Cellular physiology Flashcards

Question

How is a heartbeat initiated?

Answer 1

The activity of the pacemaker cells in the sinoatrial node (in the right atrium) 1. The SA node spontaneously generates action potential 2. the action potential propagates homogeneously across the atrial walls 3. the action potential is delayed at the atrio-ventrcularh node (AV node) 4. the action potential is propagated rapidly along the Purkinje fibres to activate rapidly the ventricles. initially these originate as a single tract from the AV node (bundle of His) before dividing into two bundles and then as separate fibre bundles

Answer 2

P wave – atrial depolarization QRS complex – ventricular depolarization T wave – ventricular repolarization ``` PR interval (0.12 – 0.2 seconds) – determined by the delay of the impulse at the AV node (if this is prolonged it indicates heart block) QRS complex time (0.08seconds) - time for the depolarizing wave to activate the ventricles (if this is prolonged, it indicates imparied Purkinje conduction) ``` QT interval (0.25-0.4 seconds) – mean duration of the ventricular action potential (affected by many physiological and pathological factors) ST segment – an isoelectric region on the ECG indication no net flow in the heart. The ST segment shows characteristic changes during certain cadiac diseases

Answer 3

Heart valves ensure unidirectional flow from heart atria to ventricle to either aorta or pulmonary artery Right side. Blood flows from the great veins (superior and inferior vena cavae) and right atrium through the TRICUSPID to fill the right ventricle. When the right ventricle contracts blood flows through the PULMONARY VALVE to the lungs. Left side Blood flows from the pulmonary vein and left atrium through the MITRAL VALVE to fill the left ventricle When the left ventricle contracts blood flows through the AORTIC VALVE to the aorta.

Answer 4

1. electrical activity precedes the contractile events: - the P wave precedes atrial contraction - the QRS complex precedes the onset of ventricular contraction - the T wave precedes ventricular relaxation. 2. opening and closing of valves depends on pressure changes - At the beginning of ventricular contraction the mitral valve closes and pressure rises until it equals arterial pressure when the aortic valve opens and ejection begins. - At the beginning of relaxation the aortic valve closes and ejection is terminated. Ventricular pressure falls rapidly until it equals atrial pressure. The mitral valve opens and filling of the ventricle begins. 4. Heart sounds are associated with the cardiac cycle. The first sound occurs at the beginning of ventricular contraction. The second sound occurs at the end of ventricular contraction. 5. Changes in the veins mirror changes in the atrium: - the a wave – atrial systole - the c wave – the beginning of ventricular systole - the v wave – end of systole

Answer 5

1. The P wave (80ms) - depolarisation of the atria 2. isoelectric line between P wave and Q coincides with the depolarisation of the AV node, bundle branches and Purkinje system 3. QRS complex (100s) - Q goes from isoelectric line downwards, then R is a large upwards line (1mV) and then S goes downwards past the isoelectric line represents the depolarisation of the ventricles - it is big because ventricles are a large muscle mass 4. the intervals between S and T is on the isoelectric line because all the myocardial cells are at the same potential 5. T wave is the repolarisation of the ventricular myocardium, this represents ventricular relaxation the whole cycle is around 600ms the distance from the end of the S line to the end of the T wave is around 300ms

Answer 6

Osmotic pressure is the hydrostatic pressure of the solution that is just sufficient enough to prevent the movement of water into a solution across a semi-pereable membrane it depends on the number of particles present per unit volume of solvent and not on their chemical make-up (Pi = MRT) it plays an important role in the transport of molecules across membranes. the osmotic pressure of a solution is expressed in osmolality and is related to the number of particles present per kg of solution

Answer 7

intracellular (67%, 28L) extracellular = plasma water, 2.8L, 7% (blood) + interstitial water (water outside blood 27%, 11.2L vessels that bathes cells ) + lymphatic fluid

Answer 8

connective tissue (mainly collagen) proteoglycan filaments ultra filtrate of plasma

Answer 9

water of the interstitial fluid hydrates the proteoglycan filaments to form a gel so that in normal kisses there is very little free flowing liquid

Answer 10

dilution of Evans Blue - it does not pass across the capillary endothelium into the interstitial space

Answer 11

- physiologically inert | - evenly distributed in that compartment

Answer 12

= heart rate x stroke volume the volume of blood pumped from the ventricle in one minute usually 4-7L/min HR = the number of beats per min SV = the volume of blood pumped from the heart per beat - it depends on resistance, the more resistance, the greater the contraction needed to maintain the same CO

Answer 13

• The heart beats spontaneously, and has an inherent rhythmicity independent of any nerve supply • Excitation is initiated by a group of specialized pacemaker cells in the sinoatrial node • Action potentials initiated in the SA node travel throughout the whole myocardium • Ventricles – the action potentials are conducted rapidly via the bundle of His and its branches via the Purkinje fibers to the myocytes • The action potentials recorded from the atria, ventricles and conducting system have a fast initial upstroke followed by a prolonged plateau phase o The plateau phase ensures that the action potential lasts along as the contraction and ensures unidirectional contraction of the myocardium

Answer 14

it is the movement of water through a semi-permeable membrane from an area of low osmotic pressure to high osmotic pressure

Answer 15

Characteristics of the myocardium - regulate by neural and hormonal factors 1. heart rate 2. myocardial contractility characteristics of the heart and vascular system 3. preload 4. afterload

Answer 16

preload - the greater the EDV - the greater the preload - the more forceful the cardiac contraction - greater the output output

Answer 17

afterload - increase in after load only causes a transient fall in stroke volume (the blood ejected from LV/heart beat) - the venous return remains the same and so the preload increases (as there is more blood in the ventricle as less was ejected but the same amount returned) - the increased preload increases the force which the left ventricle contracts and normal stroke volume is restored and so CO is constant

Answer 18

if resistance increases, the heart has to contract more forcibly to maintain the cardiac output

Answer 19

The output and the input of the heart are the same the input of the right ventricle and the output of the right ventricle is equal to the input and output of the left ventricle

Answer 20

a muscle stretched at rest will produce a greater contraction up to a certain point due to the sliding filament theory In dystole there is passive increase in force due to elastic rebound. Systole – increase in the active force due to muscle contraction. (longer sarcomere – more cross links – increased force). Cardiac myocytes have also higher affinity of troponin for Ca2+.

Answer 21

number of beats per minute

Answer 22

amount of blood pumped from the heart per beat SV = EDV - ESV = the amount of blood in heart prior to heart beat - the amount of blood after heart beat

Answer 23

CNS: brain, spinal cord PNS: somatic, autonomic somatic - sympathetic, parasympathetic autonomic - sympathetic, parasympathetic, enteric

Answer 24

Action potentials are propagated along the axons by local circuits UNMYELINATED: continuous conduction (wave of depolarization, opening and closing ion channels) – like current flow. MYELINATED: saltatory conduction – current can only cross the membrane at the nodes of Ranvier. Faster conduction because of myelin gives insulation and this decreases capacitance of the axon membrane.

Answer 25

The activity of the sodium pump leads to the accumulation of K+ ions inside the cells. Membrane is largely impermeable to Na+ ions (unable to replace loss K+ ions). The resting membrane potential in mainly determined by the K+ gradient across the plasma membrane. Some K+ leak out of the cells via K+ channels in the plasma membrane. In quiescent cell – membrane potential = resting membrane potential. As the K+ diffuse out of the cell there is a build-up of negative charge inside the cell – membrane potential. K+ ions tend to move down their conc gradient out of cells. This is offset by the negative membrane potential, which attracts K+ ions into the cell. When two tendencies exactly balance = K+ equilibrium potential. Nernst equation! -mammalian skeletal muscles (rest) = -90 mV, are excitable -hepatocytes = -40 mV, non-excitable.

Answer 26

Motor nerve AP – Ach secretion by nerve endings – End-plate potential – muscle action potential – depolarizes T tubules and open Ca2+ channels in SR – increase in Ca2+ level – contraction – pumping Ca2+ into SR – relaxation. The contractile respond is initiated after the muscle AP and lasts much longer than the AP. Latent period – Contraction period – Relaxation period.

Answer 27

CARDIAC MUSCLES are connected end to end at the intercalated discs for mechanical and electrical continuity, at desmosomes (fascia adherens) and gap junction – forming myocardium, functional syncytium. Muscle cells are electrically coupled and depolarization of one cell (SA node-dominant pacemaker) causes current to pass between cells for depolarization. Current spreads across a whole population of cells. They have intrinsic rhythm that is modulated by Aps in autonomic nerved (myogenic contraction). AP are longer than in skeletal muscles due to influx of Ca+ ions (voltage gated), forming long plateau. And relaxation period is build up in APs. SKELETAL MUSCLES are activated by AP in the motor nerves (neurogenic contraction) – somatic NS and it is under voluntary control. They are supplied by nerve fibers that are myelinated (from CNS). When it enters muscle it branches so that one motor axon makes synaptic contact with a number of muscle fibers. The motor neuron, its axon and all the muscle fibers supplied by the axons it branches forming a motor unit. If frequency of AP is high, contractions can summate and forming fused tetanus. This not seen in cardiac myocytes.

