Renal Physiology Part 2 Flashcards
Auto-regulation
- kidney guards filtration carefully
- accomplished by the glomerulus being situated between 2 arteriolar beds
- vascular tone in these 2 beds protects the delicate glomerular architecture at times of high blood pressure and preserves GFR at times of low systemic blood pressure
You can control GFR by
adjusting resistance of afferent and efferent arterioles
Afferent arteriolar constriction
- greater pressure drop upstream of glomerular capillaries
- Pgc falls, which lowers GFR
- renal blood flow falls due to increased resistance
- want to protect again hyperperfusion; high pressure
Efferent arteriolar constriction
- pooling of blood in glomerular capillaries
- increased Pgc increase GFR
- renal blood flow decreased
- want to protect against hypo perfusion; low pressure
In a patient with hypertension secondary to renal artery stenosis, treatment with an ACE inhibitor will
- decrease BP, RBF, and intraglomerular pressure below normal due to the stenosis.
- although auto regulation normally maintains glomerular pressure/GFR by increasing efferent arteriolar constriction, an ACE inhibitor decreases formation of angiotensin II and blunts this response with a net effect of lowered GFR
Moderate efferent arteriolar constriction
- increased Pgc
- increased GFR
- decreased RBF
Effects of Sympathetic stimulation
- invoked in any situation which results in hypo perfusion of the renal vasculature bed
- constriction of afferent and, to a lesser extent, efferent arterioles: decreased RBF, GFR–diverts the renal fraction to vital organs
- increased renin secretion by granular cells
- angiotensin II thus produced restores blood pressure (systemic vasoconstriction)
- angiotensin II promotes arteriolar constriction (efferent > afferent): raises bp, may stabilize GFR (moderate ang II)
- stimulates Na+ reabsorption in proximal tubule, thick ascending limb of Henle’s loop, distal convoluted tubule, collecting duct
Renal prostaglandins
-dampen vasoconstriction by angiotensin II and sympathetic activity
high doses of chronic use of NSAIDS
-block prostaglandin production and may have a deleterious effect on renal function
Renal Clearance
- volume of plasma form which a substance is completely removed (cleared) by the kidneys in a given time period
- units are volume/time, e.g. ml/min, l/hr, etc
- describes how effectively the kidneys remove a substance form the bloodstream and excrete it into the urine.
- different substances have different clearances
Clearance of substance X=
concentration of X in urine x urine volume/concentration of X in plasma
Creatinine clearance approximates
GFR
Pcreatinine
- long term monitoring of GFR
- inversely proportional to GFR
- in reality, inverse relationship isn’t perfect: differences in lean muscle mass among patients; compensatory increased proximal tubule secretion
- useful for long-term monitoring of renal function
Theoretically, if GFR falls to 50% of normal, Pcreatinine
- should increase 2x over a few days
- e.g. if a patient has a plasma creatinine of 1 mg/dL and a creatinine clearance (GFR) which drops from 100 ml/min to 50 ml/min, then the expectation is that their plasma creatinine will rise to approximately 2 mg/dL over several days
BUN/creatinine ratio >20/1
- prerenal problem
- BUN reabsorption is increased
- BUN is disproportionately elevated relative to creatinine in serum
- reduced renal perfusion due to hypovolemia
BUN/creatinine ratio 10-20/1
- normal range or postern
- normal range; can also be postern disease (obstruction)
- BUN reabsorption within normal limits
BUN/creatinine ratio
- intrarenal problem
- renal damage causes reduced reabsorption of BUN and a lower BUN:Cr ratio
BUN and creatinine are both
-freely filtered by glomerulus, however urea reabsorbed by the tubules can be regulated (inquired or decreased) whereas creatinine reabsorption remains the same (minimal reabsorption)
Filtration Fraction (FF)
- fraction of total renal plasma flow which is filtered through glomerular membrane
- the proportion of fluid reaching the kidneys which passes into the renal tubules
- FF=GFR/RPF
- normally, approximately 20%
In renal artery stenosis or severe hemorrhage,
- blood flow (RPF) to kidney is reduced, so increased filtration fraction
- a higher proportion of that flow reaching the kidney must be passed into the renal tubules in order to perform the normal tasks of the kidney in balancing fluid and electrolytes in the body and maintain homeostasis
- this higher proportion of the total blood flow being passed into the tubules results in a higher filtration fraction
- i.e. the kidneys have to do more work with the fluid they are receiving
- reflected in a higher FF
Glomerular Filtration
-filtration of plasma from glomerular capillaries into Bowman’s capsule
Filtered load of a substance x=
GFR x Px
Tubular reabsorption
-transferral of substances from tubular lumen to peritubular capillaries
Tubular secretion
-transferral of substances from peritubular capillaries to tubular lumen
Excretion
-voiding of substances in the urine
urinary excretion=
amount filtered - amount reabsorbed OR amount filtered + amount secreted
-product of urine flow rate x concentration of substance in the urine
Tubular reabsorption=
glomerular filtration - urinary excretion
net rate of reabsorption or secretion of a substance=
difference between glomerular filtration and urinary excretion (assuming substance is not produced or metabolized by the kidneys)
If excretion
net reabsorption occurred
