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Physiology Flashcards

1
Q

What is blood

A

Blood is a specialized fluid (technically a tissue)
It is composed of cells suspended in a liquid
The liquid is plasma

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2
Q

What are the 3 main types of blood cell

A

Red blood cells
White blood cells
Platelets

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3
Q

What do you have more of, red or white blood cells

A

Lot more red cells produced than white cells

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4
Q

What is the production of blood cells called

A

Haematopoiesis

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5
Q

What are the sites of haematopoiesis

A

As a foetus - yolk sac initially (up to week 10)
Then the liver (week 6), spleen and marrow (week 16)
At birth - bone marrow with liver and spleen when needed
Adult - bone marrow in the axial skeleton only

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6
Q

Which bones are sites of haematopoiesis in adults

A

The axial skeleton

The skull, ribs sternum, pelvis, proximal ends of femur

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7
Q

Why is bone marrow sensitive to chemo

A

It undergoes constant division to keep up with blood production demands
Chemo interrupts cell division to try and kill rapidly dividing cancer cells - also affects normally dividing cells

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8
Q

In what state are most haematopoietic stem cells

A

Most stem cells sit in a quiecent state - inactive

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9
Q

Why is haematopoiesis considered dynamic

A

The production can dynamically respond to an individuals needs – e.g. if you have an infection you produce more white cells

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10
Q

Can haematopoietic stem cells self-renew

A

The stem cells are able to self renew

As you go further down the differentiation pathways the ability to self renew decreases

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11
Q

At what stage of development does an erythrocyte enter the bloodstream

A

When they become reticulocytes

Reticulocytes are immature RBCs – they still have RNA in the cytoplasm

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12
Q

Describe erythropoiesis

A

This is the development of RBC
Nucleus is large at the start of the process but gradually gets smaller – shuts down eventually as no longer needed
Normoblasts become reticulocytes then mature RBC
In mature RBC there is no nucleus, DNA or RNA

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13
Q

What is a megakaryocyte

A

Very large cell with a large cytoplasm

The cytoplasm will bud off and form the platelets

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14
Q

What are the functions of a RBC

A

Carry oxygen

Buffer for CO2 etc

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15
Q

What are the functions of platelets

A

Stop bleeding

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16
Q

What are the functions of white blood cells

A

Fight infection

Others e.g. cancer prevention

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17
Q

Which WBC are granulocytes

A

Eosinophils
Basophils
Neutrophils

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18
Q

What are granulocytes

A

Type of WBC
Most common type of white cells
Have granules in the which take up the stains

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19
Q

What is the most common type of granulocyte

A

Neutrophils

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20
Q

Describe the structure of neutrophils

A

Segmented nucleus
Also called polymorphs as each one has a slightly different shaped nucleus
Neutral staining granules

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21
Q

What are the functions of neutrophils

A

Works in the tissues – releases it’s granules to kill invading cells and signal acute inflammation
Phagocytose invaders
Kill with granule contents and die in the process
Attract other cells
These cells form pus

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22
Q

What can increase neutrophil count

A

Increased by body stress – infection, trauma, infarction

Steroids impair the neutrophils ability to leave the bloodstream – people on these drugs may have high counts

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23
Q

Describe the structure of eosinophils

A

Usually bi-lobed nucleus
Bright orange/red granules
Live slightly longer – less condensed

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24
Q

What are the functions of eosinophils

A

Fight parasitic infections
Involved in hypersensitivity (allergic reactions)
Often elevated in patients with allergic conditions (e.g. asthma, atopic rhinitis)

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25
Q

Describe the structure of basophils

A

Large deep purple granules obscuring nucleus
Granules contain histamine
Infrequent in the circulation

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26
Q

What are the functions of basophils

A

Circulating version of tissue mast cell
Granules contain histamine
Mediates hypersensitivity reactions
FcReceptors bind IgE

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27
Q

Describe the structure of monocytes

A

Large single nucleus

Faintly staining granules, often vacuolated

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28
Q

What are the functions of monocytes

A

Circulate for a week and enter tissues to become macrophages
Phagocytose invaders, kill them and present antigen to lymphocytes
Attract other cells