Answer 28

Autonomic NS innervate smooth muscle of internal organs and glands and is self regulatory. Sympathetic and Parasympathetic. In both neurons are arranged in series that communicate between CNS and the effector organ (preganglionic neurons - cell bodies in CNS, postganglionic – cell bodies in peripheral ganglia). Communicate via synapses in peripheral autonomic ganglia. PARASYMPATHETIC (cranial – brain stem and sacral outflow: S2,3,5) Originate in the brain stem and sacral spinal cord. Preganglionic fibers are fairly long and terminate in ganglia close to or with the effector organ. Sacral preganglionic neurons do not join with the spinal nerves but with other parasympathetic preganglionic neurons. Axons of the cranial portion originate from cranial nerve nuclei and travel with axons in the cranial nerves. SYMPATHETIC (thoracic and lumbar, L1,2,3 outflow) Originate in grey matter of the lateral horn. Fibers pass via the white rami to the sympathetic ganglia, which are segmentally arranged and lie each side of the spinal cord. Ganglia linked together to form the sympathetic chain. Two sympathetic trunks Sympathetic ganglia distributed down (segmentally as far as coccygeal, except cervical region. They have shorter preganglionic efferent nerves, except adrenal medulla. Some organs have only sympathetic supply, adrenal medulla, sweat glands, spleen …

Answer 29

DORSAL COLUMN SYSTEM • Large diameter afferents therefore fast conduction velocity • Intensity and localization of mechanical stimulus (touch, pressure, movement against skin, position sense). It ascends ipsilateral to stimulus in dorsal column to dorsal column nuclei in medulla, cross the contralateral side in medial lemniscus and ascend to thalamus, synapses and ascend to sensory cortex. ANTERO-LATERAL (SPINOTHALAMIC) • Small diameter afferents – slower conduction velocity. • Touch, pressure but less localized, poor stimulus discrimination. • Temperature and noxious information Neurons may ascend few segments in Lissauer’s tract but form synapse with 2nd order neurons in dorsal horn (SG), cross to opposite side of cord and ascend in anterolateral quadrant of cord to thalamus and synapse to ascend to sensory cortex.

Answer 30

- main nt ACh, NA - sympathetic NS pre ACh, post NA -parasympathetic pre ACh, post ACh ACh - nicotinic receptors in autonomic ganglia ACh - muscaranic receptors in target tissue NA - acts on beta and alpha adrenoreceptors that are in most tissues and cells alpha-adrenoreceptors is contraction of smooth muscle beta-adrenoreceptors causes the relaxation of smooth muscles in the heart, activation of beta-adrenoreceptors to increase the HR and produce more forceful muscle contractions

Answer 31

both parasympathetic and sympathetic NSs innervate a tissue that work to produce opposing effects e.g. heart rate

Answer 32

pulmonary circulation: lung, left heart, pulmonary vein, aorta systemic circulation: tissue, right heart, pulmonary artery - most of the systemic capillary beds are arranged in parallel (except the hepatic portal system spleen -> liver) - each capillary bed receives blood directly from left ventricle - the flow to each individual capillary bed can be altered selectively as the body demands - -resistance determined the regulation of flow, where vasoconstriction increases the resistance

Answer 33

- greatest cross-sectional area -the walls have the largest surface area (of all the blood vessels) - capillary walls are permeable to nutrients and tissue waste products - lowest mean velocity of blood

Answer 34

MABP = diastolic pressure + 1/3(pulse pressure) pulse pressure = systolic pressure - diastolic pressure

Answer 35

Q = cross sectional area x velocity L/min it is constant, whereas velocity varies with vessel diameter Q = the cardiac output = the system flow

Answer 36

at the arterioles, there is the largest proportional pressure drop and so maximum resistance at the arterioles

Answer 37

flow (Q) is dependent on the pressure gradient delta P = Q x resistance (like V = IR, when I is the flow of current and Q is the flow of blood)

Answer 38

properties of the blood and properties of the fluid | R = change in pressure/Q

Answer 39

systemic pressure change = MABP - RAP mean arterial blood pressure - right atrial pressure pulmonary pressure change = mean pulmonary arterial pressure - left atrial pressure

Answer 40

systemic resistance = (MABP - RAP)/ cardiac output

Answer 41

pulmonary resistance = (MPABP - LAP)/ cardiac output

Answer 42

Pouiseulle's Law Q = change in pressure / resistance = (change in pressure x pi x r^4) / (8 x blood viscosity x length of the vessel) if the radius increases, the resistance goes down if the viscosity increases the resistance goes up radius changes have the greatest effect on resistance

Answer 43

in arterioles | the vascular radius is changed through vasoconstriction and vasodilation

Answer 44

relative to water (nrel = 1) for water | average nrel = 3

Answer 45

their viscosity is higher

Answer 46

the flow (Q) = (change in pressure x pi x r^4) / (8 x viscosity x length) the main factor affecting viscosity is haematocrit = the proportion of total blood volume occupied by erythrocytes (usually 0.4 - 0.47) hypoxia increases the number of red blood cells, so that the body can carry more oxygen around the blood this makes the blood more viscose so the heart has to work harder ignored to produce the same flow, the same cardiac output

Answer 47

the heart - prior to atrial systole, blood has been flowing into the atria via the vena cavae and passively into the ventricle from the atria via the AV valve (mitral valve) - during atrial systole, the atria contracts and only a small amount of blood is ejected into the ventricles - atrial systole is over before the ventricles start to contract atrial pressure - the 'a wave' of atrial pressure rises atrial contracts - atrial pressure drops when the atria stops contracting - blood arriving at the atrium can not enter atrium and so it backup in the jugular vein causing the first jugular venous pulse ECG - impulse from the SA ode results in depolarisation and contraction of the right and then left atra - P wave = atrial depolarisation - PR segment is electrically quiet as the depolarisation proceeds to the AV node so that the ventricles can fill completely with blood heart sounds - S4 is abnormal and is associated with atrial emptying after atrial contraction due to hypertrophic congestive heart failure, massive pulmonary embolism, tricuspid incompetence or for pulmonale

Answer 48

1. atrial systole - P wave 2. isovolumetric contraction = beginning of systole - AV valves close when ventricular pressure > atrial pressure - SLV (aortic, pulmonary) open - ventricular systole = QT interval - as ventricles contract, the volume is constant but pressure builds until the ventricular pressure > aortic and pulmonary artery pressure - electrical impulses travel fro =m AV node through Bundle of His and Purkinje fibres (contraction from apex to base of heart) - QRS = ventricular depolarisation (masks atrial repolarisation) - S1 sounds 'lub' is closing of AV valves 3. rapid ejection - SLV valves open at the beginning of ventricular systole - no ECG - ventricle continue contracting until the ventricular pressure > aortic pressure and the SLVs open - > blood flows into aorta from LV and into the pulmonary artery from the right ventricle - aortic pressure peaks as blood flows into aorta - ventricular volume rapidly decreases ``` 4 reduced ejection = end of systole - arterial pressure decreases - ventricular volume decrease - when VP S2 sound - AV valves are still closed - during ejection atria have been filling with blood - v wave - jugular venous pulse as back flow of blood hits AV valves ventricular pressure continues to drop - ventricular volume is at a minimum ``` 6. rapid ventricular filling - AV valves open and ventricular volume rises - abnormal S3 sounds due to rapid ventricular filling from congestive heart failure, severe hypertension, myocardial infarction, mitral incompetence 7. reduced ventricular filling (diastis) - ventricular filling continues more slowly until they are almost full with blood

Answer 49

cardiac output = heart rate x stroke volume heart rate - heart beats around 70 times per minute stroke volume - for each heartbeat, the heart ejects around 70ml of blood into the circulation - > CO = 70ml x 70/min - > CO ~ 5L

Answer 50

- a small volume of blood in centrifuged in a capillary tube until cellular component become packed at the bottom of the tube (because they are heavier) - these are separated from the plasma - white blood cells and platelets

Answer 51

Anemia is a group of conditions when the O2 carrying capacity of the blood is reduced. Principal function of RBC is to carry CO2 and O2 and is facilitated by the presence of Hb within the cell. • Reduction in RBC number • Iron, folic acid or vitamin B12 deficiencies • Defective Hb (sickle-cell anemia)

Answer 52

the result of electrical coupling between neighbouring cells at intercalated discs and gap junctions.

