44. Blood (HT) Flashcards
(164 cards)
1
Q
What is the proper name for RBCs?
A
Erythrocytes
2
Q
Is haemoglobin acidic or basic? What type of dye does it bind?
A
- It is basic
- Binds acidic dyes, like eosin (stains pink)
3
Q
What important organelles are erythrocytes lacking?
A
- Nucleus
- Mitochondria
4
Q
What is a blood film?
A
A thin layer of blood on a microscope slide, stained in a way that allows the study of cells.
5
Q
How do erythrocytes arrange themselves in a blood stain? What is this called?
A
- They tend to pile up in stacks due to their surface area
- This is called “rouleaux”
6
Q
What maintains the shape of erythrocytes?
A
Cytoskeleton, including spectrin, ankyrin and other membrane proteins.
7
Q
What does the shape of erythrocytes depend on?
A
Water content -> Affected by solutes, especially ions
8
Q
Draw the different possible shapes of erythrocytes.
A
The discocyte is the standard shape (when isotonic). Stomatocyte is when in hypotonic solution, while echinocyte is when in hypertonic solution.
9
Q
Why must erythrocytes be able to deform?
A
In order to pass through capillaries.
10
Q
What is the size of an erythrocyte?
A
7μm
11
Q
What property of blood does the deformity of erythrocytes contribute to?
A
- Viscoelasticity
- This is when a fluid exhbits both fluid and elastic properties at the same time
- The elastic properties are due to the deformity of the erythrocytes
12
Q
Which part of a vessel do erythrocytes tend to keep to?
A
The central axis.
13
Q
How do erythrocytes appear in blood film?
A
14
Q
What is the normal number of erythrocytes per litre of blood?
A
5 x 1012 cells/L
15
Q
How can the viscosity of blood be described?
A
‘Anomalous’ viscosity
16
Q
Describe the anomalous viscosity of blood.
A
- Viscosity of blood increases as blood velocity decreases (up to 10x increase) because:
- Formation of rouleaux (stacks of RBCs) and adherence of erythrocytes to vessel wall
- Shear forces insufficient to deform erythrocytes, so they appear more rigid
17
Q
Give some factors that can increase the anomalous viscosity of blood.
A
- Rigidity of membrane (e.g. spectrin defect)
- Age of erythrocytes
- Inclusions inside cells (e.g. sickled cells)
18
Q
Give some advantages of erythrocytes being anucleate.
A
- Better SA:V ratio
- Improved deformability
- Less work for heart to pump (since less mass)
19
Q
Give some disadvantages of erythrocytes being anucleate.
A
- No protein synthesis or repair, so cells wear out
- Cells can’t change proteins under different conditions
20
Q
What is the normal turnover time for erythrocytes?
A
120 days
21
Q
What is the name for RBC production?
A
Erythropoiesis
22
Q
What is the consequence of erythrocytes not containing mitochondria?
A
They rely on glycolysis.
23
Q
What are the main energy requirements of erythrocytes?
A
Energy for ion pumps.
24
Q
How much haemoglobin is there in the adult body?
A
About 750g.
25
What two things does haemoglobin transport?
Oxygen and carbon dioxide
26
Describe the structure of haemoglobin.
* 2 alpha chains
* 2 beta chains
* Haem prosthetic group -\> One Fe2+ per haem
27
What conditions must be kept in erythrocytes for proper haemoglobin function?
* Reducing conditions
* Otherwise the iron will oxidise to Fe3+ (methaemoglobin)
28
Aside from haemoglobin, what are the other contents of erythrocytes?
* Enzymes
* Ions
29
What types of enzymes are found in erythrocytes?
Glucose metabolising enzymes:
* In anaerobic glycolysis
* In pentose phsophate shunt
30
What is the enzyme involved in the pentose phosphate shunt in erythrocytes and why is it important?
