ESA 2 Clinical Conditions Flashcards
Hereditary Spherocytosis/Eliptocytosis
Autosomal Dominant - Spectrin within RBC (cytoskeletal component) depleted by 50%, erthyrocytes become more rounded (sphero) or rugby ball shape (elipto), more prone to lysis/likely to be removed by spleen. Results in haemolytic anaemia, treat with normal blood transfusion
Mysathenia gravis
Autoimmune destruction of end plate ACh receptors, which leads to less depolarization throughout the muscle fibre (so APs have less amplitude), and due to excitation- contraction coupling, difficulty with contraction. Causes muscle fatigue (classically drooping eyelids) and extreme weakness, which are exacerbated by exercise
Familial hypercholesterolaemia
Relevant cause for this unit is defect in the LDL receptor, can be one of three things:
Receptor deficiency – mutation prevents expression of LDL receptors
Non-functional receptors – no binding of LDL, receptor/coated pit complex still formed
Receptor binding normal – no interaction w/ coated pits, dotted across cell membrane instead, can’t form proper coated vesicles
Leads to excess circulating cholesterol, which is deposited as tendon xanthomas, xanthelasmas or corneal arcus (in young people, can just be age). High circulating cholesterol leading to atherosclerosis and then ischaemic heart disease which can result in MI and death
Pheochromocytoma
Noradrenaline secreting tumour of the chromaffin cells of the adrenal medulla. Can be detected by levels of vanillylmandelic acid (VMA, end product of noradrenaline breakdown) in urine. Symptoms are consistent with excessive sympathetic stimulation (sweating, tachycardia etc). Can be treated by administering alpha-methyl tyrosine, which blocks biogenic amine synthesis by inhibiting tyrosine hydroxylase, reducing the levels of noradrenaline produced
Reitintis pigmentosa
Caused by loss of function in rhodopsin GPCR, leads to progressive degeneration of vision due to the damage to rod cells, genetically inherited
Nephrogenic diabetes insipidus
Caused by a loss of function in the V2 vasopressin receptor (vasopressin is aka ADH), means that kidneys do not retain water, leading to huge volumes of urine being passed, leading to dehydration and death (this kind of diabetes does NOT relate to blood sugar levels). Genetically inherited usually
Familial male precocious puberty
Caused by a gain of function in the luteinizing hormone receptor, meaning that androgens are produced in larger quantities more quickly, kickstarting puberty anywhere from 2 years old onwards. Leads to short stature as the epiphyseal growth plates close a lot earlier than they would in someone who develops usually in puberty
Asthma
Bronchoconstriction resulting in shortness of breath, wheezing etc (all symptoms of inability of the lungs to function at the level they’re required to). Caused by release of inflammatory mediators (eg histamine) in response a to an irritant or allergen. Bronchi/bronchioles parasympathetically driven by M3 receptors (leads to G aq leading to phospholipase Cthen Ca2+ release) to constrict (they contain smooth muscle). B2 adrenergic receptors present but not normally innervated, are stimulated by adrenaline in a fight/flight situation. Clinically, we give B2 agonists (salbutamol, salmetrol) to activate the B2 receptors (G S leading to an inc cAMPthus PKAand myosin light chain kinase stopped) to cause bronchodilation. Can give steroids/antihistamines to dampen the immune response long term (preventer medications) or methylxanthines (inhibit phosphodiesterase to preserve cAMP). Don’t use muscarinic antagonists as they’re not specific and give anti-constriction rather than active dilation
Hypertension (Dont include treatments)
Systolic > 140 OR diastolic > 90.
95% of cases are idiopathic (primary) hypertension.
