Renal Physiology: Clearance-Solutes Flashcards
What does volume balance refer to?
-ECF volume homeostasis, more specifically plasma
What does volume balance NOT refer to?
- not total body water
- Not ICF volume
What is effective circulating volume?
-a functional blood volume that reflects the adequacy of regional tissue perfusion
When does total ECF volume not parallel effective circulating volume?
- CHF
- Chronic kidney disease
- hepatic cirrhosis
What does a change in water balance refer to?
- a discrepency between water intake and excretion
- coses a change in body fluid osmolarity, with minimal change in ECF volume homeostasis
What does a change in Na balance refer to?
- discrepency between Na intake and excretion
- implies a change in volume homeostasis
What is the main driver of extracellular fluid volume?
-sodium balance
What is clearance?
-the hypothetical minimum renal plasma flow needed to deliver enough solute that is measured
What is the formula for Clearance?
Cx =( Ux)(V.) / (Px)
What is an indirect way to determine RPF?
- calculate the clearance of PAH
- all of PAH is excreted, so Clearance = RPF
What is the general formula for total excretion?
Excretion = filtration + secretion - reabsorption
What is the filtered load?
- glomerular filtration rate times solute concentration of (x)
- assumes free filterability of x
What is fractional excretion?
- what portion of the solute filtered in the glomerulus becomes excreted
- time independent
What is fractional reabsorption?
-the converse of fractional excretion
What makes up ultrafiltrate?
-contents of blood except large proteins and RBCs
How can renal plasma flow be calculated from hematocrit?
RPF = (1-Hct) x RBF
What is permselectivity?
-restriction of permeation of macromolecules across a glomerular capillary wall on the basis of molecular size, charge, and physical configuration.
What does it mean to have a sieving coefficient of 1?
-the concentration of the solute in the ultrafiltrate is the same as that of blood plasma
What are the qualities of a solute that make it an ideal marker for GFR?
- Freely filtered
- Not secreted or reabsorbed
- not synthesized or metabolized by the kidey
What is inulin?
-a synthetic molecule that can be used, although not easily, to measure GFR
(T/F) the concentration of inulin in the collecting duct is equal to the concentration of inulin in the efferent arteriole leaving bowman’s capsule.
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When is creatinine clearance a less reliable measure of GFR?
- Renal disease
- if GFR has changed
- conditions associated with muscle damage
What forces oppose ultrafiltration?
- The glomerular capillary osmotic/oncotic pressure
- the bowman’s space hydrostatic pressure
- permeability of the filtration barrier
What forces contribute to ultrafiltration?
- The glomerular capillary hydrostatic pressure
- bowman’s space oncotic/osmotic pressure
- permeability of the filtration barrier
What is oncotic pressure?
-osmotic pressure
What is filtration fraction (FF)?
FF = GFR/RPF
The ratio between GFR and RPF
What is RPF?
- renal plasma flow
- how much plasma is flowing through the kidneys
What is glomerulotubular balance?
- the ability of each successive segment of the proximal tubule to reabsorb a constant fraction of glomerular filtrate and solutes delivered to it
- if GFR were to double, so would the filtered load of the solute. Thus GT balance will increase tubular reabsorption to keep the same ratio of reabsorbed:filtered
What is tubuloglomerular feedback?
- cells of the macula densa sense an increase in GFR, and generate signals that increase afferent arteriolar resistance
- this returns GFR towards dormal
What does the macula densa do?
- detects increases in solute concentration in the distal tubule
- changes in solute concentrations represent changes in GFR
Where is the majority of Na reabsorbed?
-proximal tubule
66%
What is solvent drag?
-When water drags ions along with it as it diffuses across a membrane
What is the stoichiometry of the Na, K, Cl transporter of the thick ascending loop of henle?
Na:K:Cl
1:1:2
(T/F) Water transport in the nephron is always passive.
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Where is the nephron permeable to water? Impermeable?
- Permeable in PCT, PST, thin descending limb normally
- Impermeable from TDL on, unless ADH is present, which increases permeability in the cortical and medullary collecting ducts
Tell me about glomerulotubular balance and its role in regulating Na transport.
