Haem- physiology and pathophysiology Flashcards
what is blood
a specialised fluid (tissue) composed of cells suspended in a liquid (plasma)
three types of blood cells
red blood cells
white blood cells
platelets
Haematopoiesis
production of blood cells
site of Haematopoiesis in an embryo
yolk sac (stops by week 10)
then liver (starts by week 6)
then marrow (starts by week 16)
3rd-7th month in the spleen
site of Haematopoiesis at birth
mostly bone marrow, liver and spleen when needed
site of Haematopoiesis from birth to maturity
number of active sites in bone marrow decreases but retain ability for haematopoiesis
site of Haematopoiesis in adults
haematopoiesis restricted to skull, ribs, sternum, pelvis, proximal ends of femur (axial skeleton)
different types of white blood cells
granulocytes
monocytes
lymphocytes
examples of granulocytes
eosinophils
basophils
neutrophils
neutrophils granules
neutral staining granules
function of neutrophils
immediate defence cell- phagocytosis
most abundant white blood cell
neutrophils
neutrophils nucleus
segmented nucleus
eosinophils nucleus
bilobed nucleus
eosinophils granules
bright orange/red granules
function of eosinophils
fight parasitic infections
involved in hypersensitivity- allergies
basophils granules
large deep purple granules obscuring nucleus
contain histamine
largest type of white blood cell
monocyte
monocytes become-
macrophages
which cell is longer lived- monocytes/neutrophils
monocytes
Immunophenotyping
expression profile of proteins (antigens) on the surface of cells
Bioassays
culture in vitro and show lineage of progeny in different growth conditions
common sites for bone marrow aspiration and biopsy
posterior iliac crests/sternum
tibia in children
RBCs structure
biconcave disc
flexible
PROS AND CONS of RBCs being full of haemoglobin
pros- carries oxygen
cons- high oncotic pressure, oxygen rich environment (oxidation risk)
PROS AND CONS of RBCs having no nucleus
pros- more deformable, and more room for Hb molecules
cons- can’t divide, can’t replace damaged proteins - limited lifespan
PROS AND CONS of RBCs high surface area/volume ratio
pros- gas exchange
cons- need to keep water out
PROS AND CONS of RBCs flexibility
pros- to squeeze through capillaries
cons- specialied membrane requirements that can go wrong
structure of haemoglobin
tetrameric globular protein
one haem group attached to each globular chain
which is the major form of haemoglobin present in adults
HbA
HbA structure
2 alpha chains
2 beta chains
HbA2 structure
2 alpha chains
2 delta chains
HbF (fetal haemoglobin) structure
2 alpha chains
2 gamma chains
alpha like genes are on chromosome _
16
beta like genes are on chromosome _
11
functions of haemoglobin
delivers oxygen to tissues
acts as a buffer for H+
CO2 transport
Erythropoiesis
production of red blood cells
where does red cell destruction usually take place
spleen (and liver)
average lifespan of a red blood cell
120 days
carbon dioxide transport distribution
10% disolved in solution
30% bound to carbamino-Hb
60% bicarbonate
oxygen dissociation curve for Hb shape
sigmoidal
neutrophils lifespan
7-8 hours
platelets lifespan
7-10 days
where do haemopoietic stem cells originate embryonically
mesoderm
bone marrow
a complex organ surrounded by a shell of bone with a neurovascular supply
increase in yellow/red marrow with age
yellow- inactive marrow
ferric form of iron
Fe3+
ferrous form of iron
Fe2+
where does iron absorption mainly occur
duodenum
how many oxygen molecules can each haemoglobin bind
up to 4
how much atoms of iron does each haemoglobin molecule contain
4
how do the oxygen saturation curves of foetal Hb and myoglobin compare to that of adult Hb
both are shifted to the left of that of adult Hb
cooperative binding occurs between which molecules during oxygen transport
oxygen binding to haem
what does 2-3 DPG binding promote
the release of oxygen from haemoglobin
what is the effect of 2-3 DPG on the oxygen saturation curve
shifts the curve to the right
-penia =
shortage of
-cytosis or -phillia =
an excess
platelets nucleus
anucleate
where are platelets formed
in marrow
For a day or two the new red cell looks a bit more blue than older ones on the blood film.
Why?
The more immature cells have some RNA in them still
what is Malignant haemopoiesis usually characterised by
increased numbers of abnormal and dysfunctional cells
loss of normal activity
Malignant haemopoiesis due to
Increased proliferation
Lack of differentiation/maturation
Lack of apoptosis
driver mutations
confer growth advantage on the cells and are selected during evolution of the cancer
passenger mutations
happen to be present in an ancester of the cancer cell when it acquired one of its drivers- ‘bystander’
‘clones’
population of cells derived from a single parent cell
types of lymphocytes
B cells
T cells- T helper cells, T cytotoxic cells
NK cells
Predominant B cell immune response-
autoimmune conditions
infection
Predominant T cell immune response
viral infections, drugs e.g. phenytoin, dermatopathic
Troiseries sign
Virchows node- enlargement of a left-sided supraclavicular lymph node indicating metastasis from an abdominal malignancy
Sentinel lymph node
the first lymph node to which cancer cells are most likely to spread
spleen location
located high in the left upper quadrant of the abdomen
spleens vascular supply
Supplied by splenic artery and drained by splenic vein
function of the spleen
acts as a filter for the blood
features of hyposplenism in the blood
Howell-Jolly bodies
monocyte nucleus
single nucleus that is usually kidney-shaped, but can also be round, folded, indented, or horseshoe-shaped
philadelphia chromosome
t (9:22)
where are mast cells derived from
common myeloid progenitor cells
What usually stimulates platelet production
thrombopoietin
