Renal Physiology V Flashcards
The most abundant intracellular cation
K+
In order to prevent the massive loss of filtered K+ in the excreted urine, what percentage of the filtered load of K+ is reabsorbed per day?
80-90%
As with Na+, the majority of filtered K+ (approximately 80%) isreabsorbed in the
Proximal tubule
Passive K+ reabsorption occurs via
Paracellular junctions
Active K+ reabsorption is mediated by
Basolateral K+ pumps and channels
Basically, a lot of K+ recycling between forming urine and interstitium occurs between the
Ascending and Descending limbs
In general, the ascending limb resorbs more K+ than the descending limb
Secretes
This results in a net K+ reabsorption along the
Loop
Supports an interstitial K+ gradient that tightly regulates K+ secretion
Medullary K+ trapping
K+ reabsorption is charge-driven and occurs by both paracellular and transcellular routes in the
Thick Ascending Limb (TAL)
Which two factors regulate K+ secretion in the CCT?
- ) Activity of principal cells
2. ) Rate of flow
Principal cells secrete K+ due to a favorable electrochemical gradient called a
Lumen-negative transepithelial voltage
This is established by the rapid reabsorption of Na+ from the forming urine in the CCT when compared to that of
Cl-
The apical membrane of the CCT contains
ROMK2 and K+-Cl- symporters
Basolateral K+ channels and Na+/K+ ATPases in the CCT support
K+ excretion
Mediate K+ reabsorption in the CCT through the coordinated actions of apical K+-H+ ATPases as well as basolateral Na+/K+ ATPases and K+ channels
Intercalated cells
Increased lumenal flow will result in a decrease in
Lumenal K+
In and of itself, this provides a favorable gradient for the secretion of K+ into the
Forming urine
This is apparent during certain diuretic regimens, an effect known as
Kaliuresis
An increase in lumenal Na+ will promote Na+ reabsorption by the tubule epithelium, and the translocation of positive charge induces cell membrane depolarization. This provides an electrochemical gradient that promotes
K+ secretion
The trade-off for aldosterone dependant Na+ reabsorption is K+ secretion within the
ASDN
This mechanism involves the acute effects of aldosterone on ENaC, whereas, the subsequent changes in membrane potential promote
K+ Secretion
However, during an episode of volume hyponatremia or volume reduction, what will we see?
GFR is reduced, thus lumenal flow is decreased. This signals an increase in Na+ reabsorption and a decrease in K+ secretion
What are the effects of decreased lumenal flow?
Increased Na+ reabsorption and decreased K+ secretion
What effect does SNS activity have on K+ secretion and excretion?
It reduces K+ excretion and secretion
Stimulate the uptake of K+ by extrarenal cells, which decreases plasma [K+] and thus lowers the filtered load of K+
Catecholamines
In addition, SNS activity directly down-modulates K+ secretion within the
Nephron
In order to maintain a healthy acid-base balance, each day the kidneys must:
- ) Reabsorb
- ) Generate
- ) Greater than 4500 meq of HCO3-
2. ) 70 meq HCO3-
The kidneys aggressively oversee normal acid-base balance in which three ways?
- ) Generation of HCO3-
- ) Reclamation of HCO3-
- ) Excretion of H+
In the kidneys, the majority of HCO3- reabsorption and generation occurs within the
Proximal tubule
However, some HCO3- reabsorption also occurs within the
Distal Nephron
In regards to the renal contribution to body acid-base balance, what is more important, prevention of HCO3- loss or excretion of H+?
Prevention of HCO3- loss
Under basal conditions, how much nonvolatile acid do humans accumulate due to metabolism and the excretion of OH- in feces?
1mmole of nonvolatile acid/Kg body weight/day
A simple relationship defines net urinary acid secretion. It is simply the difference bewteen HCO3- secretion in the urine and the collective loss of H+ in the forms of
H2PO4-, uric acid, NH4+ and/or H+ bound to creatinine
Keep in mind that all secreted H+ is no excreted. In fact much of the secreted H+ is used for the
Regeneration of HCO3- within the nephron
Interestingly, the pathways that facilitate the excretion of H+ in the forms of H2PO4- and NH4+ also promote
HCO3- generation
Is HCO3- within the filtrate simply just absorbed?
No (that is biochemically cumbersome)
Instead, filtered HCO3- reacts with
Carbonic Anhydrous Type IV (CAIV)
CAIV is located within the
Apical membrane of tubule epithelium
CAIV catalyzes the dissociation of HCO3- into
OH- and CO2
Rapidly and passively diffuses into the epithelium
CO2
In the meantime, the lumenal OH- reactes with
Secreted H+ (forms H2O)
By providing OH- to react with secreted H+, CAIV in effect maintains a favorable gradient for
Proton secretion
Like CO2, H2O rapidly diffuses into the tubule epithelium. What happens once H2O is in the cells?
It dissociates into H+ and OH-
Within the epithelial cytosol, the formationof HCO3- from OH- and CO2 is catalyzed by
CA type II (CAII)
Then the HCO3- is rapidly reabsorbed into the interstitium and delivered back into
Circulation
Is the exact molecule of HCO3- that was filtered from glomerular circulation the same molecule that is then reabsorbed?
