Renal Anatomy, Physiology, Pharmacology, and Evaluation of Function

Question 1

The kidney is divided into an outer layer, the cortex, which receives …% of the renal blood flow (RBF), and an inner medulla

Answer 1

85% to 90%

Question 2

The kidneys receive …% of the total cardiac output but extract relatively little oxygen

Answer 2

20%

Question 3

The medulla receives only 6% of the RBF and has an average oxygen tension (PO2) of …mmHg.
Thus, severe hypoxia could develop in the medulla despite a relatively adequate total RBF; the metabolically active medullary … is particularly
vulnerable

Answer 3

8 mmHg

thick ascending loop of Henle (mTAL)

Question 4

In normal kidneys, 80% of the energy is required for Na+/K+-ATPase that maintains the osmotic gradient needed for the resorption of filtered molecules. In spite of this highenergy demand, the tubular system is supplied by only …% of the RBF and is a key etiology for … after hypotension

Answer 4

10% to 15%

acute tubular necrosis

Question 5

Angiotensin II stimulates two pathways that have opposing effects.

The principal receptor is … that is found on the luminal epithelial surface of the proximal tubular cell (PTC), thick ascending loop of Henle, macula densa, distal tubules, and collecting ducts.The angiotensin II-… interaction serves to maintain systemic blood pressure through vasoconstriction, and enhancement of tubular transport mechanisms to reabsorb sodium and water.

The binding of angiotensin II to “non-classical” receptors such as … opposes these actions and causes vasodilatation through …, and reduced oxidative stress

Answer 5

AT1

AT1

AT7

nitric oxide (NO) and prostaglandin-mediated natriuresis, diuresis

Question 6

… resides in the inner lipid layer of the
cell membrane and controls prostaglandin production through its formation of the prime precursor, …

Answer 6

Phospholipase A2

arachidonic acid

Question 7

Prostaglandin production in the renal tisse is stimulated by …

Thus, the factors that induce and mediate the stress response simultaneously activate prostaglandins, which defend the
kidney against their actions

Answer 7

ischemia, hypotension, norepinephrine, angiotensin II, and arginine vasopressin (AVP)

Question 8

… acts on arachidonic acid to form the vasodilator prostaglandins that include PGD2, PGE2, and PGI2 (prostacyclin).

Vasodilation is through activation of…to oppose the action of catecholamines, angiotensin II, and AVP

Answer 8

Cyclooxygenase-1

cyclic adenosine monophosphate (cAMP)

Question 9

Kinins act directly as vasodilators, as well as stimulate phospholipase A2, prostacyclin production, and endothelial cell NO formation.

Kinins are produced by cleavage of kininogen by the serine protease kallikrein. Over 90% of
renal kallikrein is produced by the … in the cortex with decreased concentrations from outer to inner zones.

Answer 9

distal convoluted tubules

Question 10

Renal kininase, which controls the level of
bradykinin, is inhibited by ACE inhibitors and is the reason for …

Answer 10

angioedema

Question 11

By far the most potent trigger for AVP release
is systemic arterial hypotension, mediated by aortic and carotid baroreceptors. It overrides all other triggers, and plasma AVP may reach levels 10- to 1000-fold greater than normal.

At these concentrations, AVP acts as a vasoconstrictor, especially in the outer renal cortex. It does so by stimulating the … receptor that exists on vascular smooth muscle, glomerular mesangial cells, and the vasa recta and promotes vasoconstriction through the
phosphatidylinositol pathway.

Answer 11

V1A

Question 12

AVP maintains effective glomerular filtration pressure because it is …

Answer 12

an extremely potent constrictor of the efferent arteriole, and unlike catecholamines and angiotensin, it has little effect on the afferent arteriole, even at high plasma levels

Question 13

What happenes when APV bind to V2 receptors in the medullary collecting ducts?

