week #7 Flashcards

Question

Myocardial infarction at 1 to 3 days

Answer 1

* At this stage there are few myocytes left in the site of the infarct-i.e. mainly neutrophils and debris-pus * and gross morphology also looks like pus * so no muscle-is just yellow soft pus * at around this time-1 days the troponin level is at its highest * and then gradually decreases after that * we can look at the troponin levels and perhaps guess as to what stage the myocardial infarction is at

Answer 2

* Macrophages now enter and lay down granulation tissue so still a bit like a jelly, not that strong. * macroophages ingest dead myocytes * fibroblasts and vessels of granulation tissue appear * collagen begins to be laid down at 5-6 days **Gross mophology** * red ring of vascular granulation tissue with central yellowing

Answer 3

* The damaged myocytes are unstable-ARRHYTHMIA * The damaged myocytes are being destroyed-CARDIAC FAILURE * The damaged wall isn’t moving normally-MURAL THROMBUS * The wall is necrotic and weakened-RUPTURE * Inflammatory mediators abound-PERICARDITIS

Answer 4

* Rupture of the lateral wall and blood is pushed into the pericardium and can actually push back on the heart and stop it from beating

Answer 5

1. Rupture of Free Ventricular Wall * Blood into pericardium “Haemopericardium” * Compressing the heart until it stops “Cardiac Tamponade” 2. Rupture of Papillary Muscle * New onset murmur * Mitral regurgitation * Cardiac Failure 3. Rupture of IV Septum * New onset murmur * Ventricular Septal Defect * Cardiac Failure

Answer 6

**Under the microscope** * early and then late granulation tissue * is initially very cellular and vascular with neutrophils and then more collagen is laid down as vessels and cell number decreases **Gross Morhology** * at 3 weeks * collagen is pale grey and white flecks appearing but still some granulation tissue * at this point the collagen tissue is still quite flexible and may stretch causing thinning of the wall * at 6 weeks * more fibrous white tissue building up * *

Answer 7

arrythmia and cardiac failure are now somewhat less likely but we can get: * Mural Thrombus * and * Aneurysm (infarct expansion) This is due to the still immature collagen and though the wall is strong again, it is soemwhat flexible to wall stress and may stretch, thin and bulge out. which can lead to aneurysm which can lead to thrombus due to blood stasis

Answer 8

**Under the microscope** * Extensive fibrosis in the area of infarction * fixed dense collagen with the occasional cell **Gross Morhology** * wall may be thinner and is white fibrotic tissue * may see evidense of aneurysms or mural thrombi *

Answer 9

Now the risks are not as great and the damage has pretty much healed but heart may still be susceptible to: * **Arryhtmia** is now less likely but possibel due to fibrosis which could result in the formation of electrical islands * **Cardiac failure** could occur as remainign myocytes will have to compensate for the death of the other myocytes and this could result in hypertrophy and then eventual decompensation * Any Aneurysms formed will not be removed but with all the fibrotic tissue are now unlikely to rupture but are still a place for blood stasis and therefore potential **thrombosis**

Answer 10

**Acute** * myocardial infarction, sudden death cardiac death and unstable angina **Chronic** * Stable angina, chronic myocardial ischemia

Answer 11

* Presents as reproducible cardiac chest pain that occurs on exertion and goes away with rest * due to atherosclerotic narrowing * endothelium will be dysfunctional and will not dilate itself-innapropriate vasoconstriction * at 70% Stenosis symptoms ussually start

Answer 12

* Presents as cardiac chest pain that may occur at rest or minimal exertion and may not resolve with rest * acute plaque event that could occur via heamorrhage and thromobosis * it does resolve though-i.e. we can break the clot down and there is no permenant damage * can occur at rest or with exertion

Answer 13

* Small areas of subendothelial ischaemia * ongoing chronic narrowing of the vessels and overtime we get little patches of necrosis and fibrosis due to gradual loss of blood supply * Similar to the sort of fibrosis you might see in myocardial hypertrophy * Carries similar risk of cardiac failure and arrhythmia

