Renal - Physiology

Question 1

Fluid compartments

• Potassium location
• % of body weight
  
  • Total body water
  • ICF
  • ECF
• Plasma volume measured by…
• Extracellular volume measured by…
• Osmolarity

Answer 1

• Potassium location
  
  • HIKIN’: HIgh K INtracellular.
• 60–40–20 rule (% of body weight):
  
  • 60% total body water
  • 40% ICF
  • 20% ECF
• Plasma volume measured by radiolabeled albumin.
• Extracellular volume measured by inulin.
• Osmolarity = 290 mOsm/L.

Question 2

Glomerular filtration barrier

• Responsible for…
• Composed of…
• Pathology of the charge barrier

Answer 2

• Responsible for filtration of plasma according to size and net charge.
• Composed of…
  
  • Fenestrated capillary endothelium (size barrier)
  • Fused basement membrane with heparan sulfate (negative charge barrier)
  • Epithelial layer consisting of podocyte foot processes
• Pathology of the charge barrier
  
  • The charge barrier is lost in nephrotic syndrome, resulting in albuminuria, hypoproteinemia, generalized edema, and hyperlipidemia.

Question 3

Renal clearance

• Cx equation
• Cx vs. GFR
  
  • Cx < GFR
  • Cx > GFR
  • Cx = GFR

Answer 3

• Cx = (Ux * V) / Px = volume of plasma from which the substance is completely cleared per unit time.
  
  • Cx = clearance of X (mL/min).
  • Ux = urine concentration of X (mg/mL).
  • V = urine flow rate (mL/min)
  • Px = plasma concentration of X (mg/mL).
• Cx vs. GFR
  
  • Cx < GFR: net tubular reabsorption of X.
  • Cx > GFR: net tubular secretion of X.
  • Cx = GFR: no net secretion or reabsorption.

Question 4

Glomerular filtration rate

• Inulin clearance
• GFR equations
• Normal vs. reduced GFR
• Creatinine clearance

Answer 4

• Inulin clearance
  
  • Can be used to calculate GFR because it is freely filtered and is neither reabsorbed nor secreted.
• GFR
  
  • = (U_inulin × V) / P_inulin = C_inulin
  • = Kf [(P_GC – P_BS) – (π_GC – π_BS)].
    
    • GC = glomerular capillary
    • BS = Bowman space
    • π_BS normally equals zero.
• Normal vs. reduced GFR
  
  • Normal GFR ≈ 100 mL/min.
  • Incremental reductions in GFR define the stages of chronic kidney disease
• Creatinine clearance
  
  • An approximate measure of GFR.
  • Slightly overestimates GFR because creatinine is moderately secreted by the renal tubules.

Question 5

Effective renal plasma flow

• Effective renal plasma flow (ERPF)
• ERPF equation
• RBF equation

Answer 5

• Effective renal plasma flow (ERPF)
  
  • Can be estimated using para-aminohippuric acid (PAH) clearance because it is both filtered and actively secreted in the proximal tubule.
    
    • Nearly all PAH entering the kidney is excreted.
  • Underestimates true renal plasma flow (RPF) by ~10%.
• ERPF = (U_PAH × V) / P_PAH = C_PAH.
• RBF = RPF / (1 - Hct).

Question 6

Filtration

• Equations
  
  • Filtration fraction (FF)
    
    • Normal FF
  • Filtered load (mg/min)
• Estimations
  
  • GFR
  • RPF

Answer 6

• Equations
  
  • Filtration fraction (FF) = GFR / RPF.
    
    • Normal FF = 20%.
  • Filtered load (mg/min) = GFR (mL/min) × plasma concentration (mg/mL)
• Estimations
  
  • GFR can be estimated with creatinine clearance.
  • RPF is best estimated with PAH clearance.

