Lecture 3-Renal Concentrating Mechanisms And Urine Formation Flashcards
___ is a protein enzyme released by the kidneys when BP is too low
Renin
The ___ apparatus is the site of renin synthesis
Juxtaglomerular apparatus
The JGA consists of (4) components: 1) modified smooth muscle cells in ___ arteriole; 2) modified smooth muscle cells in the ___ arteriole; 3) extraglomerular ___ cells; 4) ___ cells in the distal tubule
1) modified smooth muscle cells in the afferent arteriole; 2) modified smooth muscle cells in the efferent arteriole; 3) extraglomerular mesangial cells; 4) macula densa cells in the distal tubule
Glomerulus blood supply in = ___ arterioles; glomerulus blood supply out = ___ arterioles
In = afferent; out = efferent
Renin Angiotensin Pathway—renin causes ___ to be cleaved to ___; ___ converted to ___ in the lung by ___ (inhibited by ___); ___ is the most potent vasoconstrictor known
Renin causes angiotensinogen to be cleaved to angiotensin I; angiotensin I converted to angiotensin II in the lung by angiotensin converting enzyme (inhibited by ACE inhibitors); angiotensin II is the most potent vasoconstrictor known
Actions of angiotensin II—vaso___ and ___ (increased/decreased) blood pressure; increased ___ synthesis and release; increased ___ release; increased thirst; feedback inhibition of ___ release
Vasoconstriction and increased blood pressure; increased aldosterone synthesis and release; increased ADH (antidiuretic hormone) release; increased thirst; feedback inhibition of renin release
Although angiotensin II constricts both afferent and efferent arterioles, it releases ___, which act to maintain GFR in spite of its constrictive effects
Prostaglandins
Angiotensin II acts on the ___ gland to stimulate the release of aldosterone
Adrenal
Aldosterone acts on the kidneys to stimulate reabsorption of ___ and ___
Salt and water
Aldosterone is a steroid hormone synthesized in the zona ___ of the adrenal cortex
Zona glomerulosa
Stimulation for aldosterone release and synthesis include: ___ (increased/decreased) K+ levels in the ECF; angiotensin ___; ___ (increased/decreased) Na+ levels
increased K+ levels in the ECF; angiotensin II; decreased Na+ levels
Aldosterone acts on the ___ tubule and collecting ducts to cause K+ and H+ ___ in exchange for ___; net effect is to get rid of ___ and ___
Aldosterone acts on the distal tubule and collecting ducts to cause K+ and H+ secretion (removal) in exchange for Na+; net effect is to get rid of K+ and H+
Aldosterone helps to control blood pressure by holding onto ___ and losing ___ from the blood
Holding onto salt and losing potassium
___ is a hormone antagonistic to the angiotensin pathway
ANP
ANP ___ (increases/decreases) blood volume and pressure by: ___ (increasing/decreasing) the glomerular filtration rate; ___ (increasing/decreasing) reabsorption of Na+ by nephrons; inhibiting the release of ___, ___, and ___
ANP decreases blood volume and pressure by: increasing the glomerular filtration rate; decreasing reabsorption of Na+ by nephrons; inhibiting the release of renin, aldosterone, and ADH
Clinical relevance of aldosterone—___ syndrome
Conn’s
Conn’s syndrome = ___aldosteronism
Hyper
Conn’s syndrome—aldosterone secreting tumor causes ___tension, ___natremia, ___kalemia; eventually, the increased Na+ load exceeds the distal tubule and collecting duct ability to ___ Na+; however, ___ excretion continues and this can be fatal (___kalemia will cause ___polarization of nerve and muscle cells)
Hypertension, hypernatremia, hypokalemia; eventually, the increased Na+ load exceeds the distal tubule and collecting duct ability to reabsorb Na+; however, K+ excretion continues and this can be fatal (hypokalemia will cause hyperpolarization of nerve and muscle cells)
Renal concentrating and diluting mechanisms—___ hormone; ___ peptide; the ___ multiplier; the role of ___
Antidiuretic hormone (ADH); atrial natriuretic peptide (ANP); the countercurrent multiplier; the role of urea
The kidneys can excrete a large volume of dilute urine or a small volume of concentrated urine without major changes in rates of excretion of solutes such as sodium and potassium—T/F?
