Cardiology Week 1-2 Flashcards
1
Q
Does symp or parasym have greater influence on HR at rest
A
Parasymp
2
Q
What happens to HR if block symp and parasymp
A
heart keeps beating - because intrinsic pacemaker cells
3
Q
describe phases of SA node pacemaker cell AP
A
phases:
4 - unstable membrane potential -60mV, spontaneous depolarisation - Ifunny (mostly Na, Ca)
0 - depolarisation Ca in
3 - repolarisation K out
4
Q
Phases of ventricle AP
A
phases: 4 - stable membrane -90mV 0 - rapid depolarisaiton Na in Ca in (some) 1 - rapid repolarisation Kout 2 - plateau Ca in 3 - repolarisation K out
5
Q
how does parasym lower HR
A
M2 receptors coupled to Gi to cause decrease in cAMP and opening of K+ channels –> K efflux causes hyperpolarisation, slowed Na and Ca fluxes, longer to reach threshold
6
Q
How does symp increase HR
A
NA and A through B1 coupled to Gs to increase cAMP cause opening of Ca channels –> causes increased slope of phase 4, increase SA firing rate, and more rapid conduction (AV node)
7
Q
intrinsic factors leading to dysrhythmias
A
changes to cardiac tissue structure and function - ischaemia, infarction, fibrosis, cardiomyopathy
8
Q
extrinsic factors leading to dysrhythmias
A
hypo/hyperthermia, neural syndromes, jaundice, raised intracranial pressure, stress, smoking, caffeine, drugs
9
Q
3 mechanisms underlying dysrhythmias
A
altered impulse formation
altered impulse conduction
triggered activity (early or late after-depolarisations)
10
Q
early afterdepolarisation
A
excitation during plateau or rapid repolarisaiton phase - aberrant Ca or Na channel opening
11
Q
delayed afterdepolarisation
A
excitation on completion of repolarisation - Ca overload activation of 3Na/Ca exchange
12
Q
4 major classes of antidysrhythmias
A
- Na channel blockers - 1a moderate 1b weak 1c strong
- Badrenoceptor antagonism
- K channel blockade
- Ca channel blockade
(SOME BLOCK POTASSIUM CHANNELS)
13
Q
action of Na channel blockers
A
RHYTHM
reduce phase 0 slope and peak of ventricular AP
14
Q
action of Badrenoceptor antagonists
A
RATE
decrease rate and conduction, membrane stabilising effects on purkinje fibres
15
Q
action of K channel blockade
A
RHYTHM
delay phase 3 of ventricular AP, prolong ADP
16
Q
action of Ca channel blockade
A
RATE
most effective at SA and AV nodes - reduce rate and conduction
17
Q
lignocaine
A
class 1b Na channel blocker - mild Na block, shorten repolarisation, decrease ERP
18
Q
lignocaine taken at home?
A
no - only hospital - concentration dependent side effects
19
Q
adverse effects of Badrenoceptor antagonists
A
bradycardia, reduced exercise capacity, hypotension, AV conduction block, bronchoconstriction, ANXIETY
20
Q
amiodarone
A
K channel inhibitor, also Na and Ca and Badrenoceptor blocker
21
Q
Verapamil
A
cardioselective Ca channel blocker- acts preferentially on SA and AV nodal tissue
22
Q
drug types effecting rhythm
A
Na and K channel blockers
23
Q
drugs types effecting rate
A
Ca channel blockers, Badrenoceptor antagonists
24
Q
what is considered HIGH BP
A
> 140/90
25
risk factors for hypertension
smoking, diet, weight, stress
26
antihypertensive drugs ABCD
a - angiotensin system inhibitors
b - Badrenoceptor antagonists
c - calcium channel blockers
d - diuretics
27
renin-angiotensin system
antiotensiogen converted to angiotensin I by Renin
angiotensin I to II by angiotensin converting enzyme
converted then to aldosterone
28
actions of angiotensin II
cell growth, vasoconstriction
29
how symp effects renin system
NA acts on B1adrenoceptors on kidney - promote renin release
30
ACE inhibtors actions
reduce vascular tone
reduce aldosterone production
reduce cardiac hypertrophy
31
Prils
ACE inhibitors
32
Problem with ACE inhibitors
ACE = kinninase II - stops bradykinin breakdown - dry cough etc.
