foundation for physiology 2

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Hearing

sound waves - conversion of sound waves to mechanical in middle ear - electrical energy in inner ear - action potentials to brain. compression high pressure. rarefraction - low pressure. pitch - frequency, loudnes - amplification in decibels. f=v/wavelength. external ear - auricle, external auditory canal. middle ear - ossicles - malleus, incus, stapes. Inner ear - semicircular canals, vestibule, cochlea. 

sound waves - auditory canal - induce vibrations in tympanic membrane - vibrations acorss ossicles - oval window and inner ear (sounds waves to mechanical vibrations) - cochlea fluid vibrates - fluid and pressure differences over cochlear duct - sensory epithelium on basilar membrane vibrates - sheering forces between tectorial membrane and sterocillia - stereocillia deflect pulling tip link - openning of ion channels K influx - depolarisation - release of neurotransmittors.

cochlea - fluid filled (endolymph), converts mechanical to nerve signals via streocillia. contains sensory epithelium the organ of corti on the basilar membrane. also vestibular cavity and tympanic cavity. mechano receptor hair cells and supporting cells. one row 'inner' 3 rows 'outer'. convert mechanical energy to electrical impulses. actin filaments network cross linked by espin and fimbrin for support. 

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hearing 2

vascular and tympanic perilymph low in K and high Na opposite in cochlea duct endolmyph - high positive potential. gluatamate is the neurotransmittor released at base of hair cells into afferent neurones. KCNQ4 K channels open. K recyling - pass through gap junctions in supporting cells - return to stria vascularis - secreted into endolymph by stria vascularis. receptor potential not action potential! inner hairs - transformers, convert mechanical to electrical impulses. outer hair cells - amplify sound to enhance inner hair response, electromobility due to rapid size changes in response to sound protein prestin causes this, recieve many efferent nerve endings from brain, shorten when depolarised, lengthen when hyperpolarised. 

glutamate release - graded potential in afferent neuron end - specific sequence of action potentials to brain - along auditory nerve - cortex in brain for sound perception

deafness - conductive - sound waves not transferred to inner ear, causes - infection, wax, rupture tympanic membrane. sensorineural - sound waves not translated to nerve signals, cause defects in organ of cort or auditory nerve. age related - damaged hair cels dont regrow. hereditory - mutations in myosin, actin cross linking proteins and adhesion proteins affect sterociallia organisation + degeneration. espin mutation - hair cells degenerate upon hearing and vestibular dsyfunction due to Ca influx during transduction

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circulation

2 closed circuits - pulmonary and systemic circulation. vascular system - ateries and arterioles, veins and venules, capilaries. right ventricle to lungs, left to whole body so bigger. endothelium cells line whole circulatory system. pericardial fluid to reduce friction. 

superior + inferior vena cava from body - right atrium - ventricle via tricuspid AV valve - pulmonary ateries via pulminary semiluna valve - lungs. 

pulmonary veins from lungs - left atrium - left venticle via bicuspid AV valves - aorta via aortic semilunar valve- arteries to body. 

cardiac muscle - much shorter than skeletal msucles cells, not connected to bone or tendons. pores between cell membranes permeable to Na, Ca, K and Cl so each cell is electrically connected to each other. crossbridge contraction actin + myosin. 

heart beat - SAN right atrium - AVN (slight delay) - bundle of his - purkinji fibres. atrial systole (p wave), ventricular systole (QRS) , diastole (t wave). SAN and AVN dont have rapid depolarisation like the rest, no steady resting membrane potential as changing consistantly as always depolarising, 

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heart 2

ventricular systole - Na causes depolarisation, voltage gated channels, K plays same role as skeletal muscle. Ca responsible for contraction of cell to move tropomyosin. Pacemaker potential - 'funny K current, no resting potential, causes Ca to open and then close. cannot be restimulated during refractory period. ECG - p- qrs-t. qrs usually 0.3sec. 

systole - isovolumetric ventricular contraction (valves closed), ventricular ejection (valves open), end systolic volume. diastole - isovolumetric ventricular relaxation (valves cloes), ventricular filling 80% before atrial systole, end-diastolic volume. stroke volume = end diastolic volume - end systolic volume. lub closure of AV valves, dub closure of aortic and pulmonary valves. 

cardiac output + stroke volume x heart rate. typical SV = 70ml. Plasma epinephrine (adrenaline) affects heart rate so do sympathetic and parasympathetic nerves. control of stroke volume - frank-sterling mechanism, intrinsic control, when heart is fuller beats more forcefully due to changes in distance of myosin, actin overlap. sympathetic stimulation, extrinisic, e.g adrenaline - causes a stronger more rapid contraction and a more rapid relaxation. 