Answer 53

baroreceptors - detect blood pressure changes - stimulates heart to increase contractility and heart rate - stimulates vasoconstriction / vasodilation chemoreceptors - detect changes in pH and carbon dioxide - stimulates an increase in blood flow to metabolising tissues ADH - regulated blood pressure by regulating plasma osmolarity aldosterone - regulated kidneys to reabsorb more water from collecting duct atrial natriuretic peptide (ANP) - secreted by atria to lower effective circulatory volume by natriuretic (Na+ secretion)

Answer 54

- S1 and S2 determine systole and diastole S1 - beginning of sytsole - caused by sudden closer of tricuspid and mitral (AV) valves - ventricular pressure exceeds atrial pressure and the valves close - mitral valve closed before tricuspid valve because pressure in the left ventricle is greater than pressure in the right ventricle S2 - end of systole - ventricular relaxation - pressure in heart is less than in the aorta and pulmonary arteries -back flow of blood causes the semilunar valves to close aortic valves close before the pulmonary valves because pressure in aorta is higher than pressure in pulmonary artery

Answer 55

When someone stands up the venous return falls due to gravity. Cardiac input diminishes and arterial blood p is reduced (preload diminished – starling law). Possibly feeling faint and cerebral flow is reduced due to arterial blood p. Baroreceptors afferent firing is reduced – medullary centres inhibition reduced. Increased sympathetic tone to arterioles and veins (vasoconstriction). Reduced vagal tone to SA node. Therefore increased myocardial sympathetic tone – tachycardia – raised stroke work – increased blood pressure – return to normal blood p.

Answer 56

Metabolizing tissue sense levels of CO2 and pH and has intrinsic control to promote vasodilation of the blood vessels. So it matches it by local regulation by stimulating higher venous return – higher cardiac output and increased blood flow to respiring tissues by vasodilation of vessels. (I.e muscle activity). It is also regulated by systemic regulation (neuronal and endocrine). Systemic capillaries are in parallel: • Each capillary receives arterial blood directly from the left ventricle • Flow to different capillary beds can be altered selectively as situation demands. (regulation of flow is determined by resistance that preceeds each capillary bed). Vasoconstriction – increased R, vasodilation – decreased R.

Answer 57

• Blood flow Q=dP/R (pressure difference/total peripheral resistance which is sum of serial and parallel vessels). • Resistance R=nL/r^4 • Viscosity: Q=1/n • Starling law: net filtration = hydrostatic p. – oncotic p. • Vessel radius. Cardiac output is controlled by the sum of local tissue flows, increased venous return (preload) – increased cardiac output.

Answer 58

Nervous system and hormonal activity determines the heart rate and also the demand for oxygen in the body. Tissue metabolism, tissue blood flow, venous return determines preload which enters the heart. When is it higher there has to be bigger myocardial contractility to increase stoke volume which is opposed by total peripheral resistance (Q=dP/R) – afterload. Sympathetic NS increases heart rate via norepinephrine, which work on b-receptors coupled to G-proteins. (b[adrenergic receptors, increase in cAMP – stimulating). It also increases stroke volume by increasing contractility. Adrenaline also increases heart rate in stress situations. Opposite affect is by parasympathetic (vagus nerve), where Ach acts on cholinergic muscarinic receptors (Gi-inhibits adenylyl cyclase). But it does not have an effect on contractility of cardiac muscles. Regulation of the frequency of the heart beat by the changing the shape of Aps in the SA node (slow depolarization, activated by Funny channels which are sensitive to repolarization, therefore no resting potential). • Changing the slope of depolarization • Change the threshold potential • Change of resting potential Factors determining cardiac output: Cardiac output=heart rate x stroke V. • Heart rate and myocardial contractility – these are characteristics of the myocardium and are regulated by neuronal and hormonal factors. • Preload and afterload – these depend upon the characteristics of both the heart and vascular system and are fundamental to the functioning of the cardiovascular system.

Answer 59

• Blood flow Q=dP/R (pressure difference/total peripheral resistance which is sum of serial and parallel vessels). • Resistance R=nL/r^4 • Viscosity: Q=1/n • Starling law: net filtration = hydrostatic p. – oncotic p. • Vessel radius. Cardiac output is controlled by the sum of local tissue flows, increased venous return (preload) – increased cardiac output.

Answer 60

Metabolizing tissue sense levels of CO2 and pH and has intrinsic control to promote vasodilation of the blood vessels. So it matches it by local regulation by stimulating higher venous return – higher cardiac output and increased blood flow to respiring tissues by vasodilation of vessels. (I.e muscle activity). It is also regulated by systemic regulation (neuronal and endocrine). Systemic capillaries are in parallel: • Each capillary receives arterial blood directly from the left ventricle • Flow to different capillary beds can be altered selectively as situation demands. (regulation of flow is determined by resistance that preceeds each capillary bed). Vasoconstriction – increased R, vasodilation – decreased R.

Answer 61

CO = (oxygen consumption in lungs)/(oxygen concentration in pulmonary artery - oxygen consumption in pulmonary vein)

Answer 62

CO = Heart rate x stroke volume altering either of these will change the cardiac output HR - determined by frequency of action potentials at SA node SA node is innervated by ANS parasympathetic nerves (VAGUS) released ACh to slow the heart rate (BRADYCARDIA) sympathetic releases NA to quicken the heart rate (TACHYCARDIA)

Answer 63

sympathetic stimulation by adding adrenaline to the heart the stroke work increases with an increase in EDP, preload, as in the Starling relationship the curve shifts upwards, the stroke work is higher for each EDP value when the sympathetic nerves are stimulated POSITIVE INOTROPIC EFFECT = each myocyte contracts more efficiently for the same tension therefore CARDIAC CONTRACTILITY is increase

Answer 64

Where a system tries to restore the value of blood pressure back to a set value after an initial disturbance 1. the value of a controlled variable may be influenced by external factors 2. the value of arterial blood pressure is measured by baroreceptors (in the neck, at the bifurcation of the common carotid artery into the external and internal arches, in aortic arch respond to higher pressure) 3. the 'feedback/afferent' information is conveyed from carotid sinus by branches of the SINUS NERVE (that is a branch of the glassopharyngeal nerve, CN IX) and aortic arch information is conveyed via vagal afferents (CN X) to a comparator, the MEDULLA OBLONGATA in the brainstem, upon which it exerts an inhibitory influence - The cardiovascular centres also receive information form other parts of the brain that can change the value of the set-point blood pressure, e.g. during exercise the blood pressure can be set to a higher value by in formation from the cortex 4. the comparator determines any difference between the set value and the actual value 5. the efferent activity is via the ANS to affect the target organs that restore the variable towards the set point: - 1 The sino-atrial node to determine heart rate. The principal influence if from the vagus (parasympathetic) – increased activity of which slows the heart rate. There are also sympathetic fibres that quicken the heart rate 2 The myocardium to increase stroke work. The principal influence is from sympathetic fibres – increased activity of which exerts a positive inotropic effect 3 Vascular smooth muscle. The principal influence is from sympathetic fibres – increased activity of which generates a vasoconstriction, decreased activity generates a vasodilatation. In addition sympathetic fibres innervate smooth muscle in the veins and venules. Increased activity will reduce the compliance of the venous system, facilitate venous return and so increase preload on the heart.

