Placenta.pdf

In terms of blood flow, we can divide the skin into Œ“apical” (glabrous) skin اي ا ﻣ ﺎ ﻛﻦ ا ﻟ ﺠ ﻠ ﺪ ا ﻟ ﻤ ﻜﺸﻮف . The apical skin which is present on the nose, lips, ears, hands, and feet The apical skin at the extremities of the body has a very high surface-to-volume ratio that fa...

In terms of blood flow, we can divide the skin into Œ“apical” (glabrous) skin اي ا ﻣ ﺎ ﻛﻦ ا ﻟ ﺠ ﻠ ﺪ ا ﻟ ﻤ ﻜﺸﻮف . The apical skin which is present on the nose, lips, ears, hands, and feet The apical skin at the extremities of the body has a very high surface-to-volume ratio that favors heat loss. The apical skin blood flow is under the control of sympathetic fibers that release norepinephrine and thereby constrict the arterioles, anastomotic vessels, and venules. The apical skin circulation has (arterio-venous (a-v) anastomoses or AV s h u n t scalledglomus bodies).AV s h u n t scan reach a density of ~500 per cm2in the nail beds.AV s h u n t sare short vessel segments with a large inner diameter and a very thick muscular wall. AV s h u n t swhen open, they provide a low-resistance connection between arteries and veins, shunting blood directly into the venous plexuses of the limbs. AV s h u n t s a r e densely innervated by adrenergic axons. AV s h u n t s a r e maintained in a constricted state by sympathetic tone.AV s h u n t s p l a y a n i m p o r t a n t r o l e i n t e m p e r a t u r e r e g u l a t i o n i n h u m a n s i n t h e i r t h e r m o n e u t r a l zone, which for a naked resting human is about 26°C to 36°C, but lower when active and clothed. From the temperature control center in the hypothalamus,bursts of nerve impulses are sent simultaneously to all AV shunts. AV s h u n t sand small veins are all closed near the lower end of the thermoneutral zone. AV s h u n t sand small veins are all open near the upper end of the thermoneutral zone. ↓ in core temperature (or shock)→↑sympathetic tone → vasoconstriction in the a-vanastomoses→ the blood returns to the heart through the deep veins →cools the arterial blood through a countercurrent mechanism (the reverse is also true) “Non-apical” skin. Non-apical (hairy) skin is present over most of the body surface.The difference in vasculature between non-apical skin and apical skin 1Non-apical skinvasculature is almost completely lack a-vanastomoses Non-apical(hairy) skin blood flow is primarily nutritive in function.2Non-apical skin have two types of sympathetic neurons innervating the vessels of the skin. a. Vasoconstriction occurs in response to sympathetic neurons that release norepinephrine. b. Vasodilation occurs in response to sympathetic neurons that release acetylcholine. Mechanical stimuli elicit local vascular responses in the skin.White ReactionIf the skin is stroked mildly with a sharp instrument, a blanched line appears in the trailing path of the instrument. During the next 15 to 60 seconds, thewhite reactionthat ensues is caused by contraction of microvascular smooth muscles and pericytes in response to mechanical stimulation. This active response has the effect of emptying the capillary loops, the collecting venules, and the subpapillary venous plexus of blood in a sharply delineated manner. “Triple Response” or Lewis's triple response:The triple response is caused by firm stroking of the skin with a pointed object.If a pointed instrument is drawn across the skin more forcefully, a series of reactions ensues that is collectively known as thetriple response.a. red reaction (15 seconds)Within several seconds, a band (or line) of increased redness appears due to a local dilation and increased perfusion of capillaries and venules within the perturbed area. The presumed cause is the local release of a vasodilator substance (e.g., histamine) from cells that were disturbed by the mechanical response.Thisred reactionis independent of innervation and may persist for one to several minutes. b. flare reaction (15–45 seconds):If the stimulus is sufficiently strong or repeated, the reddening of the skin is no longer restricted to the line that was stroked but spreads to the surrounding region. Thisflare reactionappears several seconds after the localized redness and reflects the dilation of arterioles. The mechanism of the flare reaction is a local nervous response known as theaxon reflex,which depends on the branching of a single nerve fiber. A stimulus applied to one branch (containing the sensory receptor) gives rise to an action potential that travels centrally to the point of fiber branching. From this branch point, the afferent signal travels both orthodromicallyto the spinal cord and antidromically