33
"sartans"
angiotensin R antagonists
34
clinically useful to block which AT receptor
AT1
35
actions of angiotensin R antagonists
same as ACE inhibitors except at receptor level
| not as bad side effects
36
"olols"
Badrenoceptor antagonists
37
actions of Badrenoceptor antagonists
reduce CO (rate, contractility), reduce renin release (blood volume, TPR)
38
side effects of Badrenoceptor antagonists
symp blockade - cold extremities etc.
fatigue, dreams, insomnia
bronchoconstriction
39
Calcium channel blockers action
block L-type Ca channels in myocardium and vasculature
40
dihydropyridines
Calcium channel blocker - vascular selective
41
calcium channel blocker adverse effects
verapamil - oedema, headache, bradycardia,
dihydropyridines - oedema, headache, reflex tachycardia
42
Hydrochlorothiazide
diuretic - reduce blood volume for hypertension
43
why do we need oxygen carrier in blood
1. cant carry enough to meet demands
2. oxygen diffuses slowly
3. oxygen v reactive - oxidation
44
heme structure
Fe(II) - 6 coordinating bond positions:
4 bonds to N
5th to histidine F8
6th bond to O in oxygenated Hb
45
colour of haem group for - Hb02, Hbde02, HbCO
Hb02 - scarlet
Hbde02 - dark
HbCO - cherry (CO binds 200x more strongly to Hb)
46
myoglobin or haemoglobin monomeric or tetrameric
myoglobin - monomeric
haemoglobin - tetrameric
47
what allows o2 access to heme in buried hydrphobic pocket in myoglobin
transient "breathing" of alpha helices
48
myoglobin - does O2 affinity change with O concentration
NO - myoglobin is saturated at low pressures of O2
49
structure of haemogloibn
2 alpha and 2 beta chains
| alpha and beta subunits associate more strongly with each other than with the same subunits
50
T and R state haemoglobin
T - deoxy
| R - oxy
51
curves of myoglobin vs haemoglobin binding
myoglobin - hyperbolic
| haemoglobin - sigmoidal
52
23-BPG acts as a
heterotropic allosteric modulator (external ligand that modulates function)
53
what does 23-BPG do
binds to cavity of positve amino acids, decrease Hb affinity for O keeps haem in deoxy state to help Hb release O in tissues
(forced to unbind at high O2)
54
how CO2 transported in blood
1 - carried by Hb on amino terminal groups of deoxy-Hb as carbamate
2 - CO2 converted to HCO3- by carbonic anhydrase - soluble in plasma
55
Bohr effect
binding of H+ to Hb lowers affinity for O2
56
in absence of effectors (H, 23-BPG) what happens to curve
approaches Mb-like properties
57
foetal Hb
Hb-F - binds O with higher affinity than mothers HbA - gives foetus access to O carried by mothers HbA
also less able to bind 23-BPG - so not locked into deoxy state
gamma subunits instead of Beta
58
HbS
sickle cell anaemia Hb - abnormal beta chain
59
HbC
mutation in beta gene
60
HbE
mutation in beta gene
61
HbS mutation
HbS has val instead of Glu in beta globulin
Val is hydrophobic, Hb shouldnt have hydrophobic residues on surface because they sticky - subunits stick to each other
62
pancytopenia
not enough blood cells
63
leukopenia
neutropenia
lymphopenia
not enough white BCs
64
thrombocytopenia
not enough platelets
65
polycythaemia
too many red cells
66
leukocytosis
too many white BCs
67
thrombocytosis
too many platelets
68
dyserythropoiesis
RBCs not working properly
69
anaemia defined as
a Hb level below that which is normal for age and gender
70
tissue oxygen delivery equation
| IMPORTANT
tissue oxygen delivery = CO x Hb x %Satn x 1.34
71
%Satn
oxygen saturation
72
ability of body to compensate due to anaemia
anaemia from chronic blood loss (slow) - over months compensate by increasing SV
acute - cant increase SV immediately
73
clinical signs of anaemia
pale, lethargic, failure to thrive, hypoxic (confused), ischaemia, tachycardia
74
sign used to monitor if anaemia getting better
tachycardia/ HR - because consistent sign for anaemia
75
causes of anaemia
failure of production
increased destruction/loss
inappropriate production
76
Hct
fraction of cells vs plasma (haematocrit)
77
MCV
mean cell volume
78
MCH
mean cell haemoglobin
79
blood film
morphology of red cells, white cells and plts
80
words denoting size of RBCs
normocytic, microcytic, macrocytic
81
words denoting colour of RBC
normochromic
hypochromic
polychromasia (blue - probably still have some RNA in them - fresh out of bone marrow - means marrow working overtime to get cells out)
82
classifications of anaemia
1. regenerative (bone marrow working) vs aregenerative (not working)
2. RBC size
83
signs of increased RBC production
reticulocytes, polychromasia
84
signs of increased destruction
jaundice (increased serum bilirubin - byproduct of RBC breakdown), haptoglobins, LHD (storage proteins in blood - if hap low and LHD high - evidence of RBC destruction
85
is increased destruction of RBC more dangerous than failure of production
YES - capacity for rapid reduction in Hb
86
how much blood is good, when replaced
RBCs - 3-5x10^12/L, replaced 120 days
WBCs - 2-6 x10^9/L (less than RBCs), replaced every 3-5 days
Platelets - 150-400 x10^9/L, replaced every 10 days
87
site of haemopoiesis
yolk sac - first few weeks
liver and spleen - 6weeks-7months
bone marrow - 7months - life
88
50% of marrow consists of
fat spaces (even in active haemopoietic areas)
89
haemopoiesis
pluripotent stem cell differentiates into all haemopoietic cell lines (also lymphocytes and osteoclasts)
capable of self renewal
90
bone marrow stroma
microenironment for bone marrow to grow
91
bone marrow communication with blood
bone marrow in constant communication with blood - circulates through v quickly
92
why progenitors dont leave bone marrow until mature
progenitor cells held with adhesion molecules onto stroma, changes in expression of adhesion molecules driven by GFs determines when cells leave marrow
93
bone marrow aspirate
needle into bone marrow, suck out, put on slide - no achitecture of marrow
94
do you see precursors in peripheral blood?
