Topic 9 - Blood Flashcards
(141 cards)
1
Q
What is an artery?
A
Brings blood (generally oxygenated) to the heart from the organs and tissues
2
Q
What is a vein?
A
Returns blood (generally deoxygenated) from the organs and tissues to the heart
3
Q
What happens to the blood in one pump of the heart?
A
- Deoxygenated blood from tissues/organs travels through the Vena Cava into the right atrium.
- Right ventricle pumps the blood through the pulmonary artery to the lungs.
- Valves prevent backflow.
- Reoxygenated blood travels from the lungs to the left atrium through the pulmonary vein.
- Left ventricle pumps blood via the Aorta to the tissues and organs.
4
Q
What are the functions of the blood?
A
- Hydration of tissues and organs
- Delivery of oxygen to tissues and organs
- Provision of nutrients to tissues and organs
- Fight infection: innate and adaptive responses
- Regulation of body temperature and pH
- Distribution of endocrine hormones
- Prevent it’s own (blood) loss
5
Q
Which WBCs contribute to immune response to allergic reactions?
A
- Eosinophils
- Basophils
6
Q
What are endocrine hormones?
A
They are secreted directly to the blood stream.
7
Q
What are exocrine hormones?
A
They are secreted through ducts opening on to an epithelium rather than directly into the blood.
8
Q
How does blood prevent it’s own loss?
A
- Platelets (small anucleate cells that clump together)
- Blood coagulation pathway (through the formation of thrombin a fibrin clot is formed)
9
Q
What is the common progenitor cell that all blood cells are derived from?
A
The multipotential haematopoietic stem cell
10
Q
What are the two major lineages of blood cells?
A
- Myeloid
- Lymphoid
11
Q
Which two blood cells can be found in body tissues?
A
- Mast cells
- Macrophages
12
Q
Which 5 blood cells are found in the blood marrow?
A
- Hemocytoblast (stem cell)
- Common myeloid progenitor
- Megakaryocyte
- Myeloblast
- Common lymphoid progenitor
13
Q
Which 11 blood cells can be found within blood specifically?
A
- Platelets
- Basophil
- Neutrophil
- Eosinophil
- Monocyte
- Natural killer cell (large granular lymphocyte)
- Small lymphocyte
- T lymphocyte
- B lymphocyte
- Plasma cell
14
Q
How can plasma be separated from blood cells?
A
Centrifugation
15
Q
What volume of blood is blood plasma?
A
55%
16
Q
What are the 3 most abundant blood plasma proteins?
A
- Albumin
- Immunoglobulins
- Fibrinogen
17
Q
What is blood serum?
A
Plasma without the clotting factors
18
Q
What percentage of blood is taken up by RBC?
A
45%
19
Q
What occurs if incompatible blood groups are mixed?
A
Antibodies in the plasma reacts with antigens on the RBC membrane, causing haemolysis.
Potential complication during blood transfusion/pregnancy.
20
Q
What is the ABO blood group?
A
Based on the carbohydrate antigen present on the RBC membrane. A, AB, B and O types.
21
Q
Which ABO blood type is a universal donor?
A
O
22
Q
Which ABO blood type is a universal acceptor?
A
AB
23
Q
What are the main symptoms of an acute hemolytic reaction?
A
- Hypotension
- Kidney failure
- Bleeding
- Chills/Fever
- Hemoglobinuria
24
Q
What is Hemoglobinuria?
A
Haemoglobin in the urine due to erythrocyte lysis
25
What is the Rhesus blood group?
Based on the ion-channel antigen (D-antigen) on the RBC membrane
26
When does haemolytic disease occur during pregnancy?
Rh- (no D-antigen) woman and a Rh+ fetus (D-antigen).
During birth some foetal blood enters mothers system causing an immune response. In a following pregnancy the immune response will be much larger and will attack the foetus.
27
How can haemolytic syndrome in a foetus be treated?
Intramuscular injection of mother with Rh antibody at 28 weeks, 34 weeks and within 72 hours after delivery. Intrauterine transfusion via umbilical cord may be necessary.
28
What are the diseases of blood plasma?
- Bleeding
- Thrombosis
- Hereditary angioedema
- Complement deficiency
29
What are the diseases of the blood cells?
- Haematological malignancies
- Sickle cell anemia
- Thalassaemia
- Haemoglobinopathies
- Leukopenia
- Thorombocytopenia
- Infectious mononucleosis
30
What are haemoglobinopaties?
Genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule. eg. Thalassaemia and Sickle cell anemia
31
What are diseases affecting the platelets called?
Thrombocytopaenias
32
What is a leukopenia?
A decrease in the number of leukocytes found in the blood, which places individuals at increased risk of infection.
