Physiology Flashcards

Question

Describe the structure and function of the sodium potassium ATPase pump

Answer 1

* Antiport - catalyses hydrolysis of ATP to ADP to move 3 Na out of cell in exchange for 2 K in. Maintains electrochemical gradient ECG (net +1 out) and is large part of basal energy consumption. Is couples to transport of other substances eg, glucose in small intestine * Alpha and beta subunits which pass through cell membrane - both heterogenous. Alpha subunit intracellular binding sites for Na and ATP and extracellular binding sites for K and ouabain. Beta subunit has no binding sites for Na/K * When Na binds to alpha subunit, ATP also binds, ATP in converted to ADP causing change in protein configuration extruding Na out of cell. K then binds extracellularly dephosphorylating alpha subunit which returns to original configuration releasing K into cytoplasm Need brief on all three to pass

Answer 2

Approx 290mOsmol/L

Answer 3

* Principally (all but 20mOsmols) the ions (**Na, Cl**, K, HCO3) * Rest is other cations and anions, urea, glucose * Much less so proteins, possibly alcohols or mannitol Bold +1 to pass

Answer 4

Intracellularly * **K and proteins high**, many more 'miscellaneous' phosphates * **Na**, Cl and HCO3 low Bold to pass

Answer 5

* **Transcription of mRNA** * Post-transcriptional modification of mRNA * **Translation of mRNA** to amino acid chain along a **ribosome** using tRNA * Post-translational modification of the protein in endoplasmic retinaculum by hydroxylation, carboxylation, glycosylation, phosphorylation, cleavage and folding

Answer 6

* Polypeptide sequences are cleaved off, eg. pro hormones to hormones * Some proteins have leader sequences that target **endoplasmic reticulum** and are secreted by **exocytosis** * Others are secreted from cytoplasm via ATP dependent membrane transporters

Answer 7

* Inheritance - mendelian **co-dominance of A and B antigens**. * Complex oligosaccharides differing in terminal sugar. * A and B phenotypes may be homozygous or heterozygous genotypes * **O - no antigens (universal donor), anti-A and anti-B antibodies** * **A - anti-B antibodies** * **B - anti-A antibodies** * **AB - both antigens, no antibodies (universal recipient)**

Answer 8

* Presence of a vasomotor centre situated in the CNS medulla with both vasoconstrictor and vasodilatory areas * Medullary vasomotor centre is influenced by peripheral baroreceptors, peripheral chemoreceptors and higher neural centres * Noradrenergic vasoconstrictor fibres descend from medially vasomotor centre via spinal cord to the smooth muscle in the walls of arterioles * Peripheral baroreceptors in carotid sinus and aortic arch respond largely to changing BP and act to inhibit vasoconstrictor center * Peripheral chemoreceptors in carotid bodies and aortic bodies respond to hypoxia and act to excite the vasoconstrictor centre

Answer 9

Atrial stretch results in reflex afferent arteriolar renal dilatation

Answer 10

* Two theories: **myogenic or metabolic** * Myogenic: distention of vessel with increasing pressure stretches the vascular smooth muscle leading to contraction of the muscle * Metabolic theory: vasodilator metabolites accumulate in tissues when blood flow falls leading to relaxation of vascular smooth muscle * Vasodilators include local hypoxia and acidosis, CO2 build up, heat, potassium, lactate, histamine, adenosine * Serotonin causes localised vasoconstriction after vessel injury * Prostacyclin (vasodilation) and thromboxane (vasoconstriction) after local vessel injury * Endothelium Derived Relaxing Factor (NO) - many vasodilators act by activating EDRF * Endothelin is a vasoconstrictor Bold to pass

Answer 11

* **Adrenaline** acts via alpha-1 receptors to constrict arterioles in most areas and via beta-2 receptors to vasodilator muscle and liver blood vessels * **Noradrenaline** acts via alpha 1 receptors to constrict arterioles * Angiotensin II is a generalised arteriolar constrictor. It is formed from angiotensin I in the lung * Vasopressin is a potent arteriolar constrictor * Bradykinin and histamine cause arteriolar dilation Bold +2 others to pass

Answer 12

Capacity of tissues to regulate their own blood flow, which **remains relatively constant** despite moderate **changes in perfusion pressure**. This is achieved by **altering vascular resistance** Bold to pass

Answer 13

* **Myogenic** - intrinsic contractile response of smooth muscle to stretch; as pressure rises, vascular smooth muscles surrounding the vessels contract to maintain wall tension (La Place Law) * **Metabolic** - production of vasodilator metabolites by active tissues -> vessel vasodilation -> increased flow * **Endothelial products** - vasoconstrictors (endothelin, thromboxane A2) and vasodilators (nitric oxide, prostacyclin) * **Circulating neurohumoral substances** - vasoconstrictors (adrenaline, noradrenaline, vasopressin, angiotensin II) and vasodilators (kinins, VIP, ANP) * **Neural** - sympathetic (alpha adrenergic receptors - vasoconstriction; beta adrenergic receptors - vasodilation) and parasympathetic (muscarinic receptors - vasodilation) 3 bold to pass with explanation

Answer 14

Hypoxia Hypercarbia Increased temperature Hyperkalaemia Adenosine Acidosis Lactate Prostaglandins Histamine 4 to pass

Answer 15

* **Constant flow over arterial pressure range 65-140mmHg** * Sympathetic stimulation prolongs the plateau Bold to pass

Answer 16

* Positive inotrope and chronotrope * Rise in ANP/renin/aldosterone * Decreased GFR and renal blood flow

Answer 17

**Stretch** receptors in the adventitia layer of vessels Bold to pass

Answer 18

* **Aortic arch** * **Carotid sinus** * Walls of right and left atria (SVC and IVC entrances) * Pulmonary circulation Bold +1

Answer 19

* Exert an **inhibitory** input via the tractus solitarius in the medulla * In response to hypotension, the arterial **baroreceptors are less stimulated** because they are less stretched * Reduced baroreceptor discharge travels via the glossopharyngeal and vagus nerves to the medulla resulting in an **overall increase in sympathetic discharge** to increase heart rate and stimulate vasoconstriction and **reduce vagal drive** Bold to pass and understand inhibitory concept

Answer 20

* Decreased blood volume and decreased decreased venous return results in reduced stimulation of arterial baroreceptors and **increased sympathetic output** * The result is **reflex tachycardia and vasoconstriction** Bold to pass

Answer 21

* Inhibit tonic sympathetic drive and increased vagal drive, leading to **vasodilation, decreased ventilation, bradycardia and decreased cardiac output** * Allows rapid adjustments in BP in response to abrupt changes in posture, blood volume, cardiac output or peripheral resistance 3/5 bold and effects

Answer 22

SECONDS/MINUTES * **Baroreceptors** increased discharge with stretch, afferent nerve fibres pass to vasomotor area of medulla which in turn inhibits tonic discharge of vasoconstrictor nerves leading to drop in BP, catecholamine release, tachycardia * **Chemoreceptors** (stimulation leads to peripheral vasoconstriction and rise in BP) * CNS ischaemic receptors MINUTES/HOURS * **Renin-angiotensinogen system** * Blood volume changes * Fluid shift through capillaries LONGER TERM * Renal compensation via aldosterone * Blood volume changes * Salt intake * **Increased RBC production** by increased EPO Bold to pass + must understand baroreceptors

Answer 23

**CO = SV x HR** * Stroke volume related to contractility, preload and afterload * Heart rate controlled by intrinsic rate, autonomic, exogenous factors, heat and thyroid Bold to pass + 2 mechanisms from each SV and HR

Answer 24

* **Increases** * Increased venous return and hence decrease end diastolic volume * Increased myocardial contractility, so increased stroke volume * Increased sympathetic drive and heart rate Bold + one mechanism of SV and one for HR

Answer 25

* Decreased tissue PO₂ * Increased tissue PCO₂ * Accumulation of K and other vasodilator metabolites * Increased temperature in active muscle 3 to pass

Answer 26

Pressure in right atrium = 0 (range +5 - -5)

Answer 27

* **Balance between venous return and ability of heart to pump out right atrium** * Factors affecting venous return: gravity, intraabdominal pressure (pregnancy), hypo/hypervolaemia, ventilation (drugs/fainting), sympathetic tone (venoconstriction) arteriodilation (sepsis, drugs, anaphylaxis), resistance to venous return (tamponade, tumour) * Factors affecting ability of heart to pump blood: myocardial contractility, hypertrophy (athlete), cardiac failure, MI, arrhythmias, AF, resistance to right ventricle - pulmonary valve stenosis, PE, LVF, hypoxia Bold +2 examples to pass

Answer 28

* MAP at brain level * MVP at brain level * ICP * Viscosity of the blood * Local constriction/dilatation of cerebral arterioles 3 to pass

Answer 29

Increase in ICP results in: * Decreased cerebral blood flow * Sympathetic nervous system output increased * Increased systemic BP * Stimulation of baroreceptors * Stimulation of vagal outflow * Decreased heart rate and resp rate

Answer 30

* The **volume** of blood (75ml), CSF (75ml) and brain (1400g) in cranium **must be relatively constant** * Negative effects on these therefore if additional intracranial volume eg. subdural haemorrhage/extradural haemorrhage occurs

Answer 31

The process by which CBF is maintained at a constant level (approx 750ml/min) despite variation of arterial pressure (MAP 65-140mmHg)

Answer 32

* Cushing reflex * **Increased ICP compromises blood flow to medulla -> sympathetic outflow** from vasomotor centre * Increases BP in attempt to restore medullary flow -> **stretch of baroreceptors** -> vagal stimulation -> bradycardia Bold to pass

Answer 33

* Oxygen - 49ml/min = 20% of body O₂ consumption * Glucose (major energy source) - 77mg/min * Glutamate (converted to glutamine as detox mechanism NH₃) - 5.6mg/min

Answer 34

**Active neurons attract blood flow** and oxygen in excess of needs; marked variation bi flow with activity. PET fMRI imaging

Answer 35

* Aim is to maintain cerebral perfusion pressure * With high ICP need to increase MAP to maintain cerebral perfusion pressure * **CPP = MAP - ICP** * Raised MAP results in systemic hypertension and reflex bradycardia with vagal stimulation Bold to pass

Answer 36

**Glucose**, glutamate, in prolonged starvation amino acids Bold to pass

Answer 37

250ml/min or 5% of cardiac output

Answer 38

* **Greater flow in diastole compared with systole** due to higher pressures required in the LV to overcome aortic pressure in systole * **LV subendocardium most vulnerable** as only gets diastolic flow * RV flow continuous throughout systole and diastole due to lower RV pressures Bold to pass

Answer 39

* **Hypoxaemia** * Local increase in **CO₂, H⁺**, K⁺, **lactate**, prostaglandins, adenosine and adenine nucleotides 2/4 bold

Answer 40

* Coronary arterioles have **alpha receptors - vasoconstriction** * **Beta receptors - vasodilation** * Cholinergic receptors - vasodilation 1/2 bold

Answer 41

* **Physiologic: tachycardia:** shorter diastole; reduced left coronary flow in particular * **Pathologic**: aortic stenosis: increased LV pressures required to overcome stenosis and decreased flow; vasospasm; coronary artery disease; heart failure; increased venous pressure; reduced coronary perfusion pressure Bold +2 pathologic

Answer 42

* Aortic pressure changes, chemical and neural factors * Autoregulation * **Chemical**: low O2 increased CO2, H⁺, ⁺, lactate, prostaglandins, adenine nucleosides * **Neural**: noradrenaline - positive inotropic and chronotropic effects -> vasodilator metabolites * Beta-blocker for inotropic and chronotropic effects then noradrenaline then coronary vasoconstriction via alpha receptors * Beta receptors and vagus -> vasodilation * Low blood pressure -> metabolic changes in myocardium -> coronary artery vasodilation * **Phase of cardiac cycle** - more flow in diastole especially left coronary > right

Answer 43

* Poiseulle's law and formula and describe these factors * F is the rate of flow * P is the pressure differntial * R is the resistance * r is the radius of the tube * n is the viscosity of the fluid * L is the length of the tube

Answer 44

Expressed by Reynold's number - above 2000-3000 * p is the fluid density * D is the diameter of the tube * V is the velocity of flow * u is the viscosity of the fluid

Answer 45

Velocity relates to cross sectional area -> capillaries, 1000x area aorta, low velocity same flow

Answer 46

P = T/r * Smaller = less tension in the wall for the same distending pressure eg. aorta: vena cava: capillaries = 170,000: 21,000: 16 dynes/cm * Small vessels unlikely to rupture

Answer 47

Ventricular dilation means more tension required to generate same pressure = more work

Answer 48

* Increased flow mainly local regulation due to chemical effects on muscle arterioles leading to vasodilation * Response to reduction in oxygen in muscle tissue. Hypoxic releases vasodilatory substances (especially adenosine), arterioles cannot maintain contraction in hypoxic conditions. Other vasodilatory chemicals: potassium ions, ATP, lactic acid and CO2 * Other controlling factors: sympathetic vasoconstrictor nerves, circulating adenosine

Answer 49

1.2-1.3L/min or approx 25% CO

Answer 50

**Substances/Chemicals** * Noradrenaline constricts renal vessels and stimulates renal nerves to increase renin secretion * Dopamine and acetylcholine cause vasodilation * Angiotensin II causes arteriolar constriction **Renal nerves** * Stimulation nerves - increase renin secretion and increase juxtaglomerular sensitivity, increase sodium resorption and renal vasoconstriction * Strong stimulation sympathetic decreases blood flow * Fall in BP - vasoconstriction **Autoregulation** * Renal vascular resistance varies with pressure to keep renal blood flow fairly constant * Present in denervated kidney * Factors = direct contractile response are NO and angiotensin II 3 substances plus nerve or auto with examples

Answer 51

* Fick principle - substances taken up/unit time * PAH used to measure renal plasma flow * Renal blood flow using plasma flow and haematocrit One to pass

Answer 52

* Arteriovenous oxygen different for kidney = 14ml * Cortical blood flow = 5ml/g/min - little oxygen consumption * Medulla blood flow low (outer 2.5ml, inner 0.6ml) - maintenance of osmotic gradient, high oxygen consumption

Answer 53

* Renal blood flow is 25% of the cardiac output * The glomerular capillary is 40% of systemic arterial pressure * The peritubular capillary network and renal veins are low pressure systems * The renal cortex gets higher blood flow, but has low oxygen extraction (filtration) * Renal medulla gets less blood flow, but high oxygen extraction (osmolality) and sensitive to hypoxia 2 to pass

Answer 54

* Decreased MAP - decreased baroreceptor firing - renal vasoconstriction - decreased renal blood flow * Exercise decreases renal blood flow * Prostaglandins increase renal cortex blood flow, decrease renal medullary blood flow * Proteins increase renal blood flow and decrease glomerular capillary pressure * Dopamine and acetylcholine cause vasodilation and increased renal blood flow * Noradrenaline causes vasoconstriction and constricts afferent arterioles and interlobular arteries and decreases renal blood flow * Posture - lying to standing, decreases renal blood flow

