Quiz 2 Flashcards
Two ways substances can be transported?
Tubular reabsorption: Lumen–>peritubular capillary
Tubular secretion: Peritubular capillary–>lumen
Amount excreted equation
(amount filtered) - amount reabsorbed(+ amount secreted)
What is Transcellular transport across the renal epithelial cells?
Transport through the cell across TWO membranes (luminal and basolateral
What is Paracellular transport across the renal epithelial cells?
Transport b/w cells (across tight junctions by simple diffusion)
Most renal tubular transport occurs via what route?
the transcellular route
Three types of trans-membrane transport systems
1) channel-mediated diffusion
2) carrier-mediated diffusion
3) carrier mediated “active transport”
Channel-mediated diffusion requires what?
Electrochemical gradient since its “passive”
Carrier-mediated diffusion has what types of transport?
Uniport, symport, antiport
Carrier-mediated “active transport” needs what?
energy to transport against the electrochemical gradient
Where is there absolute dependence on Na+/K+ ATPase?
ONLY on the basolateral membrane to maintain LOW intracellular Na+ concentration
In the Cortical Collecting Tubule, Na+ enters the cell via…
luminal membrane Na+ selective channels
The proximal tubule has what type of transporter?
luminal membrane Na+ glucose co-transporter
In the proximal tubule, the “downhill” movement of Na+ across the luminal membrane into the cell facilitates what?
The “uphill” movement of glucose
What does the glucose uniporter transport do?
transports glucose out of the cell across the basolateral membrane
Two co-transporters for glucose? What is their capacity and affinity for each?
SGLT-2: high capacity-low affinity
SGLT-1: low capacity-high affinity
What type of inhibitors are used for type-2 diabetics?
SGLT-2 inhibitors
How are proteins absorbed?
Receptor mediated endocytosis
Endocytised proteins are degraded to what? And how are they released?
amino acids
basolaterally
Approximately how much of the glomerular filtrate is reabsorbed in the proximal tubule?
2/3
Many solutes are completely absorbed proximally except what?
Cl- which is reabsorbed (passively) in the later proximal tubule
In the proximal tubule, what is the net fluid movement?
Isosmotic fluid reabsorption b/c 2/3 of filtered water and 2/3 of the filtered solute is reabsorbed
In the proximal tubule, complete reabsorption of the isotonic fluid is a two-step process. What are the two steps?
1) Movement from lumen–>interstitium
2) Movement from interstitium–>peritubular capillaries
What promotes peritubular capillary (PC) fluid uptake?
Low Ppc (downstream of afferent / efferent resistance points)
High PIEpc (filtration creates high PC plasma protein concentration
The proximal tubule reabsorbs a CONSTANT percentage of the filtered load. What is this percentage?
What is this called?
~67%
Glomerulotubular (GT) balance
Glomerulotubular (GT) balance helps to do what?
maintain a relatively constant delivery of fluid to the distal nephron
What cant be assessed using In Vivo Micropuncture to analyze renal tubular function? Why?
Cant assess collecting tubule function by micropunction, or transport in the juxtamedullary nephrons
B/c neither are accessible from the surface of the kidney
Transport capacity of essentially any sub-segment of the nephron can be assessed by what method?
microperfusion
What does “Splay” represent?
The slight variance in Tm b/w individual nephrons
Where is the primary site of secretion for organic anions and cations?
proximal tubule
Cortical / juxtamedullary nephron ratio correlates with what?
the capacity to concentrate urine
increase percent juxtamedullary = increase concentrating ability
Transport characteristics of the thin descending limb of Henle’s loop?
Reabsorbs H20
Does NOT reabsorb NaCl (or other solutes)
In the thin descending limb (TDL) of henle’s loop, tubular fluid osmolarity __increases or decreases__ as it flows toward the papilla. This is due to what?
increases
water reabsorption
TDL system is capable of reabsorbing how much H2O/day?
~30-40 L H2O/day
Characteristics of the ascending limb of Henle’s loop?
Avidly reabsorbs NaCl
Does NOT reabsorb H2O
In the ascending limb of Henle’s loop, what percent of the filtered load of NaCl gets reabsorbed?
20-25%
The ascending limb of Henle’s loop generates what type of tubular fluid? Whats the nickname for this segment?
hypotonic
its considered the “diluting segment” of the nephron
The thick ascending limb of Henle’s look is dependent on what? Where are they located?
