What is the SAN innervated by?
- Parasympathetic vagal fibres inhibit K+ channel closure via muscarinic cells - Sympathetic cadiac plexus fibres increase K+ channel closure in beta-adrenoreceptors
How long should PR interval last?How long should the QRS complex last?
What causes:The P wave?The QRS complex?The T wave?
Atrial depolarisationVentricular depolarisationDifferences in time of ventricle repolarisation
What are the ECG leads?
6 Limb leads: I, II, III, aVR, aVL, aVF6 Chest leads: V1, V2, V3, V4, V5, V6
What would you see on an ECG of AF?
No P wave on II or aVRIrregularly irregular QRS complexHigh heart rateIrregular R-R intervals
AFDefinitionRisk FactorsPathophysiologySigns & SymptomsDifferentialTreatement
Definition: Abnormal heart rhythm characterised by rapid and irregular beatingRisk factors: (CHA2DS2-VASc score) CAD, Hypertension, Age, Diabetes, Stroke (prior), MI, Heart failure, Valvular disease, Thyroid disorders, GeneticsPathophysiology: anatomically and histologically abnormal atria as a result of underlying heart disease. Progressive atrial fibrosis causes dilation and inflammation causes difference in refractory periods and promotes electrical re-entry. Multiple wavelets. S&S: palpitations, dizziness, SoB, swelling, fatigueDifferential: atrial flutter (saw tooth waves), Wolff-Parkinson-White Syndrome, atrial tachycardiaTreatment: Rate control: beta blockers (atenolol, bisoprolol), non-dihydropyridine CCB (diltiazem), cardiac glycosides (digoxin - if sedentry), amiodrine can be used if all others inaffective. Cardioversion: electrical shock, or e.g. amiodrone. Surgery: Ablation/maze proceedure, need pacemaker afterwards
Why are patients with AF commonly placed on anticoagulants?
Atria do not depolarise/contract in coordinated way. Blood pools in atria -> thrombus formation -> in circulation -> enters brain -> stroke or e.g. pulmonary embolism in lungs
What is alfuzosin and how does it work?
Antagonist of alpha-1 adrenergic receptor (GPCR), relaces muscles in prostate and bladder neck, used to treat BPH
What happens is the baroreceptors are not stretched enough?
Decrease in AP number and rate -> CN IX and X afferents -> NTS -> projects to:1. Nucleus ambiguus: cardioinhibitory centre is inhibited = decreases parasympathetic vagal output to SAN 2. Vasomotor sensor in rostral venterolateral medulla -> sympathetic output increases via: lateral reticulospinal tract to preganglionic neurons of sympathetic nervous system in intermediate part of thoracolumbar ventral horn -> postganglionic neurons to vasoconstrict arteriole SM via NA on alpha-1 adrenoreceptors -> raised TPR which increases BP
What happen if baroreceptors are stretched too much?
Nucleuus ambigious cardioinhibitory centre increases parasympatheric vagal output to SANVasomotor sensor sympathetic output is inhibited
What do the adenoreceptors do:alpha-1alpha-2beta-1beta-2?
contracts vascular SMpresynaptic nerve terminals, decreases NA release by negative feedback - decreases BPin heart, increases force and rate of contractionrelaxes bronchiole smooth muscle
Definition: a fall in systolic BP of at least 20mmHG or diastolic of at least 10mmHG within 3 minutes of standing upright. Occurs predominantly by delayed constriction of lower body BVs so blood pools in legs and less is returned to heart -> reduced CO and lower arterial pressure.Cause: Hypervolemia and intravascular fluid depletion, diseases (e.g. addison's disease - not enough steroid hormone produced), diabetes, parkinson's, pheochromocytoma, atherosclerosis), medication (diuretics, sedatives, adrenergic blockers, beta blockers, nitrates, TCAs, MAOIs), autonomic disordersTreatment: Lifestyle first (water, elevate head of bed etc.), then fludrocortisone (raises BP when given with high salt intake, corticosteriod, causes kidney to retain Na and thus blood volume. If unsuccessful: midodrine (vasopressor/antihypotensive agent, raises reduced BP, alpha-1 adrenergic agonist, used for autonomic dysfunction), or droxidopa (aa precursor, prodrug to NA, cross BBB, narrows BVs and increases BP)
Why might alfuzosin cause postural hypotension?
