglobin A2; in severe cases hemoglobin F is detected
MCV
mean cell volume
hemoglobin A2
two delta globins bound to two alpha globins
migrates differently from hemoglobin A
hemoglobin F
fetal hemoglobin: two alpha globins and two gamma globins
hemoglobin A
adult hemoglobin: two alpha and two beta globins
Alpha thalassemia 1 trait
1 defective alpha allele
no clinical/ lab findings
alpha thalassemia 2 trait
- morphology
- lab
- Dx
2 defective alpha alleles 1. mild microcytic anemia 2. normal Hgb electrophoresis as adults 3. PCR based 3% african americans
Hgb Bart’s
four defective alpha alleles: four gamma chains
lethal in utero or soon after birth
Hgb H disease
3 defective alpha alleles
- variable microcytic anemia
- Hgb electrophoresis: 15-30% Hgb H
Hgb H
four beta chains
Folate deficiency
megaloblastic anemia
B12 deficiency
takes years of inadequate dietary intake
megaloblastic anemia
increased homocysteine and methyl malonate
neurological problems
cobalamin
B12
What happens if you give a B12 deficient person folate without B12?
worsens neurological symptoms
haptocorrin (HC)
binds Vit. B12 in saliva
IF
intrinsic factor: binds B12 in jejunum after HC dissolves away
made by parietal cells in stomach
megaloblastic anemia
occurs in impaired DNA syntesis: large nucleus and chromatin does not condense down into heterochromatin
cytoplasm continues to mature
RNA that is blue begins to degrade and hemoglobin’s red color predominates
How are folate derivatives stored?
polyglutamation
anemia of chronic inflammation
infection increases IL-6 which stimulates the liver to increase hepcidin causing anemia
get decreased transferrin, increased ferritin
Erythroferrone (ERFE)
Stimulated by EPO
Down regulates hepcidin: iron moves into transport (transferrin) to make it more available for RBC precursors
B-thalassemia: increased ERFE can cause hemochromatosis