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circulation 2

blood composition 5.5L- red blood cells (membrane bound nonnucleated cells for blood clotting, erythrocytes) 99% of blood plasma - carry 02, contain heamoglobin and shift co2, haematocrit - fraction of blood volume thats red. white blood cells (leukocytes), platelets (cell fragments), plasma (55%). 

majority of blood found in veins as large + stretchy with low pressure so a gradient across organs. flow is dependant of pressure difference and resistance - F=P/R. difference in pressure is important not actual pressure values. blood flow is dependant on resistance which relies on fluid viscosity, length of tube and radius. poiseuilles law. diff radiuses in blood vessels so diff in pressure. higher in systemic than pulmonary circulation, pressure of blood returning to heart =O. compliance = change in volume/ change in pressure. compliance is important in circulatory sysetem as arteries need to change volume to reduce pressue so dont burst = store energy from heart. 

arterial pressure - can store constant pressure between heart beats for a mean pressure which is driving force for all blood! dependant on stroke volume, speed of ejection and arterial compliance, typically represented as systolic pressure/ diastolic pressure which gives pulse pressure. 

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circulation 3

arterioles - determine relative blood flow to organs. regulate diameter to control vlood pressure + flow to body controlled by smooth muscle regulation. 

control of arteriolar blood flow: local controls where arteriole changes pressure/size - active hyperemia (response to metabolic demand changes), flow autoregulations (when arteriole pressure drops), reactive hyperemia (pins +needles), response to injury. Extrinsic controls - sympathetic and parasympathetic nerves, hormones in blood. vasoconstricts and dilates to accomodate controlled by nerves, hormones or local ions/pressure. 

capillaries - 5% of circulating blood, monolayers of endothelial cells, no smooth muscle, exchange gases, nutrients and metabolic products. leaky so white blood cells +plasma can get out except in brain due to BBB. 

relationship between flow velocity and cross sectional area - speed drops quickly. 

veins - low resistance to flow, low pressure, diameters respond to changes in blood flow, vlaves prevent back flow, skeletal muscle pump, most systemic blood in veins. 

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transport of ions

cellular compartmentalisation - lipid membranes are essential compartment barriers. permeable for: gases, small non-polar and uncharged molecules e.g steroids, ethanol and slightly water and urea. diffusion - driven by concentration gradient. ficks law - surface areas, conc gradient and diffusion gap width (permeability coefficient). transport systems for non-diffusible molecules - enhance tranposty, define specificity, control direction. 

osmosis - conc of 1l pure water - 55.5 M. addition of solutes reduces conc of water e.g 1m of solute - 54.5M. osmolarity: conc of solutes per volume, also defines conc of solute particles, regardless of chemical composition. 1osmol = 1 mole of solute particles. 1mole NaCL - 2Osm as Na and Cl ions.

osmosis: net diffusion of water across a membrane caused by tendancy to generate an equilibrium state = state of minimal energy, depends on conc of solutes. when membrane permeable solutes - solutes move so equal concentration and volumes unchanged. with non-permeable solutes water moves so volumes change. hypertonic solution, higher Osm value outside cell shrinks. Isotonic - no change. Hypotonic solution, lower Osm value cell swell. osmotic pressure - necessary to balance the osmotic flow of water. water - polar molecule, aquaporins (water specific transporters) facilitate transport of water to speed it up. 

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transport 2

facilitated diffusion - e.g glucose tranport by GLUT1-transporters. protein transporter conformational changes. transport depends on glucose gradient, transport only downhill down conc gradient. GLUT1 - tissure specific, substrate specific, substrate affinity. 

faciliatated diffusion: uniporters. rate of transport higher, transported molecule never enters the lipid bilayer, transport is reversible. facilitated diffusion: requires proteins. follows gradient, no energy required. uniporter: glucose, channels: H20, Na, K, Ca, Cl. has limited maximal flux rates due to protein. when ions pass through channel - hydration water molecules are stripped off, selectivity silter binds ions due to size, carbonyl oxygens are part of bind domain. can have N-type inactivation e.g KV1.4 transporters or C-type inactivation e.g HERG channel transporters (both transport K) conformational changes of protein structure in both. 

active transport - against gradient, coupled to ATP hydrolysis, small hydrophilic molecules. Na,K ATPase pump, 3Na out 2K in ATP hydrolysis provides energy. Na and ATP bind - phosphorylation of aspartate (ADP released) - conformational change - Na released K binds - dephosphorylation and conformational change - K released. Ca ATPase in sarcoplasmic reticulum of muscle cells transport 2 Ca ions, similar to Na/K ATPase. 

