Respiratory Block Flashcards

Question

What are the general steps to Type I hypersensitivity after IgE mediated inflammatory response to antigens?

Answer 1

Sensitisation phase which is followed by; Response phase: local (common) or systemic (rare). Locally it will cause rhinitis, bronchoconstriction and conjuctivitis. Systemically will cause anaphylaxis. Responses have both immediate and late phase.

Answer 2

Allergens, Th2 cells, IgE, FceR1, mast cells and eosinophils

Answer 3

Pollen, house dust mite, food, etc. Should have repeated exposure, highly soluble (to pass through mucus), very stable and hard to degrade and introduced in low doses.

Answer 4

Low dose Antigen enters the mucosal route. It is taken up by APC and displayed to naive T cells. The APC produce IL-33 that indirectly releases IL-4 when stimulating the T-cell. This leads it to differentiate to Th2 cells (increasing in IL-4, IL-5 and IL-13) Upon re-exposure the Th2 already present will promote IgE secretion proliferation and isotype switching.

Answer 5

The DC's do not actually produce IL-4 to co-stimulate the naive T-cell. DCs produce IL-33 which activate basophils to directly secrete IL-4 onto the naive T-cell. This aids the differentiation to Th2 and productiong of IgE.

Answer 6

They can act as APC (express MHC I and II, PRR) and importantly secretes IL-4.

Answer 7

The activated Th2 cells can stimulate B-cells to isotype switch to IgE.

Answer 8

Found in mucosal and epithelial tissue near blood vessels. Mast cells contain pre-formed granules, binds IgE to FceR1 and surface bound IgE is very stable. Once allergen is bound it will result in granular exocytosis and the synthesis of lipid mediators, cytokines and chemokines.

Answer 9

Occur in seconds due to pre-formed granules that are rapidly metabolised. It causes blood vessels to dilate and leak plasma. Localised swelling around the site of challenge (wheal). The blood vessels dilate further and engorge with blood (flare)

Answer 10

Induced mediators released such as chemokines, cytokines and leukotrienes. Involves cell infiltration and prolonged oedema and may/or may not cause smooth muscle contractions.

Answer 11

GI tract - Diarrhoea vomiting Skin - swelling itching urticara Airways - nasal blockage, coughing, phlegm and asthma Blood vessels - increase tissue fluid and cell infiltration, anaphylatic shock

Answer 12

Present in mucosal lining as protective role against parasites. Found LATE in allergic reactions. Produce toxic granule derived proteins and free radicals (which is usually for parasites - but will cause tissue remodeling). Eosinophils will also produce chemical mediators leading to epithelial cell activation and inflammatory cell recruitment and activation.

Answer 13

Increased production in bone marrow due to IL-5 from Th2 and mast cells. The eosinphils are activated and infiltrate into tissue. There is decreased threshold for activation due to the sensitisation phase of IgE binding to FceR1.

Answer 14

Adrenanine - Anaphylaxis (reforms tight endothelial junctions, relaxes smooth muscle as bronchodilator, increase HR) Inhaled B-agonists - Asthma (Bronchodilators) Antihistamines - hives and allergic rhinitis (Block histamine and reduces itching and decreases oedema) Corticosteroids - provides broad non-antigen specific treatment of symptoms (suppresses chronic inflammation and broad immunosuppression by blocking gene transcription - multiple side effects and tolerance builds)

Answer 15

Administer increasing dose of allergen to induce T-cell tolerance. Tolerance by: Anergy (decreased T cell proliferation), deviation of secreted cytokines, stimulate apoptosis and production of Treg cells.

Answer 16

Cell mediated with heavy involvement of T cells and macrophages - mostly Th1 but sometimes CTL. Generally caused by microbial infection, intradermal injection of protein antigens and contact with chemicals through the skin.

Answer 17

The antigen is taken up through the skin of mucosa that is taken up by APC and presented in the lymph node. This activates Th1 and CD8 T cells. The T cells leave the lymph nodes into the circulation and to the tissue of interest.

Answer 18

There is an accumulation because of antigen persistence. Leads to continuous release of the cytokines and chemokines. Means more infiltration, tissue destruction, adhesion molecules, monocyte production and ROS and RON.

Answer 19

1. Contact sensitivity - poison ivy and TB tests will have central and effector memory cells triggered when re-exposed after previous sensitisation. 2. M. Tuberculosis - Cannot clear organism 3. Celiac Disease - Exposure to wheat products induce Th1 dependent immunopathology of intestinal wall.

Answer 20

Usually takes a few days because the cells involved are slower

Answer 21

First exposure to antigen will be taken up by APC leading to production of memory T cells. When re-exposed to the antigen the memory T-cells will activate and cause excessive inflammation (a lot of IFN-gamma and recruit macrophages)

Answer 22

Inhale TB that multiply in resisdent alveolar macrophages. This results in increase cytokine and chemokine production inducing monocyte influx. DCs migrate to lymph node that activates and recruits CD8, Th1 cells to the infection to further activate macrophages. But after all of this the myocobacteria still persists leading to prolonged infection.

Answer 23

M. TB induces granuloma formation essentially walling off the pathogen.

Answer 24

Results from hypersensitivity to components of gluten (gliadins). But it requires exposure unlike the persistence of TB. The celiac disease results in damage to the small intestine.

Answer 25

\>90% have HLA-DQ2

Answer 26

The T cells recognise gliadin peptides through HLA-DQ2. Generally prefers to bind -ve AA side chains. Unmodified gliadin proteins are +ve charged so cannot bind. But when tissue transglutaminase 2 will change gliadin proteins to -ve charged. Deamidated gliadin will bind to the HLA-DQ2 effectively now. Able to trigger immune response.

Answer 27

Chronic inflammation of airways associated with hyper-responsiveness leading to recurrent episodes of wheezing, breathlessness, chest tightness and coughing. Often reversible airflow limitations (not fixed airway obstruction).

Answer 28

Host: Genetic, atopy, airway hyper-responsiveness (narrow too early and too much), Gender and obesity. Environmental Factors: Indoor allergens, outdoor allergens, occupational sensitisers, tobacco smokes, air pollution, respiratory infection and diet.

Answer 29

Allergen activate mast cells: to eosinophil and neutrophil leading to nerve activation. Allergen activate macrophage/DC and Th2 cell. Eventual responses lead to mucus hypersecretion, vasodilation (angiogenesis), plasma leak (oedema), bronchoconstriction and even subepithelial fibrosis.

Answer 30

Bronchospasm, airway mucosal oedema and mucus plugs (other mechanism to narrowing especially in smaller airways).

Answer 31

Airway smooth muscle contraction - reliever, controller and preventer Bronchial oedema - Preventers Mucus hypersecretion - Preventers

Answer 32

Inflated airways the airway smooth muscles will open the airways the most. Deflated usually has very little pool and therefore is likely to have more resistance.

Answer 33

They are arranged circumferentially around the airways that narrows the lumen when contracted. Found in the bronchioles. There is no direct SNS but there is PS. The B-adrenoceptor comes from Adr.

Answer 34

Load decreases during expiration causing increase in airway resistance and also increases likelihood of airways collapse. Unloaded muscle shorten faster

Answer 35

Similar to skeletal muscle contraction. It is important to regulate calcium levels. Increase in calcium usually done by PLC and IP₃that releases calcium stores. Plasma Ca²⁺ ATPase, SR ATPase taking it back up into internal stores.

Answer 36

The balance between contraction (ACh, HA, LTC₄, LTD₄) and relaxation (PGE₂, adrenaline, PGI₂)

Answer 37

Calcium will affect myosin light chain kinase. When the MLC is phosphorylated it becomes more calcium sensitive that can influence the contraction. On the otherhand protein kinase A can dephosphorylate the MLC-phosphate.

Answer 38

Not only constrict and relax it also contributes to wall volume in airway remodeling and inflammation. - Proliferation, migration, secretion of cytokines and secretion of ECM proteins. Shows subepithelial collagen thickening, infiltration of inflammatory cells, increase mucosal vascularity and smooth muscle volume.

Answer 39

FEV₁ numbers

Answer 40

Salbutamol with rapid onset and B2 selectivity leading to bronchodilator. The adverse effects may be tremors, tachycardia and hypokaelamia. Tolerance build up.

Answer 41

Increase in cAMP and PKA inhibits IP₃ leading to reduced calcium levels. Reduced calcium levels means less MLCK (myosin light chain kinase) activation.

Answer 42

Salmeterol are longer acting B2 agonists. The duration can be up to 12 hours. Usually used for prophylaxis and used in combination. Monotherapy is associated with increase in mortality and morbidity.

Answer 43

Within seconds the receptors are phosphorylated that desensitises it by PKA. Within minutes the receptors are sequestrated (internalised) - may be degraded or recycled to plasma membrane. Within hours the receptors are down regulated by decreased mRNA stability and rate of transcription.

Answer 44

Not generally used in asthma - more for COPD. Less bronchodilation than B2 agonists. Usually M3 receptors on ASM.

Answer 45

Level I - Systematic review of randomised clinical trials Level IV - Case series Randomised controlled trials are the best

Answer 46

P - Population I - Intervention C - Comparator/Control O - Outcome T - timing Used to help determine what therapy to commence on.

Answer 47

Extent of validity of results that come from the study. Did it answer the question proposed? How well is the study design and data collection?

Answer 48

Reduce confounding in studies. Try to make treatment groups identical in all aspects other than the intervention. Reduces selection bias (investigators may assign subjects with bias)

Answer 49

Break up key confounders and randomise people into those groups to make it more even. Makes the composition of groups even more similar and therefore reduces potential of confounding.

Answer 50

Shows the base line characteristics of trials and more important should show that groups are evenly matched. The parameters are confounders.

Answer 51

Non-awareness of intervention allocated. This will reduce information bias. Knowing what intervention you get can influence the outcomes.

Answer 52

Outcomes must be strict, standardised and have objective criteria. Multi-centre studies need to have a centralised process. - Reduce information bias.

Answer 53

Assume subjects remain in the groups they were randomised in. This is to reduce selection bias. Since drop outs selects for healthier group in drug group. Misrepresentation of new drug being better than placebo. It always gives underestimate of the treatment effect - gives us more confidence of the results.

Answer 54

P value and confidence interval (this gives precision) P value - gives probability that chance gave us the results. Conventionally set it as p \< 0.05 significant. Confidence interval: 95% chance the true value lies within this particular interval.

Answer 55

Number of people needed to undergo treatment to prevent one outcome. Marker of intervention efficiency.

Answer 56

NNT = 1 / (absolute risk or rate reduction)

Answer 57

Affected by relative effect (often constant) and the underlying likelihood of outcome. It is important to work out what the chance of the outcome is of occuring.

Answer 58

How similar is the PICOT in the study to my patient? Should I use the particular intervention for my case specifically?

Answer 59

Oxygen the pulmonary arterial blood, remove carbon dioxide from blood and maintain acid-base balance.

Answer 60

At rest (BMR) - 250mL/min O₂ and 200mL/min CO₂ During exercise - \>4000mL/min O₂ and \>4000mL/min CO₂

Answer 61

4 oxygen molecules per Hb molecule

Answer 62

1. Dissolved - 10% 2. Attached to proteins (include Hb) - 30% 3. Bicarbonate - 60%

Answer 63

Alveolar and capillary membrane (AC membrane)

Answer 64

Very thin layered with two cells (alveolar and endothelial). Has a large surface area. These two qualities make it ideal for gas exchange.

Answer 65

Fick's Law

Answer 66

0.75 seconds that is normal for rest. During exercise there is only 0.25 seconds available.

Answer 67

When there is ventilation to perfusion matching.

Answer 68

Upper airway - nose, mouth, pharynx and larynx Trachae and bronchi. Multiple branching of bronchi into bronchioles eventually terminating into alveoli.

Answer 69

Inspiratory - diaphragm, external intercostals and sternocleidomastoids Expiratory - Internal intercostals and abdominal muscles

Answer 70

Inspiration via negative pressure created. Contraction of diaphragm increases longitudinal and lateral dimensions of the thorax (negative intra-pleural pressure). Contraction of the external intercostals increases the AP diameter of the thorax (negative intra-pleural pressure).

Answer 71

Inspiration requires muscle to create the negative pressure but the expiration is generally passive because of the lung recoil to push the air back out.

Answer 72

1. Resistive - the airflow through bronchi 2. Elastic - the expansion of lungs and chest wall (lungs have some degree of stiffness and want to collapse down).

Answer 73

PO₂ - 100mmHg PCO₂ - 40mmHg pH - 7.4

Answer 74

Increased sensation of breathing, increased use of respiratory muscles, active exhalation, longer inspiration, longer expiration and reduced maximum ventilation.

Answer 75

There may be an increase in load (such as stiff lungs, narrow airways, chest wall and diaphragm that makes it harder to breath). There could be a larger drive to breath (usually by receptors or even when we purposely hyperventilate). There is a larger work required of our body. Such as when we exercise but we perceive it as normal.

Answer 76

It is breathlessness. Sensation when it is normal for it to occur whereas symptom when it is inappropriate.