Answer 55

**Baroreceptors** (carotid sinus, aortic arch, atria) * Reduced stretch - increased sympathetic stimulation - tachycardia and generalised vasoconstriction (sparing of brain and heart) * With increased shock, paradoxical bradycardia (unmasking of vagal depressor reflex) then tachycardia again with further shock **Chemoreceptors** (carotid body, aorta) * Stimulated by reduced blood flow and acidosis * Simulates vasomotor areas in medulla with increased vasoconstriction Receptors plus concepts to pass

Answer 56

* **Renal response**: efferent arterioles constricted more than afferent. Renal plasma flow decreased more than GFR - filtration fraction * **Sodium retention** - retained nitrogenous products of metabolism (uraemia) * **Angiotensin II**: plasma renin causing angiotensin II, angiotensin II maintains BP and causes stimulation shirts center in brain * **Vasopressin**: retain sodium and H2O * **Aldosterone**: stimulated by circulating angiotensin II and ACTH * **Adrenal stimulation**: adrenal medulla secretion catecholamines * **Increased circulation noradrenaline**: increased discharge sympathetic noradrenaline nerves Renal plus 2

Answer 57

**Systemic hypoperfusion due to reduced effective circulating blood volume** resulting in **impaired tissue perfusion** and cellular hypoxia

Answer 58

* **Thoracic pump**: inspiration resulting in negative pressure in the thorax and positive pressure in the abdomen. Blood flow towards the heart because of venous valves * Effect of heart beat: during systole, AV valves are pulled downward -> increase the capacity of the atria * Muscle pump: contraction of muscles around the veins in the limbs during activity * Differential resistance: resistance of the large veins near the heart is less than peripheral veins Thoracic pump plus one other

Answer 59

* **Decrease the CVP**: fluid loss; blood loss * **Increase the CVP**: excessive fluid replacement; other pre-existing conditions eg. CCF; positive pressure ventilation; increased thoracic pressures

Answer 60

4.6-5.8 mmHg or 6-8 cm H2O

Answer 61

5-5.5 L/min

Answer 62

* Circulating blood volume * Sympathetic and parasympathetic tone * Muscle pump * Right atrial pressure (intrathoracic and intracardiac pressures and factors that influence them like phases of respiration, tamponade, PEEP)

Answer 63

* **Adrenal medulla: adrenaline, noradrenaline**, dopamine * Intrinsic cardiac adrenergic cells: adrenaline * Sympathetic nervous system cells: dopamine Bold to pass .

Answer 64

* **Metabolic**: glycogenolysis, increased metabolic rate, mobilisation of free fatty acids, increased lactic acid * Cardiovascular - **vasoconstriction and dilation, increase heart rate and strength** * Alpha 1: constriction of blood vessels, smooth muscles (especially norad) * Alpha 2: mixed smooth muscle effects (esp adrenaline) * Beta 1: cardiac inotropy and chronotropy, irritability (both) * Beta 2: dilated blood vessels liver and muscle, other smooth muscle relaxation (adrenaline) * Beta 3: lipolysis, detrusor relaxation (esp adrenaline) One metabolic and bold cardiovascular

Answer 65

Low concentrations - some beta effects, high concentrations alpha predominates

Answer 66

Aldosterone causes sodium and water retention expanded ECF volume and shutting off the stimulus to increase renin secretion

Answer 67

* Primary - stress hormone, low pressure/volume states * Secondary - hyperaldosteronism (eg, CCF, cirrhosis and nephrosis) * Drugs

Answer 68

* Mild increase in sodium/chloride * Fluid retention (follows sodium) * Decreased potassium due to K+ diuresis * Alkalosis (alkaemia only if potassium depletes) * Urine K/H increases, increased urinary acidity .

Answer 69

* Medullary mineralocorticoid * Via principal cells in the collecting ducts Two effects 1) Genomic - intracellular to nuclear signalling mRNA - increased ENAC insertion/activity (quick) - increased ENAC production (slow) 2) Membrane bind IP3 mediated Na/K exchange

Answer 70

* Increase resorption of Na from urine - acts on principal cells (P cells) of collecting ducts, leading to increased amounts of sodium exchanged from K+ and H+ in renal tubules, producing a K+ diuresis and fall in urine pH * Increase reabsorption of Na from sweat, saliva and colon

Answer 71

* ACTH from pituitary * Renin from kidney via angiotensin II * Direct stimulatory effects of rise in plasma K+ concentration on adrenal cortex * Clinical causes: surgery, anxiety, physical trauma, haemorrhage, high K intake, low sodium intake, standing, constriction of IVC in thorax, secondary hyperaldosteronism

Answer 72

* Fall in ECF/blood volume -> reflex increase in renal nerve discharge & decrease in renal artery pressure * Increase in renin secretion -> increase in angiotensin II -> increase in aldosterone secretion * Increased sodium and water retention -> expanded ECF volume -> decrease in stimulus that initiated renin secretion

Answer 73

* Renin-angiotensin system * ACTH * Rise in plasma K concentration

Answer 74

* Permissive action - **catecholamine effects - pressor/vascular reactivity**; bronchodilation * **Metabolic** - increase protein catabolism; increase hepatic glycogenolysis and gluconeogenesis -> increase in plasma glucose; anti-insulin effects on peripheral tissues; increase lipolysis * Free water excretion (decreased vasopressin) * Immunological - decreased inflammation/allergic/lymphocyte activity * Haematological - increase neutrophils/platelets/red blood cells * CNS - EEG slowing, personality changes

Answer 75

* **Glucocorticoids** (cortisol) - **secreted from the adrenal cortex**: secretion **dependent on ACTH secretion** from the **anterior pituitary** * ACTH secretion is regulated by CRH released from the hypothalamus (in response to low cortisol levels or stress) * **Glucocorticoids** provide a **negative feedback loop on the hypothalamus and the anterior pituitary** to **reduce ACTH secretion** Bold to pass

Answer 76

* Vascular smooth muscle becomes **unresponsive to noradrenaline and adrenaline** * Capillaries dilate and increase permeability * Failure to response to noradrenaline **impairs vascular compensation** for hypovolaemia and promotes **vascular collapse** Must have general concept to pass

Answer 77

Effect on **vascular activity to catecholamines** plus necessary for catecholamines to mobilise **free fatty acids** for emergency energy source Bonus questions

Answer 78

* **Bone** - 99% * **Plasma - bound to protein** * **Plasma - unbound (free/ionised)** - important second messenger and is required for coagulation, nerve function and muscle contraction Bold to pass

Answer 79

* **Parathyroid hormone**: increases plasma calcium by mobilising calcium from bone, increases calcium reabsorption in kidney and increases formation of 1,25 dihydroxycholecalciferol * **1,25 DHCC** (from Bit D) increases calcium absorption from intestine and kidneys * **Calcitonin** (from thyroid) lowers circulating calcium levels. Effect by inhibition of bone reabsorption. It also increases calcium excretion in urine * **Glucocorticoids** - decrease plasma calcium by inhibition osteoclast formation and activity * **Oestrogens** - inhibit stimulatory effects of cytokines on osteoclasts * **Growth hormone** - increases calcium excretion in urine and absorption in intestine. Net balance may be positive

Answer 80

* **Osteoclasts** are monocytes that develop from stromal cells under influence of **RANKL** * Attach to bone via integrins in sealing zone of the membrane * Hydrogen dependent proton pumps move into cell and acidify the area * Acid dissolves hydroxyapatite and acid proteases break down collagen * Products move across osteoclasts into interstitial fluid Bold + 1 other

Answer 81

* Kidneys - increased calcium reabsorption, increased 1,25 - dihydroxycholecalciferol formation, decreased urinary excretion of calcium * Increased plasma 1,25-dihydroxycholecalciferol levels cause increased calcium absorption in intestine * Increased plasma 1,25-dihydroxycholecalciferol levels cause increased bone resorption and increased release of calcium into plasma 1 of each system to pass

Answer 82

* **Negative feedback** by calcium via a membrane calcium receptor and G-protein * 1,25 - dihydroxycholecalciferol acts to decrease preproPTH mRNA * Increased phosphate increases PTH by decreasing calcium and 1,25-dihydroxycholecalciferol * Magnesium is required for PTH secretion

Answer 83

* Protein binding - depends on plasma protein level and pH * Total body calcium: bound in bone, bone calcium readily exchangeable or slowly exchangeable (resorption/deposition); intake; GI absorption under influence of vitamin D; renal excretion under vitamin D influence; PTH; calcitonin

Answer 84

* Increased absorption of calcium from the intestine by induction of calbindin-D proteins * Increased resorption of calcium in the kidneys * Increased osteoblast activity * Aids calcification of bone matrix 3 to pass

Answer 85

* Not closely regulated * Low calcium leads to increased PTH secretion and increased vitamin D is produced * High calcium inhibits PTH and the kidneys produce inactive metabolites * Low phosphate increases vitamin D production (and high phosphate inhibits it) * Vitamin D inhibits the enzyme involved in the synthesis

Answer 86

* Dietary intake and glucose absorption from **intestine** * Rate of entry into peripheral cells (muscle, adipose tissue, brain, red cells and **liver**) * **Gluconeogenesis** activity in liver * Reabsorption in **kidney** * Insulin-independent increase in GLUT4 transporters in muscle cell membranes 3 to pass

Answer 87

* Liver glycogen broken down-glucose released into bloodstream * In prolonged fasting, glycogen depleted - increase gluconeogenesis from glycerol and amino acids in liver Both to pass

Answer 88

* **Hypoglycaemia** * Increased sympathetic drive to pancreas * Vagal stimulation * Protein load * Amino acids oral or IV infusion * Exercise * Stress * Starvation * Cholecystokinin * Gastrin * Cortisol * Theophylline Bold +2 to pass

Answer 89

* **Gluconeogenesis** * Glycolysis * Lipolysis * Ketogenesis * Calorigenic - through hepatic deamination of amino acids * Positive inotropic effect in large doses * Stimulates secretion of growth hormone, insulin and pancreatic somatostatin Bold +1 to pass

Answer 90

**Stimulators** * Beta adrenergic stimulants * Cortisol * Protein meal * Vagal stimulation * Starvation, stress, exercise * CCK * Gastrin * Theophylline **Inhibitors** * Glucose - most important * Insulin * Somatostatin * Free fatty acids * Ketones * Alpha adrenergic stimulators * GABA * Phenytoin 3 to pass from each

Answer 91

Hyperglycaemia due to * **Decreased peripheral uptake** of glucose into muscle and fat (direct effect) * **Reduced glucose uptake by liver** (indirect effect) * **Increased glucose output** by the liver and lack of glycogen synthesis * GIT renal, brain and red cells glucose uptake unaffected 2 bold to pass

Answer 92

* Intracellular glucose deficiency * Extracellular excess * Protein and fat catabolism

Answer 93

* B cells as a precursor hormone * Insulin released from the cell with C peptide

Answer 94

2 alpha and 2 beta glycoprotein subunits

Answer 95

* **Decreased peripheral utilisation** of glucose * **Hyperglycaemia** but low intracellular glucose * Derangement of the glucostatic function of the liver * Hyperglycaemia with no decrease in gluconeogenesis * Secondary osmotic diuresis with dehydration * Electrolyte and calorie loss * Catabolism of protein and fat due to low intracellular glucose * **Contributes to ketosis - acidosis** * Breakdown of amino acids for energy * Increased free fatty acids from breakdown of triglycerides * Secondary acidosis, coma, raised cholesterol 3 bold essentials

Answer 96

* Decreased ketogenesis * Increased protein synthesis * Increased lipid synthesis * Decreased glucose output due to decreased gluconeogenesis * Increased glycogen synthesis * Increased glycolysis 2 to pass

Answer 97

* Storage of carbohydrate, protein and fat, varies with tissues * Rapid - seconds, glucose, amino acids and potassium into insulin sensitive cells * Intermediate - minutes - stimulates protein synthesis, inhibits protein degradation, activates glycolytic enzymes and glycogen synthase, inhibits phosphorylase and gluconeogenic enzymes * Delayed - hours, increase in mRNA for lipogenic and other enzymes

Answer 98

* Binds to a cell membrane-based stereospecific insulin receptor on insulin-sensitive cells * Insulin binding triggers tyrosine kinase activity of beta subunits -> autophosphorylation of beta subunits on tyrosine residues * This triggers phosphorylation and de-phosphorylation of proteins that are effectors and secondary mediators

Answer 99

It would go up

Answer 100

* The insulin is exocytosed from the beta cells of the Islets of Langerhans within 3-5 minutes followed by a plateau at 2-3 hours by activation of the enzyme system * Glucose is metabolised by the glucokinase and this involves ATP, decreased potassium efflux and increase calcium entry into cells that cause release of insulin by exocytosis

Answer 101

Adrenocorticotropic hormone (ACTH)

Answer 102

* **Increased by stress** (pain, emotional) * Drive for circadian rhythm through the hypothalamus via release of CRH (corticotropin releasing hormone) * **Inhibited by circulating glucocorticoids** and afferent from baroreceptors

Answer 103

**Slowly increases over weeks** - the pituitary may not be able to secrete normal amounts of ACTH for as long as a month. Presumed to be secondary to diminished ACTH synthesis

Answer 104

**Slowly decreasing the dose over a long period of time**

Answer 105

* **Increased ACTH secretion** * **Mediated through hypothalamus** * CRH produced in paraventricular nuclei, secreted in medial eminence and transported in portal hypophysial vesicles to anterior pituitary * Multiple nerve endings converge on paraventricular nuclei * Destruction of median eminence means stress response is blocked 2 bold + 1

Answer 106

* **Low glucocorticoid levels with inability to increase** * **Prolonged exogenous glucocorticoid inhibits ACTH secretion - normally a drop in resting corticoid levels stimulate ACTH secretion** * **Adrenal atrophic and unresponsive** * Pituitary unable to secrete normal amounts of ACTH for one months, probably secondary to decrease ACTH synthesis * After one month a slow rise in ACTH levels to supranormal levels, stimulates adrenal with increased glucocorticoid output * Avoid by tapering dose over long period 3 bold +1 to pass

Answer 107

* **ACTH** * **TSH** * Growth hormone * LH * FSH * Prolactin

Answer 108

* **Adrenal cortical atrophy**: glucocorticoid and sex hormone levels fall - mineralocorticoid secretion maintained (slat loss/hypovolaemic shock does not occur * Hypothyroidism * Growth inhibition * Gonadal atrophy * Sexual cycle cease, loss of some secondary sex characteristics * Tendency to hypoglycaemia (increased insulin sensitivity) Bold +2 to pass

