urinary system

what is the maximal clearance value in a normal kidney?

*625 ml/min* - 125 is filtered - 500 is secreted - case with PAH - occurs if 100% is filtered, 0% is reabsorbed, and 100% is secreted

extrinsic controls of GFR

*by nervous and endocrine systems* - work to maintain blood pressure (in extreme changes of blood pressure, extrinsic controls take precedence over intrinsic controls in an effort to prevent damage to brain and other crucial organs)

what process is involved in water reabsorption?

*osmosis* - occurs everywhere except the descending limb and the DCT - obligatory water reabsorption (by aquaporin-1s) and facultative water reabsorption (by aquaporin-2s) - movement of Na+ and other solutes establishes a strong osmotic gradient and water moves by osmosis into the peritubular capillaires - transmembrane proteins called aquaporins help by acting as water channels across the plasma membranes - water reabsorption concentrates the solutes in the filtrate that remains in the tubule --> thus increasing their concentration gradient and facilitating the passive reabsorption

what sign related to the urinary system might a patient with uncontrolled diabetes exhibit?

*polyuria* - excessive urination and increased urine output (because glucose increases osmolarity of filtrate --> draws in more water --> higher urine volume) - increased specific gravity (slightly) --> could potentially become decreased if persistently uncontrolled and progresses into diabetes insipiditus - glucosuria (glucose in urine)

intrinsic controls of GFR

*renal autoregulation* - acts locally within the kidney to maintain GFR - very effective

what are the 2 main parts of a nephron?

*renal corpuscle* -- located entirely in renal cortex *renal tubule (and ducts)* -- begin in the cortex and then pass into the medulla before returning to the cortex

what is the primary neural innervation of the kidney?

*renal plexus* - a variable network of autonomic nerve fibers and ganglia - provides the nerve supply of the kidney and its ureter - an offshoot of the celiac plexus - largely supplied by the sympathetic fibers form the most inferior thoracic and lumbar splanchnic nerves, which course along with the renal artery to reach the kidney

role of collecting ducts in osmotic gradient

*the collecting ducts of all nephrons use the gradient to adjust urine osmolarity* - under the control of ADH, the collecting ducts determine the final concentration and volume of urine - collecting ducts deep in medulla are also permeable to urea - deep in medullary regions, urea diffuses out of collecting ducts-- until equilibrium is reached - urea accounts for about 1/2 of the osmolarity of the medullary interstitial fluid

countercurrent multiplier

*the interaction between the flow of filtrate through the ascending and descending limbs of the long nephron loops of juxtamedullary nephrons* - long nephron loops of the juxtamedullary nephrons create the gradient by acting as countercurrent multipliers - filtrate flows in opposite directions (countercurrent) through 2 adjacent parallel sections of a nephron loop - descending limb is permeable to water, but not to salt - ascending limb is impermeable to water, but pumps out salt - salt is pumped out of ascending limb --> increases interstitial fluid osmolality --> water leaves descending limb --> increase in osmolality of the filtrate in the descending limb --> increase in osmolality of filtrate entering ascending limb --> salt is pumped out of ascending limb (cyclic!) - as water and solutes are reabsorbed, the loop first concentrates the filtrate, then dilutes it

what are the metabolic sources of urea, uric acid, and creatinine?

*they are all nitrogenous wastes found in urine* urea --> derived from the normal breakdown of amino acids uric acid --> end product of nucleic acid metabolism creatinine --> metabolite of creatinine phosphate, which is found in large amounts in skeletal muscle tissue, where it stores energy to regenerate ATP

countercurrent exchanger

*vasa recta preserve the gradient by acting as countercurrent exchangers* - entire length of vasa recta is highly permeable to water and solutes - circulation in vasa recta is adapted to maintain, rather than dilute the osmolarity of the interstitium - due to countercurrent exchanges between each section of the vasa recta and its surrounding interstitial fluid, the blood within the vasa recta remains nearly isosmotic to the surrounding fluid - vasa recta protect the medullary gradient by preventing the rapid removal of salts from the interstitial fluid in the medulla - as a result, the vasa recta do not undo the osmotic gradient as they remove reabsorbed water and solutes

explain the physiologic mechanisms involved in maintaining homeostasis when osmolarity of body fluid decreases

*when the osmolarity increases, ADH is secreted. Conversely, when the osmolarity decreases, ADH release is suppressed* - osmolarity of body fluids decreases --> over hydrated --> decreases ADH secretion --> collecting ducts become relatively impermeable to water (water reabsorption decreases) --> large volume of dilute urine

explain the physiological mechanisms involved in maintaining homeostasis when the osmolarity of body fluids increases

