Supporting Life Flashcards
1
Q
Where in the coronary vessels do plaques usually form?
Which coronary vessel can a plaque form that causes the most damage?
A
Proximal region within 6 cm of aorta
L anterior descending coronary artery
2
Q
What is the major action of the haemodynamic effects of nitrates?
A
Relaxes veins + venules
↓ CVP, so ↓ cardiac wall tension
↓ cardiac O2 demand
3
Q
What is the minor action of the haemodynamic effects of nitrates?
A
Dilate larger coronary arteries, ↑ing blood flow thru coronary collaterals
↓ TPR + afterload, so ↓ O2 demand
4
Q
What are the side effects of nitrates?
Why?
A
Headache, facial flushing
↓ BP, reflex ↑ HR
Due to vasodilatation
5
Q
What is the most commonly used beta blocker in UK for angina?
Against what receptors?
A
Bisoprolol
Beta 1 selective
6
Q
How do beta blockers work in angina?
A
Inhibit sympath stimul heart + inhibit renin release
Aim resting HR 55-60 bpm, + ↑ HR of <75% of rate causing ischaemia during exercise
↓ contractility, ↓ O2 demand
7
Q
How do beta blockers ↑ perfusion of l ventricle?
A
L ventricle gets blood only during diastole - systole squeezes arterioles
Slower HR, more time spent in diastole
8
Q
Why are beta blockers contraindicated in asthma and vasospastic angina?
A
Asthma - adren bronchodilator via beta receptors
V angina - beta receptors vasodilating effect on coronary arteries
9
Q
What are the side effects of beta blockers?
A
Fatigue, exercise intolerance, hypoglycaemia, disturbed sleep, cold/tingling extremities
10
Q
What are the common Ca channel blockers used?
A
Amlodipine (dihydropyridine, DHP)
Verapamil
Diltiazem
11
Q
What are the effects of the different types of Ca channel blockers in angina?
A
DHPs vasodilate → reducing afterload, so cardiac work
Verapamil acts by direct (–) inotropic effect, some reduction in afterload
Dilate coronary arteries, useful angina associated mit coronary vasoconstriction
e.g. Prinzmetal’s, also oft occurs in mixed angina
12
Q
What enzyme do statins block?
A
HMG-CoA reductase
13
Q
What is the coronary flow reserve?
A
Ability of coronary vessels to↑ blood flow during greater O2 demand e.g. exercise
14
Q
How does nitrous oxide work to prevent vascular smooth muscle cell contraction?
A
Opens K+ channels to prevent depolarisation
Activates Ca2+ pumps - to remove Ca2+ from cells
Ca2+ desensitisation
15
Q
How is GTN taken so it works immediately?
A
Sublingually
16
Q
How quickly does tolerance to organic nitrates happen?
How to avoid this?
A
After 12 hours
Daily 8 hour drug free period - usu at night
17
Q
What is the late Na+ current in cardiac myocytes?
A
Upstroke of AP in cardiac myocytes due rapidly developing Na+ current - inactivates few millisec
Inactivation incomplete - late Na+ current
18
Q
What can a late Na+ current in cardiac myocytes cause?
A
AP prolongations → arrhythmias
Myocardial stunning - contractile abnormality even after reperfusion
Diastolic stiffness → ↑cardiac work, ↓ coronary blood flow
19
Q
How does the drug ranolazine help with angina?
A
Inhibits late Na+ current in cardiac myocytes
Reduces cardiac wall tension, ↓ cardiac work
20
Q
What type of angina is the drug ranolazine used to treat?
A
Microvascular angina
May have anti-oxidant + inflammatory effects
Improve coronary endothelial function
21
Q
How does the drug nicorandil work to reduce symptoms of angina?
A
Opens ATP-sensitive K+ channels in vascular sm cells
Stimulates guanylate cyclase → ↑ vascular sm cell [cGMP]
Relaxation of sm
22
Q
How does the drug ivabradine work to reduce symptoms of angina?
A
Blocks If (‘funny’ current), involve SAN pacemaking,
↓ HR, ↑es perfusion
‘Use-dependency’ - ivabradine block more when HR ↑
23
Q
What are the hemodynamic effects of ivabradine?
A
↓ HR allows more time for blood to perfuse myocardium, reduces ischaemia
↓ HR → ↓ afterload → ↓ O2 demand
24
Q
What 2 revascularization techniques can be used to treat stenosis in coronary vessels?
A
Percutaneous intervention (PCI) - stents Coronary artery bypass grafting (CABBAGE) - pieces of saphenous vein/diverted internal mammary artery
25
When would a coronary artery bypass be used instead of PCI?
Patients with mehr serious/advanced coronary artery disease
| Improves survival compared to PCI
26
What is definition of:
a) Sinus rhythm?
b) Junctional rhythm?
a) Heartbeat originate from SAN
| b) Heartbeat originate from AVN/Bundle of His
27
How do tachyarrhythmias arise?
Re-entry, impulse delayed/‘trapped’ 1 region of heart
Adjacent tissue finishes depolarising, x refractory
Delayed impulse re-enters adjacent tissue, spreads throughout heart
1nce; premature beat
Indefinitely; sustained tachycardia
28
What are the classes of antiarrhythmic drugs?
Class 1: Na+ channel blockers - suppress conduction
Class 2: beta blockers - reduce excitability, inhibit AVN conduction
Class 3: K+ channel blockers - prolong AP + refractory period
Class 4: Ca 2+ channel blockers - inhibit AVN conduction
29
What 2 drugs are antiarrhythmic but don't fit the different classes?
Adenosine: slows AV nodal conduction
Digoxin: stimulates vagus, slows AV nodal conduction
30
```
Examples of:
a) Class 1
b) Class 2
c) Class 3
d) Class 4
antiarrhythmic drugs?
```
a) flecainide
b) bisoprolol
c) amiodarone
d) verapamil
31
What is rate control in treatment of arrhythmias?
Reduce proportion of impulses conducted thru AV node
| Atrial tachycardia continues, but ventricles slow down, improving cardiac output
32
What drugs are used in rate control of arrhythmias?
Class 2, Class 4, Adenosine, Digoxin
33
What is rhythm control in treatment of arrhythmias?
Target source of arrhythmia/conduct impulse away from source, by blocking re-entrant pathway
34
What drugs are used in rhythm control of arrhythmias?
