Download Physiology Ch 19 p213-228 [4-25

Physiology Ch 19 p213-228
Role of Kidney in Long-Term Arterial Pressure and Hypertension
-Sympathetic nerves control short-term arterial pressure, whereas homeostasis of fluid-volume
regulates arterial pressure week after week, determined by balance between fluid intake and output
-Kidneys regulate excretion of salt and water, and are locally and hormonally controlled
Renal-Body Fluid System for Arterial Pressure Control – if blood volume increases and vascular
capacitance is not altered, arterial pressure will increase, which causes kidneys to excrete excess volume
to return the pressure back to normal
-an increase in pressure of only a few mmHg can double renal output of H2O, called pressure diuresis,
as well as double the output of salt, called pressure natriuresis
Quantitation of Pressure Diuresis as a Basis for Arterial Pressure Control – a graph of arterial pressure
vs urinary volume output shows that an increase in pressure = increase in urinary volume output;
pressure diuresis
-the curve is called a renal urinary output curve (renal function curve)
-at 50mmHg, urine output is 0, at 100mmHg the output is normal, and at 200mmHg it is 6x normal
-increasing pressure increases volume output as well as causes equal increase in pressure natriuresis
-an experiment in dogs where they blocked nervous BP control, they infused 400mL of blood
-caused rapid cardiac output increase to double normal and increase in mean arterial pressure
to 205mmHg
-both cardiac output and arterial pressure returned to normal within 1 hour; thus the kidneys
eliminate fluid volume form body in response to high arterial pressure
Arterial Pressure Control by Renal-Body Fluid Mechanism – Near Infinite Feedback Gain Feature – to
analyze renal-arterial fluid system, two intersecting curves can be analyzed
1. renal output curve for H2O and salt in response to rising arterial pressure (same as above)
2. line that represents net water and salt intake
-over a long period, water/salt output must equal the intake
-the equilibrium point is where both curves intersect; it is the point where output = intake
-if pressure rises above equilibrium point, renal output is much greater than intake and the body
will lose fluid, blood volume decreases, and arterial pressure decreases
-this negative balance of fluid will not stop until pressure falls back to equilibrium level
-happens if arterial pressure is even slightly above normal
-if pressure falls below equilibrium point, intake of water and salt is greater than output; body
fluid volume increases, blood volume increases, and arterial pressure rises again until it returns
EXACTLY to the equilibrium point
-return to equilibrium point is called near infinite feedback gain principle
Two Determinants of Long-Term Arterial Pressure Level – as long as the two curves of renal output of
salt and H2O and intake of salt and H2O remain the same, mean arterial pressure will adjust to
100mmHg
-there are only two ways that equilibrium point can change from 100mmHg; (1) shifting pressure level of
renal output curve for salt and H2O, and (2) changing level of water and salt intake line
-Therefore, the two primary determinants of long-term arterial pressure are:
1. Degree of pressure shift of renal output curve for H2O and salt
2. level of H2O and salt intake
-if some abnormality of kidneys caused renal output to shift 50mmHg in
higher pressure, equilibrium point has also shifted 50mmHg to higher
direction
-if renal output curve shifts to new pressure level, arterial
pressure will follow this pressure within a few days
-if some abnormality causes change in level of salt/water intake, it will
also change arterial pressure
-if intake level increases 4-fold, equilibrium point shifts to a
pressure of 160mmHg higher
-it is IMPOSSIBLE to change the long-term mean arterial pressure level
to a new value without changing one or both of the two basic
determinants of long-term arterial pressure
-if either of those are changed, arterial pressure would be regulated at a
new level, the pressure at which the two new curves intersect
Chronic Renal Output Curve is Much Steeper than the Acute Curve – an important characteristic of
pressure natriuresis is that chronic changes in arterial pressure have much greater effect on renal output
of salt and water than observed during acute changes in pressure
-when kidneys are functioning normally, the chronic renal output curve is much steeper than the acute
curve
-chronic increases in arterial pressure are powerful on urine output because increased pressure not only
has direct hemodynamic effects on kidney to increase excretion but also indirect effects mediated by
nervous and hormonal changes that occur when blood pressure is increased
