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Hypertension: A New Clinical Concept of its Etiology1
HYPERTENSION: A NEW CLINICAL CONCEPT OF ITS ETIOLOGY 1 A. RAVICH
Every one who is interested in hypertension owes a debt of gratitude to Dr. Harry Goldblatt for his epoch-making experiments on living dogs which he proved the all important role of renal ischemia in the causation of high blood pressure. By varying the degree of compression of the main renal arteries in the same dog he could proportionately increase or decrease the degree of renal ischemia, and in direct ratio, influence the rise or fall of the arterial tension. Pressor theory. Unfortunately, however, Goldblatt was apparently baffled by the conflicting results in his experiments on dogs and their application to human beings. Thus he was led to assume the existence of a hypothetical pressor substance which is elaborated by the kidney and when liberated into the circulation produces hypertension. In adopting this theory he overlooked the fact that a simple interpretation of the process is more likely to be conclusive than a more complex one which is subject to variations. The introduction of a third element, a pressor substance, which he admits is hypothetical and has never been isolated has led him, his co-workers and followers to pursue a long tedious and possibly endless trail. If such a humoral substance is actually elaborated, why does it not occur in all similar pathologic conditions? Why are there so many exceptions? Furthermore, if it is true that an entire kidney is involved in the development of hypertension, why does not the same process produce hypertension to a lesser degree when half a kidney or only 1 calyx is involved::' Hypertension of severe degree causes arteriolar lesions and petechiae everywhere in the body except in the lungs and in the ischemic kidney, because in these 2 organs the blood pressure is lower than in the rest of the circulation. If a pressor substance is liberated in the blood, it must reach the pulmonary circulation as well as that in the ischemic kidney and should produce the same type of arteriolar changes in these organs as in the rest of the body. It is difficult to conceive that a freely circulating substance can be so selective. 1
The diodrast employed in this study was supplied by the Winthrop Chemical Co., Inc. 641
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Dock and Rytand, in their extensive work on rats, failed to find any evidence of such a vasoconstrictor substance in the blood. Boylston, McEwen and Ivy were also unable to obtain a pressor substance in significant amounts from ischemic kidneys of hypertensive dogs by perfusing them with Locke's solution. Increased pressor properties of the blood in dogs with renal ischemia and hypertension could not be demonstrated by many other workers. There is no conclusive proof of the existence of a known or new pressor agent in the blood, spinal fluid or urine in experimental hypertension due to renal ischemia. Extra-renal surgical treatment. Recent surgical treatment of hypertension consists of denervation of the adrenals or kidneys, section of splanchnic nerves and of anterior nerve roots, and excision of celiac or lumbar ganglia connected with the vasomotor apparatus of the abdomen. Some of these procedures have been combined with unilateral or partial bilateral adrenalectomy. Irradiation of the adrenals by x-ray and partial adrenalectomy alone have also been tried. After all these operations, the percentage of cures has been very small. In evaluating the benefit of any surgical treatment, one must consider that the rest in bed and during convalescence of itself will aid in a lowering of the pressure. Queries. To every student of hypertension many conflicting problems and questions must present themselves and still further mystify him with regard to the etiology and proper management of the condition. Why is unilateral or bilateral pyelonephritis accompanied by hypertension in 1 case and not in another? Why is hypertension absent in the vast majority of cases of bilateral nephrolithiasis although the pathological process would favor its occurrence? Why is not hypertension present in all cases of renal hypoplasia and why is there not a permanent reduction of blood pressure in all patients who have undergone nephrectomy for hypoplastic kidney? Furthermore, why does a reduction of blood pressure follow nephrectomy for calculous pyelonephritis in some cases and not in others, and why even if it has occurred does the pressure remain more or less permanently lowered in 1 patient and only for a time in another? Also why are some cases of urinary obstruction associated with hypertension and not in others, and why is a reduction of the blood pressure after prostatectomy observed in only a certain number? Why is the pressure so often higher in the erect than in the recumbent posture and why is it not always reduced by rest in bed? Finally, why is hypertension present in only 45 per cent of polycystic cases, according to MacKenzie and Seng, and why are there so many renal neoplasms without hypertension?
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of For many years the above questions baffled and plagued me. Essential hypertension remained a purely medical problem and such a case was almost never referred to the urologist, partly because of the prevailing dependence on uncatheterized specimens of urine, especially in females, and on stale specimens. Too much reliance was placed on the presence of albumin before renal disease was considered as a possible etiologic factor of hypertension. Gradually, however, many patients with vague primary urological problems, secondarily afflicted with hypertension, were referred to me. After appropriate measures had been instituted it was amazing to find a fall of blood pressure to normal in some of these patients. However, there was a return of hypertension in a certain number of these cases while in others the blood pressure remained normaL Viewing such cases more closely and encouraged by Goldblatt's experimental work on hypertension, I had recently been struck with the remarkable regularity with which hypertensive cases were almost invariably associated with kidneys having an intrarenal pelvis. The degree and type of pathological change varied considerably. On the other hand, in none of the patients under my observation whose kidneys had an extrarenal pelvis was hypertension present, irrespective of the degree and type of disease. Furthermore, I was impressed by the fact that the cure or recurrence of hypertension depended upon whether one type of kidney or the other was left behind after nephrectomy. The situation that precipitated the discovery of this interesting phenomenon was due to a study of several recent spectacular cures obtained in hopeless cases of anuria after unilateral decapsulation. In examining some of these kidneys at operation in order to consider the feasability of nephrostomy and pyelotomy, the latter procedure was found somewhat technically difficult on account of the presence of an intrarenal pelvis_ Armed with these observations, I looked back through my files at many of the intravenous urograms in which blood pressure readings were taken, and was astounded at the remarkable regularity of concurrence of hypertension with pathological changes in the intrarenal peivis type of kidneys (fig_ 1); on the contrary, there was a striking absence of hypertension in the extrarenal type of pelvis in kidneys with many more gross changes (fig. 2). In examining some intravenous urograms of hypertension taken by several other investigators I was also surprised by the regularity with which minor but important deviations from normal were completely overlooked, especially if they occurred in intrarenal pelves. Proper interpretation of intravenous urograms and recognition of even slight abnormalities are of paramount importance when one considers the
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fact that essential hypertension can progress for a long time without any apparent functional impairment of the kidney. Gross changes in the pelvic outline cannot therefore be expected until very late in the disease. Comparative anatomy. Some veterinarians conjecture that since the pre-historic pig and man were both primarily omnivorous, their kidneys are more like each other than those of other animals which were primarily either herbivorous or carnivorous. While the extrarenal pelvic kidney is the outstanding type in pig and man (fig. 3), the most common in the
FIG. 1 FIG. 2 FIG. 1. Intravenous urogram showing early dilatation of an intrarenal pelvis in remaining kidney after removal of opposite kidney for tuberculosis. Blood pressure 250/140 before and 200/140 after nephrectomy. FIG. 2. Intravenous urogram showing moderately dilated extrarenal pelvis in a single remaining kidney following nephrectomy 24 years ago when patient was 10 years old. In spite of 2 pregnancies, patient runs a persistently low systolic blood pressure between 86/60 and 120/70.
