Physiology chapter 19

Explain how the overall mechanism by which increased extracellular fluid volume may elevate arterial pressure, if vascular capacity is not simultaneously increased:

(1) increased extracellular fluid volume (2) increases the blood volume, which (3) increases the mean circulatory filling pressure, which (4) increases venous return of blood to the heart, which (5) increases cardiac output, which (6) increases arterial pressure. The increased arterial pressure, in turn, increases real excretion of salt and water and may return extracellular fluid volume to nearly normal if kidney function is normal.

Two general classes of drugs that are used to treat hypertension:

(1) vasodilator drugs that increase renal blood flow and (2) natriuretic or diuretic drugs that decrease tubular reabsorption of salt and water.

What is Angiotensin II?

--An extremely powerful vasoconstrictor

Neurogenic Hypertension

--Caused by strong stimulation of the sympathetic nervous system. --Leads to peripheral vasoconstriction everywhere in the body, and acute hypertension ensues

Give an example of an indirect effect of chronic BP increase mediated by nervous and hormonal changes

--increased arterial pressure decreases activity of the sympathetic nervous system and various hormones such as angiotensin II and aldosterone that tend to reduce salt and water excretion by the kidneys -- Reduced activity of these antinatriuretic systems therefore amplifies the effectiveness of pressure natriuresis and diuresis in raising salt and water excretion during chronic increases in arterial pressure

Name the two ways by which increased cardiac output increases blood pressure

1) Direct effect of increasing cardiac output 2) Indirect effect through "auto regulation"

How does salt increase extracellular fluid volume?

1) Excess salt in the extracellular fluid increases the osmolality, which in turn stimulates the thirst center in the brain, making the person drink more water to dilute extracellular salt concentration 2) The increased osmolality also stimulates the hypothalamic-posterior pituitary gland secretory mechanism to secrete increased quantities of antidiuretic hormone. These hormones cause the kidneys to reabsorb more water, increasing the extracellular volume.

The lethal effects of hypertension are caused mainly in three ways. Describe them:

1) Excess workload on the heart leads to early heart failure, leading to heart attack. 2) The high pressure frequently damages a major blood vessel in the brain, followed by death of major portions of the brain; this is a cerebral infarct. Clinically it is called a "stroke." 3) High pressure almost always causes injury in the kidneys, producing many areas of renal destruction and, eventually, kidney failure, uremia, and death.

Pathological contributions to preeclampsia

1) Ischemic placenta releasing toxic factors causing decrease in the release of NO (nitric oxide) a vasodilator. 2) Thickening of the kidney glomerular membrane, which reduces the rate of glomerular fluid filtration.

Name a few mechanisms of the direct renal effects of Angiotensin II to cause renal retention of Salt and Water:

1) One major effect is to constrict the renal arterioles, thereby diminishing blood flow through the kidneys. The slow flow of blood reduces the pressure in the peritubular capillaries, which causes rapid reabsorption of fluid from the tubules. 2) Angiotensin II also has important direct actions on the tubular cells themselves to increase tubular reabsorption of sodium and water.

Name a a couple of systems that control arterial pressure?

1) Short-term control of arterial pressure by the sympathetic nervous system 2) The renal-body fluid system

Divide volume-loading hypertension into two separate sequential stages:

1) The first stage results from increased fluid volume causing increased cardiac output. This increase in cardiac output mediates the hypertension. 2) The second stage is characterized by high blood pressure and high total peripheral resistance but return of the cardiac output near to normal.

Short-term control of arterial pressure by the sympathetic nervous system occurs primarily through the effects of the nervous system on what three things?

1) Total peripheral vascular resistance 2) Total peripheral vascular capacitance 3) Cardiac pumping ability

What are Angiotensin II's two principle effects that can elevate arterial pressure?

1) Vasoconstriction, increasing total peripheral resistance. 2) Decrease excretion of both salt and water by the kidneys. This increases extracellular fluid volume, eventually raising BP.

the powerful effects of chronic increases in arterial pressure on urine output are because?

1) increased pressure has direct hemodynamic effects on the kidney to increase excretion 2) also indirect effects mediated by nervous and hormonal changes that occur when blood pressure is increased.

Name the ways that Angiotensin II causes the kidneys to retain both salt and water:

1. Angiotensin II acts directly on the kidneys to cause salt and water retention. 2. Angiotensin II causes the adrenal glands to secrete aldosterone, and the aldosterone in turn increases salt and water reabsorption by the kidney tubules.

the two primary determinants of the long-term arterial pressure level are?