-increased arterial pressure decreases activity of sympathetic nervous system and various
hormones such as angiotensin II and aldosterone that reduce Na and H2O excretion by kidneys
-reduced activity of the antinatriuretic systems amplifies effectiveness of pressure natriuresis
and diuresis in raising Na and H2O excretion during chronic increases in arterial pressure
-when blood pressure is reduced, sympathetic nervous system is activated and formation of
antinatriuretic hormones is increased, adding to the direct effects of pressure to decrease renal output
of water
-combination of direct effects of pressure on kidneys and indirect effects of pressure on
sympathetics and hormone systems make pressure natriuresis and diuresis powerful long-term
control of arterial pressure
-neural/hormonal influences on pressure natriuresis is evident during chronic changes in Na intake
-if kidneys and nervous/hormonal mechanisms are functioning normally, chronic increases in intakes of
Na and H2O to as high as 6x normal are usually associated with only small increases in pressure
-decreases in Na and H2O intake to as low as 1/6th normal has little effect on pressure
-many people are said to be salt insensitive because large variations in salt intake do not change
BP more than a few mmHg
-people with kidney injury or excessive antinatriuretic hormone like angiotensin II or aldosterone may be
salt sensitive with attenuated renal output curve; moderate increases in salt intake increase pressure
-some factors include loss of functional nephrons due to kidney injury, excessive formation of
antinatriuretic hormones, surgical reduction of kidney mass
-in these cases, greater than normal increases in arterial pressure are required to raise
renal output sufficiently to maintain a balance between intake and output of salt/H2O
-long-term salt intake can damage kidneys and make BP MORE SALT SENSITIVE
Failure of Increased Total Peripheral Resistance to Elevate Long-Term Level of Arterial Pressure if Fluid
Intake and Renal Function Do Not Change – basic equation for arterial pressure is:
Arterial pressure = cardiac output * total peripheral resistance
-when total peripheral resistance is acutely increased, arterial pressure does rise immediately
-if kidneys are normal, the rise in BP is not maintained and will return to normal within the day
-this is because increasing resistance in blood vessels everywhere EXCEPT the kidneys does NOT change
the equilibrium point for blood pressure control as dictated by the kidneys
-instead, kidneys begin to respond to high arterial pressure, causing pressure diuresis and
pressure natriuresis where large amounts of Na and H2O are lost, which continues until arterial
pressure returns to equilibrium point
-although increase in pressure in the periphery cannot cause chronic changes to arterial pressure, many
times when total peripheral resistance increases, it also increases intrarenal vascular resistance at the
same time to cause renal hypertension and shifting the renal function curve to a higher pressure level
Increased Fluid Volume can Elevate Arterial Pressure by Increasing Cardiac Output or Total Peripheral
Resistance – increased extracellular fluid volume may elevate arterial pressure if vascular capacity is not
simultaneously increased; sequential events are IN ORDER:
1. increased cellular fluid volume
2. increases blood volume
3. increases mean circulatory filling pressure
4. increases venous return to the heart
5. increases cardiac output  increase arterial pressure OR increase total peripheral resistance
6. increases arterial pressure
-increased arterial pressure, in turn, increases renal excretion of salt and H2O and may return
extracellular fluid volume to normal
-increasing cardiac out put has direct affect on increasing arterial pressure and an indirect effect of
increasing total peripheral vascular resistance through autoregulation of blood flow
-whenever excess amount of blood flows thorugh a tissue, the local tissue vasculature constricts
and decreases the blood flow back toward normal, called autoregulation
-when increased blood volume increases cardiac output, blood flow increases to all tissues of
the body  autoregulation mechanism constricts ALLL vessels to increase peripheral resistance
-because arterial pressure is = to cardiac output * total peripheral resistance, secondary increase in
total peripheral resistance resulting from autoregulation mechanism helps to increase arterial pressure
Importance of NaCl in Renal-Body Fluid Schema for Arterial Pressure Regulation – an increase in salt
intake is far more likely to elevate BP than increase in H2O intake
-reason is that pure water is normally excreted by kidneys almost as rapidly as it is ingested, but salt is