- it controls sodium reabsorption in the proximal tubule when GFR fluctuates.
- the fractional reabsorption of sodium remains constant
How will a loss or gain of potassium affect cellular pH?
-potassium excretion will lower pH
Are there any sodium potassium pumps on the lumenal side of the cell membrane of nephrons?
No
What does it mean for a solute to be freely filtered?
- it has a sieving coefficient of 1
- the concentration of the solute in the ultrafiltrate is equal to the the concentration of that solute in the plasma
What does the ultrafiltration coefficient (Kf) represent?
-the permeability of the filtration barrier of the glomerulus
What is filtration equilibrium?
-the point along the glomerular capillary where the glomerular capillary osmotic pressure cancels out the hydrostatic pressure of the glomerular capillary, and filtration stops
How does angiotensin II do work on the kidney?
- increases renal vasoconstriction, especially in efferent arteriole
- contraction of the mesangial cells, decreasing glomeurlar srface area
- lowers GFR
- decreases medullary blood flow
What portions of the nephron are responsible for day to day fine tuning of urinary sodium excretion?
- distal tubule
- collecting duct
In which portions of the nephron is sodium reabsorbed?
- proximal convoluted tubule
- thick ascending limb
- distal convoluted tubule
- cortical collecting tubule
How does sodium enter the tubule cell in the PCT during reabsorption?
- diffuses passively down it’s concentration gradient as the cell is more negative than the lumen, and the concentration of sodium is lower inside the cell
- enters via cotransport or countertransport
is the descending thin limb permeable to sodium?
-no, not really
What type of sodium reabsorption occurs in S1 of the PCT?
- mostly transcellular
- not so much paracellular because of the electrochemical gradient, but solvent drag still occurs
What type of sodium reabsorption occurs in the thin ascending limb?
-paracellular
What type of sodium reabsorption occurs in the thick ascending limb?
- paracellular
- transcellular via Na/K/Cl cotransporter, and the Na/H countertransporter
What do loop diuretics inhibit?
the Na/K/Cl cotransporter of the thick ascending limb
What type of sodium reabsorption occurs in the distal convoluted tubule?
- Transcellular
- Na/Cl cotransporter
What diuretics block the Na/Cl cotransporter of the DCT?
-thiazides
What type of sodium reabsorption occurs in the cortical collecting tubule?
- pretty much only transcellular
- only in principal cells via epithelial sodium channels
What types of cells are in the cortical collecting tubule?
- principal
- intercalated
What diuretic blocks epithelial sodium channels in the cortical collecting tubules?
-amiloride
What type of Cl reabsorption occurs in the proximal tubule?
- early tubule is mostly paracellular fueled by electrochemical gradient generated by Na transport
- later tubule is more transcellular
- Solvent drag along whole proximal tubule
How does chloride exit the basolateral memrane of tubule cells?
- chloride channels
- K/Cl cotransporter
How is chloride reabsorbed in the loop of henle?
- no reabsorption in descending limb
- paracellular passive in thin ascending limb
- active and transcellular in TAL via Na/K/Cl cotransporter
How does chloride exit the basolateral membrane of loop of henle cells?
-Cl channels
How does chloride reabsorption occur in the distal convoluted tubule?
- mostly transcellular
- uptake from lumen via Na/Cl cotranspoter
How does chloride exit the basolateral membrane of distal convoluted tubule cells?
-via Cl channels
How does chloride reabsorption occur in the cortical collecting tubule?
- Principal cells = paracellular
- Intercalated = transcellular via apical chloride/bicarb countertransport
How does Chloride exit the basolateral membrane of cortical collecting tubule cells?
Cl channels
Where in the nephron is chloride reabsorbed?
- Proximal tubule
- ascending loop of henle
- Distal convoluted tubule
- cortical collecting ducts
Is water reabsorbed more transcellularly or paracellularly in the PCT?
-probably transcellularly due to aquaporins
What are the three anti-natriuretic neurohumoral factors that affect sodium transport?
- aldosterone
- norepinephrine
- AVP/ADH
How does aldosterone affect sodium reabsorption?
- it stiumlates Na/Cl reaborption in principal cells of the collecting tubules
- activates apical sodium channels and the basolateral Na/K-ATPase
How does noreipinephrine affect sodium reabsorption?