Class 1, Class 3
35
How do the drugs used in rate control of arrhythmias work to treat them?
Class 2 drugs suppress norad-mediated stimulation of AVN conduction
Class 4 drugs depress AVN conduction
Digoxin stimulates vagus nerve, suppresses AVN conduction
Adenosine inhibits AVN Ca2+ channels + stimulates K+ channels, ↓ing conduction
36
How do the drugs used in rhythm control of arrhythmias work to treat them?
Both block re-entry
Class 1 - suppress/block conduction (instead of slowed)
Class 3 - prolong refractory period
37
What class of antiarrhythmic drugs can be used to treat polymorphic VT?
Class 2
38
How do implantable defibrillators work?
Connected to electrodes in r ventricle + SVC
Senses + differentiate arrhythmias by rate + location
Delivers an appropriate shock/shock sequence, causing cardioversion i.e. return to sinus rhythm
39
What is defibrillation?
Used to terminate VF/ ‘pulseless’ VT
DC cardioversion: Momentary discharge large current across chest via paddles placed at sternum + RV apex
Applied onset QRS complex (if present)
Stops heart, allows SAN reassert itself
Combined mit cardiopulmonary resuscitation; adrenaline can also be used
Absence any equip, thump to chest can occasionally terminate VF
40
What is the definition of arteriosclerosis?
| What are the 3 distinct morphological variants?
Group disorders, thickening + loss elasticity arterial walls
| Atherosclerosis, Monckeberg's medial sclerosis, arteriolosclerosis
41
What is Monckeberg's medial sclerosis?
Calcification of media of muscular arteries
42
What is Arteriosclerosis?
Proliferative/hyaline thickening of walls of small arteries + arterioles
43
What are the major risk factors for atherosclerosis?
Diet + hyperlipidemias (hypercholesterolaemia, hypertriglyceridemia)
Hypertension – both systolic + diastolic
Cigarette smoking - ↑es heart disease in women
Diabetes mellitus – 2x risk of MI, 8x-150x risk of gangrene of extremities
44
What are minor risk factors for atherosclerosis?
```
Obesity
Physical inactivity
Male gender
↑ing age
Family history
Stress (“type A” personality – competitive, stressful lifestyle) - controversial
Oral contraceptives –controversial
High carbohydrate intake - controversial
```
45
What are some features of normal aortic intima?
Innermost layer of a blood vessel + extends from flattened endothelial cells on luminal surface to internal elastic lamina
Mostly composed of subendothelial collagen
46
What is the layer deep to the internal elastic lamina in the aorta?
Media composed of sm cells + elastin fibres
47
What features can you see of a Type 1 lesion under a microscope (in atherosclerosis)?
Macrophages in aortic intima phagocytose LDLs that progressively accumulate within cytoplasmic vacuoles AKA foamy macrophages from their appearance
48
What features can you see of a Type 2 lesion under a microscope (in atherosclerosis)?
Sm cells migrate from media → intima thru fenestrations in internal elastic lamina
Also phagocytose lipid (seen as cytoplasmic vacuoles in cells with spindle-shaped nuclei).
Modified sm cells (myofibroblasts) also start producing collagen in intima
49
What is hyperlipoproteinemia?
Inability to break down lipids in body, esp cholest/trigly
50
What is the definition of an infarct?
An area of ischaemic necrosis within a tissue/organ, produced by occlusion of either its arterial supply/its venous drainage
51
What are the usual causes of an infarct?
Acute arterial occlusion
1. Thrombosis e.g. coronary arteries → MI
2. Embolism e.g. lung, kidney, spleen
3. Either thrombosis/embolism e.g. brain (but also
hypotension)
52
Why is venous infarction less common?
Most tissues have numerous venous anastomoses
53
What places can venous infarction take place in?
Thrombosis of mesenteric veins → intestinal infarction
| Brain following thrombosis in superior sagittal sinus
54
What is the most common type of myocardial infarct?
TRANSMURAL INFARCT
Ischaemic necrosis of full/nearly full thickness of ventricular wall in distribution of single coronary artery
Usu associated mit coronary atherosclerosis, plaque rupture + super-imposed thrombosis
55
What is another type of myocardial infarct?
SUBENDOCARDIAL INFARCT
Ischaemic necrosis, inner 1/3/ 1/2, ventric wall
Diffuse stenosing coronary atherosclerosis + global reduction of coronary flow but x plaque rupture + x thrombosis
56
What are the 4 morphological complications following MI?
Cardiac rupture
Pericarditis
Mural thrombosis
Ventricular aneurysm
57
Definition of embolism?
Transfer of abnormal material by bloodstream + its impaction in a vessel
Impacted material = embolus
58
What are the types of emboli?
```
Fragments of thrombus (commonest type)
Material from ulcerating atheromatous plaques (common in distal leg arteries)
Septic emboli
Fragment of tumour growing into a vein
Fat globules
Air emboli
Parenchymal cells
```
59
What is the ejection fraction of the heart?
| Normal value for healthy individual?
Fraction of volume of ventricle pumped out during each beat
| - Amount of blood pumped out at each beat >55%
60
What are the 3 main causes of heart failure?
Pressure overload
Volume overload
Contractile dysfunction
61
What are the 3 phases of heart failure?
Short-term acute failure - functional reserves overwhelmed by overload
Compensated hypertrophy - heart enlarges + adapts
Chronic failure - exhaustion, cell death + necrosis
62
What are the short term mechanisms of the body to cope with acute heart failure?
Sympathetic activation
Activation of renin-angiotensin system
↑ secretion of aldosterone
Myocardial hypertrophy
63
How would you take a sample of fluid in a pleural effusion?
Thoracentesis
Patient faces away from practitioner + leans over table
Needle inserted into pleural space to remove excess fluid
Goes above rib
64
How would you classify pleural fluid based on its protein content?
<25g/L - transudate
>35g/L - exudate
If 25-35 use Light's criteria
65
What is Light's criteria when it comes to classifying pleural fluid (based on protein content)?
Classed as exudate if 1/more is true
Pleural protein > half of serum protein
Pleural LDH > 0.6 of serum LDH
Pleural LDH > 2/3 upper limit of lab normal LDH
66
What are the common causes of transudates (pleural fluid)?