Answer 109

Renal retention of water in excess of solute reducing body fluid osmolality or concept

Answer 110

* TRH from hypothalamus -> TSH from anterior pituitary -> T4 (& small amount T3) -> T3 in periphery * **Negative feedback on TSH by free T3 and T4** (in hypothalamus and pituitary). Effect of **T3 greater than T4** * Both secretion and synthesis of TSH affected * Increased by cold, decreased by warmth (especially in infants, effects in adults not clear) * Decreased by stress (TRH) and glucocorticoids (TSH) * Decreased by dopamine and somatostatin Bold +1 factors

Answer 111

* **Calorigenic** - increased metabolic rate, increased stimulation O2 consumption) * Adipose tissue: catabolic (stimulates lipolysis) * Muscle: catabolic (increased protein breakdown) * Bone: developmental (promote normal growth and skeletal development * Nervous system: promote normal brain development and mentation * Gut: metabolic (increase carbohydrate absorption) * Cholesterol: formation of LDL receptors and removal of circulating cholesterol Bold +1 to pass

Answer 112

CNS * **Development CNS** - cerebral cortex, basal ganglia, cochlea * **Activity, mutation speed/agitation** - catecholamines, dopamine, direct brain effect * **Reflexes** CVS * **Vasodilatory** - secondary to heat * **Increased circulating volume, heart rate and cardiac output** * **Increased sensitivity to catecholamines** - synergistic effect and up regulated beta receptors and effector systems, heart rate, contractility * **Increased myosin heavy chains** - faster twitch genes and down regulating others - increase contraction, heart rate 3-4 overall at least 1 in each

Answer 113

* Thyroid epithelial cells secrete **thyroglobulin** and **iodine** into colloid * Iodide transport is via a symport with sodium (NIS). * Thyroid peroxidase makes iodotyrosines (MIT and DIT) then combines them to **make T3 and T4** * Some reverse T3 (inactive) also made * Endocytosis and lysis of colloid releases free hormone * All steps TSH controlled * T3 also made peripherally by deionisation of T4

Answer 114

* Binds to intracellular thyroid receptors in the nuclei * Complex binds to DNA and alters gene expression * T3 more rapid and potent * **Increased metabolism and catabolism** of most cells (brain and others excluded) * Lipid and carbohydrate mobilisation and usage * **Increased CNS and CVS activity** * Normal reproductive cycle and growth * Effects increased by catecholamines

Answer 115

By breakdown of haemoglobin (heme is converted to biliverdin and then on to bilirubin)

Answer 116

* Bound to albumin in the circulation * Dissociates in the liver and free bilirubin enters liver cells * **Conjugation in liver cells** (UDP glucoronyl transferase located in smooth endoplasmic reticulum acts on the bilirubin to form bilirubin-diglucuronide (BIIG) which is water soluble) * BIIG is actively transported to biliary canaliculi, bile ducts and then to intestine (small amounts of BIIG and free bilirubin leak into the circulation) * **Intestinal phase**: intestinal bacteria acts on the BIIG to form unconjugated bilirubin and urobilinogen. These are excreted via the gut * **Enterohepatic circulation**: unconjugated bilirubin and urobilinogen can re-enter the portal circulation * Urobilinogen may enter the general circulation to be excreted by the kidneys

Answer 117

* 97% water * Bile pigments (conjugated bilirubin + biliverdin) * Bile salts (cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocolic acid) * Inorganic salts * Others: cholesterol, fatty acids, lecithin. fat 3 to pass

Answer 118

* **Excess production of bilirubin (eg. haemolytic anaemia)** * Decreased uptake of bilirubin into hepatic cells * Disturbed intracellular protein binding or conjugation * Disturbed secretion of conjugated bilirubin into the bile canaliculi * **Intra or extrahepatic bile duct obstruction** * 1st three liberate free bilirubin, last 2 result in elevated conjugated bilirubin in blood Bold to pass

Answer 119

* **Salivary amylase** * **Duodenum - pancreatic amylase** * **Brush border oligosaccharides** * Examples of these oligosaccharides are: alpha-dextrinase (isomaltase), lactase, sucrase, maltase and trehalase * Final oligosaccharides: alpha-dextrins, maltotriose, maltose, trehalose, lactose, sucrose are metabolised to one of the hexoses Bold to pass

Answer 120

* Two phases: first into intestinal mucosal cell and second into interstitial fluid (ICF) and thus into capillaries and portal blood * Glucose/galactose "secondary active transport" with sodium - low concentration of Na inhibits transport (co-transporters SGLT-1 and SGLT-2) * Glucose/Galactose - "facilitated diffusion" into ICF by GLUT-2 * Fructose - "facilitated diffusion" from intestinal lumen by GLUT-5, thence GLUT-2 into ICF * Ribose/deoxyribose diffusion

Answer 121

* Lingual lipase (Ebner's Gland) - active in the stomach on triglycerides * Pancreatic lipase - requires colipase for maximal activity (triglycerides) * Pancreatic bile-salt activated lipase (not only triglycerides but also cholesterol esters, some vitamins and phospholipids) * Cholesteryl ester hydrolase (cholesterol) 2 to pass

Answer 122

* Emulsification * Micelles - formed from bile salts, lecithin and monoglycerides surrounding fatty acids, monoglycerides and cholesterol * Transport lipids through "unstirred layer" to brush border of mucosal cells 2 to pass

Answer 123

* Two phases: first into intestinal mucosal cell and second into interstitial fluid (ECF) and thus into capillaries and portal blood (free fatty acids) or into lymphatics (chylomicrons) * Into enterocytes: passive diffusion and carriers * Out of enterocytes: depending on size (<10-12 carbons - directly into portal blood or >10-12 carbons - re-esterified to triglycerides or cholesteryl esters and packaged in chylomicrons (coating of protein, cholesterol and phospholipids) Bonus question

Answer 124

* **Stomach - pepsinogens are activated by the gastric acid to produce pepsins and these cleave bond between amino acids** * Small intestine - powerful proteolytic enzymes from pancreas and intestinal mucosa * Endopeptidases and exopeptidases hydrolyse amino acids Bold to pass

Answer 125

* **Two phases: 1) mucosal cell and 2) interstitial fluid and then into capillaries and portal blood** * Seven transport system: five required Na and two Na independent * Absorption is rapid in duodenum and jejunum and slow in ileum

Answer 126

* Infants absorb more undigested protein * Results in more food allergy but passive immunity

Answer 127

* Stomach - pepsinogens activated by gastric HCl acid (pH 1.6-3.2) to pepsins result in polypeptides * Small intestine lumen (pH 6.5) - proteolytic enzymes of the pancreas and intestinal mucosa * Examples: endopeptidases (trypsin, chymotrypsin and elastase) and exopeptidases to amino acids * Brush border: (amino, carboxy, ends and di) peptidases to amino acids * Cytoplasm of mucosal cells: after absorption by active transport 3 out of 5 to pass

Answer 128

* **Lipase** - triglycerides * Trypsin - proteins, polypeptides * Chymotrypsins - proteins, polypeptides * Elastase - elastin and some proteins * Carboxypeptidase A and B - proteins, polypeptides * Co-lipase - fat droplets * Amylase - starch * Ribonuclease - RNA * Deoxyribonuclease - DNA * Phospholipase A2 - phospholipids Lipase +2 to pass

Answer 129

* Primarily under hormonal control * **Secretin acts on the duct to cause production of copious amounts of very alkaline pancreatic juice poor in enzymes** * As flow of pancreatic juice increases it becomes more alkaline because exchange of HCO₃^- for Cl^- in the distal duct is inversely proportional to flow * **CCK** acts on acinar cells to cause of release of zymogen granules and **pancreatic juice rich in enzymes** * Acetylcholine also stimulates release of zymogen granules Bold to pass

Answer 130

* **Cations** * **Anions** * **Bicarb** * **Digestive enzymes** - proenzyme trypsinogen converted to trypsin by enteropeptidase (enterokinase) from brush border * Trypsin converts chymotrypsinogens, proelastase, procarbboxypeptidases to active enzymes * Digestive enzymes in zymogen granules in acinar cells in alveolar glands, discharged by exocytosis into pancreatic ducts

Answer 131

* Neural and hormonal OR * Cephalic, gastric and intestinal * **Cephalic**: food in mouth -> vagus, psychological states eg. anger hostility -> hypersecretion * **Gastric**: food in stomach, local receptors eg to amino acid and protein digestions -> post-ganglionic neurons -> parietal cells -> acid secretion * **Intestinal**: fats, carbohydrates, and acid in duodenum inhibit gastric acid secretion and pepsin secretion as well as motility by neural and hormonal mechanisms eg. peptide YY * **Neural**: vagal increases gastrin secretion in G cells by GRP. Gastrin stimulates gastric acid and pepsin secretion as well as motility * Hypoglycaemia via vagus to stimulate acid and pepsin secretion * Also alcohol and caffeine stimulate gastric secretion Need to name both and give an examples of each (vagus, hormonal, eg. gastrin)

Answer 132

* Specific GLUT 2 transporter in beta cells of the pancreas, converted to pyruvate, metabolised to glutamate via citric acid cycle, which primes insulin granules for release * Production of ATP also triggers (via K efflux) calcium influx which causes granules to be released

Answer 133

* **Gastric acid** aids reduction **Fe³⁺ to Fe²⁺** (ferrous) and formation of soluble complexes * **Duodenum = major site of absorption** * **Fe³⁺ converted to Fe²⁺ by ferric reductase** * **Fe²⁺ transported into enterocytes** via apical membrane iron **transport** (DMT1) * **Dietary heme** transported into enterocyte by heme transporter (HT) * Heme oxidase releases Fe²⁺ from heme * Some intracellular Fe²⁺ converted to Fe³⁺ and bound to ferritin * Remainder binds to basolateral Fe²⁺ transporter ferroportin (FP) and transported to interstitial fluid aided by hephaestin (Hp) 2 bold and 1 other

Answer 134

* **Dietary** - phytic acid (cereals), oxalates & phosphates bind Fe to produce insoluble compounds * **Surgical** - partial gastrectomy (decreased acid)/duodenal surgery-loss or illnesses (ulcers, sprue) * **Physiological** - high iron stores, high recent FE diet, amount of erythropoiesis * **Drugs** - antacids, acid lowering, some antibiotics

Answer 135

Fe²⁺ converted to Fe³⁺ & bound to **transferrin**

Answer 136

* Most ingested iron is ferric (3+) but the ferrous (2+) form is absorbed * Minimal absorption in stomach but gastric secretions dissolve iron and aid conversion to the ferrous form * Almost all absorption in duodenum. Iron is transported into enterocytes via DMT1 * Some stored as ferritin * Remainder transported out via ferroportin 1 (basolateral transporter) in the presence of hephaestin. Then converted to ferric form and bound to transferrin * Dietary heme is absorbed by an apical transporter and iron is removed from the porphyrin in cytoplasm

Answer 137

Precise mechanisms uncertain, probably relate to: * Recent dietary intake of iron * State of body iron stores * State of erythropoiesis in bone marrow * The regulatory mechanisms are unclear

Answer 138

* Gut cells * Menstruation

Answer 139

* **Bile formation** - 500ml/day * **Synthesis** - protein, coagulation factors, albumin * **Inactivation**/detoxification - drugs, toxins, active circulating substances * Nutrient vitamin **absorption, metabolism**/control (eg. glucostat), AAs, lipids, fat soluble vitamins * **Immunity** (especially gut organisms) - Kuppfer/macrophages in sinusoid endothelium 3 to pass

Answer 140

**Absorption**: * After meals - **fluid reuptake due to coupled transport of nutrients**, e.g. glucose and sodium (water reabsorbed 8800ml) * Between meals - NaCl enters across the apical membrane via the coupled activity of a Na/H exchanger and a Cl/HCO3 exchanger (electroneutral mechanism in small intestine and colon) * In distal colon, sodium enters the epithelial cell via epithelial sodium channels (electrogenic mechanism) Bold and 1 mechanism of sodium absorption somewhere

Answer 141

**Secretion** * **Chloride secretion occurs continuously in the small intestine and colon** * Chloride uptake occurs via Na/K/2Cl co-transporter and is secreted into the lumen via Cl channels (CFTR) * **Water endogenous secretions** - 7000ml Bold + 1 mechanism of chloride secretion

Answer 142

* **SA node** - pacemaker * **Atria** - 3 internodal pathways * **AV node; Bundle of His; right and left bundle branch** * **Anterior and posterior fascicles on left** * **Purkinje fibres** * **Ventricular muscle** - left side of IV septum first, spread down septum to apex. Up AV grooves, spread from endocardial to epicardial surfaces 6 out of 8 bold

Answer 143

* **P wave: atrial depolarisation** * **QRS complex: ventricular depolarisation** * **T wave: ventricular repolarisation**

Answer 144

* **Pre-potential is initially due to a decrease in potassium efflux**, then completed by calcium influx through CaT channels (prepotential) * The **action potential is due to influx of calcium** via CaL channels * **Repolarisation is due to potassium efflux** Bold - need approx correct shape of curve and approx potential values

Answer 145

* P wave - atrial depolarisation * PR - AV conduction * QRS - ventricular depolarisation * ST - plateau of ventricular depolarisation * QT - ventricular action potential * T wave - ventricular repolarisation

Answer 146

* **P wave** - depolarisation initiated in the **SA node** * Spreads radially through the atria, converges on the AV node (atrial depolarisation 0.1 seconds) * **PR - atrial depolarisation and AV nodal delay** - delay of about 0.1 seconds * **QRS** - bundle of His, right and left bundles and Purkinje fibers (**ventricles** 0.08-0.1 seconds) * Left to right across interventricular septum then down septum to apex * Along ventricular walls to AV groove from endocardial to epicardial surface * Last parts to be depolarised are posterobasal portion of LV, pulmonary conus and uppermost septum Bold to pass

Answer 147

* Abnormal pacemakers * Re-entry circuits * Conduction deficits * Prolonged repolarisation * Accessory pathways * Electrolyte disturbance 4 to pass

Answer 148

* Greater negative resting membrane potential * Fast depolarisation via sodium versus slower calcium dependent * No pre potential and no automaticity * Plateau phase

Answer 149

* Abnormal pacemakers - **ectopic beats**, pacemaker failure (sinus arrest), **fibrillation (atrial or ventricular)** * Re-entry circuits - leading to tachyarrhythmias * Conduction delays - **heart block**, bundle branch blocks * Prolonged repolarisation - long QTc * Accessory pathways - WPW 2 bold and 2 others to pass

Answer 150

* Noradrenaline binds to beta 1 receptor raises cAMP, resulting in increased opening of L channels and calcium influx. **Thus increased slope of pre potential and firing rate** * Acetylcholine binds to M2 receptor and decreases cAMP, resulting in both slowing of calcium channel opening and opening of special K channels leading to greater fall in pre potential **thus decreased slope of pre potential and firing rate**