NOT USUALLY
if you do, not good for one of two reasons:
1. overwhelming infection - bone marrow throws out WBCs even when not ready cos need lots of them
2. leukaemia - no room for normal cells in marrow
95
bone marrow transplant
iv - cells know where to go - attach straight to stroma
96
haemopoietic growth factors
glycoprotein hormones, local and circulating action
97
do haemopoietic GFs act across multiple cell linages?
some do, some only on specific linages
98
redundancy in H GFs?
YES LOTS - lots of overlap
99
granulocyte colony stimulating factor
reduce amount of time cancer patients are neutropanic - reduce life threatening infections, enables more aggressive chemotherapy
100
do Haemopoietic GFs cause same thing in all cells?
NO
cause different things depending on what cell (i.e. what R they activate)
if early cell - stimulates proliferation
if late cell - activation
101
haematinics
nutrients required for formation and development of blood cells
iron
vitamin B12
folate
102
iron deficiency as a toddler
may or may not become anaemic but will lose IQ points
103
vitamin B12 sources, important for what
animal products only, important for all blood cell production
104
folate sources, important for what
green leafy vegies, important for all blood cell production and all cells
105
haemostasis
coagulation
106
fibrinolytic process
fibrinolysis - dissolving clot to get back to laminar flow
107
primary secondary haemostasis
primary - vasoconstrictin, platelet adhesion and aggregation
secondary - activation of coagulation factors, formation of fibrin
108
virchow's triad
vessel wall, blood composition, blood flow
all lead to thrombosis if small abnormality in any one of these
109
role of vessel wall in clotting
can be antithrombotic or prothrombotic depending on expression of surface molecules and secretion of proteins
110
coagulation system
tissue factor - starter motor
complex system of positive and negative feedback
key enzyme=thrombin
all proteins in system work in other regulatory systems as well
individual interactions between protiens happen on cell surfaces
111
3 phases of coagulation
initiation - kick start
activation - produce lots of thrombin
propagation - clot inreases in size, plugging with fibrin
112
action of thrombin
converts fibrinogen to fibrin
113
inactivation of thrombin
at least 3-4 mechanisms
114
thrombin actions outside of coagulation pathway
activation of PAR's (protease-activated receptors)
| embryonic growth, tumour spread, vascular disease
115
coagulation system tests for risk of bleeding, risk of clotting, monitor anticoagulant drugs - types of tests
risk of bleeding - global tests, specific assays, genotype for specific disorders
risk of clotting - NO global tests, yes to other two
monitor anticoag- all three
116
important principles of coagulation tests
sample integrity - CRUCIAL
| multiple consistent tests before diagnosis
117
global tests for bleeding
ACT (activated clotting time)
APTT (Activated Partial Thromboplastin time)
thrombin generation
118
specific assays for bleeding
factor assays
collagen binding assays
fibrinogen
119
chromogenic assays
type of specific assay
have chromogenic substrate taht protein can cleave to cause light emission
tells you how much function that protein has
(but problem - sometimes can cleave chromogenic substrate but not physiological one)
120
global functional assay
PT (prothrombin time)
PT ratio
INR =(patient PT/mean normal PT)^ISI
121
ISI
international sensitivity index - reflects sensitivity of reagent to reduction in Vit K dependent factors
122
APTT
| can you cross compare between labs?
