Renal Quiz 2 (4/14 and 4/16)

Tubular Maximum (Tm)

Highest reabsorption rate; units: Amount per unit time

F =

GFR * [X] plasma; when substance is freely filterable

E = 1st of 2 ways

Ux * V

E = 2nd of 2 ways

F - R + S

When substance is freely filterable at the glomerulus

Not reabsorbed by tubules

Not secreted by tubules

Not synthesized by tubules

Not broken-down by tubules

Clearance of ‘X’, Cx = GFR
EX: inulin (NOT produced endogenously)

If substance freely filtered and completely secreted

Cx = renal plasma flow
EX: PAH (Para-aminohippurate)

Is glucose secreted?

NO!

what substance is filtered and PARTIALLY reabsorbed?

Bicarb

clearance can never exceed…

renal plasma flow

If plasma glucose is BELOW renal threshold, E =

E = 0

If plasma glucose is ABOVE renal threshold, E =

E = F - Tm (glucose has S = 0)

What percent of the filtrate reaches the LH?

30%

LH reabsorbs how much of filtered water

15% (descending limb)

LH reabsorbs how much of filtered NaCl

25% (ascending limb)

Which is reabsorbed more in LH?

salt more than water, creating conc gradient when it goes to IF

LH thin descending

permeable to water moderate to urea and ions

LH thin ascending

only permeable to ions (not water)

LH thick ascending

NaCl active transport, impermeable to water

What does blocking Na+ channels (ENaCs) in principle cells cause / Why might someone be concerned when taking meds that inhibits Na channel to treat hypertension?

Hyperkalemia, less K+ secreted into urine as a result of the Na+ gradient, so more K+ in plasma

What does low plasma pH cause?

More H+ in the plasma, so Type A intercalated cells activated: more H+ secreted into urine, therefore more K+ reabsorbed, so less K+ in urine

Type A intercalated cells

respond during ACIDOSIS: secrete H+ and reabsorb K+

Type B intercalated cells

respond during ALKALOSIS: reabsorb H+ and secrete bicarb

• flipped transporter expression in membrane: Type A apical is on its basolateral and vice versa

• if body has ongoing pH imbalance, some cells normally B can become Type A

renal clearance

clearance from BLOOD
measurement of renal excretion ability
volume of plasma from which ‘x’ is completely cleared per unit time

clearance of x (Cx) =

Cx = [(U]x * Vx) / [X]plasma

substance has lowest clearance in healthy person

glucose

in kidney disease, GFR always

decreases

% of plasma filtered at glomerulus to Bowman’s capsule

20%

% of plasma goes directly to efferent arteriole

80%

Creatinine

produced endogenously (result of protein breakdown)

small amount secreted into urine in PCT, therefore is OVERestimation of GFR (Cx = E / [X]plasma; E > F and not E = F)

renal clearance units

volume per unit time

renal plasma flow units

volume per unit time

GFR units

volume per unit time

Renal Blood flow =

RBF = Renal Plasma Flow / (1-Hct)

Renal Blood Flow units

volume per unit time

What percent % of water and salts reabsorbed at PCT?

70%

How much of nutrients reabsorbed at PCT?

~100%

LH; descending loop permeability

ONLY water

LH Ascending loop permeability

ONLY salts: Na+, K+, Cl-, Ca2+, HCO3-

Distal Convoluted Tubule permeability

more selective; hormones can regulate water and salt reabsorption

selective reabsorption of Na+ and Cl-, water

active secretion of ions, acids

Collecting Duct

primarily reabsorbs Na+, Cl-, urea, water (if ADH)

adjusts final osmotic conc of urine

Loop of Henle generates

osmotic gradient b/c of these unique reabsorption patterns

reabsorption principles

Na+ reabsorbed via active transport

electrochemical gradient of Na+ drives anion reabsorption

water follows solute reabsorption via osmosis (AQP1 ALWAYS in PCT and LH; will talk about AQP2-4 later)

Concentration of remaining solutes in lumen increases as water leaves, so permeable solutes reabsorbed via passive diffusion

renal threshold

PLASMA CONC at which a specific compound or ion will begin appearing in urine (saturation of mediated transport)

Graph of Glucose movement (mg/min) vs Glucose Plasma Conc (mg/100 mL)

GFR is the slope, the GFR is constant

filtration line, reabsorption line, and excretion line

the point where reabsorption is last equal to filtration is the turning point —> X value is renal threshold

Tubular Maximum (Tm)

highest / maximal reabsorption RATE

Tm units

amount per unit time (i.e. mg/min)

At renal threshold, what is equal?

F = R = Tm

Increasing Tm affects graph by

shifting curve up (higher glucose mvmt) and to the right (higher renal threshold)

how to find renal threshold?