L ventricular failure
Liver cirrhosis
Renal failure
67
What are the common cause of exudates (pleural fluid)?
Lung cancers
Parapneumonic effusions
TB
68
What are the general causes of transudates and exudates (pleural fluid)?
Transudates - systemic problemos
| Exudates - local problemos
69
What measurement can mirror pleural fluid glc?
Pleural pH - if it's low, glc is low
If <7.20 - complicated parapneumonic effusion
Indication for tube drainage
70
What is empyema? (in context of lungs)
Pus in the pleural space
Have to drain pus
Very smelly
71
What is cachexia?
Extreme weight loss and muscle wasting
72
What are some causes of a malignant pleural effusion?
Lung/breast/ovarian cancer
73
What can you use to stick together 2 layers on pleural membrane?
Why?
Medical grade talc
Causes inflammation so 2 layers stick together
Can survive with it, helps reduce efflusion
74
What is orthopnea?
Breathlessness when lying down
| Relieved by sitting/standing
75
What would a chest X-ray show in heart failure?
Bilateral pleural effusions
76
What is a PEA arrest?
Pulseless Electrical Activity
| ECG shows heart rhythm but no pulse produced
77
What are viridans streptococci?
| What do they cause?
Gram +ve bact, green colouration on blood agar plates
| Pneumonia. emphysema, sepsis, meningitis
78
What are the 4 types of hypersensitivity?
Type I: Immediate Hypersensitivity (Allergy Anaphylaxis + Atopy)
Type II: AntiBody Mediated
Type III: Immune Complex Mediated
Type IV: Cell Mediated (Delayed)
79
What is kyphoscoliosis?
Abnormal curvature of spine in coronal (side-side) and sagittal plane (back-front)
80
What are some environmental causes of ILD?
Pneumoconiosis - occupational lung disease related to inhalation exposures to inorganic dusts e.g. silicon, asbestos
Henoch-Schonlein Purpura (HSP) - exposure to protein antigens e.g. farmer's lung, pigeon breeder's lung
Radiation e.g. radiotherapy
81
What are some drugs that can cause ILD?
Cytotoxic drugs e.g Amiodarone, Nitrofurantoin, Bleomycin, Chemotherapy, Methotrexate
82
What does IIP mean in causes of ILD?
| What are the IIP classifications?
```
Idiopathic Interstitial Pneumonia
UIP - Usual IP (aka IPF, Idiopathic Pulmonary fibrosis)
NSIP - Non Specific IP
AIP - Acute IP
COP - Cryptogenic Organising Pneumonia
```
83
What are the risk factors of IPF/UIP?
Smoking (2-3x day)
Metal/wood dust
Genetic (familial)
84
What is the aim of treatment in IPF/UIP?
| What are the treatment options?
Reduce disease progression
Oxygen
Pulmonary Rehabilitation
Palliative Care
Lung transplant
Pirfenidone- antifibrotic, oral, slows disease progression (FVC) + reduces mortality
Nintedanib- Triple tyrosine kinase inhibitor (similar effect)
85
What are the main causes of death in IPF/UIP?
```
Resp failure
Heart failure
PE
Pneumonia
Lung cancer
```
86
What are some CT findings in non-specific interstitial pneumonia?
Ground glass opacities + fibrosis
| Treatment response + prognosis better that UIP/IPF
87
What are the drug therapies in the different ILDs?
IPF/UIP - pirfenidone, nintedanib
NSIP/AIP/COP - steroids (cortico)
HP (hypersensitivity) - steroids
CTD (connective tissue disease) - immunosuppressants
88
What are the hallmarks of type I hypersensitivity?
IgE production, activation of Th2 cells
| Mediated IgE-mast cells
89
What is contained in the storage granules of mast cells?
| What do they do?
Histamine → ↑ed vascular permeability, sm contraction
| Tryptase → tissue remodelling, ↑ed mucus secretion
90
What are the characteristics of the main allergens in type I hypersensitivity?
Individuals repeatedly exposed to them
| X induce macrophage/dendritic cell typical responses
91
What are some examples of the main allergens in type I hypersensitivity?
Inhaled: pollens, spores, dander, dust mite
Ingested: peanut, egg, fruits, sesame
Venoms: bee, wasp stings and bites (Hymenoptera)
Drugs: antibiotics, chemotherapeutics
92
What are some symptoms of type I hypersensitivity?
```
Lung – asthma, wheezing
Nose – rhinitis, sneezing, runny nose
Eye – conjunctivitis
Skin – atopic dermatitis
Gut – food allergy
```
93
What are some diagnostic tests of type I hypersensitivity?
```
Skin prick test > 3 mm wheal (swelling)
Laboratory tests:
- Total IgE (>100 IU/mL)
- Specific IgE raised (e.g. RAST)
- Tryptase levels – transient (24-48h)
```
94
What happens in type II sensitivity?
Antigens bound on cell membranes
| Activate complement cascade + recruit immune cells
95
What is the most severe form of type I hypersensitivity?
Anaphylaxis
96
What are some examples of antigens in type II hypersensitivity?
Drugs e.g. penicillin, quinine
Bacteria
Rhesus antigen
97
What are the main types of antibodies in type II and III hypersensitivity?
IgM, IgG
98
What does the complement cascade lead to in type II hypersensitivity?
↑ed inflammatory mediators
Opsonization - phagocytosis
MAC (membrane attack complex) formation, cell lysis
NK cell activation
99
What are some examples of antigens in type III hypersensitivity?
Foreign serum - antivenom, monoclonal antibody
| Group A streptococcus
100
What is an arthus reaction in type III hypersensitivity?
Inflammation caused by deposition of immune complexes at localised sites
101
What is serum sickness in type III hypersensitivity?
Foreign serum from animal/monoclonal antibodies cause systemic adaptive immune response
Antibody production against foreign serum/MA
102
What is type IV hypersensitivity?
Antibody independent, 24-48 hr after antigen exposure
| Cytokine mediated inflamm, T cell mediated cytotoxicity
103
What are the 5 types of asthma?
| ICS - inhaled corticosteroids
Allergic asthma: childhood, past/FHx allergic disease, eosinophilic airway inflamm, good response to ICS
Non-allergic asthma: sputum neutrophilic/eosinophilic / mit few inflammatory cells, less response to ICS
Late-onset asthma: more common women, tendency non-allergic, ↑er doses ICS required
Asthma mit fixed airflow limitation: long-standing asthma, airflow limitation due airway wall remodelling
Asthma with obesity: prominent respiratory symptoms, little eosinophilia
104
What types of cells are responsible for producing large amounts of IL-5 and IL-3 in asthma?