Answer 77

Normally very low at around 3% of total oxygen usage. Involves stimulation of phrenic nerve for diaphragm and external intercostal muscles through intercostal nerves. Increasing volume of thorax will lead to generation of negative intra-pulmonary pressure.

Answer 78

Respiratory muscles need to generate higher pressures to overcome the obstruction to air flow (resistive work of breathing). It also makes expiration become active.

Answer 79

1. Recruiment of accessory muscles (scalene and sternocleomastoid muscles). 2. Increased oxygen consumption by respiratory muscles. 3. Risk of respiratory muscle fatigue if the airway obstruction is severe.

Answer 80

PaO₂ \<60mmHg and PaCO₂ \> 50mmHg

Answer 81

Intra-alveolar pressure \< Patmospheric during inspiration Intra-alveolar pressure \> Patm during expiration Intra-alveolar pressure = Patm at the end of inspiration and expiration Intra-pleural pressure is ALWAYS \< intra-alveolar pressure because of the elastic recoil of lungs and chest wall.

Answer 82

Spirogram involves breathing in TLC then exhaling as quickly and much out as possible. The graph will increase significantly during FEV1 (70-80% of FVC) until it stabilises to give FVC. Airflow obstruction will generally give a more linear curve meaning that exhalation is much longer.

Answer 83

Use of flow-volume loops. Involves taking a breath in to TLC then blow out as quickly as possible - once it has been exhaled the patient needs to breath in through the tube again to TLC. Different locations of obstruction will lead to different flow-volume loops.

Answer 84

1. Increased sensation of breathing 2. Increased respiratory muscle effort 3. Active exhalation 4. Prolonged inspiration and exhalation

Answer 85

There will always be a decrease in P_aO₂ and increase in P_aCO₂

Answer 86

Gas exchange is most efficient when this matching is 1 for individual AC units (alveolar capillary unit)

Answer 87

Normal people have even distribution and COPD has mismatch between the two.

Answer 88

Not all oxygen binds to Hb molecules - reduce P_aO₂so that some blood returning to the LA is not fully oxygenated. Usually as a result from less ventilation than perfusion.

Answer 89

Extremely low form of V/Q unit where there is no ventilation at all and V/Q = 0.

Answer 90

Usually results in vasoconstriction of blood around the areas with low ventilation to reduce hypoxaemic effects. Sometimes the vasoconstriction may elevate the pulmonary artery pressure.

Answer 91

Usually results in wasted ventilation because there will be more ventilation of the units than required to oxygenate the blood. - Leads to increase in physiological dead space

Answer 92

Measure the CO₂ levels.

Answer 93

1. Bronchial smooth muscle constriction which is responsive to B agonists, anticholinergics, methyl-xanthines. 2. Airway inflammation: responsive to corticosteroids, leukotriene antagonists and mast cell stabilisers.

Answer 94

COPD is smoking related disease that causes inflammation of bronchial mucosa, loss of elastic support of small airways and destruction of the alveolar-capillary membrane. 1. Collapse of small airways -\> airflow obstruction. 2. Impaired gas exchange -\> because of VQ mismatch and loss of A/C membrane 3. Reduced capillary bed -\> pulmonary hypertension

Answer 95

Typically COPD has a lack of AC membrane integrity.

Answer 96

PAO2 = PiO2 – PACO2 / RQ PaCO2 = PACO2 and RQ = 0.8 and PiO2 = 150 at sea level. Then for gradient you need PAO2 - PaO2 Normal levels \< 15-30.

Answer 97

The conducting part is what carries the air along whereas the respiratory part is where gas exchange actually occurs.

Answer 98

This is the nose area.

Answer 99

The sinuses is used for phonation and conditioning air. Olfactory epithelium is for the sense of smell. Turbinates warm and moisten the air so that the air will not dehydrate the airways.

Answer 100

The epiglottis and larynx divert food away from the airways. Larynx is involved in phonation (speech). The larynx is the uppermost part of the trachae.

Answer 101

Lines the airways and much of the nasopharynx (lines conducting part instead of respiratory part) Pseudostratified epithelium with ciliated cells, secretory cells (goblet and deeper glands) of mucus and sensory cells to initiate coughing to expel irritants.

Answer 102

This is to protect against air that have dust particles, fungal and bacterial spores.

Answer 103

The mucus layer traps particles that are then swept up by the cilia to the epiglottis. Ends up in the stomach for sterilisation. Smokers who have damaged cilia cells rely heavily on coughing to shift the mucus upwards of the lungs.

Answer 104

Long tube reinforced with hyaline cartilage. The cartilage is in C-shaped formation with smooth muscle bridging it. The trachae has three layers - mucosa, submucosa and adventitia.

Answer 105

Mucosa is much thinner than the submucosa layer. Submucosa is much broader with connective tissue and glands that secrete mucus.

Answer 106

It contains cartilage and outer layer of connective tissue.

Answer 107

The trachae splits into five different bronchi that lead to different lobes in the lungs (3 - right and 2 -left). Initialy looks like trachae but with thinner walls. As you progress down the airways cartilage rings become cartilage plates instead (lose C-shaped rings). Smooth muscle, glands and lymphoid nodules still present.

Answer 108

Bronchioles no longer have the cartilage. Over the length of the bronchiole they being to lose goblet cells and ciliated columnar cells and gain Clara cells. Still have radial connective tissue, smooth muscle and ciliated cells extend further down than goblet cells (lose the goblets earlier).

Answer 109

These are columnar to cuboidal cells with short microvilli (instead of cilia). Generally found deeper in bronchioles. They secrete surfactants to destroy surface tension (causes alveoli to collapses). They may also neutralised toxin.

Answer 110

Last level of the conducting system. No golbet cells. Clara cells plus cuboidal epithelium with some cilia. There is one or two layers of smooth muscles and they give rise to respiratory bronchioles (first site of gas exchange).

Answer 111

First respiratory structures to appear where alveoli will appear intermittently. Alveoli are thin walled pouches. The epithelium of the respiratory bronchiole are made up of cuboidal to squamous cells.

Answer 112

Surface for gas exchange. Lined with simple squamous epithelium. The wall contains many pulmonary capillaries (deoxygenated blood within them). Also the individual alveoli are connected by pores so that they become connected.

Answer 113

This contains reticular fibres and elastin fibres between the alveoli. They prevent the alveoli from collapse during breathing when negative pressure is generated. Positive air pressure helps it stay open.

Answer 114

They form dense anastomising network of vessels for exchange of gases. The pulmonary epithelium is very thin.

Answer 115

These are present in alveoli made up of simple squamous epithelium. It provides about 95% of the surface area of alveoli. It provides the exchange surface. The basal lamina is prominent because it limits the gas exchange process. - There are tight junctions between the pneumocytes to limit ECF leakage.

Answer 116

More numerous than type I but only found on 5% of the surface area. These are cuboidal cells in the angles between alveoli. They consist of short microvilli and lamellar bodies. - The lamellar bodies secrete surfactants to prevent collapse from surface tension.

Answer 117

There is turnover of pneumocytes that involves Type I dying and being replaced by stem cells. The Type II can divide and give rise to new type I and II as required (stem cells).

Answer 118

This is where the exchange of air takes place across the Type I pneumocyte and endothelial of the capillaries.

Answer 119

Contains mucus, surfactants, type I pneumocytes, basal lamina, connective tissue, basal lamina, endothelial cell then finallay plasma. The thinnest barrier is when there is essentially no connective tissue between the two basal laminas.

Answer 120

These are macrophages that exist in the alveoli and essentially outside of the body.

Answer 121

They can migrate up the airways until they are carried away by ciliated cells. Or some macrophages end up in the interalveolar septum with the particles they ingested (return to body and eventually die and release their contents).

Answer 122

There is abundant lymphatic systems in the pleura to drain fluids. But there are also vessels opened on the surface of the pleura (releases fluid into the space). The consequence of this is that tumour cells can use this pathway to metastasise.

Answer 123

The lag phase is when the virus components are being synthesised and eventually assembled together to form viable viruses. The number of viruses produced are enormous.

Answer 124

Attachment, penetration, uncoating, genome replication, RNA synthesis, protein synthesis, assembly and release of viral particles.

Answer 125

The viral attachment protein must bind to a receptor found on the cell surface of the host. This could be proteins or glycoproteins expressed on the surface (these receptors are just used for normal cell processes)

Answer 126

HIV viruses uses two different cell receptors. gp120 binds to CD4 as primary receptor. This induces conformational change in the glycoproteins - gp41 now binds to CCR-5 as a secondary receptor.

Answer 127

This is achieved via two ways. 1. Lipid envelope viruses fuse with the host cell membrane and then releases the virus nucleocapsid directly into cytoplasm. 2. Other viruses enter the cell via endocytosis

Answer 128

It just refers to the release of viral genome from its protective capsid.

Answer 129

Togavirus does this - it triggers endosome release when the pH is low.

Answer 130

Nucleic acid replication will produce new viral genomes. DNA replicate in nucleus and RNA based virus replicate in cytoplasm. mRNA is produced and used to produce proteins.

Answer 131

DNA dependent DNA polymerase, DNA dependent RNA polymerase and ribosomes, tRNA and AA. - no RNA-dependent RNA polymerase present for RNA invading viruses.

Answer 132

Means the strand of genetic material is the same as mRNA. Negative sense means that it is the complementary base sequence.

Answer 133

Linear, single stranded, plus sense RNA.

Answer 134

The RNA can be replicated to produce more mRNA but that would require RNA-dependent RNA polymerase. Another pathway is that it will be directly translated into proteins. This protein is then autocleaved by itself to produce structural coat proteins, proteases and RNA POLYMERASE.

Answer 135

The RNA polymerase can now enter the through the other pathway. It will allow the RNA to replicate to form new plus strands. It will produce negative and positive strands.

Answer 136

The -RNA viruses carry RNA polymerase with it.

Answer 137

The DNA viruses do not need it because the host cells have the enzymes already.

Answer 138

Negative strands - must carry their own polymerase Positive strands - do not need to carry it

Answer 139

Translation of the proteins occur on the ribosomes in cytoplasm. After the polypeptide is formed it is cleaved by virus-coded proteases. Glycosylation of envelope glycoproteins occur in RER and golgi vesicles -\> allows them to be deposited on cell membrane.

Answer 140

For non-enveloped animal viruses: All have icosahedral structure. It can simply spontaneously assemble with capsid proteins around the nucleic acid genome. Final cleaving will need it to produce mature infectious virions. It will accumulate in the cell and eventually lyse. For enveloped viruses: Release occurs by budding from the cell surface. Patches of viral envelope glycoproteins accumulate on membrane. Capsid proteins and nucleic acid condense directly adjacent to cell membrane. The nucleocapsid then bulges out and forms a new enveloped virion. Another pathway for enveloped viruses is to use secretory pathway to exit the cells. Enclosed in Golgi derived vesicles that are then released through fusion of membrane.

Answer 141

- Lytic infection (overwhelming the cell - enteroviruses, reoviruses): Fast release and death of cell. - Chronic inflammation (Hep C): Slow release without cell death. - Latent infection (herpesviruses): No harm to cell and can emerge later as lytic infection. - Transformation to tumour cells (oncogenic retroviruses)

Answer 142

This is the morphological changes that can be seen due to infection through a light microscope.

Answer 143

Inclusions are accumulated areas of viral proteins at the site of viral assembly.

Answer 144

Viruses encode for oncogenes that is associated with tumour production. These oncogenes were meant to promote growth promoting properties but their expression can lead to uncontrolled proliferation. Other viruses can affect tumours because of the cellular version of the oncogene is activated.

Answer 145

Mutation (errors in RNA replication due to the lack of proof reading - or two viruses infect the same cell), recombination (exchange of stretches of nucleic acid between genomes of SIMILAR sequences especially DNA viruses), reassortment (swapping of segments for viruses that have segmented genomes - with many different properties of viruses).

Answer 146

Antibody blocks the uptake and/or neutralises progeny virus. Killing of the infected cells by cytotoxic T cells, NK cells or antibody mediated processes. The interferons released will initiated a large number of anti-viral mechanisms. Blocking the replication cycle by using specific antiviral drugs.

Answer 147

It is used for herpesvirus infections. Works by attaching the nucleoside analogue to the extending DNA strand. But it does not have the 3' OH group so it can no longer extend the chain further. Acyclovir is an guanosine analogue. It is specific for Herpes because the nucleoside analogue must be phosphorylated three times before it can be attached. The virus' thymidine kinase is required for this step - giving specificity for infected cells.

Answer 148

Must gain entry to body, multiply, spread, target appropriate organ. To maintain nature viruses it must be shed into environment, taken up by arthropod (insect) vectors or needle and passed congenitally. Viral replication can be local or systemic. It will either be cleared or persist. The virus infection location will be determined by whether or not they have the receptor for the viruses.

Answer 149

Conjuctiva, respiratory, parenteral inoculation, alimentary (food and digestive) tract, urogenital tract and skin. Enters through epithelial cells with mucosa. Other areas have dying cells and keratinisation making it a bad environment for viruses.

