Exam 3 Britton Renal Physiology II Flashcards
Movement of solutes and H2O is via either ____ or ____
Paracellular transport or transcellular transport
What is paracellular transport?
Between cells and across tight junctions
What is transcellular transport?
Across both the luminal (apical) and the basolateral membrane
What primarily provides the driving force for solute movement?
Na+/K+-ATPase pump in the basolateral membrane
What are some mechanisms by which substances move across membranes for reabsorption or secretion?
- Diffusion
- Active transport (pumps)
- Facilitated diffusion
- Co-transport
- Counter transport (exchangers)
- Osmosis
Reabsorption can be ____ or ____
Active or passive
The mechanisms for reabsorption involve transporters where?
In the membranes of the nephron
Reabsorption depends mostly on ____
Active transport
Active transport of Na+ from tubule to blood creates a ____
Transepithelial electrical gradient
What is the transepithelial electrical gradient?
- Active transport of Na+ from tubule into blood
- Anions follow Na+ out of lumen
- Water leaves tubule via osmosis
- K+ reabsorption is due to solvent drag
____ is a hallmark of proximal tubular function
Isosmotic reabsorption
During isosmotic reabsorption, ____ and ____ are coupled to each other and are ____ to each other
Solute and H2O; Proportional
Glucose reabsorption in the proximal tubule requires what transporters?
- Na+/K+ ATPase pump
- SGLT2
- GLUT2
What is SGLT2?
Sodium glucose co-Transporter 2
____ establishes the concentration gradient for Na+
Na+/K+ ATPase pump
Normally, ___ of filtered glucose is reabsorbed
100%
The SGLT2 and GLUT2 mechanism in the _____ is responsible for ___ of glucose reabsorption. The remaining ____ is reabsorbed in the ____ involving SGLT1 and GLUT1
Early proximal tubule; 90%; 10%; Late proximal tubule
Where is SGLT2 located on the proximal tubule?
Apical membrane
Where is Na+/K+ ATPase pump located on the proximal tubule?
Basolateral membrane
Where is the GLUT2 transporter located on the proximal tubule?
Basolateral membrane
____ enables glucose to leave the cell down a concentration gradient
GLUT2
____ transports Na+ and glucose into the cell simultaneously
SGLT2
As plasma glucose increases, the filtered load will increase ____
Linearly
When the plasma concentration of glucose is less than 200 mg/dL, ____ is reabsorbed
All filtered glucose
When the plasma concentration of glucose is less than 200 mg/dL, why is reabsorption = filtration?
Because SGLT2 transporters are plentiful
When the plasma concentration of glucose is greater than 200 mg/dL, what happens?
Some of the filtered glucose is not reabsorbed, since the number of SGLT2 transporters is limited
At P>350 mg/dL, what happens? (glucose)
SGLT2 transporters are completely saturated and thus reabsorption levels off at maximal value (transport maximum)T
True or false: For glucose, when [P] < 200 mg/dL, all filtered glucose is reabsorbed and none is excreted
True
For glucose, when [P] > 200 mg/dL, the SGLT2 carriers are near ____. Glucose that is not reabsorbed is ____
Saturation; excreted
What is renal threshold for glucose?
[P]glucose at which glucose is first excreted in the urine (glucosuria)
At [P] glucose > 350 mg/dL, Tm is reached and SGLT carriers are ____. Glucose excretion in urine _____
Fully saturated; Now increases linearly
Excess glucose in diabetes: Tm occurs as ___ are saturated. Excess glucose in nephron tubule will ____. What symptoms will the patient experience?
SGLT; Osmotically hold water; Excess urination and thirst
What is splay?
Where reabsorption is approaching saturation but is not fully saturated
Of all functions of the kidney, ____ is the most important
Reabsorption of Na+
Na+ is the major cation of the ____
ECF compartment
What occurs during positive Na+ balance?
Hypernatremia
What is hypernatremia?
Abnormal increase of blood Na+
Hypernatremia can be caused by:
Hormonal imbalances
Describe what happens during hypernatremia
- Increased Na+ content in ECF
- Increased ECF volume (termed ECF volume expansion, attracts more water)
- Increased blood volume and MAP
- May be edema in the limbs
What happens in negative Na+ balance?
Hyponatremia
What is hyponatremia?
An abnormal decrease of blood Na+
Describe what happens during hyponatremia
- Decreased Na+ content in ECF
- Decreased ECF volume (ECF volume contraction)
- Decreased blood volume and MAP
What diseases/situations can lead to hyponatremia?
- Sweating
- Vomiting
- Diarrhea
- Diuretics
- Diabetes
___% of the filtered load of Na+ is subsequently reabsorbed in various segments throughout the nephron. ___% is excreted
99%; 1%
What % of Na+ is reabsorbed in the proximal tubule?
~65%
What % of Na+ is reabsorbed in the thick limb of the ascending loop of Henle?
