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
2
Q
What are the 3 main types of blood cell
A
Red blood cells
White blood cells
Platelets
3
Q
What do you have more of, red or white blood cells
A
Lot more red cells produced than white cells
4
Q
What is the production of blood cells called
A
Haematopoiesis
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
6
Q
Which bones are sites of haematopoiesis in adults
A
The axial skeleton
The skull, ribs sternum, pelvis, proximal ends of femur
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
8
Q
In what state are most haematopoietic stem cells
A
Most stem cells sit in a quiecent state - inactive
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
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
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
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
13
Q
What is a megakaryocyte
A
Very large cell with a large cytoplasm
The cytoplasm will bud off and form the platelets
14
Q
What are the functions of a RBC
A
Carry oxygen
Buffer for CO2 etc
15
Q
What are the functions of platelets
A
Stop bleeding
16
Q
What are the functions of white blood cells
A
Fight infection
Others e.g. cancer prevention
17
Q
Which WBC are granulocytes
A
Eosinophils
Basophils
Neutrophils
18
Q
What are granulocytes
A
Type of WBC
Most common type of white cells
Have granules in the which take up the stains
19
Q
What is the most common type of granulocyte
A
Neutrophils
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
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
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
23
Q
Describe the structure of eosinophils
A
Usually bi-lobed nucleus
Bright orange/red granules
Live slightly longer – less condensed
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)
25
Describe the structure of basophils
Large deep purple granules obscuring nucleus
Granules contain histamine
Infrequent in the circulation
26
What are the functions of basophils
Circulating version of tissue mast cell
Granules contain histamine
Mediates hypersensitivity reactions
FcReceptors bind IgE
27
Describe the structure of monocytes
Large single nucleus
| Faintly staining granules, often vacuolated
28
What are the functions of monocytes
Circulate for a week and enter tissues to become macrophages
Phagocytose invaders, kill them and present antigen to lymphocytes
Attract other cells
29
Describe the structure of lymphocytes
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
30
How can you recognise the early precursors/ haematopoietic stem cells
```
Morphology is unremarkable
Needs immunophenotyping (surface antigen profile) or bio-assay
```
31
Which investigations can be done to assess blood components
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.
32
How do you get a bone marrow biopsy
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
33
Describe the key properties of RBC
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
34
What is the consequence of RBC being full of Hb
High oncotic pressure
| It becomes an oxygen rich environment so there is an oxidation risk
35
What is the consequence of RBC not having a nucleus
Can’t divide and can’t replace damaged proteins
| Gives it a limited cell lifespan
36
What is the consequence of RBC not having mitochondria
Limited to glycolysis for energy generation (no Krebs’ cycle)
Cant produce as much energy as other cells
37
What is the consequence of RBC having a high surface area/volume ratio
Need to try and keep water out
38
What is the consequence of RBC being flexible
Requires a specialised membrane required that can go wrong
39
Describe the structure of the red blood cell membrane
Not just a lipid bilayer - complex
Has spectrin protein spars which acts as structural support
They adhere to the membrane
40
How do RBC maintain oncotic pressure and keep water out
Sodium-potassium pump
It maintains the ion concentrations/gradient
Requires energy
41
Describe the structure of adult haemoglobin
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
42
In which state does iron need to be in to carry oxygen
Fe2+ - ferrous state
| When oxidised it becomes Fe3+ which cannot carry oxygen so is useless in RBC
43
What are the functions of Hb
Deliver oxygen to the tissues
Act as a buffer for H+
CO2 transport
44
How do the kidneys affect red cell production
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
45
Where are RBC broken down
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
46
What is the average lifespan of a RBC
120 days
47
What happens to the components of RBC when they are broken down
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)
48
How do RBC create energy
Glycolysis
Produces lactate as it cant go into the Krebs cycle as lack of mitochondria
Net gain of ATP
49
How is iron kept in the ferrous (Fe2+) state
NADH is sacrificed to keep Fe2+ in this state – proton donor
NADH is produced in glycolysis
50
What is metHb
Oxidised haemoglobin
Iron is in the Fe3+ state
Cannot carry oxygen
51
What is superoxide
A reactive oxygen species - O2 with a free electron
| It is very damaging – can damage DNA and proteins
52
How do RBC prevent oxidative damage
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)
53
How is glutathione replenished
Glutathione is replenished by NADPH
| The NADPH is generated by the hexose monophosphate shunt
54
What is the purpose of the hexose monophosphate shunt in RBC glycolysis
Bypasses the normal pathway and generates NADPH
| This is used to replenish glutathione – protects us from oxidative damage
55
What is the limiting enzyme in the hexose monophosphate shunt
Glucose-6-phophsate
56
How is CO2 transported
