Practice MCQ PDF

Human fungal pathogens Superficial mycoses ○ Malassezia furfur Cutaneous mycoses ○ Tinea capitis ○ Tinea cruris ○ Tinea pedis Subcutaneous mycoses ○ Sporotrichosis ○ Mycotic mycetoma Systemic mycoses ○ Candida ○ Cryp...

Human fungal pathogens Superficial mycoses ○ Malassezia furfur Cutaneous mycoses ○ Tinea capitis ○ Tinea cruris ○ Tinea pedis Subcutaneous mycoses ○ Sporotrichosis ○ Mycotic mycetoma Systemic mycoses ○ Candida ○ Cryptococcus ○ Histoplasmosis ○ Aspergillus Fluconazole Fungistatic Dose dependent fungicidal Excreted largely unchanged in urine so good in candiduria Terbinafine = use half normal dose if eGFR less than 50mL/minute/1.73m2 Polyenes Nystatin = local oral, oropharyngeal and perioral infections Amphotericin B = IV for systemic Highly protein bound Penetrates poorly into tissues Less toxic ampho B = ampho B liposomal formulations 5-FC + ampho B Amph B = increases cell permeability 5-FC = forms false nucleotide Disrupting nucleic acid and protein synthesis 5-FC = hepatotoxicity + blood disorders Echinocandins = fungicidal against candida but fungistatic against aspergillus Griseofulvin Dermatophytosis Causes disruption of mitotic spindle, inhibiting mitosis Induces hepatic CYP450 Causes dyspepsia + fatigue  Drug class MoA Pharmacokinetics Tri-azoles Block CYP450 and sterol 14 alpha Fluconazole = good penetration into demethylase in cell wall CSF, oral, urine excretion Itraconazole = capsules need acidic environment (stomach), hepatotoxic, drug interactions Voriconazole = drug interactions Posaconazole = for invasive infections unresponsive Terbinafine Inhibits squalene epoxidase that accumulates toxic sterols in cell wall Polyenes Inhibit form pores in fungal membrane Ampho B = IV infusion Nystatin = locally oral Not absorbed when given by mouth Flucytosine Inhibit protein synthesis (5-FC) Echinocand Inhibit 1,3-beta-glucan in cell wall IV only ins polysaccharide Griseofulvin Inhibit fungal mitosis Treatment for invasive candidiasis Echinocandin Fluconazole - clinically stable Ampho B - for CNS candidiasis or alt Voriconazole - fluconazole resistant candida, oral therapy, or intolerant to ampho B + echinocandin Histoplasmosis = parenteral itraconazole or ampho B Aspergillosis treatment ABPA = steroids + itraconazole Aspergilloma = surgery + itraconazole/voriconazole Invasive aspergillosis = voriconazole or liposomal ampho Classifying viruses = baltimore classification system - based on mechanisms of mRNA production HIV, adenosine, tenofovir HSV, aciclovir, guanine  HIV Contains reverse transcriptase = RNA dependent DNA polymerase, making a DNA copy of viral RNA DRUG TYPE TARGET MOA EXAMPLE/FIRST LINE Env gp120 and Effects cell entry env gp41 NRTIs Reverse Compete with reverse transcription, preventing viral Tenofovir - transcriptase, pro-DNA synthesis adenosine RNA → DNA NNRTIs Reverse Bind directly to RT causing conformational change Efavirenz transcriptase, which stops enzyme working RNA → DNA Integrase inhibitors Integrase Integration of provirus DNA into host chromosomal Dolutegravir DNA Protease inhibitors Protease Cleaves initially translated polypeptides into Darunavir, with PK functional viral proteins enhancer Antiretroviral therapy in HIV = 2 NRTIs and 1 from NNRTI, PI, or integrase inhibitor Undetectable + non transmissible Chronic HBV Immunomodulatory - pegylated IFNalpha Nucleotide therapies - active against RT step ○ Tenofovir Influenza = neuraminidase inhibitors Oseltamivir - oral Zanamivir - inhalation Competitively binds NA bindings site, preventing viral release Aims of therapy Viral eradication = HepC + influenza Long term suppression = HIV + HepB Management of flares = HSV Asthma = narrowing, reversible, hyper-responsiveness, inflammation 90% of inhaler swallowed, 10% deposited in lung Drug type MoA Examples Step Beta 2 agonists - Stimulate bronchial smooth muscle SABA = salbutamol 1 = intermittent receptors, relax+dilute = reduce LABA = salmeterol reliever breathlessness 3 = Initial add on - Inhibits mediator release from mast cells + TNFalpha release from monocytes - Increases ciliary action of airway epithelial cells - airway clearance Glucocorticoids - Bind to receptor, modify immune Beclomethasone + 2 = regular response budesonide preventer - Inhibits cytokine formation - Inhibits activation + recruitment of inflammatory cells - Inhibits inflammatory prostaglandins + leukotrienes = less mucosal edema - Decreased mucosal inflammation, widens airways, reduces mucus secretion LTRA - Block bronchoconstriction CysLT1 effects Montelukast 4 = Additional in airways = bronchodilation controller therapy - Reduce eosinophil recruitment, less inflammation, epithelial damage, and airway hyper-reactivity Methylxanthines - PDE inhibitors Theophylline + 5 = specialist - PDE involved in inflammatory cells - aminophylline therapies inhibition reduces inflammation - Increases intracellular cAMP in bronchial smooth muscle = bronchodilation - Blocks adenosine receptors = bronchodilation - Activates histone deacetylase = immunomodulatory SAMAs + LAMAs - Bronchodilation SAMA = ipratropium 5 = specialist - Decreased mucus secretion LAMA = tiotropium - therapies - Increased mucociliary clearance M3 Monoclonal Severe persistent allergic asthma Omalizumab 5 = specialist antibodies - Steroid sparing therapies - Anti IgE treatment Acute moderate asthma = 50-75% PEF Acute severe asthma = 33-50% PEF + resp 25/min + HR 110 bpm + no sentences Life threatening asthma = under 33% PEF Near fatal = raised PaCO2 / ventilation Acute severe asthma Oxygen SABA via neb IV/oral steroids = hydrocortisone or prednisolone Abx? SAMA via neb? No improvement ○ IV magnesium sulphate ○ Neb → IV SABA or IV aminophylline COPD LAMA or LABA LAMA + LABA LABA + LAMA + ICS Others ○ Methylxanthines ○ PDE4 inhibitor - roflumilast - for severe repeated exacerbations ○ Long term O2 High risk COPD pt 2+ exacerbations in one year FEV1 less than 50% Acute severe COPD exacerbations SABA or SAMA via neb Oral prednisolone Abx? 24-28% O2 Extreme = NIV, intubation Resistance mechanisms Enzymatic inactivation - beta lactamases Enzymatic addition - aminoglycosides Impermeability - beta-lactams Efflux - tetracyclines Alternative pathway - MRSA mecA Altered target - rifampicin Resistance transmission Transformation - penicillin in s.pneumoniae Conjugation - beta lactamases Transposons - erythromycin in s.pyogenes ○ Allow genome plasticity Superbug - gained resistance to critical or multiple abx, e.g., MRSA, VRE, GISA, ESBLs CF = autosomal recessive, defect in gene coding for CFTR on chromosome 7, coding for energy dependent chloride channel Diagnosis = sweat test or newborn screening ○ Pilocarpine iontophoresis, chloride conc = more than 60 mmol/L Exacerbation characterised by 2 or more ○ Change in sputum volume or colour ○ Increased cough ○ Increased malaise ○ Anorexia ○ Peak flow more than 10% drop ○ X ray changes ○ Increased dyspnoea Mutation classes ○ Premature stop codon ○ folding/trafficking defect ○ Narrow channel ○ Gating defect ○ Decreased stability ○ Splicing defect Novel therapies ○ Suppressors of premature stop codons Treats nonsense mutations Aim to read thru these stop codons and allow ribosome to continue translating a full length, functional CFTR protein ○ CFTR correctors Helps misfolded CFTR protein reach cell surface ○ CFTR potentiators Enhance function of CFTR proteins already present at cell surface Spirometry measures FVC = total volume forcibly exhaled after full inspiration ○ Indicates lung size ○ Reduces in restrictive lung disease FEV1 = volume forcibly exhaled during first