True
The kidney is able to excrete excess water by forming a ___ (dilute/concentrated) urine
Dilute
The kidney conserves water by ___ (diluting/concentrating) the urine
Concentrating
Obligatory urine volume is dictated by the maximum ___ ability of the kidney
Maximum concentrating ability of the kidney
Obligatory urine volume = ___ L/Day
0.5 L/Day
Example: A normal 70 kg human must excrete 600 mOsm of solute each day; assuming a maximum urine concentrating ability of 1200 mOsm/L. (600 mOsm/Day) / (1200 mOsm/L) = 0.5 L/Day
When there is a water deficit in the body, the kidneys form ___ urine by continuing to excrete solutes while ___ (increasing/decreasing) water reabsorption and ___ (increasing/decreasing) the volume of urine formed.
The kidneys form concentrated urine by continuing to excrete solutes while increasing water reabsorption and decreasing the volume of urine formed
The human kidney can produce a maximal urine concentration of ___ to ___ mOsm/L, ___ to ___ times the osmolarity of plasma
1200 to 1400 mOsm/L, 4 to 5 times the osmolarity of plasma
Antidiuretic hormone (ADH) is also called ___
Arginine vasopressin
ADH is synthesized in the ___; it is stored and released from the ___
ADH is synthesized in the hypothalamus; it is stored and released from the posterior pituitary
ADH plays a major role in ___ water by ___ urine
Conserving water by concentrating urine
Plasma hypotonicity ___ (stimulates/suppresses) ADH release, resulting in excretion of ___ (concentrated/dilute) urine
Suppresses ADH release, resulting in excretion of dilute urine
Hypertonicity ___ (stimulates/suppresses) ADH release, which ___ (increases/decreases) the permeability of the collecting duct to water and ___ (increases/decreases) water reabsorption
Hypertonicity stimulates ADH release, which increases the permeability of the collecting duct to water and increases water reabsorption
In response to changing plasma sodium levels, changing secretion of ADH can vary urinary osmolality from ___ to ___ mOsm/kg and urinary volume from ___ to ___ L/day
Vary urinary osmolality from 50 to 1200 mOsm/kg and urinary volume from 0.4 to 20 L/day
Osmoreceptor-ADH feedback—1) an ___ (increase/decrease) in extracellular fluid osmolarity (which in practical terms means an ___ (increase/decrease) in plasma sodium concentration), causes the special nerve cells called ___ cells, located in the ___ hypothalamus near the ___ nuclei to shrink
An increase in extracellular fluid osmolarity (which in practical terms means an increase in plasma sodium concentration), causes the special nerve cells called osmoreceptor cells, located in the anterior hypothalamus near the supraoptic nuclei to shrink
Osmoreceptor-ADH feedback—2) shrinkage of the osmoreceptor cells causes them to fire, sending nerve signals to additional nerve cells in the ___ nuclei, which then relay these signals down the stalk of the pituitary gland to the ___ (anterior/posterior) pituitary
Sending nerve signals to additional nerve cells in the supraoptic nuclei, which then relay these signals down the stalk of the pituitary gland to the posterior pituitary
Osmoreceptor-ADH feedback—3) these action potentials conducted to the posterior pituitary stimulate the release of ___, which is stored in secretory granules (or vesicles) in the nerve endings
ADH
Osmoreceptor-ADH feedback—4) ADH enters the bloodstream and is transported to the kidneys, where it ___ (increases/decreases) the water permeability of the late ___ tubules, ___ collecting tubules, and ___ collecting ducts
Where it increases the water permeability of the late distal tubules, cortical collecting tubules, and medullary collecting ducts
Osmoreceptor-ADH feedback—5) the increased water permeability in the distal nephron segments causes ___ (increased/decreased) water reabsorption and excretion of a ___ (small/large) volume of ___ (dilute/concentrated) urine
Increased water reabsorption and excretion of a small volume of concentrated urine
Stimuli for ADH release—___receptors in the hypothalamus respond to effective ECF osmolality—___ (increased/decreased) osmolality stimulates ADH release
Osmoreceptors in the hypothalamus respond to effective ECF osmolality—increased osmolality stimulates ADH release
Stimuli for ADH release—___receptors in the atria and aorta will detect ___ (increases/decreases) in volume and stimulate ADH release
Mechanoreceptors in the atria and aorta will detect decreases in volume and stimulate ADH release
Other stimuli for ADH release include angiotensin II, fright, nausea, pain, anesthesia, nicotine—T/F?
