Chapter 5: Renal and Acid-Base Physiology Flashcards
Total Body Water (TBW)
60% of body weight
High in newborns and adult males.
ICF
2/3 of TBW
Mg++ and K+ are major cations
Anions are Protein and Organic Phosphates
ECF
1/3 of TBW
Interstitial Fluid (3/4 of ECF) and PLasma (1/4 of ECF).. Ultrafiltrate of Plasma with little protein.
Cation: Na+
Anion: Cl- and HCO3-
TBW marker
H30, D2O and Atnipyrene
( distributes throughout body compartments)
ECF Marker
Mannitol, Inulin and Sulfate
goes into plasma and interstitial fluid
Plasma Marker
Evans blue, RISA
(binds albumin and cannot leave plasma fluid)
Equation for Volume
Volume = g/(g/ml) aka grams/Conentration
How can you calculate Interstitial Fluid ?
Interstitial = ECF (Mannitol, Innulin or sulphate) - Plasma (Evans Blue and Risa
How can you calculate Intracellular Fluid (ICF)
TBW (H30, D20) - ECF (Mannitol, Innulin)
What happens to ICF and ECF when you add an Isotonic fluid to a system ?
ECF will expand with no change in the osmolarity
ISOOSMOTIC VOLUME EXPANSION
Decreased hematocrit
What kind of fluid is lost in diarrhea ?
Isotonic Fluid
Leads to a decrease in the ECF only (Osmolarity is unchanged )
Increased Hematocrit
Hyperosmotic Fluid Expansion (Intake of excessive NaCL soulution)
Fluid will move from the ICF into the ECF expanding the ECF and decreasing the ICF
Hematocrit will decrease due to expanded ECF
Osmolarity of Both will be increased
Hyperosmotic Fluid Loss (sweating excessively)
ICF and ECF will become smaller (initially ECF then ICF )
Osmolarity of both will Increased.
Hematocrit does not increase despite ECF Fluid loss because fluid volume is lost from inside the RBC’s as well.
Hypoosmotic Fluid Expansion (SIADH)
Both the ECF and ICF will increase
Osmolarity Decreases
Hematocrit is unchanged since more water will go into the RBC’s expanding them.
Hypoosmotic Volume Contraction (Loss of NaCL. Adrenocortical insufficiency)
ECF osmolarity decreases leading to fluid shift into the ICF
ICF expands while ECF contracts
Osmolarity of Both Decreases
Hematocrit will increase due to loss of H20 from the ECF
Clearance
The amount of blood that can be cleared of solute per unit time ( mL/min)
C= UV/P
U= Urine Concentration (mg/mL) V= Urine Volume TIme (ml/min) P= Plasma Concentration (mg/mL)
Renal Blood Flow (25% of CO) Is directly proportional to …
The difference in pressure between Renal Artery and Renal Vein
Inversely proportional to Renal Resistance
What leads to Renal Arteriole vasoconstriction and decreased RBF ?
Sympathetic NS Angiotensin II (Dilates the EFFERENT arteriole leading to Increased GFR)
What leads to vasodilation of renal arterioles ?
Prostaglandins E2, I2 , Bradykinin, NO and DOPAMINE.
–> Increased Renal Blood Flow
What is the range of Renal blood pressures that renal blood flood is held constant due to Autoregulation ?
80-200 mmHg
Autoregulation: Myogenic Mechanism and Tubuloglomerular feedback
Tubuloglomerular feedback
Increased RBF leads to increased fluid being brought to the macula densa. Macula densa senses this and cause constriction of the AFFERENT arteriole to lower GFR and maintain proper blood flow.
Renal Plasma Flow
Amount of plasma that come through the kidney (measured by the clearance of PAH , a substance that is filtered and secreted only)
RPF = C(PAH) = UV/ P
U= Urine Concentration of PAH V= Urine Flow Rate P= Plasma Concentration of PAH
Renal Blood Flow
Amount of blood to come through the kidney over a set time
RBF = RPF/ (1-hematocrit)
1- hematocrit = Proportion of plasma in blood.