Type 2 Innate Lymphoid Cells (ILC2)
105
What is the dominant cause for asthma exacerbation?
Viruses
106
What are the bronchodilators used in the treatment of asthma?
Selective β-2 adrenoceptor agonists: Inhaled/IV in intensive care
Short-acting: Salbumatol
Long-acting: e.g. Formoterol (12h), Vilanterol (24h)
Anticholinergic / muscarinic receptor antagonists: Inhaled
Short-acting: Ipratropium
Long-acting: Tiotropium, Umeclidinium
107
What is the action of salbutamol in the treatment of asthma?
Stimulates β2 adrenergic receptors – predom receptors in bronchial sm
↑ levels cAMP relaxes bronchial sm + inhibits release bronchoconstrictor mediators e.g His + leukotrienes from mast cells in airway
108
What is the mechanism of anticholinergic / muscarinic receptor antagonists in treating asthma?
Block AcH effects released from cholinergic parasympathetic nerve fibres to sm + mucus glands
Prevents airway sm contract + mucus hypersecretion
Less effective than β-2 adrenoceptor agonists
Side effects unusual: dry mouth, palpitations, headache, dizziness, blurred vision
109
How do leukotriene receptor agonists help treat symptoms of asthma?
What types of patients benefit from this?
CysLT1 receptor mediates bronchoconstrictive + proinflammatory effects of cysteinyl-leukotrienes (LTC4, LTD4, + LTE4)
Montelukast comp antagonist of CysLT1 receptor
1nce daily oral administration
Work best subgroup asthma patients mit ‘aspirin exacerbated respiratory disease’ (AERD)
- ↑ed production of cysteinyl-leukotrienes
Side effects rare: headache + GI disturbances
110
How do inhaled corticosteroids (ICS) reduce asthma symptoms?
Suppress Th2 / ‘Type 2’ airways inflammation
| Reduce infiltration + activation of eosinophils, Th2 cells, + other inflammatory cells
111
Example of long lasting ICS for asthma?
| How does it work?
```
Fluticasone furoate (FF) enhanced affinity glucocorticoid receptor (fast association + slow dissociation)
Longer duration action + prolonged retention in lung; enables use as once-daily ICS
Improve patient convenience + enhance compliance
```
112
When are steroids more effective in asthma?
If asthmatic has eosinophil inflammation
113
What is the aim of drug treatment in angina?
↓ing myocardial O2 demand
| ↑ing O2 supply
114
Why is it good to have a drug free period at night with nitrates in the treatment of angina?
Nitrates build up to form superoxides
| Cause vasoconstriction, opposite action of nitrates
115
What happens to the alveoli in pneumonia?
Fill with pus
Congestion - vascular engorgement, intra-alveolar fluid
Red hepatisation - exudation of red cells, neutrophils, fibrin
Grey hepatisation - disintegration RBC, persisting inflammatory cells
116
What is the common pathogen that causes pneumonia?
S. pneumoniae, esp post influenza
117
What are some complications of pneumonia?
```
Septic shock
Adult Respiratory Distress Syndrome
Parapneumonic effusion & empyema
Cavitation & abscess
MI
```
118
What are the signs of acute exacerbation in COPD?
Any 2: ↑ed dyspnoea/sputum volume/ purulence
| Any 1 above + any 1: ↑ed cough, wheeze, sore throat, cold
119
What are the signs of severe exacerbation in COPD? (Non-invasive ventilation)
Respiratory acidosis (PaCO2 >6 kPa, pH <7.35)
Fatigue + ↑ed work of breathing
Persistent hypoxaemia
120
What are the signs of severe exacerbation in COPD? (Invasive ventilation)
```
Unable tolerate NIV/NIV failure
Post cardiorespiratory arrest
Reduced consciousness
Haemodynamic instability/arrhythmia
Life threatening hypoxaemia
Aspiration/vomiting
pH <7.25
```
121
What are the emergency treatments of acute exacerbation of COPD?
```
Bronchodilators e.g salbutamol
Corticosteroids e.g. prednisolone
Antibiotics e.g doxycycline
Controlled oxygen - consider target levels
Consideration of NIV/intubation
```
122
What symptoms would help with a diagnosis of COPD in a patient over 35?
Progressive persistent SOB, usu worse exercise
Chronic cough (maybe intermittent + unproductive)
Chronic sputum
Frequent 'winter bronchitis'
123
What are the 3 high value interventions for COPD?
Treating tobacco dependance
Providing vaccination
Support patient to complete pulmonary rehab
SUPPORTING BEHAVIOUR CHANGE
124
What type of patients would you treat with inhaled corticosteroids in COPD?
History of hospitalization for exacerbations of COPD
2/more moderate exacerbations per yr
Blood eosinophils > 300 cells/microlitre
History/Concomitant asthma
125
What type of patients would you NOT treat with inhaled corticosteroids in COPD?
Repeated pneumonia events
Blood eosinophils < 100 cells/microlitre
History of mycobacterial infection
126
What is pulsus paradoxus AKA paradoxical pulse?
Abnormally large ↓ in stroke volume, systolic BP + pulse wave amplitude during inspiration
127
What is the difference between hypoxia and hypoxaemia?
Hypoxia - insufficient O2 at cellular level
| Hypoxaemia - reduced O2 tension in blood (arterial hypoxaemia – low PaO2)
128
What are the 4 types of hypoxia?
Hypoxic hypoxia - low arterial blood PO2, inadequate Hb saturation
Anaemic hypoxia - reduced O2-carrying capacity of blood.
Circulatory hypoxia - too little oxygenated blood delivered to tissues
Histotoxic hypoxia - normal O2 delivery to tissue, cells unable use O2 available to them (cyanide poisoning).
129
What are routine lung function tests?
Spirometry - (inspired/expired volume/flow)
Lung volume (+/- airway resistance)
Gas transfer
Resp muscle strength (volitional tests)
130
What 2 types of drugs can reduce oxidative stress caused by smoking?
Antioxidants
| Antiproteases
131
What molecules are involved in inflammation in COPD?
