Cheri Pies DrPH, MSW

• Clinical Professor Emerita , Public Health

https://publichealth.berkeley.edu/people/cheri-pies/

The site of amyloid deposition provides an important clue for recognizing localized amyloidosis medicine 4839 cheap 300 mg penisole mastercard. The most frequent sites of localized amyloid deposits are the respiratory tract, genitourinary tract, and skin medications you can take while pregnant for cold generic penisole 300mg mastercard. The usual treatment is resection of the tissue with an yttrium­aluminum­garnet laser symptoms nicotine withdrawal 300mg penisole visa. Amyloid can involve the vocal cords and false vocal cords and cause traction on the structures, leading to hoarseness medicine vile purchase cheap penisole line. Eighty-five percent of patients with this type of amyloidosis present with hematuria schedule 8 medications list buy penisole with a mastercard. Nephrectomy is commonly performed because the ureteral mass preoperatively is thought to represent a transitional cell malignancy, but the recognition of amyloidosis avoids nephrectomy. Patients may present with dysuria and hematuria when amyloidosis involves the urethra. The lichen and macular forms are localized,146 innocuous conditions that usually are associated with a history of local skin trauma or inflammation. Degraded keratin molecules are the source of macular and papular amyloid deposits. We have regularly seen patients who have proteinuria for more than a decade without renal failure. The absence of a monoclonal immunoglobulin disorder or the absence of free light chains in the serum is an important distinguishing feature. However, only immunohistochemical staining or sequencing of the amyloid can differentiate these entities definitively. However, all were homozygous for the G allele encoding valine at position 40 in the mature protein. Regression of amyloid deposits has been reported199 when liver transplantation is performed before the development of disabling peripheral neuropathy, autonomic neuropathy, or advanced cardiomyopathy. Amyloid has also been localized to breasts,152 mesenteric lymph nodes, colonic polyps, thyroid,153 retroperitoneum, and ovaries. Localized deposits of amyloid commonly are observed in trace amounts within the cartilage on the hip surface after a total hip arthroplasty. Amyloid deposits are identified during autopsy for half of all patients who sustained a spinal cord injury 10 years or more before death. The distinction between immunoglobulin and nonimmunoglobulin amyloidosis is important because nonimmunoglobulin amyloidosis does not benefit from chemotherapy. Laser capture microdissection mass spectroscopic analysis is the most direct method to identify the protein subunit comprising the amyloid and is recommended for all positive tissue biopsies. All patients received the diagnosis within 30 days of presentation at our institution. Multiple myeloma also is more common in men, but the male-to-female ratio is 52:48. Although we have seen patients with amyloidosis who were as young as 27 years, the median age of patients with amyloidosis was 67 years (range, 39 to 89 years). Echocardiographic examinations have dramatically increased the ability to recognize cardiac amyloid deposits. Congestive heart failure was present in only half of these patients; for the other half, the presenting symptoms of cardiac amyloidosis were fatigue and dyspnea. These patients had poor cardiac filling and low cardiac output, but the ejection fraction was preserved. Lower-extremity paresthesias, nephrotic-range proteinuria, orthostatic hypotension, and weight loss were observed for 34. The median survival of our entire cohort was 12 months, and the 2- and 5-year survival rates were 33. The number of patients with elevated alkaline phosphatase levels was close to the number of patients with clinical hepatic amyloid involvement. For patients with intact monoclonal g globulins, the serum heavy chain was IgG, IgA, and IgM for 58%, 10%, and 8. Synovial membrane biopsy may establish the diagnosis, and chemotherapy may effectively alleviate the joint manifestations. Distribution of bone marrow plasma cells of patients with primary amyloidosis (N = 486). The whitish deposits represent the amyloid and are the lardaceous changes first recognized by Rokitansky. Moreover, the ejection fraction is preserved because amyloid deposition is an infiltrative process with diastolic dysfunction only. This constellation of findings is frequently misinterpreted, and the presence of amyloid may be overlooked completely. An echocardiographic examination usually shows that contractility is normal, but because of poor diastolic filling, the end-diastolic volume is reduced and cardiac output is low. Electrocardiographic findings are clinically suspicious of silent ischemic disease, and patients invariably undergo coronary arteriography. Patients with cardiac amyloidosis have restriction to blood inflow that is characteristic of the disease. The Doppler filling patterns accurately indicate the extent of amyloid infiltration. Patients with a wall thickness greater than 15 mm and a fractional shortening less than 20% have a median survival of 4 months. An important measurement is the deceleration time; a short deceleration time is indicative of restrictive physiologic characterisitics, and a deceleration time shorter than 150 milliseconds is associated with worse outcomes than that of a deceleration time longer than 150 milliseconds. The most common echocardiographic feature of cardiac amyloidosis was thickening of the right ventricular wall, septum, and left ventricular free wall. Approximately 20% of patients had congestive heart failure, but echocardiographic studies showed that twice as many had cardiac amyloid deposits. Patients with overt cardiac amyloidosis often presented with mild symptoms of fatigue and dyspnea on exertion. The median survival time of patients with cardiac amyloidosis and a septal thickness greater than or equal to 15 mm or less than 15 mm at diagnosis was 1 year and 4 years, respectively. However, functional abnormalities may be detected before any morphologic echocardiographic abnormalities are evident. The hazards of surgery for patients with cardiac amyloidosis are well established. Chapter 99 Immunoglobulin Light-Chain Amyloidosis (Primary Amyloidosis) the combination of subtle, widespread heterogeneous myocardial enhancement on delayed postcontrast inversion recovery in T1-weighted images, with ancillary features of restrictive cardiac disease, may be highly suggestive of cardiac amyloidosis. For such patients, standard exercise tests show ischemia,231 but the diagnosis of intracoronary amyloid is difficult to establish before death. Right ventricular myocardial biopsy may show amyloid deposits in small intramural vessels. Virtually all patients were assigned the diagnosis of cardiac amyloidosis during autopsy, which reflects the difficulty of recognizing small-vessel coronary arteriolar amyloidosis. A follow-up report of obstructive intramural coronary amyloidosis showed that 63 of 96 patients (66%) did not have obstruction of epicardial coronary arteries. Most patients with primary systemic amyloidosis and cardiac involvement have obstructive intramural coronary amyloidosis and microscopic changes of myocardial ischemia. All amyloid deposits are positive for Congo red stain, so positive staining cannot be used as a criterion to classify patients with different types of amyloidosis. A quarter of patients older than 90 years (general patient population) have cardiac amyloid deposits. Clinicians must remember that all forms of cardiac amyloidosis are not derived from immunoglobulin light chains. All patients presenting with proteinuria should have immunofixation of the urine performed during the first evaluation to exclude light-chain­associated syndromes. Patients with higher levels of albumin loss have a shorter time from diagnosis to the development of end-stage renal disease. Monoclonal light-chain proteins were more likely to be found when the urinary protein loss was high; for example, 85% of patients with urinary protein loss exceeding 1 g/day had detectable monoclonal light chains. The ratio of patients with underlying l clones to patients with k clones is 5:1 among those with nephrotic-range proteinuria. The l light chain may predispose patients to a higher level of renal involvement, but no difference in the frequency of renal failure in k or l amyloidosis is observed. The median survival of patients with urinary l light chains, urinary k light chains, or no detectable urinary light chains is 1, 2. Bilateral catheter embolization of renal arteries reduces the loss of urinary protein and increases the serum total protein of patients with advanced anasarca. No survival difference has been recognized between hemodialysis and peritoneal dialysis. Chemotherapy slowed progression to end-stage renal disease and showed a trend toward improved survival. In addition to younger age, normal values of serum calcium and creatinine at presentation favor longer survival. Cardiac amyloidosis with renal failure regularly results in dialysis that is complicated by severe hypotension (a difficult clinical condition to manage). The amount of protein in the urine and the extent of amyloid deposits in a kidney biopsy specimen correlate poorly. Computed tomography is useful for diagnosing hepatic rupture with subcapsular hematoma. The serum alkaline phosphatase value was the most important screen for determining whether a patient had clinically significant hepatic involvement. In a study of 98 patients,281 72% had involuntary weight loss and 89% had proteinuria. Clinicians considered amyloidosis as the cause of the hepatic dysfunction in only 26% of patients. None had hepatic rupture or death resulting from liver biopsy, and only 4% had bleeding. The predictors of a poor prognosis were heart failure, elevated bilirubin levels, and thrombocytosis. Amyloid deposits are found in liver biopsy specimens distributed in the portal tract and perisinusoidally. The findings are nonspecific and include irregular distribution of the radionuclide and, occasionally, splenic uptake is absent. Although spontaneous hepatic rupture has been described,292 rupture after a percutaneous liver biopsy has not been reported. Despite the relative safety of the procedure, if amyloidosis is suspected appropriately, liver biopsy usually is not required. In a statistical