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92 Cards in this Set
- Front
- Back
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3 processes of urine formation
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- filtration
- reabsorption - secretion |
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filtration
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- excretory tubule collects a filtrate from blood
- water and solutes are forced by BP across the selectively permeable membranes of a cluster of capillaries and into excretory tubule - obligatory - nondiscriminate - renal corpuscles |
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reabsorption
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- transport epithelium reclaims valuable substances from filtrate
- returns them to body fluids - selective obligatory or faculative - pumps and channels reabsorb filtered matter |
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secretion
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- other substances, toxins and excess ions, are extracted from body fluids
- added to contents of excretory tubule - selective movement of substrates from peritubular capillaries into tubular lumen - moves substances from peritubular capillaries to tubules - gains access to urine after filtration |
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ultrafiltration
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- produce primary urine, urine in Bowman's capsule and proximal convoluted tubule
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filtration in glomerulus
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- filtrate is produced by means of ultrafiltration
- hydrostatic pressure of the blood and osmotic pressure pushes stuff out - capillary endothelium is perforated with many fenestrations - cellular way of Bowman's consist of podocytes - podocytes have processes that interdigitate complexly, forming slits between juxtaposed elements - ends up in Bowman's capsule |
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fenestra
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- 75-90 nm in diameter
- barrier to whole cells - anionic glycocalyx hindering anionic molecules = albumin |
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glomerular basement membrane
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- collagen and glycoproteins
- collagen a barrier for size and shape - glycoproteins are strongly negatively charged repelling albumin and other plasma proteins small enough to pass through fenestra - major size, shape, and charge barrier - less than 1% of filtrate is plasma proteins - excludes molecules larger than 8 nm |
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slits
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- between interdigitations of podocytes
- slits are 20-30 nm spaces - slows that rate of filtration - barrier for large anions |
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substances filtered
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- almost any molecule small that 3 nm can pass freely through filtration membrane
- includes water, electrolytes, glucose, fatty acids, amino acids, nitrogenous waste, vitamins - they have same concentration as blood plasma |
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glomerulus and Bowman's capsule
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- filtration occurs as BP forces fluid from blood in glomerulus into lumen of Bowman's capsule
- filtration of small molecules is nonselective - filtrate in Bowman's capsule is mixture that mirrors concentration of various solutes in blood plasma |
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3 physical forces involved in glomerular filtration
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- glomerular capillary blood pressure
- plasma colloidal osmotic pressure - hydrostatic pressure in Bowman's capsule |
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glomerular capillary blood pressure
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- hydrostatic pressure
- averages about 45-60 mmHg - driving force of filtration - caused by afferent arteriole being larger than efferent - intrinsically regulated - arterial blood pressure is driving force that drives blood in glomerulus |
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afferent and efferent arterioles
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- can alter hydrostatic pressure of blood
- rises with dilation of afferent = increases filtration - falls with constriction of afferent = decreases filtration - adjust filtration that occurs - positive pressure |
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plasma colloidal osmotic pressure
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- 20 mmHg
- opposes filtration - filtrate is almost protein free - filtrate contains no blood cells unlike the blood - draw stuff back into blood - negative pressure |
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hydrostatic pressure in Bowman's capsule
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- 10-32 mmHg
- opposes filtration - due to accumulation of fluid in capsular space - draw stuff back into blood - negative pressure |
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filtration pressure
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- hydrostatic pressure of blood minus both colloidal osmotic pressure of blood plasma and hydrostatic pressure of capsular fluid
- filtration only occurs if filtration pressure is positive |
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glomerular filtration rate
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- amount of filtrate formed per minute by two kidneys
- 1 mmHg of net filtration pressure the kidneys of young adult male produce 120 mL of filtrate per minute - properties of glomerular membrane = filtration coefficient Kf - depends on permeability and surface area of filtration barrier - GFR = Kf x Net Filtration Pressure |
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rate at which fluid is filtered is dependent upon:
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- pressure forcing fluid out of capillary = glomerular hydrostatic pressure
- pressure drawing fluid into capillary - capillary membrane permeability |