activated partial thromboplastin time
cant cross compare between labs
tells us: factor deficiency, lupus anticoagulant (an Ab), heparin monitoring
123
epithelium of epicardium
simple squamous epithelium
124
myocardiocytes
cardiac muscle cells
125
intercalated discs consist of what
| vertical and horizontal parts
consist of adhernes junctions, desmosomes and gap junctions
vertical - adherens junctions
horizontal - gap junctions
126
why cardiac cells have gap junctions
electrically couple cells and coordinate APs
127
purkinje fibres - contractile?, intercalated discs?, glycogen?, bundles?
modified cardiac muscle cells - larger, irregular, limited contractile machinery, NO intercalated discs, FULL of glycogen, form bundles in subendocardium, terminate on cardiac msucle fibres
128
3 layers of blood vessel
tunica intima, tunica media, tunica adventitia/externa
129
structure of tunica intima
simple squamous epithelium (often aligned in direction of blood flow), with basal lamina
supported by thin subendothelial connective tissue layer
elastic lamina - part of connective tissue, boundary between intima and media
130
3 roles of endothelium
barrier
blood clotting
release vasoactive substances - endothelin (constrictor), NO (dilator)
131
tunica media function, what do they secrete
luminal diameter
| smooth muscle cells secrete the connective tissue in which embedded (collage type III, elastin, ground substance)
132
tunica adventita structure, blood supply
connective tissue comprises: collagen type I, elastin, ground substance, embedded fibroblasts
anchors vessel to tissue
has its own blood supply - vasa vasorum IN LARGER VESSELS
133
two types of arteries
1. elastic - close to heart - dampen large fluctuations in BP while maintaining BP, elastin, pulsatile
2. muscular - further from heart, distributing arteries, little elastin - concentrated in internal elastic laminae
134
vessle that has greatest contribution to BP
resistance equation
arterioles - theres heaps of them (massive length), resistance proportional to inverse of radius ^4
so if small radius, more able to control resistance
135
metaarteriole
intermediate between arterioles and capillaries incomplete smooth muscle coat
136
3 structure types of capillaries
fenestrated
sinusoidal - large spaces that can accomodate more than one RBC - particularly in areas where need to exchange cells
continous
137
structure of capillary endothelial cell
single endothelial cell rolled into tube, tight junction, basal lamina, v little cytoplasm, sometimes pericyte (modified smooth muscle cell), surrounded by only few collagen fibres (adventitia)
138
where fenestrated capillaries found
pancreas, intestines, endocrine glands
139
fenestrated capillaries structure
continuous basal lamina, pores spanned by diaphragm (contain 8 wedge shaped channels and radially oriented fibrils)
sometimes diaphragm missing- kidneys
140
sinusoidal capillaries where are they found
liver, lymphoid tissue, endocrine organs, bone marrow, spleen
141
Structure of sinusoidal capillaries
discontinous basal lamina, larger pores, +-diaphragm , endothelial cells may lack tight junctions
142
layers of veins
same as arteries BUT thinner media, thicker adventita
143
preferred site of diapedesis of leukocytes
venules
144
characteristics of medium to large veins
subendothelial connective tissue well developed
| adventitia enlarged, often at expense of media
145
embolism
when a thrombus travels somewhere it shouldnt
146
muscular arteries elastin
internal and external elastic lamina
147
arteriosclerosis
hardening of arteries/thickening of intima (healing but with fibrosis)
148
hyaline arteriolosclerosis
smooth muscle cells produec too much matrix, proteins from blood leak across damaged endothelium into arteriole wall
149
3 sequelae of arteriolosclerosis
1 - cerebral haemorrhage
2 - benign nephrosclerosis - ischaemia from narrowed arterioles
3 - hypertensive retinopathy
150
consequences of arteriosclerosis
arteries lose elasticity, become narrowed
impairs artery's role in BP
impair blood supply to downstream tissues
151
atherosclerosis
build-up of inflammatory, fibrotic, necrotic and fatty material in intima of arteries
