Physiology and Pharmacology of Systems Flashcards
(447 cards)
1
Q
What is haematopoiesis?
A
Process by which mature blood cells are generated from precursor cells
2
Q
What are the 3 main contents of blood and main constituents of each?
A
Plasma - soluble proteins + mediators, 50-60%
Packed cellular volume - haematocrit, 40-45%
WBS + platelets
3
Q
What is the fancy name for platelets?
A
Thrombocytes
4
Q
Average location and amount of:
a) RBC?
b) Platelets?
c) WBC?
A
a) Confined to blood vessels, 4-6 x 10^6 / microlitre
b) Confined to blood vessels, 1.5-4 x 10^5 / microlitre
c) Use circulation in transit to + from tissue, 4-11 x 10^3 / microlitre
5
Q
When does haematopoiesis occur?
A
2-2.5 weeks in utero
6
Q
What cells are the blood islands surrounded by?
Why for one of them?
A
Surrounded by mesenchymal cells
Enveloped by endothelial cells
- arranged spatially so BC group into lumen of primitive blood vessels
7
Q
What type of cell do all blood cells arise from?
Origin of circulating blood cells?
A
Pluripotent stem cells
Haematocrit stem cells
8
Q
What type of stem cells do not have the potential for self renewal?
A
Unipotent/Progenitor
9
Q
What do these committed cells arise to?
a) Erythrocyte progenitor?
b) Megakaryocyte?
c) Myeloblast?
d) Monoblast?
e) B-lymphoblast?
f) T-lymphoblast?
A
a) Erythrocytes
b) Platelets
c) Neutrophils, Eosinophil, Basophil
d) Monocyte, Macrophages
e) B lymphocyte
f) T lymphocyte
10
Q
What is the shape, size (diameter) and lifespan of:
a) RBC?
b) Platelets?
c) Megakaryocytes (only size)?
d) Monocytes?
e) Small lymphocytes (only size)?
f) Large lymphocytes (only size)?
g) Neutrophils (only shape)?
h) Eosinophils (shape + lifespan)?
A
a) Biconcave discs, 7 micrometres, 120 days
b) Anuclear, discoid shape, 2-4 micrometres, 8-12 days
c) 50-70 micrometres
d) Mononuclear (horseshoe), 20, month/years for macrophages
e) 6-9 micrometres
f) 9-15 micrometres
g) Polymorphonuclear - multilobed
h) Bi-lobed nucleus, several days
11
Q
What is the penultimate precursor of RBC and the size?
A
Normoblast
8-10 micrometres
12
Q
In development of RBC, when nucleus abandoned, what is cell called?
A
Reticulocyte
1-2 days for RNA + organelles to be lost
13
Q
How do platelets form clots?
A
Adhere to fibrin filaments + damaged endothelial surfaces
14
Q
What does Fe combine with to form haem and where?
A
Protoporphyrin
Mito
15
Q
What types of cells act as nurse cells in development of RBC?
A
Macrophages
16
Q
What is the half life of neutrophils in blood?
A
6-7 hours
17
Q
When can neutrophils damage healthy tissue?
A
During chronic inflammatory diseases
e.g. RA, MS, COPD
18
Q
What is the main function of:
a) Uropods
b) Pseudopods
in neutrophils?
A
a) Acts as anchor, traction on tissue
b) Chemokine gradient
19
Q
What are the 4 main cytotoxic secretory products in eosinophils?
A
Major basic protein
Eosinophil cationic protein
Eosinophil derived neurotoxin
Eosinophil peroxidase
20
Q
What are small lymphocytes sub-divided into?
A
B lymphocytes + T lymphocytes
21
Q
What markers are present on:
a) T helper cells?
b) Cytotoxic T cells?
A
a) CD4 marker
b) CD8 marker
22
Q
What are natural killer cells?
A
Large lymphocytes
Kill virus infected/tumour cells with no involvement of specific antigens
23
Q
What is the relative refractory period?
A
AP overshoots to more -ve potentials
Stronger stimulation needed for another AP
24
Q
What is the normal cardiac AP duration at rest?
A
350-380 ms
25
What should the QTc be below?
Less than 400 ms
26
Why can't tetanise cardiac muscle?
Due to long AP
27
What is the hierarchy of pacemakers from fastest to slowest?
SA node
AV node
Bundle of His ==> left + right bundle branches
Purkinje fibres
28
What is diastolic depolarisation?
X have resting stable membrane potential
29
Name 3 features of cells from SA nodes
X cyto
Numerous caveolae
Lots membrane
30
What are 2 theories for diastolic depolarisation?
Membrane clock
| Calcium clock
31
What is a funny current?
Inward current activated when membrane potential gets more negative (hyperpolarized)
32
What is the only drug that lowers heart rate?
Ivabradine
33
What stimulates and inhibits funny current?
Stimulate - adrenaline
| Inhibit - AcH
34
What is the function of the AV pause?
Allows ventricles to fill
| Prevents transmission of fast heart rates from atria
35
What is atrial fibrillation?
Atria contract randomly + fast
36
What are connexons made up of?
2 hemi-channels
| Subsequently made up 6 connexins
37
Where are connexons commonly found in the cell?
End of cells
38
What is anisotropic conduction?
Muscle cell to muscle cell contraction
39
What are the 2 electrodes of the ECG called?
Reference electrode
| Recording electrode
40
What do each part of ECG wave represent?
P - Atrial Depolarisation
Q - Depolarisation of septum (towards atria)
R - Depolarisation of ventricles (towards apex)
S - Depolarisation of ventricles (towards atria)
T - Repolarization of ventricles (towards endocardium)
41
Which part of the electrical impulse doesn't show up on an ECG?
When it spreads down Bundle of His and left and right bundle branches
42
Why is the Q wave negative?
Towards head so wave of +veness away from recording electrode
43
Why is R wave rapid?
Specialised rapidly conducting Purkinje fibres
44
What does the PQ interval indicate?
| Pathology
Atrial conduction
AV node delay
AV block
45
What does the ST segment indicate?
| Pathology
Heterogeneity of ventricular polarisation
Myocardial infarction
46
What does the QRS duration indicate?
| Pathology
Ventricular conduction velocity
(Depolarisation of ventricles)
Bundle branch block
47
What does the QT interval indicate?
| Pathology
Ventricular AP duration
Long QT syndrome
48
What is resting Ca level?
100 nM
49
Definition of:
a) Chronotropy?
b) Inotropy?
c) Lusitropy?
a) Heart rate
b) Strength of contraction
c) Rate of relaxation
50
What are 2 examples of +ve chronotropic agents and what is the type of stimulation?
Adrenaline, Noradrenaline
| Sympathetic stimulation
51
What does +ve chronotropic agents cause?
Increase funny current
Faster rate diastolic depolarisation
Faster heart rate
52
What an example of -ve chronotropic agents and what is the type of stimulation?
AcH
| Parasymp stimulation
53
What does -ve chronotropic agents cause?