GFR
Calculated by clearance of INULIN ( Filtered not secreted or reabsorbed)
GFR = UV/P
U=Urine Concentration of Inulin
V= Urine flow Rate
P = plasma concentration of Inulin
What is the relationship between Decreasing GFR and BUN ?
BUN increases as GFR decreases
Pre-reanal azotemia
BUN:Creatinine of >20:1
Post renal : > 15
Primar Azotemia : <15
Filtration Fraction
Fraction of RPF that is filtered
FF = GFR/ RPF
Normally .2 !
Increased Filtration Fraction
Lead to increased [protein] of peritubular capillary blood –> Increased reabsorption in proximal tubule
Opposite is true of Decreased FF
Starling Forces For GFR
GFR = Kf ( Pc + Oi) - (Pi + Oc)
Glomerular Capilllary Hyrodstatic Pressure
Increased by dilation of Afferent or Constriction of Efferent .. Increasing this leads to increased GFR (all others held same)
Glomerular Capillary Oncotic Pressure
Increases along the capillary ( primary driving force is plasma proteins)
Increases in this decreases GFR and net filtration pressure
Bomans space Oncotic pressure
Essentially is zero
Bowmans Space Hydrostatic pressure
resists filtration, increases in this pressure leads to decreased GFR
Filtered Load
GFR x [Plasma] (g/min)
Excretion Rate
=Urine Flow (V) x [U]
Reabsorption Rate
FIltered Load - Excretion Rate
Less in blood than was filtered)
Secretion Rate
Excretion Rate - Filtered Load (More in urine than was filtered)
What is responsible for Glucose reabsorption in the proximal tubule
Na/Glucose co transport.
If plasma glucose is over 350 , you will see glucose in the blood (less than 250 all glucose is reabsorbed)
Splay is in between
Note: in the early proximal tubule, nearly all Glucose, HCO3 and Amino acids have been reabsorbed
What has higher clearance : A substance that is filtered and secreted or a Substance that is filtered ?
Filtered and secreted
In which conditions will The HA form of a weak acid be more prevalent than the A- form ?
At acidic pH
No reason to lose H+ to the solution
If it were basic solution, the A- would predominate since it would be easier to donate H+
In which conditions will The BH+ form of a weak base be more prevalent than the B form ?
In acidic environments. More readily accepts the B
Where is Reabsorption of Na+ the greatest along the nephron ?
Proximal Tubule
Reabsorbs 2/3’s of the filtered Na and H20
Done in Isoosmotic fashion so that reabsorption of Na is proportional to reabsorption of water.
What drives the Reabsorption of Na in the early prox tubule ?
Na/K+ pump on the basolateral side ** (sodium into the blood, K+ into the cell)
On the lumina side : Na/Glucose symport and Na+/H+ anti port
Note: Na/H+ antiport is due to activity of Carbonic ANhydrase. Carbonic Anhydrase inhibitors work as diuretics by blocking this (Acetozolamide, give this for Altitude sickness also to treat Respiratory Alkalosis)
How is Na+ reabsorbed in the Late Proximal Tubule ?
With Cl- ( Na/Cl- Symport)
How does ECF volume contraction affect tubular reabsorption ?
Increases it since ECF (Plasma and Interstitial fluid) decreases lead to increased plasma protein concentration and great Capillar oncotic pressures.
Opposite is true of ECF Expansion
How much of Na+ is reabsorbed in the Thick Ascending Loop of Henle ?
25% of filtered
NCCK Transporter
What diuretic class works on he NCCK transporter /
Loop Diuretics
What is different about the TALH and the Proximal tubule ?
Unlike in the Proximal Tubule, the TALH is impermeable to H20, so when The NCCK reabsorb ions, H20 cannot follow leading to a dilution of the Tubule osmolarity (
How much of Na+ is reabsorbed in the Distal Convoluted Tubule and Collecting duct ?
8%
Like in the Late Proximal Tubule, how is Na+ reabsorbed in the Early Distal Convoluted Tubule ?
with Cl- (Na/Cl- Symport
What diuretics work on the Na/Cl- Symport in the Early Distal Convoluted tubule ?
Thiazide Diuretics
Is the Early Distal Tubule permeable to H20 ?