Answer 150

Most important site of entry. Usually from aerosal inhalation or transmission of infected nasal secretions. The smaller the virus the further down it will lodge in the airways. Viruses will attach to specific receptors on epithelial cells. It can either localise or spread away.

Answer 151

Mucus, cilia, alveolar macrophages, temperature gradient and IgA.

Answer 152

Upper respiratory tract infection - Rhinovirus (better in cooler temperatures), coronavirus and adenovirus. Pharyngitis - Adenovirus Influenza-like illness - influenza virus, RSV (respiratory synctial virus). Croup (larynx and trachae) - Parainfluenza Brochiolitis - RSV and parainfluenza 3 Pneomonia - RSV, parainfluenza 3, influenza virus and adenovirus.

Answer 153

Respiratory synctial viruses in the lungs are that the infect virus cells will fuse together to form a synctial (multinucleated).

Answer 154

Primary replication in URT epithelial cells. Infects local macrophages, lymphocytes and DCs through receptors. They then drain to the lymph nodes and enter the circulation. Eventually returns to the epithelial cells on the lungs and mouth. Rash is due to the immuno response not the viral infection. Transient immunosuppression since it affects immune cells.

Answer 155

Constant movement of contents, mucus, stomach acidity, intestinal alkalinity, proteolytic enzymes from pancreas, lipolysis of bile acid, IgA and scavenging macrophages.

Answer 156

They must be acid and bile resistant (therefore have no envelope). If viruses do not have receptors for the epithelial cells it must enter via a breach of the epithelial surface (HIV - through abrasions of rectal route).

Answer 157

Rotavirus - destroys walls of the stomach or other mechanisms.

Answer 158

Poliovirus and Hepatitis A

Answer 159

M cells ingest the virus and delivers the antigens to underlying lymphoid tissue by transcytosis. M cells are found between enterocytes with tight junctions. Other viruses can infect and destroy M cells. This creates a gap for viruses to enter the intestinal tract.

Answer 160

They have triple shelled capsid and infect and destroy epithelial cells of the intestinal vili and the M cells then cause inflammion and diarrhoea.

Answer 161

Destruction of enterocytes decreases absorption. Also secretion from the virus NSP4 proteins from infected cells make the diarrhoea even worse. NSP secretes fluids from the remaining cells. Usually death through dehydration.

Answer 162

Enters the body then replicates at the primary site. From here it can move into the blood stream (viraemia) and replicate in lymph nodes such as Peyer's Patch. It will then reach the secondary viremia target tissue causing disease. Moves to meninges, CNS, skin and muscles.

Answer 163

Picornavirus

Answer 164

Transcutaneous route (bypassing skin) - minor trauma, injection via needles or blood products or insect/animal bites. Genital tract. Conjuctiva (very rare route of entry).

Answer 165

Local spread around epithelial surfaces. It can invade the subepithelial layer then invade the lymphatic system. Spread through the blood - also known as viremia. It is also able to spread neurally.

Answer 166

Epithelium to lymph nodes to epithelium. This is also so that the viruses will face the lymphatic/immune system first. To trigger the immune system earlier.

Answer 167

This is when the viruses are free in the plasma.

Answer 168

These phases refer to the growth phases. Secondary phase is when it infects other organs that can replicate enormous amounts before re-entering the blood stream again. The goal is to make enough to escape the immune system.

Answer 169

Neutralised by developing antibody response that is then removed by the macrophages (1-2 weeks).

Answer 170

Invades epithelial cells and multiply. Moves to lymph nodes then multiples. It becomes primary viremia when it moves into the blood initially. Moves to other organs and replicates there. Returns to blood (secondary viremia) and moves to the skin and multiplies. Typically takes about 6 days for it to leave the skin so it would have avoided the immune system altogether.

Answer 171

The virus must be able to cross the placenta. The fetus may die from cytocidal viruses such as small pox.

Answer 172

It can cause death or abortion if it is cytocidal. It may not kill the fetus but will cause abnormal development - especially rubella and CMV (cytomegalovirus).

Answer 173

Yes! There can be many other infected sites (even faeces) that the baby may come into contact during birth.

Answer 174

The viremia may cause the fetus to develop an immunological tolerance to the virus (will no longer recognise it to be foreign in later life).

Answer 175

Rubella slows down the rate of cell division leading to impaired growth and organ development in the first trimester. Microcephaly, heart defects, cataracts and deafness.

Answer 176

The right receptor for the virus, temperature, pH, ability to replicate in macrophages and lymphocytes (to other tissues), polarised release (depends if viruses leave apically or basolateral - more systemic) and the presence of activating enzymes.

Answer 177

Death of cells directly from viral replication (cytocidal virus), death due to the toxins released by the viruses, initiation of apoptosis and loss of function of the cells.

Answer 178

Immunopathology - virus elicits immune response, symptoms may be fever (IL-1 and TNF) and enlarged lymph nodes. Antibody-mediated pathology - antibody dependent enhancement of infection as well as antigen-antibody complexes (cannot clear the viruses). T cell mediated pathology - CD4 T cell mediated responses causes some viral rashes (measles) because it induces cytokines to recruit eosinophils. Kidney damage due to deposition of Ag-Ab complex. CD8 T cell mediated responses contributes to liver damage. Autoimmunity - molecular mimicry can affect myelin basic protein or heart muscles. Polyclonal B cell activation. Immunosuppression - HIV replicates in CD4 T cells amd kills them. Measles temporarily immunosuppresses - stops T cell proliferation by infected DC - suppressing IL-12. This will lead to susceptibility to secondary infections.

Answer 179

Virus infects cells and are taken up by macrophages/DCs. They will both release IFN alpha/B (type I IFN), macrophages will produce pro-inflammatory cytokines and IL-12. Combination of both IL-12 and IFN alpha/B to stimulate NK. NK cells leads to lysis of virus-infected cells and are the dominant sourceo f IFN-gamma (T cells as well).

Answer 180

Inhibit viral replication, activate NK cells, enhance MHC I expression and are produced by virus-infected macrophages, DC and tissue cells.

Answer 181

Inhibits viral replication, activates macrophages, enhances MHC Class I and class II expression and produced by NK cells (and T cells).

Answer 182

1. Not being recognised by the immune system 2. Interfering with functioning of particular immune mechanisms. Large complex DNA viruses have acquired many other strategies to evade the immune system (Herpesviruses and poxviruses).

Answer 183

Antibody and T cell latency, antibody - antigenic variation, T cell priming by DC, Tc cell recognition, NK cell recognition, IFN, cytokines (blocking of cytokine production, apoptosis inhibition and complement.

Answer 184

Change in antigenic structure of viruses due to spontaneous mutation (errors in RNA replication - no proof reading) that are then selected by escape neutralisation. Antigenic drift can occur within a single patient for long term infections such as HIV.

Answer 185

Immature DC process the pathogen and becomes matured. It will then be able to interact with naive T cells to activate them. - Block cytokine induced maturation of DCs - Blocks signal transduction within immature DC - Blocks TLR from initiating signal transduction to maturation (the signal pathway binds to a homologue instead) Block T cell stimulation by DCs.

Answer 186

Usually virus antigens are expressed on MHC I. Achieved by viral proteins made in cytosol that enter a proteosome complex to be cleaved. It is taken up to the ER via transporter of antigenic peptides (TAP). It is processed with MHC to be expressed on the cell surface for recognition.

Answer 187

Viruses can cause the MHC I to be endocytosed back into the cytoplasm. HIV. Antigenic variation in the virus displayed can allow viruses to escape the T cells. The T cells will raise its number for the wrong antigen. HIV. Viruses can bind to cytosolic side of TAP and prevent peptides moving into ER - HSV. No receptors will be no the surface. Viruses can bind to TAP on the luminal side to prevent peptide entering ER - CMV. The peptide complex is retained in ER - adenovirus. (Anchors to ER so it cannot reach surface). Infected cells will have virus disrupt the proteosome complex so fragmentation cannot occur. EBV. Decrease in class I gene transcription - HIV, RSV and adenovirus.

Answer 188

Kill virus-infected cells non-selectively. Recognises cell surface receptors that result from virus infections to send a killing signal. The MHC I molecules send inhibitory signals to the NK cell. If the MHC I cell is absent or reduced the NK cell will not have inhibitory signals engaged and end up killing the target cell.

Answer 189

Balance between activation and inhibitory stimulation. MHC Class I molecule activate inhibitory receptor. Other ligands on cell activate activation receptor. Viruses that reduce MHC I expression can except CD8 T cell recognition but become more susceptible to NK killing.

Answer 190

NKp44, NKp46, NKG2D receptors will bind to its ligand.

Answer 191

Present the presentation of ligands to activate NKG2D by retaining it in the ER - Murine CMV. (Decrease activation ligand on surface). Present MHC Class I-like molecule on the surface of infected cells so it delivers negative signal to NK BUT does not present peptides to CD8 T cells.

Answer 192

Soluble factor released from virus-infected cells that inhibit viral replication in neighbouring cells. Type I and II IFN stimulate signalling pathway to upregulate transcription/translation of certain cellular proteins. Especially PKR (protein kinase R) that has antiviral activity.

Answer 193

IFN will aid in the activation of PKR inactive state. But it requires autophosphorylation to become active where dsRNA is a cofactor. dsRNA is only found in the presence of RNA viruses during replication. The PKR active state will cause elF2alpha to become inactivated. This will stop the initiation of translation to occur (both viral and cellular).

Answer 194

Simply because RNA needs to be present to allow the PKR to hook around and autophoshorylate.

Answer 195

Viruses produces small RNA that bind to PKR so it prevents dsRNA from binding - EBV, adenovirus. Virus can encode proteins that bind to dsRNA preventing it from activating PKR - reovirus, vaccinia. Virus encoded homologue of elF2 so it competes for PKR inhibition of the true elF2alpha (by phosphorylation) - vaccinia.

Answer 196

Inherited defects such as Ig class, polymorphism in the genes controlling immune responses, IFN inducible genes and receptor genes (such as CCR5 for HIV as secondary receptors).

Answer 197

Age - newborns and the elder are more susceptible, malnutrition - decrease resistance, hormones, dual infections - more severe disease.

Answer 198

Fatal, full recovery, recovery buut permanent damage (such as cancer), persistent infections (not completely cleared and can resurface to cause disease).

Answer 199

The epiglottis.

Answer 200

URT - Has own normal biota LRT - Does not have a normal biota Also paranasal air sinuses and middle ear will be free of microbiota in the URT.

Answer 201

Viridan streptococci (not a pathogen in respiratory tract but can cause endocarditis), Neisseria species, Corynebacterium species, Gram Negative anaerobes (majority), H. Influenza, C. albicans and Strept. pneumoniae (15-85% - large range of population it affects).

Answer 202

Strept. pyogenes (Group A) and meningococci

Answer 203

Enterobacteria, Pseudomonas, C. Diphtheriae (Unique to humans - humans are the only carriers)

Answer 204

Lungs - P. jirovecii (carinii - causes PCP (pneumocystis pneumonia) this is an AIDs dependent infection) and M. Tuberculosis. In lymph nodes and sensory nerves - CMV, HSV and EBV. After the primary infection with these viruses they become resident and when you become immunosuppressed it will resurface as blisters.

Answer 205

The anaerobe outnumbers the aerobe by 10:1. There are microenvironments in the URT that allow microbiota to grow.

Answer 206

Common cold, Pharyngitis/tonsilitis (sore throat syndrome), sinusitis, otitis media, epiglottis and Croup.

Answer 207

The same syndrome can have different causes - each of these pathogens can cause many other syndromes.

Answer 208

No they do not.

Answer 209

Secondary bacteria infection risk is increased when exposed to cold again.

Answer 210

Rhinovirus, parainfluenza, RSV, enterovirus (summer enteric virus more prevalent), coronavirus, human metapneumovirus (HMPV).

Answer 211

It is less likely going to be bacteria.

Answer 212

Adenovirus, enterovirus, parainfluenza and influenza - mostly viruses.

Answer 213

It could be either virus or bacteria (10-20%). With bacteria it is important to treat with antibiotics.

Answer 214

Adenovirus, enterovirus, reovirus, influenza, Strept. pyogenes (Rash is more likely to be bacteria), Strept groups C and G.

Answer 215

The rash is a result of toxic amoxicillin due to active EBV (Epstein Barr Virus).

Answer 216

The infection can spread along the respiratory epithelial cells to the sterile sinus. Once the mucus of epithelial cells are damaged it becomes susceptible to secondary infection (from the normal biota present).

Answer 217

Primary - Viral (usually part of the common cold syndrome) Secondary - H. Influenzae, Strept. pneumoniae

Answer 218

Otitis media is the inflammation of the middle ear most commonly found in children. The reason why is because children's Eustachian tube is much wider, shorter and straighter than adults. This means that it can be easily infected because it is not sterile. Typically these begin with a virus infection that are not symptomatic - will eventually display symptoms from the secondary bacterial infection.

Answer 219

It used to be H. Influenza B but there are many other pathogens that can cause it now.

Answer 220

The treatments are very different.

Answer 221

Parainfluenza, influenza A and RSV.

