13 Flashcards
What are some common symptoms of pulmonary TB?
- Haemoptysis.
- Cough.
- Sputum.
- Chest pain.
- Systemic symptoms of infection.
Antimuscarinics MOA in asthma
Block muscarinic acetylcholine receptor which prevents ACh binding to muscarinic receptors
Results in bronchial dilation + decreased secretions
Side effects of amiodarone (class III anti-arrthymatic)
- Blue-grey skin discolouration
- Photosensitivity
- Lung fibrosis
- Corneal deposits
What is coarctation of the aorta?
Narrowing of a short section of the aorta
It’s rare
What do Th2 cells produce?
IL-4 which stimulates IgE
IL-5 which activates eosinophils
What does an atheroma contain?
o Macrophage cells
o Lipids
o Calcium
o Variable amount of fibrous connective tissue
What 2 types of test for TB are there?
1) Mantoux tuberculin skin test
2) Interferon gamma release assay
Blue bloaters (bronchitis)
- Sputum cough
- Oedematous ankles
- Cyanosed
- Overweight
- Sleep apnoea
Tissue changes in the kidney in hypertension
- Glomerular damage
- Shrink
- Renal artery stenosis
- Arteriosclerosis leading to progressive ischaemia of the nephrons
Types of calcium channel blockers.
All calcium channel blockers inhibit the L-type calcium channel on cells.
They are divided into 2 major categories based upon their predominant physiologic effects:
- Dihydropyridines: are predominantly vasodilators, have chronotropic and inotropic effects
- Non-dihydropyridines: are less potent vasodilators, slow cardiac contractility and conduction
Dihydropyridines:
- Nifedipine, isradipine, felodipine, nicardipine, nisoldipine, lacidipine, and amlodipine
- Potent vasodilators that have little or no negative effect upon cardiac contractility or conduction
- Indication: hypertension, chronic stable angina
- Longer-acting agents are generally safer and are increasingly preferred
Non-dihydropyridines
- Verapamil and diltiazem
- Indication: hypertension, chronic stable angina, cardiac arrhythmias, proteinuria reduction
- Are somewhat less potent vasodilators compared with dihydropyridines, but they have a greater depressive effect on cardiac conduction and contractility
What are arterial blood gases? When is it indicated?
Gives the:
- PaO2
- PaCO2
- Acid-base balance (pH, HCO3, H+ etc)
Indicated when oxygen sats are 90-92% or lower.
Pharmacological treatment of patients with LV HF
- ACE inhibitors
- Beta blockers
- ARBs
For the rest of their life because the cumulative effect of these drugs doubles life expectancy (triple therapy).
What is the point of a granuloma?
What happens within it in TB?
What is the main disadvantage of this?
To try and contain the focus of infection.
- Caseating necrosis to prevent dissemination of TB.
- Dampens the host immune response.
What is wheeze?
A musical noise produced by air moving through narrowed airways (airway obstructed)
o Obstruction of airways within chest causes wheezing with expiration – airways get narrower because lungs get smaller
Contrast with stridor which occurs in inspiration – e.g. whooping cough, epiglottitis, foreign body
How is sinus bradycardia treated?
Investigate and remove cause:
- Beta blockers
- Hypothyroidism
- Heart block: recent MI, digoxin toxicity, B-blockers
Usually managed conservatively
Haemodynamic model for progression of heart failure
- Sympathetics and RAAS activated
- Increased preload and afterload
- Consequence is very dilated heart
MOA and example of a biguanide
- Metformin
- Increases utilisation of glucose by increasing uptake and decreasing gluconeogenesis
List and explain the 3 factors regulating stroke volume
o Preload: the degree of stretch before contraction
o Contractility: the forcefulness of contractions
o Afterload: the pressure that must be exceeded for the ventricle to eject blood
Non-dihydropyridines calcium channel antagonists
- E.g. verapamil, diltiazem (class IV antiarrhythmics)
- Slow heart rate
- Useful for angina
- Not for use in heart failure
MOA of acarbose
Inhibits intestinal alpha-glucosidases and delays absorption of starch and sucrose
- Antidiabetic drug for DM2
- Not used anymore
- Cause unpleasant GI side effects
What does low compliance indicate?
Stiff lung which indicates high elastic recoil.
E.g. pulmonary fibrosis
Compliance affects how much energy is required to generate pressure gradient for ventilation.
Torsades de pointes
o Commonly seen in patients with pre-existing bradycardia especially if give class I anti-arrhythmic drugs
o A feared side-effect of drugs
o Exacerbated by low potassium and magnesium
o Treatment – magnesium
Mycobacterium tuberculosis
- Gr+
- Obligate aerobe
- Stains with Ziehl-Neelson
- Bacilli are non-motile, non-sporing and non-capsulated
- Rod
Consequences of left ventricular dysfunction?
- SOB
- Peripheral oedema
- Paroxysmal nocturnal dyspnoea (PND)
- Raised JVP
- Orthopnoea
Pheochromocytoma
- Adrenal medullary (neuroendocrine) tumours secreting catecholamines
- Alpha mediated vasoconstriction
- Beta mediated cardiac stimulation
- Raised BP and tachycardia (may cause cardiomyopathy)
MI treatment for STEMI
o Primary percutaneous coronary intervention (PCI)
o Thrombolysis >20% of patient given thrombolysis do not achieve reperfusion so start with PCI
Significantly lower mortality with PCI compared to thrombolysis because of high rate of reperfusion
What % of all CHD deaths are attributable to smoking?
20
Left bundle branch block ECG pattern
Negative V1 - W
Positive V6 - M
WiLLiaM
Cardiogenic shock
- Extreme version of heart failure
- Large heart attack where they kill off so much heart that brain and kidneys profusion drops
- Results in death
Pathophysiology of right sided heart failure
Fall in cardiac output
Fall in renal perfusion
RAAS:
- Increased ADH and aldosterone
- Na+ and H2O retention
What is alveolar ventilation?
The amount of air sitting in the terminal airways where gas exchange is taking place.
(tidal volume - dead space) x respiratory rate.
3 unique properties of cardiac cells
- Automaticity
- Excitability
- Refractoriness
When are beta blockers contraindicated?
Asthma Cardiogenic shock Hypotension AV block Untreated pheochromocytoma side effects (neuroendocrine tumour of medulla of adrenal glands)
What 3 factors contribute to the level of transmission of TB?
1) Number of individuals susceptible to the disease.
2) Number of people exposed to the disease.
3) Duration of time a person with TB is undiagnosed and infectious for.
What is cardiac neurosis?
Da Costa’s Syndrome
- A set of symptoms similar to heart disease e.g. chest pain, dyspnoea, fatigue etc.
- No physical findings
- It’s considered as a form of anxiety disorder
Causes of haemoptysis
o Lung cancer – haemoptysis is a red flag for lung cancer; is most common cause of cancer deaths
o TB – kills 3,000,000 people every year (more than AIDS +tropical diseases (malaria) combined)
o Bronchiectasis – chronic mucoid sputum production, may have v. inflamed, fragile airways so may
o Pulmonary oedema – causes pink frothy sputum
o Pulmonary embolism – sudden blockage of a major artery in the lung, usually by a blood clot
o Pneumonia – causes rusty sputum, blood is mixed through the purulent sputum
What tests would you perform prior to treating TB?
- HIV.
- Hep B and C.
- Liver function test, ALT.
- Visual acuity when using ethambutol.
Which sites are involved in TB?
Pulmonary TB (85% of all cases)
Extra-pulmonary sites
Aortic dissection
- Sudden, tearing, knife-like pain
- Excruciating
- Radiate to back
- Abdominal pain (20-40% of cases)
- Often seen in elderly population with hypertension
- Seen in people with stressful jobs with hypertension at a young age
Which immune cells are involved in asthma?
o Antigen presenting cells
o T cells (CD4+)
o B cells – produce IgE which stick to mast cells + eosinophils
o Mast cells – activate eosinophils vis leukotriene B4
o Eosinophils – cause late reaction
High eosinophil count means allergy or parasites (worms)
MOA of Isoniazid
Disrupts synthesis of mycolic acid
TB drug (bacteriostatic)
QRS narrow and ragged atrial spikes rather than P waves
Atrial fibrillation
How is any tachycardia with hypotension/collapse treated?
Emergency electrical cardioversion with sedation if necessary
Treatment for collapsed patient with VT same for VF
Tissue changes in chronic hypertension
- Coronary atheroma
- Left ventricular hypertrophy
- Increased peripheral resistance
- Decreased flow in cardiac vessels and endothelial dysfunction
Define atheroma
A nodular accumulation of degenerative material in the tunica intima of the artery walls
How do ADH antagonists work?
E.g. tolvaptan
Bind to vasopressin receptors + block the action of ADH – this is a newer treatment
What is the primary site of infection known as in TB?
The Ghon focus.
How to diagnose aortic coarctation?
Compare femoral pulse to radial pulse.
Innate defences of the respiratory tract
- Alveolar macrophages - phagocytose and produce cytokines
- Dendritic cells - APC and cytokine production
- Cytokines important for inflammatory response
What type of diuretics are these?
o Bendroflumethiazide o Chlortalidone o Cyclopenthiazide o Metolaone o Indapamide
Thiazide and thiazide like diuretics
Inhibits sodium reabsorption in the distal convoluted tubule (DCT) by blocking Na+/Cl- co-transporter in the luminal membrane
Act on thiazide-sensitive Na+-Cl− symporter.
The combined presence of S3 and S4 is a quadruple gallop. (Aka hello-goodbye gallop)
When does it occur?
Heart failure
What is primary hypertension?
o 90-95% of all hypertension
o Unknown aetiology
o Probably environmental (high salt intake) or genetic
o There are 2 phases of abnormally as people develop hypertension – early + late
Other than the SAN, what other pacemaker sites are there?
Bundle of His - 40 bpm
Purkinje cells - 15 bpm
Cholestyramine
A positively charged drug which binds to negatively charged bile acids, inhibiting their absorption.
It is a bile acid sequestrant.
Cholestyramine may also be used to treat itching in people with too much bile acid caused by a certain type of liver/bile duct disease (partial biliary obstruction). This medication is known as a bile acid-binding resin. It works by removing bile acid from the body.
What is the definition of type 2 respiratory failure (hypercapnia)?
- Low PaO2 (less than 8kPa).
- High PaCO2 (greater that 6kPa).
Location of ectopic pacemakers can change its effect on SAN and its rhythm.
List 3 different types of pacemakers
o Atrial pacemaker: an ectopic pacemaker located in the atria - can cause atrial conduction to be faster
o Junctional pacemaker: ectopic pacemaker located near AVN and septum
o Ventricular pacemaker: located in ventricles
Other pacemakers can lie within the pulmonary vein and thoracic vein walls
How do baroreceptors determine BP?
From moment to moment the firing of the baroreceptors (they are the most important system in BP control)
V. sensitive to changes in BP – change firing rate within course of a single heartbeat (diastolic vs systolic pressure)
Examples of obstructive lung diseases
- COPD
- Asthma
- Bronchiectasis
- CF
What is purulent sputum?