~25%
What % of Na+ is reabsorbed in the early distal tubule?
5-10%
What % of Na+ is reabsorbed in the principal cells of the late distal tubule and collecting duct?
1-5%
In the early proximal tubule, Na+ is co-transported with:
- Glucose
- Amino acids
- Phosphate
In the early proximal tubule, Na+ is exchanged for:
H+ (via Na+/H+ exchanger)
Na+ co-transporters and exchangers are located on what surface of the PT cell?
Apical
On which membrane is the Na+/K+ ATPase located? (early PT)
Basolateral
The late proximal tubule allows for additional Na+ movement across the membrane through what mechanism?
Cl- gradient (paracellular transport)
In the proximal tubule, ____ reabsorption is always linked to Na+ reabsorption. This mechanism is described as ____
H2O; isosmotic
How is Na+ reabsorbed in the thick ascending limb of LoH?
Via the Na+-K+-2Cl- co-transporter (NKCC) on apical membrane
NKCC is inhibited by:
Loop diuretics
How is Na+ reabsorbed in the early distal tubule?
Via the NaCl co-transporter (NCC) on the apical membrane
NCC is inhibited by:
Thiazide diuretics
How is Na+ reabsorbed in the principal cells of the late DT and collecting duct?
- Via epithelial Na+ channels (EnaC) on the apical membrane
- Na+ diffuses through these channels down its electrochemical gradient
The nephron Na+ reabsorption at the late DT and collecting duct is regulated by what hormone?
Aldosterone
ENaC are inhibited by:
K+-sparing diuretics
What mechanisms regulate renal Na+?
- Sympathetic nerve activity
- Atrial Natriuretic peptide (ANP)
- Starling forces in peritubular capillaries
- Renin-angiotensin-aldosterone system
Describe how sympathetic nerve activity regulates renal Na+
- Decreased MAP activates the baroreceptor mechanism
- Causes vasoconstriction of afferent arterioles
- Leads to decreased GFR and increased Na+ reabsorption in PT
Describe how atrial natriuretic peptide (ANP) regulates renal Na+
- Increase in ECF volume
- ANP secreted by atria
- Vasodilation of afferent arterioles and vasoconstriction of efferent arterioles
- Increases GFR, decreases Na+ reabsorption
ANP secretion leads to ____ Na+ reabsorption
Decreased
Sympathetic nerve activity leads to ____ Na+ reabsorption
Increased
Increase in ECF volume leads to ____ Na+ reabsorption in the PT
Decreased
Decrease in ECF volume leads to ____ reabsorption in the PT
Increased
RAAS system is activated in response to:
Decreased MAP (decreased renal perfusion pressure)
Na+ reabsorption is governed by what 2 hormones?
- Angiotensin II
- Aldosterone
Angiotensin II stimulates Na+ reabsorption in the ___ via ___
PT; Na+-H+ exchange
Aldosterone stimulates Na+ reabsorption in the ____
Late DT and collecting duct
The actions of Angiotensin II cause:
Increased total body Na+, total body H2O, and vascular tone
Aldosterone is a steroid hormone secreted by:
Zona glomerulosa of the adrenal cortex
Aldosterone release is stimulated by:
Angiotensin II
- Aldosterone is delivered to the ____ via the circulation and diffuses into cells across the ____
- Aldosterone transfers to the ____, where it stimulates the synthesis of mRNA involved in Na+ reabsorption, including ____ and ___
- Principal cells; Basolateral cell membrane
- Nucleus; ENaC and Na+/K+ pump
What is the function of the principal cells in the late distal tubule and collecting duct?
- Reabsorb Na+ from tubular filtrate
- Secrete K+ into the filtrate
(thus aldosterone causes increased Na+ reabsorption and H2O)
____ increases K+ secretion
Aldosterone
How much K+ is reabsorbed in the proximal convoluted tubule?
67%
How much K+ is reabsorbed in the thick ascending limb of LoH?
20%
What is responsible for fine tuning K+ excretion that occurs when dietary K+ varies?
- Distal tubule
- Collecting duct
True or false: Principal cells in the DT reabsorb K+
False - secretes K+
____ reabsorb K+ in the DT and CD
alpha-intercalated cells (also H+ secretion)
What are the 4 renal effects of aldosterone?
- Decreased Na+ excretion in urine
- Decreased Cl- excretion in urine
- Increased K+ excretion in urine
- Increased NH4+ excretion in urine
A number of sensors detect changes in the blood volume or plasma Na+ concentrations, such as:
- Carotid baroreceptors
- Juxtaglomerular cells (intrarenal baroreceptirs)
- Macula densa
- Stretch receptors in atria (ANP release)
The release of renin ultimately leads to ____ production, increased ____ reabsorption and ____ retention
ANG II; Na+; H2O
H2O reabsorption occurs mainly in the ____. Reabsorption is by ____
Proximal tubule; osmosis
What are the different segments of the loop of Henle? What are these segments responsible for?