Answer 151

* RMP -90mV (+/- 20) * No pre potential * Phase 0 rapid upstroke to +20mV * Phase 1 short-lived rapid depolarisation to around 0mV * Phase 2 prolonged plateau * Phase 3 moderately fast repolarisation to resting membrane potential * Phase 4 is the resting membrane potential

Answer 152

* Phase 0 - opening of voltage-gated Na channels allows **sodium influx** * Phase 1 - due to closure of sodium channels and transient potassium efflux * Phase 2 - due to slower but prolonged opening of voltage-gated calcium channels with **calcium influx** * Phase 3 - due to closure of calcium channels and opening of various types of potassium channels allowing **potassium efflux** * Phase 4 - resting membrane potential is due to membrane permeability at rest being much higher for potassium than for sodium

Answer 153

* **Upstroke on QRS** * Plateau occupies QT interval * **Repolarisation at T wave**

Answer 154

Muscle still contracting in relative refractory period and beyond the duration of action potential so cannot develop tetany

Answer 155

* IHD * Previous repair of congenital heart disease * Structural heart disease * Channelopathies (congenital or acquired) * Electrolyte imbalances (K, Mg, Ca) * Sympathomimetic agents * Infiltrative cardiac diseases 1 to pass

Answer 156

Torsades de Pointes

Answer 157

Monomorphic ventricular tachycardia

Answer 158

* **Widespread peaked T waves**, mild tachycardia, some inverted T waves, ST elevation * **Suggestive of hyperkalaemia** Bold

Answer 159

* Peaked T waves (repolarisation abnormality) * P wave flattening, loss of P waves (progressive atrial paralysis) * QRS widening/bizarre QRS (conduction abnormality) * Sinusoidal ECG * Ventricular arrhythmias * Asystole 3 to pass

Answer 160

* K+ is filtered at the glomerulus * **Most filtered potassium is actively reabsorbed at the proximal tubules** * **Potassium is then secreted into the fluid by the distal tubules** * At distal tubule: K+ secretion is passive and sodium is reabsorbed * In a healthy person: the amount of K secreted = K intake and K balance is maintained * Normally >93% K is reabsorbed by the kidneys * K secretion and excretion alter depending on serum K and H Bold to pass

Answer 161

* ST elevation in II, III and aVF. * Q-wave formation in III and aVF. * Reciprocal ST depression and T wave inversion in aVL * ST elevation in lead II = lead III and absent reciprocal change in lead I (isoelectric ST segment) suggests a left circumflex artery occlusion

Answer 162

* Abnormally rapid repolarisation of the infarcted muscle (accelerated opening of potassium channels). Current flow out of infarct (normal region negative relative to infarct). Occurs within seconds of infarction and last a few minutes * Decreased resting membrane potential (due to loss of intracellular potassium). Begins in first few minutes secondary to process above. Current flow into infarct during diastole (ECG configured to record as ST elevation) * Slowed depolarisation of affected cells compared with normal cells. Occurs at 30 minutes into infarct process. Current flow out of infarct. 2 of 3 to pass

Answer 163

* PR interval - 0.12-0.2 seconds * QRS duration - 0.08-0.12 seconds * QT interval - 0.40-0.43 seconds * ST interval - 0.32 seconds

Answer 164

* Long PR * ST depression * Inverted T waves * U wave

Answer 165

* Atrial systole: Phase 1 - P to R wave - **small** amount of increased **ventricular filling** due to atrial contraction * **Ventricular systole**: Phase 2 = **isovolumetric contraction** - R wave to ST segment; mitral valve closes; ventricular contraction occurs with no change to volume. Phase 3 = **ventricular ejection** - ST segment to end T wave; aortic valve opens; ventricular systole * **Diastole**: Phase 4 = **isovolumetric ventricular relaxation** - aortic valve closes. Phase 5 = **ventricular filling** - mitral valve opens.

Answer 166

Graph with appropriate axis, curves and approximate pressures

Answer 167

* **a) to b)** Start of systole, **mitral valve closes** * **Isovolumetric contraction**, until left ventricular pressure is greater than aortic pressure (120mmHg) then **aortic valve opens** * End systolic volume 50ml

Answer 168

* **c) to d)** * Momentum of ejected blood is overcome by arterial pressure, then the **aortic valve closes** * **Isovolumetric relaxation** as the ventricular pressure drops rapidly below atrial pressure. * Then **AV valve opens** to start ventricular filling * End diastolic volume 130ml, stroke volume 70-90mls

Answer 169

* A wave - contraction of the right atrium * C wave - ventricular contraction * V wave - relaxation of the right atrium combined with a closed tricuspid valve * X descent - atrial filling during ventricular contraction * Y descent - atrial filling at tricuspid valves open

Answer 170

* **The 'a' wave is due to atrial systole as some blood regurgitates into the great veins when the atria contract and venous inflow** * The 'c' wave is the transmitted rise in atrial pressure produced by the bulging of the tricuspid valve into the atria during isovolumetric ventricular contraction * The 'x' descent is due to increased atrial volume consequent upon the tricuspid valve ring being pulled distally during ventricular emptying * **The 'v' wave mirrors the rise in atrial pressure before the tricuspid valve opens during diastole** * The 'y' descent is due to emptying of the atrium after the tricuspid valve opens during diastole Bold to pass

Answer 171

* Heart rate * Wall tension * Myocardial contractility 2 to pass

Answer 172

* Rate and stroke volume * Adrenaline and sympathetic discharge * Venous return 2 to pass

Answer 173

* Starling * La Place P=2T/R

Answer 174

* **CO = HR x SV** * Stroke volume is related to preload and afterload of the heart and the intrinsic contractility of the myocardial cells * HR - sympathetic vs parasympathetic stimulation Bold to pass

Answer 175

The dashed lines indicate portions of the ventricular function curves where maximum contractility has been exceeded Correctly draws and labels curve and able to discuss reason for dotted lines

Answer 176

**Shift the curve up and to the left** * Circulating catecholamines * Inotropes (caffeine, theophylline, digitalis) * Sympathetic input **Shift the curve down and to the right** * Acidosis / hypercapnia / hypoxia * Vagal / parasympathetic stimulation * Pharmacological depressants (quinidine, procainamide & barbiturates) * Intrinsic depression (with heart failure) Two positives and two negatives

Answer 177

* **Direct Fick method or indicator (or thermal) dilution** * Can also measure by **doppler ultrasound** techniques 2 to pass

Answer 178

* Variation in heart rate due to induction of **arrhythmias or heart block** * **Reduced preload** (venodilation with reduced venous return due to anaphylaxis) * Increased afterload * **Reduced contractility** (i.e. ischaemia, venoms, drugs)

Answer 179

* Degree of stretch of cardiac muscle compared to resting length * Equivalent to end diastolic volume

Answer 180

* **Blood volume** * **Change in driving pressure** (pericardial (tamponade), intrathoracic (tension pneumothorax)) * **Venous return** * Sympathetic tone * Muscle pump * Loss of atrial contraction * Venous compression (eg. uterus in pregnancy) * Reduced cardiac compliance * Diastolic dysfunction/infiltrative diseases 2 bold to pass

Answer 181

Positively inotropic * Sympathetic stimulation via nerves or circulating catecholamines * Post-extrasystolic potentiation * Increased heart rate (small effect) * Drugs such as xanthines, glucagon, cardiac glycosides, adrenergic agents * Increased myocardial mass Negatively inotropic: * Parasympathetic stimulation (small) * Metabolic abnormalities: hypercapnoea, hypoxia, acidosis * Drugs such as calcium channel blockers, beta blockers, quinidine, barbiturates * Cardiac failure (intrinsic myocardial depression) * Cardiomyopathy or infarction 2 of each to pass

Answer 182

* Increasing contractility moves the curve upwards and to the left * Decreasing contractility moves the curve downwards and to the right

Answer 183

* **Decreasing heart rate** decreases oxygen demands * At a slower heart rate there is more time for coronary **circulation which occurs in diastole**

Answer 184

* **Both increase** Ventricular work per beat correlates to oxygen consumption * Work = SV x MAP * Stroke work of left ventricle is 7 x that of right ventricle * Theoretically, volume changes and pressure changes should affect myocardial oxygen consumption equally. However, pressure work produces a greater increase in oxygen consumption than does volume work. * **Changes in afterload have greater effect than changes in preload**

Answer 185

Stroke volume - 70-90mls

Answer 186

* **In parallel intrafusal muscle fibres** (3 types - dynamic nuclear bag, static nuclear bad and nuclear chain) * **Sensory nerve endings** - Group Ia afferent to all and efferent axons; Group II to nuclear chain and static nuclear bag) * Dynamic gamma **motor nerves** to dynamic bag fibers, static gamma motor nerves (to static nuclear bag and chain fibres) Bold to pass

Answer 187

* Stimulus - muscle **stretch** * Muscle * Sensory organ (muscle **spindle**) within the muscle body * Efferent **sensory** nerve * **Synapse** in spinal cord to **motor** neuron supplying same muscle * Transmitter - glutamate 3 bold to pass

Answer 188

Correct shape, axes, testing membrane potentials and durations

Answer 189

* Discharge of motor neuron * Release of transmitter (acetylcholine) at motor endplate * Binding of acetylcholine to nicotinic acetylcholine receptors * Increased sodium and potassium conductance in end plate membrane * Generation of end plate potential * Generation of action potential in muscle fibers * Inward spread of depolarisation along T tubules * Releases of calcium from terminal cisterns of sarcoplasmic retinaculum and diffusion to thick and thin filaments * Binding of calcium to troponin C, uncovering myosin-binding sites on actin * Formation of cross-linkages between actin and myosin and sliding of thin on thick filaments, producing movement 5 to pass

Answer 190

* **Calcium pumped back into sarcoplasmic retinaculum** * Release of calcium from troponin * **Cessation of interaction between actin and myosin** Bold to pass

Answer 191

* The electrical response of a muscle fibre to repeated stimulation * Contractile mechanism does not have a refractory period, so repeated stimulation before relaxation has occurred produces additional activation and a response added to the contraction already present * With rapidly repeated stimulation, individual responses fuse into one continuous contraction (tetanus; tetanic contraction) * Incomplete tetanus: periods of incomplete relaxation between summated stimuli

Answer 192

**Type 1** * Slow oxidative red * Moderate calcium pumping, diameter and glycolytic capacity * Slow myosin ATPase rate * High oxidative capacity **Type 2** * Fast glycolytic white * High calcium pumping, diameter and glycolytic capacity * Fast myosin ATPase rate * Low oxidative capacity Two types and three differences

Answer 193

* Binding of acetylcholine to muscarinic receptors * Increased influx of calcium into the cell * Activation of calmodulin-dependent myosin light chain kinase * Phosphorylation of myosin * Increased myosin ATPase activity and binding of myosin to actin * Contraction * Dephosphorylation of myosin light chain phosphatase * Relaxation of sustained contraction due to latch bridge and other mechanisms

Answer 194

* **Stretch of visceral smooth muscle causes contraction in the absence of innervation** * Cold increases activity * Acetylcholine decreases smooth muscle potential and increases spike frequency so resulting in more active muscle * Adrenaline and noradrenaline increase smooth muscle potential and decrease spike frequency causing decreased muscle activity * Neural Bold to pass

Answer 195

* Synthesis: Acetyl CoA and choline * Release from the synaptic vesicle * Bind to post-synaptic receptor

Answer 196

* Diffusion * **Acetylcholinesterase** * Re-uptake of choline into presynaptic nerve terminal Bold to pass

Answer 197

* Binds to post-synaptic cholinergic receptors * Catabolism by acetylcholinesterase at the post-synaptic membrane * Re-uptake of choline * No acetylcholine re-uptake * Catabolism by pseudocholinesterase in the circulation 3 to pass

Answer 198

* **Divided on basis of pharmacological properties in muscarinic and nicotinic** * Muscarinic - actions mimicked by muscarine and blocked by atropine. Found in smooth muscle, glands and brain. G-protein coupled to adenylyl cyclase and/or phospholipase. 5 types. * Nicotinic - actions mimicked by nicotine. Found in neuromuscular junction, autonomic ganglia and the central nervous system. Ligand-gated sodium ions channels. 5 subunits - alpha, beta, gamma, delta and epsilon Bold + 2 sites to pass

Answer 199

* **Tyrosine** - tyrosine hydroxylase * **DOPA** - dopa decarboxylase * **Dopamine** - dopamine hydroxylase * **Noradrenaline** - phenylethalonamine methyltransferase (PNMT) * **Adrenaline**

Answer 200

* **Re-uptake** - into presynaptic neuron then metabolised by MAO to inactive deaminated derivates or recycled * **Catabolised synaptic cleft** by COMT to normetanephrine

Answer 201

Removed by post-synaptic and pre-synaptic binding, re-uptake and catabolism

Answer 202

* **Noradrenaline** * **Adrenaline** * Dopamine

Answer 203

* Noradrenaline, which has been **stored in granulated vesicles** is released into the synaptic cleft by **exocytosis** * Noradrenaline acts on post-synaptic and to a lesser extent presynaptic and glial receptors * In addition to binding to receptors, noradrenaline is also removed from the synaptic cleft by: 1) **reuptake** into presynaptic neuron (via Neuro Transmitter Transporter) and then is broken down to inactive product by MAO located on mitochondria and 2) **broken down** to inactive product by Catechol-O-methyl transferase (COMT) located on the post-synaptic membrane Bold to pass

Answer 204

In depends on the change in conductance of sodium and potassium ions * When a **depolarising stimulus** occurs, the voltage-gated **sodium channels** become active, sodium enters the cell * When the **threshold potential** is reached the voltage-gated sodium channels overwhelms the K channels * Entry of sodium causes opening of more voltage-gated sodium channels and further depolarisation (positive feedback loop) resulting in the upstroke of action potential * The membrane potential moves close to the equilibrium potential for sodium (+60mV) * The voltage gated sodium channels then enter an inactivated state for a few milliseconds before returning to the resting state * Reversal of membrane potential limiting further sodium influx and **opening of voltage-gated potassium channels** results in **repolarisation** and end of action potential * Slow return of K channels returns in hyperpolarisation * Returns to resting membrane potential Bold to pass

Answer 205

* Latent period of -70mV then upslope until firing level is reached at -55mV * Spike potential with overshoot to +35mV * Rapid repolarisation then slow after-depolarisation * After-hyperpolarisation beyond -70mV * Return to latent period

Answer 206

* At firing level, rapid influx of sodium towards equilibrium (+60mV) * Sodium channels rapidly close (inactivated state) and inhibits further sodium influx * Voltage-gated K channels open * Slow K efflux completes repolarisation * Decrease in extracellular calcium decreases the sodium and potassium conductance required for an action potential