Answer 222

The virus infects and is absorbed by the cells in the nasal epithelium. Virus will replicate within that cell until it bursts. At this stage there will be a clear discharge of fluid from the lamina propria. The cell is damaged and the infection will spread. At this stage the host immune system will kick in and begin to phagocytose the cell debris. Virus infection is about over and there will be overgrowth of the commensals - changing the fluid from clear to yellow (purulent). After a while the body will finally recover.

Answer 223

The middle ear to the nasal pharynx.

Answer 224

This is mostly done clinically. However some laboratory diagnosis can be carried out, it varies which syndrome truly needs a diagnosis though. Common cold syndrome - Not needed Pharyngitis/Tonsilitis - If possible to test for Strept Group A found in URT (usually low in carrier numbers) Sinusitis - Seldom necessary Otitis media - Seldom necessary Epiglotiss - Whenever possible Croup - Seldom necessary

Answer 225

Avoid touching an inflamed epiglottis as it could kill a person by suffocating them as you push on the epiglottis. Instead clinicians should take X-rays to check if it is swollen then take a blood culture to confirm the pathogens.

Answer 226

Yes. Blisters (Herpangina) is caused by enteroviruses and rash can be caused by coxsackie virus.

Answer 227

It is mostly supportive treatment - to relieve symptoms such as pain. Typically use aspirin in adults and not children due to liver damage - but antiinflammatory drugs are immunosuppressive so it makes the patient more infectious. So it may be beneficial to use panadol instead. Common cold - nothing available unless for specific patients Pharyngitis/Tonsilitis - Only treat if it is bacterial to prevent downstream complications (especially delayed complications like autoimmunity). Sinusitis - Only treat bacterial infections and if they are severe. (Use antibiotic against the specific agent). Otitis media - Only treat if they are \<2 y.o or prolonged and severe. Epiglottitis - Essential to treat properly Croup - Usually no treatment, can use inhaled steroids if severe.

Answer 228

If you treat with antibiotics the secondary infection is generally very resistant and make it hard to treat.

Answer 229

Acute bronchitis, Acute exacerbation of chronic bronchitis, bronchiolitis, pneumonia, lung abscess and empyema (pus in the cavity of the body).

Answer 230

Usually it is the viral part of the URT infections.

Answer 231

Usually pneumococcia and/or H. Influenzae

Answer 232

The production of sputum.

Answer 233

It is thought to be an immune reaction between the antigen and pre-formed antibodies inherited from the mother. The complex will deposit on tissues and attract complements and start inflammation.

Answer 234

It is during expiration where the airways collapse. This is because of the already inflamed bronchioles.

Answer 235

RSV (respiratory syncytial virus).

Answer 236

Typical (acute bacterial), atypical and others (caused by fungi)

Answer 237

Typical pneumonia is generally localised to lobar infections. Whereas atypical pneumonia is patchy and have be diffuse. Typical pneumonia will have acute onset of the infection symptoms whereas atypical will be very gradual on and off. Typical - inflammation of alveoli, caused by bacteria. Atypical - inflammation of interstitial fluid, may be caused by viruses or bacteria.

Answer 238

Pneumococci (mostly -from normal respiratory biota). The other pathogens could be H. Influenzae, Staphylococcus, Klebs (acquired from hospital, Staph and Klebs), Legionella (immunocompromoised - older?), TB and Chlamydophila (intracellular bacteria that has a life cycle of replicating and infecting).

Answer 239

Mycoplasma (no cell wall so has no fixed shape), Chlaymydia (usually in babies 1st month of life - acquired from the mother), M. Catarrhalis, influenza, RSV, adenovirus, etc

Answer 240

Histoplasma, Aspergillus and pneumocystis (Fungis)

Answer 241

Mixed anaerobes. Staph and Klebsiella.

Answer 242

This is pus found in the pleural space. Primary infection is Staph. Aureus and secondary to pneumonia.

Answer 243

To prescribe appropriate antibiotics. There are a few must know pathogens: SARS, MERS, Influenza (some types such as swine flu is important), Legionella species (public health), Bioterrorism agents (anthrax and plague), community acquired MRSA (prognosis and treatment of methacillin resistant Staph Aureus). There are also some 'should know' pathogens: Penicillin G resistant Staph. Pneumonia and Gram Negative Rods such as P. Aeruginosa.

Answer 244

Clinical, radiological and laboratory tests. The laboratory tests include types of specimens, microscopy, detectiong of antigens, nucleic acids, culture and serology.

Answer 245

Whether it is community or hospital acquired. How severe the disease is. Are there any underlying diseases such as COPD, AIDs, cystic fibrosis? Any other risk factors that could contribute such as occupation (animals, hides, air conditioning, soil), travel or even homelessness.

Answer 246

Properly collected sputum (not spit - since the saliva organisms can cause pneumonia too). The sputum sample will be checked for the presence of inflammatory cells (important to know it was collected properly), then gram stained to differentiate pneumonia causing agents. Gram positive diplococci - Pneumococci (then do further testing) Gram negative - Klebsiella Other specimen types: Transtrachael aspirate, aspiration via tracheostomy (useless because it is easily contaminated), aspiration via bronchoscope, pleural tap (if effusion), lung biopsy (needle and open) or blood for culture and serology.

Answer 247

Mycoplasma pneumonia, Legionella pneumophila, Chlamydophila and Chlamydia species and Coxiella burnetti (intracellular bacteriam different from Chlamydia because it does not have a life cycle - Typhus fever) Used to look for specific IgM and rising titre. Can be used to detect common antigen for common viruses, Bordetella, Legionella and pneumophila type 1 (from urine for legionella).

Answer 248

It is generally useless because it contains the microbiota of the URT that can cause LRT infections. But the swabs are useful when looking for virus diagnosis, because the presence of virus higher up in the URT could lead to LRT infections.

Answer 249

For community acquired pathogens we can use the best guess approach. We can assume it will be pneumococcus. - Administer Penicllin G/Amoxicillin with doxycycline/Macrolide (usually antagonistic but we get plenty in the lungs). Once you confirm pathogen you can remove one of the drugs. - Modify treatment if it is severe, know the cause of specific risk factors. For hospital acquired pathogens: It will depend on the severity and risk group of the patients.

Answer 250

Influenza vaccine (to specific strains and has no effect on developing pneumonia). Pneumococcal vaccines are available as well as specialised vaccines.

Answer 251

This is literature review focused on a single question. It involves identification, appraisal, selection and synthesis of high quality evidence to answer the question. Can reviewl both clinical trials and observational data. This is the highest level of evidence (generally - sometimes randomised controlled trials can be better)

Answer 252

This is a statistical analysis of all the combined data from multiple studies. The purpose of it is to increase power, resolve uncertainty, improve estimates of effect size (precision)

Answer 253

PICOT or a clear clinical/research question.

Answer 254

MEDLINE, EMBASE, CENTRAL, CINAHL, DARE are the general big journal publications. Important to use standard terms when searching and include all relevant spellings (US vs UK). Once a search has been done remember to limit the papers acceptable (such as random controlled trials only). Check the reference list sourced in the papers to find any other relevant papers. Grey literature may be used as well for additional information.

Answer 255

Make sure the papers are relevant to the question we are answering (PICOT). But be careful not to let this introduce bias (selection).

Answer 256

Done by at least 2 people who read all the abstracts (but sometimes may not be representative of the full paper), apply inclusion/exclusion criteria, obtain full papers then assess for quality.

Answer 257

This is to outline the process needed to be done as well a checklist to improve the quality of report. The risk of bias table is used to assess the protocol used.

Answer 258

This is generally done by statistical software such as STATA.

Answer 259

The outcomes give the weighted average effect size (which can be a relative measure - RR or OR, or absolute measure - mean difference). Individual studies are weighted differently because of the different sample size and inverse variance (the more variant it is from the mean the less weighting it will have). The impact of heterogeneity will impact on the effect sizes. This will require chi-square test to see how similar the studies are.

Answer 260

For heterogeneity tests we want P\>0.05 because that would indicate low heterogeneity. Line of null effect on the right uses '1' value as ratio. Whereas the line on the left will indicate '0' value as absolute changes. Interpreting effect size of study - larger area of square gives relative weighting of contribution. The width indicates the confidence interval (line is used if sample size is small).

Answer 261

The validity of meta-analysis relies on whether or not the studies are similar enough to be pooled together. This can be done through non-statistical methods as well such as comparing PICOT. This is not an objective method to assess it.

Answer 262

Generally use PRISMA checklist and flow chart to aid in our presentation of the review.

Answer 263

It is to provide validity to whether or not to use the tests.

Answer 264

True positive - Positive test and has disease False positive - Positive test but has no disease True negative - Negative test and has no disease False negative - Negative test but has the disease

Answer 265

%people with the disease that test positive Given by: TP/(TP + FN) \*100

Answer 266

%people without the disease that test negative Given by: TN/(TN+FP)\*100

Answer 267

Positive predictive value - % positive tests that are truly positive Given by: TP/(TP+FP)\*100 Negative predictive value - % negative tests that are truly negative Given by: TN/(TN+FN)\*100

Answer 268

PPV and NPV are dependent on sensitivity and specificity as well as the underlying prevalence of disease.

Answer 269

You want a high PPV. If you have a low PPV the positive tests that come back will most likely be without disease.

Answer 270

Overall decrease in inflammatory cell number and activation. This will decrease the probability and severity of asthma episode. - Reduces activation/recruitment of eosinophils, T cells. - Reduces cytokine production from macrophages, mast cells, SMC and fibroblasts.

Answer 271

GC will enter the cell and bind to its receptor causing chaperone proteins to dissociate. Depending on whether or not the GCR/GC complex is a momer or dimer it will result in different responses. Transrepression - monomer: It inhibits the activation of pro-inflammatory proteins (COX-2, IL-8, iCAM-1 and NOS-2). This is done by protein-protein interaction of the monomer with NFkB found on the gene. The GC will attract HDAC that will tighten up the DNA. Transactivation - dimer: These will bind to the GRE (response element) to promote transcription of anti-inflammatory proteins (GILZ, MKP-1 and IkBa).

Answer 272

Increase in IkBa that will inhibit NFkB by forming the complex. IkBa is dissociated by phosphorylation by IKK. GILZ - directly inhibits NFkB activity before it reaches the nucleus. MKP-1 inactivates JNK-P to form JNK. This will reduce AP-1 and therefore not promote the pro-inflammatory gene expression.

Answer 273

Used to treat asthma when the patient requires \>3 times/week of B2 agonists. Also can be used for COPD - but the results are not as impressive as asthma.

Answer 274

The disease both have different inflammatory processes. The GCs target the component that is significant in asthma - eosinophils and mast cells. Whereas for COPD it is predominantly macrophages and neutrophils.

Answer 275

Budesonide and fluticasone propionate (combination with LABA). Beclomethasone diproprionate Start at an effective dose then eventually step down.

Answer 276

Prenisolone (oral administration). A. Several days - used for acute exacerbation. B. Chronically - Severe asthma only (because the adverse effects are significant)

Answer 277

Inhaled is generally well tolerated. Dysphonia (change in voice), oral candidiasis (thrush - white on tongue), decrease serum cortisol. Mouthwash decreases absorption of GCs (locally).

Answer 278

These are the GCS that have dose and indication limitations. Osteoporosis, diabetes, muscle wasting, hypertension, growth suppresion (caution in children), suppression of HPA axis (requires tapering off if using chronically - to avoid withdrawal).

Answer 279

Cortisol and synthetic GC inhibit CRH by direct actions on the particular sites. This causes failure of the trophic hormones that causes the adrenal glands to undergo atrophy so it reduces the endogenous cortisol production. Acute stop in the synthetic GC could lead to acute adrenal crisis due to the reduced capacity of the adrenal glands. Negative feedback to anterior pituitary and hypothalamus leading to reduced stimulation on adrenal glands.

Answer 280

These reduce the degradation of cAMP therefore increases its levels (in bronchiole SMC - refer to myosin LC and IP3 receptors). This leads to muscle relaxing effects. Theophylline - PDE inhibition/smooth muscle relaxant, HDAC2 activation and adenosine antagonism. Roflumilast - selective PDEI because it reduces side effects compared with theophylline (approved for COPD).

Answer 281

Nausea, vomiting diarrhea, CNS stimulation (low safety margin), cardiostimulation (dysrhythmias). Very low therapeutic index.

Answer 282

Intermittent - SABA (\< daily) Mild persistent - SABA + inhaled GCS (daily) Moderate persistent - SABA + inhaled GCS + inhaled LABA (LABA always with GCS) Severe Persistent - SABA + inhaled GCS (increase dose) + inhaled LABA + if needed theophylline, anti-leukotrienes, Oral GCS Severe deteriorating - Add oral prenisolone on top of the other treatment.

Answer 283

Major ones: Tobacco smok, lung growth development (start at lower functional point), age. Others: exposure to particles in bad environment, air pollution, gender, respiratory infections (acceleration of decline), socioeconomic status, asthma/bronchial hyperreactivity, chronic bronchitis.

Answer 284

It is preventable and treatable disease with significant extrapulmonary effects. It is not fully reversible. Associated with airflow limitation that is progressive and abnormal inflammation of lungs against gases or noxious particles. Usually see loss of plung parenchyma, small airways inflammation, fibrosis and thickening and pulmonary hypertension (could lead to cor pulmonale meaning it leads to RH failure).

