A- Main Study Deck (physiology) Flashcards

Question

Diving reflex

Answer 1

- Sensor/stimulus: pain, temperature, chemical and mechanosensitive stretch receptors detect pressure to globe of eye, pain in trigeminal nerve distribution, cold temperature, or noxious stimulus of anterior ethmoidal nerve - Afferent: trigeminal nerve - Processor: NTS (vagal response), Rostral medulla (sympathetic response), ventral response (apnoea) - Efferents/effectors: Vagus nerve via cardiac ganglion to SA, AV nodes; phrenic nerve to respiratory muscles - Effects: bradycardia, cerebral vasodilation + systemic vasoconstriction, apnoea ○ Net effect is to prevent aspiration and maximise blood flow to CNS at the expense of skin, muscle and splanchnic organs

Answer 2

- Sensor/stimulus: Emotional distress/orthostatic changes, increased ITP (eg. Defecation, cough/sneeze, laughter) - Afferent: unknown - Processor: ?NTS/Nucleus ambiguus - Efferents/effectors: vagus & SNS to SA, AV nodes, peripheral smooth muscle - Effects: Vagal - bradycardia, sympathetic - systemic vasodilation

Answer 3

Jugular - 55% Muscles - 72% Renal - 81% IVC - 71% SVC - 79% Hepatic - 66%

Answer 4

40mmHg & 70-75%

Answer 5

1 MET = 3.5 ml O2/kg/minute

Answer 6

* Seen as early as wk 20 * Compression of IVC by gravid uterus - decreases venous return & reduced CO * Blood returns to heart via paravertebral epidural veins draining into azygous * Uterine perfusion diminished secondary to increased uterine venous pressure * Compression of aorta may be present & associated with uterine arterial hypotension + reduced uteroplacental perfusion * Can be relieved by positioning mother to left side

Answer 7

Afterload (reduced) --> TPR decreases by 30% by wk 12& 35% (by 20th wk, then remains at 30% below non-pregnant values) * Vasodilation mediated by progesterone, prostaglandins & downregulation of alpha-receptors * SBP + DBP - decrease (~10%) & reach nadir at 20wks * Vascular system as whole becomes more refractory to vasoconstrictors * Note re: RV afterload □ CVP + PCWP - remain stable throughout pregnancy. PCWP balance by decreased PVR

Answer 8

○ Preload (increased) --> By term, maternal blood volume increased by 35-40% (approx 1-1.5L) § Plasma volume increases by 45% - Na + H2O retention by oestrogen stimulation of RAAS § RBC volume increases by 20% due to renal erythropoietin synthesis § Disproportionate rise in plasma volume vs red cell mass accounts for fall of haematocrit to 33% ("anaemia of pregnancy")

Answer 9

CO increases by 40-45% by 12-28wks, peaks at 50% 32-36wks, then reaches 47% at term - Heart rate: HR increases by 17% at end of first trimester,(increases to 25% at middle of third trimester); - Stroke volume increases by 20-30% (predom in 1st trim)

Answer 10

- Distribution (regional flow changes) ○ Renal blood flow - increases by 80% in first trimester (may fall slightly towards term) ○ Large proportion of blood flow is directed to uteroplacental circulation, that increases its blood flow 10-fold to 750mL/min at term ○ Increased blood flow to breasts, GIT, skin

Answer 11

Physical/mechanical changes: - LV mass increases by 40g by 3rd trimester - Heart is more rotated to left ○ May see Q waves + TWI in inferior leads - Colloid oncotic pressure falls by 14% - may predispose to oedema

Answer 12

- Pressure: ○ Maternal SBP + DBP increase 10-20mmHg during uterine contraction - Volume: ○ Each uterine contraction squeezes ~300mL blood from uterus into central maternal circulation - Cardiac output: ○ CO increases by ~15% during latent phase of labour, by 30% during the active phase & 45% during the expulsive stage ○ Immediately after delivery, CO ~60-80% above pre-labour values as a consequence of autotransfusion & increase venous return associated with uterine involution - CO & SBP/DBP return to non-pregnant values by 2 wks post delivery

Answer 13

After birth: * FRC and RV return to normal within 48h * Vt returns to normal within 5 days

Answer 14

- Compliance ○ increased adipose tissue and breast mass --> decreased chest wall compliance (lung compliance unchanged) - Resistance ○ Increases in early pregnancy - mucosal oedema ○ Progesterone-mediated bronchodilation - decreased resistance in later pregnancy (35%)

