Unit 3

Question 1

most common form SCID

Answer 1

X linked IL2 R gene

Question 2

Most common mutation CF

Answer 2

delta F 508

Question 3

What enzyme does newborn screening in CF pick up

Answer 3

Immunoreactive trypsinogen

Question 4

Testing for lupus which is more sensitive vs specific

Answer 4

Anti nuclear AB - auto AB to nuclei cells.
98% peoplesystemic lupus have a positive ANA test * most sensitive. Also called immunofluorescent antinuclear antibody test.

Anti-double-stranded DNA antibody (anti-dsDNA) = specific ANA antibody found in about 30% of people SLE + less than 1% of healthy individuals * specific.

The presence of anti-dsDNA antibodies suggests more serious lupus, such as lupus nephritis (kidney lupus). When the disease is active, especially in the kidneys, high amounts of anti-DNA antibodies are usually present.
Use enzyme-linked immunosorbent assay (ELISA)

Question 5

How chronic infection CF leads decreased lung funcion

Answer 5

o Chronic infection – launch Th17 response against extracellular bacteria. Repeating cycle of infection and neutrophilic inflammation develops. Neutrophil releases lysosomal enzymes + peroxidase. Increased vascular permeability + fluid build-up lungs increasing diffusion distance * limiting effective gas exchange. TGF-ß and endothelin, cause smooth muscle proliferation, intimal thickening, interstitial fibrosis.

o Cleavage of complement receptors CR1 and C3bi and immunoglobulin G (IgG) by neutrophil elastase (NE) results in failure of opsonophagocytosis * bacterial persistence. NE leads production (IL)–8 from epithelial cells and elastin degradation * persistence of inflammation and infection, structural damage, impaired gas exchange, and, ultimately, end-stage lung disease and early death. As chronic inflammation gets resolved get formation scar tissue each time * builds up which reduced lung function.

o Airway obstructed due build up mucus * harder exhale air * reduced FEV

o Struggle expel air quickly as airways could collapse during exhalation – breathe out slowly pursed lips positive pressure maintain airway patency.

Question 6

Warm type haemolytic anemia

patho

Answer 6

Breakdown tolerance -IgG auto AB produced against rhesus antigen rbc

igG coat RBC binding Fc R receptor phagocytes - phagocytosis esp sleen as splenic macrophages best affinity FC region.

Repeated partial pahgocytosis - damages membrane - spherocyte

Question 7

Cold type haemolytic anemia

patho

Answer 7

Breakdown tolerance- IgM auto AB against polysaccaride 1 antigen.

Form IC peripheries <37 - Igm binds anitgen low affinity. Igm fixes complement classical * when RBC enter warmer region igM detaches leaving complement bound - kupffer cells high affinity C3b extra vascular hemaolysis liver

Question 8

Warm type haemolytic anemia testing

Answer 8

Blood film - leucoerthroblastic, poly chromatic spherocytes

+ve direct Ab test IgG C3d
postive coombs for IgG

Question 9

Cold type haemolytic anemia testing

Answer 9

Blood film normocytic, poly chromatic spherocytes

+ve Cooms complement

Question 10

Folate cycle

Answer 10

dUMP -> thymidylate via thymidylaye synthase. Thymine needed DNA synthesis.

Question 11

erythropoesis

Answer 11

Multipotent heamatopoetic stem cell
common myeloid progenitor
pro-erthroblast
basilic erthroblast
polychromatic erthroblast 
Orthochromatic eryhtroblast/normoblast
poly-chromatic erythrocyte/ reticulocyte
erthyrocyte

Question 12

Causes micro cytic anemia

Answer 12

Microcytic anaemia- > Hypo chromatic -> Iron deficiency, Thalassaemia, anaemia chronic disease, hyperthyroidism + lead poisoning

Question 13

Clotting diseases with prolonged prothrombin time

Answer 13

Owen parahemophillia (factor 5 deficiency) 
Liver failure - deficiency gamma carboxylated coagulation factors - II (prothrombin), VII, IX and X.