analysis, hepatomegaly had a significant impact on survival within the first year after diagnosis, perhaps because hepatomegaly for some patients may be due to congestive heart failure rather than hepatic infiltration. In an autopsy series of nine patients with amyloidosis and hepatomegaly,293 three did not have anatomical evidence of deposits, and liver enlargement was attributable to passive congestion. In a second autopsy study,293 20% of patients with palpable hepatomegaly and amyloidosis did not have histologically evident deposits. Only 2% of patients with amyloidosis have proteinuria eventually if it is not present at diagnosis. It is possible that patients treated before routine organ transplantation might not have survived long enough for renal amyloid nephrotic syndrome to develop. Amyloid deposits penetrate the glomerular basement membrane and result in proteinuria. Randall-type light-chain deposition disease indicates granular deposition of nonamyloid immunoglobulin light chain along the glomerular basement membrane. Light-chain deposition disease and amyloidosis in the same patient has been reported. Of 22 patients with renal amyloidosis, poor cortisol reserves were identified for 7, and hypoadrenalism resulted in the death of 4. One sixth of patients had a symptomatic hepatic amyloid syndrome, which typically included an increased serum alkaline phosphatase or g-glutamyltransferase level and unexplained hepatomegaly. Most clinicians suspect that unexplained hepatomegaly is due to hepatic metastases, but radionuclide imaging, computed tomography, or magnetic resonance imaging demonstrate homogeneous patterns. A high proportion of patients with hepatic amyloidosis also have renal involvement. Half the patients with hepatic amyloidosis have proteinuria in excess of 1 g every 24 hours. A patient who presents with an increased serum alkaline phosphatase value and proteinuria may have liver dysfunction resulting from a systemic disorder such as amyloidosis. Several key clues may be helpful in establishing the diagnosis of hepatic amyloidosis: (1) hepatomegaly out of proportion to the degree of liver function abnormality; (2) presence of Howell-Jolly bodies in a peripheral blood film (suggestive of reduced splenic function, a consequence of splenic replacement with amyloid deposits); (3) monoclonal protein (detectable by immunofixation) in the serum or urine; (4) proteinuria; and (5) increase of the alkaline phosphatase value with minimal increase in transaminase values. Biochemically, patients with hepatic amyloidosis tend to have low levels of aspartate aminotransferase and alanine aminotransferase-almost always less than twice the maximum normal value at diagnosis-and the bilirubin value is typically normal. Twelve patients with autopsy-proven diffuse splenic involvement have been reported in whom Howell-Jolly bodies were not found. Only 15% of our patients with gastrointestinal tract amyloidosis had hepatomegaly, and less than one third had increased alkaline phosphatase values. For three of these four patients, diagnosis was delayed because the surgical specimens were not routinely stained with Congo red. These patients were not distinguishable clinically from those with celiac sprue, Whipple disease, or bacterial overgrowth. A prolongation of prothrombin time, primarily from malabsorption of vitamin K, was present in one fourth of patients. Factor X deficiency also was seen in one fourth, but only one patient had factor X activity below 30%. A multivariate analysis showed that the degree of weight loss and the hemoglobin value at diagnosis affected survival. For patients presenting with a weight loss of 20 pounds or more, the median survival was 10 months. Ten patients died as a consequence of nutritional failure and five died of heart failure.

Muscles and tendons the anterior fold of the axilla is formed by the pectoralis major, and its posterior fold by the teres major and latissimus dorsi treatment management system 300 mg penisole buy mastercard. The digitations of serratus anterior can be seen in a muscular subject on the medial axillary wall medications made from plants order generic penisole from india. The biceps and brachialis constitute the bulk of the anterior aspect of the arm, and the triceps its posterior aspect medicine 2355 order 300 mg penisole with mastercard. The tendon of biceps is easily felt, and often seen, at the elbow when this is flexed to a right angle treatment esophageal cancer penisole 300mg low cost. Firm pressure immediately medial to this will, in turn, produce paraesthesiae in the hand as the median nerve is palpated treatment goals for anxiety penisole 300mg order online. When the forearm is flexed against resistance, the brachioradialis presents prominently along its radial border. The tendon medial to this is that of the flexor carpi radialis, then palmaris longus (which may be absent), then the cluster of tendons of flexor digitorum superficialis. The tendon of flexor carpi ulnaris lies most medially, inserting into the pisiform; the ulnar pulse can be felt just to the radial side of this tendon. The tendons of extensor digitorum are seen in the extended hand passing over the dorsal aspects of the proximal phalanges of the fingers. Vessels Feel the pulsations of the subclavian artery against the first rib, the brachial artery against the humerus, the radial and ulnar arteries at the wrist and the radial artery again in the anatomical snuffbox. Surface anatomy and surface markings of the upper limb 173 Flexor carpi radialis Radial artery Median nerve Palmaris longus Flexor digitorum superficialis Flexor carpi ulnaris Ulnar artery and nerve Thenar muscles Flexor retinaculum Recurrent motor branch of median nerve Hypothenar muscles. Extensor digiti minimi Extensor carpi ulnaris Extensor digitorum Abductor pollicis longus Extensor pollicis brevis Extensor pollicis longus Radial artery Extensor carpi radialis longus and brevis Extensor indicis. These superficial veins can be seen as a dorsal venous network on the back of the hand that drains into a lateral cephalic and medial basilic vein. The cephalic vein at its origin lies fairly constantly in the superficial fascia just posterior to the radial styloid; even if not visible it can be cut down upon confidently at this site. It then runs up the anterior aspect of the forearm to lie in a groove along the lateral border of the biceps and then, after piercing the deep fascia, in the groove between pectoralis major and the deltoid, where again it can readily be exposed for an emergency cut-down. The basilic vein runs along the posteromedial aspect of the forearm, passes on to the anterior aspect just below the elbow and pierces the deep fascia at about the middle of the upper arm. At the edge of the posterior axillary fold it is joined by the venae comitantes of the brachial artery to form the axillary vein. Linking the cephalic and basilic veins just distal to the front of the elbow is the median cubital vein, usually the most prominent superficial vein in the body and visible or palpable when all others are hidden in fat or collapsed in shock. Since this area is 176 the upper limb so often used in venepuncture, you will soon be familiar with these two appearances. In more modern times one tries to avoid using this vein for injection of intravenous barbiturates and other irritant drugs because of the slight risk of entering the brachial artery and also because of the danger of piercing a superficially placed abnormal ulnar artery in occasional instances of high brachial bifurcation. Nerves A number of nerves in the upper limb can be palpated, particularly in a thin subject; these are the supraclavicular nerves, as they pass over the clavicle, the cords of the brachial plexus against the humeral head (with the arm abducted), the median nerve in the mid-upper arm, crossing over the brachial artery, the ulnar nerve in the groove of the medial epicondyle and the superficial radial nerve as it passes over the tendon of extensor pollicis longus at the wrist. The median nerve lies first lateral then medial to the brachial artery, crossing it at the mid-upper arm, usually superficially but occasionally deeply. Place three fingers along the lateral aspect of the upper end of the radius; the uppermost finger lies on the radial head (feel it rotate on pronation and supination), and the lowermost lies over the nerve. In the hand, it passes on the radial side of the pisiform and then lies on the hook of the hamate. If you press with your fingernail just lateral to the pisiform bone, you will experience tingling in your ulnar two fingers. Its strong muscular coverings protect the scapula and only rarely is it fractured, and then only as a consequence of direct and severe violence. The clavicle is made up of a medial two-thirds, which is circular in section and convex anteriorly, and a lateral one-third, which is flattened in section and convex posteriorly. Medially it articulates with the manubrium at the sternoclavicular joint, which contains a cartilaginous disc (an important, and often overlooked, structure). It is a ball-and-socket joint that moves reciprocally with the movements of the shoulder joint, around its fulcrum ­ the costoclavicular 178 the upper limb ligament. Put a finger on the medial end of your clavicle; raise your shoulder ­ the sternoclavicular joint is depressed; retract your shoulder ­ the sternoclavicular joint protracts, and so on. Laterally it articulates with the acromion at the acromioclavicular joint (the joint containing an incomplete articular disc) and, in addition, is attached to the coracoid process by the tough coracoclavicular ligament. The third parts of the subclavian vessels and the trunks of the brachial plexus pass behind the middle third of the shaft of the clavicle, separated only by the thin subclavius muscle. Fractures of the clavicle are common, yet associated injury of the underlying subclavian vessels (except in penetrating gunshot wounds) is extremely rare because of the protection offered by this functionally insignificant slip of a muscle. Rarely, these vessels (protected by the subclavius) are torn by the fragments of a fractured clavicle; this was the cause of death of Sir Robert Peel (Prime Minister of the United Kingdom 1834­1835, and again 1841­1846) following a fall from his horse. The sternal end of the clavicle has important posterior relations; behind the sternoclavicular joints lie the common carotid