Renal Q2 Flashcards
What is the principal mechanism for modifying the composition of the filtered fluid?
Tubular reabsorption
Movement from the lumen into the Peritubular capillary is…
Movement from the Peritubular capillary into the lumen is…
Tubular reabsorption
Tubular secretion
Amount excreted =
Amount filtered (+ secreted) - amount reabsorbed
If amount X excreted
A % of X was reabsorbed
What are 2 examples of substances that are fully reabsorbed?
amount excreted = 0
Glucose
Bicarb
T/F
A homeostatic mechanism is altering the amount of reabsorption of the filtered load
**Are there exceptions to this????
True
What are the 2 membranes of Renal Epithelial cells?
Luminal
Basolateral
What type of transport occurs across both membranes (luminal and basolateral) of renal epithelial cells?
What type of transport occurs between renal epithelial cells across tight junctions by simple diffusion?
What type of transport is most common?
Transcellular
Paracellular
Transcellular
What does the Transcellular route require on both membranes?
Transport proteins
What does Passive Transport require?
favorable electrochemical gradient
Name 4 types of Transport.
Simple diffusion
Ion channels
Facilitated (uniporter, symporter, antiporter)
Energy Dependent (ATPases)
What is the rate limiting step in the reabsorption of sodium (and many other solutes)?
Na/K pump
ATP ase
What is the Glucose transporter of the kidney?
GLUT 2
How does the Collecting tubule transports Sodium out through the Luminal membrane?
Na+ selective channels through luminal side
exits cell via Na/K pumps (ATP powered)
How does the Proximal tubule transport Sodium out through the Luminal membrane?
Na+ crosses lumen via Na+/Glc symporter
exits cell via Na/K pump (ATP powered)
What fraction of glomerular filtrate is reabsorbed by the Proximal Tubule?
2/3
How much water is filtered per day?
How much is reabsorbed at the Proximal Tubule?
180L
120L
How is Glucose reabsorbed in the Proximal Tubule?
Na+ symporter on Luminal side
(Downhill Na+ carries Glc Uphill)
*SGLT-1/SGLT-2 are Na+/Glc cotransporters
GLUT2 (uniporter) on basolateral membrane
What is one of the principal techniques used to assess tubule function?
In vivo micropuncture
What are 2 of the anatomical limitations of In Vivo Micropuncture?
(what can’t the pipette reach)
Collecting tubule
Juxtamedullary nephron
*these aren’t accessible from the surface of the kidney
What 3 solutes are absorbed early in the Proximal Tubule?
Glucose
Amino Acids
Bicarb
What solute is absorbed late in the Proximal Tubule?
Cl-
What is absorbed throughout the entire length of the Proximal Tubule?
Water
The filtration of water and solute at the Lumen of the Proximal Tubule is what type of fluid reabsorption?
Isosmotic
If there is an isotonic relationship between the tubular fluid and interstitial fluid in the Proximal Tubule, what accounts for the Isosmotic fluid reabsorption?
Small transepithelial osmotic gradient
tubular fluid osmolality slightly lower than EC fluid
What are the 2 phases of Proximal Tubule reabsorption?
Water/Solutes from Lumen > Interstitium
Interstitium > Peritubular Capillaries
What are 2 Starling forces within Peritubular capillaries that promote fluid uptake?
Low hydrostatic pressure
High Oncotic pressure
What happens to the fluid if it’s not taken up into the capillaries?
Excreted in the Urine
T/F
The Proximal tubule reabsorbs a constant percentage of the filtered load (67%)
True
The constant percentage of filtered load reabsorbed by the Proximal Tubule is know as…
Glomerulotubular Balance
Why is Glomerulotubular Balance important?
Delivers fluid to distal nephron continuously
Name 2 ways Efferent Arteriole resistance increases Proximal Tubule reabsorption (export)
Peritubular pressure goes down
Increased filtration fraction causes increases Oncotic pressure within Peritubular capillaries
Where are pipette A and B sampled in In Vivo Micropuncture?
