Haemopoiesis, Spleen and Bone Marrow Flashcards

1
Q

What is haemopoiesis?

A

production of blood cells

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2
Q

where does haemopoiesis occur?

A

bone marrow

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3
Q

bone marrow in infants

A

extensive throughout skeleton

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4
Q

where is bone marrow in adults found?

A

pelvis
sternum
skull
ribs
vertebrae

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5
Q

Trephine biopsy

A

used to take sample of bone tissue

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6
Q

Haemopoietic stem cells

A

unique ability to give rise to all of the different mature blood cell types
given appropriate stimuli can differentiate into variety of specialised cells

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7
Q

what is the differentiation of Haemopoietic stem cells determined?

A

-hormones
-transcription factors
-interactions with non-haemopioetic cell types

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8
Q

what cells can Haemopoietic stem cells form?

A

platelets
basophil
neutrophil
eosinophil
monocyte
t lymphocyte
erythrocyte

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9
Q

Thrombopoiesis

A

production of platelets
Platelets have no nuclei and are essentially membrane bound fragments of cytoplasm that bud off from megakaryocytes

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10
Q

Erythropoiesis

A

production of red blood cells

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11
Q

Granulopoiesis

A

production of neutrophils, eosinophils, and basophils

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12
Q

Monocytopoiesis

A

production of monocytes

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13
Q

What do granulocytes arise from?

A

myeloblast cells which in turn arise from common myeloid progenitor cells

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14
Q

what do monocytes do?

A

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.

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15
Q

lymphopoiesis

A

production of lymphocytes

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16
Q

erthropoietin

A

Secreted by the kidney and stimulates RBC development

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17
Q

thrombopoietin

A

produced by liver and kidney regulates production of platelets

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18
Q

sources of HPSC

A

bone marrow aspiration
GCSF mobilised peripheral blood stem cells
umbilical cord stem cells Leicester has cord bank

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19
Q

haematological procedure

A

HPSC transplantation

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20
Q

extra medullary hematopoiesis

A

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

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21
Q

what are haemopoietic cells capable of?

A

self renewal

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22
Q

what is the reticuloendothelial system?

A

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

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23
Q

what is the reticuloendothelial system made up of?