NOPE (Just like the TALH)
What are the two types of cells important to ion regulation found in the Late Distal Convoluted Tubule/Collecting Ducts ?
Principal Cells
a-Interaclated cells
Pricinple Cells
Reabsorb Na+ and H20 , Secrete K+
Aldosterone mediates the function of Principle Cells !!!!! (Increases Na+ reabs and K+ secretion)… ENAC channels are placed on the lumenal side of Principal Cells and allow for the Movement of Na+ into the cell. Aldosterone also stimulates the activation of Na/K pump
Gradient is maintained by Basolateral Na/K+ Pump ( Na into blood, K+ into cell –> increased K+ which leave cell via lumenal K+ channel into urine)
Effect of Acidosis on K+ secretion
Acidosis leads to decreased K+ secretion
(H+ enters principal cell, this somehow causes K+ to leave the cell on basolateral side
H+/K+ anti-port ?
Effect of Alkalosis on K+ secretion
Alkalosis leads to increased K+ Secretion
(H+ does not enter principal cell, this somehow causes K+ to leave the cell on lumenal side due to increased [K+]
What is the effect of Thiazide and loop diuretics on K+ Secretion ?
They increase the secretion of K+ by increasing flow rate in distal tubule and thus diluting the K+ concentration–> K+ moving from principle cell into the lumen. –> Hypokalemia
Loops: Inhibit NCCK (more fluid retained, dilutes K+ concentration)
Thiazides: Inhibit Na Cl transporter.
How do the Potassium Sparring Diurectics (Spironolactone, Amilioride, Triamitrine) work ?
Directly inhibiting Principal Cell Secretion of K
Spironolactone is an inhibitor of Aldosterone (given in patients with Conn Snydrome, can lead to Hyperkalemia and Man tits)
What is the effect of increased luminal ANIONS on K+ secretion ?
Increases it ( more anions = more need for cations to come into the lumen to balance charges)
Where is most Urea reabsorbed ?
Proximal Tubule (50%)
The nephron is impermeable at all other places along the path except at the Medullary Collecting Ducts (NOT CORTICAL COLLECTING DUCT)–> medullary gradient
Where is most Urea reabsorbed ?
Proximal Tubule (50%)
The nephron is impermeable at all other places along the path except at the Medullary Collecting Ducts (NOT CORTICAL COLLECTING DUCT)–> medullary gradient
How is flow linked to urea reabsorption and secretion ?
At low flow, urea absorption is high ! at high flow reabsorption is minimal
How is flow linked to urea reabsorption and secretion ?
At low flow, urea absorption is high ! at high flow reabsorption is minimal
Where is most Phosphate reabsorbed along the nephron ?
In the proximal tubule (85%) via Na/Phosphate symport.
DISTAL PORTIONS OF THE NEPHRON ARE IMPERMEABLE TO PHOSPHATE… remaining 15% is excreted
Where is most Phosphate reabsorbed along the nephron ?
In the proximal tubule (85%) via Na/Phosphate symport.
DISTAL PORTIONS OF THE NEPHRON ARE IMPERMEABLE TO PHOSPHATE… remaining 15% is excreted
Where in the nephron will you find the greatest amount of Ca++ reabsorption and what is it coupled to ?
Proximal TUbule and TALH (90%)
Coupled to Na+ Transport (reabsorption)
Where in the nephron will you find the greatest amount of Ca++ reabsorption and what is it coupled to ?
Proximal TUbule and TALH (90%)
Coupled to Na+ Transport (reabsorption)
What is the effect of loop diuretics on Ca++ reabsorption ?
Loop Diuretics (Like furosemide) inhibit the NCCK transporter. This will cause a disruption of the Ca++ reabsorption since it is linked to Na+ reabsorption.
Can give Loop Diuretics to treat Hypercalcemia !
What is the effect of loop diuretics on Ca++ reabsorption ?
Loop Diuretics (Like furosemide) inhibit the NCCK transporter. This will cause a disruption of the Ca++ reabsorption since it is linked to Na+ reabsorption.
Can give Loop Diuretics to treat Hypercalcemia !
PTH
Activates Adenyl Cyclase in the distal tubule –> Ca++ reabsorption
PTH
Activates Adenyl Cyclase in the distal tubule –> Ca++ reabsorption
What diuretic can you give to help increased Ca++ reabsorption in the distal tubule ?