Answer 14

* defined as a sudden death due to cardiac causes in a time frame less than an hour in someone with no previous cardiac conditions * mostly ischeamic heart disease and frequently due to an early arrythmia * or could be a silent infarct and then we get an acute rupture and pass away- would be classified as sudden cardiac death even though disease progression may have been occuring for awhile * Other causes include * Anomalous coronary arteries * Left Ventricular Hypertrophy (genetic, acquired) * Floppy mitral valve * Cardiomyopathy (genetic, acquired, infective) * Cardiac Conduction Syndrome (genetic)

Answer 15

converted in the body to form nitric oxide which is a powerful vasodilator

Answer 16

* give oxygen * give aspirin-blood thinner * give GTN-decrease preload on the * measure troponin levels and ECG

Answer 17

1. incorparated into VLDL in the liver for delivery around the body 2. made into bile acids for fat emulsification and stored in the gall bladder 3. used for membrane synthesis

Answer 18

* *Cholesterol can be sythesised in liver or from diet** * *From intestine** it is packaged into chylomicrons and then circulates **From liver**, VLDL cholesterol Once chylomicrons and VLDL reach capillaries lipoprotien lipase hyrodlyses the TGs and then we get release of free fatty acids and then they are taken up by tissue and used for energy this means that the VLDL and chylomicirn remanats are now dense in cholesterol and then the remnant circualte in bloodstream and then if they are transported to liver they can be taken up through LDL hepatic receptors for re-use into VLDL OR they can be converted to LDL and then they can circualte and deposit cholesterol into extra-hepatic tissue and then this can form atherosclerosis HDL are good ad they are involved in reverse cholesteral transport, they take cholesterol that has been deposited in the tissues and take it back to the liver and may use it for bile acid synthesis

Answer 19

Allow for cholesterol transport into tissues and into vessel walls * IDL, LDL, VLDL

Answer 20

lower, increase

Answer 21

**Precautions** * avoid grapefruit juice due to common cytochrome p450 pathway * avoid drugs with same metabolism pathway * mild elevation in aminotransferase * minor increases in creatine kinase * can lead to muscle pain and tenderness **Adverse effects** * common adverse effects * mild GI symptoms, headache, insomnia, dizziness * rare but serious adverse effects * myopathy (minimised by UQ10 treatment?) * rhabdomyolysis (breakdown of muscle resulting in myoglobin release into the bloodstream) * renal failure * hepatitis, liver failure * Contraindicated in preganancy * impaired fetal myelination * withold during infection, post surgery and post trauma

Answer 22

* bind bile acid (cholesterol metabolites) preventing gut absorption * up to 10-fold increase in bile excretion * increased demand for cholesterol for bile acid synthesis causes upregulation of hepatic LDL receptors, removal of LDL from plasma and more cholesterol metabolism **Adverse effects** * bile acid sequestrations can result in bloating and constipation etc so need to drink enough water * more serious can get increase TGs, steatthorea and feacal impaction and decreased absorption of fat soluble vitamins * can also get decreased absorption of other drugs

Answer 23

* specifically inhibits cholesterol absorption in the intestine by binding to a sterol transporter (NiemannPick C1-like 1 protein) * does not affect absorption of bile acids, fat soluble vitamins * lowers LDL **Possible adverse effects** * diarrhea, headache, tiredness * allergic reactions, severe joint or stomach pain

Answer 24

* Mechanism remains unclear * decrease secretion of VLDL particles from liver * reduces plasma LDL and triglycerides (so also for mixed hyperlipidaemia) * increases HDL * can potentially lower athergenic lipoprotein Lp(a) formed from LDL. * Lp(a) is found in plaques and inhibites thromboylsis * so vitamin B is good in that it lowers Lp(a) **Adverse effects** * common adverse effects * vasosodilation, flushing, hypotension * nausea, vomiting * tolerance develops to gastric upsets * rare adverse effects * itching * glucose intolerance * uric acid retention * may increase hepatic impairment * not widely used except in combination