True
Alcohol stimulates ADH release—T/F?
False—alcohol inhibits ADH release
Increase ADH—___ (increased/decreased) plasma osmolarity, ___ (increased/decreased) blood volume, ___ (increased/decreased) blood pressure
Increased plasma osmolarity, decreased blood volume, decreased blood pressure
Decrease ADH—___ (increased/decreased) plasma osmolarity, ___ (increased/decreased) blood volume, ___ (increased/decreased) blood pressure
Decreased plasma osmolarity, increased blood volume, increased blood pressure
How does ADH work? It increases the permeability of the collecting system to ___
Water
In the absence of ADH, the collecting system is relatively ___ to water, leading to ___ (increased/decreased) water conservation and a ___ (dilute/concentrated) urine
In the absence of ADH, the collecting system is relatively impermeable to water, leading to decreased water conservation and a dilute urine
ADH also increases ___ permeability in the medullary collecting ducts
Urea
In order for ADH to work, there must be a driving force to move water out of the tubules and into the interstitium—i.e.: a ___tonic interstitium
A hypertonic interstitium
Regardless of whether ADH is present or absent, fluid leaving the early distal tubular segment is ___osmotic, with an osmolarity of only about ___ the osmolarity of plasma
Fluid leaving the early distal tubular segment is hypoosmotic, with an osmolarity of only about 1/3 the osmolarity of plasma
The mechanism for forming dilute urine is to continue reabsorbing ___ from the distal segments of the tubular system while failing to reabsorb ___
Continue reabsorbing solutes while failing to reabsorb water
In healthy kidneys, fluid leaving the ascending loop of Henle and early distal tubule is always dilute, regardless of the level of ADH—T/F?
True
In the absence of ADH, urine is further diluted in the late distal tubule and collecting ducts, and a large volume of dilute urine is excreted, decreasing osmolarity to as low as ___ mOsm/L
50 mOsm/L
The basic requirements for forming a concentrated urine are: 1) a ___ (high/low) level of ADH, which increases the permeability of the distal tubules and collecting ducts to water, thereby allowing these tubular segments to avidly reabsorb water; 2) a ___ (high/low) osmolarity of the renal medullary interstitial fluid, which provides the osmotic gradient necessary for water reabsorption to occur in the presence of high levels of ADH; 3) water moves through the tubular membrane by osmosis into the renal ___; from there, it is carried away by the ___ back into the blood
1) a high level of ADH; 2) a high osmolarity of the renal medullary interstitial fluid; 3) water moves through the tubular membrane by osmosis into the renal interstitium; from there, it is carried away by the vasa recta back into the blood
The renal medullary interstitium surrounding the collecting ducts is normally ___osmotic (hypo/hyper), so when ADH levels are high, water moves through the tubular membrane by osmosis into the renal ___
Hyperosmotic, renal interstitium
The urine-concentrating ability is limited by the level of ___ and by the degree of ___osmolarity of the renal medulla
By the level of ADH and by the degree of hyperosmolarity of the renal medulla
Key features of the countercurrent multiplier that help the kidneys to concentrate urine: 1) ___ shape of the loop of Henle allows for flow in ___ directions (this is where the word countercurrent comes from); 2) differences in ___ of certain nephron segments which flow in opposite directions to one another
1) “U” shape of the loop of Henle allows for flow in opposite directions; 2) differences in permeability of certain nephron segments
Energy to run the countercurrent multiplier comes from ___
ATP—Na+/K+/ATPase
The human kidney can produce a maximal urine concentration of ___ to ___ mOsm/L…___ to ___ times the osmolarity of plasma
1200 to 1400 mOsm/L…4 to 5x the osmolarity of plasma
The countercurrent multiplier mechanism depends on the special anatomical arrangement of the ___ and the ___, the specialized peritubular capillaries of the renal medulla
Special anatomical arrangement of the loops of Henle and the vasa recta, the specialized peritubular capillaries of the renal medulla
Anatomy of the medullary countercurrent multiplier system—___ nephrons with ___ (long/short) loops of Henle and ___ peritubular capillaries reach into the medulla
Juxtamedullary nephrons with long loops of Henle and vasa recta peritubular capillaries
The anatomical relationship of the juxtamedullary nephrons and collecting ducts allows the creation of a ___osmotic gradient in the renal medulla interstitium