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regulation of GFR
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- plasma colloidal pressure and Bowman's capsule hydrostatic pressure do not vary much
- can change pathologically = burn patients lose plasma, dehydrating dirreaha, kidney stone blockage - change results from changes in glomerular capillary blood pressure - increases in proportion to increase in arterial pressure - intrinsically regulated by tubuloglomerular feedback mechanism |
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intrinsic regulatory controls
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- prevents increase
- myogenic mechanism - vasoconstriction of afferent arteriole decrease GFR - vasodilation of afferent increase GFA tubuloglomeular feedback |
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increase afferent arterial volume/pressure
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- increase afferent arterial stretch
- increase automatic constriction of afferent arteriole - limits blood flow to glomerulus |
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decrease afferent arteriole volume/pressure
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- decrease afferent arteriole stretch
- vasodilation of afferent arteriole - increase flow into glomerulus |
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justaglomerular apparatus
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- involved in tubuloglomeular feedback mechanism
- vasomotion - monitor salinity - smooth muscle of efferent arterioles - thick layer of loop of Henle = muscula densa - release renin = converts angiotensin to angiotensin 1 |
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GFR extrinsically regulated
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- mediated by sympathetic nervous system
- parasympathetic exerts no control on kidney - nerve fibers attach to juxtaglomerular system |
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GFR influenced by changes in filtration coefficient
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- instead of net filtration pressure
- each tuft of glomerular capillaries is held together by mesanglial cells |
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mesanglial cells
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- specialized pericytes
- function as phagocytes - function as contractile elements - function in maintenance of basement membrane - constrict and dilate themselves - unsure how it works |
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sympathetic stimulation
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- certain hormones and local mediators of mesanglial cells cause them to contract
- contraction shuts off a portion of glomeular capillaries - reduces surface area for filtration but doesn't change net filtration pressure - reduction if filtration coefficient (surface are for filtration) results in reduced GFR |
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podocytes
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- posses actin-like contractile filaments
- contraction and relaxation can decrease or increase number of filtration slits opened - more slits open = greater filtration surface - seems to be under some physiological control |
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reabsorption
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- proximal convoluted tubule
- loop of Henle - distal convoluted tubule - collecting tubules - highly selective process - involves trans-epithelial transport - permeability to water achieved by aquaporins |
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reabsorption in proximal convoluted tubule
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- stereocilia point into urine = have protein carriers
- tight junction prevents urine flow between two cells but allows water to pass through - carriers different in basal and apical surface - solvent drag due to the water passing through tight junction - large surface area = apical and basolateral surface |
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process of reabsorption in PCT
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- substance binds to transporter on apical surface
- substance passes through the cytoplasm - substance binds to transporter on basolateral surface - moved to interstitial fluid - substance diffuses through interstitial fluid - substance penetrates capillary wall into blood |
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passive reabsorption
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- ion channels
- carrier proteins |
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active reabsorption
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- active transporters
- secondary active transport |
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formation of urine by active solute secretion
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- energy from ATP is used to secrete solute X into tubule
- increases osmotic pressure of tubular fluid - water enters the tubular fluid by osmosis - dilutes solute Y - solute Y diffuses inward, following concentration gradient |
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proximal tubule
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- most amino acids, proteins and glucose
- 60% of fluid and ions - apical surface has long microvilli = stereocilia - basolateral surface = membrane is folded - Na,K ATPase pump creates electrochemical gradient - gradient used to drive processes at apical surface - secondary active transport of glucose and AA into cell |
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transport
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- transport maximum determined by number of transport proteins present
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tight junctions
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- prevent substances except water from moving between tubular cells
- solvent drag brings some substances through - solvent drag due to pressure in interstitial fluid |
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reabsorption in peritubular capillaries
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- fluid in filtrate entering proximal tubule is reabsorbed