Yellow/green
- Due to myeloperoxidase from granulocytes (neutrophils/eosinophils)
- Myeloperoxidase involved in free radical generation pathway to kill bacteria
List causes of HF
o Past heart attacks o CHD o Hypertension o Heart valve disease o Heart muscle disease or inflammation of the heart o Congenital heart defects o Lung conditions o Alcohol/drug abuse
List causes of HF
o Past heart attacks o CHD o High blood pressure o Heart valve disease o Heart muscle disease or inflammation of the heart o Congenital heart defects o Lung conditions o Alcohol/drug abuse
What is pleuritic pain?
o Injured/inflamed parietal pleura
o Sharp, stabbing, worse on inspiration
o Pneumonia, pulmonary embolism, pneumothorax
Colours of sputum
Mucoid (clear/creamy)
Purulent (yellow/green) - myeloperoxidase from granulocytes
Bloodstained – haemoptysis
JVP waveform summary
- A wave – atrial systole
- X descent – atrial relaxation
- C wave – tricuspid valve bulging into atria with ventricular contraction
- V wave – passive atrial filling
- Y descent – atrial empty into ventricle (tricuspid valve opens)
JVP waveform summary
- A wave– produced by atrial systole
- X – descent occurs when atrial contraction finishes
- C wave – caused by rapid increase in RV pressure before tricuspid valve closure
- V wave – develops as venous return fills the RA during ventricular systole
- Y descent – follows the V wave when the tricuspid valve opens (atrial empty into ventricle)
Adverse effects of thiazide diuretics?
o Hyponatraemia, hypokalaemia, hypomagnesemia
o Hyperuricemia, hypercalcaemia
What can cause acidaemia (low pH) in the blood?
- Resp: high CO2 (hypercapnia).
- Metabolic: low HCO3.
Stenosis vs sclerosis
Aortic stenosis is thickening and tightening of the valve that leads to the heart having to work harder and the possibility of not enough blood being delivered to the body.
Aortic sclerosis is thickening of the valve without any significant effect on the function of the valve itself.
Langerhans giant cells (TB)
What you see when looking at TB under microscope
Fused macrophages oriented around tuberculosis antigen with multiple nuclei in periphery
It represents the most successful type of host tissue response
When the population of activated lymphocytes reaches a certain size:
• Cutaneous delayed reactivity to tuberculin, or tissue hypersensitivity manifests
• The spread with which this occurs, varies, but generally will have development within 3-9 weeks after infection
Some macrophages may migrate to lymph nodes + carry bacterium spreads infection
Cause of type II respiratory failure
Alveolar hypoventilation
Cisplatin
Folate antagonist
- Interferes with thymidylate synthesis (essential for DNA synthesis)
- Forms a reactive complex that causes intrastrand cross-linking and denaturation of DNA
Indication:
- Testicular cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Lung cancer
- Head and neck cancer
MOA of cisplatin
- Forms a reactive complex that causes intrastrand cross-linking and denaturation of DNA
Atopy and asthma
- Dendritic cell presents to T cell which causes the production of IL-4 and IL-5
- Th2 signals to B cells to produce IgE
- Mast cells degranulate when antigen binds
- Cytokines activate T and B lymphocytes and attract eosinophils
What can cause normal ventilation but decreased perfusion?
- Right to left cardiac shunt (no oxygenation of blood).
- Pulmonary emboli (areas left un-perfused).
- V/Q mismatch.
Enough ventilation but not being perfused!
Course of heart failure
- First acute event e.g. MI
- Acute heart failure
- Treated and recovery OR chronic heart failure
- Chronic heart failure can only occur if acute is treated
Chemo-reflexes in HF
o Reflex initiated by the stimulation of chemoreceptors (e.g. carotid + aortic bodies) by changes in CO2, H+, O2 conc. in blood
o This is abnormally activated in people with HF and leads to increased ventilation
How do beta blockers improve myocardial function?
- Protect cardio myocytes
- Slowing the heart
- Increases diastolic coronary blood flow and reduce myocardial oxygen demands
- Anti-ischaemic
- Anti-arrhythmic
MOA and examples of sulphonylureas
- Gliclazide and tolbutamide
- Block ATP dependent K+ channels in membrane of pancreatic beta cells, causing depolarisation, calcium influx and insulin release
When are class III antiarrythmics used?
In Wolff-Parkinson-White syndrome
(Sotalol:) ventricular tachycardias and atrial fibrillation
(Ibutilide:) atrial flutter and atrial fibrillation
(Amiodarone): hemodynamically stable ventricular tachycardia[6]
How would you treat stable supraventricular tachycardia?
IV adenosine
Panacinar emphysema
Dilatation of terminal acinus
Nicorandil
Minoxidil
Diazoxide
Potassium channel opener
- Good vasodilator - hence it’s used for hypertension
- Fall in peripheral resistance: reflex increase in CO and fluid retention
- Use with diuretic and beta-blocker
MOA of minoxidil
- Opens K+ channels
- Good vasodilator - hence it’s used for hypertension
- Fall in peripheral resistance: reflex increase in CO and fluid retention
- Use with diuretic and beta-blocker
Examples of lower respiratory tract infections
- Bronchitis
- Pneumonia
- Lung abscesses
Would patients with obstructive lung disease have more difficulty breathing in or out?
Breathing out.
Organisms that cause atypical community acquired pneumonia?
- Mycoplasma pneumonia
- Chlamydophila pneumoniae
- Legionella pneumophila
ACS (acute coronary syndrome) is an umbrella term for what?
- Unstable angina
- ST elevation myocardial infarction (STEMI)
- Blocked (full) coronary artery - Non-ST elevation myocardial infarction (NSTEMI)
- Partially occluded coronary artery + raised troponin
- Acute chest discomfort that lasts more than 10 minutes
- Usually some myocardial necrosis, evident by rise in cardiac enzymes
Symptoms of simple bronchitis
- Illness begins with irritating, non-productive cough + discomfort behind the sternum
- Later the cough becomes productive with yellow or green sputum
Tissue changes in the brain in hypertension
Thromboembolic stroke - carotid atheroma, effects internal capsule
Haemorrhagic stroke - small vessels
Give 6 factors that make TB more common in low/middle income settings.
1) Stigma (don’t seek treatment)
2) Infrastructure problems
3) Conflict
4) HIV (immunosuppression)
5) Migration
6) Poverty (cramped conditions no healthcare)
Give 6 factors that make TB more common in low/middle income settings.
1) Stigma (don’t seek treatment).
2) Infrastructure problems.
3) Conflict.
4) HIV (immunosuppression).
5) Migration.
6) Poverty (cramped conditions no healthcare).
Hypoxia can be caused by?
o Impaired diffusion
o Hypoventilation
o Ventilation/perfusion (V/Q mismatch)
What happens to the lungs in restrictive lung disease?
- SA reduces.
- Reduced compliance.
- Thickened alveolar membrane.
- Relatively normal airways and airflow
Impaired diffusion.
Silicosis
- Rare
- Caused by inhalational of silicone dust
- Upper lobe nodules and lymph node calcification
- Looks like sarcoidosis - this also affects upper lobes and is associated with granuloma formation
- Predisposes to TB and lung cancer
Chest wall compliance is affected by which factors
Curvatures of spine (kyphosis, scoliosis) Rib fractures Ossification of costal cartilage Obesity Position (supine/prone) Pneumothorax, hydrothorax
Typical pneumonia causative agents
- Streptococcus pneumonae
- Haemophilus influenzae
- Moraxella catarrhalis
Aortic valve stenosis
- Aortic S2 often soft
- Slow rising carotid pulse
- Often left ventricular hypertrophy on ECG
What does QRS complex correspond to?
Ventricular depolarisation
o Reflects slow conduction from the AVN, down the bundle of His and up the purkinje fibres
Why must TB droplets be small?
- To remain suspended in the air for a longer period of time.
- To reach the terminal air passages (alveoli).
What is protodiastolic gallop aka ventricular gallop?
S3 added heart sound
- Heard at beginning of diastole after S2
- Low pitch
- Benign in youth, some trained athletes, sometime in pregnancy
- Occurs with cardiac problems: failing LV + dilated congestive HF
- Caused by oscillation of blood back + forth between the walls of the ventricles after a rush of blood from atria
Small cell carcinoma treatment
Limited stage (to one side of chest, above diaphragm)
• Radical chemotherapy + radiotherapy
• Median survival time 18 months, <20% achieve cure, 5 year survival 25%
Extensive
• Palliative chemotherapy + radiotherapy
• Median survival time 9 months
What does giant V waves (JVP waveform) indicate?
Tricuspid regurgitation
What is an acid-fast bacteria?
What type of test is used for this?
Bacteria which maintains its colour integrity when acid is applied to it.
- Ziehl-Neelsen stain.
Acid-fast organisms like Mycobacterium contain large amounts of lipid substances within their cell walls called mycolic acids.
These acids resist staining by ordinary methods such as a Gram stain.
It can also be used to stain a few other bacteria, such as Nocardia.
What is an acid-fast bacteria?
What type of test is used for this?
Maintains its colour integrity when acid is applied to it.
- Ziehl-Neelsen stain.
Acid-fast organisms like Mycobacterium contain large amounts of lipid substances within their cell walls called mycolic acids.
These acids resist staining by ordinary methods such as a Gram stain. It can also be used to stain a few other bacteria, such as Nocardia.
MOA of alpha blockers (treats HTN)
- Block peripheral alpha-1 receptors
- First dose hypotension
- Example: doxazosin
Pulmonary oedema
- Abrupt (mins)
- Breathlessness
- Difficulty talking
- Orthopnoea – lying down may kill them becuasefluid accumulates in alveolar spaces.
- Frightening – experience ‘angor animi’ fear of certain impending death
- Use of accessory breathing muscles
- Pink, frothy sputum – alveolar fluid with blood
- Sweating
- Cold, clammy
What is the main virulence factor of TB and the reason it isn’t phagocytosed?
It’s thick waxy mycolic acid capsule.
What is NEP? How is it involved in diuresis?
- Neutral endopeptidase
- Converts ANP and BNP to breakdown products
- Blocking it gives more ANP and BNP so more diuresis
E.g. Sacubitril
What are the 2 types of drug resistant TB and what are they resistant too?
1) MDR (multi drug resistant) TB: Rifampicin and isoniazid.
2) XDR (extensively drug resistant) TB: Rifampicin, isoniazid, fluroquinolone, other drugs.
Law of Laplace
Tension in wall of left ventricle = pressure within ventricle x volume within ventricle DIVIDED by wall thickness (this ratio is the other factor in setting the afterload).
- As ventricle dilates, wall tension increases
- As heart starts to contract, it has to exceed wall tension before it contracts
- As afterload increases, CO decreases
MI treatment for NSTEMI
o Antiplatelets: aspirin and clopidogrel or ticagrelor or prasugrel
o LMWH
o Statin: high dose to reduce cholesterol and stabilise plaque
o Anti-ischaemic (beta blocker, nitrates) – beta blocker therapy decreases heart rate + amount of stress of plaque
MI treatment for NSTEMI
o Anti-platelets – aspiring and one of: clopidogrel, ticagrelor, prasugrel
o LMWH
o Statin – high dose to reduce cholesterol + stabilise plaque
o Anti-ischaemic (beta blocker, nitrates) – beta blocker therapy decreases heart rate + amount of stress of plaque
MoA of calcium channel blockers
Slows the movement of calcium into the heart and blood vessel walls
Reduces heart rate, LV contraction, blood pressure and reduced myocardial O2 demand
Examples of angiotensin II receptor blockers (ARBs) and their suffix
- Losartan
- Valsartan
- Candesartan
-sartan
Used to lower blood pressure
Large volume of sputum expected in?
Bronchiectasis and bronchioloalveolar carcinoma
Nicotinic acid
Vitamin B3
- Increases HDL
- Reduces release of VLDL from the liver
Indication:
- Lipid disorders
- Atherosclerotic cardiovascular disease
MOA of nicotinic acid
Vitamin B3
- Increases HDL + reduces release of VLDL from the liver
lipid disorders and atherosclerotic cardiovascular disease
What are the 2 types of presentation of TB by site?
1) Pulmonary TB.
2) Extra-pulmonary TB.
