Kinga Vereczkey-Porter, MD

• Clinical Assistant Professor of Medicine
• Division of Rheumatology, Allergy and Immunology
• Thurston Arthritis Research Center
• University of North Carolina School of Medicine
• Chapel Hill, North Carolina

The rectus abdominis is a powerful flexor of the thoracic and especially lumbar regions of the vertebral column medicine lookup cheap actonel uk, pulling the anterior costal margin and pubic crest toward each other medications pictures actonel 35mg without a prescription. The oblique abdominal muscles also assist in movements of the trunk symptoms queasy stomach cheap actonel online american express, especially lateral flexion of the lumbar vertebrae and rotation of the lower thoracic vertebral column medications that cause dry mouth buy 35mg actonel overnight delivery. The transversus abdominis probably has no appreciable effect on the vertebral column (Standring treatment magazine generic 35mg actonel, 2016) medications similar to abilify buy actonel 35 mg overnight delivery. The exception occurs at the L1 level, where the L1 anterior ramus bifurcates into two named peripheral nerves. Each dermatome begins posteriorly overlying the intervertebral foramen by which the spinal nerve exits the vertebral column and follows the slope of the ribs around the trunk. Iliohypogastric and ilio-inguinal nerves: terminal branches of the anterior ramus of spinal nerve L1. The thoraco-abdominal nerves pass infero-anteriorly from the intercostal spaces and run in the neurovascular plane between the internal oblique and the transversus abdominis muscles to supply the abdominal skin and muscles. The lateral cutaneous branches emerge from the musculature of the anterolateral wall to enter the subcutaneous tissue along the anterior axillary line (as anterior and posterior divisions), whereas the anterior abdominal cutaneous branches pierce the rectus sheath to enter the subcutaneous tissue a short distance from the median plane. T11, plus the cutaneous branches of the subcostal (T12), iliohypogastric, and ilio-inguinal (L1), supply the skin inferior to the umbilicus. During their course through the anterolateral abdominal wall, the thoracoabdominal, subcostal, and iliohypogastric nerves communicate with each other. Cutaneous veins surrounding the umbilicus anastomose with para-umbilical veins, small tributaries of the hepatic portal vein that parallel the obliterated umbilical vein (round ligament of the liver). A relatively direct lateral superficial anastomotic channel, the thoraco-epigastric vein, may exist or develop (as a result of altered venous flow) between the superficial epigastric vein (a femoral vein tributary) and the lateral thoracic vein (an axillary vein tributary). The deeper veins of the anterolateral abdominal wall accompany the arteries, bearing the same name. A deeper, medial venous anastomosis may exist or develop between the inferior epigastric vein (an external iliac vein tributary) and the superior epigastric/internal thoracic veins (subclavian vein tributaries). The superficial and deep anastomoses may afford collateral circulation during blockage of either vena cava. The primary blood vessels (arteries and veins) of the anterolateral abdominal wall are as follows: Superior epigastric vessels and branches of the musculophrenic vessels from the internal thoracic vessels. Inferior epigastric and deep circumflex iliac vessels from the external iliac vessels. Superficial circumflex iliac and superficial epigastric vessels from the femoral artery and greater saphenous vein, respectively. The distribution of the deep abdominal blood vessels reflects the arrangement of the muscles: the vessels of the anterolateral abdominal wall have an oblique, circumferential pattern (similar to the intercostal vessels;. It enters the rectus sheath superiorly through its posterior layer and supplies the superior part of the rectus abdominis and anastomoses with the inferior epigastric artery approximately in the umbilical region. The inferior epigastric artery arises from the external iliac artery just superior to the inguinal ligament. It runs superiorly in the transversalis fascia to enter the rectus sheath below the arcuate line. It enters the lower rectus abdominis and anastomoses with the superior epigastric artery. Lymphatic drainage of the anterolateral abdominal wall follows the following patterns. Superficial lymphatic vessels inferior to the transumbilical plane drain to the superficial inguinal lymph nodes. Deep lymphatic vessels accompany the deep veins of the abdominal wall and drain to the external iliac, common iliac, and right and left lumbar (caval and aortic) lymph nodes. For an overview of superficial and deep lymphatic drainage, see Chapter 1, Overview and Basic Concepts. When closing abdominal skin incisions inferior to the umbilicus, surgeons include the membranous layer of subcutaneous tissue when suturing because of its strength. Between this layer and the deep fascia covering the rectus abdominis and external oblique muscles is a potential space where fluid may accumulate. Although there are no barriers (other than gravity) to prevent fluid from spreading superiorly from this space, it cannot spread inferiorly into the thigh because the deep membranous layer of subcutaneous tissue fuses with the deep fascia of the thigh (fascia lata) along a line approximately 5. It provides a plane that can be opened, enabling the surgeon to approach