Answer 285

Mild - \>80% predicted FEV1 Moderate - between 50-80% predicted Severe - 30-50% predicted Very severe - \<30% predicted All of these are post-bronchodilators.

Answer 286

The lung function decline due to age is constant. The smokers generally further the decline so they have a low starting point (less redundancy). After that it will decline as usual.

Answer 287

Gives initial boost in lung function then after that the lung function will decline as usual.

Answer 288

Layer of surfactant, type 1 alveolar cell, basement membrane and vascular endothelial cell.

Answer 289

It is very thin (0.5 micron) and has a large surface area (50-100m squared).

Answer 290

Inflammation, infection, fibrosis, emphysema, fluid, cancer etc.

Answer 291

Pneumonia is a subtype of pneumotitis that is generally caused by infectious agents.

Answer 292

1. Abnormal gas exchange 2. Abnormal lung mechanics 3. Pulmonary vascular complications

Answer 293

The diffusion process is passive because it is driven by the different in partial pressures of gases on either side of AC membrane.

Answer 294

The PaO2 will go down and the PaCO2 will go up.

Answer 295

This is given by the Fick's Law. V rate is proportional to (A.D.(P1-P2))/T A - surface area D - solubility of gas and molecular weight T - Thickness P - Partial pressures of gases

Answer 296

Usually oxygen diffusion is complete with 0.25 seconds. At rest we have 0.75 seconds for oxygen diffusion to occur. This allows time for redundancy when we need to increase our cardiac output (decrease transient time).

Answer 297

Usually occurs during exercise with less severe disease because the exercise highlights the limitation (less transient time). It is typically still fully oxygenated at rest. However at rest it is highly unlikely to see diffusion limitation. It only occurs in severely abnormal AC membrane.

Answer 298

Diffusion of CO2 is similar to oxygen but it is 20 times faster. Therefore diffusion limitations of CO2 is extremely rare (severe abnormalities).

Answer 299

It is due to inadequate ventilation.

Answer 300

Low PaO2 if: - Low PiO2 - Low ventilation - Abnormal gas exchange: Low VQ (most common), shunt (extreme VQ mismatch), diffusion impairment (usually manifests during exercise). High PaCO2 if: - Low ventilation.

Answer 301

Usually feels like a tight band around your chest. This increases breathlessness, increased work of breathing (WOB), reduced lung volumes, altered pattern of breathing and reduced maximum ventilation.

Answer 302

This will increase WOB, because greater forces are needed to overcome the stiffness (reduced compliance) of the lungs. This is known as elastic WOB. Consequences of increased WOB, leads to accessory muscle recruitment, increased oxygen consumption by muscles, risk of respiratory muscle fatigue and ventilatory fati (O2 \< 60mmHg and CO2 \> 50mmHg).

Answer 303

Restrictive (no change in airflow in the airways): Reduced FVC, reduced FEV1, normal FEV1/FVC. Obstructive: Normal FVC, Reduced FEV1 and reduced FEV1/FVC.

Answer 304

1. Tissue composition 2. Surface tension (which is reduced by surfactants). Reduced surface tension leads to increase in compliance. Usually not a problem unless it is in hyaline membranes in premature babies.

Answer 305

This is the loss of AC membrane that will cause diffusion problems. The loss of tissue makes the lungs more compliant (also loss of elastic tissue). So we usually see the barrel chest appearance.

Answer 306

Increased in compliance - emphysema Decreased in compliance - Pulmonary fibrosis

Answer 307

For a particular minute ventilation a person will adopt a pattern of breathing to mimise WOB. Stiffer lungs - Usually take rapid shallow breaths Obstructive lungs - Will take slower longer breaths. But essentially the same minute ventilation is achieved.

Answer 308

The maximum ventilation is only reduced in restrictive lung disease (e.g. 35 \* FEV1). In normal people the limitation is usually cardiac related. Exercise usually worsens both hypoxia and pulmonary hypertension.

Answer 309

This is to ensure that the fluid will not be exiting out of the capillary and into the interstitial fluid (eventually alveoli). Pulmonary artery pressure - mean 15 mmHg Capillary pressure - 12-8 mmHg

Answer 310

Thin walled RA and RV. Recives all right heart ouputs. And at rest the capillary volume is about 60-80mL. During exercise pulmonary artery pressure DOES NOT increase because of vessel dilation. It is a reservoir for blood because blood pooling occurs during inspiration. Decrease VR, decrease CO, decrease systolic BP on inspiration.

Answer 311

Increase in fluid leaking out of capillaries and increase pressure on the pulmonary arteries.

Answer 312

JVP - reflects RA pressure Cyanosis - More than 4g/100mL of deoxygenated Hb Crepitation - Implies fluid or fibrosis of the terminal lung units

Answer 313

Usually implies fluid overload by heart failure.

Answer 314

pH \< 7.35 - 7.4 and there is no increase in PaCO2 levels. A better indication will be to look at the bicarbonate level. When acid is added bicarbonate will act as a buffer, we will see a reduced level.

Answer 315

The kidneys will excrete bicarbonate that will lead to metabolic acidosis because there is less buffer.

Answer 316

Sum of positive ions (Na+ and K+) and sum of anion ions (Cl- and HCO3-). The difference between the cation and anion. The difference is usually about 15 mmol/L. In metabolic acidosis the H+ will be buffered by HCO3-. This will make the anion gap \>15mmol/L because of the buffer and the blood test not showing bicarbonate being produced. The second type of metabolic acidosis is when the anion gap is normal. Because a reduction in bicarbonate also increases chlorine (normal \<15 mmol/L gap).

Answer 317

Pulmonary oedema first from the heart failure, this will impair the gas exchange and therefore oxygen delivered to the tissues. The lack of oxygen to the tissues results in lactic acid being formed. Metabolic acidosis.

Answer 318

1. Hydrostatic pressure inside and outside the capillary. 2. Oncotic pressure inside and outside the capillary (usually retains water). 3. Permeability of the capillary.

Answer 319

Increase in capillary hydrostatic pressure (increase in pulmonary venous and left heart pressures) and increase in permeability of capillary. These are the most likely causes. Other factors that will increase capillary fluid leaking. Decrease in oncotic pressure and reduction in lymphatic drainage.

Answer 320

This implies that the cause of pulmonary oedema is most likely due to increase in capillary permeability.

Answer 321

pH \> 7.4 and there should be reduced PaCO2 levels.

Answer 322

The lymphatic flow usualyl drains the fluid 20mL/hour. The fluid moves into the interstitium but if the rates are mismatched with the drainage - fluid will fill up the interstitium. Eventually the fluid will move into the alveoli.

Answer 323

There will be decrease in compliance, decrease in lung volume (lungs will collapse), increase in airway resistance (fluid can press on the airways - clinically leads to wheezing as well as creps) and increase WOB (elastic and resistive - increased elastic work because of reduced compliance and only sometimes resistive work). Hypoxia due to shunt or low V/Q units that leads to diffusion impairment. Decrease PaO2, decrease CO2 and increase pH. If it is very severe it will cause: Increase PaCO2 and decrease pH. Typically metabolic and respiratory acidosis. Metabolic acidosis generally occurs with poor cardiac output. Finally may lead to pulmonary vascular resistance.

Answer 324

Bronchus still has cartilage whereas bronchioles no longer have any.

Answer 325

This is all the sites where gas exchange occur after the respiratory bronchioles. Includes respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli.

Answer 326

Made up of 3-5 acinus units and usually includes the same parts of the system as well as the terminal bronchiole.

Answer 327

Chronic, diffuse and non-infectious.

Answer 328

Obstructive - decrease FEV1, almost normal FVC Restrictive - FEV1 decreases/normal (no real obstruction) but it is mostly decreased FVC for restrictive.

Answer 329

COPD is caused by smoking that cause chronic injury to the small airways. Leading to emphysema and chronic bronchitis. (Overinflation and productive cough). Asthma is caused by hyper-responsiveness triggered by allergens and infections. It is reversible obstruction.

Answer 330

Increased responsiveness of aiways to various innoculus stimuli leading to episodic bronchoconstriction that is at least partly reversible.

Answer 331

Atopic or allergic asthma - IgE levels and specific external allergens. Non-allergic asthma - Normal IgE with non-specific triggers. Others.

Answer 332

Acute/immediate response: increase permeability, increase mucus production and bronchospasm (can be targeted by B2 agonists). Late response: Chemotaxis of eosinophils, mast cells, lymphocytes, macrophages leading to ongoing inflammation. Epithelial tissue damage. (NOT affected by bronchodilators). Recruitment of neutrophils will destroy the underlying cells.

Answer 333

Short term could lead to death, atelectasis (partial collapse of lungs), spontaneous pneumothorax. In severe chronic asthma: Airway remodelling by fibrosis leading to irreversible obstruction. The chronic hypoxia leads to pulmonary hypertension and eventually cor pulmonale (RHF - Right heart failure).

Answer 334

Wheezing, SOB, coughing, anxiety (salbutamol or lack of oxygen to brain), hyperinflated lungs.

Answer 335

Acute severe asthma that is not responding to bronchodilators.

Answer 336

Abnormal, permanent enlargement of air spaces distal to the terminal bronchioles due to destruction of the alveolar wall WITHOUT fibrosis.

Answer 337

Smoking. This is the enlargement of the respiratory bronchioles.

Answer 338

Tobacco produces ROS that can trigger neutrophil infiltration (nicotine from smokes can do this too). The ROS will also inactivate antiproteases (resulting in more protease). The neutrophils will release elastases on top of the existing proteases. Both the proteases and ROS will cause tissue damage. Alveolar macrophages will also activate to increase elastase and metallo-proteinases. Smoking results in an imbalance between proteases and anti-proteases in the lungs.

Answer 339

Loss of elastic recoil because of the lack of supporting elastic tissue around the small airways will cause it to collapse. During expiration the flow of air out will cause the airway to collapse.

Answer 340

Hypoxia due to airflow obstruction (main problem) or loss of surface area of your lungs (VERY RARE). Could lead to pulmonary hypertension then cor pulmonale. Pneumothorax.

Answer 341

Bullous emphysema - large discs of air that could burst and cause pneumothorax. Interstitial emphysema - air escaping into the soft tissue NOT your normal emphysema.

Answer 342

Persistent productive cough of sputum for at least three months in the past two years.

Answer 343

Affects larger and smaller airways where as emphysema affects the distal tubules.

Answer 344

Chronic irritation by inhaled substances, increased mucus production in the large airways (protective response to flush out the chemicals) and airway inflammation that could lead to scarring and narrowing of the smaller airways. Mucus and the inflammation cause the obstruction in the airways.

Answer 345

Excess mucus - hypertrophy of mucus secreting glands (Reid index \> 0.4) and increased goblet cells. Mild increase in lymphocytes, macrophages and plasma cells and oedema. Peribronchial fibrosis in small airways. There may or may not be squamous metaplasia.

Answer 346

The most important one is superimposed infective exacerbations (usually the common respiratory pathogens will cause infective bronchitis). Also hypoxia, pulmonary hypertension, cor pulmonale. Squamous metaplasia, squamous dysplasia (change in size which is premalignant).

Answer 347

Affects the terminal bronchioles (very small airways) that is caused by cigarette smokes.

Answer 348

Chronic inflammation, fibrosis and obstruction of terminal bronchioles (\<2 mm).

Answer 349

Chronic obstructive pulmonary disease. It is an umbrella term that consists of emphysema, chronic bronchitis and small airways disease (there is some reversible bronchospasm - very minor component). It is characterised by slow progression with superimposed infective exacerbations.

Answer 350

Bacterial bronchitis. Also associated with increase in bronchospasm.

Answer 351

Predominant bronchitis: Early copius sputum, 40-45 y.o, common infections, mild dyspnea late, increased airway resistance, normal elastic recoil and blue bloater. Predominant emphysema: Late scanty sputum, 50-75 y.o, occasional infections, severe early dyspnea, normal airway resistance, low elastic recoil and pink puffer.

Answer 352

Inhibition of the muco-ciliary escalator leading to increased mucus production. Smoking also inhibits the leukocyte function and can do direct damage to the epithelial layer.

Answer 353

Irreversible, abnormal dilatation of bronchi/bronchioles.

Answer 354

Severe destructive inflammation of airways (or recurrent infection that may or may not lead to obstruction) causing loss of surrounding elastic tissue, and muscle outweigh the contraction of fibrous tissue. This leads to impaired clearance of organism and fluid.

Answer 355

Necrotising infections - Staph Aureus, Influenza or Aspergillus Obstruction (+infection) could lead to fluid stasis and make it optimal for infections. Cystic fibrosis, cilia disorders and other non-infectious inflammatory conditions.

Answer 356

Dilated airways full of pus. Severe productive cough that has foul smell, episodic fever, SOB and cyanosis, cor pulmonale, metastatic infection (to the brain) and amyloidosis (rare).