33
What may cause bleeding?
- Acute injury
- Chronic disease
- Low platelet count
- Coagulation deficiencies
- Vitamin K deficiency
- Drugs
- Liver disease
- Infection/sepsis
- Aneurysm repture
34
Which drugs can cause bleeding?
- Aspirin
- Warfarin
- Heparin
35
What is the ultimate killer in heart disease and stroke?
Thrombosis
36
What are the causes of thrombosis?
- Atherosclerosis
- Cancer
- Immobilisation
- Surgery
- Hypercoagulability
- Thrombocythaemia
- Factor V Leiden
37
Why does hypercoagulability occur?
Inhibitor deficiencies - PC, PS, AT
38
What is atherosclerosis?
A disease in which plaque builds up inside your arteries
39
What is neoplasia?
Uncontrolled cell growth. May be benign/malignant (therefore not necessarily cancer)
40
Which two classes of genes are implicated in neoplasia?
Tumour suppressor genes
| Oncogenes
41
What are oncogenes?
Genes directly causative of cancer – includes growth factors and their receptors, DNA binding proteins
42
What are tumour suppressor genes?
Loss of suppressor activity leads to cancer.
43
What initiates cancer?
- point mutations (UV, radiation, carcinogens)
- chromosome translocation
- viral genes
44
Which retrovirus is associated with leukemia?
Human T-Lymphotropic Virus (HTLV-1)
45
What is an example of a cancer caused by chromosomal translocation?
Burkitt's Lymphoma
46
How are haemotological malignancies classified?
Blood cell lineage (myeloid neoplasm/lymphoid neoplasm)
| Location (leukemia - blood/lymphoma - lymph nodes)
47
What cells are the precursors of platelets?
Megakaryocytes
48
What are Myeloproliferative disorders?
A group of slow-growing blood cancers in which the bone marrow makes too many abnormal red blood cells, white blood cells, or platelets, which accumulate in the blood
49
What are some myeloproliferative disorders?
- Myeloid neoplasia
- Polycythaemia (^ RBC)
- Thrombocythaemia (^ platelets)
- Myelofibrosis (^ megakaryocyte)
- Chronic myeloid leukemia (^ granulocytes)
50
What does leukemia result in?
Accumulation of WBC in the bone marrow and blood, bone marrow failure.
Decrease in RBC, platelets and eventually WBC themselves in advanced disease.
-blood hyperviscosity
-infection
-tiredness/anemia
-bleeding
-bone pain in children
51
What is lymphoma?
T or B lymphocyte neoplasia - affecting the lymph nodes
52
What are the typed of lymphoma?
Non-Hodgkin and Hodgkin
53
How is Hodgkin lymphoma characterised?
By Reed-Sternberg cells
54
Where do Reed-Sternberg cells originate?
B lymphocytes, which become enlarged and are multinucleate or have a bilobed nucleus.
55
What is anemia?
Loss of oxygen delivery
56
What are the haemoglobin levels in anemia?
<13.5 g/dl (men)
| <11.2 g/dl (women)
57
What are the symptoms of anemia?
- Tiredness
- Pallor
- Fainting
- Tachycardia
- Shortness of breath
58
What is tachycardia?
A heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults.
59
What is anemia caused by?
- RBC or haemoglobin production abnormalities
| - RBC destruction abnormalities
60
What are Colony Stimulating Factors involved in?
Haemopoiesis of myeloid cells including RBCs.
61
What are lymphokines involved in?
Haemopoiesis of lymphocytes and NK cells.
62
What are two examples of growth factors?
Epo and Thpo
63
How is Epo produced?
By interstitial fibroblasts in the kidney as an endocrine hormone
64
What are the causes of an iron deficiency?
- Diet induced
- Blood loss (acute or chronic)
- Infection (hookworm)
- Growth spurts (children), Pregnancy
65
What is distinctive of RBC in hypochromic microcytic anemia?
- Smaller cells with increased zone of central pallor
- Increased anisocytosis
- Increased poikilocytosis
- Some RBC become elongated
66
What is anisocytosis?
A medical term meaning that a patient's red blood cells are of unequal size. This is commonly found in anemia and other blood conditions.
67
What is poikilocytosis?
Variation in cell shape.
68
What are Vitamin 12 and Folate involved in?
DNA replication
69
What does a deficiency in either Vitamin 12 or Folate cause?
- Issues with mitosis of the proerythroblast
| - Causing megaloblastic or macrocytic anemia (large RBCs)
70
What causes Vitamin 12 deficiency?
Reduced absorption
71
What causes Folate deficiency?
- Poor nutrition
- Alcoholism
- Malabsorption
- Certain drugs (barbiturates, antibiotics and anti-epileptics)
72
What is a barbiturate?