Neurohormonal model for progression of heart failure
- ADH - drink more and retain more fluid
- Natriuretic peptide - ANP, BNP - excrete more Na+, and hence water
- Aldosterone (Na+ and water retention, K+ and Mg2+ loss)
- Endothelin - vasoconstrictor
- Neuropeptide Y - adrenaline
- VIP - parasympathetic
Risk factors for atheroma
Modifiable:
- Smoking
- Hypertension
- Obesity
- Diabetes mellitus
- Hyperlipidaemia
- Lack of physical activity
Non-modifiable:
- Family history
- Gender
- Age
- Ethnicity
Modifiable risk factors for atheroma
- Smoking
- Hypertension
- Obesity
- Diabetes mellitus
What is “gas trapping” in obstructive lung disease?
When part of the lung cannot empty.
- Keep filling and filling, hyper-expansion.
- Ventilation-perfusion mismatching occurs.
- Results in hyperventilation.
Large cell carcinoma
- Poorly differentiated
- Poor prognosis
What is extra-pulmonary TB?
What type of patient is it found in?
- TB that is outside the lung via haematogenous or lymphatic spread.
- More common in children and old people, immunosuppressed
- TB of spine can cause back pain
- TB of kidneys can cause blood in the urine
- Miliary TB
Treatment of stable ventricular tachycardia
Check and correct hypokalaemia and hypomagnesaemia
Intravenous amiodarone (preferably via a central line)
Electrical cardioversion if goes on for 10-15 minutes
Class Ia example and effect on AP
Disopyramide
- Block Na+ channels
- Prolongs AP
Where is the infarction in an inferior MI?
Right coronary artery
Which TB drug may cause vision problems?
Ethambutol.
What are type 2 cardiac cells?
Myocytes
They only fire when simulated (depolarised)
How does digoxin alter the frank-starling curve?
Up and to the left
- It is a positive inotrope
Physiological defences of the respiratory tract
- Cough
- Epiglottic reflex
- Nasopharynx clears organism for swallowing
- Epithelial cells produce airway surface liquid
Ventricular fibrillation
o Chaotic depolarisation of the ventricles, resulting in an arrested cardiac pump function and immediate death
o VF can only be treated by immediate defibrillation
o Rate is O – no QRS complexes
o Rates are so rapid that the ventricles twitch in a disorganised and chaotic manner
o ECG shows no identifiable waves, no pattern of impulses – hence no CO
Why do patients with heart failure under diuresis become hypokalemic?
- Aldosterone causes K+ excretion
- Diuretic use leads to more Na+ in DCT which leads to resulting in greater K+ excretion
Atypical pneumonia causative agents
- Legionella pneumophila
- Mycoplasma pneumoniae
- Chlamydiophila pneumoniae
Special points about digoxin
- Big loading dose
- Narrow therapeutic window
- Excreted unchanged by the kidneys - don’t use if kidney diseased
Emphysema
- Abnormal enlargement of airspace, distal to terminal bronchioles
- Destruction of alveoli walls
Which drugs should be avoided in HF?
o Calcium antagonists – e.g. amlodipine
o Positive inotropes – e.g. digoxin, levosimendan
o Antiarrhythmics – stop in people with HF except amiodarone which is ok
What are the 2 mineralocorticoid (aldosterone) antagonists?
Spironolactone
Eplerenone - new + expensive
What is renal artery stenosis?
What is its effect on blood pressure?
- Fibromuscular hyperplasia
- In young women with hypertension which is difficult to control
- Kidneys don’t get enough blood so they think BP is low
- Decreased pressure in the afferent arteriole
- Increase in renin release = increase in angII and aldosterone
Where do loop diuretics work?
Block Na+/K+/2Cl- cotransporter in the thick ascending loop of Henle
• Work from lumen of the tubule – need some glomerular function to filter the drug into the tubule
Ventricular tachycardia
o Is a sequence of 3(+) ventricular beats
o Frequency is usually 110-250bpm
o Often origin around old scar tissue in the heart – e.g. post-MI
o CO is strongly reduced during VT, resulting in hypotension and loss of consciousness
o Can deteriorate into ventricular fibrillation
o Due to rapid discharge of ectopic beats from multiple sites in vernicles
o Patient has palpations and need defibrillation
What is ventilation/perfusion mismatch?
- Part of the lung is not ventilated but IS being perfused.
- Part of the lung is being ventilated but IS NOT being perfused.
- Hypoxia.
- Results in shunt of deoxygenated blood from R -> L heart.
Treatment of asthma
o Inhaled corticosteroids and bronchodilators are fine for most people
o Some people make too much IgE (highly atopic) – some drugs can mop up excess IgE
o Monoclonal antibodies
o IL-5 blocker e.g. Mepoluzimab – work for people who have a high eosinophil count in airway + lungs
o If the patient is receiving treatment and not getting better may be due to:
Poor compliance – not taking medication
Poor technique – not using proper inhaler technique
Misdiagnosis
What are the causes of loss of consciousness?
Cardiac
o Sudden onset, no aura, no jerks/incontinence, injury common, very pale, immediate recovery
Neurological
o Prodrome/aura, convulsive movements, incontinence, self-harm (tongue), post-ictal confusion
Vasodepressor syncope
o After prolonged standing response to stress, gradual developing faintness, greying out of vision
Carotid sinus hypersensitivity
o Rubbing neck causes syncope
What are some of the side effects of Rifampicin?
- Orange secretions (pee, tears).
- Nausea.
- Abdo pain.
- Hepatitis.
Pink puffers (emphysema)
• Thin because of work of breathing
• Pursed lips breathing + leaning forwards
o To give ‘auto ‘PEEP’ expiratory resistance to prevent airway collapse
o Prominent use of accessory breathing muscles
• Go into ventilatory failure later
• May be very breathless but have normal blood gases up to end of disease
Mutations in non-small cell carcinoma
EGFR, KRAD, CD44, P16
What is the anterolateral papillary muscles blood supply?
LAD and Left circumflex
Name 2 classes of potassium sparing diuretics
Mineralocorticoid receptor antagonists (used to be called aldosterone antagonists because they block effects of aldosterone)
Epithelial sodium channel blockers (ENaC) - block K/Na pump
Frank-starling law
o The more the heart fills with blood, the greater the force of contraction
Increasing pre-load leads to increases ventricular work
o In people with HF, the curve falls downwards and to the right until patient needs an extremely high preload just to have heart function at rest
MoA of digoxin
Inhibits Na+K+ATPase membrane pump, resulting in increased intracellular Na+ and decreased intracellular K+
Sodium calcium exchanger tries to extrude the sodium by pumping in more calcium – positive inotropic effect
Strengthens ventricular contractions so that the heart is able to pump more blood with each beat
Chronic bronchitis involves?
o Mucus glands hypertrophy
o Smooth muscle hypertrophy
o Goblet cell hyperplasia
o Inflammatory cell infiltrate – lymphocytes + neutrophils (not eosinophils)
o Excess mucus – because goblet cells + mucus glands increase in number
Atrial flutter with 2:1 AV conduction
- 2 P waves for every 1 QRS
- Sawtooth appearance of P wave!!
- Narrow complex tachycardia
- Atrial rate 280bpm, ventricular 140bpm
What are some of the problems with the Mantoux test? (TST).
False positives:
- Low specificity
- Previous BCG or incorrect reading
False negatives:
- Low sensitivity
- Immunosuppression could impact
Chronic heart failure symptoms
o Exertional breathlessness, relieved by rest – may also be related ischaemia
o Orthopnoea
o Swollen abdomen – ascites caused by severe LV dysfunction, R heart failure
o Nocturnal cough
o Episodes of PND
o Ankle oedema
Why is pyridoxine indicated in TB?
- To prevent peripheral neuropathy
- Side effect of isoniazid
- It is vitamin B6
Pulmonary embolism
- Over infarcted area
- Pleuritic pain
- Associated with SOB
- Tachycardia/AF
- Tachypnoea
Which conditions can trigger acute heart failure?
o Infection o Kidney disease/poor kidney function o Anaemia o Abnormal heart rhythm o Overactive thyroid gland
Asthma medications
o Short acting beta agonists (SABA) (salbutamol_
o Long-acting beta agonists (LABA) (formoterol + salmeterol)
o Inhaled corticosteroids
o Leukotriene receptor antagonists
o Combination inhalers - Mixture of LABA + corticosteroid
What does the PR segment represent?
PR segment – conduction from the AVN, down the bundle of his and up the purkinje fibres
What type of resp failure is seen in acute asthma (normal)?
Type 1.
- Hyperventilation with hypoxia.
- They have ventilatory capacity to match the demand.
How does renal artery stenosis cause secondary hypertension?
Narrowing of arteries that carry blood to kidneys leads to decreased pressure in afferent arteriole
Kidney thinks BP is low so it releases renin
Renin increases BP by increasing angiotensin II and aldosterone
Angiotensin II promotes cardiac and vascular hypertrophy
Increased blood volume, cardiac output, vascular resistance all leads to hypertension
Interleukins
o IL4 – stimulates production of IgE
o IL5 – Activates locally recruited eosinophils
o IL13 – stimulates mucus secretion from bronchial submucosal glands + also promote IgE production by B cells
Mycobacterium species
M. tuberculosis – main cause of TB
o Rod shaped bacterium
o Mycolic acid present in cell wall making it acid-fast
o Aerobic + non-motile
o Multiplies slowly and can remain dormant for decades
M. afriticanum – important opportunistic infection in HIV; commonly found in West Africa
M. bovis – Widespread; causes bovine TB in cattle, cats, dogs, badgers, deer, possums…
o Nonvirulent vaccine strain of M bovis used in the BCG vaccine
M. canatii – emerging disease in East Africa
M. microti – mostly infects voles, human infections are rate (more common in immunocompromised patients
Extra-pulmonary TB
Metastatic spread to any organs: abdomen, bone, brain, retina, muscles, lymph nodes
~30% of TB cases are exclusively extra pulmonary
o TB of spine may cause back pain + kyphosis
o TB of kidney may cause blood in the urine
o Extra-pulmonary TB should be considered in the differential diagnosis of ill persons who have systemic symptoms + who are at high risk for TB
Why is the SAN the pacemaker?
Fastest intrinsic firing - 105 bpm
Pioglitazone
Reduce peripheral insulin resistance, leading to reduction in plasma glucose
Drug for DM II
What is the Mantoux tuberculin skin test? (TST).
- Intadermal injection of tuberculin.
- If T cells have been previously sensitised, inflammatory response at the site within 48-72 hours.
Bundle branch block
- Block either in right or left bundles that branch from the Bundle of His
- Wide double peak QRS
- Inverted T wave
What are Janeway lesions?
- Non-painful, black spots on thenar + hypothenar eminences of hands + feet
- Septic emboli within dermis of skin
Left sided heart failure
L side is responsible for receiving oxygen rich blood from the lungs + pumping it forward to the systemic circulation
Failure of the L side of the heart causes blood to back up into the lungs, causing respiratory symptoms as well as fatigue due to insufficient supply of oxygenated blood
There are 2 types of left-sided heart failure:
- Systolic failure: L chamber lacks the force to push enough blood into the circulation
- Diastolic failure: L chamber fails to relax normally because the muscle has become stuffer + filling is impaired
When are calcium channel blockers (class IV) contraindicated?
- Pregnancy
- Cardiogenic shock
- Severe bradycardia
- Moderate to severe heart failure
Alteplase
Tenecteplase
Streptokinase
Thrombolytics
Enzymatically activates plasminogen to give plasmin which digests fibrin and fibrinogen, lysing the clot.
Indication:
- Thrombolysis in STEMI
- Massive pulmonary embolism
- Acute ischaemic stroke
Contraindications:
- Recent surgery (10 days)
- GI bleeding (3 months)
- Active bleeding or haemorrhagic disorder
- Previous cerebrovascular accident
- Pregnancy
- Aortic dissection
- Acute pericarditis
Grade I to III cancer cells.