Answer 357

Chronic, diffuse, non-infectious. Inflammation and fibrosis of the inter-alveolar septa (interstitium) - this is usually very thin. Diffuse reticulo-nodular and/or ground-glass patterns on CXR. A specific cause or diagnosis is often not identified.

Answer 358

Cause is unknown but histologically it will show interstitial pneumonitis (UIP). This is interstitial inflammation that can have varying fibrosis stages (throughout the lungs). Survival years are usually 3 years as it will inevitably progress to end stage lung.

Answer 359

Fever/chills, cough, headache, muscle aches, fatigue and loss of appetite. CXR will come up as normal. Acute infection that can last 7 days or longer.

Answer 360

Droplet infection from sneezing and coughing.

Answer 361

Incubation period 1-5 days. Infectious for 5-6 days.

Answer 362

Droplets of virus enters the respiratory tract. Virus binds to sialic acid-containing receptors on non-ciliated respiratory epithelium. In humans it is SA alpha 2-6 chains. Infection remains localised in the respiratory tract. Occurs mostly in the large airways (can be in upper and lower tract). It will cause tissue damage and an inflammatory response leading to fever, headache and muscle aches. Pre-existing and developing immunity is sufficient to clear the virus in immunocompetent individuals. Later in infection the viruses will affect ciliated epithelium of trachae and bronchi. This is especially important because of a possibility of secondary bacterial infection (H. Influenzae, Staph. Aureus, Strep. Pneumonia) -\> bacterial pneumonia is the main cause of death in elderly (rare for viral pneumonia).

Answer 363

Very young, very old and individuals with underlying chronic conditions such as heart, lung, renal or metabolic.

Answer 364

Members of the Orthomyxoviridae family. They are enveloped viruses with a segmented genome of ssRNA of -ve sense (need to bring its own RNA polymerase).

Answer 365

Type A,B and C where A and B are the significant pathogen to humans. Type A influenza viruses are able to infect other species.

Answer 366

Hemagglutinin (HA) and Neuraminidase (NA) on the surface of the envelop. Right under the envelop is the M1 matrix that gives the virus rigidity. M2 ion channel is also found here. Contains 8 different gene segments in RNPs (ribonucleoproteins). There are also 3 polymerase subunits found in the virus. NS1 - Non-structural protein has anti-interferon activity

Answer 367

HA acts as a gripper to bind with the receptors. NA acts to cleave the sialic acid off the receptor.

Answer 368

Type A viruses have similar internal antigens. However they differ in their HA and NA. HA - 16 NA - 9 Aquatic birds have all of the different subtypes because they have been hosts for a long time.

Answer 369

HA binds to receptor (sialic acid linked to galactose) on surface respiratory epithelial cells. Virus taken up by endocytosis. Endosome becomes acidic - but this causes conformation change in virus' HA allowing it to fuse with the endosome membrane. The 8 Viral RNPs escape the endosome and enter the nucleus. Viral protein will be produced as well as new viral RNPs. These will come together to form the virus. HA and NA will go through glycosylation in ER and golgi then be expressed on the cell surface. Newly formed viruses must be cleaved by tryptase (found with Clara cells - only in respiratory tract) to become infectious. Viral NA also cuts the sialic acid receptors found on the host cell so that they will not re-bind.

Answer 370

Only Clara cells have the tryptase to active the influenza virus.

Answer 371

The cleaving will reveal a hydrophobic fusion peptide that is important for the virus to escape the endosome.

Answer 372

CD8 T cells will kill virus-infected cells. Aid in recovery from Influenza. They are abe to recognise internal antigens which gives it cross-reactivity with different types of Influenza (A). Antibody will help speed up the clearance of virus. It can act to prevent virus from binding or cleaving it self off from host cells. Can promote phagocytosis by Complement activation. Pre-existing antibody will neutralise input viruses.

Answer 373

Antigenic drift leads to new subtypes of Influenza Virus by mutations due to the lack of proof reading in RNA-polymerase. The mutations can be advantageous, neutral or bad for the virus. Mutations in the HA and NA binding site can allow it to evade antibodies.

Answer 374

It binds through 5 epitopes found on the receptor. If all five of these sites mutate the majority of the population will have no pre-existing antibodies this may lead to an epidemic.

Answer 375

Aims to create antibodies against the HA and NA to block attachment and efficient release.

Answer 376

Contains three different Influenza viruses that represent the most recent strains. H1N1 and H3N2 and Influenza B. These are chemically inactivated so that they do not induce cytotoxic T cell responses but will still create antibodies.

Answer 377

The antiviral drugs inhibit the M2 ion channel so that the virus cannot escape the endosome. They also act as NA inhibitors to block efficient release.

Answer 378

When the virus is in the endosome the virus M2 ion channel delivers the H+ from the outside of the virus to the inside. Once you acidify the inside the virus it will be able to undergo conformational change to release itself. This is blocked by the following drugs: Amantadine and rimantadine (not H5N1) not active against type B influenza.

Answer 379

Orally administered daily. Usually used prophylatically to prevent widespread outbreaks. However not readily used in the wider community because drug-resistant viruses easily arise.

Answer 380

Relenza and Tamiflu (H1N1 beginning to develop resistance). Relenza - inhalation by mouth Tamiflu - Orally as prodrug

Answer 381

Sudden appearance of new Influenza A virus of a new HA within the human population (sometimes NA). The HA usually comes from bird species. Pandemics are rare because human virus receptors see alpha 2-6 galact whereas bird viruses see SA alpha 2-3 Gal. A single amino acid change in receptor binding pocket of HA can lead to change in receptor binding specificity.

Answer 382

Swapping of gene segments when the viruses are co-infected in a single cell. This is shown in a pig example where it has both receptors for human and bird viruses.

Answer 383

Disease that is prevalent across a county or world

Answer 384

Increased fluid leakage from the capillaries, increased pressure in pulmonary arteries and obstruction in the arteries by an emboli.

Answer 385

A form of diffuse interstitial lung disease from the exposure to asbestos - this leads to progressive diffuse inflammation and fibrosis of the lung parenchyma causing disruption of the AC membrane.

Answer 386

Gas exchange and mechanical defects leading to reduced PaCO2, Increasing A-a gradient, also decreased in lung volume (from the scarring - restrictive ventilatory defect), decrease in compliance and therefore increase in work of breathing.

Answer 387

Present with progressive exertional breathlessness and cough. Clubbing, crepitations +/- cyanosis on examination.

Answer 388

1. Destruction of pulmonary capillaries (inflammation and scarring will reduce the number of pulmonary capillary beds). 2. Spasm of pulmonary arterioles.

Answer 389

Should be \<100, therefore \>100 is abnormal.

Answer 390

No. In normal individuals the oxygen saturation does not drop at all during exercise unless it is an elite athlete.

Answer 391

Would hear wheezing sounds

Answer 392

Would expecet to hear crepitation.

Answer 393

This is typically down by exclusion.

Answer 394

Get them to inhale and swallow radioactive substances so that it stays in the lungs. It will show which regions in the lungs is being ventilated and what areas are being perfused.

Answer 395

Increased RA pressure and systemic venous pressures. This will lead to peripheral oedema, ascites (accumulation of fluid in the peritoneal cavity) and pleural effusions. Right ventriculation dilatation and hypertrophy will also lead to reduced cardiac output. Leads to breathlessness and lassitude.

Answer 396

Most important one is increase in pulmonary vascular resistance. This is done by vasoconstriction, obstruction or obliteration. Other ways involve increased LA pressure and increased pulmonary blood flow.

Answer 397

Acidosis is the reduction in pH levels. Can either be respiratory (CO2 retention) or metabolic (loss of HCO3 or addition of acid). Respiratory - Lower pH, increased PaCO2 Metabolic - Lower pH, decreased HCO3 There are two compensation mechanisms: 1. Bicarbonate retention for respiratory acidosis (Days because renal is slow). 2. Hyperventilation (low PaCO2 - just below normal) for metabolic acidosis (seconds)

Answer 398

Alkalosis is increase in pH by respiratory (hypoventilation - low CO2 levels) or metabolic causes (increased HCO3 or loss of acid). Respiratory - High pH, Low CO2 Metabolic - High pH, High HCO3 Compensation by two mechanisms: 1. Bicarbonate excretion for respiratory alkalosis (days) 2. Mild hypoventilation for metabolic alkalosis (conflict of interest with reduced oxygen circulation leading to potential hypoxia)

Answer 399

3.5 HCO3 for every 10mmHg.

Answer 400

pH=7.40 PaCO2 = 40mmHg HCO3- = 25

Answer 401

It will never fully compensate to the normal pH. Acidosis will most likely be found in the lower normal ranges. Alkalosis compensation will most likely be found in the upper normal ranges.

Answer 402

Hypoxaemia, hypercapnoea (and respiratory acidosis).

Answer 403

Respiratory centre and peripheral chemoreceptors. The central controller includes the brain stem (pons and medulla) and cortex. It is important that the respiratory rate is not only driven involuntarily. The cortex allows us to voluntarily control our breathing such as hyperventilate (hypocapnoea). Brain stem outputs via phrenic nerves.

Answer 404

Central chemoceptors - on medulla and responds to CSF H+ that indirectly measures PaCO2. It does not respond to PaO2. Peripheral chemoceptors - found in carotid and aortic bodies that respond to low PaO2, pH and increased PaCO2 that result in increased ventilation. Lung and other receptors - pulmonary stretch, joint and muscle receptors, painful stimuli, upper airway receptors and J receptors.

Answer 405

Increased ventilation linearly. There are varying sensitivity responses from different people.

Answer 406

As the O2 levels drop in the artery it will only trigger an increase in ventilation if it drops below 50-60mmHg. PaO2 of this level typically correlates to 90% oxygen saturation.

Answer 407

Ventilation will increase with work to maintain PaO2 and PaCO2. Once you are beyond the anaerobic threshold you will increase ventilation more. Ventilation is matched to oxygen consumption and CO2/H+ production.

Answer 408

This is when the rate of alveolar ventilation is not meeting metabolic requirements for oxygen consumption and carbon dioxide production. This leads to reduction in PaO2 and increase in PaCO2. If it is acute it will lead to respiratory acidosis. If chronic, there is compensatory metabolic alkalosis.

Answer 409

Reduced respiratory centre activity from brain stem (injury/stroke). This will reduce the drive to breath or it can be induced by using drugs to suppress activity. Neuromuscular disease (nerve paralysis or muscle weakness). Chest wall deformity (gross) Obesity (gross) Sleep disordered breathing As a consequence of respiratory muscle fatigue secondary to severe lung disease.

Answer 410

1. Obstructive sleep apnoea 2. Central sleep apnoea 3. Obesity hypoventilation syndrome

Answer 411

Transient obstruction of airways during sleep that prevents breathing and eventually disrupts sleep. Occurs in people who snore (but not all snores have OSA).

Answer 412

Airway muscles relax when you enter REM (deep sleep), throat is already narrowed (obesity, tonsils) and tongue falls backwards to further narrow.

Answer 413

Snoring in light sleep, completion obstuction (apnoea) in deep sleep, reduced blood O2 and increased CO2, brain wakes up to lighter sleep (arousal), muscles contract and aiways open so that breathing occurs again, moves back into deep sleep then the cycle repeats. This leads to very fragmented sleep and sleep deprivation -\> maybe symptom is fatigue.

Answer 414

Air flow at mouth can measure the apnoeas and arousals. Oxygen saturation is measured as well (generally there is a lag between desaturation and arousal). Chest and abdominal wall movement may show paradoxic movement when the upper airway is obstructed. This can be used to distinguish between obstructive and central sleep apnoea.

Answer 415

Usual Nasal CPAP that provide positive pressure of air to keep airways open. Other options could be manidibular advancement splint, surgery or lie on the side (prevent tongue falling back). The goal of the management plan is to keep the airways open during sleep.

Answer 416

Generally need to manage underlying heart failure may/may not use CPAP. There are several different forms of central sleep apnoea. Not as common as OSA.

Answer 417

Usually presents as ventilatory failure with/without RHF. This is very sensitive to oxygen. It is managed with BiPAP and weight reduction.

Answer 418

The hypoventilation during sleep may cause a reset in set point of the respiratory centre leading to day-time hypoventilation. Patients will develop chronic hypoxia, chronic hypercapnoea and a compensated respiratory acidosis.

Answer 419

Their respiratory drive becomes dependent on low oxygen levels. When you shock them with high levels of oxygen it could lead them to stop breathing.

Answer 420

Inflammation of the lungs

Answer 421

Atypical pneumonia are caused by uncommon bacteria that result in a different presentation of the pneumonia. Usually has no consolidation or alveolar exudate.

Answer 422

Acute bronchopneumonia (most common) and acute lobar pneumonia.

Answer 423

1. Loss of cough reflex. 2. Impairment of the mucus-cilliary functions. 3. Accumulation of secretions. 4. Abnormal functions of alveolar macrophages. 5. Pulmonary oedema.

Answer 424

Bronchopneumonia shows patchy distribution of inflammation that can be found across different lobes. (Usually infection at the terminal bronchiole and bilateral - tends to be low virulence organisms). Lobar pneumonia has its entire lobe inflamed. (When inflammatory oedema spreads across the whole lobe - organism of high virulence, 80% caused by Strep. Pneumonia and 20% caused by Haemophilus Influenza). Lobar pneumonia is more likely to cause inflammation in the pleura.