Decrease funny current
Opens K-AcH channels
Slower rate of diastolic depolarisation
Slower heart rate
54
What an example of +ve inotropic + lusitropic agents and what is the type of stimulation?
Adrenaline + noradrenaline
| Beta receptor stimulation
55
How does PKa phosphorylation affect?
a) Pacemaker?
b) L type Ca channels?
c) ATPase subunits?
d) RYR2?
e) Myofilament?
a) +ve chronotropy
b) +ve chronotropy, +ve inotropy
c) +ve lusitropy
d) +ve inotropy
e) +ve inotropy, +ve lusitropy
56
What is the diastolic notch?
Aortic valves snapping shut
57
In a PV loop, what represents the:
a) Stroke work?
b) Stroke volume?
a) Integrated area bound by a PV loop
| b) Difference between isovolumetric contraction and relaxation
58
What are the 2 features of a jugular venous pressure wave?
Biphasic
| Low pressure
59
```
In the JVP wave, what does the:
a) A wave
b) X descent
c) C wave
d) V wave
e) Y descent
represent?
```
a) Atrial contraction (right)
b) atrial relaXation
c) Carotid pulse - interruption of x descent
d) atrial filling during Ventricular systole - bulging of tricuspid valve
e) passive atrial emptYing - tricuspid valve open
60
What are the 2 features of a arterial pulse wave?
Monophasic
| High pressure
61
At what hydrostatic pressure will the jugular vein collapse?
5 cm above heart
62
How to assess JVP in a patient?
Support patient 45 degrees
| JVP is height of collapse of internal jugular 3 cm above manubriosternal angle
63
Why does the patient have to be at 45 degrees to assess JVP?
If upright, point of collapse lower
| Jugular below level of clavicle so x see
64
Why is internal jugular preferable to external?
Closer to r atrium - external x directly drain ==> SVC
Valveless so can see pulsations - opposite external
Vasoconstriction can make external small + barely visible
External superficial + prone to kicking
65
What is tricuspid stenosis and how does the JVP wave change?
Narrowing of tricuspid valve opening
| Atrial wave enhanced + ventricular wave diminished
66
What is tricuspid regurgitation and how does the JVP wave change?
Valve x close tight enough
| Atrial wave diminished + ventricular wave enhanced
67
What does the S1 sound represent in a phonocardiogram?
Initiation of v systole + AV mitral valve closure
Low frequency
Lub
68
What does the S2 sound represent in a phonocardiogram?
Closure of semilunar valves
Higher frequency + shorter
Dub
69
What does the S3 sound represent in a phonocardiogram?
Opening of AV valves + rapid refilling
70
What does the S4 sound represent in a phonocardiogram?
Atrial systole, rarely heard
| Except when EDP raised
71
What are the;
a) Primary heart sounds?
b) Secondary heart sounds?
a) S1 and S2
| b) S3 and S4
72
What is the name of the rhythm when you can hear S3 and S4?
Gallop rhythm
73
What is a heart murmur?
Turbulence in blood
| X always pathological, occur in young/exercise
74
What are 2 pathological causes of heart murmurs?
Valve stenosis
| Valve regurgitation
75
What are 2 causes of diastolic murmurs?
Mitral stenosis - hear as ventricle fills
Aortic incompetence - early diastolic murmurs
softing + prolongation of 2nd sound
76
What are 2 causes of systolic murmurs?
Aortic stenosis - high pressure
| Mitral incompetence - pan-systolic (lush)
77
What is atherosclerosis?
Buildup of cholesterol - rich plaques
| Causes stenosis of arteries
78
What type of cells are blood vessels commonly made up of?
| What involved in?
Smooth muscle cells -
Contract + relax, control diameter
Endothelial cells -
Regulate sm cells, inhibit thrombosis
79
What is 40% of human mortality caused by?
Disruption of vasculature structure and function
80
What 3 factors regulate vascular tone?
ANS
Circulating hormones
Local mechanisms
81
In regulation of vascular tone, what are 3 features of SNS?
Constriction - splanchnic, renal, vascular beds
Alpha -1 receptors + NANC
Activation redistributes blood flow + raises TPR
82
In regulation of vascular tone, what are 3 features of PNS?
Vasodilation - salivary glands, pancreas, intestinal mucosa, penis
Muscarinic receptors + NANC
Regulates blood flow organs, activation x effect TPR
83
What circulating hormones affect vascular tone?
Adrenaline
Angiotensin II
Vasopressin
84
Why is vascular tone regulated?
Maintain necessary blood flow to all organs
85
Why is CO + TPR regulated?
Maintain adequate pressure head (arterial BP)
86
What substance does endothelium release that relaxes surrounding sm?
Nitrous oxide
87
What is NO release stimulated by?
Bradykinin, ATP, His, H+, CO2, AcH
88
What is PGI2, what is it released by and what does it do?
Prostacyclin
Endothelium
Inhibits platelet aggregation + endothelin
89
What is eNOS?
Endothelial nitrous oxide synthase
90
What is oxidative stress?
Overproduction of reactive O2 species
91
What does superoxide react with and what does it form?
| Why bad?
O2- + NO ==> peroxynitrite
| Prevents NO mediated vasodilation
92
What are EETs, what released by + what do?
Epoxyeicosatrienoic acids
Endothelium
Activates K+ channels on vascular sm cells
Causes hyperpolarization + relaxation
93
What 2 ways do vasodilating drugs work by?
Blocking processes causing contraction - VG Ca2+ channel blocker
Stimulating/ mimicking pathways causing relaxation - organic nitrates
94
How is constant blood flow maintained in vascular beds over range of pressures?
Myogenic response
95
What effects do metabolites have on vascular function?
Tonic vasodilating influence on resistance vessels
96
Which is more wichtig - myogenic/metabolic regulation?
Metabolic increases as resistance vessel diameter decreases
97
When and where does metabolic hyperaemia occur?
| What substances produced?
Cardiac + skeletal muscle
Increased metabolism during exercise
K+, H+, CO2, lactic acid, adenosine
98
When does reactive hyperaemia occur?
After static (isometric) exercise
99
What are 2 structural adaptations of coronary circulation?
Formation coronary collaterals after ischaemia
| High capillary density - 1 capillary/myocyte
100
Why is blood flow in cardiac wall occluded during systole?
Rise in wall tension compresses intramyocardial arterioles
101
What is the Circle of Willis made up of?
Anterior + Posterior cerebral
Internal carotid
Anterior + Posterior communicating arteries
102
What are 2 functional adaptations of cerebral circulation?
Strong metabolic hyperaemia - excess blood supply to organ
| Weak regulation by ANS
103
What is diameter of typical capillary?
8 microns
104
What are the 2 main layers in capillary?
Basal lamina - fibrous protein, supports endothelium
| Monolayer of endothelial cells - x sm cells (same venules)
105
What extra layer can capillaries in CNS have?
Pericytes
| Contractile cells
106
What layer does veins have?