artery on the left and the bifurcation of the brachiocephalic artery on the right. These vessels are separated from bone by the strap muscles ­ the sternohyoid and sternothyroid. The weakest point along the clavicle is the junction of the middle and outer third. Transmission of forces to the axial skeleton in falls on the shoulder or hand may prove greater than the strength of the bone at this site, and this indirect force is the usual cause of fracture. When fracture occurs, the trapezius is unable to support the weight of the arm so that the characteristic picture of the patient with a fractured clavicle is that of a man supporting his sagging upper limb with his opposite hand. The lateral fragment is not only depressed but also drawn medially by the shoulder adductors, principally teres major, latissimus dorsi and pectoralis major. The bones and joints of the upper limb 179 Sternocleidomastoid Muscle spasm Gravity. The tubercles, in turn, are separated from each other by the bicipital groove (intertubercular sulcus) along which emerges the long head of biceps from the shoulder joint. Where the upper end and the shaft of the humerus meet there is the narrow surgical neck against which lie the axillary nerve and circumflex humeral vessels. The posterior aspect of the shaft bears the faint spiral groove demarcating the origins of the medial and lateral heads of the triceps between which wind the radial nerve and the accompanying profunda vessels. The lower end of the humerus bears the rounded capitulum laterally, for articulation with the radial head, and the spool-shaped trochlea medially, articulating with the trochlear notch of the ulna. The medial and lateral epicondyles, on either side, are extracapsular; the medial is the larger of the two, extends more distally and bears a groove on its posterior aspect for the ulnar nerve. Lateral epicondyle Ulnar nerve Three important nerves thus come into close contact with the humerus ­ the axillary, the radial and the ulnar; they may be damaged, respectively, in fractures of the humeral neck, midshaft and lower end. It is an important practical point to note that the lower end of the humerus is angulated forwards 45° on the shaft. This is easily confirmed by examining a lateral radiograph of the elbow, when it will be seen that a vertical line continued downwards along the front of the shaft bisects the capitulum. Any decrease of this angulation indicates backward displacement of the distal end of the humerus and is good radiographic evidence of a supracondylar fracture. The ulna comprises olecranon, trochlear fossa, coronoid process (with its radial notch for articulation with the radial head), shaft and the bones and joints of the upper limb 181 Trochlear notch Head of radius Neck of radius Radial tuberosity Olecranon process Coronoid process Sharp interosseous border of radius Area for attachment of pronator teres Sharp interosseous border of ulna Anterior surface of ulnar shaft Rounded anterior border Rounded anterior border Head of ulna Radial styloid Ulnar styloid. In pronation and supination, the head of the radius rotates against the radial notch of the ulna, the shaft of the radius swings round the relatively fixed ulnar shaft (the two bones being connected by a fibrous interosseous ligament) and the distal end of the radius rotates against the head of the ulna. This axis of rotation passes from the radial head proximally to the ulnar head distally. If the radius is fractured proximal to this, the proximal fragment is supinated (by the action of the biceps) and the distal fragment is pronated by pronator teres. The fracture must, therefore, be splinted with the forearm supinated so that the distal fragment is aligned with the supinated proximal end. If the fracture is distal to the midshaft, the actions of biceps and the pronator muscles more or less balance and the fracture is, therefore, immobilized with the forearm in the neutral position. This fracture is, therefore, held reduced in the neutral position, midway between pronation and supination. The shortening which results brings the styloid processes of the radius and ulna more or less in line with each other. Another forearm injury resulting from a fall on the outstretched hand is fracture of the head of the radius, due to its being crushed against the capitulum of the humerus. In these circumstances the bone ends are widely displaced and operative repair, to reconstruct the integrity of the elbow joint, becomes essential. Although I have seen many miners with this lesion, I have yet to see a medical student thus disabled. In the proximal row, from the lateral to the medial side, are the scaphoid, lunate and triquetral, the last bearing the pisiform on its anterior surface, into which sesamoid bone the flexor carpi ulnaris tendon is inserted. In the distal row, from the lateral to the medial side, are the trapezium, trapezoid, capitate and hamate. This is maintained by: 1 the shapes of the individual bones, which are broader posteriorly than anteriorly (except for the lunate, which is broader anteriorly);. Note the separate osseofascial compartment for the tendon of flexor carpi radialis. In front of the head of this metacarpal are two tiny sesamoid bones (in the insertions of the heads of flexor pollicis longus), which are easily visible on a plain radiograph of the hand. Distally, the metacarpals articulate with the phalanges, of which there are two in the thumb and three in each of the other four fingers. The important articulations between these small bones of the hand are considered on page 194. The dislocated carpus may then reduce spontaneously, only to push the lunate forwards and tilt it over so that its distal articular surface faces forwards (dislocation of the lunate). The blood supply of the scaphoid in one-third of cases enters distally along its waist so that, if the fracture is proximal, the blood supply to the bones and joints of the upper limb 185. The flexor retinaculum forms the roof of a tunnel, the floor and walls of which are made up of the concavity of the carpus. Packed within this tunnel are the long flexor tendons of the fingers and thumb together with the median nerve. Any lesion diminishing the size of the compartment ­ for example, an old fracture or arthritic change ­ may result in compression of the median nerve, resulting in paraesthesiae, numbness and motor weakness in its distribution. Since the superficial palmar branch of the median nerve is given off proximal to the retinaculum, there is usually no sensory impairment in the palm. It is interesting that this syndrome also often occurs, especially in elderly women, without any very obvious cause, although symptoms are relieved by dividing the retinaculum longitudinally. The joint capsule is lax and is attached around the epiphyseal lines of both the glenoid and the humeral head. However, it does extend down on to the diaphysis on the medial aspect of the neck of the humerus, so that 186 the upper limb. The capsule is lined on the inside by synovial membrane, which is prolonged along the tendon of the long head of the biceps as this traverses the joint. The synovium also communicates with the subscapular bursa beneath the tendon of subscapularis. Movements of the shoulder girdle the movements of the shoulder joint itself cannot be divorced from those of the whole shoulder girdle. Even if the shoulder joint is fused, a wide range of movement is still possible by elevation, depression, rotation and protraction of the scapula, leverage occurring at the sternoclavicular joint, the pivot being the costoclavicular ligament. Abduction of the shoulder is initiated by the supraspinatus; the deltoid can then abduct to 90°. Further movement to 180° (elevation) is brought about by rotation of the scapula upwards by the trapezius and serratus anterior. As soon as abduction commences at the shoulder joint, so rotation of the scapula begins. Test this on yourself or on a colleague by palpating the lower pole of the scapula. Movements of the scapula occur with reciprocal movements at the sternoclavicular joint. Place a finger on this joint; elevate the shoulder and the joint will be felt to depress; swing the shoulder forwards and it will be felt to move backwards, and so on. The muscles are the supraspinatus, infraspinatus and teres minor, which are inserted from above down into the humeral greater tubercle, and the subscapularis, which is inserted into the lesser tubercle. It passes over the apex of the shoulder beneath the acromion process and coracoacromial ligament, from which it is separated by the subacromial bursa. This bursa is continued beneath the deltoid as the subdeltoid bursa forming, together, the largest bursa in the body. The supraspinatus initiates the abduction of the humerus on the scapula; if the tendon is torn as a result of injury, active initiation of abduction becomes impossible and the patient has to develop the trick movement of tilting his body towards the injured side so that gravity passively swings the arm from his trunk. The investigation of soft-tissue lesions around the shoulder has been greatly facilitated by magnetic resonance 188 the upper limb (a) Acromion Supraspinatus Head of humerus Glenoid fossa Deltoid (b). Note that the supraspinatus tendon lies close against the acromion ­ if this tendon is inflamed, there is a painful arc of movement as the shoulder is abducted from 60° to 120°, because, in this range, the inflamed tendon impinges against the acromion. Its inferior aspect is completely unprotected by muscles and it is here that, in violent abduction, the humeral head may slip away from the glenoid to lie in the subglenoid region, whence it usually passes anteriorly into a subcoracoid position. The axillary nerve, lying in relation to the surgical neck of the humerus, may be torn in this injury. Assess this in the patient before reducing the dislocation by testing for loss of cutaneous sensation over the deltoid. The head of the humerus is drawn medially by the powerful adductors of the shoulder; its greater tubercle, therefore, no longer remains the most lateral bony projection of the shoulder region, being replaced for this honour by the acromion process. The normal bulge of the deltoid over the greater tubercle is lost; instead, there is the characteristic flattening of this muscle. The elbow is then swung medially across the trunk, thus levering the head of the humerus laterally so that it slips back into place.