not excreted so easily, and it can accumulate in the body; indirectly increases fluid volume due to:
1. when there is salt excess in extracellular fluid, osmolality of fluid increases and stimulates thirst
center of the brain, making person drink extra water to combat salt concentration
a. this increases extracellular fluid volume
2. increase in osmolality caused by excess salt in extracellular fluid also stimulates hypothalamicposterior pituitary gland secretory mechanism for antidiuretic hormone secretion, which causes
kidneys to greatly reabsorb H2O from kidney tubules to diminish excreted volume of urine and
increasing extracellular fluid volume
-thus, the amount of salt that accumulates in the body is the main determinant of the extracellular fluid
volume; because only small increases in fluid/blood volume can increase arterial pressure, accumulation
of even a small amount of salt can lead to considerable elevation of BP
Chronic Hypertension – means that a person’s mean arterial pressure is greater than the upper range
of accepted normal pressure
-a mean arterial pressure of >110mmHg (normal is 90mmHg) is considered hypertensive
-this level of mean pressure occurs when diastolic is >90 and systolic is >135mmHg
-in SEVERE hypertension, mean arterial pressure can rise to 150-170mmHg with diastolic as high as
130mmHg and systolic as high as 250mmHg
-can shorten life expectancy; lethal effects are caused in 3 ways:
1. excess workload on heart leads to early heart failure and coronary heart disease  MI
2. high pressure damages blood vessels, followed by death of portions of brain  cerebral infarct
or stroke; a stroke can cause paralysis, dementia, blindness, or other serious brain disorders
3. high pressure almost always causes renal damage, can cause kidney failure, uremia and death
Volume-loading hypertension is hypertension caused by excess accumulation of extracellular fluid in
the body, and mechanisms are helpful to understanding renal-body fluid mechanism
Experimental Volume-Loading Hypertension Caused by Reduced Renal Mass Along with Simultaneous
Increase in Salt Intake – when 70% of dog kidney is removed and dogs given salt solution to drink, which
fails to quench thirst, dogs drank 2-4 times the normal amounts of volumes, and after a few days, their
average BP rose about 40mmHg above normal
-after 2 days, dogs were given normal water, and BP returned to normal within 2 days
-at the end of the experiment, dogs were given salt solution again, and this time the pressure rose much
more rapidly and to a higher level because dogs had already learned to tolerate the salt solution and
drank much more; this demonstrates volume-loading hypertension
-this occurs because reduction of kidney mass to 30% of normal reduces ability of kidneys to excrete
H2O and salt, and so H2O and salt accumulated in the body to increase arterial pressure high enough to
finally excrete the excess salt and H2O intake
Sequential changes in circulatory function during the development of Volume-Loading Hypertension –
-acute effect of increasing intake of salt and H2O with 30% of functioning kidney was increase in
extracellular fluid volume, blood volume, and cardiac output to 20-40% above normal
-arterial pressure began to rise but not so much as did fluid volumes and cardiac output
-slower rise in pressure can be discerned by studying total peripheral resistance curve, which
shows an initial DECREASE in total peripheral resistance caused by baroreceptor mechanism
-after 2-4 days, baroreceptors adapted and were no longer able to control rise in pressure
-after these acute changes in circulatory variables, more prolonged secondary changes occurred during
next few weeks; especially important is a progressive increase in total peripheral resistance, and at the
same time the cardiac output decreased almost all the way back to normal as a result of long-term
blood flow autoregulation
-after cardiac output had risen to a high level and initiated hypertension, the excess blood flow
through tissues caused progressive constriction to return local blood flows back to normal, and
causing cardiac output back to normal, while simultaneously causing a secondary increase in
total peripheral resistance
-extracellular fluid and blood volumes returned back to normal along with decrease in cardiac output,
resulted from:
1. the increase in arteriolar resistance decreased capillary pressure, which allowed fluid in tissue spaces
to be reabsorbed back into blood
2. elevated arterial pressure now caused kidneys to excrete excess volume of fluid that had initially
accumulated in the body
Final State of Circulation Several Weeks After Initial Onset of Volume Loading – we find
HYPERTENSION, INCREASE IN PERIPHERAL VASCULAR RESISTANCE, and complete return of extracellular