Answer 15

1. Storage - Metabolic fuel: Glycogen- ~100g & fat - Fat soluble vitamins ○ Vitamin A → stored in stellate cells --> converted to retinol (active form). Contains 1-2yr supply ○ Vitamin D → ~ 1-4 month supply ○ Vitamin E & vitamin K - minimal - Vitamin B12 + folate (50% of body's storage for both) - Trace elements - iron (as ferritin), zinc, copper, selenium - Blood reservoir - ~ 500mL of blood

Answer 16

Synthetic - Plasma proteins- albumin, α+ β globulins, fibrinogen - Nutrients - glucose, ketones, lipids, cholesterol, amino acids - Regulatory molecules (thrombopoetin, angiotensinogen) - Bile acids → stored in gallbladder

Answer 17

Metabolic - Carbohydrate metabolism ○ Liver is a glucostat --> maintains strict BSL § in conditions of ↑ glucose, glycogenesis & FFA synthesis will normalise BSL § in conditions of ↓ glucose, gluconeogenesis will normalise BSL - Lipid metabolism → free fatty acids (FFA). synthesised & packaged with as lipoproteins be transported to adipose tissue for storage § FFA oxidation will also produce energy. - Protein Metabolism - amino acids can be transaminated, deaminated or decarboxylated to give acetyl- CoA

Answer 18

Detoxification & excretion - Immunological detoxification: ○ Kupfer cells act as scavengers & phagocytes & secrete prostaglandins - Ammonia → urea conversion via urea cycle - Conjugation of bilirubin & excretion in bile - Processing of drugs via: ○ Phase I (oxidation & hydrolysis) and ○ Phase II (conjugation) reactions

Answer 19

Length: 10-16cm Diameter: (internal) 2.5cm Origin: C6 Termination: carina, T4 (sternal angle)

Answer 20

Generation 1-4 - Bronchi (cartilaginous) Generation 5-14 - bronchioles (non-cartilaginous) Gen 15-18 - Respiratory bronchioles (some gas exchange) Gen 23 - alveolar sacs

Answer 21

**Muscles** - various muscles attaching to the various structures. Important movements: * Phonation: cricothyroid (brings cords together by moving thyroid down), interarytenoid (transverse + oblique), vocalis (subset of muscles from thyroarytenoid) - mediates tension in vocal ligament to modulate pitch * Inspiration: + cricoarytenoid (posterior + lateral) - rotate arytenoids outwards * Expiration: thyroarytenoid adduct cords to increase resistance and provide intrinsic PEEP (3-4 cmH2O), which maintains patency of small airways & maintains FRC * Effort closure - aryepiglottic muscles contract strongly to act as a sphincter, allowing airway to withstand up to 120cmH2O pressure

Answer 22

Dalton's Law: * In a mixture of gases, the pressure exerted by each gas is the same as the pressure exerted if the gas was the only gas in that mixture: * PTOTAL = PGas1 + PGas2 + PGas3

Answer 23

Boyle's Law: * For a fixed mass of gas at constant temperature, the pressure (P) and volume (V) are inversely proportional, such that P ×V = k, where k is a constant.

Answer 24

Henry's Law * The amount of a given gas dissolved in a given liquid is directly proportional to the partial pressure of the gas in contact with the liquid: P = Hv × M Where * P is pressure * M is the molar concentration of gas * Hv is Henry's Proportionality Constant

Answer 25

Graham's Law: * The rate of diffusion is inversely proportional to the √MW

Answer 26

Fick's Law of diffusion: * Passive movement of molecule from an area of high concentration to low - There are many different iterations of Fick's Law - V_gas∝A/T D (P_1− P_2) V_gas = Flow of gas D∝ Solubility/√MW MW = molecular weight A = surface area P_1 − P_2= difference between partial pressure in alveolus vs capillary T = diffusion distance (or thickness of membrane)

Answer 27

The pressure of a fixed mass of gas at constant volume is directly proportional to its absolute temperature (P/T = k).

Answer 28

Equal volumes of gases at the same temperature and pressure contain the same number of molecules (6.023 × 1023, Avogadro’s number).