along the collateral branch. As a result, this collateral branch releases the vasodilating neurotransmitters(substance P). Sectioning of the nerve fiber central to the site of the collateral branch eliminates the awareness of the stimulus but does not eliminate the flare reaction until the nerve fiber degenerates.c. wheal (1-3 minutes)When the stimulus is even more intense, as caused by the lash of a whip, the skin along the line of injury develops localized swelling known as awheal.This local edema results from an increase in capillary permeability (e.g., in response to histamine) as filtration exceeds absorption. The wheal is preceded by and ultimately replaces the red reaction, appearing within a few minutes from the time of injury, and it is often surrounded by the flare reaction. Placental and fetal circulation:Non pregnant uterus:The blood flow of the uterus 1parallels the metabolic activity of the myometrium and endometrium and2undergoes cyclic fluctuation that correlate well with the menstrual cycle.During pregnancy: Blood flow increasesrapidly as the uterus and fetus increase in size. Va s o d i l a t o r m e t a b o l i t e s a r e u n d o u b t e d l y p r o d u c e d i n t h e u t e r u s , a s t h e y a r e i n o t h e r a c t i v e t i s s u e . In early pregnancy the artero-venous oxygen difference across the uterus is small, and it has been suggested that estrogen act on blood vessels to increase uterine blood flow in excess of tissue oxygen needs.With the growth of the embryo, the amountof oxygen extracted from the uterine blood, though, is increasingly larger, causing theoxygen saturation and the average venoussaturation in the mother's blood to sink, even though blood flow is increasedby a factor of 20.In latter part of pregnancy more oxygen is extracted from the uterine blood Just before parturition there is a sharp decline in uterine blood flow. PlacentaPlacental barrier has four layers: ŒSyncytiotrophoblast.Cytotrophoblast.ŽConnective tissue of villus.Endothelium of fetal capillariesAfter 20 weeks the Cytotrophoblasdisappear and only 3 layers remain Placenta allows the transfer of many drugs and dietary substances.Lipid soluble compounds rapidly crosses the placenta,water soluble substances pass less.The greater the molecular weight the less it passes through placenta. The drug molecules not bound to plasma protein diffuse along a concentration gradient. Functions of placenta:ŒTransfer function:Transport is facilitated by the close approximation of maternal and fetal vascular systems within the placenta. It is important to recognize that there normally is no mixing of fetal and maternal blood within the placenta.Respiratory function:Intake of O2 & output of CO2 takes place by simple diffusion.Oxygen supply to fetus rate of 5ml/kg/min & this achieved with cord flow of 165-330ml/min. ŽExcretory function:Waste products uric acid, creatinine CO2, Heat, Hormones, Urea, water are excreted to maternal blood by simple diffusion.Nutritive function:i. GlucoseGlucose is the major energy substrate provided to the placenta and fetus. Glucoseis transported across the placenta by facilitated diffusion via hexose transporters. Although the fetus receives large amounts of intact glucose, a large amount is oxidizedwithin the placenta to lactate, which is used for fetal energy production.ii. Amino acids Amino acid concentrations in fetal blood are higher than in maternal blood. Amino acids are therefore transported to the fetus by active transport. iii. Lipids (triglyceride and fatty acids) Lipids directly transported from mother to fetus in early pregnancy but synthesized in fetus later in pregnancy. Thus, fetal fat has got dual origin .iv. Hormones, water, and vitamins. v. Wa t e r & e l e c t r o l y t e s a. Sodium, Potassium, Chloride passes by simple diffusion.b. Calcium, Phosphate, iron passes by active transport. Barrier function:Placenta act as a Protective barrier to the fetus against noxious agents circulating in maternal blood. Materials higher than 500daltons do NOT pass.‘Immunological function:Fetus & placenta contain paternally determined antigens, foreign to the mother. In spite of this, no evidence of graft rejection. Probably: 1. Fibrinoid & sialomucincoating of trophoblast may suppress the troblasticantigen. 