↑ed neutrophils, macrophages + T cells
(CD8 > CD4) in lungs
Eosinophilic inflammation
132
What are sources of oxidants? (COPD)
Cigarette smoke
| Reactive O2 + N2 species from inflamm cells
133
What happens during oxidative stress?
Inactivates antiproteases
Stimulates mucus production
Amplifies inflamm by enhancing transcrip factor activation + gene expression of pro- inflamma mediators
134
What happens to the lung parenchyma in COPD?
Proteolytic enzymes destroy alveolar tissue
| Elastin + collagen, loss of elastic recoil
135
What happens to the airways in COPD? (Mucus)
Hypertrophy + hyperplasia of bronchial submucosal
glands + ↑ no goblet cells
LEADS TO MUCUS HYPERSECRETION
Destruction of cilia – Difficulty expelling mucus
136
What happens to the airways in COPD?
Narrowing of airways due remodelling
- starts mit smaller airways <2mm
↑ed airways resistance
137
What does compliance mean in relation to lungs?
Extend to which lungs can expand
138
What is FRC?
How is it affected in:
a) Lung fibrosis?
b) Emphysema?
Inward recoil of lung exactly balances outward recoil
a) ↑ed lung recoil → reduced FRC
b) Reduced lung recoil → ↑ed FRC (barrel chest)
139
What is the state of the lungs at rest during COPD?
Hyperinflated, FRC + RV ↑ed
140
What is expiratory flow limitation?
Flow ceases ↑ mit ↑ing expiratory effort
Can occur tidal breathing (in COPD)
Max expiratory flow reached during Vt, min time lung emptying fixed
X empty lungs faster by pushing harder in expiration
141
What is the hoover sign in COPD?
Inward movement of lower rib cage during inspiration instead outward - flat but functioning diaphragm
142
What are the common causes of COPD exacerbation?
Bacterial infections e.g influenza, catarrhalis, pneumonia
| Viral infections less common cause
143
How is the severity of COPD exacerbations classified?
Mild (treat mit shrt acting bronchodilators only, SABDs)
Moderate (treat mit SABDs + antibiotics +/ oral corticosteroids)
Severe (patient requires hospitalization/visit ER)
144
What are the 5 common causes of hypoxaemia?
```
Ventilation-Perfusion mismatch
Impaired diffusion
Alveolar hypoventilation
Low pp of inspired O2
Anatomical R-L shunt e.g. PAVM, lobar pneumonia
```
145
What happens during impaired ventilation?
O2 x move from alveoli → blood
| Causes: ILD, thickened alveoli so x diffuse
146
What can be the causes of low pp inspired O2?
High altitude non commercial flights
| High altitude mountaineering
147
What happens during a shunt in V-P mismatch?
Perfusing under ventilated lung
Gases alveoli equate venous blood - low O2, high CO2
Re-enters systemic circulation, blood with alveoli gas
148
What happens in dead space in a V-P mismatch?
Ventilating under-perfused lung
X blood flow, x GE
Wasted ventilation + energy
149
What are the main causes of hypercapnia?
↑ed resp load
Reduced internal resp drive
Reduced muscle capacity
150
Is oxygen useful in cases of MI or stroke?
| Why?
No as it can worsen area ischaemia,
High level of O2 causes vasoconstriction, affects delivery of O2 - worsens hypoxia
Only use O2 in cases of hypoxia
151
What are some reasons a patient would need acute non-invasive ventilation?
Hypercapnic resp failure, is decompensated (acidosis)
| Failed standard therapy
152
What are the common conditions for acute non-invasive ventilation?
COPD
| Obesity related resp failure
153
What is ECMO in ventilation?
```
Extra Corporeal Membrane Oxygenation
Removes blood from circulation
Replaces O2, removes CO2
Returns to Venous circulation
Requires anticoagulation
```
154
When does COPD cause resp failure?
| What lung function measurements can reassure you COPD x cause resp failure?
Other pathologies e.g. obesity, obstructive sleep apnoea
| FEV1> 1L
155
How would you detect:
a) Type 1 resp failure
b) Type 2 resp failure
in COPD patients?
a) Pulse oximetry
| b) ABG for diagnosis, unlikely in COPD without hypoxia
156
What is Obesity hypoventilation syndrome?
Obesity - BMI >30kg/m^2
Sleep disordered breathing
Daytime hypercapnia
Absence of another pathology explaining hypoventilation
157
What is:
a) Pharmacodynamics?
b) Pharmacokinetics?
a) what effects drugs have on body
| b) how body processes drug
158
What are the common induction agents (anaesthetics) used?
```
Propofol
Barbiturates
Etomidate
Benzodiazepines
Ketamine
```
159
What are the common opioids used?
```
Morphine
Fentanyl
Codeine
Tramadol
Remifentanil
```
160
What are the uses of propofol?
Anaesthetic induction
Maintenance of anaesthesia
Sedation
Anti-emesis - effective against nausea + vomiting
161
What are the pros of using propofol as an anaesthetic?
X Malignant Hyperpyrexia trigger
Pleasant dreams
Relieves pruritus from opiates
Anti-emetic
162
What is malignant hyperpyrexia?
Cause: Underlying disease of muscle
Trigger: Volatile anesthetic gas
Drastic, sustained rise body temp, metabolic acidosis, widespread muscular rigidity
163
What are the con of using propofol as an anaesthetic?
Anaphylaxis (v rare)
Pancreatitis (Hypertriglyceridemia)
Pain on injection (rare); thrombophlebitis
164
What is thrombophlebitis?
Inflammatory process
| Blood clot forms + blocks 1/more veins, usu in legs
165
What are the uses of barbiturates?
Thiopental: Induction, cerebral protection (e.g. status epilepticus)
Methohexital: Induction (for ECT)
Phenobarbital: Seizure suppression
Anxiolysis
166
What are the endocrine effects of etomidate?
Dose dependent inhibition of 11B-hydroxylase - formation of cortisol + aldosterone
Potential acute adrenal insufficiency
Impaired stress response may be harmful
167
What are common benzodiazepines?
Midazolam (short acting)
Lorazepam (intermediate)
Diazepam (long acting)
168
What are the adverse effects of benzodiazepines?
