Cardiopulmonary Physiology

Cardiopulmonary Physiology
Millersville University
Dr. Larry Reinking
Chapter 7 - Renal Considerations
As stated at the end of Chapter 1, the kidneys are essential adjuncts to the cardiovascular
system. These organs control erythrocyte production (p. 2, chapter 2), direct the release of
vasoactive hormones and regulate both the blood composition and volume. The concepts of
renal function will be reviewed in this chapter in order to serve as a basis for better understanding
the materials in Chapter 8, Regulation of Arterial Blood Pressure.
Perhaps the best way to appreciate the role of the kidneys is to consider their blood
supply. The kidneys are placed in a strategic position in the circulation and, at rest, receive 2025% of the cardiac output. This is a huge amount of blood for a pair of organs that represent
only about 1% of the body mass. It is important to consider that fluid processing, by the kidney,
alters blood volume and an altered blood volume, in turn, alters cardiac filling.
General Structures
The following simplistic diagram illustrates a nephron, the functional working unit of the
kidney. Detailed representations of renal structures are shown in the lecture pack, Figures -.
caps ule
thin segment
(loop of Henle)
dis tal
Figure 7.1
Combined, both human kidneys have about two million nephrons. There are two basic
parts to the nephron, a glomerulus and a renal tubule. The glomerulus, a knot of capillaries,
receives blood from the afferent arteriole. Blood leaves the glomerulus via the efferent arteriole
which then forms vessels that cover the renal tubule (see the peritubular capillaries and vasa recta
in Figures  and ). The renal tubule is comprised of Bowman’s capsule, the proximal
convoluted tubule, the loop of Henle and the distal convoluted tubule. Many nephrons feed into
a collecting duct and, ultimately, many collecting ducts flow into the ureter. In Figure ,
especially for the juxtamedullary nephron, note the arrangement of the loop of Henle and
collecting duct in reference to the renal cortex and medulla.
Filtration - As blood flows through the glomerulus, fluid is filtered into Bowman’s capsule. As
we saw in the microcirulation lab, a number of osmotic and hydraulic forces influence this fluid
movement. In humans, the glomerular filtration rate is about 125 ml fluid/min. This process is
rather indiscriminate since everything except for the cells and large protein molecules filter from
the glomerulus into Bowman’s capsule. In other words, many valuable components such as
Chapter 7
water, ions, amino acids, vitamins and glucose are lost from the blood during filtration. If all of
the glomerular filtrate resulted in urine, an individual would excrete (and replace) 180 liters per
day. Obviously, further processing steps must recover most of this filtrate.
Reabsorption - The proximal convoluted tubule is lined with cells that actively transports
solutes from the lumen of the tubule back into the blood (remember that the tubule is cover with
peritubular capillaries). This process is specifically referred to as tubular reabsorption. Water
movement is linked to this active transport of solutes and results in reabsorption of most of the
filtered water. Additional reabsorption of solutes also can occur in other portions of the renal
tubule. Sodium for example is mostly reabsorped in the proximal tubule but a small portion is
reabsorped in the loop of Henle and in the distal tubule. The reabsorption of sodium in the distal
tubule is significant because it is under the control of the adrenal hormone, aldosterone (more on
aldosterone, later).
Secretion - As the forming urine passes through the renal tubule, some solutes are moved, via
active transport, from the blood to the lumen of the tubule. This process is called tubular
secretion. In particular, substance such as creatinine, urea, organic acids and potassium are
secreted. Potassium secretion in the distal convoluted tubule is of particular interest because it is
linked to sodium reabsorption and, thus, is also under the control of aldosterone.
Concentration - As the forming urine reaches the end of the distal tubule, the osmotic
concentration is about the same as that of the blood (≈300 mosm/liter). If urine was excreted at
this concentration, a person consuming a normal amount of fluid would become dehydrated due
to a large water loss. In cases of normal hydration, urine must be concentrated before it leaves
the kidney. They key to urine concentration is a solute gradient that is established in the tissues
of the renal medulla. If we were to measure osmotic concentrations of tissue in the kidneys, we
would find that the osmotic concentration in the cortex is about 300 mosm/liter and progressively
increases until it reaches 1,200 mosm/liter in the innermost zone of the medulla. Passing through
the medullary solute gradient are the loops of Henle, the vasa recta and the collecting ducts. The
following diagram depicts this situation:
medullary solute gradient
in creas ed bloo d
os motic co ncentration
lo op o f Henle
vasa recta
water moving d own
concentration gradient
Figure 7.2
collecting d uct
excreted urine
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A number of factors contribute to the formation of the medullary solute gradient and
include 1) sodium and chloride transport in the upper, thick portion of the loop of Henle, 2) a
countercurrent multiplier in the loop of Henle, 3) water impermeability of the distal tubule, 4)
urea moving from the collecting duct and 5) the unique, hairpin shape of the vasa recta. The
exact mechanism involved in forming this gradient is beyond the scope of this course.