fluid volume, blood volume, and cardiac output back to NORMAL
-therefore, we can divide volume-loading hypertension into two separate sequential stages:
1. results from increased fluid volume causing increased cardiac output; mediates hypertension
2. second stage in volume-loading hypertension is characterized by high BP and high total
peripheral resistance but a return of cardiac output very close to normal
-thus, increased total peripheral resistance in volume-loading hypertension occurs after
hypertension has developed and is secondary to hypertension rather than being a cause
Volume-Loading Hypertension in Patients who Have Artificial Kidneys – a patient with artificial kidneys
needs to have fluid volume at a normal level; important to remove an appropriate amount of H2O/salt
each time during dialysis
-if not enough H2O/salt is removed, hypertension will develop by this mechanism:
1. cardiac output increases and causes hypertension
2. autoregulation mechanism returns cardiac output to normal, causing increase in peripheral
resistance
3. in the end, hypertension is a high peripheral resistance type of hypertension
Hypertension Caused by Primary Aldosteronism – this is another type of volume-loading hypertension
due to extra aldosterone or excess of other steroids
-a small tumor in one of the adrenal glands occasionally secretes large quantities of aldosterone, called
primary aldosteronism, which increases reabsorption of Na and H2O by kidneys and decreases the loss
of these in urine, while at the same time increasing blood/extracellular fluid volume
-this causes hypertension, which can damage kidneys over time to cause even more hypertension
-in this hypertension, cardiac output is initially increased but returns to normal while total peripheral
resistance becomes secondarily elevated
Renin-Angiotensin System: Role in Arterial Pressure Control – besides ability of kidneys to control
arterial pressure through changes in extracellular fluid volume, kidneys also control pressure through
the renin-angiotensin system
-Renin is a protein enzyme released by the kidneys when the arterial pressure falls too low, and it helps
raise arterial pressure in many ways
Components of Renin-Angiotensin System – renin is synthesized in inactive form called prorenin in the
juxtaglomerular cells (JG) of the kidneys
-JG cells are modified smooth muscle cells in the walls of afferent arterioles just proximal to glomeruli
-when BP falls, intrinsic reactions in the kidneys cause many of the prorenin molecules in the JG cells to
split and release renin
-renin enters renal blood and passes out of the kidneys to circulate throughout the entire body, but
renin does also stay in the kidney and initiates several intrarenal functions
-renin acts on a plasma clobulin called angiotensinogen (renin substrate) to release a 10-AA peptided
called angiotensin I
-angiotensin I has mild vasoconstrictor properties but not enough to cause significant changes in
circulatory functions; renin persists for 30min to 1 hour and continues to release angiotensin I
-within a few seconds to minutes after formation of angiotensin I, two additional AA are split from the
molecule to form an 8AA peptide angiotensin II
-this conversion occurs greatly in the LUNGS while blood flows through the small vessels and is
catalyzed by an enzyme called angiotensin converting enzyme present on lung endothelium
-kidneys and blood vessels also have converting enzyme and can form angiotensin II locally
-Angiotensin II is a POWERFUL vasoconstrictor, and it also affects circulatory function as well, but
persists in the blood for only 1-2 minutes because it is rapidly inactivated by multiple tissue enzymes
called angiotensinases
-in the blood, angiotensin II has 2 effects that can elevate blood pressure:
1. Vasoconstriction in many body areas – occurs rapidly and intensely in arterioles, less so in veins
a. Constriction of arterioles increases total peripheral resistance to raise arterial pressure
b. Mild constriction of veins promotes increased venous return to heart and helps heart
pump against the increasing pressure
2. Decrease excretion of both salt and H2O by kidneys – this slowly increases extracellular fluid
volume and increases arterial pressure during subsequent hours/days;
a. This is a LONG-TERM effect more powerful than vasoconstrictor method
Rapidity and Intensity of Vasoconstrictor Pressure Response to Renin-Angiotensin System – an
experiment showed effect of hemorrhage on arterial pressure comparing when renin-angiotensin
system functioning and non-functioning
-after hemorrhage, which decreases BP to 50mmHg, arterial pressure rose back to 83mmHg when reninangiotensin system was functional, but only rose to 60mmHg when renin-angiotensin system blocked
