For aerobic exercise, O2 consumed increases linearly with work load.

Trained athlete has more muscle mass with more mitochondria and capillaries. They are not more efficient at using ATP.

O2 supply = Cardiac Output X O2 Extraction

Functional Hyperemia in striated muscles allows reduction in TPR and increase in CO without an increase in MAP.

Regulation of Body Temperature

Humans use 1800 calories/day for BMR

Thermoregulatory Zone – bounded by peak sweating and heat production

Thermoneutral Zone – Core temperature maintained with no extra energy input – bounded by begining of sweating and shivering. (20-30C)

Thermal Comfort Zone – bounded by feeling too warm or too cold (26/79)

Circadian Variation: zenith at 4-6PM – 37.5, nadir in early morning (35.5)

Passive Heat Loss

• 60% – Radiation – remote
• Conduction – contact (water 25x air)
• Convection – movement of fluid (windchill) (Piloerection)
• 20% – Evaporation

Active Heat Loss

• Sweating – eccrine glands, regulated by hypothalamus autonomic, cholinergic, catecholamines. Baseline – little NaCl in sweat. Maximum – high NaCl (L/hr.). Acclimatization (2-6 weeks)(2-3 L/hr)(less NaCl loss via aldosterone)
• Vasodilation – can accommodate up to 30% of CO. Regulated by hypothalamus.

Heat Generation:

• Shivering
  • Regulated by posterior hypothalamus, inhibited by anterior hypothalamus
  • Lateral columns to anterior motor neurons, muscle spindle stretch reflex.
  • 4-5x heat production
• Nonshivering – Brown fat activated by sympathetics and thyroid. Thermogenin

Endocrine Mechanisms

Thyroid – Cooling > Sympathetics > Anterior Hypothalamus > Release TRH > Pituitary release TSH > Thyroid release T4/T3. Thyroxine increases BMR.

Adrenal – Cooling > Anterior/preoptic HT signals adrenal medulla to produce Epi/NE > Increase MR.

Temperature sensors in skin (more cold, constantly firing in response to rate of change), deep tissues (abdominal, spinal cord, great veins), and central (hypothalamus, medulla)

Anterior and Preoptic Hypothalmus – more heat receptors, sweating and vasodilation

Psoterior Hypothalamus – gets signals from periphery and anterior hypothalamus, more cold receptors, shivering.

Fever – reseting hypothalamic thermostat

• PAMPs activate leukocytes to produce cytokines (IL-1)
• Cytokines or toxins stimulate COX2 in bloo-brain barrier to make PGE2 in brain
• Stimulates preoptic anterior HT to increase temperature set point.

Antipyretics – central and peripheral

• Inhibit PGE2 via COX
• Reduced adhesion of leukocytes
• Decreased cytokine production
• Stimulation of antiinflammatory mediators (adenosine)
• Enhanced endogenous antipyretics – glucocorticoids

Fever augments host defense mechanisms

Fever may result in collateral tissue damage

Fever is very bad for the injured brain

Heat Stroke – 106-108, 41-42, high humidity, RX rapidly decrease body temperature

Malignant hyperthermia via inhalational anesthetics

Hypothermia – core temp below 35/95, Rx slow rewarming

Hemorrhage

Cerebral Ischemic Response may trigger at very low pressures, but if medulla blood flow is compromised the vaga centers iwll be activated and worsen hypotension.

Capillary pressure falls, fall in plasma oncotic pressure

Baroreceptors – vassopressin

Renal vascular pressure – angiotensin II > aldosterone

Opoids from sympathetics and CNS can depress the brain

Reticuloendothelial system is depressed, endotoxin accumulates

Work on: Fluid replacement, ion balance, naloxone to block opiods

Patent ductus arteriosus and ductus venosus

Equal R/L pressures in heart

Highly oxygenated blood to brain and myocardium, less oxygenated blood to lower body.

Only 8% goes to lungs because pulmonary resistance is high

RV pumps 2/3 of output

Ductus venosus carries 40-60% of umbilical venous blood.

