Supporting Life Flashcards
Where in the coronary vessels do plaques usually form?
Which coronary vessel can a plaque form that causes the most damage?
Proximal region within 6 cm of aorta
L anterior descending coronary artery
What is the major action of the haemodynamic effects of nitrates?
Relaxes veins + venules
↓ CVP, so ↓ cardiac wall tension
↓ cardiac O2 demand
What is the minor action of the haemodynamic effects of nitrates?
Dilate larger coronary arteries, ↑ing blood flow thru coronary collaterals
↓ TPR + afterload, so ↓ O2 demand
What are the side effects of nitrates?
Why?
Headache, facial flushing
↓ BP, reflex ↑ HR
Due to vasodilatation
What is the most commonly used beta blocker in UK for angina?
Against what receptors?
Bisoprolol
Beta 1 selective
How do beta blockers work in angina?
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
How do beta blockers ↑ perfusion of l ventricle?
L ventricle gets blood only during diastole - systole squeezes arterioles
Slower HR, more time spent in diastole
Why are beta blockers contraindicated in asthma and vasospastic angina?
Asthma - adren bronchodilator via beta receptors
V angina - beta receptors vasodilating effect on coronary arteries
What are the side effects of beta blockers?
Fatigue, exercise intolerance, hypoglycaemia, disturbed sleep, cold/tingling extremities
What are the common Ca channel blockers used?
Amlodipine (dihydropyridine, DHP)
Verapamil
Diltiazem
What are the effects of the different types of Ca channel blockers in angina?
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
What enzyme do statins block?
HMG-CoA reductase
What is the coronary flow reserve?
Ability of coronary vessels to↑ blood flow during greater O2 demand e.g. exercise
How does nitrous oxide work to prevent vascular smooth muscle cell contraction?
Opens K+ channels to prevent depolarisation
Activates Ca2+ pumps - to remove Ca2+ from cells
Ca2+ desensitisation
How is GTN taken so it works immediately?
Sublingually
How quickly does tolerance to organic nitrates happen?
How to avoid this?
After 12 hours
Daily 8 hour drug free period - usu at night
What is the late Na+ current in cardiac myocytes?
Upstroke of AP in cardiac myocytes due rapidly developing Na+ current - inactivates few millisec
Inactivation incomplete - late Na+ current
What can a late Na+ current in cardiac myocytes cause?
AP prolongations → arrhythmias
Myocardial stunning - contractile abnormality even after reperfusion
Diastolic stiffness → ↑cardiac work, ↓ coronary blood flow
How does the drug ranolazine help with angina?
Inhibits late Na+ current in cardiac myocytes
Reduces cardiac wall tension, ↓ cardiac work
What type of angina is the drug ranolazine used to treat?
Microvascular angina
May have anti-oxidant + inflammatory effects
Improve coronary endothelial function
How does the drug nicorandil work to reduce symptoms of angina?
Opens ATP-sensitive K+ channels in vascular sm cells
Stimulates guanylate cyclase → ↑ vascular sm cell [cGMP]
Relaxation of sm
How does the drug ivabradine work to reduce symptoms of angina?
Blocks If (‘funny’ current), involve SAN pacemaking,
↓ HR, ↑es perfusion
‘Use-dependency’ - ivabradine block more when HR ↑
What are the hemodynamic effects of ivabradine?
↓ HR allows more time for blood to perfuse myocardium, reduces ischaemia
↓ HR → ↓ afterload → ↓ O2 demand
What 2 revascularization techniques can be used to treat stenosis in coronary vessels?
Percutaneous intervention (PCI) - stents Coronary artery bypass grafting (CABBAGE) - pieces of saphenous vein/diverted internal mammary artery
When would a coronary artery bypass be used instead of PCI?
Patients with mehr serious/advanced coronary artery disease
Improves survival compared to PCI
What is definition of:
a) Sinus rhythm?
b) Junctional rhythm?
a) Heartbeat originate from SAN
b) Heartbeat originate from AVN/Bundle of His
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
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
What 2 drugs are antiarrhythmic but don’t fit the different classes?
Adenosine: slows AV nodal conduction
Digoxin: stimulates vagus, slows AV nodal conduction
Examples of: a) Class 1 b) Class 2 c) Class 3 d) Class 4 antiarrhythmic drugs?
a) flecainide
b) bisoprolol
c) amiodarone
d) verapamil
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
What drugs are used in rate control of arrhythmias?
Class 2, Class 4, Adenosine, Digoxin
What is rhythm control in treatment of arrhythmias?
