PHYSIOLOGY Flashcards
where are bone marrow biopsy/aspirates taken from
PSIS
bone marrow hyperplasia definition
increased bone marrow production
bone marrow dysplasia definition
disordered bone marrow production
bone marrow hypoplasia definition
decreased bone marrow production
bone marrow aplasia definition
no bone marrow production
hypercellular bone marrow definition
increased cell production (eg RBCs) from bone marrow
hypocellular bone marrow definition
decreased cell production (eg RBCs) from bone marrow
what is in yellow marrow
fat
what is in red marrow
the haemopoietically active bit
whats the normal ratio of red to yellow marrow
50:50
what does yellow>red marrow mean
is it hypo or hypercellular
bone marrow suppression
hypocellular (the red bit is the active bit)
causes of hypocellular bone marrow
drug induced aplasia
aplastic anaemia
what does red>yellow marrow mean
is it hypo or hypercellular
bone marrow over activation
hypercellular (the red bit is the active bit)
causes of hypercellular bone marrow
peripheral destruction of cells eg hypersplenism, autoimmune haemolytic anaemia
what is immunophenotyping of cells used for
to tell which lineage a cell has come from
by looking at antigen expression
what does -cytosis mean
high …
what does -philia mean
high …
what does -penia mean
low …
which cells have the ability to self renew
stem cells
which hormone produced by the kidney regulates the production of RBCs
EPO (erythropoietin)
which hormone regulates production of platelets
thrombopoietin
where does haematopoiesis start in the fetus
yolk sac
which bones does haematopoiesis occur in in the fetus
all bones
which bones does haematopoiesis occur in in the adult
skull ribs sternum proximal humerus pelvis proximal femur
where do you get bone marrow samples from in children
tibia
how long do RBCs live for
3-4 months
what is the process of making RBCs called
erythropoiesis
another name for RBCs
erythrocytes
what is the function of RBCs
to carry oxygen in the blood to tissues
how is most oxygen transported in the blood
what % is bound to haemoglobin
60% dissolved as bicarbonate
30% transported by binding to haemoglobin
10% dissolved in solution
apart from directly binding O2 to hemoglobin, what other function does RBCs have in transporting O2 in the blood
RBCs are need to make bicarbonate (which is how 60% of O2 is transported)
what are the RBC precursors (in order) (4 precursors)
stem cells
common myeloid progenitor cell
erythroblast/normoblast
reticulocyte
then erythrocyte (RBC)
what genetic material does an erythroblast contain
has a nucleus
what genetic material does a reticulocyte contain
has RNA
what genetic material does an erythrocyte contain
none!
what do reticulocytes look like in comparison to RBCs
bigger
more purple
as RBCs develop during erythropoiesis, what is added to each of the cell types to form the next
what is taken away, by what process
haemoglobin is added
genetic material is removed = enucleation
when is EPO produced by the kidneys
hypoxia (occurs with anaemia)
what happens to RBC production in kidney failure
decreased = anaemia
bc kidneys cant sense hypoxia = cant produce EPO = no negative feedback to compensate for anaemia
what does EPO (erythropoietin) directly do
causes erythroid hyperplasia = increased RBC production in bone marrow
what shape are RBCs
biconcave
do RBCs have a nucleus
no - no DNA, enucleation occurs to produce RBCs
do RBCs have mitochondria
no
the nucleus of what cell type should be the same size as a RBC
nucleus of lymphocyte = same size as RBC
in the mitochondria, what 2 things combine to make a haem group
Fe2+ and photoporphyrin ring
what do haem groups bind with to make haemoglobin
where does this happen
globin
in the cytoplasm
in adults (HbA) what are the 4 haemoglobin subunits
2 alpha
2 beta
in fetus (HbF) what are the 4 haemoglobin subunits
2 alpha
2 gamma
which state must iron be in for O2 to bind to
Fe2+
if Fe3+ needs to be reduced
where is iron absorbed
duodenum
is haem iron or non-haem iron better absorbed
haem iron
non-haem iron is in plants (veggie diet)