Crista dividens and Eustacian valve direct blood through foramen ovale.

Little volume crosses the aortic isthmus.

At Birth

• Pulmonary resistance drops > 50% of output
•  Flow through PDA decreases
• Umbilical vessels constrict and close, peripheral resistance increases, ductus venosus closes
• Left atrial pressure increases
• Foramen ovale closes
• PDA reverses then ceases

CHD – 8/1000, 40% are VSDs

Signs:

• furrowed brow
• color
• respiratory effort – happy tachypnea
• murmur – ejection
• poor lower extremity pulses – coarctation – usually stable until PDA closes in a week.

Right coronary artery usually most important

Artery-Artery anastomoses called collaterals. Density lowest at epicardium.

Extraction is 13 ml/100 ml blood, 90%, so must increase CBF for more oxygen.

A decrease in supply or an increase in consumption will decrease balance.

Myocardium has little preference for substrate. Glucose uptake is stimulated during hypoxia – sympathetics.

Autoregulation is excellent in coronary circulation. Blood pressure usually remains constant.

Flow in ventricle decreases markedly with each systole, especially in the endocardium. But these vessels are more numerous and more dilated. So average flow is equal. Reduction in transmural pressure below normal will decrease end/epi ratio below 1.

Hypoxia is most potent stimulator of dilation. Adenosine released by parenchymal cells.

Sympathetics can produce dilation and parasympathetics barely.

Skeletal Muscle Circulation

Muscle mass is 43% of body weight.

Blood flow can vary from 250-12500 ml/min.

Huge contributor of peripheral resistance, blood pressure in toto.

In exercise – skeletal muscles can increase both flow and extraction

At rest – 25% of total, during exercise – 90%

Flow regulation at arteriole level. 1.5-150 w/ exercise.

Also metabolic dilation.

Local control overrides neural control during exercise. Ignore sympathetics. Functional sympatholyasis

Cerebral Circulation

Very weak sympathetic control

As intracranial pressure rises, transmural pressure falls, and vessels tend to collapse. Collapse leads to myogenic and metabolic dilation and flow is autoregulated up to a point.

When flow falls to a critical level, a massive sympathetic discharge is triggered and the arterial pressure begins to rise in parallel with the rise intracranial pressure. Called Cushing Response.,

Regional metabolic control. Adenosine, K and H

Cutaneous Circulation

Low resting flow. Range from 50-2800.

Arteries and arterioles control perfusion of subdermal venous plexuses and capillary loops

Capillary loops run perpendicular to skin surface.

Subcutaneous venous plexus, secondary route for heat exchange, large volume, run parallel, core temperature regulation, prevent freezing, filling controlled by A-V anastomoses.

When warm, open shunts, venous plexus is major surface for heat loss to regulate core temperature.

Countercurrent: superficial arteries and veins are separated, deep vessels run parallel. When cold, superficial vessels contract. Blood in deep arteries runs next to blood in deep veins and exchange.

CNS role: preoptic region of anterior hypothalamus is major control. Temperature receptors are both in skin and hypothalamus, initiate reflex to change sympathetic tone

Kinin system: Heat > sympathetic cholinergic signal to sweat glands > kallikrein acts on kininogen to form bradykinin. Dilates and opens A-V anastomoses.

White reaction – due to vasoconstriction, not neural

Triple response – red line (vessel trauma), flare or red blush (axon reflex from mechanical stimulation via histamine), wheal (increased capillary permeability followed by fluid and protein leaks.

Intestinal

Supply to muscularis and mucosa

Capillary loops with countercurrent flow to facilitate absorption of Na and H2o and shunting of o2

Neural control is exclusively sympathetic

Local control: autoregulation is poorly developed, functional hyperemia is well developed, glucose and FA are mediators along with gastrin and chol.

Hepatic Blood Flow

Large flow – 25% of CO at rest

75% inflow from portal vein

25% O2 inflow via portal vein (Mean pressure is 10mmHg), 75% from hepatic artery (Mean pressure is 90).