Answer 25

* agonists at nuclear receptors, so regulate gene expression * peroxisome proliferator activated receptor alpha (PPARalpha) * PPARalpha is a nuclear receptor responsible for regulating gene transcription and its activation results in increased synthesis of lipoprotein lipase (LPL) * Lipoprotien lipase breaks down TGs into free fatty acids so increase sythesis is good as we get more fatty acid release and less cholesterol * increase lipolysis of lipoprotein triglyceride * moderate reduction in plasma triglycerides * moderate increase in HDL * variable effects on LDL * generally used as adjunct to dietary changes for high TGs, mixed hyperipidaemia, and second line therapy for hypercholesterolaemia **Adverse effects** * mild elevation of serum aminotransferase * monitor at 3 month intervals, reduce dose or discontinue if necessary * common adverse effects * nausea, dry mouth, headache, rash * rare adverse effects * arrhythmias * gallstones * photosensitivity * impotence * depression

Answer 26

* Results in reduced VLDL and reduced TGs * and increased HDL

Answer 27

* dilate coronary arteries * decrease heart rate-arteries less compressed

Answer 28

* strangled breast * imbalance between O2 supply and O2 needs * insufficient O2 to meet cardiac demands * reduced perfusion rather than inadequate blood O2

Answer 29

* coronary vasospasm at rest * mediator unknown

Answer 30

* decrease O2 demand * increase O2 supply

Answer 31

* Dilate the coronary arteries * But difficult to dilate arteries becasue they are stiff and cannot dilate that well and arterioles are already maximally dilated * So we could reduce heart rate? * reduce compression of arteries * heart spends longer in relaxatio phase * coronary arteries have longer time to fill

Answer 32

* reduce cardiac output * decrease HR-Beta adrenoceptor antagonists * decrease SV-Beta adrenoceptor antagonists, Calcium channel blockers * Decrease preload-Nitrates (GTN) * dilate veins and get less venous return * Decrease afterload-Calcium channel blockers * dilate arteries and reduce TPR

Answer 33

**Mechanism** cGMP dephosphorylates the myosin light chain so that it cannot bind to actin and we get vascular relaxation **Site of action** * nitrates work on all vessels but major site is the veins **Example** * GTN * a pro-drug * subject to first pass liver metabolism so we give sublingual therapy so it can be absorbed directly into blood for acute attack * for an emergency we may use IV * for prophylaxis can use sub-cutaneous injection * care must be taken in storage as drug can be absorbed by plastics **Side effects** * effects on other smooth muscle * brief relaxation of gut, airways * not clinically significant * postural hypotension - venous pooling * headache, flushing - cerebral, head, neck arterial dilatation * reflex tachycardia – usually used in combination with β-blockers or cardiac-selective calcium channel blocker to minimise this **A dangerous drug interaction** * Viagra and GTN can be fatal * Viagra is phosphodiesterase inhibitor so it inhibts the breakdown of cGMP * So could get a massive increase in cGMP and so we get too much increase of vasodilatation **Tolerance** Decreased effect of nitrates with prolonged use * “classic” mechanism involves depletion of tissue thiols required for NO production from GTN * treatment with N-acetyl cysteine restores GTN effect * Increased release of and/or sensitivity to constrictors e.g. AII * increased endothelial free radical production scavenging NO, reducing NO bioavailability * reduced/abnormal activity of muscle mitochondrial ALDH2, decreased NO production, increased free radicals * ALDH2 involved in NO production * Drug-free period required to minimise tolerance remove patch over night

Answer 34

Calcium channel blockers can be vascular or cardio selective. Vascular:Cardio selectivity * verapamil 1:1 (not for heart failure) * diltiazem 7:1 * nifedipine 14:1 (also for hypertension) So cardio selective drugs act on SA node and AV node to block Ca infux and therefore prevent depolarisation as frequently and lower HR. They also reduce the contractility of the cardiac muscle Vascular selective Ca2+ channel blockers prevent cotnraction of the vascular smooth muscle-reduce arterial contraction and therefore reduce **afterload** **Adverse effects** Cardio selective Ca channel blockers * flushing, headache, oedema * bradycardia, atrioventricular (AV) block never taken with Beta-blocker Vascular selective Ca2+ channel blockers * flushing, headache, oedema * hypotnesion * reflex tachcardia * so can be taken in combination with a Beta Blocker

