trigger 2 - ischaemia Flashcards
1
Q
central nervous system - CNS
A
brain and spinal cord
2
Q
peripheral nervous system - PNS
A
all the nerves
split into somatic and autonomic
3
Q
protection of the brain
A
1 - skull
2 - meninges (3 membranes)
3 - cerebrospinal fluid (CSF)
4
Q
somatic nervous system
A
voluntary control
relationship with external environment
5
Q
autonomic
A
involuntary
regulate vital internal functions
split into sympathetic and parasympathetic
6
Q
grey matter
A
consists of:
- neurons cells bodies and their dense network of dendrites
- centre of spinal cord
- thin outer layer of cereal hemispheres (cerebral cortex)
7
Q
white matter
A
myelin sheath
8
Q
brain stem
A
responsible for a variety of automatic functions, such as control of respiration, heart rate, and blood pressure, wakefullness, arousal and attention.
9
Q
cerebrum structure
A
divided into a right and a left hemisphere
4 lobes:
frontal, parietal, temporal, and occipital
10
Q
stroke involving cerebellum
A
may result in a lack of coordination, clumsiness, shaking, or other muscular difficulties
important to diagnose early, since swelling may cause brainstem compression or hydrocephalus.
11
Q
blood supply to the brain
A
right/left common carotid arteries
right/left vertebral arteries.
12
Q
external carotid arteries
A
supply face and scalp with blood
13
Q
vertebro-basilar arterial system
A
back of brain
supplies vital brain structures (brain stem, occipital lobes, cerebellum) with blood, oxygen and nutrients
14
Q
Circle of Willis
A
found central base of brain
a circle of communicating arteries - carotid and verterbrobasilar
other arteries arise from this and travel to all parts of the brain
15
Q
anterior cerebral artery (ACA)
A
extends upward and forward from the internal carotid artery
supplies the frontal lobes (logic, personality, and voluntary movement, especially of the legs)
16
Q
what happens if there is stroke in one or both of the ACAs
A
weakness in the leg on the opposite side
if both ACAs are affected - mental symptoms e.g. akinetic mutism
17
Q
middle cerebral artery (MCA)
A
largest branch of internal carotid artery
supplies parts of frontal/parietal/temporal lobes
often most obstructed artery in strokes
18
Q
posterior cerebral artery (PCA)
A
stem from basilar artery (mostly)
supply temporal and occipital lobes
visual defects common if infarction occurs
19
Q
lenticulostriate arteries
A
small, deep penetrating arteries - arise from anterior part of Circle of Willis(by MCA) and affect basal ganglia
20
Q
lacunar strokes
A
arise when small lenticuloistriate arteries are occluded
v common - high incidence in patients with chronic hypertension
21
Q
zymogen
A
an inactive substance which is converted into an enzyme when activated by another enzyme
e.g. all enzymes present in plasma of clotting cascade found in this form
22
Q
final step of clotting cascade
A
thrombin causes fibrinogen to convert to fibrin
fibrin aggregates strengthen the platelet plug
23
Q
common pathway
clotting cascade
A
thrombin formation
24
Q
excitotoxicity
A
glutamate becomes toxic and causes damage to neurones due to over excitability
- intracellular calcium ion overload
- activation of NDMA receptors
25
calcium ion sinks
mitochondria
endoplasmic reticulum
overloading of sinks reduces ATP synthesis
26
formation of reactive oxygen species (ROS)
danger point reached
| positive feedback exaggerates process
27
problems caused by raised calcium ion conc.