Answer 65

When blood flow to the tissues in not adequate and they do not meet their nutrient demands

Answer 66

too high - capillary damage, fluid exudation into the extravascular space too low - inadequate perfusion of tissue, impaired metabolism, necrosis

Answer 67

mean arterial blood pressure - right atrial pressure = CO x peripheral resistance - right atrial pressure is constant - CO can be regulated by myocardial contractility and heart rate - the peripheral resistance is regulated by vasoconstriction and vasodilation

Answer 68

- vascular volume - kidney regulated sodium ion reabsorption through the renin-angiotension system if the blood volume is too low (HYPOVOLAEMIA), the preload decreases, the cardiac output decreases and the arterial blood pressure drops In the longer- term blood pressure is kept within physiological limits by regulation of effective circulating volume (equivalent to circulating blood volume in the normal state). This is achieved by the kidney through the maintenance of Na+ regulation at the distal tubule. This is brought about by the renin-angiotensin system, and the regulation of aldosterone secretion by the adrenal cortex. The details are explained in the renal part of this course. However, it is important to remember that the functions of the kidney and cardiovascular system are intimately connected. Specific disruption of blood flow to the kidney will therefore have profound effects on cardiovascular function through the tendency to retain excess Na+ and hence fluid. Furthermore, the atria release another hormone, atrial natriuretc peptide (ANP), when effective circulating volume is large. This causes a natriuresis (loss of Na+ in the urine) and hence a reduction of circulating fluid

Answer 69

- standing and so blood pools in lower extremities -> reduced venous return to the heart - reduced filling pressure (preload) -> stroke volume and hence cardiac output decreases - blood pressure falls (postural hypotension) - baro receptor activation reduced -> afferent nerve frequency firing reduced - inhibitory influence on CV centre diminished - efferent arm activated to restore blood pressure towards normal - > vasoconstriction, increased sympathetic - increased HR, increased sympathetic and decreased parasympathetic - positive ionotropy, increase sympathetic

Answer 70

The cutaneous circulation serves several functions: it supplies nutrient blood to the tissues, and is also involved in extrinsic vascular control as with many other tissues. However, it also has a role in temperature regulation and protection against injury. Apart from the normal arrangement of vessels as arterioles, capillaries and venules, there are also arterio-venous anastomoses that by-pass the capillaries. When opened they greatly increase cutaneous blood flow and so increase heat loss through the skin. They are under the influence of the sympathetic nervous system activated by temperature receptors or higher centres in the central nervous system. Similarly, exposure to cold elicits cutaneous vasoconstriction. Skin vessels also show direct responses to cold, moderate cooling produces vasoconstriction but more severe exposure leads to vasodilatation –and the dangers therefore of exposure. The skin also shows a characteristic response to trauma - the triple response: a local red response, a wheal, a more diffuse flare. The integrated response will assist in the local haemostasis, as well as increasing flood flow in the surrounding to neutralise any foreign particles that may enter the tissues. Interest in this is also due to the fact that such a response occurs in many tissues to cause irritation and pain The red response is probably due to capillary dilatation after injury. The wheal is caused by increased capillary permeability to proteins and hence exudation of water. The flare results from dilatation of local blood vessels, caused by the fact that local sensory fibres, responding to the initial stimulus, also sent branches to nearby blood vessels.

Answer 71

The resting blood flow and O2 consumption is very high for a metabolising tissue, and moreover can be increased greatly when cardiac work is increased. O2 extraction by myocardial tissue is very efficient (there is a large difference of the arterio-venous O2 content) and so O2 delivery to the tissues can only be augmented by increased blood flow. There is therefore a very close relationship between metabolic work and coronary flow, adenosine is suggested as an important vasoactive mediator. Sympathetic stimulation increases coronary blood flow: this may result from increased cardiac work associated with the positive inotropic and chronotropic effect. In spite of the importance between coronary artery blood flow (CABF) and cardiac work, flow during systole is low (between the dotted lines), and may even be zero in the parts of the left ventricle. It is only after the aortic valve has closed, at the onset of ventricular relaxation that flow is substantial. Therefore, anything that impedes cardiac relaxation will attenuate blood flow. A reduction of myocardial blood flow (myocardial ischaemia) can manifest Influence of PaCO2 on cerebral blood flow. Note the pressure scale: 1 kPa ≈ 7.5 mmHg in the patient with symptoms of angina pectoris, a crushing or constricting chest pain, radiating down the arms, usually the left side. The relief of angina with nitrites involves a dilation of narrowed coronary arteries, possibly by an increased production of NO (nitric oxide) or other endothelial derived relaxing factors. Alternatively it has been suggested that the relief is a result of the decreased cardiac work due to the moderate hypotension induced.

Answer 72

The brain has a dual arterial input with arterial communications – the circle of Willis - assists continued supply. Carotid and basilar arteries connect by posterior communicating arteries and anterior cerebral arteries by anterior communicating arteries. Thus any reduction of flow through one arterial input could be alleviated by flow from the other. Cerebral tissue has a high metabolic rate (about 20% of the resting O2 consumption) and a respiratory quotient (RQ) of about 1.0, indicating a carbohydrate metabolism. However, the brain has few glycogen stores (enough for about two minutes) and so is dependent on nutrients from the blood: it is thus very intolerant to ischaemia. Local blood flow increases profoundly during neural activity, reflecting the increased metabolic activity. Cerebral tissue exhibits autoregulation of blood flow over a wide pressure range (60-200mm Hg), as is principally regulated by local CO2 gas tensions, as cerebral vascular resistance is profoundly affected by local PCO2. A reduction of flow will tend to increase local PCO2 as the metabolite is washed away less readily, this will vasodilate the cerebral artertioles and restore flow back towards normal. Because the brain is enclosed in a rigid cranium the total volume of the vascular and extravascular space must be constant. This any increase of extravascular space will compromise blood flow. This is why an accumulation of a solid mass, fluid (such as an intracranial haemorrhage) or even gas is such a serious consideration.

Answer 73

Blood flow to tissues is regulated by altering the resistance offered by the pre-capillary vessels, the arterioles. In principle there are two reasons why arteriolar resistance should be varied. 1. Intrinsic mechanisms. To match blood flow to metabolic rate – and increase of metabolic rate requires a greater blood flow. 2. Extrinsic mechanisms. To perform homeostatic functions, such as the control of blood pressure or body temperature. In this case alteration of blood flow is not necessarily adjusted in concordance with the metabolic requirements of the tissues.

Answer 74

Intrinsic regulation. In this case an increase of blood flow is required when metabolic activity rises. This is achieved by the action of local waste products of metabolism. The greater is the metabolic rate so more metabolic waste products are produced. These have a vasodilatory effect in general, so that the extent of vasodilatation is determined by the rate of waste product generation. Different tissue beds seem to utilise different waste products but the principle is the same. Some examples: cerebral circulation (brain) utilises CO2; coronary circulation (heart) probably utilises adenosine; skeletal muscle is less discriminating, a rise of PCO2, a fall of PO2, acidosis, a local rise of the [K+] all have a vasodilatory action. It has been proposed that the endothelium, the inner lining of the blood vessels, releases a vasodilator, nitric oxide (NO). NO release may be elicited by shear stress (increase of lumen pressure) or the local release of chemicals such as acetylcholine, bradykinin, histamine, serotonin or ATP.

Answer 75

Extrinsic regulation. This is achieved by the nervous system (sympathetic generally) or hormones (e.g. adrenaline). The postganglionic neurotransmitter is noradrenaline and acts on α-receptors on vascular smooth muscle to cause vasoconstriction. Certain capillary beds have an extensive functional sympathetic control, e,g, the splanchnic (gut, liver, pancreas and spleen), the cutaneous (skin), renal, skeletal muscle capillary beds. Others such as the coronary and cerebral beds have little functional control. Thus, when there is a sympathetic drive to the peripheral circulation, for example during an acute hypovolaemia, the α-regulated beds have a reduced blood flow as the body attempts to restore blood pressure by increasing systemic (total) peripheral resistance. The heart and brain do not suffer in this way, as they do not participate in this homeostatic control. Thus, blood is re-directed to these vital organs. Some capillary beds also respond to circulating adrenaline by vasodilating, as adrenaline binds to β-receptors (the β2-subtype). The best example is the skeletal muscle circulation that responds to adrenaline release during exercise and can therefore accommodate the large increase of cardiac output. There are several other circulating vasoactive compounds, eg angiotensin II (constriction), ANP (renal dilation), vasopressin or ADH (constriction). Adrenaline and noradrenaline have important cardiac effects, via β1-receptors, including a positive inotropic effect (increase of cardiac contraction strength) and a positive chronotropic effect (increase of heart rate or tachycardia). Autoregulation. This is a phenomenon whereby blood flow to a tissue stays relatively constant despite changes to arterial blood pressure. The two best examples are the cerebral and renal circulations, when blood flow remains fairly constant despite changes of blood pressure over a range as large as 60 -180 mm Hg. This phenomenon is particularly important in those tissues that require a reasonably constant and stable blood flow

Answer 76

1. amine - based on tryptophan: dopamine, adrenaline, thyroid hormone 2. steroids - based on cholesterol: oestrogen, testosterone, B3, cortisol, thyroxine 3. proteins - peptides - TSH, LH, FSH, insulin

Answer 77

HYDROPHOBIC - work on longer time scale - enters cells - receptor is a soluble protein inside the cytoplasm - Forming complex which enters nucleus - Hormones cannot be stored are synthesized on demand (estrogens, testosterone, thyroid hormones T3/T4, vitamin B3, cortisol) - They are bound to serum proteins but only the free hormone is active – specific globulins exist for diff hormones (albumin) - Cortisol binds to cortisol binding globulin - Changes in binding proteins can also affect the conc of free hormone. (corticotrophin releasing hormone – adrencocortico stimulating hormone - cortisol – nucleus – transcription factor for adrenaline) HYDROPHILIC - will not enter the cells - bind to cell surface receptors, which are integral membrane proteins - stored in secretory vesicles (adrenaline, GH, ADH, insulin). - - - They circulate in the blood in unbound form. - Some hydrophilic hormones work via 2nd messenger system (G-proteins), or kinases (insulin – tyrosin kinase, tyrosine phosphorylation).