Answer 35

Beta 1 adrenoceptor antagonists act on SA and AV node to decrease HR which can increase diastole and increase coronary perfusion and therefore increase O2 supply to heart Beta-1 Adrenoceptor antagonists also act cardiac muscle to decrease contractility and therefore stroke volume which will also decrease cardiac output and decrease O2 demand of heart **Adverse effects** * Contraindicated in asthma due to potential B2 adrenoceptor activity that will constrict brinchiols

Answer 36

* “pure” heart rate reduction * “specific” and selective inhibition of the inward sodium-potassium I_f current in the sinus node * decreases the velocity of diastolic depolarization by reducing the ‘steepness’ of the I_f current slope * reduces myocardial oxygen demand and maximizes oxygen supply **Uses and Adverse effects** * used in patients with IHD and LV dysfunction and in patients with HR \> 70 bpm * No reduction if HR is \< 70bpm * brigtness in virual field due to retinal effects (same target, different site) * conduction abnormalities (same target and site) * levels increased by some antibiotics and antifungals * small increased risk of MI(?) doesn't seem great...? *

Answer 37

* Can be intrinsic * i.e. gram negative bacterial resisitnace to vancomycin * acquire * mutation * horizontal gene transfer

Answer 38

* transformation * phage mediated * plasmid mediated conjugation

Answer 39

* DNA uptake by competent cells * Bacteria immune system can protect bacteria against the foreign DNA and cut DNA using restriction * enzymes EcoR1 etc * So only related DNA will be incorparated so there is some homologous recombination * So must be some complimentary DNA **Example** * 90 different types of pneumococci due to their capsular antigen * pneumococci that we live in us as part of of our micriobiota have a lot of resistance genes and can transfer resistance DNA to other more dangerous pneumococci (i.e. transformation can occur because of relatedness)

Answer 40

* most bacteriophages are dsDNA they have enzymes that break down peptidoglycna and then inject DNA through the cell wall and then it will be intergrated in particular spots ogf the geneome does not require homologus recombination as the virus uses enzymes to integrate the DNA * After isertion the bacteria may replicate with the phage DNA and this is the **temperate phage** i.e. nothing hapens (called the lysogenic cycle) may not kill the bacteria but may encode toxins and diptheria toxin is actually encoded by a bacteriophage * **Virulent phage** or lytic cycle the virus kills the bacteria-lysis from within. This happens when the phage senses that there is somehting wrong with the bacterium *

Answer 41

* shiga toxin * cholera toxin

Answer 42

* when we eat them we get diahrroea and we might use bacteria at which point the phage decides that the bacteira is no longer safe to stay there anymore and so the phage replicates and produces heaps of toxin and so it is not reccomended to take antibiotics for E.coli O157 diarrhoea

Answer 43

* We can get transfer of genetic material and possibly antibacterial resistance * staph epidermidis can tansfer resistance to staph aureus * this is a very unlikely event but with that many bacteria and many phages and many people infected then it can easily occur and resistant variants arise

Answer 44

* Bacteria can link together if there is contact between the bacteria and the plasmid makes a copy of itself as it moves through the cytoplasmic bridge and now there is a copy in each bacterial cells * conjugation can occur between unrelated species * so this is often the most dangerous method of transfer as it can go across different bacterial species * E.coli in gut can transfer plasmid with resistance to more pathogenc bacteria * we can also get **multi resistant plasmids** * so by treating with one antibiotic you may be selecting for resistance of another antibiotic as well

Answer 45

* Minimum concnetration of antibiotic that inhibits bacterial growth * can be determined by either * diffusion methods * E test strip-read MIC straight off the strip * dilution methods

Answer 46

Some clinical conditions must be treated before results are known from labratory testing

