Microsoft PowerPoint - specific circulation.ppt []
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1. Define the special features of the circulation in the brain, coronary vessels, skin, and fetus, and how these are regulated.
2. Delineate how the oxygen needs of the contracting myocardium are met by the coronary.
3. Understand how the fetus is supplied with oxygen and nutrients in utero, and the circulatory events required for a transition to independent life after birth.
4. List the vascular reactions of the skin.
Circulation
Cerebral circulation--- vessels
Blood is supplied to the brain, face, and scalp via two major sets of vessels: the right and left common carotid arteries and the right and left vertebral arteries.
1. The total cerebral blood flow: 55 ml/min/100g brain. 2. Brain is the least tolerant of ischemia (> 5 seconds ---- loss of consciousness)
Circle of Willis
1. Cerebrospinal Fluid (CSF) fills the ventricles and subarachnoid space.
2. 2/3 of the CSF is formed in the choroid plexuses and the remainder is formed around blood vessels and along ventricular walls. The CSF in the ventricles flows through the foramens of magendie and luschka to the subarachnoid space and is absorbed throuh the arachnoid villi into veins.
3. The most critical role for CSF is to protect the brain.
4. The composition of CSF is essentially the same as that of brain extracellular fluid.
The BBB maintains the constancy and protects the brain from endogenous and exogenous toxins in the blood.
Blood-Brain Barrier
• Postganglionic Cholinergic neurons---acetylcholine, vasoactive intestinal peptide (VIP), and peptide histidyl methionine (PHM-27)
• Sensory nerves---substance P, neurokininA, and calcitonin gene-related peptide (CGRP)
• Vasodilation substance P, CGRP, VIP, and PHM-27 • Vasoconstrictor neruopeptide Y
Local factors • Total cerebral blood flow is constant. However, regional cortical blood
flow is associated with regional neural activity. (nitric oxide and adenosine may be involved).
Different stimuli elicit specific regional blood flow in human cerebral cortex
• The cerebral vessels are very sensitive to blood CO2 tension  (PaCO2).Increased PaCO2 elicit marked cerebral vasodilation;  reduced PaCO2 causes hyperventilation, decreased cerebral blood  flow.
• This change may be probably due to alteration of intracellular pH,  vessels diameter (blood flow) and pH are inversely related
• PaCO2  pH       leads to vessels vasodilation, increases blood  flow.
• O2
Regulation of cerebral circulation
The cerebral circulation shows reactive hyperemia and excellent autoregulation between pressure of about 60 and 160 mm Hg; pressure > 160 mm Hg may increase the permeability of the blood brain barrier and cause cerebral edema. The noradrenergic discharge (NE) occurs when the blood pressure is markedly elevated.
produced by sympathetic stimulation
Brain metabolism
• O2 consumption by human brain about 3.5 ml/100g brain/min  approximately 20% of the total body resting O2 consumption.
• Brain is extremely sensitive to hypoxia. • Glucose is the major ultimate source of energy for the brain. • In general, glucose utilization at rest parallels blood flow and O2
consumption. • The brain’s uptake of glutamate is approximately balanced by its 
output of glutamine. • Ammonia is very toxic to nerve cells. • In brain glutamate + ammonia and release glutamine as a 
detoxifying mechanism
Coronary circulation
Coronary arteries
Heart chambers
Arteriouluminal vessels
Thebesian veins
Extracoronary arteries
Pressure (mm Hg) in
Aorta Left Vent
80 80 800 0
Coronary blood flow
• Changes of aortic pressure generally shift coronary blood flow • Heart influences the coronary blood flow by squeezing effect 
of the contracting myocardium on the blood vessels • The force is so great during early ventricular systole that blood 
flow in left coronary artery is briefly reversed. • Left coronary inflow is maximal in early diastole, when the 
ventricles have relaxed and extravascular compression of the  coronary vessels is absent. 
• Right coronary artery shows a similar pattern, but because of  the lower pressure developed by the thin right ventricle  during systole, blood flow does not reverse in early systole.
• During systole there is no blood flow in the  subendocardial portion of the left ventricle, this region is  prone to  ischemic damage and is the most common site  of myocardial infarction.
• Patients with stenotic aortic valves develop symptoms  of myocardial ischemia.
• Coronary flow is also decreased when the aortic diastolic  pressure is low  in congestive heart failure
Regulation of Coronary blood flow ---Chemical factors
• A decrease in the ratio of O2 supply / O2 demand release a vasodilators from myocardium into the interstitial fluid, leading to relax the coronary resistance vessels.
• Numerous metabolites such as CO2, K+, H+, lactate, prostaglandins, adenine nucleotides and adenosine cause coronary vasodilation.