other groups is the intrarenal pelvis. In the normal evolution of the human intrarenal pelvic type of the fetus and early childhood to the elongated extrarenal pelvic type of kidney, greater circulatory freedom is thereby obtained in both the erect and supine positions (fig. 4). A minority among humans, however, never develop a kidney form beyond the squatty fetal intrarenal type. One often finds a persistence of this retarded development in successive generations of the same family tree. Most of the cases of essential hypertension seem to occur sooner or later in this important retarded group. It is this type that has failed to keep
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Dog Fm. 3. Casts of intrarenal pelvis in the dog and extrarenal pelvis in the pig (a.fter Hyrtl)
F1G. 4. Longitudinal section showing cramped quarters of hilum with intrarenal pelvis in infant kidney contrasted with roominess at hilum and extrarenal pelvis of adult kidney (after Kelly and :Burnam)
pace in its anatomical development with the exigencies of human adult life. When such a pelvis becomes pathological in any way, the forces
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that are set loose, even though very mild, from our present anatomical knowledge, may exert a tremendous influence on the circulation of the involved kidney. It is in this phase of the subject that Goldblatt's experimental work satisfactorily explains essential hypertension with all its sequelae, without much, if any, interference with the functional or physiological capacity of the kidney. In the living, the most satisfactory method of diagnosis now available is by intravenous urography. Further perfection in chemical agents and in technique for delineating the renal vessels in the living subject may make the examination still more accurate and reliable. Surgeons must be more observant when operating on kidneys with regard to the type of pelvis and its relation to the renal vessels. The exact relation of the kidney and its vessels is usually overlooked even at autopsy. The escape of blood and urine disturbs the true relationship present during life by rendering the parenchyma and renal pelvis empty and flaccid. In the later fetal stages and in the newborn, the poles bend toward the hilum, causing the upper and lower calyces to do likewise and, according to Kelly and Burnam, compress the pelvis at its exit to a mere slit. The straighter upper and lower calyces of the normal adult kidney and its pelvis are more capacious, the latter being situated more outside the parenchymal border at the hilum. The kidney of the newborn is short, broad and thick, and the parenchyma of its poles closes tightly down upon the pelvis at the hilum while it appears unrolled or straightened out in the normal adult. In the latter the hilum is wide open and the pelvis is freely palpable. Fat deposits around the infected pelvis encroach still more upon the available space. In the intrarenal pelvis the hilum is short, the notches and poles are close together, like a closed flower bud. If the pelvis is far outside the hilum, the poles and parenchymal lips are far apart like an open flower (fig. 5). The infantile kidney is more subject to compression, particularly by an expanding force from within outwards constricting the renal vessels at their entrance. In old age the pelvis again becomes slightly smaller and therefore more vulnerable to abnormal pressure. The renal artery divides either outside, just at the entrance, or inside the kidney into 4 or 5 branches (fig. 6). Extrahilar arteries, if sufficiently large, may account for the failure of some kidneys with intrarenal pelvis to develop hypertension, unless the obstructing condition is fairly severe. Corrosion specimens often show marked constrictions of the larger arteries at their points of origin, a condition which frequently causes diminution of blood pressure inside the kidney.
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Importance renal circulation. Hinman and others state that the kidney is supplied with about 20 times the amount of blood needed for its own nutrition. Homer W. Smith found that the average renal blood flow in normal man, measured by the rate of diodrast excretion, is 1300 cc per minute or about one-third of the average cardiac output (3800 cc per minute). Since the kidneys receive such a large fraction of the cardiac output their influence on the general circulation must be very great. One can readily surmise, therefore, that any interference with the arterial blood supply of such an important avenue of the blood stream must
A C
E
F
FIG. 5. A, B, C show different types of normal kidney hilum in which renal vascular impairment is rare. D, E, F show varieties of small kidney hilum in which renal ischemia and hypertension are common (after Papin).
produce immediate repercussion in the general circulation. If the constriction or con1pression. of the renal artery is moderate, the arterial wall proximal to it becomes hypertrophied or thickened tc withstand the extra back pressure, and the heart muscle in time becomes hypertrophied to pump against this increased pressure, just as the bladder wall hypertrophies when there is vesical neck obstruction to overcome. When the compression becomes severe, the peripheral blood pressure rises to such a degree that petechiae or small ruptures occur in the arterioles of various organs except the ischemic kidney and the lungs. An obstructive process may lead to infection which in turn increases
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the obstruction, or the latter may follow the infectious condition. Early pelvic dilatation is more manifest with low obstructions, whereas early blunting of the minor calyces is more characteristic of upper ureteropelvic obstruction. Hydronephrosis occurs with obstructive conditions anywhere along the urinary tract.
Minor calyx
Major calyx
Ren.V.
R~n. A. Ur. br.
--:-S-~-+- Corrical column ( Bertini) Middle papill~ of post. group
Papi II. zone of pyr.
d.,1-~Boundary
n
»
FIG. 6. Longitudinal section of normal human adult kidney showing relationship of renal vessels to pelvis and vulnerability of renal vessels to compression by any pelvic distension (after Kelly and Burnam).
Partial obstruction of the renal vein raises intrarenal pressure while partial obstruction of the renal artery lowers it. In both, the blood flow is slowed and oliguria follows. However, increased blood pressure will force more blood through the kidney with a resulting increase in urinary filtration and output. Hinman states that lowering intrarenal pressure
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by partial obstruction of the renal artery hastens the development of hydronephrosis because of increased ischemia. Raising the intrarenal pressure by partial obstruction of the renal vein also accelerates the velopment of hydronephrosis up to the period when collateral veins compensate for the partial venous block. In the usual form of extrarenal pelvis the hump on the superior mesial aspect of the free border of the pelvis and the ureter acts as a widespread cushion which takes up and dissipates most, if not all, of the urinary back
FrG. 7. Intravenous urogram showing large left renal calculus and dilated extrarenal pelvis and ureter on both sides, yet blood pressure varies between 120 /80 and 130 /85.
pressure, leaving very little force to affect the renal artery and circulation (fig. 7) The persistence of the intrarenal pelvis into adult life presupposes a tenacious membrane or capsule which holds the 2 lips of the hilum close together. hydronephrotic change in such a kidney will produce an expanding force to press against the unyielding parenchymal lips and the renal blood vessels, thus still further increasing the ischemia and indirectly the hydronephrosis and hypertension (fig. 8). Furthermore, in the extrarenal type, any hydronephrotic change in the absence of a tenacious membrane between the lips of the hilum, easily forces these lips to spread
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out still further like a flower. Thus direct pressure on the renal vessels as they enter the kidney is still further minimized with the result that no hypertension occurs. In the intrarenal pelvis, the compressibility of its expanding force and back pressure is much more formidable and the first attack seems to be against the renal artery, producing ischemia and hypertension. In such a kidney, dilatation of the calyces seems to occur much earlier than in extrarenal hydronephrosis. In the latter the dilating force extends over a much wider area (ureter, pelvis and calyces) while in an intrarenal pelvis with ureteropelvic obstruction the expanding force is concentrated within
FIG. 8. View of intrarenal type of renal pelvis with narrow hilum in which the renal vessels appear to fit in too snugly for safety (after Kelly and Burnam).
