week 10 Flashcards
Where does haemopoeisis occur in the embryo 2
yolk sac
liver
where does haemopoeisis occur in the foetus
liver
spleen
where does haemopoeisis occur in a developed feotus
bone marrow
where does haemopoesis occur in an adult 5
bone marrow of skull ribs and sternum
tibula and femur
what type of cell is the haematopoetic stem cell (multipotent., pleuripotent, unipotent)?
Pleuripotent
why is a HSC pluripotent 3
self renewing
ability to make any blood cell
can also make non haematopoetic stem cells
what does cytosis or philia mean
over production
what does penia mean
underproduction
what do colony stimulating factors stimulate
they stimulate different stafes of haematpetic stem cell differentiation
what are the colony stimulating factors 3
M-CSF
GM-CSF
G-CSF
what does M-CSF do
HSC into monocytes and macrophages
what does GM-CSF do
HSC into granulocytes and macrophages
what does G-CSF do
stimulates neutrophil release from the bone marrow
what does thrombopoeitin do
increase the production and maturation of platelets from megakaryocytes
structure of red blood cells
biconcave disc
lack of nucleus
where does haem synthesis begin
in the mitochondria
process of haem synthesis 3
amino acids converted into immediates known as porforins
porforins and iron bound together = produces haem
haem bound with haemoglobin protein chains
structure of haemoglobin
4 protein chains; two alpha and two beta
haemoglobin F 2
foetal haemoglobin dominant till birth
contains alpha and gamma chains
what has a higher affinity for oxygen Haemoglobin F or Haemoglobin A
Haemoglobin F
What happens morphologically to erythroblasts as they mature 4
cell size and nucleus decreases
cytoplasmic ratio increases
cytoplasmic staining changes from blue to pink
nucleus eventually disappears
where is erythropoetin released from
by the JG cells of the juxtamedullary apparatus in the kidneys
EPO production and stimulation of erythrocyte production
oxygen assessed at kidneys
if insufficient EPO released
stimulates the bone marrow
increases RBCs
increases haemoglobin oxygen
detected by kidneys
stop releasing EPO
where is the spleen located
left upper hypochondriac abodominal quadrant beneath ribs 9-11
where is thymus located
bilobed organ located under the sternum, above the heart
function of spleen4
immune response
removes old/dysfunctional RBCs
iron recycling
haemoptosis in foetus
white pulp key function
immune response
function of red pulp
filter and remove bad RBCs
marginal sinus of the spleen
plexus of veins located between the white pulp and red pulp
what is the marginal zone of the spleen
areas surrounding the marginal sinus containing specialised macrophages and b cells
what do periarteriolar lymphoid sheats (PALS) contain in the spleen
T cells and DCs
marginal sinus of the lymph node
channels through which lymph travels through the lymph node
movement of lymph through a lymph node 7
afferent lymph vessels
marginal sinus
cortex
paracortex
medulla
medullary sinus
efferent lymphatic vessels
which follicle, primary or secondary, in the lymph nodes is the germinal centre for b cells
secondary follicles
what doe the medullary cords of lymph nodes contain 1
plasma cells whcih produce antibodies which then rapidly enter the blood stream
progression of lymph vessel structure
lymph capillary->lymphatc vessels->lymphatic trunk->lymphatic duct
right sided lymphatic drainage
drains via right lymphatic duct->right subclavian
equates to drainage of 1/3rd of body
left sided lymphatic drainage
drains via large thoracic duct->left subclavian vein
equates to drainage of 2/3rds of body
important lymph nodes in the head 2
auricular and occipital
important lymph nodes in the neck
cervical chains
important lymph nodes in the upper limbs
axillary
important lymph nodes in the upper chest
mediastinal
important lymph nodes in the abdomen
coeliac
important lymph nodes in the pelvis 3
external iliac
common illiac
inguinal
important lymph nodes in the lower limbs
popliteal
what is the plant version of iron and what is its 2 property
Fe3+ it has high soluability but low oxygen affinity
what is the animal product of iron and what is its two properties
Fe2+ it has low soluability and high oxygen affinity
what transporter transports iron from the intestinal lumen into the enterocyte
DNMT-1 transporter
what transporter tranports iron from the enterocyte into the bloodstream
ferroportin
what transporter transports the iron around the body via the the bloodstream
transferrin
process of iron absorption 3 chunky
- Fe3+ converted to Fe2+ by DNMT1 transporters as all iron transporter from intestinal lumen into enterocytes
- All Fe2+ in enterocyte transported into bloodstream via ferroportin
- All fe2+ changed to Fe3+ by transporter transferrin and then transported arouond the body
what facttors influence iron absoption 4
hypoxia
erythropoeitin
inflammation
haemochromatosis
how does hypoxia influence iron absorption 2
increases DNMT1
decreases hepacidin
=
increased iron absorption
how does erythropoeitin influence iron absorption
decreases hepacidin
how does inflammation influence iron absorption
increases hepacidin
how does haemochromatosis influence iron absorption
decreases hepicidin
ferritin
globular protein taht stores iron
apoferritin