Target source of arrhythmia/conduct impulse away from source, by blocking re-entrant pathway
What drugs are used in rhythm control of arrhythmias?
Class 1, Class 3
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
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
What class of antiarrhythmic drugs can be used to treat polymorphic VT?
Class 2
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
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
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
What is Monckeberg’s medial sclerosis?
Calcification of media of muscular arteries
What is Arteriosclerosis?
Proliferative/hyaline thickening of walls of small arteries + arterioles
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
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
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
What is the layer deep to the internal elastic lamina in the aorta?
Media composed of sm cells + elastin fibres
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
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
What is hyperlipoproteinemia?
Inability to break down lipids in body, esp cholest/trigly
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
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)
Why is venous infarction less common?
Most tissues have numerous venous anastomoses
What places can venous infarction take place in?
Thrombosis of mesenteric veins → intestinal infarction
Brain following thrombosis in superior sagittal sinus
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
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
What are the 4 morphological complications following MI?
Cardiac rupture
Pericarditis
Mural thrombosis
Ventricular aneurysm
Definition of embolism?
Transfer of abnormal material by bloodstream + its impaction in a vessel
Impacted material = embolus
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
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%
What are the 3 main causes of heart failure?
Pressure overload
Volume overload
Contractile dysfunction
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
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
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
How would you classify pleural fluid based on its protein content?
<25g/L - transudate
>35g/L - exudate
If 25-35 use Light’s criteria
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
What are the common causes of transudates (pleural fluid)?
L ventricular failure
Liver cirrhosis
Renal failure
What are the common cause of exudates (pleural fluid)?
Lung cancers
Parapneumonic effusions
TB
What are the general causes of transudates and exudates (pleural fluid)?
Transudates - systemic problemos
Exudates - local problemos
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
What is empyema? (in context of lungs)
Pus in the pleural space
Have to drain pus
Very smelly
What is cachexia?
Extreme weight loss and muscle wasting
What are some causes of a malignant pleural effusion?
Lung/breast/ovarian cancer
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
What is orthopnea?
Breathlessness when lying down
Relieved by sitting/standing
What would a chest X-ray show in heart failure?
Bilateral pleural effusions
What is a PEA arrest?
Pulseless Electrical Activity
ECG shows heart rhythm but no pulse produced
What are viridans streptococci?
What do they cause?
Gram +ve bact, green colouration on blood agar plates
Pneumonia. emphysema, sepsis, meningitis
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)
What is kyphoscoliosis?
Abnormal curvature of spine in coronal (side-side) and sagittal plane (back-front)
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
What are some drugs that can cause ILD?
Cytotoxic drugs e.g Amiodarone, Nitrofurantoin, Bleomycin, Chemotherapy, Methotrexate
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
What are the risk factors of IPF/UIP?
Smoking (2-3x day)
Metal/wood dust
Genetic (familial)
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)
What are the main causes of death in IPF/UIP?
Resp failure Heart failure PE Pneumonia Lung cancer
What are some CT findings in non-specific interstitial pneumonia?
Ground glass opacities + fibrosis
Treatment response + prognosis better that UIP/IPF
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
What are the hallmarks of type I hypersensitivity?
IgE production, activation of Th2 cells
Mediated IgE-mast cells
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
What are the characteristics of the main allergens in type I hypersensitivity?
Individuals repeatedly exposed to them
X induce macrophage/dendritic cell typical responses
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
What are some symptoms of type I hypersensitivity?
Lung – asthma, wheezing Nose – rhinitis, sneezing, runny nose Eye – conjunctivitis Skin – atopic dermatitis Gut – food allergy
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)
What happens in type II sensitivity?
Antigens bound on cell membranes
Activate complement cascade + recruit immune cells
What is the most severe form of type I hypersensitivity?
Anaphylaxis
What are some examples of antigens in type II hypersensitivity?
Drugs e.g. penicillin, quinine
Bacteria
Rhesus antigen
What are the main types of antibodies in type II and III hypersensitivity?
IgM, IgG
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
What are some examples of antigens in type III hypersensitivity?
Foreign serum - antivenom, monoclonal antibody
Group A streptococcus
What is an arthus reaction in type III hypersensitivity?
Inflammation caused by deposition of immune complexes at localised sites
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
What is type IV hypersensitivity?
Antibody independent, 24-48 hr after antigen exposure
Cytokine mediated inflamm, T cell mediated cytotoxicity
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
What types of cells are responsible for producing large amounts of IL-5 and IL-3 in asthma?
Type 2 Innate Lymphoid Cells (ILC2)
What is the dominant cause for asthma exacerbation?