the kidney itself and is still further restricted by its more or less unyielding renal fibrous capsule. Usually both kidneys are structurally alike, and this may be the reason why, when a nephrectomy is done on one side for a pathologic process associated with intrarenal pelvis and hypertension, the blood pressure often returns sooner or later to its previous high level since the extra load plus the previously existing causative factors undermine the remaining kidney. In those cases in which the blood pressure becomes normal and remains so, it is probable that the remaining kidney has an extrarenal pelvis. Further observation may show a greater incidence of Bright's disease in intrarenal pelvic kidneys. It is possible that with more extensive use of intravenous pyelography and more detailed pathological study of the
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kidneys, many such cases associated with hypertension may also show the existence of this type of pelvis. If this is so, an early investigation of these cases may lead us to initiate appropriate remedial measures long before the condition becomes hopelessly chronic. For years we had been taught that polycystic kidneys and renal tumors were usually accmnpanied by hypertension. More recent reports, however, show that a
FIG. 9. Stages of polycystic disease of kidney. (After Hinman.) a Extrarenal pelvis without pelvic encroachment.. b, c, d Increasing depth of pelvis within renal substance corresponding with degree of cystic degeneration. Degree of hypertension is in direct ratio with pressure exerted on pelvis and renal vessels by cysts.
fairly large proportion of these conditions are associated with normal blood pressure. Here too, apparently, the blood pressure depends upon the degree of compression exerted on the main renal vessels by the or tumor tissue and the type of pelvis Those starting at or near the hilum seem to develop hypertension much earlier than those developing at the periphery of the kidney (fig. 9)
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The acute arteriolar lesions produced by severe constriction in Goldblatt's experiments are associated with hypertension and uremia. The resvlting fibrinoid and hyaline degeneration and necrosis of the arterioles and petechiae are most marked in the vessels of the intestines and retina. The changes in the kidneys are mainly in the tubules and are probably products of stagnation which interfere with the normal processes of absorption and reabsorption. These findings seem to imply that the increased intravascular pressure is responsible for the alterations in the vessel walls. The pressure in the intrarenal vessels however cannot rise greatly on account of the constricting action of the clamp. Wilson and Byrom working on rats showed when 1 renal artery was constricted, renal vascular lesions were limited to the other nonischemic kidney. Renal ischemia. The control of the arterial pressure is chiefly dependent upon the peripheral resistance, the cardiac output and blood volume. In one type of hypertension it is due to the resistance offered to the flow of blood in the renal arterioles. The early lesions in experimental acute diffuse glomerulonephritis consist of a general swelling and proliferation of the endothelial cells of the glomerular capillaries, together with an accumulation of inflammatory exudate within the loops. These changes give rise to ischemia of the glomeruli, and in this respect there is a similarity between acute glomerulonephritis in humans and hypertension in animals resulting from renal ischemia as produced by the Goldblatt method. The ischemia starting at the periphery in the smaller vessels of the kidney is due to toxic or bacterial invasion, whereas the ischemia beginning in the large renal vessels is usually primarily mechanical. Both lead to hypertension. The former, being toxic, usually attacks both kidneys simultaneously; the latter rarely involves both organs at the same time and often remains unilateral. The bilateral type embarrasses the renal circulation still more by edema and inflammation and may be relieved by decapsulation; the unilateral may be benefited by various kinds of corrective operations plus possible decapsulation. A rapid onset of hypertension can manifest itself with an acute overwhelming involvement of the glomeruli and tubules, as in toxemia of pregnancy. A slower elevation of the blood pressure may, however, occur with a progressive involvement of these structures. Both cause an intrarenal ischemia which starts peripherally and gradually spreads until it affects the entire kidney and its vessels and will have the same action on blood pressure as Goldblatt's type of compression of the main renal vessels. The difference is that in the first type, there is distinct loss of renal function before hypertension develops, whereas in the second
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group the function remains fairly normal until late in the disease. Renal inefficiency of itself does not necessarily produce hypertension. Whether the origin of renal ischemia is at the hilum and due to impeded renal arterial supply or to augmented pelvic tension with resulting increased compression of the renal arteries, or whether it arises within the kidney itself from a generalized involvement of the smaller arterioles, the resistance and back pressure against the circulation is enhanced. If only a calyx is involved, the extent of arterial supply implicated is too small in proportion to the entire circulation to have any effect, But when the entire kidney or both kidneys are involved, the effect is much more profound. Inasmuch as the kidney is about 20 times more vascular than any other organ in the body and takes up about one-third of the entire cardiac output, the renal circulation is so abundant that any interference with the blood supply will bring about a greater back pressure in the aorta, which in turn undergoes a compensatory hypertrophy. Consequently, the left heart must work harder to offset this resistance, with resulting increase of the blood pressure to overcome the blockage at or in the kidney and ultimately a thickening of the arterial walls occurs. As the pulmonary circulation is a separate unit and is cushioned by the right heart, it shows no evidence of any elevation in its blood pressure. After nephrectomy the blood volume which is very copious in the involved kidney is correspondingly reduced. Furthermore, since no more resistance is encountered at this point, the blood pressure drops because the heart is no longer called upon to force the blood through an ischemic kidney. One may compare this situation with that familiar in a traffic jam where a large side road branches out from a main highway. For a long distance traffic will be slowed up by cars waiting to pass into this bottle neck. If the branch road is completely blocked off there will be no interruption of travel on the main highway. Similar conditions occur if the flow of blood to the kidneys is impeded by a bottle neck created by an obstructed renal artery, either at its entrance or within the kidney. There is a general slowing up of the circulation near the involved kidney and this in turn causes back pressure with resulting increase of heart action, hypertension and cardiac hypertrophy. Under normal circumstances if no pathological change is associated with the intrarenal pelvis, there is no effect on blood pressure. Infection, displacement, injury or anatomical abnormalities singly or in combination may interfere with the blood supply to the kidney and initiate the production of hypertension. Man is the only mammal with 4 extremities who stands and walks in
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the erect posture. Intrarenal pelvic kidneys, frequently present in other animals, are naturally not particularly vulnerable in quadrupeds because of their horizontal position. In them renal mobility and the consequent angulation or compression of the renal artery is definitely minimized. In man, however, the kidney is extremely vulnerable because the open lower part of the perirenal fatty capsule which represents a developmental failure affords inadequate support In extremes of up and down mobility this results in compression and tension on the vessels as they course around the upper lip of the hilum in the intrarenal pelvic type of kidney. In the extrarenal types, even in the presence of the same changes, there is much less likelihood of interference with the blood supply. According to Goldblatt, if there is adequate collateral circulation, hypertension does not develop as readily, and this is particularly true in cases of intrarenal pelves which otherwise may be potentially hypertensive. Temporary ligature of the renal artery or vein produces renal albuminuria similar to the orthostatic type. The latter is caused by interference with the venous backflow from the left kidney as the left renal vein crosses the aorta at the site of the lumbar curvature. Loesch found a moderate persistent hypertension in dogs in which intermittent brief occlusion of the renal arteries, veins and ureters was produced repeatedly. In humans such observations could only be made under conditions closely simulating normal activity. Cash, and Blalock and Levy have shown that marked interference with the arterial supply to the kidneys results in a significant elevation of blood pressure, provided the entire arterial circulation including that through the main artery, the small vessels of the pedicle, those of the ureter and capsule is not completely occluded. In other words, complete absence of the kidneys does not cause an elevation of blood pressure, whereas a marked reduction in the renal blood supply produces at least a temporary nse. Hypertension diminishes when the patient is in a recumbent position because the renal blood supply becomes more adequate. N ephroptosis with its pull on the renal artery is thus corrected, and as the intrarenal pelvis is better able to empty itself, there will also be less chance for further interference with the renal blood supply. The older the person, the less elastic the arteries and the greater the constriction of the renal artery in even mild degrees of nephroptosis. Compression at the hilum is a mechanical "bottle neck" blockage and
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1s apt to be more transient than the peripheral resistance induced intrarenal disease, such as glomerulonephritis, arterial and arteriolar sclerosis of the kidneys.. In the latter toxic group the influence of recumbency on hypertension is not very great, while in the former it is often quite striking unless unfavorably influenced by infection, distended intrarenal pelvis due to persistent mechanical obstruction, or to other chronic pathology within the kidney that recumbency does not ameliorate.