Thiazide diuretics.
What diuretic can you give to help increased Ca++ reabsorption in the distal tubule ?
Thiazide diuretics.
What is the effect of Mg++ on Ca++ reabsorption ?
In the TALH, Mg++ and Ca++ compete for reabsorption. Hypermagnesemia can lead to decreases Ca++ reabsorption and vis versa.
What is the effect of Mg++ on Ca++ reabsorption ?
In the TALH, Mg++ and Ca++ compete for reabsorption. Hypermagnesemia can lead to decreases Ca++ reabsorption and vis versa.
Circulating ADH will lead to the formation of what kind of urine ?
Hyperosmotic !
Circulating ADH will lead to the formation of what kind of urine ?
Hyperosmotic !
ADH causes the Medullary Collecting duct to be more permeable to …
UREA !
ADH causes the Medullary Collecting duct to be more permeable to …
UREA !
Corticopapillary Osmotic Gradient is mainly due to
NaCL and UREA.
Corticopapillary Osmotic Gradient is mainly due to
NaCL and UREA.
What blood vessels are responsible for the countercurrent multiplication in the LOH ?
Vasa Recta (equilibrate with the interstitial fluid of the papilla which has a large amount of NaCl and Urea)
What blood vessels are responsible for the countercurrent multiplication in the LOH ?
Vasa Recta (equilibrate with the interstitial fluid of the papilla which has a large amount of NaCl and Urea)
What is the TF/P value of the TALH ?
less than 1 since solute is being reabsorbed but LOH is impermeable to H20 (dilutes out the tubular fluid)
What is the TF/P value of the TALH ?
less than 1 since solute is being reabsorbed but LOH is impermeable to H20 (dilutes out the tubular fluid)
Free Water Clearance (equation)
Estimate of the ability to concentrate or Dilute Urine
(in the presence of ADH, free water is absorbed and C(H20) is negative
In the absence of ADH free water is excreted and C(H20) is positive.
Free Water Clearance (equation)
Estimate of the ability to concentrate or Dilute Urine
(in the presence of ADH, free water is absorbed and C(H20) is negative
In the absence of ADH free water is excreted and C(H20) is positive.
Free Water Clearance (equation)
C(H20) = V - Cosm
V= Urine Flow rate (mL/min)
C= Osmolar Clearance ( [U]x V/ [P])
Free Water Clearance (equation)
C(H20) = V - Cosm
V= Urine Flow rate (mL/min)
C= Osmolar Clearance ( [U]x V/ [P])
What is the Free Water Clearance when urine is isoosmotic to plasma ?
0
If you work through the equation where Osmolar Clearance (Cosm) is ( [U]x V/ [P]). If [U] and [P] are the same then you are left with V = Cosm
C(H20) = V - Cosm , and since Cosm =V you get 0
What is the Free Water Clearance when urine is isoosmotic to plasma ?
0
If you work through the equation where Osmolar Clearance (Cosm) is ( [U]x V/ [P]). If [U] and [P] are the same then you are left with V = Cosm
C(H20) = V - Cosm , and since Cosm =V you get 0
What is the Free Water Clearance of Urine that is Hypoosmotic to plasma ?
C(H20) is greater than 0 (if you plug the numbers in and solve for Cosm you will see it is less than V .
LOW ADH
What is the Free Water Clearance of Urine that is Hypoosmotic to plasma ?
C(H20) is greater than 0 (if you plug the numbers in and solve for Cosm you will see it is less than V .
LOW ADH
What is the Free Water Clearance of Urine that is Hyperosmotic to plasma ?
C(H20) is negative since Cosm will be greater than V .
High ADH
What is the Free Water Clearance of Urine that is Hyperosmotic to plasma ?
C(H20) is negative since Cosm will be greater than V .
High ADH
What is the effect of PTH on Phosphate reabsorption in the kidney ?
Decreases it
What is the effect of PTH on Phosphate reabsorption in the kidney ?
Decreases it
What kind of G-protein is associated with the ADH V2 receptor ?