-renin-angiotensin system is powerful enough that it can return arterial pressure at least halfway back to
normal within a few minutes after severe hemorrhage
-slower to act than sympathetic norepinephrine-epinephrine system
Effect of Angiotensin II in Kidneys to Cause Renal Retention of Salt and H2O – happens in two ways
1. Angiotensin II acts directly on kidneys to cause salt/water retention
2. Angiotensin II causes adrenal glands to secrete aldosterone, and the aldosterone in turn
increases salt and water reabsorption by the kidney tubules
-whenever excess amounts of angiotensin II circulate in the blood, entire long-term renal-body fluid
mechanism for arterial pressure control automatically becomes set to higher arterial pressure level than
normal
Mechanisms of the Direct Renal Effects of Angiotensin II to Cause Renal Retention of Salt and Water –
angiotensin has several direct renal effects that make the kidneys retain salt and water
-one major effect is to constrict the renal arterioles, diminishing blood flow through the kidneys
-the slow flow of blood reduces pressure in peritubular capillaries, which causes rapid reabsorption of
fluid from tubules
-angiotensin II also has direct actions on tubular cells themselves to increase tubular reabsorption of Na
and H2O; total result of these effects can decrease urine output to less than 1/5th normal
Stimulation of Aldosterone Secretion by Angiotensin II; Effect of Aldosterone to Increase Salt and
Water Retention by Kidneys – angiotensin II is one of MOST POWERFUL aldosterone stimulator by
adrenal glands
-when renin-angiotensin system is activated, rate of aldosterone secretion also increases, and an
important subsequent function of aldosterone is to cause increase in Na reabsorption by kidney tubules
to increase total body extracellular sodium
-increased Na causes H2O retention, which increases extracellular fluid volume and leading secondarily
to long-term elevation of arterial pressure
-Direct effect of angiotensin on kidneys is 3x more potent than the indirect effect through aldosterone
Quantitative Analysis of Arterial Pressure Changes Caused by Angiotensin II – a curve of arterial
pressure vs Na intake and output was described in two conditions: one where dogs had impaired reninangiotensin system through an ACE inhibitor, and the second where dogs were infused with angiotensin
II
-there is a shift of renal output curve toward higher pressure levels under influence of angiotensin II,
caused by both direct effects of angiotensin II on kidney and indirect effect through aldosterone action
-there are two equilibrium points, one for 0 angiotensin showing an arterial pressure of 75mmHg and
one for elevated angiotensin showing pressure of 115mmHg
-shift in equilibrium shows that angiotensin’s ability to promote chronic elevation of arterial pressure
Role of Renin-Angiotensin in Maintaining Normal Pressure Despite Large Variations in Salt Intake –
one of the most important functions of renin-angiotensin is to allow a person to eat either very small or
very large amounts of salt w/o causing great changes in extracellular fluid volume or arterial pressure
-sequential events by which increased salt intake increases arterial pressure:
-increased salt intake  increased extracellular volume  increased arterial pressure  decreased
renin/angiotensin  decreased renal retention of salt/water  return of extracellular volume to almost
normal  return of arterial pressure almost to normal
-thus, renin-angiotensin system is an automatic feedback mechanism that helps maintain arterial
pressure at or near the normal level even when salt intake is increased
-when renin/angiotensin is normal, pressure rises NO MORE than 4-6 mmHg in response to a 50 fold
increase in salt intake
-when renin/angiotensin system is blocked, same salt intake increases pressure 10x normal increase
Types of Hypertension in Which Angiotensin is Involved – Hypertension Caused by a Renin-Secreting
Tumor or by Infusion of Angiotensin II – a tumor of renin-secreting juxtaglomerular cells (JG) cells can
occur and secrete large quantities of renin, which causes equally large amounts of angiotensin II to be
formed
-in all patients, severe hypertension develops here; also infusion of angiotensin II causes hypertension
-it is already known that angiotensin II can increase arterial pressure by:
-constricting arterioles throughout the body to increase total peripheral resistance and arterial
pressure within seconds after angiotensin infusion
-causing kidneys to retain salt/water over a period of days and causes hypertension long-term
“One-Kidney” Goldblatt Hypertension – when 1 kidney is removed and a constrictor is placed on renal
