Renal Flashcards
What is the equation for urinary clearance?
C = ([U] x urine flow)/[P]
What is the equation for urinary excretion?
[U] x Urine Flow
What is the pattern for metabolic acidosis?
CO2 + H2O: Decreased (Resp. comp) H+: Increased HCO3-: Decreased* Resp. Comp.: Hyperventilation Renal Comp: -
What is the pattern for metabolic alkalosis?
CO2 + H2O: Increased (Resp. comp) H+: Decreased HCO3-: Increased* Resp. Comp.: Hypoventilation Renal Comp: -
What is the pattern for respiratory acidosis?
CO2 + H2O: Increased* H+: Increased HCO3-: Increased Resp. Comp.: - Renal Comp: Increased H+ Excretion, Increased HCO3- Reabsorption
What is the pattern for respiratory alkalosis?
CO2 + H2O: Decreased* H+: Decreased HCO3-: Decreased Resp. Comp.: - Renal Comp: Decreased H+ Excretion, Decreased HCO3- Reabsorption
What is the equation for strong ion difference?
[Strong cations] - [Strong anions]
[Na + K + Ca + Mg] - [Cl + Lactate]
*NOT affected by albumin concentration → anion gap is!
What occurs with an increased strong ion difference?
Metabolic Alkalosis
*Increased Na or Decreased Cl
What occurs with a decreased strong ion difference?
Metabolic Acidosis
*Decreased Na or Increased Cl
Tubular Reabsorption:
- Filtered only
- Filtered with partial reabsorption
- Filtered with complete reabsorption
- Filtered and secreted
- Inulin and creatinine
- Electrolytes
- Amino acids and glucose
- Organic acids and bases
Describe renal blood flow. Why is this unique?
Renal artery → interlobar → arcuate → interlobar → afferent → glomerular capillaries → efferent → peritubular capillaries → interlobar → arcuate → interlobar → renal vein
*Unique because it has 2 capillary beds
What is the MOA of ADH?
Goes to distal/collecting ducts → V2 receptors → adenylyl cyclase → cAMP → Protein kinase A → phosphorylation of membrane proteins → transient placement of aquaporin channels in the membrane → permeable to water
*Released in response to osmoreceptors in the anterolateral hypothalamus near the supraoptic nuclei
What is the net filtration pressure equation?
NFP = P(GC) - P(BC) - π(GC)
P = hydrostatic pressure π = oncotic pressure
What is responsible for RAAS inhibition?
Atrial Natriuretic Peptide (ANP)
- Comes from cardiac atrial muscle fibers
Approx. 90% of the filtered glucose is reabsorbed by ____ in the ____ part of the proximal tubule
- SGLT2
2. Early (S1)
Which portions of the nephron are impermeable to water?
- Thick ascending loop of Henle
2. Early distal tubule
Where do the following act (segment & receptor)?
- Carbonic anhydrase inhibitors
- Thiazide diuretics
- Loop diuretics
- K sparing diuretics
- Early proximal tubule → inhibit HCO3 reabsorption
- Early distal tubule → inhibits Na-Cl cotransporter
- Thick ascending loop of Henle → inhibit Na-K-2Cl cotransporter
- Late distal tubule → aldosterone receptor antagonist
Where is Na reabsorbed in the nephron?
*99% filtered Na is reabsorbed
- Proximal tubule - 65% (Active)
- Thin ascending LoH - 7% (Passive)
- Thick ascending LoH - 20% (Active)
- Distal tubule - 8% (Active)
- Collecting duct - 3% (Active)
Where is K reabsorbed/secreted in the nephron?
- Proximal tubule - 67% reabsorbed
- Thick ascending LoH - 20% reabsorbed
- Distal tubule & collecting duct → reabsorbs or secretes based on dietary K
Where is phosphate reabsorbed in the nephron?
*85-90% of filtered phosphate is reabsorbed
- Proximal tubule - 75-80%
- Distal convoluted tubule - 10%
- Loop of Henle and collecting tubules - <1%
- ~15% of filtered load is excreted in the urine
Where is the majority of Ca reabsorbed in the nephron?
*99% of filtered Ca is reabsorbed
- Proximal tubule - 65% (active and passive)
- Thick LoH - 25-30% (passive)
- Distal tubule and collecting duct - 4-9% (active)
How does PTH influence the phosphorous balance by the kidneys?
Decrease transport mechanism for phosphate by the renal tubules → more is lost in the urine
Magnesium competes with ___ in the thick ascending loop for reabsorption
Calcium
*Hypercalcemia causes an increase in Mg excretion
The corticopapillary osmotic gradient occurs in the presence of (high/low) ADH and is mostly composed mostly of ___ and ___.
- High
2. NaCl and Urea
Interpret:
- TF/P = 1
- TF/P < 1
- TF/P > 1
- There has either been no reabsorption or reabsorption is exactly proportional to water
- Reabsorption is greater than reabsorption of water → tubular fluid concentration < plasma concentration
- Reabsorption is less than reabsorption of water → tubular fluid concentration > plasma concentration (there has been no secretion)
What is the consequence of no ADH in terms of urine concentrating ability?