fibrosis outside, necrotic tissue inside
152
fibroinflammatory lipid plaque (atheroma)
fibrous cap, necrotic lipid core
153
formation of atherosclerosis
1. fatty streaks
2. stable atherosclerotic plaque
3. unstable atherosclerotic plaque
154
fatty streaks
collections of foam cells in intima - macrophages (and smooth muscle cells) that have phagocytosed lipid
155
unstable (vulnerable plaques)
prone to rupture leading to 'acute plaque events'
| thinner fibrous cap, more necrotic core, more inflammatory cells, less stenosed lumen (than stable)
156
main complication of atherosclerosis
acute plaque events
157
acute plaque events - whats wrong
| what leads to
something wrong in plaque- rupture, haemorrhage into plaque, erosion of endothelium
leads to thrombosis, thromboembolism, atheroembolism,
158
aneurysm
stretching of artery due to weakness in media- weak so easily ruptures
159
claudication
crushing central leg pain
| result of chronic ischaemia
160
how are risk factors for atherosclerosis linked to endothelim
hypertension - low-grade shear effect
smoking - toxic and pro-inflammatory
high blood sugar and lipids - damage endothelium
161
LDL
bad cholesterol, taken up into intima, oxidised - becomes pro-inflammatory
taken up by macrophages and smooth muscle cells - they become foam cells
162
how activated endothelium act differently
1. adhesion molecule expression
2. produces cytokines and GFs
3. change from anti-coagulant to pro-coagulant
4. becomes leaky - macrophage entry into intima
163
HDL
circulating HDL absorbs lipids from plaques
164
role of inflammation in atherosclerosis
perpetuates endothelial dysfunction, attracts more infalmmatory cells - vicious cycle
165
role fo smooth muscle cells in atherosclerosis
GOOD
migrate into intima, change phenotype, proliferate adn produce ECM - collagen
gives thicker fibrous cap - more stable atheroma
166
10 morphological features of atherosclerosis
narrowed lumen, thickened intima, thinned media, fibrous cap, necrotic core, foam cells, cholesterole clefts, inflammatory cells (monocelular), clacification, neovascularisation
167
two ways pathological calcification arises
1. dystrophic calcification - appears in areas of cell degeneration
2. metastatic calcification - serum calcium adn phosphate levels too high - fall out of solution
168
AAA (abdominal aortic aneurysm) -- associated with what, often contain what
associated with atherosclerosis, often contain thrombus
169
berry aneurysm, where, weakening of what, major cause of
in cerebral circulation, weakening of a congenital defect, major cause of subarachnoid haemorrhage
170
cardiac tamponade
compression of heart by fluid (or blood) accumulation in pericardium
171
exsanguination
blood loss to a degree that causes death
| can be caused by ruptured aneurysm into thorax
172
causes of ventricular hypertrophy
hypertension, aortic stenosis, genetic
173
childhood growth of ventricles
ventricles start out v similar - right ventricle pumping into lower pressure system so doesnt hypertrophy as much
174
normal heart size depends on
body size, genetics, athletic, BP, angiotensin II and catecholamiens
175
mean left ventricular mass
160g
176
relative wall thickness =
LV wall thickness/LV chamber size
177
cardiac remodeling
changes in size, shape and function of heart after cardiac injury - more general -includes hypertrophy among other things
178
causes of cardiac remodeling
MI, cardiac damage (e.g. myocarditis), volume or pressure overload
179
concentric hypertrophy
increase LV mass
| increase relative wall thickness
180
eccentric hypertrophy
increase LV mass
| normal relative wall thickness
181
remodeling
normal LV mass
| increase relative wall thickenss
182
concentric hypertrophy often due to, more sarcomeres in ...
```
pressure overload (high afterload) - hypertension, aortic stenosis
more sarcomeres in parallel
```
183
eccentric hypertrophy often due to
| more sarcomeres in...
```
volume overload (high preload) - mitral and aortic regurgitaiton, ventricular septal defect
myocyte stretching - more sarcomeres in series
```
184
hypertrophy increased myocardial cell size or number??