All have extended effects
Post-op amnesia, drowsiness, cognitive dysfunction
Paradoxical reactions, irritability, aggressiveness (oft elderly patients)
169
What is flumazenil?
Reverse sedating effect of benzodiazepines
Comp antagonist
Short 1/2-life, may get rebound agonist effect
Infusion may be necessary
Can cause seizures in:
Patients on chronic benzodiazepines
Mixed overdoses (tricyclic antidepressants)
170
What are the uses of ketamine?
Dissociative anaesthesia
Sedation
Analgesia
Bronchodilatation
171
What are the 2 pain pathways?
Ascending - transmitting stimulus
| Descending - inhibiting transmission
172
What area of the spinal cord do pain fibres travel?
Dorsal horn
| Substantia Gelatinosa
173
What are the 4 opioid receptors?
MOP (mu)
KOP (kappa)
DOP (delta)
NOP (nociceptin)
174
What receptor do opioid analgesics mostly bind to?
MOP
175
What opioid receptor does morphine act on?
MOP
176
What are the uses of morphine?
Analgesia
Palliation
Peri-operative
177
How can morphine be administered?
Oral (poor bioavailability; 40-60%) - metabolised liver b4 reaches brain
Subcutaneous/IV/intrathecal/transdermal
178
What other effects can morphine have on the body?
Constipation (GI receptors)
| Pruritus
179
How does fentanyl work?
Synthetic analogue of morphine - 80-100x more potent
Targets DOP + MOP, rapid onset
Few cardiovascular effects, less His release
180
What type of fentanyl is available for use in cancer?
Transdermal fentanyl - patch on skin
| Replace patch every 72 hrs
181
How does codeine work?
50% analgesic potency compared to morphine
Weakly targets MOP + KOP
Given orally
182
What is a pro drug?
Metabolized into pharmacologically active drug by body
183
When is codeine banned?
Neonate
| Risk breastfeeding mother are rapid metabolizers, infant can overdose via breast milk
184
How does tramadol work?
```
Atypical opioid
Dual action i) mu agonist (weak)
ii) serotinergic / noradrenergic reuptake inhibition
Safer cardio - respiratory profile
Risk of serotonin syndrome
```
185
How is tramadol administered?
Oral/IV
186
What is naloxone?
Reduce side effects of opioids
Pure opioid antagonist
Short acting
Rebound agonist effect possible - may need infusion
187
What are the adverse effects of naloxone?
Hypertension
Pulmonary oedema
Cardiac arrhythmias
188
How does remifentanil work?
Synthetic derivative of fentanyl
Potent MOP agonist
Ultra-short acting drug
189
What are the pharmacokinetics of remifentanil?
Metabolized by non specific blood/tissue esterases
| Rapid onset + offset
190
What are the uses of remifentanil?
Pain relief during surgery
Sedation in ICU
PCA in obstetrics - patient controlled analgesia
Total IntraVenous Anaesthesia ( TIVA)
191
What are the pros of TIVA?
```
Propofol + Remifentanil infusions
Avoids conventional anaesthetic gases
Improved cardiovascular profile
Less nausea + vomiting
Improved tube tolerance
```
192
What are the cons of TIVA?
Need dedicated IV line
Based on algorithms (Compartment model assumptions)
Risk of awareness
193
What are the common outcomes of delirium?
↑ed rates of:
cognitive impairment + functional disability
length of hospital stay/institutionalisation
death
falls
194
What acronym can help remember causes of delirium?
```
Drugs (withdrawal/toxicity, anticholinergics)/Dehydration
Electrolyte imbalance
Level of pain
Infection/Inflamm (post surgery)
Resp failure (hypoxia, hypercapnia)
Impaction of faeces
Urinary retention
Metabolic disorder (liver/renal failure, hypoglycaemia)/MI
```
195
What NT are implicated in delirium?
Cholinergic deficiency
| Dopaminergic excess
196
How does having dementia affect risk of delirium?
↑ risk 5x
197
What would you look out for in a full examination of a patient to look out for frailty?
Causes of delirium/presence of delirium
Look for infection, dehydration, sensory impairment
Baseline cognitive assessment (e.g. AMT, MMSE)
Assess for pain
198
What medications are high risk for delirium?
```
Analgesics - opioids
Anticholinergics
Antidepressants
Sedative-hypnotics
Corticosteroids
Dopamine agonists
```
199
When should pharmacological management of delirium be used?
If non-pharmacological methods have failed
If patients: severely distressed by delirium symptoms
At risk to self/others
Requires urgent medical interventions
200
What is the strongest RF for persistent delirium?
Pre-existing dementia
201
What is persistent delirium?
Cognitive disorder, meets criteria for delirium on/after admission to hospital + continues meet criteria at discharge + beyond
202
How is sleep entered?
Via nonREM (NREM)
203
What stages of sleep dominate the:
a) 1st third of the night?
b) last third of the night?
a) SWS - slow-wave sleep, phase 3 sleep
| b) REM
204
What stage of sleep is the majority of sleep?
Stage 2
205
How does SWS change as we get older?
↓s by 2% per decade until 60
206
What are the 2 types of circadian rhythm sleep disorders?
Intrinsic (primary) - alterations circadian timekeeping system e.g DSPD (delayed sleep phase), ASPD (advanced sleep phase)
Extrinsic (2ndary) - misalignment between intrinsic + extrinsic signals e.g shift work disorder, jet lag disorder
207
What is delayed sleep phase disorder (DSPD)?
Sleep out of phase mit socially acceptable sleep-wake times
Prevalence 0.2 to 16%, depending on age
Evening chronotype preference
About 9.25h of sleep required
Sleep deprivation may → worse academic performance, health + wellbeing
208
What are clinical features of DSPD?
Unable to advance sleep onset
Restriction to conventional bedtimes results in sleep deprivation
Insomnia +/ excessive sleepiness
Sleep normal when can sleep at desired times
209
How would you treat DSPD?
```
Does person want treatment?
Combo of:
1. Phototherapy
2. Melatonin
3. CBT-I
4. Examine for psychiatric co-morbidity
```
210
What is a chronotype?
Behavioral manifestation of underlying circadian rhythms of myriad physical processes
i.e circadian typology
211
What is the shift work disorder?