• Accumulation of vasoactive metabolites (adenosine) may also be responsible for reactive hyperemia in the heart.
• Increased metabolic activity of the heart decreases coronary resistance, whereas a reduction in cardiac metabolism increases coronary resistance.
• Under normal conditions, blood pressure is kept within relatively narrow limits by the baroreceptor reflex.
• Therefore, changes in coronary blood flow are caused primarily by caliber changes of the coronary resistance vessels in response to the metabolic demands of the heart.
Neural factors • The coronary arterioles contain • -adrenergic receptors ----- vasoconstriction, • -adrenergic receptors ----- vasodilation
• Activity in noradrenergic nerves to the heart and injections of norepinephrine cause coronary vasodilation.
• However, norepinephrine increases the heart rate and the force of cardiac contraction, and the vasodilation is due to production of vasodilator metabolites in the myocadium secondary to the increase in its activity.
• Stimulation of vagal fibers to the heart dilate the coronaries.
Cutaneous circulation
• Core temperature and skin temperature.
• The primary function of the cutaneous circulation is maintenance of a constant body temperature.
• Blood flow to the skin widely depends on the need for loss or conservation of body heat. ----- mainly by changes in ambient and internal body temperatures.
AV anastomoses shunt
V
• AV anastomoses  thick muscle walls and richly supplied  with nerve fibers.
• AV anastomoses are highly sensitive to sympathetic nerves  vasoconstrictor agents such as epinephrine and  norepinephrine causing vasoconstriction.
• In skin, neural control is more important than local factors • Thus, the regulation of blood flow through these 
anastomotic channels is governed mainly by temperature  receptors or by higher centers of the central nervous system  (CNS).
• Parasympathetic vasodilator nerve fibers not supply the cutaneous blood vessels.
• Sweat glands innervated by cholinergic fibers of sympathetic nervous system vessels dilation
• Sweat contains an enzyme to release of bradykinin, act locally to dilate the arterioles and increase blood flow to the skin
CNS control: particularly in the head, neck and upper chest • Blushing: inhibition of sympathetic nerve fibers to the face • Blanching : stimulation of the sympathetic nerve fibers to
the face.
Under normal conditions, ambient temperature is main factor in  the regulation of skin blood pressure
• Respond to cold causing direct vasoconstriction may be mediated by the nervous system
• Cooled blood returning to the general circulation and stimulating the temperature-regulating center in the anterior hypothalamus ----- reflex vasoconstriction
• Prolonged exposure of the hand to severe cold ( near 0 oC) has a secondary vasodilator effect ----- reddening, alleviation of pain.
• Heat causes local vasodilation of cutaneous vessels is regulated by temperature-regulating center in the anterior hypothalamus.
• The rosy face in the cold is a example of cold vasodilation. However, blood flow through the skin of the face may be very low despite the flushed appearance.
• The reddness is largely the result of the reduced O2 uptake by the cold skin and the change in the affinity of hemoglobin for O2 as reflected by the cold-induced an increased O2 affinity for hemoglobin.
• Amount of blood in the skin and degree of oxygenation of blood in the subcutaneous vessels determine the color of face.
Skeletal muscle circulation
• Blood flow to skeletal muscle varies directly with the contractile activity of the tissue and the type of muscle.
• Blood flow and capillary density in red muscle are greater in red muscle than in white muscle.
• In resting muscle the arterioles exhibit asynchronous intermittent contractions and relaxations.
• Total blood flow in quiescent muscle (1.4~ 4.5 ml/min/100g), exercise may increase 15 to 20 times its resting level.
Skeletal muscle circulation
• At rest, neural and myogenic control predominates, during exercise ---- metabolic control is much more important. Basal tone and sympathetic nerve activity to muscle vessels regulate blood flow in resting condition
• The tonic activity of the sympathetic nerves is greatly influenced by the baroreceptor reflex.
• At rest, the effect of norepinephrine release from the sympathetic nerves is more important than epinephrine released from adrenal medulla.
• In skeletal muscle and skin do not receive parasympathetic innervation.
Autoregulation of blood flow
Over the pressure range of 20 to 120 mm Hg, the steady-state flow is relatively constant.
Myogenic mechanism
The vascular smooth muscle contracts in response to  increased stretch and relaxes with a reduction in  stretch.
An abrupt increase in perfusion pressure initially  distends the blood vessels then followed by  contraction of vessels and return of blood flow to the  previous control level.
Metabolic hypothesis • Blood flow is governed by the metabolic activity of
the tissue. • When the metabolic rate of the tissue increases or
the O2 delivery to the tissue decreases, more vasodilator substance is formed and blood flow increases.