Leads to severe cardiovascular complications, the most important of which is ischaemic heart disease. Influenced by the baroreceptor reflex short term and the renin-angiotensin- aldosterone system (RAAS) long term. Treated with a variety of drugs that have varying receptor targets:
Hypertension treatments
Diuretics (loop)
Nephron (NKCC2 channels)
Block Na+ and H2O reabsorption so blood volume/venous return falls, and then so does CO (Starlings Law)
Minor, headaches, increased thirst etc
ACE inhibitors
Angiotensin converting enzyme Blocks ATIATII and so stops inc in TPR and stops inc Na+/H2O retention (both directly and via aldosterone)
Of little use in afro-carribbean and young people (RAAS system less active)
Beta blockers
B1 adrenoceptors in myocardium
Block B1 adrenoceptors and so cause –ve chronotropy through less cAMPleading to HCN channels closing (SAN/AVN) and –ve inotropy through decrease number of Ca2+ channels open (ventricular myocardium)
High sensitivity to adrenaline/NorAd when you come off (inc sensitivity of receptors), GI motility etc
A1 adrenoceptor antagonists
A1 adrenoceptors in peripheral arterioles
Blocks A1 adrenoceptors and so causes dilation of arterioles (decrease IP3/DAG activity), decreasing TPR
Postural hypotension (baroreceptor reflex fails due to constant vasodilation), GI motility etc
Thyrotoxicosis
Result of hyperthyroidism. T4 upregulates the number of adrenoreceptors present, so in the context of M and R we have increased heart rate through B1 receptors, increased sweating through sympathetic innervation etc. Whilst you would usually give carbimazole (blocks iodine uptake and therefore thyroxine synthesis) as a treatment long term, for short term relief of symptoms a non-specific beta adrenoceptor antagonist can be useful for symptom relief (ie propranolol)
Compartment syndrome
Bleeding into compartment raises pressure, if this gets high enough it will compress nerves, giving intense pain, and blood vessels, causing ischaemia and potential oncosis if left long enough. Treat with fasciotomy (cut fascia to relieve pressure).
Hypotonia
Loss of muscle tone (which will have a negative effect on function), due to a number of potential causes:
Primary degeneration of muscle (myopathies such as DMD)
Lesion of sensory afferents (proprioreceptors) in skeletal muscle
Cerebral/spinal neural shock
Lesions of the cerebellum
Lesions of lower motor neurones ie polyneuritis (multiple neurones)
Tetanus
Infection of wound by clostridium tetanii, toxin released, leading to a permanent state of contraction (tetany) due to temporal summation. Antibiotics to treat, once toxin binds the neurone is essentially useless
Amelia
Complete lack of a limb due to a congential defect
Meromelia
Lack of one particular part of a limb. Good example is phocomelia (hands and feet attached to abbreviated arms and legs) as a result of thalidomide’s teratogenic effects
Syndactyly
Lack of apoptosis between two or more digits leading to webbed feet or hands (fused)
Polydactyly
More than a normal number of digits (usually just one extra)
Slipped disc
Nucleus polposus (remnants of the embryonic notochord) herniates, and as a result leaks out from the centre of the intervertaebral disk in either a postero-lateral or posterior direction.
Postero-lateral will cause pain (both due to nerve root compression and local inflammatory mediator release), but posterior herniation can compress the spinal cord, possibly causing a paralysis in a worst-case scenario
Kyphosis
Abnormal posterior convexity of thoracic spine (over 60 degrees), causes a hunch back and leads to back pain, stiffness etc. Can correct with brace if young
Lordosis
Abnormal posterior concavity of lumbar or cervical spine, causes a saddle back, can lead to back pain, stiffness etc. Can also be corrected with brace if young
Scoliosis
Abnormal three-dimensional abnormality of the spine, with some lateral deviation, and potentially a degree of twisting. Can lead to issues with posture etc, but back pain is rare. Treat with bracing usually
Spina bifida
Hole in vertebral column due to an unknown cause, but lack of folic acid during and just before pregnancy has been identified as a strong risk factor. Leaves spinal cord exposed, so nerve damage and infection incredibly likely. Usually closed with surgery at birth, but is rare for no nerve damage to have already occurred
Whiplash
Sudden jerking movement of the head, damages ligaments and muscles, but more importantly can dislocate vertebrae. Rapid jerk causes cervical spine to adopt sigmoid shape, which forces C5 and C6 to hyperextend, moving them outside of their range of movement and leaving them vulnerable to a dislocation. Pain, and some partial paralysis can occur if this damages the spinal cord (but as the foramen of the cervical vertebrae is very large, there is some degree of movement before it impacts the cord)