Pipette A - Proximal convoluted tubule
Pipette B - Distal convoluted tubule
What are the samples from In Vivo Micropuncture compared to?
A (Proximal tubule) compared with Plasma
A and B (Proximal and Distal) compared to ascertain late Proximal tubule and Loop of Henle
What is the advantage to In Vitro Microperfusion?
Any segment of nephron can be analyzed
What is the Primary site of secretion of organic anions and cations?
Proximal Tubule
What are 3 reasons a substance must be secreted?
can’t be filtered by Glomerulus
Molecular size
Charge
Plasma binding protein
Name 2 anionic Organic Ion Transporters on the basolateral membrane.
(used in Secretion)
OAT-(1,3)
NaDC
*(Na-dicarboxylate co-transporter)
Name 2 anionic Organic Ion Transporters on the Luminal membrane
(used in secretion)
OAT4
MRP2
Name a cationic Organic Ion Transporter on the Basolateral side.
Name 2 cationic Organic Ion Transporter on the Luminal side.
OCT
OCTN
MDR1
What is the rate limiting step in Tubular Secretion?
Na/K ATPase
T/F
Organic anion and cation transporters are non-selective
True
*relatively non-selective
How might the secretory system in the kidney be manipulated to enhance the effect of drugs?
Block transporters with inert substances increases uptake
What are 2 drugs that are completely dependent on tubular secretion to be effective?
Furosemide
Bemetanide
*Diuretics
T/F
The Proximal Tubule is the only site of secretion in the nephron.
False
Equations for the following:
Amount filtered
Amount excreted
Amount reabsorbed
Filtered: GFR x Plasma conc.
Excreted: Volume x Urine conc.
Reabsorbed: Amount filtered - Amount excreted
How do we experimentally illustrate the transport maximum concept?
Renal handling of Glucose
The plasma concentration at which Tm is exceeded is called?
Threshold
The variance in Tm between individual nephrons is called?
Splay
The maximal transport capacity when all carriers/channels are maxed is called…
Tm
What is the relationship between GFR and Threshold?
Generally GFR is proportional, but Glucose Threshold is exceeded/excreted until 2mg/ml, then curves toward proportionality
*normal plasma glc conc. well below threshold
T/F
Diabetes mellitus is a compensatory response of the kidneys to lower Plasma Glucose
False
Why is there Glc in urine (glcosuria) in Diabetes Mellitus?
Filtered load of Glc (GFR x Pglc)»_space;> Tm
Why can Inulin and Creatinine be used to measure GFR?
2 reasons
Not reabsorbed or secreted
Not metabolized or produced by Kidney
T/F
The clearance of Inulin or Creatinine is equal to the GFR
True
What is the Clearance Forumula?
Cx = V x Ux / Px
Clearance of X = Volume plasma cleared / time
For inulin and creatinine, all of the plasma filtered by the glomeruli is effectively “cleared”
True
*not reabsorbed
T/F
Using inulin or creatinine when testing GFR will yield slightly different results. The same inert substance should be used with each test to ensure consistent results.
True
Using Inulin or Creatinine in addition to another solute will tell us what?
How much solute is cleared
Why does the amount of PAH into the kidney = Renal Plasma Flow?
All PAH excreted
T/F
The amount of PAH in the renal artery will equal the amount in the urine
PAH will not be present in the renal vein
True
True
T/F
The same fundamental formula is used to measure Renal Plasma Flow and GFR
True
How do we calculate renal blood flow from renal plasma flow?
Add the Hematocrit back in
*about .45
45%
What progressively increases from the cortex/medulla border to the papilla tip?
Interstitial osmolarity
What establishes the increasing hypertonicity as you travel deeper into the nephron?
Interstitial NaCl and Urea
T/F
The absolute values for the osmolarity changes to the interstitium are universal
False
Rats have 2x concentration
Why is the unique environment of the Interstitium so important?
Essential for urine concentration
Are there examples of the same kind of Interstitial environment found in the nephron elsewhere in the body?