FIG. 10. Intravenous urogram showing fairly noirnal bilateral intrarena.l pelvis in Jow kidneys and slight enlargement of prostate in patient with blood pressure ranging from 190/ 145 to 160/120.
To recapitulate: In quadrupeds an intrarenal pelvis is not much of a hazard because the vessels pass directly down into the hilum. The upright posture of man, however, causes intermittent constriction of the renal artery as it winds around the projecting lip of the short, stocky intrarenal pelvic type of kidney. In the wide open hilum of an extrarenal pelvis this effect is minimized even in ptosis where the renal artery is cushioned and protected by the soft yielding pelvis. Peripheral resistance of terminal cortical disease may be localized and does not estab-
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lish a mass resistance as readily as with hilum constriction. In the latter, pressure is exerted on the main source of arterial supply to the kidney. If accessory vessels are present hypertension is less likely to develop unless they too are constricted. In accordance with the above reasoning, mechanics and gravity seemingly play an important role in the production of essential hypertension. Nature fortunately guards normal man against the danger of an intrarenal pelvis by endowing him early in life with an extrarenal pelvis with its cushioning safety factors in case pathological changes do develop. In an individual handicapped by an intrarenal pelvis, infection, ureteral spasm or calculus, nephroptosis, pressure of an enlarging uterus, prominent psoas muscle, hypertrophied prostate, etc., even though slight, may accelerate the development of hypertension (fig. 10). With extrarenal pelvic kidneys, however, hypertension rarely develops even with the additional burden of the above factors. SUMMARY
The etiological relation of renal ischemia in the production of so-called essential hypertension has been proven beyond a doubt in animals by Goldblatt and substantiated by many other investigators. In attempting to correlate this important scientific contribution with clinical hypertension, Goldblatt and others, finding themselves at the cross-roads of the unknown, apparently sought refuge by creating an admittedly fanciful, hypothetical pressor substance. This substance, which they claim is elaborated by the ischemic kidney into the circulation, is productive of essential hypertension. Its existence, however, is seriously doubted by most scientific investigators. Hypertension can be caused by increased peripheral resistance and ischemia within the kidney due to generalized toxic effects on the intra.renal circulation such as occurs in the nephritides. It may also result from mechanical compressive forces at or near the kidney hilum, producing renal ischemia, augmented back pressure against the general circulation and increased heart action. The kidney in a normal human adult has been provided by nature with an extrarenal pelvis and a wide hilum as an efficient shock absorber against renal ischemia and hypertension. A certain proportion of humans, not so fortunate, are afflicted with a persistent fetal type of kidney with its intrarenal pelvis and narrow hilum. Although in the lower animals this kind of kidney is not much of a handicap, in man with his
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erect posture, such organs are vulnerable to various stresses and strains that lead to renal ischemia and hypertension. Because of the cramped quarters in the hilum of these intrarenal pelvic kidneys, even minor pathological forces may do considerable harm. The increased mobility of the human kidney due to the open inferior end of its fatty capsule has an important influence on the patency of the large renal vessels at the hilum. The renal circulation ,,vhich comprises one-third of the entire blood volume when impeded by the cramped hilum of an intrarenal pelvis creates a traffic jam within the blood stream as certain in its effect as that of a bottle neck on a highway. The resulting back pressure increases the burden on the heart and results in hypertension. In a series of 200 cases, the author was recently amazed at discovering the regularity with which .,hypertension was accompanied by disease in intrarenal types of kidney pelves. On the other hand, because of the cushioning effect inherent in the extrarenal type, essential hypertension in such protected kidneys appeared extremely unlikely even though the existing pathological changes were of considerable degree. Since essential hypertension may exist for a long time without apparent impairment of renal function, the status of the kidney and its circulation as the source of the trouble is unfortunately usually overlooked. Careful interpretation and recognition of even mild abnormalities ascertainable by intravenous pyelogram is essential for early diagnosis and prophylaxis. Numerous clinical impressions gained by the author over many years of urological practice have convinced him that the anatomical peculiarities of the kidney, as described above, when influenced by even mild pathological conditions, play an important part in the production of hypertension. From the intravenous urograms carefully interpreted, one should be able to make a long range forecast of hypertensive possibilities in those with intrarenal pelvic kidneys. This should be particularly interesting to insurance companies in their studies of life expectancy and its relation to hypertension, arteriosclerosis, cardiac hypertrophy, cerebral accidents, toxemia of pregnancy, etc. From the huge actuarial statistics maintained by these companies it should be relatively simple for them to ascertain what proportion of cases with extrarenal pelvic kidneys, if any, ever develop hypertensi011. The clinical study of essential hypertension in the living requires an open mind and an interpretation of even minor abnormalities in pyelo-
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graphic studies and operative findings. Since renal impairment comes late in essential hypertension we must learn to recognize early kidney lesions long before increased pressure manifests itself. It is only by such early recognition that we can ever hope to develop efficient prophylactic and curative measures.
101 Lafayette Ave., Brooklyn, N. Y. REFERENCES BLALOCK, A., AND LEVY, S. E.: Studies on etiology of renal hypertension. Ann. Surg., 106: 826-847, 1937. BOYLSTON, G. A., McEVEN, E.G., AND IVY, A. C.: Pressor substance is not present in perfusate of ischemic kidneys. Proc. Soc. Exper. Biol. & Med., 39: 559-562, 1938. CASH, J. R.: Further studies of arterial hypertension. Proc. Soc. Exper. Biol. & Med., 23: 609, 1926. DocK, W., AND RYTAND, D. A.: Renal blood flow after subtotal nephrectomy. Proc. Soc. Exper. Biol. & Med., 36: 196-198, 1937. GOLDBLATT, H.: Experimental observations on surgical treatment of hypertension. Surg., 4: 483-486, 1938. ' HINMAN, F.: The Principles and Practice of Urology. W. B. Saunders Co., Philadelphia and London, 1935. KELLY, H. A., AND BURNAM, C. F.: Diseases of the Kidneys, Ureters and Bladder, with Special Reference to the Diseases in Women. D. Appleton and Co., New York, N. Y., 1914, 2nd ed., 1922. LOESCH, J.: Ein Beitrag zur experimentallen Nephritis und zum arteriellen Hochdruck. Zentralbl. f. inn. Med., 64: 145 and 177, 1933. MACKENZIE, D. W., AND SENG, M. I.: Urological aspects of hypertension. Surg., Gynec. & Obst., 70: 578-583, 1940. SMITH, H. W.: New aspects of renal physiology. J. Urol., 41: 867-876, 1939. WILSON, C., AND BYROM, F. B.: Renal changes in J:Qalignant hypertension; experimental evidence. Lancet, 1: 136-139, 1939.