Grade I: Cancer cells that resemble normal cells and aren’t growing rapidly
Grade II: Cancer cells that don’t look like normal cells and are growing faster than normal cells
Grade III: Cancer cells that look abnormal and may grow or spread more aggressively
What is Fick’s Law of Diffusion? How does it apply to the lungs?
The rate of transfer of a gas through a tissue is proportional to the tissue area, and inversely proportional to thickness.
- Large and thin = lots of transfer.
- Large SA in the lungs (50-100sq. metres) and extremely thin alveoli.
Commensals of the respiratory tract
- Streptococcus pneumoniae
- Haemophilus influenzae
- Streptococcus viridian’s group
Ventricular flutter
o Mostly caused by re-entry with a frequency of 300bpm
o The ventricles depolarise in a circular pattern, which prevents good function
o Most often this results in a minimal CO and subsequence ischaemia
o Often deteriorates into VF
Omapatrilat
A combined ACEi and NEP inhibitor which increases diuresis
Omapatrilat is an experimental antihypertensive agent that was never marketed. It inhibits both neprilysin (NEP) and angiotensin-converting enzyme.
NEP inhibition results in elevated natriuretic peptide levels, promoting natriuresis, diuresis, vasodilation.
How can hypokalaemia be prevented in patients with HF under diuresis?
Give K+ sparing diuretic e.g. spironolactone or amiloride
What is presystolic gallop (aka atrial gallop)?
S4 added heart sound
Heard just after atrial contraction + end of diastole before S1
Best heart at the cardiac apex
Produced by the sound of blood being forced into a stiff or hypertrophic ventricle
- Aortic stenosis
- Hypertension
- Hypertrophic cardiomyopathy
Describe changes in the heart due to hypertension
o Coronary atheroma – increases risk of MI
o Atheroma in L side circulation doesn’t affect pulmonary artery – pulmonary atheroma only seen in pulmonary hypertension, this shows that hypertension is vital in pathogenesis of atheroma
o Concentric LV hypertrophy (fairly early on in hypertension) - myocyte number remains constant but individual cells hypertrophy
There also may be fibroblast proliferation and LV fibrosis which would lead to impaired LV relaxation
What is centrilobular emphysema?
- Primarily the upper lobes, occurs with loss of the respiratory bronchioles in the proximal portion of the acinus, with sparing of distal alveoli
- Centrilobular emphysema is one of the first changes in smokers
TB transmission
Person-to-person
Through the air by person with active TB (droplet infection)
Ingestion of M. bovis
Found in unpasteurised milk
Inoculation
Transplacental route (rare)
Causes of tachycardia from decreased PNS activity
- 1st seconds of exercise
- Falling arterial pressure (blood loss etc. until syncope)
- Heart failure
- Atropine (muscarinic receptor blockade
Development of atherosclerosis
- Development of fatty streak which forms an intermediate atherosclerotic region
- Fibrous cap can develop over it - the lipid core can become necrotic
- Thinning and rupture of fibrous plaque
- Necrotic core ruptures which exposes lipid below to circulating blood resulting in thrombus formation
If in diagnostic doubt whether SVT or VT inject what?
Incremental boluses (6-18mg) of adenosine
Adenosine should slow rate markedly if it is SVT
What is the difference between obstruction and restriction?
- Obstruction: narrowing of the airways, increased resistance to air flow (like breathing through a straw).
- Restriction: increased work to expand the chest or reduced lung compliance/increased stiffness.
How is bradycardia due to bundle branch block treated?
Pacemaker – mostly monitors heart;
If HR too slow, it sends electrical impulses to prevent bradycardia
Aortic stenosis
- Obstruction to normal flow through the valve
- Usually a result of calcification or genetically bicuspid aorta
- Stenosed valve increases after load of left ventricle = increasing the force required to eject blood into aorta
- Causes left ventricular hypertrophy
- Reduction in CO can cause breathlessness
- Inadequate perfusion to brain can cause syncope
- Reduced myocardial perfusion can cause angina
How is sinus tachycardia treated?
Investigate and remove cause: • Hyperthyroidism • Anxiety • Heart failure • Hypovolaemia • Septicaemia
Risk factors for pneumonia
- Alteration in host consciousness
- Smoking
- Alcohol
- Sepsis
- Immunosuppression
- Iatrogenic manipulation
- Drugs
- Congenital
What are Osler’s nodes?
Tender red nodules on finger pulps/thenar eminence (infective endocarditis)
- Painful lesions on finger pulps
- Deposition of immune complexes in fingers
Viral, fungal, mycobacterial + parasitic causes of pneumonia
- Viral - Influenza A, B + respiratory syncytial virus (RSV)
- Fungal - Aspergillus
- Mycobacterium - mycobacterium tuberculosis
- Parasitic - pneumocystitis jirvecci
Acute airway changes in asthma
SMOPS
- Smooth muscle contraction
- Mucus hypersecretion
- Oedema
- Plasma leakage
- Sensory nerve
Anatomical defences of the respiratory tract
- Nasal hair
- Nasal turbintes
- Cilia
- Sneezing
- Saliva
Triggers of asthma
- Smoke
- Faeces of dust mites
- Mould spores
- Foods
- Industrial chemicals
- Pollen
Non-infective causes of consolidation
- Fluid - inflammatory/heart failure
- Cells - cancer
- Protein - alveolar proteinois
- Blood - pulmonary haemorrhage
Pathophysiology of left bundle branch block
LBBB: aortic stenosis, dilated cardiomyopathy, MI, CAD
What does high CO2 indicate? What sign is characteristic of this?
Ventilatory failure.
- Flapping tremor
How is TB spread?
By inhalation of droplet nuclei.
- Infectious particles are aerosolised by coughing, sneezing or talking.
If D-dimer test (inflammation and clot measure) negative after 6 hours. What is unlikely?
Aortic dissection + pulmonary embolism unlikely
Occupational causes of COPD
o Coal mining o Agriculture o Construction o Dock workers o Brick making
What type of resp failure is seen in late severe asthma?
Type 2.
- Respiratory muscles get tired and can’t expel all the CO2.
- Worrying sign.
What species is the definitive host of TB?
Humans
How does damage to papillary muscle present?
Acute onset of hypertension + pulmonary oedema with a mid-, late- or holosystolic murmur
The intensity of the murmur does not necessarily correlate with severity
Atrial fibrillation
o Commonest sustained arrhythmia (1% of adults)
o Prevalence increases with age
o Increases risk of stroke by x4
o Can cause tachycardiomyopathy if untreated
o ~1/2 patients with AF also have HF
o ~1/3 of patients with HF have AF
What is the QRS interval and what does it represent?
- Beginning of Q wave to end of S wave
- Reflect slow conduction through ventricular myocardium
- Onset and end of depolarization
- Less than 3 small squares
How would you treat stable ventricular tachycardia?
- IV amiodarone
- Electrical cardioversion
Non-pharmacological treatment of pulmonary oedema?
Ventilatory support
CPAP – continuous positive airways pressure
IPPV – intermittent positive pressure ventilation
Inotropic support
Try to avoid as may cause worse prognosis – only used when shock/incipient shock
Usually dobutamine
Typical pathogens that cause pneumonia
Streptococcus pneumoniae (pneumococcus):
o Typically colonises the respiratory tract, sinuses, and nasal cavity, wo/ causing harm
o However, in susceptible individuals with weaker immune systems, the bacterium may become pathogenic and spread to other locations to cause disease
o It Is the main cause of community acquired pneumonia + meningitis in children and the elderly
Haemophilus influenzae:
o Most strains of H. influenzae are opportunistic pathogens
Moraxella catarrhalis:
o Causes bronchitis + pneumonia at any age with underlying chronic lung disease
o Occasionally a cause of bacteraemia + meningitis, especially in immunocompromised persons
Rupture of interventricular septum
- Where does it develop?
- What does it cause?
- Rupture develops at margin of necrotic and non-necrotic myocardium
- Left to right shunting
- Loud, harsh murmur
What is asbestosis?
- Chronic inflammatory and fibrotic medical condition caused by inhalation of asbestos
- Restrictive - lungs small and thick
- Worse at bottom of lungs than at top
Retinal complications of hypertension
- Hypertensive retinopathy
- Papilloedema
List the main drugs used in the treatment of chronic HF
ACE inhibitors
Angiotensin receptor blockers (ARBs)
Beta-blockers
Mineralocorticoid receptor antagonist (MRAs)
What are the 2 types of cells in the heart?
Type 1: SAN, AVN, conducting tissue - these are automatic/spontaneous
Type 2: atria, ventricles, depolarise upon stimulation
What are the 2 types of cells in the heart?
Type 1 - SAN, AVN, conducting tissue - these are automatic/spontaneous
Type 2 - atria, ventricles - depolarise upon stimulation
What are the 4 steps of TB infection?
1) TB bacilli reach the alveoli.
2) The bacilli multiply and and phagocytosed by alveolar macrophages.
3) Alveolar macrophages attempt to destroy the TB but made difficult by thick waxy mycolic acid capsule.
4) Bacilli replicate inside the macrophage and kill it OR be presented to the immune system.
Causes of acute pulmonary oedema?
- Acute ischaemia
- Arrhythmia – AF, flutter, VT
- Mechanical disaster – e.g. rupture of papillary muscle to mitral valve
- Non-compliance with medication
- PE
- Environment – stress, drugs
What can affect the outcome of a diffusion test?
Thickness of the alveolar membrane.
Describes the forces acting on fluid balance across a capillary in a tissue?
Hydrostatic pressure: pressure in capillary that is forcing fluid out
Colloid osmotic pressure: osmotic pressure provided by albumin + other proteins (pull the fluid back in again)
Other influences:
Lymphatic drainage – drains any excess fluid outside of tissues
Alveolar-capillary membrane – provides some resistance against the movement of fluid
Alpha blockers
o Block peripheral alpha 1 receptors which normally mediate sympathetic vasoconstriction
o Side effect – first dose hypotension (vasodilation)
o Doxazosin is the only one commercially available for hypertension treatment
What can cause hypoxia?
- Impaired diffusion.
- Hypoventilation.
- V/Q mismatch.
Can tetanus occur in cardiac muscle?
No
What is the risk with AF?
Increases risk of stroke by 4x
Incomplete/subacute rupture of LV free wall
Can occur when organised thrombus + the pericardium seals the perforation
This may progress to either:
Frank rupture
Formation of pseudo-aneurysm (false aneurysm) – walled off by pericardial tissue + communicating with the LV through the perfusion
• True aneurysm – lined with muscle itself
Formation of a left ventricular diverticulum
Apart from lab work, what other techniques are used to identify TB?
CXR.
What are the most common sites of EP.TB?
- Pleura (pleural TB).
- Brain (Tuberculoma).
- Spine (Pott’s disease).
- Lymph node (Adenitis).
- CSF (TB meningitis).
- Retina (retinal TB).
What are the risk factors for DR TB (drug resistant TB)?
- People with a history of TB drug use.
- Poor compliance.
- Malabsorption of drugs.
- Foreign born people from areas of DR TB.
- People receiving inadequate treatment regimes.
What is malar flush?
A plum-red discolouration of the high cheeks classically associated with mitral stenosis due to the resulting CO2 retention and its vasodilatory effects.
• Can be associated with SLE or polycythemia rubra vera
MOA of amiodarone
- Class III and some class I, II, IV activity
- Prolongs AP
- Used in SVT and VT
- 6 days onset
- Long elimination
What can cause alkalaemia (high pH) in the blood?
- Resp: low CO2.