Sympathetic NS keeps arterioles slightly contracted. Alfuzosin blocks sympthetic NS (it is an alpha-1 adrenergic receptor antagonist so decreases blood pressure by ihibiting vasoconstriction usually initated by the baroreflex upon postural change). Blood pools in lower limbs -> decreases BP
How do you calculate MAP?
MAP = DIASTOLIC + 1/3 PULSE PRESSURE (PP is SYSTOLIC - DIASTOLIC)
What is amiloride and what is it used to treat?
How does it work?
A potassium-sparing diuretic ofen used for hypertension and congestive heart failure. They are competitive antagonists and compete with aldosterone or block Na+ channels (ENaC). Thus Na/K sites do not work, Na+ is not reabsorbed, and K+ and H+ is not secreted.
Often used with loop diuretics that would otherwise lower K+ levels dangerously.
What does SCNN1B encode?
Beta subunit for epithelium ENaC (heterotrimer) involved in generating APs in neurons an body fluid regulation. Strongly inhibited by amiloride.
Signs & Symptoms
Definition: autosomal dominant genetic disorder, early severe hypertension involving abnormal kidney function with excess Na+ reabsorption and K+ loss from renal tubule.
Cause: proline -> leucine mutation on c terminal of beta and gamma subunit of ENaC (normally transports Na into cells). It is no longer degraded by ubiquitin proteasome system becuase PY motif altered so Nedd4 no longer recognises channel). This increases ENaC activation in the CD -> "hyperaldosteronism-like state" -> increased Na and H2O reabsorption -> increased extracellular vol -> hypertension. There is excretion of K+.
Signs & Symptoms: early onset severe hypertension, hypokaleamia, metabolic alkalosis (decreased H+ conc), weakness
Diagnosis: blood test and genetic testing
Treatment: low Na diet, potassium-sparing diuretics specific for Na channel e.g. amiloride and triamterene
What would you see on a blood test of someone with Liddle Syndrome?
Low plasma renin and aldosterone levels
Elevated serum Na+
Elevated serum bicarbonate (low extracellular K+, so K+ leaves cells, and H+ enters, raising blood pH)
Reduced serum K+
What happens if there is persistant low Na in the DCT?
persistant low Na in DCT -> macula densa signals to juxtaglomerular cells -> renin released to efferent arteriole -> cleaves angiotensinogen from liver to angiotensin I -> to lungs -> cleaves by angiotensin-converting enzyme (ACE) to angiotensin II:
1) vasoconstrictor of systemic arterioles -> increases afterload, BP and GFR
2) aldosterone secretion from adrenal cortex -> acts on DCT receptors (ENaC and Na/K pump expression) and stimulates Na resorption -> H2O reabsorption -> blood volume increase -> increases preload, BP and GFR
Describe the actions of aldosterone in the kidney
- Upregulation and activation of basolateral Na/K pumps
- Upregulation of ENaCs
- Increase in K+ secretion
- Increase Na reabsorption and thus H2O retention
Another name for ADH?
How can hypertension lead to development of L ventricular hypertrophy?
Hypertension -> increased afterload -> heart works harder to eject same volume of blood in systole -> over time this may lead to thickening of myocardium
Describe transcellular pathway for Na reabsorption within the cortical and medullary tubule in kidney.
1) Passive Na entry into cell from tubule lumen across apical membrane via epithelial Na channels via ENaC facilitated by electrochemical gradient
2) Active extrusion of Na out of cell across basolateral membrane mediated by Na/K ATPase pump
VC is a measurement of what?