An essential cofactor for gamma-carboxylation is vitamin K,

Question 14

Oculomotor n. parasympathetic component

Answer 14

Preganglionic neurons: midbrain (Edinger-Westphal nucleus)
Postganglionic neurons: Ciliary ganglion

Targets: Ciliary muscle & sphincter pupillae

Function: Accommodation of the lens, constriction of pupil

Question 15

Facial nerve parasympathetic component

Answer 15

Preganglionic neurons: pons (superior salivatory nucleus)
Postganglionic neurons: pterygopalatine & submandibular ganglia

Targets: Lacrimal glands, submandibular gland, sublingual gland

Function: Increased secretion (tears and/or saliva)

Question 16

Glossopharyngeal n. parasympathetic component

Answer 16

Preganglionic neurons: pons (inferior salivatory nucleus)
Postganglionic neurons: Otic ganglion

Target: Parotid gland

Function: Increased secretion

Question 17

Vagus n parasympathetic component

Answer 17

Preganglionic neurons: medulla (Dorsal vagal motor nucleus)
Postganglionic neurons: within walls of viscera

                                                        E.g. enteric NS!

Target: Thoracic & abdominal viscera (up to the splenic flexure)
Function: Rest & digest

Question 18

Pelvic splanchnic nerves

Answer 18

Preganglionic neurons: S2-S4
Postganglionic neurons: within walls of viscera

Target: Hindgut & pelvic viscera

Function: Peristalsis, glandular secretion, engorgement of erectile bodies, urination

Question 19

Obstructive airway disease

Answer 19

Airflow obstruction due narrowing airways. Fev1 decreases much more FVC (same or drop slightly)* ratio drops.

Question 20

Restrictive airway disease

Answer 20

Restrictive: Decreased lung volume – fibrosis. Not able create as great pressure difference due lack compliance * draw out smaller volume air. Fev1 and FVC drop by the same amount * ratio remains the same.

Question 21

Pelvic pain line

Answer 21

Pain from viscera ‘above or in contact with inferior layer of parietal peritoneum’ travels via sympathetic splanchnic nerves

Pain from sub-peritoneal organs is conveyed via parasympathetic nerves

Question 22

Pseudomonas virulence factors

Answer 22

Type 4 pilli
twitching motility + cell adhesion

LPS
Inflam signal + resistance phagocytosis

Type 3 secretion system
Injection toxins into host cells

Alginate
Slime layer + resistance IC + proteins

Flagellum
Motility + inflam signal

Phospholipse
Tissue invasion

Exoenzyme S/A
Inhibit elongation factors - kills

Sidophores
Iron sequesration + cell death

Elastase/protease
Tissue invasion

Question 23

How siderphores allow iron sequestration

Answer 23

Siderophores are essential to iron sequestration in pseudomonas but in the process, they strip iron from human cells. Host cells need Fe for oxidative phosphorylation, siderophores are released from bacteria to scavenge Fe3+ from host cells – metabolic stress kills cell + iron sequestered into bacterium via transferrin. Neutrophil response – oxidative burst leads peroxide secretion from phagocytes. Fe3+ strips oxygen from peroxide * no damage to bacterium.

Question 24

How does pseudomonas cause a respiratory tract infection in CF? 4 mark

Answer 24

o Initially pseudomonas adopts a non- mucoid phenotype, no biofilm formation, motile, cytotoxic with immunogenic LPS -> elicits strong IR.
o Normally bacteria eliminated by non-specific barrier defences – ventilation also have mucus trapping, defensin secretion + ciliary action- poor ventilation or entry bacteria increased by external devices infection occurs normally macrophages detect bacteria + drive inflammation. DC recruits Th17 help, neutrophils recruited + pathogen cleared.
o In CF patients produce excess/thick mucus that bacteria can live inside – mucus not removed by ciliary action * colonisation occurs + replication bacteria cannot be controlled.
o Once inside mucus pseudomonas changes its phenotype to a mucoid alginate secreting phenotype. Biofilm formation which is impenetrable to therapy, resorbs flagella, limited toxin production + this limit immune response as IS only encounter organisms if reach edges of mucus.