- increased glutamate release from nerve terminals
- activation of proteases and lipases (membrane damage)
- activation of nitric oxide synthase
- arachidonic acid release
28
activation of reactive oxygen species
generate free radicals
| - damage membrane lipids, proteins and DNA
29
oxidative stress
over production of ROS which produce free radicals
- the body's inability to detoxify them
- neurons susceptible to excitotoxic damage
e.g. hypoxia
30
kainic acid
glutamate receptor agonist(activator)
31
arachidonic acid
increases free radical production
| inhibits glutamate uptake
32
reducing excitotoxicity
glutamate antagonists
calcium channel blocking drugs
free radical scavengers
33
ischaemia and excitotoxicity
ischaemia causes depolarisation of neurones and lots of glutamate release
NMDA receptors activated and Calcium accumulation occurs
34
alteplase
stroke drug
recombinant tissue plasminogen activator
helps restore blood flow by dispersing thrombus
given within 3 hours
35
2 types of stroke
ischaemic - lack of blood flow (atherosclerosis)
| hemorrhagic - weakened blood vessel ruptures (less common)
36
Hypoxia Inducible Factor (HIF)
transcription factors that respond to decreases in available oxygen in the cellular environment
37
stent
small mesh tube used to treat narrow/weak arteries
38
stent surgery procedure
percutaneous coronary intervention (PCI)or angioplasty
restores blood flow in blocked arteries
supports inner wall of artery
drug-eluting stents can prevent arteries from becoming blocked again
39
hypertension
high blood pressure
| 140/90 mmHg
40
VCAM-1
vascular cell adhesion molecule
produced by endothelial cells after damage has occurred
cause monocytes and T-lymphocytes to adhere(using cytokines) to endothelium as part of inflammatory response
41
oxidation of LDLs
occurs due to exposure to nitric oxide, macrophages, and some enzymes e.g. lipoxygenase
macrophages take them up and become foam cells
42
fatty streaks
the first signs of atherosclerosis that are visible without magnification
consist of lipid-containing foam cells in the arterial wall just beneath the endothelium
commonly occur in aorta/coronary arteries of 20/30yr olds
can form atherosclerotic plaques
43
T-lymphocytes in the intima
secrete cytokines
- induce smooth muscle cells to migrate from the media to the intima
smooth muscle cells proliferate due to growth factors and accumulate in intima
44
ruptured plaques
trigger acute thrombosis (activate platelets and clotting cascade)
45
blood gas test
tests oxygen levels in your blood
| tests your blood pH - too acidic = acidosis or too alkaline/basic =alkalosis
46
sample collecting for blood gas test
arterial blood used
Allen test checks enough wrist circulation for sample
47
where is the respiratory centre found
```
brain stem
(medulla oblongata and pons)
```
48
function of respiratory centre
control the rate and depth of respiratory movements of the diaphragm and other respiratory muscles
49
what chemoreceptors are involved with the respiratory centre
central chemoreceptors:
| - found on the ventrolateral surface of medulla oblongata - detect changes in the pH of spinal fluid
50
what can desensitise the central chemoreceptors
chronic hypoxia (oxygen deficiency) and increased carbon dioxide
51
oedema
excess fluid retention tissues/cavities
| can cause swollen ankles
52
importance of circle of willis
provides multiple paths for oxygenated blood to supply the brain
allows brain function to continue if one supplier is constricted
53
myocardial infarction (MI)
heart attack
54
where are the subunits of HIF-1 found
HIF-a in cytoplasm - gets hydroxylated in normoxia
HIF-B in nucleus
dimerisation of HIF-a and HIF- causes transcription
55
atheroma
accumulation of atherosclerotic plaque
56
4 steps of plaque formation
1 - endothelial dysfunction - formation of foam cells
2 - stable plaque formation - fibrous cap formation
3- T-cell activation - pro-inflammatory cytokines produced
4 - thrombus formation - extrinsic clotting cascade
57
step 1 of plaque formation
| endothelial dysfunction
- monocytes attach to endothelium via VCAM-1 receptors
- monocytes converted to macrophages in intima
- uptake of modified LDLs
- macrophages oxidise LDLs and become foam cells
- foam cells are what cause the fatty streaks
58
step 2 - stable plaque formation
- foam cells accumulate in intima
- vascular smooth muscle cells migrate from the intima to epithelium