Thin tunica media
107
What is diameter of typical vein?
5mm
108
What happens to venules near sites of infection?
Permeable to leukocytes
Enter tissues via diapedesis - passage of cells via capillaries
Immune response
109
What is the respiratory pump related to venous system?
Inspriration reduces pressure within thorax
Decreases pressure within vena cava
Increase pressure gradient from venules ==> vena cava
110
What 3 factors can CVP vary due to?
Blood volume
Venous constriction
Posture
111
What is haemostasis?
Arrest of blood loss from damaged vessels
112
What is thrombosis?
Formation of occlusive thrombi, leading to MI, ischaemic stroke
113
What is primary haemostasis?
Aggregation of platelets + vasoconstriction
114
What receptors are present on platelets and what do they bind to?
GP1b - vWF
GPVI - collagen binding
Integrin alpha2beta1 - collagen 1
115
What are platelets exposed to in the ECM which they aren't usually?
Collagen
| Von Willebrand Factor
116
What is role of thrombin?
Catalyzes conversion fibrinogen ==> fibrin
| Activates procoagulant factors V, VI, XI, XIII
117
What is COX and what does it activate?
Cyclooxygenase enzyme
| Activate prostanoid thromboxane (TXA2)
118
What does 5 hydroxytryptamine do?
Vasoconstriction blood vessels
119
What does ADP do to platelets?
Activate adjacent platelets
Functional confirmation of receptor GP IIb/IIIa
Adjacent platelets come together by fibrinogen crosslinking
120
What is secondary haemostasis?
Clotting pathway
121
What causes initiation of clotting pathway?
Tissue Factor (TF)
122
What causes amplification of clotting pathway?
Thrombin
| Activates factors FV, FVIII, FIX, FX
123
What are
a) Arterial
b) Venous
thrombi associated with?
a) Atherosclerosis
| b) Stasis of blood/vascular injury following surgery/trauma
124
What are the main components of:
a) Arterial thrombi?
b) Venous thrombi?
a) Platelets
| b) Fibrin, RBC
125
What is the prophylaxis for:
a) Arterial thrombi?
b) Venous thrombi?
a) Anti-platelet drugs
| b) Anti-coagulants
126
What makes up Virchow's triad?
Endothelial/vascular damage
Low blood flow (stasis)
Hypercoagulabilty
127
What is the action of aspirin?
Irreversible inhibition of COX-1
128
What does TXA2 do?
Platelet agonist
| Vasoconstrictor
129
What are 4 side effects of aspirin?
Blood disorders
GI haemorrhage
GI irritation
Increased bleeding time
130
What are 2 irreversible P2Y12 antagonists?
Clopidogrel
| Prasugrel
131
Why is Clopidogrel reduced pharmacological effect on 20-30% of pop?
Genetic polymorphisms CYP450 + CYP2C19
132
What are 2 P2Y12 antagonists developed by design?
Ticagrelor - oral
| Cangrelor - i.v
133
Why do the P2Y12 antagonists developed by design have a rapid onset action?
Non-thienopyridine derivatives
| X require metabolism
134
What are 2 types of GP IIb -IIIa antagonists and examples?
| How taken?
F-ab fragments - aboximab, tirofiban
| Small molecule inhibitors - Eptifibatide
135
What are 3 sub-optimal problems with current antiplatelet drug therapy?
Limited clinical efficacy
Variable in patient response + toxicity
Risk major haemorrhage
136
What does HIT stand for?
Heparin induced thrombocytopaemia
137
What is heparin made up of?
Glycodaminoglycans
138
Pros and cons of unfractionated heparin?
```
Pro:
Cheap, shrt 1/2 life, reversible with protamine
Con:
Continuous infusion
HIT
Haemorrhage
Unpredictable pharmacokinetics
```
139
Pros and cons of low molecular weight heparin (LMWH)?
```
Pro -
Low chance HIT
High bioavailability
Con -
Expensive
Haemorrhage
```
140
What factor on platelets bind to heparin to cause HIT?
Platelet Factor 4 (PF4)
141
What does the binding of PV4 to heparin complex cause?
Heparin-induced thrombocytopenia type 2
142
What does coumarin (Warfarin) inhibit?
Inhibit Vit K dependant epoxide-reductase
143
What does epoxide-reductase do?
Modifies FVII, FIX, FX, FII during synthesis in liver
144
What can affect Warfarin activity?
Diet
| Genetic variation
145
What is the antidote for major bleeding event caused by warfarin?
Vit K
| Replace clotting factors by plasma transfusion
146
What factor Xa inhibitors directly inhibit and examples?
Orally available
Rivaroxaban, Apixaban, Edoxaban
X frequent blood monitoring
147
What are examples of factor Xa inhibitors via injection?
| What effect?
Fondaparinux, idraparine
Pentasaccharides
Act indirectly via antithrombin
148
What does antithrombin do?
Produced liver
| Inactivates FX + FII
149
What type of thrombin does thrombin inhibitor work on?
Clot bound + free thrombin
150
Examples of:
a) I.V thrombin inhibitor?
b) Orally active thrombin inhibitor?
a) Hirudin, Lepirudin, Desirudin
| b) Dabigatran
151
What things do traditional anticoagulants require?
Monthly blood tests
Dietary consultations
Possibility uncontrolled bleeding
152
What are DOAC?
Directly oral anticoagulant
153
What DOAC has an antidote?
Dabigatran
154
What does fibrinolytics do?
Activate plasminogen
| Remove arterial thrombi
155
What is the risk of fibrinolytics and how treat?
Haemorrhage
| Tranexamic acid
156
2 example of fibrinolytics + properties
```
Streptokinase:
non enzyme protein from streptococci
Plasminogens ==> plasmin
Allergenic
Alteplase:
non-allergenic
Clot selective - only activate plasminogens bound to fibrin in thrombus
```
157
What is the common rhesus group peeps have and why?
Rh+ (85%)
| Gene for D antigen dominant
158
How is antibody to D antigen formed?
Exposure to D antigen and sensitisation
159
When does antigen to D antigen formed?
Transfusion
| Rh- mother birth to Rh+ baby + blood mixes
160
What are 5 complications with blood transfusions?
```
Blood type incompatible
Transmission of infection
Fe overload
Fever
Impaired clotting
```
161
What percentage of stroke volume is stored in aorta and large arteries after systole?
75%
162
What percentage of stroke volume is pushed forward into smaller arteries during systole?
25%
163
4 short term factors that affect BP?
Sleep
Posture
Exercise
Stress
164
Where are baroreceptors located?
Carotid sinus in upper arch
165
What is orthostasis?
Decrease in BP soon after standing
166
What is afterload?
Force against which left ventricle pumps to eject blood into aorta
167
What is preload?
Degree of cardiac stretch
| Amount of blood in ventricles before they contract
168
What is the IX cranial nerve?
Glossopharyngeal
169
What are baroreceptors?