second of a forceful exhalation ○ Indicates degree of obstruction ○ Reduced in obstructive lung disease FEV1/FVC ratio Reduced in obstructive lung disease = less than 0.7 Normal in restrictive lung disease = more than 0.7 Important asthma mediators IL4,5,13 Leukotriene B4 and Cysteinyl-leukotrienes Tissue damaging eosinophil proteins COPD = persistent airflow limitation, progressive, enhanced chronic inflammatory response in airways to noxious particles or gases COPD pathophysiology Inflammation + fibrosis of bronchial wall Hypertrophy of submucosal glands + hypersecretion of mucus Loss of elastic, parenchymal lung fibres - emphysema Alpha1 antitrypsin deficiency COPD at 45 years Lower zone dominant emphysema Liver enzyme counteracting proteinases = tissue damage Autosomal co-dominance Decreased gas transfer in restrive lung disease If disproportionate to decreased lung volumes, consider co existent emphysema or pulmonary hypertension Prognostic indicators for restrictive lung disease 6 minute walk test Changed FVC over 6 months Composite physiological scores GAP score in IPF IPF most common + most feared + most progressive Almost always diagnosed on CT scan Broad spectrum penicillins Ampicillin + amoxicillin Extended spectrum penicillins Carbenicillin Good for pseudomonas aeruginosa Beta-lactam resistant penicillins Methicillin Carbapenems Binds PBPs permanently, acylating them Cephalosporins Oral = cephalexin Overuse = C.diff emergence Glycopeptide Active against cell membrane, targeting C terminal D-ala-D-ala, preventing transglycosylation + transpeptidation Vancomycin - interferes with peptidoglycan elongation, good for MRSA Cyclic peptide Targets C55-isopropyl pyrophosphate Bacitracin - ointment for skin + eye strep and staph infections Phosphonic acids Targets MurA protein Fosfomycin Lipoproteins Targets cell wall stress stimulon, calcium dependent membrane depolarisation Daptomycin Bacterial folate antagonists Inhibits folate pathway Sulfonamides + trimethoprim = cotrimoxazole = toxoplasmosis treatment Sulphonamides + pyrimethamine = drug resistant malaria + toxoplasmosis Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit Erythromycin Clarithromycin - QT prolongation Clindamycin - pseudomembranous colitis (c.diff) Aminoglycosides Diffuses into cytoplasm to bind to bacterial ribosomes Streptomycin Good for serious and rare conditions - so reserved Do not give in severe sepsis as can cause acute renal failure Tetracyclines Prevents tRNA attachment to acceptor site on mRNA-ribosomal complex Good for chronic acne Tigecycline Chloramphenicol Inhibits peptide bond formation Aplastic anaemia risk Meningitis good for Topoisomerase IV Catalyses ATP dependent relation of … DNA gyrase Breaks DNA and repairs them Fluoroquinolones Ciprofloxacin Best in enterobacteriaceae Polymyxins Branches chain decapeptides with cationic detergent properties Topical for cutaneous pseudomonas infections Nitrofurans Nitrofurantoin Metronidazole Anaerobic - generates toxic radicals damaging bacterial DNA Effective in therapy of pseudomonas colitis Treat H.pylori infection, with omeprazole, amoxicillin Common cold = rhinovirus Acute pharyngitis + tonsillitis Virus = EBV, CMV Bacteria = strep pyogenes Always IgM serology for resp tract infection test Glandular fever (EBV) complications Burkitt's lymphoma Nasopharyngeal carcinoma Guillain barre syndrome Parotitis = mumps virus Complications ○ CNS ○ Epididymo-orchitis Acute epiglottitis = H.influenzae - life threatening, no throat swab + give IV ceftriaxone or chloramphenicol Diphtheria - bull neck, give penicillin or erythromycin Whooping cough = catarrhal (contagious, 1 week, erythromycin) and paroxysmal stage (whoop cough, 1-4 weeks) Bordetella pertussis Acute bronchitis = rhinovirus Chronic bronchitis = anatomical disturbance of resp system Immune deficiency = SCID Ciliary deficit = kartagener syndrome, smoking Excessively thick mucus = CF Bronchiolitis = RSV Measles = koplik's spots Can cause giant cell pneumonia in immunocompromised, fatal Give ribavirin if severe Antigenic drift in influenza Small point mutations in H and N antigens occurring constantly Allows virus to multiply in individuals with immunity to preceding strains New subtype can reinfect community Antigenic shift in influenza Sudden major change based on recombination between 2 different strains when they infect same cell Produce virus with novel surface glycoproteins New strain can spread thru previously immune populations - new pandemic Cor pulmonale Right sided heart hypertrophy Severe emphysema Congestive heart failure Hypersensitivity pneumonitis - extrinsic allergic alveolitis Type III + IV Young people Sarcoidosis Granulomas Bilateral hilar lymphadenopathy Increased ACE Benign lung cancer = mesenchymoma, papilloma, inflammatory myoblastic tumour Malignant lung cancer  Malignant primary epithelial = metaplasia and dysplasia - commonest ○ Squamous, adenocarcinoma, small cell undifferentiated, carcinoid, large cell undifferentiated, molecular Malignant secondary = sarcoma, renal carcinoma, lymphoma NSCLC - squamous = 40% NSCLC - adenocarcinoma = 40%, more amenable to immune checkpoint treatment NSCLC - adenocarcinoma, bronchoalveolar = intrapulmonary dissemination SCLC - undifferentiated = neuroendocrine, paraneoplastic effects Paraneoplastic effects In undifferentiated SCLC Bioactive amines or peptides produced - ADH, PTN like peptides, ACTH Signs + symptoms not directly caused by the cancer Immunological Acanthosis nigricans - EGF Finger clubbing Increased epo Immune complex GTN Molecular treatment EGFR amplification ALK rearrangements Assessment of PDL1 ○ Immune checkpoints ○ Checkpoint inhibition = so treatment would be to block these signals Mesothelioma Asbestos - crocidolite 20-40 year lag Male 5:1 (same as squamous carcinomas) Fibrous pleural plaques Carcinoid Malignant spectrum Typical = less aggressive Atypical = more aggressive Resp acidosis causes Resp depression Emphysema Chronic bronchitis Lung collapse Drugs reducing resp drive - morphine  Hypoventilation Ventilation perfusion mismatch Resp alkalosis causes Hyperventilation as blowing off more CO2 ○ Brain stem damage ○ Infection driving fever High altitude - reduced O2 stimulates ventilation via peripheral chemoreceptor response Hypoxic drive in pneumonia Metabolic acidosis causes Bicarb loss - diarrhea Aspirin overdose Ketogenesis - DKA Failure to secrete hydrogen, e.g., renal failure Metabolic alkalosis Vomiting - loss of hydrogen chloride from stomach Ingestion of alkali substance Potassium depleting - diuretics Base excess From pH and pCO2 Amount of acid required to restore 1 litre of blood to its normal pH at pCO2 of 5.3kPa Bicarb predominant Normal range +/-2mmol/l Significant negative = metabolic acidosis Significant positive = metabolic alkalosis Anion gap Sum of routinely measured cations in venous blood minus routinely measured anions Always a gap Increased gap = presence of metabolic acidosis Normal anion gap = 12-16 Normal anion gap, without potassium = 8-12 (sodium + potassium)-(chloride + bicarb) Minute volume = tidal volume x resp rate SARS-COV2 ssRNA virus, no.7 Cell entry - via ACE2 Covid signs on CXR = bilateral sings, fine creps  Prognostic biomarkers in covid Lymphopenia Ferritin LDH D-dimer Acute management of covid STRAPP ○ Steroids - dexamethasone ○ Tocilizumab ○ Research ○ Antivirals - remdesivir ○ Proning ○ Positive pressures Treatment pathways - for high risk list Line Name Administration Setting given 1st Paxlovid Oral Outpatients, early infection, community hospital 2nd Sotrovimab IV Hospital, day