Kidney Physiology Flashcards
Prerenal insufficiency
Reduced blood flow to kidney- htn, atherosclerosis, renal artery stenosis
Intrarenal insufficiency
-glomerular, tubular (drugs), vascular (autoimmune)
Postrenal insufficiency
-obstruction of urinary tract- kidney stones, tumor
homeostatic fxn of kidney
regulate ECV, ECF electrolyte composition, ECF acid-base balance
excretory fxn of kidney
metabolic waste products, foreign substances and toxins
Endocrine fxn of kidney
regulation of blood pressure, erythropoiesis, calcium metabolism
Volume overload leads to
- dec GFR
- high serum creatinine, azotemia, uremia
- low tubular fxn, less K+ secretion
- electrolyte imbalance
- oliguria
- sodium retension–> peripheral edema –> htn
Major sites of control for RBF
- afferent and efferent arterioles- physiologic changes
- decrease in prerenal blood flow will lead to decreased filtration,
Hydrostatic pressure
is greater than oncotic pressure in glomerular capillaries, causing filtration
-major force causing filtration
Oncotic pressure is
greater than hydrostatic pressure in peritubular capillaries, causing absorption
GFR regulated by
modifying pressure in glomerular capillaries (modified in physiologic conditions), osmotic pressure, hydrostatic pressure at bowman’s space
-surface area and permeability (determining Kuf) of glomerular membrane are also important factors
Basement membrane has what charge
-negative
- positively charged molecules will filter more readily (negatively charged albumin does not filter)
- loss of negative charges will lead to increased filtration of negative charged molecules
Filtration pathway
renal corpuscle is formed by glomerular capillaries and bowman’s capsule.
-3 layer membrane between the two is composed of capillary endothelium containing pores, basement membrane of negatively charged glycoproteins and proteoglycans, type IV collagen, laminin and fibronectin, and a third layer facing lumen the bowman’s capsule formed by large cells called podocytes projecting finger like extensions and gaps called filtration slits
Tubules
- single layer epithelium
- Transcellular pathway and paracellular pathway
- basement membrane- Na K ATPase (Na out into blood stream, K in)
- High Na in the tubular lumen, so Na channel on apical side pumps Na+ into cell (which is then pumped out into blood stream by NaKATPase).
- Because Na has a positive charge, anions will travel through paracellular pathway to enter into blood stream
- Water will also follow Na+ out into blood stream
Estimation of GFR
- clearance of creatinine
- creatinine is freely filtered; end product of protein metabolism and always present in blood- GFR is proportional to 1/PCR (plasma creatinine) - decreasing 1/PCR value means decreasing kidney function
- Normal values of GFR is 100-125 ml/min (Kidney failure <15 ml/min)
- GFR varies with gender, age, race
Estimation of tubular fxn
- Fractional excretion of solute- Na
- Normal value is 1-3%
- FEna= (U/P)Na/(U/P)Cr
(U/P/U/P) x100%
BUN/Cr
Estimate of bloth glomerular and tubular fxn
- Creatinine is mainly filtered (GFR), and urea is filtered and reabsorbed (GFR and tubular fxn)
- normally between 15-20
- can determine where failure is
Prerenal failure BUN/Cr
glomerular fxn impaired-Decreased GFR, Azotemia, oliguria
- Causes both BUM and Cr to increase in blood, but because tubules intact, BUM continues to be reabsorbed and increases even more
- Increased BUN/Cr (>15) with normal FeNa
Intrarenal failure BUN/Cr
- tubules affected and GFR initially maintained
- Cr remains relatively constant or increases, but because tubules are damaged, BUN is not reabsorbed, and part is lost in urine, so it will be decreased
- BUN/Cr will decrease below 15
- inability to concentrate urine
- FeNa >3%
Postrenal insuf BUN/Cr
-not a good indicator
Both glomerular and tubular fxn will be eventually impaired