Question 7

Changes in glomerular dynamics

• For each effect (increased/decreased)
  
  • RPF
  • GFR
  • FF (GFR / RPF)
• Afferent arteriole constriction
• Efferent arteriole constriction
• Increased plasma protein concentration
• Decreased plasma protein concentration
• Constriction of ureter

Answer 7

• Afferent arteriole constriction
  
  • RPF: Decreased
  • GFR: Decreased
  • FF (GFR / RPF): No effect
• Efferent arteriole constriction
  
  • RPF: Decreased
  • GFR: Increased
  • FF (GFR / RPF): Increased
• Increased plasma protein concentration
  
  • RPF: No effect
  • GFR: Decreased
  • FF (GFR / RPF): Decreased
• Decreased plasma protein concentration
  
  • RPF: No effect
  • GFR: Increased
  • FF (GFR / RPF): Increased
• Constriction of ureter
  
  • RPF: No effect
  • GFR: Decreased
  • FF (GFR / RPF): Decreased

Question 8

Calculation of reabsorption and secretion rate (equations)

• Filtered load
• Excretion rate
• Reabsorption
• Secretion

Answer 8

• Filtered load = GFR × Px.
• Excretion rate = V × Ux.
• Reabsorption = filtered – excreted.
• Secretion = excreted – filtered.

Question 9

Glucose clearance

• Glucose at a normal plasma level
• At plasma glucose of ~200 mg/dL
• At plasma glucose of ~375 mg/dL
• Glucosuria
• Normal pregnancy

Answer 9

• Glucose at a normal plasma level
  
  • Completely reabsorbed in proximal tubule by Na+/glucose cotransport.
• At plasma glucose of ~200 mg/dL
  
  • Glucosuria begins (threshold).
• At plasma glucose of ~375 mg/dL
  
  • All transporters are fully saturated (Tm).
• Glucosuria
  
  • An important clinical clue to diabetes mellitus.
• Normal pregnancy 
  
  • Decreases reabsorption of glucose and amino acids in the proximal tubule Ž–> glucosuria and aminoaciduria.

Question 10

Amino acid clearance

• Reabsorption
• Hartnup disease
  
  • Definition
  • Findings
  • Treatment

Answer 10

• Reabsorption
  
  • Sodium-dependent transporters in proximal tubule reabsorb amino acids.
• Hartnup disease
  
  • Definition
    
    • Autosomal recessive disorder.
    • Deficiency of neutral amino acid (e.g., tryptophan) transporters in proximal renal tubular cells and on enterocytes.
  • Findings
    
    • Leads to neutral aminoaciduria and decreased absorption from the gut
    • Results in pellagra-like symptoms
  • Treatment
    
    • Treat with high-protein diet and nicotinic acid.

Question 11

Nephron physiology:
Early proximal convoluted tubule (PCT)

• Functions
• Important hormones
• % Na+ reabsorbed

Answer 11

• Functions
  
  • Contains brush border.
  • Reabsorbs all of the glucose and amino acids and most of the HCO3–, Na+, Cl–, PO₄3–, K+, and H2O.
  • Isotonic absorption.
  • Generates and secretes NH3, which acts as a buffer for secreted H+.
• Important hormones
  
  • PTH
    
    • Inhibits Na+/PO₄3– cotransport → PO₄3– excretion.
  • AT II
    
    • Stimulates Na+/H+ exchange → ↑ Na+, H2O, and HCO3- reabsorption (permitting contraction alkalosis).
• % Na+ reabsorbed
  
  • 65–80%

Question 12

Nephron physiology:
Thin descending loop of Henle

• Functions

Answer 12

• Functions
  
  • Passively reabsorbs H2O via medullary hypertonicity (impermeable to Na+).
  • Concentrating segment.
  • Makes urine hypertonic.