Na+-K+-ATPase located on the basolateral membrane
In the thick ascending limb, the reflux of K+ entering into the tubular lumen via a selective channel generates what type of potential? This provides the driving force for what?
lumen-positive
paracellular transport of multiple cations (Na+,K+,Ca2+,Mg2+)
AND
ensures adequate supply of cotransporters
What are furosemide and bumetanide?
Drugs that inhibit Na+-K+-2Cl- cotransporters in the thick ascending limb
They are “loop diuretics” (allow salt to be passed and excreted in the urine)…prescribed for hypertension, edema, etc.
What occurs as a result of adrenal insufficiency?
decrease urine diluting and concentrating ability
Transport in the thick ascending limb (TAL) is increased by what?
antidiuretic hormone
insulin
glucagon
isoproterenol
Transport in the thick ascending limb (TAL) is inhibited by what?
atrial natriuretic peptide
adenosine
dopamine
bradykinin
Distal nephron consists of…
distal convoluted tubule collecting tubule (cortical-->papillary)
In the distal nephron, distal delivery is __% of the filtered load of H2O and ___% of the filtered load of NaCl (and KCl)
both 10%
What regulates distal nephron transport of H2O?
Antidiuretic hormone (ADH)
Distal nephron transport of NaCl is regulated by what?
Aldosterone
What does ADH do to the collecting tubule?
makes it permeable to water which promotes water reabsorption and generates a smaller volume of concentrated (hypertonic) urine
i.e ANTIDIURESIS
In the absence of ADH, is the collecting tubule permeable to water?
NO
Reabsorption of water by the collecting tubule system is dependent on the presence of what in the luminal membrane?
water channels called aquaporins
ADH stimulates insertion of what?
pre-existing AQP-2 channels into the luminal membrane
Increase in cyclic AMP ultimately results in what?
increase water permeability
AQP-3 channels are constitutively expressed in the _____
basolateral membrane
What explains the water impermeability of the ascending limb?
lack of luminal aquaporins
Whats being reabsorbed and whats being secreted in the cortical collecting tubule?
Na+ is reabsorbed
K+ secreted
How does aldosterone control reabsorption?
Increase number of luminal membrane Na+ channels
Increase sodium-potassium-ATPase (de novo synthesis of pumps)
Increase Krebs cycle enzyme synthesis
(thus more ATP)->increaseATPase activity
Aldosterone and cortisol have similar affinity for what type of receptor?
mineralocorticoid
Parathyroid Hormone (PTH) stimulates what?
Increases Ca2+ reabsorption in the DISTAL TUBULE
Plasma ADH levels control ____ and ____
medullary interstitial urea
medullary osmolarity
Decrease in ADH->decrease urea reabsorption->decrease med.int.urea–> decrease med. osmolarity
If ADH levels increase, what happens to medullary osmolarity?
increases
Medullary blood supply is essential for what?
Nutrient supply
Removal of reabsorbed H2O and NaCl
Countercurrent exchange in the vasa recta capillaries preserves what?
The hypertonic gradient in the medullary interstitium
In the countercurrent exchange, plasma flowing out of the medulla has a higher or lower osmolality than that entering?
What about exiting plasma flow rate?
higher
higher
Important function of the vasa recta?
remove ALL water reabsorbed by the descending limbs and medullary collecting tubules, and MOST of the NaCl reabsorbed by the ascending limb
What is the only output that can be precisely controlled?
urine output
Maximum DIURESIS
Urine Volume:?
Urine Osmolality:?
20-25 L/day
50-75 mOsm/kg
Maximum ANTIDIURESIS
Urine Volume:?
Urine Osmolality:?
0.5 L/day
1200-1400 mOsm/kg
Where is ADH synthesized?
In the neural cell bodies located in the supraoptic and paraventricular nucleii of the hypothalamus
Where is ADH stored?
In nerve terminals in the posterior pituitary
ADH is regulated by what receptors?
hypothalamic osmoreceptors
volume receptors
Which receptors are more sensitive for ADH secretion:
Osmoreceptor system or baroreceptor system?
What does this mean?
osmoreceptor system
Small changes in plasma osmolality can elicit large changes in ADH secretion
Small changes in ADH can elicit large changes in _____
urine osmolality
increase osmolality–> decrease in urine VOLUME
Causes of Syndrome of Inappropriate ADH secretion (SIADH)?
head trauma, encephalitis, meningitis
ADH secreting tumors (lung, pancreas)
Drug-induced (nicotine, morphine, chemotherapeutic agents)
Effects of Syndrome of Inappropriate ADH secretion (SIADH)?
increase ADH->increase H2O reabsorption-> HYPONATREMIA
decrease serum Na->dec. plasm osm->inflush of H2O into brain cells—>leads to coma
Causes of Diabetes Insipidus (D.I.)