structures on or in the anterior aspect of the posterior abdominal wall, such as the kidneys or bodies of lumbar vertebrae, without entering the membranous peritoneal sac containing the abdominal viscera. An anterolateral part of this potential space between the transversalis fascia and the parietal peritoneum (space of Bogros) is used for placing prostheses. Protuberance of Abdomen 999 A prominent abdomen is normal in infants and young children because their gastrointestinal tracts contain considerable amounts of air. In addition, their anterolateral abdominal cavities are enlarging and their abdominal muscles are gaining strength. Abdominal muscles protect and support the viscera most effectively when they are well toned; thus, the well-conditioned adult of normal weight has a flat or scaphoid (lit. The six common causes of abdominal protrusion begin with the letter F: food, fluid, fat, feces, flatus, and fetus. Eversion of the umbilicus may be a sign of increased intra-abdominal pressure, usually resulting from ascites (abnormal accumulation of serous fluid in the peritoneal cavity), or a large mass. Excess fat accumulation due to overnourishment most commonly involves the subcutaneous fatty layer; however, there may also be excessive depositions of extraperitoneal fat in some types of obesity. Tumors and organomegaly (organ enlargement such as splenomegaly-enlargement of the spleen) also produce abdominal enlargement. When the anterior abdominal muscles are underdeveloped or become atrophic, as a result of old age or insufficient exercise, they provide insufficient tonus to resist the increased weight of a protuberant abdomen on the anterior pelvis. The pelvis tilts anteriorly at the hip joints when standing (the pubis descends and the sacrum ascends) producing excessive lordosis of the lumbar region. Abdominal Hernias the anterolateral abdominal wall may be the site of abdominal hernias. Umbilical hernias are common in neonates because the anterior abdominal wall is relatively weak in the umbilical ring, which had failed to close normally, causing a protrusion at the umbilicus, especially in low-birth-weight infants. Umbilical hernias are usually small and result from increased intra-abdominal pressure in the presence of weakness and incomplete closure of the anterior abdominal wall after ligation of the umbilical 1000 cord at birth. The lines along which the fibers of the abdominal aponeuroses interlace are also potential sites of herniation. Occasionally, gaps exist where these fiber exchanges occur-for example, in the midline or in the transition from aponeurosis to rectus sheath. These gaps may be congenital, the result of the stresses of obesity and aging, or the consequence of surgical. These types of hernia tend to occur in people older than 40 years and are usually associated with obesity. The hernial sac, composed of peritoneum, is often covered with only skin and fatty subcutaneous tissue, but may occur deep to the muscle. Intense guarding, board-like reflexive muscular rigidity that cannot be willfully suppressed, occurs during palpation when an organ (such as the appendix) is inflamed and in itself constitutes a clinically significant sign of acute abdomen. The involuntary muscular spasms attempt to protect the viscera from pressure, which is painful when an abdominal infection is present. The common nerve supply of the skin and muscles of the wall explains why these spasms occur. Palpation of abdominal viscera is performed with the patient in the supine position with thighs and knees semiflexed to enable adequate relaxation of the 1001 anterolateral abdominal wall. Otherwise, the deep fascia of the thighs pulls on the membranous layer of abdominal subcutaneous tissue, tensing the abdominal wall. Some people tend to place their hands behind their heads when lying supine, which also tightens the muscles and makes the examination difficult. Superficial Abdominal Reflexes the abdominal wall is the only protection most of the abdominal organs have. With the person supine and the muscles relaxed, the superficial abdominal reflex is elicited by quickly stroking horizontally, lateral to medial, toward the umbilicus. Usually, contraction of the abdominal muscles is felt; this reflex may not be observed in obese people. Similarly, any injury to the abdominal skin results in a rapid reflex contraction of the abdominal muscles. Thus, they are distributed across the anterolateral abdominal wall, where they run oblique but mostly horizontal courses. They are susceptible to injury in surgical incisions or from trauma at any level of the abdominal wall. Injury to nerves of the anterolateral abdominal wall may result in weakening of the muscles. An oblique subcostal incision, used for liver/pancreas surgery (in the past for open cholecystectomy), can result in denervation of part of the abdominal wall if the nerves are not carefully identified and spared, which is not always possible. In the inguinal region, such a weakness may predispose an individual to development of an inguinal hernia (see the Clinical Box "Inguinal Hernias," p. When possible, the incisions follow the cleavage lines (Langer lines) in the skin. The incision that allows adequate exposure, and secondarily, the best possible cosmetic effect, is chosen. The location of the incision also depends on the type of operation, the location of the organ(s) the surgeon wants to reach, bony or cartilaginous boundaries, avoidance