Renal Hormones Flashcards
how does kidney accomplish its homeostatic role?
1) filter blood to generate fluid in renal tubule free of cells/proteins.
2) reabsorbs solutes and water from tubular fluid
3) secretes other solutes (uric acid) into tubular fluid
4) excretes tubular fluid (urine)
specific renal functions
1) regulation of body fluid volume
2) regulation of BP and volume
3) regulation of concentration of plasma electrolytes
4) regulation of plasma pH
5) elimination of waste products from metabolism (ex: urea from protein, uric acid from nucleic acids)
5) removal of drugs and foreign compounds from circulation
6) synthesis of certain hormones (renin, erythropoeitin)
urine drains from ______ that form renal pyramid into _______ and then into _______.
urine drains from RENAL PAPILLAE that form renal pyramid into RENAL CALYX and then into PELVIS.
kidneys receive __% of cardiac output
kidneys receive 25% of cardiac output
osmolarity of cortex vs of medulla
Cortex (outer area): 300 mOsm – ~same as plasma
Medulla (inner area): 1200 mOsm (4x higher to better concentrate the urine
where in the nephron is 2/3 of the water and sodium reabsorbed?
proximal tubule
blood enters glomerulus via ______, and exits via ___________
blood enters glomerulus via afferent arteriole, and exits via efferent arteriole
(NOT a venule)
thin descending tubule
Very permeable to water.
Water leaves due to increasing concentration gradient.
thin ascending tubule
Impermeable to water.
Na+ reabsorption (Na concentration decreases in cortex as tube ascends, so Na+ leaves tubule)
thick ascending tubule
Impermeable to water.
Na+ reabsorbed.
TRANSPORTER: Na/K/2Cl co-transporter
also luminal positive transepithelial potential drives paracellular uptake of cations (Na, Ca, etc.)
juxtaglomerular apparatus (general and components)
Distal tubule in v close proximity to glomerulus.
Macula densa and juxtaglomerular cells
macula densa
Senses concentration of solute in fluid flow (mainly Na conc)
juxtaglomerular cells
Sense fluid flow.
Produces renin to control constriction of afferent/efferent arterioles
processes involved in urine formation
1) glomerular filtration
2) tubular reabsorption
3) tubular secretion
4) excretion
formula for urine excretion
excretion = filtration - reabsorption + secretion
Substances that are reabsorbed reenter circulation via _______
peritubular capillaries
this is from efferent arterioles
layers of the capillary membrane
1) capillary endothelial cells (fenestrated)
2) basement membrane
3) podocytes (form filtration slits)
how does basement membrane prevent proteins from entering Bowman’s space?
1) negative charge causes electrostatic repulsion of proteins
2) has only small holes that can only allow water and sodium to pass
nephrin
Transmembrane protein embedded in podocyte membrane.
Covers filtration slits. But interdigitations of nephrins leave gaps, allowing fluid to flow through
mutation of nephrins
Causes loss of protein in urine.
Leads to edema, heart failure.
NEPHROTIC SYNDROME
GFR
Glomerular filtration rate.
The rate at which fluid is filtered thru the glomerulus.
Typical: 125 mL/min
RPF
Renal Plasma Flow.
Rate at which plasma is delivered to kidneys.
Typical: 650 mL/min
Filtration Fraction
GFR/RPF
Fraction of plasma entering the kidney which undergoes filtration across the glomerular capillary membrane.
Typical: 20%
glomerulonephritis
Renal disease initiated by an immune response.
Streptococcal infection causes antigen-antibody complexes to build up in glomerulus, damaging it.
DECREASES GFR.
Increases permeability/leakage, so proteins are lost (proteinuria)
kidney stones
Block flow of renal filtrate.
Increase hydrostatic pressure of Bowman’s Capsule.
DECREASES GFR
normal oncotic pressure of Bowman’s capsule
0
because no proteins
Filtration Coefficient depends on (2)
1) properties of glomerular membrane
2) surface area
how does the oncotic pressure of the glomerular capillary bed change from afferent to efferent arterioles?
Increase in oncotic pressure.
Water was filtered out, but protein was not (increases protein concentration)
RBF vs RPF
RBF = renal BLOOD flow
All blood flow, including hematocrit (volume of blood occupied by cells).