Answer 78

HORMONAL SIGNALING – hormones secreted by specialized cells (endocrine glands), which circulate in the blood and acts on distant target organs. PARACRINE – chemicals secreted are acting on neighbouring adjacent cells – short distance. If self recognize – autocrine signaling.

Answer 79

Oxytocin – lactation – stimulates ejection of milk from the mammary glands parturition – contraction of the smooth muscle of the uterus ADG – acts on kidneys to permit water to be re-absorbed, making the urine concentrated and making water available to dilute the osmolality of body fluids.

Answer 80

PITUITARY GLAND - master gland - secretes hormones regulating homeostasis (including trophic factors that stimulate other glands) - hypothalamus controls pituitary gland POSTERIOR LOBE - contains terminals of NEUROSECRETORY CELLS whose cell bodies are located in the hypothalamus - Peptide hormones secreted are oxytocin causes lactation and ADH (vasopressin) acts on kidneys to reabsorb water - Hypothalamic neurons project into posterior lobe and secrete hormones that are released upon nervous stimulation ANTERIOR LOBE - contains ENDOCRINE CELLS that secrete a range of hormones, which stimulate other endocrine glands - It is connected by a private blood supply to the hypothalamus. Different hypothalamic neurons produce hormones (releasing and release-inhibiting) that are secreted to the anterior lobe by hypothalamic-hypophisal portal system. - These stimulate the anterior lobe and regulate the release of hormones. ANTERIOR PITUITARY HORMONES: - TSH (thyroid stimulating hormone, throtrophs) – thyroid gland (T3, T4) - ACTH (adrenocorticotrophin, corticotrophs) – adrenals/kidneys (cortisol). Also stimulates the growth of adrenal gland. - Prolactin, lactotrophs – breasts (growth of mammary glands). Incuding mammary gland growth and milk secretion during lactation. High levels during pregnancy as stimulates by estrogens. - GH (growth hormone, somatotrophs) – liver (IGF-1, IGF-2). Has powerful effect on hrowth and metabolism. Long term growth effect and short term growth effect. - FSH (follicle stimulating hormone, gonadotrophs) – gonads (sex steroid hormones) - LH (luteinizing hormone, gonadotrophs) – gonads (sex steroid hormones)

Answer 81

1. Hypothalamus releases growth hormone releasing hormone (GHRH) into anterior pituitary gland via hypothalamic-hypophisal portal system. 2. This acts on vesicles where GH is stored, which is synthesized in ant pituitary and sored in somatotrophs. 3. Upon release is released into circulation and acts on livers, where is binds to surface receptors and work via tyrosine kinases which phosphorylates further proteins/enzymes. 4. Liver secrete insulin like growth factors (IGF-1 and IGF-2). 5. When there is sufficient secretion oh hormones, the release from hypothalamus is inhibited by negative feedback or in anterior pituitary. Long term effects: stimulates amino acid uptake by muscle cells – increased protein synthesis. Stimulation of the growth and calcification of cartilage – growth of bone length. Short term effects: influences fat and CH metabolism. During starvation – low glucose induces GH release and switch from CH utilization to fats, sparing glucose for the brain.

Answer 82

``` Cortex: • Zona glomerulosa (aldosterone) • Zona fasciculate (cortisol) • Zona reticularis (androgens: testosterone, estrogens) Medulla: • Adrenaline and noradrenaline ``` Cortisol: blood glucose regulation, protein turnover, stress survival with adrenaline. Cortisol secretion in the morning when is low glucose level in brain. CRH-ACTH-cortisol. It rises blood glucose level by regulating metabolism of CH, proteins and fats (protein to glycogen). Adaption to stress, immune suppressive, anti-alergic, anti-inflammatroy. Increases lipolysis in fat cells to glycerol and fatty acids. In skeletal muscles proteolysis to amino acids. This synthesized to glucose in livers (gluconeogenesis). Aldosterone: Na/K balance – osmoregulation, maintains normal extracellular fluid volume, conserves Na in exchange for K. (renin-angiotensin1-angitensin2-aldosterone).

Answer 83

When giving a blood transfusion it is important that the blood group of the donor and recipient are known, to prevent agglutination. It is the antigens on the blood cells that are important in transfusion. Person with blood group 0, doesn’t have antigens but had serum A,B antibodies. Can give blood to O,A,B and AB. Receives only from O. universal donor. Group A, has A antigens on surface cell, serum B antibodies and can give blood to A, AB and receive blood from A and O. Group B, has antigens B, antibodies A. can give blood to B, AB and receive blood from B and O. AB group has antigens A and B, no serum antibodies and therefore can give blood only to AB, but can receive from all blood groups.

Answer 84

- activating substances released by bacteria + damaged tissues activate adhesion molecules known as E selectin on the endothelial wall of the blood vessel - CD15 present on neutrophils is recognized by E-selectin and slows down the complex - E-selectin+CD15 signals cause the expression of integrins on neutrophils (adhesion molecules) - Other adhesion molecules are expressed in the endothelial wall of the blood vessel such as I-CAM1 in response to lipopolysaccharides, interlukin and tumor necrosis factor-alpha - adhesion to cell wall followed by Diapedesis allows the immune system cell to move between the blood vessel and the target tissue as the wall loosens due to the above secreted molecules - C3a, C5a - complements components as they act as chemo-attractants which direct the neutrophil to the site of infection

Answer 85

It consists of phagocytic cells: Neutrophils, Monocytes, Eosinophils and Basophils. It is the first defense mechanism against invading pathogens and it not specific. It occurs in response to a tissue damage itself, which is responsible for inflammation. Molecules of the immune system: antibodies, complement (stimulates inflammation), cytokines (intracellular communication), adhesion molecules (cellular localization), microbicidal compounds, apoptosis inducing protein.

Answer 86

Immune cells in adaptive response: T and B lymphocytes, antigen presenting cells (dendritic, macrophages, B-lymphocytes – producing antibodies). B lymphocytes produce antibodies with the help of T helper cells. • Humoral activity (antibody-mediated) • Cell – mediated immunity (T killer cells) Chemical antibodies produced by B cells are carried in the blood to the rest of infection. Antibodies coat bacteria, viruses and other foreign antigen molecules. They respond to foreign antigen when activated by T helper cells. They multiply to form memory cells and plasma cells, which secrete the antibodies. Antibodies bind to micro-organisms and destroy them. Memory cells preserve experience, save antibodies ready to react to same antigen again.

Answer 87

C6H12O6 + 6CO2 – 6CO2 + 6H2O + work + heat O2 consumption = CO2 production Respiratory Quotient (RQ) -= CO2 production/O2 consumption = 1. Tells us how much O2 is required to oxidize energy substances. It can be used to calculate the energy value of 1l of O2. Usually we burn a mixture of hydrocarbons for a cellular energy.

Answer 88

``` Rest V(O2)= 0.3L/min Vmax (O2)= 3-4 L/min – max aerobic power and depends on age, weight… ```

Answer 89

Fats – 70% Protein – 25% CH- less tan 1% Factors affecting the metabolic rate: - diet: at absorptive state the rate increases - temperature: as the ambient T falls, the metabolic rate increases to produce heat. - Endocrine factors – thyroid hormones (T3, T4) – promotion of growth, adrenaline stimulates glycogenolysis and triacylglycerol breakdown (exercise, stress). - Muscle activity

Answer 90

Three pairs of salivary glands: • Parotid – serous (watery) secretion, contains a-amylase • Submandibular: mucous and serous acini present • Sublingual: largely mucus acini Gland: acini cells (protein and fluid secretion) + ducts (ion exchange). Functions: digestion (a-amylase), lubrication (mucus), antibacterial action (lysozymes, IgG). Formation: primary isotonic fluid from acinar cell Secondary: Na\K exchange, ducts low H2O permeability – hypotonic Control of secretion: Mediated by parasympathetic efferent fibers from salivar nuclei in medulla. Neurons receive input from receptors in mouth, pharynx and olfactory areas. Response modulated by facilitating and inhibitory impulses from apetite area in hypothalamus and taste-smell areas of cerebral cortex. Conditional reflexes: controlled in cortical areas Unconditional reflexes: mediated by stimulation of receptors in mouth, tounge, stomach. Parasympathetic stimulation (contraction of myoepithelial) produces abundant flow of watery saliva from parotid gland, vasodilation. Sympathetic no effect and also no hormonal control

Answer 91

Stomach secretes aprox 2L of gastric juice day, which is isotonic with pH=2-3. HCl secreted from Parietal cells. Pepsinogen from Chief cells. HCl kills bacteria, denaturates diatery proteins, activates pepsinogen, it is co-factor for pepsin action. Intrinsic factor: essential for vitamin B12 uptake in lower ileum. Enterochromaffin cells – histamine – activates secretion of HCl Pyloric gland : G cells – gastrin – secreted into the blood and than works on the glands D cells – somatostatin – works locally and inhibits gastrin secretion.