Low O2 and high substrate from gut

Paired arteriole and venule pass in parallel with bile ductule into hepatic acinus. Then to hepatic sinusoids (capillaries)

Blood leaves liver via hepatic venules.

Blood enters lobule with same pressure, thus pressure drop in arterioles is large

Elevation of pressure causes filtration out of sinusoids and into peritoneal cavity.

Local control is well developed, sensitive to O2

Sympathetic innervation, most important as volume reservoir, contains 15% of volume.

Ionotropic state and output of heart determine right atrial pressure. Right atrial pressure determines preload.

Mean circulatory filling pressure – Pmc – estimate of cardiovascular volume. Use central venous pressure, arterial pressure and cardiac output. Pressure in system is determined by capacitance and volume. Venous capacitance is 19X the arterial.

Only if you have pumping will there be a difference in volume between the two sides. If you decrease pumpin, you increase venous pressure.

Pressure is reduced as blood flows through the system.

Decreased vascular resistance causes greater cardiac output for any given filling pressure.

Combine vascular function and starling curve.

Increased resistance will lower venous return and cardiac output and central venous pressure. But it also raises the blood pressure (afterload) causing cardiac output to fall. The net result is decreased CO with little change in central venous pressure.

Cardiac failure will cause your body to increase volume, which will increase central venous pressure and CO.

Change in HR will decrease preload, increase afterload and increase contractility.

Negative pressure breathing will increase CO.

Changes in resistance control filtration, flow, diffusion.

Bleeding causes neurally mediated constriction of blood vessels.

Blood-Brain barrier protects it from vasoconstrictor stimuli.

VSM capable of graded contraction.

Spontaneous tone due to high leak of Ca

Agonist tone via neural (NE) or humoral (Epi)

Stretch induced – myogenic response

Endothelial cell cooperation: Mechanical, Electrical, Chemical (paracrine factors)

No is produced from arginine, activates GC to produce cGMP which reduces intra Ca and desensitizes myosin to Ca. Phosphodiesterase 5 removes the cGMP (Viagra inhibitsP5)

Endothelium derived hyperpolarizing factor (EDHF) – dilates, with secondary reduction in Ca

Arachidonic Acid metabolites

Endothelin – constriction peptide, potent, hypertension.

Intrinsic control at precapillary vasculature. Pre dilation accompanied by post dilation.

Reactive hyperemia – excess flow that follows reduced flow. Recovery depends on contration of VSM.

Autoregulation stabilizes blood flow and capillary pressure in the face of changing arterial blood pressure.

Functional hyperemia – increased flow with increased metabolic activity.

Myogenic mechanism very important in autoregulation and reactive hyperemia.

Look at flow to metabolic rate ratio to determine myogenic vs. metabolic component.

Vasomotor Center – CNS control from dorsal medulla

• Regulates cardiac function with SNS and PNS
• Vascular regulation only by SNS
• Sympathetic tone
• Traube Herring Waves – cyclical pressure changes associated with respiration

Depressor Area – Ventromedial and caudal medulla

• Dilation through vasomotor and spinal pathways

Hypothalamus

• stimulation of anterior causes decreased blood pressure, vasodilation, and bradycardia
• stimulation of posterolateral causes tachycardia and vasoconstriction
• cutaneous thermal receptors induce vasodilation or vasoconstriction in response to temperature.