stores iron in organs such as the liver
transferrin role
transports iron around the blood
it regulates iron levles
hepacidin (function, were produced, when produced)
binds to ferroportin and degrades it preventing the release of iron into the blood stream
released during inflammation, infection and when iron stores are high
produced by the liver
types of microcytic anaemia
(TAILS)
thalassemia
chronic disease anaemia
iron deficiency anaemia
lead poisoninig
sideroblastic anaemia
types of macrocytic anaemia
(FATRBC)
Folate deficiency
Alcoholic liver disease
Hypothyroidism
Reticulocytosis
B12 deficiency
Cirrhosis
2 ways that anaemia is classified
size via mean cell volume
reticulocyte count
low reticulocyte count anaemia causes (MARBL)
myelofibrosis
aplastic anameia
renal failure
bone marrow failure
leukaemia
high reticulocyte count anaemia causes 1
sickel cell disease
thalassemia
reduction/absence of a globin chain (Haemoglobin) resulting in the imabalance of alpha and beta chains
alpha thalassemia
deletions in the globin alpha locus causing impaired/absent production of alpha chains
results in excessive beta chains
beta thalassemia
mutations in the haemoglobin beta locus resulting in impaired/absent production of beta globin chains
genetic differences between alpha thalassemia and beta thalassemia 2each
alpha:
due to deletions
affects chromosome 16
beta:
due to mutations
affects chromosme 11
thalassemia minor
individual has one normal and one mutated/deleted gene
thalassemia major
both gense for the loci are affected
what is the consequence of thalassemia (3 steps)
abnormal haemoglobin molecules
cuases structural changes to RBCS
RBCS have shorter lifespans and reduced oxygen carrying capacity
majore consequence of beta thalassemia major
iron overloading which results in iron deposition in organ tissues
complications of iron overloading (heart, liver, endocrine, bone marrow, immune system)
heart = heart failure
liver = cirrhosis and fibrosis
endocrine = diabeters and hypothyroidism
bone marrow suppression leading to reduced erythropoeisis
immune system weakened
causes of iron deficiency anaemia 5
increased demand without supply - kids and pregnancy
dietary lack
malabsorption due to GIT issues
bleeding incl menstruation GI malignancy
impaired iron recycling
which population groups are most at risk to becoming anaemic 4
pregnant women
non pregnant women
children
elderly
4 mechanisms for anaemia pathogenesis in chronic inflammatory diseases
mech 1: inflammation->cytokines->increases hepcidin->degrades ferroportin->iron not released from enterocytes
mech 2:inflammation->cytokines->haemopoesis bias to myeloid cell production->inhibits erythropoeis
mech 3: inflammation->cytokines->activate macrophages to initiate erythropoeisis
mech 4: inflammation->cytokines->reduces erythropoeitin
food pairing to increase iron (one to do two to avoid)
vitamin c w high iron meals
avoid: caffeine+dairy w high iron meals
what decreases iron absorption 4
caffeine
dairy
reduced stomach acids
antacid usage
what increases iron absorption 4
stomach acid
vitamin c
meat factor protein
high demand for RBCs
where does vitaminb12 absorption occur
in the ileum of the small intestine
where is folate absorbed
in the duodenum and jejunum
why are b12 and folate important in erythropoeisis
help in RBC production, formation and maturation
what can macroyctic anaemia be further subdivided into 2
magaloblastic or non megaloblastic
the 2 causes of megaloblastic anaemia
b12 deficinecy
folate deficiency
megaloblastic def
erythroblasts have delayed nucleus maturation due to defective DNA synthesis
causes of b12 deficiency (think Joe 2)
veganism
crohn’s disease
causes of folate deficiency 6
povery
old age
pregnancy
cancer
liver disease
alcoholism
autoimmune causes of b12 deficiency mech 3
- autoimmune destruction of the stomach’s gastric mucosa
- lack of intrinsic factor seceretion
- prevents b12 absorption
anticonvulsants and associated anaemia
causes folate deficiency
3 key characteristics of haemolytic anaemia
increased red cell breakdown
increased red cell production
damaged red cells
intrinsic haemolytic anaemia def 2
hereditary red blood cell defects due to gene mutations and G6PD deficiency
extrinsic haemolytic anaemia (3 examples of causes)
acquired red blood cell defects which can be due to:
- drugs
- autoimmune
- infection
intravascular haemolytic anaemia 2
occurs within blood vessels
indication is fragemnetd RBCs present in blood
extravascular haemolytic anaemia
occurs outside of blood vessels in locations such as the spleen and liver
sickle cell disease 2
due to amino acid swap in beta globulin gene
autosomal recessive
sickle cell disease = homoxygous
sickle cell trait = heteroxygous
results of sickle cell disease 5
- redcued oxygen carrying capacuty due to morphology
-tissue damage due to morphology
-shorter lifespan
-more prone to ruptue
-increase blood viscosisty
general organ tests when suspecting anaemia 3
thyroid function
renal function
liver functino
specific blood tests 6
CBE
blood film
iron studies
vitaminb12 and follate assay
Hb electrophoresis
bone marrow biopsy
indications of haemolysis
high bilirubin
high reticulocyte count
high LDH
anaemia management (case dependent but…)
vitamin b12/folate injection
iron replacement
transfusion