iron transporter between duodenal epithelium and blood stream (for iron to be transported in blood)
ferroportin
how is free iron transported round the body in the blood
as transferrin
where is the majority of the bodys iron
where else is it
70% in haemoglobin
rest; liver, bone marrow, macrophages etc
why must Fe2+ be bound (ie to oxygen or transferrin)
otherwise free radical production
in what form is iron stored in the liver
ferritin (also small amount in blood as ferritin)
which parts of the body have transferrin receptors (hence transferrin can transport iron there)
liver
bone marrow
marker of circulating iron
transferrin
marker of iron stores
serum ferritin - small amount of ferritin in blood is representative of the ferritin stores in liver/macrophages
excretion of iron
doesn’t happen naturally
need iron chelating drugs to excrete in urine/faeces
how many oxygens bind to 1 haemoglobin subgroup
how many oxygens bind to 1 RBC
1 O2 per subgroup
4 O2 per RBC (bc 4 subgroups)
how does oxygen bind to RBCs
what does this mean
what shape of curve does this produce on a graph
by cooperative binding
once one O2 has bound, there is increased affinity for the next O2 to bind = allosteric effect
sigmoidal curve
does fetal Hb saturate more or less at the same pO2 compared to adult Hb
saturates more at same pO2 = bc needs to take O2 from maternal circulation
methods of shifting O2-Hb curve to the right (ie increasing O2 binding when higher O2 demands)
increase temp
increase CO2
increase DPG
DEcrease pH - rest are increase!
what shunt generates DPG
what is this important for
rapapoport-lubering shunt
shifts the O2-Hb curve to the right = increases O2 binding
how much O2 does 1g of saturated Hb bind
1.34ml O2
where are RBCs destructed
spleen
what cells remove old RBCs from circulation and take them to the spleen for destruction
macrophages
in RBC destruction, what are globin chains broken down into
amino acids
in RBC destruction, what are the haem groups broken down to
porphyrin ring and Fe2+
in RBC destruction, after haem has broken down into porphyrin ring and Fe2+, what is the porphyrin ring broken down into
then what
haem
then porphyrin ring (+ Fe2+)
then biliverdin
then bilirubin
after RBC destruction, where is bilirubin taken to, what happens to it
bilirubin taken to liver
liver conjugates bilirubin = excreted in bile (urine and faeces)
if there is no mitochondria in RBC, where do they get their energy from
glycolysis (needs glucose)
what chemical prevents the oxidation of Fe2+ to Fe3+by free radicals
NADH
what chemical prevents the formation of free radical forming (which is important to prevent oxidative damage to RBCs)
what is this chemical made form
what is the rate limiting enzyme involved in its formation
glutathione (GSH)
made from NADPH
G6PD is the rate limiting enzyme
function of WBCs
fight infection
3 categories of WBCs
monocytes
lymphocytes
granulocytes (3)
3 types of granulocytes
neutrophils
basophils
eosinophils
where do you find monocytes
in circulation
in the tissues they are called macrophages
where do you find macrophages
in tissues
in the circulation they are called monocytes
WBC
larger horseshoe shaped nucleus
monocyte
what does a monocyte look like
how many nuclei
large single horseshoe shaped nucleus
mono= one nucleus
function of monocytes/macrophages
phagocytosis
types of lymphocyte
NK cells
T cells
B cells
dendritic cells
where are T cells made
thymus
T cells = Thymus
where are B cells made
bone marrow
B cells = Bone marrow
what do mature lymphocytes look like
what do activated lymphocytes look like
mature lymphocytes - small, condensed nucleus, rim of cytoplasm
activated lymphocyte - large, ‘open’ nucleus, lots of cytoplasm
when are lymphocytes ‘activated’
viral infection
lymphocytes with lots of cytoplasm and an ‘open’ nucleus
activated lymphocytes = viral infection
what should the lymphocyte nucleus be the same size as
RBC
when do you get lymphocytosis (high lymphocytes)
viral infection
childrens infection
CLL
are granulocytes in the myeloid or lymphoid lineage
myeloid
are platelets in the myeloid or lymphoid lineage
