Nephrology Flashcards
Where do the sympathetic nerves running to the kidney innervate?
afferent arteriole, efferent arteriole, PCT, and Thick ascending limb of the loop of Henle
What is the basic function of the nephron?
remove unwanted substances from plasma including metabolic waste and extra electrolytes, this process is called clearance; filters 1/5 of renal plasma flow in to tubules
What function does the macula densa perform?
sense Na+ and signal granular cells
What function do the granular cells perform?
Juxtaglomerular cells- contain granules of renin, they are smooth muscle cells and contract to release the renin
What function do they mesangial cells?
contract to change filtration and permeability; loosen muscles increases filtration, tightening deceases filtration
What is the renal fraction of cardiac output?
20-21%, can vary from 12-30%
How is renal plasma flow calculated?
RPF= RBF x (1-hematocrit)
How is blood flow distributed throughout the kidney?
90% to the cortex, 8 % to the outer medulla, 2% to the papillae
How is flow calculated?
(arterial pressure - venous pressure) / Resistance
What are the two sites of major decrement in pressure in the glomerulus? What does this mean?
afferent arteriole and efferent arteriole; these structures are the main resistance to flow
What effects renal flow and how?
neural: sympathetic innervation to afferent and efferent arteriole, vasoconstriction= reduction of flow; Humoral: hormones norepinephrine and epinephrine and angiotensin II affect renal resistance by action on afferent and efferent arteriole increasing resistance, bradykinin, ACh, and dopamine cause vasodilation and increase flow
How is the total resistance in the kidney?
Total Resistance (Rt)= Ra + Re + Rcap + Rv
How is renal blood flow autoregulated?
influenced by hormones and nerves; as pressure increases resistance increases to maintain flow; myogenic hypothesis and/or Tubularglomerular Feedback
What is the myogenic hypothesis?
increased mean arterial pressure passively distends afferent arteriole diameter which stretches the vascular smooth muscle cells, the smooth muscle cells contract which decreases the diameter of the afferent arteriole which increases the resistance of the afferent arteriole which decreases flow
What is tubularglomerular feedback?
operates on a single-nephron level and every nephron has a TGF capability, the macula densa cells sense alterations in tubular fluid composition, changes are transduced to evoke a change in afferent arteriole resistance which impact GFR and RBF; this is a negative feedback because increase in GFR will increase solute and fluid to macula densa which results in return of GFR to normal
How do changes in arteriole resistance effect RBF and GFR?
decrease in RA (afferent resistance) increases RBF and GFR, increase RA decreases RBF and GFR, decreased RE ( efferent resistance) increases RBF and decreases GFR, increased RE decreases RBF and increases GFR
what mainly drives GFR?
glomerular capillary hydrostatic pressure (PC)
What affect does nitrous oxide have on the afferent and efferent arterioles?
dilates both
What affect does prostaglandin I2 have on the afferent and efferent arterioles?
dilates both
What affect does prostaglandin E2 have on the afferent and efferent arterioles?
dilates afferent and has no effect on efferent
What affect does Angiotensin II have on the afferent and efferent arterioles?
constrict or no effect on afferent and constrict efferent
What affect does vasopressin have on the afferent and efferent arterioles?
constrict or no effect on afferent and constrict efferent
What affect does norepinephrine have on the afferent and efferent arterioles?
constrict both afferent and efferent, efferent (SNS)
What affect does endothelin have on the afferent and efferent arterioles?
constricts both afferent and efferent
What affect does Thromboxane have on the afferent and efferent arterioles?
constricts both
What affect does Atrial natriuretic peptide have on the afferent and efferent arterioles?
dilate afferent, constrict or no effect on efferent
What substances are involved in intrinsic control of RBF?
NO, prostaglandins, Angiotensin II
What substances are involved in extrinsic control of RBF?
NE, ANF, ADH (vasopressin)
what makes up the renal corpuscles?
glomerulus, basement membrane, and bowman’s capsule
What is filtration fraction? How is it calculated?
1/5 is filtered, fraction of renal plasma flow, FF= GFR/RPF; 4/5 goes to peritubular capillary
How is GFR calculated?
