Haemopoiesis, Spleen and Bone Marrow Flashcards
What is haemopoiesis?
production of blood cells
where does haemopoiesis occur?
bone marrow
bone marrow in infants
extensive throughout skeleton
where is bone marrow in adults found?
pelvis
sternum
skull
ribs
vertebrae
Trephine biopsy
used to take sample of bone tissue
Haemopoietic stem cells
unique ability to give rise to all of the different mature blood cell types
given appropriate stimuli can differentiate into variety of specialised cells
what is the differentiation of Haemopoietic stem cells determined?
-hormones
-transcription factors
-interactions with non-haemopioetic cell types
what cells can Haemopoietic stem cells form?
platelets
basophil
neutrophil
eosinophil
monocyte
t lymphocyte
erythrocyte
Thrombopoiesis
production of platelets
Platelets have no nuclei and are essentially membrane bound fragments of cytoplasm that bud off from megakaryocytes
Erythropoiesis
production of red blood cells
Granulopoiesis
production of neutrophils, eosinophils, and basophils
Monocytopoiesis
production of monocytes
What do granulocytes arise from?
myeloblast cells which in turn arise from common myeloid progenitor cells
what do monocytes do?
Monocytes circulate in the blood for ~1-3 days before moving into tissues where they differentiate into macrophages or dendritic cells
can also perform phagocytosis after recognising antibodies or complements that coat pathogen or by binding directly via pattern-recognition receptors that recognize pathogens.
lymphopoiesis
production of lymphocytes
erthropoietin
Secreted by the kidney and stimulates RBC development
thrombopoietin
produced by liver and kidney regulates production of platelets
sources of HPSC
bone marrow aspiration
GCSF mobilised peripheral blood stem cells
umbilical cord stem cells Leicester has cord bank
haematological procedure
HPSC transplantation
extra medullary hematopoiesis
production outside of the bone marrow -liver, spleen, or other tissues happens in pathological conditions
myelofibrosis or thalassaemia can mobilise into circulating blood to colonise other tissues
what are haemopoietic cells capable of?
self renewal
what is the reticuloendothelial system?
is a network of cells located throughout the body and is part of the larger immune system. The role of this system is to remove dead or damaged cells and to identify and destroy foreign antigens in blood and tissues
what is the reticuloendothelial system made up of?
monocytes
main organs in reticuloendothelial system
spleen and liver
macrophage in liver
Kupffer cell
macrophage in tissue histiocyte
connective tissue
macrophage in microglia
cns
macrophage in peritoneal macrophage
peritoneal cavity
macrophage in red pulp macrophage
spleen
Macrophage - Langerhan
skin and mucosa
RES cells in spleen do what?
filtering blood to remove deformed and old cells from the circulation
red pulp
sinuses lined by endothelial macrophages and cords- remove cells
white pulp
similar structure to lymphoid nodules; contains lymphocytes
stimulate immune system.
functions of spleen in adults
sequestration and phagocytosis
blood pooling
extra medullary haemopoiesis
immunological function
sequestration and phagocytosis
old/abnormal red cells removed by macrophages
blood pooling
platelets and red cells can be rapidly mobilised during bleeding
immunological function of spleen
25% of T cells and 15% of B cells are present in spleen
how does blood enter spleen?
via the splenic artery
White cells and plasma preferentially pass through the white pulp
Red cells preferentially pass through the red pulp
splenomegaly
enlargement of the spleen
Causes of splenomegaly
Back pressure- portal hypertension in liver disease Overwork (red or white pulp) Reverting to what it used to do
-extramedullary haemopoiesis Expanding as infiltrated by cells
- Cancer cells of blood origin e.g. leukaemia
- Other cancer metastases
Expanding as infiltrated by other material
* Sarcoidosis (granulomas)
role of spleen
blood filter
How to examine the spleen
start to palpate in right iliac fossa
feel for spleen edge moving towards your hand on inspiration
measure in cm from costal margin in mid clavicular line
Massive splenomegaly
Chronic myeloid leukaemia
Myelofibrosis
Malaria
Schistosomiasis
Moderate splenomegaly
Lymphoma
Leukaemias
Myeloproliferative disorders
Liver cirrhosis with portal hypertension
Infections such as Glandular Fever
and same as massive
Mild Splenomegaly
Infectious hepatitis
Endocarditis
Infiltrative disorders such as
sarcoidosis
Autoimmune diseases such as AIHA,
ITP, SLE
and same as massive and moderate
hypersplenism
condition in which the spleen removes blood components at an excessive rate
low blood counts can occur due to pooling of blood in enlarged spleen
what to avoid if you have splenomegaly?
avoid contact sports and vigorous activity
risk of rupture if spleen enlarged and no longer protected by rib cage
Hyposplenism
lack of functioning splenic tissue
causes of hyposplenism
splenectomy
sickle cell disease- due to infarcts and fibrosis in liver
gastrointestinal diseases
autoimmune disease
gastrointestinal diseases which forms hyposplenism
Coeliac disease
Crohn’s disease
Ulcerative colitis
autoimmune disorders which forms hyposplenism
Systemic lupus
Rheumatoid arthritis
Hashimoto’s disease
what does a blood film from a patient with hyposplenism show?