No
The mechanism by which H+ is buffered within the distal nephron utilizes secreted
Ammonia (NH3) and H+ to form NH4+
As within the proximal nephron, H+ in the distal nephron is freed from H2O resulting in
- ) H+ secretion and buffering by NH3
2. ) Production of HCO3-
Within the proximal tubule, NH3 serves to buffer secreted H+ by forming
NH4+
This NH4+ travels within the forming urine until it is reabsorbed at the
Thick Ascending limb
NH4+ actually competes for the K+ binding site on
NKCC
Once inside the less acidic tubule epithelium, NH4+ dissociates. The NH3 then freely diffuses into the
Renal Medullary intersitium
Once there, NH3 follows gradients to regions of relatively low NH3 concentrations, one of which is the
Proximal tubule (WHERE NH3 combines with an H+ to once again become NH4+)
However, some of the NH3 from the tubule epithelium follows concentration gradients to the
Collecting tubule (where it forms NH4+ too)
What is the fate of the NH4+ formed in the collecting tubule?
Remains in forming urine and is excreted (thus reducing some of the acid load)
When faced with an alkaline load, the kidneys do not necessarily upregulate HCO3- excretion. Rather, their initial response is to
Lower excretion of NH4+
Remember that each NH4+ that is resorbed also generates
HCO3-
Thus, by dampening urinary acid excretion, the renal sytem in effect suppresses
HCO3- reclamation
Usually involves a defect in renal HCO3- secretion and excretion due to effective volume depletion and Cl- loss
Maintained Metabolic alkalosis
Which two conditions are common with metabolic alkalosis?
Hypokalemia and hypochloremia
Abnormally increased K+ excretion may induce
Metabolic alkalosis
Volume contraction, diminished GFR, and aldosterone excess also often accompany
Metabolic Alkalosis
What three ways is H+ secretion stimulated?
- ) Aldosterone excess
- ) Hypovolemia
- ) Hypokalemia
In general, acidosis causes a net decrease in
Tubular K+ secretion
Suppresses H+ secretion within the renal tubules
Hyperkalemia
Within the principal cells, aldosterone-dependant Na+ reabsorption creates a lumen negative potential which drives
H+ secretion
Within the intercalated cells, aldosterone stimulates a H+- K+ exchanger, as well as a H+ ATPase, which each mediate
H+ Secretion
Although there is no evidence that acid-base disturbances directly alter aldosterone secretion, hyper- and hypoaldosteronisms can affect
Acid-base balance
A metabolic acidosis resulting from impaired net H+ secretion from the kidney
Renal Tubule Acidosis (RTA)
There are three types of RTAs which are subcategorized into
- ) Proximal (type 2)
2. ) Distal (types 1 and 4)
Can be autoimmune in origin or can be induced by certain drugs and toxins
Type 1 RTA
During a type 1 RTA, within the kidneys there is a net reduction in H+ secretion within the
Collecting tubules
Type 1 RTA involves an impairment in the secretion of
NH4+ and titratable acid
Since acid secretion is suppressed, one clinical sign of Type 1 RTA is a urine pH of
Greater than 5.3 in adults and greater than 5.6 in children
A normal anion gap (hyperchloremic) acidosis
-believed to be due to impaired H+ ATPase and Cl-/HCO3- exchanger
Type 1 RTA
It is of clinical importance to note that chronic acidemia results in the release of
CaPO4 from bone
Therefore, other signs of a type 1 RTA include
Hypercalciuria, hyperphosphaturia, and nephrolithiasis
High pH in the forming urine is conductive to forming Ca2+ precipitates and thus
Nephrolithiasis (Kidney stones)
Type 1 RTA can also be accompanied by either
Hyp- or hyperkalemia
A proximal RTA that is usually accompanied by the urinary loss of not only HCO3-, but also glucose, amino acids, and phosphate
Type 2 RTA
Interestingly, during a type 2 RTA, what do we see with HCO3- reabsorption impairment?
Proximal tubule reabsorption is impaired but distal tubule reabsorption is in tact
However, the HCO3- resorptive capacity of the distal tubule is much less than that of the proximal tubule; therefore, this becomes the limiting factor for maintaining
Plasma HCO3-
Generally, in a type 2 RTA, plasma HCO3- achieves a new steady state t around
14-20 meq/L
Defects in the Na+/ H+ exchanger, Na+/K+ ATPase, and/or carbonic anhydrase are all implicated as
mechanisms controlling
-all assist with HCO3- reabsorption from the proximal tubule
Type 2 RTA
In a type 2 RTA, disruptions in proximal HCO3- transport set in motion electrochemical cascades which impair the reabsorption of
K+ and NaCl
This collectively leads to
Na+ wasting and hyperaldosteronism
Hyperaldosteronism exacerbates the hypokalemia that is associated with
Type 2 RTA
What are two other common things seen in a type 2 RTA?
Phosphate wasting and vitamin D deficiency
A relatively mild form of hyperchloremic metabolic acidosis that is due to aldosterone deficiency or resistance
Type 4 RTA
What are the 3 hallmarks of patients with type 4 RTAs?
1/) Volume depleted
- ) hyperkalemic
- ) Plasma HCO3- of no less than 15 meq/L
Type 4 RTAs are caused by the lowered level of tubule
H+-ATPase activity
The hyperkalemic state associated with a type 4 RTA impedes NH4+ production and excretion, which blocks
NH4+ recycling and NH3 secretion in distal nephron
Since the excretion of NH4+ and titratable acid is disrupted in a type 4 RTA, urine is not acidified below approximately
pH 5.5
-results in positive acid balance
UAG is only useful for helping to diagnose
Normal AG metabolic acidosis
Assuming the kidneys are healthy and the metabolic acidosis is being driven by diarrhea, when pH drops, the kidneys will excrete H+, most of which is in the form of NH4+. This is the proccess of
Distal acidification
In order to maintain electroneutrlity, what is excreted with the NH4+?
Cl-
The nitrogenous end-product of protein (amino acid) metabolism
-generated from NH4+
Urea
For urea, is the amount reabsorbed greater than or less than that secreted?
Greater reabsorption than secretion
However, very little of the filtered load of urea is returned to
Systemic circulation