F = GFR * [X]plasma = Tm —> solve for [X]plasma

Apical side of membrane faces what

lumen of tubule

basolateral side of membrane faces what

blood

transporters on apical side

Majority SGLT2 in PCT, some SGLT1 (Distal side of PCT)

transporters on basolateral side

GLUT2

SI vs Tubule

No SLGT2 in SI, so meds can be targeted to certain transporters to have differentiated effects

dynamic expression of SGLT transporters

Elevated plasma glucose does what to SGLT2

higher expression of SGLT2 (dynamic expression like in SI)

type 2 diabetes

GFR only affected by hydrostatic pressure so doesn’t change (slope is the same)

overexpression of SLGT2 —> Tm increases —> graph shifts up and right

later onset of glucose excretion (b/c Tm increased)

Type 2: higher plasma glucose due to lack of cell uptake, so more glucose filtered into tubule, causing more SGLT2 expression, causing more glucose reabsorption back into plasma

plasma glucose STILL HIGH

Type 2 diabetes, plasma glucose still high so…

meds need to target GLUT2 (antagonist or stop expression), to enhance excretion rate; since SGLT2 is dynamically expressed no matter what

PCT

lots of active transporter / selective

NaHCO3 and Na-organic solutes primarily reasborbed in first half

• Sodium reasborption: co transport

  • Basolateral side: NKA pump sets up Na+ gradient

  • Apical side: Na+ comes in and co-transports glucose, AA, organic solutes

• bicarb transport on basolateral side (absorbed)

  • bicarb made IN the cell and goes into blood

• H+ ion transport on apical side (secretion)

Passive reabsorption in the PCT

urea: goes down its conc gradient and is reabsorbed

• via

  • paracellular means (more common)

  • transcellular means (less efficient)

transcytosis in the PCT

glomerular ultrafiltration can still miss some proteins and they come into filtrate (small proteins and peptides)

most of the filtered proteins are reabsorbed and broken down by enzymes: receptor-mediated endocytosis AKA renal digestion

• how kidneys terminate peptide signal and get rid of hormones

Fanconi’s syndrome

renal disease that results from impaired ability of the PCT

• less reabsorption: everything (HCO3-, AA, glucose, low MW proteins) increase in urine

• leads to muscle weakness, slow development, bowed legs, acidosis b/c bicarb not reabsorbed

PCT secretion

H+ (apical Na+ / H+ exchanger, NHE)

Ammonium ions via Na+ NH4+ antiport —> how we get rid of nitrogen

Organic compounds; PCT secretion

transported across the tubule epithelium primarily by secondary and tertiary active transport

• direct active transporter: NKA

• secondary indirect active transoprt: Na-DC

• tertiary indirect active transporter: OAT

Organic Anions

broad specificity —> bile salts, urate, vitamins (Ascorbate, folate), PAH, penicillin, toxic chemicals

• compete for the same transporter —> can prolong penicillin in body / plasma and therefore longer effect

clearance of penicillin is <, >, or = to GFR

clearance of penicillin is > GFR (b/c E > F since there is also secretion)

Organic Cations

broad specificity —> creatinine, dopamine, epinephrine, atropine, morphine, cimetidine (Histamine H2 antagonist for gastric ulcer), isoproterenol, procainamide (antiarrhythmic medicine)

• compete for the same transporter —> can prolong substance in body / plasma and therefore longer effect

• side effects possible if there’s cross-talking

Adrenal Glands secrete…

Aldosterone

Hypothalamus secretes…

ADH

DT and CD reabsorption of Na+ and Cl- is sensitive to…

Aldosterone

DT and CD reabsorption of water is sensitive to…

ADH

DT and CD secretion of K+ is sensitive to…

aldosterone

DT and CD secretion of H+ is dependent on…

pH

DT and CD exchange of K+ for

for Na+

DT and CD exchange of H+ for

K+

most cells in CD are

principle cells (some in DT)

principle cells are…

aldosterone-ADH sensitive, regulate how much salt and water you reabsorb

• Na+ in, K+ out; set up by NKA pump

Intercalated cells are…

pH regulated; chemosensitive, not hormone sensitive

ADH causes

binds to basolateral side receptors (from blood) and causes insertion of vesicles with aquaporins into APICAL membrane of CD, pee less / more water reaborption

ADH signaled by

increased osmolarity of fluid (that’s why more water is reabsorbed)

Aldosterone causes

has intracellular receptor (it’s a steroid that can diffuse past the membrane), modifies gene transcription AND protein channels + pumps that results in more Na+ reabsorption and K+ secretion

Aldosterone signaled by

LONG loop: lowered BP

SHORT loop: high extracell K+

in proximal tubule cell

• Na+ and HCO3- are filtered and in filtrate

• H+ secreted via Na+/H+ apical exchanger

• H+ combines with HCO3- in filtrate to make CO2 and H2O

• CO2 diffuses into cell, combines with H2O, and makes bicarb and H+

  • bicarb reabsorbed into blood

  • H+ secreted and excreted

• Glutamine metabolized into NH4+ and bicarb

  • NH4+ is secreted and excreted

  • bicarb reabsorbed into blood