No
T/F
Nephron only interstitium in body that can stand a Hypertonic environment
True
How do the transport characteristics of the thin descending and ascending limbs of the Loop of Henle differ?
Thin descending: reabsorbs Water (no NaCl)
This ascending: reabsorbs NaCl (no Water)
How much water does the thin descending limb reabsorb per day?
30-40 Liters
How much (%) NaCl does the thin/thick ascending loop of Henle reabsorb per day?
20-25% of Filtered load
The thin descending limb concentrates fluid from 300 to _____ mOsm/L
(long looped nephrons)
1200
The thick ascending limb dilutes fluid from 1200 mOsm/L to _______
100
At the tip (of the Loop of Henle), what is the osmolarity of short nephrons?
long looped nephrons?
800 (short looped)
1200 (long looped)
What immediately transports water away from the interstituim, thereby preventing the neutralization of the osmotic gradient?
Vasa Recta
specialized capillaries
What is the common term for the ascending limb of the loop of Henle?
**Why?
Diluting Segment
**resorption results in dilution
What is the unique transporter found on the Luminal membrane of the Thick Ascending Limb?
What is on the Basolateral side?
Na/K/2Cl co-transporter
Na/K ATPase
What are 2 reasons the tubular lumen must have a high concentration of K+
Na/K/2Cl cotransporter
Generates Lumen positive potential to drive Paracellular transport of other cations
How are Na, K, Ca, Mg reabsorbed Paracellularly?
K gradient in Lumen
Which class of drugs affect transport in the Thick Ascending Limb?
Name 2
Loop Diuretics
Furosemide
Bumetanide
What do Loop Diuretic inhibit?
Na/K/2Cl Cotransporter
The Distal Nephron is made up of what two structures/segments?
Distal Convoluted Tubule
Collecting Tubule
What fraction of the filtered load of Water and NaCl remain by the time the Distal Nephron is reached?
10% Water
10% NaCl
What 2 hormones regulate Water and Na reabsorption in the Distal Nephron?
ADH - water
Aldosterone - Na
What happens to the distal collecting tubule in the presence of ADH?
Antidiuresis
Distal Collecting Tubule more permeable to water
T/F
In Diuresis, the distal collecting tubule is impermeable to water due to lack of ADH
True
Why does tubular fluid become even more dilute from beginning to end of Distal nephron?
NaCl further reabsorbed
How does ADH make the collecting tubule cell permeable to water?
What side is affected?
Aquaporin II inserted on Luminal side
What second messenger does ADH use to stimulate AQP-2 on the Luminal membrane?
What is the pathway?
cAMP
Basolateral ADH > cAMP > PKA > AQP-2
AQP-2 is in what membrane?
AQP-3 is in what membrane?
Luminal
Basolateral
Where are Aquaporins in the low ADH state?
Intracellular vescicles
*storage
T/F
Both AQP-2 and AQP-3 are under the influence of ADH
False
*AQP-3 on basolateral side constitutively expressed
What are the 2 effects of Aldosterone and where does it act?
Reabsorbs Na+
Secretes Potassium
Cortical collecting tubule
What is the intracellular mechanism of Aldosterone?
Steroid hormone, so stimulates Transcription factors for Na/K pumps
ADH is _____, while Aldosterone ______
Fast acting
Takes hours
Circulating Glucocorticoid (cortisol) is prevented from affecting Na reabsorption by what enzyme?
11 B-hydroxysteroid dehydrogenase type 2
*mutations of which cause hypertension (also licorice)
What is countercurrent multiplication?
Deposition of NaCl
T/F
Without countercurrent multiplication, isotonic fluid of 100 mM NaCl would flow through the ascending limb into the distal tubule
True
3 Step model of Countercurrent Multiplication
Step 1: NaCl from ascending tubule flows into interstitium via Active Transport
Step 2: Water from descending tubule follows Na via Passive Diffusion
Step 3: Multiple cycles sets up Vertical Gradient
The Vertical Gradient goes from 590 to 315, but the Horizontal Gradient is always within…
100-200 mOsm
What section of tubule cannot reabsorb urea?
