mod 11 Flashcards
Renal system includes:
kidneys, ureters, bladder, urethra
- Function of kidneys:
○ To regulate…
§ Water balance
§ Electrolyte levels
§ pH of the blood
§ Long-term regulation of arterial pressure
other functions of kidneys
○ Remove nonessential substances from plasma (waste metabolites, excess water, electrolytes)
○ Recover essential substances (glucose)
○ Conserve water + electrolytes by reducing amount removed by body
○ Act as endocrine gland - make hormones
anatomy of kidneys
- Size of fist
- Outer renal cortex, middle renal medulla, inner calyces - then drain into central renal pelvis - to ureter
- Renal medulla has renal pyramids - which is where nephrons are
- Nephron drains through a collecting duct into a calyx
Blood supply to nephron
- Renal artery -> interlobular artery -> afferent arteriole -> glomerulus (filtration) -> efferent arteriole -> peritubular capillaries (dense network of capillaries surrounding tubes of nephron) -> interlobular vein -> renal vein
Renal corpuscle
- Made of glomerular capsule + glomerulus
- Where blood is filtered (glomerular filtration)
- Glomerular filtration facilitated by highly permeable capillary endothelium surrounded by podocytes
○ Also enhanced by Large diameter of afferent arteriole + smaller diameter of efferent arteriole
Nephron functions
- Excretion = filtration + secretion - reabsorption
- Filtration - mvmt of fluid through glomerular capillary due to hydrostatic pressures
- Filtrate - solution created by filtration
- Reabsorption - mvmt of substance from lumen back into blood
- Secretion - mvmt of substance from blood into lumen
- Excretion - removal of substance from body
Glomerular filtration
- Bulk flow of filtrate (fluid from blood) into glomerular capsule - has same stuff as plasma, no large proteins or RBC
- Is affected by extremely permeable capillaries + starling forces
- Podocytes (special epithelial cells) surround capillaries and have large filtration slits btwn pedicles
○ These increase filtration
Glomerular filtration - starling forces
- Blood hydrostatic pressure (60mmhg) - due to diff in diameter btwn afferent (large) arterioles and efferent (small) arterioles
- Colloid osmotic pressure due to plasma proteins (-32mmhg) = causes reabsorption of fluid into plasma
- Capsular hydrostatic pressure (-18mmhg) = causes reabsorption of fluid)
- No colloid osmotic force in glomerular capsule bc few proteins are filtered
- Net filtration pressure is 10 mmhg out of glomerulus into capsular space
Glomerular filtration rate (GFR) and Filtered load
- Filter 180L/day
- GFR - volume of fluid filtered by glomerulus during certain time period
- Filtered load - substances filtered by kidney per day
○ Filtered load = GFR x plasma conc of substance - e.g. glucose almost completely filtered, but all reabsorbed in healthy ppl, so glucose should be excreted in urine
- e.g. should see some Na ions in urine bc it is filtered and excreted
- Amount excreted (g) = urine conc (g/L) x amount of water excreted per day (1.8L / day)
- Amount reabsorbed = filtered load - amount excreted
- Fraction excreted = (amount excreted/ filtered load) x 100%
Tubular transport mechanisms
- Over 99% filtered out by glomerulus are reabsorbed back into circulation
- When reabsorbed, 2 possible routes
○ Paracellular transport
§ When substances diffuse btwn tubular cells through tight junctions (usually don’t let stuff through, but can be leaky)
§ Non-regulated, no hormone control
○ Transcellular transport
§ Substances go across membrane from lumen into cell
§ Then into interstitial fluid and into blood
§ Can be regulated by hormones, but for most part not regulated
- When reabsorbed, 2 possible routes
- Na/K pump
○ Is active transport - 3 Na out, 2 K in
○ High conc Na outside cell + low inside, high conc K inside + low outside
○ Is active transport - 3 Na out, 2 K in
○ High conc Na outside cell + low inside, high conc K inside + low outside
- Secondary active transport
○ Na conc gradient from Na/ K pump powers other transporters
○ Stuff moves in w Na or moves out in exchange w incoming Na
○ Na/ glucose, Na/ H exchanger
○ Na/ glucose co-transporter - luminal side of each tubule cell
§ Each Na diffuses into cell, single glucose carried in w it
○ Na/ H exchanger - moves 1 H out for every Na in
§ Also on luminal side of cells
- Secretion
○ Kidneys remove unwanted substances from blood into lumen of nephron
○ Hormonally regulated process, can be non-regulated (no hormonal control)
○ Most substances that are secreted are eventually excreted in the urine
○ Secreted are H and K
○ Secretion of K relies on Na/K pump
- Na reabsorption
○ In proximal tubule, ascending limb of loop of henle, early distal tubule
○ Non-regulated mechanisms
○ Reabsorption in proximal tubule can be regulated by hormone angiotensin II
