T/F: there are a few, scattered glomeruli in the renal medulla?
False; the renal medulla = tubules + vessels (no glomeruli)
Describe the vasculature of the kidney?
Renal artery -> afferent arteriole -> glomerula caps -> efferent arteriole -> peritubular caps
Vasa recta = peritubular caps of the juxtamedullary nephrons
What comprises the glomerular filtration barrier?
1. Capillary endothelial cells
2. Glomerular basement membrane
3. Glomerular epithelial cells (podocytes)
What are barriers to glomerular filtration?
- Size (MW under 5,500 = freely filtered)
- Charge (major determinant for MW 5.5-44K, fixed negative charges on filtration surface)
- Shape (minor determinant)
Names for inner tubule surface?
Luminal or apical
Names for outer tubule surface?
Peritubular or basolateral
What is reabsoprtion?
Transport of water/solutes form inside -> outside the tubule
What is secretion?
Transport of water/solutes form outside -> inside tubule
Urine volume = ?
Urine volume = filtration - reabsorption + secretion
What is the role of the proximal nephron (PCT or PST)?
Bulk reabsorption of water and solutes (Na, Cl, HCO3, glucose)
What is the role of the Loop of Henle (tDLH, tALH, TALH)?
- Moderate solute reabsorption
- Urine concentration and dilution
What is the role of the distal nephron (DCT, CND, collecting tubule- initial, cortical, outer/inner medullary)?
- "Fine-tune" urine composition
What is the distribution breakdown of water in the extracellular vs. intracellular compartment?
Extracellular ~40% (17 L)
- Blood plasma = 3 L
- Interstitial fluid = 13 L
- Transcellular fluid = 1 L
Intracellular ~ 60% (25 L)
(Total body water = 42 L)
Solute composition of plasma?
- Na: 142
- K: 4.4
- Ca: 1.2 (ionized)
- Mg: 0.6 (ionized)
- Cl: 102
- HCO3-: 22
- Proteins: 7 g/dL
- Glucose: 5.5 mM
pH = 7.4
Osmolality = 291
Volume balance: synonymous terms for intravascular volume?
- Plasma volume
- Effective circulating volume
- 1/4 of extracellular fluid (ECF) volume
These determine blood pressure
In what conditions will you see a dissociation between total body volume and effective circulating volume?
Some disease states:
- Kidney disease
T/F: Volume balance = water balance?
Change in water balance changes what factors? Salt balance?
Change in water balance:
- Relatively BIG change in osmolarity
- Relatively SMALL change in ECF volume
Change in salt balance:
- Reflected by ECF volume
- Represents a minimal change in serum sodium (Na) osmolarity
Describe the renin-angiotensin-aldosterone axis (picture)
What triggers renin release? Inhibits?
- Increased sympathetic outflow to JGA
- Renal hypoperfusion (renal baroreceptors)
- Endothelin, PGE2, PGI2
- Hormones (Angiotensin II, AVP)
- Other: high [K], nitric oxide
What triggers anigotensin II release?
- Increase systemic blood pressure
- Aldosterone release
- Increase sensitivity of Tubuloglomerular feedback
- Stimulate Na-H countertransport
- Stimulate AVP and thirst centers
- Efferent arteriolar vasoconstriction
ICF volume is a reflection of what?
What are sensors of ICF volume?
What are effector pathways of ICF volume
- AVP (via ADH)
What solutes are excreted by tubules:
- Not at all
- Completely: PAH
- Partially: creatinine, Na
- Not at all: glucose, bicarbonate
Equation for arterial content?
Equation for venous content?
Equation for urine content?
(RPFa)(Px,a) = (RPFv)(Px,v) + (V)(Ux)
Basically, arterial content = venous content + urine content
Equation if solute is completely extracted?
Px,v = 0,
therefore: (RPFa)(Px,a) = (V)(Ux)
(RPFa) = (Ux)(V)/(Px,a)
What is clearance?
Cx = (Ux)(V)/(Px)
What are characteristics of the ideal marker to estimate glomerular filtration rate? What is it?
- Freely filtered in the glomerulus
- No tubular reabsorption or secretion
- Not synthesized or metabolized
- Physiologically inert
This is Creatinine
- Endogenous product of muscle metabolism
- Easy to measure its value in the blood
- Stable rate of production
Is creatinine filtered? Reabsorbed? Excreted?
- NOT reabsorbed
What is the rate of creatinine production for males/females?
Males: 15-20 mg/kg ideal body weight
Females: 15-20 mg/kg ideal bod weight
Alternate markers to creatinine?
- Inulin (gold standard)
Clearance of creatinine estimates what?
The glomerular filtration rate (GFR)
What is normal GFR?
100-125 mL/min (adults)
- Males > females
- Declines with age
Does stable serum creatinine = stable kidney disease?