Insomnia/excessive sleepiness mit recurring work schedule, overlaps usual time for sleep
Symptoms associated mit work schedule for 1 month
Sleep disturbance X explained by another sleep disorder, medication/substance misuse
Supported by sleep log/actigraphy
212
How is sleep deprivation defined?
Sufficient lack of restorative sleep over cumulative period so it causes physical/psychiatric symptoms
+ affects daily performance
213
What are the parasomnias?
```
Abnormal behaviours occur in association mit sleep
Occur during NREM + REM sleep
Diagnostically challenging
Poor patient recall
Limited history if x witness account
Routine investigations oft normal
```
214
When do SWS/NREM parasomnias occur?
1st third of the night
1-3 episodes p/night
Frequency varies
Onset in childhood
215
What are some examples of SWS/NREM parasomnias?
```
Confusional arousal
Sleep Walking (somnambulism)
Night terrors (pavor nocturnus)
Sleep-related Eating Disorder
Sexsomnia - engaging in sexual acts while in NREM
```
216
What are treatments for night terrors?
Education. CBT-I to stabilise sleep-wake patterns
Scheduled awakening: 30min alarm method for children
Keep room safe; be aware of new environs
Only wake fully if episode lasts >45 mins
Pregablin, Clonazepam
217
What are some RF of SWS/NREM parasomnias?
| How do patients describe selves after night terrors?
Family History
Exacerbated: sleep depriv, stress, alcohol, OSA, fever
Patient oft amnesic for event, partial recollection
Partner may describe tearfulness/confusion
218
What is the treatment for SWS/NREM parasomnias?
Reassurance (benign)
Education – CBT-I to improve sleep pattern
Avoid triggers
Safety
Antidepressants (e.g. Fluoxetine, Trazadone)
Clonazepam
Melatonin
219
When do REM parasomnias occur?
2nd half of night
1-2 episodes p/night
Frequency varies
220
What are some examples of REM parasomnias?
REM sleep Behaviour Disorder
Nightmares – Rx: Stop causative meds (e.g. β-blockers, L-Dopa), CBT, Prazosin
Recurrent sleep paralysis
221
What is REM sleep Behaviour Disorder? (RBD)
Loss of muscle atonia during REM sleep + history of abnormal behaviours in sleep
Oft correlate mit recalled vivid dreams – usu aggressive
May injure patient / bed partner
222
What is the relationship between RBD and Parkinson's disease?
Non-motor predictor of developing Parkinson’s
Disease, predictor of early cognitive impairment
Present other neurodegenerative conditions (mainly
synucleinopathies) such as MSA/DLB
223
How would you diagnose RBD?
Clinical history highly suggestive but a v-PSG would confirm diagnosis (catching episode/REM without atonia)
224
What are some differential diagnoses of RBD?
Severe OSA
Severe PLMS, RMD (sleep related rhythmic movement)
Sleep talking, confusional arousals, night terrors (possible overlap disorders)
Nocturnal seizures
Nocturnal dissociative episodes
225
How would you treat RBD?
Patient education
If possible, discontinue meds, may be contributing
Safety - separate beds from partner
Consider simple home oximetry (rule out OSA)
226
How can pneumonia be classified based on area of infection?
```
Lobar - lobe of 1 lung
Bronchopneumonia - parts of both lungs
Interstitial - fibrosis of interstitium
Cryptogenic organising pneumonia - autoimmune?
inflamm of alveoli + bronchioles
```
227
What pathogen is the common cause of pneumonia in IVDU?
Staphylococcus aureus
| S, aureus already present on skin
228
What are some rheumatological/CT (connective tissue) causes of ILD?
Scleroderma
Rheumatoid arthritis
Mixed CT disease
SLE
229
What are some idiopathic causes of ILD?
Chronic fibrosing from -
Idiopathic pulmonary fibrosis
Non-specific IP
Acute/subacute IP
230
What acronym help remember what affects upper lobe CT?
```
C - Coal Worker's Pneumoconiosis
H - Histiocytosis
A - Ankylosing spondylitis
R - Radiation
T - TB
S - Sarcoidosis + Silicosis
```
231
What acronym help remember what affects lower lobe CT?
```
R - RA
A - Asbestosis
S - SLE, Slerdoma, Sjogren's syndrome
I - Idiopathic
O - Other e.g. drugs
```
232
How would you approach a patient to try and tackle harmful drug use/dependance?
F - Feedback, discuss risks associated mit that
person’s drug use + listen to responses
R - Responsibility, up to them to change
A - Advice, harm minimisation advice + how to change
M - Menu, give people options
E - Empathy, non-judgemental, warm clinical approach
S - Self-efficacy, project optimism, ability make +ve change
233
What are some common symptoms of alcohol withdrawal symptoms?
```
↑ed pulse, BP, temp
Sweating, Shaking, Agitation
Sensitivity light + sound
May be confused, hallucinating: tactile, auditory, visual
May develop seizures
X have to be BAC 0.00mg/l
```
234
What receptor does alcohol affect?
GABA-A receptor, brain's major inhib system
↑ activity of system, lead to:
Reduced anxiety, ataxia, slurred speech, disinhibition, sedation, reduced levels of consciousness
235
What happens to the sensitivity of GABA-A receptor with chronic alcohol?
Receptor sensitivity is reduced
236
How does GHB affect the body? (What receptors act on?)
Presynaptic GABA-B + GHB receptors, ↓ GABA release
High concs binds postsynaptic GABA-B receptors – inhibit postsynaptic neuron
GHB metabolised to GABA
237
How do opioids suppress respiration?
Central control of resp occurs in brainstem + medulla
Chemoreceptors detect pO2 + pCO2, usu stimulate resp drive
MOP in brainstem, medulla, chemoreceptors
Stimulation receptors slows resp
238
What is the half life of naloxone?
60-90 min
239
What is delirium tremens?
Delirium occurring cos of alcohol withdrawal
240
What is Wernicke-Korsakoff's syndrome?
| Common symptoms?
```
Secondary to thiamine deficiency
Triad ophthalmoplegia (weakening of eye muscles), ataxia, confusion
```
241
What is ataxia?
Degenerative disease of nervous system, damage to cerebellum
| Symptoms mimic being drunk: slurred speech, stumbling, falling
242
What are 2 ways to care for patients in uncomplicated alcohol withdrawal?
