Renal I Flashcards
8 major functions of the kidneys
- excretion of metabolic waste and foreign substances
- regulation of water and electrolytes
- regulation of extracellular fluid volume
- regulation of plasma osmolality
- regulation of RBC production
- regulation of vascular resistance
- regulation of acid-base balance
- regulation of vitamin d production
path through kidneys
bownman’s capsule/renal corpuscle - proximal convoluted tubule- HENLE (straight proximal tubule- descending thin limb- ascending thin limb- ascending thick limb)- macula densa- distal convoluted tubule- cortical collecting duct- medullary collecting duct- papillary duct
parts of the JG apparatus
macula densa + extraglomerular mesangial cells (EGM)+ JG cells that produce renin/angiotensin II of afferent arterioles
3 layers of the filtration barrier for capillaries in the glomerulus
- endothelium of capillaries
- capillary basement membrane
- interdigitated podocytes
structure-function: glomerulus
(passive) ultrafiltration of low molecular weight substances & H20 from capillaries to bowman’s space
segments of proximal tubule
proximal convoluted tubule, proximal straight tubule
segments of henle’s loop
descending thin limb
ascending thin limb
ascending thick limb
(includes macula densa)
segments of collecting duct
connecting tubule
cortical collecting duct
outer medullary collecting duct
inner medullary collecting duct
structure-function: proximal tubule
- high volume, low gradient re-absorption
- has brush border to increase surface area
- has lots of mitochondria to pump Na
3 basic processes of urine formation
1) ultrafilration- into bowman’s capsule
2) reabsorption of water from ultrafiltrate into tissue
3) secretion of solutes IN to tubular fluid to be excreted
structure-function: loop of henle
- makes high interstitial osmolarity
- poorly developed apical & basolateral surfaces
structure-function: distal tubule
low-volume, high gradient re-absoption
- lots of mitochondria & extensive infoldings (well developed apical & basolateral surfaces)
structure-function: macula densa
contains the JGA, senses tubular flow
structure-function: collecting duct
- concentration/dilution of final urine
- has principal and intercalated cells
principal cells
moderately invaginated basolateral membrane, few mitochondria- reabsorb NaCl and secrete K+
- acted on by aldosterone
intercalated cells
- NO CILIUM
- regulate acid-base
- have high density of mitochondria
- some secrete H+ (reabsorb HCO3-) and some secrete HCO3-
what are the two renal blood flow routes after the efferent arteriole?
1) peritubular capillaries- reabsorption of water & solutes from CORTEX= 90%
2) vasa recta capillaries- reabsorption of water and solutes in the medulla= 10% (8% outer)
what is clearance and what are its units?
the volume of plasma completely cleared of any substance in 1 min; mL/min
what is the mass-balance relationship for the kidney?
PaRPFa= (PvRPFv)+(U*V)
two equations for excretion
Excretion= Filtration+ Secretion- Reabsorption
Or
Excretion= urine concentration* urine flow rate
what is the formula for clearance?
Cx= Ux * V/Px
or remember UV=PC
C < GFR
C= GFR
C > GFR
C < GFR- filtered & reabsorbed
C= GFR- filtered
C > GFR- filtered & secreted
what is inulin used to measure? what are some advantages/disadvantages?
- with inulin, GFR= clearance - tells you how well the kidneys are filtering
- good b/c R=0, S=0; no hidden reserve, isn’t eaten or made, is measurable
what is creatinine used to measure? what are some advantages/disadvantages?
- also used to measure GFR (GFR=clearance), but is a little off because there is some secretion
- overestimates GFR
- easy to measure in plasma, see constant relationship between GFR and plasma creatinine
- remember creatinine increases in a muscular person
What is BUN used for?
- BUN= plasma creatinine x 10, so also used to measure GFR BUT is less stable
what is PAH used to measure? what are some advantages/disadvantages?
- the clearance rate is larger than the GFR normally (lots of secretion), but in people with low plasma, its almost all excreted
- is used to measure renal plasma flow
what is eRPF?
effective renal plasma flow measured with PAH; assuming venous plasma concentration is 0 (which is isn’t, is actually about 10%, so RPF= 1.1xeRPF
how do you calculate RBF from RPF?
RBF= RPF/1-hct
what is the filtration fraction?