- Metabolic: high HCO3.
What would a wide QRS interval suggest?
Intra/interventricular conduction delay
What is carbocysteine?
A mucolytic - agent which dissolves thick mucus, used to help relieve breathing difficulties
What are the 3 outcomes of a macrophage being infected by TB?
1) Clearance of the infection: TB is presented to the immune system and destroyed.
2) Latent infection: Bacteria in the macrophage become dormant until patient is immunosuppressed.
3) Primary TB: Macrophage is killed. Progression to TB disease.
What is bronchoalveolar carcinoma
o Glandular cells produce lots of mucus (bronchorrhoea)
What cells form a granuloma?
- Macrophages.
- Giant cells (langhans).
- T lymphocytes.
- B lymphocytes.
- Fibroblasts.
What is bronchiectasis?
o Airways abnormally dilated
o Secretions pool + aren’t properly cleared by the mucociliary escalator
o Gets infected + colonise with bacterial
o Patient constantly coughs up purulent sputum
How is stable supraventricular tachycardia (SVT) managed?
Many revert spontaneously
Vagotonic manoeuvres – stimulates increased vagal tone e.g. get patient to blow out against pressure, put child head under cold water, press on carotid sinus
Rapid IV adenosine bolus
Avoid digoxin and verapamil unless you are expert
What is Poiseuille’s law?
Flow = radius4
Baroreceptors alter sympathetic outflow to all the smooth muscle cells in the vasculature of the body (arterioles)
Flow down a tube – proportional to 4th power of radius so only have to change radius a tiny bit to affect BP
Acute bronchitis
- Acute infection of trachea and bronchi
- Usually viral
- Influenza
- Adenovirus
- Rhinovirus
- No change on CXR
Some patients (especially with mitral stenosis) can develop compensatory mechanisms such as?
- Thickened alveolar capillary membrane
* Increased lymphatic drainage
What is theophylline?
Example of methylxanthine which acts as bronchodilator (used in COPD and asthma)
How is perfusion measured?
Imaging type tests.
- CT pulmonary angiogram to check for PE and malformations of vasculature.
- Echocardiogram to check for shunts.
Sinus arrest
Failure of sinus node discharge resulting in absence of atrial depolarization
- Periods of ventricular asystole
Atrial flutter
Atria contract at 300 bpm
What groups other than immigrants is TB present in in the UK?
- Homeless
- IV drug users
- Alcoholics
- Prison inmates
- Urban poor
When are steroids indicated in TB?
- TB meningitis.
- Pericardial TB.
Risk factors for HAP
- Over 70
- Severe underlying disease
- Surgical procedures
What is pulse oximetry?
- A machine placed on the finger.
- Shines a red light and measures light absorption, gives estimation of O2 sats.
- Oxygenated blood is red, deoxygentaed dark red/purple colour.
How do long acting muscarinic antagonists (LAMA) work in asthma treatment?
E.g. Tiotropium – causes a 20% improvement in FEV1
o Response is the same a year later – shows deterioration of patient
o Delays lung function deterioration by around 4 years, reduced mortality, but doesn’t make it stable
o In people under 50 with milder disease there is a disease modification so improved outcomes
Type B personality
- Work steadily
- Enjoy achievement
- Don’t mind defeat
Syncope is a symptom, the defining clinical characteristics of which are?
- Transient
- Self-limited loss of consciousness
- Leads to falling
- Onset is relatively rapid
- Recovery is spontaneous, complete, and usually prompt
How many people in the world have TB?
1/3rd of the worlds population infected with TB
Differential diagnosis for ankle oedema
- Nephrotic syndrome
- Chronic venous insufficiency e.g. previous DVT or varicose veins
- Drugs - dihydropyridines
- Hypoalbuminaema
- Fat
How do we confirm a diagnosis of angina?
Stress testing
What does high compliance indicate?
Pliable lung (low elastic recoil)
E.g. emphysema/COPD
MOA of pyrazinamide
Is converted to pyrazinoic acid which disrupts membrane and inhibits membrane transport in mycobacterium tuberculosis
What type of lung disease is there with an FEV1/FVC ratio of less than 70%
Obstructive
Atrial flutter treatment
Anticoagulants – due to stroke risk
External electrical cardioversion
Electrophysiological ablation
An anti-leukotriene is a drug which functions as either?
o Leukotriene-related enzyme inhibitor
o Leukotriene receptor antagonist
They oppose leukotrienes (product released by mast cells that cause bronchoconstriction, inflammation, microvascular permeability, mucus secretion in asthma, and COPD)
Lobar pneumonia
- Involve a whole/large continuous area of lobe
- Bacterial – Streptococcus pneumoniae, Klebsiella spp.
- Most lobar pneumonia’s are pneumococcal – but most pneumococcal pneumonia are not lobar
What are ventilatory capacity and ventilatory demand? How are they balanced in health?
- Ventilatory capacity: maximum amount of ventilation we can maintain before respiratory muscle fatigue.
- Ventilatory demand: amount on ventilation required to maintain a normal CO2 level.
In health, capacity far outweighs demand.
What does the ST segment correspond to?
ST segment – time when the ventricles are depolarised during the plateau phase of action potential
Myocardial wall rupture
o When there is thin damaged myocardium next to healthy, actively contracting myocardium, this is a hinge point where the damage myocardium can rupture
o Sudden deterioration
o Leads to arterial bleeding into the pericardium + rapid death – not survivable
What is the ergo-reflex?
o Reflex generation by exercising muscles – with exercise, muscle being exercised sends signals to the brain to breath more
o The ergo-reflex increases as exercise capacity falls + increases as ventilatory response to exercise increases
- Normally ventilation increases with exercise, decreases after
- In heart failure, ergoreflex is activated meaning heavy breathing long after exercise
First line drugs for TB
RIPE (first line drugs)
• Rifampin: inhibits RNA synthesis - Often turns urine bright orange if taken properly
• Isoniazid: inhibits cell wall synthesis
• Ethambutol: inhibits cell wall synthesis
• Pyrazinamide: exact target unclear, disrupts plasma membrane + energy metabolism
Rifampicin + isoniazid are given for 6 months with pyrazinamide + ethambutol for those first 2 months
What is breathlesness?
- Defined as an unpleasant sensation of feeling increased demand for breathing
- It is a symptom not a sign – do not say ‘the patient appears breathless’
- Poor correlation with: respiratory rate (tachypnea), hypoxaemia, hypercapnia
What are propanolol and timolol examples of?
Non-selective (B1 and B2) beta blockers
Side effects of spironolactone
- Gynaecomastia
- Hyperkalaemia
Which asbestos fibres are the most damaging?
Straight fibres - blue/brown
Ethambutol
Inhibits the formation of the cell wall in dividing TB bacilli
Acute community acquired pneumonia
- Older patients and elderly
- Peak mid-winter/spring
Where is the infarction in a lateral acute MI?
Left circumflex artery
Cases of uneven radial pulses
Aortic dissection
Coagulation of aorta
Atheroscleoris
What is torsades de pointes exacerbated by?
Low potassium and magnesium
Cardiac markers
- Troponin I
- Troponin T
- Myoglobin
- CK-MB
What is minute ventilation? How is it calculated?
The amount of breath taken in and out in a minute.
- Tidal volume x respiratory rate.
Causes of COPD
Tobacco – main cause, need ~15 pack years to develop emphysema
Recreational drug use
Passive smoking
Chronic asthma
Biofuels
Occupational – coal mining, cotton, wielding
Familial – alpha-1 antitrypsin deficiency
What type of respiratory failure would you see in restrictive lung disease patients?
How does this differ from interstitial lung disease (i.e. IPF)?
Type 2: chest wall deformities etc. cause ventilatory failure earlier than IDL.
ILD is type 1, CO2 rise is a sign of morbidity.
Causes of bradycardia
- Sick sinus syndrome - damage to SAN (tachy-brady syndrome)
- AV block
- Drugs
- Non-cardiac - hypothyroidism etc.
Aortic valvue sclerosis
- Normal or loud S2
- Carotid pulse often brisk or normal
- Usually no LV hypertrophy unless severely hypertensive
- Due to wear + tear to valve overtime
What is elevated JVP due to?
o Heart failure o Constrictive pericarditis o Cardiac tamponade o Renal disease o SVC obstruction
Where is a rupture most common in papillary muscles?
Posteromedial as there is only 1 blood supply from posterior descending artery
Describe changes in the aorta due to hypertension
o Atheroma
o Aneurysm – may rupture/dissect
o Aortic dissection – quite common, cystic medial necrosis, aortic wall tears (intima is torn off rest of the aorta by the pressure)
NSTEMI ECG features
- Frequently normal
- May be minor T wave changes/inversion
- May be significant ST depression
Torsades de pointes
- Commonly seen in patients with pre-existing bradycardia, especially if given type I anti-arrhythmias
- Patient conscious but ECG looks like VF
- Long QT
What would the spirometry of a patient with restrictive lung disease show?
- Reduced FEV1.
- Reduced FVC.
- No change or raised FEV1/FVC.
MOA of thiazides
- Block Na+/Cl- co-transport in DCT
- Loss of Na+, K+ and Mg2+
Early and late phases of hypertension pathophysiology.
Early phase:
- Blood volume and CO increase
- Due to Na+ retention
Late phase:
- Blood volume and CO normal
- Increase in systemic vascular resistance
What happens to the granuloma in primary TB?
It is liquefied and the macrophage is killed, TB bacilli released.
- TB may be spread by connection to the bronchi.
- May be other spread by blood or lymphatic system.
What are the 2 factors involved in homoeostasis of ventilation?
- Ventilatory capacity
- Ventilatory demand
Describe kidney changes due to hypertension
o Small vessel (hypertensive) disease causes glomerular damage
o Gradual parenchymal loss accelerates decline in function
o Large vessel atheromatous disease
MOA of dobutamine
- B1-agonist catecholamine
- Can cause arrythmia through toxicity
Which cells in the heart conduct fastest?
His and purkinje cells conduct the fastest (2-5m/s)
How is anasarca (extreme generalized oedema) treated?
By inducing diuresis
- Bed rest with legs elevated
- Catheter below level of bladder
- LMWH to prevent DVT
- Fluid restriction
- Diuretics
Nature of simple bronchitis
Pathophysiology:
- Cells of bronchial tissue irritated
- Mucous membrane becomes hyperaemic and oedematous
- Diminishes bronchial mucociliary function
- Air passages become clogged with debris and irritation increases
- Copious secretion of mucous develops causing characteristic cough
- Infection with Strep pneumoniae or H. Influenzae
Symptoms:
- Irritating, non-productive cough
- Retrosternal discomfort
- Productive cough later with yellow or green sputum
Consequnces of atheroma
- Ventricular fibrillation + sudden death
- ½ of all patients have MI, die before getting to hospital
- Cardiovascular disease is second only to cancer as cause of death for men + women
MOA of GTN
Nitroglycerin is converted to NO which stimulates cGMP synthesis. Ca2+ ions released resulting in SM relaxation and vasodilation.
How do the kidneys respond to heart failure?
- Less perfusion to kidneys
- Activates RAAS
- Retains Na+ and H2O
- Increases blood volume
- Increases preload
What can untreated AF cause?
Tachy-cardiomyopathy
Name some common obstructive lung diseases.
- Asthma
- COPD
- Bronchiectasis (mixed)
Potential causes of secondary hypertension?
Renal artery stenosis
Chronic renal disease
Primary hyperaldosteronism
Pheochromocytoma
Coarctation of the aorta
Cushing’s disease – excess production of glucocorticoids, all cause some salt + water retention
Pregnancy – towards the end of pregnancy, BP increases in some women (may lead to pre-eclampsia)
Thyroid disease
Sleep apnoea
Alcohol
Syndrome of apparent mineralocorticoid excess – autosomal recessive; causes hyperextension, hypokalaemia
Liddle syndrome – rare hereditary abnormality of intra-renal metabolism
What is hypersensitivity pneumonitis?