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transport 3

type of ATP powered pumps.P-class pumps - e.g Na/K, Ca, H/K and H pumps in plasma membrane of eukaryotes, plants and fungi and sarcoplasmic reticulum.

V-class - H ions vacuolar membrane in plants yeast and fungi, endosomal and lysosomal membranes in animal cells and plasma membrance of osterclasts (acid secreting cells) and some kindey tubule cells.

F-class - H ions bacterial plasma membrane, inner mitochondrial and thylakoid membrane of choloroplasts.

ABC superfamily - important for medicine, bacterial plasma membrane and endoplasmic reticulum (amino acid, sugar and peptide transporters), mamalian plasma membranes (transporters of phosopholipids, small lipophilic drugs, cholesterol and other small molecules). 

secondary active transport - existing gradients drive transport. Energy for transport of ligand A is provided by gradient of ion B. Uniporter, symporter or antiporter. symporter - e.g 2 Na/ glucose transporter, simultanous binding, conformational change, release of both, reversion to original structure. Antiporter - e.g Cl/HCO3 antiporter, anion antiporter AE1, essential for co2 transport in blood, direction depends on conc of ions

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transport 4

uniporter - GLUT-1, glutamate, gradient coupled, specific, saturability rate 1-10^2. Symporters e.g SGLT1 and 2, neutrl aminoacids, Na/H, gradient coupled, same direction, specific, saturability rate 1-10^2. Antiporters - e.g Na/Ca and Cl/Hco3, gradient coupled, opposite direction, specific, saturable rate 1-10^5. 

facilitated diffusion of glucose. GLUT 1-5. GLUT 1-4 do glucose. GLUT 5 and 2 do fructose. 2 - liver and intestine. 4 - muscle, adipose tissue. 5- intestine. Na coupled transport of glucose SGLT1 and 2. 1 does 2Na molecules, 2 does 1 molecule of Na. 1 does galactose aswell. 1 in intestine and kidney, 2 just kidney. 

summary - primary active transport - transport independant of gradients ATP as energy. Ion channels and facilitated - gradients drive transport, direction is definined by gradient. Secondary active transport - gradient drives transport, transporter defines specificity. 

combination of transport mechanisms (transcellular transport) e.g Na through epithelial cells from lumen to blood needs import of Na using ion channel and generation of Na gradient using Na/K ATPase. same for transcellular transport of glucose to blood - active transport of glucose (Na/glc symporter) - generation of Na gradient (Na/k ATPase) - facilitated diffusion (GLUT2 uniporter)

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Kidney

filtrates plasma - entire plasma 3L, every 20 mins, 180L a day. 

functions: excretion of metabolic waste - ammonium to urea from catabolism of proteins, uric acid from nucleic acids, creatinin, small peptides e.g hormones, toxins and drugs. REgulation of extracellular volumes - control of water reabsorption and control of osmoregularity (Na) in tissues. Regulation of electrolytes. Control of acid/base balnce regulation of HCO3 and H. control of arterial pressure by hormones renin, angiotesnin 1 and 2 and by filtration. Production of hormones e.g erythropoetin and hormones for calcium metabolism . Gluconeogenesis produces glucose from glycerol and amino acids. 

basic functions - filtration, secretion and absorption. compartmentalization. Outer layer cortex, inner core medulla, ureter tube to urinary bladder. Nephrons are major elemnts composed of glomerulus for filtration, loops of henle. Juxtemedullary nephron goes through medulla and cortex, cortical only in cortex. nephron central filtration unit 0.8-1.5mil, 0.1ml filtered by nephron/day. input: blood via capillaries, output: filtrate via tubular system. 

Glomerular filtration: blood from afferent arteriole goes into bowmans space/ glomerulus through glomerular capillary which is a really long blood vessel in the capsule. endothelial cells make blood vessels - in glomerular capillary cells are podocytes. 

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kidney 2

filtration happens all along glomerular capillary, filtrate is collected in bowmans capsule. Filtrate is pressed into the tubular system for transport. Blood pressure drives filtration. Filtration barrier - 2 cellular elements; podocytes and capillary endothelium. and 2 exrtacellular structure; slit diaphragm and glomerular basement membrane. capsular space is after filtration which is free of proteins, product of filtration is here called primary filtrate. 