Answer 425

The air space is filled with lots of neutrophils, pus, vasodilation and congestion. This will come up as consolidation in the lungs.

Answer 426

Where normal air space becomes full of fluid or non-compressible substances.

Answer 427

Air space filled with fluids will lead to poor gas exchange. The patient may present as being hypoxic, SOB, with pleuridic chest pains, cough and purulent sputum.

Answer 428

It will show up as pale and solid areas across multiple lobes.

Answer 429

There will be solid and pale consolidation of the entire lobe. Also known as grey hepatization. The step before the consolidation is known as red hepatization because of the presence of RBC (haemorrhage) before its broken down and taken over by neutrophils (pus).

Answer 430

There will be consolidation areas seen as pale opaque areas in the CXR.

Answer 431

This is a collection of pus found in the lungs.

Answer 432

Aspiration (movement of foreign bodies into the airways) are usually mixed with anaerobic bacteria (bacteroides). Obstruction of the bronchial tree. Haematogenous seeding of the lung from an extra-pulmonary infection (infection originating from the blood). Certain types of bacterial pneumonia - Strep. Pyogenes, Staph. Aureus and Klebsiella pneumonia. Acute bronchopneumonia in debilitated hosts (usually post operation where pathogens are introduced into the patient).

Answer 433

It does NOT produce consolidation (No pus formation or heavy exudate, but oedema can occur. Viral pneumonia causes lymphocytes to infiltrate instead.) Usually causes bronchiolitis and alveolar septum inflammation. Viral pneumonia is cytopathic causing epithelial cell death leading to secondary bacterial infections or severe pulmonary oedema.

Answer 434

Lumen of the bronchioles show eosinophils not neutrophils. The cells surround the bronchioles are lymphocytes. Important to know that viral pneumonia does not have pus.

Answer 435

This is defined as the permanent irreversible dilatation of cartilage containing airways. Dilatation is a consequence of scar tissue deposition around the bronchi, weakening of bronchial wall (by inflammation) and pooling of lung secretions due to the dilations leading to optimal environment for infections.

Answer 436

Chronic bronchial infection

Answer 437

Copius offensive sputum production, poor drainage of secretions lead to recurrent bacterial pneumonia and abscesses, rupture of vessels in bronchial walls leads to haemoptysis (dilation), pulmonary fibrosis could lead to right ventricular failure (cor pulmonale), cerebral abscesses (associated with lung abscesses) and amyloidosis.

Answer 438

Breathlessness arises when there is a recognition by the subject of an inappropriate relationship between respiratory work and total body work. Up to the individual to determine whether or not the breathlessness is occurin inappropriately.

Answer 439

It is the same as ventilatory work that involves stretching work (elastic) and airflow work (resistive). Generally resistive forces contribute a small proportion of work because we usually have laminar airflow. Becomes significant when there is airway obstruction.

Answer 440

Load and drive feed into the respiratory work. This will lead to appropriate or inappropriate change in work. This will then be perceived to be either normal or abnormal sense of breathing.

Answer 441

Can either approach it as either increase in load or drive. Can approach the dyspnoea in terms of systems (use associated features from patient presentation to help identify system).

Answer 442

Cardiac, respiratory, muscle weakness, metabolic, anaemia and psychogenic.

Answer 443

1) AIRWAYS DISEASE a) Upper airways - tumour, foreign body, angioneurotic odema, CROUP b) Lower airways - asthma, COPD, bronchiolitis 2) ALVEOLAR DISEASE Pneumonia, lung collapse, pulmonary odema, pulmonary fibrosis 3) PULMONARY VASCULAR DISEASE Pulmonary embolism, vasculitis, primary pulmonary hypertension 4) PLEURAL and CHEST WALL DISEASE Pleural effusion, pneumothorax, chest wall deformity 5) RESPIRATORY MUSCLE DISEASE Respiratory muscle weakness, phrenic nerve palsy

Answer 444

Lung function tests - spirometry and flow volume loop. CXR - Alveolar and parenchymal defects. CT scan - check for COPD. Wells Score - Cumulative score to test likelihood of event from risk factors.

Answer 445

Medically undiagnosed dyspnoea.

Answer 446

Is worsen dyspnoea a new clinical manifestitation on top of what we already know? Disease or deconditioned (obese patients)? At maximum effort is the breathlessness sensation or symptom? (Elite athletes) Psychogenic or disease?

Answer 447

Might be normal sensation on effort, anxiety or disease. Atopic asthma and exercise induced bronchoconstriction can be diseases that lead to dyspnoea. There is also vocal cord dysfunction (Laryngeal Dysfunction) not to be confused with asthma.

Answer 448

Best test is to use incremental exercise test to check maximum. Look for anaerobic threshold and total capacity. Can also attempt three month aerobic training problem then re-measure exercise capacity.

Answer 449

Take a good medical history and the absence of particular symptoms will increase suspicion of MUD.

Answer 450

It is localised to the airways.

Answer 451

Suggests terminal lung units such as the alveoli being filled with fluid along with air. It may suggest late inspiratory crepitations (when lungs are stiff and scarred - interstitial lung disease).

Answer 452

Myocbacterium. Tuberculosis is an acid fast bacteria (thick waxy cell wall layer). Recently multiple drug resistant strains have risen.

Answer 453

TB is characterised by granulomatous inflammation (collection of macrophages), type IV hypersensitivity and inability to clear foreign bodies completely leading it to be walled off in a granuloma. It resembles caseous necrosis.

Answer 454

Macrophages surround the granuloma with a caseous necrotic core.

Answer 455

This is the first time the patient is exposed to TB. Self-limiting illness. Two areas where the granulomatous inflammation can be found - peripherally (usually middle) and hilar lymph nodes. Ghons focus = peripheral area of granuloma Ghon complex = peripheral + involved node. Most patient's immune system can control the infection and healing by fibrosis, often with calcification.

Answer 456

Patient had previous exposure to TB and is re-exposed. Affects apical areas of upper lobe, tubercles and caseations. Caseation progressive spreads through the lungs, erodes blood vessels (haemoptysis), cavitation into bronchial tree, pleural inflammation and fibrosis and lung scarring. Lung scarring from the host response as defence.

Answer 457

This type of TB has numerous small granulomas in the lungs. It is more common in secondary TB and patients who are immunocompromised.

Answer 458

Yes a bad stress job is as bad as being out of work.

Answer 459

Through droplets via coughing, sneezing or spitting.

Answer 460

Vast majority of TB is in those of the poorest segments of society. It is associated to biological, social and economical factors rather than just performance of TB programs.

Answer 461

Biomedical approaches and programs (DOTS) decreases incidence of TB. But we need to tackle the underlying factors that make these groups of people more vulnerable to TB such as social status.

Answer 462

The poorer you are the more likely you wll contract TB.

Answer 463

Exposure to infectious droplets, host defences (HIV), malnutrition, indoor airpollution, alcohol abuse, depression and stress (affects cell-mediated immunity). - Malnutrition, smoking, HIV, diabetes, alcohol and air pollution. - Malnutrition and air pollution are direct markers of poverty. Smoking is consistently higher in lower social economical groups.

Answer 464

Higher quality DOTS, address the needs of the poor and vulnerable populations, strengthen health system based on primary health care, engage all care providers, empower peopl with TB through partnership and promote research.

Answer 465

Thrombus forms in any veins (superficial or deep) but majority is formed in the deep veins of the lower limb.

Answer 466

Anterior and posterior tibial veins join to the form the popliteal veins to femoral veins and eventually into the IVC.

Answer 467

They form around the venous valves (a little upstream). They are able to continue propagating against the flow of blood. Venous thrombus are typically occlusive, red (high RBC from stasis).

Answer 468

The venous thrombus will have layers of red and pink. Red - erythrocytes Pink - Platelets and fibrin

Answer 469

Virchow's Triad - Change in vessel wall (from trauma such as IV catheterisation or bacterial infection of the vessel wall). - Changes in blood hypercoagulable states. - Changes in blood flow: stasis, turbulence, prolonged immobilisation, dehydration, hypotension, congestive cardiac failure and polycythaemia.

Answer 470

COMMON Factor V Leiden - point mutation in factor V prevents activated Protein C from binding to the cleavage site. Natural anticoagulant will not work. Prothrombin III deficiency leading to circulating levels of prothrombin. UNCOMMON Antithrombin III deficiency, Protein C deficiency and Protein S deficiency.

Answer 471

Surgery, massive trauma and burns, malignancy, obesity, smoking, hyper oestrogenic states (pregnancy or OCP contraceptives), nephrotic syndrome, antiphospholipid antibody syndrome.

Answer 472

Lysis and resolution, organisation of the thrombus to form scar tissue, recanalisation (new blood vessels that resupply blood to the area) and embolism.

Answer 473

Arises from deep vein thrombus in the lower legs (pelvic and abdominal less commonly). The thromboemboli travel to the right side of the heart and enter the pulmonary arterial circulation via the pulmonary artery.

Answer 474

The venous thrombus will be mainly red with pale areas, coiled shape (reflects shaped of the vein of origin) and occlusive. Can cause sudden death (there will be electrical activity but lack of cardiac output because of the occlusion). This is known saddle thromboembolus.

Answer 475

It could lead to sudden death, dysphnoea, chest pain and circulatory failure mimicking myocardial infarction. For clinical signs similar to MI we need to think about pulmonary embolus and aortic dissection.

Answer 476

Could lead to pulmonary infarct that is wedge shaped, sharply demarcated, pleural base, red (reperfusion from bilateral blood supplies), occluded artery at the apex. Clinically: dyspnoea, haemoptysis (area of haemorrhage into the infarct), pleuritic chest pain (because infarct will be based around the pleura).

Answer 477

Must consider the chance of pulmonary embolus.

Answer 478

Basal cell carcinoma and squamous cell carcinoma are the most commonly cancers found in Australia but they rarely lead to death.

Answer 479

Neoplasia is excessive unregulated cell division. Begins with multistep mutations in a single cell. Affecting the cell cycle, cell death and DNA repair of the cell. As you mutate you also acquire different features. Neoplasia is made up of the neoplastic cells and a reactive stroma. It can be either benign or malignant.

Answer 480

This is a lesion of mass of any kind but typically these days we refer it as neoplastic lesion.

Answer 481

Resisting cell death, inducing angiogenesis, sustaining proliferating signaling, enabling replicative immortality, evading growth suppressors and activating invasion and metastasis. An emerging hallmark is also the ability to evade the immune system.

Answer 482

Leading cancer is prostate and breast for males/females. Lung is third for common. But leading death is by lung cancer then the prostate/breast cancer.

Answer 483

Most of paediatric cancers are referred to as blastoma because it resembles cells from the embryo. E.g. Certain leukaemia, neuroblastoma, Wilm's tumour (kidney), certain lymphomas, retinoblastoma and certain bone cancers (osteosarcoma).

Answer 484

Benign: Locally expansive, slow growth, well circumscribed (most of the times), well differentiated cells and cannot metastasise. Malignant: Locally invasive, locally destructive, often poorly circumscribed, sometimes necrosis because of outgrowing the blood supply, variable differentiation, potential to metastasise (through lymphatics, blood vessels and transcoelomic - body cavities). Also induces desmoplasia in stroma as they grow.

Answer 485

This is another group of malignant cancer that histologically look like benign and malignant tumours.

Answer 486

Cancers tend to grow in lymph nodes and they like to grow in the first lymph node they are drained to. The tumour can enter the draining veins and enter the systemic circulation. Or it can translocate by transcoelomic spread (migrating along the pleural space - body cavity).

Answer 487

Hilum lymph nodes, brain, liver, bone and lungs.

Answer 488

Cytological atypia: Larger nuclei, pleomorphic nuclei (vary in size and shape), coarser nuclear chromatin, hyperchromatic nuclei (takes up more H&E), larger more prominent nucleoli and may see more mitotic activity. Architectural disorganisation. Benign neoplastic cells show less atypia than malignant cells.

Answer 489

This is a stroma that has more fibroblasts therefore making it stiffer to touch.

Answer 490

They only occur in malignant tumours.

Answer 491

Epithelial - glandular, squamous, uroethelial and endocrine. Mesenchymal - osteoblasts, endothelial cells, smooth muscle, skeletal and adipose tissue. Others - melanocytes, myeloid cells, lymphoid cells and astrocytes.

Answer 492

Formation of glandular lumina, formation of mucin (lots of mucus) and signet ring cells (mucus within the cells).

Answer 493

Keratinization in the lumen, intercellular bridges (between the bridges are desmosomes) and eosinophilic cytoplasm. It shows features of stratified sqamous epithelium - often have lots of eosinophilic cytoplasm and intercellular bridges.

Answer 494

Neoplastic or Non-neoplastic? If it is neoplastic, is it benign or malignant? Also what type is the neoplastic tissue? If the tissue is malignant - is it primary or metastatic?

Answer 495

Must biopsy the tissue. They look at its cytological features, architecture (may or may not have necrosis), stroma and cell lineage.