*when the osmolarity increases, ADH is secreted. Conversely, when the osmolarity decreases, ADH release is suppressed* osmolarity of body fluids increases --> dehydrated --> increases ADH secretion --> number of aquaporins increase in collecting duct --> H2O is reabsorbed --> small volume of concentrated urine

urine formation: GLOMERULAR FILTRATION

- "dumping into waste container" - takes place in the renal corpuscle - solutes move from glomerulus into renal tubule - produces a cell- and protein-free filtrate

urine formation: TUBULAR REABSORPTION

- "reclaiming what the body needs to keep" - the process of selectively moving substances from the filtrate back into the blood - takes place in the renal tubules and collecting ducts - tubular reabsorption reclaims almost everything filtered (all of the glucose and amino acids, some 99% of water and other components) - anything that is not reabsorbed becomes urine in the collecting duct

urine formation: TUBULAR SECRETION

- "selectively adding to the waste container" - the process of selectively moving substances from the blood into the filtrate - occurs along the length of the tubule and the collecting duct (like tubular reabsorption)

describe what happens during tubular reabsorption

- *H2O and solutes move from the tubule lumen to the blood of the peritubular capillaries or vasa recta* - our total plasma volume filters into renal tubules about every 22 minutes, so all of our plasma would drain away if we didn't reabsorb it - occurs via 2 routes: paracellular reabsorption and transcellular reabsorption - in healthy kidneys, virtually all organic nutrients such as glucose and amino acids, are reabsorbed while the reabsorption of water and many ions is continuously regulated and adjusted in response to hormonal signals - reabsorption in DCT and collecting duct is fine tuned by influence from endocrine hormones, ADH, aldosterone, and ANP

substances reabsorbed in PCT

- *Na+ ions*: by primary active transport via ATP-dependent Na+/K+ pumps on basolateral membrane --> sets up electrochemical gradient for passive solute diffusion, osmosis, and secondary active transport (cotransport involving symporters or anti porters) with Na+ - *virtually all nutrients* (glucose, amino acids, vitamins, lactate, etc...) mostly via cotransport/secondary active transport with Na+ - *electrolytes* (K+, Mg2+, Ca2+, Cl-, HCO3-, and others) - *anions* (Cl- and HCO3-) via paracellular diffusion driven by electrochemical gradient for Cl- - *water*- obligatory water reabsorption via osmosis (by aquaporins) - *urea and some lipid-soluble solutes*-- passive diffusion driven by electrochemical gradient - *small proteins*-- reabsorbed via endocytosis, then digested inside the PCT cells to amino acids

what organs comprise the urinary system?

- *kidneys* (2): form urine - *ureters* (2): paired tubes that transport urine from the kidneys to the urinary bladder - *urinary bladder* (1): a temporary storage reservoir for urine - *urethra* (1): a tube that carries urine from the bladder to the body exterior

describe what happens during tubular secretion

- *solutes are moved from the blood in the peritubular capillaries through the tubule cells into the filtrate* - materials moved from blood --> filtrate - allows unwanted or unnecessary materials to be removed from the blood - the urine eventually excreted contains both filtered and secreted substances - with one major exception (K+), the PCT is the main site of secretion, but the collecting ducts are also active

basic histological characteristics of the COLLECTING DUCT

- 2 cell types: principal cells and intercalated cells

reabsorption in PCT: OVERVIEW

- 65% of filtrate volume reabsorbed here - most active site of reabsorption - normally reabsorbs all of the glucose and amino acids in the filtrate and 65% of the Na+ and water - bulk of electrolytes are absorbed by the time the filtrate reaches the nephron loop - nearly all of the uric acid and 1/2 of the urea are absorbed in PCT, but both are secreted later back into filtrate - chemical composition of filtrate at end of PCT is very different than the plasma, but the osmolarity is similar (because losing both solutes and solvents!) - filtrate volume is substantially reduced in PCT

chemical composition of urine

- 95% water - remaining 5% is solutes - largest component of urine by weight (besides water) is urea --> derived from normal breakdown of amino acids - other nitrogenous wastes in urine: uric acid (end product of nucleic acid metabolism), creatinine - normal solute constituents of urine, in order of decreasing concentration include: urea, Na+, K+, (PO3)4-, (SO4)2-, creatinine, uric acid - much smaller but highly variable amounts of Ca2+, Mg2+, and HCO3- are also present - unusually high concentrations of any solute or the presence of abnormal substances such as blood proteins, WBCs, or bile pigments, may indicate pathology

effect of ADH on urine volume and concentration

- ADH inhibits urination - makes principal cells of collecting ducts more permeable to water by causing aquaporins to be inserted into their apical membranes - amount of ADH determines number of aquaporin-2s and thus the amount of water that is reabsorbed there - when body is overhydrated, ECF osmolality decreases, decreasing ADH secretion by posterior pituitary and making the collecting ducts relatively impermeable to water - also increases urea reabsorption by collecting ducts

how does NFP affect GFR?