-Creatinine will not be filtered and will increase, BUN will also increase due to lack of filtration and tubules will not reabsorbed and does not increase much. So BUN/Cr will decrease below 15
-inability to concentrate urine
-FeNa >3%
RBF
1.2 L/min
RPF
renal plasma flow
660 mL/min
Hypertension
leads to increased intravascular volume, sodium retention, alteration of kidney regulatory mechanisms, renin-angiotensin-aldosterone system, enhanced activity of sympathetic nervous system
Kidney has barorecepter in
afferent arteriole
ADH
- also called vasopressin
- Controlled mainly through osmoreceptors in hypothalamus which are sensitive to changes in intracellular volume or osmotic concentration
- ADH released from posterior pituitary- goes to collecting ducts to reabsorb water. Urine will be more concentrated and lower in volume
- Acts on V2 receptors which activate adenylate cyclase and increase intracellular cAMP–> phosphorylation cascade which puts Aquaporin 2 in vesicles and onto apical membrane of principle cells of collecting duct
- Gradient of water absorption via the countercurrent mechanism in collecting duct only possible with ADH
ANP
- Inhibits ADH, and aldosterone, and reabsorption of Na
- Diuretic effect
- causes renal vasodilation, increasing blood flow to glomerulus, raising GFR- inc Na and fluid load, reduce renin and aldosterone– inhibition of salt reabsorption by collecting ducts
Renin-Angiotensin-Aldosterone system
- Causes vasoconstriction peripherally and in the kidney
- Na reabsorption in proximal tubules
Efferent Sympathetic nerve activity
- can activate juxtaglomerular apparatus and activate renin system
- causes vasoconstriction of arterioles, reducing RBF and GFR- increase salt and water reabsorption in proximal tubule
- via b receptors- inc renin release
- stimulates tubular salt and water reabsorption via alpha receptors on proximal and distal tubule and ascending limb
Tx of renal insufficiency
-sodium restriction
-diuretics- loop diuretics
-ACE inhibitors/ ARBs
_beta blocker
-Ca channel blockers
-Minoxidil
Proximal tubules fxn
- high water and salt permeability
- 60% of GFR absorbed including salt and water
- 100% glucose and AA absorbed
- Uric acid and drugs secreted
- Na/K-ATPase driving all transport located in basolateral membrane
- Na coupled transport of H, glucose and AA in apical membrane
- calcium mainly reabsorbed in proximal tubule
Descending Loop of Henle fxn
- permeable to water and ions
- Diffusion of NaCl, water, urea paracellularly
- osmotic concentration increases as it flows toward the bend
Ascending loop of henle fxn
- reabsorbs salt but very little water
- reduces salt concentration (by 25%) of the high osmotic concentration when comes from the thin descending loop
Distal tubules fxn
- low permeability to water and ions in early segment, later segment water permeability is iunder control of ADH
- reabsorb NaCl, reabsorb and secrete K
- receives hypotonic fluid and reabsorbs more Na and Cl
Collecting tubule fxn
- reabsorption of NaCl and secretion of K
- Secretion of H and HCO3
- NaCl reabsorption dependent on aldosterone
- water reabsorption depends on ADH
Principle cells
- located on inner medullary segment of collecting ducts
- reabsorb Na and water, and secrete K+ from ISF into luminal space
- Basal: NaK ATPase
- Apical- Na channel, ENac
Intercalated cells
- secrete protons to luminal fluid and bicarb to ISF
- protons extruded by H+ -ATPase pump (instead of exchanged for Na+ like in proximal tubule)
Countercurrent principle
1) ascending limb is impermeable to water, but permeable to Na- so Na flows out from the ascending limb into the ISF, which becomes concentrated (reabsorption of salt w/o water)
2) the concentrated solution of the ISF causes water to move out of desecnding limb, raising the concentration of the descending limb as it flows towards tip of loop. Na and Cl diffuse from medullary ISF down chemical gradient into descending limb also raising osmotic concentration.