Answer 47

* To delay emergence of resistance when we treat TB we treat with 4 drugs * we know that it may be resistant to 2 drugs * we want to use two effective antibacterials at least because we want to make sure that even if resistance emerges to one of the drugs the 2nd drug can kill the bacteria becasue the chance of getting resistance arising in the same bacteria to two antibiotics is very unlikely

Answer 48

* Indifference-or an additive effect * i.e. adding the extra antibiotic "B" would produce the same effect as adding more of antibiotic "A" * Antagonistic effect * i.e. adding antibiotic "B" to antibiotic "A" reduces the efficacy of antibiotic "A" and we end up with the lower efficacy of antibiotic "B" * Synergy * i.e. adding antibiotic "B" to antibiotic "A" greatly improves the efficacy of "A"

Answer 49

**Penicillin G and tetracycline therapy** * together did worse than patients treated with penicillin alone * Becaue penicillin only acts on growing bacteria-on peptidoglycan synthesis * but tetracycline is bacteriostatic and so penicillin has no effect anymmore sdo you are only getitng the effect of tetracycline **ampicillin and piperacillin** * ampicillin is destroyed by beta-lactamases and actually induces more beta lactamase production by the bacteria. * piperacillin alone is a low inducer of beta-lactamases

Answer 50

1. aminolgycoside and Beta lactam * aminoglycosides enter cell poorly but Beta lactam disrupt petidoglycna wall and allows for better entry of aminoglycoside 2. Sulmphonamides and Trimethoprim * act on different stages of folic acid synthesis in bacteria 3. amoxycillin and clavulonic acid * co-amoxycillin therapy, clavulonic acid is a weak beta lactam antibiotic but a strong anti beta lactamase and so it inhibits the breakdown of amoxycillin which is a strong beta-lactam

Answer 51

* Bacteriostatic + bacteriostatic = additive or indifferent * Bacteriostatic + bactericidal = antagonistic * Bactericidal + bactericidal = synergistic ## Footnote *Note that there are exceptions*

Answer 52

* **Visceral pleura** surrounds the organ then folds back on itself at the lung hilum and forms the **parietal pleura** * different areas of the parietal pleura is named for the areas it is arround (see image) * The **Parietal cavity** is a potential sopace beteeen the two layers and allows for a friction free glide of the lung as it expands * pneumothrax-area is filled with air * heamothorax-area is filled with blood

Answer 53

* The visceral pleura is not tight around the lung root and it hangs down * This is called the pulmonary ligament-provides some slack so the neurovascular structures can expand

Answer 54

A1=dull and not well localised A2=sharp and well localised If we get inflammation of the visceral pleural the pain is quite dull and poorly localised, as is the pain from pericardium as they share nerve supply from structures that they cover. So they have a visceral nerve supply and pain refferred from the visceral nerve supply will not be localised and will be quite dull But if the inflammation reaches the parietal pleura the pain will be severe and sharp as the parietal pleura lines the internal surface of the thoracic walls where they get there nerve supply from and these strucutres that have a somatic nerve supply and so pain is sharp, severe and well localised

Answer 55

* Trachea starts at C6 and devides into the left and right main Bronchus at T4/T5 * Right main bronchus is shorter and wider and more vertical than the left

Answer 56

* trachea is series of U shaped cartilage rings and is closed posteriorly by trachealis muscle that flattens trachea posteriorly

Answer 57

Trachea, Main Bronchi, Lobar Bronchi, Segmental Bronchi

Answer 58

* Each segmental bronci supplies a bronchopulmonary segment * Bronchopulmonary segments are pyramid shaped and has its point towards the hilum of the lung and the base of the pyramid on the lung surface * Each segment has its own segmental bronchus, own artery and own vein. * Each segment is functionally distinct section so that if something goes wrong with one or two the rest of the lung can continue to function Segments can be surgically resected

Answer 59

* Each lung has a concave inferior surface and apex protruding up and rounded costal surface baring imprints of the ribs and a mediastinal surface that bares the imprint of mediastinal structures * The right lung is larger than the left * The right lung has three lobes * Two fissures devide right lung into three lobes * long oblique fissure and shorter horizontal fissure *