Answer 92

Glucose has to pass from lumen of the small intestine to the plasma via transcellular route. At apical membrane of enterocytes it is coupled to Na transport (symport into the cells) via secondary active transport. It diffuses through basolateral membrane via carrier mediated protein by facilitated diffusion into the blood stream.

Answer 93

• 101.5 L/day, isotonic and alkaline. • pH buffering, high levels of bicarbonates and neutralizes HCl emptying from stomach. • Digestion: lipases, amylase and proteolytic enzymes important for nutrient digestion (chymotrypsin, trypsin, elastase, carboxypeptidase, lipase, amylase). Proteolytic enzymes require activation (trypsionegen – trypsin) • HCO3- production (secretion) depends on Cl- (HCO3- -Cl- antiport). Cl has to be regulated. And at basolateral membrane Na-H exchange. H + HCO3 (CA anhydrase) – H2CO3 – CO2 + H2O. CO2 diffuses into cell (H20 + CO2 – H2CO3). HCO3 – Cl- antiporter. HCO3 enters cells also via symport with Na+. • Cl- is normally secreted into the ductal lumen via the cystic fibrosis transmembrane regulator (CFTR) – provides driving force for the fluid movement necessary to maintain solubility of ductal enzymes. Control of pancreatic secretion: • Nerves: parasympathetic – vagal stimulation • Hormones: - cholecystokinin (CCK) - secretin - gastrin – from stomach. CCK and secretin from small intestine. Cephalic phase – 10% total due to smell Gastric phase – less than 20% total – gastric distension, peptides. Hormones are mostly responsible for the intestinal phase of pancreatic secretion.

Answer 94

Absorption of vitamin B12 requires intrinsic factor, which is secreted by the parietal cells of the stomach. B12 and intrinsic factor bind together in the jejunum and are absorbed as a complex in the terminal ileum. This vitamin binds to intrinsic factor secreted by stomach, which protects it against enzyme breakdown. It passes through duodenum and is then absorbed in ileum. (B12-IF enters ileal cell. Only B12 transferred to blood, IF broken down within cell. In blood make a complex with TC – transcobalamin-II, and then transported to site of storage or use of B12).

Answer 95

Unlike peristalsis, which predominates in the esophagus, segmentation contractions occur in the large intestine and small intestine, while predominating in the latter. While peristalsis involves one-way motion in the caudal direction, segmentation contractions move chyme in both directions, which allows greater mixing with the secretions of the intestines. Segmentation involves contractions of the circular muscles in the digestive tract, while peristalsis involves rhythmic contractions of the longitudinal muscles in the GI tract. Unlike peristalsis, segmentation actually can slow progression of chyme through the system.

Answer 96

Both are down their electrochemical gradient and is a passive transport, no metabolic energy required. Simple diffusion is movement of water, CO2 and O2. Facilitated is carrier mediated (diff binding sites) – example of glucose from basolateral membrane to the plasma.