Answer 29

The state of a fixed mass of gas is determined by its pressure, volume and temperature (PV = nRT)

Answer 30

VD/VT = (FACO2 - FECO2) / FACO2 Where: VD = dead space volume VT = tidal volume FECO2 = fraction of expired CO2 FACO2 = fraction of alveolar CO2 *Note: Enghoff modification: P_A 〖CO〗_2 is substituted by P_a 〖CO〗_2 as arterial CO2 is measurable (and arterial CO2 is the mixed product of all lung units (theoretically representative of the average CO2 of all alveoli put together))

Answer 31

PAO2 = (FiO2 × (Patm - PH2O)) - (PaCO2 / RQ) Where PAO2= Partial pressure of alveolar oxygen FiO2 = fraction of inspired oxygen Patm = Atmospheric pressure (usually 760 mmHg) PH2O = partial pressure of water vapour at the alveolus (usually 47 mmHg) PaCO2 = Partial pressure of arterial carbon dioxide RQ = respiratory quotient, usually 0.8

Answer 32

(sO2 × ceHb × BO2 ) + (PaO2 × 0.03) Where: ceHb = the effective haemoglobin concentration (conc of hb species capable of carrying & releasing O2) PaO2 = the partial pressure of oxygen in arterial blood 0.03 = the content, in ml/L/mmHg, of dissolved oxygen in blood (for a PaO2 of 100 mmHg, the O2 content is 0.03 × 100 = 3ml/L BO2 = the maximum amount of Hb-bound O2 per unit volume of blood (normally 1.39 of dry Hb, or 1.30 in "real" conditions) sO2 = oxygen saturation:

Answer 33

Qs/Qt = (CcO2 - CaO2) / (CcO2 - CvO2) Where Qs/Qt = shunt fraction (shunt flow divided by total cardiac output) CcO2 = pulmonary end-capillary O2 content, same as alveolar O2 content CaO2 = arterial O2 content CvO2 = mixed venous O2 content

Answer 34

J_v=L_p S [(P_c − P_i) - σ(π_c− π_i) Where: Jv = filtration rate Lp = Hydraulic permeability S = Surface area Pc = Capillary hydrostatic pressure Pi = Interstitial hydrostatic pressure σ = Reflection coefficient (protein permeability, range 0-1) πc = Intracapillary plasma oncotic pressure πi = Interstitial oncotic pressure *Note: LpS = K = kf = capillary filtration constant* **Note2: πi becomes πegl in the revised Starling model to represent the endothelial glycocalyx layer**

Answer 35

○ LpS - surface area ~140m2 (compared to 4000-7000m2 in systemic circulation) ○ Pc = 4-12mmHg ○ Pi = interstitial hydrostatic pressure - essentially equal to alveolar pressure = atm pressure. Increases during PPV § Surfactant decreases hydrostatic pressure by decreasing surface tension ○ πc = 25mmHg throughout circulation; affectd by blood protein count ○ πi = ~3mmHg at alveoli ○ σ= 0.5-0.7 in lung

Answer 36

2mLH2O/L/s

Answer 37

* Bind to 30s Ribosomal subunit, which interferes with protein synthesis by causing misreading and premature termination of mRNA translation. * Diffuse through porin channels in the outer membrane into periplasmic space. Transport through inner membrane is oxygen dependent (/electron dependent). Antimicrobial activity is markedly reduced in anaerobic conditions (eg. Abscess). * Concentration dependent killing - higher the concentration, the greater the rate at which bacteria are killed. * Post-antibiotic effect exists (bactericidal effect persists after conc

Answer 38

- **Disinfectants** are chemical agents or physical procedures that inhibit or kill microorganisms - **Antiseptics** are disinfectants with sufficiently low toxicity to host cells that can be used directly on skin, wounds or mucosa

Answer 39

**Main action:** Likely act by denaturing proteins. Optimal bacteriocidal concentration is 60-90% **Onset/duration** Rapid/ Lack residual action because they evaporate completely **Advantages:** Evaporative effects are useful when sinks with running water are not available **Limitations:** Flammable- must be allowed to dry fully before diathermy or laser surgery 2. Corneal damage; 3. Skin drying; 4. Ineffective against C. Dif spores **Spectrum of activity:** - Gram positives and negatives, Acid fast bacteria are susceptible, - Lipophilic viruses may be susceptible, Many fungi **Ineffective against:** Spores and prions. Hydrophilic viruses are less susceptible

Answer 40

**Main action:**Cationic biguanide -strongly adsorbs to bacterial membranes causing leakage of small particles and precipitation of cytoplasmic proteins **Onset/Duration:** Delayed/Sustained residual activity **Advantages:** Resistant to inactivation by blood and organic material; Low skin irritation **Limitations:** 1. Neurotoxic 2. Delayed effect 3. No direct spore activity 4. Agents in moisturisers, neutral soaps, and surfactants may neutralised its action **Spectrum of activity** - Bacteria (G+ve>G-ve) - Moderate fungal and viral activity - Inhibits spore germination **Ineffective against** Spores and prions Hydrophilic viruses are less susceptible **Other** Can be combined with 70% alcohol Preferred antiseptic for central venous access Not absorbed orally

