6 Blood disorders Flashcards
1
Q
Describe basophils
A
- very dark blue/purple granules when stained
- basophil granules are large and usu obscure the nucleus bc of their density
2
Q
Basophil fxn
A
fxn in hypersensitivity rxn
-can be increased in non-hypersensitivity rxns (CML)
3
Q
Eosinophils description
A
- contain large, strikingly ‘eosinophilic’ granules
- bilobed nuclei
4
Q
eosinophil fxn
A
- inflamm response to parasites too large to be engulfed by individual immune cells
- some allergic rxns
5
Q
neutrophil description
A
-contain neutrophilic granules
6
Q
neutrophils predominate where, work where
A
predominate in blood, work in tissues
7
Q
neutrophils are first line defense against
A
bacterial pathogens
8
Q
platelets description
A
- fragments of larger, multinucleated cells (megakaryocytes)
- have no nuclei
9
Q
platelets distribution
A
most in circulation, some are trapped in spleen
10
Q
coagulation factors are generally active or inactive
A
inactive as serine proteases
11
Q
where are coagulation factors made
A
- most are made by the liver
- factor XIII from platelets
- factor VIII be endothelial cells
12
Q
Anemia definition
A
abnormally low hemoglobin conc in blood
13
Q
microcytic cells
A
small cells, with low MCV
14
Q
macrocytic cells
A
larger cells, with high MCV
15
Q
poikilocytosis of cells
A
relative nonuniformity of cell shape
16
Q
anisocytosis of cells
A
relative nonuniformity of cell size
17
Q
microcytic anemia def
A
due to abnormalities in Hb production, either in # of Hb molecules per cell or in type of Hb molecules (hemoglobinopathies)
18
Q
microcytic anemia examples
A
- iron deficiency anemia (from chronic blood loss)
- thalassemias
19
Q
macrocytic anemia problem
A
- abnormal nuclear maturation
- higher fraction of young, large red cells (reticulocytes)
20
Q
megaloblastic anemia def
A
-when the nuclei of maturing red cells appear too young and large for the amount of Hb in the cytoplasm
21
Q
Cause of macrocytic anemia
A
- vitamin deficiencies
- drugs that interfere with DNA synth
- clonal proliferation in bone marrow -> preleukemic state = myelodysplastic syndrome
- hypothyroidism
- alcohol
- liver dz
22
Q
Normocytic anemia cause
A
- decreased # of rbc precursors in the marrow (aplastic anemia)
- low levels of EPO (chronic renal failure)
- chronic inflamm dz that affect the availability of iron in the marrow
- decreased life span (autoimmune hemolytic anemia, sickel cell anemia, hereditary spherocytosis or hereditary elliptocytosis)
23
Q
Erythrocytosis
A
elevated Hb conc
24
Q
Who has the highest incidence of iron deficiency, why
A
premenopausal women bc of recurrent menstrual blood loss; losses even higher in preggers (baby steals mom’s iron for its own hematopoiesis)
25
Cause of iron deficiency in men and postmenopausal women
GI bleeding due to PUD, ateriovenous malformations, or angiodysplasia (small vascular abnormalities along the intestinal walls)
-severe: IBS or malignancy
26
Where is dietary iron absorbed
duodenum
27
iron absorption is increased when
with anemia, hypoxia, and systemic iron deficiency
28
iron recycling
from senescent erythrocytes via macrophage phagocytosis and lysis
29
Who regulates the transport of iron from cells to plasma
hepcidin
30
Hepcidin is produced where
liver
31
What does hepcidin bind to
-binds to ferroportin (transmem protein) -> internalization and lysosomal degradation
32
What happens to hepcidin and ferroportion when iron is low
hepcidin production is reduced and ferroportin molecules are expressed on the basolateral mem of enterocytes
-ferroportin transfer Fe from the cytoplasm of enterocytes to plasma transferrin
33
what happens to hepcidin production in inflammatory states
hepcidin production is increased -> internaliazation of ferroprotin on macrophages and the trapping of recycled iron within macrophage stores
34
How is iron stored in the body
- as ferritin (combo of iron and apoferritin)
| - as hemosiderin (ferritin partly stripped of the apoferritin protein shell)
35
How is iron transported in blood
bound to carrier protein tranferrin
36
Where is iron predominantly found
- Hb
| - some in myoglobin
37
What step of heme synth is interrupted in iron deficiency
final step where ferrous iron is inserted into protoporphyrin IX by ferrochelatase
-don't have enough heme
38
how is globin biosynthesis inhibited by heme deficiency
-through a heme-regulated translational inhibitor (HRI)
39
what happens in early Fe def
Hb level of blood falls but individual erythrocytes appear normal
- in response to falling O2 level, EPO levels rise and stimulate the marrow, but Hb level can't rise in response bc of Fe def
- stimulated marrow -> inc platelet
40
target cells in Fe def
- see anisocytosis and poikilocytosis
- target shape in cells bc there is excess of red cell mem compared with the amount of Hb within cell; mem bunches up in the center
41
Problem with diagnosing Fe def
- ferritin levels rise in acute or chronic inflamm
- serum Fe levels fall in many illnesses
- levels of transferrin fluctuate
42
What is diagnostic of Fe def
low serum ferritin (but levels can be normal)
43
Fe def dx transferrin
measure soluble tranferrin receptor (sTfR) in serum (Fe: transferrin -> inside cells)
- erythroid precursors inc their expression of mem TfR in the setting of Fe def but not anemia of chronic dz
- high ratio of sTfR:ferritin -> Fe def
44
confirm Fe def dx
bone marrow biopsy