Every one who is interested in hypertension owes a debt of gratitude to Dr. Harry Goldblatt for his epoch-making experiments on living dogs which he proved the all important role of renal ischemia in the causation of high blood pressure. By varying the degree of compression of the main renal arteries in the same dog he could proportionately increase or decrease the degree of renal ischemia, and in direct ratio, influence the rise or fall of the arterial tension. Pressor theory. Unfortunately, however, Goldblatt was apparently baffled by the conflicting results in his experiments on dogs and their application to human beings. Thus he was led to assume the existence of a hypothetical pressor substance which is elaborated by the kidney and when liberated into the circulation produces hypertension. In adopting this theory he overlooked the fact that a simple interpretation of the process is more likely to be conclusive than a more complex one which is subject to variations. The introduction of a third element, a pressor substance, which he admits is hypothetical and has never been isolated has led him, his co-workers and followers to pursue a long tedious and possibly endless trail. If such a humoral substance is actually elaborated, why does it not occur in all similar pathologic conditions? Why are there so many exceptions? Furthermore, if it is true that an entire kidney is involved in the development of hypertension, why does not the same process produce hypertension to a lesser degree when half a kidney or only 1 calyx is involved::' Hypertension of severe degree causes arteriolar lesions and petechiae everywhere in the body except in the lungs and in the ischemic kidney, because in these 2 organs the blood pressure is lower than in the rest of the circulation. If a pressor substance is liberated in the blood, it must reach the pulmonary circulation as well as that in the ischemic kidney and should produce the same type of arteriolar changes in these organs as in the rest of the body. It is difficult to conceive that a freely circulating substance can be so selective. 1
The diodrast employed in this study was supplied by the Winthrop Chemical Co., Inc. 641
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Dock and Rytand, in their extensive work on rats, failed to find any evidence of such a vasoconstrictor substance in the blood. Boylston, McEwen and Ivy were also unable to obtain a pressor substance in significant amounts from ischemic kidneys of hypertensive dogs by perfusing them with Locke's solution. Increased pressor properties of the blood in dogs with renal ischemia and hypertension could not be demonstrated by many other workers. There is no conclusive proof of the existence of a known or new pressor agent in the blood, spinal fluid or urine in experimental hypertension due to renal ischemia. Extra-renal surgical treatment. Recent surgical treatment of hypertension consists of denervation of the adrenals or kidneys, section of splanchnic nerves and of anterior nerve roots, and excision of celiac or lumbar ganglia connected with the vasomotor apparatus of the abdomen. Some of these procedures have been combined with unilateral or partial bilateral adrenalectomy. Irradiation of the adrenals by x-ray and partial adrenalectomy alone have also been tried. After all these operations, the percentage of cures has been very small. In evaluating the benefit of any surgical treatment, one must consider that the rest in bed and during convalescence of itself will aid in a lowering of the pressure. Queries. To every student of hypertension many conflicting problems and questions must present themselves and still further mystify him with regard to the etiology and proper management of the condition. Why is unilateral or bilateral pyelonephritis accompanied by hypertension in 1 case and not in another? Why is hypertension absent in the vast majority of cases of bilateral nephrolithiasis although the pathological process would favor its occurrence? Why is not hypertension present in all cases of renal hypoplasia and why is there not a permanent reduction of blood pressure in all patients who have undergone nephrectomy for hypoplastic kidney? Furthermore, why does a reduction of blood pressure follow nephrectomy for calculous pyelonephritis in some cases and not in others, and why even if it has occurred does the pressure remain more or less permanently lowered in 1 patient and only for a time in another? Also why are some cases of urinary obstruction associated with hypertension and not in others, and why is a reduction of the blood pressure after prostatectomy observed in only a certain number? Why is the pressure so often higher in the erect than in the recumbent posture and why is it not always reduced by rest in bed? Finally, why is hypertension present in only 45 per cent of polycystic cases, according to MacKenzie and Seng, and why are there so many renal neoplasms without hypertension?
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of For many years the above questions baffled and plagued me. Essential hypertension remained a purely medical problem and such a case was almost never referred to the urologist, partly because of the prevailing dependence on uncatheterized specimens of urine, especially in females, and on stale specimens. Too much reliance was placed on the presence of albumin before renal disease was considered as a possible etiologic factor of hypertension. Gradually, however, many patients with vague primary urological problems, secondarily afflicted with hypertension, were referred to me. After appropriate measures had been instituted it was amazing to find a fall of blood pressure to normal in some of these patients. However, there was a return of hypertension in a certain number of these cases while in others the blood pressure remained normaL Viewing such cases more closely and encouraged by Goldblatt's experimental work on hypertension, I had recently been struck with the remarkable regularity with which hypertensive cases were almost invariably associated with kidneys having an intrarenal pelvis. The degree and type of pathological change varied considerably. On the other hand, in none of the patients under my observation whose kidneys had an extrarenal pelvis was hypertension present, irrespective of the degree and type of disease. Furthermore, I was impressed by the fact that the cure or recurrence of hypertension depended upon whether one type of kidney or the other was left behind after nephrectomy. The situation that precipitated the discovery of this interesting phenomenon was due to a study of several recent spectacular cures obtained in hopeless cases of anuria after unilateral decapsulation. In examining some of these kidneys at operation in order to consider the feasability of nephrostomy and pyelotomy, the latter procedure was found somewhat technically difficult on account of the presence of an intrarenal pelvis_ Armed with these observations, I looked back through my files at many of the intravenous urograms in which blood pressure readings were taken, and was astounded at the remarkable regularity of concurrence of hypertension with pathological changes in the intrarenal peivis type of kidneys (fig_ 1); on the contrary, there was a striking absence of hypertension in the extrarenal type of pelvis in kidneys with many more gross changes (fig. 2). In examining some intravenous urograms of hypertension taken by several other investigators I was also surprised by the regularity with which minor but important deviations from normal were completely overlooked, especially if they occurred in intrarenal pelves. Proper interpretation of intravenous urograms and recognition of even slight abnormalities are of paramount importance when one considers the
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fact that essential hypertension can progress for a long time without any apparent functional impairment of the kidney. Gross changes in the pelvic outline cannot therefore be expected until very late in the disease. Comparative anatomy. Some veterinarians conjecture that since the pre-historic pig and man were both primarily omnivorous, their kidneys are more like each other than those of other animals which were primarily either herbivorous or carnivorous. While the extrarenal pelvic kidney is the outstanding type in pig and man (fig. 3), the most common in the
FIG. 1 FIG. 2 FIG. 1. Intravenous urogram showing early dilatation of an intrarenal pelvis in remaining kidney after removal of opposite kidney for tuberculosis. Blood pressure 250/140 before and 200/140 after nephrectomy. FIG. 2. Intravenous urogram showing moderately dilated extrarenal pelvis in a single remaining kidney following nephrectomy 24 years ago when patient was 10 years old. In spite of 2 pregnancies, patient runs a persistently low systolic blood pressure between 86/60 and 120/70.