Cells of the late distal tubule and collecting duct are impermeable to H2O
Urine is dilute
Where is free H2O produced in the nephron
Diluting segments → TAL and early distal tubule
Where is ADH produced and stored?
- Hypothalamus - supraoptic nuclei (majority)
2. Posterior pituitary
At what positions do the liver and kidney hydroxylate vitamin D?
- Liver → 25 → “25-OH-D (Calcidiol)”
2. Kidney → 1 → “1,25(OH)2-D (Calcitriol)”
What substances are used to measure:
- ECF
- Plasma
- Intersitial Fluid
- ICF
- Sulfate, Inulin, Mannitol
- Evans Blue, RISA (Radioiodinated serum albumin)
- Measure indirectly (ECF-plasma)
- Measured indirectly (TBW-ECF)
How is renal plasma flow measured?
- PAH
- Filtered and secreted by renal tubules
- Clearance of PAH measures effective RPF but underestimates true RPF by ~10%
What is the equation to calculate renal blood flow?
RBF = RPF/(1-HCT)
RPF = PAH clearance
What is the equation used to calculate GFR (starling equation)? What does a (+) value indicate?
GFR = Kf [(P(GC)-P(BS)) - (π(GC) - π(BS)]
(+) = filtration is favored
Where is glucose reabsorbed in the nephron? How is this accomplished?
- Early proximal tubule
2. Na-Glucose co-transport
What is the MOA of ANP in RAAS inhibition?
- Stimulus → dilution of the atria
- Effects
- Inhibit renin release
- Inhibit action of angiotensin II
- Inhibits Na reabsorption
What is the plasma osmolality equation?
2(Na+K) + Glucose/18 + BUN/2.8
Osmolality = # of osmoses per kilogram of solvent
How does ECF volume affect proximal tubular reabsorption
- ECF volume contraction → increase reabsorption
- Peritubular capillary protein increases = increased π(capillary) = decreased P(capillary) = increase in proximal tubular reabsorption
- Opposite is also true
What are the mechanisms of K reabsorption and secretion in the distal tubule and collecting duct?
- Reabsorption → α intercalated cells
- H/K ATPase countertransport - Secretion → Principal cells
- Basolateral membrane: K actively transported into cell via Na/K pump
- Luminal membrane: K passively secreted into lumen through K channels
How does ADH affect urea regulation?
Acts on UT-A1 and UT-A3 transporters
Increases urea in the interstitial → increases concentrating ability
What stimulates ADH secretion?
- Increase plasma osmolality
- Osmoreceptors in anterior hypothalamus - Decrease atrial pressure/blood volume
- Baroreceptors
What is the relationship between BUN and serum creatinine in prerenal azotemia? Why?
- BUN increases more than creatinine
2. Hypovolemia increases urea reabsorption in the proximal tubule
- How are weak acid and weak base forms affected by:
a. acidic urine
b. alkaline urine - How does this affect their excretion?
1a. HA form and BH+ form predominate
1b. A- and B form predominate
2.a. More back diffusion of acid = decrease excretion
Less back diffusion of base = increase excretion
2b. Less back diffusion of acid = increase excretion
More back diffusion of base = decrease excretion
What is the mechanism of phosphate reabsorption in the proximal tubule?
Na-Phosphate cotransport
What inhibits phosphorous reabsorption in the proximal tubule? How?
- PTH
- Activates cAMP → inhibits Na-phosphate co-transport
- Causes phosphaturia and increased urinary cAMP
*FGF23 (fibroblast growth factor) is secreted by bone and also inhibits the Na-phosphate co-transporter
How do the following affect Ca excretion/resorption in the nephron?
- Loop diuretics
- PTH
- Thiazide diuretics
- Increase excretion in the LoH
- Increase reabsorption in the distal tubule
- Increase reabsorption in the early distal tubule
Where is magnesium reabsorbed in the nephron?
- 85-90% reabsorbed
- LoH - 65% (mostly from thick)
- Proximal tubule - 25%
- Distal convoluted tubule and collecting duct - <5%
Where does PTH act in the nephron?
- Thick limb of the LoH
2. Distal convoluted tubule and collecting duct
What are the transport mechanisms for Na in
- Early proximal tubule
- Distal proximal tubule
- Cotransporters → glucose, amino acids, phosphate, and lactate
Countertransport → Na-H exchange linked to HCO3 reabsorption - Reabsorbed with Cl
What are the transport mechanisms for Na in
- Thick ascending LoH
- Early distal tubule
- Late distal tubule
- Na/K/2Cl cotransporter
- Na/Cl cotransporter
- Na Channels (stimulated by aldosterone)
What are the different vasopressin receptors?