Hyperosmotic gradient
The osmolarity of the interstitial fluid in the medulla of the kidney is much ___ (lower/higher), and may increase progressively to about ___ to ___ mOsm/L in the pelvic tip of the medulla
Much higher, 1200 to 1400 mOsm/L
How does the countercurrent multiplier work?—active transport of ___ and ___ in the ___ loop increases the osmolality of the interstitial space
Active transport of Na and Cl in the thick ascending loop increases the osmolality of the interstitial space
Because the thick ascending limb is virtually impermeable to ___, the solutes pumped out (Na and Cl) are not followed by the osmotic flow of ___ into the interstitium
Impermeable to water, are not followed by the osmotic flow of water
Fluid that enters the descending limb is still ___-osmotic, but much of it is absorbed in the descending limb, allowing the tubular fluid to become more ___
Iso-osmotic, allowing the tubular fluid to become more concentrated
A high concentration of Na Cl in the tubular fluid is delivered to the ___, where solute is pumped to the interstitium, ___ (increasing/decreasing) its osmolality
Thick ascending limb, increasing its osmolality
How does solute concentration build up into the renal medulla?—1) active transport of ___ ions and co-transport of ___, ___, and other ions out of the ___ limb of the loop of Henle into the medullary ___; 2) active transport of ions from the ___ ducts into the medullary ___; 3) facilitated diffusion of ___ from the inner medullary collecting ducts into the medullary ___; 4) diffusion of only small amounts of ___ from the medullary tubules into the medullary ___—far less than the reabsorption of ___ into the medullary interstitium
1) active transport of sodium ions and co-transport of potassium, chloride, and other ions out of the thick ascending limb of the loop of Henle into the medullary interstitium; 2) active transport of ions from the collecting ducts into the medullary interstitium; 3) facilitated diffusion of urea from the inner medullary collecting ducts into the medullary interstitium; 4) diffusion of only small amounts of water from the medullary tubules into the medullary interstitium—far less than the reabsorption of solutes into the medullary interstitium
The buildup of solute concentration into the renal medulla multiplies the concentration gradient established by the active pumping of ions out of the ___ loop of Henle, eventually raising the interstitial fluid osmolarity to ___ to ___ mOsm/L
Out of the thick ascending loop of Henle, eventually raising the interstitial fluid osmolarity to 1200 to 1400 mOsm/L
As solute builds up in the renal medulla, the interstitium becomes very ___osmolar, but unless ___ is present, the tubular fluid stays dilute; when ___ is present, the collecting duct is ___ permeable and the tubular fluid will ___ with the interstitium, creating a concentrated urine
Interstitium becomes very hyperosmolar, but unless ADH is present, the tubular fluid stays dilute; when ADH is present, the collecting duct is water permeable and the tubular fluid will equilibrate with the interstitium, creating a concentrated urine
As fluid flows into the cortical collecting tubule, the amount of water reabsorbed is critically dependent on the plasma concentration of ___
ADH
In the absence of ADH, this segment [the cortical collecting tubule] is almost impermeable to ___ and fails to reabsorb ___ but continues to reabsorb ___ and further ___ (dilutes/concentrates) the urine
Is almost impermeable to water and fails to reabsorb water but continues to reabsorb solutes and further dilutes the urine
When there is a high concentration of ADH, the cortical collecting tubule becomes highly permeable to ___, so large amounts of water are now ___ from the tubule into the cortex interstitium, where it is swept away by the rapidly flowing peritubular capillaries; the fact that these large amounts of water are reabsorbed into the ___, rather than the renal medulla, helps to preserve the ___ (high/low) medullary interstitial fluid osmolarity
Cortical collecting tubule becomes highly permeable to water, so large amounts of water are now reabsorbed from the tubule into the cortex interstitium; the fact that these large amounts of water are reabsorbed into the cortex, rather than the renal medulla, helps to preserve the high medullary interstitial fluid osmolarity
The TAL is located in the ___ (inner/outer) medulla, but the osmotic gradient is maximal in the ___ (inner/outer) medulla…how does this work?