other groups is the intrarenal pelvis. In the normal evolution of the human intrarenal pelvic type of the fetus and early childhood to the elongated extrarenal pelvic type of kidney, greater circulatory freedom is thereby obtained in both the erect and supine positions (fig. 4). A minority among humans, however, never develop a kidney form beyond the squatty fetal intrarenal type. One often finds a persistence of this retarded development in successive generations of the same family tree. Most of the cases of essential hypertension seem to occur sooner or later in this important retarded group. It is this type that has failed to keep
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Dog Fm. 3. Casts of intrarenal pelvis in the dog and extrarenal pelvis in the pig (a.fter Hyrtl)
F1G. 4. Longitudinal section showing cramped quarters of hilum with intrarenal pelvis in infant kidney contrasted with roominess at hilum and extrarenal pelvis of adult kidney (after Kelly and :Burnam)
pace in its anatomical development with the exigencies of human adult life. When such a pelvis becomes pathological in any way, the forces
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that are set loose, even though very mild, from our present anatomical knowledge, may exert a tremendous influence on the circulation of the involved kidney. It is in this phase of the subject that Goldblatt's experimental work satisfactorily explains essential hypertension with all its sequelae, without much, if any, interference with the functional or physiological capacity of the kidney. In the living, the most satisfactory method of diagnosis now available is by intravenous urography. Further perfection in chemical agents and in technique for delineating the renal vessels in the living subject may make the examination still more accurate and reliable. Surgeons must be more observant when operating on kidneys with regard to the type of pelvis and its relation to the renal vessels. The exact relation of the kidney and its vessels is usually overlooked even at autopsy. The escape of blood and urine disturbs the true relationship present during life by rendering the parenchyma and renal pelvis empty and flaccid. In the later fetal stages and in the newborn, the poles bend toward the hilum, causing the upper and lower calyces to do likewise and, according to Kelly and Burnam, compress the pelvis at its exit to a mere slit. The straighter upper and lower calyces of the normal adult kidney and its pelvis are more capacious, the latter being situated more outside the parenchymal border at the hilum. The kidney of the newborn is short, broad and thick, and the parenchyma of its poles closes tightly down upon the pelvis at the hilum while it appears unrolled or straightened out in the normal adult. In the latter the hilum is wide open and the pelvis is freely palpable. Fat deposits around the infected pelvis encroach still more upon the available space. In the intrarenal pelvis the hilum is short, the notches and poles are close together, like a closed flower bud. If the pelvis is far outside the hilum, the poles and parenchymal lips are far apart like an open flower (fig. 5). The infantile kidney is more subject to compression, particularly by an expanding force from within outwards constricting the renal vessels at their entrance. In old age the pelvis again becomes slightly smaller and therefore more vulnerable to abnormal pressure. The renal artery divides either outside, just at the entrance, or inside the kidney into 4 or 5 branches (fig. 6). Extrahilar arteries, if sufficiently large, may account for the failure of some kidneys with intrarenal pelvis to develop hypertension, unless the obstructing condition is fairly severe. Corrosion specimens often show marked constrictions of the larger arteries at their points of origin, a condition which frequently causes diminution of blood pressure inside the kidney.
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Importance renal circulation. Hinman and others state that the kidney is supplied with about 20 times the amount of blood needed for its own nutrition. Homer W. Smith found that the average renal blood flow in normal man, measured by the rate of diodrast excretion, is 1300 cc per minute or about one-third of the average cardiac output (3800 cc per minute). Since the kidneys receive such a large fraction of the cardiac output their influence on the general circulation must be very great. One can readily surmise, therefore, that any interference with the arterial blood supply of such an important avenue of the blood stream must
A C
E
F
FIG. 5. A, B, C show different types of normal kidney hilum in which renal vascular impairment is rare. D, E, F show varieties of small kidney hilum in which renal ischemia and hypertension are common (after Papin).
produce immediate repercussion in the general circulation. If the constriction or con1pression. of the renal artery is moderate, the arterial wall proximal to it becomes hypertrophied or thickened tc withstand the extra back pressure, and the heart muscle in time becomes hypertrophied to pump against this increased pressure, just as the bladder wall hypertrophies when there is vesical neck obstruction to overcome. When the compression becomes severe, the peripheral blood pressure rises to such a degree that petechiae or small ruptures occur in the arterioles of various organs except the ischemic kidney and the lungs. An obstructive process may lead to infection which in turn increases
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the obstruction, or the latter may follow the infectious condition. Early pelvic dilatation is more manifest with low obstructions, whereas early blunting of the minor calyces is more characteristic of upper ureteropelvic obstruction. Hydronephrosis occurs with obstructive conditions anywhere along the urinary tract.
Minor calyx
Major calyx
Ren.V.
R~n. A. Ur. br.
--:-S-~-+- Corrical column ( Bertini) Middle papill~ of post. group
Papi II. zone of pyr.
d.,1-~Boundary
n
»
FIG. 6. Longitudinal section of normal human adult kidney showing relationship of renal vessels to pelvis and vulnerability of renal vessels to compression by any pelvic distension (after Kelly and Burnam).
Partial obstruction of the renal vein raises intrarenal pressure while partial obstruction of the renal artery lowers it. In both, the blood flow is slowed and oliguria follows. However, increased blood pressure will force more blood through the kidney with a resulting increase in urinary filtration and output. Hinman states that lowering intrarenal pressure
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by partial obstruction of the renal artery hastens the development of hydronephrosis because of increased ischemia. Raising the intrarenal pressure by partial obstruction of the renal vein also accelerates the velopment of hydronephrosis up to the period when collateral veins compensate for the partial venous block. In the usual form of extrarenal pelvis the hump on the superior mesial aspect of the free border of the pelvis and the ureter acts as a widespread cushion which takes up and dissipates most, if not all, of the urinary back
FrG. 7. Intravenous urogram showing large left renal calculus and dilated extrarenal pelvis and ureter on both sides, yet blood pressure varies between 120 /80 and 130 /85.
pressure, leaving very little force to affect the renal artery and circulation (fig. 7) The persistence of the intrarenal pelvis into adult life presupposes a tenacious membrane or capsule which holds the 2 lips of the hilum close together. hydronephrotic change in such a kidney will produce an expanding force to press against the unyielding parenchymal lips and the renal blood vessels, thus still further increasing the ischemia and indirectly the hydronephrosis and hypertension (fig. 8). Furthermore, in the extrarenal type, any hydronephrotic change in the absence of a tenacious membrane between the lips of the hilum, easily forces these lips to spread
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out still further like a flower. Thus direct pressure on the renal vessels as they enter the kidney is still further minimized with the result that no hypertension occurs. In the intrarenal pelvis, the compressibility of its expanding force and back pressure is much more formidable and the first attack seems to be against the renal artery, producing ischemia and hypertension. In such a kidney, dilatation of the calyces seems to occur much earlier than in extrarenal hydronephrosis. In the latter the dilating force extends over a much wider area (ureter, pelvis and calyces) while in an intrarenal pelvis with ureteropelvic obstruction the expanding force is concentrated within
FIG. 8. View of intrarenal type of renal pelvis with narrow hilum in which the renal vessels appear to fit in too snugly for safety (after Kelly and Burnam).