GFR= Puf x Kf, Kf= ultrafiltration coefficient which depends on membrane properties, Puf= net ultrafiltration pressure which depends on driving pressure
What is ultrafiltrate? What are some of its properties?
a fluid which contains all of the solutes found in plasma in same concentrations with the exception of plasma proteins, small molecular weight substances are freely filtered (Na, Cl, K, urea, glucose, amino acids), volume filtered by glomerulus is much greater than that filtered by other capillary beds, due to Kf (primarily permeability of filtering membrane) and relatively high Pgc
What separates plasma from the filtrate and what makes it up?
filtration barrier, endothelial layer of glomerular capillary, basement membrane, and epithelial cell layer of renal tubule
How does the glomerulus permeability compare to systemic capillaries?
100 to 500 times more permeable, but still very selective in respect to size, charge, and shape
What is proteinuria and what causes it?
presence of protein in the urine, is hallmark of glomerular injury, may be due to increased pore size or decreased negative charge on the basement membrane; filtration of protein that exceeds the rate the PCT can reabsorb the protein
What is the driving pressure for the GFR? how is it calculated?
ultrafiltration pressure is the driving force, Puf= (Pgc-Pt) - (Pigc - Pit) or Ultrafiltration Pressure = ( Hydrostatic Pressure of blood in glomerular capillaries - Hydrostatic pressure of the fluid in Bowman’s space) - (Osmotic pressure of proteins in the plasma - Osmotic pressure of proteins in the fluid in Bowmen’s space)
What happens to GFR when Pgc increases?
when systemic arterial pressure increases Pgc increases which increases Puf and therefore GFR
How can Pt change? How does this affect GFR?
blockage of urinary outflow like a renal calculi could increase Pt which could decrease GFR
What can change Pigc? How can this change GFR?
can increase if a patient receives an infusion of solution without plasma proteins like normal saline which decreases Pigc and increases GFR
What can change Pit? How does this affect GFR?
could increase if excess protein leaked through the filtering membrane or if a person was infused with a solution with a high concentration of a compound small enough to be filtered, which then decreases GFR
How can Kf change? How does this affect GFR?
many disease states alter the permeability of filtering membrane, the surface area for filtration is changed when a part of a kidney is removed or one kidney is removed and can also be changed physiologically altered, increase Kf increases GFR and decrease Kf decreases GFR
How can Pgc be altered physiologically?
afferent constriction decreases filtration pressure, efferent constriction increases filtration pressure; hormones, nerves, and angiotensin II
How is the amount reabsorbed and the amount secreted calculated?
Reabsorbed= filtered - excreted; Secreted = excreted - filtered
what is reabsorption?
movement of substances from the tubular lumen across the tubular epithelium into interstitial spaces and then into the blood of the peritubular capillaries; basic mechanism: active transport and passive transport
What things affect the amount transported of an actively reabsorbed molecule?
transport sites mediated by carriers suggesting specificity, concentration gradient suggesting saturability, and length of time the luminal fluid is in contact with the luminal membrane (rate of urine flow)
What is the relative transport maximum (Tm) for different molecules?
Tm usually > [Plasma]; Phosphate Tm near [Plasma] - kidney involved in reg.; Sodium unlimited - very high transport
What are the rate limiting factors for passive reabsorption?
amount of water reabsorbed (changes the concentration in the tubular fluid), permeability of the tubular membrane
What molecule and why is it used as an indication of renal failure?
plasma concentration of urea; because urea is passively reabsorbed so increased urine flow increased urea excretion causes decreased plasma concentration of urea normally; in renal disease, renal flow decreases and urea reabsorption increases
What is tubular secretion? What are examples of things secreted in the kidneys?
movement of molecules into the tubular fluid from peritubular capillaries or from tubular cells; hydrogen and potassium are two key examples, relatively less things are secreted than reabsorbed in the kidney and its usually foreign substances like penicillin
What is an example of active secretion?
para-aminohippuric acid (PAH), actively secreted by the proximal tubule, used to measure renal blood flow
What is renal clearance?
aka plasma clearance, measure of effectiveness of kidney to remove unwanted substances from the plasma; measured as volume of plasma per unit time which is cleared of a substance usually mL/min, vol. of plasma cleared of a substance= vol of plasma per min needed to excrete quantity of substance appearing in urine
What is used to determine GFR? Why?