Fine nerve endings with mechanoreceptors
170
If BP decreases, what receptors are affected on parasympathetic drive?
M2
| Beta-1
171
If BP decreases, what is effect of parasympathetic drive?
HR increase
Force increase
CO increase
172
If BP decreases, what receptors are affected on sympathetic drive?
Beta 1
| Alpha 1
173
If BP decreases, what is effect of sympathetic drive?
Venoconstriction
CVP increase
Arterial constriction - TPR increase
174
What is the blood level of adrenaline?
0.2-1nM
175
What receptors does noradrenaline effect?
Beta - 1
| Alpha - 1
176
What receptors does adrenaline effect?
Beta - 1
Alpha - 1
Beta -2
177
What is the effect of these receptors when activated?
a) Beta 1
b) Alpha 1
c) Beta 2
a) Increase HR, Cardiac contractility
b) Vasoconstriction in most vascular beds
c) Vasodilation in skeletal muscle
178
What is used for long term regulation of arterial BP?
Maintenance of constant ECF volume
179
What is pressure natriuresis?
Increased renal perfusion due to higher BP
180
What 4 things directly affect cardiac output?
Preload
Afterload
Contractility
HR
181
What is Starling's Law of heart?
Energy released during contraction depends in initial fibre length
182
What is skinned cardiac muscle?
Removes cell membrane
183
What are 3 consequences of Starling's law?
SV of l and r ventricles are perfectly matched
Any given rate + functional state of heart, CVP will determine CO
Helps maintain CO even in face of increased afterload/decreased contractility
184
What happens to the Starling curve in heart failure?
Becomes depressed
185
What are 3 compensatory mechanisms for heart failure?
Reduce in pressure natriuresis - retention of Na + H2O
Activation of SNS + RAAS
Greater venous blood volume + vasoconstriction increase CVP
186
What is the abbreviation for:
a) Atmospheric pressure?
b) Alveolar pressure?
c) Mouth/nose pressure?
a) Pb
b) PA
c) Pm
187
What is Boyle's law?
Pressure of fixed number of molecules (at constant temp) related to volume of a container in which they're placed
PV = constant
188
What value is -ve intrapleural pressure?
-5cm H2O at resting end expiration
| Relative to Pb
189
What type of muscles are used at rest during inspiration and what are they?
```
Obligate Inspiratory Muscle
Diaphragm
External Intercostal muscles
Scalenes
Parasternal intercostal
```
190
What muscles are used for inspiration if need increase resp intake?
Accessory intercostal muscle
| Sternocleidomastoid
191
What is FRC?
Functional Residual Capacity
| Volume of lung at end of normal expiration
192
What is the meaning of these abbreviations?
a) Pw
b) Pl
c) Prs
d) Ppl
a) Trans chest wall
b) Transpulmonary pressure
c) Trans total system
d) Intrapleural pressure
193
How to calculate:
a) Pw
b) Pl
c) Prs
a) Ppl - Pb
b) PA - Ppl
c) PA - Pb
194
What 4 factors change with inspiratory pressure?
Intrapleural pressure
Alveolar pressure
Transpulmonary pressure
Inspiratory muscles
195
What is a pneumothorax?
Collapsed lung due to air in pleural cavity
| Lungs inwardly directed elastic recoil
196
What are the typical values for:
a) Vt?
b) VC?
c) IRV?
d) ERV?
e) IC?
f) TLC?
g) FRC?
h) RV?
a) 500ml
b) 5500ml
c) 3300ml
d) 1700ml
e) 3800ml
f) 7300ml
g) 3500ml
h) 1800ml
197
What measurement cannot be taken by spirometry - what is technique?
TLR
FRC
RV
Bodyplevismography
198
What is dead space and it's abbreviation?
Airway volume with no gas exchange
| Vd
199
Calculation for physiological dead space?
Anatomical Vd - Alveolar Vd
200
What is
a) Anatomical
b) Physiological
dead space?
a) All except alveoli + respiratory bronchioles - 15oml approx
b) Areas where GE dysfunctional
201
Calculation for alveolar ventilation?
Total ventilation p/min - dead space ventilation
202
Calculation for total ventilation?
Vt x frequency
203
What are the 2 main sources of resistance the lung needs to overcome?
Elastic resistance of lung
| Airway resistance of lung
204
What is elastic resistance of lung?
Resistance to stretch of lung tissue + air-liquid interface lining alveoli
205
What is airway resistance of lungs?
Resistance due to friction between layers of flowing air + airway walls
206
Calculation for lung compliance?
Change in lung volume/ Change in transmural pressure gradient
207
Calculation for airway resistance (RAW)?
(Alveolar pressure - mouth pressure)/ Airflow at mouth
208
What 3 factors can disrupt laminar flow and lead to turbulence?
Increased velocity
Sharp edges
Branch points
209
What causes lung sounds?
High velocity airflow due to narrowed airways
210
What lung sounds are heard in asthma and how are they generated?
Wheezing
| Oscillations in walls of airways near point of closure
211
Why is silent chest ominous is asthma?
X generate enough airflow to breath
212
What factors can affect bronchodilation on airway smooth muscle?
CO2
Inhibitory NANC nerves (NO, VIP)
Beta-adrenergic agonists via beta-2 receptors - adrenalin + salbutamol
213
What factors can affect bronchoconstriction on airway smooth muscle?
Pulmonary stretch receptors (inhibit) + Airway irritant receptors (activate) on brain stem
Excitatory NANC nerves (SP, neurokinins)
His, prostaglandins, leukotrienes - Mast cells + eosinophils
214
What equipment can be used measure Ppl?
Oesophageal balloon
215
In a static pressure volume loop, when is compliance:
a) Max?
b) Min?
a) Around normal tidal volume
| b) At high and low lung volume
216
Calculation for compliance?
Change in lung volume/Change in transmural pressure
217
What is the shape of a static pressure volume loop?
Hysteresis shape
| Lines x touch
218
Where is the most compliant part of a static pressure volume loop?
Middle bit where line steepest
219
What special about volume of lung in expiration in a static pressure volume loop?
Greater at any given transmural pressure than inspiration
220
What factors can:
a) Increase lung compliance?
b) Decrease lung compliance?
a) Emphysema - destroy elastic fibres
| b) Stiff lungs, lung fibrosis (TB, asbestosis)
221
In what condition does the honeycomb appearance of the lungs occur?
UIP fibrosis
| Usual Interstitial Pneumonia
222
What conditions are associated with COPD?
Bronchiolitis
| Emphysema
223
What is bronchiolitis?
Thick, narrow bronchioles mit excess mucus
224
Where does centrilobular emphysema occur?
Affects upper lobes of lungs
225
What is LaPlace equation?
P = 2T/R
226
What is surfactant produced by?
Type II alveolar cells
227
What is surfactant made up of?
Phospholipids e.g phosphatidylcholine
| Surfactant proteins
228
How do surfactants work?