When the abdominal muscles contract, they increase abdominal pressure and push the abdominal contents against the relaxed diaphragm, forcing it upward into the thoracic cavity medications going generic in 2016 buy penisole 300mg lowest price. They also help depress the lower ribs and pull down the anterior part of the lower chest medications ranitidine cheap 300mg penisole with mastercard. Contraction of the internal intercostal muscles depresses the rib cage downward in a manner opposite to the actions of the external intercostals symptoms xxy penisole 300mg purchase free shipping. Active expiration compresses the thorax and causes positive intrapleural pressure medications just like thorazine buy discount penisole online. This has important effects on the respiratory system, which will be discussed later in this chapter, and on pulmonary blood flow, which will be discussed in Chapter 34 treatment for pink eye order generic penisole on-line. For the purpose of clarity, inspiration and expiration are considered to be of equal duration, although during normal quiet breathing, the expiratory phase is longer than the inspiratory phase. Initially, alveolar pressure equals atmospheric pressure, so no air flows into the lung. Contraction of the inspiratory muscles causes intrapleural pressure to become more negative as the lungs are pulled open and the alveoli are distended. As the alveoli are distended, the pressure inside them decreases below atmospheric pressure and air flows into the alveoli, as seen in the tidal volume panel. As the air flows into the alveoli, alveolar pressure returns to 0 cm H2O and airflow into the lung ceases. At the vertical line, the inspiratory effort ceases and the inspiratory muscles relax. Alveoli expand (according to their individual compliance curves) in response to the increased transmural pressure gradient. Alveolar pressure falls below atmospheric pressure as the alveolar volume increases, thus establishing a pressure gradient for airflow 9. Air flows into the alveoli until alveolar pressure equilibrates with atmospheric pressure Expiration (passive) 1. Thoracic volume decreases, causing intrapleural pressure to become less negative and decreasing the alveolar transmural pressure gradientb 4. Decreased alveolar transmural pressure gradient allows the increased alveolar elastic recoil to return the alveoli to their preinspiratory volumes 5. Decreased alveolar volume increases alveolar pressure above atmospheric pressure, thus establishing a pressure gradient for airflow 6. Air flows out of the alveoli until alveolar pressure equilibrates with atmospheric pressure a Note that numbers 4­8 occur simultaneously. This raises alveolar pressure above atmospheric pressure so that air flows out of the lung until an alveolar pressure of 0 cm H2O is restored. As mentioned before, the alveolar-distending pressure is often referred to as the transpulmonary pressure. Of course, this relationship is not a straight line: the lung is composed of living tissue, and although the lung distends easily at low lung volumes, at high lung volumes the distensible components of alveolar walls have already been stretched, and large increases in transpulmonary pressure yield only small increases in volume. The lung also is difficult to distend at very low lung volumes because some alveoli may be collapsed and extra energy is necessary to reopen them. The slope between two points on a pressure­volume curve is known as the compliance. Lungs with high compliance have a steep slope on their pressure­volume curves, that is, a small change in distending pressure will cause a large change in volume. It is important to remember that compliance is the inverse of elasticity, or elastic recoil. Compliance denotes the ease with which something can be stretched or distorted; elasticity refers to the tendency for something to oppose stretch or distortion, as well as to its ability to return to its original configuration after the distorting force is removed. The curve obtained is the same whether the lungs are inflated with positive pressure (by forcing air into the trachea) or with negative pressure (by suspending the lung, except for the trachea, in a closed chamber and pumping out the air around the lung). So when the lung alone is considered, only the transpulmonary pressure is important, not how the transpulmonary pressure is generated. One possible explanation for this hysteresis is the stretching on inspiration and the compression on expiration of the surfactant that lines the air­ liquid interface in the alveoli (discussed later in this chapter). Another is that some alveoli or small airways may open on inspiration ("recruitment") and close on expiration ("derecruitment") as noted above. Some researchers believe that lung volume changes primarily by recruitment and derecruitment of alveoli rather than by volume changes of individual alveoli. Finally, it can be helpful to think of each alveolus as having its own pressure­volume curve like that shown in the figure. The compliance curve for the lungs can be generated by having the patient take a very deep breath and exhale in stages, stopping periodically for pressure and volume determinations. During these determinations, no airflow is occurring; alveolar pressure therefore equals atmospheric pressure, 0 cm H2O. Similar measurements can be made as the patient inhales in stages from a low lung volume to a high lung volume. Such curves are called static compliance curves because all measurements are made when no airflow is occurring. The compliance of the chest wall is normally obtained by determining the compliance of the total system and the compliance of the lungs alone and then calculating the compliance of the chest wall according to the above formula. Many pathologic states shift the curve to the right; that is, for any increase in transpulmonary pressure, there is a smaller increase in lung volume. A proliferation of connective tissue called fibrosis may occur in sarcoidosis or after chemical or thermal injury to the lungs. This will make the lungs less compliant, or "stiffer," and increase alveolar elastic recoil. Similarly, pulmonary vascular engorgement or areas of collapsed alveoli (atelectasis) also make the lung less compliant. Emphysema increases the compliance of the lungs because it destroys the alveolar septal tissue that normally opposes lung expansion. The compliance of the chest wall is decreased in obese people, for whom moving the diaphragm downward and the rib cage up and out is much more difficult. Musculoskeletal disorders that lead to decreased mobility of the rib cage, such as kyphoscoliosis, also decrease the chest wall compliance. Because they must generate greater transpulmonary pressures to breathe in the same volume of air, people with decreased compliance of the lungs must do more work to inspire than those with normal pulmonary compliance. Similarly, more muscular work must be done when chest wall compliance is decreased. However, there is another component of the elastic recoil of the lung-the surface tension at the air­ liquid interface in the alveoli. Surface tension forces occur at any gas­liquid interface and are generated by the cohesive forces between the molecules of the liquid. These cohesive forces balance each other within the liquid phase but are unopposed at the surface of the liquid. In this experiment, a pressure­volume curve for an excised lung was first generated with air inflation, so an air­liquid interface was present in the lung, and surface tension forces contributed to alveolar elastic recoil. Then, all the gas was removed from the lung, and it was inflated again, this time with saline instead of with air. In this situation, surface tension forces were absent because there was no air­liquid interface. Whatever causes the hysteresis appears to be related to surface tension in the lung. The curve at left (saline inflation) therefore represents the elastic recoil due to only the lung tissue itself; the curve at right demonstrates the recoil due to both the lung tissue and the surface tension forces. The difference between the two curves is the recoil due to surface tension forces. The demonstration of the large role of surface tension forces in the recoil pressure of the lung led to consideration of how surface tension affects the alveoli. If surface tension is independent of surface area, the smaller the alveolus on the right becomes, the higher the pressure in it. Thus, if the lung were composed of interconnected alveoli of different sizes (which it is) with a constant surface tension at the air­liquid interface, it would be inherently unstable, with a tendency for smaller alveoli to collapse into larger ones. This is usually not the case, which is fortunate because collapsed alveoli require very great distending pressures to reopen, partly because of the cohesive forces at the liquid­liquid interface of collapsed alveoli. At least two factors cause the alveoli to be more stable than this prediction based on constant surface T P1 r T P2 2r (3) P1 T r P2 T 2r (4) where this the wall tension, P the pressure inside the alveolus, and r the radius of the alveolus. The surface tension of most liquids (such as water) is constant and not dependent on the area of the air­liquid interface. If the surface tension is the same in both alveoli, then the smaller alveolus will have a higher pressure and will empty into the larger alveolus. The first factor is a substance called pulmonary surfactant, which is produced by specialized alveolar cells, and the second is the structural interdependence of the alveoli. Pulmonary surfactant is a complex consisting of about 85­90% lipids and 10­15% proteins. The lipid portion is about 85% phospholipid, approximately 75% of which is dipalmitoyl phosphatidylcholine. Pulmonary surfactant appears to be continuously produced in the lung, but it is also continuously cleared from the lung. Surfactant is also cleared from the alveoli by alveolar macrophages, absorption into the lymphatics, or migration up to the small airways and the mucociliary escalator (discussed in Chapter 31). The clinical consequences of a lack of functional pulmonary surfactant occur in several conditions. Surfactant is not produced by the fetal lung until about the fourth month of gestation, and it may not be fully functional until the seventh month or