Typical: 1250 mL/min
RPF = renal PLASMA flow
Excludes hematocrit
Typical: 687 mL/min
renal clearance
Corresponds to volume of plasma per unit time from which x has been COMPLETELY removed and excreted.
GFR corresponds to the clearance of a compound with the following properties:
1) freely filtered (not bound to plasma proteins)
2) not absorbed or secreted
3) Not metabolized or produced by the kidney
4) does not alter GFR
Inulin is used to calculate _________.
also: properties, why it is used
Inulin is used to calculate GFR.
Small, fructose molecule.
Not absorbed//secreted.
Not made by body (have to inject it)
**Not typically used to calculate GFR. Creatinine clearance is more typical bc don’t need to infuse it
PAH is used to calculate ____________.
also: properties
Clearance of PAH is used to calculate RENAL PLASMA FLOW.
Freely filtered. Efficiently secreted (not 100% --> must be corrected for by dividing by 0.9). Not reabsorbed. Small organic anion. Introduced by infusion.
how are RBF and GFR regulated?
constriction/dilation of afferent/efferent arterioles
upstream constriction: impact on RBF/GFR
Decrease GFR
Decrease RBF
downstream constriction: impact on RBF/GFR
Increase GFR
Decrease RBF
downstream dilation: impact on RBF/GFR
Decrease GFR.
Increase RBF.
upstream dilation: impact on RBF/GFR
Increase GFR
Increase RBF
vasoconstrictor effect on GFR/RPF
Ex: norepinephrine
Constricts both afferent/efferent arterioles.
Decreases both GFR and RBF.
Effect: conserve fluid, increase BP
vasodilator effect on GFR/RBF
Ex: nitric oxide
Dilates both afferent/efferent arterioles.
Increases both GFR and RBF.
Effect: excrete water/salt, reduce BP
kidneys filter ____L of fluid per day
180 L per day
__% of filtered water, Na, Cl, and HCO3 are reabsorbed
99% of filtered water, Na, Cl, and HCO3 are reabsorbed
100% of glucose
reabsorption in proximal tubule
fraction, osmolarity, driving force
2/3 (67%) of Na and water are reabsorbed in PCT.
Iso-osmotic: Na is reabsorbed, and water follows so net is same
Driving force: (Na/K)-ATPase in basolateral membrane maintains a low cytoplasmic [Na]
transporters present in PCT
(Na/K)-ATPase, basolateral: maintains low cytoplasmic [Na+]
Na/H antiporter, apical: uses Na+ gradient to pump H+ out of cell into filtrate.
Na+-coupled transporters, apical: use Na+ gradient to pump glucose/AAs out of filtrate
Passive transporters, basolateral: glucose/AAs move passively back into blood
diabetes mellitus
Failure to produce/respond to insulin leads to high blood sugar levels.
Na+/glucose cotransporter becomes saturated, so excess glucose appears in the urine.
High urine volume bc water follows solutes (glucose) –> polyuria
reabsorption by thin parts loop of henle
percentages, driving force, permeability
25% of Na/Cl
23% of water.
Driving force: high osmolarity of interstitial fluid of inner medulla
Descending: IMPERMEABLE to water
Ascending: permeable to water
diuretics
Prevent uptake of solute –> water is not reabsorbed and stays in filtrate
lumenal positive transepithelial potential
Drives paracellular uptake of cations.
Between cells, do not have to enter cell.
transporters in thick ascending loop of henle
(Na/K/2Cl) co-transporter: Na flowing down gradient into cell drives Cl and K to enter too.
Lumenal positive transepithelial potential: drives cations between cells into blood.
transporters in distal tubule
IMPERMEABLE TO WATER.
Na/Cl cotransporter: Na moving down gradient drives Cl into cell
transporters in principal cells (CD)
Na+ channels: Na+ flows down gradient into cell.
Aquaporins: water enters cell (exits filtrate, reabsorbed) – controlled by ADH
K+ channel: K+ flows down gradient out of cell into filtrate (secreted) – controlled by aldosterone
ADH
secreted in response to high PLASMA OSMOLARITY.
Increases water reabsorption
diabetes insipidus
Fail to make/secrete ADH, or principal cells fail to respond to ADH.