the kidney itself and is still further restricted by its more or less unyielding renal fibrous capsule. Usually both kidneys are structurally alike, and this may be the reason why, when a nephrectomy is done on one side for a pathologic process associated with intrarenal pelvis and hypertension, the blood pressure often returns sooner or later to its previous high level since the extra load plus the previously existing causative factors undermine the remaining kidney. In those cases in which the blood pressure becomes normal and remains so, it is probable that the remaining kidney has an extrarenal pelvis. Further observation may show a greater incidence of Bright's disease in intrarenal pelvic kidneys. It is possible that with more extensive use of intravenous pyelography and more detailed pathological study of the
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kidneys, many such cases associated with hypertension may also show the existence of this type of pelvis. If this is so, an early investigation of these cases may lead us to initiate appropriate remedial measures long before the condition becomes hopelessly chronic. For years we had been taught that polycystic kidneys and renal tumors were usually accmnpanied by hypertension. More recent reports, however, show that a
FIG. 9. Stages of polycystic disease of kidney. (After Hinman.) a Extrarenal pelvis without pelvic encroachment.. b, c, d Increasing depth of pelvis within renal substance corresponding with degree of cystic degeneration. Degree of hypertension is in direct ratio with pressure exerted on pelvis and renal vessels by cysts.
fairly large proportion of these conditions are associated with normal blood pressure. Here too, apparently, the blood pressure depends upon the degree of compression exerted on the main renal vessels by the or tumor tissue and the type of pelvis Those starting at or near the hilum seem to develop hypertension much earlier than those developing at the periphery of the kidney (fig. 9)
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The acute arteriolar lesions produced by severe constriction in Goldblatt's experiments are associated with hypertension and uremia. The resvlting fibrinoid and hyaline degeneration and necrosis of the arterioles and petechiae are most marked in the vessels of the intestines and retina. The changes in the kidneys are mainly in the tubules and are probably products of stagnation which interfere with the normal processes of absorption and reabsorption. These findings seem to imply that the increased intravascular pressure is responsible for the alterations in the vessel walls. The pressure in the intrarenal vessels however cannot rise greatly on account of the constricting action of the clamp. Wilson and Byrom working on rats showed when 1 renal artery was constricted, renal vascular lesions were limited to the other nonischemic kidney. Renal ischemia. The control of the arterial pressure is chiefly dependent upon the peripheral resistance, the cardiac output and blood volume. In one type of hypertension it is due to the resistance offered to the flow of blood in the renal arterioles. The early lesions in experimental acute diffuse glomerulonephritis consist of a general swelling and proliferation of the endothelial cells of the glomerular capillaries, together with an accumulation of inflammatory exudate within the loops. These changes give rise to ischemia of the glomeruli, and in this respect there is a similarity between acute glomerulonephritis in humans and hypertension in animals resulting from renal ischemia as produced by the Goldblatt method. The ischemia starting at the periphery in the smaller vessels of the kidney is due to toxic or bacterial invasion, whereas the ischemia beginning in the large renal vessels is usually primarily mechanical. Both lead to hypertension. The former, being toxic, usually attacks both kidneys simultaneously; the latter rarely involves both organs at the same time and often remains unilateral. The bilateral type embarrasses the renal circulation still more by edema and inflammation and may be relieved by decapsulation; the unilateral may be benefited by various kinds of corrective operations plus possible decapsulation. A rapid onset of hypertension can manifest itself with an acute overwhelming involvement of the glomeruli and tubules, as in toxemia of pregnancy. A slower elevation of the blood pressure may, however, occur with a progressive involvement of these structures. Both cause an intrarenal ischemia which starts peripherally and gradually spreads until it affects the entire kidney and its vessels and will have the same action on blood pressure as Goldblatt's type of compression of the main renal vessels. The difference is that in the first type, there is distinct loss of renal function before hypertension develops, whereas in the second
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group the function remains fairly normal until late in the disease. Renal inefficiency of itself does not necessarily produce hypertension. Whether the origin of renal ischemia is at the hilum and due to impeded renal arterial supply or to augmented pelvic tension with resulting increased compression of the renal arteries, or whether it arises within the kidney itself from a generalized involvement of the smaller arterioles, the resistance and back pressure against the circulation is enhanced. If only a calyx is involved, the extent of arterial supply implicated is too small in proportion to the entire circulation to have any effect, But when the entire kidney or both kidneys are involved, the effect is much more profound. Inasmuch as the kidney is about 20 times more vascular than any other organ in the body and takes up about one-third of the entire cardiac output, the renal circulation is so abundant that any interference with the blood supply will bring about a greater back pressure in the aorta, which in turn undergoes a compensatory hypertrophy. Consequently, the left heart must work harder to offset this resistance, with resulting increase of the blood pressure to overcome the blockage at or in the kidney and ultimately a thickening of the arterial walls occurs. As the pulmonary circulation is a separate unit and is cushioned by the right heart, it shows no evidence of any elevation in its blood pressure. After nephrectomy the blood volume which is very copious in the involved kidney is correspondingly reduced. Furthermore, since no more resistance is encountered at this point, the blood pressure drops because the heart is no longer called upon to force the blood through an ischemic kidney. One may compare this situation with that familiar in a traffic jam where a large side road branches out from a main highway. For a long distance traffic will be slowed up by cars waiting to pass into this bottle neck. If the branch road is completely blocked off there will be no interruption of travel on the main highway. Similar conditions occur if the flow of blood to the kidneys is impeded by a bottle neck created by an obstructed renal artery, either at its entrance or within the kidney. There is a general slowing up of the circulation near the involved kidney and this in turn causes back pressure with resulting increase of heart action, hypertension and cardiac hypertrophy. Under normal circumstances if no pathological change is associated with the intrarenal pelvis, there is no effect on blood pressure. Infection, displacement, injury or anatomical abnormalities singly or in combination may interfere with the blood supply to the kidney and initiate the production of hypertension. Man is the only mammal with 4 extremities who stands and walks in
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the erect posture. Intrarenal pelvic kidneys, frequently present in other animals, are naturally not particularly vulnerable in quadrupeds because of their horizontal position. In them renal mobility and the consequent angulation or compression of the renal artery is definitely minimized. In man, however, the kidney is extremely vulnerable because the open lower part of the perirenal fatty capsule which represents a developmental failure affords inadequate support In extremes of up and down mobility this results in compression and tension on the vessels as they course around the upper lip of the hilum in the intrarenal pelvic type of kidney. In the extrarenal types, even in the presence of the same changes, there is much less likelihood of interference with the blood supply. According to Goldblatt, if there is adequate collateral circulation, hypertension does not develop as readily, and this is particularly true in cases of intrarenal pelves which otherwise may be potentially hypertensive. Temporary ligature of the renal artery or vein produces renal albuminuria similar to the orthostatic type. The latter is caused by interference with the venous backflow from the left kidney as the left renal vein crosses the aorta at the site of the lumbar curvature. Loesch found a moderate persistent hypertension in dogs in which intermittent brief occlusion of the renal arteries, veins and ureters was produced repeatedly. In humans such observations could only be made under conditions closely simulating normal activity. Cash, and Blalock and Levy have shown that marked interference with the arterial supply to the kidneys results in a significant elevation of blood pressure, provided the entire arterial circulation including that through the main artery, the small vessels of the pedicle, those of the ureter and capsule is not completely occluded. In other words, complete absence of the kidneys does not cause an elevation of blood pressure, whereas a marked reduction in the renal blood supply produces at least a temporary nse. Hypertension diminishes when the patient is in a recumbent position because the renal blood supply becomes more adequate. N ephroptosis with its pull on the renal artery is thus corrected, and as the intrarenal pelvis is better able to empty itself, there will also be less chance for further interference with the renal blood supply. The older the person, the less elastic the arteries and the greater the constriction of the renal artery in even mild degrees of nephroptosis. Compression at the hilum is a mechanical "bottle neck" blockage and
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1s apt to be more transient than the peripheral resistance induced intrarenal disease, such as glomerulonephritis, arterial and arteriolar sclerosis of the kidneys.. In the latter toxic group the influence of recumbency on hypertension is not very great, while in the former it is often quite striking unless unfavorably influenced by infection, distended intrarenal pelvis due to persistent mechanical obstruction, or to other chronic pathology within the kidney that recumbency does not ameliorate.