Answer 60

* Left lung only has one fissure that seperates the uppper lobe from the lower lobe * On the left lung there is a point which is cut out on the from the heart which is called the cardiac notch * bellow that is a lump which is called the lingular

Answer 61

* The right main bronchus has already devided into the right upper lobe bronchus and the bronchus intermedius. * Can see arterial structures anterior to the bronchus strucutres * The two pulmonary veins are the most anterior and inferior structures-i.e. one anterior and one inferior * There also must be a blood supply and they are bronchiol arteries and bronchiol veins, lymphatics and nerves entering the hilum as well (cannpt be seen) * Lymphatics drain to the hilar lymph nodes and can see them stained black due to carbon

Answer 62

* Left side only one main bronchus and one artery going in at the hilum and then an anterior an inferior pulmonary vein and carbon stained lymph nodes * can see a large imprint from aorta and the left ventricle

Answer 63

Azygous system

Answer 64

* autonomic nerve supply to the lungs where we have the sympathetics coming from the ganglia from the sympathetic trunk and the parasympathetics come from the vagus nerve * There is a pulmonary plexus associated with the devision of the trachea and then nerves enter the hilums of the lung

Answer 65

* Surface of the lungs have a reticulated pattern of dark staning-superfical lymphatics just bellow the visceral pleura * a spiderweb appearance coloured black due to carbon * There is also a deeper system that follows airways and vessels that then head to the hilum and drain into hilar lymph nodes. * From those hilar lymph nodes we have lymphatic channels that will head to thoracic duct on the left and right lymphatic duct on the right and that lymph will then be emptied into the venous system around the junction of the internal jugular veins and subclavian veins. * Remember that the thoracic duct on the left drains 3/4 of the body and the right lymhatic duct only drains the right side of head and neck and right upper limb and right side of thorax

Answer 66

* Electron beam from a piece of metal heated up then hits an anode and X rays are given off * X rays convert silver-halide crystals to black * more X rays passing through = black * less X rays=white * The image is not 3D though and everything is collapsed down flat * X rays interacts with electrons so anything with high atomic number in high concentration, i.e. bone, has lots of calcium and X rays are stopped

Answer 67

* We must have something different around the tissue to seperate the different structures

Answer 68

* X-ray is done in full inspiration * X ray passes from posterior to anterior because we want the heart to be as close to the detector as possible so we don't get any magnification * Get scapulae out of the way so hug the X ray cassette * Erect so that we can determine blood flow distribution in the lungs

Answer 69

* If all conditions are right then the maximal transverse diameter of the cardiac silhouette must be less than 50% of the maximmal transverse diameter of the thoracic cavity from the inside of the ribs * if greater than 50% then patient has a big heart

Answer 70

* Apex, upper, middle, lower and base * becasue we cannot see the fissures in an X-ray unless they are inflamed * or lateral view-the fissure can be more easily seen

Answer 71

* Angle of louis is an anatomical line that goes from menuebrio-sternal junction to the T4/T5 disc on the back * We use the angle of louie to devide the mediastinum-superior and inferior

Answer 72

* There will be a meniscus in the hydrothorax but no meniscus in the hydropneumothorax * this is due to the negative pressur ein the pleural cavitity

Answer 73

* very similair to X ray in the method which X rays are produced * However film is not used to detect * instead use a radiation detector * and the beam of X-rays rotate around the person in the CT machine * Get 3D image of the person as it rotates around the patient * Can look at any part of the image with post processing * CT has poorer spatial resolution than plain X-ray * CT has far better contrast resolution than plain X-ray * Can add IV dye to better diferentiate-i.e. iodine-highelectron density * can easily identitify fissures in the lung using CT scan

Answer 74

* absolute measure of x-ray attenuation * digital “grey scale” rather than film density * maintains the convention of film * air = black, bone = white