case, need to manage anaphylaxis 3rd Remdesivir IV, 3 day course Hospital, day case, need to manage anaphylaxis 4th Molnipiravir Oral Acute severe COVID - drugs for patients with covid + requiring oxygen to maintain sats Dexamethasone ○ 6mg OD for 10 days Tocilizumab ○ Added when hypoxia/hyperinflammation/critical illness Remdesivir + baricitinib ○ 5 day course Type What is it? Use Examples Live Organism capable of normal infection + replication Not used against MMR + polio - pathogen that can currently given in cause severe Gaza 2024 disease Attenuated Organism live, but ability to replicate + cause MMR + polio - disease reduced by chemical treatment or growth currently given in adaption in non human cell lines Gaza 2024 Recombinant Genetically engineered to alter critical genes - often HepB vaccine can infect + replicate but does not induce associated disease Killed Organism killed by physical or chemical treatment B.pertussis + so incapable of infection/replication but still cause typhoid strong immune response DNA/mRNA Naked DNA or mRNA injected - host cells pick up Pfizer for covid19 DNA + express pathogen proteins stimulating immune response Extract Materials derived from disrupted or lysed organism When risk of Flu + pneumococcal organism surviving + diphtheria + inactivation steps tetanus Dendritic cells in vaccination - causes activation of T cells and initiation of adaptive immune responses Also express pattern recognition receptors, members of TLR TLR4 = detects lipopolysaccharide, heat shock protein TLR9 = detects CpG - cytosine phosphate guanosine, bacterial DNA CpG in HepB + Flu vaccines = increased antibody or IFN gamma secretion HAI is not present on admission but occurs over 48 hours after admission 1.1% of NHS scotland budget Average length of stay = 7.8 days Contact precautions C.diff, MRSA, S.pyogenes Droplet precautions More than 0.5 microns N.meningitidis, mumps, rubella, covid, flu, RSV, all resp Airborne precautions Less than 0.5 microns FFP3 mask for all aerosol generating procedures TB, chicken pox, measles Invasive medical devices - long or short term, all break skin or mucous membrane barrier Indwelling prosthetic devices long term devices which are buried into tissue under skin E.coli = most common cause of bloodstream infections S.aureus in VADs is a concern Acidosis Rise in PCO2 Fall in bicarb Alkalosis Fall in PCO2 Rise in bicarb Alveolar ventilation = rate at which new air reaches areas, major factor determining O2 + CO2 conc in alveoli Pleural pressure less at apex than the base, and with inspiration, it decreases further Underinflated Smaller alveoli at base more compliant So receive more tidal volume Over Inflated Expanded alveoli at top have lower compliance Receive less tidal volume Pulmonary capillary pressure = low = 7mmHg Interstitial fluid pressure = -8mmHg Colloid osmotic pressures of pulmonary interstitial fluid = 14mmHg Zone 3 receives a continuous blood flow during the entire cardiac output Zone 1 receives no blood flow during all portions of cardiac cycle Ventilation-perfusion matching = relationship between air reaching the alveoli (ventilation) and blood flow through the pulmonary capillaries (perfusion) Ventilation exceeding perfusion = over 1 Perfusion exceeding ventilation = under 1 Normal = 0.85 Causes of hypoxaemia Anatomical shunt - cyanotic congenital heart diseases most common Physiological shunt - atelectasis most common V/Q mismatching - chronic bronchitis, asthma Hypoventilation - muscular dystrophy or diaphragmatic paralysis Absolute polycythaemia Primary ○ Haematocrit levels rise due to overproduction of RBCs in bone marrow ○ Mutation in 2nd messenger system - JAK-STAT ○ Most common type = PV Secondary ○ Increase of epo in response to hypoxia ○ Low O2 levels = mRNA for epo increased + epo produced ○ Causes Hypoxia due to high altitude = 3000m plus Local renal hypoxia or renal artery stenosis Congenital high affinity haemoglobin Tumours producing epo, e.g., renal, uterine Drug, e.g., androgens + abuse of therapeutic epo Smoking, partly due to CO exposure Altered O2 sensing ○ Mutations in genes that bring about increased epo production, e.g., chuvash polycythaemia Treatment for chronic excess epo = removal of 500ml bags of blood to reduce haematocrit to less than 52%-55% JAMA 1944 - must always consider complete bed rest as highly non physiologic and definitely hazardous form of therapy, to be ordered only for specific indications and discontinued as early as possible Experience of a patient Hospital environment Entering the role of a pt Loss of control - therapeutically and organisationally desirable ○ Behavioural control ○ Cognitive control  ○ Decision control ○ Informational control Depersonalisation Institutionalisation Children's tendency to show separation distress peaks at 15 months Issues relating to children as inpatients - separation distress, illness misconceptions, faulty representations Stages of separation ○ Protest, despair, detachment Impact of hospitalization on child behaviour ○ Regression, nightmares, irritable Centre Location Role Importance VRG Nucleus ambiguus Forced respiration Provides powerful and nucleus Mixed inspiratory + expiratory signals to retroambiguus expiratory abdominal muscles during heavy In increased expiration  ventilatory drive, contributes to extra resp drive DRG Nucleus tractus Controls basic rhythm solitarius of breathing Emit repetitive inspiratory neuronal AP bursts Receives sensory input from thorax + abdo organs Pneumotaxic Dorsally in nucleus Modulates rhythm by Weak signal = parabrachialis inhibiting DRG, inspiration over 5 medialis of upper promoting expiration seconds pons Strong signal = inspiration under 0.5 sections Apneustic Stimulates DRG to prolong inspiration Hypercapnia and acidosis detected by central resp centres Hypoxia detected by peripheral chemoreceptors in carotid and aortic bodies, also detects hypercapnia and acidosis Carotid bodies have multiple highly characteristics glandular like cells - glomus cells - that synapse directly or indirectly with nerve endings Hering breuer reflex Helps prevent over inflation of lungs Stretch receptors in muscle of walls of bronchi + bronchioles Sends signals thru vagus to DRG neurons when lungs overstretched Feedback response initiated = turn off inspiratory ramp Reflex not activated until TV increases to 3x normal = 1.5L/breath Type of slowly adapting pulmonary stretch receptors C fibre receptors In alveoli + conducting airways, close to capillaries Respond to chemical + mechanical stimuli Become stimulated by ○ Pulmonary oedema ○ Pneumonia ○ Congestion ○ Endogenous chemicals, e.g., histamine  ○ Glottis closed by vagal efferent activity ○ Forced expiration against closed glottis ○ Pressure increases Rapidly adapting pulmonary stretch - irritant - receptors Cough flex Preparatory inspiration Compression phase ○ Glottis closed by vagal efferent activity ○ Forced expiration against closed glottis ○ Pressure increases Expulsion phase ○ Glottis opened suddenly ○ Trapped air forced out by contraction of internal intercostal muscles + abdo muscles O2 transport Combined with Hb - 98% Physically dissolved in plasma - 2% HbS causes sickle cell anaemia = glutamate at position 6 in the beta-globin replaced with valine O2 capacity = amount of O2/L of blood attached to Hb, at full saturation, depending on the Hb concentration in blood May take 2 years to convert all HbF into HbA Bohr effect - resp acidosis - rightward shift Carbon monoxide increases O2 affinity of Hb - leftward shift Metabolism generates 200ml CO2/min at rest Solubility of CO2 in