• Lactic acid, CO2, H+, Na+, inorganic phosphate ions, adenosine and nitric oxide have been proposed as mediators of metabolic vasodilation.
• Because blood pressure is kept fairly constant, tissue metabolic activity and blood flow may vary together under physiological conditions.
Metabolic regulation of tissue blood flow
The peak flow and duration of the reactive hyperemia (as a result of the accumulation of these metabolites) are proportional to the duration of the occlusion period.
Occlusion ---- decrease O2 delivery ----- metabolites accumulation ------ vasodilation --- -- increase blood flow
Splanchnic circulation
The blood of splanchnic capillary beds ultimately flows into the portal vein, which normally provides most of the blood supply to the liver. However, the hepatic artery also supplies blood to the liver.
Intestinal circulation
Neural regulation • Neural control of the mesenteric circulation is almost
exclusively sympathetic causing constriction mediated by a- receptors.
• However, b-receptors are also present causing vasodilation. Autoregulation
• The principal mechanism responsible for autoregulation is metabolic, although a myogenic mechanism probably also participates. Functional hyperemia
• Food ingestion and food absorption increase intestinal blood flow. The principal mediator are glucose and fatty acids.
• Secretion of gastrin and cholecystokinin augments intestinal blood flow
Hepatic circulation
Regulation of flow • Blood flow in the portal venous and hepatic arterial  systems varies reciprocally. When blood flow is curtailed  in one system, the flow increases in the other.
• The sympathetic nerves constrict the vessels in the  portal venous and hepatic arterial systems mediated by  receptors.
• The liver contains about 15% of the total blood volume  of the body. If hemorrhage liver act as an important  blood reservoir in human.
Clinical case
• Extensive fibrosis of the liver, such as hepatic  cirrhosis, increases hepatic vascular resistance,  which raises portal venous pressure  substantially.
• The increased capillary pressure throughout  the splanchnic circulation leads to extensive  fluid transduction (ascites) into the peritoneal  cavity.
Placental and fetal circulation
Uterine circulation--- During pregnancy, blood flow increases rapidly as the uterus increase in size.
Vasodilator metabolites Estrogens Corticotrophin-releasing hormone
Placenta
• The placenta is the fetal lung and also the route providing nutritive materials
• O2 is taken by the fetal blood and CO2 is discharged into the maternal circulation. However the exchange is much less efficient than in lung.
Fetal circulation
• The blood in the umbilical vein ----- ductus venosus ----- inferior vena cava, the remainder mixes with the portal blood of the fetus -- --- to the left atrium via foramen ovale (FO) ----- left ventricle (better-oxygenated blood) ----- head of fetus
• Blood in superior vena cava to right ventricle and expelled into the pulmonary artery.
• Since the resistance of the collapsed lung of fetus is high ----- most of the blood in the pulmonary artery passes through the ductus arteriosus (DA) to the aorta ----- to the trunk and lower body ( lower O2 saturation).
• From the aorta, some of the blood is pumped into umbilical arteries and back to the placenta.
Changes in fetal circulation at birth
• The fetal red cells contain fetal hemoglobin F with greater affinity to O2. After 4 months 90% of the circulating hemoglobin is hemoglobin A.
• After birth ----- placental circulation cut off ----- the peripheral resistance suddenly rise.
• Lung expansion ----- the pulmonary vascular resistance falls ----- pulmonary blood flow increases markedly ----- returning to left artium - ---- closing the foraman ovale ----- the ductus arteriosus constricts within a few hours after birth producing functional closure.
• The increase in arterial O2 tension plays an important role • Relatively high concentrations of vasodilators (prostaglandin)are
present in the ductus in utero.
Thermoregulation
• Homeostasis--- All homeostatic mechanisms use negative feedback to maintain a 
constant value (called the set point). • Thermoregulatory responses to cold
• Thermoregulatory responses to heat
Introduction • Alterations of metabolic activity and temperature of  environment body temperature change
• Different regions of the body have different  temperatures at rest.
• The highest temperature (core temperature): brain,  thoracic and abdominal cavities
• The lowest temperature (shell temperature): skin • When temperature is measured in the mouth: (95%)  36.337.1oC
The circadian rhythm of core body temperature in day.
Effect of ambient temperature on body temperature.
In women: an increase in body temperature of about 0.5oC following ovulation, which persists until steroid levels fall.