- Thin descending limb, thin and thick ascending limb
- Responsible for countercurrent multiplication
Countercurrent multiplication is essential for:
The concentration and dilution of urine
Where does H2O reabsorption occur?
In the descending limb of the LoH and at the collecting duct via aquaporins in the membrane
The structure of the ___ and associated ____ create a countercurrent multiplier system
LoH and vasa recta
In the countercurrent multiplier system, where does the term countercurrent come from?
The fact that the descending and ascending limbs of the LoH are next to each other and their fluid flows in opposite directions
In the countercurrent multiplier system, where does the term multiplier come from?
Due to the action of solute pumps that increase (multiply) the concentrations of urea and Na+ deep in the medulla
There is ____ osmolality as you go deeper into the medulla
Increased
In the countercurrent multiplier system:
____ concentrates the filtrate
____ dilutes the filtrate
Descending loop; Ascending loop
Is the descending loop permeable to water?
Yes, aquaporin channels are present and is impermeable to Na+ and Cl-
Is the ascending loop permeable to water?
No, but transporters such as NKCC are present for reabsorption
Anti Diuretic Hormone (ADH) is secreted from ____
Pituitary gland
What stimuli cause the release of ADH?
- Osmoreceptors
- Baroreceptors
- ANG II
What are the two major effects of ADH?
- Arteriole constriction in the peripheral circulation – reduces blood flow to the kidney
- Causes epithelial cells that line the nephron collecting duct to insert aquaporins into the apical cell membrane
INCREASES water reabsorption into the blood
Actions of ADH in the Kidney
- ADH acts via V2 receptor
- Causes aquaporins to be inserted into the apical membrane of principal cells
- dramatically increases the reabsorption of H2O to the blood
Cardiovascular: ADH vascular receptor is ____
V1
What is the action of ADH in the cardiovascular system?
Potent vasoconstrictor and increases blood pressure
What is the effect of ADH on water reabsorption in the collecting duct?
- Without ADH, the late DT and CD are impermeable to water
- With ADH release, AQP-2 channels are present. Late DT and CD become permeable to H2O
What are the critical roles of phosphate in the body?
- Constituent of bone
- Urinary buffer for H+ (acid base balance)
What regulates blood phosphate concentration?
Kidneys
Where is phosphate localized primarily in?
- Bone matrix
- ICF
- ECF
In the ICF, phosphate is a component of:
- Nucleotides
- High energy molecules (ATP)
- Metabolic intermediates
In the ECF, phosphate is present in its ____ form and serves as a ____ for H+. ~10% phosphate in plasma is ____
Inorganic; buffer; Protein bound
Phosphate not bound to plasma proteins is ____
Filtered
What % of phosphate is reabsorbed?
85% (70% in the PCT, 15% in the proximal straight tubule)
Phosphate reabsorption is via what transporter in the nephron membrane?
Na+-phosphate cotransporter
True or false: Phosphate reabsorption is saturable and therefore exhibits a Tm
True (when Tm is reached, any phosphate not reabsorbed will be excreted)
What % of phosphate is excreted?
15%
The high level of excretion of phosphate (15%) is important because:
Unreabsorbed phosphate is a urinary buffer for H+ (titratable acid)
What regulated phosphate reabsorption in the PT?
Parathyroid hormone
Parathyroid hormone ____ Na+/phosphate co-transport which ____ the Tm for phosphate reabsorption
Inhibits; decreases
99% of the body’s Ca2+ is contained in ____. 1% is present in ____ and ____
Bone; ICF and ECF
What is the total [Ca2+] in plasma?
10 mg/dL
Of the total plasma Ca2+:
____ is bound to plasma proteins
____ is bound to other anions such as phosphate and citrate
____ is in the free, ionized form
40%; 10%; 50%
Can Ca2+ bound to plasma proteins be filtered across glomerular capillaries?
No - therefore only 60% plasma Ca2+ is filtered
What % of filtered Ca2+ is reabsorbed?
> 99%
Renal handling of Ca2+
____ is reabsorbed in the PT
____ is reabsorbed in the TAL
____ is reabsorbed in the DT
67%; 25%; 8%
Plasma [Ca2+] is regulated by ____
Parathyroid hormone
____ stimulates Ca2+ reabsorption at the DT
Parathyroid hormone
____ plasma Mg2+ is filtered
____ Mg2+ reabsorbed
80%; 95%
____ Mg2+ reabsorbed in the PT
____ Mg2+ reabsorbed in the DT
____ Mg2+ reabsorbed in the TAL
30%; 5%; 60%
What is Mg2+ reabsorption driven by?
The potential difference generated by NKCC
What is the major site of Mg2+ reabsorption?
Thick ascending limb of LoH