Reduce surface tension in proportion to surface concentration
229
What are the 3 effects of surfactants?
Increase compliance
Reduces tendency for alveoli to collapse
Reduces tendency to suck fluid into alveoli
230
What is neonatal respiratory distress syndrome?
Occurs premature babies due inadequate surfactant production
| Increased work breathing due reduced compliance + alveolar collapse
231
What is alveolar dependency?
Joining of alveoli to each other to help resist collapse
232
What are the airways like in asthma?
Narrowed bronchoconstriction
| Mucosal oedema
233
What are the airways like in chronic bronchitis?
Wall damage
Hypertrophied glands
Mucus production
234
What are the airways like in emphysema?
Poorly supported
235
What are the alveoli like in:
a) Asthma?
b) Chronic bronchitis?
c) Emphysema?
a) Normal
b) Normal
c) Destroyed
236
What are the airways like in:
a) Lung fibrosis?
b) Respiratory muscle weakness?
a) Normal
| b) Normal
237
What are the alveoli like in:
a) Lung fibrosis?
b) Respiratory muscle weakness?
a) Stiff
| b) Normal
238
What is the difference between obstructive lung disease and restrictive lung disease?
Obstructive - Airflow impeded
| Restrictive - Poor lung expansion
239
Calculation for forced expiratory ratio?
FEV1/FVC
240
In a peak flow meter, if patient has reduced expiratory flow, what can this suggest?
Resistance in lungs has increased
241
What happens to FEV1, FVC and FEV1/FVC ratio in:
a) Obstructive disease?
b) Restrictive disease?
a) FEV greatly decrease, FVC decrease/normal, FEV1/FVC decrease
b) FEV + FVC decrease, FEV1/FVC normal
242
Features of maximum flow-volume loops of obstructive disease?
Concave appearance of forced expiratory curve
| Forced inspiratory flow less affected than forced expiratory flow
243
What is the name of the chest shape in emphysema?
Barrel chest
244
What is dead space in lungs?
Airway volume with x gas exchange
245
What is the name and abbreviation for the total pressure of air?
Barometric pressure
| PB
246
Equation for Henry's law and meaning of letters?
```
C = kP
C = conc of dissolved gas at equilibrium
k = Henry's law constant
P = pp of gas
```
247
What is the constant water vapour pressure in the lungs?
6.3 kPa
248
What rate does CO2 diffuse at compared to oxygen and why?
85% of rate of O2
| Higher molecular weight
249
What is the value of the solubility coefficient of:
a) CO2
b) O2
in plasma?
a) 0.7ml/L/mmHg
| b) 0.03 ml/L/mmHg
250
What is DLCO?
CO diffusing capacity
251
What 3 things is DLCO reduced by?
Reduction in alveolar-capillary membrane area
Increased thickness of alveolar-capillary membrane
Anaemia
252
What 2 things is DLCO increased by?
Increased pulmonary blood volume (exercise)
| Polycythaemia - mehr RBC, mehr ability pick up O2
253
How much oxygen does the mitochondria need?
PO2 > 1mmHg (0.13kPa)
254
What happens to tissue if capillary PO2 falls too low?
Hypoxic
255
What 3 factors cause O2-Hb curve to shift left?
Increase pH, low pCO2
Low temp
Low 2,3 DPG
256
What 3 factors cause O2-Hb curve to shift right?
Decrease pH, high pCO2
High temp
High 2,3 DPG
257
What are the neural controls of ventilation?
Role of brain stem
| Lung receptors + other inputs
258
What are the chemical controls of ventilation?
Responses to changes in pCO2, pO2, pH
Central chemoreceptors
Peripheral chemoreceptors
259
What is apnoea?
Temporary cessation in breathing, esp in sleep
260
What is eupnoea?
Normal pattern of breathing
261
What is apneusis?
Deep, gasping inspiration with pause at full inspiration followed by a brief, insufficient release.
262
What are the 4 main respiratory nuclei in the medulla?
| Full descrip
Dorsal resp group (DRG) within nucleus tractus solitarius (NTS)
Ventral resp group (VRG) containing nucleus ambiguus (NA) + nucleus retroambiguus (NRA)
Pre-Botzinger (PBC) + Botzinger complex located near nucleus retrofacialis (RTN)
263
What neural input does the DRG receive?
Chemoreceptors
Lung mechanoreceptors
Higher brain centres
264
Where are the stretch receptors located?
Smooth muscle of bronchial walls
265
What do the stretch receptors do?
Make inspiration shrter/shallower
| Delays next inspiratory cycle
266
What reflexes are the stretch receptors involved in?
Hering-Breuer inflation reflex - inflation inhibits inspiration
Deflation reflex - deflation augments inspiration
267
Where are the juxtapulmonary receptors located?
Alveolar/bronchial walls, close to capillaries
268
What do the juxtapulmonary receptors do?
Apnoea/rapid shallow breathing
Fall HR + BP
Laryngeal constriction
Relaxation skeletal muscle
269
Where are the irritant receptors located?
Throughout airways between epithelial cells
270
What do the irritant receptors do?
Receptors in trachea lead to cough
Reflex bronchial + laryngeal constriction
Deep augmented breaths every 5-20 min at rest - reverse slow collapse of lung in quiet breathing
271
Where are the proprioceptive receptors located?
Respiratory muscles
272
What do the proprioceptive receptors do?
Wichtig coping mit increased load + achieving optimal tidal volume + frequency
273
What are 3 other types of receptors in the control of ventilation?
Pain receptors
In Trigeminal region + larynx
Arterial baroreceptors
274
Why is there a plateau of ventilation in the ventilatory response to CO2?
Always breathing, never 0
275
Why is the combination of hypoxia and hypercapnia synergistic?
Combined effect greater than sum of individual effects
276
Do the peripheral chemoreceptors respond to O2?
No
277
What are the 2 types of cells found in the carotid bodies?
Type 1/Glomus cells
| Type 2/Sheath cells
278
What are the 3 functions of the carotid bodies
Increase in pCO2/H+ increases discharge
Decrease in pCO2 increases discharge
V fast response
279
What are 3 examples of breathing disorders?
Loss of CO2 drive
Cheyne-Stokes respiration
Central sleep apnoea
280
What occurs in obstructive central sleep apnoea?
Muscles relax + airways collapse
Snore, x airflow
O2 sats fall so wake up
281
What is the curse of Odine?
Brain x respond to changes in CO2 + O2
282
What is ventilation-perfusion relationship?
Va/Q
| Alveolar ventilation per min + Blood flow per min
283
What percentage of venous blood passes through lungs?
98%
284
What veins are involved in normal R==>L shunt?
Bronchial veins
| Thebesian veins
285
What are Thebesian veins?
Small veins draining wall of l ventricle
286
What are 3 causes of abnormal R==>L shunt?
Collapsed lung
Consolidation
Congenital heart disease
287
What is atelectasis?
Collapse of lung tissue with loss of volume
288
What is Fallot's tetralogy?