2. Placental hormones, steroids, Human Chorionic gonadotrophic hormone have got weak immunosuppressive effect, may be responsible for producing sialomucin.’Endocrinal function: many hormones are secreted by placenta. Flow Chart fetal circulation: Fifty-five percent of the fetal cardiac output goes through the placenta.The blood in the umbilical vein is believed to be about 80% saturation with oxygen, compared with 98% saturation in the arterial circulation of the adult.The "ductus venosus" diverts some of this blood directly to the inferior vena cava, and remainder mixed with the portal blood of the fetus. Most of the blood entering the heart through the inferior vena cava is diverted directly to the left atrium via the "patent foramen ovale".Most of the blood from the superior vena cava enters the right ventricle and is expelled into the pulmonary artery. The resistance of collapsed lung is high, and the pressure in pulmonary artery is several mmHg higher than it is in the aorta, so most of the blood in the pulmonary artery passes through the "ductus arteriosus" to aorta. In this fashion, the relatively un-saturated blood from the right ventricle is diverted to the trunk and lower body of the fetus, while the head of the fetus receives the better-oxygenated blood from the left ventricle. From the aorta, some of the blood is pumped into the umbilical arteries and back to the placenta. Fetal respirationThe tissues of the fetal and newborn mammals have a remarkable but poorly understood resistance to hypoxia. The fetal RBC contains fetal hemoglobin (hemoglobin F) whereas the adult RBC contains adult hemoglobin (hemoglobin A). The cause of the difference in oxygen affinity between the two is that hemoglobin F bind 2,3-DPG less effectively than hemoglobin A dose. Differences between fetal and adult circulation:ŒPresence of shunts which allow oxygenated blood to bypass the right ventricle and pulmonary circulation, flow directly to the left ventricle, and for the aorta to supply the heart and brain. These shunts are Ductus venosus, Foramen ovale, Ductus arteriosus.Ventricles of the fetal heart work in parallelcompared to the adult heart which works in sequence.ŽFetal cardiac output per unit weight is 3 times higher than that of an adult at rest. Which is accomplished by ↑ heart rate and ↓ systemic peripheral resistance. This compensated for low O2 content of fetal blood. Changes in fetal circulation and respiration after birthAt birth,The placental circulation is cut offêThe peripheral resistance suddenly rises+ Expansion of the lungêêThe pressure in the aorta rises The pulmonary vascular resistance falls to less than 20% of the in-utero value, and pulmonary blood flow increased markedly.êThe pressure in the aorta rises until it exceeds that in the pulmonary artery.êBlood returning from the lung raises the pressure in the left atrium, closing the foramen ovaleby pushing the valve that guards it against the intra-atrial septum. Changes in fetal circulation after birth:The left ventricle is now coupled to the high-resistance systemic circulation→↑ left ventricle wall thickness and mass. The left ventricle in the fetus pumped blood only to the upper part of the body and brain. After birth, left ventricle must deliver the entire systemic cardiac output (≈450 mL/kg/min). (Almost 200% increase in output) This marked increase in left ventricular performance is achieved through a combination of hormonal and metabolic signals, including an increase in the level of circulating catecholamines. The myocardial receptors (β-adrenergic) through which catecholamines have their effect.The right ventricle is now coupled to the low-resistance pulmonary circulation→↓ right ventricle wall thickness and mass.Ductus Arteriosus become ligamentum arteriosum. Foramen ovalebecome Fossa ovalis.Ductus venosus become ligamentum venosus.Umbilical arteries become umbilical ligaments.Umbilical vein become ligamentum teres. Causes of hypotension (<90 mmHg systole, <60 mmHg diastole)::A. Cardiac causes:1. Arrhythmia: Tachycardia, bradycardia, fibrillation.2. Structural diseases: Valve diseases, Ischemic heart disease, Pericardial diseases, Cardiac tamponade, congenital heart disease, obstructive and dilated cardiomyopathy, Primary pulmonary hypertension.3. Hypovolemia: hemorrhage, diarrhea, dehydration, drugs (diuretics).B. Vascular:1. Systemic vasodilation: sepsis, anaphylaxis, neurogenic, autonomic dysfunction, drugs (vasodilators).2. Obstructive: Pulmonary embolism.C. Neurogenic:Diabetes mellites with autonomic neuropathy, Parkinson disease, dementia; drugs (sympatholytic, tricyclic) drug.Other causes of hypotension:Orthostatic (postural) hypotension 1Orthostatic (postural) hypotension is a transient hypotensive condition resulting from insufficient compensatory responses to the gravitational shifts in blood when a person moves from a horizontal to a vertical position, especially after prolonged bed rest, may occur in individuals whose baroreceptors reflex mechanisms impaired (e.g., individuals treated with sympatholytic agents) or who are volume depleted. 