As fluid moves down the collecting duct, it encounters an increasingly greater osmotic gradient
in the surrounding medullary tissue. Water, in response to the concentration gradient, tends to
diffuse out of the collecting ducts into the surrounding tissue. As a result of this water extraction
the urine in concentrated. Water, entering the medullary tissue, is then picked up by the vasa
recta and returned to the circulation
Vasopressin (or antidiuretic hormone, ADH) regulates water extraction from the collecting
duct. When increased blood osmotic concentration is sensed in the osmotic center of the brain,
ADH is released by the posterior pituitary (neurohypophysis). This hormone travels through the
blood, binds to receptors on the collecting ducts and causes increased water permeability. As a
result, more water is extracted and the urine becomes more concentrated. In cases of overhydration, ADH is no longer released, the collecting duct becomes less permeable to water and
more water is lost to the urine. ADH is also called vasopressin because this molecule promotes
increased blood pressure via vasoconstriction (i.e., a vasopressor action).
Renin-Angiotensin-Aldosterone System (RAAS)
This regulatory system, based in the kidneys, plays a key role in regulating blood sodium
concentration, blood potassium concentration, blood volume and blood pressure. Refer, again, to
Figure  in your lecture packet and note the juxtaglomerular apparatus. The juxtaglomerular
apparatus involves a portion of the distal tubule that has folded back toward the glomerulus
(called the macula densa) plus a section of cells lining the afferent arteriole (the juxtaglomerular
to the glomerulus
cross section of the
Figure 7.3
juxtaglomerular cells of
the afferent arteriole
macula dens a of
the distal tubule
afferent arteriole
The juxtaglomerular apparatus is able detect changes in sodium levels and renal blood pressure
and flow. If sodium levels drop or if pressure or flow in the afferent arteriole drops, renin, a
molecule stored in the juxtaglomerular cells in a precursor form, is released into the circulation:
Figure 7.4 The Renin-Angiotensin-Aldosterone System
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adren al
reabs orption
blood press ure
angiotensin I
angiotensin II
(destroyed by angiotensinase)
renal blo od flow
or pres su re
angio tens in
vaso con striction
plas ma K
In the blood, renin converts circulating angiotensinogen into a decapeptide, angiotensin
I. As angiotensin I passes through the lungs it is converted into angiotensin II (an octapeptide)
by angiotensin converting enzyme (ACE) contained within the endothelial cells of the
pulmonary vessels (minor conversion also occurs in other organs). Angiotensin II is a powerful
vasoconstrictor and will cause an increase in blood pressure. Note that this action counters the
original stimulus of decreased renal blood pressure. Angiotensin II also stimulates thirst via the
central nervous system and stimulates ADH release. These actions will eventually increase blood
volume. Recall, also, that ADH causes vasoconstriction. A final action of angiotensin II is to
stimulate aldosterone production and release from the adrenal cortex. Aldosterone is a steroid
hormone that promotes sodium reabsorption in the distal tubule. Increased sodium reabsorption
counters the other stimulus that triggers renin release. Increased sodium reabsorption will be
accompanied water retention and increased blood volume.
Control of Serum Potassium
The renin-angiotensin-aldosterone system also plays a crucial role in regulating plasma
potassium levels. Recall that hyperkalemia, increased serum potassium, causes cardiac
paralysis (chapter 4). An increase in serum potassium directly stimulates the adrenal cortex to
produce and release aldosterone. The increased sodium reabsorption in the distal tubule, caused
by aldosterone, is linked to potassium secretion; the end result will be a reduced serum
potassium concentration.
Relation of the RAAS to other Vasoactive Substances
The renin-angiotensin-aldosterone system is closely linked to a clotting factor, plasmin
and the kallikrein-kinin system. Kinins are vasodilators that are formed from tissue substrates
called kininogens. This conversion is promoted by the action of kallikreins, a class of proteolytic
enzymes. These interrelationships are shown below:
Figure 7.5 The Kallikrein-Kinin System
Chapter 7
activated clotting
Factor XII
plas min
kinog ens
angiotens ino gen
angiotens in I
inactive fragments
angiotens in II
Diuretic therapy is commonly used to treat cardiovascular disorders such as congestive
heart failure. The actions of some types of diuretics are listed below. Water, alcohol, caffeine
and acidifying salts are typically not used in clinical situations. Keep in mind that when a solute
is excreted water will follow. The following table (Table 7.1) summarizes the actions of
common diuretics.
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Table 7.1 Actions of Diuretics
Diuretic Agent
Acidifying salts (CaCl2, NH4Cl)
Carbonic anhydrase inhibitors
acetazolamide (Diamox)
Metolazone (Zaroxolyn) and
thiazides such as chlorothiazide (Diuril)
Loop diuretics such as furosemide (Lasix) and
ethacrynic acid (Edecrin)
Potassium sparing, sodium diuretics
spironolactone (Aldactone)
Potassium sparing, sodium diuretics
triamterene (Dyrenium), amiloride (Colectril)
Mechanism of Action
Inhibits ADH release
Inhibits ADH release
Constricts efferent arteriole, glomer.
H+ buffered, Na+ excreted with excess anions
Decrease H+ excretion, results in increased
Na+ and K+ excretion
Inhibit Na+/K+/Cl- cotransport in early distal
Inhibit Na+/Cl- reabsorption in loop of Henle
Decreases Na+/K+ exchange pump in distal
tubule by inhibiting aldosterone
Decreases Na+/K+ exchange pump in distal
tubule by inhibiting Na+ reabsorption
Chapter 7