Viruses
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
What is the action of salbutamol in the treatment of asthma?
Stimulates β2adrenergic receptors – predom receptors in bronchial sm
↑ levels cAMP relaxes bronchial sm + inhibits release bronchoconstrictor mediators e.g His + leukotrienes from mast cells in airway
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
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
How do inhaled corticosteroids (ICS) reduce asthma symptoms?
Suppress Th2 / ‘Type 2’ airways inflammation
Reduce infiltration + activation of eosinophils, Th2 cells, + other inflammatory cells
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
When are steroids more effective in asthma?
If asthmatic has eosinophil inflammation
What is the aim of drug treatment in angina?
↓ing myocardial O2 demand
↑ing O2 supply
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
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
What is the common pathogen that causes pneumonia?
S. pneumoniae, esp post influenza
What are some complications of pneumonia?
Septic shock Adult Respiratory Distress Syndrome Parapneumonic effusion & empyema Cavitation & abscess MI
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
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
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
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
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’
What are the 3 high value interventions for COPD?
Treating tobacco dependance
Providing vaccination
Support patient to complete pulmonary rehab
SUPPORTING BEHAVIOUR CHANGE
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
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
What is pulsus paradoxus AKA paradoxical pulse?
Abnormally large ↓ in stroke volume, systolic BP + pulse wave amplitude during inspiration
What is the difference between hypoxia and hypoxaemia?
Hypoxia - insufficient O2 at cellular level
Hypoxaemia - reduced O2 tension in blood (arterial hypoxaemia – low PaO2)
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).
What are routine lung function tests?
Spirometry - (inspired/expired volume/flow)
Lung volume (+/- airway resistance)
Gas transfer
Resp muscle strength (volitional tests)
What 2 types of drugs can reduce oxidative stress caused by smoking?
Antioxidants
Antiproteases
What molecules are involved in inflammation in COPD?
↑ed neutrophils, macrophages + T cells
(CD8 > CD4) in lungs
Eosinophilic inflammation
What are sources of oxidants? (COPD)
Cigarette smoke
Reactive O2 + N2 species from inflamm cells
What happens during oxidative stress?
Inactivates antiproteases
Stimulates mucus production
Amplifies inflamm by enhancing transcrip factor activation + gene expression of pro- inflamma mediators
What happens to the lung parenchyma in COPD?
Proteolytic enzymes destroy alveolar tissue
Elastin + collagen, loss of elastic recoil
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
What happens to the airways in COPD?
Narrowing of airways due remodelling
- starts mit smaller airways <2mm
↑ed airways resistance
What does compliance mean in relation to lungs?
Extend to which lungs can expand
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)
What is the state of the lungs at rest during COPD?
Hyperinflated, FRC + RV ↑ed
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
What is the hoover sign in COPD?
Inward movement of lower rib cage during inspiration instead outward - flat but functioning diaphragm
What are the common causes of COPD exacerbation?
Bacterial infections e.g influenza, catarrhalis, pneumonia
Viral infections less common cause
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)
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
What happens during impaired ventilation?
O2 x move from alveoli → blood
Causes: ILD, thickened alveoli so x diffuse
What can be the causes of low pp inspired O2?
High altitude non commercial flights
High altitude mountaineering
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
What happens in dead space in a V-P mismatch?
Ventilating under-perfused lung
X blood flow, x GE
Wasted ventilation + energy
What are the main causes of hypercapnia?
↑ed resp load
Reduced internal resp drive
Reduced muscle capacity
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
What are some reasons a patient would need acute non-invasive ventilation?
Hypercapnic resp failure, is decompensated (acidosis)
Failed standard therapy
What are the common conditions for acute non-invasive ventilation?
COPD
Obesity related resp failure
What is ECMO in ventilation?
Extra Corporeal Membrane Oxygenation Removes blood from circulation Replaces O2, removes CO2 Returns to Venous circulation Requires anticoagulation
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
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
What is Obesity hypoventilation syndrome?
Obesity - BMI >30kg/m^2
Sleep disordered breathing
Daytime hypercapnia
Absence of another pathology explaining hypoventilation
What is:
a) Pharmacodynamics?
b) Pharmacokinetics?
a) what effects drugs have on body
b) how body processes drug
What are the common induction agents (anaesthetics) used?
Propofol Barbiturates Etomidate Benzodiazepines Ketamine
What are the common opioids used?
Morphine Fentanyl Codeine Tramadol Remifentanil
What are the uses of propofol?
Anaesthetic induction
Maintenance of anaesthesia
Sedation
Anti-emesis - effective against nausea + vomiting
What are the pros of using propofol as an anaesthetic?