- GFR is directly proportional to NFP - NFP is the main controllable factor of GFR - anything that changes the pressures can affect GFR - of the pressures determining NFP, most important is glomerular hydrostatic pressure --> can be changed by changing the diameter of the afferent (and sometimes efferent) arterioles - huge surface area and high permeability of filtration membrane explain how 10 mmHg NFP can produce large amounts of filtrate - NFP in glomerulus favor filtration over enter length of capillary, unlike other capillary beds, where filtration only occurs at the arterial end and reabsorption occurs at the venous end

secretion in distal convoluted tubule (DCT)

- H+ may be secreted depending on the pH state of the body --> if blood is acidotic, more H+ will be secreted

describe the micturition reflex

- at age 2-3 able to override reflexive urination -urination or voiding, is the act of emptying the bladder -3 things must occur simultaneously: 1. the detrusor must contract 2. the internal urethral sphincter must open 3. the external urethral sphincter must open - afferent impulses from bladder stretch receptors are relayed to pons and higher brain centers that provide the conscious awareness of bladder fullness - pons has 2 centers that participate in control of micturition: pontine storage center (inhibits micturition) and pontine micturition center (promotes the micturition reflex) - lower bladder volumes primarily activate the pontine storage center, which inhibits urination by suppressing parasympathetic and enhancing sympathetic output to the bladder - when a person chooses not to void, reflex bladder contractions subside within a minute or so and urine continues to accumulate - because the external sphincter is voluntarily controlled, we can choose to keep it closed and postpone bladder emptying temporarily - after additional urine has collected, the micturition reflex occurs again (cycle)` - urge to void gradually becomes greater and greater and micturition usually occurs before urine volume exceeds 400 ml - after normal micturition, only about 10 ml of urine remains in the bladder *detrusor and its internal urethral sphincter composed of smooth muscle and innervated by both PNS and SNS. External urethral sphinc. is skeletal muscle and therefore innervated by somatic nervous system. as urine accumulates, distension of bladder activates stretch receptors in its walls; impulses from activated receptors travel via visceral afferent fibers to sacral region of spinal cord; visceral afferent impulses excite parasympathetic neurons and inhibit sympathetic; as a result, detrusor contracts and internal sphincter opens. visceral afferent impulses also decrease the firing rate of somatic efferents that normally keep the external sphincter closed. this allows the sphincter to relax so urine can flow.

describe how bicarbonate ions are reabsorbed in the PCT. what role do Na+/H+ antiporters play in this process?

- HCO3- ions are an important part of the HCO3- buffer system --> most important inorganic blood buffer - complex because tubule cells are almost impermeable to the HCO3- in the filtrate -- cannot reabsorb it - breakdown and rebuild HCO3- in order to reabsorb it (as a result of splitting carbonic acid into HCO3- and H+) - HCO3- leaves the tubule cell either accompanied by Na+ or in exchange for Cl- - H+ is actively secreted, mostly by Na+-H+ anti porter, but also by a H+ ATPase - in filtrate, H+ combines with filtered HCO3- --> reabsorption of HCO3- depends on active secretion of H+ - for each filtered HCO3- that disappears from the filtrate, a HCO3- generated within the tubule cells enters the blood: a 1:1 exchange - when large amounts of H+ are secreted, correspondingly, large amounts of HCO3- enters the peritibular blood --> net effect is to remove HCO3- almost completely from the filtrate - reabsorbed in PCT by secondary active transport linked to H+ secretion and Na+ reabsorption --> occurs via paracellular diffusion driven by the electrochemical gradient for Cl- NOTE: when acidosis occurs, less Cl- is coupled with Na+ because HCO3- reabsorption is stepped up to restore blood pH to its normal range --> choice between Cl- and HCO3- serves acid-base regulation

Na+ reabsorption

- Na+ ions are most abundant cations in filtrate - about 80% of energy used for active transport is devoted to Na+ reabsorption - almost always after and via the transcellular route - occurs mainly by solute pumping (Na+/K+ pumps) and provides the means by which many other solutes and water are reabsorbed - involves Na+ transport across apical and basolateral membranes of tubule cells

sodium transport across basolateral membrane

- Na+ is actively transported out of the tubule cell by primary active transport by a Na+-K+ ATPase pump in the basolateral membrane - from there, bulk flow of water sweeps Na+ into the peritubular capillaries --> rapid because low hydrostatic pressure and high osmotic pressure (most proteins remain in blood instead of filtering into tubule)

why is the clearance value for PAH an index of renal blood flow?