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
57
How many O2 molecules bind to each haem group
One to each
58
When does Hb need to be able to bind O2
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)
59
When does Hb need to be able to release O2
Needs to release O2 when PO2 is low - at the tissues
60
Describe the allosteric effect of O2 binding to Hb
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
61
Does foetal Hb have a higher or lower affinity for O2
Higher
It is able to saturate more at a lower PO2
Can take O2 from mum as needed
62
When is 2,3 BPG generated
Generated in chronic anaemia or hypoxia when more oxygen is needed
Formed by the Rapapoport-Lubering Shunt
63
What is the function of 2,3 BPG
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
Which molecules can shift the O2 dissociation curve to the right
H+, CO2 and 2,3 BPG
| This causes O2 to be released more easily at the tissues
65
Why might cell counts be low
Increased destruction
Reduced production
Redistribution - may not have more of a cell, just a lower proportion is found in the blood now
66
Why might a blood cell count be high
Increased production in response to stimulus - e.g. infection
Increased production with no stimulus
Redistribution
67
What terms are used to describe a high cell count
- cytosis or -philia
| e. g. thrombocytosis = excess platelets
68
What is a thrombophilia
Excess clotting
69
What terms are used to describe a low cell count
- penia = a shortage of
| e. g. neutropenia
70
What is marrow aplasia
No production of blood cells
71
How are B12 and folate involved in RBC production
They catalyse important biochemical steps allowing cell division
Essential for RBC production but are not used up by the process
72
What is the erythron
Intact cellular mechanisms ‘machinery’ generating red cells
73
How long after production are reticulocytes found in the blood
Appear as reticulocytes for the first few days before maturing
74
What is the function of erythropoietin
Stimulates cell division of red cell precursors and recruits more cells to red cell production in the marrow
75
What is iron used for in the body
```
Oxygen transport
Electron transport (e.g. mitochondrial production of ATP)
```
76
Where is iron found in the body
```
Haemoglobin - most of the bodies iron is here
Myoglobin
Enzymes eg cytochromes
Macrophage stores
Liver stores
```
77
How do you lose iron from the body
Loss is due to loss of cells – any bleeding, shedding of skin cells or gut cells
Cant control this
78
Where is iron absorbed
Mainly in the duodenum
79
What factors can enhance iron absorption
Haem vs non-haem iron
dedicated haem iron transporter
Ascorbic acid (reduces iron to Fe2+ form)
Alcohol
80
What factors inhibit iron absorption
Tannins eg tea
Phytates eg cereals, bran, nuts and seeds
Calcium eg dairy produce
81
What is the function of duodenal cytochrome B
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
What is the function of DMT (divalent metal transporter) -1
Transports ferrous iron into the duodenal enterocyte
83
What is the function of ferroportin
Facilitates iron export from the enterocyte
| Passed on to transferrin for transport elsewhere
84
What is the function of hepcidin
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
What happens to Herceptin levels when you are iron deficient
The levels decrease
86
How does the red cell get into the blood from the bone marrow
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
In what circumstances might nucleated red cells appear in the blood
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
Why does reticulocytotic present with a polychromatic blood film
Reticulocytes have a small amount of RNA in them which stains blue
89
How do you measure functional iron
Hb concentration
90
How do you measure transport iron
% saturation of transferrin with iron
91
How do you measure storage iron
Serum ferritin
| Tissue biopsy - rarely needed
92
What is transferrin
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
When is transferrin saturation too high
In iron overload
94
When is transferrin saturation too low
Iron deficiency
95
What can increase ferritin
It rises with iron stores
| It is an acute phase protein so rises with infection, malignancy etc
96
What are the subtypes of lymphocytes and their roles
```
B cells - humoral immunity (antibodies)
T cells - cell-mediated immunity and regulatory functions
Natural killer (NK) cells -Anti viral/tumour
```
97
What is the function of an erythrocyte
O2 / CO2 transport
98
What is the function of the platelets
Primary haemostasis
99
Which blood cells lack a nucleus
Erythrocytes - RBC
| Platelets
100
What is the average lifespan of neutrophils
7-8 hours
101
What is the average lifespan of platelets
7-10 days
102
What are myelocytes
Nucleated precursor between myeloblasts and neutrophils etc
103
What is a 'blast'
A nucleated precursor cell in the haemopoietic system
| e.g. erythroblast (RBC) or myeloblasts (WBC)
104
What is the common precursor to all blood cells
Haemopoietic stem cells
105
Where do you take a bone marrow biopsy from
In adults its from posterior iliac crest or sternum
| In young children you take from the proximal tibia
106
What is the bone marrow
A complex organ surrounded by a shell of bone
| with a neurovascular supply
107
What cells and structures make up the bone marrow
```
Haemopoietic cells
Adipocytes
Fibrocytes
Osteoclasts and osteoblasts
Connective tissue matrix
Vascular elements
```
108
Describe the blood supply and drainage of the bone marrow
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
How are blood cells released from the marrow
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