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29
Q

Describe the structure of lymphocytes

A

Mature cells are small with condensed nucleus and rim of cytoplasm
Activated cells are large with plentiful blue cytoplasm extending round neighbouring red cells and the nucleus with a more open structure

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30
Q

How can you recognise the early precursors/ haematopoietic stem cells

A 
Morphology is unremarkable 
Needs immunophenotyping (surface antigen profile) or bio-assay
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31
Q

Which investigations can be done to assess blood components

A

Peripheral blood tests - cell counts, blood films
Bone marrow tests- biopsy
Look at other sites of relevance to blood production e.g. splenomegaly, hepatomegaly, lymphadenopathy.

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32
Q

How do you get a bone marrow biopsy

A

Get bone marrow samples from the pelvis – part of the axial skeleton so is a site of blood production
Common site is the posterior iliac crest
Use a large needle
Need high pressure to suck out the bone marrow

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33
Q

Describe the key properties of RBC

A

Full of haemoglobin to carry oxygen
No nucleus makes it more deformable, and more room for Hb molecules
No mitochondria either
High Surface area/volume ratio to allow for gas exchange
Flexible to squeeze through capillaries

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34
Q

What is the consequence of RBC being full of Hb

A

High oncotic pressure

It becomes an oxygen rich environment so there is an oxidation risk

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35
Q

What is the consequence of RBC not having a nucleus

A

Can’t divide and can’t replace damaged proteins

Gives it a limited cell lifespan

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36
Q

What is the consequence of RBC not having mitochondria

A

Limited to glycolysis for energy generation (no Krebs’ cycle)
Cant produce as much energy as other cells

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37
Q

What is the consequence of RBC having a high surface area/volume ratio

A

Need to try and keep water out

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38
Q

What is the consequence of RBC being flexible

A

Requires a specialised membrane required that can go wrong

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39
Q

Describe the structure of the red blood cell membrane

A

Not just a lipid bilayer - complex
Has spectrin protein spars which acts as structural support
They adhere to the membrane

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40
Q

How do RBC maintain oncotic pressure and keep water out

A

Sodium-potassium pump
It maintains the ion concentrations/gradient
Requires energy

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41
Q

Describe the structure of adult haemoglobin

A

A tetrameric globular protein
Made up of 2 alpha and 2 beta chains
Each one has a haem group (Fe2+) in a flat porphyrin ring

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42
Q

In which state does iron need to be in to carry oxygen

A

Fe2+ - ferrous state

When oxidised it becomes Fe3+ which cannot carry oxygen so is useless in RBC

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43
Q

What are the functions of Hb

A

Deliver oxygen to the tissues
Act as a buffer for H+
CO2 transport

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44
Q

How do the kidneys affect red cell production

A

They have O2 sensors in the nephron
If hypoxia is detected then erythropoietin is secreted to stimulate more RBC production
Once hypoxia is sorted then EPO drops - negative feedback

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45
Q

Where are RBC broken down

A

In the spleen and to a lesser extent liver

The macrophages take them up when they detect that they are damaged – near end of lifespan - and take them to spleen etc

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46
Q

What is the average lifespan of a RBC

A

120 days

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47
Q

What happens to the components of RBC when they are broken down

A

Globin chains recycled to amino acids
Haem group broken down to iron and bilirubin
Iron is recycled or stored
Bilirubin taken to liver and conjugated
Then excreted in bile (colours faeces and urine)

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48
Q

How do RBC create energy

A

Glycolysis
Produces lactate as it cant go into the Krebs cycle as lack of mitochondria
Net gain of ATP

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49
Q

How is iron kept in the ferrous (Fe2+) state

A

NADH is sacrificed to keep Fe2+ in this state – proton donor
NADH is produced in glycolysis