Rheumatoid arthritis
Arthritis as a result of an inflammatory response, which causes inflammation of (initially) the synovial membrane, leading to pain when moving the joint. The condition progresses to fibrosis of affected joints, affecting mobility and causing them to seize completely eventually essentially destroying the joint. Not associated with age, and usually starts by affecting one side of the body, but in all types of joints (large and small). Progress can be slowed with steroids, but physiotherapy and lifestyle changes usually necessary
Surgery in severe cases can either involve complete joint replacements, joint resurfacing or joint fusion (arthrodesis, this is bad as it stops movement in that joint)
Osteoarthritis
‘Wear and tear’ arthritis as a result of the persistent movement stripping the articular surface (cartilage) from joints. This leads to bone grinding against bone, leading to joints seizing and pain. Usually associated with age as it’s wear and tear, tends to be limited to one class of joints on one side of the body before spreading (such as all MCP joint in right hand). Steroids don’t do much, physiotherapy and lifestyle changes etc are usually much more effective
Surgery in severe cases can either involve complete joint replacements, joint resurfacing or joint fusion (arthrodesis, this is bad as it stops movement in that joint)
Sarcopenia
Gradual loss of muscle mass due to aging. Typical value is 0.5 to 1% loss every year after the age of 50. Differs from cachexia (weight loss) as this is secondary to an underlying pathology ie kwashiorkor . Not always considered a disease or even a symptom, some considering it a normal part of aging. However, it contributes (along with osteoporosis) to an increased risk of mortality/death following a fall/other trauma in the elderly – this is known as frailty syndrome
Cardiac tamponade
Pericardial effusion (infection) or haemorrhagic effusion lead to pericardium filling with fluid – heart finds it harder to contract, and will eventually stop. Pericardiocentesis (aspiration of fluid within pericardium) to treat
Pericarditis
Infection of pericardium leading to pericardial effusion. Potential cause of tamponade
Congenital heart defects (rule of thumb)
Rule of thumb, left to right shunt doesn’t cause cyanosis and isn’t as serious, right to left puts deoxygenated blood in systemic circulation so causes cyanosis, more serious
Think of the heart like plumbing, imagine the normal setup, visualise the element that’s damaged/added in and work out how you divert blood flow around this/where the blood would go. This makes learning these (and understanding them) a lot easier
Atrial septal defect
Hole in atrial septum that allows communication between atria, left to right shunt due to pressure (blood does pulmonary circuit more than once), huge flow can overload RV and lead to right heart failure
Ventricular septal defect
Hole in ventricular septum (usually the membranous portion) that allows communication between the two, left to right shunt due to pressure (blood does pulmonary circuit more than once), pulmonary hypertension due to increased blood passing through, can get so high that the pressure gradient reverses and you get a paradoxical shunt (Eisenmenger syndrome)
Patent ductus arteriosus
PDA stays open after birth, communication between aorta and pulmonary trunk/arteries, blood does pulmonary circuit twice, pulmonary hypertension (similar to VSD)
Patent foramen ovale
Fails to close at birth, largely asymptomatic, as it’s so small, but can be a route for venous embolism to join systemic circulation
Coarctation of the aorta
Constricting of the aorta in the region near the DA, leads to hypoperfusion in vessels distal to this (lower limbs, femoral pulses will be weak), leads to hypertension in vessels before this (aortic arch) in an effort to increase perfusion to lower limbs by the body
Tetralogy of Fallot
4 key defects giving rise to a cyanotic patient, due to the circulation of deoxygenated blood:
- Ventricular septum misalignment – leads to right ventricular hypertrophy (and therefore hypertension) due to increased difficulty of pumping to pulmonary trunk
- Pulmonary stenosis – narrowing of pulmonary valve causes hypertension in right ventricle
- VSD – due to 1 and 2, the pressure in RV exceeds LV, causing a shunt of deoxygenated blood from right to left
- Over-riding aorta – misaligned aorta takes some blood from RV as well as LV, leading to more deoxygenated blood circulating
Tricuspid atresia