* G6PDH
* It generates NADPH (using glucose), which slows the accumulation of oxidised proteins that are associated with erythrocyte ageing
* This maintains glutathionine in its reduced state
31
Give an example of an ion that is important to maintain in erythrocytes, how it is maintained and the clinical relevance of this.
* K+
* High intracellular K+ maintained by sodium-potassium pump
* Red cell lysis can be life-threatening because severe hyperkalaemia occurs
32
What is a crenated erythrocyte?
One placed in a hypertonic solution, so that it shrivels into a echinocyte shape.
33
What makes the erythrocyte cell membrane semi-permeable?
Aquaporins
34
Describe the structure of erythrocyte membranes.
* Anchoring proteins -\> Spectrin, ankyrin, band 3
* Glycoproteins with carbohydrate external -\> e.g. Blood group substances
35
How do erythrocytes become aged?
Oxidation products build up.
36
What is glucose required for in erythrocytes?
Maintianing reducing conditions and for ion pumps.
37
Where and by what are aged erythrocytes destroyed?
In the spleen (and liver) by macrophages.
38
What factors may shorten the lifespan of erythrocytes?
* Abnormal shape
* Haemoglobin mutation (e.g. sickle cell anaemia)
* Cytoskeleton proteins altered
* Accelerated clearance
* Overactive phagocytosis in spleen and liver (e.g. autoimmune disease or overactive macrophages)
39
What is the normal rate of erythrocyte production in a healthy human per hour?
About 1 x 1010 per hour
40
What are some sources of erythropoietic stem cells?
* Bone marrow (in adult)
* Liver (in foetus)
* Embryonic yolk sac
* Early embryonic aorto-gonado-mesonephros region
* Umbilical cord blood at partuition
41
How can you test for 'stem'-ness? (Experimental evidence)
In a host where bone marrow erythropoeitic cells are destroyed by radiation or chemo-treatment:
* Transplant cells to be tested
* Determine whether all blood cell types are reconstituted fully
* The host's bone marrow can be transplanted into further recipients for treatment purposes
42
Describe briefly the development of erythrocytes.
* Begins with a stem cell (hemocytoblast)
* Turns into committed cell (proerythroblast)
* Then developmental pathway:
* Phase 1 - Ribosome synthesis
* Phase 2 - Haemoglobin accumulation
* Phase 3 - Ejection of nucleus
* During developmental pathway, goes from early erythrocyte to late erythrocyte to normoblast to reticulocyte to erythrocyte
43
What chemical controls erythropoiesis?
Erythropoietin (EPO)
44
Describe the EPO system.
45
What stimuli can trigger the EPO response?
Hypoxia due to:
* Decreased RBC count
* Decreased availability of O2 to blood
* Increased tissue demands for O2
46
What organ releases erythropoietin (EPO)?
Kidney (and the liver to a smaller extent)
47
Draw the graph showing erythropoietin levels in response to haemoglobin levels.
48
Draw a diagram to show a summary of erythrocyte turnover.
49
What is haematocrit?
The percentage volume of RBCs in blood.
50
What is the approximate composition of blood?
* About 50% plasma
* About 50% cells and platelets
* 5,000,000 RBC per microlitre
* 7,000 WBC per microlitre
* 250,000 platelets per microlitre
51
What is anaemia?
A decrease in the total amount of red blood cells (RBCs) or haemoglobin in the blood.
52
What are the main general causes of anaemia?
* Decreased production
* Disturbed proliferation and differentaition of stem cells
* Disturbed proliferation and maturation of erythrocytes
* Increased destruction (generally haemolytic anaemias)
* Intrinsic (internal) abnormalities -\> e.g. Sickle-cell anemia due to abnormal haemoglobin
* Extrinsic (external) abnormalities
* Antibody mediated
* Mechanical trauma
* Blood loss
53
What is mean corpuscular volume (MCV)?
The average volume of an erythrocyte.
54
Draw a chart to show the different types of anaemia.