Large volume of urine (up to 18L per day).
Must drink tons of water to compensate.
3 types of diuretics
furosamide: loop diuretic
thiazide: targets distal tubule
amiloride: inhibits Na channels in collecting duct
Na+ excretion responds to ________
Na+ excretion responds to VOLUME
water excretion responds primarily to __________
water excretion responds primarily to plasma osmolality
sympathetic nerve activity
stimulated by, effect
STIMULATED BY:
volume contraction
EFFECT:
Increased renin
Decreased GFR
Increased Na+ reabsorption in PCT
renin/angiotensin
stimulated by, effect
STIMULATED BY:
Increased sympathetic nerve activity.
Decreased afferent arteriole pressure.
Decreased GFR.
EFFECT:
Increase BP
Increase Na reabsorption in PCT
Increase secretion of aldosterone/ADH
aldosterone
stimulated by, effect
STIMULATED BY:
Increased angiotensin II.
Increased [K+] in plasma
EFFECT:
Increased Na reabsorption in CD.
Increased K secretion in CD
ADH
stimulated by, effect
STIMULATED BY:
Increased plasma osmolarity.
Volume contraction.
Angiotensin II.
EFFECT:
Increased water reabsorption in CD
ANP - Atrial Natriuretic Peptide
stimulated by, effect
STIMULATED BY:
volume expansion
EFFECT:
Increased GFR.
Decreased renin/aldosterone/ADH.
Decreased Na reabsorption in CD
response to volume contraction
Increase sympathetic activity (^renin,
K+ secretion by principal cells
Controlled by aldosterone (secreted in response to high [K+]).
More K+ channels open on apical side, allowing K+ to flow out into filtrate.
Increased activity of Na/K ATPase on basolateral side: more K+ pumped in = more K+ flowing out on apical side)
Increased activity of Na+ channels on apical side: positive in balances the positive out
Ca++ reabsorption by late distal tubule and CD
Apical Ca channels
Basolateral Ca-ATPase
Basolateral Na/Ca exchanger
*only transcellular uptake in collecting duct are regulated
Ca++ uptake by PT and thick ascending loop of henle
Apical Ca channels
Basolateral Ca-ATPase
Basolateral Na/Ca exchanger
AND
paracellular uptake of Ca (via luminal positive transepithelial potential)
Hypocalcemia
Calcitriol secretion = Ca2+ reabsorption in gut and by late distal tubule/CD.
Parathyroid Hormone (PTH) secretion = increased bone resorption and Ca2+ reabsorption by late distal tubule/collecting duct.
Hypercalcemia
Calcitonin secretion = Bone formation (decreases [Ca2+] plasma).
alpha intercalated cells of collecting duct contain…
- ATP-driven proton pump (V-ATPase) in apical membrane
- actively pumps protons from the cytoplasm of the cell into the renal fluid - Cl-/HCO3- exchanger in basolateral membrane
- allows secretion of bicarbonate, preventing cytoplasm from
becoming too alkaline during acid secretion
endogenous anions secreted by proximal tubule
prostaglandins
uric acid
anionic drugs secreted by proximal tubule
penicillin
salicylate
ibuprofin
adefovir (anti-HIV)
endogenous cations secreted by proximal tubule
epinephrine
norepinephrine
cationic drugs secreted by proximal tubule
morphine
amiloride
verapamil
vinblastine
How are organic anions secreted via the proximal tubule?
basolateral:
anion/alpha-ketoglutarate antiporter
apical:
anion/Cl– exchanger
^drives uptake of OA- from circulation.
How are organic cations secreted via the proximal tubule?
basolateral:
passive transporter brings organic cations in
apical:
1. organic cation/proton antiporter
- MDR (ABC ATPase) drives OC+ out actively
Competition between different organic anions or cations for the same transporters in the proximal tubule can lead…
altered rates of drug clearance and drug toxicity
Name an example of a positive benefit of drug competition in the proximal tubule…
competition between PAH and penicillin for secretion by proximal tubule –> increased half life of penicillin in circulation
excretion rate
units: mg/ml
calculated via ([x] in urine * urine flow rate)
clearance
ml/min
Cl= excretion rate (mg/ml) / [x] in plasma (mg/ml)
