lecture 8, renal physiology II

measurement of renal function

• measured by determining

  1. glomerular filtration rate

     • GFR is measured by determining plasma renal clearance (amount of plasma being cleared)

     • renal plasma clearance

       • volume of plasma per unit time of which all of a substance is removed

       • clearance of X = excretion rate of X (mg/min)/ [X]_plasma (mg/mL of plasma) (per 100mL want it to be 1mL)

       • example: substance is excreted into urine at a rate of 0.5 mg/min

         • [X]_plasma = 50 mL/min (cleared of substance per minute)

if clearance is less than GFR

• the substance is reabsorbed

• must have reabsorbed

if clearance is greater than GFR

• the substance is secreted

• must move in

GFR can be calculated by considering a substance that isn’t secreted or reabsorbed

• example: inulin (very invasive)

• you have to infuse in blood

• GFR = excretion rate of inulin/[inulin]_plasma

  • **clinically creatinine is used

    • produced as an end product from skeletal muscle metabolism of creatine

    • proportional to skeletal muscle mass

  • filtered load of X = [X]_plasma x GFR

    • filter load that actually leaves body

tubular reabsorption

• most of the filtered nutrients, ion, and fluid must be reabsorbed back into the blood

  • occurs via a very selective process

  • also works to concentrate filtrate with nitrogenous wastes and excess materials

• reabsorbed substances include

  • 99% of filtered water

  • 100% of filtered sugar (should never have in urine)

  • 99.5% of filtered salt (can let more go if body has too much)

  • 50% of filtered urea (use as a tool to create osmolarity gradient, good for water reabsorption, obligatory route)

actives tubular reabsorption

• sodium reabsorption occurs via an active Na+/K= ATPase

  • Na+ is actively pumped across the basolateral membrane into ISF

    • sodium reabsorbed back

  • increase [Na+] in the interstitial fluid

  • uses ~80% of total energy requirement of the kidneys (works other locations too)

  • **very important process

  • working all the time!

  • part of the daily energy drain

  • want sodium? Na+ - 3

  • want potassium? K+ - 2

Na+ reabsorption occurs

• ~65% from the proximal convoluted tubule (right away)

• ~25% from the ascending loop of henle (descending has permeability only to water) (sodium permeable)

• ~8-10% from the late distal convoluted tubule and cortical collecting duct (under the influence of hormones, aldosterone !)

• As much as 2% of filtered Na+ can be excreted

  • Not reabsorbed

filtered load = GFR x plasma concentration

• Plasma concentration of sodium= 140mEq/L

  • 3.206g/L

  • 0.003g/mL

  • GFR=125mL/min

  • Filtered load for sodium= 125mL/min x 0.003g/mL

    = 0.4g/min

  • We could excrete as much as 2% of this (0.008g/min or 11.52g/day)

role of Na+ reabsorption

1. in the loop of henle Na+/K+/2Cl- co-transport plays an important role in forming urine of varying concentrations/volumes (allow to form urine different depending on body’s need)

2. regulation of extra-cellular fluid volume

   • in the distal portion of the nephron Na+ reabsorption is variable and under the influence of hormones

     • natriuretic peptide (high BP), aldosterone, angiotensin II, vasopressin (ADH)

3. passive reabsorption/secondary active reabsorption

role of Na+ reabsorption: aldosterone

• released from adrenal gland

• stimulates the insertion of Na+ channels and Na+/K+ ATPases in principle cells of the late distal convoluted tubule and the cortical (early) collecting duct

  • low BP

  • hyperkalemia - K+ levels in ISF are too high

role of Na+ reabsorption: atrial natriuretic peptide (ANP)

• secreted by the atria in response to excessive myocardial stretching (experience more push than normal)

  • increased blood volume

role of Na+ reabsorption: renin-angiotensin aldosterone control

• granule cells of the afferent arteriole release renin in response to

  • decreased intrarenal blood pressure

  • decreased [NaCl] in fluid passing by the macula densa cells

  • an increase sympathetic stimulation (try to conflict blood pressure)