* Microcytic = Small RBCs
* Normocytic = Normal RBCs
* Macrocytic = Large RBCs
55
What three deficiencies that cause anaemia do you need to know about?
* Iron
* Vitamins
* Folate
* VItamin B12
56
How does iron deficiency cause anaemia and what type of anaemia is it?
* Iron is required to produce haemoglobin, which cannot occur if iron levels are too low
* It results in microcytic anaemia
57
How does folate or vitamin B12 deficiency cause anaemia and what type of anaemia is it?
* It causes there to be large, spherical erythrocytes that do not function properly and there are fewer of them
* This is a type of macrocytic anaemia
58
Describe some types of haemoglobinopathies and how they may affect an erythrocyte.
* Mutations in the subunits of haemoglobin (alpha or beta)
* Cause improper function of the haemoglobin
* Sickle-cell anaemia is an example of this
* Diminished production of one of the two types of subunit
* Mutations that produce this are called thalassemias
* Hemoglobin chain imbalance damages and destroys RBC, thereby producing anemia
* Abnormal associations of otherwise normal subunits
59
Describe the pathophysiology of sickle-cell anaemia.
* In haemoglobin, the alpha chain is normal, but there is a mutation in the beta chain, giving the molecule the structure, a2bS2.
* People who have one sickle mutant gene and one normal beta gene have sickle cell trait which is benign.
* The loss of red blood cell elasticity is central to the pathophysiology of sickle cell disease.
* In low oxygen conditions, RBC sickling occurs due to the mutation.
* Although reoxygenation may return the cell to its normal shape, repeated episodes of sickling damage the cell membrane and decrease the cell's elasticity.
* As a consequence, these rigid permanently-sickled blood cells are unable to deform as they pass through narrow capillaries, leading to vessel occlusion and ischaemia.
* The actual anaemia of the illness is caused by haemolysis, the destruction of the red cells, because of their shape. Although the bone marrow attempts to compensate by creating new red cells, it does not match the rate of destruction.
60
What are the two most important blood group systems?
* ABO system
* Rh system
61
Describe the principle of the rhesus blood group system.
* The rhesus system includes five antigens D, C, c, E, and e
* A person may be classified as rhesus positivie or negative based on the presence of the D antigen
* This is symoblised by a + or - after the ABO group name
62
Describe the dangers of the rhesus blood group system in pregnancy.
63
What is the number of erythrocytes per litre of blood? [IMPORTANT]
5 x 1012
64
What is the proper name for white blood cells?
Leucocytes
65
What is the number of leucocytes per litre of blood? [IMPORTANT]
7 x 109
66
Draw the pathway for the development of different RBCs and WBCs.
67
What are the different types of leucocytes?
* Granulocytes:
* Neutrophils
* Eosinophils
* Basophils
* Monocytes (which give rise to macrophages)
* Lymphocytes:
* B-cells
* T-cells
68
List simply the 5 main types of white blood cells.
* Neutrophils
* Eoisinophils
* Basophils
* Monocytes
* Lymphocytes
69
What are the two main types of immunity?
* Innate (natural) -\> “Always-on” and not greatly enhanced by previous antigen exposure
* Adaptive -\> First exposure to antigen primes for secondary response upon reinfection. Response is specific to the priming antigen.
70
What are the main cell types involved in innate (natural) immunity?
* Mast cells
* Monocytes/Macrophages
* Neutrophils
71
What are the main cell types involved in adaptive immunity?
B and T lymphocytes
72
Describe how different leucocyte types in blood can be separated.
* A preparation of diluted blood and prep fluid can be centrifuged
* Granulocytes end up at the bottom since they are more dense
* Mononuclear cells end up at the top since they are less dense
73
What are the different types of mononuclear leucocytes?
* Monocytes
* Lymphocytes
74
What percentage of all leucocytes do different white blood cell types make up?