| -Fe in the macrophages of the marrow; use Prussian blue stain to check
45
Classic symps of all anemias
dec O2 carrying capacity (fatigue, weakness, SOB, DOE)
| -tachycardia, vasoconstriction of superficial bvs
46
GI symps of Fe def
glossitis (normal tongue papillae are absent)
| gastric atrophy with achlorhydria (need HCl for absorption)
47
kids with Fe def
developmental probz (physical and mental)
- reverse with early Fe therapy
- pica (eat dirt, clay)
48
2,3 BPG increase
increase ability to unload O2 in tissues
| -see increase in chronic anemia (adaptation)
49
hematochezia
gross blood in stool; bleeding sites near rectum
50
melena
black, tarry, metabolized blood in stool; more proximal sites
51
Pernicious anemia: what's wrong, what's normal, cause
- megaloblastic anemia
- abnormal erythrocyte nuclear maturation
- Hb synth is normal
- autoimmune dz
52
What cells are most often affected in pernicious anemia
rapidly proliferating cells (bone marrow, GI epithelium); B12 -> DNA synth (& myelin synth)
53
You lose which vitamin with pernicious anemia
B12 (cobalamin)
54
Cobalamin deficiency due to
- pernicious anemia
- bacterial overgrowth in intestine
- intestinal malabsorption of B12 involving terminal ileum (Crohn's)
- surgical removal of the antrum of the stomach (gastrectomy)
- dietary deficiency (strict vegetarians)
55
Who gets pernicious anemia
-older pts of Scandinavian descent
| US: black females
56
What happens in the stomach in pernicious anemia
autoimmune -> loss of gastric acid (achlorhydria) and loss of intrinsic factor
-interferes with initial availability and absorption of B12
57
What is stomach acid needed for
release of B12 from food
58
What is intrinsic factor needed for
binds B12 and is needed for absorption of B12 in terminal ileum
59
Who makes stomach acid and intrinsic factor
parietal cells
60
How is pernicious anemia an autoimmune disorder
- infiltrating lymphocytes are predominantly antibody-producing B cells (also some CD8 T)
- pts have antibodies in serum directed against parietal cell membrane proteins -> gastric mucosa atrophy
- 1/2 of pts have antibodies to intrinsic factor itself
- pts have higher incidence of other autoimmune disorders
- corticosteroids may help
61
What is the major protein antigen in pernicious anemia
H/K ATPase (produces stomach acid)
62
Where is B12 stored
liver, years supply
63
B12 and folate are cofactors for
synth of deoxythymidine from deoxyuridine
64
What does B12 do in DNA synth
accepts a methyl group from methyl-THF -> 2 imp cmpds (methylcobalamin and reduced THF)
65
What is methylcobalamin needed for
production of metionine from homocysteine
66
what is reduced THF needed for
needed as the single carbon donor in purine synth
67
How does B12 def affect DNA synth
- no more reduced THF
| - imapir DNA snyth bc of low purine production
68
How does folate help in B12 def, what happens
other reduced folates may substitute for THF
- but can't reverse neurological changes
- methyl-THF accumulates (can't be polyglutamated and retained in cell) -> rel folate def in pernicious anemia
69
Demyelination in pernicious anemia
-imbalance of cytokines and growth factors -> nerve damage
70
What happens in methionine in pernicious anemia
-not produced = problem
71
Methionine and TNF
synth of TNF is regulated by S-adenosyl-methionine; get unregulated production of TNF with methionine def
72
Gastric disorders in pernicious anemia
- chronic atrophic gastritis
- tall columnar epithelium is replaced by very thin mucosa, obvious infiltration of plasma cells and lymphocytes
- inc risk of gastric adenocarcinoma
73
Early peripheral blood smear in pernicious anemia
mild macrocytic anemia, large ovoid erythrocytes
74
Full blown megaloblastic anemia blood smear
abnormalities in all cell lines
- significant anisocytosis and poikilocytosis of red cells
- hypersegmented neutrophils
- red and white cells can be mistaken for acute leukemia
75
What are megaloblastic changes
nuclei that are too large and immature in cells with mature, Hb-filled cytoplasm
-seen in bone marrow
76
Why aren't megaloblastic changes seen in peripheral blood smear
abnormal erythrocytes are destroyed in bone marrow (intramedullary hemolysis)
77
Spinal cord abnormalities in pernicious anemia
- demyelination of posterolateral spinal columns = subacute combined degeneration
- demyelination of peripheral nerves
- demyelination -> neuronal cell death
78
Lab findings pernicious anemia
- inc LDH (directly released from lysed rbcs)
- and sometimes indirect bilirubin consistent with the hemolysis occurring in bone marrow (free Hb is metabolized to bilirubin)
- low serum B12
- antibodies to intrinsic factor
79
Serum elevations of what (2) are highly predictive of B12 def
methylmalonic acid (MMA) and homocysteine together
80
Clinical manifestations of pernicious anemia (most common)
anemia is most common and severe (Hb
81
Symps of pernicious anemia
- fatigue, dyspnea, dizziness
- high-output congestive heart failure with tachycardia and L ventricular failure
- inc in 2,3BPG
82
GI symps in pernicious anemia
malabsorption, muscle wasting (unusual), diarrhea (common), glossitis (most common)
83
What symps are least likely to improve with B12 therapy
neurologic symps
84
Neurological symps in pernicious anemia
- paresthesias (most common)
- damage to posterolateral tracts -> positional info -> loss of balance and coordination
- impaired proprioception and vibration sense
- true dementia