• renin cleaves angiotensinogen into angiotensin I

  • angiotensin I so then converted into angiotensin II by ACE (vasoconstrict)

changes in filtrate composition

• tubular reabsorption causes a dramatic decrease in filtrate

  • bicarbonate (buffer)

  • amino acids (pull them back immediately because your body needs them)

  • glucose

  • filtered proteins (shouldn’t be filtered but if small enough goes through, so take it back)

  • lactate (sugar 3 C molecule)

• filtrate Cl- increases due to ion co-transport (make sure charge is balanced

• osmolarity of filtrate is maintained

passive reabsorption

1. glucose and amino acids

2. chloride reabsorption

3. water

4. urea

passive reabsorption: glucose and amino acids

• glucose and amino acids are co-transported from the tubule lumen with Na+ against their concentration gradient (high → low)

  • secondary active transport

• limited number of co-transport carriers in the plasma membrane of the tubule cells

  • some solutes have a maximum transport limit T_m

    • T_m = 375 =mg/min

      • if you have an increase in glucose you can exceed this, can’t reabsorbed glucose → dump in urine)

    • 125 mg/min is normally filtered

  • membrane is sided

  • insulin increased GLUT transporters

• no ATP

• follow natural gradient

glucose transport maxima

• composite graph shows the relationship between filtration, reabsorption, and excretion of glucose

passive reabsorption: chloride reabsorption occurs

• via a paracellular route

  • passively follows the electrical gradient formed by Na+ uptake

• transcellular route

  • used chloride/base antiporters

  • buffering capacity

  • bicarbonate porter in RBC

  • proton acceptor → base

passive reabsorption: water

• Solute reabsorption decreases lumen osmolarity

  • Increases interstitial fluid osmolarity

• Water diffuses into the interstitial fluid by osmosis

  • Uses aquaporins

    • Pores in the luminal (apical) and basolateral (bottom) plasma membranes

    • Some water is able to pass intercellularly in the proximal convoluted tubule

    • Elevated oncotic pressure in the peritubular capillaries will pull water out of the interstitial fluid

• water permeability is always there

• water naturally going to follow

passive reabsorption: 6 different aquaporins isoforms are used in the kidney

• In the proximal convoluted tubule and the thin descending loop of henle, aquaporins are always present (really important)

  • 75% of water is obligatorily absorbed via this route

  • happens by itself because follows capacity of solutes

• A specific isoform, aquaporin 2 (AQP2) is inserted in the principle cells (increased aquaporin under influence of vasopressin) of the late distal convoluted tubule and the collecting duct under the hormonal influence of vasopressin

  • Vasopressin binds to membrane receptors

  • Activates cAMP secondary messenger system

    • AQP2 pores are inserted into the luminal membrane (apical)

    • Increases water reabsorption

    • last minute changes to end of a nephron

osmolarity of tubular fluid

passive reabsorption: vasopressin is released from the posterior pituitary when

1. extracellular fluid osmolarity rises above 280mOsm/L

   • detected by osmoreceptors in the hypothalamus

   • extracellular fluid of your tissue

   • vasopressin → retain in urine

2. blood pressure/blood volume decrease

   • carotid and aortic baroreceptors in the atria stimulate vasopressin release

   • stretch sensitive receptors in the atria simulate vasopressin release

     • if you’re not getting pushed

• diabetes insipidus

  • inability to produce vasopressin or

  • inability to principle cells to respond to vasopressin

passive reabsorption: urea

• Reabsorption of solutes and water create a concentration gradient for urea reabsorption

• Tight junctions only permit ~50% of urea (molecule itself is kind of large) to be reabsorbed

• Thin regions (make impermeable) of the loop of henle have urea transporters

  • Secrete an equivalent amount of urea back into the nephron tubule (can control water within this location)

• Urea impermeability is found due to tight junctions (problematic) in:

  • Loop of henle

  • Distal convoluted tubule

  • Collecting duct (late collecting duct use transport)

• Half of the urea is again reabsorbed back into the late collecting duct

  • Uses transporters

• Increased vasopressin (works with water charge it permeability)

  • Increased amount of urea reabsorption

  • Increased vertical osmotic gradient in the medulla