plasma is 20 times that of O2 CO2 transport Bicarb in RBCs - 70% CO2 dissolved in plasma - 10% Carbaminohaemoglobin - 20% Haldane effect in CO2 dissociation curve As blood enters pulmonary capillaries and binds O2, CO2 carrying capacity falls and blood dumps CO2 O2 consumption in adults 250ml/min, rising to 4L/min in heavy exercise High PO2 in lungs facilitates O2 binding to Hb Leftward shift Decreased PCO2 Decreased temp Increased pH Low PO2 in lungs encourages O2 release Rightward shift Bohr effect Increased PCO2 Increased temp Decreased pH Anatomical dead space - 150mls, up to generation 17 Dalton's law of partial pressures = total pressure of a mixture of gases is the sum of their individual partial pressures Henry's law = concentration of O2 dissolved in water is proportional to the partial pressure in gas phase Alveolar gas composition O2 in lungs is lower (104mmHg) CO2 is higher (40mmHg) Water vapour is higher - so N2 lower PO2 alveolar air = 100mmHg PO2 of venous blood = 40mmHg, so diffusion rapid as conc gradient large At rest, 0.75-1 second for blood to pass thru pulmonary capillaries O2 equilibrium takes 0.25s In exercise, capillary transit time can be reduced to 0.3s PCO2 alveolar air = 40mmHg PCO2 venous blood = 45mmHg, so smaller conc gradient, opposite direction, greater solubility Diffusion limitations on gas exchange Odema = thickness barrier increased Emphysema = breakdown of tissue and alveolar sacs Pulmonary fibrosis = deposition of fibrotic tissues Mucus, inflammation airway, tumours = reduced gas entry  Altitude - Acclimation ○ 1. Blood Epo release stimulated Hb conc increased to 200g/L ○ 2. Vasculature Hypoxia stimulates angiogenesis Capillary density increases throughout body ○ 3. Cardiopulmonary systems Vascular + ventricular remodelling Smooth muscle growth, increasing vascular wall thickness Right ventricular hypertrophies Acute physiological adaptations to altitude ○ Hypoxia sensed by peripheral chemoreceptors ○ Increased ventilatory drive but blunted by central chemoreceptors responding to decreased PaCO2 due to increased ventilation ○ Increased cardiac output due to cardioinhibitory central suppression Adaptive physiological adaptations to altitude ○ Central chemoreceptors adapt so ventilation rate increased ○ PaCO2 decreased = resp alkalosis, so kidneys compensate by decreasing acid excretion, blood pH normalises ○ Alkalosis stimulates 2,3DPG production = rightward shift Diving Atmospheric pressure increases by 760mmHg (1 atmos) every 10m depth Effects of depth ○ Increased partial pressure ○ Nitrogen and oxygen dissolve into blood at lethal excess ○ Volume decrease N2 narcosis ○ Partial pressure of nitrogen rises at 40m or below + starts to dissolve into tissues O2 poisoning ○ System saturated At high pressure, O2 dissolves in blood in excess of buffering capacity of Hb Heliox ○ Nitrogen replaced by helium + percentage of O2 tailored to reduce harm ○ Helium less readily dissolves into body tissues and less narcotic Congenital diaphragmatic hernia 1 in 2000 births Posterolateral - 95% of cases  Parasternal - 2% of cases Intervention = FETO = trachea blocked with inflated balloon, fluid pressure stimulates lung development, left in situ for 6 weeks Pharyngeal arches 4 (superior laryngeal) and 6 (recurrent laryngeal) = larynx Has mesenchymal core with neural crest cells, ectoderm outer layer, and endoderm inner layer Week 24 is the earliest the baby can be born prematurely + survive Lung development Pseudoglandular = weeks 5-16 ○ Branching up of terminal bronchioles Canalicular = week 16-26 ○ Forms primitive alveoli with cuboidal epithelium, capillaries Saccular = weeks 26-birth ○ Increased alveoli + resp bronchioles + capillaries, epithelial changes, formation of type I and II pneumocytes, surfactant production Alveolar = birth to 8 years ○ Increased alveoli number, divisions within alveoli increasing surface area Esophageal atresia and tracheoesophageal fistula 1 in 3000 births Defect in partitioning Diagnosed in utero due to excess amniotic fluid Surgical correction after birth Respiratory distress syndrome Premature birth = insufficient surfactant Alveoli collapse 20% newborn mortality Managed by artificial surfactant or giving mother glucocorticoids to stimulate surfactant Congenital pulmonary airway malformation 1 in 30,000 births Lobe replaced by non functional cystic tissue Asymptomatic (75%) Surgical excision after birth Most important muscles raising rib cage External intercostals SCM - lift upward on sternum Anterior serrati - lift many ribs Scaleni - lift first two ribs Most important muscles that lower rib cage Abdo recti Internal intercostals Intrapleural pressure = pressure of fluid in thin space between lung pleura and chest wall pleura - usually slightly negative pressure At start of respiration = -5cm H2O Inspiration expansion of chest cage pulls lungs outward, so negative pressure increases = -7.5cm H2O Alveolar pressure = pressure of air inside lung alveoli Alveolar pressure decreases to -1cm H2O Transpulmonary pressure = pressure difference between that in alveoli and that on outer surfaces of lungs Measure of elastic forces that tend to collapse the lungs - recoil pressure Greatest resistance to airflow = segmental bronchi Static compliance = extent to which lungs will expand for each unit increase in transpulmonary pressure High compliance = low elastic recoil Pulmonary fibrosis Deposition of fibrous tissue - stiff lungs Decreased lung compliance Smaller than normal changes in lung volume for small changes in transpulmonary pressure Shallow and fast breathing Decreased RV, FRC, TLC Emphysema Alveolar + capillary walls progressively destroyed, particularly elastic tissue Lung compliance increased = larger than normal changes in lung volume for small changes in transpulmonary pressure As airways tend to collapse on expiration, airway resistance increased Slower and deeper breaths Increased RV, FRC, TLC Chronic bronchitis Mucus + inflammation = increased resistance Increased RV, FRC, TLC, but normal compliance Surface tension = measure of force acting to pull liquid’s surface molecules together at an air liquid interface LaPlaces law = pressure within fluid line alveolus is dependent on surface tension of fluid and radius of alveolus Surfactant = DPPC + proteins + calcium Alveolar macrophages help in degrading surfactant, type II cells take up rest + recycle or destroy Surfactant reduces pressure by 4.5 times Tidal volume = volume of air inspired or expired with each normal breath 0.5L Inspiratory reserve volume = extra volume of air that can be inspired over and above normal tidal volume 2.5L Expiratory reserve volume = max extra volume of air that can be expired by forceful expiration after end of normal tidal expiration 1.1L Residual volume = volume of air remaining in lungs after most forceful expiration 1.2L Inspiratory capacity = TV + IRV Volume of air breathed in by max inspiration at end of normal expiration 3.8L Functional residual capacity = ERV + RV Volume of air left in lungs at end of normal expiration 2.4L Vital capacity = IRV + TV + ERV Volume of air that can be breathed by maximum inspiration following max expiration 4.8L Total lung capacity = VC + RV Only fraction of TLC used in normal breathing 6L At rest, lung is subject to 2 opposing forces  Surface tension + elastic elements in lung tissue favour collapse - elastic recoil Elastic elements in chest wall favour expansion + prevent collapse AVSD most common in DS Down syndrome identified at metaphase, by metaphase spread DiGeorge’s syndrome 22q11.2 deletion ○ Pleiotropic mutation - one gene influencing several seemingly unrelated traits Causes TBX1 gene loss of function, which plays role in pharyngeal pouches 3+4, so thymus and heart defects (TOF, VSD, aortic arch interruption) CATCH-22 Interchromosomal events (deletions or duplications, common) or intrachromosomal events (deletions or ring chromosome) Reduced penetrance = can have mutation but not show symptoms Variable expression = where all affected have disease but to different severities, e.g., Marfan’s syndrome Locus heterogeneity = mutations in different genes cause same phenotype Gain of function mutations PCSK9 mutations = high LDL-C, so premature heart disease (Asp372Tyr) SCN5A sodium channel staying open, so too much goes into cell = constant depolarisation, difficult to repolarise Loss of function mutations KCNQ1 potassium channel in LQTS = not enough potassium leaving cell, so delayed repolarisation - allelic heterogeneity Allelic heterogeneity = different mutations in the same gene cause same disease Blood cultures are for testing candida or bacteria Each hour of delay in initiating appropriate antimicrobials leads to a 9% increase in odds of mortality of sepsis patients Veins to get blood cultures from = median cubital, cephalic vein, basilic vein Blood culture sample collection order 1. Blood culture bottles  a. Aerobic b. Anaerobic 2. Coagulation tubes 3. Tubes with no additives 4. Other tubes with additives 8-10 mls of blood for each blood culture bottle Overfilling = false positive result 1ml of blood increases sensitivity of blood cultures by 3% Type Cause Risk Consequence Aortic stenosis Calcification of LV hypertrophy, Increases work on congenital bicuspid syncope, sudden heart, ventricular valve, senile calcific cardiac death hypertrophy, causes degeneration, cardiac failure late in rheumatic fever clinical course Aortic regurgitation Infective endocarditis, Increases volume of rheumatic fever, blood pumped, Marfan’s syndrome increases work on heart, cardiac hypertrophy, cardiac failure, Mitral regurgitation Rheumatic heart Pulmonary disease, floppy valve, hypertension, right marfan syndrome, ventricular infective endocarditis, hypertrophy post MI Mitral stenosis Congenital, post Restricts blood flow rheumatic fever, to left ventricle, AF, back pressure = pulmonary HT, right heart failure Infective endocarditis Risk factors ○ Valve damage - esp after rheumatic fever ○ Bacteraemia - dental, catheterisation, IV drug abuse ○ Immunosuppression 3 weeks post streptococcal infection, usually pharyngitis Children - 4 to 16 years Vegetation composition ○ Group D streptococcus, gut commensals, skin strep Acute native valve endocarditis Valves maybe normal Aggressive Staph aureus, group B strep Sub acute native valve endocarditis Abnormal valves Indolent Alpha haemolytic streptococci, enterococci Prosthetic valve endocarditis 10-20% of cases 5% of mechanical and bioprosthetic valves become infected Mitral most susceptible Early onset = staph aureus, gram neg bacilli, candida species Late onset = staphylococcus, alpha haemolytic strep, enterococci IV drug abuse 75% have no underlying valvular abnormalities 50% = tricuspid valve Staph aureus most common Internal jugular vein central line technique = Seldinger Normal CVP = 2-8mmHg Atherosclerotic aneurysms occur distal to renal arteries Saccular or fusiform 15-25 cm length Wall diameter more than 50% Mural thrombus Dissecting aortic aneurysms Intimal tear 1-2 cm from aortic valve Pain radiating to the back Most common cause of death is rupture of dissection outward into pericardial, pleural, or peritoneal cavities Berry aneurysms Circle of willis Young people Hypertensive Subarachnoid haemorrhage  Capillary microaneurysms HT + diabetes associated Small aneurysms in branches of middle cerebral artery Associated with intra cerebral haemorrhage Mycotic aneurysms Wall of artery weakened by infection - bacteria or fungi Often in brain, secondary to embolism Vasculitis type What is it? Victims Giant cell temporal Granulomatous inflammation of large to small sized arteries Over 50, average onset of arteritis - temporal, ophthalmic, vertebral 70, women Takayasu arteritis - Granulomatous vasculitis of medium to large arteries of Women, under 30 pulseless disease upper limbs + aortic arch - steroids, intermittent claudication of upper limbs Polyarteritis nodosa Medium small sized muscular arteries of kidneys, heart, liver, and GI tract, fibrinoid necrosis fatal without steroids Kawasaki disease High fever, conjunctival and oral lesions, self limited Children under 4 Vascular tumours Benign ○ Angioma ○ Haemangioma Juvenile - skin Capillary - skin, spleen, kidneys Cavernous - skin, spleen, liver, pancreas ○ Lymphangioma Capillary Cavernous Malignant ○ Angiosarcoma Skin, soft tissue, breast, bone, liver, spleen Kaposi’s sarcoma - HIV association ○ Angioproliferative tumour derived from endothelial cells Atherosclerosis begins with endothelial injury, caused by factors like hypertension, smoking, or hyperlipidemia This increases permeability, allowing LDL cholesterol to accumulate in the intima  The LDL becomes oxidized, triggering an inflammatory response. Monocytes migrate into the intima, differentiate into macrophages, and engulf oxidized LDL to form foam cells, creating fatty streaks. Smooth muscle cells migrate to the intima, proliferate, and secrete extracellular matrix, forming a fibrous cap over the fatty streak. Over time, plaques can calcify, grow, or rupture. Plaque rupture exposes thrombogenic material, leading to thrombus formation and potential vessel occlusion, causing ischemia or infarction. Coarctation of aorta signs = systemic hypertension + radio femoral delay PDA = left ventricular hypertrophy Bounding peripheral pulses Failure to thrive Continuous murmur as pressure in pulmonary artery lower than aorta 9-12% of all CHD First line treatment = iburprofen, good efficacy + good safety profile MoA ○ Foetal ducts have intrinsic tones + patency maintained by low O2 and diluting factors ○ Circulating prostaglandins produced by placenta = PGE2 and PG12 ○ After birth, systemic O2 sats increase with onset of breathing = ductus contracts ○ Level of circulating prostaglandins falls as placenta removed from circulation Decreased systemic perfusion responsible for increased incidence of necrotising enterocolitis and intraventricular haemorrhage seen in preterm infants with PDA ASD = right atrial/ventricular enlargement mod/severe = ejection systolic murmur in pulmonary area Caused by increased pulmonary valve blood flow, not through ASD Split 2nd heart sound Untreated ○ Exercise intolerance + atrial arrhythmias in 3rd + 4th decades of life Pulmonary valve stenosis acquired in Noonan's syndrome Ejection systolic murmur Pressure gradient greater than 10mmHg Most common valve defect Types ○ Subvalvular ○ Supravalvular ○ Peripheral Duct dependent coarctation of aorta  When duct closes, aorta constricts, causing severe LVOT obstruction Collapse due to LVOT obstruction - 2 days of age Sick baby with severe HF Absent femoral pulses Severe metabolic acidosis Treatment ○ Alprostadil = prostaglandin Ei ○ Maintains ductal patency ○ Surgical repair preferred 5-8% of all CHDs, more in males, sporadic Large VSD treatment Most common CHD - 20% Diuretics + high cal formula + closure of defect - cathartic procedure or open heart surgery Untreated ○ High BP scars lung arteries ○ Pulmonary hypertension + irreversible damage ○ Shunt reversal = eisenmengers syndrome ○ Develops after 2 years Screening for CHD = Ultrasonography in 2nd trimester and postnatal clinical examination VSD most