FEV1 is a measurement of what?
FVC is a measurement of what?
Greatest vol of air that can be expelled from lungs after taking deepest poss breath.
Vol exhaled at end of first second of forced expiration
VC determination from max forced respiratory effort
What is the main muscle of respiration?
Where is the main site of airway resistance?
Small bronchi and bronchioles
Describe the function of the alpha-1 antitrypsin enzyme in the lung
It's a protease inhibitor - proteases are released by inflammatory cells which break down elastin. Lack of the enzyme may lead to emphysema.
What types of WBC are found in alveoli?
Neutrophils, eosinophils. + mast cells.
Describe the airway tree
Mouth and nose -> parynx -> trachea -> main bronchus -> lobar bronchi -> segmental bronchi -> conducting bronchioles -> terminal bronchioles -> respiratory bronchioles -> alveolar ducts -> alveolar sacs
Divides 23 times
What muscles are involved in:
a) quiet inspiration
b) quiet expiration
c) deep inspiration
d) deep expiration
a) dipahragm, external intercostals
b) passive (recoil)
c) scalene, SCM, pectoralis minor
d) interosseus part of internal intercostals, abdominal, serratus posterior inferior
How can you distinguish obstructive and restrictive lung disorders from FEV1, FVC and the FEV1/FVC ratio?
FEV1: reduced (<80%) in O and R
FVC: reduced but to a lesser extent in O than R (<80%)
FEV1/FVC: Reduced (<0.7) in O, normal (>0.7) in R
What 2 main lung diseases does smoking cause?
How does smoke affect the lungs?
What happens if a pt quits smoking?
COPD and lung cancer
Overproduction of mucus via promotion of goblet cell growth, paralyses cilia, asthma trigger
Mucocillary clearance, goblet cell numbers decline, low FEV1 may improve, reduced risk of lung cancer (but never back to normal)
State the normal arterial Hb saturation for a healthy adult.
State 2 lung function tests that would help diagnose asthma.
How can asthma be diagnosed from other obstructive diseases e.g. COPD during lung function testing?
1. spirometry (FEV1/FVC) - <80% of predicted 2.Peak expiratory flow test (20% or more difference in PEF rate on at least 3 days in a week for at least 2 weeks)
Reversibility testing. Does breathing improve on or after administration of medication (inhaler)?
LIst 4 signs that could indicate a severe asthma attack
Define hypocapnia and explain why an asthmatic patient may have it.
1. cyanosis 2. Tachycardia 3. peak expiratory flow rate <33% 4. predicted 4. SaO2 <92%. Also silent chest, feeble respiratory effort, repiratory rate >25/min, inability to complete sentances in 1 breath
Abnormally low arterial CO2. They are breathless and hyperventilating but still have good minute ventilation and are clearing CO2 from the blood.
Name 1 class of drug that could be used for treatment of asthma and describe its main mechanism of action,
Inhaled short acting beta-2 adrenergic receptor agonist: mimics sympathetic bronchodilator action. Activates adenalate cyclase to increase cAMP andmay also reduced mediator release from inflammatory cells and airway nerves.
Inhaled corticosteroids (ICSs): antiinflamm. actions reduce oedema of airways and bronchial gland secretions thus widening airways
Muscarinic receptor antagonists: bronchodilators, blocks ACh release by parasympathetic nerves and thus blocks bronchoconstriction and hypersecretion of mucus
Orally administered leukotrine receptor antagonists
Differentiate between blue and brown asthma inhalers.
What can hypocapnia cause?
Blue: immediate rescue when experiencing symptoms like chest tightness or SoB, contains salbutamol
Brown: contain low doses of steroids that help reduce airway sensitivity. Used regularly should decrease liklihood of attacks by building up resistance to triggers.