Cerebral Cortex

• blushing and fainting
• connections to vasculature via hypothalamus

Cardiovascular sensors

• Peripheral Blood Gas – carotid and aortic, glossopharangeal and vagus nerves
  • Control respiration
  • cardiac acceleration and vasoconstriction
• Central Blood Gas – vasomotor
• Blood Pressure Sensors – carotid and aorta
  • work through vasomotor via intermediate inhibitory nucleus
  • sensitive to both mean and pulse pressure
  • increased sympathetic activation of VSM in artery increases sensitivity of sinus
  • rapidly adapting
  • stretch receptors work through glosspharangeal and vagus nerves to inhibit vassomotor center
    • inhibits sympathetics
    • increased parasympathetic flow – HR
• Blood Pressure Sensors – low pressure side – atria, ventricles, pulmonary artery
  • Atrial A receptors are stimulated by contraction, B stimulated by distension
  • Important in blood volume control
  • Stimulation inhibits release of angiotensin, aldosterone, vasopressin
• Enteric Sensors
• Cutaneus Receptors – Superficial produce constriction, deep produce vasodilation

• Sympathetic Adrenergic Fibers – NE, ATP , NPY

• receptors in blood vessels
  • alpha – contraction of smooth muscle (DOMINANT with NE)
  • beta – relaxation of smooth muscle
• Epi is a more potent beta stimulator at low doses, at high doses alpha are stimulated
• Arterioles and venules are both innervated but NOT capillaries

Extracellular fluid compartment is divided between interstitial fluid and plasma.

If venous pressure rises, more fluid is filtered from capillaries. The initial change in tissue weight is due to the expansion of the vessels.

Driving pressure is Arterial pressure – Venous pressure. This affects flow.

Sympathetic stimulation constricts arterioles more than venules, so the capillary pressure falls.

Contraction of veins shifts blood from the periphery to the central circulation, called venous volume mobilization. Happens during hemorrhage.

Skin is the most sensitive to sympathetic stimulation, brain is the least.

Sympathetic cholinergic fibers use ACh to induce active vasodilation. Not major. These fibers are not tonically active and do not innervate capacitance vessels. They are activated by emotion and anticipation of exercise.

Parasympathetic Dilator Fibers use ACh. Fibers of cranial origin supply the head and viscera. Sacral origin serve pelvis.

Salivary glands: parasympathetic discharge > dilation of glands > formation of kallikrein > formation of bradykinin from plasma proteins > vasodilation

Bradykinin also formed in sweat glands and is involved in cutaneous vasodilation.

NO at work in penis for vasodilation.

Cutaneous sensory neurons release substance P which degranulates mast cells and increases capillary permeability.

Adrenal Medullary Hormone – Epi – Release is stimulated by lots of things including baraoreceptor, works on muscle and skin.

Adrenal cortical hormones

• Corticosterone – permissive role
• Aldosterone – Major action in the kidney, increases salt and water retention, elevates BP.

Angiotensin II – formation initiated by low NaCl and low BP in kidney. Vasoconstrictor. ACE inhibitors

Antidiuretic Hormone – ADH – Vasopressin – released by posterior pituitary – vasoconstrictor – hemorrhage.

Histamine – released by mast cells – dilates arterioles, constricts venules, increases capillary permeability.

Prostas from AA – synthesized on demand, release associated with injury.

Precapillary sphincters present only in few tissues like liver. Dominated by local control.

A-V Anastomoses have large smooth muscle fraction. Mainly in skin. Involved in body temperature regulation.

In capillary wall:

• Tight junctions
• Fenestrations – capillaries and postcapillary venules, large molecules
• Vesicles – can carry fluid and solute
• Fused chains of vesicles – path for large solutes

Collecting capillaries – leakage site for macromolecules, major site for WBC adherance

Venules – regulate distribution of blood in circulation, mainly neural control

Law of Laplace – small vessel can withstand pressure more easily than large vessels because tension is less. T=PxR. 12 vs. 200dynes. Or S=Pxr/w

Ficks first law of diffusion: Flux = Permeability x Area x Concentration Difference

Area depends on molecule and endothelial cell

Vant Hoff and Oncotic Pressure: Pi = RT(deltaC)

Starling balance of forces: 1) flow can be induced by hydrostatic or oncotic pressure difference.

Filtration = K[(Pp-Pt)-(Pip-Pit)]

K also called the CFC, it is proportional to the size and number of pores and number of capillaries perfused. Pp runs from 32 > 15. Pt is 0. Pip is 25. Pit is 3.