Question 25

Risk factors for pseudomonas

Answer 25

o Failure immunity o Structural defect o Lack adequate ventilation o Devices

Question 26

How does the mucoid phenotype helps evade IS

Answer 26

How does the mucoid phenotype helps evade IS o Biofilm prevents penetration of immune proteins + compounds. Lipid A of LPS binds less efficiently to TLR4 -reduced inflammation + reduced bacterial clearance leading to chronic infection with repeated flare ups. o Increased neutrophil mediated damage respiratory epithelium, elastic + connective tissues. Neutrophils undergo NETosis form extracellular traps + neutrophil granule contents released. Wheeze, cough, mucus hyper-production -> bronchitis, bronchiectasis + pulmonary failure inevitable. Need antimicrobial therapy prevent colonisation + eliminate bacteria during flare ups.

Question 27

How pseudomonas has developed antimicrobial resistance (natural feature of overdose)

Answer 27

o Hydrophobic penicillins (Penicillin V, flucloxacillin) + glycopeptides cannot enter outer membrane channels o Hydrophilic penicillins (Amoxicillin) + cephalosporins can enter but chromosomally encoded beta-lactamases degrade them o Constantly expressed outer membrane efflux pumps pump protein synthesis inhibitors + folate antagonists out cell (Macrolides, Tetracyclines, Trimethoprim + Fusidate)