- driven by Na,K ATPase in basolateral membrane of epithelial cells close to capillaries |
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luminal side of proximal tubule epithelium
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- sodium enters cells
- symporter membrane proteins = co-transport with glucose, galactose, phosphate, sulfate, vitamins, or amino acids - SGLT example of symporter - antiporter membrane proteins = co-transport with protons |
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reabsorption of bicarbonate
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- liked to Na+ reabsorption and H+ secretion
- help from luminal and intracellular carbonic anhydrase - alters pH |
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bicarbonate reabsorption process
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- filtered bicarbonate and secreted H+ from tubular cell forms with help of luminal carbonic anhydrase
- H2CO3 dissociates to carbon dioxide and water - CO2 enters tubule cell and binds OH- to bicarbonate - Na+/HCO3- co-transporter in basal membrane returns bicarbonate into blood - in case of alkalosis = bicarbonate can be secreted to balance acid-base homeostasis |
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chloride
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- follows sodium because of electrical attraction
- antiports for chloride with anions - chloride and potassium are driven out the basolateral surface by K+,Cl- symport |
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another route for water and ions
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- water can pass through tight junctions
- as it travels, water drags solutes with it = solvent drag - potassium, magnesium, and phosphate |
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potassium
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- 60-70% of filtered is reabsorbed in proximal tubule
- no specific K-transporter - reabsorption managed with absorption of water (solvent drag), simple diffusion, and K+ ion channels |
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calcium
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- 60% is reabsorbed in proximal tubule
- solven drag and active transport mechanism |
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proteins
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- mostly stay in the lumen
- if in filtrate, removed by receptor mediated endocytosis - bind receptors - coated vesicles endocytosed - vesicles fuse with lysosomes - digested lysosome - amino acids leave cell across basolateral surface |
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protein digestion
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- hydrolytic enzymes that are integral membrane proteins on microvilli
- many of these proteins are hormones - destruction by PCT is important means of regulating blood levels |
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amino acids
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- different sodium-amino acid co-transporter is responsible for reabsorption of AA in proximal tubule
- seven different transporters - acidic amino acids (Glu, Asp), basic amino acids (Arg, Lys, Orn) and 5 other systems of neutral amino acids |
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nitrogenous waste
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- urea
-uric acid - creatine not reabsorbed at all |
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urea
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- reabsorbed from 40-60% in PCT
- passes through with water |
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uric acid
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- PCT reabsorbs nearly all
- secreted back |
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uptake by peritubular capillaries
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- reabsorb water and solutes from PCT
- osmosis = water reabsorbed - concentration gradient - narrowness of efferent arterioles lowers blood hydrostatic pressure = 8 mmHg - unsually high collodial osmotic pressure of blood - solvent drag = water carries other solutes - fenestrae |
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loop of Henle
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- concentrate urine and conserves water
- plays important role in concentrating urine by generating an osmotic gradient - gradient used by collecting ducts to concentrate and conserve water - each loop consists of descending thin loop, ascending thin loop, and ascending thick loop - vasa recta parallel loops of Henle through medulla |
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salt through loop of Henle
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- more salt is continually added by PCT
- higher the osmolarity of ECF, the more water leaves descending limb by osmosis - more water that leaves descending limb, the saltier the fluid is that remains in tubule - saltier the fluid in ascending limb, the more salt the tubule pumps into ECF - more salt that is pumped out of ascending limb, the saltier the ECF is in renal medulla |
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descending loop
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- enters medulla
- permeable to water - mostly impermeable to ions - contains water channel aquaporin 1 in both luminal and basolateral membrane |
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thin ascending loop of Henle
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- Na+/K+ ATPase active transport of Na and K
- Cl- moves in through Cl- channels = secondary active transport |
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thick ascending limb
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- reabsorb sodium chloride which dilutes urine
- produces concentration gradients that drive counter current multiplier system in medulla and medullary rays - concentrates urine - reabsorb large amounts of potassium, calcium, and magnesium in energy-efficient manner |
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NaCl reabsorption
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- primary energy comes from Na+/K+ ATPase pump in basolateral