Answer 41

- Potency is defined as the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug's maximal effect/a specified response in 50% of the population ○ Two drugs may have the same efficacy but one may achieve the effect at a lower dose ○ A drug with lower EC50 or ED50 has higher potency

Answer 42

- Efficacy - a measure of the magnitude of the effect once the drug is bound ○ Different agonists produce varying responses, even when occupying the same proportion of receptors ○ Efficacy can be expressed numerically - as a ratio of the drug's maximal efficacy to the maximal efficacy of some known potent agonist (aka intrinsic activity or maximal agonist effect)

Answer 43

A compound that competes with endogenous agonists for the same binding site - it may be reversible or irreversible ○ In the presence of a competitive antagonist, the Emax of the agonist is unaffected, but the potency is reduced

Answer 44

A compound that binds at a different site to the natural receptor and produces a conformational change that prevents receptor activation

Answer 45

The volume of air in the lungs at end of expiration during tidal breathing. It is the point at which alveolar pressure = atmospheric pressure, and is equal to expiratory reserve volume (ERV) plus residual volume (RV).

Answer 46

_Blood supply:_ * **Upper half**: superior branch of the super thyroid artery * **Lower half**: inferior branch of the inferior thyroid artery _Venous drainage:_ * **Upper half**: superior branch of the superior thyroid vein * **Lower half**: inferior branch of the interior thyroid vein --\> brachiocephalic vein _Nerve supply:_ All muscles are supplied by the recurrent laryngeal nerve except cricothyroid muscle, which is innervated by the external laryngeal _Lymphatics_ * Upper and lower groups of deep cervical nodes

Answer 47

* This is specific to laminar flow (fastest velocity at centre of vessel, little to no movement at periphery)

Answer 48

If Re\<2000, flow more likely to be laminar, 2000-4000 = transitional & \>4000 turbulent

Answer 49

* PaO2 = partial pressure of oxygen in arterial blood (measured value, in mmHg) * This is the pressure that 'dissolved' oxygen (ie oxygen unbound to Hb) exerts on the measuring oxygen electrode * Although the pressure of oxygen is an important indicator of Hb saturation and total oxygen content, it is not a measure of content (ie mass or volume) * SaO2 = oxygen saturation (measured value, in %) * This is the percentage of all the heme sites in all the available haemoglobin that is taken up by an oxygen molecule * Similarly to above, this is an important surrogate measure for oxygen availability however is also not a measure of content * CaO2 = blood content of oxygen (can be measured directly, or calculated by the oxygen content equation, in mL of oxygen/100ml or 1000mL of blood - ie mL/dL or mL/L) * This measures total oxygen content (dissolved plus bound)

Answer 50

The maximal volume of gas in the lungs at which small airways begin to collapse in dependent parts of the lung

Answer 51

The heat required to convert a substance from liquid to vapour at a given temperature. Latent heat of vapourisation decreases as ambient temperature increases, and is reduced to zero at the critical temperature of that substance.

Answer 52

* Vapour pressure = pressure exerted by a vapour above the surface of a liquid. * The more solutes you add to a solution, the lower vapour pressure, at any given temp + pressure * Saturation vapour pressure = pressure exerted by a vapour in equilibrium with liquid of the same substance. It is influenced by temperature and pressure * AKA equilibrium vapour pressure. It is the point at which the rate of evaporation = rate of condensation * Substances with a higher vapour pressure is more volatile. (eg. Sevo has SVP of 157mmHg at sea level, room temp vs H2O which is 18.6mmHg) * SVP increases with increasing temp - at body temp, H2O SVP is 47-48mmHg

Answer 53

The temperature at which vapour pressure equals atmospheric pressure. A lower atmospheric pressure will result in a lower boiling point temperature * Note: evaporation different to boiling - evaporation takes place from surface; bubbles form within the liquid when boiling.

Answer 54

* Critical temperature is the temperature above which it is not possible to liquefy a given gas by increasing its pressure * A substance is a gas when it is above its critical temperature, and a vapour when it remains in gaseous phase below its critical temperature * Nitrous has a critical temp of 36.5o and a critical pressure at this temp of 73atm. At 20O (temp of normal operating room), its critical pressure is 55atm

Answer 55

Minimum pressure which would suffice to liquefy a substance at its critical temperature

Answer 56

The point of minimum pressure and maximum temperature at which both a gaseous and a liquid phase of a given compound can coexist

Answer 57

Volume of space occupied by 1kg of a gas at its critical point

Answer 58

* Absolute humidity is the mass of water vapour present in a given volume of air. * Relative humidity is the percentage ratio of the mass of water vapour in a given volume of air to the mass required to saturate that given volume of air at the same temperature

Answer 59

The amount of a substance filtered per unit time

Answer 60

Any weakly ionised acid or base in equilibrium with its fully ionised salt that can resist changes in pH when a stronger acid or base is added.