X Malignant Hyperpyrexia trigger
Pleasant dreams
Relieves pruritus from opiates
Anti-emetic
What is malignant hyperpyrexia?
Cause: Underlying disease of muscle
Trigger: Volatile anesthetic gas
Drastic, sustained rise body temp, metabolic acidosis, widespread muscular rigidity
What are the con of using propofol as an anaesthetic?
Anaphylaxis (v rare)
Pancreatitis (Hypertriglyceridemia)
Pain on injection (rare); thrombophlebitis
What is thrombophlebitis?
Inflammatory process
Blood clot forms + blocks 1/more veins, usu in legs
What are the uses of barbiturates?
Thiopental: Induction, cerebral protection (e.g. status epilepticus)
Methohexital: Induction (for ECT)
Phenobarbital: Seizure suppression
Anxiolysis
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
What are common benzodiazepines?
Midazolam (short acting)
Lorazepam (intermediate)
Diazepam (long acting)
What are the adverse effects of benzodiazepines?
All have extended effects
Post-op amnesia, drowsiness, cognitive dysfunction
Paradoxical reactions, irritability, aggressiveness (oft elderly patients)
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)
What are the uses of ketamine?
Dissociative anaesthesia
Sedation
Analgesia
Bronchodilatation
What are the 2 pain pathways?
Ascending - transmitting stimulus
Descending - inhibiting transmission
What area of the spinal cord do pain fibres travel?
Dorsal horn
Substantia Gelatinosa
What are the 4 opioid receptors?
MOP (mu)
KOP (kappa)
DOP (delta)
NOP (nociceptin)
What receptor do opioid analgesics mostly bind to?
MOP
What opioid receptor does morphine act on?
MOP
What are the uses of morphine?
Analgesia
Palliation
Peri-operative
How can morphine be administered?
Oral (poor bioavailability; 40-60%) - metabolised liver b4 reaches brain
Subcutaneous/IV/intrathecal/transdermal
What other effects can morphine have on the body?
Constipation (GI receptors)
Pruritus
How does fentanyl work?
Synthetic analogue of morphine - 80-100x more potent
Targets DOP + MOP, rapid onset
Few cardiovascular effects, less His release
What type of fentanyl is available for use in cancer?
Transdermal fentanyl - patch on skin
Replace patch every 72 hrs
How does codeine work?
50% analgesic potency compared to morphine
Weakly targets MOP + KOP
Given orally
What is a pro drug?
Metabolized into pharmacologically active drug by body
When is codeine banned?
Neonate
Risk breastfeeding mother are rapid metabolizers, infant can overdose via breast milk
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
How is tramadol administered?
Oral/IV
What is naloxone?
Reduce side effects of opioids
Pure opioid antagonist
Short acting
Rebound agonist effect possible - may need infusion
What are the adverse effects of naloxone?
Hypertension
Pulmonary oedema
Cardiac arrhythmias
How does remifentanil work?
Synthetic derivative of fentanyl
Potent MOP agonist
Ultra-short acting drug
What are the pharmacokinetics of remifentanil?
Metabolized by non specific blood/tissue esterases
Rapid onset + offset
What are the uses of remifentanil?
Pain relief during surgery
Sedation in ICU
PCA in obstetrics - patient controlled analgesia
Total IntraVenous Anaesthesia ( TIVA)
What are the pros of TIVA?
Propofol + Remifentanil infusions Avoids conventional anaesthetic gases Improved cardiovascular profile Less nausea + vomiting Improved tube tolerance
What are the cons of TIVA?
Need dedicated IV line
Based on algorithms (Compartment model assumptions)
Risk of awareness
What are the common outcomes of delirium?
↑ed rates of:
cognitive impairment + functional disability
length of hospital stay/institutionalisation
death
falls
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
What NT are implicated in delirium?
Cholinergic deficiency
Dopaminergic excess
How does having dementia affect risk of delirium?
↑ risk 5x
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
What medications are high risk for delirium?
Analgesics - opioids Anticholinergics Antidepressants Sedative-hypnotics Corticosteroids Dopamine agonists
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
What is the strongest RF for persistent delirium?
Pre-existing dementia
What is persistent delirium?
Cognitive disorder, meets criteria for delirium on/after admission to hospital + continues meet criteria at discharge + beyond
How is sleep entered?
Via nonREM (NREM)
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
What stage of sleep is the majority of sleep?
Stage 2
How does SWS change as we get older?
↓s by 2% per decade until 60
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
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
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
How would you treat DSPD?