later. Prematurely born infants who do not have functional pulmonary surfactant experience great difficulty in inflating their lungs, especially on their first breaths. Even if their alveoli are inflated for them with positive-pressure ventilation, the tendency toward spontaneous collapse is great because their alveoli are much less stable without pulmonary surfactant. Therefore, the lack of functional pulmonary surfactant in a prematurely born neonate may be a major factor in the infant respiratory distress syndrome. Pulmonary surfactant may also be important in maintaining the stability of small airways. Alveolar hypoxia or hypoxemia (low oxygen in the arterial blood), or both, may lead to a decrease in surfactant production or an increase in surfactant destruction. This condition may be a contributing factor in the acute respiratory distress syndrome (also known as adult respiratory distress syndrome or "shock lung syndrome") that can occur in patients after trauma or surgery. This process opposes the increased elastic recoil of the alveoli and the tendency for spontaneous atelectasis to occur because of a lack of pulmonary surfactant. Exogenous pulmonary surfactant is now administered directly into the airway of neonates with infant respiratory distress syndrome. In summary, pulmonary surfactant helps decrease the work of inspiration by lowering the surface tension of the alveoli, thus reducing the elastic recoil of the lung and making the lung more compliant. Surfactant also helps stabilize the alveoli by lowering even further the surface tension of smaller alveoli, equalizing the pressure inside alveoli of different sizes. Alveolar Interdependence A second factor tending to stabilize the alveoli is their mechanical interdependence, which was discussed at the beginning of this chapter. Alveoli do not hang from the airways like a "bunch of grapes" (the translation of the Latin word "acinus"), and they are not spheres. They are mechanically interdependent polygons with flat walls shared by adjacent alveoli. If an alveolus were to begin to collapse, it would increase the stresses on the walls of the adjacent alveoli, which would tend to hold it open. This process would oppose a tendency for isolated alveoli with a relative lack of pulmonary surfactant to collapse spontaneously. Conversely, if a whole subdivision of the lung (such as a lobule) has collapsed, as soon as the first alveolus is reinflated, it helps to pull other alveoli open by its mechanical interdependence with them. Thus, both pulmonary surfactant and the mechanical interdependence of the alveoli help stabilize the alveoli and oppose alveolar collapse (atelectasis). If the integrity of the lung­chest wall system is disturbed by breaking the seal of the chest wall. Lung volume decreases, and alveoli have a much greater tendency to collapse, especially if air moves in through the wound (causing a pneumothorax) until intrapleural pressure equalizes with atmospheric pressure and abolishes the transpulmonary pressure gradient. At this point, nothing is tending to hold the alveoli open and their elastic recoil is causing them to collapse. Similarly, the chest wall tends to expand because its outward recoil is no longer opposed by the inward recoil of the lung. When the lung­chest wall system is intact and the respiratory muscles are relaxed, the volume of gas left in the lungs is determined by the balance of these two forces. Therefore, at high lung volumes, the elastic recoil of both the lung and chest wall are inward. The reason for this decrease of about 30% is the effect of gravity on the mechanics of the chest wall, especially the diaphragm. When standing up or sitting, the contents of the abdomen are being pulled away from the diaphragm by gravity. When lying down, the abdominal contents are pushing inward against the relaxed diaphragm. This decreases the overall outward recoil of the chest wall and decreases the lung volume at which the outward recoil of the chest wall is equal and opposite to the inward recoil of the lungs. These factors are primarily the frictional resistance of the lung and chest wall tissue, and the frictional resistance of the airways to the flow of air. Pulmonary tissue resistance is caused by the friction encountered as the lung tissues move against each other as the lung expands. The airway resistance plus the pulmonary tissue resistance is often referred to as the pulmonary resistance. Pulmonary tissue resistance normally contributes about 20% of the pulmonary resistance, with airway resistance responsible for the other 80%. Pulmonary tissue resistance can be increased in such conditions as pulmonary sarcoidosis and fibrosis. Because airway resistance is the major component of the total resistance and because it can increase tremendously both in healthy people and in those suffering from various diseases, the remainder of this chapter will concentrate on airway resistance.

Terrestrial animals must be able to independently control excretion of salt and water, because their ingestion and loss is not always linked (see Tables 44­1 and 44­3) treatment works cheap generic penisole uk. When examining chloride reabsorption, it is helpful to keep in mind the absolute constraint of electroneutrality: any finite volume of fluid reabsorbed must contain equal amounts of anion and cation equivalents treatment borderline personality disorder order penisole 300 mg on line. One liter of normal filtrate contains 140 mEq of sodium, and thus must contain about 140 mEq of anions, mainly chloride (110 mEq) and bicarbonate (24 mEq) medications hypothyroidism buy penisole 300 mg on line. Therefore, 91 mEq of some combination of chloride and bicarbonate must also be reabsorbed to accompany this sodium treatment endometriosis buy penisole 300mg lowest price. As will be described in Chapter 47, about 90% of the filtered bicarbonate is reabsorbed in the proximal tubule (0 medications given during labor purchase 300mg penisole otc. This leaves 91 ­ 22 = 69 mEq of chloride that must be reabsorbed in the proximal tubule. This is more than 60% of the 110 mEq of filtered chloride and almost as much as the fractional reabsorption of sodium and water. Regardless of hydration state, the proximal tubule reabsorbs water and solute in equal proportions (isosmotic reabsorption), but the loop of Henle reabsorbs proportionally more solute than water. This is a key step in the separation process-reabsorption of solute, leaving water in the tubule. By the time tubular fluid leaves the loop of Henle and enters the distal tubule, the loss of solute has typically decreased the osmolality to about 110 mOsm/kg H2O. If an individual is overhydrated and, therefore, requires maximum water excretion, most of this dilute fluid simply passes through the collecting duct system to appear in the urine, with only limited further water reabsorption. In contrast, when an individual is dehydrated, the vast majority of this dilute water is reabsorbed in the collecting ducts, leaving a low volume of concentrated final urine. The human kidney can produce a maximal urinary concentration of 1,400 mOsm/kg in extreme dehydration. The sum of the urea, sulfate, phosphate, other waste products, and a small number of nonwaste ions excreted each day normally averages approximately 600 mOsm per day. These solutes continue to be excreted even in severe dehydration; therefore, the minimal volume of water in which this mass of solute can be dissolved is roughly 600 mOsm/1,400 mOsm/L = 0. It is not a strictly fixed volume but changes with different physiological states. For example, increased tissue catabolism, as during fasting or trauma, releases excess solute and so increases obligatory water loss. The obligatory water loss contributes to dehydration when a person is deprived of water intake. The obligatory solute loss also explains why a thirsty sailor cannot drink seawater for hydration. To excrete all the salt in the seawater plus the obligatory solute would require more urinary water than was contained in the seawater consumed. These hydrogen ions, once in the lumen, combine with filtered bicarbonate and secreted organic base (see text and Chapter 47 for further explanation). In the early portion, a large fraction of the filtered sodium enters the cell across the apical membrane via antiport with protons. As will be described in Chapter 47, these protons, which are released when carbon dioxide combines with water, cause the secondary active reabsorption of filtered bicarbonate. Organic nutrients and phosphate are also absorbed with sodium, and their luminal concentrations also decrease rapidly. A major percentage of chloride reabsorption in the proximal tubule occurs via paracellular diffusion. Then, as the fluid flows through the middle and late proximal tubules, this concentration gradient, maintained by continued water reabsorption, provides the driving force for paracellular chloride reabsorption by diffusion. There is also an important component of active chloride transport from lumen to cell in the later proximal tubule. Inorganic phosphate, bicarbonate, glucose, and lactate are preferentially reabsorbed with sodium early in the proximal tubule, and their concentrations rapidly fall. In contrast, the concentration of chloride increases somewhat because chloride reabsorption lags behind sodium and, hence, water reabsorption in the early proximal tubule. The concentration of sodium and the total concentration of all solutes (osmolarity) remains nearly the same as in plasma. These include formate and oxalate, which are continuously generated in the cell by dissociation of their respective uncharged acids into a proton and the base. Simultaneously, the protons released within the cell by the dissociation of those acids are actively transported into the lumen by the Na­H antiporters. In the lumen, the protons and organic bases recombine to form the neutral acids, which then diffuse across the apical membrane back into the cell, where the entire process is repeated. Notice that both the protons and the organic bases endlessly recycle, moving into the cells while paired as a neutral molecule and then move out via separate transporters after the proton dissociates. The overall achievement of the parallel Na­H and Cl­base antiporters is the same as though the Cl and Na were simply cotransported into the cell together. Importantly, the