- it causes renal vasoconstriction, lowering GFR and RPF
- increases Na/H-countertransport in PCT cells, along with basolateral exit via Na/K-ATPase
How does AVP/ADH affect sodium transport?
- it stimulates the Na/K/Cl cotransporter in the thick ascending limb
- increases number of open sodium channels on apical membrane of principal cells in collecting ducts
What are teh five natriuretic neurohumoral factors that affect sodium transport in the kidneys?
- ANP
- endogenous adenosine triphosphatase inhibitor
- dopamine
- Bradykinins
- Prostaglandins
How does ANP affect sodium transport?
- increases Na excretion via increasing RPF and GFR
- inhibits sodium reabsorption in the inner medullary collecting duct
How does Endogenous adenosine triphosphatase inhibitor affect sodium transport?
-it inhibits the basolateral Na/K-ATPase, which decreases transcellular Na transport
How does dopamine affect sodium transport?
- it increases RPF and GFR
- inhibits tubular Na/H exchange
- Inhibits basolateral Na/K-ATPase activity
How do bradykinins and prostaglandins affect sodium transport?
- inhibit sodium transport by modifying Na channels in the cortical collecting tubule
- Indirect: decreasing K-dependent lumen positive charge in the thick ascending limb
Where does most potassium reabsorption occur?
the proximal tubule
How is potassium reabsorbed in the proximal tubule?
- passive and paracellular
- solvent drag in early proximal tubule due to negative lumen voltage
Describe the voltage of the lumen of the proximal tubule?
early it is negative, then it becomes more positive later
Describe the movement of potassium in the descending loop of Henle.
-potassium is secreted paracellularly due to a high potassium concentration in the medullary interstitial space
What is the process of potassium secretion into the descending limb called?
potassium recycling
How is potassium reabsorbed in the thin ascending limb?
-passive paracellular driven by high luminal potassium concentration
Why is there such a high potassium concentration as you round the loop of henle to the ascending limb?
- medullary potassium recycling, lots of potassium secretion in the descending limb
- passive water reabsorption in the thin ascending limb raises lumen osmolarity
How is potassium reabsorbed in the thick ascending limb?
- both paracellular and transcellular
- Paracellular: positive lumen as driving force
- Transcellular via Na/K/Cl Cotransporter
How does potassium exit the lumenal cells in the thick ascending limb?
-potassium channels
Why are there apical potassium channels in cells of the thick ascending limb?
- so that potassium may leak out into the lumen
- this prevents the lumenal potassium concentration from falling so low that the Na/K/Cl cotransporter is inhibited.
In what portion of the nephron is potassium balance regulated?
- portions after the loop of henle
- however, reabsorption always occurs in the medullary collecting ducts regardless of overall potassium balance
Why is potassium always reabsorbed in the medullary collecting ducts regardless of overall potassium balance?
-to initiate medullary potassium recycling by increasing the [K] in the medullary interstitium
How is potassium reabsorbed by alpha intercalated cells of the cortical collecting duct?
- transcellular
- active H/K-ATPase
How does potassium exit the basolateral membrane of alpha intercalated cells of the cortical collecting duct
via a potassium channel
How are principal cells of the cortical collecting duct involved in potassium transport? What is the mechanism of transport?
- they secrete potassium back into the lumen
- basolateral Na/K-ATPases bring K into the cells, then they are secreted into the lumen by apical K channels and K/Cl cotransporters
What are the two catagories of factors that regulate potassium excretion in the kidneys?
- Luminal
- Peritubular
What is the most important factor that determines the rate of potassium excretion?
the luminal flow rate of tubular fluid
What compromises luminal factors that regulate potassium excretion?
- luminal flow rate of tubular fluid
- things that affect luminal voltage
What compromises peritubular factors that regulate potassium excretion?
- overall state of potassium balance
- Aldosterone
- Glucocorticoids
What happens when we have a high overall [K}?
- increased [K] stimulates cellular potassium entry in luminal cells via Na/K-ATPase
- Next, aldosterone is synthesized, which stimulates K secretion in the collecting ducts
How does aldosterone increase K excretion?