Question 13

Nephron physiology:
Thick ascending loop of Henle

• Functions
• % Na+ reabsorbed

Answer 13

• Functions
  
  • Actively reabsorbs Na+, K+, and Cl-.
  • Indirectly induces the paracellular reabsorption of Mg2+ and Ca2+ through (+) lumen potential generated by K+ backleak.
  • Impermeable to H2O.
  • Makes urine less concentrated as it ascends.
• % Na+ reabsorbed
  
  • 10–20%

Question 14

Nephron physiology:
Early distal convoluted tubule (DCT)

• Functions
• Important hormones
• % Na+ reabsorbed

Answer 14

• Functions
  
  • Actively reabsorbs Na+, Cl-.
  • Makes urine hypotonic.
• Important hormones
  
  • PTH
    
    • ↑ Ca2+/Na+ exchange → Ca2+ reabsorption.
• % Na+ reabsorbed
  
  • 5–10%

Question 15

Nephron physiology:
Collecting tubule

• Functions
• Important hormones
• % Na+ reabsorbed

Answer 15

• Functions
  
  • Reabsorbs Na+ in exchange for secreting K+ and H+ (regulated by aldosterone).
• Important hormones
  
  • Aldosterone
    
    • Acts on mineralocorticoid receptorŽ → insertion of Na+ channel on luminal side.
  • ADH
    
    • Acts at V2 receptor Ž→ insertion of aquaporin H2O channels on luminal side.
• % Na+ reabsorbed
  
  • 3–5%

Question 16

Renal tubular defects

Answer 16

• The kidneys put out FABulous Glittering Liquid:
• FAnconi syndrome is the 1st defect (PCT)
• Bartter syndrome is next (thick ascending loop of Henle)
• Gitelman syndrome is after Bartter (DCT)
• Liddle syndrome is last (collecting tubule)

Question 17

Fanconi syndrome

• Type of condition
• Definition
• Findings
• Due to…

Answer 17

• Type of condition
  
  • Renal tubular defect
• Definition
  
  • Reabsorptive defect in PCT.
  • Associated with increased excretion of nearly all amino acids, glucose, HCO3–, and PO₄3–.
• Findings
  
  • May result in metabolic acidosis (proximal renal tubular acidosis).
• Due to…
  
  • Hereditary defects (e.g., Wilson disease)
  • Ischemia
  • Nephrotoxins/drugs.

Question 18

Bartter syndrome

• Type of condition
• Definition
• Findings

Answer 18

• Type of condition
  
  • Renal tubular defect
• Definition
  
  • Reabsorptive defect in thick ascending loop of Henle.
  • Autosomal recessive
  • Affects Na+/K+/2Cl– cotransporter.
• Findings
  
  • Results in hypokalemia and metabolic alkalosis with hypercalciuria.

Question 19

Gitelman syndrome

• Type of condition
• Definition
• Findings

Answer 19

• Type of condition
  
  • Renal tubular defect
• Definition
  
  • Reabsorptive defect of NaCl in DCT.
  • Autosomal recessive.
  • Less severe than Bartter syndrome.
• Findings
  
  • Leads to hypokalemia and metabolic alkalosis, but without hypercalciuria.

Question 20

Liddle syndrome

• Type of condition
• Definition
• Findings
• Treatment

Answer 20

• Type of condition
  
  • Renal tubular defect
• Definition
  
  • Increased Na+ reabsorption in distal and collecting tubules (increased activity of epithelial Na+ channel).
  • Autosomal dominant.
• Findings
  
  • Results in hypertension, hypokalemia, metabolic alkalosis, decreased aldosterone.
• Treatment
  
  • Amiloride.

Question 21

Relative concentrations along proximal tubules (529)

• Tubular inulin
• Cl- reabsorption

Answer 21

• Tubular inulin 
  
  • Increased in concentration (but not amount) along the proximal tubule as a result of water reabsorption.
• Cl- reabsorption
  
  • Occurs at a slower rate than Na+ in early proximal tubule and then matches the rate of Na+ reabsorption more distally.
  • Thus, its relative concentration increases before it plateaus.