```
4 congenital abnormalities
Ventricular septal defect
Misplaced aorta
Pulmonary vein stenosis
Thickened r ventricular wall
```
289
If r border heart x visible on chest x-ray, what can you say about the pneumonia?
Lobar pneumonia of r middle lobe
290
What is an air bronchogram?
Aerated bronchi surrounded by solid consolidated lung
291
What causes L==> R shunts?
Atrial septal defects
| Ventricular septal defects
292
What percentage of live births have VSDs?
0.2%
293
What septal defect can turn into a R==>L shunt + why?
VSDs
Increase in pressure in pulmonary circulation lead to pulmonary vascular remodelling + increased resistance e.g r ventricle hypertrophy
294
Effect of increased ventilation/FIO2 in R==>L shunt?
Low PaO2, normal/low CO2
295
Why does breathing 100% O2 have a modest effect on arterial PO2 in R==>L shunt?
Doesn't reach shunted blood
296
How do these effects alter VA/Q?
a) Dead space effect
b) Shunt effect?
a) High VA/Q
| b) Low VA/Q
297
What is the response of
a) Pure R==>L shunt
b) Ventilation perfusion mismatch
to O2 enriched inspired air?
a) Little improvement to arterial pO2
| b) Marked improvement, PO2 in under ventilated areas improved
298
What area of the lung is the VA/Q higher?
Top of lungs
299
Where is the relative change of the alveoli greater?
Bottom of lung
300
What do the pulmonary blood vessels do in response to hypoxia + why?
Vasoconstrict
| Divert blood flow from poorly ventilated areas ==> well ventilated areas
301
When is hypoxic pulmonary vasoconstriction not useful?
In global hypoxia
| e.g. Hypoxic lung disease, resp failure, altitude
302
What 5 mechanisms lead to arterial hypoxia?
```
Low inspired pO2
Hypoventilation
Diffusion impairment
R==>L shunt
Ventilation-perfusion mismatch
```
303
What mechanism increases PaCO2?
Hypoventilation
304
What mechanisms increase A-a pO2 gradient?
Diffusion impairment
R==>L shunt
Ventilation-perfusion mechanism
305
Why does blood continue to flow while we stand up?
At any given level above/below heart, arterial pressure greater than venous pressure
306
What happens to the venous valves in the lower limbs when we stand?
Shut transiently
| Shrt time, outflow blood from heart greater than inflow
307
What 3 mechanisms limit effect of orthostasis?
Lowered stroke volume + C,O, blood flow to brain, MABP in upper prt body
Arterial constriction reduces blood flow on standing
Skeletal muscle pumping
308
What leads to varicose veins?
Valve failure in tributary superficial veins exposes them to chronic high pressures
309
By what percentage does cerebral blood flow reduce by when standing?
20%
310
What does gravity do to CSF?
Downward displacement within subarachnoid space
| Creates -ve intracranial pressure, prevents veins within cranium collapsing
311
Why is negative pressure within cerebral veins dangerous in neurosurgery?
Risk of air embolism if opened
312
What 3 things occur during prolonged standing?
Progressive venous pooling
Progressive fall in pulse pressure
Progressive rise in heart rate + TPR
313
What is vasovagal syncope?
Fainting that occurs to response in to sudden drop in heart rate/blood pressure
Vagally mediated bradycardia - v slow heart rate
314
Why is it bad to keep a person upright when they're fainting?
BP remains low and brain damage possible
315
How to calculate O2 consumption?
O2 consumption =
| C.O (arterial - mixed venous blood O2 content)
316
How are these factors affected by exercise?
a) Arterial O2 content
b) Venous O2 content
c) Cardiac output
a) Unaffected
b) Falls progressively as exercise intensity increases
c) Increases progressively with increasing exercise intensity
317
What is the main factor determining VO2 max?
Max cardiac output produced
318
What happens to blood flow in active muscle?
Vasodilation + capillary recruitment due local metabolites
319
What happens to blood flow in inactive muscle + splanchnic circulation?
Sympathetic vasoconstriction
320
What happens to blood flow in skin during exercise?
Vasoconstriction then vasodilation due temp rise
| At max exercise, vasoconstriction dominates
321
What 3 factors can increase stroke volume?
Enhanced filling of heart
Increased CVP, increases skeletal muscle pump
Enhanced emptying
322
How is BP affected in dynamic exercise?
Little change diastolic
Systolic increased
Mean BP moderate increased
323
How is BP affected in isometric exercise?
Systolic + diastolic increase
| Any given O2 consumption, BP greater than dynamic + fails to plateau
324
Why may TPR rise during isometric exercise?
Compression of blood vessels in contracting muscles
325
What is the difference between:
a) Revealed haemorrhage
b) Concealed haemorrhage
a) Obvious bleeding, quantity hard to measure
| b) E,g, ruptured organs, can be due to trauma
326
What is the result of:
a) Chronic, slow persistent bleeding?
b) Acute large blood loss?
a) Fe deficiency anaemia
| b) Reduced circulatory volume + circulatory shock
327
What is the most common cause of circulatory shock and the others?
```
Haemorrhage
Sepsis
Cardiogenic
Anaphylaxis
Other hypovolemic e.g. burns, severe vomiting/diarrhea
```
328
What is pulse pressure?
Difference between systolic and diastolic pressure
329
What is the average blood volume in:
a) Men?
b) Women?
a) 77 ml/kg
| b) 67 ml/kg
330
What is the reverse stress contraction in immediate compensation for blood loss?
Veins shrink around reduced blood volume
Helps maintain venous pressure, therefore venous return
Maintains CO
331
What are cardio-pulmonary stretch receptors and what do they do?
Mechanoreceptors in heart + large pulmonary vessels
| Respond to changes in blood volume
332
Why is arterial BP normal in moderate haemorrhage?
Low C.O offset by high TPR
333
What is a reticulocyte and its normal number in body?
Immature RBC
| <2% of RBC
334
What is non-progressive shock?
Shock gets better without treatment
| e.g. donating blood
335
What is haemodilution?
Increased blood volume but lower conc of RBC
336
How quickly should blood transfusion be given in shock?
1 hour (golden hour)
337
What are 4 cardiovascular effects of aging?
Atherosclerosis
Rise in systolic BP + fall in diastolic BP
Reduced baroreflex sensitivity
Impaired cardiac performance during exercise
338
What happens to the forward pressure wave and reflected pressure wave in:
a) Youth + normotension?
b) Age + hypertension?
a) Prt of pulse wave reflected almost immediately
| b) Forward + reflected pressure waves summate
339
Why is heart less able to increase cardiac output when stressed?
What reasons?
Max attainable HR falls (220- age in years)
Fall in cardiac contractility reduces stroke volume
Decreased response to beta-1 receptor activation + loss of myocytes
340
What are drugs in term of exogenous + endogenous?
Drugs are exogenous molecules that mimic/block action of endogenous molecules/systems
341
What are 3 types of pharmacological receptors?