> 42oC : proteins and enzymes denaturation ----- cell damage, death
< 33oC : temperature regulation is impaired and consciousness is lost
Heat exchange • The more metabolically active, the more heat produced. • The most heat production in organs such as brain, skeletal 
muscle, liver and kidney. • Thermoneutral zone: the range of environmental temperature 
2731oC easy for the body to maintain its core temperature. • Within thermoneutral zone thermoregulation is achieved 
solely by alterations in the blood flow to the skin. • Superficial venous plexus : accommodate a large volume of 
blood • In toes, ears, fingers and nose, arteriovenous anastomoses can 
open and close according to thermoregulatory requirement  leading to loss or reduce of heat
Mechanisms of heat exchange
• The evaporation of sweat
Evaporation • Approximately 580 Kcal of heat are lost for each  liter of water that evaporates from the body  surface.
• The insensible water loss is about 600 ml/day =  390 Kcal of heat per day. (from lung, mucosa of  the mouth, skin in resting state.
• During vigorous muscle activity increases more  sweat production 16 liters/h.
• Body temperature is chiefly regulated by neurons that lie within the hypothalamus
• Hypothalamus receives afferent input from peripheral thermoreceptors in skin and central thermoreceptors
• The skin has two kinds of thermoreceptor. Cold receptor : δ-myelinated afferents (maximal rate of discharge at 25-30oC); warm receptor: C-fibers (maximal rate of discharge at 40oC)
Regulation of body temperature – Role of the hypothalamus
• Body temperature regulation  set point = 37oC controlled by the  hypothalamus.
• The hypothalamus exerts its thermoregulatory actions on the vasculature of  the skin, sweat glands, and adipose tissue via autonomic nervous system.
Thermoregulatory responses to cold
1. Cutaneous vasoconstriction • Within the thermoneutral zone, blood flow to the  skin is around 200 ml/min
• Increase in sympathetic outflow to the cutaneous  vessels initiated by the neurons in the posterior  hypothalamus (chiefly by the action of  norepinephrine at receptor)  reduce blood flow  (20 ml/min) reduce heat lost
During long periods of cold exposure, Hunting reaction is designed to reduce the risk of ischemic tissue damage. The mechanism is unclear but may result from a temporary loss of sensitivity to norepinephrine.
Periodic vasodilation is thought to delay the onset of tissue damage.
2. Increased heat production from shivering • Metabolic heat production is increased by voluntary  muscle contraction or shivering in response to  signals  from the somatic motor neurons arised in the  hypothalamus.
• When muscle contracts, ATP is hydrolyzed and heat is  produced.
3. Nonshivering thermogenesis • Heat stimulated by calorigenic hormones :  glucocorticoids, insulin and glucagon; or stimulation of  brown fat metabolism
Thermoregulatory responses to heat 1. Cutaneous vasodilation • The dilatation is mediated by the autonomic nervous system, 
mainly through a reduction in vasomotor tone   increases heat  loss
2. Enhanced sweating • > 3032 oC increase sweating to 1.56 L/day from 500 ml/day in 
cold condition  • The sweat glands are innervated by sympathetic fibers, most of 
cholinergic via muscarinic receptors • Sweat rates increase  in response to increased circulating 
catecholamines form adrenal medulla • It is important that fluid and salt must be replaced quickly. • The sodium chloride content of sweat may be lower, possibly as a 
result of increased aldosterone secretion.
Disorders of thermoregulation
Hypothermia • It is inadvisable to warm the surface of a
hypothermic patient too rapidly, since the increased blood flow to the periphery may compromise blood flow to the body’s vital organs such as brain and lead to further problems.
Fever • Most often associated with infectious diseases,
dehydration, pyrogen produced by bacteria or by immune system (monocytes , macrophages and astrocytes in brain) in response to infection.
• The development of fever seems to involve a shift in the set-point which the core temperature is regulated.
• The mechanism may involve an alteration in the firing rates of preoptic neurons in the hypothalamus.
The time-course of typical febrile profile
Temperature regulation in newborn infant
• The neonate has a high surface area to volume ratio  readily lost from the skin’s surface; its layer of  insulating fat is comparatively thin  causes the  core temperature of the body to drop to around 35  oC during the first hours of its life.
• The thermoregulatory mechanisms are only partly  functional at birth
• The extra heat is generated by nonshivering  thermogenesis via the metabolism of brown adipose  tissue or brown fat.
Brown fat in neonate
• Metabolism of brown fat is triggered by increased plasma levels of circulating norepinephrine released by sympathetic nerve endings.
• Cold stress increases sympathetic nerve activity and secretion of epinephrine and norepinephrine by the adrenal medulla.
• The brown fat as a effective source of heat for the newborn baby.
References
• Ganong’s Review of Medical Physiology 23rd edition ,  Chapter 34.
• Vander’s Human physiology, Chapter14.
• Guyton & Hall, Textbook of Medical Physiology.  Chapter 73
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