Answer 13

It stimulates adenylate cyclase to form cAMP that enhances aquaporin-2 channels of the principal cells to increase water reabsorption

Question 14

Anesthetics have little direct effect on AVP secretion, except via the changes that they
induce in arterial blood pressure, venous volume, and serum osmolality. Surgical stimulation is a major stimulus to AVP secretion. This stress response, whether mediated by pain or by intravascular volume changes, is profound
and lasts at least … after the surgical procedure

Answer 14

2 to 3 days

Question 15

They dilate vascular smooth muscle through activation of cyclic guanosine monophosphate by blocking the phospholipase C-linked receptors to the actions of norepinephrine and angiotensin II

Answer 15

Natriuretic Peptides

Question 16

Natriuretic peptides actions

Answer 16

They promote afferent arteriolar dilatation with or without efferent arteriolar constriction, antagonize endothelin (the endogenous vasoconstrictor peptide produced by vascular endothelial cells), inhibit renin secretion, and decrease angiotensin-stimulated aldosterone. These peptides also inhibit the release of
aldosterone in the adrenal cortex and block its actions at the distal tubules and collecting ducts. Moreover, they inhibit the secretion of AVP through their effects on the brain and
pituitary, which can lead to an enhanced diuresis. NaCl is resorbed, and diuresis is promoted

Question 17

Aldosterone is a steroid hormone secreted
by the … of the adrenal cortex in response
to …

Angiotensin II and adrenocorticotropic hormone also trigger its release.

It acts at the … to increase active absorption of sodium and passive absorption of water, culminating in an expanded blood volume

Answer 17

zona glomerulosa

hyperkalemia or hyponatremia

thick ascending limb of the loop of Henle, the principal cells of the distal tubule, and the collecting duct

Question 18

There are at least two subtypes of dopaminergic (DA) receptors.

DA1 receptors are present on the renal and splanchnic vasculature and also on the proximal tubule. Stimulation of the DA1 receptor activates … and induces …

Stimulation of D2 receptors on the presynaptic terminal of postganglionic sympathetic nerves inhibits the … to facilitate …

Answer 18

cAMP

renal vasodilation, increased RBF and GFR, natriuresis, and diuresis.

release of norepinephrine from presynaptic vesicles

vasodilation

Question 19

The two cell types lining the collecting tubules are the principal cells and two types of intercalated cells.

Principal cells use Na+/K+ ATPase to 1…
These cells are the sites of action for 2…
An additional mechanism is Na+ channel blockade by diuretics such as 3…

Type A intercalated cells use 4… to secrete 5… formed by carbonic anhydrase against a large concentration gradient. Bicarbonate ions are absorbed from the basolateral membrane.

In contrast, the Type B intercalated cells transport 6… out of the cell on the basolateral side while bicarbonate is excreted into the tubular lumen.

These cells are critical to the maintenance of acid-base balance, sodium reabsorption, and intravascular volume

Answer 19

1) resorb Na+ and K+

2) the potassium-sparing diuretics such as spironolactone, a competitor of aldosterone

3) amiloride

4) H+-ATPase and H+/K+- ATPase transporters

5) hydrogen ions

6) hydrogen

Question 20

An increase in GFR provides enhanced NaCl delivery to the distal tubules.
The increased … concentration is sensed by the … and triggers the renin-angiotensin cascade to
decrease the GFR through angiotensin II constriction of the afferent arteriole

Answer 20

chloride

macula densa

Question 21

Difference between osmolality and osmolarity

Answer 21

Osmolality is a measure of the osmoles (Osm) of solute per kilogram of solvent (Osm/kg) while osmolarity is defined as the number
of osmoles of solute per liter of solution (Osm/L). Osmolarity is affected by changes in water content, temperature, and pressure. Osmolarity is slightly less than osmolality because
the total solvent weight excludes any solutes. Clinically, the values for osmolarity and osmolality are very similar, and the terms are usually used interchangeably

Question 22

Formula of plasmatic osmolarity

Answer 22

Osmolaridade plasmática (mOsm/L) = 2x [Na+] +. [glicemia (mg/dL)/18] + [ureia (mg/dL)/6]

Question 23

The organization of the loop of Henle is designed to maintain hyperosmolarity of the medullary interstitium that can approach 1200
mOsm/L.
The major process for this is the active transport of … from the lumen of the thick limb of the loop of Henle that is … to water to the interstitium.