FF= GFR/RPF= Cinulin/CPAH
normally, 20%
volume relationship between renal liquid volumes
RBF > RPF> GFR> V
characteristics of glomerular capillaries
- large filtration coefficient
- low resistance
- negatively charged
- form ultrafiltrate
- exclude plasma proteins
what is the equation for GFR?
GFR= Kf * (Pgc-Pbs-^gc+^bs)
what is Kf? greater in glomerular or systemic capillaries?
an intrinsic property of the glomerular capillary; Kf= permeability of gc * area of gc
- greater in glomerular caps
how is GFR normally regulated?
- changes in hydrostatic glomerular capillary pressure by changing afferent/efferent arteriolar resistant or pressure (amt of blood flow)
what is the equation for renal blood flow? what is the normal value?
RBF= (Prenal artery-Prenal vein)/ Rrenal vasculature
~ 4 mL blood/min *gm tissue
~ 1200 mL blood/min
ranking of blood flow in different areas of the kidney
renal cortex (90%) outer medulla (8%) inner medulla (2%)
where is the greatest decrease in hydrostatic pressure? where does oncotic pressure increase and decrease?
- across arterioles (efferent & afferent) b/c of high R
- increases in glomerular capillaries & decreases in peritubular capillaries
what happens to GFR, Pgc, and RBF when you constrict the efferent arteriole?
GFR and PGC increase
but constriction ALWAYS decreases renal blood flow
ways intrinsic autoregulation occurs to regulate GFR and RBF
1) smooth muscle myogenic theory
2) tubuloglomerular feedback theory
3) intrinsic vasodilators and vasoconstrictors
steps of tubuloglomerular feedback theory
1) increased GFR
2) increased NaCl content in Henle’s loop (not re-absorbed)
3) increased NaCl sensed by macula densa
4) signal generated to increase the resistance in the afferent arteriole
5) GFR is decreased
what is the difference between renal shutdown and renal death?
- renal shutdown- GFR=0, RBF= +, Urine production- none; happens when bp<70
- renal death- RBF=0, happens when bp=0
ways extrinsic regulation occurs to regulate GFR and RBF
1) sympathetics
2) blood borne & metabolic substances
3) stress factors (hypoxia, hemorrage, RAAS)
major vasoconstrictors & vasodilators
vasoconstrictors- sympathetics, angiotensin II, endothelin
vasodilators- prostaglandins (no change on GFR), NO, bradykinin, natriuretic peptides (no effect on RBF)
2 routes for the reabsorption of solute & water
1- paracellular- 1 step- around cells
2- transcellular- 2 steps- through cells
3 types of membrane transport mechanisms
- passive (simple, facilitated, osmosis)
- 1* active- move up concentration gradient from hydrolysis of ATP
- 2* active- required indirect energy source such as an ion gradient
what is the take away from Fick’s principle in the kidney?
if blood flow is restricted to the kidney, the kidney requires less oxygen
what are Tm and RPT? which is reached first and why?
Tm- transport maximum
RPT- renal plasma threshold (mg/ml)
- RPT reached first because of splay
what is actively occurring in glucose transport? how to calculated Tm for glucose?
- normally filtered and ACTIVELY reabsorbed, if not get excretion
- Tm= PaGFR-UV
what is actively occurring in PAH transport? how to calculated Tm for PAH?
- normally excreted and ACTIVELY secreted, if not get filtration
Tm= UV-PaGFR - filtered is always linear
what is diuresis and what are two examples of things that cause it?
- urine flow rate > 1 mL/min
- mannitol (filtered but not reabsorbed), glucose (when its not reabsorbed)
what percent of water/Na/Cl/K is reabsorbed in the proximal tubule?
what percent of glucose/aa’s is reabsorbed in the proximal tubule?
67% & 100%
how is Na+ transported in the proximal tubule? what is the gradient driven by?
- Na-H+ antiporter (H+ from H20+CO2 9n cells)
- Na-organic substance symporter
- later, have Na-2Cl-H+-anion paracellular antiporter
what are the major regulatory hormones for the proximal tubule?
angiotensin II, NE, E, Dop
how is Na+ transported in the loop of henle? what is the percent reabsorbed? which segment is impermeable?
- Na/K/2Cl symporter
- 25%
- thin descending loop
how is Na+ transported in the distal tubule? what is the percent reabsorbed?
- NaCl symporter early
- Na+ channels late
~5 %
how is Na+ transported in the collecting duct? what is the percent reabsorbed?
- Na channels
- ~3%
major regulatory hormones for the loop of henle and distal tubule?