1. The degree of pressure shift of the renal output curve for water and salt 2. The level of the water and salt intake (LOOK AT GRAPH 19.4 TO UNDERSTAND)

Some of the characteristics of primary hypertension caused by excess weight gain and obesity include:

1.Cardiac output is increased (due, in part, to the additional blood flow required for the extra adipose tissue) 2.Sympathetic nerve activity, especially in the kidneys, is increased in overweight patients. (Leptin released from adipose tissue) 3.Angiotensin II and aldosterone levels are increased twofold to threefold in many obese patients. (caused partly by increased sympathetic nerve stimulation)

than the upper range of the accepted normal measure. A mean arterial pressure greater than what is considered hypertensive?

110 mm Hg (normal is about 90 mm Hg) -This is the same as saying Diastolic BP of 90 mm hg Systolic BP of 135 mm hg

In severe hypertension, the mean arterial pressure can rise to?

150-170 mm Hg

The renin-angiotensin vasoconstrictor system requires about how many minutes to become fully active?

20 minutes

What does Renin do once released from the kidneys due to low intrarenal BP?

Acts enzymatically on another plasma protein, a globulin called renin substrate/angiotensinogen to release a 10-amino acid peptide, "angiotensin I"

Explain "primary aldosteronism" caused hypertension

Aldosterone (secreted by adrenal glands) increases the rate of reabsorption of salt and water by the tubules of the kidneys, thereby reducing the loss of these in the urine while at the same time causing an increase in blood volume and extracellular fluid volume. Consequently, hypertension occurs.

The Effect of Aldosterone to Increase Salt and Water Retention by the Kidneys:

Aldosterone causes marked increase in sodium reabsorption by the kidney tubules, thus increasing the total body extracellular fluid sodium. This increased sodium then causes water retention, increasing the extracellular fluid volume and leading secondarily to still more long-term elevation of the arterial pressure.

When blood pressure is reduced, the sympathetic nervous system is activated and formation of what is increased?

Antinatriuretic hormones like angiotensin II and aldosterone

How can accumulation of even a small amount of extra salt in the body can lead to considerable elevation of arterial pressure?

Because only small increases in extracellular fluid and blood volume can often increase the arterial pressure greatly if the vascular capacity is not simultaneously increased. But if the kidneys are functional, and little antinatriuretic hormones are released, kidney eliminates salt and bloop volume is hardly altered.

Difference between chronic and acute changes in arterial pressure:

Chronic changes in arterial pressure, lasting for days or months, have much greater effect on renal output of salt and water than observed during acute changes in pressure. Thus, when the kidneys are functioning normally, the chronic renal output curve is much steeper than the acute curve. This leads for very little BP change during chronic changes, while moderate to severe BP change during acute changes.

There is some evidence that long-term high salt intake, lasting for several years, may actually do what to the kidneys?

Damage the kidneys and eventually make blood pressure more salt sensitive.

preeclampsia:

Hypertension in a pregnant mother

Essential hypertension

Idiopathic hypertension, which has no identifiable cause.

What type of individuals suffer from salt sensitivity?

Individuals with kidney injury or excessive secretion of antinatriuretic hormones such as angiotensin II or aldosterone. In these instances, greater than normal increases in arterial pressure are required to raise renal output sufficiently to maintain a balance between the intake and output of salt and water.

Renin?

Is a protein "enzyme" released by the kidneys when the arterial pressure falls too low. It help elevate the arterial pressure.

Describe how the Renal-Body fluid system operates:

It act slowly as follows: If blood volume increases and vascular capacitance is not altered, arterial pressure will also increase. The rising pressure in turn causes the kidneys to excrete the excess volume, thus returning the pressure back toward normal.

What do Current guidelines for treating hypertension recommend as a first step?

Lifestyle modifications that are aimed at increasing physical activity and weight loss in most patients

Where are the JG cells located?

Located in the walls of the afferent arterioles immediately proximal to the glomeruli.

Do changes in total peripheral resistance effect the "long-term" level of arterial pressure if function of the kidneys are normal?

No. If kidneys are functioning normally, they will respond to the increased BP (due to increased peripheral resistance) via pressure diuresis and pressure natriuresis

Where is the Renin located?

Renin is synthesized and stored in an inactive form called prorenin in the juxtaglomerular cells (JG cells) of the kidneys.

What happens to Angiotensin I when it reaches the lungs?