Does person want treatment? Combo of: 1. Phototherapy 2. Melatonin 3. CBT-I 4. Examine for psychiatric co-morbidity
What is a chronotype?
Behavioral manifestation of underlying circadian rhythms of myriad physical processes
i.e circadian typology
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
How is sleep deprivation defined?
Sufficient lack of restorative sleep over cumulative period so it causes physical/psychiatric symptoms
+ affects daily performance
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
When do SWS/NREM parasomnias occur?
1st third of the night
1-3 episodes p/night
Frequency varies
Onset in childhood
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
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
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
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
When do REM parasomnias occur?
2nd half of night
1-2 episodes p/night
Frequency varies
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
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
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
How would you diagnose RBD?
Clinical history highly suggestive but a v-PSG would confirm diagnosis (catching episode/REM without atonia)
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
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)
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
What pathogen is the common cause of pneumonia in IVDU?
Staphylococcus aureus
S, aureus already present on skin
What are some rheumatological/CT (connective tissue) causes of ILD?
Scleroderma
Rheumatoid arthritis
Mixed CT disease
SLE
What are some idiopathic causes of ILD?
Chronic fibrosing from -
Idiopathic pulmonary fibrosis
Non-specific IP
Acute/subacute IP
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
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
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
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
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
What happens to the sensitivity of GABA-A receptor with chronic alcohol?
Receptor sensitivity is reduced
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
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
What is the half life of naloxone?
60-90 min
What is delirium tremens?
Delirium occurring cos of alcohol withdrawal
What is Wernicke-Korsakoff’s syndrome?
Common symptoms?
Secondary to thiamine deficiency Triad ophthalmoplegia (weakening of eye muscles), ataxia, confusion
What is ataxia?
Degenerative disease of nervous system, damage to cerebellum
Symptoms mimic being drunk: slurred speech, stumbling, falling
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
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
What drugs are used for patients in uncomplicated alcohol withdrawal?
Benzodiazepines, reduces dose over 5 days
Diazepam/Chlordiazepoxide
Lorazepam/oxazepam (cirrhosis)
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
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
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
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
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
What receptor does naloxone have the highest affinity for?
Mu opioid receptor
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
What are common medically unexplained symptoms?
Pain, fatigue, dizziness, headaches, changes gut motility. visual + auditory disturbances
Singly/symptom clusters
What is chronic fatigue syndrome?
Persistent/relapsing, debilitating fatigue
At least 6 months
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
What are insensible losses of water from the body?
Skin + Lungs
X measure water loss
What percentage of total body sodium is non-exchangeable?
25% e.g in bones
What 3 mechanisms regulate sodium excretion?
Kidneys: Renin-Angiotensin-Aldosterone
Natriuretic Peptides
Intrinsic Renal mechanisms
Where is potassium mainly stored?
In cells
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
What are some causes of normal anion gap (AG) acidosis?
GI losses bicarb: diarrhoea, surgical drains/fistulae
Renal losses bicarb: renal tubular acidosis
What can cause lactic acidosis?
Lactate production from anaerobic resp
Shock e.g hypovolaemic, Cardiogenic, Septic, Anaphylactic
What is:
a) Anuria?
b) Oliguria?
a) failure kidneys produce urine, patient x produce urine
b) Reduced urine output
What hormones do the kidneys produce?
Renin, Vit D, Erythropoietin, Prostaglandins
What is uremia?
What can it cause?
Retention metabolic waste products (sulphate, urea, ammonia, creatinine, phosphate etc)
Pericarditis, Pleurisy, Encephalopathy
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
What is an AVM in the brain?
Arteriovenous malformation, tangle of abnormal blood vessels connecting arteries + veins in brain
Who is more at risk to blood in subdural space? Why?
Elderly, wider subdural spaces
What is diffuse spectrum imaging (DSI)?
Tracks how water molecules through nerve fibres of brain to expose large-scale pics of axons
How can you modulate spinal reflexes?
↑ sensitivity flexor network - anticipate heat
Inhibit flexor response - still touch heat but x withdraw
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
What is the blood supply of the motor cortex?
Middle cerebral artery (MCA)
Anterior cerebral artery (ACA)
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
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
What is the average postural sway?
How does it change as you get older?
A-P 7mm
Gets larger
What can stroke mimic? (5 S’)
S: SYNCOPE S: SEIZURES S: SEPSIS S: SPACE OCCUPYING LESION S: SOMATISATION
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)
What age group does TGA affect?
Middle aged or elderly
What is horripilation?
Erection of hairs on skin due to cold/fear/excitement
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)