SIZE
| also increased fibroendothelil cell numbers, interstitial matrix
185
eccentric hypertorphy maintains SV by
increasing LVEDV and EF (ejection fraction)
186
long term decompensations of hypertrophy
LV dilation, increased LDEDV, LVESV and decreased EF
reduced systolic functiona nd CO
increased LVEDP
187
identification of LVH
clinical - forceful apex beat, S4, S3
ECG - tall voltages, T wave inversion
CXR - large hart in ecentric, may be normal size in concentric
188
diastolic dysfunction
```
thick muscle is stiff
increased LVEDP
increased LA adn pulmonary vein pressure
pulmonary congestion
atrial kick more important
```
189
LV remodeling
causes
what happens
following MI
| increase LV volume and spherical shape, myocyte hypertrophy and apoptosis\, interstital fibrosis
190
LV remodeling reduced by
angiotensin blocking, Badrenoceptor blocking
191
causes of RV hypertrophy
congenital (transposition of great arteries), pulmonary hypertension, right heart valves regurgitation or stenosis
192
hypertrophic cardiomyopathy
autosomal dominant, mutations in genes for sarcomere proteins
increased LV wall thickness (esp septum), cellular hypertrophy, myocyte disarray
most common cause of cardiac death in young people
193
phenotype of hypertrophic cardiomyopathy
heterogeneous phenotype - same mutation may cause differnet phenotypes
194
dilated cardiomyopathy
proteins taht hod muscle cells together weaken - most common cardiomyopathy
195
athlete's heart
eccentric hypertrophy, cardiac function normal
196
how can you measure RVEDP
JVP
197
how can you measure LVEDP
catheter inserted via artery across aortic valve - measure left atrial pressure because at end of diastole atrial pressure =ventricular pressure =pulmonary artery wedge pressure (pumonary venous pressure)
198
capillary pressure more like venous pressure or arteriole pressure
venous pressure
199
starling forces
forces across capillaries
200
what causes oedema
increase in venous pressure - heart failure
decreased osmotic pressure - plasma protein loss (renal or liver failure)
blocked lymphatics - cancer
201
two uses of EDP
1 measure of filling of ventricles
| 2 measure of venous pressure driving fluid out of capillaries
202
LVEDP =
=preload:LV function
| = LAP=PVP: lung capillaries
203
RVEDP =
=preload: RV function
| = RAP = JVP: peripheral capillaries
204
how does body compensate for heart failure and decreased CO
| problem?
fluid retention
| problem - oedema in legs and lungs
205
clinical features of left and right heart failure
left - shortness of breath, fatigue, tachycardia, lung reps
right - oedema
206
cardiac failure inappropriate adaptations
Na and water retaition
K loss
vasoconstriction
these three by renin system
also symp activation
207
mechanisms and consequences of fluid retention
decreased CO - decreased renal blood flow - activation of renin system - fluid and NA retention, K loss (arrythmias) vasoconstriction
208
mechanisms and consequences of symp NS activation
increased NA - initial increased contractility - long term deleterious effect (vasoconstriction, ventricular arrhythmias, direct toxic effect)
209
3 right heart failure mechanisms
global heart disease - cardiomyopathy
2 specific right heart disease
3 - left heart failure
210
cardiac failure treatment
diuretics, aldsterone antagonists, ACE inhibitors, AT R antagonists
digoxin (mild positive ionotropic effect), beta blockers
211
escape rhythm
rhythm not caused by SA node
212
leads of ECG
lead 1 - right arm to left arm
lead 2 - right arm to left leg
lead 3 - left arm to left leg
213
current moving away from lead
negative deflection on ECG
214
current moving towards lead
positive deflection on ECG
215
current moving perpendicular to lead
zero on ECG
216
P wave - maximal in leads
II and V1
217
ectopic beat
extra beat coming from ventricle
218
result of beat coming from ectopic pacemaker cell on ECG
wider QRS - because signal goes from cell to cell rather than through conduction system - takes longer
219
sinus bradycardia: junctional escape
no P wave - SA node stopped firing
| get junctional escape beat - AV takes over for a beat
220
retrograde P wave
if get beat coming from AV - can go backwards up into atria
| atria contrac same time as ventricle
221
sinus pause and junctional escape
SA node stops - no P wave
| then get junctional escape rhythm (may take several seconds)
222
escape beats vs ectopic beats
escape - late, after sinus bradycardia or pause, pacemaker cell at normal rate (slower than SA)
ectopic - early, after a normal beat, pacemaker cell firing early (faster than SA)
223
1st degree AV block
prolonged P-R
224
2nd degree AV block
some beats not conducted
wenckebach block/mobitz 1 block -progressively prolonged PR until dropped beat - block at level of AV node
Mobitz 2 block - constant PR interval with dropped beat - block at level of HIs bundle
225
3rd degree AV block
no beats conducted