Gs… Leads to an increase in cAMP and the up regulation of aquaporin II
What kind of G-protein is associated with the ADH V2 receptor ?
Gs… Leads to an increase in cAMP and the up regulation of aquaporin II
What actions does Aldosterone have on the kidneys ?
Increases ENaC channels for Na+ Reabsorption
Stimuluates K+ secretion
Increases H+ secretion ( leading to metabolic alkalosis which causes further K+ Secretion)
What actions does Aldosterone have on the kidneys ?
Increases ENaC channels for Na+ Reabsorption
Stimuluates K+ secretion
Increases H+ secretion ( leading to metabolic alkalosis which causes further K+ Secretion)
Describe the Role of Atrial Naturetic Pepetide
Released in response to increased stretch in the atria.
Decreases Na+ reabsorption, increases GFR ( dilating the afferent arteriole via cGMP ? )
Describe the Role of Atrial Naturetic Pepetide
Released in response to increased stretch in the atria.
Decreases Na+ reabsorption, increases GFR ( dilating the afferent arteriole via cGMP ? )
What is the effect of Angiotensin II on the proximal tubule ?
Leads to an increased Na/H+ exchange (anti-port) and increases Na reabsorption
What is the effect of Angiotensin II on the proximal tubule ?
Leads to an increased Na/H+ exchange (anti-port) and increases Na reabsorption
What is the major ‘volatile’ acid produced in the body and what enzyme creates it ?
CO2
Carbonic Anhydrase .
What is the major ‘volatile’ acid produced in the body and what enzyme creates it ?
CO2
Carbonic Anhydrase .
What is the main extracellular buffer ?
HCO3 (pK of 6.1)
What is the main extracellular buffer ?
HCO3 (pK of 6.1)
List a minor extracellular buffer ?
Phosphate (pK of 6.8)
List a minor extracellular buffer ?
Phosphate (pK of 6.8)
List major intracellular buffers ?
Organic Phosphates
Proteins ( Hemoglobin and Deoxyhemoglobin)
List major intracellular buffers ?
Organic Phosphates
Proteins ( Hemoglobin and Deoxyhemoglobin)
Is there a net secretion of H+ in the proximal tubule when Na/H+ anti port leads to HCO3- reabsorption ?
NO!
The H+ will then bind with FILTERED HCO3 and dissociate to CO2 and H20 . So in essence only HCO3 is reabsorbed while H+ Is not secreted.
Is there a net secretion of H+ in the proximal tubule when Na/H+ anti port leads to HCO3- reabsorption ?
NO!
The H+ will then bind with FILTERED HCO3 and dissociate to CO2 and H20 . So in essence only HCO3 is reabsorbed while H+ Is not secreted.
What will the effect of increased PCO2 be on HCO3 reabsorption ?
Increased PCO2 leads to increased reabsorption of HCO3
PC02 will go into the tubular cell, be converted to HCO3 and H+ . HCo3 will be reabsorbed, H+ will go into the lumen and bind a filtered HCO3 leading, bruch border CA will lead to CO2 + H20 and the process starts again.
What will the effect of increased PCO2 be on HCO3 reabsorption ?
Increased PCO2 leads to increased reabsorption of HCO3
PC02 will go into the tubular cell, be converted to HCO3 and H+ . HCo3 will be reabsorbed, H+ will go into the lumen and bind a filtered HCO3 leading, bruch border CA will lead to CO2 + H20 and the process starts again.
What is the effect of ECF volume on HCO3 reabsorption ?
Expansion = less reabsorption Contraction= More Reabsorption
has to do with RPF. Will be increased with Expansion leading to less time for reabsorption.
What is the effect of ECF volume on HCO3 reabsorption ?
Expansion = less reabsorption Contraction= More Reabsorption
has to do with RPF. Will be increased with Expansion leading to less time for reabsorption.
How are fixes H+ ions excreted ?
As NH4+ or Titratable acids (H2P04)
THIS RESULTS IN NET SECRETION OF H+ AND NET REABSORPTION OF HCO3-
How are fixes H+ ions excreted ?