Answer 97

``` Macromolecules (enzymes, receptors, hormones) are transported out of the membrane by exocytosis. A vesicle (membrane bound compartment) containing the secreted material fuses with the cell membrane to release the macromolecules into the extracellular space ``` EXOCYTOSIS/SECRETION can be constitutive or regulated (neurotransmitters) • Constitutive: vesicles docking fusion with membrane secretion • Regulated: may be triggered by chemicals or electrical signals (rise in Ca2+) Hormone secretion, exocrine and endocrine glands Some secretion is passive (steroid hormones). Area of plasma membrane is increased ENDOCYTOSIS • Phagocytosis: membrane engulfing large particles – phagosome – lysosome • Pinocytosis: dissolved molecules – endosome • Receptor-mediated transport: molecule – receptor protein – coated pit – clathrin.

Answer 98

If down their electrochemical gradient is by ion channels (ligand gated or voltage gated) – this is passive transport. (no ATP). Carrier proteins transport ions and small org molecules by facilitated diffusion (passive) and it can also transport against their electrochemical gradient (active transport – primary transport). I.e. sodium pump. By secondary transport cells exploit ion gradients to transport molecules against electrochemical gradient – symport, antiport. This important for transport of amino acids and glucose across sheets of epithelial (intestine, kidneys). Na/H ion exchange (antiport) – secondary active. H+ out against electrochemical gradient and Na+ down electrochemical gradient. Driving force for H+ out because Na+ gradient established by the Na pump. Ca2+ regulation: pumped out by Ca2+ ATPase against el.chem gradient. Na/Ca exchanger – secondary active (antiport). Cotransport of Na/ HCO3 into the cells to increase intracellular HCO3 (buffering) Cl-/HCO3 exchange (when cell is alkaline)

Answer 99

It is a carrier protein (has binding site for specific particles, two sides). The sodium pump is a ubiquitous feature of mammalian cells. It uses ATP (hydrolysis) to pump 3Na+ out of the cell in exchange for 2K+. (Antiport). It transports molecules (ions) against electrochemical gradient (active transport, primary). Important for establishing ion gradients, which can be used for secondary transport. It results in the cytoplasm being rich in K+ and low Na+ - establishing electrochemical gradient end membrane potential.

Answer 100

When the motor neuron, its axon and all the muscle fibers supplied by the axon and it branches forming a motor unit. Single twitch is due to contraction of all the muscle fibers in a motor unit in a response to single AP.

Answer 101

Amount of force depends on: • The number of active motor units (number of muscle fibers that are contracting) • The cross-section area of the muscle – more parallel myofibrils • The frequency of stimulation – summation of contraction (fused tetanus) • The rate at which the muscle shortens (force velocity curve) • The initial resting length of the muscle (over stretched muscle is harder to contract). Lightly loaded muscles contract more quickly than heavy loaded ones.

Answer 102

SKELETAL MUSCLE: multinucleated, made of long parallel cylindrical dell fibers. 30-10 microns diameter, length from mm-10cm (some may run whole length of fibre). Made of myofibrils (1micron diameter). Cross striation due sarcomere arrangement. CARDIAC MUSCLES: rod shaped, intercalated discs, gap junctions, cross striations, mononucleated, 10-20 microns diameter, 50-100micron length. Cardiac muscle has pacemaker which initiates each contraction. SMOOTH MUSCLE: more narrow, spindle shaped, mononucleated, 20-10 diameter, 100-400 length. Joined together both by mechanically (intermediate junctions) and electrically (gap junctions) to form units in bundles of sheets. Don’t have T tubules to excite all parts of the muscle fibers quickly. The loose arrangement of the contractile proteins allows greater degree of shortening than striated muscle. No troponin but calmodium (AP + second messenger). Cardiac and smooth muscles are also under hormonal regulation but not skeletal.

Answer 103

Renal function depend on the blood flow to the kidneys renal blood flow determines filtration rate (GFR). It is highly regulates and receives 25% of the cardiac output. If arterial BP is altered renal blood flow remains constant to maintain the filtration rate. Even when renal nerves are cut (intrinsic control). Autocorrection by changing diameter of afferent arterioles. Renal blood flow is autoregulated by varying renal vascular resistance (RVR) – the resistance of the afferent and efferent arterioles. • Myogenic hypothesis: mainly due to response of renal artery to stretch • Tubuloglomelular hypothesis – GFR increased – filtrate flow rate through nephron increases – sensed by juxta-glomelural apparatus (renin) – increase afferent arteriolar resistance – lower GFR. • Metabolic hypothesis. Autoregulation important so the plasma can be effectively filtered (so constant GFR), any deviations from that would result in lower filtrate conc or higher, where reabsorption of nutrients would not be efficient and lost in urine.

Answer 104

The kidneys regulate the osmolality of the plasma by producing urine of varying osmolality. 1. The establishment of the osmotic gradient in the renal medulla • Transport of NaCl by ascending loop of Henle • The counter-current multiplier in the thin descending and ascending loop of Henle. 2. Regulation of the absorption of H2O from the collecting duct by ADH The loop of Henle concentrates salts in the tissue of the medulla by means of the counter-current mechanism because fluid flow pass each other in opposite direction. ASCENDING LIMB: upper walls thicker and impermeable to water. Na and CL ions are actively transported out into the tissue fluid, so it is high in salt. DESCENDING LIMB: walls permeable to water. The fluid in the limb less concentrated so moves out by osmosis. At the same time Na and Cl ions travel down their conc. gradient diffusing into the tube. Outward movement of water and inward movement of ion result in an increase in salt concentration as you go down the tube. At the hairpin the solute is most concentrated. As you go up, Na and Cl move out so it becomes less concentrated. Concentration is always lower in ascending limb. The loop produces high concentration of Na and Cl in the kidney tissue. The collecting duct passes through this region and as fluid flows through, the H2O is drawn out of the urine by osmosis. At steady state the tubular fluid (water) is impermeable in the collecting duct but relatively permeable to Na ions. When there is high osmolality in the plasma this is sensed by osmoreceptors in hypothalamus. It releases ADH from posterior pituitary gland. In collecting duct ADH binds to a receptor on the baso-lateral membrane of the tubule cell. This acts via G-proteins and stimulates adenylyl cyclase to generate cAMP, which then activates protein kinase A. this increases the insertion of water channel (aquaporins) into the apical surface cell (P cells) – increased H2O permeability. Consequently collecting duct is more permeable to water, urea permeability increases in the inner medullary region of the collecting duct and also NaCl reabsorption in the thick ascending limb.

Answer 105

RENAL CLEARANCE: volume of plasma completely cleared of a given substance in one minute. This can be done by creatine. It can be used to determine several components of renal functions. It is a measure of the rate at which blood can be cleared of a substance by the kidneys. Clearance GFR – substance must be secreted C = (Urine con of substance X amount of urine produced per minute) / (plasma conc of substance) Glomerular filtration rate: amount of filtrate formed in all the renal corpuscles of both kidney in 1min and relates to pressures that determine net filtration rate (hydrostatic and oncotic). Glucose reabsorption is carrier mediated and therefore has max transport rate – the tubular transport of Tmax. The kidney can reabsorb completely the filtered glucose load at normal plasma and clearance of glucose = 0. Diabetes: can exceed critical level and carriers are full saturated and the excess glucose appears in urine.

Answer 106

- Counter-current sytem (look above) - Chemoreceptor stimulation and release ADH from pituitary gland, making distal convoluted tubule and collecting duct more permeable to water. - When body is dehydrated there is drop in BP, this sensed by baroreceptors in juxtaglomerolous apparatus to trigger renine-angiotensin-aldosterone system, which reabsorbs also more water with Na ions for exchange K ions.

Answer 107

They are reabsorbed in proximal convoluted tubule. It is the net movement from apical to baso-lateral membrane. Movement is transcellular and paracellular. GLUCOSE: the coupled transport (co-transport) of Na ions is linked to glucose transporters. These nutrients then leave baso-lateral membrane by facilitated diffusion. The number of transporters is sufficient to ensure all solutes are generally reabsorbed. AMINO ACIDS: the coupled transport of Na ions is linked to amino-acid transporters. These leave baso-lateral membrane by facilitated diffusion. Na ions pumped out by ATPase, Cl and H2O follows NaCl so solution is isotonic. There is max saturation of transporters. If glucose is secreted with urine this indicates diabetes or just after heavy meal.

Answer 108

* Gas exchange: removal of CO2 and provides O2 in the lungs * Acid-base balance, regulates the pH/[H+] of blood - acts because lungs regulate the level of CO2 in the blood and bicarbonate is important blood buffer. * Speech – due to ability to voluntary control activity of respiratory skeletal muscles and therefore change airflow through the vocal cords. * Defense mechanism – airways warms and humidifies air, intrinsic cells and some reflexes protect the lung from pollutant, swallow microbes phagocytosis of blood clots * Metabolism – some pulmonary cells modify bioactive material: convert angiotensin 1 into angiotensin 2 in capillaries, makes dipalmitoyl lecithin, releases prostacyclin, removes toxic substances

Answer 109

INSPIRATION: intrapleural p upward and outwards movement of ribs -> INCREASE IN THORACIC VOLUME - lungs are forced to increase in volume because of the change in intrapleural pressure -> increase in alveoli volume throughout the lung -> the pressure within the alveoli drops below atmospheric (Boyle's law) -> the difference in pressure causes a bulk flow of air into the alveoli. - By the end of inspiration the pressure in the alveoli is again atmospheric. EXPIRATION alveolar p > atm p PASSIVE at rest - At the end of inspiration the nerves to the diaphragm and inspiratory intercostal muscles cease firing and these muscles relax. - The chest wall and hence the lungs passively return to their original dimensions - As the lungs shrink, air in the alveoli becomes temporarily compressed and therefore alveolar pressure exceeds atmospheric -> air flows from the alveoli through the airways out into the atmosphere -> Thus expiration at rest is completely passive depending only upon the RELAXATION OF THE INSPIRATORY MUSCLES AND RECOIL OF STRETCHED LUNGS - Under certain conditions (during EXERCISE for example) expiration of larger volumes is achieved by CONTRACTION OF THE EXPIRATORY/INTERNAL INTERCOSTAL MUSCLES AND ABDOMINAL MUSCLES -> actively decreases thoracic dimensions. The expiratory intercostal muscles pull in the chest wall when they contract and contraction of the abdominal muscles increases intra-abdominal pressure and forces the diaphragm up into the thorax.

Answer 110

Chemoreceptors respond to a rise in pCO2, H+, fall in pO2. There are central and peripheral chemoreceptors. PERIPHERAL: act is seconds • Carotid body - contain unmyelinated sensory nerve endings and dopamine containing cells, both are closely associated with capillaries. Only chemoreceptors able to elict ventilation respond to hypoxia. Located between carotid sinus and external carotid artery in the neck. Supplied by Glossopharyngeal nerve. • Aortic body – longer term metabolic compensation. Supplied by vagal nerve. CENTRAL CHEMORECEPTORS: response to hypercapnia – respond to change in pH. Make adaption to high altitude and chronic respiratory disease. They are located close to ventral surface of medulla. H+ cannot be buffered in CFS and cannot pass capillary walls.

Answer 111