recycling of protons and bases means that most of the protons are not acidifying the lumen but are simply combining with base and moving back into the cells. Regarding water reabsorption, the proximal tubule, as mentioned, has a very high permeability to water, allowing very small differences in osmolality (less than 1 mOsm/L) to drive the reabsorption of very large quantities of water, normally about 65% of the filtered water. This osmolality difference is created by the reabsorption of sodium and the various solutes linked directly or indirectly with sodium (Table 44­4). If the tight coupling between proximal sodium and water reabsorption is disrupted, we have a phenomenon known as osmotic diuresis. The term diuresis simply means increased urine flow, and osmotic diuresis denotes the situation in which the increased urine flow is due to an abnormally high amount of any substance in the glomerular filtrate that is reabsorbed incompletely or not at all by the proximal tubule. As water is reabsorbed in the proximal tubule, the concentration of any unusual unreabsorbed solute rises, and its osmotic presence retards the further reabsorption of water (here and downstream as well). The failure of water to follow the sodium being removed from the lumen means that the sodium concentration in the proximal tubular lumen decreases slightly below that in the interstitial fluid. This concentration difference, even though small, drives a passive diffusion of sodium across the epithelium (mostly the tight junctions) back into the lumen, that is, sodium transport reaches the gradient limit we described in Chapter 42. Creates transtubular osmolality difference, which favors reabsorption of water by osmosis; in turn, water reabsorption concentrates many luminal solutes. Achieves reabsorption of many organic nutrients, phosphate, and sulfate by cotransport across the luminal membrane 3. Achieves secretion of hydrogen ion by countertransport across the luminal membrane; these hydrogen ions are required for reabsorption of bicarbonate (as described in Chapter 47) 4. Besides transcellular routes, some sodium also moves paracellularly in response to the lumen positive potential. The apical membranes and tight junctions have a very low water permeability, and water is not reabsorbed in this segment. Because the cells reabsorb salt, but not water, the thick ascending limb is the point in the nephron at which salt is separated from water. This ultimately allows water excretion and salt excretion to be controlled independently. Thus, osmotic diuretics inhibit the reabsorption of both water and sodium (as well as other ions). Osmotic diuresis can occur in persons with uncontrolled diabetes mellitus; the filtered load of glucose exceeds the tubular maximum (Tm) for this substance, and the unreabsorbed glucose then acts as an osmotic diuretic. This is a key difference from the proximal tubule, which reabsorbs water and sodium in essentially equal proportions. Also as shown in Table 44­2, the reabsorption of salt and reabsorption of water occur in different parts of the loop. In contrast, the ascending limbs (both thin and thick) reabsorb sodium and chloride but little water. As a whole, the loop reabsorbs some water and more salt, leaving a dilute fluid in the lumen. The differences between the two limbs reveal that the cells lining the descending and ascending regions have different permeability properties. The basolateral membranes of all renal cells are quite permeable to water due to the presence of aquaporins. As a result, the cytosolic osmolality is always close to that of the surrounding interstitium. The descending limbs contain aquaporins, so water is reabsorbed there, driven by the increasing osmolality of the medullary interstitium. The ascending limbs do not express aquaporins in the apical membranes, and the tight junctions are not permeable to water. Therefore, even though an osmotic gradient exists between the lumen (dilute) and interstitium (concentrated), water does not move down the gradient, and water flowing into the ascending limb remains there and is passed on to the distal tubule. What are the mechanisms of sodium and chloride reabsorption by the ascending limbs These are mainly passive in the thin ascending limb and active in the thick ascending limb. Then when tubular fluid, now containing an increased sodium concentration, reaches the epithelium of the thin ascending limb, this gradient drives reabsorption, probably by the paracellular route. As tubular fluid then enters the thick ascending limb, the transport properties of the epithelium change again, and active processes become dominant. The apical membrane of this segment also has a Na­H antiporter isoform, which, like the isoform in the proximal tubule, provides another mechanism for sodium movement into the cell. In addition to the active transcellular reabsorption of sodium, a large percentage (approaching 50%) of total sodium reabsorption in this segment occurs by paracellular diffusion. There is a high paracellular conductance for sodium in the thick ascending limb, and the luminal potential in this segment is positive, which is a significant driving force for cations. To summarize the most important features of the loop of Henle, the descending limb reabsorbs water but not sodium chloride, whereas the ascending limb reabsorbs sodium chloride but not water. Activity of these channels is controlled by the hormone aldosterone (see Chapter 45). The ascending limb is called a diluting segment (it dilutes the tubular fluid), and fluid leaving the loop to enter the distal convoluted tubule is hypo-osmotic (more dilute) compared with plasma. This transporter differs significantly from the Na­K­2Cl symporter in the thick ascending limb and is sensitive to different drugs. Like the ascending limb of the loop of Henle, the distal tubule is not permeable to water, so that it further dilutes the already somewhat dilute fluid entering it from the thick ascending limb. The principal cells reabsorb sodium, the luminal entry step being via epithelial sodium channels. Regulation of this entry step is enormously important in controlling sodium excretion, and we will expand on this topic in Chapter 45. Some sodium chloride reabsorption continues in the medullary collecting ducts, probably via some form of epithelial sodium channels. Although with modern diets containing excess sodium there is usually a substantial amount of sodium in the final urine, it is possible to reabsorb virtually all of the remaining sodium if dietary access to sodium is limited. Principal cells in the collecting ducts are also the crucial players in reabsorbing water. As indicated earlier, there is always a substantial amount of dilute fluid entering the collecting duct system, which reabsorbs variable amounts of the water. When this fluid reaches the medullary portion of the collecting ducts, there is now a huge osmotic gradient favoring reabsorption, which occurs to some extent. The result is the excretion of a large volume of very hypo-osmotic (dilute) urine, or water diuresis. As the hypo-osmotic fluid entering the collecting duct system from the distal convoluted tubule flows through the cortical collecting ducts, most of the water is rapidly reabsorbed. This is because of the large difference in osmolality between the hypo-osmotic luminal fluid and the isosmotic (285 mOsm/kg) interstitial fluid of the cortex. In other words, the cortical collecting duct reverses the dilution carried out by the diluting segments. Once the osmolality of the luminal fluid approaches that of the cortical interstitial fluid, the cortical collecting duct then behaves analogously to the proximal tubule, reabsorbing approximately equal proportions of solute (mainly sodium chloride) and water. The result is that the tubular fluid, which leaves the cortical collecting duct to enter the medullary collecting duct, is isosmotic with cortical plasma, but its volume is greatly reduced compared with the amount entering from the distal tubule. Therefore, the tubular fluid becomes more and more hyperosmotic, and reduced in volume. Interstitial Fluid at Tip of Medulla (mOsm/L) Concentrated urine Urea = 650 Na + Cl - = 750 Dilute urine Urea = 300 Na+ + Cl- = 350a a Urine (mOsm/L) Urea = 700 a + Nonurea solutes = 700 (Na+, Cl-, K+, urate, creatinine, etc. Depending on the sodium balance state, sodium in the urine can vary between undetectable and the majority of the osmolytes. The production of hyperosmotic urine is also straightforward in that reabsorption of water from the lumen into a hyperosmotic interstitium concentrates that luminal fluid, leaving concentrated urine to be excreted. The question is: how do the kidneys generate a hyperosmotic medullary interstitium Not only is the medullary interstitium hyperosmotic, but there is also a gradient of osmolality, increasing from a nearly isosmotic value at the corticomedullary border to a maximum of greater than 1,200 mOsm/kg at the papilla. It is highest during periods of water deprivation and dehydration, when urinary excretion is lowest, and is "washed out" to only about half of that during excess hydration and when urinary excretion is high (see Table 44­5). However, the essential points are clear, and it is these essential points on which we now focus. Let us begin with a condition in which there is no gradient and follow its establishment. Assume that both the plasma entering the medulla and the medullary interstitium have a normal sodium concentration (140 mEq/L) and that the medullary interstitium is isosmotic with normal plasma. The reabsorption of sodium and chloride by the thick ascending limb in the outer medulla is the first step. As sodium is deposited in the interstitium, the interstitial sodium concentration begins to increase above 140 mEq/L. Because the cortex contains abundant peritubular capillaries and a high blood flow, the reabsorbed material immediately moves into the vasculature and returns to the general circulation. However, in the medulla, the vascular anatomy and blood flow are quite different, and reabsorbed sodium that is deposited in the outer medullary interstitium is not immediately removed, that is, it accumulates. The degree of accumulation is a function of the arrangement of the vasa recta, their permeability properties, and the volume of blood flowing within them.