Answer 61

Bicarbonate Phosphate (note: conc too low) Protein (note: conc too low)

Answer 62

HCO3 Hb Plasma protein Phosphate (note: conc too low)

Answer 63

Urinary: - Phosphate - Ammonia Bone: - Ca carbonate

Answer 64

HCO3 (important as low proteins, & negligible PO4)

Answer 65

RBCs phagocytosed by macrophages in liver or spleen, or haemolysed in circulation. Heme is degraded to bilirubin, Fe 2+ is recycled

Answer 66

Heme synthesised in mitochondria & cytosol of immature RBCs, globin synthesised by ribosomes in cytosol

Answer 67

**Normal range** 10-13s **Therapeutic values** 20-30s (warfarin) **Coagulation pathway assessed** Extrinsic & common **Method** - Sample collected in citrated blood tube & centrifuged (only plasma analysed) - Recombinant tissue factor added **Abnormal in:** ○ Problems with: § Vit-K dependent factor eg.warfarin § FVII eg. haemophilia § Factor Xa eg. apixaban § Thrombin eg. dabigatran

Answer 68

**Normal range** 30-40 sec **Therapeutic values** usually 50-90 or 60-100s **Coagulation pathway assessed** Intrinsic & Common **Method** - Collected + centrifuged as per PT - Phospholipid & negatively charged FXII activator added **Abnormal in:** - Factor deficiency (XII, XI, X, IX, II), heparin therapy, direct thrombin inhibitor therapy, direct Xa inhibitor therapy, antiphospholipid syndrome

Answer 69

**Normal range** 110-130sec **Therapeutic values** 200sec for ECMO, 400sec for bypass **Coagulation pathway assessed** Whole clotting cascade & platelet function **Method** - Whole fresh blood collected - Point of care test - contact activator (eg. Kaolin) added - Endogenous platelets are used as the source of phospholipid **Abnormal in:** Any coagulopathy. Most useful when there is one single predictable source of clotting dysfunction

Answer 70

Cytochalasin D (platelet inhibitor) - isolates fibrinogen testing

Answer 71

tissue factor

Answer 72

Phospholipid & ellagic acid

Answer 73

Ellagic acid & heparinase

Answer 74

- 500IU of Factor IX - 500IU of Factor II (prothrombin) 500IU of Factor X

Answer 75

- Factor VII (will reduce PT) - Factor IX, XI (will reduce aPTT) - Factor X, II 200IU of Factor VIII per adult dose

Answer 76

Adsorption of coagulation factors from plasma onto an ion exchange medium --> selective elution

Answer 77

Separation (by centrifuge) from whole blood, either by donation or by apheresis. Must be prepared within 6-18hrs

Answer 78

25-50IU/kg Warfarin: INR < 2 - 20U/kg, 2-4: 30U/kg, >4: 50U/kg

Answer 79

Glycogen: 100g Fat: 75g

Answer 80

○ Vitamin A → stored in stellate cells --> converted to retinol (active form). Contains 1-2yr supply ○ Vitamin D → ~ 1-4 month supply ○ Vitamin E & vitamin K - minimal

Answer 81

Primary: Formed in liver from cholesterol (by action of cholesterol 7α hydroxylase) □ Cholic + Chenodeoxycholic acid Secondary: formed by bacterial action on primary bile acids □ Deoxycholic + Lithocholic acid

Answer 82

Tolerance is the requirement of higher doses of a drug to produce a given response

Answer 83

- Pharmacokinetic tolerance - Pharmacodynamic tolerance ○ Receptor downregulation ○ Receptor deactivation ○ Receptor subunit modification ○ Second messenger systems ○ Drug target depletion - Physiological tolerance - Learned/behavioural tolerance - Others: ○ Sensitisation ○ Cross-tolerance

Answer 84

Persistent exposure makes drug clearance mechanisms more active; classically by induction of metabolic enzymes (eg. Effect of ethanol on CYP450 enzymes)