If excretion > filtration
net secretion occurred
Simple diffusion
- down electrochemical gradient via lipid bilayer or aqueous channels
- rate of diffuse not limited, will increase with increased concentration of substance
Facilitated diffusion
- down electrochemical gradient; specific carriers required
- carrier gets saturated at certain amount of substance and will tail off as it reaches Vmax
Primary active transport
-against electrochemical gradient; ATP hydrolysis provides energy
Secondary active transport
- downhill movement of one substance provides energy for uphill movement of another substance
- uses concentration gradient of an ion as its energy source
- often coupled with a primary active transport pump which creates the gradient
- cotransport/countertransport
Proximal tubular transport
- reabsorbs most of filtered water, Na+, K+, Cl-, bicarbonate, Ca2+, phosphate
- normally, reabsorbs all the filtered glucose, amino acids
- several organic anions and cations (including drugs, drug metabolites, creatinine, rate) are secreted in proximal tubule
Proximal Tubular Cl-
goes up because Na+ is reabsorbed with water, glucose, amino acids, Pi and HCO30 more rapidly
Proximal Tubular Sodium, osmolality
unchanged due to isosmotic reabsorption
Proximal Tubular concentration of glucose, amino acids, Pi and HCO3-
go down due to rapid reabsorption with Na+ and water
Proximal tubular Na+ reabsorption
provides driving force for reabsorption of water, other solutes
- polarity of epithelial cell membranes facilitates net unidirectional transport
- ultimately powered by Na+, K+ ATPase in basolateral membrane
- Na+ reabsorption usually coupled to transport of other solutes
Sodium Reabsorption mechanisms in proximal tubule
- contransport with glucose, amino acids, phosphate
- countertransport with H+ (Na+/H+ exchange)
Sodium reabsorption mechanism in thick ascending limb
Na+, K+, 2Cl- cotransport
Sodium reabsorption mechanism in Early distal convoluted tubule
- Na+, Cl- cotransport
- site of action of thiazides
Sodium reabsorption mechanism in late distal convoluted tubule, collecting duct
-luminal membrane channels
Water reabsorption
- always passive; can be transcellular or paracellular
- follows osmotic gradients established by reabsorption of sodium, other solutes
Chloride reabsorption
- always linked, either directly or indirectly, to Na+ reabsorption (Cl- can balance the + charges)
- specific mechanisms differ in different tubular segments
SGLT-2 inhibitors
new class of anti hyperglycemic agents which lower the Tmax for glucose excretion
PTH
- inhibits proximal tubular phosphate reabsorption
- increases the amount of phosphate excreted at any given plasma phosphate concentration
Tubular handling of organic acids and bases is affected by
pH of luminal fluid
-increased [H+] in the tubular lumen favors reabsorption of organic acids, but traps organic bases in the lumen
Overdose of an organic acid (acetylsalicylate or aspirin) may
be treated by alkalization of urine through HCO3 administration
-promotes urinary excretion by trapping the acid int eh tubular lumen
Descending limb loop of Henle
- freely permeable to water
- impermeable to Na+, Cl-
Ascending limb loop of Henle
- always impermeable to water
- thin segment: NaCl reabsorption mechanism is controversial
- thick segment: active Na+, K+, 2Cl- cotransport
Late DCT and Collecting Duct
- major site of physiological control of salt and water balance
- aldosterone stimulates Na+ reabsorption, K+ secretion, H+ secretion in this segment
- ANP inhibits Na+ reabsorption (medullary collecting duct)
- ADH stimulates water reabsorption
Aldosterone action in late DCT, CD
Aldosterone action in late DCT, CD -stimulates sodium reabsorption
- results in lumen-negative potential difference
- electroneutrality maintained by passive Cl- reabsorption and K+/H+ secretion
- stimulates potassium secretion
- stimulates H+ secretion (increased H+-ATPase activity in intercalated cells of CCD)
Anything that causes hypokalemia/acidemia causes
potassium to move out of ICF and into ECF
-acidemia causes hyperkalemia
Anything that causes hyperkalemia/alkalemia causes
K+ to move from ECF to ICF
-alkalemia causes hypokalemia
The lack of insulin can
-significantly compromise tolerance to K+ loading and can predispose to hyperkalemia.
Administering B-adrenergic blockers in the treatment of hypertension
impairs sequestration of an acute K+ load
Renal tubular handling of K+
- freely filtered into Bowman’s capsule
- 67% reabsorbed in PT
- 20% reabsorbed in TAL (Na+, K+, 2Cl- cotransport)
- physiological control exerted in CD
- principal cells: either reabsorb or secrete K+, depending on body’s K+ balance
5 factors which affect K+ secretion in CD
- extracellular K+ concentration
- Na+ reabsorption; negative luminal voltage ‘attracts’ K+
- luminal fluid flow rate: dilution of secreted K+ resulting in concentration gradient
- extracellular pH: K+ and H+ exchange across cell membranes
- Aldosterone: stimulates K+ secretion in CD to maintain electroneutrality when Na+ is reabsorbed
Anytime K+ increases in body,
aldosterone is released
Situations that alter K+ handling
- most classes of diuretics increase Na+ and volume delivery to late distal tubule and CD, which increases K+ secretion
- low-sodium diet: less Na+ delivery to late distal tubule, CD–>less K+ secretion, excretion–>may cause hyperkalemia
Hyperkalemia may be treated by
increasing downstream delivery of Na+ to distal tubules/CDs
-results in increased Na+ reabsorption and K+ secretion