- PAH = para-aminohippuric acid - PAH is freely filtered, not reabsorbed, and is completely secreted by the kidney --> all of the plasma that enters the kidney is completely cleared of PAG - all of the PAH should leave the kidney in the urine of a healthy body - allows us to measure how the glomerulus is functioning (to see if everything is being secreted that was filtered through the glomerulus) - 625 ml/min

specific gravity of urine

- SG = ratio of the mass of a substance to the mass of an equal volume of distilled water - because urine is water plus solutes, a given volume has a greater mass than the volume of distilled water - SG of water is 1.0 but that of urine ranges from 1.001-1.035 depending on the solute concentration

basic histological characteristics of the NEPHRON LOOP (LOOP OF HENLE)

- U-shaped - has ascending and descending limbs - *thick descending limb*-- proximal part of descending limb; is continuous with the primal tubule and its cells are very similar (cuboidal cells) - *thin descending limb*-- the rest of the descending limb; consists of a simple squamous epithelium - *thin ascending limb*-- present in some nephrons as the thin segments extend around the bend; simple squamous epithelium - *thick ascending limb*-- the epithelium becomes cuboidal or even low columnar - NOTE: in most nephrons, the entire ascending limb is *thick*

where are the macula densa cells located? what is their function?

- a group of tall closely packed cells in the ascending limb of the nephron loops that lies adjacent to the granular cells - chemoreceptors that monitor the NaCl content of the filtrate entering the DCT - monitor changes in the solute concentration of the filtrate

cortical nephrons

- account for 85% of the nephrons in the kidneys - except for small parts of their nephron loops that dip into the outer medulla, they are located entirely in the cortex

sodium transport across apical membrane of tubule cells

- active pumping of Na+ from tubule cells results in a strong electrochemical gradient that favors its entry at the apical face via secondary active transport (cotransport) carriers or via facilitated diffusion channels - occurs because: 1) the pump maintains the intracellular Na+ concentration at low levels and 2) the K+ pumped into the tubule cells almost immediately diffuses out into interstitial fluid via leakage channels, leaving the interior of the tubule cell with a net negative charge

effects of aldosterone on principal cells of collecting ducts and late DCT

- acts on principal cells to increase Na+ reabsorption/K+ secretion - due to effects of aldosterone, there is virtually no urinary Na+ excretion --> important because Na+ is the primary cation in the ECF --> this helps prevent progressive dehydration and electrolyte imbalance

internal urethral sphincter

- at bladder-urethra junction - formed by thickening of detrusor muscle - involuntary sphincter controlled by ANS - keeps urethra closed when urine is not being passed and prevents leaking between voiding

describe the role of the macula densa and JG cells in the tubuloglomerular feedback mechanism

- autoregulation by flow-dependent tubuloglomerular feedback mechanism is directed by macula densa cells of the JG complex - macula densa cells respond to NaCl concentration (which varies directly with filtrate flow rate)

extraglomerular mesangial cells

- lie between the arteriole and tubule cells - interconnected by gap junctions - these cells may pass regulatory signals between macula densa and granular cells

external anatomy of a kidney

- bean-shaped - mass of 150g (5 ounces) - avg dimensions are 11 cm long, 6 cm wide, and 3 cm thick --> abt the size of a large bar of soap - lateral surface is convex - medial surface is concave and has a vertical cleft called the *renal hilum* that leads into an internal space called the *renal sinus* - the ureter, renal blood vessels, lymphatics, and nerves all join each kidney at the hilum and occupy the sinus - on top of each kidney is an adrenal/suprarenal gland - 3 layers of supportive tissue surround each kidney; from superficial to deep: renal fascia --> perineal fat capsule --> fibrous capsule

reabsorption in loop of Henle: OVERVIEW

- beyond PCT, permeability of the tubule epithelium changes dramatically - water reabsorption is not coupled to solute reabsorption here - water can leave descending limb but not ascending limb, where aquaporins are scarce or absent in the tubule cell membranes - opposite is true for solutes --> virtually no solute reabsorption occurs in descending limb, but solutes are reabsorbed actively and passively in ascending limb

obligatory water reabsorption

- by aquaporin-1s - in continuously water-permeable regions of the renal tubules, such as the PCT, aquaporin-1s are always present in the tubule cell membranes --> their presence causes the body to absorb water in the proximal nephron regardless of its state of hydration

facultative water reabsorption

- by aquaporin-2s - aquaporins are virtually absent in the apical membranes of the collecting duct and late distal convoluted tubule unless ADH is present --> this water reabsorption is dependent on ADH

how is release of atrial natriuretic peptide (ANP) stimulated? what are the effects of ANP?

- cardiac hormone - ANP reduces blood Na+ --> decreasing blood volume and pressure - released by cardiac atrial cells when blood volume or blood pressure is elevated - exerts several effects that lower blood Na+ content, including direct inhibition of Na+ reabsorption at the collecting ducts

renal pelvis

- central collecting region in the kidney - funnel-shaped reservoir that collects the urine and passes it to the ureter

what role does the vasa recta play in maintaining the medullary osmotic gradient?