Symptom triggered - measure withdrawal every 2-4 hrs for 24 hrs and dose accordingly
Fixed dose - prescribe fixed dose, estimate what you think patient needs
243
What are the cons of the 2 ways to care for patients in uncomplicated alcohol withdrawal?
Symptom triggered - needs adequate nursing staff trained in assessment of alcohol withdrawal
Fixed dose - risks excess sedation, longer stay than needed
244
What drugs are used for patients in uncomplicated alcohol withdrawal?
Benzodiazepines, reduces dose over 5 days
Diazepam/Chlordiazepoxide
Lorazepam/oxazepam (cirrhosis)
245
How would you treat patients with delirium tremens?
Universal intervention to peeps mit delirium - 1:1 nurse, side room, family present
Manage delirium - hrly ↑ dose lorazepam/diazepam until symptoms controlled
Monitor resp depression and have flumazenil prn
246
What drugs would you use to treat Wernicke's Encephalopathy?
Parenteral thiamine - window for effect is short
Pabrinex - cocktail thiamine + other B vitamins
Preventative: 1 pair of ampoules x 3 IM or IV
Treatment: 2 pairs ampoules 3x day for 5 days
247
How would you care for a patient that's G intoxicated?
Supportive - keep airways clear, O2
Aware of mixed intoxication e.g. X hypotension + bradycardia if also taken cocaine
X intubate unless vomiting, seizing/other indication
X naloxone unless picture ambiguous
248
How would you classify G dependance?
```
Using every couple of hours every day
Using alcohol/benzos manage withdrawal symptoms
Waking at night to use
Preoccupation
Prioritising G over other things
```
249
How would you carry out a GBL detox if it's planned?
CIWA evaluate withdrawal severity
Give baclofen 10mg tds week before, increase to 20mg tds
In withdrawal, add benzodiazepines (diazepam/librium) May need large doses, 10-14 days treatment
250
What receptor does naloxone have the highest affinity for?
Mu opioid receptor
251
What are medically unexplained symptoms?
Physical symptoms x explained by underlying pathology
Cause signif functional disability/distress
X soley attribute anxiety, depression, health anxiety, psychosis
252
What are common medically unexplained symptoms?
Pain, fatigue, dizziness, headaches, changes gut motility. visual + auditory disturbances
Singly/symptom clusters
253
What is chronic fatigue syndrome?
Persistent/relapsing, debilitating fatigue
| At least 6 months
254
What is fibromyalgia?
Widespread pain index + symptom severity scores
Symptoms present at similar level for at least 3 months
Patient X have disorder otherwise explain pain
255
What are insensible losses of water from the body?
Skin + Lungs
| X measure water loss
256
What percentage of total body sodium is non-exchangeable?
25% e.g in bones
257
What 3 mechanisms regulate sodium excretion?
Kidneys: Renin-Angiotensin-Aldosterone
Natriuretic Peptides
Intrinsic Renal mechanisms
258
Where is potassium mainly stored?
In cells
259
What mnemonic can help remember causes of increased AG acidosis?
```
G - Glycols (ethylene, propylene)
O- Oxyproline
L - L-lactate
D - D-lactate
M - Methanol
A - Aspirin
R - Renal failure
K - Ketoacidosis
```
260
What are some causes of normal anion gap (AG) acidosis?
GI losses bicarb: diarrhoea, surgical drains/fistulae
| Renal losses bicarb: renal tubular acidosis
261
What can cause lactic acidosis?
Lactate production from anaerobic resp
| Shock e.g hypovolaemic, Cardiogenic, Septic, Anaphylactic
262
What is:
a) Anuria?
b) Oliguria?
a) failure kidneys produce urine, patient x produce urine
| b) Reduced urine output
263
What hormones do the kidneys produce?
Renin, Vit D, Erythropoietin, Prostaglandins
264
What is uremia?
| What can it cause?
Retention metabolic waste products (sulphate, urea, ammonia, creatinine, phosphate etc)
Pericarditis, Pleurisy, Encephalopathy
265
Why would you consider renal replacement therapy/dialysis in a patient with AKI?
Life threatening complication of AKI e.g.
Life threatening pulmonary oedema
Severe metabolic acidosis
Severe hyperkalaemia, esp if ECG changes present
Uraemia: uraemic pericarditis/encephalopathy
266
What is an AVM in the brain?
Arteriovenous malformation, tangle of abnormal blood vessels connecting arteries + veins in brain
267
Who is more at risk to blood in subdural space? Why?
Elderly, wider subdural spaces
268
What is diffuse spectrum imaging (DSI)?
Tracks how water molecules through nerve fibres of brain to expose large-scale pics of axons
269
How can you modulate spinal reflexes?
↑ sensitivity flexor network - anticipate heat
| Inhibit flexor response - still touch heat but x withdraw
270
What are the motor areas of the cortex and what do they do?
Premotor cortex: conceptualization of movement goal
PLAN
Supplementary cortex: strategy → achieve goal PROGRAMME
Primary motor cortex: activate spinal motor neurones
INITIATE MOVEMENT
271
What is the blood supply of the motor cortex?
Middle cerebral artery (MCA)
| Anterior cerebral artery (ACA)
272
Where do the pyramidal descending tracts originate from?
What types of cells are present?
What is the NT?
Precentral gyrus in the primary motor cortex
Large Betz cells → large diameter corticospinal axons
Glutamate
273
What is the most common area of the brain for stroke?
| Why?
Internal capsule in corona radiata
Blood supply comes from branch of MCA
Vessel comes off at right angle, fat can deposit/high BP can push and cause aneurysm
274
What is the average postural sway?
| How does it change as you get older?
A-P 7mm
| Gets larger
275
What can stroke mimic? (5 S')
```
S: SYNCOPE
S: SEIZURES
S: SEPSIS
S: SPACE OCCUPYING LESION
S: SOMATISATION
```
276
What is transient global amnesia? (TGA)
Sudden disorder of memory
For a period (some hours), X memorise any
current info (anterograde amnesia)
Oft X recall events of past few days/weeks (retrograde amnesia)
277
What age group does TGA affect?
Middle aged or elderly
278
What is horripilation?
Erection of hairs on skin due to cold/fear/excitement
279
What is reverse stress relaxation in immediate compensation for shock?
Veins shrink around reduced blood volume
| Helps maintain venous pressure\venous return (starts after ~10 min, takes an hour or so to develop fully)