of (especially motor) nerves, maintenance of blood supply, and minimizing injury to muscles and fascia of the abdominal wall while aiming for favorable healing. Thus, before making an incision, the surgeon considers the direction of the muscle fibers and the location of the aponeuroses and nerves. Consequently, a variety of incisions are routinely used, each having specific advantages and limitations. Instead of transecting muscles, causing irreversible necrosis (death) of muscle fibers, the surgeon splits them in the direction of (and between) their fibers. The rectus abdominis is an exception; it can be transected because its muscle fibers run short distances between tendinous intersections and the segmental nerves supplying it enter the lateral part of the rectus sheath where they can be located and preserved. Generally, incisions are made in the part of the anterolateral abdominal wall that gives the freest access to the targeted organ with the least disturbance to the nerve supply to the muscles. Muscles and viscera are retracted toward, not away from, their neurovascular supply. Cutting a motor nerve paralyzes the muscle fibers supplied by it, thereby weakening the anterolateral abdominal wall. However, because of overlapping areas of innervation between nerves, one or two small branches of nerves may usually be cut without a noticeable loss of motor supply to the muscles or loss of sensation to the skin. Median incisions can be made rapidly without cutting muscle, major blood vessels, or nerves. Median incisions can be made along any part or the length of the linea alba from the xiphoid process to pubic symphysis. Because the linea alba transmits only small vessels and nerves to the skin, a median (midline) incision is relatively bloodless and avoids major nerves; however, incisions in some people may reveal abundant and well-vascularized fat. Conversely, because of its relatively poor blood supply, the linea alba may undergo necrosis and subsequent degeneration after incision if its edges are not aligned properly during closure. Paramedian incisions (lateral to the median plane) are made in a sagittal plane and may extend from the costal margin to the pubic hairline. After 1004 the incision passes through the anterior layer of the rectus sheath, the muscle is retracted laterally without sectioning to prevent tension and injury to the vessels and nerves. The posterior layer of the rectus sheath and the peritoneum are then incised to enter the peritoneal cavity. The external oblique aponeurosis is incised inferomedially in the direction of its fibers and retracted. The musculo-aponeurotic fibers of the internal oblique and transversus abdominis are then split in the line of their fibers and retracted. The iliohypogastric nerve, running deep to the internal oblique, is identified and preserved. Carefully made, the entire exposure cuts no musculo-aponeurotic fibers; therefore, when the incision is closed, the muscle fibers move together and the abdominal wall is as strong after the operation as it was before. These incisions-horizontal with a slight convexity-are used for most gynecological and obstetrical operations. The linea alba and anterior layers of the rectus sheaths are transected and resected superiorly, and the rectus muscles are retracted laterally or divided through their tendinous parts allowing reattachment without muscle fiber injury. Transverse incisions through the anterior layer of the rectus sheath and rectus abdominis provide good access and cause the least possible damage to the nerve supply of the rectus abdominis. This muscle may be divided transversely without serious damage because a new transverse band forms when the muscle segments are rejoined. Transverse incisions are not made through the tendinous intersections because cutaneous nerves and branches of the superior epigastric vessels pierce these fibrous regions of the muscle. Transverse incisions can be increased laterally as needed to increase exposure but are not utilized for exploratory procedures because superior and inferior extension is difficult, for example, for colostomy or ileostomy. Subcostal incisions provide access to the gallbladder and biliary ducts on the right side and the spleen on the left. Pararectus incisions along the lateral border of the rectus sheath are undesirable because they may cut the nerve supply to the rectus abdominis. If the muscular and aponeurotic layers of the abdomen do not heal properly, an incisional hernia can result. Thus, the potential for nerve injury, incisional hernia, or contamination through the open wound and the time required for healing are minimized. Reversal of Venous Flow and Collateral Pathways of Superficial Abdominal Veins When flow in the superior or inferior vena cava is obstructed, anastomoses between the tributaries of these systemic veins, such as the thoraco-epigastric vein, may provide collateral pathways by which the obstruction may be bypassed, allowing blood to return to the heart. Muscles: the anterolateral abdominal muscles consist of concentric, flat muscles located anterolaterally and vertical muscles placed anteriorly adjacent 1007 to the midline. The fibers of the aponeuroses interlace in the midline, forming the linea alba, and continue into the aponeuroses of the contralateral muscles. This brings them into a functional relationship with the flat muscles in which the vertical muscles brace the girdles anteriorly.