A

monocytes

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24
Q

main organs in reticuloendothelial system

A

spleen and liver

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25
macrophage in liver
Kupffer cell
26
macrophage in tissue histiocyte
connective tissue
27
macrophage in microglia
cns
28
macrophage in peritoneal macrophage
peritoneal cavity
29
macrophage in red pulp macrophage
spleen
30
Macrophage - Langerhan
skin and mucosa
31
RES cells in spleen do what?
filtering blood to remove deformed and old cells from the circulation
32
red pulp
sinuses lined by endothelial macrophages and cords- remove cells
33
white pulp
similar structure to lymphoid nodules; contains lymphocytes stimulate immune system.
34
functions of spleen in adults
sequestration and phagocytosis blood pooling extra medullary haemopoiesis immunological function
35
sequestration and phagocytosis
old/abnormal red cells removed by macrophages
36
blood pooling
platelets and red cells can be rapidly mobilised during bleeding
37
immunological function of spleen
25% of T cells and 15% of B cells are present in spleen
38
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
39
splenomegaly
enlargement of the spleen
40
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)
41
role of spleen
blood filter
42
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
43
Massive splenomegaly
Chronic myeloid leukaemia Myelofibrosis Malaria Schistosomiasis
44
Moderate splenomegaly
Lymphoma Leukaemias Myeloproliferative disorders Liver cirrhosis with portal hypertension Infections such as Glandular Fever and same as massive
45
Mild Splenomegaly
Infectious hepatitis Endocarditis Infiltrative disorders such as sarcoidosis Autoimmune diseases such as AIHA, ITP, SLE and same as massive and moderate
46
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
47
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
48
Hyposplenism
lack of functioning splenic tissue
49
causes of hyposplenism
splenectomy sickle cell disease- due to infarcts and fibrosis in liver gastrointestinal diseases autoimmune disease
50
gastrointestinal diseases which forms hyposplenism
Coeliac disease Crohn's disease Ulcerative colitis
51
autoimmune disorders which forms hyposplenism
Systemic lupus Rheumatoid arthritis Hashimoto's disease
52
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.
53
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
54
Erythrocytes
red blood cells
55
what does red blood count show?
how many red blood cells 4.4-5.9 X 10^12
56
Hb
haemoglobin how effective? 13.5- 16.7 g/dI
57
MCV
mean corpuscular volume how large? 80-100 fI
58
shape of erythrocytes
shape of erythrocytes
59
lifespan of erythrocytes
120 days
60
Functions of Erythrocytes
Deliver oxygen to tissues Carry haemoglobin Maintain haemoglobin in its reduced (ferrous) state Maintain osmotic equilibrium Generate energy
61
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
62
when does haemoglobin switch from fetal to adult?
at 3-6 months
63
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
64
Haemolytic anaemia
Anaemia with chronic premature destruction of red blood cells
65
what changes shape in RBC shape?
changes in the components of the cell membrane
66
what happens if there's changes in plasma membrane
less deformable and more fragile
67
spectrin
actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton.
68
what proteins are involved in hereditary spherocytosis?
spectrin ankyrin band 3 protein 4.2
69
Ankyrin
links integral membrane proteins to the underlying spectrin-actin cytoskeleton.
70
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).
71
protein 4.2
ATP-binding protein which may regulate the association of band 3 with ankyrin
72
what causes jaundice?
excess unconjugated bilirubin in blood
73
faeces
brown colour comes from sterocobilin
74
urine
yellow colour comes from urobilin
75
degradation of haem
1. The haemoglobin removed from senescent erythrocytes is recycled by the spleen being degraded to its constitutive amino acids and haem 2. haem metabolised to bilirubin, 3. bilirubin removed in the liver where it is conjugated with glucuronic acid and secreted in bile. 4. Bacteria in the intestines deconjugate and metabolise the bilirubin into colourless urobilinogen which is subsequently oxidized to form stercobilin 5. A smaller amount of the urobilinogen is reabsorbed into blood and processed by the kidneys where it is oxidised to urobilin
76
How is unconjugated bilirubin transported in the blood?
bound albumin
77
Cytopenia
reduction in the number of blood cells
78
cytosis
increase in the normal of blood cells
79
decrease and increase of RBC
Increase- erythryocytosis decrease- anaemia
80
increase and decrease of wbc
increase- leucocytosis decrease- leucopenia
81
increase and decrease of lymphocytes
increasing- lymphocytosis decrease- lymphocytopenia
82
increase and decrease of monocytes
increase- monocytosis decrease- monocytopenia
83
increase and decrease neutrophils
increase- neutrophilia decrease- neutropenia
84
increase and decrease eosinophils
increase- eosinophilia decrease- eosinopenia
85
increase and decrease basophils
increase- basophilia decrease- basopenia
86
thrombocytosis
abnormally high platelet count
87
Thrombocytopenia
low platelet count
88
Panmyelosis
increased level of all bone marrow components, red blood cells, white blood cells, and platelets
89
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
90
what controls maturation to form neutrophils
hormone G-CSF, a glycoprotein growth factor & cytokine
91
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
92
what is administered when more neutrophils needed?
recombinant g-csf is routinely administered
93
Neutrophilia
increase in the number of circulating neutrophils
94
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
95
haemorrhage
brings more cells out from marginated pool
96
Neutropenia
decreased number of neutrophils in the blood < 1.5 x 10^9
97
Causes of neutropenia
reduced portion: B12/folate deficiency, infiltration, aplastic anaemia, radiation, viral infection, congenital, drugs increased removal: immune destruction, sepsis, splenic pooling
98
consequences of neutropenia
Severe life threatening bacterial infection Severe life threatening fungal infection Mucosal ulceration e.g. painful mouth ulcers
99
what is neutropenic sepsis?
medical emergency intravenous antibiotics must be given
100
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.
101
How long do monocytes circulate in the blood?
1-3 days
102
Causes of monocytosis
Bacterialinfectione.g.tuberculosis Inflammatoryconditionse.g.rheumatoidarthritis,Chron's Ulcerative colitis Carcinoma MyeloproliferativedisordersandLeukaemias
103
Eosinophils
Responsible for immune response against multicellular parasites e.g. Helminths Mediator of allergic responses Phagocytosis of antigen - antibody complexes
104
How long do eosinophils circulate?
3 - 8 hours
105
life span of eosinophils
8 -12 days
106
life span of eosinophils
Granules contain array of cytotoxic proteins (e.g. eosinophil cationic protein & elastase)
107
what happens if eosinophils inappropriately activated?
responsbile for tissue damage and inflammation e.g. in asthma
108
common causes of eosinophilia?
allergic diseases parasitic infection drug hypersensitivity charge-strauss- inflammation of small blood vessels skin diseases
109
Rare causes of eosinophilia
hodgkin lymphoma actuel lymphoblastic leukaemia actue myeloid leukaemia myeloproliferative conditions eosinophilic leukaemia idiopathic hypereosinophilic syndrome
110
basophils
active in allergic reactions and inflammatory conditions large granules containing histamine, heparin, hyaluronnic acid, serotonin
111
Reactive Basophilia
Immediate hypersensitivity reactions Ulcerative Collitis Rheumatoid Arthritis
112
myeloproliferative basophilia
CML MPN: ET/PRV/MF Systemic mastocytosis
113
Where do lymphocytes come from?
bone marrow
114
lymphocytes
A type of white blood cell that make antibodies to fight off infections
115
B cells (B lymphocytes)
specialized lymphocytes that produce antibodies forming cells attack invaders outside cell
116
T cells (T lymphocytes)
lymphocytes that mediate cellular immunity;CD4 + helper cells, CD8 + cells attacked infected cells
117
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
118
Reactive Lymphocytosis
Viral infections Bacterial infections-especially whooping cough Stress related: MI/cardiac arrest Post splenectomy Smoking
119
Lymphoproliferative
The proliferation of the bone marrow cells that give rise to lymphoid cells
120
Lymphoproliferative Lymphocytosis
* Chronic Lymphocytic Leukaemia (B cells) * T- or NK- cell leukaemia * Lymphoma (cells 'spill' out of infiltrated bone marrow)
121
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
122
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
123
which organ is responsible for endogenous production of erythropoietin?
kidney
124
Erythropoietin
A hormone produced and released by the kidney that stimulates the production of red blood cells by the bone marrow.
125
what long term treatment in given to patient that has had a splenectomy?
vaccination against Haemophilus influenzae
126
panctyopenia
deficiency of all types of blood cells