Net filtration over length of capillary is 3mmHg

Proteins are not very permeable in the capillaries and the situation approaches that for an ideal osmotic system.

Reflection coefficient describes deviation from ideality.

Any force producing filtration will be positive.

Decrease in proteins causes increase in permeability.

Histamine, TNFalpha, analphylatoxins, free radicals all increase permeability.

Two types of leads – bipolar and unipolar (+)

12 Lead ECG has 3 bipolar leads (I, II, III) and 9 unipolar leads (aVR, aVL, aVF) and (V1-V6). 10 electrodes

Bipolar leads (limb leads) record potential difference between 2 electrodes. 4th electrode on right leg serves as an electrical ground. Positive poles of these leads lie inferiorly and to the left.

6 leads: limb leads (I, II, III) and augmented leads (aVR, aVL, aVF) are in coronal plane and are derived from the four limb electrodes.

Augmented leads fill gaps between limb leads. Lead aVR stands opposite from others, superior and to the right.

The precordial leads (V1-V6) are in horizontal plane. They point positively towards the chest. add 3D.

A positive vector towards a positive lead will have a positive deflection on ECG.

Cardiac repolarization is opposite of cellular depolarization (positive T wave). Due to repolarization delay (out to in) away from positive electrode.

Charge reverse in endocardium

PR interval is time between beginning of P wave and beginning of QRS complex. Time through AV node (0.2 sec in adult)

QRS Complex – (0.08 sec)

Initial negative = Q

Initial positive = R

Negative after R = S

ST segment – no signature – phase 2 – very important.

T wave is repolarization. Beginning of QRS complex to T wave is QT interval, a measure of AP duration (.44 sec) (should be less than 1/2 RR interval). T wave abnormalities are common.

SAN depolarization gives positive deflection in I and aVF

As it passes from left ventricle to right ventricle, you get negative Q wave in lead I and a positive R wave in aVF.

Endocardium > Epicardium gives a positive R wave in I and aVF

Depolarization of left lateral wall is last, gives R wave in I and negative S wave in aVF

Repolarization is superior and to the right giving T wave a positive deflection in I and avF

Thin lines are .04 sec, thick lines are .20 seconds (25mm/sec). Each lead displayed for 2.5 seconds.

Right Ventricle is tough to see.

• Inferior wall of left ventricle – II, III, aVF
• Lateral – I, aVI, V5, V6
• Anterior – V1-V4
• Posterior – V1, V2, V8, V9
• Right Ventricular – RV1-RV6

Capacitance is larger in arteries compared to arterioles.

Capacitance is ability to distend.  Change in volume/Change in pressure

Capacitance is less at high pressure than at low pressure and decreases with aging and disease.

Veins have large capacitance.

Venous blood volume is variable. Passive postural change. When you stand, transmural pressure increases in abdomen and legs. Almost 1L of blood can be displaced into legs.

Intrathoracic pressure increases during exhalation.

Skin, liver, lungs and spleen are important blood reservoirs because they undergo substantial venoconstriction.

Mean Pressure – 100mmHg = Pd + (Ps-Pd)/3

Pressure = Flow x Resistance

Flow = Cardiac Output

So systemic pressure = CO x R = SV x HR x R

Pulsatile pressure – Stroke volume and arterial capacitance are key determinants

When mean pressure rises with nonlinear capacitance, elevation of systolic pressure is greater than diastolic pressure.

Pressure pulse of radial artery. Velocity varies inversely with capacitance. High frequency components tend to be damped out. Systolic portions are more pronounced.

Increased tension produced from a fixed preload is called positive contractility or positive inotropy. (NE)

Ventricles are not well innervated with parasympathetics, so the PNS is more important for HR.

For same internal pressure a larger sphere has greater wall stress. During isovolumetric phase, wall tension increases 25X. Increases to 50x during systole.

Treppe or Staircase phenomenon describes rate induced regulation. Increase HR and you increase force due to cytoplasmic Ca.