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The lateral medicine vicodin buy generic actonel from india, fan-like radial collateral ligament extends from the lateral epicondyle of the humerus and blends distally with the anular ligament of the radius treatment 5ths disease order cheapest actonel and actonel, which encircles and holds the head of the radius in the radial notch of the ulna medicine university actonel 35 mg discount, forming the proximal radio-ulnar joint and permitting pronation and supination of the forearm treatment 1 degree av block purchase actonel 35mg line. The fanlike radial collateral ligament is attached to the anular ligament of the radius bad medicine 1 purchase generic actonel canada, but its superficial fibers continue on to the ulna medicine gabapentin 300mg capsules generic 35mg actonel. The ulnar collateral ligament has a strong, round, cord-like anterior band (part), which is taut when the elbow joint is extended, and a weak, fan-like posterior band, which is taut 667 when the joint is flexed. The medial, triangular ulnar collateral ligament extends from the medial epicondyle of the humerus to the coronoid process and olecranon of the ulna and consists of three bands: (1) the anterior cord-like band is the strongest, (2) the posterior fan-like band is the weakest, and (3) the slender oblique band deepens the socket for the trochlea of the humerus. It is said to enable the swinging limbs to clear the wide female pelvis when walking. This angle is made 668 by the axes of the arm and forearm when the elbow is fully extended. Note that the forearm diverges laterally, forming an angle that is greater in the woman. This is said to allow for clearance of the wider female pelvis as the limbs swing during walking; however, no significant difference exists regarding the function of the elbow. In turn, their function and efficiency in the other movements they produce are affected by elbow position. The brachioradialis can produce rapid flexion in the absence of resistance (even when the chief flexors are paralyzed). Normally, in the presence of resistance, the brachioradialis and pronator teres assist the chief flexors in producing slower flexion. The chief extensor of the elbow joint is the triceps brachii, especially the medial head, weakly assisted by the anconeus. Of the several bursae around the elbow joint, the olecranon bursae are most important clinically. Intratendinous olecranon bursa, which is sometimes present in the tendon of triceps brachii. The bicipitoradial bursa (biceps bursa) separates the biceps tendon from, and reduces abrasion against, the anterior part of the radial tuberosity. The anular ligament attaches to the radial notch of the ulna, forming a collar around the head of the radius. The articular cavity of the joint is continuous with that of the elbow joint, as demonstrated by the blue latex injected into that space and seen through the thin parts of the fibrous layer of the capsule, including a small area distal to the anular ligament. The synovial membrane lines the deep surface of the fibrous layer and nonarticulating aspects of the bones. The synovial membrane is an inferior prolongation of the synovial membrane of the elbow joint. The deep surface of the anular ligament is lined with synovial membrane, which continues distally as a sacciform recess of the proximal radio-ulnar joint on the neck of the radius. This arrangement allows the radius to rotate within the anular ligament without binding, stretching, or tearing the synovial membrane. The head of the radius rotates in the "socket" formed by the anular ligament and radial notch of the ulna. Supination is the movement of the forearm that rotates the radius laterally around its longitudinal axis, so that the dorsum of the hand faces posteriorly and the palm faces anteriorly. Pronation is the movement of the forearm, produced by pronators teres and quadratus, that rotates the radius medially around its longitudinal axis, so that the palm of the hand faces posteriorly and its dorsum faces anteriorly. The actions of the biceps brachii and supinator in producing supination from the pronated position at the radio-ulnar joints. The interosseous membrane connects the interosseous margins of the radius and ulna, forming the radioulnar syndesmosis. The general direction of the fibers of the interosseous membrane is such that a superior thrust to the hand is received by the radius and is transmitted to the ulna. The axis for these movements passes proximally through the center of the head of the radius, and distally through the site of attachment of the apex of the articular disc to the head (styloid process) of the ulna. During pronation and supination, it is the radius that rotates; its head rotates within the cup-shaped collar formed by the anular ligament and the radial notch on the ulna. Almost always, supination and pronation are accompanied by synergistic movements of the glenohumeral and elbow joints that produce simultaneous movement of the ulna, except when the elbow is flexed. The distal radio-ulnar joint is the pivot type of synovial joint between the head of the ulna and the ulnar notch of the radius. The inferior end of the radius moves around the relatively fixed end of the ulna during supination and pronation of the hand. The two bones are firmly united distally by the articular disc, referred to clinically as the 678 triangular ligament of the distal radio-ulnar joint. It has a broad attachment to the radius but a narrow attachment to the styloid process of the ulna, which serves as the pivot point for the rotary movement. During pronation, the inferior end of the radius moves anteriorly and medially around the inferior end of the ulna, carrying the hand with it. Pronation is produced by the pronator quadratus (primarily) and pronator teres (secondarily). Pronation is