Howell-Jollybodies which are basophilic nuclear remnants(clusters of DNA) in circulating erythrocytes. During erythropoiesis erythroblasts normally expel their nuclei but in some cases a small portion of DNA remains. Normally such cells would be removed by the spleen so the presence of Howell-Jolly bodies is a good indicator of reduced splenic function.
what are patients with hyposplenism at risk of?
are at risk of sepsis from encapsulated bacteria
e.g.
* Streptococcus pneumonia
* Haemophilus influenzae
* Meningococcus
Patients must be immunisedand given life long antibiotic prophylaxis
Erythrocytes
red blood cells
what does red blood count show?
how many red blood cells
4.4-5.9 X 10^12
Hb
haemoglobin
how effective?
13.5- 16.7 g/dI
MCV
mean corpuscular volume
how large?
80-100 fI
shape of erythrocytes
shape of erythrocytes
lifespan of erythrocytes
120 days
Functions of Erythrocytes
Deliver oxygen to tissues
Carry haemoglobin
Maintain haemoglobin in its reduced (ferrous) state
Maintain osmotic equilibrium
Generate energy
Haemoglobin
Tetramer of 2 pairs of globin chains each with its own haem group
Globin gene clusters on Ch 11 & 16
Different globin chains combine to form different haemoglobins with different properties
when does haemoglobin switch from fetal to adult?
at 3-6 months
2 configurations of Hb
oxyhaemoglobin- relaxed binding structure
deoxyhaemoglobin- tight binding structure
When shifting between the oxygen unbound and oxygen bound states haemoglobin undergoes a conformational change which enhances the binding affinity of subsequent oxygen molecule
Haemolytic anaemia
Anaemia with chronic premature destruction of red blood cells
what changes shape in RBC shape?
changes in the components of the cell membrane
what happens if there’s changes in plasma membrane
less deformable and more fragile
spectrin
actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton.
what proteins are involved in hereditary spherocytosis?
spectrin
ankyrin
band 3
protein 4.2
Ankyrin
links integral membrane proteins to the underlying spectrin-actin cytoskeleton.
band 3
facilitates chloride and bicarbonate exchange across membrane and also involved in physical linkage of
membrane to cytoskeleton (binds with ankyrin and protein 4.2).
protein 4.2
ATP-binding protein which may regulate the association of band 3 with ankyrin
what causes jaundice?
excess unconjugated bilirubin in blood
faeces
brown colour comes from sterocobilin
urine
yellow colour comes from urobilin
degradation of haem
- The haemoglobin removed from senescent erythrocytes is recycled by the spleen being degraded to its constitutive amino acids and haem
- haem metabolised to bilirubin,
- bilirubin removed in the liver where it is conjugated with glucuronic acid and secreted in bile.
- Bacteria in the intestines deconjugate and metabolise the bilirubin into colourless urobilinogen which is subsequently oxidized to form stercobilin
- A smaller amount of the urobilinogen is reabsorbed into blood and processed by the kidneys where it is oxidised to urobilin
How is unconjugated bilirubin transported in the blood?
bound albumin
Cytopenia
reduction in the number of blood cells
cytosis
increase in the normal of blood cells
decrease and increase of RBC
Increase- erythryocytosis
decrease- anaemia
increase and decrease of wbc
increase- leucocytosis
decrease- leucopenia
increase and decrease of lymphocytes
increasing- lymphocytosis
decrease- lymphocytopenia
increase and decrease of monocytes
increase- monocytosis
decrease- monocytopenia
increase and decrease neutrophils
increase- neutrophilia
decrease- neutropenia
increase and decrease eosinophils
increase- eosinophilia
decrease- eosinopenia
increase and decrease basophils
increase- basophilia
decrease- basopenia
thrombocytosis
abnormally high platelet count
Thrombocytopenia
low platelet count
Panmyelosis
increased level of all bone marrow components, red blood cells, white blood cells, and platelets
Neutrophils
A type of white blood cell that engulfs microbes by phagocytosis
First-responder phagocyte
Most common white cell
Essential part of innate immune
system
Circulate in bloodstream & invade
tissues – live for 1-4 days
what controls maturation to form neutrophils
hormone G-CSF, a glycoprotein growth factor & cytokine
what do hormone G-CSF do?