Due to: bird features/droppings, mouldy hay, metalworking fluids.
o Hypersensitivity pneumonitis is a type 3 hypersensitive reaction (immune complex deposition)
o It’s an inflammation of the alveoli within the lung caused by hypersensitivity to inhaled organic dust
o Symptoms include: cough + breathlessness
o Lung function test: there is a restrictive effect because it mainly affects lung interstitium
What is papilloedema?
Optic disc swelling
Whereabouts in the lung does TB usually accumulate?
The upper lobe
How do B2 agonists work in asthma treatment?
Bronchoconstriction is contraction of bronchial smooth muscle
o They relax muscles of the airways – widens airways + results in easier breathing
o Act on beta-adrenoceptors found on bronchial smooth muscles
o Activated adenylate cyclase which leads to activation of cAMP, this activates protein kinase A (PKA) which phosphorylates target proteins
o Ultimately induces smooth muscle relaxation
Atenolol
Acebutolol
Selective (B1 only) beta blockers
How does hypoxia in the lungs differ to the rest of the body?
- Hypoxia in systemic tissues causes vasodilation.
- Hypoxia in pulmonary tissues causes vasoconstriction.
Use of lidocaine and MoA?
Used in VT when amiodarone is contraindicated or ineffective
Mechanism of action:
Sodium channel blocker
Raises the depolarisation threshold
Making the heart less likely to initiate or conduct early action potentials that may cause an arrhythmia
What would eliciting a bronchodilator response distinguish between?
COPD and asthma
- Asthma responds, COPD doesn’t
Siderosis
o Is the deposition of iron in tissue, it usually refers to an environmental disease of the lung
o CXR – shadowing of iron
o Not associated with any symptoms or functional abnormality
o Iron stays in lung but has no effect – no associated fibrosis or narrowed airways
Diagnosis of lung carcinoma
o Cytology – bronchial brush + wash, BAL
o Biopsy – bronchoscopy
o Surgery – lobectomy, pneumonectomy
Atrial flutter with variable block
- 300bpm atria contract
- Ventricles contract at slower rate - 150bpm
- Due to refractory period in AV node
- Multiple P waves
- Regular QRS
What percentage occlusion is there for angina?
75%
What factors may influence transmission of TB droplets?
- Infectivity of droplets (small).
- Duration and level of exposure.
- Susceptibility of exposed person.
What is alpha-1 antitrypsin deficiency?
- Lobular
- Neutrophils attracted to airways which produce proteolytic enzymes
- Enzyme needs to be switched off
- People with this do not have anything to switch it off
- Neutrophil elastase therefore destroys alveoli wall
Which drug leads to reduced rna synthesis in the bacterial cell?
Rifampicin - inhibits bacterial DNA-dependent RNA polymerase
Neutrophils vs eosinophils in COPD and asthma?
Asthma - eosinophils present
COPD - neutrophils present
Why do you get a cough with ace inhibitors?
ACE breaks down kinins so if you block ACE you have more kinins which increases vasodilation but also induces cough
What is the posteromedial papillary muscles blood supply?
Posterior descending artery
How does the SNS respond to heart failure?
- Sympathetics activated
- Vasoconstriction
- Increases afterload
Which is more likely to be a diffusion problem, CO2 or O2? What does this mean?
O2.
- CO2 not affected as it diffuses extremely quickly.
- Hypercapnia is more likely to be a ventilation problem i.e. emphysema.
How does chronic renal disease lead to secondary hypertension?
Kidney damaged (e.g. due to diabetic nephropathy, glomerulonephritis)
Loss of pressure diuresis due to decreased sodium excretion hence water retention. This leads to increased blood volume and cardiac output
Due to kidney damage, kidney wants to increase its own perfusion by increases BP to restore GFR so it increases renin release –> Ang II and aldosterone –> increased blood volume and CO
With increased blood volume the heart stretches, this releases what?
Natriuretic peptides into circulation which go to the kidney and cause increased urination, getting rid of salt and water
List 4 major determinants of BP
Baroreceptors
Poiseuille’s law
Renin angiotensin aldosterone system
Renal function
Paroxysmal nocturnal dyspnoea symptoms
o Wake from sleep (2-4 hours) o Cough, wheeze o Have to sit up while sleeping – asking how many pillows hey sleep with at night o Frightening o Last 15-30 minutes
On a standard ECG, how many small squares does the normal PR interval, QRS complex and QT interval contain?
PR = <6 small squares
QRS = <3 small squares
QT = <12 small squares
How does the PNS affect the SA node?
- Increased PNS causes a decrease in HR
- Sleep
- Vasovagal syncope
- Fitness
What is a full thickness (transmural) infarct?
Involves entire thickness of LV wall (isolated infarct of RV + RA are extremely rare)
E.g. block anterior intraventricular descending artery from L coronary artery – supplies left side of heart
Adverse effects of loop diuretics like furosemide, bumetanide, torsemide?
o Hyponatraemia – low blood sodium levels
o Hypokalaemia = low blood potassium level
o Hyperuricemia – excess uric acid in blood, acute gout is v. common
Toxic pneumonitis
- Acute, usually by inhalation
- Irritant gases of high NH3 or NO2, organic chemicals such as paraquat, metallic Hg, Cd and complex mixtures
Examples of stress tests
- Exercise ECG
- Stress ECHO
- Myocardial perfusion scan
Name some countries in which TB is particularly prevalent.
- Russia.
- India.
- China.
- Kenya.
- South Africa.
- Indonesia.
Which medication would you give to someone following a STEMI?
- Anti-ischaemics - nitrates/beta-blockers
- Statin
- Anti-platelet - clopidogrel, aspirin
- LMWH
What happens to hydrostatic pressure in a failing heart? What are the consequences of this?
It increases
- Heart requires a higher filling pressure in order to fill heart enough
- There becomes a point where heart filling pressure in the left ventricle causes the hydrostatic pressure in the pulmonary circulation to go so high that fluid move out into pulmonary bed faster than lymphatics can drain it away = pulmonary oedema
In what way do respiratory gases not diffuse identically?
CO2 diffuses across the membrane 20x faster than oxygen
What are the 2 types of COPD patients?
- Blue bloaters - overweight, cyanotic, oedema & sleep apnoea - chronic bronchitis
- respiratory failure earlier - Pink puffers - pursed lip breathing, leaning forward, prominent accessory muscles - respiratory failure late
HF causes almost every hormone system in he body to become abnormal. Name these systems
o Activation of RAAS – biggest one o Adrenergic activation o Increased endothelin (vasoconstrictor) o Increase ADH – increases thirst + fluid retention o Increased natriuretic peptides
Pathology of chronic bronchitis
MEGIS
Mucous gland atrophy Excess mucous Goblet hyperplasia Inflammatory cell Smooth muscle hypertrophy
Eosinophils in sputum is a marker of what?
Asthma
What is the bacteria that mainly causes TB?
Mycobacterium tuberculosis.
Asthma treatment steps.
Step 1:
- Inhaled short acting B2 agonist - salbutamol
Step 2:
- B2 agonist and steroid
Step 3:
- Corticosteroid + long acting beta agonist combination (salmeterol) - Regular use
- Short acting beta agonist (symptomatic)
Causes of tachycardia
- Supraventricular - AF, atrial flutter
- Ventricular - VT, VF, torsades de pointes
How does resistance affect flow rate?
Narrowing of the airway, increased resistance, flow reduced.
Occupational causes of asthma
Bakers
Welders
Paint sprayers
Laboratory workers
Which are the inferior leads of an ECG?
II, III, AVF
2 types of acquired immunity
Humoral - antibody production
Cell-mediated - associated with CD8
How is COPD and asthma treatment different?
Eosinophilic bronchitis responds to steroids
Neutrophilic bronchitis does not
Yet every patient is give corticosteroids on admission with obstructive airway problem
Causes of cough hypersensitivity
o Airway/lung infection o Left heart failure o Lung cancer o Foreign body inhalation o Interstitial lung disease/pulmonary fibrosis/pneumoconiosis o Tracheal compression by lymph nodes, aortic aneurysm, tumour o ACE inhibitors o Asthma o Gastro-oesophageal reflux o Chronic bronchitis + emphysema (COPD)
What is S1 and S2 heart sounds due to?
S1 - 1st heart sound – closure of atrioventricular valves (tricuspid + mitral)
S2 - 2nd heart sound – closure of semilunar valves (aortic and pulmonary)
Normally, which of inspiration and expiration is passive, and which is active?
- Inspiration: active.
- Expiration: passive (elastic recoil).
What are some of the issues of DR TB?
- Difficult to treat.
- Toxic treatments.
- Expensive drugs.
- Isolation and quarantine of patients.
- Higher mortality rate.
Chronic heart failure can be classified using NYHA classification. From Class I to IV describe how they are defined.
o Class I – no symptoms
o Class II – symptoms on severe exertion, but more than a normal person
o Class III – symptoms on modest exertion
o Class IV – symptoms at rest - mortality after 1 year of class IV = 50%
What is the body’s response to heart failure?
Same response to acute blood loss
Sympathetic outflow:
Raised BP, HR
Preserved flow to vital organs at expense of limbs
Salt + water conservation:
Thirst, ADH
Shut down kidneys
What is pulmonary oedema?
Fluid in air spaces of lungs
Impaired LV requires higher filling pressure to maintain output, eventually the pressure exceeds the lymphatic drainage + fluid accumulates in the alveoli
Early stage CXR – heart enlarged, interstitial lines, beginnings of alveolar oedema, lungs look white wit ‘bat-wing’ appearance if fluid stretching out from the hila of the lungs
Findings of investigation of bronchitis?
o Bloods – often normal
o Spirometry – obstructive picture
o Chest x-ray – normal
Conduction velocities of ventricular and atrial muscles and AVN?
Ventricular + atrial muscles (1m/s)
AVN conducts the slowest (0.05m/s)
Allows atria sufficient time to contract before ventricles are activated
Paraseptal emphysema
Involves air spaces at periphery of lobule
Atrial flutter
Usually not stable over a long period of time
Revert to sinus rhythm
Likely to recur
Often degenerates to AF
Difficult to modify atrial rate or control ventricular rate:
Changing block creates abrupt change in HR
2:1 4:1 block means ventricular rate drops from 150mp to 75bpm
Summary of asthma Tx
- Treat the 2 components of asthma – bronchoconstriction + inflammation
- We use 2 hormone receptors = corticosteroid + adrenaline
- Inhalers at the correct dose can minimise systemic effects
- Getting the right combination of therapy is key
- Step 1 – salbutamol (if pt. using more than once per day) –> step 2 corticosteroid (if ineffective) –> step 3 long acting beta agonist
o Long acting beta agonist + corticosteroid combination regular use + short acting beta agonist when required
What is post-primary/secondary TB?
- Reactivation or reinfected TB
- Occurs in immune deficiency such as disease, drugs and old age
- Reactivation as granuloma breaks up
Management of bronchitis
o Symptomatic o Bronchodilators o Steroids – inhaled vs oral o Possibly antibiotics o Limited evidence of benefit from treatments
What is an ectopic pacemaker?
Ecopic pacemaker: an excitable group of cells that cause a premature heart beat outside the normally functioning SAN
- An ectopic pacemaker can reside within a part of the electrical conduction system of heart or within muscle cells of atria or ventricles
Complicated coal-workers pneumoconiosis
- Rare
- AKA progressive massive fibrosis (PMF)
- Coal they worked with contaminated with silicase
- Marked disability
What happens when a muscle is stimulated to contract by an action potential?