Answer 85

Persistent exposure to the drug produces and adaptive homeostatic response that results in a decreased pharmacological effect ○ Receptor downregulation - receptors are inactivated or endocytosed in response to sustained stimulation ○ Receptor deactivation - receptor protein is phosphorylated in response to excess stimulus (eg. Nicotine and nicotinic receptor) ○ Receptor subunit modification - modified receptor complex is selectively expressed, with diminished selectivity for the drug but maintained sensitivity for the endogenous ligand (eg. GABA-A receptor and benzodiazepines) ○ Second messenger systems - deactivation of post receptor second messenger systems (eg. B-agonists) Drug target depletion - some key molecule is used up in the drug action. Subsequent drug dosing will have diminished effect until the key molecule is regenerated (eg noradrenaline depletion due to ephedrine therapy)

Answer 86

Tolerance to the effects of the drug rather than to the drug itself at the receptor level. Physiological adaptive mechanisms may maintain homeostasis. Eg. Vasodilator antihypertensives may be offset by increased heart rate and CO, which maintains BP

Answer 87

The development of learned behavioural adjustments that compensate for the drug's effects

Answer 88

"reverse tolerance" - subsequent dosing increases the drug effect (eg. Amphetamines)

Answer 89

Development of tolerance to multiple drugs belonging to the same class, after exposure to only one of them (eg. Nitrates)

Answer 90

Decreased response to a drug with repeated short-term use. It occurs over minutes-hours & cannot easily be overcome with increase dose

Answer 91

(DR SVC) Diuretics - Carbonic anhydrase Inhibitors - Loop diuretics - Thiazides - K+ sparing diuretics RAAS antagonism - ACE Inhibitors - ARBs - Direct renin inhibitors Sympatholytics - alpha blockers - beta blockers - mixed alpha + beta - centrally acting (eg clonidine) Vasodilators - Arterial - hydralazine - Arterial + venous - nitrates Ca channel blockers

Answer 92

○ 37 kDa proteolytic enzyme with half life 40-120min ○ Produced in and released from juxtaglomerular (granular) cells in juxtaglomerular apparatus Role: ○ Cleaves angiotensiongen into angiotensin-I ○ Rate-limiting step in RAAS

Answer 93

Stimulus for release: ○ ↓ Na delivery to macula densa ○ ↓ blood pressure or renal perfusion pressure (sensed by intrarenal baroreceptors) --> likely cell stretch-mediated mechanism of renin release ○ Activation of β1 receptors on juxtaglomerular cells Inhibits release: ○ Negative feedback: ↑ Renin --> ↑ Angiotensin II (ATII) --> binds AT1 receptors on juxtaglomerular cells --> ↓ renin secretion

Answer 94

(mnemonic: DR SVC) - Diuretics (see renal) - RAAS antagonists - ACE inhibitors - ARBs - Direct renin inhibitors- eg.Aliskiren - Sympatholytics - B-blockers - A-blockers - Mixed A + B - Centrally acting (eg clonidine) - Vasodilators - Arterial - Arterial + venous - Ca- Channel antagonists

Answer 95

- **Alter ion permeability** - act on ligand gated ion channels (membrane spanning complexes that can form a transmembrane channel for ions). Types: -- *Pentameric* -> 5 membrane spanning units (eg, nicotinic Ach receptor at NMJ - Na+ flux, GABA A receptor - Cl- flux)   -- *Ionotropic glutamate* -> NMDA, AMPA and kainate iontropic ligand gated ion channels. They form Na, K and (NMDA only) Ca channels when glutamate binds    -- *Purinergic receptors* -> activated by purines such as adenosine & ATP. Permeable to Na, K and Ca - **Produce intermediate messengers** - act on membrane bound systems which transduce signal from an extracellular ligand to an intracellular signal transmitted by intermediate messengers. Eg: ○ *G proteins* (most common) - eg, Nad and Adr    ○ *Tyrosine kinase* - eg, insulin    ○ *Guanylyl cyclase* - Membrane bound - eg. atrial natriuretic peptide on its receptors - Soluble - eg. NO  - **Regulate gene transcription**  ○ Steroids & thyroid hormones act on intracellular receptors to alter the expression of DNA and RNA  

Answer 96

Mnemonic VAPPE - **Physiochemical properties** ○ Antacids - neutralise gastric acid    ○ Chelating agents (eg, resonium - on gut K)    - **Enzymes** ○ Concentration of the substrate normally metabolized by the enzyme is increased, and product of reaction is decreased    ○ Eg, ACE inhibitors (captopril, enalapril) prevent the conversion of ACEI to ACEII & bradykinin into its breakdown fragments    - **Voltage gated Ion channels** ○ Involved in the conduction of action potentials in excitable tissues    ○ Eg, local anaesthetics (eg, lignocaine) block Na channels, calcium channel blockers (eg, diltiazem) acts on vascular smooth muscle ion channels   - **Alteration on transport proteins** - eg. Frusemide on NKCC2   - **Prodrugs** ○ Require conversion to activated form by a metabolic pathway Eg. Levodopa --> dopamine