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50
Q

What is metHb

A

Oxidised haemoglobin
Iron is in the Fe3+ state
Cannot carry oxygen

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51
Q

What is superoxide

A

A reactive oxygen species - O2 with a free electron

It is very damaging – can damage DNA and proteins

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52
Q

How do RBC prevent oxidative damage

A

Superoxide dismutase is an enzyme which converts any superoxide’s into H2O2
Catalase then turns this into water with help from glutathione (reacts with the H2O2 to form water)

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53
Q

How is glutathione replenished

A

Glutathione is replenished by NADPH

The NADPH is generated by the hexose monophosphate shunt

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54
Q

What is the purpose of the hexose monophosphate shunt in RBC glycolysis

A

Bypasses the normal pathway and generates NADPH

This is used to replenish glutathione – protects us from oxidative damage

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55
Q

What is the limiting enzyme in the hexose monophosphate shunt

A

Glucose-6-phophsate

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56
Q

How is CO2 transported

A

Only 10% is dissolved in solution
Around 30% is bound directly to Hb as carbamino-Hb
The other 60% gets there as bicarbonate and the red cell has an important role in generating that bicarbonate

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57
Q

How many O2 molecules bind to each haem group

A

One to each

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58
Q

When does Hb need to be able to bind O2

A

High PO2 you want haem to be able to bind O2 well – fully saturated
I.e in the lungs
Also needs to hold on to it as the pO2 drops a little (ie in transport in blood vessels)

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59
Q

When does Hb need to be able to release O2

A

Needs to release O2 when PO2 is low - at the tissues

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60
Q

Describe the allosteric effect of O2 binding to Hb

A

As you bind the first oxygen, the haem groups change slightly making it easier to bind the next one – increases affinity
This is known as an allosteric effect

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61
Q

Does foetal Hb have a higher or lower affinity for O2

A

Higher
It is able to saturate more at a lower PO2
Can take O2 from mum as needed

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62
Q

When is 2,3 BPG generated

A

Generated in chronic anaemia or hypoxia when more oxygen is needed
Formed by the Rapapoport-Lubering Shunt

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63
Q

What is the function of 2,3 BPG

A

These molecules burrow into the haemoglobin molecules – interfere with the position of the haem group
This makes it harder for O2 to bind but also that more can be released at the tissue

64
Q

Which molecules can shift the O2 dissociation curve to the right

A

H+, CO2 and 2,3 BPG

This causes O2 to be released more easily at the tissues

65
Q

Why might cell counts be low

A

Increased destruction
Reduced production
Redistribution - may not have more of a cell, just a lower proportion is found in the blood now

66
Q

Why might a blood cell count be high

A

Increased production in response to stimulus - e.g. infection
Increased production with no stimulus
Redistribution

67
Q

What terms are used to describe a high cell count

A
  • cytosis or -philia

e. g. thrombocytosis = excess platelets

68
Q

What is a thrombophilia

A

Excess clotting

69
Q

What terms are used to describe a low cell count

A
  • penia = a shortage of

e. g. neutropenia

70
Q

What is marrow aplasia

A

No production of blood cells

71
Q

How are B12 and folate involved in RBC production

A

They catalyse important biochemical steps allowing cell division
Essential for RBC production but are not used up by the process

72
Q

What is the erythron

A

Intact cellular mechanisms ‘machinery’ generating red cells

73
Q

How long after production are reticulocytes found in the blood

A

Appear as reticulocytes for the first few days before maturing

74
Q

What is the function of erythropoietin

A

Stimulates cell division of red cell precursors and recruits more cells to red cell production in the marrow

75
Q

What is iron used for in the body

A 
Oxygen transport 
Electron transport (e.g. mitochondrial production of ATP)‏
76
Q

Where is iron found in the body

A 
Haemoglobin - most of the bodies iron is here 
Myoglobin
 Enzymes eg cytochromes
Macrophage stores 
Liver stores
77
Q

How do you lose iron from the body

A

Loss is due to loss of cells – any bleeding, shedding of skin cells or gut cells
Cant control this

78
Q

Where is iron absorbed

A

Mainly in the duodenum

79
Q

What factors can enhance iron absorption

A

Haem vs non-haem iron
dedicated haem iron transporter
Ascorbic acid (reduces iron to Fe2+ form)
Alcohol