common congenital heart defect Pulmonary valve stenosis most common valve defect ASD most missed until adulthood ToF most common cyanotic defect Duct dependent coarctation of aorta most common outflow obstruction 42% of doctors believe that discussions over smoking cessation are too time consuming Pts with heart failure with reduced LVEF should be given a BB + ACEi as first line Rheumatic fever is the most common cause of mitral stenosis A common chronic cause of RBBB is right ventricular hypertrophy Nitrates cause a decrease in intracellular calcium Loop diuretics  Inhibit NKCC2 At TAL LoH Thiazide diuretics Inhibiting NCC At DCT Potassium sparing diuretics Inhibit ENaC At CCD Zona glomerulosa - aldosterone Conn’s syndrome Zona fasciculata - cortisol Cushing's syndrome Adrenal medulla - adrenaline/noradrenaline Pheochromocytoma Xiphisternal joint = T9/T10 Jugular notch = T2/T3 Sternal angle = T4/T5 Commonest cause of thrills = aortic stenosis Savulescu’s arguments against CO Inefficiency + inequity Discrimination Inconsistency Commitments of a doctor Aortic coarctation associated with turner’s syndrome, berry aneurysms, and neurofibromatosis Features = cyanotic, radiofemoral delay, HF in infants, HT in adults Avoid giving ACEi/ARB in bilateral renal artery stenosis Boyle mariottes law = increase in volume will reduce pressure in thorax and will cause air to be drawn into thoracic cavity Ductus arteriosus closures Functional closure = 1st hour Structural closure = 1-4 months Anatomical closure via intima thickening Increased O2 Decreased prostaglandins  Smooth muscle wall constriction on wall of DA Symp trunks fuse with each other in single ganglion impar, opposite coccyx Areas of supply - symp Head from T1-T3 Upper limb from T4-T6 Heart from T1-T5 Thoracic and abdominal walls from T1-T12 Lower limb from T12-L2 Heart gets referred pain to T1/T2 (medial aspect of arm) + T3-T5 Supranormal excitability Cells more easily depolarised than normal, therefore weaker than usual stimulus can trigger an AP Occurs towards end of repolarisation, phase 3 Flow directly proportional to: Pressure difference Resistance Flow inversely proportional to; Vessel diameter Vessel length Viscosity of blood Length tension relationship = EDV increases, increased ventricular wall stretch, increased force of contraction Reactive hyperaemia = when blood supply blocked, blood flow increases 4-7x normal Active hyperaemia = if tissue highly active, flow rate increases, by up to 20x in skeletal muscle Reynolds number = turbulent if High velocity flow Large diameter vessels Low blood viscosity Abnormal vessel wall Orthostatic hypotension Immediate effect in going from supine to upright 500ml of blood from upper body → legs Decreased venous return Decreased cardiac output + decreased BP  Reflex vasconstriction in legs + lower abdo, few seconds to start Postural effects of standing still Pressure increased by 1mmHg for each 13.6mm below surface By feet +90mmHg MABP at level of heart = 100mmHg So in feet 150mmHg Leg oedema = 10-20% blood volume within 15-30 minutes MCCVC Integrated BP control Sensory area = input from baroreceptors Lateral portion = efferent sympathetic nerve Medial portion = efferent parasympathetic (vagus) nerve Nervous control of arterial pressure = rapid ○ Increases arterial pressure 2x with 5-10 seconds ○ Decreases arterial pressure 50% within 10-40 seconds Angiotensin II roles Resistance vessels → increases TPR Kidneys → constricts renal arteries, therefore decreased kidney blood flow Releases aldosterone from adrenal gland → increases sodium + water reabsorption Stimulates ADH release from pituitary Valsalva manouvre Start ○ Increased intra-thoracic pressure ○ Increased BP due to thoracic aorta compression ○ Decreased HR due to baroreceptor activation from initial BP increase Continued strain ○ Sustained high intra-thoracic pressure, decreased venous return ○ Decreased venous return = decreased SV + decreased CO = decreased BP ○ Reflex tachy as baroreceptors detect decreased BP, activating SNS to maintain CO Release ○ Sudden decrease in intra-thoracic pressure + transient decreased BP as thoracic aorta expands again ○ Slight HR increase as body briefly experiences decreased BP, and compensates through sympathetic activation Return to baseline ○ Venous return + CO normalise as intra-thoracic pressure returns to normal ○ Increased venous return = rapid increase SV + increased CO = BP overshoot  ○ Reflex brady as baroreceptors sense increased BP and activate PSNS to bring HR back to normal Loss of oncotic pressure in blood Liver disease, e.g., cirrhosis Nephrotic syndrome Malnutrition, e.g., kwashiorkor ○ Essential amino acid intake compromised - peripheral wasting of muscle + stick like arms/legs + swollen stomach due to fluid accumulation centrally ○ Limited oedema at periphery as no tissue volume left to support it Burns + skin loss Sepsis or inflammation Certain meds, e.g., corticosteroids Causes of increased hydrostatic pressure at venule end Heart failure ○ Right ventricular heart failure causes… Back log of blood, increasing venous pressure as heart not pumping returning volume onwards Will cause peripheral oedema, symmetrically Observable at JVP DVT ○ Decreased blood volume ○ Subsequent build up of hydrostatic pressure at venule end ○ More localised, asymmetrical oedema Increased blood volume, e.g., renal failure Increased capillary permeability Pregnancy Prolonged standing/sitting Four quadrant approach Step 1 = what is the ethical/moral issue Step 2, 1 = medical implications Step 2, 2 = pt preferences Step 2, 3 = quality of life Step 2, 4 = contextual factors Step 3 = ethical decision Clinical need rationing = deontological or consequentialist QALY = consequentialist or utilitarisum Maximising health gains = consequentialist Equal access to treatment = deontological Dermatomes Suprapubic region = T10 Nipple = T5 Xiphoid process = T7 Umbilicus = T10 Foramen ovale closure Clamping of the cord = forces closure ○ Increased systemic resistance = increased left sided pressure First breath = reduces right → left shunts ○ Decreased pulmonary resistance = decreased right sided pressure CK-MB levels in MI Rises in 4-6 hours Peaks at 12-24 hours Normal after 48-72 hours Troponin levels in MI Rises in 3-6 hours Peaks at 12-24 hours Remains elevated for 7-10 days Oxygen as treatment Carbon monoxide poisoning ○ Carbon monoxide binds to Hb more effectively than O2, reducing O2 carrying capacity of blood ○ High flow O2 can help to displace carbon monoxide from Hb Long term treatment of hypoxaemia Pneumothorax Pneumonia ○ Accelerate reabsorption of air in pleural space, even if not severely hypoxaemic Hypovolaemic shock complication = elevated right sided heart pressures, impaired venous return = signs of right HF, causing raised CVP, with jugular venous distention Most common misconception = more pain causes more damage to heart FITT principle Frequency - 3x per week Intensity - moderate intensity, but also include balance, coordination, and flexibility Type - aerobic Time - minimum 20 minutes Relaxation techniques used in CR Laura Mitchell method Guided imagery Diaphragmatic breathing Making goals SMART Specific Measurable Achievable Realistic Time based Primary health promotion Prevent disease before it occurs Done by legislation + education E.g., asbestos banned, seatbelt laws, and immunisations for vaccines Secondary health promotion Reduce impact of disease/injury that has already occurred E.g., screening programmes + education of noticing personal changes + daily low dose aspirin Tertiary health promotion