- Calcium channels open in the sarcoplasmic reticulum
- Release calcium into sarcoplasm
- Calcium then binds to troponin, causing it to change shape and reveal the myosin binding site on actin
- Cross-bridge forms
- Contraction can occur
Mechanism of asthma
o Dendritic cells present allergen antigen to t-cell
o Th2 cells produce IL4, IL5, IL13
o Production of these interleukins signals B cells to produce IgE
o IgE binds to mast cells in the airways
o In the presence of the antigen, IgE causes mast cells to degranulate
o Degranulation of mast cells releases inflammatory mediators like histamine, leukotrienes (promote bronchospasm)
o These cytokines activate T and B lymphocytes further + attract eosinophils
What is pan-lobular emphysema?
- Involves all lung fields, occurs with loss of all portions of the acinus from respiratory bronchiole to alveoli
- This pattern is typical for alpha-1 antitrypsin deficiency
Clinical course of pulmonary oedema
o Patients get better or die
o Time course of hours – not a chronic problem
o Following recovery, the patient is started on oral diuretics + ACE inhibitors – treatment for chronic heart failure
Second line drugs for TB
- Capreomycin
- Cycloserine - inhibits early stages of peptidoglycan synthesis
- Streptomycin - inhibits bacterial protein synthesis
- Flouroquinolones
Ezetimibe
Blocks sterol carrier protein in brush border of enterocytes therefore reducing amount of biliary and dietary cholesterol delivered to liver via chylomicrons
What is the Interferon gamma release assay? (IGRA). What is the advantage of IGRA over TST?
- Blood test to measure cell mediated immune response by quantifying IFN-g released by T cells in response to TB antigens.
- More specific and sensitive than Mantoux.
Atypical pathogens that cause pneumonia
Legionella pneumophilia: o Legionella resides in stagnant water o Causes 2 syndromes: Legionnaire’s disease (pneumonia) + Pontiac fever (less severe) o Severe disease associated with extra-pulmonary findings: Fever Diarrhoea Headaches Liver enzyme rise Mental state changes Hyponatraemia o CXR: patchy infiltrates o Treat with macrolide or quinolone
Mycoplasma pneumoniae:
o More common in older children + young adults
o Course usually mild but can be severe when multiple systems involved
o CXR: much more extensive than clinical chest findings (discrepancy)
Chlamydophila pneumoniae:
o Usually milk in adults/self-limiting
o Associated with exacerbations of COPD
Why are large TB droplets not infectious?
- Fall out of the air due to the size.
- Are removed from the body by coughing and mucociliary action.
Conn’s syndrome
- Primary hyperaldosteronism
- Tumour in adrenal gland producing aldosterone
- Increased aldosterone leads to increased sodium and water retention
- Hypertension with low K+ = Conn’s
- Renin:aldosterone ratio is wrong
How to differentiate between renin overproduction and aldosterone overproduction causing secondary hypertension?
High aldosterone, low K+, low renin means – problem at adrenal glands with aldosterone overproduction
High aldosterone, high renin – means problem at kidneys with renin overproduction
MOA of spironolactone
Aldosterone antagonist (aka mineralocorticoid nuclear receptor antagonist)
Competitive binding to receptors on the aldosterone dependent Na+/K+ exchanger in the DCT
Pericarditis
Pericardial inflammation • Sharp, stabbing • Worse with inspiration • Worse lying flat • Eased by sitting up + NSAIDs • Hours to days
Causes:
o Infection
o Pericardial effusion: with infection, malignancy, lymphoma
Changes on ECG:
o Concave scooped ST elevation – different to ST elevation in MI
o PR depression – best seen on lead 4
What rate would a denervated heart beat at?
105 bpm (SANs intrinsic rate)
How much time does blood spend in the pulmonary capillaries on exercise and rest?
What is the significance of this?
- 3/4 of a second at rest.
- 1/4 of a second on exercise.
- CO2 diffuses very quickly so unaffected, is then ventilated out.
- On exercise, not enough O2 is always taken up in the short amount of time.
- In respiratory illness within thickened membrane it is even worse.
Not enough time for gas exchange to take place!
Most prosthetic valve produce a normal flow murmur.
Difference between aortic valve and mitral valve prosthesis?
Aortic valve prosthesis – systolic ejection murmur
Mitral valve prosthesis – diastolic flow murmur
Causes of multi-drug resistant TB
Poor treatment compliance Single drug therapy Poor calculation or regimes Malabsorption of drugs Prescribing/dispensing errors
Describe the electrical pathway of the heart
o Electrical impulses begin at SAN
o Signals spread from SAN across atria causing atrial muscular contraction)
o Signals stimulate AVN and AVN delays the signal
o Impulses pass down bundle of His and splits into the left and right
o Impulses pass up the purkinje fibres which are spread throughout the ventricles
o Impulses cause the ventricles to contract from base up
o Repolarisation takes a while in cardiac muscle to prevent the muscle from going into tetanus
What is the baroreflex?
- Baroreceptors in carotid sinus and aortic arch
- Detect BP change
- Carotid sinus signals via glossopharyngeal nerve to nucleus tractus solitarus in the medulla
- Aortic arch signals via vagus nerve to nucleus tractus solitarus in the medulla
Causes of hypersensitivity pneumonitis
Bird fancier’s lung
• Due to feathers + bird droppings
Farmer’s lung
• Due to mouldy hay (moulds + bacteria)
Metalworking fluids HP
• Due to mist from metalworking fluids (no-TB mycobacterium)
Steroids are very effective at getting rid of eosinophils, they cause apoptosis.
How to they work?
Steroid molecule attaches to inactive steroid receptor activating it
Receptors form a dimer
Dimer acts on DNA by:
Up regulating beta-receptor gene – more beta receptors
Down regulating cytokine genes – less inflammation
Where is the infarction in an anterior acute MI?
Left anterior descending artery
aka
The anterior interventricular branch of left coronary artery is a branch of the left coronary artery.
What is the difference between compensated and decompensated type 2 resp failure in COPD?
Decompensated = acutely unwell, CO2 rapidly goes up.
Compensated = chronic over time, bicarbonate from the kidneys.
Spectrum of coronary disease
- Asymptomatic
- Stable angina
- Acute coronary syndrome
- Heart failure
- Sudden death
What is Wolff-Parkinson-White syndrome?
A disorder due to a problem with the electrical system of the heart
The underlying mechanism involves an accessory electrical conduction pathway between the atria and the ventricles
What are amiloride and triamterene examples of?
Epithelial sodium channel blockers which are potassium sparing diuretics.
Treatment of hypertension and congestive heart failure.
Gemfibrozil
- Fibrate
- Increase transcription of genes for lipoprotein lipase and ApoA1 + ApoA5
- Increased risk of gallstones
Histological changes in accelerated hypertension?
o Fibrinoid necrosis of small arteries + arterioles
o Damage to RBCs – as they negotiate vessels obstructed by fibrin with resulting microangiopathic haemolytic anaemia
Which are the lateral ECG leads?
I, V5, V6, AVL
List all cardiac markers
o Troponin I o Troponin T o CK o CK-M8 o LDH o Myoglobin
Name the 2 major types of emphysema?
Panlobular
Centrilobular
Pharmacological treatment of pulmonary oedema
Diamorphine - anxiety relief, possible role as vasodilator
Oxygen - patient will be hypoxic
Diuretic - almost always IV furosemide
Vasodilator:
Often given nitrate IV – GTN, isosorbide mononitrate, etc.
Titrated against BP
Drops blood pressure (may be a problem in very ill people)
Acutely reduce left ventricle end diastolic pressure by vasodilation
How does resistance to acute pulmonary oedema occur?
Mitral stenosis!!
- Thickened alveolar capillary membrane
- Increased lymphatic drainage
Symptoms of stable angina
- Central tight chest pain
- Radiates to jaw, teeth, back and arm
- Brought on by exercise, big meals, cold etc.
- Relieved by rest and nitrates
What is cor pulmonale?
- Right sided heart failure as a result of chronic lung disease
- Ventilation-perfusion mismatch due to chronic hypoxia of the alveoli
- Constriction of capillaries, results in pulmonary hypertension
- RV has to work harder against resistance, becomes dilated - can become RHF
- If so raised JVP and peripheral oedema (ankles) due to stasis
Left ventricular aneurysm
- Ballooning out of heart
- Associated with signs and symptoms of heart failure
- Decreased cardiac output
- LV thrombus formation
- Ventricular arrhythmias and sudden death
Causes of R bundle branch block
Atrial septal defect,
PE,
MI
Large A waves on JVP can indicate what?
o Pulmonary hypertension
o Tricuspid stenosis
o Cannon waves in CH8 or VT
Note:
If no A wave present – AF
What does aldosterone do?
Encourages excretion of K+ in exchange for reabsorption of Na+ in the late DCT.
How is bradycardia due to heart block treated?
Investigate and remove cause
• Recent (inferior) MI
• Digoxin toxicity, beta-blockers, rate limiting calcium channel blockers
• Intravenous atropine
2nd/3rd degree heart block usually requires pacing
Mitral papillary muscles
The mitral valve has 2 cusps, help by papillary muscles
The posteromedial papillary muscle is typically supplied via the posterior descending artery
• 80% of people PDA Is supplied by RCA
• 20% of people PDA is supplied by LCx
The anterolateral papillary muscle has a dual supply from the LAD + LCx
• Collateral supply means if there is an anterior infarct, you can still get blood supply from the LCx
Rupture of the posteromedial papillary muscle occurs 6-12x more frequently than anterolateral papillary muscle
- Methylxanthines act as bronchodilators by relaxing bronchial smooth muscle + helps the constricted airways to dilate
- They are used in the treatment of asthma + COPD
What is their MOA?
Exact mechanism is no well understood but it’s thought to…
o Inhibits phosphodiesterase (which usually degrades cAMP)
o Increases concentration of cAMP
o Activates PKA
o Inhibits TNF-alpha + leukotriene synthesis
o Reduces inflammation + innate immunity
Pathophysiology of chronic stress
- Increased output from sympathetic nervous system and increased HPA output
- Results in insulin resistance, central obesity, bone density drops, inflammation, hypertension and ANS dysfunction
List classes of drugs used for hypertension treatment
A - ACE inhibitors
B - Beta blockers
C - Calcium antagonists
D - Diuretics (thiazide)
Examples of thiazide and thiazide-like drugs
- Bendroflumethiazide
- Chlortalidone
- Metolazone
Right sided heart failure
o R side is responsible for receiving deoxygenated blood from systemic circulation + pumping it to lungs to be oxygenated
o This may be due to muscle injury, MI localised to RV, damage to valves in R side of heart or elevated pressure in the lungs
o However, HF commonly affects both sides of the heart and this is called biventricular HF
o The R heart fails usually because the L heart fails
Systemic disease associated with COPD
Muscle wasting,
Increased osteoporosis,
Peripheral neuropathy
Depression
Mnemonic –
- No (Na blocker)
- Boy (Beta-blocker)
- Keeps (K blocker)
- Clean (Ca blocker)
Antiarrhythmic type - x channel blocker - phase of cardiac AP: 1-N-0 2-B-4 3-K-3 4-C-2
Type I - Na+ channel blockers (phase 0)
Type II - Beta blockers mainly (phase IV)
Type III - K+ channel blockers (phase III)
Type IV - Ca2+ channel blockers (phase II)
1234 = 0432 = NBKC
Causes of pulmonary oedema?
What would be observed in a CXR?
Causes: MI, left ventricular dysfunction, renal artery stenosis
CXR – cardiomegaly, bats-wing appearance (fluid + congestion, fluid in interstitial spaces
What is the mechanism of action of atrial natriuretic peptide?