- in thick ascending limb much Na+ entry into cell occurs mainly by means of Na-K-2Cl co-transporter - K+ and Cl- carried inward by secondary active transport - loop diuretics inhibit co-transporter - electrical and concentration gradient drives more reabsorption of Na+ as well as Mg++ and Ca++ - cortical thick ascending limb drains urine into distal convoluted tubule |
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osmotic pressure increase
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- inner zone contains more salt = more capable to concentrate urine
- increases with depth in medulla - medullary vertical osmotic gradient permits excretion of urine of differing concentrations |
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single effect
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- difference in osmotic pressure and NaCl concentration between ascending limb, adjacent interstitial fluid, and descending limb
- oriented side to side - only about 200 mOsm difference between interstitial fluid and filtrate |
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generation of single effect
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- active transport of NaCl out of fluid into ascending limb dilutes that fluid
- concentrates the interstitial fluid - walls of descending limb are permeable to water - fluid becomes concentrated by losing water osmotically to interstitial fluid - sometimes by gaining Na+, C- by diffusion |
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multiplier effect
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- multiplied difference of concentration is established from end to end
- effect is multiplied in vertical gradient because of counter current multiplier |
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counter current multiplication
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- single effect is generated
- fluid moves in counter current fashion through loop - single effect is again generated - fluid concentration at inner end of loop increases and continues to increase |
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cell volume regulation
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- kidney first establishes a vertical osmotic gradient in medullary interstitial fluid
- gradient in turn is used by collecting tubules to concentrate tubular fluid so that urine can be more concentrated than normal body fluids - fluid is hypotonic as it enters distal portions of tubules - enable kidney to excrete a urine more dilute than normal body fluids |
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urea and NaCl
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- collecting ducts permeable to urea
- inner medulla has high concentration of urea - urea diffuses out of collecting duct - traverses the inner medulla - urea and NaCl form osmotic gradient that enables kidney to produce urine that is hyperosmotic to blood |
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2 kinds of cells in DCT and collecting tubules
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- principal cells
- intercalated cells |
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principal cells
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- more abundant
- receptors for hormones - chiefly involved in salt and water balance - main target of aldosterone which causes cells to synthesize channels and Na+/K+ ATPase pump |
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intercalated cells
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- reabsorb K+
- secrete H+ - involved mainly in acid base balance - maintain blood pH |
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lumen side cells of DCT
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- have a Na-Cl co-transporter
- permeable to Ca via a calcium channel - basolateral surface/blood side - produces gradient for Na to be absorbed from apical surface via Na/Cl symport - Ca reclaimed into blood by Na/Ca basolateral antiport - secondary active Na/Ca transporeter = antiport - ATP dependent Ca transporter |
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DCT and collecting tubules
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- establish aquaporins to increase water
- impermeable to water except in presence of antidiuretic hormone (vasopressin) |
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antidiuretic hormone
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- arginine vasopressin
- aquaporin-2 is inserted into membrane of collecting tubules to increase water permeability - water diffuses out of collecting tubule and comes to osmotic equilibrium with gradient of increasing concentration in medullary interstitial fluid - increases permeability of epithelium to water |
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ADH
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- binds to ADH receptor
- triggers GPCR to release second messenger - aquaporins inserted into apical surface and basal surface - alcohol effects by interfering with ADH binding - apical surface undergoes exocytosis to make storage vesicles with aquaporins |
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function of ADH
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- release of ADH triggered when osmoreceptors in hypothalamus detect increase in osmolarity of blood
- ADH causes thirst and increases permeability of water in collecting ducts = water reabsorption - drinking and water reabsorption decrease blood osmolarity |
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renin angiotensin aldosterone system
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- acts in antidiuresis
- stimulated by low blood pressure - juxtaglomerula doesn't experience enough stretch so renin is released - activates angiotensin in liver to convert to angiotensin 1 - angiotensin converting enzyme in the lungs convert angiotensin 1 to angiotensin 2 - angiotensin cause arterioles throughout body to vasoconstrict = raise BP - afferent arteriole constricts = decrease filtration - angiotensin acts on adrenal cortex to release aldosterone - aldosterone causes DCT to reabsorb Na+ and water = increase blood volume - renin production discontinued |
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juxtaglomerular cell
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- in wall of afferent arteriole
