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MEH > Haemopoiesis, Spleen and Bone Marrow > Flashcards

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
Q

macrophage in liver

A

Kupffer cell

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26
Q

macrophage in tissue histiocyte

A

connective tissue

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27
Q

macrophage in microglia

A

cns

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28
Q

macrophage in peritoneal macrophage

A

peritoneal cavity

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29
Q

macrophage in red pulp macrophage

A

spleen

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30
Q

Macrophage - Langerhan

A

skin and mucosa

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31
Q

RES cells in spleen do what?

A

filtering blood to remove deformed and old cells from the circulation

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32
Q

red pulp

A

sinuses lined by endothelial macrophages and cords- remove cells

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33
Q

white pulp

A

similar structure to lymphoid nodules; contains lymphocytes
stimulate immune system.

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34
Q

functions of spleen in adults

A

sequestration and phagocytosis
blood pooling
extra medullary haemopoiesis
immunological function

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35
Q

sequestration and phagocytosis

A

old/abnormal red cells removed by macrophages

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36
Q

blood pooling

A

platelets and red cells can be rapidly mobilised during bleeding

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37
Q

immunological function of spleen

A

25% of T cells and 15% of B cells are present in spleen

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38
Q

how does blood enter spleen?

A

via the splenic artery
White cells and plasma preferentially pass through the white pulp
Red cells preferentially pass through the red pulp

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39
Q

splenomegaly

A

enlargement of the spleen

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40
Q

Causes of splenomegaly

A

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)

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41
Q

role of spleen

A

blood filter

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42
Q

How to examine the spleen

A

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

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43
Q

Massive splenomegaly

A

Chronic myeloid leukaemia
Myelofibrosis
Malaria
Schistosomiasis

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44
Q

Moderate splenomegaly

A

Lymphoma
Leukaemias
Myeloproliferative disorders
Liver cirrhosis with portal hypertension
Infections such as Glandular Fever
and same as massive

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45
Q

Mild Splenomegaly

A

Infectious hepatitis
Endocarditis
Infiltrative disorders such as
sarcoidosis
Autoimmune diseases such as AIHA,
ITP, SLE
and same as massive and moderate

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46
Q

hypersplenism

A

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

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47
Q

what to avoid if you have splenomegaly?

A

avoid contact sports and vigorous activity
risk of rupture if spleen enlarged and no longer protected by rib cage

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48
Q

Hyposplenism

A

lack of functioning splenic tissue

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49
Q

causes of hyposplenism

A

splenectomy
sickle cell disease- due to infarcts and fibrosis in liver
gastrointestinal diseases
autoimmune disease

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50
Q

gastrointestinal diseases which forms hyposplenism

A

Coeliac disease
Crohn’s disease
Ulcerative colitis

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51
Q

autoimmune disorders which forms hyposplenism

A

Systemic lupus
Rheumatoid arthritis
Hashimoto’s disease

52
Q

what does a blood film from a patient with hyposplenism show?

A

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
Q

what are patients with hyposplenism at risk of?

A

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
Q

Erythrocytes

A

red blood cells

55
Q

what does red blood count show?

A

how many red blood cells
4.4-5.9 X 10^12

56
Q

Hb

A

haemoglobin
how effective?
13.5- 16.7 g/dI

57
Q

MCV

A

mean corpuscular volume
how large?
80-100 fI

58
Q

shape of erythrocytes

A

shape of erythrocytes

59
Q

lifespan of erythrocytes

A

120 days

60
Q

Functions of Erythrocytes

A

Deliver oxygen to tissues
Carry haemoglobin
Maintain haemoglobin in its reduced (ferrous) state
Maintain osmotic equilibrium
Generate energy

61
Q

Haemoglobin

A

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
Q

when does haemoglobin switch from fetal to adult?

A

at 3-6 months

63
Q

2 configurations of Hb

A

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
Q

Haemolytic anaemia

A

Anaemia with chronic premature destruction of red blood cells

65
Q

what changes shape in RBC shape?

A

changes in the components of the cell membrane

66
Q

what happens if there’s changes in plasma membrane

A

less deformable and more fragile

67
Q

spectrin

A

actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton.

68
Q

what proteins are involved in hereditary spherocytosis?

A

spectrin
ankyrin
band 3
protein 4.2

69
Q

Ankyrin

A

links integral membrane proteins to the underlying spectrin-actin cytoskeleton.

70
Q

band 3

A

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
Q

protein 4.2

A

ATP-binding protein which may regulate the association of band 3 with ankyrin

72
Q

what causes jaundice?

A

excess unconjugated bilirubin in blood

73
Q

faeces

A

brown colour comes from sterocobilin

74
Q

urine

A

yellow colour comes from urobilin

75
Q

degradation of haem

A
  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
Q

How is unconjugated bilirubin transported in the blood?

A

bound albumin

77
Q

Cytopenia

A

reduction in the number of blood cells

78
Q

cytosis

A

increase in the normal of blood cells

79
Q

decrease and increase of RBC

A

Increase- erythryocytosis
decrease- anaemia

80
Q

increase and decrease of wbc

A

increase- leucocytosis
decrease- leucopenia

81
Q

increase and decrease of lymphocytes

A

increasing- lymphocytosis
decrease- lymphocytopenia

82
Q

increase and decrease of monocytes

A

increase- monocytosis
decrease- monocytopenia

83
Q

increase and decrease neutrophils

A

increase- neutrophilia
decrease- neutropenia

84
Q

increase and decrease eosinophils

A

increase- eosinophilia
decrease- eosinopenia

85
Q

increase and decrease basophils

A

increase- basophilia
decrease- basopenia

86
Q

thrombocytosis

A

abnormally high platelet count

87
Q

Thrombocytopenia

A

low platelet count

88
Q

Panmyelosis

A

increased level of all bone marrow components, red blood cells, white blood cells, and platelets

89
Q

Neutrophils

A

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
Q

what controls maturation to form neutrophils

A

hormone G-CSF, a glycoprotein growth factor & cytokine

91
Q

what do hormone G-CSF do?