junctional escape rhythm
complete disconnection between atria and ventricle
226
atrial fibrillation characteristics
fast rate, irregular rhythm, no P waves, impulse conducted irregularly through av node due to chaos in atrium - av node hit with irregular rhythm
fast rate decreases LV filing time so increased LA pressure - pulmonary congestion
227
2 mechanisms of tachycardias
1 automatic focus
| 2 reentry
228
reentry tachycardia
transient conduction block in one limb of circuit
| if timing right tissue no longer in refractory so impulse can reenter circuit
229
3 re-entry tachycardias
1 - atrial flutter - re-entry circuit in right atrium
2 - AV nodal re-entry tachycardia
3 - ventricular tachycarida - reentry circuit in ventricle around scar
230
where does atrial fibrillation originate
left atrium at entry of pulmonary veins
231
what structure determines the ventricular pulse rate in atrial fibrillation
av node
232
management of AF
1 slow ventricular rate - digoxin, B blocker, Ca Blocker
| 2 revert to sinus rhythm - antiarrhythmics, DC shock
233
autotransfusion
transfusion of blood from venous side to arterial side
234
arterial or venous pressure more sensitive to changes in volume
arterial pressure
235
mean circulatory filling pressure
pressure when heart stops - depends on volume of blood and compliance of vessles
=7mmHg
236
venous function curve
describes what happens to venous pressure as Co increases
237
what happens to venous function curve with Increased blood volume
decreased TPR
curve moves up - increased blood volume
| curve moves up but maintains x axis - decreased TPR
238
central venous pressure
| assessed by what
pressure in SVC/IVC just outside of heart
| JVP
239
cardiac function curve
describes what happens to CO as venous pressure increases
240
what substances does endothelium produce
NO - vasodilation
endothelin - vasoconstriction (potent - irreversible binder)
PGs (both depending on PG)
241
WBCs release
NO
histamine
cytokines
242
platelets release
thrombin - clotting and vasoconstriciton
ADP-clotting and vasoconstriction
thromboxane A2
243
for any given volume of blood, pressure depends on
```
compliance
active tension (of the wall)
```
244
ESV
75mL
245
LV pressure volume curve in diastole and systole
see curves
246
frank-starling relationship
more stretch = more tension
| more EDV = more SV
247
contractility increases due to
acidosis, symp, caffeine, adrenaline, hypercapnia (high Co2)
248
ABCD points of LV volume pressure circuit
B - EDV
D - ESV
249
what happens to graph when :
increase contractility
decrease compliance
increase aortic pressure
up and back
loop right border to the left
up and forwards
250
afterload
load encountered by ventricle as commences contraction
251
preload
stretch on monocyte fibres before they commence contraction
252
why do local mediators act locally
labile OR rapidly metabolised OR diluted beyond biologically active range close to site of release
253
local mediators mostly what response
inflammatory response
254
stimuli inducing histamine relase
```
antigen via IgE
complement C3a/C5a
neuropeptides
cytokines and chemokines
bacterial components
physical trauma
```
255
Histamine receptors and where located
H1 2
H3 - CNS
H4 - immunomodulation
256
histamine triple response
reddening
wheal (increase vascular permeability causing swelling)
flare (spreading response through sensory nerve fibres
257
3 types of H1R antagonists
1 sedative - chlorpheniramine, promethazine
2 non-sedative - terfenadine, astemizole
3 - new non-sedative - cetrizine, loratidine
258
H2R antagonist uses
peptic ulcer treatment - decreases stomach acid production (but not used anymore)
259
gastric acid secretion
ach acts on enterochromaffin-like cell to release Histamine
acts on H2R on parietal cell
causes increase in cAMP
activates H+/K+ exchanger
260
bradykinin production
prekallikrein (inactive plasma protien) converted to kallikrein by Factor XII
kallikrein converts HMW kinninogen into bradykinin
261
actions of bradykinin
```
vasodilation
increase permeability
stimulates seonsory nerve endings - pain
contract uterus, airways, gut
epithelial secretions in airways and gut
```
262
breakdown of bradykinin
kinninase I and II (kinninase II=ACE)
263
hereditary angioedema
C1 esterase inhibitor deficiency
kallikreins are C1 esterases. if C1 esterase inhibitors deficient, get overactivity of these proteases
- defects in coagulation
angioedema (plasma exudation from deeper blood vessels)
264
icatibant
B2 R antagonist for hereditary angioedema
265
why ach sometimes vasoconstrictor and sometimes vasodilator in vitro
endothelium removed - helical strip - vasoconstriction with ach
endothelium intact - transverse ring - vasodiation with ach - ach acts on endothelium to release NO
(if increase ach concentration eventually get constriction as acting on smooth muscle)
266
endothelium derived vasoactive factors