§ Aldosterone in late distal tubule + collecting duct
○ In healthy - all glucose that is filtered at glomerulus is reabsorbed in proximal tubule
§ Amino acids reabsorbed in proximal tubule
- Water reabsorption
○ In proximal tubule and descending limb of loop of henle through non-regulated mechanisms
○ No water reabsorbed in ascending loop of henle
Regulated by antidiuretic hormone (ADH) in late distal tubule and collecting duct
- K reabsorption
○ Proximal tubule and ascending limb of loop of henle
○ Secretion of K in small amounts in ascending limb of loop of henle
○ Larger amount secreted in late section of distal tubule and collecting duct under influence of aldosterone
- H secretion
○ Happens in proximal tubule and ascending limb of loop of henle + late distal tubule and collecting duct
○ Can be regulated and non-regulated
- Proximal convoluted tubule
○ Reabsorbs ~ 66% of total filtrate
○ Na reabsorbed by simple diffusion, Na/glucose co-transporter, Na/H exchanger
○ Na/ H regulated by angiotensin II
○ Reabsorbs amino acids using Na/ amino acid co-transporter
- Healthy vs diabetes - Na/glucose
○ Healthy - Na/glucose co-transporter reabsorbs all glucose in filtrate
- Diabetes - proximal convoluted tubule
○ Affects pancreas ability to make insulin
○ Insulin takes up + stores glucose after a meal, so w/o glucose conc builds up
○ Glucose in urine is how they can tell u have diabetes
○ Bc high conc, glucose filtered by glomerulus and Na/glucose co-transporters can’t reabsorb everything so it goes out in urine
○ Co-transport system is secondary active transport, so can be saturated (so glucose can get by pumps bc its going too fast + too much)
- Reabsorption of water - proximal convoluted tubule
○ Filtrate will have lower solute conc + higher water conc vs cell / interstitial fluid
○ Water reabsorbed by osmotic gradient + aquaporins (water channels)
○ By paracellular transport btwn cells
○ By transcellular transport across cells
○ Only happ AFTER solutes been reabsorbed (esp Na)
- K and Cl - proximal convoluted tubule
○ 65% of all K and CL reabsorbed in proximal tubule
○ Through 2 types of paracellular transport, both not regulated
○ The 2 are solvent drag + simple diffusion
○ Solvent drag - reabsorp of K w movement of water, as water goes in, takes some solute (including K)
○ Simple diffusion - down conc gradient, water keeps going in and K stays out, so as more water goes in, the K conc outside is higher, so now diffusion of K in
○ Bc tight junctions in proximal tubule are leaky
○ Cl also reabsorbed by transcellular transport
- Reabsorption of filtrate back into circulation
○ Na leaves tubule cells by Na/ K pump
○ K reabsorbed by paracellular transport, so already in interstitial fluid
○ Glucose + amino acids across basal membrane of cells by specific facilitated diffusion transporters
○ All this due to starling forces
○ In kidney, hydrostatic force (13), interstitial hydrostatic force (6), osmotic force from proteins in plasma (32), interstitial osmotic force (15), so net filtration pressure is -10 (10mmhg back into capillary)
○ Large osmotic pressure bc of plasma proteins bc during glomerular filtration, almost all substances filtered except large proteins
- Proximal convoluted tubule - conc of filtrate
○ Conc of filtrate leaving proximal tubule will not have changed from what it was at beginning of tubule
○ Still ~ 290-300 water
○ So same proportion of solutes + water reabsorbed in proximal tubule
○ Only volume has changed, same conc
- Loop of henle - conc gradient in medulla of kidneys
○ 15% of filtered water + 20% of filtered Na is reabsorbed in loop
○ Conc increases as descends in loop
○ Descending v permeable to water, not rlly for ions - water moves out by osmosis
○ Result is loss of water from filtrate, so increasing conc of filtrate by the time it reaches ascending limb
- Loop of henle, ascending limb - reabsorption of Na, K, Cl, water
○ Ascending loop not permeable to water, no ware reabsorbed at this section
○ Ascending is v permeable to Na, K, Cl
○ Na/K pumps create conc gradient that let Na go in, this Na gradient drives co-transporter that carries Na, K and Cl into tubule cells all at once
○ This increase K conc inside, so some K will be secreted by back out by simple diffusion through leaky channels
○ Na reabsorbed also through Na/H exchanger
○ Overall filtrate conc decreases
- Distal convoluted tubule - reabsorp Na and water
○ 12% Na reabsorbed here
○ Reabsoption of water here controlled by antidiuretic hormone (ADH, aka vasopressin) and will depend on level of hydration of person
○ Water reabsorp is 0-15%
○ Na go in bc of conc gradient from Na/K pump, later segments -> Na reabsorp regulated by aldosterone
○ Aldosterone increases activity of Na/K pump, which dec conc of Na in cell + makes cell make more Na channels, so more Na into cells, then out by Na/K pump
