Renal Physiology 1 Flashcards
what determines effective osmolarity in the body?
effective osmolarity is created by effective solutes – those that cannot passively diffuse across cell membranes, example – Na+, glucose (glucose doesn’t accumulate within cells because it is metabolized)
Na+ set tonicity: relative concentration that determines the direction and extent of H2O diffusion
Ineffective solutes (ex, urea) pass freely through cell membranes, and therefore do not create osmotic gradient
How is total blood osmolarity versus effective osmolarity calculated?
total blood osmolarity =
2([Na+]blood) + (blood glucose/18) + BUN/2.8)
Effective osmolarity =
2([Na+]blood) + (blood glucose/18)
innervation by which of the following does the kidney NOT receive:
a. SNS
b. PSNS
The kidneys are innervated exclusively by the sympathetic nervous system – controls vasoconstriction of the renal microcirculation, sodium reabsorption, and secretion of renin
How can the early stage of renal disease be detected?
early stages of renal disease are silent – can only be detected by lab analysis of renal function using glomerular filtration rate (GFR)
GFR is measured using blood creatinine or creatinine clearance
*however note that hyperfiltration can be seen in the early phases of some kidney diseases (ex, diabetic) due to compensatory increase in single nephron GFR which masks a loss in nephron number
do cationic or anionic substances more easily cross the glomerular filtration barrier and why?
glomerular filtration barrier carries a net negative charge - cationic substances tend to cross this barrier with less resistance than anionic substances
What is the normal GFR in men and women, respectively (before age 35), and what the value of GFR is associated with a high risk for the development of cardiovascular disease?
men: GFR ~ 130
women: GFR ~ 120
GFR < 60 = high risk for CV disease, and mortality from CV disease exceeds the risk of progression to renal failure
GFR < 15 indicates renal failure (requires dialysis or transplant)
Which molecule is used in clinical practice to measure glomerular filtration rate and what is a normal value of this molecule in the serum?
creatinine (closest naturally occurring thing to inulin) - basal serum creatinine falls between 0.4-1.5 mg/dL
as GFR rises, SCr (serum creatinine) decreases, and vice/versa
how will the following factors affect serum creatinine?
a. Kidney disease.
b. Large muscle mass.
c. Rhabdomyolysis.
d. Vegetarian diet.
e. Malnutrition.
f. Ketoacidosis.
a. Kidney disease: increase (because of decreased GFR)
b. Large muscle mass: increase
c. Rhabdomyolysis: increase
d. Vegetarian diet: decrease (low protein intake)
e. Malnutrition: decrease
f. Ketoacidosis: increase (interferes with assay)
which of the following will have a renal clearance of 0?
a. Large proteins.
b. Inulin.
c. urea
d. Glucose.
e. Albumin.
f. Creatinine.
a. Large proteins: not filtered, Cx = 0
d. Glucose: filtered and completely reabsorbed, Cx = 0
e. Albumin: filtered and mostly reabsorbed, Cx ~ 0
b. Inulin: filtered only, Cx = GFR
c. urea: filtered and partially reabsorbed, Cx < GFR
f. Creatinine: filtered and secreted, Cx ~ GFR
describe how the tubular glomerular feedback system works
As GFR is increased, increased urine NaCl reaches the macula densa in the thick ascending limb, stimulating depolarization
—> macular cells secrete factors which promote vasoconstriction of the nearby afferent arterial (ATP, adenosine, thromboxane) to decrease GFR (don’t want pressure overload)
basically uses sodium in forming urine as a marker of GFR to indirectly interpret volume-pressure status (note this system will become desensitized if there is exaggerated volume expansion with low Na+ concentration)
describe the effect of the renin angiotensin system (RAS) on the kidneys
angiotensin II is a potent vasoconstrictor and also stimulates Na+ reabsorption —> increase BP, increase GFR
All components of RAS (renin, angiotensinogen, ACE) are expressed within the kidney at much higher levels than in the plasma - angiotensinogen is expressed within the proximal tubule cells and ACE is present within the proximal tubule brush border
How is renin secretion regulated? (5)
renin - produced/secreted by JG cells, regulated by:
- SNS tone (JG cells express beta1 adrenoreceptors)
- elevated BP (distention of afferent arteriole epithelium)
- signals from macula densa in nearby thick ascending limb
- ANP (atrial natriuretic peptide)
- negative feedback by angiotensin II
What is the function of renin?
catalyzes the conversion of angiotensinogen to angiotensin I
Angiotensin I is targeted by intrarenal ACE or travels via plasma to extrarenal tissues that express ACE (which converts angiotensin I to angiotensin II)
note all tissue rely on renin from JG cells
what are the two ways in which ACE promotes vasoconstriction?
- production of angiotensin II (vasoconstrictor) from angiotensin I
- Degradation of bradykinin (vasodilator)
where is the AT1 angiotensin II receptor located and what is the effect of its activation (3)?
AT1 (GPCR): predominant AT receptor isoform, expressed in smooth muscle of afferent and efferent arterioles, renal tubules, and peripheral vasculature
AII binding as result of low BP induces:
1. efferent vasoconstriction
2. enhanced Na+ reabsorption - activates Na+ channels (NHE3, NKCC, NCC, ENaC)
3. aldosterone production/secretion (adrenal cortex)
