Renal Physiology Flashcards
water distribution in body
intracellular vs extracellular compartments
majority of water is intracellular
types of solutes
two types of solutes: effective and ineffective
effective: can be sequestered in a compartment to contribute to an osmotic gradient - need active transport to get across a membrane ex. sodium, glucose
ineffective: diffuse freely based on relative concentration ex. urea
total blood osmolality
effective osmolality
total osmolality = 2[Na} + [blood glucose}/18 + BUN/2.8
effective osmolality = 2[Na] + [blood glucose]/18
renal autonomic innervation
NOT INNERVATED BY PSNS
SNS activity controls
- vasoconstriction
- Na reabsorption
- renin secretion
basics renal functions/processes
- filtration: movement of plasma constituents from glomerulus into Bowman’s capsule
- reabsorption: movement of constituents from forming urine into renal interstitium/back into circulation [vast majority of filtrate is reabsorbed back into circulation. 1-1.5L of 180L gets excreted daily]
- secretion: movement of constituents from renal circ, interstitium, or tubule epithelium into the forming urine
nephron structure and how it can impact GFR
- afferent arteriole: vsm capable of contraction
- glomerulus: site of filtration via fenestrations (net negative charge; cations move through more easily)
- efferent arteriole
- peritubular capillaries
rise/fall in glomerular bp - rise/fall in filtration
clearance equation
clearance refers to the proportion of a substance that is excreted in urine
C = [urine] * volume of urine / [plasma] C = UV/P
glomerular regulation of intraglomerular pressure
renal autoregulation
- kidneys will act to protect glomerular filtration at level of nephron
- high bp: contraction of afferent arteriole to reduce glom filt low bp: contraction of efferent arteriole to increase glom filt
filtered load vs fractional excretion
filtered load: how much solute makes it into Bowman’s capsule per unit time
fractional excretion: ratio of solute excreted to filtered load (how much of what’s filtered is actually excreted)
give examples of solute that are…
- not filtered.
- filtered; no reabs, no sec.
- filtered; partly reabs.
- filtered; mostly reabs.
- filtered; completely reabs.
- filtered; secreted.
- not filtered. - large proteins
- filtered; no reabs, no sec. - inulin
- filtered; partly reabs. - urea
- filtered; mostly reabs. - albumin
- filtered; completely reabs. - glucose
- filtered; secreted. - creatinine
virtually no pressure drop occurs between afferent and efferent ends of glomerulus, even in cases where MAP changes a lot describe the mechanisms that regulate glomerular filtration pressure
glomerular pressure regulated mainly at afferent artiolar level
- efferent constriction can also raise glomerular pressure afferent arteriolar vsm constriction/dilation can be triggered by…
1. SNS tone - norepi adrenoceptor dependent vasoconst
2. autoregulation - concerted action of SNS, natriuretic peptides, paracrine factors (NO, prostaglandins), and RAAS - happens due to either PRESSURE INDUCED DISTENSION OF AFF ART or TUBULAR GLOM FEEDBACK SYSTEM
describe how distension of vsm and vascular endothelium in efferent arteriole can affect autoregulation
stretch induced activation of cation channels, depolarization, mobilization of Ca within vsm, contraction!
TGF - tubular glomerular feedback
describe one physiological conditions where TGF varies from its normal functioning
regulated by concentrations of sodium in forming urine in the thick ascending limb
how it works:
- urine in TAL flows past macula densa, whose cells sense Na concentration (in close proximity with JG cells that secrete renin)
- elevated Na conc stimulates macula densa cells to release factors that stimulate aff arteriole to vasoconstrict (ATP, adenosine, thromboxane)
- GFR lowered
special case: volume expansion
-in these cases, you DONT want TGF to work because you need pressure natriuresis to run its course -increased water content keeps Na conc relatively low, so TGF is desensitized! and diuresis can occur
name the key hormones involved in renal regulation of GFR and RBF
- renin
- angiotensin
- atrial natriuretic peptide
- arginine vasopressin (ADH, vasopressin)
- norepi
- aldosterone [no direct effect - resp for Na retention]
name the key players in the RAS and where they are typically found
- angiotensinogen [in proximal tubule cells - also hepatocytes]
- renin [from renal JG cells]
- ACE [in proximal tubule brush border - also lungs/heart/periph vasc/brain]
describe the function of ACE2
found in renal and cardiac tissues
ACE2 converts AII into angiotensin 1-7
- angiotensin 1-7 binds to Mas receptor (Gprotein coupled) and stimulates:
- vasodil, blocks prolif
- promotes bradykinin -counteracts effects of AII
- possibly cardioprotective and antiHTN
how is renin regulated?
renin secretion from jg cells is REGULATED in response to:
- negative feedback from AII
- SNS tone (jg cells have beta1 receptors)
- -distension of aff arteriole (high bp)*
- -macula densa signals (TGF)*
- -ANP*
- [volume related]*
how does ACE effect vasoconstriction?
- produce vasoconstrictor: renin conversion to AII can happen, leading to vasoconstriction
- degrade vasodilator: ACE, while in town to convert AI to AII, also degrades bradykinin (vasodilator)
how does renin secretion help correct hypovolemia?
- AII leads to systemic vasoconstriction, higher bp
- facilitates RENAL CONSERVATION
- AII vasoconst of renal arteries steadies glomerular pressure AND drops flow in peritubular capillaries
- key for establishing hemodynamics favoring reabsorption of water, sodium
describe the expression AT1 receptors and the effects of binding
AT1 = main receptor form in humans
expression
- vsm (afferent and predominantly efferent artioles, renal tubules, periph vasc)
- adrenal cortex
- renal tubule epithelium/JG cells
effects of binding to AT1
- vasoconst in efferent arterioles = maintains optimal filtration
- might activate Na reabs through transporters NHE3, NKCC2, NCC, ENaC as well as Na/K ATPase
- stimulus for aldosterone production/release from zona glom in adrenal cortex
describe the expression AT2 receptors and the effects of binding
AT2 involved in fetal organogenesis
expression in adult: lung, renal coronary, myocardial tissues, cardiac fibroblasts
effects of binding to AT2
- might mediate natriuresis and vasodilation via NO, guanylyl cyclase, bradykinin
- regardless, AT2 has a more modulatory effect (AT1 vasoconst effects will predominate)
how do renin and ACE inhibitors work?
how does this link to ACE escape???
block active sites within renin and/or ACE disrupts production of AII, which precludes its vasoconstrictive and antrinatriuretic effects.
also stops ACE-dependent bradykinin degradation to preserve its vasodil effect
- also knocks out the negative feedback of AII on renin, which means more renin, which means ACE escape…
what is ACE escape?
- drop in AII also leads to drop in feedback inhibition on renin, which leads to upregulation of renin
- even with ACE blocked, this renin can lead to AII formation if it finds pathways of ACE-independent II production (chymases)
describe the effect of norepi on renal regulation
norepi targets both afferent and efferent arteriors, effecting…
- vasoconstriction : lowers gfr and renal blood flow via ALPHA1 RECEPTORS (to maintain volume/conserve/establish favorable hydrostatic gradients)
- renin secretion : stimulates secretion of renin from JG cells via BETA1 RECEPTORS
- some Na/water reabs : high SNS activity can enhance reabs from tubules via ALPHA2 RECEPTORS