- Distal convoluted tubule - secretion of K
○ K secretion is response to aldosterone
○ Bc aldosterone inc Na/K pump, so more K inside and more Na channels, so higher conc of K inside
○ Aldosterone also inc number of K channels, so this plus the higher conc of K inside, so K secreted IN RESPONSE TO ALDOSTERONE
○ If aldosterone wasn’t there, it wouldn’t be secreted
- Collecting duct - reabsorp of Na and water
○ Collects filtrate from many nephrons + is final area for processing filtrate into urine
○ Plays role in determining final conc of urine
○ 10% Na and water reabsorp here, but always regulated
○ Increase in aldosterone = inc in Na reabsorp
○ Inc in ADH = inc in water reabsorp
- Collecting duct - secretion of K
○ K secretion in collecting duct due to presence of aldosterone
○ Inc activity of Na/K pump = inc conc of K incell, plus more K channels, which lets K leak down conc gradient into lumen of collecting duct
Water balance
- Internal enviro must stay at relatively constant levels, including Na and water
- Water gained - drinking, eating, metabolism of energy stores
- Water lost - urine, sweating, lungs, feces
Water balance regulation
- One of main functions of kidneys (they don’t make water, but reabsorb)
- Water balance regualted by antidieuretic hormone (ADH - aka vasopressin)
- ADH made by hypothalamus of brain + released from posterior pituitary
- Relies on neg feedback
Water balance - osmoreceptors
- Sensors for neg feedback are osmoreceptors
- Osmoreceptors located in hypothalamus of brain + respond to changes in body fluid conc
- In cells, too much water (overhydration), too little (dehydration) = can cause changes in fluid conc
- Filtrate : get water = diluted; lose water = concentrated
Water balance - ADH
- dehydration = concentrates body fluid (inc osmolarity) - osmoreceptors lost water by osmosis and shrink, which signals posterior pituitary to release ADH, which causes kidneys to reabsorb water from distal tubule and collecting ducts
- Overhydration = dilutes body fluids, decreases osmolarity, causes osmoreceptors to swell, and less ADH released, less water reabsorbed in distal tubule and collecting duct, and more water excreted in urine
- Dehydration - lower blood volume, lower blood pressure
- Overhydration - inc blood volume, inc blood presure
- Change in blood volume detected by volume receptors on wall of left atrium
- Change in blood pressure detected by baroreceptors in aortic arch and carotid sinus
- Osmoreceptors and volume receptors can control release of ADH - lower BV = release ADH, inc BV = decrease ADH release
Water balance - ADH’s effect on the cells
- ADH makes cells make special water channels (aka aquaporins) = more water reabsorp by osmosis and less excreted in urine
Alc effect on water balance
- Pee more after drinking bc alc stops release of ADH from pituitary gland
- Less ADH = fewer water channels = less water reabsorbed = more water in urine
Regulation of Na
- Na regulated by renin-angiotensin system (RAS) and aldosterone - when combines, its called renin-angiotensin-aldosterone system (RAAS)
- Remember ion moving - Na, Cl, Ca in; K out
Sodium balance - aldosterone
- Aldosterone is steroid hormone made by adrenal glands, secreted when Na low or K high, brings conc back to normal
- Secreted in response to angiotensin II and adrenal corticotropic hormone (ACTH) ((in small amounts))
Sodium balance - renin-angiotensin system
- RAS regulates Na balance by inc reabsorp of Na in proximal convoluted tubule
- Converts angiotensinogen (inactive) into angiotensin II (active)
- Angiotensinogen made in liver, reacts w renin made by juxtagolumerular cells (in walls of afferent + efferent arteriole) which converts to angiotensin I, which converts to angiotensin II (by angiotensin converting enzyme aka ACE), which is made in lungs
- Renin released when BP or plasma Na levels are low
- Angiotensin II inc reabsorp of Na in proximal convoluted tubule and ascending limb of loop of henle and it inc activity of Na/H exchanger, also stimulates secretion of aldosterone
- Angiotensin II made when Na levels low, blood pressure low
Effects of ang II
- V v v potent vasoconstrictor = inc total peripheral resistance = inc BP
- Stimulates sensation of thirst to trigger drinking = you drink = inc blood volume = inc BP
- Stimulates release of ADH from posterior pituitary = reabsorption of water by kidneys, + absorption of water and Na from digestive tract
Changes to the filtrate
- Filtrate in glomerular capsule and at beginning of proximal tubule is isotonic, but doesn’t have large proteins
- As goes through proximal tubule, Na and water absorbed in equal amounts (solution being reabsorbed is isotonic too) = so filtrate conc still isotonic to plasma