Bainbridge Reflex and atrial receptors, stretch induced, ensure inflow and outflow are equal. Increase in venous return will accelerate HR.

Thyroid Hormone increases HR and cardiac output. Also influences myosin ATPase in cardiac cells.

Hypoxia – modest reduction – causes increase in HR and contractility.

Marked reduction causes depressed function

Alkalosis – mild decrease in Co2 – augments cardiac function via effects on myocardium

Acidosis – mild increase in Co2 – depresses heart function

Adrenergic fibers from lower cervical and upper thoracic ganglia. Right nerves work on SA node to increase HR. Left nerve increases contractility via ventricles.

Activation of cAMP dependent kinases phosphorylate Ca channels and phospholamban.

Cannot regulate heart on beat to beat basis, slow fx

B-blocker propanolol

Phosphodiesterase inhibitors slow down removal of Ca, but increase myocardial oxygen need.

Parasympathetics. Right works on SA node to slow HR. Left slows the AV node. Acts on muscarinic receptor, opens K channels, slows phase 4 depolarization.

Blocked by atropine

Fast effects. Keeps HR down at 70 when at rest. Exercise increases vagal tone and decreases HR. This can also happen with increased intracranial pressure.

Thalamic and medullary centers are critical in the control of vasculature

Frontal lobes and orbital cortex have input

Baroreceptor reflex: High BP causes vagal firing and inhibits sympathetics. Receptors in aortic arch and carotid sinus. Acute hypertension may cause bradycardia.

Sinus arrhythmia: HR varies with breathing, increases with inspiration. Due to increased sympathetic firing  due to parallels to phrenic nerve>vasomotor center and increases venous return/Bainbridge reflex. HR decreases during expiration due to increased parasympathetics, decreased venous return.

Chemoreceptor reflex – low o2 or high co2 have small effects on lungs and heart, but bigger effects on vaculature.

Ventricular Receptor Reflex – sensory receptor in wall of ventricle may slow the HR and lower peripheral vascular resistance when stimulated. Mechanical or chemical.

Specific gravity of Hg = 13.6 g/cm3

Normal blood pressure will support 130cm of water, 10cm/100mm Hg

760mmHg used as 0.

Perfusion pressure = difference between input and output.

Transmural pressure = pressure across walls.

Flow = Area x Velocity = Q

Potential Energy = Pressure x Volume

Kinetic Energy = 1/2 x density x volume x velocity squared

Friction results in decrease in pressure.

When area is halved, velocity doubles, and pressure decreases .

Calculating hydrostatic pressure in head standing up. 39cmH20 > 390mmH20/13.6 = 29mmHg. Then you subtract that value from 99 and get 70mmHg. For feet you add 96mmHg to 98mmHg.

Newtonian/Streamline Flow: Velocity is 0 and the wall of the tube where the fluid wets the surface. Velocity is 2x mean in center of tube.

Turbulence increases with velocity, density, and area of tube (inertial forces).

Turbulence decreases with viscosity.

Reynolds Number = ratio of inertial forces to the viscous forces. Above 3 000 turbulence occurs. Sounds of Korotkoff.

Blood flows in proportion to perfusion pressure and inverse proportion to resistance. Q=PP/R. This equation can be used to predict a pressure gradient required to drive fluid through tube.

Resistance = Hindrance x Viscosity

H = 8L/Pi(r)4

Viscosity = (F/A)/Shear Rate. Water = 1 centipoise

Shear Rate is greatest at the walls and least at the center. Wall shear stress can cause atherosclerosis. T = (4 x viscosity x Q)/Pr3

Poiseuille-Hagen Equation describes flow in ideal situation

As number of R’s in parallel increases, the total R decreases. Rt=R/n

Hematocrit can vary from 15-75%

Fahraeuas-Lindqvist Effect – when tube approaches size of blood cell, the hematocrit falls. 1)Exclusion phenomenon, cell poor layer near walls. 2) Axial accumulation, cells tend to curve towards center.

At low flow rates, shear rate important due to interactions in plasma (fibro)