Increases production of neutrophils
* Speeds up release of mature cells from BM
* Enhances chemotaxis
* Enhances phagocytosis and killing of pathogens
what is administered when more neutrophils needed?
recombinant g-csf is routinely administered
Neutrophilia
increase in the number of circulating neutrophils
Causes of neutrophilia
- Infection
- Tissue damage
- Smoking
- Drugs (e.g. steroids)
- Myeloproliferative diseases
- Acute inflammation
- Cancer
- Cytokines (G-CSF)
- Metabolic disorders
- Endocrine disorders
- Acute Haemorrhage
haemorrhage
brings more cells out from marginated pool
Neutropenia
decreased number of neutrophils in the blood
< 1.5 x 10^9
Causes of neutropenia
reduced portion: B12/folate deficiency, infiltration, aplastic anaemia, radiation, viral infection, congenital, drugs
increased removal: immune destruction, sepsis, splenic pooling
consequences of neutropenia
Severe life threatening bacterial infection
Severe life threatening fungal infection
Mucosal ulceration e.g. painful mouth ulcers
what is neutropenic sepsis?
medical emergency
intravenous antibiotics must be given
monocytes
move into tissues where they differentiate into macrophages or dendritic cells.
protect tissues from foreign substances by phagocytosis, antigen presentation and cytokine production.
Monocytes in the blood can also perform phagocytosis after recognising antibodies or complement that coats pathogens or by binding directly via pattern- recognition receptors that recognize pathogens.
How long do monocytes circulate in the blood?
1-3 days
Causes of monocytosis
Bacterialinfectione.g.tuberculosis
Inflammatoryconditionse.g.rheumatoidarthritis,Chron’s Ulcerative colitis
Carcinoma
MyeloproliferativedisordersandLeukaemias
Eosinophils
Responsible for immune response against multicellular parasites e.g. Helminths
Mediator of allergic responses
Phagocytosis of antigen - antibody complexes
How long do eosinophils circulate?
3 - 8 hours
life span of eosinophils
8 -12 days
life span of eosinophils
Granules contain array of cytotoxic proteins (e.g. eosinophil cationic protein & elastase)
what happens if eosinophils inappropriately activated?
responsbile for tissue damage and inflammation e.g. in asthma
common causes of eosinophilia?
allergic diseases
parasitic infection
drug hypersensitivity
charge-strauss- inflammation of small blood vessels
skin diseases
Rare causes of eosinophilia
hodgkin lymphoma
actuel lymphoblastic leukaemia
actue myeloid leukaemia
myeloproliferative conditions
eosinophilic leukaemia
idiopathic hypereosinophilic syndrome
basophils
active in allergic reactions and inflammatory conditions
large granules containing histamine, heparin, hyaluronnic acid, serotonin
Reactive Basophilia
Immediate hypersensitivity reactions
Ulcerative Collitis
Rheumatoid Arthritis
myeloproliferative basophilia
CML
MPN: ET/PRV/MF
Systemic mastocytosis
Where do lymphocytes come from?
bone marrow
lymphocytes
A type of white blood cell that make antibodies to fight off infections
B cells (B lymphocytes)
specialized lymphocytes that produce antibodies forming cells
attack invaders outside cell
T cells (T lymphocytes)
lymphocytes that mediate cellular immunity;CD4 + helper cells, CD8 + cells
attacked infected cells
Natural Killer cells
A type of white blood cell that can kill tumor cells and virus-infected cells; an important component of innate immunity.
cell mediated cytotoxicity
Reactive Lymphocytosis
Viral infections
Bacterial infections-especially whooping cough
Stress related: MI/cardiac arrest
Post splenectomy
Smoking
Lymphoproliferative
The proliferation of the bone marrow cells that give rise to lymphoid cells
Lymphoproliferative Lymphocytosis
- Chronic Lymphocytic Leukaemia (B
cells) - T- or NK- cell leukaemia
- Lymphoma (cells ‘spill’ out of infiltrated bone marrow)
what increases haemoglobin affinity for oxygen and which way does the graph move?
decrease in 2-3-DPG
decrease temp
decreases in partial pressure of carbon dioxide
increase pH
graph moves to the left
what decrease haemoglobin affinity for oxygen and which way does the graph move?
to the right
increase 2-3-DP, temp, particle pressure of carbon dioxide
decrease pH
which organ is responsible for endogenous production of erythropoietin?
kidney
Erythropoietin
A hormone produced and released by the kidney that stimulates the production of red blood cells by the bone marrow.
what long term treatment in given to patient that has had a splenectomy?
vaccination against Haemophilus influenzae
panctyopenia
deficiency of all types of blood cells