Answer 75

* axial – from the feet up * coronal – from the front * sagittal – from the left

Answer 76

* can post process and look exclusively at a smaller section of spectrumm and use contrasting to better differrentiate between differences in electron densities and thus different strucutures

Answer 77

Red green * X-linked recessive disorder * Men=8% * Women=0.4% Blue yellow * autosomal dominant

Answer 78

* R isomer works as intended to assist in morning sickness * S isomer caused horrible congenital defects

Answer 79

* autosomal recessive * 1 in 14,000 * 1 in 60 are carriers * Cause mental retardation, seizures, tremors and behavioral disorders * Caused by a lack of phenylalanine hydroxylase * Nn normal people excess Phe is converted to Tyr by penylalanine hydroxylase * but if we don't have this enzyme Phe is converted by a different pathway to phenylpyruvate which builds up * this can damage the brain and also inhibit the tyrosinase enzyme (responsible for syntheisiing melanin) * Now we can easily screen for the disease using the **Guthrie test** * And treat the disease by limiting phenylalanine in the diet

Answer 80

* most common life threatening genetic disorder in australia * autosomal recessive disorder * 1 in 25 people are carriers * 1 in 2,500 live births * CF primarily affects the respiratory system (lungs), digestive system (pancreas and sometimes liver) and reproductive system. * People with CF will have a persistent cough and recurrent lung infections due to mucous build up * Guthrie heal prick test also used for diagnosis which detects elevated immunoreactive trypsin (IRT) * also salty sweat * Product of the mutated gene is a cystic fibrosis transmembrane conductance regulator (CFTR) * This mutation effects the permeability of conducatance of a membrane-allows chloride to go through a cloride channel * diminised chloride perfusion into the airway results in build up of mucous * 3 base deletion deletes Phe508 in the large protein *

Answer 81

* Gly-Pro-Ala repeating subunits * about half of the prolines are hydroxylated * this allows for the OH group to form cross links with other collagen chains * alpha chain structure with glycines positioned in the middle

Answer 82

* The glycine at position 748 becomes cysteine * now the collagen is kinky and this can make bones incredibly weak. * Some people have bad teeth and some people cannot walk * can be autosomal dominant or autosomal receissive

Answer 83

* Can be caused by mutation in one of a family of collagen genes * most forms are autosomal dominant can be varrying degrees of disease * Mutations in these genes alter the structure, production, or processing of collagen or proteins that interact with collagen or proteins that interact with collagen. * Get extra bendy limbs etc

Answer 84

* Mutation in tyrosinase which is responsibelt for the synthesis of melanin * Tyrosinase initially maked DOPA from tyrosine and there are variations of DOPA which are then made into polymers which are melanin * Melanocytes-make melanin and give to skin cells-unfortuantely they can become melanomas and move off and lodge in the brain (often)

Answer 85

* autosomal recessive pattern of inheritence * Sickle cell anaemia single base change that results in hydrophilic Glutamic acid to Valine change in the Beta globin gene * hydrophobic Valine binds to a hydrophobic pocket that is present in deoxy-haemoglobin and forms an insoluble structure-leads to sickle cells that can lodge in caplillaries **Symptoms** * Anaemia and weakness * Failure to thrive * Splenomegaly * Repeated infections * Crises: * ischaemia, thrombosis, infarctions, (especially in spleen, brain, lungs, and kidneys) **Under the microscope** * Severe normocytic * or macrocytic * haemolytic anaemia * can see the sickle cells * sufferers may have normal MCV and MCH * Hb significantly decreased * Can see HbS on HPLC

Answer 86

* Skeletal system involvement is characterized by bone overgrowth and joint laxity. The extremities are disproportionately long for the size of the trunk (dolichostenomelia). * The fibrillin 1 gene FBN1 is mutated in Marfan syndrome. * FBN1 produces a protein which is transported out of the cell and deposited in the extracellular matrix. * Fibrillin becomes part of extracellular matrix. Fibrillin becomes part of microfibrils, which in turn help build elastic fibres essential for the function of flexible structures such as blood vessels, the lungs, and skin.