80
Q

What factors inhibit iron absorption

A

Tannins eg tea
Phytates eg cereals, bran, nuts and seeds
Calcium eg dairy produce

81
Q

What is the function of duodenal cytochrome B

A

Found in the luminal surface of the duodenum
It reduces the ferric iron Fe3+ to the ferrous form
This is the state needed for transport

82
Q

What is the function of DMT (divalent metal transporter) -1

A

Transports ferrous iron into the duodenal enterocyte

83
Q

What is the function of ferroportin

A

Facilitates iron export from the enterocyte

Passed on to transferrin for transport elsewhere

84
Q

What is the function of hepcidin

A

The major negative regulator of iron uptake
Produced in liver in response to increased iron load and inflammation
Binds to ferroportin and causes its degradation
Iron therefore ‘trapped’ in duodenal cells and macrophages

85
Q

What happens to Herceptin levels when you are iron deficient

A

The levels decrease

86
Q

How does the red cell get into the blood from the bone marrow

A

Bone marrow has a rich blood supply so reticulocytes formed here can move into the circulation
Capillaries in the bone marrow are sinusoids
The endothelial cells can be moved by connective tissue cells and allows red cells to squeeze through
EPO causes the endothelial cells to move apart to that more cells can get out

87
Q

In what circumstances might nucleated red cells appear in the blood

A

Increased demand for red cells (released prematurely to try and compensate)
Acute hypoxia
Disruption to the barriers in the bone marrow
Neonates often have nucleated cells (precursors) circulating as they are switching their blood cells to adult (big production of new cells)
In some malignancies nucleated cells are released

88
Q

Why does reticulocytotic present with a polychromatic blood film

A

Reticulocytes have a small amount of RNA in them which stains blue

89
Q

How do you measure functional iron

A

Hb concentration

90
Q

How do you measure transport iron

A

% saturation of transferrin with iron

91
Q

How do you measure storage iron

A

Serum ferritin

Tissue biopsy - rarely needed

92
Q

What is transferrin

A

Protein with two binding sites for iron atoms
Transports iron from donor tissues to tissue with transferring receptors
Whole complex gets internalised – iron is removed – transferrin released again
The greater the cells demand for iron, the more transferrin receptors they will express – developing erythroid cells have lots

93
Q

When is transferrin saturation too high

A

In iron overload

94
Q

When is transferrin saturation too low

A

Iron deficiency

95
Q

What can increase ferritin

A

It rises with iron stores

It is an acute phase protein so rises with infection, malignancy etc

96
Q

What are the subtypes of lymphocytes and their roles

A 
B cells - humoral immunity (antibodies)
T cells - cell-mediated immunity and regulatory functions
Natural killer (NK) cells  -Anti viral/tumour
97
Q

What is the function of an erythrocyte

A

O2 / CO2 transport

98
Q

What is the function of the platelets

A

Primary haemostasis

99
Q

Which blood cells lack a nucleus

A

Erythrocytes - RBC

Platelets

100
Q

What is the average lifespan of neutrophils

A

7-8 hours

101
Q

What is the average lifespan of platelets

A

7-10 days

102
Q

What are myelocytes

A

Nucleated precursor between myeloblasts and neutrophils etc

103
Q

What is a ‘blast’

A

A nucleated precursor cell in the haemopoietic system

e.g. erythroblast (RBC) or myeloblasts (WBC)

104
Q

What is the common precursor to all blood cells

A

Haemopoietic stem cells

105
Q

Where do you take a bone marrow biopsy from

A

In adults its from posterior iliac crest or sternum

In young children you take from the proximal tibia

106
Q

What is the bone marrow

A

A complex organ surrounded by a shell of bone

with a neurovascular supply

107
Q

What cells and structures make up the bone marrow

A 
Haemopoietic cells
Adipocytes 
Fibrocytes 
Osteoclasts and osteoblasts 
Connective tissue matrix 
Vascular elements
108
Q