The vital capacity is the total volume of air that can be breathed out after a maximal inspiration It is the difference between the total lung volume and the residual volume It is normally around 5 litres The FEV1 is the percentage of the vital capacity that can be expired in one second Full expiration to residual volume takes around 4 seconds For a normal subject this is around 80% (1 mark) but during an asthmatic attack the FEV1 is decreased and can be as low as 40% FVC – forced vital capacity FEV1 – forced expired volume in 1s. Forced expiratory ratio (FER) = FEV1/FVC. If it is under 0.8 – indicates obstructive lung disease. Vital capacity – V of gas inhailed and exhailed between two points of max inspiration and max expiration. In normal subject = as FVC. FVC - the max V of gas that can be rapidly and forcibly expired from max inspiration. FEV1 – the V of gas that can be rapidly and forcibly expired from max inspiration in 1s. ( decreasing with age, obstructive airways ).

Answer 112

CO2 is carried in the blood in 3 ways: • Dissolved in plasma (5-10%) • Carried as bicarbonate ion in RBC (80-90%) • Chemically combined with Hb, carbamino compounds (5-10%)

Answer 113

Oxygen is carried in the blood in RBC bound to Hb. Hb has a 4 glubin units (two alpha and two beta), each with the haem group with the Fe in the middle to which oxygen binds. Binding of oxygen to Hb is cooperatively as the last molecule binds easier. (sigmoidal curve). Bohr effect – curve gets shifted to the right in higher pH, CO2 and T.

Answer 114

The respiratory system can be considered to consist of two parts: - Conducting airways - Area of gas exchange (bronchioles, alveoli) Not all air taken in in one breath reaches the alveolar surface, some must occupy the airways that connect the respiratory surface to the atmosphere = anatomical dead space (air that does not play part in gas exchange, does not mix with the air in the alveoli during breath). Physiological dead space – air reaches alveoli but is poor perfusion with capillaries so cannot take a part in gas exchange. Dead space = Tidal V (1-fraction CO2 expired air/fraction CO2 alveolar air).

Answer 115

LUNG COMPLIANCE: the change in the volume of the chest that results from a given change in intrapleural pressure is called compliance. It is a measure of the ease with which the lungs can be inflated. C=change in lung V/change in inflation p …… C= dP/dP (L/kPa) If compliance is high – little resistance to expansion, low – chest expands with difficulty. Depends on: • The elasticity of the lung tissue • The surface tension forces at gas/liquid interface within the lungs (with alveoli) – surface tension at the liquid film that lines the alveoli. Laplace-s Law: the relationship between radius (r ) of a small bubble of air in liquid, the transmural pressure (P) across the wall of the bubble and the surface tension (T) of the air/liquid interface is described by this law. P=2T/r. If T is constant, than the p in small alveoli will be greater than that in larger alveoli – air will move from small to large alveoli. Small alveoli will require higher p to inflate them. Type II alveolar cells produce a phospholipid known as pulmonary surfactant (dipalmitoyl lecithin), which reduced surface tension forces and increases lung compliance, making lungs easier to expand. (polar head groups in aqueous phase, on expiration molecules compressed and H2O excluded and surface tension falls). Surfactant is a mix of phospholipids. Trauma and hypoxia (low O2 level) increase breakdown of phospholipids. Activity depends n surface area - larger effect on smaller areas.

Answer 116

1. action potential the nerve terminal 2. secretes a specific chemical known as a neurotransmitter into the synaptic cleft. 3. neurotransmitter diffuses across the synaptic cleft 4. NT binds to specific receptors to cause a short-lived change in the membrane potential of the post-synaptic cell. 5. excitatory synapse - depolarisation of the membrane potential which is called an excitatory post-synaptic potential or epsp. inhibitory synapse - hyperpolarisation of the membrane potential which is called an inhibitory post-synaptic potential or ipsp. Epsps and ipsps are GRADED in intensity unlike action potentials which are all or none in amplitude. They greatly outlast the action potentials that initiated them. As a result, synaptic potentials can be superimposed on another leading to temporal and spatial summation. one-way signalling mechanism excitatory synapse inhibitory synapse. In mammals, including man, synapses generally operate by the SECRETION OF CHEMICALS, NEUROTRANSMITTER from the nerve terminal. This type of synapse is called a chemical synapse. In some instances, a synapse operates by transmitting the electrical current generated by the action potential to the post- synaptic cell via GAP JUNCTIONS. Synapses of this type are called electrical synapses. They are rare in man and other mammals but occur more commonly in some invertebrates. At a chemical synapse the axon terminal is separated from the post-synaptic membrane by a small gap known as the SYNAPTIC CLEFT. Many different kinds of chemical can serve as neurotransmitters. Examples are acetylcholine, nor-adrenaline and peptides such as vasoactive intestinal polypeptide (VIP). Some nerve terminals secrete more than one kind of neurotransmitter and some neurotransmitters activate more than one kind of receptor at the same synapse.

Answer 117

The nerves that transmit signals from the CNS to the skeletal muscles are known as motor nerves and the process of transmitting a signal from a motor nerve to a skeletal muscle to cause it to contract is called neuromuscular transmission. The motor nerves release acetylcholine that activates nicotinic cholinergic receptors to depolarize the muscle membrane. The depolarisation is known as an endplate potential or epp. The epp is confined to the endplate region of the muscle and is not seen elsewhere along the muscle fibre. If the electrical activity of the muscle membrane at the endplate is examined closely, small spontaneous depolarisations of about 1 mV are observed. These small depolarisations are similar in time course to the epp and are called miniature endplate potentials or mepps. The mepps occur only in the junctional region and are both random and relatively infrequent in the resting muscle membrane. Each mepp is thought to reflect the release of the acetylcholine contained within a single synaptic vesicle. It is now generally agreed that depolarisation of the motor nerve terminal triggers the simultaneous release of many synaptic vesicles to give rise to the epp. The effect of acetylcholine is terminated by acetylcholinesterase. If this enzyme is inhibited, the muscle membrane becomes depolarized and neuromuscular transmission is blocked. Neuromuscular transmission can also be blocked by drugs that bind to the nicotinic receptors such as curare. The epp triggers an action potential in the muscle membrane that leads to contraction of the muscle. This is called excitation-contraction coupling.

Answer 118

Action potentials are generated when a neuron is activated by a stimulus of a certain minimum strength known as the threshold. With stimuli above threshold each action potential has approximately the same magnitude and duration. This is known as the “all or none” law. The action potential is caused by a large, short-lived increase in the permeability of the membrane to sodium. The increase in sodium permeability is caused by the opening of voltage-gated sodium channels. After they have opened, sodium channels spontaneously inactivate and this limits the duration of the action potential to about 1 ms. Voltage-gated sodium channels cannot reopen until they have been reprimed by spending a period at the resting membrane potential. Immediately after the passage of an action potential the axon cannot propagate action potential. This period of inexcitability is known as the absolute refractory period and lasts for 1-2 ms. Following the absolute refractory period the axon is less excitable than normal. This period is known as the relative refractory period. Large diameter axons conduct faster than small diameter axons and myelinated axons conduct impulses faster than unmyelinated axons. Myelinated axons conduct impulses by saltatory conduction in which action potentials jump from one node of Ranvier to another. Unmyelinated axons conduct impulses as a continuous wave of depolarization.

Answer 119

- air containing sacs - large supply of blood from pulmonary capillaries - thin wall (0.5microns) for efficient gas exchange

Answer 120

change in the volume of the chest that results from a given change in intrapleural pressure

Answer 121

Total lung capacity = when the chest is expanded to its full extent and there has been enough time for lungs to inflate fully, the amount of air inside lungs = volume of gas contained in the lungs and airways following a maximal inspiration Residual volume (RV) = the amount of air left in lungs after a max expiration that was preceded by a max inspiration Vital capacity (VC) = the amount of air breathed out in a maximum expiration after a max inspiration Tidal volume (VT) = air taken in and exhaled with each breath Inspiratory reserve volume (IRV) = VC - lung volume after a normal inspiration = TLC - (VT + FRC) Expiratory reserve volume (ERV) = VC - amount of air that can be forced form the lungs after a normal expiration = FRC - RV Functional residual capacity (FRC) = the amount of air left in the lung after a normal expiration Inspiratory capacity = TLC - FRC

Answer 122

i) Forced Vital Capacity FVC, the maximum volume of gas that can be rapidly and forcibly expired from maximum inspiration (in a healthy person FVC = VC) ii) Forced Expired Volume in 1 second FEV1, the volume of gas that can be rapidly and forcibly expired from maximum inspiration in 1 second.

Answer 123

C = change in lung volume/change in inflation pressure - a measure of the ease with which the lungs can be inflated: The smaller the ΔP required to produce a given ΔV the more compliant the lungs. The more difficult the lungs are to inflate (i.e. the greater the ΔP required to produce a given ΔV) the lower the lung compliance. Lung compliance depends equally on: 1. the elasticity of the lung tissue and 2. the surface tension forces at the gas/liquid interface within the lung. Laplace's law describes the relationship between the radius (r) of a small bubble of air in liquid, the transmural pressure (P) across the wall of the bubble and the surface tension (T) at the air/liquid interface. The alveoli can be regarded as small bubbles. If T was constant then smaller alveoli could not co-exist in equilibrium with larger alveoli. The smaller alveoli would collapse into the larger ones (air will move from an area of higher pressure into an area of lower pressure). If, however, as in healthy lungs T varied such that in the smaller alveoli it decreased in proportion to the reduction in r then the pressures inside connecting alveoli of different sizes would be equalised. -> small alveoli will require higher pressures to inflate them

Answer 124

The most important determinant of lung compliance is surface tension at the air/water interfaces within the alveoli. The surfaces of the alveolar cells are moist and so can be represented as air filled sacs lined with water. At the air/water interface the attractive forces between the water molecules make the water lining like a stretched balloon that is trying constantly to shrink and resist further stretching. **Expansion of the lung therefore requires energy not only to stretch the connective tissue of the lung but to overcome the surface tension of the water lining the alveoli. If the lungs were lined with pure water the surface tension forces would be so great that it would require an enormous amount of effort for inflation and therefore the lungs would tend to collapse. Fortunately the type II alveolar cells produce a phospholipid known as pulmonary surfactant which markedly reduces the cohesive forces on the alveolar surface. Therefore surfactant lowers the surface tension and increases lung compliance, making the lungs easier to expand.

Answer 125

Oxygen must move across the alveolar membranes into the pulmonary capillaries, be transported by the blood to the tissues, leave the tissue capillaries and enter the extracellular fluid, and finally cross plasma membranes to enter the cells. Carbon dioxide must follow a similar path in reverse. In the steady state, the volume of oxygen that leaves the tissue capillaries and is consumed by the body cells per unit time is exactly equal to the volume of oxygen added to the blood in the lungs during the same time period. Similarly, the rate at which carbon dioxide is produced by the body cells and enters the systemic blood is identical to the rate at which carbon dioxide leaves the blood in the lungs and is expired.

Answer 126

Fick’s Law States : “The amount of a substance moving from one region to another depends on the area available for diffusion, the concentration gradient, and a constant known as the diffusion coefficient”. Thus: Amount moved = area x concentration gradient x diffusion coefficient.

Cellular physiology Flashcards

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