clearance of inulin, it is freely filtered at the glomerulus and neither secreted or reabsorbed by the renal tubules, or synthesized by the kidney (it is not toxic, not metabolized and can be chemically determined in plasma and urine)
How do we measure GFR?
infuse inulin I.V. until Pin (rate of inulin into afferent tubule) is stable, measure urine volume produced in a known period of time (V) (UIN), measure PIN and UIN, Calculate GFR= Clearance of Inulin (Cin)= V x Uin/Pin
What is another substance that can be used to measure GFR and why?
creatinine- product of creatinine phosphate metabolism, Ccr is slightly greater than Cin, because a small amount of creatinine is secreted but is not synthesized, metabolized or reabsorbed by the kidney so its a reasonable estimate of GFR, produced endogenously no iv infusion is necessary, plasma measurement of creatinine is a little high which counteracts the secretion
How is ERPF measured?
clearance of PAH because it is freely filtered at glomerulus, if [PAH] in plasma kept below Tm for PAH then all in the plasma in peritubular capillaries will be secreted, not reabsorbed, non-toxic and easily measured, not metabolized, not synthesized; True RPF would take into account PAH level in the renal vein which is dangerous to measure to effective RPF is used
How is renal blood flow calculated?
RBF= RPF/1-hematocrit
What is fractional excretion and how is it calculated?
FEx, the fraction (%) of filtered substance (Q) that is excreted in the final urine; FEx = Cx/ Cin = [(Ux-V)/ Px] / [(Uin x V)/ Pin] or Mass excreted/ mass filtered = (Ux x V)/ GFR x Px
What is fractional reabsorption?
FRx, the fraction % of filtered substance that is reabsorbed by the tubules; Frx = 1 - FEx
What is the amount of H2O filtered, excreted, reabsorbed, proportion filtered load is reabsorbed %?
H2O= 180 L/day, 1.5 L/day, 178.5 L/day, 99.2%
What is the amount of Na filtered, excreted, reabsorbed, proportion filtered load is reabsorbed %?
Na= 25,000 mmol/day, 150 mmol/day, 24,850 mmol/day, 99.4%
What is the amount of HCO3 filtered, excreted, reabsorbed, proportion filtered load is reabsorbed %?
4,500 mmol/day, 2 mmol/day, 4,498 mmol/day, 99.9+%
What is the amount of Cl- filtered, excreted, reabsorbed, proportion filtered load is reabsorbed %?
18,000 mmol/day, 150 mmol/day, 17,850mmol/day, 99.2%
What is the amount of glucose filtered, excreted, reabsorbed, proportion filtered load is reabsorbed %?
800mmol/day, ~0.5 mmol/day, 799.5 mmol/day, 99.9+%
How does the osmolality change in the PCT? How is water reabsorbed?
same entering, reabsorbing, exiting; through AQ1 then starling forces from interstitium to peritubular capillaries
How does the osmolality of fluid change in the Loop of Henle?
300mOsm entering, 1200mOsm at bottom tip of LOH, 100mOsm at the end of LOH
What percent of filtered sodium and water reabsorbed at the loop of henle?
25% sodium filtered is reabsorbed, 15% of H2O filtered is reabsorbed
The percent of renal blood flow to the medulla is 8% what percent goes through the peritubular and what percent goes through the vasa recta?
98% and 1-2%
what is the permeability of the thin descending limb of the loop of henle?
freely permeable to water, impermeable to sodium and chloride and slightly permeable to urea
what is the permeability of the thin ascending limb of the loop of henle?
impermeable to water, sodium and chloride move out of the Thin AL into the interstitial fluid, extremely high permeability to Na and Cl, favorable NaCl gradient
what is the permeability of the thick ascending limb of the loop of henle?
water impermeable, NaCL transport occurs by neutral co-transport mechanism in which a carrier in luminal membrane transports 1 Na, 1 K, and 2 Cl ions together from the lumen into the cell driven by transmembrane electrochemical gradient for Na
what is the permeability of urea in the distal nephron?
thick ascending limb of LOH, distal tubule, the cortical collecting tubule and outer medullary collecting duct are urea impermeable, the inner medullary collecting duct is urea permeable
What is the source of urea in the medullary interstitium? Where does it go?