What is the difference between red and yellow marrow
Red is haemopoetically active marrow
| Yellow marrow is more fatty and inactive
111
What happens to the proportions of red vs yellow marrow with age
Increase in yellow marrow with age
| Get a reduction of marrow cellularity in the elderly
112
What is the myeloid:erythroid ratio
Relationship of neutrophils and precursors to proportion of nucleated red cell precursors
Ranges from 1.5:1 to 3.3:1
113
What regulates haemopoeisis
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
Which cell lineage usually requires immunophenotyping
Lymphoid - need to identify the antigens
| Non-lymphoid cells can be analysed by simple blood counts or films
115
What is immunophenotyping
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
Where do lymphocytes mature
B cells mature in the bone marrow
| T cells mature in the thymus
117
What are the primary lymphoid tissues
Bone marrow
Thymus
Also called central
118
What are the secondary lymphoid tissues
```
Lymph nodes
Spleen
Tonsils (Waldeyer’s ring)
Epithelio-lymphoid tissues
Bone marrow
```
Also called peripheral
119
What is the function of the lymphoid tissue
Filtration of circulatory fluid
| Location for cells of the immune system
120
What is the function of the lymphatic system
Return lymph to the circulation - maintains homeostasis and prevents oedema
Allows cell traffic, trapping and interaction of cells with the immune system
121
Which lymph node groups are palpable
cervical, axillary and inguinal
122
Describe the structure of lymph nodes
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
Describe how lymph passes through a lymph node
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
Where does all lymph renter the venous system
At the junction of the L or R subclavian and jugular veins
125
What is found at a lymph node hilum
Arterial and venous vessels serving the node
| The efferent lymph vessel
126
Which cell populations are found in lymph nodes
```
B cells
T cells - helper and cytotoxic
Natural killer cells
Mononuclear phagocytes (macrophages), antigen presenting cells, and dendritic cells.
Endothelial cells
```
127
The lymphoid system helps with which branch of the immune system - innate or adaptive
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
Where in the lymph node are plasma cells found
Medulla
129
Where in the lymph node are B cells found
Follicles
130
What is lymphadenopathy
Lymph node enlargement
131
What can cause lymphadenopathy
Local inflammation - infection etc
Systemic inflammation - infection or autoimmune
Malignancy - haem or mets
Sarcoidosis
132
What is lymphagitis
Red lines extending from an inflamed lesion - following the lymph vessel
Seen with superficial infections
133
What is generalised lymphadenopathy more suggestive of
A systemic inflammatory process or widespread malignancy
| Lymphoma/leukaemia are high on the differential
134
If a lymph node has predominantly a B cell response, what does it suggest
Auto-immune conditions
| Infections
135
If a lymph node has predominantly a phagocyte response, what does it suggest
That this node is draining a tumour site
136
If a lymph node has predominantly a T cell response, what does it suggest
Viral infections
| Drugs e.g.Phenytoin
137
What is the blood supply to the spleen
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
What are the key aspects (surfaces) of the spleen
Diaphragmatic surface
| Visceral surface - Left Kidney, gastric fundus, tail of pancreas, splenic flexure of colon.
139
Describe the structure of the spleen
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
What cells are found in the cords of the spleen
Cords contain macrophages and some fibroblasts and cells in transit (RBC, WBC, PC and some CD8+ T cells)
141
What is the function of the spleen
Acts as a filter for blood
Detect, retain and eliminate unwanted, foreign or damaged material
Facilitate immune responses to blood borne antigens
142
What happens in the white pulp of the spleen
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
Describe the clinical features of splenic enlargement
Dragging sensation in LUQ
Discomfort with eating
Pain if infarction
Hypersplenism
144
What is the triad seen in hypersplenism
1. splenomegaly
2. fall in one or more cellular components of blood
3. correction of cytopenias by splenectomy
145
What can lead to splenomegaly
```
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
What conditions can cause hypersplenism
```
Most commonly from splenectomy
Coeliac disease
Sickle cell disease
Sarcoidosis
Iatrogenic – non-surgical
```
147
What is the underlying pathology in hypersplenism
Features mainly from reduced red pulp function
| May see Howell-jolly bodies
148
What is the consequence of hypersplenism
May be some immune deficiency
| Need immunisations
149
What are the functions of B cells
Part of the adaptive immune system
Antibody production
Act as antigen presenting cells
150
What are immunoglobulins
Antibodies produced by B-cells and plasma cells
Proteins made up of 2 heavy and 2 light chains
Each recognises a specific antigen
151
What are the structures of the immunoglobulins
IgD, E and G are monomers
IgA is a dimer
IgM is a pentamer
152
Once a B cell meets its target in the periphery, what can it become
May return to the marrow as plasma cell or circulate as memory B cell
153
What are plasma cells
A factory cell that pumps out antibodies
154
Describe the structure of a plasma cell
Plentiful blue cytoplasm - lots of protein
Clock face nucleus
Pale perinuclear area - Golgi apparatus
155
What is meant by polyclonal
Cell population has been produced by many different clones