myeloid
are RBCs in the myeloid or lymphoid lineage
myeloid
are lymphocytes (NK cells, B cells, T cells, dendrites) in the myeloid or lymphoid lineage
lymphoid
eosinophil appearance
granule stain
nucleus shape
granules stain red
bi lobed nucleus
neutrophil appearance
granule stain
nucleus shape
neutral stain (don't colour) segmented nucleus (hence polymorph)
basophil appearance
granule stain
nucleus shape
granules stain dark blue (Basophils = Blue)
nucleus is obscured by granules
eosinophil function
parasitic infection
hypersensitivity IgE reaction (allergy)
basophil function
hypersensitivity IgE reactions (contains histamine)
RARE in circulation
neutrophil function
phagocytosis
chemoattraction of other immune cells
margination (stick to vessel walls)
which type of granulocyte is least common in circulation
basophils
what is the circulating version of a mast cell
basophils
another name for neutrophils
polymorphs
which type of granulocyte is most common in circulation
neutrophil
how long is the life span of a neutrophil
clinical significance of this
7-8 hours
in pancytopaenia (bone marrow failure), neutropenia is the first symptom (RBCs last 3 months)
how do steroid cause neutrophilia (high neutrophils)
inhibit margination of neutrophils to vessel walls = more in circulation (not actually ore made)
neutrophilia aetiology
infection
trauma
steroids
life span of platelets
clinical significance of this
7-10 days
need to stop anti platelet (aspirin) 1 week before surgery
function of platelets
stop bleeding via primary haemostasis
platelet precursor
megakaryocyte
how are platelets made from megakaryocytes
‘budding’ cytoplasm ‘buds off’ = platelet
rest of cell remains in bone marrow
what are plasma cells
mature B cells that have returned to bone marrow
where are lymphoid cells made
primary lymphoid tissues - thymus and bone marrow
primary lymphoid tissues
thymus and bone marrow
after production in primary lymphoid tissues (thymus and bone marrow) where do lymphoid cells go
secondary lymphoid organs - lymph nodes, spleen, tonsils
what does the lymph node filter
lymphatic fluid
what does the spleen filter
blood
where does lymph from L torso and arms drain
between L subclavian and jugular veins
where does lymph from R torso and arms and lower limbs drain
thoracic duct (between the R subclavian and jugular veins)
causes of enlarged lymph nodes (4)
local infection
systemic inflammation - TB, autoimmune
malignancy
other stuff - sarcoidosis, SLE
enlarged cervical lymph nodes with atypical lymphocytes
local infection
EBV (glandular fever)
atypical lymphocytes = viral infection
are lymph nodes painful in local infection
yes
bc fast growing
types of malignancy that can present as enlarged lymph nodes
haematological - lymphoma, leukaemia
metastatic
most common cause of enlarged lymph nodes
local infection (though always consider malignancy)
are lymph nodes painful if malignancy cause
no
bc slow growing
consistency of lymph nodes in lymphoma
soft/rubbery
other causes = hard
what aetiology of enlarged lymph nodes causes irregular consistency of hard lymph nodes
metastatic cancer
lymph node biopsy; predominantly B cells
autoimmune condition
infection
lymph node biopsy; predominantly T cells
viral infection
drugs - phenytoin
lymph node biopsy; predominantly phagocytes
tumour
what is accumulation of lymph fluid in the peritoneal cavity called
what causes it
chylous ascites
caused by trauma/obstruction of lymphatic system
causes of splenomegaly
infection eg EBV
portal congestion
haemotological disease eg lymphoma, leukaemia, haemolytic anaemia
inflammatory conditions
how can splenomegaly present on the skin
how does it occur
jaundice
hypersplenism = increased function of spleen =increased destruction of RBCs = increased RBC degradation products (bilirubin) = liver cant cope = accumulation of bilirubin = jaundice
how does hyposplenism present on histology
what are they
how do they occur
Howell joly bodies
RBCs with small fragments of DNA
they are normal RBCs but are usually removed by the spleen, so hyposplenism = underactive spleen = doesn’t remove them