Changes in lung volume also affect the regional distribution of pulmonary blood flow and will therefore affect the boundaries between zones symptoms quivering lips 300 mg penisole purchase. Finally, changes in body position alter the orientation of the zones with respect to the anatomic locations in the lung, but the same relationships exist with respect to gravity and alveolar pressure treatment that works penisole 300 mg buy overnight delivery. The site of vascular smooth muscle constriction appears to be in the arterial (precapillary) vessels very close to the alveoli treatment xerophthalmia penisole 300mg. Hypoxia may act directly on pulmonary vascular smooth muscle to produce hypoxic pulmonary vasoconstriction treatment 5th metatarsal avulsion fracture order 300 mg penisole with mastercard. Hypoxia inhibits an outward potassium current, which causes pulmonary vascular Pulmonary edema is the extravascular accumulation of fluid in the lung medications to avoid during pregnancy purchase penisole paypal. This pathologic condition may be caused by one or more physiologic abnormalities, but the result is inevitably impaired gas transfer. As the edema fluid builds up, first in the interstitium and later in alveoli, diffusion of gases-particularly oxygen-decreases. The capillary endothelium is much more permeable to water and solutes than is the alveolar epithelium. Edema fluid therefore accumulates in the interstitium before it accumulates in the alveoli. B) Perfusion of a hypoventilated alveolus results in blood with a decreased Po and an increased Pco entering the left atrium. D) this diverts blood flow away from the hypoventilated alveolus to better-ventilated alveoli, thus helping to maintainV Q matching. The components of the Starling equation are very useful in understanding the potential causes of pulmonary edema, even though only the plasma colloid osmotic pressure (pl) can be measured clinically. The pulmonary capillary hydrostatic pressure is estimated to be about 10 mm Hg under normal conditions. If the capillary hydrostatic pressure increases dramatically, the filtration of fluid across the capillary endothelium will increase greatly, and enough fluid may leave the capillaries to exceed the lym- phatic drainage. The pulmonary capillary hydrostatic pressure often increases as a result of problems in the left side of the circulation, such as infarction of the left ventricle, left ventricular failure, or mitral stenosis. As left atrial pressure and pulmonary venous pressure increase because of accumulating blood, the pulmonary capillary hydrostatic pressure also increases. Other causes of increased pulmonary capillary hydrostatic pressure include overzealous administration of intravenous fluids and diseases that occlude the pulmonary veins. These appear to be limited mainly to potential actions of the health care worker, such as rapid evacuation of chest fluids or treatment of a pneumothorax. Situations that increase alveolar surface tension, for example, when decreased amounts of pulmonary surfactant are present, could also make the interstitial hydrostatic pressure more negative and increase the tendency for the formation of pulmonary edema. Note that as fluid accumulates in the interstitium, the interstitial hydrostatic pressure increases, which helps limit further fluid extravasation. Any situation that permits more solute to leave the capillaries, such as a decreased reflection coefficient, will lead to more fluid movement out of the vascular space. Obviously, no gas exchange can occur distal to a particle embedded in and obstructing a capillary, so this mechanism is limited by the ability of the lung to remove such filtered material. If particles are experimentally suspended in venous blood and are then trapped in the pulmonary circulation, the diffusing capacity (see Chapter 35) usually decreases for 4­5 days and then returns to normal. The mechanisms for removal of material trapped in the pulmonary capillary bed include lytic enzymes in the vascular endothelium, ingestion by macrophages, and penetration to the lymphatic system. Patients on cardiopulmonary bypass do not have the benefit of this pulmonary capillary filtration, and blood administered to these patients must be filtered for them. The colloid osmotic pressure of the plasma proteins normally exceeds the pulmonary capillary hydrostatic pressure. This tends to pull fluid from the alveoli into the pulmonary capillaries and keep the alveolar surface free of liquids other than pulmonary surfactant. This protects the gas exchange function of the lungs and opposes transudation of fluid from the capillaries to the alveoli. Drugs or chemical substances that readily pass through the alveolar­capillary barrier by diffusion or by other means rapidly enter the systemic circulation. The lungs are frequently used as a route of administration of drugs and for anesthetic gases, such as halothane and nitrous oxide. Aerosolized drugs intended for the airways only, such as the bronchodilator isoproterenol and anti-inflammatory corticosteroids, may rapidly pass into the systemic circulation, where they may have clinically significant effects. The effects of isoproterenol, for example, could include cardiac stimulation and vasodilation. Decreases in the colloid osmotic pressure of the plasma, which helps retain fluid in the capillaries, may lead to pulmonary edema. Plasma colloid osmotic pressure, normally in the range of 25­28 mm Hg, decreases with low plasma protein concentration or overadministration of certain intravenous solutions. On the other hand, increased colloid osmotic pressure in the interstitium will pull fluid from the capillaries. Any fluid that makes its way into the pulmonary interstitium must be removed by the lymphatic drainage of the lung. The volume of lymph flow from the human lung is capable of increasing as much as 10-fold under pathologic conditions. It is only when this large safety factor is overwhelmed that pulmonary edema occurs. Conditions that block the lymphatic drainage of the lung, such as tumors or scars, may predispose patients to pulmonary edema. Pulmonary edema can be associated with head injury, heroin overdose, and high altitude. The causes of the edema formation in these conditions are not known, although high-altitude pulmonary edema may be caused by high pulmonary artery pressures secondary to the hypoxic pulmonary vasoconstriction. The entire cardiac output passes over the very large surface area of the pulmonary capillary bed, allowing the lungs to act as a site of blood filtration and storage, as well as for the metabolism of vasoactive constituents of the blood, as was discussed in Chapter 31. A typical adult male has a pulmonary blood volume of about 500 mL, which allows the pulmonary circulation to act as a reservoir for the left ventricle. If left ventricular output is transiently greater than systemic venous return, left ventricular output can be maintained for a few strokes by drawing on blood stored in the pulmonary circulation. Because virtually all mixed venous blood must pass through the pulmonary capillaries, the pulmonary circulation acts as a filter, protecting the systemic circulation from materials that enter the blood. The particles filtered, which may enter the circulation as a result of natural processes, trauma, or therapeutic measures, may include small fibrin or blood clots, fat cells, bone marrow, detached cancer cells, gas bubbles, agglutinated erythrocytes (especially in sickle cell disease), masses of platelets or leukocytes, and debris from stored blood or intravenous solutions. If these particles were to enter the arterial side of the systemic circulation, they might occlude vascular beds with no other source of blood flow. This occlusion would be particularly disastrous if it occurred in the blood supply to the central nervous system or the heart. At rest, his heart rate is 105/min, blood pressure is 120/90 mm Hg, and his respiratory rate is increased at 20/min. The patient does not have dyspnea (the feeling of difficult breathing or "shortness of breath") at rest and his blood pressure is within the normal range. His heart rate at rest is slightly above the normal range (50­100/min; tachycardia) and