- circulation in vasa recta is adapted to maintain, rather than dilute the osmolarity of the interstitium - vasa recta preserve the gradient by acting as countercurrent exchangers - highly permeable to water and solutes - countercurrent exchange occurs between each section of the vasa recta and its surrounding fluid --> blood within the vasa recta remains nearly isosmotic to the surrounding fluid and the vasa recta are able to reabsorb water and solutes into the general circulation without undoing the osmotic gradient created by the countercurrent multiplier - vasa recta able to preserve the osmotic gradient as they remove reabsorbed water and solutes - countercurrent flow of fluid moves through 2 adjacent parallel sections of the vasa recta - prevents rapid removal of salts from interstitial fluid of the medulla

color and transparency of urine

- clear and pale to deep yellow - yellow color due to urochrome (a pigment that results when body destroys Hb) - the more concentrated the urine, the deeper the color - abnormal colors (pink, brown, smoky) can result from eating certain foods or from the presence of bile pigments or blood in the urine - some drugs and vitamin supplements can alter the color of urine - cloudy urine may indicate a UTI

visceral layer of the glomerular capsule

- clings to glomerular capillaries - consists of highly-modified, branching epithelial cells called *podocytes* - podocytes: octopus-like; terminate in foot processes, which interdigitate as they cling to the basement membrane o the glomerulus - the clefts or openings between the foot processes of the podocytes are called *filtration slits* --> through these slits filtrate enters into the capsular space

muscularis of ureter

- composed chiefly of 2 smooth muscle sheets: an internal longitudinal layer and an external circular layer - an additional smooth muscle layer called the external longitudinal layer appears in the lower third of the ureter

how does urea recycling help establish the medullary osmotic gradient and promote water reabsorption?

- conserving water is so important that the kidneys use urea to help form the medullary gradient - urea enters filtrate by facilitated diffusion in the ascending limb of the nephron loop - as filtrate moves on, cortical collecting duct usually reabsorbs water, leaving urea behind - when filtrate reaches the portion of the collecting duct deep in the medullary region, the now highly concentrated urea moves by facilitated diffusion out of collecting duct into the interstitial fluid of medulla --> these movements create a pool of urea that recycles back into the ascending thin limb of the nephron loop - urea contributes substantially to the high osmolality in the medulla - urea is reabsorbed into the body --> to be secreted again into the tubule --> in order to help maintain the osmotic gradient - ADH increases recycling of urea and enhances urea transport out of collecting duct --> strengthens medullary isosmotic gradient, allowing more concentrated urine to be formed

describe the structure of the renal corpuscle

- consists of a tuft of capillaries called a *glomerulus* and a cuff-shaped hollow structure called the *glomerular capsule* - glomerular capsule is continuous with its renal tubule and completely surrounds the glomerulus

aquaporin-1

- constitutively expressed in the PCT and parts of the LOH - when they are present, they make the tubule freely permeable to H2O - obligatory water reabsorption

mucosa of ureter

- contains a transitional epithelium that is continuous with the mucosa of the kidney pelvis superiorly and the bladder medially

mesangial cells

- contractile cells that help regulate glomerular filtration by controlling blood pressure and filtration in the kidneys - smooth muscle-like cells adhering to the wall of the small blood vessels of the KIDNEY at the glomerulus and along the vascular pole of the glomerulus in the JUXTAGLOMERULAR APPARATUS. They are myofibroblasts with contractile and phagocytic properties

basic histological characteristics of the DISTAL CONVOLUTED TUBULE (DCT)

- cuboidal cells - confined to the cortex - thinner and almost entirely lack microvilli

location of the kidneys

- lie in a retroperitoneal position (between the dorsal wall and the parietal peritoneum) in the superior lumbar region - extend approximately from T12-L3 - receive some protection from the lower part of the rib cage - R kidney is crowded by the liver --> lies slightly lower than the left

what factors trigger aldosterone release?

- decreased blood volume - decreased blood pressure - hyponatremia (decreased Na+) - hyperkalemia (K+ increase) - renin-angiotensin system NOTE: except for hyperkalemia (which directly stimulates the adrenal cortex to secrete aldosterone), these conditions promote the renin-angiotensin system, which then stimulates aldosterone secretion (indirect)

what is aldosterone stimulated by?

- decreased blood volume or BP - hyponatremia - hyperkalemia - renin-angiotensin system

how do changes in blood pressure affect urine volume?

- direct correlation between blood pressure and urine volume - higher blood pressure --> higher urine volume - lower blood pressure --> lower urine volume

factors that trigger renin release: SYMPATHETIC NERVOUS SYSTEM

- direct stimulation of the JG cells - as part of the baroreceptor reflex, renal sympathetic nerves activate beta1-adrenergic receptors that cause the granular cells to release renin

what is tubular secretion important for?