- produce collagen and proliferate to form fibrous cap
59
T cell activation in atherosclerotic plaque formation
Th1 and Th2 recruited to break down fibrous cap
MMPs produced by foam cells
pro inflammatory cytokines produced
60
4th step of plaque formation
| - thrombus formation
```
fibrous cap broken down
endothelium becomes exposed
tissue factor released - extrinsic clotting cascade
binds to factor VII
factor VIIa
```
61
3 cardiac biomarkers
cardiac troponins (Tni and Tnt)
creatine kinase MB
myoglobin
62
cardiac troponins
```
cardiac biomarker
i and t
correlate to severity of infarction
detected after 12hours of symptoms
long persistence - up to 12 days
high specificity
high sensitivity
```
63
creatine kinase MB
```
cardiac biomarker
enzyme
peaks 24 hours after symptoms
lower sensitivty than troponins
only used when troponin not available
```
64
myoglobin
cardiac biomarker
released quickly after onset of symptoms
not specific
high levels seen when any muscle tissue is damaged
65
CRP used to predict thrombotic events
found in serum or plasma as a result of inflammatory response
66
ischaemic stroke
when a blood blot blocks a blood vessel in the brain
narrowing/stenosis of brain blood vessel
most common type of stroke
causes oxygen deprivation and reduced blood flow
67
2 types of ischaemic stroke
thrombotic
| embolic
68
embolic stroke
type of ischaemic stroke
| blood clot develops elsewhere then travels in the blood to the brain
69
important risk factor for ischaemic stroke
high blood pressure
70
insoluble protein fibres that cause blood clot
fibrin
71
process of primary homeostasis
| platelets forming network
endothelium of blood vessel damaged
connective tissue exposed
platelets adhere to and form a plug
seal reinforced by fibrin clot
72
clotting factors
proteins in the blood that control bleeding
| respond in clotting cascade and strengthen platelet plug
73
where do clotting factors come from
platelets
damaged cells
plasma
74
tPA
| tissue plasminogen activator
enzyme catalyses conversion of plasminogen to plasmin
used to treat embolic or thrombic stroke
75
what releases tPA
endothelium
76
junctions important in BBB
tight junctions
77
excitotoxicity
when neurons are damaged or killed by over-stimulation of glutamate receptors
78
why does hypoxia causes increased H+ conc
anaerobic respiration
| lactic acid production
79
effect of reduced ATP on calcium storage
SERCA pump requires ATP
| calcium can no longer be stored in ER
80
deleterous Ca2+ effects of excitotoxicity
NOS/ROS production - damage cell membrane and DNA
| hydroxyl free radicals
81
how does excitotoxcity activate apoptosis
glutamate release causes increased intracellular Ca2+ conc
production of ROS/NOS
activation of caspases
apoptosis
82
ischaemic cascade
biochemical reactions in aerobic tissue induced by hypoxia following ischaemia
83
can ischaemic cascade continue even when blood flow returns
yes
84
effect of decreased blood supply to tissue
decreased oxygen
decreased ATP
anaerobic metabolism
85
effects of anaerobic metabolism in ischaemic cascade
lactic acidosis
disruption of acid-base balance
failure of neural system - regional brain dysfunction
86
which pumps break in ischaemic cascade
Na+ and Ca2+ pumps
87
overview of ischaemic cascade
blood supply reduced
anaerobic metabolism
pumps broken - intracelluar Na and Ca conc increased
damage
88
effects of increased intracellular Na+ conc. in ischaemic cascade
H2O influx
swelling
cytotoxic oedema
necrotic cell death
89
effects of increased Ca2+ conc in ischaemic cascade
production of free radicals and ROS - mitochondrial injury - release of apoptotic factors
excitotoxicity - glutamate accumulation
degrading enzymes - proteases/lipases - necrotic cell death
90
reperfusion injury
tissue damage caused when blood flow is restored following ischaemia/hypoxia
91
effects of return of blood supply
increased oxygen and ATP
reactivation of dysfunctional Na+ and Ca2+ pumps
production of ROS and free radicals
92
why does mitochondrial permeability increase in reperfusion injury
ROS/free radicals cause damage to plasma membrane macromolecules and ER
mitochondrial pore
93
why does intracellular Ca2+ increase in reperfusion injury
ROS causes damage to ER membrane
| Ca2+ released
94
damage caused by Ca2+ in reperfusion injury
activation of degradative enzyme
endothelial injury - clots
pro-inflammtory cytokine release