essentially a function of the median nerve, whereas supination is a function of the musculocutaneous and radial nerves. Distal Radio-Ulnar Joint the distal (inferior) radio-ulnar joint is a pivot type of synovial joint. A fibrocartilaginous, triangular articular disc of the distal radio-ulnar joint (sometimes referred to by clinicians as the "triangular ligament") binds the ends of the ulna and radius together and is the main uniting structure of the joint. The base of the articular disc is attached to the medial edge of the ulnar notch of the radius, and its apex is attached to the lateral side of the base of the styloid process of the ulna. The proximal surface of this disc articulates with the distal aspect of the head of the ulna. Hence, the joint cavity is L-shaped in a coronal section; the vertical bar of the L is between the radius and ulna, and the horizontal bar is between the ulna and the articular disc. The articular disc separates the cavity of the distal radio-ulnar joint from the cavity of the wrist joint. In radiographs of the wrist and hand, the "joint space" at the distal end of the ulna appears wide because of the radiolucent articular disc. This coronal section of the right hand demonstrates the distal radio-ulnar, wrist, intercarpal, carpometacarpal, and intermetacarpal joints. Although they appear to be continuous 681 when viewed radiographically in parts A and C, the articular cavities of the distal radio-ulnar and wrist joints are separated by the articular disc of the distal radio-ulnar joint. Lansdown, Professor of Medical Imaging, University of Toronto, Toronto, Ontario, Canada. Kucharczyk, Professor and Neuroradiologist Senior Scientist, Department of Medical Resonance Imaging, University Health Network Toronto, Ontario, Canada. Observe the palmar radiocarpal ligaments, passing from the radius to the two rows of carpal bones. These strong ligaments are directed so that 683 the hand follows the radius during supination. Observe the nearly equal proximal articular surfaces of the scaphoid and lunate and that the lunate articulates with both the radius and the articular disc. Only during adduction of the wrist does the triquetrum articulate with the articular disc of the distal radio-ulnar joint. The synovial membrane extends superiorly between the radius and ulna to form the sacciform recess of the distal radio-ulnar joint. This redundancy of the synovial capsule accommodates the twisting of the capsule that occurs when the distal end of the radius travels around the relatively fixed distal end of the ulna during pronation of the forearm. These relatively weak transverse bands extend from the radius to the ulna across the anterior and posterior surfaces of the joint. During supination, the radius uncrosses from the ulna, its distal end moving (rotating) laterally and posteriorly so the bones become parallel. Wrist Joint the wrist (radiocarpal) joint is a condyloid (ellipsoid) type of synovial joint. The position of the joint is indicated approximately by a line joining the styloid processes of the radius and ulna or by the proximal wrist crease. The wrist (carpus), the proximal segment of the hand, is a complex of eight carpal bones, articulating proximally with the forearm via the wrist joint and distally with the five metacarpals. The distal end of the radius and the articular disc of the distal radio-ulnar joint articulate with the proximal row of carpal bones, except for the pisiform. The pisiform lies in a plane anterior to the other carpal bones, articulating with only the triquetrum. The synovial membrane lines the internal surface of the fibrous layer of the joint capsule and is attached to the margins of the articular surfaces. They are strong and directed so that the hand follows the radius during supination of the forearm. The dorsal radiocarpal ligaments take the same direction so that the hand follows the radius during pronation of the forearm. These movements are accompanied (actually, are initiated) by similar movements at the midcarpal joint between the proximal and distal rows of carpal bones. Circumduction of the hand consists of successive flexion, adduction, extension, and abduction. In this sagittal section of the wrist and hand during extension and flexion, observe the radiocarpal, midcarpal, and carpometacarpal articulations. Most movement occurs at the radiocarpal joint, with additional movement taking place at the midcarpal joint during full flexion and extension. The arrows indicate the direction the hand would move when tendons of the primary ("carpi") muscles acting at the "four corners" of the joint act individually or in unison. Palmar ligaments of the radio-ulnar, radiocarpal, intercarpal, carpometacarpal, and interphalangeal joints. The knuckles are formed by the heads of the bones, with the joint plane lying 688 distally. Most activities require a small amount of wrist flexion; however, tight grip (clenching of the fist) requires extension at the wrist. The midcarpal joint, a complex joint between the proximal and distal rows of carpal bones. The continuity of the articular cavities, or the lack of it, is significant in relation to the spread of infection and to arthroscopy, in which a flexible fiberoptic scope is inserted into the articular cavity to view its internal surfaces and features. The synovial membrane lines the fibrous layer and is attached to the margins of the articular surfaces of the carpals. Flexion and extension of the hand are actually initiated at the midcarpal joint, between the proximal and the distal rows of carpals. Most flexion and adduction occur mainly at the wrist joint, whereas extension and abduction occur primarily at the midcarpal joint. A common synovial membrane lines the internal surface of the fibrous layer of the joint capsule, surrounding a common articular cavity. Although the opponens pollicis is