Answer 207

* Voltage-gated sodium channels concentrated in **node of Ranvier** and initial segment * Sodium channels flanked by K channels Bold to pass

Answer 208

* Myelinated vs demyelinated * Saltatory vs non-saltatory * Size * Direction of the conduction

Answer 209

* Diameter and speed of conduction * Function: large and fast for proprioception, conscious touch and somatic motor; small and slow for pain, temperature and autonomic * Gasser - ABC * Numerical - Ia, Ib, II, III, IV

Answer 210

Pain fibres are smaller and better penetrated by local anaesthetic leading to to loss of pain before loss of touch or proprioception

Answer 211

* Post-synaptic: direct or indirect (refractory periods, after-hyper polarisation) * Pre-synaptic: mediated by neurons that end on excitatory endings (axe-axonal synapses)

Answer 212

* Increased chloride conductance - **reduced calcium influx** and amount of excitatory transmitter released * Voltage-gated K channels - K also decreases calcium entry * Direct inhibition of excitatory transmitter release, independent of calcium influx Bold to pass

Answer 213

* Direct during the course of an IPSP and not the consequences of a previous discharge * Indirect due to the effect of a previous post-synaptic neuron discharge 1 to pass

Answer 214

This was a rubbish question anyway haha

Answer 215

* **Potential difference** across cell at rest, as a result of separation of positive and negative electronic charges across cell membrane (**inside negative** relative to outside of cell) * Normal RMP of neuron = -70mV Bold to pass

Answer 216

* Main ions involved - **sodium and potassium** * **Na/K/ATPase pump** creates **electrochemical gradient** by pumping out 3 Na for every 2 K pumped in * **Na and K diffuse down concentration gradient** across permeable cell membrane (K diffuses from inside to outside of cell; opposite for Na) * Cell membrane **more permeable to K** at rest -> that's why RMP is close to equilibrium potential for K * RMP represents an equilibrium state: driving force for ions down concentration gradient = driving force down electrical gradient

Answer 217

RMP moves **closer to threshold potential for eliciting action potential** (becomes less negative on the inside of the cell)

Answer 218

* Lipid bilayer * Unequal distribution of ions * Membrane must be permeable to ions * Concentration gradient

Answer 219

* Regulation of **vomiting reflex** * Regulation of **mood** * Control of respiration * Platelet aggregation and smooth muscle contraction * Facilitate GI secretion and peristalsis * Regulation of circadian rhythms Bold to pass

Answer 220

* Hydroxylation and decarboxylation of tryptophan to form serotonin * Released serotonin from serotonergic neurones is recaptured by an **active re-uptake mechanism and inactivated by MAO** to form 5HIAA * 5HIAA is excreted as a urinary metabolite Bold to pass

Answer 221

* Activation of voltage gated calcium channels in presynaptic membrane * Calcium influx into the cell * Exocytosis of preformed ACh into synaptic cleft * Diffusion of ACh across synaptic cleft * Binds to post-synaptic nicotinic receptor * Increase Na and K conductance in end plate membrane * Generation of end plate potential * Generation of action potential in muscle fibres * Spread of depolarisation along T tubules * Calcium released from sarcoplasmic reticulum (diffusion to thick and thin filaments) * Binding of calcium to troponin C uncovering myosin-binding sites on actin * Actin-myosin binding and sliding of thin on thick filaments producing movement 6 to pass

Answer 222

* **Conductive deafness** - due to impaired sound transmission in external or middle ear, affects all frequencies. Examples: blockage of external canal (foreign body, wax), otitis external or media, perforated eardrum, osteosclerosis * **Sensorineural deafness** - due to loss of cochlear hair cells (commonest) or problems with CN VIII or within central auditory pathways, affects some frequencies. Examples: degeneration, damage to outer hair cells (prolonged noise exposure), aminoglycoside antibiotics, CN VIII tumours, CVA in medulla Explain both and 2 examples of each

Answer 223

Weber/Rinne's test - 256Hz tuning fork Bonus questions

Answer 224

* Bacterial **toxins** eg. endotoxin act on monocytes, macrophages, and Kupffer cells to produce cytokines that act as **endogenous pyrogens** * IL-1, IL-6, IFN-beta and IFN-gamma and TNF-alpha can act independently to produce fever * Cytokines are also produced by cells in CNS when these are stimulated by infection - may act directly on the thermoregulatory centers * Activated the pre-optic area of the **hypothalamus** * Causes release of **prostaglandins** eg. PGE2. This causes a raise in **temperature set point** resulting in fever Concept to pass

Answer 225

Mechanisms activated by **cold** (posterior hypothalamus) * **Increased heat production**: shivering, hunger, voluntary activity, noradrenaline/adrenaline release * **Decreased heat loss**: skin vasoconstriction, curling up, horripilation Mechanisms activated by **heat** (anterior hypothalamus) * **Decreased heat production**: anorexia, apathy and inertia * **Increased heat loss**: cutaneous vasodilation, sweating, respiration 1 mechanism for each bold

Answer 226

* Characteristic jerky movement of the eye seen at the start and end of period of rotation * Different types: horizontal, vertical, rotatory * Direction of eye movement is identified by the direction of the quick component

Answer 227

* Reflex that maintains visual fixation on stationary points while the body rotates, although not initiated by visual impulses * When rotation starts, the eyes move slowly in a direction opposite to the direction of rotation, maintain visual fixation (vestibulo-ocular reflex) * When the limit of this movement is reached, the eyes quickly snap back to a new fixation point and then again move slowly in the other direction

Answer 228

* Slow component is initiated by impulses from the labyrinths * Quick component is triggered by a centre in the brain stem

Answer 229

* Retina * **Optic nerve** * **Optic chiasm** * **Optic tract** * Lateral geniculate body (thalamus) * Geniculocalcarine tract * **Primary visual cortex (occipital lobe)** * **At optic chiasm, nasal fibres decussate to the contralateral side** Other connections: * Optic tract (via superior colliculus) to pretectal midbrain, then to Edinger-Westphal nuclei in oculomotor nerve (pupillary reflexes, eye movement) * Frontal cortex (refined eye movement - mergence, near point response) * Retinal ganglion cells to suprachiasmatic nucleus hypothalamus (endocrine & circadian responses to day/night cycle)

Answer 230

* **A** - A lesion that interrupts one optic nerve causes blindness in that eye. * **B** - Lesions affecting the optic chiasm destroy fibers from both nasal hemiretinas and produce a heteronymous (opposite sides of the visual fields) hemianopia. * **C** - A lesion in one optic tract causes blindness in half of the visual field and is called homonymous (same side of both visual fields) hemianopia (half-blindness). * **D** - Occipital lesions may spare the fibers from the macula because of the separation in the brain of these fibers from the others subserving vision.

Answer 231

* Sense organ - **naked nerve endings** * Transmission via 2 fibre types: 1) small, fast myelinated **A-delta fibres**; 2) large slow unmyelinated **C fibres** * Spinal cord: both fibre groups end in **dorsal horn of spinal cord ("gate")** * From spinal cord to brain via **ventrolateral system - second order** (including lateral spinothalamic tract) to **thalamus** and then third order neurons on to **cerebral cortex**

Answer 232

* **"Gate theory"** - eg. stimulation of large touch/pressure afferents causes inhibition of pain pathways in dorsal horn of spinal cord * Stress-induced analgesia * Drugs (eg. opioids) * Higher centre interpretation Bold +1 other

Answer 233

* Receptors in afferent nerve fibres * Dorsal horn region of spinal cord * Periaqueductal grey matter in brain Bonus question

Answer 234

* **Myelinated** A delta fibres * 2-5um diameter * Conduction rates 12-30m/s * End in dorsal horn (laminated 1 and 5) * Neurotransmitter is glutamate Bold + 2

Answer 235

Irritation of a visceral organ causing pain in a distant somatic structure

Answer 236

**Diaphragm**

Answer 237

Dermatome rule. Referred pain is usually to a structure that **developed from the same embryonic segment or dermatome** as the structure from which the pain originates

Answer 238

* Cardiac pain to arm * Ureteric pain to testicle

Answer 239

* Convergence-projection theory * Somatic and visceral pain fibres converge on the same second-order neurons in dorsal horn that then go on to thalamus and sensory cortex via common path. * Sensory cortex cannot determine whether the stimulus came from viscera or area of referral

Answer 240

* Centres within network regulate respiratory, cardiovascular, vegetative and endocrine functions * Non-specific activation from any modality * Sends signals mostly to the thalamus * Increases cortical electrical activity * Increased consciousness, alert state, heightened sensory perception

Answer 241

* **Complex polysynaptic network** * Mid ventral portion of medulla + midbrain * Converging sensory fibres from long tracts and cranial nerves Bold to pass .

Answer 242

Upper motor neurons usually refer to **corticospinal neurons that innervate spinal motor neurons** (also include brain stem neurons that control spinal motor neurons) Bold to pass

Answer 243

Damage **initially causes muscles to become weak and flaccid** but eventually leads to **spasticity, hypertonia, hyperactive stretch reflexes and an abnormal plantar extensor** reflex

Answer 244

Loss of descending cortical input to inhibitory neurons called Ranshaw cells, and therefore **loss of inhibition of antagonists**, resulting in repetitive sequential contractions of ankle flexors and extensors Bold to pass

Answer 245

* Ulcers * Protein/muscle degradation * Hypercalcaemia * Renal stones (calcium) * Urinary tract infection 2 to pass

Answer 246

* Withdrawal reflex is a polysynaptic reflex * Also has afferent and efferent limbs, but sensory organ is **nociceptor (painful stimulus)**. * Central integrator consists of **polysynaptic connections in the spinal cord** i.e. one or more interneurons and interposed between afferent and efferent neurons * Efferent limbs are motor nerves to effector muscles on the ipsilateral and contralateral sides * **Flexion and withdrawal of the ipsilateral limb** and extension of the contralateral limb Bold to pass

Answer 247

Regular, repetitive, rhythmic contractions of a muscle subject to sudden, sustained stretch

Answer 248

* Knee jerk * Ankle jerk

Answer 249

* Following prolonged stretch or muscle contraction, the contracted muscles suddenly relax * Stimulate the Golgi tendon organ, integrator (synapse on motor neurone for stretch and on inhibitory interneuron for inverse stretch), efferent limb (ventral root for both) and effector (extrafusal fibres muscle fibres)

Answer 250

* **Radiation and conduction** (70%) * **Vaporisation of sweat** (27%) * Respiration (2%) * Urination and defecation (1%)

Answer 251

The posterior **hypothalamus**

Answer 252

**Heat production** * Basic metabolic process * Specific dynamic action of food * Muscular activity **Heat is lost by** * Radiation and conduction * Vaporisation of sweat * Respiration * Urination and defecation 2 of each

Answer 253

**Hypothalamus** - diencephalon

Answer 254

* **Increase in osmotic pressure in plasma** - sensed by osmoreceptors in the anterior hypothalamus * **Decrease in ECF volume** (e.g. haemorrhage) - 1) sensed by baroreceptors in heart and blood vessels, increases thirst 2) increase in renin - causes increased AT II - acts on the diencephalon neurons - increases thirst * Psychological - e.g. acute psychosis * Others - 1) increase lipids during eating (prandial drinking) 2) other poorly understood mechanisms such as increased osmolality as food absorbed and GI hormones acting on the hypothalamus Bold with understanding

Answer 255

* Hypothalamic disease * Direct damage to the diencephalon * **Altered mental state** * Psychosis * Lesion of the anterior communicating artery (supplies the hypothalamus) * Diet high in protein (products of protein metabolism cause water diuresis) Bold + 1 others

Answer 256

Point where **visual acuity greatest**; fovea is the centre of the macula, a thinned out rod-free portion of the retina where the **cones are densely packed** and each synapses on a single bipolar cell, which, in turn, synapses on a single ganglion cell, providing a direct pathway to the brain. One of **bold plus one** other to pass

Answer 257

* **Optical factors**: state of the image-forming mechanisms eg. cataracts, keratitis, astigmatism, myopia, hyperopia * **Retinal factors** eg. the state of cones, retinopathies, optic neuritis * **Stimulus factors** eg. illumination; brightness of the stimulus; contrast between stimulus and background; length time exposed to stimulus 3 factors

Answer 258

Measurement from **Snellen chart** viewed at a distance from **6m** or 20 feet; **6/24 indicates reduced visual acuity** Numerator is the distance at which the chart is read; the denominator is the **smallest line** that can be read

Answer 259

One or more interneurons and interposed between the afferent and efferent neurons

Answer 260

* Prolonged effect as different time for stimulus to reach effector * Reverberation circuit as some interneurons turns back on themselves further prolonging the effect

Answer 261

Is the effector protein in the renin-angiotensin system: integral to control of volume regulation Increased secretion due to: * Increased sympathetic activity * Increased circulating catecholamines * Prostaglandins Decreased secretion due to: * Increased sodium and chloride re-absorption across macula densa * Increased afferent arteriolar pressure * Vasopressin

Answer 262

* **Arteriolar constriction** * Directly on adrenal cortex to increase aldosterone - facilitation release or noradrenaline release * Contraction of mesangial cells causing decreased GFR * Direct effect on renal tubules to increase sodium re-absorption * On the brain to decrease sensitivity of baroreceptor reflex * On brain (circumventricular organ) to increase water intake and increase secretion vasopressin and ACTH Bold +2 others

Answer 263

* Concentrating mechanism depends on maintaining a **gradient of increasing osmolality along medullary pyramids** * **Gradient is produced by countercurrent multipliers** in the **loop of Henle and maintained by vasa recta acting as counter current exchanges** * **Water moves out of the thin descending limb** (via aquaporin 1) * **Active transport of sodium and chloride out of thick ascending limb of loop of Henle** * Continued inflow of isotonic fluid into the proximal tubule and out of descending tubule, H2O moves out of collecting duct (into the hypertonic interstitium of the medullary pyramids) under the influence of ADH * Vasa recta acts as countercurrent exchangers in the kidney in which NaCl and urea diffuse out of the ascending limb of the vessel and into the descending limb, while water diffuses out of the descending into the ascending limb of the vascular loop. As a result, the solute remains in the medulla pyramid and maintain the interstitial concentration

Answer 264

* High permeability of the thin descending limb to water (via aquaporin-1) and active transport of sodium and chloride out of the thick ascending limb which is not permeable to water * A system in which sodium/potassium/2 chloride are actively transported, and the inflow runs parallel to, counter to, and in close proximity to the outflow for some distance

Answer 265

Contributes to the **osmotic gradient** in the medullary pyramids

Answer 266

* Transported by urea transporters, by **facilitated diffusion** * Amount of urea depends on the amount filtered which is influenced by dietary protein