What sections can?
In what section is Urea passively diffused into the interstiitum?
Cortical/outer medullary collecting tubule
Outer Medullary and Inner Medullary
Inner Medulla
Why is ADH important for Urea reabsorption?
Increases permeability of Inner Medullary section of the collecting tubule
What is the term for Urea diffusing from Inner Medullary Collecting tubule to the Interstitium, then re-concentrated and reabsorbed?
Urea recycling
T/F
Decrease in ADH will decrease Urea excretion
True
A decrease in ADH will decrease Urea reabsorption, which decreases general osmolarity. What else, then, is affected by a decrease in ADH?
Decrease in interstitial NaCl
What ensures the hypertonic gradient in the medullary interstitium remains Hypertonic
Countercurrent Exchange in the Vasa Recta
The osmolality of the Vasa Recta will be higher flowing out than in. Why?
Reabsorbs all water by descending limb
Reabsorbs Most NaCl by ascending limb
How is the hypertonicity of the Medulla maintained by the Vasa Recta?
As it flows out, NaCl and Urea flow from Plasma to Interstituim
Why is the flow rate of the Vasa Recta higher flowing out than in?
Picks up all water from descending limb
What happens to Medullary cells in a hypertonic environment?
In this environment, what diffuses into cells to disrupt proteins?
Shrinkage
Urea
What protects Medullary cells from their hypertonic environment full of urea?
What is the Transcription factor?
Organic Osmolytes
TonEB
What increases intracellular osmolarity and disrupts Urea effects in the cell?
Osmolytes
*by TonEB
What is the Balance Concept?
Water Input = Water Output
What are the major sources of Water Input and Output?
Input: Food, Fluid, Metabolism
Output: Insensible losses (feces, sweat, urine)
Maximum Diuresis Urine Volume:
Maximum Antidiuresis Urine Volume:
20-25L/day
.5L/day
Why can’t we shut down water excretion completely in extreme circumstances?
500mL is lowest volume to dissolve solutes that MUST be excreted in solution
What class of hormone is ADH?
Peptide hormone
Where is ADH synthesized?
Stored and Secreted?
Supraoptic and Paraventricular nucleii of hypothalamus
Posterior Pituitary
ADH secretion is regulated by what 2 receptors?
Hypothalamic osmoreceptors
Volume receptors (baroreceptors)
What regulatory mechanism of ADH secretion is more sensitive, the osmoreceptors of the hypothalamus or the volume receptors?
Osmoreceptors
Do the Barorecptors and Osmoreceptors regulating ADH interact?
Yes. Volume status influences osmolality and ADH secretion
What is the plasma osmolality at which ADH secretion = 0
Set point
T/F
Small changes in ADH can elicit large changes in urine osmolality
True
In a state of water deficit, an increase in ADH will do what?
Minimize further loss of water
*not replace
What controls thirst?
Extracellular Osmolarity
What can be caused by Trauma, Tumors, or Drugs that affects ADH?
SIADH
Syndrome of Inappropriate ADH secretion
In SIADH, there is an overproduction of ADH, leading to Hyponatremia, and can lead to coma
True
What are the 2 causes of Diabetes Insipidus?
Hypothalamic
Nephrogenic
T/F
In diabetes insipidus, you have no ability to reabsorb water, so urine output is very high. Leads to Hypernatremia.
True
2 treatments for Diabetes Insipidus:
synthetic ADH nasal spray
make sure Water output = Water input
What is the assessment of the diluting efficiency of the thick ascending limb?
Free Water Clearance
The amount of distilled water that must be added to or removed from urine to create an Isotonic fluid is Free Water Clearance, and tells us…
Diluting efficiency of Thick Ascending Limb
Is the standard Clearance formula used for Free Water Clearance?
No
Ch2o = V - Cosm
When would Free Water Clearance = 0
When excreting Isotonic Urine
When Hypertonic urine is excreted, what is the term used?
Free Water Absorption
What are 3 reasons ECF volume is directly related to total body NaCl?