Question 28

Mucoid phenotype in psedomonas

Answer 28

``` Alginate secreting Biofilm formation Resorb flagella Limited toxin production limits IR - ```

Question 29

Productive cough CF

Answer 29

Lack CFTR reduced chloride secretion increases sodium + water absorption - lowers water content mucus lining respiratory epithelium - isotonic dehydrated mucus defective mucocilliary action accumulation secretion obstruct bronchi + bronchitis triggering cough reflex

Question 30

How Pseudomonas acquires resistance

Answer 30

Chromosomal mutation. Activation of existing resistance genes. Uptake of genetic material from other organisms

Question 31

Acquired resistance Pseudomonas

Answer 31

o De-repression chromosomal ESBL + plasmid-acquired beta-lactamases (NDM1) OR carbapenemases (KPC) degrade ceftazidime, tazobactam + meropenem o Overexpression multi- drug efflux pumps actively remove fluoroquinolones (ciprofloxacin), aminoglycosides (gentamicin) + carbapenems o Changes in drug targets (topoisomerases + small ribosomal subunits) prevent fluoroquinolone + aminoglycoside binding -> expression 16s rRNA methylation enzymes + expression altered topoisomerase enzymes.

Question 32

What is pseudomonas

Answer 32

Pseudomonas aeruginosa is a Gram-negative, oxidase-positive, non-fermenting bacillus

Question 33

What pseudomonas relations

Answer 33

Acinetobacter, Burkholderia and Stenotrophomonas

Question 34

atopy

Answer 34

Atopy (genetic tendency to develop allergic disease). 40% in Caucasian populations. Atopic have higher levels IgE + Eosinophils in blood. Due polymorphism of many genes. MHC II -> enhanced presentation of allergen peptides. TRC alpha chain -> enhanced recognition of allergen peptides. Il-4R -> increased Il-4 signalling. Il-4 -> variation Il-4 protein expression. FceRI -> IgE binding. Chromosome 5 genes for Il-4,3,5,9,12,13 + GM-CSF involved isotope switching, eosinophil survival + mast cell proliferation.

Question 35

Genetic factors asthma

Answer 35

HLA DR/Q Polymorphisms ADAM33 Chromosome 5q

Question 36

Atopic asthma

Answer 36

Atopic asthma Most common type – type 1 hypersensitivity reaction. Allergic sensitisation + patients’ family hx asthma + high serum IgE.

Question 37

Stress induced asthma

Answer 37

Stress induced Initially At catecholamine -> bronchodilation. Long periods of exposure catecholamines, their receptors become downregulated * effects less severe. Reduction in catecholamine sensitivity reduces immune cell regulation, as T and B lymphocytes possess adrenergic receptors, so catecholamines can regulate IL-4, IL-5 and IL-13 expression, histamine release from mast cells and recruitment + activation of eosinophils.

Question 38

Cold induced asthma

Answer 38

Cold/ exercise induced Airway cooling - dehydration of the fluid lining respiratory epithelium. Drying of the airways increased blood flow (hyperemia) -> oedema + bronchoconstriction. Exercise induced asthma, symptomatic 5-15 minutes after exercise, as catecholamine release during exercise helps with bronchodilation.

Question 39

Drug induced

Answer 39

Drug induced 3-5%, NSAID + Aspirin sensitivity -> Drugs inhibit AA pathway inhibit production prostaglandins. Prostaglandin E inhibits enzymes generate leukotrienes * inhibit this get upregulation leukotrienes -> bronchoconstriction. Urticaria (hives) + typical asthmatic symptoms.

Question 40

Early phase asthma

Answer 40

Early phase response - sensitization o Inhaled allergens get across mucosal layer taken up DC, presented T-helper cells inducing exaggerated Th2 response to harmless environmental antigen. o Th2 produces Il-4 -> stimulate proliferation + differentiation plasma cells + IgE production. Il-13 -> stim mucus secretion from bronchial submucosal glands + IgE from plasma cells. o Plasma cell produced IgE binds to Fc on submucosal mast cells BUT by this time the antigen has already been cleared. o Second exposure to antigen the ready and waiting mast cells react immediately, releasing granule contents with immediate affects. Allergen binds mast cell bound IgE immunoglobins cross linking Fc receptors triggering degranulation + release; - Leukotrienes -> bronchoconstriction, increased vascular permeability and oedema and increased mucus secretion (B4 recruits immune cells, C4, D4, E4 bronchoconstrict) - Histamine -> potent bronchoconstrictor - Prostaglandin D2 -> bronchoconstriction and vasodilation (causing oedema)

Question 41

Late phase asthma

Answer 41

o Th2 -> IL-5 activates locally recruited eosinophils into airways which bond IgE immunoglobins through Fc receptors which cross linked bound to allergen. Eosinophils release eosinophil cationic protein + major basic protein -> damages cells respiratory tract + leukotrienes -> oedema + further bronchial constriction. o Chemokines produced T + epithelial cells recruit more T cells, eosinophils + basophils. Epithelial release eotaxin = chemokine for eosinophils. Chronic inflammation -> bronchial hyperresponsiveness to histamine, cold air, sulphur dioxide and AMP. mediated by high levels IgE * airways more responsive to contractile stimuli. Epithelial shedding from chronic inflammation exposes subepithelial tissues to inflammatory mediators + sensitises nerves * altered neural control of the airways. Airway obstruction due muscular bronchoconstriction, acute oedema and mucus plugging.

Question 42

Characteristics early phase asthma

Answer 42

bronchoconstriction, increased mucus production and increased vascular permeability and oedema, leading to symptoms of wheezing, chest tightness and breathlessness. Mast cell contents activate subepithelial vagal receptors, triggering acetylcholine release from vagal efferents that directly induces smooth muscle contraction through muscarinic receptors.

Question 43

Why is breathlessness worse at night asthma

Answer 43

Airway obstruction due bronchoconstriction + mucus plugging * respiratory muscles need work harder to generate a negative intrapulmonary pressure for inspiration. Muscle fatigue -> lead to breathlessness. Inability to draw in air-> bronchoconstriction. Increased exposure to allergens at night; cooling of the airways; being in a reclined position leading to pooling of secretions worsens airway obstruction at night * breathlessness. Cortisol peaks in the early morning hours, leading to increased inflammation

Question 44

What is asthma

Answer 44

Chronic disorder conducting airways caused immunological reaction marked episodic bronchoconstriction due increased airway sensitivity variety stimuli, inflammation bronchial walls + increased mucus secretion. Flare ups IgE mediated type I hypersensitivity reaction Allergen specific IgE AN bind mast cells via Fc receptor. When antigen binds to IgE the Cross linking of IgE induces degranulation of mast cells), following exposure environmental allergen in genetically predisposed person.

Question 45

Response to b2 agonist in asthma, COPD and restrictive

Answer 45

Asthma >15% response COPD <15% No response restrictive

Question 46

Changes in airway remodeling

Answer 46