Missing/closed tricuspid valve, so no pulmonary circuit formed, only viable if there’s a right to left ASD (necessary to form a complete circuit, possible due to accumulation in RA without filling the RV) and either a VSD of PDA (to allow access to lungs)
Transposition of great arteries
Spiral septum doesn’t form correctly, leading to the aorta being connected to RV and pulmonary trunk to LV, now two separate circuits that run parallel instead of one big one, only viable if PDA is open and maintained (completely mixes blood)
Hypoplastic left heart
LV and ascending aorta undeveloped/absent, LA small, PDA maintained, right ventricle takes over systemic and pulmonary circulation, PDA allows blood into the aorta past the ascending section, maintaining viability. Some communication between LA and RA also needed (ASD)
Pulmonary atresia
No pulmonary valve no access to pulmonary circuit except through PDA
Aortic atresia
No aortic valve meaningi no access to systemic circulation except through PDA, ASD/VSD often created artificially to stop accumulation in left side of heart
Hyperkalaemia
Too much K+ in blood too much K+ in ECF, so the concentration gradient is less steep, which permanently depolarises the membrane, inactivating some Na+ channels in the pacemaker, and through accommodation of this weak depolarisation you end up with bradycardia, bundle branch blocks and eventual heart failure. ECG features include:
Prolonged QRS complex
Prolonged PR interval
Tented T waves (very similar in shape to a healthy QRS complex)
Hypokalaemia
Too little K+ in blood leading to too little K+ in ECF, so the concentration gradient is more steep, permanently hyperpolarising the membrane, which leads to hyperexcitability of the Na+ channels, less inactivation (this somehow causes a decreased refractory period), leading to tachycardia, then atrial or ventricular fibrillation and eventual cardiac arrest. ECG features include:
Enlarged P waves
Prolonged PR interval
T wave flattening/inversion No Pot (potassium), not tea (T wave)!
Atrial fibrillation
Appears as a lack of discernable P waves, sometimes with the isoelectric line being disrupted into a ‘wavey baseline’. Not fatal as most filling of the ventricles occurs during diastole, atrial systole isn’t that important
Ventricular ectopics
Can be idiopathic, ventricles will occasionally contract without an impulse from the SAN, so initiated by AVN instead. Different place of origin means a different shaped QRS complex, will show up as always wider and sometimes taller in amongst the normal complexes
Long QT syndrome
Genetic or acquired syndrome that leads to abnormal repolarization of the heart, which prolongs the QT interval, allowing a greater chance for re-entry arrhythmias. Particularly more likely to develop torsades de pointes or ventricular tachycardia that will progress into ventricular fibrillation
Torsades de pointes
Associated with prolonged QT interval, particular type of ventricular tachycardia that gives the appearance of winding round the baseline in 3d (despite being on a 2d page) on the ECG. Most episodes are self-resolving within a few seconds but can devolve into ventricular fibrillation
Ventricular fibrillation
Ventricles no longer able to contract in a coordinated manner, immediate loss of CO and rapid death unless treated. Shows on an ECG as rounded, shallow peaks and then troughs, with no discernable PQRS or T waves/complexes at all. Must be defibrillated
1 st degree heart block
Delay between the contraction of the atria and the ventricles, due to an issue at the atrioventricular node (AVN). Shows as a prolonged PR interval on an ECG
2 nd degree heart block
Irregularity of contraction between the atria and the ventricles. The PR interval will get more and more prolonged until the AVN generates its own depolarization, showing as an abnormally shaped QRS complex. This then resets and the same thing is seen again
3 rd degree heart block
Complete dissociation between the P and QRS complexes as a result of a complete block between the SAN and AVN. If you measure the RR interval and the PP interval, you will calculate two different heart rates (the RR interval will be slower as its initiated by the less electrically active part of the heart)
Left bundle branch block
Some abnormality occurs that slows/stops the electrical conduction down the left bundle of Purkyne fibers. Shows as abnormally shaped ‘rabbits ears’ QRS complex as the two ventricles depolarize at different rates
Right bundle branch block
Some abnormality occurs that slows/stops the electrical conduction down the right bundle of Purkyne fibers. Shows as abnormally shaped ‘rabbits ears’ QRS complex as the two ventricles depolarize at different rates
Differentiating between right and left branch block
Easiest way to differentiate between a right or a left bundle branch block is to check the chest leads and apply the following mnemonic:
WiLLiaM MoRRoW
If the QRS complex is shaped like a W on the septal leads (closest thing to a right sided view, V1) and an M on the lateral leads (left side of heart, V6), it’s a LBBB
If the QRS complex is shaped like an M on the septal leads (closest thing to a right sided view, V1) and a W on the lateral leads (left side of heart, V6), it’s a RBBB
Ischaemic heart disease
Inability of the blood supply of the heart to match the demand placed on it by the body. Factors that influence either of these are as follows:
Supply
Coronary flow (determined diastolic BP and coronary resistance)
O2 capacity of blood
Demand
Heart rate
Contractility (stroke volume at a given venous pressure)
Wall tension (determined by pre-load and afterload)
Most likely cause of pathogenesis is a coronary atheroma that causes the lumen of the coronary artery to narrow, increasing coronary resistance (resistance decreases by radius 4 ) and therefore decreasing coronary flow. How badly these arteries are occluded by said atheroma determines the symptoms, and is split into the classifications below
Stable angina
Plaque usually occludes > 70% of the artery lumen, leads to ischaemia of the myocardium not at rest but when demand is increased (can meet the low resting level of demand). Pain is typically ischaemic (central/retrosternal, left sided more than right, crushing or tightening pain) and disappears within 5 minutes of ceasing exertion/with GTN spray
Unstable angina
Largely similar to stable angina yet pain appears to crescendo (increase in intensity), doesn’t always go away within 5 minutes. Can appear with no obvious exertion/trigger
Myocardial infarction in CVS
NSTEMI: The less severe form of MI, lacking ST elevation on the ECG. Is a result of partial/brief total occlusion of a coronary artery, and so leads to crushing chest pain that isn’t relieved with rest/GTN spray. Autonomic features (sweating, pallor, vomiting etc) are normally present, and the patient may have a sense of impending doom. ECG will be negative but as there has been some necrosis biomarkers will be positive
STEMI: The more severe form of MI, showing ST elevation of the ECG at the leads facing the infarct (ie V3 and V4 for anterior). Result of a total occlusion of a coronary artery, and leads to crushing pain that isn’t relieved with rest/GTN spray. Autonomic features, and accompanied with a sense of impending doom. Extensive necrosis of the area of myocardium supplied by the artery, re-opening of the blood supply within two hours is the only way to prevent/minimise necrosis
Acute coronary syndrome
A cluster of symptoms attributed to occlusion of the coronary arteries, which are described above in the MI section. It is a result of unstable angina, NSTEMI or STEMI, and there are ways to differentiate between the three
Treatment of the above varies from type to type but some common things include:
Angiography with a view to coronary bypass/stenting (elective procedure in the case unstable angina)
Coronary bypass/stenting (emergency surgery in the case of all STEMIs and some NSTEMIs)
GTN to increase venodilation to decrease the cardiac output of the heart and therefore demand (angina and unstable angina only, won’t stop occlusion that’s begun in an MI)
Long term post infarct medications to reduce either the clotting of the blood or the demand on the heart
Blood thinners: warfarin, low weight heparin, aspirin etc
Demand reducers: Ca2+ channel blockers, ACE inhibitors, diuretics, beta blockers etc
Can also give statins to reduce cholesterol synthesis and therefore (hopefully) the formation of atheromas
Unstable angina vs NSTEMI vs STEMI
Necrosis
ECG changes
Biomarkers
Unstable angina
No Necrosis
ECG changes - ST depression/none
Biomarkers - Negative troponin and creatine kinase
NSTEMI
Some Necrosis
ECG changes- ST depression/none
Biomarkers - Positive troponin and creatinine kinase
STEMI
Extensive Necrosis
ECG Changes - ST elevations in the leads facing infarct
Biomarkers - Positive Troponin and creatinine kinase
Heart failure
Syndrome of symptoms and signs that are a result of the heart being unable to pump enough blood to meet the physiological demands of the body. Caused primarily by IHD, but can have other causes, such as valve disease, chronic arrhythmias etc. One classic sign is a breakdown of the relationship described in Starling’s law – pumping becomes less efficient and so force of contraction no longer corresponds to stretch. Several systems/hormones play a huge part in the exacerbation of heart failure, but the key 4 are:
Autonomic nervous system
Baroreceptors sense down CO, so inc ANS input to heart
Inc CO increases demand on myocardium, damaging it further