A drug that acts as a central nervous system depressant, and can therefore produce a wide spectrum of effects, from mild sedation to death.
73
What does megaloblastic anemia lead to?
- Abnormally large RBCs
- Macroovalocytes
- Hypersegmented Neutrophils
74
When does chronic blood loss cause anemia?
When the volume of blood lost exceeds the capability for haematopoiesis of bone marrow
75
What kind of anemia does blood loss lead to?
Normocytic anemia (no RBC abnormalities)
76
What does growth factor Epo do?
Stimulates haemopoiesis of stem cells into erythrocytes (BFU production) in the bone marrow
77
What causes haemolytic anemia?
- Increased RBC destruction
- RBC lifespan decreases from 120 to 20 days
- Bone marrow unable to replace sufficient number of RBCs
- Acquired/Inherited
78
What are the two types of acquired haemolytic anemia?
- Immune
| - Non-immune
79
How is acquired immune haemolytic anemia caused?
- Haemolytic syndrome in newborn (Rh)
- Autoantibodies
- Complement
80
How is acquired non-immune haemolytic anemia caused?
- Drug-induced
- Snake venom
- Mechanical (heart valves)
- Infections (malaria, septicaemia)
81
What are the causes of inherited haemolytic anemia? (most haemolytic anemias are inherited)
- RBC cytoskeletal defects (mutations in alpha or bate spectrin)
- RBC enzyme defects (G6PD deficiency in NADPH metabolism)
- Haemoglobin defects (thalassaemia/sickle cell)
82
What do mutations in alpha or beta spectrin cause?
Hereditary spherocytosis
83
What is spherocytosis?
The presence in the blood of spherocytes, i.e erythrocytes (red blood cells) that are sphere-shaped rather than bi-concave disk shaped as normal. Spherocytes are found in all hemolytic anemias to some degree.
84
What is the cause of sickle cell disease?
- Mutation in the Hb beta globin gene (Glu 6 -> Val)
| - Polymerisation of Hb, distorting RBCs
85
What are the effects of sickle cell disease?
- 'Sickling' of RBCs
- Sickle cell crisis due to blockage of microvasculature
- Heterozygosity confers protection against malaria
- Increased infection risk
86
What is a sickle cell crisis?
Pain that can begin suddenly and last several hours to several days. It happens when sickled red blood cells block small blood vessels that carry blood to your bones.
87
Which haemoblobin genes are found on which chromosomes?
- Two alpha genes on chr 16
| - One beta gene on chr 11
88
What are the main haemoglobins in adults?
- HbA (alpha2beta2)
- HbA2 (alpha2delta2)
- HbF (alpha2gamma2)
89
What causes alpha thalassaemia?
Generally large deletions of the alpha-globin
90
What causes beta thalassaemia?
Point mutations in the beta-globin gene
91
What is haemostasis?
Arrest of blood flow
92
What is the function of haemostasis?
To prevent severe blood loss after injury
93
Why is bleeding a significant cause of mortality?
- Trauma
- Aneurysm rupture
- Infection/Drugs
- Haemophilia
94
What are the main two processes involved in the stemming of bleeding?
- Vasoconstriction (peptides/hormones lead to contraction of smooth muscle cells in the vessel walls)
- Haemostasis (primary and secondary)
95
What peptides/hormones lead to vasoconstriction?
- Thromboxane
- Serotonin
- Angiotensin
- Vasopressin
96
What is thromboxane produced by?
Activated platelets
97
What is serotonin secreted by?
Activated platelets
| but produced by enterochromaffin cells, mostly in the GI tract
98
What is primary haemostasis?
Platelet activation and aggregation
99
What is secondary haemostasis?
Coagulation pathway activation
100
What is the precursor or angiotensin?
Angiotensinogen (produced by the liver)
101
What is the platelet mechanism of haemostasis?
- Primary haemostatic response
- Platelets activated by thrombin & collagen
- Activated platelets change shape
- Activated platelets aggregate to form coagulum
- Platelet response alone is insufficient to stem bleed
102
What is pseudopodia?
A temporary protrusion of the surface of an amoeboid cell for movement and feeding
103
What is the coagulation mechanism of haemostasis?
- Secondary haemostasis response
- Involves cascade of proteolytic enzymes in the plasma that activate one another
- Activated by a tissue factor or contact activation
- Produces fibrin clot network
- Coagulation response alone insufficient to stem bleed
104
What are proteolytic enzymes?
Essential regulators and modulators of the inflammatory response
105
What categories of coagulation factors are there?
- Serine proteases (enzymes)
| - Co-factors
106
How do coagulation factors usually circulate in the plasma?