artery of the other kidney, immediate effect is greatly reduced pressure in the renal artery beyond the
constrictor, which causes systemic arterial pressure to rise and continues to rise for several days
-pressure rises heavily for first hour and is followed by a slower rise over next few days
-when systemic arterial pressure reaches new stable pressure level, the renal arterial pressure will have
returned almost all the way back to normal
-the hypertension produced is called “one-kidney” Goldblatt hypertension
-the early rise in arterial pressure in Goldblatt hypertension is caused by renin-angiotensin
vasoconstrictor mechanism, where poor blood flow through kidney after constriction of renal artery
causes large amounts of renin release, to increase angiotensin II and aldosterone
-angiotensin raises arterial pressure acutely
-renin returns to normal after 5-7 days when renal arterial pressure has risen to normal, so
kidney is no longer ischemic
-the second rise in arterial pressure is caused by retention of Na and H2O by constricted kidney, which is
also stimulated by angiotensin II and aldosterone
-in 5-7 days, body fluid volume will increase enough to raise arterial pressure to new sustained level
-quantitative value of this sustained pressure is determined by the degree of constriction of renal artery
-aortic pressure must rise high enough so that renal arterial pressure distal to constrictor is
enough to cause normal urine output
-a similar scenario occurs in patients with stenosis of the renal artery of a single remaining kidney, and
can occur after a person receives a kidney transplant
-functional or pathological increase in renal arteriole resistance due to atherosclerosis or excessive
levels of vasoconstrictors can cause hypertension through same mechanisms as constriction
Two-Kidney Goldblatt Hypertension – hypertension can also result when artery to only one kidney is
constricted while the other artery to the other kidney is normal
-hypertension that results occurs through this mechanism:
-constricted kidney secretes renin and also retains salt/H2O because of decreased renal arterial
pressure in this kidney
-the normal, opposite kidney retains Na/H2O because of the renin produced by ischemic kidney
-this renin causes formation of angiotensin II and aldosterone, both of which circulate to
opposite kidney and cause it to retain salt and H2O, so both kidneys become salt/H2O retainers
-clinical counterpart of Two-kidney Goldblatt hypertension occurs when there is stenosis of a single
renal artery, such as by atherosclerosis
Hypertension Caused by Diseased Kidneys That Secrete Renin Chronically – often, patchy areas of one
or both kidneys are diseased and become ischemic because of local vascular constrictions, whereas
other areas of the kidneys are normal
-the patchy ischemic kidney secretes renin, which forms angiotensin II to cause remaining kidney mass
to retain salt and water
-most common cause of renal hypertension is such patchy ischemic kidney disease
Hypertension in Upper Part of Body Caused by Coarctation of Aorta – 1/1000 infants born with
constriction/blockage of aorta at a point beyond aortic arterial branches to head and arms but proximal
to renal arteries, called coarctation of aorta
-when this occurs, blood flow to the lower part of the body is carried by multiple, small collateral
arteries in body wall, with much vascular resistance between upper and lower aorta
-causes arterial pressure in upper body to be 40-50% higher than in lower body
-when constrictor is placed on aorta above renal arteries, BP in both kidneys at first falls, renin is
secreted, angiotensin/aldosterone are formed, and hypertension occurs in upper body
-arterial pressure in lower body at kidneys rises approximately to normal, but high pressure persists in
upper body; kidneys are no longer ischemic, so secretion of renin/angiotensin/aldosterone return to
normal; and in coarctation of aorta, pressure in lower body is almost normal whereas pressure in upper
body is much higher than normal
Role of Autoregulation in Hypertension Caused by Aortic Coarcation – significant feature of
hypertension caused by aortic coarctation is that blood flow in arms, where pressure is 50% above
normal, is almost exactly normal
-blood flow in legs, where pressure is not elevated, is also normal
-long-term autoregulation develops so nearly completely that local blod flow control mechanisms have
compensated almost 100% for the differences in pressure
-in both the high-pressure area and the low-pressure area, the local blood flow is controlled almost
exactly in accord with the needs of the tissue and not in accord with level of pressure
Hypertension in Preeclampsia (Toxemia of Pregnancy) – 5-10% of expectant mothers develop a