``` Sub epithelial fibrosis Increase SM mass Goblet + mucus gland hyperplasia Angiogenesis Loss cartilage integrity Inflammation Epithelial alteration ```

Question 47

What do neutrophils release

Answer 47

Granules - cellular proteases, elastase, proteinase 3 + cathepsin - tissue damage

Question 48

Functional alpha 1 antitrypsin deficiency

Answer 48

Oxidative injury allows inactivation native antiproteases

Question 49

Part lung affected emphysema

Answer 49

Acinus - respiratory bronchiole, alveolar ducts + alveolar

Question 50

Symptoms COPD

Answer 50

Cough worse morning - productive colorless sputum Breathlessness 6th decade life due reduction FVC Wheezing ``` Severe Tachypnoea -rapid shallow breathing Acc respiratory muscles Cyanosis Elevated JVP ``` Examination Hyperinflation decreased breath sounds prolonged expiration

Question 51

Obstructive lung disease

Answer 51

obstruction due narrowing airways - fev1 decreases more fvc * ratio drops

Question 52

Restrictive lung disease

Answer 52

DECREASED LUNG VOLUME - fibrosis. not able create great pressure differnece due lack compliance * draw smaller volume air Fev1/ FVC drop by same amount * ratio remains the same

Question 53

how to episodic asthma symptoms become persistent with time

Answer 53

Persistent mucous inflammation - up regulation nerves vessels + glands in resp tract -> increased responsiveness allergens + environmental irritants (epitope spreading) -> patient sensitive wide range stimuli * episodic symptoms become persistant

Question 54

Lung mechanism of compensation

Answer 54

Physiological shunting and hypoxic vasoconstriction - area capillary not getting ventilated vasocontricts and blood shunts to area well ventilated If physiological dead space- get bronchocontriction and reduced surfactant - diverts to areas well perused alveoli

Question 55

Type I and type II respiratory failure

Answer 55

Type I hypoxaemic respiratory failure - Localized mismatching ventilation/perfusion ratio Po2 low Pco2 normal/low Type II hypercapnic respiratory failure - large portion lung pneumothroax - global reduction in flow of air to alveoli or blood to pulmonary capillaries po2 low pco2 high

Question 56

Role kidney and liver in chronic acidosis

Answer 56

liver decrease urea production and increase glutamine production Kidney up regulates glutamine dehydrogenase + PEPCK which catalyze breakdown glutamine into ammonium and bicarbonate ions

Question 57

Where is glutamine taken up

Answer 57

PCT

Question 58

Glutamine to glucose steps

Answer 58

``` Glutamine alpha ketoglutarate oxaloacetate Phosphoenolypyruvate Glucose + bircarbonate (3 bircarbonate excreted into interstium along with Na+) ```

Question 59

kidneys response to chronic alkalosis

Answer 59

Decrease plasma bicarbonate | Increase number and activity type b intercalated cells in collecting duct -> secrete HCO3 into tubule lumen

Question 60

Mechanism Warfrin

Answer 60

Competively inhibits vit K reductase needed activate vit k into usable forms by body. reduce synthesis vit K dependent clotting factors II, VII, IX X

Question 61

Mechanism Heparin

Answer 61

Binds + activated antithrombin III which activates it against 11, IX, X and slightly XII Unfractionated inactivates throbin and factor X LMWH only inactivates factor X dalteparin

Question 62

Steps clotting

Answer 62