Answer 87

* defficiency in the synthesis of heme * but symptoms are a result of accumulation of the intermediates * 7 enzymes involved * Can have mutations at each of the sites * today treated with heme replacement therapy

Answer 88

* alpha-like globin genes clusterred on chromosome 16 * Zeta and pseudo Zeta and Psuedo alpha * we have two copies of the alpha genes

Answer 89

* Beta-like genes on chromosome 11 * epsilon version * two different gammas (only differ by one base) * a pseudo Beta gene * a delta gene * and a single Beta gene

Answer 90

Embryonic Hb= ζ₂ε₂ and ζ₂γ₂ and α₂ε₂ Fetal= α₂γ₂ and α₂β₂ Postnatal= α₂γ₂ and α₂β₂ and α₂γ₂

Answer 91

clinically benign

Answer 92

* Global distribution; high in South East Asia * due to deficiency of alpha-globin chains * Majority caused by large deletions * we have 4 copies of the alpha gene and it depends on the number of mutations that determine phenotype

Answer 93

* Global distribution * Increased frequency in Southern European and Middle Eastern countries as well as North Africa, South East Asia, Indian subcontinent due to deficiency of Beta-globin chains * Majority caused by point mutations * promoter mutations * RNA splicing mutations * mRNA capping or polyA tailing mutations * nonsense * frameshift * alpha4 aggregates are insoluble and don't bind oxygen and can cause damage to blood cell membranes and then the RBCs are further destroyed-heamolytic aneamia *

Answer 94

* alpha4 aggregates are insoluble and don't bind oxygen and can cause damage to blood cell membranes and then the RBCs are further destroyed-heamolytic aneamia * Most of the cells expressing Alpha4 would die as erythroblasts in the bone marrow * Bone marrow can expand in volume in its attempts to make more Hb for the increasing O2 demand * There is also a compensatory increase in iron aborption and this can lead to systemic iron overload. * tissue anoxia can lead to skeletal deformities * can also get enlarged liver and large spleen * abnormal cells that are able to leave the bone marrow and destroyed in the spleen and so the spleen gets larger as well

Answer 95

* Hepatosplenomegaly * Frontal bossing (forehead is pronounced * thinning of long bones * hair on end appearance of skull due to thinning of cranial bone

Answer 96

* In beta thalassaemia we can see microcytic (small cells) and hypochromic (pale cells) anaemia * anisocytotic-irregular in size * tear drop shaped cells-due to accumulation of the alpha monomeric globins

Answer 97

* Points of intervention * people with an enlarged spleen may have it removed-now more susceptible to infection * For the thalassaemia we can give regular blood transfusions-this can lead to more iron introduction though * can be managed with chelation therapy-bind and excrete the iron * combined cost of blood transfusions and iron chelation therapy is in excess of 120,000 per annum * only real cure is a bone marrow transplant

Answer 98

**Normal** * **Hb(g/L)** Males=135-175. Females=120-160 * **MCV(fL)**=80-97 * **MCH(pg)=**27-34 * **HbA(%)**=97.5 * **HbA2(%)**=1.8-3.5 * **HbF(%)**\<1 **Beta thalassaemia (Heterozygotes)** * Hb-moderately reduced (102) * MCV-ussually decreased (80) * MCH- less than 27 * HbA-decreased but \>90% * HbA2-Elevated 3.5 * HbF=Elevated 1-2% **Beta thalassaemia (Homozygotes)** * Hb-30-50 * MCV-less than 80 * MCH- less than 27 * HbA-0 * HbA2-normal or elavated * HbF=greatly elevated, 90% **Sickle cell anaemia (Heterozygotes)** * Hb-slightly or moderately reduced * MCV-normal or slightly reduced * MCH-normal or slightly reduced * HbA- * HbA2- * HbF= **Sickle cell anaemia (Homozygotes)** * Hb-significantly decreased 60-80 * MCV-may be normal or slightly decreased * MCH-may be normal or slightly decreased * HbA- * HbA2- * HbF=

week #7 Flashcards

(127 cards)