Splits into Angiotensin II. This is catalyzed by an enzyme called "angiotensin converting enzyme"

Equilibrium point determines what?

The Arterial pressure at which the kidney bases whether or not it will increase or decrease urine (water & salt) output. If arterial pressure raises above equilibrium point, renal out increases. If arterial pressure falls below equilibrium point, renal output decreases to conserve water.

CASE #1: Cause of hypertension was "Two-Kidney Goldblatt Hypertension". DESCRIBE MECHANISM:

The constricted kidney (via stenosis caused by atherosclerosis) secretes renin and also retains salt and water because of decreased renal arterial pressure in this kidney. Then the "normal" opposite kidney retains salt and water because of the renin produced by the ischemic kidney. This renin causes formation of angiotension II and aldosterone, both of which circulate to the opposite kidney and cause it also to retain salt and water. Thus, both kidneys, but for different reasons, become salt and water retainers. Consequently, hypertension develops.

NOW! if the "intrarenal vascular" resistance increase along with the "peripheral resistance" what happens to the BP?

The increase in intrarenal vascular resistance alters the function of the kidney and can cause hypertension by shifting the renal function to a higher pressure level. The increase in intrarenal vascular resistance is the culprit of hypertension, not the increased total peripheral resistance.

When salt levels are increased, describe how the renin-angiotensin system helps bring the BP back to normal:

The initial effect of increased salt intake is to elevate the extracellular fluid volume, in turn elevating the arterial pressure. Then, the increased arterial pressure causes increased blood flow through the kidneys, as well as other effects, which reduce the rate of secretion of renin to a much lower level and lead sequentially to decreased renal retention of salt and water, return of the extracellular fluid volume almost to normal, and, finally, return of the arterial pressure also almost to normal.

Why does salt have a stronger influence on blood pressure then water?

The reason for this is that pure water is normally excreted by the kidneys almost as rapidly as it is ingested, but salt is not excreted so easily.

Aside from the capability of the kidneys to control arterial pressure through changes in extracellular fluid volume, what other method can the kidneys utilize?

The renin-angiotensin system.

What does it mean for a person to be salt sensitive?

This means that even moderate increases in salt intake may cause significant increases in arterial pressure.

What does it mean for a person to be salt insensitive?

This means that large variations in salt intake from normal do not change blood pressure more than a few mm Hg.

stress-relaxation mechanism

When the pressure in the blood vessels becomes too high, they become stretched and keep on stretching more and more for minutes or hours; as a result, the pressure in the vessels falls toward normal. This continuing stretch of the vessels, called stress-relaxation, can serve as an intermediate-term pressure "buffer."

Pressure natriuresis

When the renal output of salt increases due to an increase in blood pressure

Pressure diuresis

When the renal output of water/urine increases due to an increase in blood pressure

Key concept to understand. Ties in earlier flash cards to these recent ones.

Whenever excess amounts of angiotensin II circulate in the blood, the entire long-term renal-body fluid mechanism for arterial pressure control automatically becomes set to a higher arterial pressure level than normal.

What is the basic equation for arterial pressure?

arterial pressure equals= "cardiac output" times "total peripheral resistance"

without a functional renin-angiotensin- aldosterone system BP becomes?

blood pressure becomes very sensitive to changes in salt intake

equilibrium point between renal output and water/salt intake

equilibrium point of renal output and water/salt intake is the only place on the graph at which output equals input. Where the two curves intersect.

Volumeloading hypertension means?

hypertension caused by excess accumulation of extracellular fluid in the body

Leptin's affect on BP

leptin, released from fat cells may directly stimulate multiple regions of the hypothalamus, which, in turn, have an excitatory influence on the vasomotor centers of the brain medulla. This leads to increased sympathetic nerve activity, especially in the kidneys, in overweight patients

capillary fluid shift mechanism

means simply that any time capillary pressure falls too low, fluid is absorbed from the tissues through the capillary membranes and into the circulation, thus building up the blood volume and increasing the pressure in the circulation

Vascular capacitance

the relative amount of blood volume that can be held in the peripheral vascular system at a given point in time

What is "auto regulation"? Explain and elaborate.

whenever an excess amount of blood flows through a tissue, the local tissue vasculature constricts and decreases the blood flow back toward normal. This phenomenon is called "auto regulation," which means simply regulation of blood flow by the tissue itself. When increased blood volume increases the cardiac output, the blood flow increases in all tissues of the body, so this autoregulation mechanism constricts blood vessels all over the body. This in turn increases the total peripheral resistance.