- The sCr is not a great marker also because it is maintained despite loss of GFR due to tubuloglomerulofeedback (recruitment of other gloms) and increased tubular Cr secretion 15% to 35%.
Results of regulation of GFR (glomerulotubular balance)?
- No change in fractional excretion/reabsorption
- High GFR -> high absolute reabsorption / excretion
- Low GFR -> low absolute reabsorption / excretion
- Prevents excessive changes in solute excretion
How is GFR regulate?
1. Tubuloglomerular feedback (TGF)
- Macula densa (MD) senses changes in solute delivery (MD = specialized cells near distal tubule & vascular pole)
- Results in release of vasoactive substances -> change GFR
2. Neurohormonal effects- Vasoconstriction
- Angiotensin II: Arteriolar vasoconstricton efferent > afferent
- Arginine vasopressin: Renal vasoconstriction medulla > cortex
- Sympathetic nervous system activation
- Modulators: epinephrine, endothelins, leukotrienes
Does anigotensin II vasoconstrict the afferent or efferent arterioles more?
Efferent > afferent
What is the range of urine osmolality?
30-1200 mOsm (daily solute exretion ~ 600 mOsm)
What is the lowest possible urine volume? Highest?
Lowest: V = 600/1200 0.5 L/day
Highest: V = 600/30 = 20 L/day
What is the osmolarity of the fluid entering the descending thin limb? In the medullary interstitium?
- Fluid entering tDL: 300 mOsm
- Medullary interstitium: 1200 mOsm
Established by the countercurrent multiplier system
What is arginine vasopressin?
Aka aldosterone or anti-diuretic hormone (ADH)
What is the mechanism of action of ADH? What stimulates/suppresses it?
- Insertion of water channels (aquaporins) into apical membrane in collecting ducts
- Upregulate Na/K/Cl cotransport in thick limb
- Insertion of urea transporters (UT1) into apical membrane in medullary collecting ducts
- Stimulated by hyperosmolarity
- Suppressed by hypoosmolarity
What are major hormones controlling phosphorus regulation?
Parathyroid hormone (PTH)
- Decreases PO4 reabsorption (increases excretion)
- Downregulates apical transporter expression 1,25-dihydroxy vitamin D
- Increases PO4 reabsorption (decreases excretion) at distal nephron
Increase PO4 excretion:
- Increase intake
Describe calcium regulation in terms of Na and other hormones?
- Increased Na reabsoprtion -> increased Ca reabsorption (and vice versa); it follows Na!
- PTH: increases Ca reabsorption in TAL, DCT, CCT
- Vitamin D: increases Ca reabsorption in distal nephron
- Loop diuretics: decrease Ca reabsorption
What is normal blood pH? Minimal urine pH?
- Normal blood: 7.4
- Minimal urine: 4.4
What is acidemia? What causes it?
Low pH of blood, caused by either:
- Respiratory acidosis (high PCO2)
- Metabolic acidosis (low HCO3)
Acidemia does NOT = acidosis (acidemia is the net pH change; acidosis is the process leading to this)
What is alkalemia? What causes it?
High pH of blood caused by either:
- Respiratory alkalosis (low PCO2)
- Metabolic alkalosis (high HCO3)
Alkalemia does NOT = alkalosis
What are the ECF buffers? Relative importance/effectiveness?
1. Bicarbonate (CO2/HCO3)
3. Phosphate (H2PO4/HPO4)
What are the relevant equations for CO2/HCO3 buffer pair?
pKa of the bicarbonate buffer system = 6.1
pH = 6.1 + log (HCO3)/(CO2)
pH = 6.1 + log (HCO3)/(PCO2 x 0.03)
Why is bicarbonate buffer system (pKa = 6.1) better than phosphate (pKa = 6.8)?
- [HCO3] >> [total phosphates]
- Open system (respiratory adjustment of CO2 and renal adjustment of HCO3)
How does the kidney respond to respiratory processes? (speed, HCO3 handling...)
- Slow (hours or days)
- Reclamation of filtered HCO3
- Increased titratable acid excretion
- Very increased ammoniagenesis
- H secretion = HCO3 reabsorption
How does the kidney respond to metabolic alkalosis?
Suppression of proximal H+ secretion
- Inhibit basolateral Cl-HCO3 exchange
- Increase HCO3 paracellular backleak
Suppression of ammoniagenesis
Inhibit H+ secretion in Cortical Collecting Duct
- Decrease alpha-type intercalated cells (H+ secretion)
- Increase beta type intercalated cells (HCO3 secretion)
Correction of metabolic alkalosis is very sensitive to ________. Elaborate
Correction of metabolic alkalosis is very sensitive to ECF volume status
- Volume depletion limits ability to correct alkalosis
1. Decreased GFR = decreased filtered load HCO3
2. Decreased Na delivery = decreased Na reabsorption (Na-H exchange)
3. Decreased ECF volume = Increased aldosterone (Increased H+ secretion)