Physiological receptors
Other proteins e.g. enzymes, ion channels,
Nucleic acids
342
What are physiological receptors?
Endogenous proteins that are receptors for endogenous chem signalling compounds e.g. hormones/NT
343
What is an:
a) antagonist?
b) agonist?
a) Bound drug prevents receptor from being activated
| b) Bound drug activates receptor to provoke response
344
What type of drug interactions are:
a) Reversible?
b) Irreversible?
a) Ionic interactions + hydrophobic interactions
| b) Covalent bonding
345
What is pharmacodynamics?
What drug does to an organism
| Sum of all actions of drugs
346
What is pharmacokinetics?
What organism does to drug
| Absorption, distribution, metabolism + excretion of drug
347
What is the main:
a) metabolic organ?
b) excretory organ?
a) Liver
| b) Kidney
348
What 5 factors influence the amount of drg absorbed and the speed of absorption?
```
Chem properties of drug
Molecular size
Lipid solubility.ionization
Chem + metabolic vulnerability
Route of administration
```
349
What are the 3 names given to conventional drugs?
Proprietary names
Common name
Chemical name
350
What therapeutic uses can drugs be grouped to?
Analgesic - pain killer
Anti-inflammatory
Antipyretic (lowers temp in fever)
Anti-platelet
351
How many phases are there in clinical trials?
5
| Phase 0 then Phase I, II, III, IV
352
What is Emax?
Max effect/response a drug can produce
353
What is EC50?
Conc of drug that produces 50% of max response
354
What shape is given in the plotted graph of proportion of receptors occupied (p) vs drug conc [D]?
Rectangular hyperbola
355
What shape is given in the plotted graph of proportion of receptors occupied (p) vs log drug conc (Log[D])?
Symmetrical sigmoid
356
What is the affinity of a drug to its receptor quantified as and what is the symbol?
Molar conc of drug required to occupy 50% of receptors at equilibrium
KD
357
What is the value of KD of a drug with a high affinity for its receptors?
Low KD
| In micro-/nanomolar range
358
What is efficacy and what types of drugs have it?
Ability of drug to activate receptor
| Agonists
359
What molecules in body are agonists?
NTs, hormones
360
What is the difference between:
a) Partial agonist?
b) Full agonist?
a) Low efficacy, less effective
| b) High efficacy, v effective producing biological response
361
What is the difference in response between:
a) Partial agonist?
b) Full agonist?
a) Fail produce full response despite occupy all receptors
| b) Max response, activate fraction of available receptors
362
What is the difference between:
a) Competitive antagonist?
b) Non-competitive antagonist?
a) Compete for same site, x activate - affinity but 0 efficacy
b) Act at diff site on receptor
363
What are reversible competitive inhibitors used for?
Inhibit effects of NT/hormones
364
What effect does an reversible competitive antagonist have on Log[agonist] vs response graph?
Parallel shift to right
365
What is the dose-ratio?
Ratio of conc of agonist producing same response on presence + absence of antagonist
366
What is pA2?
Quantified affinity of antagonist
| -ve logarithm of molar conc of antagonist that necessitates that you double agonist conc to produce same response
367
What effect does an irreversible competitive antagonist have on Log[agonist] vs response graph?
Right shift but x parallel
| Block x surmountable
368
Calculation for probability of adverse event to drug?
Total exposure x likelihood
369
What is acceptable benefit:risk ratio dependant on?
Efficacy
Toxicity
Disease
370
What is Reye's syndrome?
Swelling in liver + brain.
| Oft affects children + teenagers recovering from viral infection e.g. flu/chickenpox
371
What is Torsades de Pointes?
Polymorphic ventricular tachycardia mit long QT interval
| Rapid, irregular QRS complexes, appear to be twisting around ECG baseline
372
What are the 3 structures in microcirculation?
Terminal arterioles
Capillaries
Lymphatic capillaries
373
What are the 3 types of capillaries?
Continuous
Fenestrated
Sinusoidal (discontinuous)
374
Where are these capillaries found?
a) Continuous
b) Fenestrated
c) Sinusoidal
a) Most tissues
b) Kidneys, joints, intestinal mucosa
c) Liver, bone marrow, spleen
375
How is the endothelium arranged in these capillaries?
a) Continuous
b) Fenestrated
c) Sinusoidal
a) Monolayer covering entire surface of capillary
b) Contains pores, 10x more permeable to smol hydrophilic molecules
c) Spaces between endothelial cells, large molecules readily diffuse
376
What is the glycocalyx?
Glycoprotein layer covering luminal surface of endothelium
377
How do small lipophobic molecules cross capillary wall?
Fenestral route
| Paracellular route
378
How do large lipophobic molecules cross capillary wall?
Vesicular transport
Trans-endothelial channel
Wide intercellular gap (acute inflammation)
379
How do lipophilic molecules cross capillary wall?
Transcellular route
380
What is Fick's 1st law?
Diffusion =
| diffusion constant x area x (change in conc/diffusion distance)
381
How many litres of plasma pass through capillaries each day?
4000L
382
How many litres of fluid flow across capillary walls in both directions?
80,000L
383
How is filtered fluid returned to the bloodstream?
Lymphatic system
384
What is an oedema?
Net filtration increases locally/systemically or lymphatic system blocked, fluid accumulates in tissue
385
What 2 pressure gradients does fluid filtration rely on?
Hydrostatic pressure
| Osmotic pressure gradient
386
What is the hydrostatic pressure in an open capillary?
Arterial end - 140 mmHg
| Venous end - 15 mmHg
387
What is the hydrostatic pressure in tissue spaces?
0 (atmospheric)
388
What is effect of these pressures on water flow?
a) Hydrostatic pressure
b) Osmotic pressure
a) Draws water out of capillaries
| b) Draws water into capillaries
389
What is the Starling equation?
Jv proportional to (Pcap - Pint) - sigma(pi-cap - pi-int)
390
What are the capillaries doing in tissues where the arterioles are open?
Mainly filtering
391
What are the capillaries doing in tissues where the arterioles are contracted?
Capillary hydrostatic pressure falls
| Absorption more important
392
What are the 4 factors that promote oedema?
Increased capillary hydrostatic pressure
Increased capillary/venular permeability
Decreased plasma oncotic pressure
Lymphatic obstruction reduces lymphatic flow
393
What are 3 functions of the lymphatic system?
Preserves fluid balance
Transfers fat absorbed in SI to circulatory system
Transports foreign materials to lymph nodes for immunosurveillance
394
What is the function of the intercellular clefts on the lymphatic capillaries?
1 way entry of fluid driven by tissue compression
395
What is a lymphangion?
Functional unit of lymph vessel that lies between 2 semilunar valves
396
By how much does the lymphangion need to be compressed to prevent pumping?
When would be useful?
40-50 mmHg
| Stop envenomation - exposure to poison/toxin from bite/sting
397
How can lymphocytes be activated?