Aldosterone, angiotensin II
major regulatory hormones for collecting duct?
aldosterne, ANP, BNP, urodilatin, uroguanylin, guanylin, angiotensin II
where is no water reabsorbed?
- thin ascending & thick ascending limbs of Henle
- distal tubule
which drugs increase NaCl and H20 reabsorption?
angiotensin II, aldosterone, sympathetic nerves
which drugs decreased NaCl and H20 reabsoption
ANP, BNP, urodilatin, uroguanylin, guanylin, dopamine
which drugs affect H20 reabsorption independent of NaCl?
ADH
what is the break down of where fluid resides?
ICF= 25 L ECF= 14 L (ISF= 10.5, P= 3.5)
what makes up most of the composition of solutes? what is the relative concentration of proteins?
- electrolytes (Na, K, Ca, Mg, Cl, HCO3)
- ICFp>Pp>ISFp
what is a positive water balance?
intake > loss ; make hypoosmotic urine
how do you measure the body’s osmolarity?
- by looking at the plasma osmolarity, specifically the concentration of Na (~290 mOSM/L)
what is another name for ADH? What makes up the preprohormone?
- vasopressin
- signal peptide, ADH, neurophysin, copeptin
relationship between ADH and urine excretion?
- increased ADH decreases urine excretion
where is ADH made and stored?
- made in endocrine cells of hypothalamus
- stores in posterior pituitary
where are the two places with sensors that stimulate ADH release? what are they’re actions? which is more sensitive?
- baroreceptors in carotid split & aortic arch (inhibits ADH release)
- osmoreceptors in hypothalamus ** more sensitive (stimulate ADH release)
pathway baroreceptors use to affect ADH
CN 9 & 10 - medulla - PVN/SO hypothalamus - posterior pituitary- exocytosis in blood
what allows ADH system to respond rapidly?
ADH is rapidly degraded in the blood
what is the threshold for change in plasma osmolarity to secrete ADH? threshold for baroreceptors?
- greater than 280 mosms
OR - decreased in bp by 10%
how does a decreased bp affect sensitivity to osmolarity?
- becomes more sensitive to osmolarity, slope is increased
where does ADH target?
extracellular receptors in distal tubules & the collecting duct
what is the ADH pathway for increased H20 retention?
- receptors - increase Gs- increase cAMP- increase PKA- insertion of aquaporin II into the membrane - increase in H20 permeability
where is urea permeable?
lower collecting duct
what are the 6 challenges to homeostasis?
hyper/hypo/iso osmotic
expansion & contraction
drink sea water
hyperosmotic expansion
blood transfusion
isosmotic expansion
saline transfusion
hyposmotic expansion
water deprivation, excessive sweating
hyperosmotic contraction
bleeding
isomotic contraction
concentrated urine
hyposmotic contraction
what is the equation for the anion gap?
[Na]- ([Cl]+[HCO3-])= ~15 meq/L
if the anion gap is not greater than 15 meq, but there is a pH problem, where should you look?
renal or GI system
what is the anion gap for vomiting? for diabetes?
vomiting= GI= 15 diabetes= pancreas= 35
which diuretics are K+ wasting? which is the strongest?
- mannitol, diamox, lasix, hydrochlorothiazide
(MDLH spare K) - lasix is the strongest
which diuretics are K+ sparing? where do they typically act?
spironolactone, amiloride, triamterene
- act on distal tubule & collecting duct
what does mannitol do?
holds H20 in proximal tubule (where majority of H20 is reabsorbed)
what does acetazolamide do?
inhibits carbonic anhydrase in the proximal tubule; no formation of CO2 & H20 which diffuse back into cell and provide H+ for antiport with Na; see more bicarb in both proximal & distal tubule b/c can’t combine with protons
what does lasix do?
inhibits Na/Ca/Mg reapsorption in thick ascending limb
what does hydrochlorothiazide do?
inhibits Na/Cl transport in distal tubule by competing with Cl site on transporters
what does spironolactone do?
compete with aldosterone in distal tubule & collecting duct
what does amiloride do?
blocks Na channels on luminal side of the collecting duct
what does triamterne do?
blocks epithelial Na channels in collecting duct
what is hyperkalemia defined as in the clinical setting?
when potassium intake exceeds output ; when you have an ECF composition of 5mEq/L (4mEq/L is normal)
what is hypokalemia defined as in the clinical setting?
<3.5 mEq/L (4mEq/L is normal)