Vasoconstriction leading to cerebral hypoxia -> transient dizziness and anxiety. Can also cause alkalosis leading to lowered plasma Ca2+ ions and increased nerve and muscle excitability = pins and needles, muscle cramps in extremities.
What phenotypic abnormality occurs specifically in alpha thalassaemia?
Describe the term reticulocyte.
What do elevated levels in the blood film indicate and why are there raised levels in beta thalassaemia major?
Affected at birth (beta = about 6m after). Also microcytic, hyperchromic anaemia, and a decreased synthesis of the alpha Hb subunit.
Immature large RBC with reticular meshwork of rRNA but no nucleus, visible under microscope with certain stains.
Number and % of reticulocytes in blood indicate erythropoiesis level. Beta thalassaemia major: loss/destruction of mature RBC (haemolysis and resulting anaemia) accompanied by ineffective by increased prod of RBC (erythropoiesis)
What is the major form of Hb in patients with beta thalassaemia major?
Explain why a patient would have an enlarged spleen and liver.
Name 2 main forms of treatment for beta thalassaemia major.
Excessive red cell breakdown. Extramedullary haemopoiesis (outside bone medulla)
Explain the role of the following in the regulation of blood coagulation:
a) degrades serine proteases thrombin and other coagulation factors e.g. IXa, Xa, XIa and XIIa.
b) proteolytically cleaves fibrin/inhibits excessive fibrin formation in blood clots
c) acts on platelets to prevent release of platelet granules (inhibits activation of additional platelets) if prolonged endothelial damage
How is heparin normally administered and why is this route chosen?
List 3 major signs of DVT
List 3 categories of factors that are thought to contribute to DVT
Parentally (outside of digestive tract) becuase it's not absorbed from the gut, so given in subcutaneous IV injection.
Pain, swelling, warmth (redness, engorged superficial veins)
Virchow's Triad: venous stasis, increase in blood hypercoagulability, damage to endothelial wall
What is the treatment for DVT?
What is pitting oedema?
What are some risk factor for DVT.
Start on heparin and give warfarin (2-3 days to work) once diagnosed. Check INR later and once 2-3 take off heparin and keep on warfarin. No warfarin if pregnant!
Accumulation of interstital fluid e.g. due to DVT or R sided heart failure. Pitting goes down because fluid can reenter veins.
Age, major surgery, cancer, pregnany, oral contraceptives and HRT, inactivity, inherited
How is DVT diagnosed?
D-dimer test (fibrin degradation product present in blood after a blood clot is degrated by fibrinolysis). +ve result = abnormally high FDP in blood - has been a significant clot. -ve = unlikely you have a clot. If +ve then ultrasound (good for proximal but can't see distal too well). If DVT suspected, Well's Score also used (>2 = likley). Gold standard: contrast venography.
What is a serious complication of DVT?
Briefly describe the venous anatomy of the leg.
Deep veins: dorsal venous arch -> anterior tibial.
Medial and lateral plantar veins -> post. tibial and fibular veins.
Ant. and post tibial and fibulat unite -> popliteal -> femoreal -> external iliac
Profunda femoris -> femoral vein.
Superficial veins: dorsal venous arch -> great saphenous -> femoral
Small saphenous -> popliteal
Where does BNP originate and what is the significance of its blood level?
Why might heart failure give a raised JVP?
Secreted from ventricles when stretched, and promotes natiuresis and vasodilation. Increased levels (>100pg/ml) indicate overstretch/enlargement of ventricles and heart disease
R heart failure -> R. heart can't pump out blood delivered to it so BP buids up in veins and circulation (increasd venous hypertension)
What 2 imaging tests might be used for a patient with heart failure, and what would be seen?
X ray: heart enlargement, evidence of pulmonary oedema
Echocardiography: dilated, poorly contracted L ventricle e.g.
List 3 classes of drugs used for heart failure and explain how they work.
1) ACE-I: decrease BP and Na+ retention = decreased preload and afterload on heart. Can also use ARBs instead.