As an inactive pro-enzyme
107
What catalyses the conversion of fibrinogen to fibrin?
Thrombin
108
Which coagulation factors are serine proteases?
```
FVIIa
FIXa
FXa
FXIa
thrombin
trypsin
```
109
Which coagulation factors are co-factors?
Tissue factor
FVa
FVIIIa
110
What is proteolysis?
A protein is cut into smaller fragments, usually by hydrolysis of peptide bonds
111
How does proteolysis by digestive enzymes differ from proteolysis by coagulation factors?
Digestive: produces many small fragments from many proteins
Coagulation: more specific - one protein, one cut
112
What is the principle of limited proteolysis and enhancement of trigger?
Small amount of trigger via intermediates leads to a larger amount of product
113
What are the advantages of a cascading enzymatic pathway?
- Allows for a small trigger to produce a larger amount of product
- Allows foe acceleration of the response
114
What are some examples of cascading enzymatic pathways?
- Coagulation pathway
- Complement pathway
- Signalling pathways
115
How is coagulation triggered?
- Exposure of the blood to tissue factor
- TF is transmembrane protein expressed on perivascular cells
- After injury clotting factor FVII from the blood binds to TF expressed on the membranes of perivascular cells
- FVII self activates
- FVIIa proteolytically cleaves and activates FX
- FXa converts prothrombin to thrombin
- Thrombin converts fibrinogen to fibrin
116
What are perivascular cells?
Situated or occurring around a blood vessel.
117
What additional reactions to consolidate thrombin generation occur in coagulation?
- Activation of FIX to TF/FVIIa
- FIXa converts FX to FXa
- Activation of FXI, FVIII and FV by thrombin
- FVIIIa and FVa act as co-factors to FIXa and FXa respectivelly
118
What does a FIX deficiency cause?
Haemophilia B
119
What does a FVIII deficiency cause?
Haemophilia A
120
What can the deficiency of FIX/FVIII/FV lead to?
Severe spontaneous bleeding
121
What can a deficiency of vWF lead to?
Moderate to severe bleeding
122
What can a deficiency of FXI lead to?
Mild bleeding
123
Which three pathways can the coagulation system be divided into?
- Extrinsic
- Intrinsic
- Common pathway
124
What is the extrinsic coagulation pathway triggered by?
TF
125
What is the intrinsic coagulation pathway triggered by?
Negatively charged surfaces (Silica, polyphosphates released by platelets and misfolded proteins)
126
Which blood clotting complexes are vitamin K dependent?
TF/FVIIa
FIXa/FVIIIa
FXa/FVa
127
How do vitamin K dependent clotting factor complexes bind to platelet surface?
Via Ca2+
128
What is FXIII?
A transglutaminase activated by thrombin that cross-links fibrin to stabilise the fibrin network and increase its resistance to fibrinolysis.
129
What can a deficiency in FXIII lead to?
- Severe and spontaneous bleeding
- Miscarriage in pregnancy
- Poor wound-healing
130
How does fibrin help to protect against infection?
Forms fibrin film with fibres behind the film, stops microbes getting in
131
What is the structure of a platelet?
- Smallest blood cell (2-3 micrometers diameter)
- No nucleus
- Contain alpha-granules and dense granules
- Lifespan 5-9 days
- Produced by megakaryotes
132
What do alpha granules contain?
- Fibrinogen
- FV
- vWF
- Growth factors
133
What do dense granules contain?
- ADP/ATP
- Serotonin
- Calcium
- Polyphosphate
134
How do platelets become activated?
Through signalling through ligand-receptor (eg. collagen) interactions.
Adrenaline activates platelets so that during fight or flight if injured your blood clots.
135
What is the process of primary haemostasis?
1. Resting platelets circulate
2. Vascular injury damages endothelium and exposes sub-endothelial collagen
3. Platelets bind to collagen via GPVI and alpa-2-beta-1, also vie GPI and vWF. Platelets activate
4. Platelets release ADP and thromboxane that further activate them though binding P2Y and TP receptors respectively
5. Alpha-llb-beta-3 is activated
6. AllbB3 binds fibrinogen and von Willebrand factor, which assist in platelet aggregation and holding the platelet plug together
136
Which platelet receptor is involved in initial adherence of platelets to collagen?
GPVI/a2b1
137
Which process is targeted by aspirin?
Thromboxane synthesis
138
What is spontaneous bleeding?
No obvious cause, but due to coagulopathy, or other disease
139
What is induced bleeding?
From trauma, surgery
| external
140
What are some examples of internal major bleeding?
- haemophilia (joint/muscle)
- aneurysm rupture
- drug-induced
- gastro-intestinal
141
What are examples of minor bleeds?
- Normal bruises
- menorhaggia
- epistaxis