Describe the blood supply and drainage of the bone marrow

A

Have a nutrient artery connected to a network of periosteal vessels
Arterioles drain into ‘sinuses’ – wide venous vessels, which open into larger central sinuses
These sinuses are larger than traditional capillaries and have a discontinuous basement membrane

109
Q

How are blood cells released from the marrow

A

They pass through the fenestrations in the endothelial cells of the sinuses to enter circulation
RBCs do this when there is increased blood flow and dilation of the sinus
Neutrophils actively migrate to the sinusoid

110
Q

What is the difference between red and yellow marrow

A

Red is haemopoetically active marrow

Yellow marrow is more fatty and inactive

111
Q

What happens to the proportions of red vs yellow marrow with age

A

Increase in yellow marrow with age

Get a reduction of marrow cellularity in the elderly

112
Q

What is the myeloid:erythroid ratio

A

Relationship of neutrophils and precursors to proportion of nucleated red cell precursors
Ranges from 1.5:1 to 3.3:1

113
Q

What regulates haemopoeisis

A

Intrinsic properties of cells
Signals from immediate surroundings and the periphery - EPO, granulocyte-colony stimulating factor (neutrophils) and thrombopoietin (megakaryocytes)
Specific anatomical area for optimal developmental signals - provides access to signalling molecules and blood etc

114
Q

Which cell lineage usually requires immunophenotyping

A

Lymphoid - need to identify the antigens

Non-lymphoid cells can be analysed by simple blood counts or films

115
Q

What is immunophenotyping

A

Technique used to identify patterns of protein (antigen) expression unique to a cell lineage
You use specific antibodies with markers to determine antigen expression
Used to assess lymphoid cells

116
Q

Where do lymphocytes mature

A

B cells mature in the bone marrow

T cells mature in the thymus

117
Q

What are the primary lymphoid tissues

A

Bone marrow
Thymus

Also called central

118
Q

What are the secondary lymphoid tissues

A 
Lymph nodes
Spleen
Tonsils (Waldeyer’s ring)
Epithelio-lymphoid tissues
Bone marrow

Also called peripheral

119
Q

What is the function of the lymphoid tissue

A

Filtration of circulatory fluid

Location for cells of the immune system

120
Q

What is the function of the lymphatic system

A

Return lymph to the circulation - maintains homeostasis and prevents oedema
Allows cell traffic, trapping and interaction of cells with the immune system

121
Q

Which lymph node groups are palpable

A

cervical, axillary and inguinal

122
Q

Describe the structure of lymph nodes

A

Small, oval bodies
Up to 2.5cm
Located along the course of lymphatic vessels
Blind-ending vascular channels that collect fluid from tissues and return to blood stream
Contain valves

123
Q

Describe how lymph passes through a lymph node

A

Enters via an afferent lymphatic vessel
Passes through the outer collagenous capsule and into the peripheral sinus
It filters through the node parenchyma
Leaves via an efferent lymphatic vessles at the hilum which drains the lymph to the thoracic duct or the L or R jugular, subclavian or bronchomediastinal trunks
After this it renters the venous system

124
Q

Where does all lymph renter the venous system

A

At the junction of the L or R subclavian and jugular veins

125
Q

What is found at a lymph node hilum

A

Arterial and venous vessels serving the node

The efferent lymph vessel

126
Q

Which cell populations are found in lymph nodes

A 
B cells 
T cells - helper and cytotoxic 
Natural killer cells 
Mononuclear phagocytes (macrophages), antigen presenting cells, and dendritic cells.
Endothelial cells
127
Q

The lymphoid system helps with which branch of the immune system - innate or adaptive

A

BOTH
Houses cells of the innate immune system
The traffic of antigen presenting cells provides the link from the innate to adaptive
This system is also the seat of the adaptive immune response

128
Q

Where in the lymph node are plasma cells found

A

Medulla

129
Q

Where in the lymph node are B cells found

A

Follicles

130
Q

What is lymphadenopathy

A

Lymph node enlargement

131
Q

What can cause lymphadenopathy

A

Local inflammation - infection etc
Systemic inflammation - infection or autoimmune
Malignancy - haem or mets
Sarcoidosis