Soften impact of an ongoing illness/injury that has long lasting effects E.g., cardiac or stroke rehab + support groups CURB65 for CAP Lung abscess types Cavitating pneumonia Mycosis - aspergillosis IV fluids = 500ml plasmalyte over 15 minutes Fluid challenge 20mls/kg Typical challenge = 250mls-500mls Root of lung/hilum Superior = pulmonary artery Anterior = superior pulmonary vein Inferior = inferior pulmonary vein Posterior = bronchi Vital graph during an asthma attack Decreased FEV1 Normal or slightly reduced FVC Reduced FEV1% Concave expiratory curve Slower upward slope Vital graph of a restrictive lung disorder Reduced FVC Reduced FEV1 Normal or elevated FEV1% Smaller overall lung volume on trace Normal shape but reduced size Treatment for persistent COPD exacerbations Azithromycin ○ Long term risk of bacterial resistance + hearing impairment Mucolytics, e.g., NAC or carbocysteine PDE4 inhibitors, e.g., roflumilast WPW = circus movement + AVRT Systolic dysfunction result Increased EDV - preload Ventricular dilation Increased ventricular wall tension Systolic dysfunction = Reduced ejection fraction - under 40%, caused by impaired contractility and increased afterload Diastolic dysfunction Preserved ejection fraction Caused by impaired diastolic filling Causes ○ Impedance of ventricular expansion - constrictive pericarditis ○ Increased wall thickness - hypertrophy ○ Delayed diastolic relaxation - aging or ischaemia ○ Increased HR Ang II binds AT1 receptors to zona glomerulosa of adrenal glands and renal tubules of kidneys Stimulates secretion of aldosterone from adrenal glands Increases sodium reabsorption in kidney Increases ECV Ang II binding AT1 receptors to hypothalamus Increases ADH release Increases water reabsorption in kidneys Increases ECV ET-1 binds ET(A) receptors, which then binds to Vascular smooth muscle cells = vasoconstriction Cardiomyocytes = increasing contractility ET-1 binds ET(B) receptors causing Production of nitric oxide using vasodilation In kidneys - promotes sodium and water excretion Amyloidosis common complications ○ Heart failure ○ Nephrotic syndrome Affecting CVS ○ Amyloid deposits in heart = restrictive cardiomyopathy, where heart walls become stiff + less able to expand, leading to diastolic HF ○ Arrhythmias + heart block Composition ○ Immunoglobulin light chains ○ Serum amyloid protein A ○ Peptide hormones ○ Prealbumin Primary benign neoplasia in heart = atrial myxoma Primary malignant neoplasia in heart = angiosarcoma + rhabdomyosarcoma Start CPR Pulseless electrical activity Pulseless VT VF Asystole Acronym Class Gram Example MoA Antibiotics aminoglycosides - Streptomycin, Inhibit protein synthesis - 30S gentamicin  Can Cephlosporins +/- Cefazolin, cefadroxil Inhibit cell wall synthesis Protect Penicillins + Penicillin G Inhibit cell wall synthesis - Ampicillin, methicillin The tetracyclines +/- Tetracycline, Inhibit protein synthesis - 30S doxycycline Queens quinolone/fluoroq +/- Ciprofloxacin Inhibit DNA replication - uinolone topoisomerase II + III Men marcolide + Erthromycin Inhibit protein synthesis - 50S Servants sulphonamides +/- sulfamethoxazole Inhibit folate synthesis Guards Glycopeptides + Vancomycin Inhibit cell wall synthesis Cross sectional survey used in Frequency Aetiology Diagnosis RCTs used in Effectiveness Side effects Cost of treatment Pt adherence to treatment Duration of effect of treatment Cohort studies used in Risks Aetiology Prognosis Diagnosis Case control study used in Prognosis questions Ordinal and nominal categories for variables Ordinal = objective or subjective Nominal = unordered, male/female green/blue eyes Quantitative data Discrete Continuous Type I error = rejecting null hypothesis when it is true False positive Concluding there is an effect when there isnt P is small Type II error = not rejecting null hypothesis when it is false False negative Concluding there is no effect when there is P is large Power = ability to reject null hypothesis when it is false Reduced type II errors Use relative risk in cohort studies and clinical trials Odds ratio in case control studies Point estimate in confidence intervals = magnitude of effect of experimental intervention compared to control intervention Pulmonary oedema signs Bats wing appearance Kerley B lines Cardio-thoracic ratio - PA only Pleural effusion sample Exudate ○ High protein ○ Consider infection, cancer, inflammation, e.g., RhA Transudate ○ Low protein ○ Consider systemic failure causes, e.g., heart, liver, renal Current first line order for TB treatment Intensive phase - 2 months ○ Rifampicin ○ Isoniazid Toxicity = hepatitis + peripheral neuropathy (give pyridoxine, vitB6) ○ Pyrazinamide ○ Ethambutol Continuation phase - 4 months ○ Rifampicin ○ Isoniazid TB pathogenesis Transmission Primary infection Latent infection Active disease Rifampicin induces liver enzymes (CYP450) increasing clearance of other drugs, including warfarin, OCP, and anti retroviral therapy Drug Line MoA Toxicity Dose Rifampicin 1st - intensive Inhibits bacterial Hepatoxicity, 10mg/kg phase, 2 months DNA dependent drug interactions + continuation RNA with steroids phase, 4 months polymerase, (OCP), + opiates bactericidal (methadone), itch, rash, GI upset, discolouration of urine, tears, sweat Isoniazid 1st - intensive Inhibits mycolic Hepatitis + 5mg/kg phase, 2 acid peripheral months, + biosynthesis in neuropathy (give continuation cell wall, pyridoxine, phase, 4 months bactericidal, vitB6) activated by KatG Pyrazinamide 1st - intensive Inhibits fatty acid Hepatotoxicity + Daily dose - phase, 2 months synthetase I, joint pain as 15-35mg/kg/day bacteriostatic, high urate but bactericidal at acidic pH Ethambutol 1st - intensive Inhibits Ocular toxicity 15mg/kg phase, 2 months arabinosyn transferase, bacteriostatic Nasal cavity, trachea, bronchi = pseudo-stratified ciliated columnar epithelium with goblet cells that lines much of conducting passages Bronchioles + terminal bronchioles = simple ciliated columnar or cubodial with club cells Type I pneumocytes = simple squamous cells for gas exchange Type II pneumocytes = produce + secrete surfactant ○ Dome shaped, cuboidal epithelial cells projecting into lumen Palate + epiglottis = stratified squamous non keratinized Alveolar wall constituting as the blood/air barrier = epithelium, basement membrane, capillary endothelium Chest wall layers needle for aspiration would have to go thru, when aspiring 2nd IC space at mid clavicular line - for tension pneumothorax treatment 1. Skin 2. Superficial fascia 3. Pectoralis major 4. External intercostal 5. Intercostal intercostal 6. Endo-thoracic fascia 7. Parietal pleura Think sepsis Pts with known infection Signs or symptoms of infection Pts with high risk of infection, e.g., chemo NEWS2 score of 5 or more Bolus injection Intermittent infusions Continuous infusion Rapid response required Incompatibilities Less compatibility concerns Unstable drugs Unstable drugs Stable drugs Concentration dependent Time dependent effects effects Long half life Short half life Into vein Dedicated IV site Meds diluted in small Addition of meds to small Syringe given via amount of diluent, e.g., volume IV fluid bag, given motorised syringe pump water or 0.9% saline, for over 10 mins, or burette 3-5 mins Morphine + insulin  Molecules accumulating in total body water ○ Small, water soluble molecules, e.g., ethanol Molecules accumulating in plasma ○ Highly plasma bound molecules ○ Highly charged molecules ○ Very large molecules ○ E.g., heparin Molecules accumulating in ECF ○ Large, water soluble molecules ○ E.g., manitol Drugs passing