``` Vascular spasm Platlet plug formation Coagulation Clot refraction + repair Fibrinolysis ```

Question 63

Endo cells release.... to prevent clotting normally

Answer 63

NO2/ PGI2 -> NATURALLY INHIBIT PLATELET PREVENT BINDING Heparin sulfate on surface which bonds AT III which degrades clotting factors II, IX X thrombomodulin of surface which binds Thrombin (II) Which activates protein C which degrades V and VIII

Question 64

Stages vascular spasm

Answer 64

Endo injury constrict BV prevent Blood loss Endo cells injured -> endothelin activates intracell PIP2 mechanism contraction Direct injury Sm- myogenic mechanism -> contraction Chemokines/pro inflam cytokines activate nociceptors - pain reflex contraction

Question 65

Parasympathetic cranial nerves

Answer 65

oculomotor, facial, glossopharyngeal and vagus nerves, which are also known as cranial nerves III, VII, IX and X

Question 66

SIRS

Answer 66

Body wide response involving inflam mediators can be caused when infections reach bloodstream. Infection BS, TNF alpha binds R endo cells. Momocytes detect pathogens PRR, complemnt R + Fc R. monocytes initiate pro inflam cytokine responce. Dissemination increase fever HR CRP + WCC

Question 67

SIRS to Sepsis

Answer 67

TNF alpha activated eno cells release TF (activates coagulation cascade - hypoperfusion other areas + ROS direct organ damage) and NO drives vasodialtion + capillary leakage. TNF alpha also activates neutrophils - produce TNF alpha. Activated neutrophils form NETS

Question 68

SIRS to septic shock

Answer 68

Increase TF hypercoagualtion, depletion clotting factors increased anticoagulation TNF alpha, CXCL8 + NO casue vasodilation - fluid loss into tissues - oedema (LUNGS + CSF) hypoperfusion + BP rapdil drops SEPTIC SHOCK - low BP/MAP

Question 69

Bacteria cause sepsis

Answer 69

``` Esherichia coli (gram neg) Stapylococcus aureus (gram = +ve) ```

Question 70

Bacteria cause meningitis

Answer 70

``` GBS E-coli Staph aureus Strep pneu Neisseria meningitis ```

Question 71

qSOFA

Answer 71

presence doc/suspected infection with organ dysfunction + qSOFA 2+ = sepsis RR >20 CNS altered mentation SBP <100mmHg

Question 72

CARS

Answer 72

compensatory anti inflam response syndrome If ongoing septic shock and IR run out of immune cells * pathogen no longer being present switch anti inflam responce Increase TGF B + IL-10 Decrease TNF alpha, CXCL8 + NO body assumes infection is over

Question 73

SOFA

Answer 73

sequential organ failure assessment for sepsis - SIRS presence infection with SOFA >2 = SEPSIS Looks at respiratory, coagulation, liver, CNS + renal

Question 74

Community acquired pneumonia

Answer 74

Strep. pneu | Amoxicillin

Question 75

Community acquired UTI

Answer 75

E- coli | Trimethoprim

Question 76

Catheter associated UTI

Answer 76

Gram neg E- coli kleibsiella spp Gentamycin

Question 77

Hospital acquired pneumonia

Answer 77

Staph aureus Pseudomonas tazocin

Question 78

ECG trace PE

Answer 78

S1Q3T3 McGinn white sign

Question 79

When does gallop heart rhythm happen

Answer 79

Diastole

Question 80

Brief study development AS plaque

Answer 80

Endothelium dysfunction + high amounts circulating LDL Increase LDL deposit intima + oxidised Oxidised LDL activate eno cells which upregulate receptors bind leukocytes Adhesion leukocytes allow monocyte + t cell entry - monocytes differentiate into macrophages as moves into tunica intima. Macrophages take in oxLDL + become foam cells Foam cells promote migration SMC from tunica media- intima + SMC proliferation. SM proliferation - heightened synthesis collagen * hardening AS plaque. Foam cells die - release lipid contents. Plaque grows + pressure - rupture. Thrombosis + coagulation impede blood flow