the prime mover, all of the hypothenar muscles contribute to opposition. These ligaments have two parts: Denser "cord-like" parts that pass distally from the heads of the metacarpals and phalanges to the bases of the phalanges. Thinner "fan-like" parts that pass anteriorly to attach to thick, densely fibrous or fibrocartilaginous plates, the palmar ligaments (plates), which form the palmar aspect of the joint capsule. The fan-like parts of the collateral ligaments cause the palmar ligaments to move like a visor over the underlying metacarpal or phalangeal heads. The interphalangeal joints have corresponding ligaments, but the distal ends of the proximal and middle phalanges, being flattened anteroposteriorly and having two small condyles, permit neither adduction or abduction. When a blow is received to the acromion of the scapula, or when a force is transmitted to the pectoral girdle during a fall on the outstretched hand, the force of the blow is usually transmitted along the length of the clavicle, that is, along its long axis. When ankylosis (stiffening or fixation) of the joint occurs, or is necessary surgically, a section of the center of the clavicle is removed, creating a pseudojoint or "flail" joint to permit scapular movement. When the coracoclavicular ligament tears, the shoulder separates from the clavicle and falls because of the weight of the upper limb. Rupture of the coracoclavicular ligament allows the fibrous layer of the joint capsule to be torn so that the acromion can pass inferior to the acromial end of the clavicle. Calcific Tendinitis of Shoulder Inflammation and calcification of the subacromial bursa result in pain, tenderness, and limitation of movement of the glenohumeral joint. This causes increased local pressure that often causes excruciating pain during abduction of the arm; the pain may radiate as far as the hand. The calcium deposit may irritate the 696 overlying subacromial bursa, producing an inflammatory reaction known as subacromial bursitis. As long as the glenohumeral joint is adducted, no pain usually results because in this position the painful lesion is away from the inferior surface of the acromion. The pain usually develops in males 50 years of age and older after unusual or excessive use of the glenohumeral joint. Recurrent inflammation of the rotator cuff, especially the relatively avascular area of the supraspinatus tendon, is a common cause of shoulder pain and results in tears of the musculotendinous rotator cuff.

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The transportation of these fuels requires sufficient blood flow through a healthy cerebral vasculature with the capacity to respond appropriately to metabolic demands. If the oxygen or glucose content or the flow of blood falls below the level needed to maintain nervous tissue viability, this precipitates a series of acute and longer term changes within the brain parenchyma. The removal of metabolic wastes such as lactate by venous drainage also plays an important role in cerebral function. Hypoxia describes a reduction in oxygen supply or content but is also sometimes applied to conditions in which the metabolic utilization of oxygen is impaired (histotoxic hypoxia). Ischaemia means a lack of blood supply but is usually used to denote a reduction in blood supply below the level needed to maintain tissue function. During ischaemia, in addition to the decreased blood supply, the removal of damaging metabolites is also impaired. The pO2 is the pressure that the oxygen would exert in a liquid or gas if it alone occupied the total volume, regardless of other molecules that may be present and irrespective of the total pressure. Hypoxia is graded as one ascends in altitude; it blends smoothly with physiology but not directly with pathology. In itself, low oxygen tension in the blood is incapable of causing cerebral necrosis, but ischaemia of even 2 minutes957 can result in necrosis within selectively vulnerable brain regions of the brain. The term hypoxia is often qualified to indicate whether it refers to the means of delivery or utilization of oxygen. Hypoxaemia Low oxygen in blood Reversible synaptic alterations without neuronal necrosis Hypobaric hypoxia Hypoxaemia accompanying decrease in ambient pO2 Reversible synaptic alterations (at very high altitudes), but without neuronal necrosis Histotoxic hypoxia Ischaemia Oligaemia Tissue hypoxia (global ischaemia) Tissue utilization of oxygen impaired Cessation of blood flow to tissue; no perfusion Low blood flow, hypoperfusion Low tissue pO2 due to global ischaemia No brain-damaging potential without accompanying hypotension Variable cellular damage, neurons most vulnerable Selective vulnerability Necrosis (both pan-necrosis and selective neuronal necrosis) in brain regions of selective vulnerability Necrosis is usually pan-necrosis and does not spare glia Ischaemic injury Tissue hypoxia (focal ischaemia) Watershed infarction Low tissue pO2 due to focal ischaemia Localized to the border zones between territories of two major arteries. Anoxia is a term often used, although there cannot be total absence of oxygen in the body. Ambient oxygen, however, can be zero, as for example on inhalation of pure nitrogen,449 in drowning939 and in an unscheduled space walk. Pure hypoxaemia of the brain can result in a prolonged coma of 2 weeks, from which a complete and remarkable recovery is possible,360,890 whereas prolonged coma after cardiac arrest or global ischaemia carries a very poor prognosis. Because hypoxia tends to occur in younger patients, recognition of a pure hypoxic insult, without accompanying ischaemia, is important in determining clinical prognosis. Hypoxia, thus, needs to be distinguished from ischaemia, while taking note that at tissue level, ischaemia always causes low tissue oxygenation (tissue hypoxia). The restitution of flow