HEMATOLOGY
1. Hematopoiesis
production of blood cells
2. Blood fx
transportation - carry O2, CO2
regulate body temp, pH, electrolytes
transport waste to kidney - excrete as urine
protection - wbc
clotting - stop internal & external bleeding
3. Component - based on density
55% plasma
1% wbc & platelet
45% rbc - Fe heavy, carry O2
4. Site
yolk sac - 1-3 mth embryo
liver & spleen - fetus
BM - 6 mth onwards
tibia
femur
rib
sternum
vertebrae
5. BM environment
fats & rbc wbc
red BM replace by fats - prone to anemia, aging
6. HSC
self-renew
multipotentiality
differentiation - myeloid or lymphoid lineage
7. Surface markers
identification for cells - Ag
flow cytometry - cell pass laser beam, fluorescence labeled Ab detect
wbc occupy BM, suppress rbc, cause anemia & thrombocytopenia
8. Cytokines/HGF
regulator - protein/peptide/hormone - myeloid, lymphoid
9. Cytokines fx
fx stimulation
maturation induction
differentiation commitment
proliferation
survival
10. Erythropoiesis 4-10d
hypoxia - low rbc count, low Hb amount, low O2 availability
EPO stimulate red BM
myeloid progenitor cells
erythroblast
normoblast eject nucleus - biconcave disc, increase surface: volume & density
reticulocyte
increase rbc count
increase O2 carrying ability of blood
11. EPO 7q21
site: kidney
fx:
proliferation
differentiation
survival
clinical use:
anemia
reduction of blood transfusion in elective surgery
autologous blood donation
12. Granulopoiesis 6-10d
myeloid progenitor
myeloblast
promyelocyte
myelocyte
meta myelocyte
N - bacteria & fungal
circulating n - free flow in bloodstream
marginating n 6-10h - can exit BV
E - parasite, allergy
B - hypersensitivity
13.
GM-CSF
G-CSF
M-CSF
IL-3
IL-5
IL-6
14. Thrombopoiesis
myeloid progenitor
megakaryoblast
promegakaryocyte
megakaryocyte
platelet
15. TPO 3q27-28
site: liver
clinical use:
chemo
platelet transfusion
RBC pathophysio
1. RBC membrane
vertical interaction: stabilize
horizontal: support sx integrity
2. membrane ds
vertical: spherocytosis
horizontal: elliptocytosis, ovalocytosis
cholesterol: acanthocytosis - spikes
hydration: stomatocytosis/xerocytosis
3. met
to survive 120d
supply energy
reduce oxidant
Hb in reduced state
release of O2
4. Embden Meyerhof pathway
anaerobic glucose met
enzyme: pyruvate kinase
product: 2 pyruvate, 4 ATP, 2 NADH
5. Hexose Monophosphate
prevent oxidative stress
enzyme: G6PD
H2O2 to H2O
6. MetHb reductase
Fe3+ to Fe2+
Fe2+ as reduced state to able carry O2
7. Leubering Rapoport shunt
enzyme: mutase
product: 2,3 DPG regulate O2 release from Hb
8. O2 dissociation curve
left shift
high O2 affinity
low H
low PCO2
low temp
CO poison
9. Hb tetramer
4 polypeptide
2a chr16 + 2b globin chr11 + 4 heme + 4 Fe + 4 O2
10. why Hb got differ subtype
gene mutation
11. Heme
Fe
site: mitochondria, cytosol
4 pyrrole rings thro methenyl bridge
biosynthesis:
12. Porphyrias
13. Aging & destruction
macrophage eat rbc
deconstruct back to aa & heme
heme
billiverdin
billirubin
excrete in bile
intestine
urobillinogen
urobillin
excrete to kidney as urine
if stercobillin - feces
Anemia class
1. define
BM has capacity to increase RBC production 5-10x
inadequate O2
not ds, exp of an underlying ds
2. clinical symptom
reduction in blood transport of O2 - deficiency in RBC
FBC/CBC parameter:
decrease Hb, RBC count, Hct/PCV
3. diagnosis
patient H/O, physical exam, lab, identification of cause
4. rapid develop if
inadequate compensatory mechanism from BM
when RBC loss or destruction exceeds capacity of production
when BM production impair
5. pathophysio
insufficient Fe, B12, folate
inefficient BM infiltration
hemorrhage, excessive destruction - reduced cell lifespan
pooling - hypersplenism
6. H/O
age, sex, geographic location, lung ds
nutritional deficiencies
external/internal blood loss
increase RBC destruct
decrease RBC produce
BM patho
infection
7. FBC
severe Hb <7
8. morphology
microcytic <80fL:
Fe def
thalassemia
chronic ds
normocytic:
aplasia
protein malnutrition
chronic renal failure
post-hemorrhagic
macrocytic >100:
B12 def
folate
myelodysplasia
chemotherapy
liver ds
increased reticulocytosis
myxedema =hypothyroidism
9. reticulocyte
immature RBC
reticulofilamentous materials = RNA
stains grey-blue with supravital stain - methylene blue or brilliant cresyl blue
10. reticulocyte count
% of total no of RBC in blood
NR adult: 0.5-2.5
infant: 2-6
if low, inadequate BM response
if high, overproduce RBC - may compensate for hemolysis/hemorrhage
11. high Hb
smoke
live at high altitude
chronic hypoxemic lung ds
right to left intracardiac shunts
low Hb
African descent
pregnancy
endurance athlete
elderly
12. MCV<80
IDA
thalassemia
chronic inflammation
MCV80-100
chronic kidney ds
acute blood loss
chronic inflammation
hospital acquired anemia
MCV>100
megaloblastic
non megaloblastic - alcohol, liver ds, hypothyroidism, myelodysplastic syndrome
13. hypo proliferative
ret index <2
chronic inflammation
nutrient def
hormone def
BM failure
hospital
hyper >3
acute blood loss
hemolysis - G6PD
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