Answer 97

β1 receptors: * Distribution: mostly cardiac * Effects: ○ CVS § ↑ SA node firing rate, ↑ HR § ↑ contractility § ↑ conduction velocity § ↑ AV node automaticity ○ Renal § ↑ renin secretion by the kidney ○ GI § ↓motility and tone of the stomach

Answer 98

β2 receptors: * Distribution: Smooth muscle * Effects: ○ Resp: § Bronchodilation ○ CVS: § Vasodilation of vascular beds (coronary arteries, arteries of abdo viscera, renal arteries) § Mild cardiac effects – β2 receptors make up 25% of total cardiac β receptor population ○ GI: § ↓motility + tone of stomach, intestine § Gallbladder relaxation ○ Skeletal muscle effects: § Increased K+ uptake § Glycogenolysis à Hyperlactataemia ○ Metabolic/endocrine § ↑glycogenolysis & gluconeogenesis in liver, insulin secretion, lipolysis, thermogenesis

Answer 99

β3 receptors: * Bladder (detrusor) relaxation * ↑ water & solute resorption at the kidney * ↑ lipolysis and thermogenesis at the adipocyte * Modulation of cardiac contractility * Relaxation of uterine contractions

Answer 100

A - no available or inactivated PO (brush border COMT) D - 0.1-0.2L/kg (Except aramine & ephedrine 4L/kg M - COMT & MAO (aramine & ephedrine not metabolised) E - urine

Answer 101

D - V (0.14) M (liver - not much) E - Urine

Answer 102

- non selective --> Prop + Sot - β-1 selective --> Bisop, Esmo, Aten, Metop, Nebiv - combined α+β --> Carvi + labet

Answer 103

PMN - prop - metop - nebiv

Answer 104

- labet - acebut - pindo

Answer 105

- Pulmonary arteries can be classified: ○ Elastic (large, contain elastin) ○ Transitional (increasing amounts of circumferential muscle fibres) ○ Muscular (enough muscle to allow vasoreactivity) ○ Non-muscular (small endothelial vessels) ○ Capillaries (form a vascular sheet) - Pulmonary veins - thinner walled, contain more collagen + less elastin - Pulmonary arteries and veins travel with bronchi (+ nerves + lymphatics) in bronchovascular bundles (à peribronchial cuffing)

Answer 106

PA systolic pressure = 18-25mmHg PA diastolic pressure = 8-15mmHg

Answer 107

Pulmonary capillary pressure = 4-12mmHg Pulmonary venous pressure = 6-12mmHg

Answer 108

A volume of blood that needs to be added to pulmonary end capillary blood to explain the observed difference between pulmonary end capillary oxygen content and arterial oxygen content

Answer 109

Normal shunt fraction/venous admixture is 3%

Answer 110

- Shunt fraction --> ratio of venous admixture to total cardiac output ○ Q_s/Q_t = ((Cc_(O_2 ) −Ca_(O_2 )))/((Cc_(O_2 )− Cv_(O_2 ))) Where: § Q_s= shunt blood flow § Q_t = cardiac output (so Qs/Qt = shunt fraction) § Cc_(O_2 ) = pulmonary end-capillary blood O2 content § Ca_(O_2 ) = arterial O2 content § Cv_(O_2 ) = mixed venous blood O2 content

Answer 111

**Mechanism** Effect on (ventricular myocyte) AP: - Moderate ↓ in phase 0 slope, ↑ APD, ↑ ERP Effect on ECG: - ↑ QRS + QT interval **Example** Quinidine Procainamide | Na channel blockers (moderate)

Answer 112

**Mechanism** Effect on (ventricular myocyte) AP: - Small ↓ in phase 0 slope, ↓ APD, ↓ ERP. Effect on ECG: - minimal Preferentially affects ischaemic or depolarised Purkinje and ventricular tissue **Example:** "I'd buy Liddy's Mexican Tacos" Lidocaine, mexiletine Phenytoin | Na channel blockers (weak)

Answer 113

**Mechanism** Effect on (ventricular myocyte) AP: - Significantly ↓ Phase 0 slope; No effect on ERP or APD in Purkinje and ventricular tissue Effect on ECG: - Significant ↑ in QRS duration, therefore ↑ Qtc - Significantly prolongs ERP in AV node + accessory bypass tracts, therefore ↑ PR interval **Example** "Can I have fries please" Flecainide, propafenone | Na channel blockers (Strong)