above the functional threshold can reverse the deficits without permanent damage. However, attempts to define precise ischaemic thresholds below which damage consistently takes place encounter difficulty because this depends on interacting factors including age, temperature, blood glucose concentration, and duration of ischaemia. The term stroke describes an acute disturbance or loss of brain function resulting from brain ischaemia or haemorrhage. The types of stroke and their pathological manifestations are described in detail later in this chapter. Vasculogenesis is the differentiation of mesodermal precursors into endothelial cells whereas angiogenesis is the formation of new vessels from preexisting vessels or plexuses. Embryonic blood vessels consist of endothelial cells and pericytes that organize and expand into highly branched conduits. This process is controlled by signalling systems involving a large number of specific receptors and their ligands, in addition to mediators of mitogenic, chemotactic, proteolytic and adhesive activities. Growth factors regulate differentiation of mesodermal cells into haemoangioblasts, which give rise to endothelial cells that proliferate to form cords and capillary tubes. Pericytes are recruited as support cells, with concomitant basal lamina production. Multiple growth factors activate specific receptors to model and prune branching vessels. The haemangioblasts differentiate into vessel-forming angioblasts and haematopoietic stem cells. Angioblasts cluster and acquire lumina, to form interconnecting tubes that constitute the primitive vascular plexus. Angioblasts from the splanchnopleuric region migrate into the head region to form a perineural vascular plexus around the developing brain (extracerebral vascularization). After development of the primitive perineural vascular plexus, brain blood vessels are formed (intracerebral vascularization) by capillary sprouts from the pre-existing vessels in this plexus. Next, another capillary plexus is formed in the intermediate zone between the subventricular precursor cell zone and the cortical plate. Angioblasts form the perineural vascular plexus around the developing brain (vasculogenesis, extracerebral vascularization: leptomeningeal vascularization). Capillary sprouts emerge from the primitive plexus (angiogenesis) and penetrate into the brain, beginning from deeper layers upwards (intracerebral vascularization). Angiogenesis may be re-upregulated, for example in ischaemia (the most important cause of the reactivation), upon metabolic demand and in neoplasia. Diagram adapted from Trollman and Gassmann1021 and redrawn courtesy of Y Yamamoto, Yamaguchi University Graduate School of Medicine, Japan. Sprouting and induction of further angiogenesis in mature vessels require destabilization of endothelium and pericyte contacts by angiopoetin-2 (Ang-2), an antagonist of Ang-1. The blood vessels penetrating the neuroectoderm form intracerebral branches of various sizes. This, together with the regression of supernumerary vessels, creates the vascular tree. The active phase of angiogenesis ceases soon after birth, after which the cerebral vasculature is expanded only to meet the needs of the growing brain, mainly by elongation of the pre-existing blood vessels. Angiogenesis in the mouse telencephalon progresses in an orderly, ventral-to-dorsal gradient regulated in a cellautonomous manner by compartment-specific homeobox transcription factors. It has also been suggested that some tumours may create vascular channels lined by tumour cells instead of endothelium, a phenomenon called vascular mimicry, which was first described in melanomas305 and has been claimed to occur even in astrocytomas. All 3 corresponding proteins are expressed in vascular endothelium and associated with cytoskeletal and interendothelial junction proteins and components of certain signal transduction pathways. The brain lacks significant energy reserves and requires a continuous supply of well-oxygenated blood. The leptomeningeal anastomoses are located at the periphery of the arterial trees and these zones tend to be the first to be deprived of sufficient blood flow in the event of arterial hypotension or a reduction in perfusion due to raised intracranial pressure. Note the small calibre of the posterior communicating arteries, which are often narrower in older people. The border zones (watershed areas) between the territories are indicated by shading. The extent of the three main arterial territories in the cerebrum along the rostro-caudal plane are shown: anterior cerebral (magenta), middle cerebral (blue) and posterior cerebral (yellow). The vascular supply to the striatum (delineated in green) includes the lateral lenticulostriate arteries, medial lenticulostriate arteries and the recurrent artery of Heubner (most medial), all of which branch off from the middle cerebral artery. The slices include several small infarcts (white circles) in the right frontal lobe, in the territory of the middle cerebral artery. Short penetrators also exist in the brain stem as paramedian branches of the basilar artery. The capillaries do interconnect but their collateral flow is so local and restricted that the occlusion of a perforator usually results in a small region of ischaemic damage, described as a lacunar infarct (see later). The anterior spinal artery may be of variable size or even discontinuous at different levels, depending on the pattern of replenishing tributary arteries along its passage downwards. Posterior spinal arteries are even more irregular, deriving from vertebral or posterior inferior cerebellar arteries. The most important and largest tributary artery is arteria radicularis magna (of Adamkiewicz), which enters the spinal canal at a variable level, between T8 and L2, below which spinal artery blood flow is mainly downward. A border