Answer 267

Amount of fluid (plasma filtrate) filtered by the glomerulus per unit time

Answer 268

Normal GFR - **125ml/min** (180L/24 hours) in normal adult. 10% lower in females

Answer 269

* Size of capillary bed * Regulated by **mesangial cells** (contractile cells) located in the glomerulus (between the basal laminate and the endothelium) * Permeability of glomerular capillaries (50 x skeletal muscle capillaries) * Hydrostatic and osmotic pressure gradients - oncotic pressure (plasma protein concentration) - glomerular capillary hydrostatic pressure * Systemic blood pressure * Afferent arterial pressure ( renal artery blood flow - kept stable by autoregulation 90-210mmHg) * Afferent or efferent arteriolar constriction * Hydrostatic pressure in Bowman's capsule * Intrarenal interstitial pressure (ureteral obstruction, renal oedema) * Age Bold + 3 others

Answer 270

* Increased - ANP, dopamine, PGE2, cAMP * Decreased - noradrenaline, vasopressin, angiotensin II, histamine, PGF2, endothelins, thromboxane A2, leukotrienes 1 of each to pass

Answer 271

* **Contractile cells** that help to **regulate GFR** * Located between the basal lamina and the endothelium, **in the glomerulus** * Common between neighbouring capillaries, and in these locations the basal membrane forms a sheath shared by both capillaries * Also secrete the extracellular matrix, take up immune complexes, and are involved in the progression of glomerular disease

Answer 272

* **Freely filtered at glomerulus** (600mmol/day) * Actively **reabsorbed in PCT** (560mmol/day) * **Secreted in distal tubule** - rate proportional to flow * Secreted in collecting ducts - **aldosterone** excreted (90mmol/day) * Total secreted load averages 50mmol/day but varies with renal tubular flow and aldosterone level Bold to pass

Answer 273

Secretin and resorption

Answer 274

* Measure excretion of a substance which is **freely filtered** through the **glomeruli neither secreted nor reabsorbed** by the **tubules** * Non toxic, not metabolised * E.g. inulin **GFR = UX x V / PX** Where Ux of the concentration of urine V is the urine flow per unit time Px is the arterial plasma of X * If X is not metabolised in the tissues then the peripheral venous plasma level can be substituted for the arterial plasma level

Answer 275

* **Freely filtered** the glomerulus * **Resorbed in the early part of the PCT** by secondary active transport * **Sodium dependent** co-transportation (SGLT2 into cells then GLUT2 facilitated diffusion into interstitial fluid) * Excreted in the urine if **renal threshold is exceeded** 1 & 2 to pass plus understanding of 3 & 4

Answer 276

Osmotic diuresis - dehydration, electrolyte loss (Na, K)

Answer 277

Proximal and distal tubules, and collecting ducts 2 to pass

Answer 278

* **Proximal tubules - Na/H exchange transporter** (one Na and one HCO3 reabsorbed for each H secretion) * Distal tubule and collecting duct - the secretion of H+ is independent of Na. ATP driven proton pump - stimulated by aldosterone. Also H-K ATPase pump, and anion exchanger 1 Bold + 1 to pass

Answer 279

* **The limiting pH is 4.5** (1000x concentration in plasma) * It is the maximal H+ gradient that can be achieved in the tubules * It occurs in the **collecting duct**. * Possible due to buffers (bicarbonate, phosphate and ammonia) Bold to pass

Answer 280

* Aims to **return serum pH to normal by increasing H+ excretion** * **Kidney reabsorbs HCO₃ by actively secreting H+** * Renal tubule cells contain carbonic anhydrase converting CO₂ to H⁺ and HCO₃^-; then PCT secrete H⁺ in exchange for Na⁺. * In the DCT, H⁺ is secreted by a proton pump, limited by urinary pH >4.5 * **Buffering in tubular fluid** pH with H₂CO₃, HPO₄ and NH₃ **allows greater H⁺ secretion**

Answer 281

* HPO₄ forms H₂PO₄ * NH₃ forms NH₄ * HCO₃ forms CO₂ and H₂O 2 to pass

Answer 282

The **respiratory system** responds by **increasing ventilation** which results in a decrease in PCO2 which causes increase in pH (this is a rapid response) Bold to pass

Answer 283

Glutamine synthesis increased in liver, to provide kidney with additional source of NH₄+ as well as NH₃ secretion increasing over days Need to mention glutamine synthesis is increased

Answer 284

* Blood: bicarbonate, protein and Hb * Interstitium: bicarbonate * Intracellular: proteins, phosphate * Urine: also uses ammonia

Answer 285

Limiting pH (-4.5) would rapidly be reached unless free H+ is buffered

Answer 286

Na and H+ Both to pass

Answer 287

Coupled to H+ secretion - if H+ secretion increased, then K+ excretion decreased as K+ is reabsorbed in exchange for H+ (H/K/ATPase) in collecting ducts

Answer 288

* **The rate of secretion is proportional to the rate of flow of tubular fluid through the distal nephron. With rapid flow the concentration of K⁺ in the fluid remains lower and secretion continues** * **In the distal nephron K⁺ and H⁺ compete for secretion in association with reabsorption of N⁺. Therefore in acidosis, K⁺ secretion is decreased** * **Aldosterone increases reabsorption of Na⁺ in the collecting ducts and thereby promotes K⁺ secretion** * Increased delivery of Na⁺ to the collecting ducts promotes increased secretion of K⁺ (e.g. thiazide diuretics) * Conversely decreased delivery of Na⁺ to the collecting ducts promotes decreased secretion of K⁺ * Inhibition of K⁺ absorption in the proximal nephron (e.g. osmotic or loop diuretics) promotes excretion of K⁺ At least 2 of the three bold

Answer 289

* Thin **descending limb water permeable** (aquaporins) and tubular **fluid becomes hypertonic** * **Thick ascending limb impermeable to water, and Na, K and Cl actively transported out, so fluid ends up more hypotonic** * K+ diffuses back passively

Answer 290

* This process **aims to maintain the constancy of the load delivered to the distal tubule**. * The macula densa **in the ascending limb of the loop of Henle senses the rate of flow and feeds back to either increase or decrease the rate of filtration** in the glomerulus

Answer 291

* Fluid in the descending limb of the loop of Henle becomes **hypertonic** as water moves out of the tubule into the hypertonic interstitium * In the ascending limb it becomes more dilute because of the movement of Na and Cl out of the tubular lumen. * When fluid reaches the top of the ascending limb (the diluting segment) it is now **hypotonic** to plasma

Answer 292

* Thin/descending. Thick/ascending. Situated mostly in the renal medulla * **Origin from proximal convoluted tubule** * Short (cortical) (85%) and long (juxtamedullary) (15%) loops * **Macula densa at distal end where joins distal convoluted tubule**

Answer 293

* **Sacral spinal reflex** mediated by S2, S3 and S4 nerve roots * **Facilitated and inhibited by higher centres, subject to voluntary control** * First urge to void at 150ml. Marked fullness at 400ml - sudden rise in intra-vesical pressure triggers reflex contraction Micturition reflex: * Stretch receptors in bladder wall. Afferent limb in pelvic nerves * **Parasympathetic efferent fibres** (via same pelvic nerves) mediate contraction of detrusor muscle. * Pudendal nerve (S2,3,4) permits voluntary contraction of perineal muscles/external urethral sphincter, to slow or half flow

Answer 294

* **Bladder**: smooth muscle arranged in spiral, longitudinal and circular bundles. Circular bundle is called the **detrusor muscle**. Contraction of detrusor is responsible for involuntary emptying * **External urethral sphincter** - skeletal muscle sphincter of the membranous urethra. Relaxes during micturition. This is voluntarily controlled. * Perineal muscles. Relaxes during micturition. Also voluntarily controlled * In males, urine left in urethra expelled by several contractions of bulbocavernosus muscle * Contraction of abdominal wall muscles aids expulsion of urine Bold to pass

Answer 295

**Oblique passage of ureters through bladder wall** keeps ureters closed except during peristaltic waves Bold to pass

Answer 296

* Glomerulus - filtration * Afferent arteriole (contain juxtaglomerular cells - secrete renin) then capillary tuft then efferent arteriole encapsulate in Bowmans capsule * PCT - resorption of most solute - Na, glucose, amino acids, reclaim HCO3 * Descending limb of LOH - thin, water permeable * Thick ascending limp of LOH - site of Na K 2Cl - generates concentration gradient * DCT - site of Na K Cl pump * Proximal part is the macula densa forms juxtaglomerular apparatus * Collecting duct - p cells - under control of ADH and aldosterone (water and sodium resorption) * I cells - involved in H+ excretion

Answer 297

* Capillary endothelial cells - afferent arteriole becomes a tuft of capillaries invaginated into Bowman's capsule. Endothelium **fenestrated** with 70-90nm pores. Separated from capsule epithelium by basal lamina * Epithelial calls of Bowman's capsule: 1) **podocytes possess pseudopodia** that interdigitate to form 25nm wide **filtration slits** over capillary endothelium. 2) Mesangial cells are stellate and lie between capillary endothelium and basal laminate. Involved in regulation of filtration, secretion of various substances and absorption of immune complexes Bold to pass

Answer 298

* Large diameter >8nm * Lack of neutrality (charged) Both to pass

Answer 299

Hypotension leads to **reduced perfusion pressure of the afferent glomerular arteriole**, stimulating release of **renin** by the juxtaglomerular cells

Answer 300

* Renin **converts angiotensinogen to angiotensin I** * **Angiotensin converting enzyme** converts angiotensin 1 to **angiotensin II** * Angiotensin II acts on the adrenal cortex's zona glomerulosa cells to **release aldosterone** * Aldosterone acts on the renal distal tubules to **retain Na and water**, thus increasing intravascular volume * Angiotensin II is also a potent arteriolar constrictor and contributes to a rise in blood pressure

Answer 301

* Increase **catecholamines** * **Sympathetic activity** through renal nerves * **Prostaglandins** * Low sodium states: cardiac failure, liver failure and sodium depletion 1 bold to pass

Answer 302

* Promotes **water resorption** in collecting duct via **aquaporins** insertion * **Vasoconstriction** Bold to pass

Answer 303

* Renin, angiotensin, aldosterone * Vasopressin

Answer 304

* Increase sodium secretion from the kidneys * Diuresis

Answer 305

1.2-1.3L/min (25% of cardiac output)

Answer 306

* **Perfusion pressure** - systemic MAP * **Renal arterial effects** - local constriction from noradrenaline and angiotensin II, dilation from ACh, PGs, and dopamine) * **Renal nerves** - sympathetic, constriction, decreased renal blood flow * **Autoregulation** - myogenic, NO and angiotensin II 3 of 4 bold

Answer 307

* Fick principle (amount of substance taken up per unit time divided by arterio-venous concentration difference) * PAH (excreted, not metabolised or stored, doesn't affect flow) is used to measure effective renal plasma flow (90% cleared) * Actual renal plasma flow = ERPF/0.9 * Renal blood flow = renal plasma flow x 1/1-HCT

Answer 308

* **Cortical flow is high** (5ml/g) and oxygen extraction is low * **Medullary blood is low** (2.5mL/g) in outer cortex, 0.6mL/g in inner cortex) and oxygen extraction is higher (more metabolic work done) * **Medulla is vulnerable to hypoxic damage** if flow is reduced (low flow, high oxygen usage) 2 to pass

Answer 309

* Medulla is vulnerable to hypoxia * Acute tubular necrosis * Uraemia

Answer 310

* **Loss of urine concentrating and diluting** capacity due to loss of countercurrent mechanism and nephron number. **Polyuria -> oliguria -> anuria** * **Uraemia** due to urea and creatinine and toxins (phenol and acids) build up * **Acidosis** - anaemia * **Sodium retention** - oedema and heart failure

Answer 311

* Proteinuria * Leucocytes * Red cells * Casts 3 to pass

Answer 312

**Proteinaceous** material precipitated in tubules washed into bladder

Answer 313

**Inhibiting renin secretion** * **Intrarenal baroreceptors** - an increase of afferent arteriolar pressure at the juxtaglomerular cells causes a decrease in renin secretion * **Amount of Na and Cl** entering the distal tubules in the macula densa cells (increase in NaCl causes a decrease in renin secretion) * Plasma K level (probably through NaCl effect) * Angiotensin II/vasopressin (inhibitory) **Stimulating renin secretion** * **Increase in sympathetic nervous system** * Catecholamines and noradrenaline * Prostaglandins

Answer 314

* Sodium depletion * Diuretics * Hypotension * Haemorrhage * Upright position * Dehydration * Cardiac failure * Cirrhosis * Constriction of renal artery * Constriction of aorta 3 to pass

Answer 315

* Arterioles (AT1 receptor) - **vasoconstriction** - increases total peripheral resistance * **Adrenal cortex - increase aldosterone production - increased Na and H₂O resorption** * Kidney - direct effect to decrease GFR and increase Na reabsorption * Brain - decreased sensitivity of brain baroreceptor reflex - potentiates pressor effect * Pituitary - increase ADH and increase ACTH secretion Bold to pass

Answer 316

Water loss lowers ECF and ICF leading to: * **Decreased BP** * **Tachycardia** * **Increased ADH secretion** * **Decreased urine output** * Decreased GFR * Increased renin-angiotensin * Increased thirst aiming to maintain IV volume. In adrenal insufficiency Na is lost not only in urine but also into cells

Answer 317

* Increased chloride and acidosis * Increased baroreceptor firing * **Decreased heart rate** * **Increased blood pressure** * Increased urine output * Decreased renin-angiotensin * Improved capillary return Bold +1 to pass

Answer 318

Hartmann's Plasmalyte 1 to pass

Answer 319

* **Primarily PCT** (60%) by Na-H exchange but also a range of co-transporters (glucose, amino acids, lactate) * 30% thick ascending limb of loop of Henle (Na/K/2Cl co-transporter, Na-H exchanger) * Nil at thin part of loop of Henle * 7% DCT - NaCl co-transporter * 3% collecting ducts through Na channels (ENaC) 2 to pass including bold

Answer 320

**Na/K/ATPase active transport**. (3 Na/2K) across basolateral membrane predominantly into the lateral intercellular spaces Bold

Answer 321

A slight increase in ECF occurs triggering various mechanisms: * Stretch receptors in right atrium and pulmonary veins -> inhibits sympathetic outflow to kidneys -> decreased sodium reabsorption * Small increase in arterial pressure -> pressure natriuresis * Suppression AT-II formation * Reduced aldosterone secretion secondary to reduced AT-II formation * Simulation of ANP 2 mechanisms to pass

Answer 322

* **Increased tubular reabsorption** of Na+ with secretion of K+ and H+ * Latent period of 10-30 minutes before effect (time delay due to need to alter protein synthesis via action on DNA) * Act principally on the collecting ducts to increase number of active epithelial sodium channels

Answer 323

* Endocytosis * Passive diffusion * Facilitated diffusion * Active transport * **Co-transporters** secondary to active transporters * **Exchangers** * Ion channels * Pumps 2 to pass