This allows for a concentration gradient of … mOsm/L

Answer 23

Na+ and co-transport of K+ and Cl−

impermeable

200 mOsm/L

Question 24

How does the renal medullary interstitium becomes hypertonic? Explain

Answer 24

By the countercurrent multiplication (in the loops of Henle of juxtamedullary nephrons)

The three segments of the loops of Henle have different characteristics that enable countercurrent multiplication:
1) The thin descending limb is passively permeable to both water and small solutes such as sodium chloride and urea.
2) The thin ascending limb is passively permeable to small solutes, but impermeable to water.
3) The thick ascending limb actively reabsorbs sodium, potassium and chloride. this segment is also impermeable to wate

Countercurrent multiplication moves sodium chloride from the tubular fluid into the interstitial space deep within the kidneys. Although in reality it is a continual process, the way the countercurrent multiplication process builds up an osmotic gradient in the interstitial fluid can be thought of in two steps:
1) The single effect. The single effect is driven by active transport of sodium chloride out of the tubular fluid in the thick ascending limb into the interstitial fluid, which becomes hyperosmotic. As a result, water moves passively down its concentration gradient out of the tubular fluid in the descending limb into the interstitial space, until it reaches equilibrium.
2) Fluid flow. As urine is continually being produced, new tubular fluid enters the descending limb, which pushes the fluid at higher osmolarity down the tube and an osmotic gradient begins to develop.

As the fluid continues to move through the loop of Henle, these two steps are repeated over and over, causing the osmotic gradient to steadily multiply until it reaches a steady state

Absorbed water is returned to the circulatory system via the vasa recta, which surrounds the tips of the loops of Henle. Because the blood flow through these capillaries is very slow, any solutes that are reabsorbed into the bloodstream have time to diffuse back into the interstitial fluid, which maintains the solute concentration gradient in the medulla. This passive process is known as countercurrent exchange

Urea recycling in the inner medulla also contributes to the osmotic gradient generated by the loops of Henle. Antidiuretic hormone increases water permeability, but not urea permeability in the cortical and outer medullary collecting ducts, causing urea to concentrate in the tubular fluid in this segment. In the inner medullary collecting ducts it increases both water and urea permeability, which allows urea to flow passively down its concentration gradient into the interstitial fluid. This adds to the osmotic gradient and helps drive water reabsorption

Question 25

A healthy person excretes 1…% of the filtered load of urea. The concentration of urea entering the tubular system is related to the prerenal plasma concentration and the GFR.
Urea contributes 40% to 50% of the osmolality of
the medullary interstitium.
The 2… are freely permeable to urea whereas the 3… have little permeability to it.

As water absorption increases with AVP action, the concentration of urea in the tubules progressively increases. With this
high concentration, urea diffuses into the interstitial fluid facilitated by specific urea transporters that are activated by AVP.

The simultaneous movement of urea and water out of the inner medullary collecting ducts maintains a high concentration of urea in the tubular fluid. As the concentration of urea increases in the medullary interstitium, it diffuses through the 4… and transits through the ascending system again before it is excreted.
This recirculation enhances the increased osmotic pressure in the medulla

Answer 25

1) 20% to 50

2) PCT

3) loop of Henle, distal tubules, and the collecting
ducts

4) thin limb of the loop of Henle

Question 26

Urea diffuses into the thin loop of Henle assisted by urea transporter …

In the collecting ducts located in the Inner medulla, the transporters … facilitate the movent of urea from de ducts to the interstitium (this action is potentiated by AVP)

This recirculation helps to trap urea in the renal
medulla contributing to its hyperosmolality (millimoles per liter)

Answer 26

UT-A2

UT-A1 and UT-A3

Question 27

Creatine phosphate in muscle transfers …, creating … necessary for contraction, and
creatine.

Creatinine results from the metabolism of creatine in …

Serum creatinine is a reasonable approximation of GFR since it is freely filtered by the glomerulus, is soluble, distributes through the total body water, and is not reabsorbed by the tubules.

Creatinine varies with …

Low GFR tends to … renal function since little creatinine is secreted

Answer 27

high-energy phosphate to ADP

ATP

the liver

muscle mass, rate of catabolism, protein intake, and physical activity

overestimate

Question 28

Urea is formed in the liver by the … of amino acids and conversion to ammonia by the …

… may increase the blood urea nitrogen (BUN), whereas … might result in its decrease

Answer 28

deamination

arginine cycle

Absorption of blood from the gastrointestinal tract, steroids, and sepsis

malnutrition or liver disease

Question 29

How to calculate fractional excretion of sodium

Answer 29

FENa = (urine Na/plasma Na) / (urine creatinine/
plasma creatinine) × 100

Question 30

Volatile anesthetics effects in the renal system

Answer 30

Volatile anesthetics induce mild to moderate reductions in RBF and GFR, primarily because of their myocardial depression and vasodilatory effects

Question 31

Ketamine ffects in the renal system

Answer 31

Ketamine increases RBF but decreases urine flow
rate, possibly through sympathetic activation; it preserves RBF during hemorrhagic hypovolemia