HYPOTHALAMIC (CENTRAL) D.I. (dec. production or release of ADH)
NEPHROGENIC D.I. (renal unresponsiveness to ADH)
Effect of Diabetes Insipidus (D.I.)
dec. ADH->dec. H2O->HYPERNATREMIA
inc. serum Na–>inc. plasma osm–>efflux of H2O (out of brain cells)——->Coma
What does free water clearance provide?
a non-invasive assessment of diluting efficiency of the thick ascending limb
Kidneys maintain constant ECF volume by adjusting what?
NaCl excretion to match NaCl intake
What percent of filtered load of sodium is excreted?
less than 1%
Aldosterone regulates the excretion of what percent of the filtered load of sodium?
5%
Total body Na+ changes are sensed as changes in what?
Effective Circulating Volume (ECV)
Extra cellular volume is monitored by what?
Baroreceptors
What is the rate-limiting step in aldosterone release from adrenal cortex?
renin (enzyme) release by kidney
Where is renin secreted within the kidneys?
granular cells of the afferent arterioles
What does angiotensin II do in its rapid-onset effects in response to decreased blood pressure (e.g. hemorrhage)?
What are its longer-onset effects?
Helps restore “normal” b.p. despite low ECV (inc. TPR and inc. CO)
Restore normal ECV (dec. NaCl and H2O excretion and increase NaCl and H2O intake)
Sustained increase in aldosterone secretion results in what?
relatively transient Na+ retention
A 15-25mm Hg increase in b.p. results in what?
pressure natriuresis and pressure diuresis= Aldosterone Escape
Describe how long renal adjustments for changes in H2O take and how long renal adjustments for NaCl intake take?
H2O intake are rapid (minutes)
Can take several days
Increased ECF causes what?
Increase in ATRIAL NATRIURETIC PEPTIDE (ANP)
What secretes atrial natriuretic peptide (ANP)?
atrial myocytes
What does ANP do?
Increase NaCl and H2O excretion to decrease b.p.
How does ANP increase NaCL and H2O excretion?
Vasodilation of afferent arteriole–>increase GFR
inhibit aldosterone secretion
inhibit NaCl reabsorption in proximal tubule and collecting tubule
Antagonized ADH action
What is the gene family that express Na+-K+-Cl- cotransporter along the nephron ?
Electro Neutral sodium Chloride Co-transporter (ENCC2)
Bartter’s Syndrome
Mutations in ENCC2 and/or luminal K+ (ROMK) channel in the THICK ascending limb
What part of the nephron does bartter’s syndrome effect?
THICK ascending limb
Physiological impact of bartter’s syndrome?
Decrease NaCl reabsorption (inc. NaCl excretion)
Volume depletion b/c water loss
Hyperreninemic hyperaldosteronism
Hypercalciuria (dec. lumen ive potential)
Hypokalemic metabolic alkalosis
How many are affected by Polycystic Kidney Disease (PKD) in the U.S?
600,000
Polycystic Kidney Disease (PKD)
Cysts (fluid filled sacs) that develop from renal tubular epithelial cells
Most cases autosomal dominant (ADPKD) (85%)
What is Autosomal Dominant Polycystic Kidney Disease (ADPKD) often associated with?
hypertension
ADPKD can lead to what in 50% of patients?
end-stage renal disease
Diuretic drugs ultimately do what?
increase NaCL water excretion
How are diuretics classified?
According to site and mechanism of action
What is Proximal tubule carbonic anhydrase inhibitors?
e.g. acetazolamide
A diuretic drug that targets this specific enzyme to
inhibit Na+HCO3- “reabsorption”
What are Collecting tubule “K+-sparing” diuretics?
e.g. amiloride
A diuretic drug that specifically inhibits luminal Na+ channels
What are thick ascending limb “loop diuretics”
(e.g.furesemide, bumetanide)?
Diuretic drug that specifically targets this transport protein and
inhibits Na+-K+-2Cl- transport
What are collecting tubule “K+-sparing” diuretics?
e.g. spironolactone
Diuretic drug that targets hormone receptors acting as an aldosterone receptor antagonist
What are Distal Tubule Luminal Na+-Cl- cotransport inhibitors?
(e.g. thiazides)
Diuretic drug that inhibits this cotransport inhibitor
what does an increase in osmolality do to urine volume?
decreases urine volume (piss less)