132
Q

What is lymphagitis

A

Red lines extending from an inflamed lesion - following the lymph vessel
Seen with superficial infections

133
Q

What is generalised lymphadenopathy more suggestive of

A

A systemic inflammatory process or widespread malignancy

Lymphoma/leukaemia are high on the differential

134
Q

If a lymph node has predominantly a B cell response, what does it suggest

A

Auto-immune conditions

Infections

135
Q

If a lymph node has predominantly a phagocyte response, what does it suggest

A

That this node is draining a tumour site

136
Q

If a lymph node has predominantly a T cell response, what does it suggest

A

Viral infections

Drugs e.g.Phenytoin

137
Q

What is the blood supply to the spleen

A

Supplied by splenic artery (branch of coeliac axis) and drained by splenic vein (with SMV forms portal vein)
It is a very vascular organ

138
Q

What are the key aspects (surfaces) of the spleen

A

Diaphragmatic surface

Visceral surface - Left Kidney, gastric fundus, tail of pancreas, splenic flexure of colon.

139
Q

Describe the structure of the spleen

A

An encapsulated organ.
Parenchyma includes red pulp and white pulp
Red pulp contains fenestrated sinusoids and cords containing importance cells
White pulp comprises the peri-arteriolar lymphoid sheath - CD4+ cells

140
Q

What cells are found in the cords of the spleen

A

Cords contain macrophages and some fibroblasts and cells in transit (RBC, WBC, PC and some CD8+ T cells)

141
Q

What is the function of the spleen

A

Acts as a filter for blood
Detect, retain and eliminate unwanted, foreign or damaged material
Facilitate immune responses to blood borne antigens

142
Q

What happens in the white pulp of the spleen

A

Antigen reaches white pulp via the blood.
APCs in the white pulp present antigen to immune reactive cells
When stimulated by antigen, T and B cell responses may occur

143
Q

Describe the clinical features of splenic enlargement

A

Dragging sensation in LUQ
Discomfort with eating
Pain if infarction
Hypersplenism

144
Q

What is the triad seen in hypersplenism

A
  1. splenomegaly
  2. fall in one or more cellular components of blood
  3. correction of cytopenias by splenectomy
145
Q

What can lead to splenomegaly

A 
Infection - EBV, malaria etc 
Portal congestion - cirrhosis, thrombosis 
Haem disorders - Lymphoma/leukaemia, haemolytic anaemia
Inflammatory conditions - RA, SLE 
Storage disease - Gaucher's 
Amyloid 
Tumours 
Cysts
146
Q

What conditions can cause hypersplenism

A 
Most commonly from splenectomy
Coeliac disease
Sickle cell disease
Sarcoidosis
Iatrogenic – non-surgical
147
Q

What is the underlying pathology in hypersplenism

A

Features mainly from reduced red pulp function

May see Howell-jolly bodies

148
Q

What is the consequence of hypersplenism

A

May be some immune deficiency

Need immunisations

149
Q

What are the functions of B cells

A

Part of the adaptive immune system
Antibody production
Act as antigen presenting cells

150
Q

What are immunoglobulins

A

Antibodies produced by B-cells and plasma cells
Proteins made up of 2 heavy and 2 light chains
Each recognises a specific antigen

151
Q

What are the structures of the immunoglobulins

A

IgD, E and G are monomers
IgA is a dimer
IgM is a pentamer

152
Q

Once a B cell meets its target in the periphery, what can it become

A

May return to the marrow as plasma cell or circulate as memory B cell

153
Q

What are plasma cells

A

A factory cell that pumps out antibodies

154
Q

Describe the structure of a plasma cell

A

Plentiful blue cytoplasm - lots of protein
Clock face nucleus
Pale perinuclear area - Golgi apparatus

155
Q

What is meant by polyclonal

A

Cell population has been produced by many different clones

Haematology (8 decks)

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