GBM supra-molecular aggregate of multiple proteins, collagen 4 is the stable network, laminins are non covalent gel-like filters, perlecan is non-covalent dense filter and nidogens are cross linkers which hold it all together. Slit diaphragm has pores but proteins cant get through. GBM barrier for blood cells, slit barrier for large molecules, nehrinin is the protein which mainly filters. cellular layers endotheliual cells and podocytes (foot preocesses) also filter. Filtration is selective for size and charge. 

diseases; defect in GBM causes Alport's disease collagen 4 is affected, symptoms hematuria, kidney failure, other organs affected. defects in slit diaphragm - hereditary proteinuria syndrome, symptoms : proteinuria and nephrotic syndrome. 

net filtration pressue = 16mmHg. globular filtration rate is volume of fluid filtered by the glomeruli per time. GFR is defined by pressure, surface area and permeability of membrane

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kidney 3

kidney 180L/day. all other capillaries 4L/day. control of GFR: dilation and constriction of afferent/efferent capillaries. contraction of mesangial cells. constriction of afferent decreases blood pressure and GFR, contriction of efferent increases both and vice versa. 

primary filtrate generated in glomerulus is collected in bowmans capsule - osmolarity is 300 Osmol/L - transported to proximal convoluted tubule. 

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gas exchange

units for pressure - 1atm = 760 torr = 760mmHg = 1x10^5Pa = 1 bar. mmHg is the pressure exerted at the base of a column of fluid exactly at 1 mm high when the density is 13.6g/cm^3 when gravity is 9.81m/s^2. partial pressure = total pressure of gases x fractional conc of gas. Po2 at sea level - 159mmHg.

crossing membranes is not rate limiting for gases, major limitation is getting through the tissue water. co2 diffuses way quicker than 02. path length also affects diffusion. conc of dissolved gas is directly proportional to the pressure of the gas at the surface. henrys law - partial pressure = henrys law solubility coefficient x molar conc. solubility of 02 in water is poor. but much better in blood 0.3ml - 20.4 ml. 68 more time o2 contained in blood.

Erythrocytes contain heamoglobin and binds 02 which is transported by proteins. myoglobin - monomer muscle storage of o2, hemo - tetramer erythrocytes transport o2. heme has planar structure and a central Fe ion which defines a specific chemical microenviro which modulates, specificity, affinity and rate of ligand binding and enables regulation. 6 coordination sites for polar atoms 4x heme, 1x proximal histine 1x free coordination site for ligand. distal his modifies the ligand binding pocket. 

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gas exchange 1

relative saturation depends on o2 pressure. low levels of 02 - dissasociation, high levels - uptake. myoglobin - simple binding curve only 1 o2 bound. hemo - 4 can bind, sigmoidal binding means the more 02 bound - the more 02 can be bound due to cooperative effect of subunits - allosteric effect. Ph bohr effect - acidity enhances release so shifts curve to right results in lower 02 affinity. e.g acitve muscle - lowered ph increased H, more o2 released as in muscle glycolysis produces acids so oxygen supple needed by oxidative phosphorylation. hemo acts like buffer taking up H ions. Co2 makes haldane effect where co2 binds and causes release of 02, because binding of c02 stabilizes salt bridges lowering affinity for o2. 

effect of BPG - heterotrophic allosteric modulator of hemoglobin activity. only binds in low affinity T-state to improve binding affinity for 02 and improves oxygen release and supply at low p02. protein part of globins define: affinity for o2, needs for storage and transport, needs for binding and release, regulation by H and CO2, tissue specific distribution, developmental distribution, adaption to specific conditions (low o2 pp, high altitude, deep sea and embryo), stability and turnover, conc of large amounts of o2 binding priteins e.g hemo in erthrocytes, needs for PH buffering as Hb is ph buffer. evolution from ancesteral globin - diversity of myo and hemo then alpha and beta chains in hemo. 

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respiratory mechanisms

functions - regulate bloods hydrogen ion conc (ph) with kidneys. phonation (forms speech sound), defense against microbes, influeneces arterial conc of chemical messengers by removal, traps and disssolve blood clots from systemic veins, conversion of angiotensin, elastic protection of heart and buffer of blood volume. upper respiritary tract - nost, pharynx and larync lower - pleural sac, lung, thorax and diaphragm. Thrachea, bronchi and brochioles. 

alveoli have pulmonary arteriole and venule and capillary network around them. Rapid exchange due to short distance blood - air <1um and large surface area of alveoli. get alveoli type I and II cells. site of gas exchange, gas goes through cellular components - endothelial cells and alveolar epithelium and extracellular componenets - Aveolar basement membrane and surfactant. 

ventilation: air goes from high pressure to low pressure Boyles law (pressure exerted by a constant number of gas molecules is inversely proportional to the container volume). difference in pressure in alveoli and nose/mouth region. Flow = pressure/resistance. inspiration - ribs out diaphragm contracts and moves down. opposite for expiration. intrapleural pressure lower than intra-alveolar to inhibit collapse of lung if burst. 