Answer 496

Prefix - line of differentiation: Adeno (gladnular), squamous cell, leimyo (smooth muscle), osteo (osteoblastic). Suffix: Benign (-oma) and malignant (epithelial - carcinoma and mesenchymal - sarcoma) There are exceptions such as seminoma (malignant testicular cancer) and lymphoma. Mixed: carinosarcoma

Answer 497

Well differentiated: Resemble mature cells more, less cytologic atypia and the architecturally more organised. Poorly differentiated: Poorly resemble to mature cell, more cytologic atypia, more mitotic activity and architecturally less organised. Degree of differentiation is referred to as its grade (of malignant tumours). Well differentiated tumours tend to be less aggressive than poorly differentiated ones.

Answer 498

It generally arises from one cell. It could be adult stem cells or it could be mature cells that acquire stem cell like qualitites leading to tumours.

Answer 499

Invasive carcinomas arise from the progression of non-invasive precursor epithelial lesions. They are known as dysplasia and intraepithelial neoplasia.

Answer 500

Abnormal development, alteration in size, shape and organisation of cells. It is graded as mild, moderate or severe (1,2,3). Low or high can also be used. High grade dysplasia is more likely to progress to malignancy.

Answer 501

Epithelial are the most common cancer and it begins with intraepithelial neoplasia - can treat it before the cancer becomes invasive. Normal epithelium as simple columnar (can be stratified squamous) in the gut and there is the basement membrane. One of the stem cell in the epithelium develops multiple mutations and starts off in one cell. Mutations can arise from carcinogenic agents, microbes, nutrients (guts) or inherited. It then becomes multiple cells that proliferate. The cells become pleimorphic because of different nuclei shape and size, mitosis (dysplasia or intra epithelium neoplasia), but it still remains in the epithelium. When it becomes very severe it becomes in situ neoplasm. If one of these cells get mutated to express MMP will allow the cells to lose its cohesiveness and escape through and become invasive neoplasm.

Answer 502

These are glandular dysplastic lesions arising from lining epithelia.

Answer 503

Cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN) and prostatic intraepithelial neoplasia (PIN). These are typically ideal for early screening so that we can prevent it before it goes malignant.

Answer 504

These are adaptive changes that are regulated. The change themselves are not premalignant (not change in genes). But in certain situations it can increase the risk of mutations to develop.

Answer 505

Deregulating cellular energetics, avoiding immune system, genome instability and mutation and tumour-promoting inflammation.

Answer 506

Cancer development needs to be looked as an entire overview and collection of the different contributing mechanisms. But essentially what happens is that there are changes in gene expressions that lead to the development of the hallmark capabilities.

Answer 507

Mutations in critical cell control factors and cancer in one cell first. Then the cell will proliferate but further mutations will occur. Typically requires multiple mutations before it reaches the stage of dangerous cell proliferation. The cells are continuously evolving.

Answer 508

Most cancers are somatic mutations while 10% are germ-line mutations. Methylation abnormalities, proto-oncogenes mutations, tumour suppressor gene mutations and additional mutations of gross chromosomal alterations.

Answer 509

Proto-oncogenes (growth promoting), growth inhibiting tumour suppressor genes, genes that regulate program cell death (apoptosis) and genes involved in DNA repair.

Answer 510

DNA repair is very good in cells mostof the times. Insufficient DNA repair will accelerate DNA mutations and eventually lead to oncogene and tumour suppressor gene mutation. Accumulation of DNA damage - balance between DNA damage and DNA repair.

Answer 511

Coding region can affect the amino acid sequence. Regulatory sequence can affect the changes in amount of protein produced. There are linked SNPs that are found outside the gene that have no effect on protein function and production.

Answer 512

- Errors in DNA replication that is not repaired: BRCA1 and BRCA2 or any damage to DNA repair genes. - Oncogenes, tumour suppresor genes and regulatory region changes. - Point mutations activate oncogenes and inactive TSG. - Amplication of oncogenes (via multiple copies).

Answer 513

Certain genes on a chromosome will express double minutes (fragments of chromosomes that are also able to express N-MYC).

Answer 514

The translocation of chromosome 9 and 22 ABL and BCR genes. ABL-BCR hybrid gene is oncogenic tyrosine kinase that contribuets to chronic myelogenous leukemia.

Answer 515

Neoplastic growth is very rapid can take 3 months for 10^9 cells (1g) to grow to 10^12 cells (1kg). The rate of proliferation is dependent on the blood supply of tumour cells too. Eventually it could lead to vascularised tumour with central necrosis.

Answer 516

These are differences in the magnitude of tumour proliferation vs tumour death. Fast: Leukaemia, lymphoma and small cell carcinoma Slow: Breast, adenocarcinoma and colon.

Answer 517

Growth factor binds to tyrosine kinase receptor to initiate signalling. Activation will lead to activation of RAS that will activate two pathways. - RAF to MAPK to activation of transcription of MYC proteins (cell cycle progression) - PI3K to Akt to mTOR that activates transcription of MYC proteins (cell cycle progression). What happens in cancer cells is that there is a mutation of one of the signalling molecules that leads it to be constitutively activated without any ligands needed.

Answer 518

p110 is found as part of PI3K that is commonly mutated that drives Akt phosphorylation. The TSG in this pathway is the PTEN that inhibits the PI3K. Mutation in cancer generally makes it inactive or complete deletion.

Answer 519

1. Overactivity mutation of oncogenes. 2. Underactivation mutation of TSG. TSG - to lose the function must lose all the alleles. Whereas with function in order to get more it simply needs change in one allele.

Answer 520

Mutation within the gene to make it non-functional. The other mechanism is complete deletion of the TSG. An alternative regulation of the gene expression is by DNA methylation on the promoter region. Arising is miRNA that are non-coding ssRNA that regulates the transcription and translation of normal genes. It can be either inhibitory or stimulatory.

Answer 521

LOH in a cell represents the loss of normal function of one allele of a gene in which the other allele was already inactivated. This is the general genetic feature involving tumour suppressors genes.

Answer 522

p53 is a transcription factor that regulates the expression of cell cycle factors. Generally initiates apoptosis, DNA repair, cell-cycle arrest and differentiation. Cancer cells have defective p53 or are deleted.

Answer 523

It regulates growth and mitotic phases. There are many cell cycle controls that could lead to increased proliferation. End of G2, middle of M, end of G1 and during S. Oncogenes inhibit the checkpoints (RAS), whereas the tumour suppressors p53 enhance the check points.

Answer 524

Pathway to apoptosis: extrinsic (Fas) leading to caspases activation. Intrinsic stress/radiation leads to DNA damage, p53 response (apoptosis) to produce BAX (pro apoptotic molecule) to act on the mitchondria. There is also the BCL-2 that acts as a key anti-apoptotic molecule. Once again a balance between the two the determine apoptosis. Reduced CD95, inactivation of death induced signalling complex by FLICE protein, up-regulation of BCL-2, reduced levels of pro-apoptotic BAX from the loss of p53, loss of AFAX-1 and up-regulation of inhibitors of apoptosis.

Answer 525

Cancer cells have good telomerases that extends the telomeres (act as buffer as cell replication shortens the chromosomes).

Answer 526

1. Detachment of tumour cells from each other 2. Degradation of ECM 3. Attachment to novel ECM components 4. Migration of tumour cells There will be alterations in the ECM of both primary and secondary locations. Mutations occur in the following four genes: integrins (cell adhesion), catenins, cadherins and connexins.

Answer 527

There are other cells aside from the tumours cells themselves. These are endothelial cells (angiogenesis) it also needs factors from the endothelial cells as well as fibroblasts are very important for growth factors. Macrophages are also essential immune cells to sell signals to maintain and accelerate tumour growth.

Answer 528

VEGFs and VEGFRs these are popular therapeutic agents to starve the tumour of blood.

Answer 529

This means that a particular chemotherapy may not be able to ablate the entire tumour because there may be some resistance.

Answer 530

The conventional cancer therapy will destroy the fast replicating cancer cells but may not necessarily kill the cancer-initiating one so that tumour relapse may occur. Cancer stem cell specific therapy kills off the cancer-initiating cell so that the tumour eventually regresses.

Answer 531

Local effect of the tumour, effect of the metastasises (local lymphadenopathy - enlargement of lymph nodes along the the lympathic pathway, bone pair or features related to hypercalcaemia, jaundice and seizures - altered electrical activity). There is also weightloss, anorexia (TNFalpha and IL-1 that is produced by the tumour or tumour microenvironment).

Answer 532

This is a syndrome as a consequence of the cancer secreting hormones/cytokines by the tumours of the body itself. Cushing syndrome - ACTH leading to excess cortisol by small cell lung cancer (produces ACTH) and pancretic cancer. Hypercalcaemia - Excess PTH-related protein that stimulates the breakdown of bone. This can be caused by squamous cell carcinoma of lung, breast carcinoma, renal cell carcinoma and adult T cell leukaemia.

Answer 533

Local effects of the primary tumour: cough, haemoptysis, wheeze, dyspnoea, pneumonia and Pancoat's syndrome (cancer in the apical lobe that can affect subclavian vessels). Effect of metastases - bone pair, hyper calcaemia, jaundice and seizures. Weight loss, anorexia and paraneoplastic effects.

Answer 534

Clinical history, examination, blood tests (where relevant), radiology and tissue sampling. Blood tests: Hb levels (typical of colon cancer), liver function tests (liver metastases) and tumour markers. But tumour markers are non-specific and are not elevated in every case. Carcinoembryonic antigen (CEA) that can be produced by colon, pancreatic cancer and benign tumours. Alpha fetoprotein are elevated in testicular and primary hepatic cancer. Radiology: CXR, CT, ultrasound - Staging of the tumour (how big and where is it to metastasised?) Endoscopy (visualisation)

Answer 535

Biopsy of the sample tissue for diagnosis for histopathological diagnosis and other features to determine prognosis and management. - Look at cytological features, architecture, stroma - After surgery removal of the specimen it is sent for testing again to see the overall picture. Cytology by fine needle aspiration (suck cells up without architecture intact) or exfoliative cytology (scrap onto slide)

Answer 536

Histopathology: H&E, Special Stains and immunohistochemistry Molecular and cytogenic techniques including: In situ hybridisation, PCR and chromosomal arrangements.

Answer 537

Specific tumour type, grade, stage, presence of lymphovascular invasion. This is important for the prognosis and management of the malignancy.

Answer 538

Non-small cell carcinoma: Sqaumous cell carcinoma, large cell (undifferentiated) carcinoma and adenocarcinoma. Neuroendocrine carcinoma: Small cell carcinoma (very aggressive) The listed cancers are the main types.

Answer 539

Tobacco smoking, asbestos and arsenic. If you are a non-smoker you are most likely going to contract adenocarcinoma.

Answer 540

Invasive small cell carcinoma in bronchus has a necrotic core. Lung carcinoma are sometimes necrotic that may manifest as cavities. A wider spread of wide area are desmoplastic stroma. Know the difference between squamous cell carcinoma and adenocarcinoma (part of lung carcinoma).

Answer 541

We can use immunohistochemistry to test for the presence of specific antigens so that we can identify the type of tumour. LCA - for lymphoma CAM5.2 - Carcinoma for epithelium

Answer 542

The stage incorporates the size or depth of the invasion as well as the location and extent of the metastases. This is done by the TNM system by pathologists. T - extent of primary tumour (size) N - Regional lymph node metastases M - Absence or presence of distal metastases. X - cannot be assessed or unknown. These are all grouped together to form a particular stage level.

Answer 543

Vascular invasion seen in primary tumour, specific genetic alterations and others depending on what tumour it is (ulceration, patterns of inflammation).

Answer 544

Screening for HER2 in breast cancer will tell us if we can use anti-HER2 drugs. Also the oestrogen and progesterone receptors in breast cancer can tell us a lot.

Answer 545

Surgery with a detailed pathology report of the specimen, radiotherapy, chemotherapy and targeted therapy.

Answer 546

It is not a non-selective treatment so will not affect normal cell. Targeted therapies block growth of cancer cells by interfering with function of specific molecules. This method requires genotype/phenotype testing of the different tumours. 2 Main types: 1. Small molecule that inhibits growth factor receptosr (tyrosine kinase). 2. Monoclonal antibodies that target specific proteins or receptors.

Answer 547

The growth factor activation process is very important. Activation of tyrosine kinase will increase proliferation, protein synthesis, cell cycle progression and cell death. There are complicated signalling pathways to reach the end points. But mutations will generally result in continuous cell division, we can use a particular drug to inhibit the activity of that abnormal protein.

Answer 548

Significant rate of EGFR mutations that contribute to non-small cell carcinomas. Involves increasing its activity leading to hyperactivation of downstream signaling pathways. New targeted therapies target this mutation by inhibiting the EGFR tyrosine kinase. But tumour needs to be tested to see if this treatment will work or not. Resistance can develop as the tumours acquire new mutations.

Answer 549

Once disseminated the patient will die from cachexia, secondary infection related to poor nutrition, effects of treatment and damage to vital organ or system by the tumours.

Respiratory Block Flashcards

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