3) is fluid flows around the bend and starts up ascending limb, Na Cl are removed and fluid is diluted as it approaches distal tubule
4) the distal tubules receive hypo-osmotic fluid from loop of henle and, in presence of ADH, transport excess fluid into cortical ISF
5) as fluid flows down medullary collecting duct, it again comes into contact with hyperosmotic medullary ISF and in presence of ADH, water is reabsorbed and tubular fluid is concentrated
Vasa recta as counter current excahnger
- essential to conserve composition of medullary interstitium
- hair pin structure and slow blood flow rate allows blood flow through medulla w/o causing disturbance of osmotic gradient
- plasma gets increasingly concentrated in the descending limb as Na and Cl diffuse in and water flows out in response to osmotic gradient. then in the ascending limb back toward cortex, interstitial fluid is more diluted, so water flows into ascending vasa recta and Na-Cl diffuse out
countercurrent flow of henle and vasa recta traps
salt and urea within medulla and minimizes water entering medullary interstitium
-high osmotic concentration of medullary interstitium causes water reabsorption from collecting tubule if ADH is present
factors affecting kidney’s ability to concentrate urine
- length of loop of henle
- adh level in collecting tubule
- blood flow through medullary capillaries
- factors that influence concentration of urea
- drugs and diuretics affect salt reabsorption in loop of henle inhibit countercurrent effect
Renin synthesized by
granular cells in afferent arteriole at juxtaglomerular apparatus
stimuli for renin
- increased activity of renal sympathetic nerves mediated via b-adrenergic receptors
- reduction of renal blood perfusion
- decrease of sodium delivery to macula densa
Renin acts on
angiotensinogen to angiogensin I
ACE converts
ang 1 to ang II
ACE produced by
endothelium of afferent and efferent arterioles in kidney
-
ang II causes
- arteriolar vasoconstriction which rises systemic artierla pressure; reduction of renal blood flow, favors uptake of water in tubules
- sodium and water retention which leads to inc in plasma volume
- activation of aldosterone secretion by adrenal cortex- inc Na reabsorption in thick ascending limb
- negative feedback mechanism inhibiting renin secretion
aldosterone
stimulated release from adrenal gland by Ang II, ACTH, and decrease in plasma Na, inc in plasma K
-aldosterone increases Na and water absorption and K secretion
Loop diuretics
thick ascending limb of henle
-block Na/K/2Cl cotransporter
Thiazide type diuretic
distal tubule
-block Na/Cl cotransporter
K+ sparing diuretic
collecting tubule
- spironolactone antagonist of Aldosterone
- others are Na channel blockers
Carbonic anhidrase inhibitors
proximal tubule
osmotic diuretics
all tubule segments, create osmotic gradient
why do loop and thiazide diuretics cause hypokalemia?
the increase in distal tubular sodium concentration stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ion, which are lost to the urine. The increased hydrogen ion loss can lead to metabolic alkalosis. Part of the loss of potassium and hydrogen ion by loop and thiazide diuretics results from activation of the renin-angiotensin-aldosterone system that occurs because of reduced blood volume and arterial pressure. Increased aldosterone stimulates sodium reabsorption and increases potassium and hydrogen ion excretion into the urine.
acid base regulation in body
mechanisms:
1- bicarb reabsorption- H+ secretion
2- urine acidification
3- ammonium production
buffer systems in body fluids are by
proteins: protein-/Hprotein
and phosphates
-normal concentration of bicarb ) transport of CO2) is 25 mM and carbonic acid is 1.25 mM
-change in respiratory ventilation which modifies bicarb in plasma
EPO
produced by kidney
-stimulated by reduction of oxygen tension in kidneys due to hypoxia, anemia, or deficient RBF
Vit D
Vit D3 is ingested in diet or synthesized in skin
-D3 is prohormone and is metabolized by liver and then kidney to form Calcitriol (active vit D)
Synthesis of calcitriol activated by pth and depressed by high levels of phosphate in plasma
-calcitriol stimulates intestinal absorption and renal reabsoprtion of calclium, increases bone resorption which produces calcium release to circulation
-def vit D results in low plasma calcium and impaired calcification of bones- rickets of osteomalacia