Question 81

ANP

Answer 81

Stretch atria causes drop BP | Decrease GFR, decrease resorption Na+, inhibit release renin, aldosterone = ADH

Question 82

MI

Answer 82

Irreversible necrosis heart muscle secondary prolonged ishemia due imbalance O2 supply + demand often caused plaque rupture thrombus formation in left anterior decending artery * reduction blood supply to ant wall left ventricle.

Question 83

Which cell type release synovial fluid

Answer 83

type B

Question 84

Pathophysiology OA

Answer 84

Initial articular cartilage damage - chondrocyte switches repair cartilage, makes less proteoglycans + more type II collagen. Then switches increase type I collagen. Type I doesn't interact proteoglycan same way + decrease elasticity. Over years chondrocytes became exhausted and apoptose. Weak cartilage - flake off into cartilage space = JOINT MICE Type A cells clear joint mice - attracting lymphocytes + macrophages - release pro inflam cytokines - synovitis Fibrilations form - cracks on articular smooth surface Cartilage wears away until rubs bone - bone eburnation Osteophytes - hebardens + bouchards nodes

Question 85

Rickets pathophysiology

Answer 85

Deficiency Vit D, hypocalceamia, increase plasma Ca, decrease plasma P. bone formation as compensation - abnormal mineralization due lack calcium and phosphate. If at growth plate = rickets. If bone matrix = osteomalacia.

Question 86

Anemia in inflam states

Answer 86

Il-6 binds to IL-6 receptors on liver cells increasing hepcidin expression. Hepcidin interacts with ferroportin causing internalisation into enterocytes, inhibiting iron mobilisation from cellular stores. TNF alpha also opposes action of EPO which reduces erythropoiesis. Reduced RBC formation and reduces iron availability reduces amount Oxygen that is transported around body causing anaemia and fatigue.

Question 87

High risk strains HPV

Answer 87

HPV 16,18,31,33,45

Question 88

HPV genital warts

Answer 88

6,11

Question 89

HPV cutaneous warts

Answer 89

1-4

Question 90

HPV oral infections

Answer 90

13+ 32

Question 91

What is target HPV virus

Answer 91

Stratum basale keratinocytes

Question 92

Whats the trigger to switch off E2 in HPV and then l1/2 promotor switches on

Answer 92

keratinisation of cell + de-condensation of nucleus

Question 93

HPV mechanism of immune evasion

Answer 93

E5 blocks MHC I peptide loading * inhibits NK recognition E6 blocks expression chemokines MIP1alpha and cxcl8 IFN prvented being transcribed by E7 Once inside cell E6 inhibits expression TLR -9

Question 94

What is the role of HPV E7

Answer 94

HPV E7 binds Rb + mimics phosphorylation E2F drives cyclin E expression

Question 95

What is the role of HPV E6

Answer 95

Decreases Rb causes increase p53 HPV E6 binds p53 stopping expression CDK1

Question 96

Measles virus 8 proteins

Answer 96

Early non structural proteins Nucleocapsid - contains + stabilises RNA Virulence protiens p/v/c immune evasion Late proteins structural proteins Matrix - form + stabilize lipid envelope upon release cell Fusion - virulence determinant allows syncytia formation Haemaglugutinin major adhesion Polymerase - replicates neg sense RNA * protein synthesis.