* Neutrophils -\> 40-70%
* Lymphocytes -\> 20-40%
* Monocytes -\> 6%
* Eosinophils -\> 3%
* Basophils -\> 1%
75
What is another name for neutrophils?
* PMNs (polymorphonuclear cells)
* "Polymorphs"
76
Describe the appearance of neutrophils.
* Multi-lobed nucleus joined by filaments (sausage-like appearance)
* About 10µm
* Has some granules
77
What is the most abundant leucocyte in blood?
Neutrophils
78
What is the function of neutrophils and how are they adapted for this?
* They are phagocytic -\> Ingest, kill and digest micro-organisms
* They are filled with granules (lysosomes) -\> Fuse with ingested phagosome and secrete toxic chemicals into the phagolysosome
79
What are neutrophils sensitive to?
Sensitive to chemotactic factors which attract them to infection site.
80
Do neutrophils stain easily?
Don’t stain strongly with either eosin or basic dyes.
81
When are neutrophils particularly abundant?
Their production is increased during an acute bacterial infection (they are part of innate immunity) by:
* Increased mobilisation from extensive reserves
* Increased production from progenitors
82
What is neutrophilia?
Raised numbers of neutrophils during acute bacterial infections.
83
How do neutrophils reach the site of acute infection?
Adhere to vascular endothelium and transmigrate by diapedesis to areas of infection in tissues.
84
What is the byproduct of neutrophil activity?
They can cause collateral damage to host cells -\> This leads to pus production
85
What do defects in neutrophils' adhesion or killing mechanism lead to?
Serious pyogenic (pus-forming) infections
86
What is pus?
A thick whitish-yellow fluid which results from the accumulation of WBCs, liquefied tissue and cellular debris.
87
Describe the appearance of eosinophils.
* Bilobular nucleus
* Larger than neutrophil (easy to confuse because of multilobular nuclei)
* Very many granules
88
Do eosinophils stain easily?
* Stain orange-pink with eosin
* Since they contain abundant basic (cationic) protein
89
What is the function of eosinophils and what adaptations do they have for this?
* Passively adsorb IgE antibodies (produced by body) -\> Gives them receptors to recognise specific antigens
* Can exocytose (spit out) toxic substances -\> Different from neutrophil secretions
* They have large ovoid granules
90
Where are eosinophils most commonly found?
Lungs and gut
91
What is the activity of eosinophils dependent on?
They are controlled by T-lymphocytes.
92
When are levels of eosinophils elevated? [IMPORTANT]
Their production is increased in response to:
* Chronic allergic conditions
* Parasitic infection
93
What are some examples of eosinophil secretions?
* Eosinophil Cationic Protein, ECP: a ribonuclease
* Eosinophil peroxidase
94
What can eosinophils protect against?
Damaging effects of long-standing allergic reactions
95
Describe the appearance of basophils.
* Simple or bilobed nucleus
* Nucleus is often difficult to see because of its most characteristic feature: a large number or coarse, purplish granules.
96
What do the granules in basophils contain?
Vasoactive substances such as histamine.
97
What is the function of basophils?
Release of vasoactive substances to aid in allergic and immune response.
98
What cell type are basophils most closely related to?
Mast cells
99
What does the histamine released by mast cells and basophils do?
Increase blood flow and vascular permeability
100
Do basophils stain easily?
They can be stained by basic dyes.
101
What is another name for mononuclear white blood cells?
Peripheral blood mononuclear cells (PBMC)
102
Describe the appearance of monocytes.
* Nucleus is kidney-shaped
* No obvious granules
103
What is the function of monocytes?
* Phagocytosis
* Antigen presentation
* Cytokine production
* Give rise to macrophages
104
Are macrophages blood cells?
No, they are found in tissues.
105
What are the functions of macrophages?
* Phagocytose and kill organisms
* Remove tissue debris by secreting enzymes (e.g. collagenase), allowing effective repair
* Involved in tissue homeostasis and remodelling (they phagocytose apoptotic bodies)
106
Are macrophages always derived from monocytes?