NorAd stimulates cardiac hypertrophy, and by proxy, myocyte apoptosis and necrosis
Renin-angiotension- aldosterone system (RAAS)
Drop in BP/renal perfusion releases renin, causing eventual creation of angiotension II (AT2)
AT2 causes vasoconstriction (inc TPR inc BP leading to inc CO leading toinc demand in heart)
AT2 increases aldosterone release, so also causes Na+ retention, so inc circulating vol inc preload
Natriuretic hormones
Released by inc atrial stretch
Oppose the effects of RAAS
Promote vasodilation, Na+ loss and inhibit renin/aldosterone release
ADH
Normally stops water loss when dehydrated and encourages it when hydrated
However reverses it in HF, no ADH release leads to no water loss leading to inc circulating vol and inc preload
Some systemic changes are also seen:
Vasculature – vasoconstriction due to several different factors
Skeletal muscle – decreased blood flow due to vasoconstriction decreased muscle mass/strength, including diaphragm respiratory issues
Renal system – GFR preserved initially, but then deteriorates and so you get too much urea and creatinine in the blood, can be sorted by angiotensin II, but due to this you’re in trouble whether you give ACE inhibitors or not
Types of heart failure
Left sided
Causes
Hypertension, IHD, aortic stenosis etc
Symptoms Extertional dyspnoea Orthopnoea Paroxysmal nocturnal dyspnoea Can also have tachycardia, cardiomegaly, mitral regurgitation and in late stages, small amounts of pulmonary and peripheral oedema
RIght Sided
Causes
Usually 2ndary to left heart failure (pressure backs all the way up) or ASD/VSD, pulmonary stenosis, chronic lung disease etc
Symptoms
Raised JVP
Pulmonary oedema (worse when laying down)
Pitting oedema
Ascites due to venous congestion at liver
All symptoms relate to build up in venous/pulmonary systems
Congestive - Both Combined causes and symptoms
Treatments for heart failure
Prevention/modification – smoking, diet (SALT), alcohol, exercise, cholesterol etc
Treat underlying factor (if present/treatable)
Drug treatment (in order they’d usually be given) – ACE inhibitor and diuretic, beta blockers, spironolactone, digoxin
Surgery – Valve replacement (stenosis/regurgitation), pacemaker implantation, revascularisation (IHD), mechanical assist devices, heart transplant
Peripheral vascular disease
Usually caused by an atheromatous plaque in arteries and thrombus in veins. More common in the lower limbs. Leads to reduced blood flow to or from limb, which can manifest in a number of ways (intermittent claudication is a classic one). Also, the thrombus in a deep vein breaking off and causing a pulmonary embolism is always a big concern. Finally, you can get valve failure in superficial veins, leading to varicose veins (more notes in lower limb MSK summary)
Shock
Inadequate perfusion of all tissues throughout the body, leading to widespread ischaemia and death
When considering shock, consider the following equations to make life 10x easier:
o Mean arterial BP = CO*TPR
o CO = Heart rate*Stroke volume
o Also remember that Poiseuille’s law states that resistance decreases with radius ^4 (so a small vasodilation = large drop in TPR)
Shock is either due to a huge fall in cardiac output (cardiogenic, mechanical or hypovolaemic) or a huge fall in TPR (toxic or anaphylactic)
Cardiogenic shock
Arises from within the heart itself. Example causes include a STEMI or a serious arrhythmia (VT or VF). Leads to poor perfusion of coronary arteries and kidneys, exacerbating your problems. Usually find a raised JVP due to blood backing up through the pulmonary system and the right side of the heart as it can’t leave the heart. Patient’s hands will be cold (poor perfusion) and clammy (autonomic nervous system activates when it senses the fall in CO). Result of reduced cardiac output
Mechanical shock
Failure of the heart to pump due a factor outside that of the heart. Classic two reasons are a cardiac tamponade or a huge pulmonary embolism
Tamponade: The pericardium fills so the heart has no space to expand, reducing the pressure in all four chambers. As the blood cannot enter through the venae cavae, your central venous pressure (CVP) raises, but your arterial pressure stays low, as you’re not pumping anything out. Result of reduced stroke volume (electrical activity not altered)
Pulmonary embolism: Embolus occludes large pulmonary artery, leading to pulmonary
hypertension. This in turn leads to mechanical failure of the right ventricle as it can’t overcome the resistance. The inability of the right side to pump leads to decreased return to the left ventricle, leading to low left ventricle and low arterial pressure. CVP rises as the blood backs up in the venous system. Result of reduced stroke volume (electrical activity not altered)