zone is created, usually at a lower thoracic level than the traditionally stated T4. She died acutely of a large fresh atherothrombotic infarct in the territory of the left middle cerebral artery, which appears hypodense in this scan. There are also perivascular cavities (left arrows), best seen in the left caudate nucleus. The main anterior (usually single) and posterior (usually paired) spinal arteries arise from the vertebral arteries, and receive tributaries from the intraosseous vertebral, intercostal, lumbar and other arteries that enter the spinal canal through the intervertebral formina at multiple levels. The levels at which the different tributaries enter the spinal canal vary considerably. In the depths of the anterior median fissure, alternate sulcal arteries deviate either left or right to supply the corresponding side of the cord. The branches from the posterior spinal arteries supply the posterior horns and columns. In addition, the cerebral venous drainage employs the dural sinuses as the final intracranial collecting blood vessels. In general, there are fewer veins than perforating arteries and the long veins also drain the cerebral cortex while coursing through it. After the veins of the superficial or cortical network exit the parenchyma and enter the subarachnoid space, they turn towards the dural sinuses. In the suprasylvian and paramedian regions, the frontal, parietal and occipital superior cerebral veins run upward to drain into the superior sagittal sinus. On the posterior lateral and inferior surfaces of the temporal lobe, and on the lateral and inferior surfaces of the occipital lobe, the veins drain into the lateral sinuses. The number and location of the cortical veins vary considerably, which makes angiographic verification of their patency difficult. The superficial veins have thin walls, no tunica muscularis and no valves, permitting dilation and flow of venous blood in various directions. These features, together with numerous anastomoses, help to achieve efficient collateral flow in the case of venous thrombosis. Within the parenchyma of the hemispheres, the veins of the superficial system anastomose extensively with the internal cerebral and basal veins of the deep network. The deep veins collect blood from the deep grey matter at the base of the brain and the choroid plexus of the lateral ventricles and drain into the centrally located great cerebral vein of Galen. The inferior sagittal sinus, running along the lower edge of the falx, also joins the straight sinus. The straight sinus then merges with the superior sagittal and occipital sinuses at the confluence of sinuses (torcula herophili). The bulk of the venous blood flows bilaterally via the transverse and sigmoid sinuses (which together form the lateral sinus), through the jugular foramen into the jugular vein. In 14 per cent of cases, the transverse portion of the left sinus is not visualized on angiography, an anomaly that may be relevant when investigating venous thrombosis. At the surface, the veins form a subarachnoid plexus, from where blood drains in three directions: from the superior part it drains into the great cerebral vein of Galen, from the anterior part into the petrosal sinuses, and from the posterior and lateral parts into the adjacent straight, occipital and lateral sinuses. Venous Drainage of the Cord the venous drainage of the cord in general corresponds to the vascular architecture of the arterial supply of the cord (see earlier), but the number of veins within and around the cord, as well as exiting the spinal canal through the intervertebral foramina, is greater than that of arteries. From the periphery, radially oriented veins drain into the superficial plexus of veins around the cord. Radicular veins convey the blood into paravertebral and intervertebral plexuses, which drain into the azygous and pelvic veins. Because these veins do not have valves, there is a high potential for infections from the abdominal cavity to spread into the spinal cord. The veins in black are on the surface of the brain; those depicted with dashed lines are within the parenchyma. The endothelial cells of the intracranial blood vessels are joined by tight junctions and have no fenestrations. The muscle layer of the intracranial arteries is thinner than in extracranial arteries of a similar size, the external elastic lamina lacking and the adventitia leaner. To complement these features the brain is endowed with structurally unique protective systems. In addition to the perivascular drainage routes,1082 the brain also has a lymphatic-like pathway, recently described as the glymphatic system. Cerebral resistance arteries dilate or constrict during changes in arterial pressure. Diagram kind courtesy of Y Yamamoto, Yamaguchi University Graduate School of Medicine, Japan. The capillaries vary in density throughout the brain, being more abundant in regions with high metabolic rates. Within grey or white matter, capillary density is richer where metabolic and, consequently, oxygen-delivery requirements are higher. The decrease in density of cortical neurons from the mouse (~142 500 neurons/mm3) to rat (~105 000 neurons/mm3), cat (~30 800 neurons/mm3), human (~10 500 neurons/mm3) and whale (~6800 neurons/mm3) is accompanied by a corresponding reduction in the rate of oxidative phosphorylation per unit volume of brain tissue. These phylogenetic and ontogenetic variations may explain the differential effects of hypoxia and ischaemia in these species (see later).

Diseases

• Methylmalonic aciduria microcephaly cataract
• Deafness congenital onychodystrophy recessive
• Dyserythropoietic anemia, congenital
• Bicuspid aortic valve
• Anotia
• Spastic paraparesis
• Renal glycosuria
• 2-Methylacetoacetyl CoA thiolase deficiency, rare (NIH)
• Sacral meningocele conotruncal heart defects
• Familial Mediterranean fever