Question 22

Renin-angiotensin-aldosterone system (530)

• AT II
• ANP
• ADH
• Aldosterone

Answer 22

• AT II
  
  • Affects baroreceptor function
  • Limits reflex bradycardia, which would normally accompany its pressor effects.
  • Helps maintain blood volume and blood pressure.
• ANP
  
  • Released from atria in response to increased volume
  • May act as a “check” on renin-angiotensin-aldosterone system
  • Relaxes vascular smooth muscle via cGMP, causing increased GFR, decreased renin.
• ADH
  
  • Primarily regulates osmolarity
  • Also responds to low blood volume states.
• Aldosterone
  
  • Primarily regulates ECF Na+ content and volume
  • Responds to low blood volume states.

Question 23

Juxtaglomerular apparatus

• Consists of…
• JGA
• β-blockers

Answer 23

• Consists of…
  
  • JG cells (modified smooth muscle of afferent arteriole) and the macula densa (NaCl sensor, part of the distal convoluted tubule).
  • JG cells secrete renin in response to decreased renal blood pressure, decreased NaCl delivery to distal tubule, and increased sympathetic tone (β1).
  • Juxta = close by
• JGA
  
  • Defends GFR via renin-angiotensin-aldosterone system.
• β-blockers
  
  • Can decrease BP by inhibiting β1‑receptors of the JGA, causing decreased renin release.

Question 24

Kidney endocrine functions

• Erythropoietin
• 1,25-(OH)2 vitamin D
• Renin
• Prostaglandins

Answer 24

• Erythropoietin
  
  • Released by interstitial cells in the peritubular capillary bed in response to hypoxia.
• 1,25-(OH)2 vitamin D [image]
  
  • Proximal tubule cells convert 25-OH vitamin D to 1,25-(OH)2 vitamin D (active form).
• Renin
  
  • Secreted by JG cells in response to decreased renal arterial pressure and increased renal sympathetic discharge (β1 effect).
• Prostaglandins
  
  • Paracrine secretion vasodilates the afferent arterioles to increase RBF.
  • NSAIDs block renal-protective prostaglandin synthesis –>Ž constriction of the afferent arteriole and decreased GFR
    
    • This may result in acute renal failure.

Question 25

``` Hormones acting on kidney: Angiotensin II (AT II) ``` * Synthesized in response to... * Causes... * Net effect

Answer 25

* Synthesized in response to... * Decreased BP. * Causes... * Efferent arteriole constriction --\> increased GFR and increased FF but with compensatory Na+ reabsorption in proximal and distal nephron. * Net effect * Preservation of renal function in low-volume state (increased FF) with simultaneous Na+ reabsorption (both proximal and distal) to maintain circulating volume.

Question 26

``` Hormones acting on kidney: Parathyroid hormone (PTH) ``` * Secreted in response to... * Causes...

Answer 26

* Secreted in response to... * Decreased plasma [Ca2+] * Increased plasma [PO₄3–] * Decreased plasma 1,25-(OH)2 vitamin D. * Causes... * Increased [Ca2+] reabsorption (DCT) * Decreased [PO₄3–] reabsorption (PCT) * Increased 1,25-(OH)2 vitamin D production (increased Ca2+ and PO₄3– absorption from gut via vitamin D).

Question 27

Hormones acting on kidney: Atrial natriuretic peptide (ANP) * Secreted in response to... * Causes... * Net effect

Answer 27

* Secreted in response to... * Increased atrial pressure * Causes... * Increased GFR and increased Na+ filtration with no compensatory Na+ reabsorption in distal nephron. * Net effect * Na+ loss and volume loss.

Question 28

Hormones acting on kidney: Aldosterone * Secreted in response to... * Causes...

Answer 28

* Secreted in response to... * Decreased blood volume (via AT II) * Increased plasma [K+] * Causes... * Increased Na+ reabsorption * Increased K+ secretion * Increased H+ secretion

Question 29

Hormones acting on kidney: ADH (vasopressin) * Secreted in response to... * Causes...