syndrome called preeclampsia, which is hypertension that usually subsides after delivery of baby
-ischemia of placenta and release by placenta of toxic factors are believed to play a role in causing many
of the manifestations of the disorder, including hypertension in the mother
-substances released by ischemic placenta cause dysfunction of vascular endothelial cells throughout
body, including blood vessels of the kidneys
-this endothelial dysfunction decreases release of NITRIC OXIDE and other vasodilator substances,
causing vasoconstriction, decreased rate of fluid filtration from glomeruli into renal tubules, impaired
renal-pressure natriuresis, and development of hypertension
-another pathological abnormality that may contribute to hypertension in preeclampsia is thickening of
kidney glomerular membranes, which reduces rate of glomerular fluid filtration
-arterial pressure level required to cause normal formation of urine becomes elevated, and the longterm level of arterial pressure becomes correspondingly elevated
-patients are especially prone to extra degrees of hypertension when they have excess salt intake
Neurogenic Hypertension – acute neurogenic hypertension can be caused by strong stimulation of
sympathetic nervous system; when person becomes excited for any reason or anxiety, sympathetic
system becomes excessively stimulated, peripheral vasoconstriction occurs everywhere
Acute Neurogenic Hypertension Caused by Sectioning the Baroreceptor Nerves – another type of acute
neurogenic hypertension occurs when nerves leading from baroreceptors are cut OR when tractus
solitarius is destroyed in each side of medulla oblongata
-cessation of nerve signals from baroreceptors has the same effect on nervous pressure control
mechanisms as a sudden reduction of arterial pressure in aorta and carotid arteries
-loss of normal inhibitory effect on vasomotor center caused by normal baroreceptor nervous signals
allows vasomotor center to become extremely active and the mean arterial pressure to increase up to
160mmHg, but returns to normal within 2 days because response of vasomotor center to absent
baroreceptor signal fades away, called resetting
Genetic Causes of Hypertension – spontaneous hereditary hypertension has been observed in several
strains of animals, including rats, rabbits, and dogs
-sympathetic nervous system considerably more active than in normal rats, and in the later stages of
hypertension, structural changes have been observed in the kidneys:
1. increased preglomerular renal arterial resistance
2. decreased permeability of glomerular membranes
-both of these can contribute to long-term continuance of hypertension
-several mutations in humans can cause hypertension, called monogenic hypertension because they are
caused by a mutation in a single gene
-all of these genetic disorders cause excessive salt and H2O reabsorption by the renal tubules
-some cases deal with mutations that increase transport of Na or Cl in renal tubular epithelial
cells; in other cases, mutations increase synthesis/activity of hormones that stimulate
reabsorption
Primary “Essential” Hypertension – 90-95% of people who have hypertension are said to have primary
hypertension, also known as essential hypertension, meaning that the hypertension is of unknown
origin, in contrast to secondary forms of hypertension such as renal artery stenosis or monogenic forms
-in most patients, excess weight gain and sedentary lifestyle play a major role in causing hypertension
-clinical guidelines for treating hypertension recommend increased physical activity and weight loss as a
first step in treating most patients with hypertension
-some characteristics of primary hypertension caused by excess weight gain and obesity include:
1. Increased Cardiac Output – due to additional blood flow required for extra adipose tissue; blood
flow to heart, kidneys, GI, and muscle also increases w/ weight due to increased metabolic rate
and growth of organs/tissues in response to increased metabolic demands
a. As hypertension is sustained, total peripheral vascular resistance may be increased
2. Sympathetic Nerve Activity – especially in kidneys, is increased in overweight patients; partially
due to hormones like leptin released from fat cells to stimulate hypothalamus
3. Angiotensin II/Aldosterone Levels – increased 2-3-fold in many obese patients, caused by
increased sympathetic nerve stimulation, which increases renin release by kidneys
4. Renal-Pressure natriuresis – mechanism is impaired and kidneys will not excrete adequate salt
and H2O unless arterial pressure is high or unless kidney function is somehow improved
-experimental studies in obese patients suggest that impaired renal-pressure natriuresis in obesity