- modified smooth muscle cells - sensitive to stretch - when stretched less they increase their secretion of renin - innervated by sympathetic nerves - regulated by paracrines from macula densa of DCT - when BP low the macula densa reduces paracrine secretion that inhibits the JG cells |
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macula densa cells
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- located within thick ascending limb at DCT junction
- basolateral membrane in contact with glomerular mesangial cells - continuous with smooth muscle cells and renin-containing granular cells of afferent arteriole - unique renal biosensor cells - detect fluid load to DCT via entry NaCl through NKCC co-transporter mechanism |
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macula densa cells detect
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- fluid load to DCT via entry NaCl through NKCC co-transporter mechanism
- changes in luminal NaCl concentration ([NaCl]/L) and transmit signals to mesangial cell of afferent arteriole - [NaCl]/L sensitive ATP-permeable large-conductace (380 pS) anion channel signals AA |
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ATP released from macula densa
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- released via a maxi anion channel in response to increased
- transmit signals to mesangial cells - activate their purinergic receptors |
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aldosterone
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- secreted when blood Na+ falls or K+ concentrations rise
- acts primarily on DCT and collecting tubule - causes Na+ reabsorption and K+ secretion - water and Cl- follow water = solvent drag |
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production of dilute urine
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- epithelial wall of collecting tubule is poorly permeable to water
- filtrate is osmotically isolated from medullary interstitial fluid - become more and more dilute as NaCl is reabsorbed along length of collecting tubule |
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atrial natiuretic factor
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- causes loss of water
- stimulated by high BP and high blood volume - inhibit reabsorption of water - dilates afferent arteriole and constricts efferent arterioles increasing GFR - antagonize renin-angiotensin-aldosterone mechanism by inhibiting renin - inhibit secretion of ADH - inhibit NaCl reabsorption in collecting ducts |
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parathyroid hormone
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- mediates Ca++ reabsorption in DCT
- released with changes in blood Ca++ levels - activates primary active transport via ATP dependent Ca++ carrier and secondary transport via Na+/Ca++ carrier in basolateral surface = moves stuff in - Ca++/H+ symporter in basolateral surface = move stuff out |
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tubular secretion
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- selective movement of non-filtered or re-admitted substance from peritubular capillaries into tubular lumen
- movement from blood back to urine - mostly through tubules - most important are H+, K+, and organic ions - involves trans-epithelial transport - H+ secretion important in acid base balance |
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tubular secretion in PCT
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- waste removal
- enter through basolateral surface and out the apical surface - urea, uric, bile salts, ammonia, catecholamines, and prostaglandins - pollutants, morphine, penicillin, aspirin, and other drugs - PCT is main site of secretion for all except K+ - acid base balance - hydrogen and bicarbonate |
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acids
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- produced continuously by body
- lungs eliminate carbonic acid by exhaling CO2 - almost all H+ is eliminated by secretion - filtration rate of H+ = plasma [H+] x GFR - since plasma [H+] is very low filtration rate is low - DCT and PCT secrete H+ - no neural or hormonal control is involved |
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acidosis
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- secrete more H+
- removes NH3 from body - happens in mitochondria - exists in tubular cells - in urine the H+ binds to phosphate buffer = normally the only buffer in urine - developing urine contains NaH2PO4/Na2HPO4 in same concentration as present in blood plasma |
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phosphate buffer
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- when saturated NH3 is secreted into tubular fluid
- NH3 synthesized from glutamine (to glutamate) in PCT cell mitochondria |
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ammonia excretion
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- NH4 is secreted across the Na+/H+ antiport with NH4 instead of H+
- becomes trapped in lumen because the PCT cells are impermeable to NH4 - reabsorbed in TAL via a K+ locus on the Na+/K+/2Cl- symporter - H+ secreted into lumen of the loop of Henle in exchange for Na+ - NH3 diffuses out the basolateral surface of the TAL into medullary interstitial fluid - high medullary interstitial NH3 diffuses into the collecting duct - NH3 binds H+ fo form NH4 and keeping the lumen [H+] low - ammonia is excreted |
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tubular secretion in DCT
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- specialized for selective secretion and reabsorption of Na+ and Cl-
- K+ and H+ secreted |
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tubular secretion in collecting tubule
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- may secrete H+, K+, or HCO3- depending on blood pH
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K+ secretion
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- nearly all thats in the urine is from aldosterone drive active tubular secretion into DCT (low) and collecting tubules (high)
- controlled by aldosterone - actively secreted in (lateral portion) DCT and collecting tubules - basolateral pump co-transports Na+ into lateral surface and K+ into tubular cell - K+ leaves the cell through channels in luminal border |