Answer 29

* Secreted in response to... * Increased plasma osmolarity * Decreased blood volume * Causes... * Binds to receptors on principal cells, causing increased number of water channels and increased H2O reabsorption.

Question 30

Potassium shifts * What shift K+ out of the cell * What shifting K+ out of the cell causes * What shift K+ into the cell * What shifting K+ into the cell causes

Answer 30

* What shift K+ out of the cell * **Patient with hyperkalemia? _DO_ _Insulin_ _LAβ_ work.** * **_D_**igitalis * Hyper**_O_**smolarity * **_Insulin_** deficiency * **_L_**ysis of cells * **_A_**cidosis * **_β_**-adrenergic antagonist * What shifting K+ out of the cell causes * Hyperkalemia * What shift K+ into the cell * Hypo-osmolarity * Insulin (increased Na+/K+ ATPase) * ****_In_**sulin shifts K+ **_in_**to cells** * Alkalosis * β-adrenergic agonist (increased Na+/K+ ATPase) * What shifting K+ into the cell causes * Hypokalemia

Question 31

Electrolyte disturbances * For each * Low serum concentration * High serum concentration * Na+ * K+ * Ca2+ * Mg2+ * PO₄3−

Answer 31

* Na+ * _Low_: Nausea and malaise, stupor, coma * _High_: Irritability, stupor, coma * K+ * _Low_: U waves on ECG, flattened T waves, arrhythmias, muscle weakness * _High_: Wide QRS and peaked T waves on ECG, arrhythmias, muscle weakness * Ca2+ * _Low_: Tetany, seizures, QT prolongation * _High_: **Stones** (renal), **bones** (pain), **groans** (abdominal pain), **psychiatric overtones** (anxiety, altered mental status), but not necessarily calciuria * Mg2+ * _Low_: Tetany, torsades de pointes  * _High_: Decreased DTRs, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia * PO₄3− * _Low_: Bone loss, osteomalacia * _High_: Renal stones, metastatic calcifications, hypocalcemia

Question 32

Acid-base physiology * For each * pH * PCO2 * [HCO3–] * Compensatory response * Metabolic acidosis * Metabolic alkalosis * Respiratory acidosis * Respiratory alkalosis

Answer 32

* Metabolic acidosis * _pH_: Decreased (compensatory response) * _PCO2_: Decreased (compensatory response) * _[HCO3–]_: Decreased (1º disturbance) * _Compensatory response_: Hyperventilation (immediate) * Metabolic alkalosis * _pH_: Increased (compensatory response) * _PCO2_: Increased (compensatory response) * _[HCO3–]_: Increased (1º disturbance) * _Compensatory response_: Hypoventilation (immediate) * Respiratory acidosis * _pH_: Decreased (compensatory response) * _PCO2_: Increased (1º disturbance) * _[HCO3–]_: Increased (compensatory response) * _Compensatory response_: Increased renal [HCO3–] reabsorption (delayed) * Respiratory alkalosis * _pH_: Increased (compensatory response) * _PCO2_: Decreased (1º disturbance) * _[HCO3–]_: Decreased (compensatory response) * _Compensatory response_: Decreased renal [HCO3–] reabsorption (delayed)

Question 33

Acid-base physiology * Henderson-Hasselbalch equation * Winters formula

Answer 33

* Henderson-Hasselbalch equation * pH = 6.1 + log { [HCO3−] / (0.03 PCO2) } * Winters formula * The predicted respiratory compensation for a simple metabolic acidosis can be calculated using the Winters formula. * If the measured PCO2 differs significantly from the predicted PCO2, then a mixed acid-base disorder is likely present * PCO2 = 1.5 [HCO3–] + 8 +/- 2

Question 34

Metabolic/respiratory acidosis/alkalosis & hyperventilation/hypoventilation * pH \< 7.4 * PCO2 \> 40 mmHg * PCO2 \< 40 mmHg * pH \> 7.4 * PCO2 \< 40 mmHg * PCO2 \> 40 mmHg