FIG. 10. Intravenous urogram showing fairly noirnal bilateral intrarena.l pelvis in Jow kidneys and slight enlargement of prostate in patient with blood pressure ranging from 190/ 145 to 160/120.
To recapitulate: In quadrupeds an intrarenal pelvis is not much of a hazard because the vessels pass directly down into the hilum. The upright posture of man, however, causes intermittent constriction of the renal artery as it winds around the projecting lip of the short, stocky intrarenal pelvic type of kidney. In the wide open hilum of an extrarenal pelvis this effect is minimized even in ptosis where the renal artery is cushioned and protected by the soft yielding pelvis. Peripheral resistance of terminal cortical disease may be localized and does not estab-
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lish a mass resistance as readily as with hilum constriction. In the latter, pressure is exerted on the main source of arterial supply to the kidney. If accessory vessels are present hypertension is less likely to develop unless they too are constricted. In accordance with the above reasoning, mechanics and gravity seemingly play an important role in the production of essential hypertension. Nature fortunately guards normal man against the danger of an intrarenal pelvis by endowing him early in life with an extrarenal pelvis with its cushioning safety factors in case pathological changes do develop. In an individual handicapped by an intrarenal pelvis, infection, ureteral spasm or calculus, nephroptosis, pressure of an enlarging uterus, prominent psoas muscle, hypertrophied prostate, etc., even though slight, may accelerate the development of hypertension (fig. 10). With extrarenal pelvic kidneys, however, hypertension rarely develops even with the additional burden of the above factors. SUMMARY
The etiological relation of renal ischemia in the production of so-called essential hypertension has been proven beyond a doubt in animals by Goldblatt and substantiated by many other investigators. In attempting to correlate this important scientific contribution with clinical hypertension, Goldblatt and others, finding themselves at the cross-roads of the unknown, apparently sought refuge by creating an admittedly fanciful, hypothetical pressor substance. This substance, which they claim is elaborated by the ischemic kidney into the circulation, is productive of essential hypertension. Its existence, however, is seriously doubted by most scientific investigators. Hypertension can be caused by increased peripheral resistance and ischemia within the kidney due to generalized toxic effects on the intra.renal circulation such as occurs in the nephritides. It may also result from mechanical compressive forces at or near the kidney hilum, producing renal ischemia, augmented back pressure against the general circulation and increased heart action. The kidney in a normal human adult has been provided by nature with an extrarenal pelvis and a wide hilum as an efficient shock absorber against renal ischemia and hypertension. A certain proportion of humans, not so fortunate, are afflicted with a persistent fetal type of kidney with its intrarenal pelvis and narrow hilum. Although in the lower animals this kind of kidney is not much of a handicap, in man with his
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erect posture, such organs are vulnerable to various stresses and strains that lead to renal ischemia and hypertension. Because of the cramped quarters in the hilum of these intrarenal pelvic kidneys, even minor pathological forces may do considerable harm. The increased mobility of the human kidney due to the open inferior end of its fatty capsule has an important influence on the patency of the large renal vessels at the hilum. The renal circulation ,,vhich comprises one-third of the entire blood volume when impeded by the cramped hilum of an intrarenal pelvis creates a traffic jam within the blood stream as certain in its effect as that of a bottle neck on a highway. The resulting back pressure increases the burden on the heart and results in hypertension. In a series of 200 cases, the author was recently amazed at discovering the regularity with which .,hypertension was accompanied by disease in intrarenal types of kidney pelves. On the other hand, because of the cushioning effect inherent in the extrarenal type, essential hypertension in such protected kidneys appeared extremely unlikely even though the existing pathological changes were of considerable degree. Since essential hypertension may exist for a long time without apparent impairment of renal function, the status of the kidney and its circulation as the source of the trouble is unfortunately usually overlooked. Careful interpretation and recognition of even mild abnormalities ascertainable by intravenous pyelogram is essential for early diagnosis and prophylaxis. Numerous clinical impressions gained by the author over many years of urological practice have convinced him that the anatomical peculiarities of the kidney, as described above, when influenced by even mild pathological conditions, play an important part in the production of hypertension. From the intravenous urograms carefully interpreted, one should be able to make a long range forecast of hypertensive possibilities in those with intrarenal pelvic kidneys. This should be particularly interesting to insurance companies in their studies of life expectancy and its relation to hypertension, arteriosclerosis, cardiac hypertrophy, cerebral accidents, toxemia of pregnancy, etc. From the huge actuarial statistics maintained by these companies it should be relatively simple for them to ascertain what proportion of cases with extrarenal pelvic kidneys, if any, ever develop hypertensi011. The clinical study of essential hypertension in the living requires an open mind and an interpretation of even minor abnormalities in pyelo-
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graphic studies and operative findings. Since renal impairment comes late in essential hypertension we must learn to recognize early kidney lesions long before increased pressure manifests itself. It is only by such early recognition that we can ever hope to develop efficient prophylactic and curative measures.
101 Lafayette Ave., Brooklyn, N. Y. REFERENCES BLALOCK, A., AND LEVY, S. E.: Studies on etiology of renal hypertension. Ann. Surg., 106: 826-847, 1937. BOYLSTON, G. A., McEVEN, E.G., AND IVY, A. C.: Pressor substance is not present in perfusate of ischemic kidneys. Proc. Soc. Exper. Biol. & Med., 39: 559-562, 1938. CASH, J. R.: Further studies of arterial hypertension. Proc. Soc. Exper. Biol. & Med., 23: 609, 1926. DocK, W., AND RYTAND, D. A.: Renal blood flow after subtotal nephrectomy. Proc. Soc. Exper. Biol. & Med., 36: 196-198, 1937. GOLDBLATT, H.: Experimental observations on surgical treatment of hypertension. Surg., 4: 483-486, 1938. ' HINMAN, F.: The Principles and Practice of Urology. W. B. Saunders Co., Philadelphia and London, 1935. KELLY, H. A., AND BURNAM, C. F.: Diseases of the Kidneys, Ureters and Bladder, with Special Reference to the Diseases in Women. D. Appleton and Co., New York, N. Y., 1914, 2nd ed., 1922. LOESCH, J.: Ein Beitrag zur experimentallen Nephritis und zum arteriellen Hochdruck. Zentralbl. f. inn. Med., 64: 145 and 177, 1933. MACKENZIE, D. W., AND SENG, M. I.: Urological aspects of hypertension. Surg., Gynec. & Obst., 70: 578-583, 1940. SMITH, H. W.: New aspects of renal physiology. J. Urol., 41: 867-876, 1939. WILSON, C., AND BYROM, F. B.: Renal changes in J:Qalignant hypertension; experimental evidence. Lancet, 1: 136-139, 1939.