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respiratory mechanisms 2

inspiratory reserve volume: maximum amount of air that can enter lungs in addition to tidal volume - 2500ml. vital capacity - 4000ml. tidal volume: during one breath at rest - 500ml, Expiratory reserve volume - maximum hat can be exhaled beyond tidal - 1000ml. Residual volume - remaining air in lings after maximal expiration - 1200ml. total volume - 5000ml. 

Pulmonary compliance - stretchability, volume change due to pressure change. dependant on - structural elasticity of tissue structure and ECM components e.g elastin (elastic component) and colllagen (non-elastic) this gives resistance of the the tissue against stretching. And surface tension of fluid in alveoli, air cell interfaces are covered by surfactant fluid, large surfaces of fluid. resistance of water surfaces against stretching. 

surfactant - surfaces of alveoli in contact with air are covered by thin film of fluid. surface tension - water molecules interact causeing drops (minimal energy) and have attractive forces to resist stretching. alveolar interphase: air-water film - cell. law of laplace: p = 2 surface tension (T)/ radius of alveoli. when radius is constant p squiggle 2T. reduction in surface tension will increase compliance. for efficient breathing resistance has to be overcome surfactant does this - mixture of phospholipds and protein, secreted by type II cells, secreted more during deep breathing. Lowers surface tension of water layer on alveoli. deficiency causes lung collapse from low lung compliance and reduced inspiration

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breathing

pulmonary fibrosis - inhilation of dust, asbestos etc, immune cells cant destroy them, form scar-tissue and deposition of ECM proteins, fibriotic tissue reduces elasticity and ihilation becomes difficult. pulmonary emphysema - smoking, elastic fibres destroyed, elasticity increases and ihilation easy, exhalation difficult and needs muscle contraction. Aging - ages connective tissue altered compliance. 

actial partial pressures in alveoli: because of mixing new inhaled air with old gas being removed P02 is lower and Pc02 is higher than in atmosphere. P02 - 105mmHg pCO2 - 40mmHg in alveoli and in atmosphere 02 - 160mmHg and Co2 - 0.23mmHg. gas goes from high partial pressure to low. inspirated air - 02 - 160 co2 - 0.3. expired air - 02 - 120 c02 - 27. co2 higher pressure in tissue so leaves tissure opposite for 02. 

regulation of respiration - sensors; chemoreceptors detect p02, pc02 and ph. propriorceptors (stretch sensors) in lungs, muscles and joints. central chemoreceptors in medulla, aortic and cartoid sinus chemoreceptors in heart detect gas conc and effect muscles in lungs to change lung ventialtion. input to respiratory centres in medulla oblongata and pons modify resp. reactions - acclimatisation: optimizing o2 supply in hypoxic conditions. adaption - long term optimization of o2. deterioration - progressive decrease of functionality in high altitudes. more erythrocytes EPO and HG in reduced 02.

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gas exchange 2

fetal hemo has loads of gamma and alpha but not much beta. after birth beta increases and gamma decreases, so fetal hemo has more affinity so can get o2 from mothers blood. llama hemo even higher as live at high altiditude so low o2 levels and myoglobin is highest as storage for o2 for high demand muscles.

carbon monoxide poisnening - CO compete for binding to the heme, block 02 binding and transport 200 times better at binding to heme in myo/hemo, so at much lower concs of CO the same level of binding is reached. at CO conc of 0.1%, 50% of all hemo will be loaded with CO. body produces CO2 at 200-800ml/min. is transported by : being dissolved in blood, formation of bicarbonate ions or attached to proteins (carbamino compounds). 

bicarbonate is an extracellular buffer. levels are contolled by kidneys (by regulating reabsorption and syntheses) and erythrocytes. tissues and cells contain loads of zinc-containing enymes carbonic anhydrase. Partial pressure of CO@ directly influences conc of HCO/H. acts in equilibrium with air creating an open system. at normal plasma pCO2 = 1.2mmol/l as non-enzymatic reaction to h2CO3 as no CA enzyme in plasma. eythrocytes has plasma level of 24mmol/l bicarbonate. so ph remains 7.4. decrease of H2CO3 causes a decrease of pCO2. decrease of CO2 is compensated by decreased breating which causes retention in blood. 

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