ECF to ICF shifts
ADH secretion/distal nephron reabsorption
Thirst
How do kidneys maintain constant ECF?
Adjust NaCl excretion to match NaCl intake
Na+ excretion is primarily regulated by _____ on the ________.
(latter is only place Aldosterone affects Na reabsorption )
Aldosterone
Cortical Collecting Tubule
In what 3 ways does Aldosterone control reabsorption of Na+?
Na+ channels on Luminal side
Na/K ATPase synth
Increases Krebs enzyme synth
(more ATP for ATPase)
The action of Aldosterone takes _______.
The action of ADH takes _______.
Hours
Minutes
Why is the measurement of extracellular fluid sodium concentration not a reliable index of total body sodium content?
What is a better measurement for sodium content?
Volume from ICF compensates and returns osmolarity to normal.
ECF Volume
What is ECV?
How is it monitored?
Effective Circulating Volume
Baroreceptors
*this is an effective measurement of Sodium
What is the rate limiting step in the Renin-Angiotensin-Aldosterone System?
Renin release from Kidney
T/F
Renin is a hormone
False
*it’s an enzyme
Where is Antiotensinogen synthesized?
Liver
*in circulation
Where is Angiotensin I converted to Angiotensin II?
Lungs
Where is Aldosterone synthesized?
Zona glomerulosa of Adrenal Cortex
What is the apparatus that regulates renal blood flow and glomerular filtration rate found by the glomerulus?
Juxtaglomerular apparatus
Where is Renin synthesized?
Granular Cells of the Juxtaglomerular Apparatus
What are the 3 mechanisms regulating Renin release?
Baroreceptors
Sympathetic nerves
Macula Densa
Why doesn’t the autoregulatory control of the Macula Densa increase pressure? Why the Renin?
Blood Pressure (macro) has to increase
What increases Cardiac Output to help restore “normal” blood pressure despite low ECV>
Angiotensin II’s Rapid Onset effects
What are the 2 longer onset effects of Angiotensin II?
Decrease NaCl and water excretion
Increase NaCl and water intake
T/F
Sustained increases in aldosterone secretion results in relatively transient Na+ retention
True
What is the cessation of Sodium retention of Aldosterone due to pressure natriuresis and pressure diuresis?
Aldosterone Escape
ECF volume after escape…
Continues to rise?
Positive sodium balance:
Negative sodium balance:
Intake > excretion
Excretion > intake
What is the most direct indication of a Positive and Negative sodium balance?
Water Retention or Water Excretion
Why do the Kidneys have a difficult time with sudden and sustained changes in sodium intake?
Because it operates on Aldosterone and is transcription/channel dependent, Kidney takes days to adjust.
Where is Atrial Naturetic Peptide synthesized?
What stimulates its release?
Atrial Monocytes
ECV increase
In what 4 ways does ANP excrete salt?
Vasodilation afferent arteriole
Aldosterone inhibition
NaCl reabsorption inhibition
Inhibits ADH release/action on collecting tubule
T/F
Under normal circumstances, ANP doesn’t do much
True
- things must be whack
- *AngII is primary means of regulation
What condition is a result of mutations in one or more ascending limb transport proteins?
Bartters Syndrome
5 physiological abnormalities of Bartter’s Syndrome:
Salt wasting Volume depletion Hyperreninemic hyperaldosteronism Hypercalciuria Hypokalemic metabolic alkalosis
What disease is marked by fluid filled sacs that develop from renal tubular epithelial cells
(and is autosomal dominant 85%)
Polycystic Kidney Disease
Name 4 classes of Diuretics
Proximal tubule carbonic anhydrase inhibitors
Thick ascending limb “loop diuretics”
Distal tubule luminal NaCl cotransport inhibitors
Collecting tubule K+ sparing diuretics (inhibit Na channels)
What is the accumulation of excess fluid in the interstitial space?
*caused by?
Edema
*Starling forces out of whack
How does normal kidney function exacerbate edema?
Reabsorbs Na and Water, which decreases Oncotic Pressure