2) Beta-blockers: as long as no evidence of T2 diabetes (b/c they can block insulin release) or metabolic syndrome, decrease work of heart by decreasing contractile force
3) Diuretics: most likely loop e.g. furosemide, decrease venous blood volume, preload and workload
Heart failure can be divided into what 2 types based on ejection fraction?
1) HF due to reduced EF - systolic heart failure (EF <40%)
2) HF with preserved EF - diastolic HF
What 5 features (ABCDE) might you see on a CXR of a patient with heart failure?
A: Alveolar oedema (batwing)
B: Kerley B lines
D: Dilated, prominent upper lobe vessels
E: Pleural effusion
Describe the consequences of untreated hypertension on the heart?
Describe the cause of angina.
Higher levels of arterial pressure puts mechanical stress on the arterial walls and increases heart workload, which can lead to ventricular hypertrophy. Prolonged and severe hypertension cna result in ventricular or heart failure.
Atherosclerotic obstructive coronary artery disease, restricted blood flow to myocardium and reduction in O2 delivery (hypoxia) in myocardial tissue.
Why does pain associated with stable (exertional) angina often occur in, or radiate to, the throat, neck and L upper arm?
Describe the pathology and presentation of Prinzmetal's (variant) angina.
We have no sensory awareness of internal organs. Pain fibres from the heart enter spinal cord through the posterior roots of the upper 4 thoracic nerves (T1-T4), thus pain is felt in the sensory dermatomes (or sensory receptive fields on the throat, neck, and upper arm) supplied by those spinal nerves.
Caused by vasospasm of a coronary artery. Unlike stable angina it occurs spontaneously at rest
Describe the administration and action of nitrates in the treatment of stable angina.
What role do statins play in angina?
Nitrates (e.g. glyceryl trinitrate - GTN) can be given sublingually (under tongue) with rapid absorption and uptake into blood stream. It relaxes SM -> vasodilation and increase in blood flow. Also decreases platelet aggregation.
Reduce blood cholestrol levels (and LDL) and should prevent further damage to the coronary arteries, thus reducing risk of a MI or stroke. Competitivly inhibit HMB-CoA reductase (1st enzyme of mevalonate path) used to make cholestrol.
What might you see on an ECG of a person with angina?
Which organs are normally first infected by TB and why?
Give the main reason why TB is difficult to treat with drugs.
What is usually the first symptom of pulmonary TB, and list 4 others that may present.
Lungs because TB prefers high levels of O2 to grow
Waxy mycolic acid capsule/CW outer layer which is v. resistant to drug penetration
First: cough. Others: weight/appetite loss, fever, night sweats, chills, cough up blood
Give 4 methods for TB diagnosis.
What 4 drugs make up the normal 1st line treatement of TB?
What are 2 second line drugs for MDR TB?
Mantoux test. IGRA. Sputum cultures. Nucleic acid amplification tests/line probe assay. Staining (Ziehl-Neeson/Auramine)
Isoniazid, rifampicin, pyrazinamide, ethambutol.
Aminoglycoside (e.g. Amikacin), Fluoroquinolone
What is a Ghon focus?
Briefly how does TB affect the lungs once breathed in?
Ca salts deposited, seen on CXR, upper part of lower lobe or lower part of upper lobe usually.
MTB reach pulmonary alveoli -> invade and replicate in endosomes of alveolar macrophages (which attempt to eliminate it via phagocytosis with ROS and acid but it's protected by its waxy mycolic acid capsule) -> MTB eventually kills the macrophage. Other macrophages, T and B lymphocytes and fibroblasts aggregate to form granulomas and surround infected macrophages -> fuse to form ginat multinucleated cell with necrosis in centre of tubercles. Immune response supressed b/c macrophages and dendritic cells in granulomas can't present antigens to lymphocytes. During active TB if granuloma ruptures, material can be coughed up. If enters blood can establish infectious foci throughout body = milliary TB.