hypertension is caused by increased renal tubular reabsorption of salt/water due to increased
sympathetic nerve activity and increased levels of angiotensin II and aldosterone
-if hypertension is not effectively treated, there may also be vascular damage in kidneys that can
reduce glomerular filtration rate and increase severity of hypertension
-eventually, uncontrolled hypertension associated with obesity leads to severe vascular injury
and complete loss of kidney function
Graphical Analysis of Arterial Pressure Control in Essential Hypertension –
-curves of this figure are called sodium-loading renal function
curves because the arterial pressure in each instance is increased
slowly over many days by gradually increasing sodium intake
-when this procedure is used in essential hypertensive patients,
two types of curves can be reported
1. salt-insensitive hypertension – arterial pressure does
not increase when changing from normal salt to high salt
2. salt-sensitive hypertension – high salt intake
significantly exacerbates the hypertension
-both curves are shifted to the right compared to the normal
-salt sensitivity of BP is NOT an all-or-none characteristic, with
some people being more sensitive than others
-salt sensitivity of BP is not fixed; instead, BP usually becomes more salt sensitive as person ages
-difference between salt sensitive and insensitive hypertension is related to differences in the kidneys of
those patients
-salt-sensitive hypertension may occur with different chronic renal disease due to loss of nephrons or to
normal aging; abnormal renin-angiotensin system can also cause salt-sensitive hypertension
Treatment of Essential Hypertension – lifestyle modifications are a FIRST step: physical activity/weight
loss
-two classes of drugs used to treat hypertension: vasodilators to increase renal blood flow and
natriuretic or diuretic drugs that decrease renal tubular reabsorption of salt and water
-vasodilator drugs cause vasodilation in many tissues and in kidneys; different ones act in these ways:
1. inhibiting sympathetic nervous signals to kidneys or blocking sympathetic transmitter on renal
vasculature
2. directly relaxing smooth muscle of renal vasculature
3. blocking the action of renin-angiotensin system on renal vasculature or renal tubules
-drugs that reduce reabsorption of salt/H2O by renal tubules block active transport of Na through
tubular wall, which also prevents reabsorption of H2O
Summary of Integrated, Multifaceted System for Arterial Pressure Regulation – arterial pressure is
regulated by multiple interrelated systems
-if person bleeds severely so pressure falls suddenly, two problems confront pressure control:
-(1) need to return arterial pressure to high level so person can live through this, and (2) return
blood volume and arterial pressure to normal levels, and not levels just for survival
-FIRST LINE OF DEFENSE against acute changes in arterial pressure is nervous control, second line of
defense is KIDNEY for long-term control
-these mechanisms can be divided
into 3 groups:
1. rapid reacting
2. intermediate reacting
3. long-term reacting
Rapid Reacting Pressure Control
Mechanisms – almost entirely
nervous responses: baroreceptor
feedback mechanism, CNS ischemic
mechanism, and chemoreceptor
mechanism
-these are all powerful and quick
responses to changes in arterial
pressure
-these systems cause (1) constriction
of veins and transfer blood into the
heart, (2) increase heart
rate/contractility to increase pumping
capacity, (3) cause constriction of
most peripheral arterioles to impede
flow of blood out of arteries
Pressure Control Mechanisms Acting After Several Minutes – (1) renin-angiotensin vasoconstriction, (2)
stress-relaxation of vasculature, (3) shift of fluid through tissue capillary walls in and out of circulation to
readjust blood volume
-stress-relaxation mechanism – when pressure in vessels becomes high, they are stretched and keep
stretching for a long time, and as a result, pressure in vessels falls toward normal “pressure buffer”
-capillary fluid shift mechanism – any time capillary pressure falls low, fluid is absorbed from tissues
through capillary membranes into circulation to maintain blood volume and increase pressure
-when pressure is too high, fluid is lost out of circulation into the tissues, reducing the blood volume
Long-Term Mechanisms for Arterial Pressure Regulation – renal-blood volume pressure control
mechanism works within a few hours; yet it develops a feedback gain for control of arterial pressure
equal to infinity (can return arterial pressure ALL THE WAY BACK to normal)
-aldosterone regulates renal fluid mechanism; decrease in pressure INCREASES aldosterone
-renin-angiotensin system is especially important for renal fluid mechanisms (salt intakes)