- V1A → vascular smooth muscle → vasoconstriction
- V2 → collecting ducts → insert aquaporin 2 channels
- V3 → anterior pituitary → ACTH release
What causes renal arterioles to
- Vasoconstrict
- Vasodilate
- Sympathetic nervous system, angiotensin II
* Angiotensin II preferentially constricts efferent arterioles at low concentrations to increase GFR - Prostaglandins E2 and I2, Bradykinin, NO, and Dopamine
* ACEi → dilate efferent arterioles
* ANP → dilate afferent arterioles
Where is urea reabsorbed in the nephron?
- Proximal tubule - 50% (simple diffusion)
- Thin descending limb - simple diffusion
- Collecting ducts - UT1 transporter only in the presence of ADH, otherwise distal tubule and collecting duct are impermeable to urea
What are the different urea transporters?
- UT-A1: Reabsorption in proximal tubule and collecting duct
- UT-A2: Secretion into the think loop of henle
- UT-A3: Reabsorption in the collecting duct
Reabsorption of filtered HCO3 occurs primarily in which nephron segment?
Proximal tubule
What is the carbonic anhydrase equation?
CO2 + H2O -> H2CO3 -> carbonic anhydrase -> H + HCO3
What is the net result of bicarb reabsorption in the proximal tubule?
- Net reabsorption of filtered HCO3
2. Does not result in net H+ secretion
What regulates reabsorption of filtered HCO3
- Filtered Load → Increased filtered load = increased HCO3 reabsorption
- PCO2 = Increased PCO2 = Increased HCO3 because supply of intracellular H is increased → bases of renal compensation for respiratory acidosis
- ECF Volume → ECF expansion = decreased HCO3 reabsorption. ECF contraction = increased HCO3 reabsorption
- Angiotensin II = stimulates Na/H exchange and thus increased HCO3 reabsorption, contributes to contraction alkalosis that occurs secondary to ECF volume contraction
In what forms is H+ excreted?
- Titratable acid (H2PO4)
2. NH4
What determines the amount of H+ excreted as a titratable acid?
- Amount of urinary buffer (usually HPO4)
2. pK of the buffer
What determines the amount f H+ excreted as ammonium?
- NH3 synthesized by renal cells
2. Urine pH
How/where is NH3 produces in the kidney? What inhibits this process?
- Produced in renal cells from glutamine
2. Hyperkalemia inhibits NH3 synthesis
What is the underlying cause of metabolic acidosis?
Overproduction/ingestion of acid
OR
Loss of base = decrease in [HCO3]a → acidemia
What are consequences of a metabolic acidosis?
- Hyperventilation → respiratory compensation
- Increased excretion of H as a titratable acid and ammonium
- Increased reabsorption of HCO3
- In chronic cases → increase NH3 synthesis
What is the underlying cause of a metabolic alkalosis?
Loss of [H+]
OR
Gain of base → increase arterial [HCO3] → alkalemia
What are the consequences of a metabolic alkalosis?
- Hypoventilation → respiratory compensation
2. Increased excretion of HCO3 → filtered load of HCO3 exceeds the kidneys ability to reabsorb it
What is contraction alkalosis?
Metabolic alkalosis is accompanied by ECF volume contraction (vomiting) → reabsorption of HCO3 increases due to ECF volume decrease and activation of RAAS → worsens alkalosis
What is the underlying cause of respiratory acidosis?
Decreased ventilation and retention of CO2 → increased arterial CO2 → increased H+
How does the kidney compensate for respiratory acidosis?
- Increased excretion of H+ as titratable acid and ammonium, increased reabsorption of HCO3
* Aided by increased PCO2 → supplies more H+ to the kidney
* Takes time, only occurs in CHRONIC cases
What is the underlying cause of respiratory alkalosis?
Increased ventilation → loss of CO2 → decreased H+
How does the kidney compensate for respiratory alkalosis?
Decreased excretion of excess H, decrease reabsorption of HCO3
*Takes time, only occurs in chronic cases
What are the effects of hypoaldosteronism on the kidney
- Decrease Na reabsorption
- Decrease K secretion
- Decrease H secretion
What stimulates the production of erythropoietin? How long does it take for HCT to increase?
- Epi, Norepi, prostaglandins, and HIF1α
2. 5 days
What happens when the macula dense senses a decrease in the NaCl in the distal tubules
- Dilates afferent arterioles → increase RBF and GFR
2. Causes renin release from JG cells → RAAS
Where does aldosterone act in the kidney? Where is the primary site of action?
- Principal cells of distal tubule and collecting duct → increase Na reabsorption, increase K secretion
- Intercalated cells of distal tubular and collecting duct → increase H secretion
- Thick LoH → increase Na-2Cl-K transporter expression, Increase Cl and Na reabsorption
- Principal cells of the cortical collecting tubule is the primary site of action
What are the actions of Angiotensin II?
- Stimulates aldosterone
- Constricts efferent and afferent arterioles (via phospholipase C)
- Increase Na reabsorption (via adenylyl cyclase)
- Increase thirst
- Increase ADH secretion
- Potentiates post synaptic norepinephrine release
- Blunt baroreceptor response
What is the equation for filtration fraction? how much is normally filtered?
Filtration fraction = GFR/Renal plasma flow
~20% of plasma