TAL is located in the outer medulla, but the osmotic gradient is maximal in the inner medulla…the answer involves urea
Urea is a byproduct of ___ metabolism, consisting of 2 ___ molecules
Byproduct of amino acid metabolism, consisting of 2 ammonia molecules
Approximately ___-___ g/day of urea are made in the liver
25-30 g/day
In cases of liver failure, ammonia levels ___ (increase/decrease) and encephalopathy and coma then develop
Ammonia levels increase
Urea contributes to about ___-___% of the osmolarity of the renal medullary interstitium when the kidney is forming a maximally concentrated urine
40-50% of the osmolarity (500 to 600 mOsm/L)
Unlike sodium chloride, urea is ___ (actively/passively) reabsorbed from the tubule
Passively
When there is a water deficit and blood concentration of ADH is high, ___ (small/large) amounts of urea are passively reabsorbed from the inner medullary collecting ducts into the interstitium
Large amounts
The medullary interstitium has a ___ (low/high) concentration of urea; this plays an important role in generating a ___tonic interstitium
High; important role in generating a hypertonic interstitium
The TAL is ___ (permeable/impermeable) to water and urea
Impermeable
When ___ is present, water is reabsorbed into the cortex and outer medulla; the tubular contents thus become ___ (more/less) concentrated, and a ___ (low/high) concentration of urea reaches the inner medulla
ADH; the tubular contents thus become more concentrated, and a high concentration of urea reaches the inner medulla
The inner medulla is permeable to urea only in the presence of ___, and urea diffuses into the interstitium and becomes trapped there
ADH
The ___ ascending limb is urea permeable, so some diffuses into the tubule and is recycled
Thin
As water flows up the ascending loop of Henle and into the distal and cortical collecting tubules, ___ (small/large) amounts of urea are reabsorbed because these segments are ___ (permeable/impermeable) to urea; in the presence of high concentrations of ADH, water is reabsorbed rapidly from the cortical collecting tubule and the urea concentration ___ (increases/decreases) rapidly because urea ___ (is/is not) very permeable in this part of the tubule
As water flows up the ascending loop of Henle and into the distal and cortical collecting tubules, small amounts of urea are reabsorbed because these segments are impermeable to urea; in the presence of high concentrations of ADH, water is reabsorbed rapidly from the cortical collecting tubule and the urea concentration increases rapidly because urea is not very permeable in this part of the tubule
Urea contributes to ___% of the osmolarity of the renal medulla gradient during max urine concentration
40%
Urea ___ (actively/passively) diffuses from the medullar collecting duct during water deficits when ___ is present
Passively diffuses during water deficits when ADH is present
Urea is recirculated from the medulla interstitium into the loop of Henle and is returned to the tubular fluid—T/F?