No, in many tissues (e.g. Kupffer cells in liver and Langerhan's cells in skin) are probably seeded in development and replaced by proliferation in tissues.
107
What are the 3 main types of lymphocytes?
* T-lymphocytes
* B-lymphocytes
* Natural killer cells
108
Describe the appearance of lymphocytes.
* Round nucleus
* Some granules in natural killer cells, otherwise no granules
109
What is the function of natural killer cells?
* Patrol body for cell surface “passport” molecules -\> If these are missing then the molecule is foreign
* Anti-viral and anti-tumour role
110
Give a summary of the function of the different leucocytes involved in innate immunity.
111
Summarise the appearance of different leucocytes.
112
What is the function of small lymphocytes? Why are they small?
* Small lymphocytes are quiescent, non-dividing cells
* They are memory cells that await activation by antigens and increase in numbr when activated
113
How do small lymphocytes (memory cells) monitor tissues for antigens to activate them?
They re-circulate continuously through tissues by migration through post-capillary venules and via tissue-fluid, lymphatics and lymph nodes back into the blood. They check for antigens with each pass.
114
What is another name for large lymphocytes?
Lymphoblasts
115
What is the function of large lymphocytes?
* Activated and dividing cells
* They are developing to produce:
* Antibody-forming cells in tissues (very rare in blood)
* Cytotoxic lymphocytes
* "Armed effector cells” (Janeway)
116
In what cells does immunological memory reside?
Lymphocytes
117
What are the 3 phases of lymphocytes acting in a secondary immune response?
Respond by dividing & differentiating:
* Phase 1. Induction
* Phase 2. Amplification
* Phase 3. Effector
118
What are the two main branches of adaptive immunity? What cell types are involved in each?
* Humoral (antibody-mediated)
* Aims to produce antibodies (immunoglobulins)
* Involves B-lymphocytes
* Cell-mediated
* Aims to directly target intracellular invaders
* Involves T-lymphocytes + Cytotoxic (killer) cells
119
What is the function of B-lymphocytes and T-lymphocytes?
B-lymphocytes:
* Mature into antibody-producing plasma cells
T-lymphocytes:
* Play a role in regulating the immune response
* Also act to kill cells directly
120
Describe how the humoral and cell-mediated immune response work.
121
Where are lymphocytes produced and where do they mature? [IMPORTANT]
* Produced from stem cells in the bone marrow
* B-cells mature in bone marrow, while T-cells mature in the thymus
122
Draw the position of the thymus.
123
What are some clinical conditions that demonstrate the roles of T and B-lymphocytes?
124
What is clonal selection and expansion?
The production of a large number of plasma cells that produce a single type of antibody in response to an infection.
125
What is clonal deletion?
The removal (through apoptosis) of B cells and T cells that have expressed receptors for self (i.e. human cells) before developing into fully immunocompetent lymphocytes.
126
How many different antigens can each B-lymphocyte recognise?
Each can only recognise ONE type.
127
What are secondary lymphoid organs? [IMPORTANT]
* Locations for antigens to encounter lymphocytes
* Here, immune reactions generate more lymphocytes
* i.e. It is where lymphocytes proliferate
128
What are the main secondary lymphoid organs?
* Lymph nodes
* Spleen
* Peyer’s patches
129
Describe the concept of Darwinian selection in the immune response.
130
Give an example of acute and chronic inflammation. [EXTRA?]
* Acute -\> Acute prostatisis
* Chronic -\> Rheumatoid arthritis
131
Compare briefly acute and chronic inflammation. [EXTRA]
132
What are some different forms of signal amplification in inflammation?
* Platelet activation
* Kinin cascade -\> Bradykinin
* Complement activation
* Histamine release
* Cytokine secretion
* Prostaglandins
133
Draw a graph to show the outcomes of inflammation.
134
What percentage of plasma (and blood) do plasma proteins make up?