- disposing of certain drugs and metabolites that are tightly bound to plasma proteins (because plasma proteins are generally not filtered, the substances they bind are not filtered and so must be secreted) - eliminating undesirable substances or end products that have been reabsorbed by passive processes (ex. urea and uric acid) - ridding body of excess K+ (because nearly all of the K+ present in filtrate is reabsorbed in PCT and ascending nephron loop, nearly all K+ in urine comes from aldosterone-driven active tubular secretion late DCT and collecting ducts) - controlling blood pH

why is plasma creatinine the more useful index for GFR in clinical situations?

- doesn't have to be injected like inulin - used to hove a "quick and dirty" estimate of GFR because does not need to be intravenously infused into the patient as inulin does

location and function of the vasa recta

- efferent arterioles serving the juxtamedullary nephrons tend not to break up into the meandering peritubular capillaries --> instead form bundles of long straight vessels called *vasa recta* - a specialized type of peritubular capillaries - extend deep into the medulla paralleling the longest nephron loops - surround the Loops of Henle of juxtamedullary nephrons in the medulla - supply oxygen and nutrients to the tissue they pass through --> the renal medulla - thin-walled - also play an important role in forming concentrated urine

describe the structure of the renal corpuscle: GLOMERULUS

- endothelium of glomerular capillaries is fenestrated (penetrated by many pores) - allows large amounts of solute-rich but virtually protein-free fluid to pass from the blood into the glomerular capsule --> this plasma-driven fluid/filtrate is the raw material that renal tubules process to form urine

glomerular hydrostatic pressure

- essentially glomerular blood pressure - chief force pushing water and solutes out of the blood and across the filtration membrane - BP in glomerulus is extraordinarily high and remains high across entire capillary bed (around 55 mmHg compared to avg 26 mmHg of other capillary beds) --> because the glomerular capillaries are drained by a high-resistance efferent arteriole whose diameter is smaller than the afferent arteriole that feeds them - filtration occurs along entire length of capillary and reabsorption does not occur as it would in other capillary beds

aquaporin-2

- expressed only in distal portions of the tubule - number varies to ADH levels - facultative water reabsorption

glomerular filtration membrane: GLOMERULAR CAPILLARY ENDOTHELIUM

- fenestrated - these fenestrations (capillary pores) allow all blood components except blood cells to pass through

how does aldosterone help regulate reabsorption in the DCT?

- fine tunes reabsorption of the remaining Na+ in the DCT - acts on principal cells of the distal DCT and collecting duct to increase Na+ reabsorption/ K+ secretion --> by prodding them to synthesize and maintain more apical Na+ and K+ channels and more basolateral Na+-K+ ATPases - due to aldosterone's effects, there is usually virtually no urinary Na+ excretion - in absence of aldosterone, these segments reabsorb much less Na+ and about 2% of Na+ filtered daily would be lost (incompatible with life) - physiological role of aldosterone is to increase blood volume and thy blood pressure, by enhancing Na+ reabsorption --> because water generally follows Na+ if aquaporins are present - helps reduce blood K+ concentrations because aldosterone-induced reabsorption of Na+ is coupled to K+ secretion in the principal cells of the collecting duct (as Na+ enters the cell, K+ moves into the lumen) - aldosterone helps increase systemic blood pressure --> indirectly regulates GFR by maintaining systemic blood pressure, which drives filtration in the kidneys

basic histological characteristics of the PROXIMAL CONVOLUTED TUBULE (PCT)

- first component of the renal tubule (located closest to the renal corpuscle) - walls formed by cuboidal cells with large mitochondria - their apical (luminal) surfaces bear dense microvilli --> creates a brush border, which dramatically increases the surface area and capacity for reabsorbing water and solutes from the filtrate and secreting substances into it

odor of urine

- fresh urine is slightly aromatic, but if left it develops and ammonia odor as bacteria metabolize the urea solutes - some drugs and vegetables alter the smell of urine as well as some diseases - ex. in uncontrolled DM, the urine may smell fruity due to its acetone content

what is GFR?

- glomerular filtration rate; the volume of filtrate formed each minute by the combined activity of all of the glomeruli of the kidneys - normally 120-125 ml/min

why is normal glucose clearance equal to 0 ml/min?