2Postprandial hypotension Postprandial hypotension is defined as the development or worsening of hypotension in about 30 minutes to 2 hours after eating a meal, specifically large meals high in carbohydrates. Caffeine with meals may help constrict blood vessels, raise blood pressure and reduce its symptoms Venous Valve Incompetence Causes “Varicose” Veins. The valves of the venous system frequently become “incompetent” or sometimes even are destroyed. This is especially true when the veins have been overstretched by excess venous pressure lasting weeks or months, as occurs in pregnancy or when one stands most of the time. Stretching the veins increases their cross-sectional areas, but the leaflets of the valves do not increase in size. Therefore, the leaflets of the valves no longer close completely.When this develops, the pressure in the veins of the legs increases greatly because of failure of the venous pump; this further increases the sizes of the veins and finally destroys the function of the valves entirely. Thus, the person develops “varicose veins,”which are characterized by large, bulbous ﺑـﺎرز protrusions ﻣﻠ ﺗ ـوي of the veins beneath the skin of the entire leg, particularly the lower leg.Whenever people with varicose veins stand for more than a few minutes, ►venous and capillary pressures become very high, ►leakage of fluid from the capillary causes’ constant edema in the legs►The edema in turn prevents adequate diffusion of nutritional materials from the capillaries to the muscle and skin cells, so that the muscles become painful and weak, and the skin frequently becomes gangrenous and ulcerates. The best treatment for such a condition is continual elevation of the legsto a level at least as high as the heart. Tight binders on the legs also can be of considerable assistance in preventing the edema and its sequelae ﻋﻘ ﺎ ﺑ ﯾل . Cardiovascular response to gravity (standing):The effects of gravity on circulation in humans depend in part upon the blood volume. When the blood volume is low, these effects are marked; when it is high, they are minimal. If the individual moves about, the operation of the muscle pump keeps the venous pressure below 30 mmHg in the feet, and venous return is adequate.When the person is lying down (supine position), gravitational forces are similar on the thorax, abdomen and legs because these compartments lie in the same horizontal plane. In this position, venous blood volumesand pressuresare distributedevenlythroughout the body. When the person lying down and then suddenly stands up or individual dose not move,gravity acts on the vascular volume causing blood to accumulatein the lower extremities.ÞBecause venouscomplianceis high and the veins readily expand with blood, most of the blood volume shift occurs in the veins.ÞTherefore, venous volume (Vol) and pressure (VP) becomevery high in the feet and lower limbs when standing and fluid begins to accumulate in the interstitial spaces because of increase hydrostatic pressure in the capillaries. If net filtration of fluid exceeds the ability of the lymphatics to return it to the circulation, edema will occur.ÞThis shift in blood volume decreases thoracic venous blood volume (CV Vol) and therefore central venous pressure(CVP) decreases.ÞThis decreases right ventricular filling pressure (preload),Þleading to a decline in stroke volume by the Frank-starling mechanism.ÞLeft ventricular stroke volume also falls because of reduced pulmonary venous return (decreased left ventricular preload).ÞThis causes cardiac output and mean arterial pressure to fall.ÞIf arterial pressure falls appreciably upon standing, this is termedorthostatic or postural hypotension. This fall in arterial pressure can reduce cerebral blood flow to the point where a person might experience syncope (fainting). Symptoms of cerebral ischemia developed when the cerebral blood flow decreases to less than about 60% of the flow in the recumbent position. If there were no compensatory cardiovascular changes, the reduction in cardiac output due to pooling on standing would lead to a reduction of cerebral flow of this magnitude, and consciousness would be lost. In the cerebral circulation, there are: ŒThe arterial pressure at head level drops 20 to 40 mmHg, but jugular venous pressure falls 5 to 6 mmHg, reducing the drop in perfusion pressure (arterial pressure minus venous pressure)Cerebral vascular resistance is reduced because intracranial pressure falls, decreasing the pressure on the cerebral vessels.