comes primarily from the inner medullary collecting ducts, 50% of osmolality of medullary interstitium is due to urea it diffuses into the tubular fluid of the thin ascending limb of LOH
What is barret’s syndrome?
salt wasting, abnormal pump (blocked channel)
What is the effect urea has on the Na Cl concentration in the descending limb of the LOH?
urea in interstitial fluid of the medulla will exert a osmotic pressure on the fluid in the descending limb of Henle’s loop and will cause water to leave the tubular fluid of the descending limb, will raise the concentration of NaCl in the tubular fluid of the descending limb (if they are impermeable to sodium chloride)
What is the vasa recta permeable to?
NaCl, H2O, and Urea;
What affect does it have on gradients? How?
maintains gradient by having low flow; lose solute as blood passes up the ascending limb the solute tends to be allowed to stay in the medullary interstitial fluid and not be removed. This countercurrent exchange across the vasa recta aids in the maintenance of the gradient
How is solute and water removed from the renal medulla by the vasa recta?
some solute and water must be removed from the medulla via the ascending limbs of the vasa recta. Net solute and water will be added to the ascending vasa recta probably by movement from the interstitial fluid response to the increased osmotic pressure of the plasma proteins in the ascending limb, the oncotic pressure of proteins here would be high because water loss from the descending limbs and because plasma proteins in this blood have been concentrated by the filtration process in the glomerulus
What amount of sodium and H2O is reabsorbed in the distal tubule?
8% of filtered sodium reabsorbed in the distal tubule, 10% of filtered H2O
How does the osmolality of the filtrate change through the distal tubule?
100mOsm to 150-200 mOsm; after a water load it may go as low as 50 mOsm
How is sodium transported across the basolateral membrane?
sodium is actively transported across the basolateral membrane, thought to be exchanged for potassium in a Na/K pump mechanism similar to the PCT
How is chloride transported in the distal tubule?
paracellular diffusion, driving force is lumen-negative PD, secondary active via Na Cl co-transporter in the luminal membrane
How is sodium transported in the luminal membrane?
Na is transported by Na Cl co-transporter into the cells of distal tubule. Also Na/H exchange mechanism but this is not as important quantitatively under normal conditions as it is in the proximal tubule
What effect of aldosterone on reabsorption of sodium?
aldosterone promotes sodium reabsorption primarily in the cortical collecting tubule (works on principle cells), about 1-2% of filtered sodium is reabsorbed under the influence of aldosterone
How is water moved across the basolateral membrane of cortical collecting duct?
water moves from cell across the basolateral membrane presumably by osmotic forces created by NaCl movement
How is water moved across the luminal membrane of the cortical collecting duct?
osmotic pressure difference between luminal fluid 100mOsm and plasma 300mOsm, water moves due to NaCl movement and due to osmotic pressure difference of luminal fluid and plasma
How does vasopressin go from being formed to acting on the body/ Receptors involved and affects?
hypothalamus (paraventricular nucleus)/ (supraoptic nucleus) to posterior pituitary where it is stored until it is released into the blood, and acts on V2 receptor which at low levels increases antidiuresis and on V1 to cause vasoconstriction at high levels
How does ADH cause diuresis?
insertion of aquaporin 2 on the luminal side
What percent of water and sodium is reabsorbed in the collecting duct?
9.3% of filtered water, 1.3% of filtered sodium
How is sodium transported by the collecting duct?
Endothelial Sodium Channels (ENaC), aldosterone causes an increase in ENaC on the luminal side
What is Liddle’s syndrome?
a mutation of the channel such as to keep it open
What drugs block ENaC channels?
Amiloride or Benzamil a diuretic
How does the osmolality change in the colleting duct?
150 to 200 under normal ADH conditions; when it leaves it is 700-800 mOsm/kg; during dehydration osmotic pressure can get as a high as 1200 mOsm; when no ADH present can go below 100mOsm
What percent of water and sodium is excreted under normal antidiuretic hormone conditions
less than 1%
In CHF what happens with the ENaC?
increased ENaC channels to retain salt; increased volume eventually too much, treat with a diuretic and something to decrease sodium