Answer 324

* Tubulo-glomerular - macula densa, increased noradrenaline and increased adenosine, calcium, afferent vasoconstriction * Glomerular/tubular balance - mainly oncotic pressure in efferent capillaries * Humeral - aldosterone, prostaglandins, endothelin, ANP 1 humeral and one other

Answer 325

* Afferent and efferent arterioles and tubule touch at one point * Macula densa and juxtaglomerular cells

Answer 326

* As plasma osmotic pressure rises, **increase thirst** and sensed via **osmoreceptors** in anterior hypothalamus (mainly organum vasculosum of the lamina terminalis IVLT) * **Vasopressin (ADH) secretion rises** (from posterior pituitary) * Increased renal **V2 receptor stimulation** * Insertion of water channels (**aquaporin**) in luminal membranes of renal collecting tubules, allowing more water to return to body Conversely as plasma osmotic pressure fall ADH secretion suppressed Bold + correct understanding of concept to pass

Answer 327

* **Decreased ECF volume** * **Pain** * Emotion * Surgical stress * Exercise * Nausea and vomiting * Standing * Angiotensin II * Meds (clofibrate & carbamazepine) Bold +1 more to pass

Answer 328

* Amount of substance excreted - amount filtered + net amount transferred * Changes in renal blood flow and systemic blood pressure * Active transport (primary and secondary) * Hormonal (aldosterone, angiotensin, endothelin) 3 to pass

Answer 329

* Increased rate of flow in loop of Henle and distal convoluted tubules increases GFR and local sodium * Macula densa adenosine A1 receptors activated by increased Na/K activity causing increased calcium vasoconstriction and decreased GFR * % solute reabsorbed remains constant (glomerulotubular balance)

Answer 330

* In the **collecting duct**, ADH binds to G-receptor * V2 activates adenylate cyclase * Increased intracellular cAMP - migration of intracellular endosomes * H2O channels (**aquaporin-2**) inserted into luminal membrane * **Increased H₂O permeability**, with increased H₂O reabsorption

Answer 331

* Begins about 15 minutes after ingestion. Maximum in about 45 minutes * The act of drinking produces a small decrease in **ADH** (vasopressin) secretion **resulting in diuresis** * Most of the inhibition is produced by the **decrease in plasma osmolality** after the water is absorbed

Answer 332

* **An appetite under hypothalamic control** * Increased plasma osmolality - osmoreceptors in anterior hypothalamus * Hypovolaemia - renin-angiotensin system - baroreceptors in heart and blood vessels * Prandial - learned or habit response, osmolality & GI hormone effects * Psychogenic * Dry pharyngeal mucous membranes

Answer 333

* Presence of large quantities of unreabsorbed solutes in renal tubules causes an increase in urine volume called **osmotic diuresis** * Solutes that are not reabsorbed in the proximal tubules exert an appreciable osmotic effect as volume of tubular fluid decreases and their increased concentration * Therefore, they "hold" water in the tubules

Answer 334

* 60-70% in the proximal tubule * 15% in the loop of Henle * 5% in the distal tubule * Up to 10% in the collecting duct depending on the presence of antidiuretic hormone

Answer 335

* CO₂ + H₂O = H₂CO₃ = H + HCO₃ * Respiratory centre response to H, mainly at peripheral chemoreceptors, also transferred to CSF by CO₂ * Metabolic acidosis -> increased ventilation, decreased CO₂ -> decreased H, decreased HCO₃ * Metabolic alkalosis -> decreased ventilation, increased CO₂ -> increased H, increased HCO₃.

Answer 336

* DKA : hypoxia -> lactic acid * Vomiting -> loss of acid

Answer 337

* In laminar flow, resistance is proportional to **the length** of the tube and **viscosity**, and inversely proportional to **fourth power of the radius** due to **Poiseuille's law** * Turbulent flow is most likely to occur at high Reynold's number, when inertial forces dominate over viscous forces * Highest in the medium sized bronchi; low in the very small airways * Airway resistance decreases as lung volume rises because the airways are then pulled open by radial traction * Bronchial smooth muscle is controlled by the autonomic nervous system, stimulation of beta-adrenergic receptors cause bronchodilation. Bold +2 other factors to pass

Answer 338

* Intrapleural pressure -> alveolar pressure causing airway compression * Dynamic compression of airways limits airflow during forced expiration Concept to pass

Answer 339

* Decreases with stimulation of beta-adrenergic receptors causing bronchodilation * Increases with parasympathetic nerve stimulation causing bronchoconstriction * Increases with histamine * Increases when lung volume reduces * Increases when pCO2 decreases * Increases with increase density and viscosity of gas Flow resistance = 8 x viscosity x length / pie r4

Answer 340

* Pulmonary fibrosis * Pulmonary oedema * Pulmonary haemorrhage * Atelectasis * Loss of surfactants such as respiratory distress syndrome Need 3 examples to pass

Answer 341

Expressed by Reynolds number * Fluid density * Diameter of the tube * Velocity of the flow * Viscosity of the fluid Laminar flow only in small airways, transitional most areas, turbulent in trachea (rapid breathing)

Answer 342

* Bronchial smooth muscle tone: sympathetic and parasympathetic activity * Lung volume

Answer 343

* Hyperventilation: decreases CO₂ > O₂ * Alkalosis: limited by movement of bicarbonate from CNS (1-2 days) and renal excretion HCO₃ * Increased 2-3,DPG - right shift O₂-Hb dissociation curve (early), then left shift at higher altitudes due to alkalosis * Alveolar hypoxia induces pulmonary vasoconstriction, then pulmonary hypertension * Decreased work of breathing 3 to pass

Answer 344

* Polycythaemia (increased EPO) * Increased viscosity of blood * Increased oxygen carriage * Pulmonary HTN resulting in right ventricular hypertrophy * More capillaries * Increased oxidative enzymes * Increased mitochondria 3 to pass

Answer 345

* **Hyperventilation** * **Mechanism: hypoxic stimulation of peripheral chemoreceptors (carotid bodies, aortic bodies)** * Low pCO2 and alkalosis work against this but CSF pH 'normalised' by movement of bicarbonate out of CSF and renal excretion of bicarbonate 'normalises' arterial pH taking this brake off.

Answer 346

* Headache * Fatigue * Dizzy * Palpitations * Nausea * Loss of appetite * Insomnia

Answer 347

* PAO2 is the alveolar oxygen partial pressure * PIO2 is the oxygen partial pressure of inspired air * PACO2 is the alveolar CO2 partial pressure * R is the respiratory quotient - CO2 production / O2 consumption, typically 0.8

Answer 348

Difference between **PAO2** (alveolar) and **PaO2** (arterial)

Answer 349

**V/Q mismatch** eg. shunting or dead space

Answer 350

* Located near ventral surface of medulla * **Rise in blood CO2 increases CO2 in CSF** * CSF has poor buffering capacity so pH changes rapidly * **Liberated H+ ions stimulate chemoreceptors (increasing pH has reverse effect)** * **Efferents stimulate medullary respiratory centre to increase ventilation and return CO2 to normal** * Chronic CO2 elevation gives normal CSF pH and insensitivity Bold to pass

Answer 351

* Located in carotid and aortic bodies that have high blood flow * Respond mostly to decrease in O2 below 100mmHg * Impulses transmitted to respiratory centre to increase ventilation * Responsible for all of the ventilatory response to hypoxaemia * Also responsible for small but rapid response to rise in CO2 and decrease in pH 3 to pass

Answer 352

* Diffusion * Carb-amino proteins * CO₂ to bicarbonate buffering 2 to pass

Answer 353

* **Bicarbonate** - 60% venous and 90% arterial * Carbamino - 5% arterial and 30% venous * Diffusion - 5% arterial and 10% venous Bold to pass

Answer 354

* Carbonic anhydrase only found significantly in red cells, major buffer for CO₂ and H⁺ * **Haldane effect** - Hb is also major buffer allowing faster H+/HCO₃^- dissociation * **Chloride shift** - allowing 70% HCO₃^- diffusion into plasma maintaining ionic neutrality / enhanced diffusion is mediated by Cl transporter in red blood cell memrbane * Hb protein is the major carbamino protein (better when deoxyHb as more negative charge) 1 to pass

Answer 355

* HCO₃^- diffuses easily out of the cell. * H⁺ doesn't because the **cell membrane is relatively impeccable to cations** * Therefore to **maintain cell neutrality** chloride diffuses from the plasma into the cell At least 1 bold to pass

Answer 356

* H⁺ + HBO₂ <-> H-Hb + O₂ * DeoxyHb binds more H⁺ than oxyHb and forms carbamino compounds more readily * Binding of O₂ to Hb reduces its affinity for CO₂ * **Enhances the removal of CO₂** from O₂ consuming tissues (eg muscle) into the blood. CO₂ can bind to amino groups on Hb to form carbaminoHb. CarbaminoHb is the major contributor to the Haldane effect * Promotes the **dissociation of CO₂ from Hb** in the **presence of O₂** (eg. the lungs) which is vital for alveolar gas exchange Bonus question

Answer 357

Note that oxygenated blood carries less CO2 for the same pCO2. Reasonable shape of the curve indicating the near linearity in the physiological range to pass

Answer 358

* The **graph moves upwards** indicating greater CO₂ content per unit pressure * Deoxygenated Hb binds more H⁺ and forms more carbamino compounds than oxyhemoglobin so venous blood carries more CO₂ than arterial blood * This is known as the Haldane effect

Answer 359

* Compliance = volume change/pressure change * Maximal in mid-inspiration, lower at extremes, approx 200ml/cm H2O

Answer 360

**Decreased** * Alveolar oedema * Pulmonary fibrosis * Pulmonary venous hypertension * Unventilated lung **Increased** * Age * Emphysema 3 to pass

Answer 361

* Increased lung compliance * Reduced work of breathing * Improved stability of alveoli * Keeps alveoli dry 2 to pass

Answer 362

* Surface tension of the alveoli (2/3rds) * Elastin / collagen fibres (1/3rd) * Alveolar surface tension depends on alveolar pressure, alveolar radius, surfactant

Answer 363

Higher at base than apex because apex is already more distended

Answer 364

* Sigmoid curve of intrapleural pressure vs volume, does not reach 0% lung volume * Shows lung volume is higher during deflation than inflation for any given pressure = hysteresis * Shows that lung contains residual air, without any expanding pressure (due to airway closure) * Shows that compliance decreases at higher lung volumes - lung becomes stiffer due to reaching limits of elasticity 3 to pass

Answer 365

* Voluntary - **cerebral cortex** * Automatic - **medulla** - pacemaker cells in pre-Botzinger complex * Pons - pneumotactic centre modifies medulla activity Bold to pass

Answer 366

* **Chemoreceptors - central and peripheral** * Central (ventral surface medulla) - **sensitive to changes in H⁺**. **CO₂** readily penetrates BBB and enters CSF and brain interstitial fluid. Increased CO₂ causes increased H⁺ in CSF, stimulating ventilation * Peripheral (carotid and aortic bodies) - fast response to **decreasing O₂**, stimulating bodies. Decreased pH causes carotid response only. Minor response to CO₂

Answer 367

* Pulmonary - stretch receptors in lungs, muscles, joints * Irritant receptors in airways and nose * Baroreceptors - stimulation may cause reflex hypoventilation * Pain/temperature - may cause initial apnoea then hyperventilation * Proprioceptors - muscle spindles from intercostals and diaphragm, other muscles/ tendons/ joints 3 to pass

Answer 368

* Blood brain barrier is permeable to CO²; relatively impermeable to HCO³ * Increased blood pCO² leads to increased pCO² and increased H⁺ in CSF which stimulates ventilation * Decreased H⁺ in CSF inhibits ventilation; causes cerebral vasodilation and enhances diffusion of pCO² into CSF Bonus question

Answer 369

200-400um below ventral surface of **medulla** Bold to pass

Answer 370

* Direct effect on **central and peripheral chemoreceptors** due to both **high CO₂** and **lower pH** * **Increase in rate and depth of ventilation** 4 of 5 bold to pass

Answer 371

* Located in the **carotid and aortic bodies** * They contain glomus cells with high concentrations of dopamine and high blood flow * **Respond to a decrease in PaO₂ and pH, increase in PaCO₂** * **Responsible for all the increased ventilation in hypoxia** - max response occurs PaO₂ < 50mmHg * Also rapid response to sudden changes in PaCO₂, while carotid body responds to a fall on pH

Answer 372

* Low arterial pH stimulates peripheral chemoreceptors to increase ventilation * Central chemoreceptors or respiratory centre itself may be stimulated in severe cases

Answer 373

* The airway volume with **ventilation and no blood flow** * The conducting airways (to division 16) **take no part in gas exchange** * Volume is approximately 150mls

Answer 374

* Anatomical dead space is determined by morphology of the airways and lung * Physiological dead space is the volume of airways and lung that does not eliminate CO2 * The two dead spaces of volume are **almost the same in normal subjects**, but the physiological dead space is **increased in many lung disease** due to inequality of blood flow and ventilation in the lung (VQ mismatch) Bold to pass

Answer 375

* Anatomical dead space - Fowler's method * Physiological dead space - Bohr's method Bonus question

Answer 376

Portion of the tidal volume that does not participate in gas exchange

Answer 377

* V/Q mismatch * Non-perfused alveoli and alveoli with excessive ventilation

Answer 378

**Gas exchange** * Increased respiratory uptake and consumption of O₂ and production and excretion of CO₂ - increases by 10-20 times * Increased lung diffusing capacity due to increased diffusing capacity of the membrane and the pulmonary blood volume * Decreased ventilation-perfusion inequality **Ventilation** * Increased respiratory rate * Decreased functional residual capacity * Increased tidal volume * Increased minute volume **Pulmonary blood flow** * Distention and recruitment of pulmonary vessels increases total cross-sectional area of the pulmonary vasculature * Increased total pulmonary blood volume * Increased cardiac output and pulmonary blood flow * Increased pulmonary vascular pressures * Decreased pulmonary vascular resistance **Other respiratory effects** * Increased respiratory exchange ratio (R) from 0.8 to 1.0 due to carbohydrate metabolism and may exceed 1.0 due to anaerobic glycolysis * The Hb-O₂ dissociation curve shifts to the right in the tissues and back to the left in the lungs * Additional capillaries open in peripheral tissues One from each bolded section and at least six to pass

Answer 379

* Arterial blood gases are little affected by moderate exercise but at high workloads pH falls due to lactic acidosis, PaCO2 often falls to compensate for the acidosis and PaO2 rises * Arteriovenous pH, PaO2, and PaCO2 differences increase Basic understanding to pass