7% of plasma (so therefore about 4% of blood)
135
Draw a diagram to show the composition of blood.
136
How can plasma proteins in a sample be identified?
Gel electrophoresis
137
What are the different types of plasma proteins?
138
What are two important transport proteins you need to know about?
* Albumin
* Transferrin
139
What percentage of plasma proteins does albumin make up?
Around 50%
140
What is the reference concentration of plasma albumin in g/L? [EXTRA]
30-50g/L
141
What are the properties of albumin? [EXTRA]
* Soluble monomeric protein MW 67kDa
* Negatively-charged (-17) at pH 7.4
* Plasma half-life ~20 days
* Heavily glycosylated
142
What are some of the roles of albumin? [IMPORTANT]
* Transport of hormones -\> Fat soluble + Thyroid
* Transport of fatty acids
* Transport of drugs -\> Affects their pharmacokinetics
* Maintains osmotic pressure of the blood
* Transports hemin and bilirubin
143
What can low plasma albumin cause and what can underlie this? [IMPORTANT]
* Low plasma albumin can lead to oedema or ascites (fluid in the abdomen)
* This is because when albumin in the blood is low, water may leave the blood vessels and collect in the tissues.
* The underlying cause for this is usually chronic liver disease (since the liver is responsible for removing conjugated molecules, such as drugs, from the albumin
144
What is the difference between plasma and serum proteins?
Serum contains fibrin and the granule contents of platelets, while plasma does not.
145
What are myelomas?
Myelomas are plasma cell cancers -\> Plasma cells are the specialised immune cells that produce antibodies for defence.
146
Add flashcards on the complement pathway from the plasma proteins lecture, if needed.
Do it.
147
Describe plasma proteins during inflammation.
148
What are some acute (inflammatory) phase reactants? [EXTRA]
149
What are some consequences of iron deficiency?
* Tiredness and lack of energy
* Shortness of breath
* Noticeable heartbeats (heart palpitations)
* Pale skin
If untreated:
* Higher risk of illness and infection
* Higher risk of developing heart or lung complications
* Higher risk of pregnancy complications
150
What is transferrin?
A glycoprotein that binds to and mediates the transport of iron through blood plasma.
151
What is the molecular size of tranferrin?
76kDa
152
What is the concentration of transferrin in the plasma?
2.5mg/ml
153
Where is transferrin made and where does it transport iron?
* It is made in the liver.
* Transports iron from the duodenum and macrophages to the liver.
154
What is transferrin important for (aside from iron transport)?
Defence against bacteria.
155
What type of molecule is alpha 1 antitrypsin and what does it do? [IMPORTANT]
* Serum anti-protease
* It protects the lung against damage from smoke, etc.
156
What is AATD?
157
What is haptoglobin and what is its role?
* A plasma protein synthesised in the liver
* Another acute phase reactant protein
* Haptoglobinin plasma binds tightly to free haemoglobin
* Haptoglobin-haemoglobin complexes are removed by macrophages in the liver and the spleen to prevent kidney damage by free iron
* This is important in conditions where RBC lysis is common
158
What are acute phase proteins?
* A class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation.
* This response is called the acute-phase reaction (also called acute-phase response).
159
What is ceruloplasmin?
160
What do plasma proteins protect us against?
* Tissue injury -\> Via acute inflammation which recruits plasma proteins to sites of sterile injury (role of albumin)
* Blood loss -\> Both internal and external (fibrinogen -\> fibrin)
* Bacteria and fungi -\> Via classical, alternative and MBP pathway activation of the complement cascade
* Excessive protease activity -\> AAT1 deficiency exemplifies this
* Cations -\> Especially excess Fe, which is very toxic (transferrin, haptoglobin, others)
161
Give a summary of plasma proteins.
162
What is the hormone that maintains iron homeostasis?
Hepcidin
163
Describe how hepcidin is involved in the iron cycle.
164