As NH4+ or Titratable acids (H2P04)
THIS RESULTS IN NET SECRETION OF H+ AND NET REABSORPTION OF HCO3-
Describe the Excretion of H+ as H2PO4
THIS RESULTS IN NET SECRETION OF H+ AND NET REABSORPTION OF HCO3-
Describe the Excretion of H+ as H2PO4
THIS RESULTS IN NET SECRETION OF H+ AND NET REABSORPTION OF HCO3-
What hormone increases the activity of the H+ ATPase that is responsible for moving H+ into the lumen where it combines with HPO4 ?
Aldosterone !!!
Remember, aldosteone increases H+ secretion which helps make the body alkalotic so that K+ is also excreted.
What hormone increases the activity of the H+ ATPase that is responsible for moving H+ into the lumen where it combines with HPO4 ?
Aldosterone !!!
Remember, aldosteone increases H+ secretion which helps make the body alkalotic so that K+ is also excreted.
How is NH3 synthesized ?
In the renal cells from Glutamine
How is NH3 synthesized ?
In the renal cells from Glutamine
What kind of breathing is seen with metabolic acidosis ?
Kussmaul (Deep rapid breathing.)… Respiratory compensation for metabolic acidosis
What kind of breathing is seen with metabolic acidosis ?
Kussmaul (Deep rapid breathing.)… Respiratory compensation for metabolic acidosis
Anion Gap
Na+ - (Cl- + HCO3-)
Gap represents unmeasured anions (phosphate, citrate, sulfate, protein)
Normal value of 12 mEq/L
Anion Gap
Na+ - (Cl- + HCO3-)
Gap represents unmeasured anions (phosphate, citrate, sulfate, protein)
Normal value of 12 mEq/L
What is the site of action for Carbonic Anhydrase inhibitors ? Main Action ?
Proximal tubule
Increase filtered HCO3 excretion (since H+ will not produced within the cell and secreted into the lumen, there is less H+ to bind HCO3 . Also, Carbonic ANhydrase in the brush border is inhibited so, you will not be able to make H20 and CO2 from lumenal H2C03.
Ex. Acetazolamide
What is the site of action for Carbonic Anhydrase inhibitors ? Main Action ?
Proximal tubule
Increase filtered HCO3 excretion (since H+ will not produced within the cell and secreted into the lumen, there is less H+ to bind HCO3 . Also, Carbonic ANhydrase in the brush border is inhibited so, you will not be able to make H20 and CO2 from lumenal H2C03.
Ex. Acetazolamide
What is the site of action for Loop diuretics ? Main Action ?
TALH at the NCCK
Increases the osmoarity of the tubular fluid leading to H20 reabsorption down the line.
Also, Ca++ will not be reabsorbed since Na+ reabsorption is nixed.
Also increases K+ excretion
Ex. Furosemide, Ethacrynic Acid
What is the site of action for Loop diuretics ? Main Action ?
TALH at the NCCK
Increases the osmoarity of the tubular fluid leading to H20 reabsorption down the line.
Also, Ca++ will not be reabsorbed since Na+ reabsorption is nixed.
Also increases K+ excretion
Ex. Furosemide, Ethacrynic Acid
What is the site of action for Thiazide Diuretics ? Main Action ?
Early Distal Convoluted Tubule, Na/Cl- Symport.
Main job is to increases excretion of Na and Cl-
Can help increase the reabsorption of Ca++
Also, increases K+ secretion
Ex. Hydrochlorothiazide, Chlorothiazide.
What is the site of action for Thiazide Diuretics ? Main Action ?
Early Distal Convoluted Tubule, Na/Cl- Symport.
Main job is to increases excretion of Na and Cl-
Can help increase the reabsorption of Ca++
Also, increases K+ secretion
Ex. Hydrochlorothiazide, Chlorothiazide.
What is the site of action for K+ Sparring Diuretics ? Main Action ?
Late distal tubule and collecting duct
Spironolactone : direct inhibitor of Aldosterone
AMilioride: act on the principal cells to increases Na+ secretion while preserving K+
What is the site of action for K+ Sparring Diuretics ? Main Action ?
Late distal tubule and collecting duct
Spironolactone : direct inhibitor of Aldosterone
AMilioride: act on the principal cells to increases Na+ secretion while preserving K+