- glucose is freely filtered, but the tubule normally reabsorbs all of the glucose that gets filtered - 100% filtered, 100% reabsorbed, 0% secreted - plasma concentration of glucose in renal artery = plasma concentration of glucose in renal vein - there are normally enough transporters to help reabsorb the glucose that was filtered --> if this mechanism becomes saturated and there aren't enough glucose transporters for the amount of glucose, the glucose won't be carried back into the bloodstream and will get secreted into the blood

compare and contrast male and female urethras: FEMALES

- length: only 3-4 cm - fibrous connective tissue binds it tightly to anterior vaginal wall - its external opening, the external urethral orifice, lies anterior to the vaginal opening and posterior to the clitoris - since its short and the external orifice is close to the anal opening --> UTIs can occur (especially in sexually active women)

describe the cotransport process involved in the reabsorption of glucose

- glucose is reabsorbed by secondary active transport - comes from gradient created by Na+-K+ pumping at basolateral membrane - an apical carrier moves Na+ down its concentration gradient as it cotransports another solute - cotransported glucose moves across basolateral membrane by facilitated diffusion via other transport proteins before moving into the peritubular capillaries

factors that trigger renin release: REDUCED STRETCH

- granular cells act as mechanoreceptors - a drop in MAP reduces the tension in the granular cells' plasma membranes and stimulates them to release more renin

what cells release renin?

- granular cells/juxtaglomerular cells of the juxtaglomerular complex - release renin when stimulated by low blood pressure through the sympathetic nervous system, activated macula densa cells, or reduced stretch

how does the structure of the filtration membrane contribute to the process of glomerular filtration?

- greater relative permeability of the filtration membrane (more porous than capillary beds) --> much more efficient filter than systemic capillaries - large surface area - glomerular blood pressure high - forms a physical barrier that blocks all but smallest proteins while still allowing the other solutes to pass - podocytes of visceral layer have filtration slits between their foot processes - if any macromolecules happen to make it through the basement membrane, slit diaphragms (thin membranes extending across filtration slits) prevent them from traveling further - large molecules pass with greater difficulty and those larger than 5 nm generally can't enter --> keeps plasma proteins in capillaries and maintains colloid osmotic pressure of glomerular blood, preventing loss of all of its water to capsular space - prevents proteins and blood cells from entering the urine

describe the structure of the renal corpuscle: GLOMERULAR CAPSULE

- has an external parietal layer and a visceral layer that clings to the glomerular capillaries

transcellular reabsorption

- how most reabsorption takes place - movement through a tubule cell followed by. movement through interstitial fluid and into capillary - transported substances move through the apical membrane --> cytosol --> basolateral membrane of tubule cell --> epithelium of peritubular capillaries

results of renal clearance of other substances from inulin

- if a patient has renal clearance value that is equal to inulin there is no reabsorption or secretion --> healthy! - if C < inulin --> the substance is reabsorbed (ex. if C is 0 such as in glucose --> reabsorption is complete or substance is not filtered) - C = inulin --> no net absorption or secretion - C > inulin --> tubule cells are secreting the substance into the filtrate (ex. with drug metabolites --> if drug renal clearance is high, dosage must also be high and administered frequently to maintain a therapeutic level)

reabsorption in ascending limb of LOH

- impermeable to H2O - in thin secgemnt of ascending limb, Na+ moves passively down the concentration gradient created by water reabsorption - in thick ascending limb, a Na+-K+-2Cl- symporter is the main means of na+ entry at the apical surface; a na+-K+ ATPase operates at the basolateral membrane to create the ionic gradient that drives the symporter - thick ascending limb also has Na+-H+ antiporters and around 50% of Na+ passes via the paracellular route in this region - Na+, Cl+ and K+ are reabsorbed together via Na+-K+-2Cl- symporters in the apical membrane of the thick ascending limb-- most of the K+ brought into the tubule cells by the symporter leaks down its concentration gradient back into the filtrate via leakage channels - Ca2+, K+, and Mg2+ are passively reabsorbed via paracellular route, driven by the electrochemical gradient

where are granular cells/juxtaglomerular cells located? what is their function?

- in the arteriolar walls - enlarged, smooth muscle cells with prominent secretory granules containing the enzyme *renin* - act as mechanoreceptors that sense the blood pressure in the afferent arteriole

what effect does a change in glomerular hydrostatic pressure have on GFR?

- increase in glomerular hydrostatic pressure would increase GFR - of pressures determining NFP, glomerular hydrostatic pressure is the most important - can be controlled by changing the diameter of the afferent and sometimes efferent arterioles - GFR can be controlled by a single variable --> glomerular hydrostatic pressure - all major control mechanisms act primarily to change this one variable - if glomerular hydrostatic pressure rises, NFP rises and so does GFR - if glomerular hydrostatic pressure falls by as little as 18%, GFR drops to zero

what characteristics of inulin make it useful in determining renal clearance and GFR?

- inulin is a polymer of fructose that is *freely filtered* across glomerulus and is *neither reabsorbed, secreted, nor metabolized* by the cells of the nephron - plant polysaccharide, not normally found in body - *has a renal clearance value equal to the GFR*

what effect does a change in plasma colloid osmotic pressure have on GFR?