- stimulates basolateral Na/K-ATPase activity
- increases apical K permeablilty
- Stimulates Na reabsorption from lumen
- Thus, lumen is more negative, luminal cell [K] is hight, so strong electrochemical gradient to push K out of cell into the lumen
How do Glucocorticoids increase potassium secretion?
- increase GFR
- increases sodium delivery which increases potassium secretion
Where does most urea reabsorption occur in the nephron?
-The majority occurs in the proximal tubule
How is urea reabsorbed by the proximal tubule?
- both para and transcellular
- most is paracellular and dependent on water reabsorption
- solvent drag
How is urea excreted in the thin descending limb?
- concentration of urea in medullary interstitium exceeds concentration in lumen
- tubular cells have UT2 urea transporter that allows urea secretion to occur
- some secretion also occurs in the ascending limb
How is urea transported in the inner medullary collecting duct?
- urea is reabsorbed transcellularly
- Apical intake via UT1 transporter
- Basolateral exit via UT4 transporter
What is a big determinant of urea reabsorption and secretion? Why?
- Urine flow rates
- this is because urea reabsorption and secretion are passive processes
- increasing urine flow will decrease urea reabsorption
What normally happens to glucose in the kidney?
-it is freely filtered but is completely reabsorbed
How is glucose reabsorbed in the proximal tubule?
- Secondary active transport via sodium-glucose cotransporter
- Proximal = SGLT2
- S3 = SGLT1
How is glucose moved across the basolateral membrane in the proximal tubule?
- GLUT2 in early PT
- Glut1 in late PT
What happens to amino acids in the kidney?
- they are freely filtered by the glomerulus
- nearly complete reabsorption in the proximal tubule
What transporters are involved in amino acid reabsorption?
- cysteine transporter
- neutral amino acid transporter
How do amino acid transporters work?
- sodium dependent secondary active transport
- Na-AA cotransport
- only a few Na-independent
How does basolateral AA exit ocur?
-facilitated diffusion
Describe renal handling of oligopeptides.
- small oligos can be filtered by the glomerulus
- most are hydrolyzed by peptidases on luminal membrane
- then reabsorbed in same way as amino acids
- some are resistant to hydrolysis, so they enter via H-Oligo cotransporter
Where is posphorus reabsorbed by the nephron?
- 80% Proximal tubule
- 10% Distal tubule
- 10% excreted
How is phosphorus reabsorbed by the proximal tubule?
- mostly transcellular
- Apical uptake via Na-Phosphate cotransport
What are the regulators of phosphate absorption?
- PTH (Big boy)
- dietary intake
- ANP
- Glucocorticoids
- Acidosis
- Vitamin D
How does PTH affect phosphate reabsorption?
- PTH inhibits phosphate reabsorption
- it removes apical Na-Phosphate transporters
Describe calcium handling in portions of the nephron.
- 65% reabsorbed in PT
- 25% reabsorbed in TAL
- 1.5% reabsorbed in Medullary collecting duct
Is handling of calcium in the PCT under hormonal control?
-no
How is calcium reabsorbed in the proximal tubule?
- mostly solvent drag
- voltage driven uptake in S2 and S3
- small amount of transcellular uptake via apical calcium channels
How does basolateral calcium exit work in the proximal tubule?
- Na/Ca countertransport
- Ca/H ATPase
How is calcium reabsorbed in the thick ascending limb?
- half passive paracellular, half transcellular
- paracellular driven by positive lumen
- transcellular entry via epithelial calcium channels
How does basolateral calcium exit work in the thick ascending limb?
- Na/Ca countertransport
- Ca/H-ATPase
How is calcium reabsorbed in the distal convoluted tubule?
-mostly transcellular
How does sodium balance affect Ca reabsorption?
- Lots of Ca reabsorption is paracellular
- when sodium reabsorption increases, so does Ca
How does PTH affect reabsorption of calcium?
-it stimulates apical calcium uptake in the thick ascending limb, DCT, and collecting duct
How do loop diuretics decrease Ca reabsorption?
-they inhibit the Na/K/Cl cotransporter, thus preventing the development of the positive voltage in the lumen that drives paracellular Ca reabsorption