Answer 34

* pH \< 7.4 = Acidemia * PCO2 \> 40 mmHg * Respiratory acidosis * Hypoventilation * PCO2 \< 40 mmHg * Metabolic acidosis with compensation * Hyperventilation * Check anion gap * pH \> 7.4 = Alkalemia * PCO2 \< 40 mmHg * Respiratory alkalosis * Hyperventilation * PCO2 \> 40 mmHg * Metabolic alkalosis with compensation * Hypoventilation

Question 35

Causes of metabolic/respiratory acidosis/alkalosis * Respiratory acidosis: Hypoventilation * Metabolic acidosis: Check anion gap * Respiratory alkalosis: Hyperventilation * Metabolic alkalosis with compensation: Hypoventilation

Answer 35

* Respiratory acidosis: Hypoventilation * Airway obstruction * Acute lung disease * Chronic lung disease * Opioids, sedatives * Weakening of respiratory muscles * Metabolic acidosis: Check anion gap * **Anion gap = Na+ – (Cl- + HCO3-)** * Increased **​**anion gap * **_MUDPILES_:** * **_M_**ethanol (formic acid) * **_U_**remia * **_D_**iabetic ketoacidosis * **_P_**ropylene glycol * **_I_**ron tablets or INH * **_L_**actic acidosis * **_E_**thylene glycol (oxalic acid) * **_S_**alicylates (late) * Normal anion gap (8-12 mEq/L) * **_HARD_-_ASS_:** * **_H_**yperalimentation * **_A_**ddison disease * **_R_**enal tubular acidosis * **_D_**iarrhea * **_A_**cetazolamide * **_S_**pironolactone * **_S_**aline infusion * Respiratory alkalosis: Hyperventilation * Pulmonary embolism * Tumor * Salicylates (early) * Hypoxemia (e.g., high altitude) * Hysteria * Metabolic alkalosis with compensation: Hypoventilation * Hyperaldosteronism * Antacid use * Loop diuretics * Vomiting

Question 36

Renal tubular acidosis * Definition * Type 4 * Defining feature * pH * Defect

Answer 36

* Definition * A disorder of the renal tubules which leads to non-anion gap hyperchloremic metabolic acidosis. * Type 4 * Defining feature * Hyperkalemic * pH * \< 5.5 * Defect * Hypoaldosteronism, aldosterone resistance, or K+-sparing diuretics. * The resulting hyperkalemia impairs ammoniagenesis in the proximal tubule --\> decreased buffering capacity and decreased H+ excretion into urine.

Question 37

Renal tubular acidosis: Type 1 * Location * pH * Defect * Assocaited with... * Due to...

Answer 37

* Location * Distal * pH * \> 5.5 * Defect * Defect in ability of α intercalated cells to secrete H+. * Thus, new HCO3- is not generated Ž--\> metabolic acidosis. * Associated with... * **Hypokalemia**, increased risk for calcium phosphate kidney stones (due to increased urine pH and increased bone turnover). * Due to... * Amphotericin B toxicity, analgesic nephropathy, multiple myeloma (light chains), and congenital anomalies (obstruction) of the urinary tract.

Question 38

Renal tubular acidosis: Type 2 * Location * pH * Defect * Associated with... * Due to...

Answer 38

* Location * Proximal * pH * \< 5.5 * Defect * Defect in proximal tubule HCO3- reabsorption results in increased excretion of HCO3- in urine and subsequent metabolic acidosis. * Urine is acidified by α intercalated cells in collecting tubule. * Associated with... * **Hypokalemia**, increased risk for hypophosphatemic rickets. * Due to... * Fanconi syndrome (e.g., Wilson disease), chemicals toxic to proximal tubule (e.g., lead, aminoglycosides), and carbonic anhydrase inhibitors.