True
Blood flow is provided to the renal medulla by the ___ to supply the metabolic needs of the cells in this part of the kidney; without a special medullary blood flow system, the solutes pumped into the renal medulla by the countercurrent multiplier system would be rapidly dissipated
Vasa recta
2 functions of the vasa recta: 1) remove ___ fluid from the interstitium; 2) ___ (minimize/maximize) solute uptake from the medulla in order to maintain medullary ___tonicity
1) remove reabsorbed fluid from the interstitium; 2) minimize solute uptake from the medulla in order to maintain medullary hypertonicity
Countercurrent exchange in the vasa recta—___ blood flow contributes to solute concentration
Medullary blood flow
Countercurrent exchange in the vasa recta—medullary blood flow is ___ (high/low); ___-___% of total renal blood flow; sluggish flow minimizes ___ loss
Medullary blood flow is low; 1-2% of total renal blood flow; sluggish flow minimizes solute loss
Countercurrent exchange in the vasa recta—___-shaped vasa recta; acts as countercurrent exchangers to minimize ___ loss; little net dilution of interstitium by U-shaped vessels
U-shaped vasa recta; acts as countercurrent exchanges minimize solute loss
Blood enters and leaves the medulla by way of the ___ at the boundary of the cortex and renal medulla
By way of the vasa recta
The vasa recta, like other capillaries, are highly permeable to ___ in the blood, except for plasma ___
Highly permeable to solutes in the blood, except for plasma proteins
In the descending VR, fluid ___ (enters/leaves) the VR; ___ (more/less) fluid ___ than solute ___
In the descending VR, fluid leaves the VR, more fluid leaves than solute enters
In the ascending VR, the situation reverses because of the ___ (increasing/decreasing) hydrostatic pressure and ___ (increasing/decreasing) osmolality of the blood
Decreasing hydrostatic pressure and increasing osmolality of the blood
Overall, more fluid is ___ than is ___
Reabsorbed than is lost
The vasa recta ___ (does/does not) create the medullary hyperosmolarity, but it does prevent it from being ___
Does not create the medullary hyperosmolarity, but it does prevent it from being dissipated
Maximum concentrating ability of the kidney is determined not only by the level of ___, but also by the ___ of the renal medulla interstitial fluid
Not only by the level of ADH, but also by the osmolarity of the renal medulla interstitial fluid
Even with maximal levels of ADH, urine-concentrating ability will be reduced if medullary blood flow increases enough to reduce the hyperosmolarity in the renal medulla—T/F?
True
Disorders of urinary concentrating ability—1) inappropriate secretion of ___—either too much or too little secretion results in abnormal water excretion by the kidneys; 2) impairment of the ___ mechanism; 3) inability of the distal tubule, collecting tubule, and collecting ducts to respond to ___
1) inappropriate secretion of ADH; 2) impairment of the countercurrent mechanism; 3) inability of the distal tubule, collecting tubule, and collecting ducts to respond to ADH
Disorders of urinary concentrating ability—2) impairment of the countercurrent mechanism—a ___osmotic medullary interstitium is required for maximal urine concentrating ability; no matter how much ADH is present, maximal urine concentration is limited by the degree of ___osmolarity of the medullary interstitium
A hyperosmotic medullary interstitium; maximal urine concentration is limited by the degree of hyperosmolarity of the medullary interstitium
Failure to produce or release ADH from the ___ pituitary = “___” diabetes insipidus
Failure to produce or release ADH from the posterior pituitary = “Central” diabetes insipidus
Central DI—the distal tubular segments cannot reabsorb ___ in the absence of ADH; results in the formation of a large volume of ___ urine with urine volumes that can exceed ___ L/day
Cannot reabsorb water in the absence of ADH; results in the formation of a large volume of dilute urine with urine volumes that can exceed 15 L/day
Central DI—the primary abnormality observed clinically in people with this condition is the large volume of ___ urine
Dilute
Treatment for central DI is administration of a synthetic analog of ADH, ___, which acts selectively on ___ receptors to ___ (increase/decrease) water permeability in the late distal and collecting tubules
Desmopressin, which acts selectively on V2 receptors to increase water permeability in the late distal and collecting tubules
“___” diabetes insipidus—___ or ___ levels of ADH are present, but the renal tubular segments ___ (can/cannot) respond appropriately
Nephrogenic diabetes insipidus—normal or elevated levels of ADH are present, but the renal tubular segments cannot respond appropriately
Nephrogenic DI—the abnormality resides in the ___
Kidneys
Nephrogenic DI can be due to either failure of the ___ mechanism to form a ___osmotic renal medullary interstitium, or failure of the distal and collecting tubules and collecting ducts to respond to ___
Failure of the countercurrent mechanism to form a hyperosmotic renal medullary interstitium, or failure of the distal and collecting tubules and collecting ducts to respond to ADH
Nephrogenic DI—many types of renal diseases can impair the concentrating mechanism, especially those that damage the renal ___
Medulla
Nephrogenic DI—impairment of the function of the loop of Henle, as occurs with diuretics that inhibit electrolyte reabsorption by this segment, such as ___, can compromise urine-concentrating ability
Furosemide
Nephrogenic DI—certain drugs such as ___ and ___ can impair the ability of the distal nephron segments to respond to ADH
Lithium and tetracyclines
Diagnosis of nephrogenic DI—can diagnose with test dose of ___
ADH