Answer 380

Starling's Law * Hydrostatic pressure in the capillaries (positive outwards) - Pc * Hydrostatic pressure in the interstitium (probably negative and thus also outwards) - Pi * Colloid osmotic pressure in the capillaries (inwards) - πc * Colloid osmotic pressure in the interstitium (outwards) - πi * Net pressure probably slightly outward * Net fluid out = K(Pc-Pi) -σ(πc-πi) * K = filtration coefficient and σ = reflection coefficient (capillary wall barrier) Lymphatic drainage Alveolar epithelial cells Both pressure +1 other to pass

Answer 381

* Gases diffuse across a surface by passive diffusion * Fick's law says that the rate of diffusion is directly proportional to the area of the diffusion membrane, the pressure gradient across the membrane and the diffusion constant * It is inversely proportional to the thickness of the membrane Concept to pass

Answer 382

* A perfusion limited gas is one where the partial pressure on both sides of the membrane equilibrates rapidly such that no further diffusion into the blood can occur from the alveoli unless the blood perfusion rate increases. N₂O is an example * A diffusion limited gas is one where the partial pressure of the gas does not achieve equilibration in the time that blood spends in the pulmonary capillaries (0.75 seconds). CO is an example

Answer 383

* Passive diffusion * Determined by **Fick's law of diffusion** * Surface area, membrane thickness, gradient of pO2

Answer 384

* **Carbon monoxide** is used for measurement because **its uptake is diffusion limited** (not dependent on amount of blood available only on diffusion properties) * Single breath method test can be used

Answer 385

* Exercise * Alveolar hypoxia * Thickening of blood gas barrier

Answer 386

* Perfusion limited * Describes O2 and Hb combination and time frame of combination (0.3 seconds)

Answer 387

* **Hypoventilation** - eg. drugs (morphine, barbiturates), chest wall damage and muscle paralysis * **Diffusion limited** - impaired diffusion process of oxygen across the pulmonary capillary eg. exercise; thickened blood gas barrier state; low mixture O2 inhaled * **Shunt** - blood entering the arterial system without going through ventilated areas of the lung eg. AV fistula, congenital heart defect * **Ventilation/perfusion inequality** - most common. V/Q ratio determines has exchange for any respiratory unit. Hypoxaemia caused by V/Q mismatch cannot be eliminated with increased ventilation eg. PE 3 of 4 bold + 2 examples altogether

Answer 388

* PCO2 - the **CO2 dissociation curve is linear** at the working range. The increased ventilation is able to correct the PCO2 by increased CO2 output, particularly in units with high V/Q ratios * PO2 - the **oxygen dissociation curve is not linear**. So high V/Q areas can only boost their PO2 a little with increased ventilation. Conversely very low V/Q areas have proportionally lower PO2 (close to mixed venous). Overall PO2 is low.

Answer 389

* **Hypoxaemia (hypoxic hypoxia)** - arterial PO2 reduced * **Anaemic hypoxia** - arterial PO2 normal but Hb reduced * **Ischaemic / stagnant hypoxia** - blood flow and O2 delivery decreased * **Histotoxic hypoxia** - because of toxin cells cannot use it 3 to pass

Answer 390

* Disorientation * Confusion * Headache * LOC * Tachycardia * Hypertension * Hypotension * AMI * Arrest * Diaphoresis * Tachypnoea 2 to pass

Answer 391

* Cooling or warming air * Hairs in nasal passages * NO in paranasal sinuses is bacteriostatic * Lymphoid tissue in adenoids and tonsils * **Secretory IgA** in bronchi * **Ciliary escalator** * Coughing reflex * Release of prostaglandin E2 protects epithelial cells * Alveolar **macrophages** are phagocytic 5 to pass

Answer 392

* Synthesised: surfactant, fibrinolytic system for pulmonary vessels, prostaglandins, histamine, kallikrein * Inactivated: prostaglandins, bradykinin, adenine, serotonin, noradrenaline, acetylcholine * Activated: angiotensin 1->2

Answer 393

* Total lung capacity - 7L * Vital capacity - 4.5-5L * Residual volume - 1.2L * Functional residual capacity - 2.4L * Tidal volume - 500ml 2 to pass

Answer 394

* Spirometer for FEV1 and FVC * TV on ventilator * Helium dilution or body plethysmography for total lung capacity, functional residual capacity and residual volume

Answer 395

* **Tidal volume**: the volume of gas moved in and out of the lung during normal breathing - 500mls * **Vital capacity**: the exhaled gas volume after a maximal inspiration (5.5-6L) * **Residual volume**: the volume of gas remaining in the lung after maximal expiration (1.5-2L) * **Functional residual capacity**: the volume of the gas in the lung after a normal expiration (3L) 3 to pass

Answer 396

* O2 dissolved (0.3ml/100ml) * Most combined with heme protein in Hb (20.8ml/100ml)

Answer 397

* Upper - if PO₂ alveolar gas falls (eg. ARDS in acute pancreatitis) loading of O₂ is little affected * Lower - steep lower part means large amounts of O₂ unloaded at peripheral tissues for only small drop in capillary PO₂

Answer 398

* Increased temperature, PCO₂, 2,3-DPG * Drop in pH (increased H⁺) At least 3 to pass

Answer 399

* CO has 240 times the affinity of O₂ for Hb, hence oxygen saturation greatly reduced and Hb oxygen carrying capacity reduced. * CO also shifts O₂ dissociation curve to left, interfering with unloading of O₂

Answer 400

* **Ventilation** * **Perfusion** * **Diffusion across the blood gas barrier** * Alveolar-pulmonary capillary oxygen gradient 3 bold to pass

Answer 401

* **Alveolar pulmonary capillary O₂ gradient** (Alveolar pO₂ - 100mmHg, pulmonary capillary pO₂ = 40mmHg) * Blood gas barrier thickness is 0.3 microns * **RBC transit time = 0.75 seconds** * Under normal circumstances, **O₂ uptake is perfusion limited** (complete in 0.25 seconds) and **alveolar end capillary O₂ difference is minimal** * Rate of rise of end capillary PO₂ is steep - O2-H₂ dissociation curve 3 to pass

Answer 402

* **Alveolar pulmonary capillary O₂ gradient is decreased** * **O₂ diffusion is decreased** * Rate of rise of pO₂ for given O₂ concentration in blood is less

Answer 403

Influenced by gravity - 3 main zones * Zone 1 (apex) - PA>Pa>Pv - least blood flow * Zone 2 (mid) - Pa > PA > Pv * Zone 3 (base) - Pa > Pv < PA - most blood flow

Answer 404

* **Hypoxic pulmonary vasoconstriction** - alveolar hypoxia constricts pulmonary arteries, directs blood away from poorly ventilated diseased lung areas * Mechanism - NO, endothelin-1, thromboxane A2, low pH, autonomic system Bold to pass

Answer 405

* Starling's Law - difference in capillary and interstitial hydrostatic and colloid osmotic pressures * Significant increases in net outward pressure of Starling equation results in interstitial oedema especially at perivascular and peribronchial spaces * Further increases of outward pressure result in fluid entering alveolar spaces

Answer 406

* Decreases linearly from base to apex * Due to hydrostatic pressure * Under normal conditions, flow almost ceases at apex * Distribution more uniform with exercise * Explanation of West zones 1-3

Answer 407

Blood flow from base to apex is almost uniform but flow in posterior segments exceeds that in anterior segments

Answer 408

* **Alveolar hypoxia** * **Gravity** - 3 main zones * Vascular resistance - pulmonary HTN/PE * Pulmonary disease - asthma, COPD, infection, infarction, cancer, fibrosis, pneumothorax, chest trauma * Vasoactive substances - NO, endothelin, prostaglandin * Low blood pH leads to pulmonary vasoconstriction * Sympathetic stimulation leads to stiff pulmonary arteries leads to vasoconstriction Bold +2 others to pass

Answer 409

* Blood volume * Cardiac output * Atmospheric pressure * Temperature * Pathology - anaemia, cancer, infection * Exercise * Posture 4 to pass

Answer 410

* R = change in pressure/blood flow * Normally very low

Answer 411

* Increasing pressure as in exercise causes a reduction in resistance by recruitment and distension * Large lung volumes pull open extra-alveolar vessels but may narrow pulmonary capillaries so that resistance rises * Small lung volumes also cause increased resistance of extra-alveolar vessels because smooth muscles tone closes them if critical opening pressure is not reached * Hypoxic pulmonary vasoconstriction directs blood away from hypoxic lung 2 to pass

Answer 412

* Alveolar hypoxia constricts pulmonary blood vessels * Direct effect of alveolar PO₂ on smooth muscle * Important at birth * Directs blood away from hypoxic areas 2 to pass

Answer 413

* Slow increase in ventilation from top to bottom but not as much as perfusion. * Highest V/Q at apex

Answer 414

* **Hypoxia** - arteriolar smooth muscle to contract * Low pH * Autonomic * Passive factors

Answer 415

* **Change in lung volume per unit change in airway pressure - measure of lung "distensibility'** * Normally 200mls/cmH2O * It occurs because of the opposing inward elastic recoil of the lungs and outward recoil of the chest wall. * It is represented by the slope of the non-linear lung pressure-volume curve Concept to pass

Answer 416

* Age * Volume of the lung * Phase of respiration (lower in deflation/expiration than inflation/inspiration) * Surfactant 3 to pass

Answer 417

* **Compliance is increased** because of **loss of lung elasticity** * Destruction of lung connective tissue & elastin (easy to inflate but reduced capacity to recoil) * Patients have to force their expiration to expel air from lungs * Resultant increase in functional residual capacity Bold to pass

Answer 418

* Lowers alveolar surface tension * Increases lung compliance * Reduces work of breathing * Improves the stability of alveoli and keeps the alveoli "dry" 3 to pass

Answer 419

* **Recruitment** of normally closed (non-perfused) pulmonary capillaries * **Distention** at higher vascular pressures, from near-flat to circular cross-section capillaries Bold to pass

Answer 420

* **Lung volume**: when low, pulmonary vascular resistance increased, due to smooth muscle and elastic tissue contraction; when high, again rises due to capillary stretching and reduction in calibre * **Hypoxia**: increases pulmonary vascular resistance from pulmonary vasoconstriction * **Drugs**: increased by serotonin, histamine and noradrenaline; decreased by acetylcholine and isoprenaline Lung volume +1 other

Answer 421

* Arterial pressure * Venous pressure * Lung volume * Alveolar hypoxia * Vascular smooth muscle tone * Area of lung * Position change

Answer 422

* Very low pressure system - few resistance vessels * Easily distensible vessels * Recruitment * Only just enough pressure for normal gravity / position to get apical flow

Answer 423

* A low resistance system * Capacity for resistance to decrease with increased pressure

Answer 424

* Vascular resistance initially decreases as lung volume increases, then rises * At very low lung volumes (eg. lung collapse) must reach a 'critical opening pressure' (several cm H2) above downstream pressure) to enable any flow * Very high lung volumes, when alveolar pressure exceeds pulmonary capillary pressure, pulmonary vascular resistance will increase (pulmonary capillary squashed)

Answer 425

* **Physiological shunt of lung (PAO2 > PaO2)** * Blood enters arterial system without passing through a ventilated area of lung * Bronchial arterial blood flows to pulmonary veins * Coronary arterial blood flows to coronary veins then thebesian veins in left ventricle * Atelectasis in lung Bold +1 to pass

Answer 426

* Surfactant is a phospholipid. DPPC is an important constituent * Produced in type 2 alveolar cells. Lamellated bodies within them are extruded into the alveoli and transform into surfactant * Fast synthesis with rapid turnover * Formed relatively late in foetal life * With surfactant present, surface tension changes greatly with surface area. It falls to very low values when area is small * Molecules of DPPC are hydrophobic at one end and hydrophilic at the other. When aligned on the surface, their **repulsive forces** oppose the normal attractive forces between the liquid surface molecules

Answer 427

Pulmonary circulation is affected by gravity * **Apex**: less blood flow, larger alveoli, slightly less ventilation, **ventilation > perfusion, high V/Q ratio** * Middle: ventilation = perfusion, V/Q = 1 * **Base**: more blood flow, smaller alveoli, more ventilation, **perfusion > ventilation, low V/Q ratio** .

Answer 428

* **Pulmonary embolism** (high V/Q ratio) * Pulmonary oedema * Pneumonia * Emphysema (low V/Q ratio) Bold +1 to pass

Answer 429

**A-a gradient** (also V/Q scan, CTPA) Bold to pass

Answer 430

* Normally 5-10mmHg * A-a gradient = measure of the difference between alveolar and arterial concentration of O₂ * Even though PAO₂ at apex 40mmHg above base, **most of blood flow (Q) comes from base where PAO₂ is low** -> decrease in PaO₂ * **Shunt**: bronchial blood and coronary blood * Also non-linear shape of O₂ dissociation curve means that addition of small amount of shunted blood with low oxygen concentration greatly decreases PO₂ of arterial blood and units with high PO₂ have little effect on oxygen concentration because curve is flat at high oxygen concentration Bold to pass

Answer 431

* The concentration of oxygen (PO₂) in any respiratory unit is determined by the ratio of the amount of air getting to the alveolus (ventilation) and blood flow through the pulmonary capillary (perfusion) * V/Q ratio is 0.8

Answer 432

* **Ventilation increases** slowly from top to bottom of the lung, and **perfusion increases more rapidly** * V/Q perfusion ratio decreases down the lung * It is **high at the top** of the lung (where blood flow is minimal) and much **lower at the bottom** of the lung

Answer 433

* **Much greater influence on PO₂ than CO₂** * **O₂ dissociation curve non-linear**. Areas with high V/Q ratio add relatively little O₂ with increased ventilation. Whereas areas with low V/Q ratio have lower PO₂ (close to mixed venous) overall PO₂ is reduced * **CO₂ dissociation curve is linear** in the working range. Chemoreceptor stimulation increases ventilation and CO₂ output especially in lung areas with high V/Q ratios. Normal PCO₂ (minimal change) Bold + demonstrates understanding

Answer 434

* V/Q inequality impairs uptake or elimination of all gases * Majority of blood returns from lung bases where the oxygen saturation is low * Results in blood PO₂ being lower than that of mixed alveolar PO₂

Answer 435

* PCO₂ reduces much more than PO₂ increases * Hypoxia cannot be corrected by increased ventilation * Hypercapnia can be corrected by increased ventilation

Answer 436

* **Elastic forces** of the lungs and chest wall * **Viscous resistance** of the airways and tissues

Answer 437

* **Larger tidal volumes** increase elastic workload * Elastic workload is increased by **reduced compliance** due to: * Lung volume - a person with only one lung has halved compliance * Slightly lesser during inflation than during deflation * Increased tissue mass - fibrosis or pulmonary congestion or chest wall restriction * Loss of surfactant Must understand both bold points

Answer 438

* Higher respiratory rates increasing flow rates * Decreased airway radius due to: lower lung volumes; bronchoconstriction * Increased air density (SCUBA diving) * Increased air viscosity 2 to pass

Physiology Flashcards

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