BBB ○ Lipophilicty ○ Low mol wt ○ Non ionised ○ Low plasma protein binding ○ Presence of specific transporters Hyperalbuminae ○ caused by dehydration ○ results in decreased free drug level Hypoalbuminaemia ○ Caused by burns, renal disease, hepatic disease, malnutrition ○ Results in increased free drug levels Isoprenaline given in bradycardia / heart block emergencies sacubitril/valsartan combination Neprilysin inhibitor prevents breakdown of BNP causing vasodilation + diuresis, but also increases ang II levels, so valsatan prevents this Risk of angioneurotic oedema - with ACEi as well Replaces ACEi/ARB in severe cardiac failure Ranolazine - given in refractory angina Risk of air embolism if central venous catheter goes into the external jugular vein Posterior triangle of the neck Anterior = posterior border of SCM Posterior = anterior border of trapezius Inferior = middle ⅓ of clavicle Anterior triangle of the neck Superior = inferior border of mandible Lateral = anterior border of SCM Medial = midline Resonant = normal Hyper resonant = emphysema or pneumothorax Dull = collapse, consolidation, fibrosis - perform vocal resonance test Increased resonance suggests consolidation or fibrosis. Decreased resonance suggests pleural effusion or collapse Stony or very dull = pleural effusion, haemothorax Polycythaemia = increased concentration of RBCs in blood = higher hematocrit levels Surgical emphysema = presence of air in SC tissue, resulting from trauma/surgery when air leaks from lungs or airways into surrounding tissue + causes swelling and crackling sensation on palpation Vesicular normal, heard over most lung fields Soft low pitched with inspiration longer + louder than expiration Bronchial abnormal when heard over lung tissue, normal when heard over trachea higher pitched Louder pause between inspiration and expiration What examination features would you expect with a left-sided pneumothorax? reduced or absent breath sounds on side hyperresonance on side decreased or absent tactile fremitus tracheal deviation to right decreased chest expansion JVP needs to be less than 4 cm vertical heart, with total 8cm as RA is 5 cm below sternum Thoracic splanchnic nerves - Greater = T5-T9 - Lesser = from T10-11 - Least = T12 Inferior cervical + T1 fuse = stellate ganglion C7-T1 Drains 60% of venous blood of heart into RA 40% is drained by smallest cardiac veins and anterior cardiac veins Cirhhotic liver disease → portal hypertension → oesophgaeal varices Hemiazygos vein has connections with left renal vein Hemiazygos crosses to the right at T9, joining azygos Accessory hemiazygos descends from 4th intercostal space, crosses to right at T8 Chest drain To evacuate air or fluid from pleural space Triangle of safety Incorrect placement = perforation of pericardium, liver, heart 1. Lateral border of pec major 2. Anterior border of lat dorsi 3. Apex towards axilla 4. Base is nipple or 5th IC space Needle angled upwards at 9th IC space on midaxillary line during expiration to remove fluid Venous drainage of diaphragm Superior phrenic vein on right Some posterior superior veins drain to azygos/hemiazygos Left inferior phrenic vein → suprarenal → renal vein Caval opening T8 IVC + right phrenic nerve + some lymphatics Oesophageal opening T10 Oesophagus + right+left vagal trunks + oesophageal branches of left gastric vessels Aortic hiatus T12 Aorta + thoracic duct + sometimes azygos and homozygous veins Bronchial carcinoma - 95% of primary tumours Tumour in apical lobe - 5% - pancoast's tumour, nerve compression Symp trunk above T4 = horner's syndrome Brachial plexus = pain in shoulder/scapula/arm, paralysis of hand Laryngeal inlet at C3 level Trachea begins at C6 level Larynx higher in newborn and infants, descending weeks 4-6 Pharyngeal recess Deep recess posterior to opening of pharyngotympanic tube Commonest site of nasopharyngeal carcinoma Risk of misplacing cannula intended for pharyngotympanic tube - ICA in proximity Frontal sinus + anterior ethmoidal sinus + maxillary sinus drain to hiatus semilunaris in middle meatus ACRONYMS Extrinsic factors causing restrictive lung disease = PAINT Intrinsic = lung parenchyma ToF = Odd People Voted Republican Overriding aorta Pulmonary stenosis VSD Right ventricular hypertrophy Thoracic aorta branches = Very Old Broke Pensioners Make Some Pretty Pathetic Soup 1. Visceral branches a. Esophageal b. Bronchial c. Pericardial d. Mediastinal e. Superior phrenic 2. Parietal branches a. Posterior intercostal b. Superior phrenic Cranial veins - Clever Doctors Save Intensely Sick Skulls During Emergencies 1. Cerebral 2. Dural venous sinuses a. Superficial sagittal sinus b. Inferior sagittal sinus c. Sigmoid sinus d. Sinus rectus 3. Diploic veins 4. Emissary veins Erb’s point = Let's Get Together, supraclavicular 1. Lesser occipital 2. Greater auricular 3. Transverse cervical 4. Supraclavicular ACUTE MI DEVELOPMENT AND REPAIR 0-24 hours = ELLIE ○ Early coagulative necrosis ○ Wavy fibres ○ Hypereosinophilia ○ Neutrophil infiltration begins  1-3 days = NEVER ○ Extensive coagulative necrosis ○ Peak neutrophil infiltration ○ Contraction band necrosis 3-7 days = MAKES ○ Macrophage infiltration ○ Granulation tissue formation at edges, clearing of necrotic debris 7-14 days = GOOD ○ Well developed granulation tissue ○ Fibroblast proliferation ○ Neovascularization 2-6 weeks = FRIENDS ○ Progressive collagen deposition ○ Scar formation Over 6 weeks = NEVERMIND ○ Fully developed fibrous scar replaces necrotic tissue Subclavian branches = VIT CD Vertebral artery Internal thoracic artery Thyrocervical artery Costocervical artery Dorsal scapular artery COMPLICATIONS FOLLOWING ACUTE MI - Very bright students study pharmacology very late, persistently ○ 0-3 days Ventricular arrhythmias Vfib or VT Primary → ischaemia cause, under 4 hours Secondary → remodelling/scar cause, over 48 hours Bradyarrythmias/heart block Common, esp post inferior MI Resolves if onset under 24 hours Cardiogenic shock Depends on infarct size 5-6% of pts with STEMI Stroke Thromboembolic from PCI Or from antithrombotic therapy Long term risk in ○ Large anterior infarct ○ Left ventricular aneurysm ○ LV rEF  ○ 3 days to 2 weeks Ischaemic MR/papillary muscle rupture Posterior papillary muscle most often Supplied by dominant artery Mitral regurgitation murmur present = pansystolic Ventricular septal rupture Most common with anterior MI Pansystolic murmur @LSB LV free wall rupture Persistent STE Upright T waves Reversal of initially inverted T waves More than 50% mortality, even with surgery ○ 2 weeks + Pericarditis Autoimmune reaction More common in large infarcts Persistent STE PR depression May have friction rub Embryological derivatives Sinus venosus Smooth part of RA Sinus venosus R horn = SVC L horn = coronary sinus Primitive atrium RA + LA Pulmonary veins Smooth part of LA Primitive ventricle LV Bulbous cordis - proximal ⅓ RV Bulbous cordis - middle ⅓ Infundibulum for RV Aortic vestibule for LV Bolbus cordis - distal ⅓ Proximal aorta + pulmonary trunk Endocardial cushions AV valves + membranous IV septum + lower IA septum + spiral septum Aortic arch embryological branches ACRONYM ARCH WHAT IT BECOMES Top 1st + 2nd Arteries in head and neck 3rd letter in alphabet 3rd R + L common carotid arteries R + L internal carotid arteries 4 limbs 4th R = R proximal subclavian artery L = middle aortic arch Sexy division 6th R = Right pulmonary artery L = Left pulmonary artery + ductus arteriosus Seven 7th R = right distal subclavian artery L = left subclavian artery Descending Dorsal aorta R = right subclavian artery L = descending aorta