his respiratory rate is high (normally 12­15/min; tachypnea). Although his left ventricle can generate a sufficient stroke volume at rest, it cannot match the increased right ventricular output during exercise, leading to increased left atrial pressure. Because there are no valves between the left atrium and the pulmonary veins and capillaries, pulmonary capillary hydrostatic pressure increases. Filtration of fluid from the capillaries into the pulmonary interstitium increases sufficiently to exceed the ability of the pulmonary lymphatic drainage to remove it, resulting in interstitial edema and then alveolar edema. Pulmonary vascular congestion (excess blood in the pulmonary blood vessels) decreases the compliance of the lungs. Interstitial and alveolar edema increases the alveolar­ capillary barrier for gas diffusion. This is particularly a problem for oxygen diffusion, as will be discussed in the next chapter. Stretch receptors in the pulmonary circulation respond to pulmonary vascular congestion and the arterial chemoreceptors respond to low arterial Po2, both contributing to the sensation of dyspnea, as will be discussed in Chapter 38. He breathes more easily in the upright position because the edema fluid collects in lower regions of the lungs, allowing better gas exchange in upper parts of the lungs. The effects of pulmonary artery pressure, pulmonary vein pressure, and alveolar pressure on pulmonary blood flow are described as the zones of the lung. Alveolar hypoxia can cause constriction of precapillary pulmonary vessels, diverting blood flow away from poorly ventilated or unventilated alveoli. Compared to the systemic circulation, the pulmonary circulation has A) greater arterial pressure. C) a more evenly distributed vascular resistance to blood flow among its arteries, capillaries, and veins. In zone 2 of the lung A) alveolar pressure > pulmonary arterial pressure > pulmonary venous pressure. D) the effective pressure gradient for blood flow is pulmonary arterial pressure minus pulmonary venous pressure. Compared to the pulmonary circulation, the bronchial circulation has A) more total blood flow. D) more even distribution of vascular resistance among the arteries, capillaries, and veins. Pulmonary arteries are more distensible, and because their intravascular pressures are lower, more compressible than systemic arteries. Explain the regional differences in the matching of ventilation and perfusion of the normal upright lung. Predict the consequences of the regional differences in the ventilation and perfusion of the normal upright lung. Distinguish between perfusion limitation and diffusion limitation of gas transfer in the lung. Describe the diffusion of oxygen from the alveoli into the blood, and carbon dioxide from the blood to the alveoli. Alveolar ventilation and pulmonary perfusion have been discussed in the previous chapters in this section. The respiratory gases must diffuse through the alveolar­capillary barrier for gas exchange to occur. For optimal diffusion, the alveolar ventilation must be matched to the pulmonary perfusion. However, ventilation and perfusion must be matched on the alveolar­capillary level for optimal gas exchange · · to occur and the V /Q for the whole lung is really of interest only as an approximation of the situation in all the alveolar­ capillary units of the lung. Similarly, the mixed venous blood brings carbon dioxide into the lung and takes up alveolar oxygen. The alveolar Po2 and Pco2 are thus determined by the relationship between alveolar ventilation and perfusion. Alterations in the ratio of ventilation to perfusion, called the · · Va /Q c for alveolar ventilation/pulmonary capillary blood flow · · (or just V /Q), will result in changes in the alveolar Po2 and Pco2, as well as in gas delivery to or removal from the lung. Similarly, carbon dioxide is delivered to the alveolus in the mixed venous blood and diffuses into the alveolus in the pulmonary capillary. As will be discussed later in this chapter, at resting cardiac outputs, the diffusion of both oxygen and carbon dioxide is normally limited by pulmonary perfusion. The alveolar partial pressures of both oxygen and carbon dioxide are therefore determined by · · · · the V /Q. If the V /Q in an alveolar­capillary unit increases, the delivery of oxygen relative to its removal will increase, as will the removal of carbon dioxide relative to its delivery. If the · · V/Q in an alveolar­capillary unit decreases, the removal of oxygen relative to its delivery will increase and the delivery of carbon dioxide relative to its removal will increase. Inspired air enters the alveolus with a Po2 of about 150 mm Hg and a Pco2 of nearly 0 mm Hg. Mixed venous blood enters the pulmonary capillary with a Po2 of about 40 mm Hg and a Pco2 of about 45 mm Hg. This results in an alveolar Po2 of about 100 mm Hg and an alveolar Pco2 of 40 mm Hg. As time goes on, the air trapped in the alveolus equilibrates by diffusion with the gas dissolved in the mixed venous blood entering the alveolar­capillary unit. No gas exchange can occur, and any blood perfusing this alveolus will leave it exactly as it entered it. The blood flow to unit C is blocked by a pulmonary embolus, and unit C is therefore completely unperfused. Because no oxygen can diffuse from the alveolus into pulmonary capillary blood and because no carbon dioxide can enter the alveolus from the blood, the Po2 of the alveolus is approximately 150 mm Hg and its Pco2 is approximately zero; that is, the gas composition of this unperfused alveolus is the same as that of inspired air. If unit C were unperfused because its alveolar pressure exceeded its precapillary pressure (rather than because of an embolus), then it would also correspond to part of zone 1, as discussed in Chapter 34. Units B and C represent the two extremes of a continuum of · · ventilation­perfusion ratios. The alveolar Po2 and Pco2 of such units will therefore fall between the two extremes · · shown in the figure: units with low V /Q ratios will have rela· · tively low Po2 and high Pco2; units with high V/Q ratios will have relatively high Po2 and low Pco2. The diagram shows the results of mathematical calculations of · · alveolar Po2 and Pco2 for V /Q ratios between zero (for mixed venous blood) and infinity (for inspired air). The position of · · the V /Q ratio line is altered if the partial pressures of the inspired gas or mixed venous blood are altered. The resulting ratio of shunt flow to the cardiac output, often referred to as the venous admixture, is the part of the cardiac output that would have to be perfusing absolutely unventilated alveoli to cause the systemic arterial oxygen content obtained from a patient. These methods include calculations of the physiologic shunt, and the physiologic dead space, differences between the alveolar and arterial Po2 and Pco2, and lung scans after inhaled and intravenously administered 133Xe or 99mTc.

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References

• Murray RD, Melmed S. A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly. J Clin Endocrinol Metab 2008; 93:2957-2968.
• Froehlich W, Bogun FM, Crawford TC. Cardiac Sarcoidosis. Circulation. 2015;132:e137-e138.
• Jorgensen H, Wetterslev J, Moiniche S, et al. Epidural local anaesthetics versus opioid-based analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane Database Syst Rev. 2000;CD001893.
• Frerman FE, Goodman SI. Deficiency of electron transfer flavoprotein or electron transfer flavoprotein ubiquinone oxido-reducatase in glutaric acidemia type II fibroblasts. Proc Natl Acad Sci USA 1985;82:4517.
• Pennathur A, Farkas A, Krasinskas AM, et al: Esophagectomy for T1 esophageal cancer: Outcomes in 100 patients and implications for endoscopic therapy. Ann Thorac Surg 87:1048, 2009.
• Fagan SM, Chan KL. Transesophageal echocardiography risk factors for stroke in nonvalvular atrial fibrillation. Echocardiography 2000;17:365-72.
• Tay KJ, Polascik TJ: Focal cryotherapy for localized prostate cancer, Arch Esp Urol 69(6):317n326, 2016.
• Muhanna N, Doron S, Wald O, et al. Activation of hepatic stellate cells after phagocytosis of lymphocytes: a novel pathway of fibrogenesis. Hepatology. 2008;48:963-977.