A. Suppress sympathetic tone
B. Agonist of aldosterone
C. Hydrolyses angiotensinogen to angiotensin I
D. Antagonist of angiotensin II
E. Agonist of angiotensin I
D. Antagonist of angiotensin II
How does B-type or brain natriuretic peptic work?
BNP named as such because it was originally extracted from pig brain
B-type natriuretic peptides suppress sympathetic tone and the RAAS
Aortic regurgitation
Pathophysiology:
- Valve fails in its function to prevent backflow
- Backflow into left ventricle causes left ventricular hypertrophy
- In order to maintain CO, hypertrophy occurs
Causes:
- Rheumatic fever
- Infective endocarditis
- Marfan’s syndrome
- Syphilis
Murmur with aortic regurgitation is best heard in the left 4th IC space (pulmonary valve)
Most common cause of infective endocarditis?
Staphylococcus aureus:
- IV drug use
Streptococci viridans:
- Poor dental hygiene
- After dental procedure
Staphylococcus epidermidis:
- Prosthetic valves
How do class Ia, Ib, Ic antiarrhythmics work
Na+ channel blockers!
- Ia – Lengthen AP duration
- Ib – Shorten AP duration
- Ic – No significant effect on AP
Class Ia antiarrhythmics
Examples:
- Disopyramide
- Quinidine
- Procainamide
MoA: Interfere with sodium channel by lengthening AP duration
Indication:
- Ventricular arrhythmias (esp. post-MI)
Adverse effects:
- VT
- VF
- TdP
- Anti-muscarinic
Class Ib antiarrhythmics
“Lidocaine
Mexiletine”
MoA:
- Blocks with sodium channel - Shortening AP duration
Indication:
- Ventricular arrhythmia following MI
Class Ic antiarrhythmics
Flecainide
Encainide
Propafenone
Moricizine
MoA:
- Interfere with sodium channel by having no significant effect on AP duration
- Acts on: SAN, AVN, atria and ventricles
Indication:
- Pre-excited AF (WPW)
- Acute AF
Class II antiarrhythmics
Examples:
- Carvedilol
- Atenolol
- Sotalol
- Metoprolol
- Propranolol
- Timolol
- Metoprolol
MoA:
- Agents that are anti-sympathetic nervous systemic
- Most are beta blockers
Indication:
- Hypertension
- IHD
- Arrhythmias
- Heart failure
Class IV antiarrhythmics
Examples:
- Verapamil
- Diltiazem
MoA:
- Non-DHP calcium channels antagonists
- Prolong conduction and regaactoriveness in SAN and AVN
Indication:
- SVT prophylaxis
- AF (rate control)
- Acute SVT
Class V antiarrhythmics
“Adenosine
Atropine
Magnesium
Digoxin”
Agents that work by other or unknown mechanisms.
Indication:
- Supraventricular arrhythmias [digoxin]
- Bradycardia [atropine]
Risk factors for TB
- Elderly
- Immunocompromised
- Diabetes
- Hodgkin lymphoma
- Chronic lung disease
- Chronic kidney failure
- Malnutrition
- Alcoholism
Types of non-small cell carcinoma?
Adenocarcinoma (>40-50%)
Squamous cell carcinoma (20%)
Large cell carcinoma (2%)
Non-small cell carcinoma treatment:
Early stage (I and II)
• Hasn’t spread to peripheral lymph nodes
• Surgical resection – 5-year survival 23-60%
• Radical radiotherapy may be offered if unfit for or refuses surgery (almost as effective)
Advanced stage (III and IV)
• Palliative chemotherapy and/or radiotherapy
• 5-year survival <1%
Paraneoplastic syndromes secondary to ectopic production of hormones by the lung cancer cells.
In particular SCC and SqCC
ADH – Hyponatraemia (commonly in small cell carcinoma).
Parathormone – Hypercalcaemia (commonly in squamous cell carcinoma)
Common presentations of lung carcinoma
o Cough (75%)
o Weight loss (40%)
o Chest pain (40%)
o Dyspnoea (20%)
Small cell lung cancer
- Develops from bronchial endocrine or APUD cells
- Associated with paraneoplastic syndrome
- Mutations in p53, RB, MYC
Lung adenocarcinoma
- Most common type in people who have smoked less than 100 cigarettes in their lifetime
- Tumours arise from glands e.g. clara cells, type II pneumocytes + goblets cells
- Slowest rate of growth
- Most common in women
Name the 2 main subtypes of lung carcinomas.
o Non-small cell carcinoma (87%)
o Small cell carcinoma (13%)
Systemic effect of lung carcinoma
o Metastatic spread
o Paraneoplastic syndromes secondary to ectopic production of hormones by the lung cancer cells
o Lambert-Eaton myasthenia syndrome – Autoantibodies against neuronal calcium channels
o Peripheral neuropathy
o Dermatological abnormalities – e.g. acanthosis nigrans
o Haematological abnormalities – e.g. leukaemia reactions
o Hypertrophic pulmonary osteoarthropathy with finger clubbing
Paclitaxel
Binds to tubulin, keeping the microtubules polymerised, preventing spindle formation in dividing cells and stopping them in mitosis
It is an anti-microtubule agent, used for non-small cell lung cancer in patients unsuitable for curative treatment
Causes of breathlessness
Sudden (mins) causes of breathlessness:
- Pulmonary oedema
- Pneumothorax
- Pulmonary embolism
- Anaphylaxis
- Foreign body inhalation
Rapid (hrs) causes of breathlessness:
- Acute asthma
- Pneumonia
- Pulmonary oedema
- Acute hypersensitivity pneumonitis
Subacute (wks) causes of breathlessness:
- Heart failure
- Anaemia
- Pleural effusion
- Lung cancer
Slow (mth/yrs) causes of breathlessness:
- COPD
- Interstitial lung disease
- Pneumoconiosis
- Pulmonary arterial hypertension
Adenocarcinoma (lung)
Infiltration of lung by abnormal glandular structures
Shows glandular differentiation
- tubular/acinar/papillary structures
- Mucin production
Precursor lesions - atypical alveolar cell hyperplasia (alveoli lined by atypical cuboidal epithelial cells)
Describe small cell carcinoma (lung)
Shows neuroendocrine differentiation
Crowded small cells with hyperchromatic glassy nuclei and extremely scanty cytoplasm
What is mesothelioma?
A type of cancer that develops from thin layer of tissues + covers internal organs
Most commonly affected are is lining of lungs + chest well
It is almost invariably caused by occupational exposure to asbestos:
• Long latency (approximately 40 years)
• Only small exposures needed
• Highly dependent on fibre type
Heart block
1st degree heart block:
- QRS normal
- P wave present
- Long PR interval
2nd degree type 1 heart block:
- QRS irregular
- P wave present
- AV node slows till P wave delivered which doesn’t get conducted to ventricles
- PR interval becomes progressively longer until QRS fails to appear
- 3:2 heart block – 3 P waves for every 2 QRS
- There is an intermittent delay in conduction of normal sinus impulses from the atria to ventricles
- PR interval becomes progressively longer until QRS complex fails to appear
- This sequence is then typically repeated
2nd degree type 2 heart block:
- QRS regular
- 2x P waves for every 1 QRS
3rd degree (complete) heart block:
- QRS regular
- Unrelated P wave to QRS
- Ventricular rate usually less than 40 bpm
Pneumonia classification
Microbiologically:
- Typical
- Atypical
Radiologically:
- Lobar pneumonia
- Bronchopneumonia
Clinically:
- Community acquired
- Hospital acquired
Examples of obstructive lung diseases
- COPD
- Asthma
- Bronchiectasis
- CF
Examples of restrictive lung diseases
- Pulmonary fibrosis (IPF).
- Chest wall deformity (kyphosis).
- Obesity.
- Neuromuscular disease.
Difference between obstructive and restrictive lung disease.
Obstruction: narrowing of the airways, increased resistance to air flow (like breathing through a straw).
Restriction: increased work to expand the chest or reduced lung compliance/increased stiffness.
What happens to the lungs in restrictive lung disease?
- SA reduces.
- Reduced compliance.
- Thickened alveolar membrane.
- Relatively normal airways and airflow
- Impaired diffusion.
How are diffusion and perfusion affected in obstructive lung disease?
Not much, it is a ventilatory problem.
- Diffusion affected in emphysema due to parenchyma destruction.
- Perfusion affected in end stage (cor pulmonale).
What would the spirometry of a patient with obstructive lung disease show?
- FEV1 is reduced in obstruction
- FVC is normal
Reduced FEV1/FVC ratio, less that 0.7 ratio.
What would the spirometry of a patient with restrictive lung disease show?
- Reduced FEV1
- Reduced FVC
- No change or increased FEV1/FVC ratio
What test is used to test lung (ventilation) function most accurately?
How can this be used to determine the type of lung disease a patient has?
Spirometry.
- FEV1/FVC ratio of 0.7 = obstructive.
- FEV1/FVC ratio of 1 = restrictive.
For obstructive FEV1 is reduced but FVC is normal.
For restrictive both FEV1 and FVC would be reduced so ratio remains normal.
What test is used to test lung (ventilation) function most accurately?
How can this be used to determine the type of lung disease a patient has?
Spirometry.
- FEV1/FVC ratio of 0.7 = obstructive.
- FEV1/FVC ratio of 1 = restrictive.
For obstructive FEV1 is reduced but FVC is normal.
For restrictive both FEV1 and FVC would be reduced so ratio remains normal.
Antiarrhythmic drug class and where they work on the cardiac action potential summary.
Phase 0:
- Class 1 antiarrhythmics
- Na+ (in)
Phase 1:
- No drugs work here
- K+/Cl- (out)
Phase 2:
- Class 4 antiarrhythmics
- Ca2+ (in)
Phase 3:
- Class 3 antiarrhythmics
- K+ (out)
Phase 4:
- Class 2 antiarrhythmics
- K+ (rectifier)
Drugs that action on different phases of the cardiac action potential summary.
Phase 0:
- Class 1 antiarrhythmics
- Na+ (in) channel blocker
- Ia (moderate): Quinidine, Procainamide
- Ib (weak): Lidocaine, Phenytoin
- Ic (strong): Flecainide, Propafenone
Phase 1:
- No drugs work here
- K+/Cl- (out)
Phase 2:
- Class 4 antiarrhythmics
- Ca2+ (in) channel blocker
- Verapamil, Diltiazem
Phase 3:
- Class 3 antiarrhythmics
- K+ (out) channel blocker
- Amiodarone, Sotalol
Phase 4:
- Class 2 antiarrhythmics
- K+ (rectifier) beta-blocker
- Propranolol, Metoprolol
Cardiac nodal action potential
o Automaticity – spontaneous depolarisation until threshold potential reaches when cell fires (phase 0)
o Phase 0 – depolarisation, inwards Ca2+ influx instead of Na+, slower rise, less overshoot
o Phase 3 – repolarisation, no rapid inactivation of Na+ channels, slow increase in K+ outflow, slow inactivation of Ca2= inflow
o Phase 4 – spontaneous depolarisation, increase slow Na2+ current
The five main classes in the Vaughan Williams classification of antiarrhythmic agents are?
Class I agents interfere with the sodium (Na+) channel.
Class II agents are anti-sympathetic nervous system agents. Most agents in this class are beta blockers.
Class III agents affect potassium (K+) efflux.
Class IV agents affect calcium channels and the AV node.
Class V agents work by other or unknown mechanisms.
When are class V antiarrhythmics used?
Used in supraventricular arrhythmias, especially in heart failure with atrial fibrillation.
Contraindicated in ventricular arrhythmias.
Magnesium sulfate used in torsades de pointes.