In lymph glands by antigen entering via afferent lymphatics
398
How much O2 do tissues remove from blood?
5 ml dl-1
399
What is peripheral cyanosis?
Reduced blood flow to region resulting in hypoxic tissue
| Blueish tinge in extremities
400
What are 4 causes of reduced blood flow?
Cardiovascular shock
Low temp
Reduced cardiac output
Poor arterial supply
401
What is central cyanosis?
Arterial hypoxaemia, reduction in O2 content
| Buccal mucosa + lips best sites to spot
402
What are 2 causes of central cyanosis?
COPD
| R==>L shunt
403
What is the solubility of CO2 in blood?
0.52 ml dl-1 kPa-1
404
What are 3 ways CO2 is carried in blood?
Dissolved CO2
Bicarbonate
Carboamine compound
405
What is the Haldane effect?
At any given PCO2, quantity of CO2 carried is greater in partially deoxygenated blood (venous) than in oxygenated blood (arterial)
406
What is the Haldane effect due to?
Hb forms carbamino compounds more readily when deoxygenated so can carry more CO2.
Hb binds to H+ better when deoxygenated, favours formation of HCO3-, increasing CO2 carriage
407
What are 3 features of the shape of the CO2 dissociation curve?
X sigmoid
X plateau
Approx linear over physiological range
408
Name 3 features of the CO2 dissociation curve
More total CO2 carrying capacity than for O2
Haldane effect
At rest, tissue produces 4ml of CO2 for 100 ml blood passing through
409
How much HCO3- is in arterial blood?
24mM
410
What is the relationship between alveolar CO2 and alveolar ventilation?
Inversely proportional
411
What are 2 ways to measure O2 consumption?
Fick's principle
| Respiratory mechanisms
412
What is hyperventilation?
Over ventilation in proportion to metabolism
| Measured with respect to arterial pCO2
413
What is hypoventilation?
Under ventilation in proportion to metabolism
| Results in higher arterial pCO2 levels
414
What are 2 causes of hyperventilation?
Anxiety, pain, excessive mechanical ventilation
| Diseases contributing to mechanical acidosis
415
What are 2 consequences of hyperventilation?
Low paCO2 - leads cerebral construction ==> cerebral hypoxia
| Alkalosis -
416
What are the causes of hypoventilation?
Head injury impairing respiration
Anaesthetics
Drugs
Chronic lung disease
417
What are the consequences of increased pCO2 due to hypoventilation?
Increasing arterial pCO2 - peripheral vasodilation
| V high pCO2 - depresses CNS function
418
What is the pCO2 and pO2 in:
a) Inhaled air?
b) Exhaled air?
c) Inspired air in airways?
a) pO2 = 21, pCO2 = 0
b) pO2 = 16, pCO2 = 3.5
c) pO2 = 20, pCO2 = 0
419
What is the pCO2 and pO2 in:
a) Mixed venous blood?
b) Alveolus?
a) pO2 = 5.3, pCO2 = 6.1
| b) pO2 = 13.3, pCO2 = 5.3
420
What is the pCO2 and pO2 in:
a) Mixed venous blood?
b) Alveolus?
a) pO2 = 5.3, pCO2 = 6.1
| b) pO2 = 13.3, pCO2 = 5.3
421
What is the pCO2 and pO2 in:
a) Arterial blood?
b) Capillary/tissues?
a) pO2 = 12.5, pCO2 = 5.3
| b) pO2 = 5.3 /less, pCO2 = 6.1/more
422
What substances follow:
a) Zero order kinetics?
b) First order kinetics?
a) Most drugs, don't accumulate
| b) Alcohol, phenytoin, overdose, accumulate
423
What type of kinetics do most drugs follow?
First order
424
What substances follow 0 order kinetics?
Alcohol, phenytoin, in overdose
425
What are 2 features of 1 compartment?
Instantaneous distribution
| Monophasic decline in in plasma conc
426
What is 1 feature of 2 compartment?
Biphasic decline
427
What is half life and its symbol?
Time taken for plasma conc of drug to fall by half
| T(1/2)
428
In what conditions can you see a monoexponential decline?
Drug cleared according to 1st order kinetics
| Only distributed by 1st compartment
429
What is absorption?
Process by which drug moves from site of administration to site of action
430
What factors can absorption depend on?
Solubility + pH dependant
431
Calculation for volume of distribution?
```
Vd = Total amount drug dosed / plasma conc at t0
Vd = Dose A /A0
```
432
What happens in:
a) Phase I
b) Phase II
in drug metabolism?
a) Body makes mehr H2O soluble so easier to excrete
| b) Body conjugates H2O soluble molecule onto drug so easier to excrete
433
What is clearance and it's calculation?
Volume of plasma cleared of drug per unit of time
| Cl = k x Vd
434
What is clearance limited by?
Organ blood flow
435
How to calculate clearance using extraction ratio?
```
Clearance = Q x Eh
Q = organ blood flow
Eh = hepatic ratio (diff 2nd letter represents which system)
```
436
What is human liver blood flow?
1.4 L/min
437
How to calculate maximum oral bioavailability?
F = 1 - Eh
438
What condition occurs when there is extra-hepatic clearance?
Total blood clearance > Q
439
What is human renal blood flow?
1.1L/min
440
What is bioavailability (F)?
Fraction of unchanged drug reaching systemic circulation
441
What 2 factors limit bioavailability in oral dosing?
Absorption from gut
| Gut/hepatic metabolism/excretion
442
How to calculate bioavailability (F)?
F = AUC oral / AUC iv
443
Intrapleural pressure is:
a) always positive
b) positive during inspiration
c) negative during inspiration
d) always negative
e) cannot be estimated
d) always negative
444
Relative to PB, during expiration PA is approximately:
a) 2 cmH2O
b) 1 cmH2O
c) 0 cmH2O
d) -1 cmH2O
e) -2 cmH2O
b) 1cmH2O
445
What is the name of the protein that mediates contraction in smooth muscle?
Calmodullin
446
Which combination of valves cause which heart sounds?
a) S1 - Aortic and Mitral, S2 - Pulmonary and Tricuspid
b) S1 - Aortic and Pulmonary, S2 - Mitral and Tricuspid
c) S1 - Mitral and Pulmonary, S2 - Aortic and Tricuspid
d) S1 - Mitral and Tricuspid, S2 - Aortic and Pulmonary
d) S1 - Mitral + Tricuspid, S2 - Aortic + Pulmonary
447
Describe smooth muscle contraction
Ca2+ enters cell (through sarcolemma/from SR)
Binds to calmodulin in cell, activates myosin kinase
Phosphorylates myosin heads to start contraction
Ends when Ca2+ pumped out of cell by ATP-dependent pump on membrane.
Some stays in cell bound to calmodulin to maintain muscle tone - less energy required to maintain contraction.
Also get ‘latch bridges’ between some myosin + actin filaments - stay contracted w/ no energy use - wichtig in some tracts + vessels