prostacyclin (PGI2)
NO = endothelium-derived relaxing factor (EDRF)
(endothelin - constriction)
267
how does ach cause NO release
```
ach acts on MRs on endothelial cells
causes increase in intracellular calcium
activates NO synthase
converts arginine to NO
NO converts GTP to cGMP - relaxation
```
268
basal release of what regulates vascular tone
NO
269
NO synthase isoforms and where located
nNOS - nerves, epithelial cells
iNOS - inducible - macrophages, smooht muscle
eNOS - endothelial
270
NOS inhibitors
L-arginine analogues - cause vasoconstriction
271
NO physiological roles
flow dependent vasodilation
inhibits platelet adhesion and aggregation
NT
272
20:4
arachidonic acid, an omega 6 fatty acid
273
dietary sources of PUFAs
indirectly as linoleic acid(converted to arachidonic acid in body)
directly as arachidonic acid
274
PLA2 activated by
increased intracellular ca
275
eicosanoids
biologically active metabolites of arachidonic acid
276
lipoxygenase
first step in metabolism of arachidonic acid to leukotrienes
277
cyclic endoperoxides
unstable PGs
278
why do PGs have a local action
metabolised by endothelial cells of pulmonary capillaries
279
PGE2
vasodilator/natriuretic
hyperalgesic
pyrogenic
angiogenic
280
PGF2alpha and PGD2
bronchoconstrictors
281
how does PGE2 enhance pain
acts before bradykinin - get prolonged and increased pain response compared to BK alone
282
IL-1B induces
increase BK1 R
| increase COX-2 adn PLA2
283
fever production
peripheral inflammation causes macrophages activation
they release cytokines which circulate to hypothalamus (outside BBB)
induce COX2 production - produces PGE2
increases cAMP - raises temperature
284
PGE2 good role
gastro-protective - increases mucous secretion, decrease gastric acid secretion
promotes blood flow, promotes angiogenesis
285
prostacyclin or thromboxane more unstable
thromboxane (30s) vs prostacyclin (3mins)
286
action of aspirin on Cox
acetylates serine in active site of COX1 and 2
287
action of aspirin acetlyated COX2
retains some activity - produces epi-lipoxins from arachadonic acid
epi-lipoxins bind to formyl peptide R2 (FPR2) which actively suppresses neutrophil recruitment
288
advantage of omega 3 fatty acids
replace omega 6 fatty acids in membrane - their metabolism produces larger amount of prostacyclin than thromboxane due to substrate preference of thromboxane synthase
289
ach biosynthesis
choline + acetyl coa --> Ach + CoA
| ach carrier into vesicle
290
NA/A biosynthesis
tyrosine to L-Dopa by tyrosine hydroxylase
L-DOPA to dopamine by DOPA decarboxylase
DA to NA by dopamine B-hydroxylase
NA to A by PNMT
291
NA uptake
neuronal - high affinity uptake 1
| extraneuronal - low affinity uptake 2
292
atropine
M R antagonist
293
d-tubocurarine
NiR antagonist
294
alpha-bungarotoxin
NiR antagonist
295
phenylepherine
alpha 1 agonist
296
isoprenaline
beta agonist
297
endrophonium
short duration anticholinesterase - diagnosis of MG
298
neostigmine
reverse effect of non-depolarising neuromuscular blockers, MG treatment
299
donepezil
enters CNS, alzheimers treatment
300
myasthenia gravis
autoimmune - Abs against AchR
301
NiRs on skeletal muscle and gangion in ANs
Nm type - skeletal
| Nn type - ganglion
302
Ni antagonists
pre-surgical skeletal muscle relaxant =non-depolarising
303
pilocarpine
MR agonist for glaucoma
304
hyoscine
MR antagonist - motion sickness
305
ipratropium
MR antagonist - chronic obstructive pulmonary disease
306
beta agonist
isoprenaline
307
beta antagonist
propranolol
308
beta 1 agonist
dobutamine
309
beta 1 antagonist
atenolol
310
beta 2 agonist
salbutamol
311
alpha antagonist
phentolamine
312
alpha 1 agonist
phenylepherine
313
alpha 1 antagonist
prazosin
314
body usually uses what type of antagonism
functional
315
verapamil
L-type Ca channel blocker - inhibits cardiac function
316
allosteric modulators modulate
orthosteric ligand affinity
orthosteric ligand efficacy
receptor activation level
317
advantages of allosteric
selectivity between receptor subtypes
incomplete activation/inactivation possible
physiological modulation can continue
318
are drugs that are surmountable in vitro always surmountable in vivo
NO- limit of endogenous agonist
319
factors effecting rout of administration
patient convenience
cost
bioavailabilty
local vs systemic
320
elimination rate proportional to
concentration in plasma
321
drug distribution affected by
molecular size
plasma protein binding
lipid solubility
322
drug resevoirs can
prolong action
quickly terminate action
lead to slow distribution
323
Vd =
X/C
| apparent volume of body water drug appears to be dissolved in after distribution
324
GFR =
120mL/min
325
renal clearance
amount of blood from which drug removed by kindeys per unit time
326
CLrenal =
GRF +TS-TR
327
CL =
rate of elimination/C
328
cytochrome p450 which phase of metabolism
1
329
tubular reabsorption dependent on
pH