ŽThe decline in cerebral blood flow increases the partial pressure of CO2(PCO2) and decrease the PO2and the pH in brain tissue, further activity dilating the cerebral vessels. The compensatory changes include:ŒBecause of operation of auto-regulation mechanisms, cerebral blood flow declines only 20% on standing.The amount of oxygen extracted from each unit of blood increases, and the net effect is that cerebral oxygen consumption is about the same in the supine and the up-right position.ŽCerebral vessels vasodilate to preserves blood flow. 2. Compensatory mechanisms:Compensatory mechanisms will attempt to increase blood pressure to normal.The carotid sinusand aortic archbaroreceptors respond to the decrease in arterial pressure by decreasing the firing rate of the carotid sinus nerves.ÞA coordinated response from the vasomotor center then increases sympathetic outflow to the heart and blood vessels and decreases parasympathetic outflow to the heart. As a result,Œheart rate increase, and contractility →↑Stroke volume.There is relatively little veno-constriction in the periphery→↑venous return →↑Preload.ŽThe arterioles constrict →↑total peripheral resistance.there is a prompt increase in the circulating levels of rennin and aldosterone. ÞIncrease blood pressure. B. Changes caused by ExerciseMuscle blood flow:The blood flow of resting muscle is low (2 to 4 mL/100gm/min).When a muscle contracts, it compresses the vessels in it if develops more than 10%of its maximal tension, when it develops more than 70% of its maximal tension, blood low is completely stopped. Between contractions (During the post-occlusion period), however, flow is so greatly increased by reactive hyperemia to repay the O2 debt by that blood flow to muscle is increased as much as 30-fold.Skeletal muscle blood supply control A. Intrinsic autoregulation of skeletal muscle blood flowIntrinsic autoregulation of skeletal muscle maintains a stable blood flow, wheneverblood pressure fluctuatesthe arterioles of skeletal muscle can control their-own blood flow by intrinsic pressure-responsive mechanisms(myogenic regulation). ↑ blood pressure→ an influx of intracellular calcium→ triggering vasoconstriction and thereby counteracting the stretch stimulus. This appears to be an intrinsic property of vascular smooth muscle because:1Arteriolesstill performs Intrinsic autoregulation even when with removal of endothelium. 2Intrinsic autoregulation is overcome, as vascular smooth muscle still dilates readily in response to exercise. B. Metabolic regulation of skeletal muscle blood flow (active hyperemia)Demand for O2 in skeletal muscle varies with metabolic activity level, and blood flow is regulated to meet demand.During exercise, when demand is high, these local metabolic mechanisms are dominant.The high blood flow by local vasodilatation maintained by local mechanisms including: fall in tissue PO2.‚rise in tissue PCO2 and decreases in pH.ƒaccumulation of lactate, hydrogen peroxide, and K.„the temperature rises in active muscle.The high blood flow by local vasodilatation caused by dilation of arterioles and pre-capillary sphincters.The high blood flow by local vasodilatation help to: the vasodilation →↑cross-sectional area of the vascular bed→↓velocity of flow →↑the capillary pressure increases until it exceeds the oncotic pressure throughout the length of the capillary → the accumulation of osmotically active metabolites more rapidly than they can be carried away →↓the osmotic gradient across the capillary walls → fluid transudation into the interstitial spaces is tremendously increased. ‚Lymph flow is greatly increased limiting the accumulation of interstitial fluid. ƒThe decreased pH and increased temperature shiftthe dissociation curve for hemoglobin to the right, so more oxygen is given up blood.„The concentration of 2,3-DPG in the RBC is increased and this further decreased the oxygen affinity of hemoglobin.…There is an up to three-fold increase in the arterio-venous oxygen difference and the oxygen consumption of skeletal muscle is increased by 100-fold. The transport of CO2out of the tissue is also facilitated.†Potassium dilates arterioles in exercising muscle, particularly during the early part of exercise. C. Endothelial regulation of skeletal muscle blood flowNumerous vasoactive mediators released by the vascular endothelium have been shown to affect the arteriolar tone of skeletal muscle, and these should probably be listed among the regulatory molecules. These include:1Nitric oxide (NO)2Adenosine triphosphate (ATP)3Adenosine4Prostaglandins5Endothelium-derivedhyperpolarization factors (EDHFs)