apoptosis
95
brain stem connects
spinal cord and cerebellum
96
order of brain stem from top to bottom
thalamus
midbrain
pons
medulla
97
role of midbrain
regulates autonomic functions e.g. HR, BR
| relays visual and auditory signals
98
where in the brain stem controls eye movements
midbrain
99
role of pons
transmission of signals from cerebrum to cerebellum
controls balance and posture
regulation of breathing
regulation of deep sleep
100
role of medulla
involuntary reflexes e..g sneezing, coughing, vomiting
| autonomic centres e..g control of BP
101
how many cranial nerves come from the brainstem
10 out of 12
102
where is respiratory centre found
pons and medulla oblongata
103
input to respiratory centre
neural, chemical and hormonal signals
| e..g peripheral chemoreceptors and central chemoreceptors
104
function of respiratory centre
control rate and depth of respiratory movements of diaphragm and other respiratory muscles
105
what is known as the pacemaker of the lungs
respiratory centre in the pons and medulla
106
3 effects of the respiratory centre
1 - altered inspiration-expiration rhythm
2 - altered magnitude of ventilation
3 - modified respiratory activity e.g. coughing/speech
107
increased arterial PCO2 causes
decreased blood pH
108
what recognsies blood pH
peripheral chemoreceptors
109
effect of ventilation on blood PCO2
increased ventilation means more CO2 exhaled
| blood pH increases
110
peripheral chemoreceptors
sensory extensions of peripheral nervous system into blood vessels
detect changes in chemical concentrattions
111
where are peripheral chemoreceptors found
blood
carotid bodies
aortic bodies
112
function of peripheral chemoreceptors
detect chemical changes and send info to respiratory centre:
- decrease in PO2
- increase in PCO2
- decrease in arterial blood pH
113
what do peripheral chemoreceptors detect
- decrease in blood PO2
- increase in blood PCO2
- decrease in arterial blood pH
114
how do signals detected from peripheral chemoreceptors in aortic arch get to RC
via vagus nerve
115
how do signals detected in carotid bodies get to RC
via glossopharyngeal nerve
116
where are central chemoreceptors found
ventrolateral medullary surfaces near the respiratory centre
in the brainstem
between cranial nerves 9 and 10
117
function of central chemoreceptors
detect pH of CSF
| decreased pH means too much CO2
118
can H+ diffuse across BBB
no
119
when CO2 crosses BBB
converted into H+ and HCO3-
decreases pH of csf
detected by medullary chemoreceptor
communicates to inspiratory respiratory centre
120
2 types of respiratory centre
dorsal inspiratory
| ventral expiratory
121
dorsal expiratory respiratory centre
always active
122
ventral expiratory centre
active breathing
123
acid-base balance
regulation of blood pH to maintain pH between 7.35 and 7.45
124
acidosis
when blood pH<7.35
| causes depression of CNS, coma
125
alkalosis
blood pH<7.45
| over-excitability of CNS causes neurons to fire without stimuli
126
how does the kidney regulate acid-base balance
addition or secretion of bicarbonate ions (HCO3-)
127
where is HCO3- reabsorbed
at the PCT along with H+ at the Na+/H+ pump
128
overview effect of hypoxia
activates angiogenic switch to icnrease blood supply by increasing HIF-1a
129
role of HIF-1a in hypoxia
activates transcription of genes involved in VEGF
130
HIF-1a mechanism in hypoxia
no O2 so no hydroxylation
HIF-1a not degraded so translocates to nucleus
HIF-1a forms a dimer with HIF-beta
binds to HRE to cause transcription
131
HIF-1a mechanism in normoxia
prolyl hydroxylase enzymes add -OH group to HIF-1a
attracts E3 ub ligase of polyubiquitin tail
ub targets HIF to proteosome
degraded
132
HRE
hypoxia response elements
133
arterial blood gas analysis
shows imbalance of O2, CO2 or pH in the blood
O2 saturation can also be calculated
134
blood O2 saturation
amount of O2 bound to haemaglobin
135
normal blood pH
7.35-7.45
136
normal blood PO2
80-100 mmHg
137
normal blood PCO2
35-45 mmHg
138
normal blood O2 saturation
95-100%
139
normal blood bicarbonate conc
22-26
140
where do you take blood samples for arterial blood gas analysis
from the radial artery in the wrist
141
why is the wrist radial artery good for sample collection
easily accessible
| blood flow easily controlled
142
where does 70% of bicarbonate reabsorption take place
PCT
143
desribe how bicarbonate is reabsorbed from the PCT into the blood
Na+/H+ exchnage pump