A

Increases production of neutrophils
* Speeds up release of mature cells from BM
* Enhances chemotaxis
* Enhances phagocytosis and killing of pathogens

92
Q

what is administered when more neutrophils needed?

A

recombinant g-csf is routinely administered

93
Q

Neutrophilia

A

increase in the number of circulating neutrophils

94
Q

Causes of neutrophilia

A
  • Infection
  • Tissue damage
  • Smoking
  • Drugs (e.g. steroids)
  • Myeloproliferative diseases
  • Acute inflammation
  • Cancer
  • Cytokines (G-CSF)
  • Metabolic disorders
  • Endocrine disorders
  • Acute Haemorrhage
95
Q

haemorrhage

A

brings more cells out from marginated pool

96
Q

Neutropenia

A

decreased number of neutrophils in the blood
< 1.5 x 10^9

97
Q

Causes of neutropenia

A

reduced portion: B12/folate deficiency, infiltration, aplastic anaemia, radiation, viral infection, congenital, drugs
increased removal: immune destruction, sepsis, splenic pooling

98
Q

consequences of neutropenia

A

Severe life threatening bacterial infection
Severe life threatening fungal infection
Mucosal ulceration e.g. painful mouth ulcers

99
Q

what is neutropenic sepsis?

A

medical emergency
intravenous antibiotics must be given

100
Q

monocytes

A

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
Q

How long do monocytes circulate in the blood?

A

1-3 days

102
Q

Causes of monocytosis

A

Bacterialinfectione.g.tuberculosis
Inflammatoryconditionse.g.rheumatoidarthritis,Chron’s Ulcerative colitis
Carcinoma
MyeloproliferativedisordersandLeukaemias

103
Q

Eosinophils

A

Responsible for immune response against multicellular parasites e.g. Helminths
Mediator of allergic responses
Phagocytosis of antigen - antibody complexes

104
Q

How long do eosinophils circulate?

A

3 - 8 hours

105
Q

life span of eosinophils

A

8 -12 days

106
Q

life span of eosinophils

A

Granules contain array of cytotoxic proteins (e.g. eosinophil cationic protein & elastase)

107
Q

what happens if eosinophils inappropriately activated?

A

responsbile for tissue damage and inflammation e.g. in asthma

108
Q

common causes of eosinophilia?

A

allergic diseases
parasitic infection
drug hypersensitivity
charge-strauss- inflammation of small blood vessels
skin diseases

109
Q

Rare causes of eosinophilia

A

hodgkin lymphoma
actuel lymphoblastic leukaemia
actue myeloid leukaemia
myeloproliferative conditions
eosinophilic leukaemia
idiopathic hypereosinophilic syndrome

110
Q

basophils

A

active in allergic reactions and inflammatory conditions
large granules containing histamine, heparin, hyaluronnic acid, serotonin

111
Q

Reactive Basophilia

A

Immediate hypersensitivity reactions
Ulcerative Collitis
Rheumatoid Arthritis

112
Q

myeloproliferative basophilia

A

CML
MPN: ET/PRV/MF
Systemic mastocytosis

113
Q

Where do lymphocytes come from?

A

bone marrow

114
Q

lymphocytes

A

A type of white blood cell that make antibodies to fight off infections

115
Q

B cells (B lymphocytes)

A

specialized lymphocytes that produce antibodies forming cells
attack invaders outside cell

116
Q

T cells (T lymphocytes)

A

lymphocytes that mediate cellular immunity;CD4 + helper cells, CD8 + cells
attacked infected cells

117
Q

Natural Killer cells

A

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
Q

Reactive Lymphocytosis

A

Viral infections
Bacterial infections-especially whooping cough
Stress related: MI/cardiac arrest
Post splenectomy
Smoking

119
Q

Lymphoproliferative

A

The proliferation of the bone marrow cells that give rise to lymphoid cells

120
Q

Lymphoproliferative Lymphocytosis

A
  • Chronic Lymphocytic Leukaemia (B
    cells)
  • T- or NK- cell leukaemia
  • Lymphoma (cells ‘spill’ out of infiltrated bone marrow)
121
Q

what increases haemoglobin affinity for oxygen and which way does the graph move?

A

decrease in 2-3-DPG
decrease temp
decreases in partial pressure of carbon dioxide
increase pH
graph moves to the left

122
Q

what decrease haemoglobin affinity for oxygen and which way does the graph move?

A

to the right
increase 2-3-DP, temp, particle pressure of carbon dioxide
decrease pH

123
Q

which organ is responsible for endogenous production of erythropoietin?

A

kidney

124
Q

Erythropoietin

A

A hormone produced and released by the kidney that stimulates the production of red blood cells by the bone marrow.

125
Q

what long term treatment in given to patient that has had a splenectomy?

A

vaccination against Haemophilus influenzae

126
Q

panctyopenia

A

deficiency of all types of blood cells

MEH (13 decks)

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