Answer 114

**Mechanism** Effect on (pacemaker) AP: - ↓ SA & AV nodal activity (↓cAMP & Ca2+ currents) - Suppress abnormal pacemakers - ↓ slope of phase 4 Effect on ECG: - AV node particularly sensitive - ↑ PR interval **Example** Metoprolol | B-blockers

Answer 115

**Mechanism** Effect on (ventricular myocyte) AP: - ↑APD, ERP, Effect on ECG: - ↑QT interval **Example** Amiodarone Sotalol | K channel blockers

Answer 116

**Mechansim** Effect on (pacemaker) AP: - ↓conduction velocity, ↑ERP Effect on ECG: - ↑PR interval **Example** Verapamil Diltiazem | Ca channel blockers

Answer 117

2-5% of VO2 or 3ml/min (<2% of BMR)

Answer 118

Any weakly ionised acid or base in equilibrium with its fully ionised salt that can resist changes in pH when a stronger acid or base is added

Answer 119

For every 10 mmHg increase in PaCO2, the HCO3- will rise by 1 mmol/L In other words, expected HCO3 = 24 + ((PaCO2-40) / 10)

Answer 120

For every 10 mmHg increase in PaCO2, the HCO3- will rise by 4 mmol/L In other words, expected HCO3 = 24 + (4 × (PaCO2-40) / 10)

Answer 121

For every 10 mmHg decrease in PaCO2, the HCO3- will fall by 2 mmol/L In other words, expected HCO3 = 24 - (2 ×(40-PaCO2) / 10)

Answer 122

For every 10 mmHg decrease in PaCO2, the HCO3- will fall by 5 mmol/L In other words, expected HCO3 = 24 - (5 ×(40-PaCO2) / 10)

Answer 123

For complete compensation, expected PaCO2 = (1.5 × HCO3-) + 8

Answer 124

For complete compensation, expected PaCO2 = (0.7 × HCO3-) + 20

Answer 125

A - Augmented B - Bizarre C - Chronic/Cumulative D - Delayed E - Withdrawal (End of use) F - Failure

Answer 126

- Ultrafiltrate of blood - composed largely of water. pH 7.32; osm 295 - Minimal protein (~0.2g/L) - Na slightly lower than plasma, K & Ca are ~ 2/3 that of plasma - Mg, Cl & CO2 are higher than plasma. - HCO3- is similar ~22mmoL/L - Glucose is about 2/3rds of the plasma value (normal ~ 2.5-4.5)

Answer 127

- 500mL/day. Total ~150mL at any one time (half in cranial vault, half in spinal column --> turnover ~4x/day - Rate of formation is independent of ICP, & decreases with CPP <70mmHg Mechanism: - ultrafiltrate of plasma filtered by fenestrated choroidal capillaries - Na+ secreted via apical Na/K/ATPase into ventricle - Carbonic anhydrase (CA) provides H+ to power Na/H+ exchange at the basal membrane - Na+ gradient created --> allows co-transport of Cl- into CSF & HCO3- diffuses slowly - Na+ flux creates osmotic gradient --> H2O crosses into CSF through aquaporins

Answer 128

Reabsorbed from subarachnoid space - 25ml/hr into dural venous blood - At normal ICP (7-18 cmH2O), filtration = absorption; ceases when ICP < 7 cmH2O - Sites of reabsorption: arachnoid villi (90% intracranial villi; 10% spinal arachnoid villi) Circulation - see pic

Answer 129

- Barrier function (the blood-CSF barrier) - Chemical stability and waste removal - Buoyancy and mechanical cushioning of the CNS ○ Prevent acceleration/deceleration injury ○ Decrease effective weight (1400g-->50g) - Hydraulic pressure buffering of ICP --> displacement of CSF from intracranial to extracranial subarachnoid space

Answer 130

Secretion: (CMPP) - [Choroid plexus - secretes CSF] - Median eminences (secretes hypothalamic hormones into pituitary circulation) - Pineal gland - secretes melatonin into circulation - Posterior pituitary - ADH & oxytocin secretion Sensor: (SOAP) - Subfornical organ (osmoreceptor, also detects ATII) - OVLT (osmoreceptor) - Area postrema (aka CTZ) - senses toxins for emesis; ADH & AT for autonomic regulation - Preoptic recess (senses sex hormones & involved in thermoregulation)

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