Question 97

Receptors blood vessels

Answer 97

Alpha 1 vasoconstriction Beta 2 vasodilation Alpha I preferentially activated high adrenaline concentrations

Question 98

Receptors in the eye

Answer 98

Miosis - pupillary constrictor muscle sphincter Parasympathetic M3 Mydriasis- pupil dilator muscles radial. Alpha 1 sympathetic

Question 99

4 ways kidney stabilizes blood pressure -long term

Answer 99

o Myogenic intrinsic -Increase BP, increase stretch SM, increase cytosolic calcium, aa constricts + reduction renin section o Tubuloglomerular intrinsic – Increase BP, increase GFR, Increase Na+ uptake macula densa cells stim adenosine release, triggers vasoconstriction aa + inhibits renin secretion from granular cells o Extrinsic - Drop BP detected baroreceptors, increase sympathetic firing, increase noradrenaline, increase proximal tubule Na/H exchange. o Extrinsic RAAS- Angiotensin II, arteriolar vasoconstriction, increase thirst, Na= appetite, increase Na/H+ exchange, aldosterone secretion (increases Na= reabsorption from principal cells distal nephron) o ANP- secreted atrial myocytes response increase BP, decrease proximal na transport vasodilation A>E o Adrenal cortex release aldosterone

Question 100

Mechanism of NO release

Answer 100

The glycocalyx transduces information on shear stress (flow-induced vasodilatation) Activation of intracellular protein kinase B (PKB) PKB phosphorylates endothelial nitric oxide synthase (eNOS)  ↑eNOS activity ↑ NO production in endothelial cells which then diffuses freely through cell membranes to act locally in VSMCs due to its very short half-life NO activates guanylate cyclase in VSMCs  ↑cGMP production  Protein kinase G (PKG) activation: Inhibition of MLCK  ↓ Ca2+ sensitivity. Phosphorylation of phospholamban  disinhibition Ca2+-ATPase pumps  ↑ Ca2+ expulsion + sequestration Activation of sarcolemma K+ channels  hyperpolarisation   opening probability of voltage-gated Ca2+ channels   Ca2+ influx

Question 101

NOD 2 hypothesis for crohns

Answer 101

1. Loss of function of NOD2 leads to reduced α-defensins, reduced recognition in macrophages and dendritic cells and bacteria thrive 2. NOD2 enhances autophagy in endothelial cells clearing bacteria. Without this the bacteria build up . Also associated with reduced α-defensins 3. NOD2 negatively regulates TLR signalling reducing inflammatory cytokine release. Mutations cause deregulated TLR signalling and excessive inflammation. TLR induces IL-12 and pro-inflammatory cytokines. Tips the balance towards Th1 and Th17 induction

Question 102

Coeliac mechanism

Answer 102

Gluten transits the epithelial cells and is altered by tissue transglutaminases into it’s peptide gliadin. Could be as a result of an infection e.g. rotavirus Dendritic cells take up the antigen and drive a TH1 response. IFNγ activates macrophages and drives inflammation TTG complexed with gliadin can be recognised by B cells which with T cell help produce antibodies to gliadin TTG perpetuating inflammation Damage and inflammation can drive IL-15 release by the epithelial cells and activate NK and CD8 responses

Question 103

NSTEMI

Answer 103

ST segment appears depressed Partial occlusion coronary vessel - depolarization drom sub endocardium first as last per-fused - depolarization towards +ve - positve deflection - baseline shift upwards towards +ve value * ST segment appears depressed

Question 104

STEMI

Answer 104

Complete occlusion coronary artery - transmural ishemia - depolrization from ishemic to healthy tissue - directiondepol away electrode - neg deflection - shift baseline down towards neg value * ST segment appear elevated

Question 105

Risk factor lupus

Answer 105

HLA DR3/2 defects C1q virus UV

Question 106

Role CFTR in respiratory vs pancreas vs sweat ducts

Answer 106

Respiratory - secretes cl- and inhibits ENAC Pancreas- SLC2 pumps HCO3 out and Cl- in Sweat ducts - active resorption chloride + activates ENAC- resorption both sodium + chloride.