- inversely proportional with GFR because BCOP opposes glomerular filtration - pressure exerted by proteins in blood (wants to draw water into blood; opposing GFR) - inhibits filtration formation by opposing glomerular hydrostatic pressure - increase in BCOP --> decrease in NFP and GFR - decrease in BCOP --> increase in NFP and GFR

reabsorption: ACTIVE TRANSPORT OF SOLUTES

- involves either primary active transport (solute pumping, with ATP expended for each turn of the pump) or secondary active transport (solute pumping creates electrical or chemical gradients that drive the secondary active transport of another solute) - Na+ reabsorption occurs mainly by solute pumping (Na+/K+ pumps) and provides the means by which many other solutes and water are reabsorbed - Na+/K+ pumps pump Na+ into the interstitial fluid and K+ into the lumen --> creates a secondary electrochemical gradient that drives another solute into the distal membranes (and these pumps are present in the basolateral membrane)

compare and contrast male and female urethras: MALE

- length: about 20cm/8in long - has 3 regions: 1) prostatic urethra-- about 2.5 cm, runs with prostate 2) membranous urethra-- intermediate part; runs through urogenital diaphragm; extends about 2 cm from prostate to beginning of penis 3) spongy urethra-- about 15 cm, passes through penis and opens at its tip via its external urethral orifice - double function: carries both semen and urine out of body

collecting duct: intercalated cells

- less numerous - cuboidal cells - abundant microvilli - 2 varieties: type A and type B --> each plays a role in maintaining the acid-base balance of the blood

filtration membrane

- lies between blood and capsular space - porous membrane that allows free passage fo water and solutes smaller than plasma proteins - 3 layers: glomerular capillary endothelium, basement membrane, foot processes of podocytes in the glomerular capsule - macromolecules that get hung up in the filtration membrane are engulfed by specialized pericytes called glomerular mesangial cells - molecules smaller than 3 nm in diameter (ex. water, glucose, amino acids, and nitrogenous wastes) pass freely form the blood into the glomerular capsule --> these substances usually have similar concentrations in the blood and the glomerular filtrate - large molecules pass with greater difficulty and those larger than 5 nm are usually barred from entering the tubule

glomerular filtration membrane: BASEMENT MEMBRANE

- lies between the other two layers and is composed of their fused basal laminae - forms a physical barrier that blocks all but the smallest proteins while still allowing other solutes to pass - the glycoproteins of the gel-like basement membrane gives it a negative charge --> electrically repels many negatively charged macromolecular anions such as plasma proteins, reinforcing the blockade based on molecular size

location and structure of juxtaglomerular apparatus (JGA)

- located at point where DCT lies against efferent arteriole of its own nephron - region where the most distal portion of the ascending limb of the nephron loops lies against the afferent arteriole, feeding into the glomerulus (and sometimes the efferent arteriole) - both the ascending limb and afferent arteriole are modified at point of contact - wall of tubule and afferent arteriole are modified smooth muscle cells called juxtaglomerular (JG) cells (aka granular cells) - includes 3 populations of cells that help regulate the rate of filtrate formation and systemic blood pressure: macula densa, granular cells/juxtaglomerular cells, and extraglomerular mesangial cells - cells of renal tubule in this spot are crowded together, forming the macula densa-- monitor the Na+ and Cl- concentrations of the filtrate in the DCT

where is the Na+/K+/2Cl- symporter located? why is it important?

- located in thick part of ascending limb of LOH - main means of Na+ entry at apical surface - a Na+-K+ ATPase operates at basolateral membrane to create the ionic gradient that drives this symporter - thick ascending limb also has Na+/H+ antiporters - most of the K+ brought into the tubule cells by this symporter leaks down its concentration gradient back into the filtrate via leakage channels --> important because keeps Na+ inside the cell - net effect is that it causes Na reabsorption and the solutes become less concentrated and therefore the filtrate will have more water and less solutes - fueled by secondary active transport of Na/H antiporter - the Na+ and Cl- can diffuse out freely, but K+ is reliant on this to come in

what factors trigger renin release?

- low blood pressure causes the granular cells of the JG complex to release renin - 3 pathways stimulate the granular cells to release renin: 1) sympathetic nervous system 2) activated macula densa cells 3) reduced stretch

factors that trigger renin release: ACTIVATED MACULA DENSA CELLS

- low blood pressure or vasoconstriction of the afferent arterioles by the sympathetic nervous system reduces GFR --> slowing down the flow of filtrate through the renal tubules - when macula densa cells sense the low NaCl concentration of this slow-flowing filtrate, they signal the granular cells to release renin --> may signal by releasing less ATP, by releasing more prostaglandin, or both

intercalated cells of collecting ducts and late DCT

- main function is to regulate the acid-base balance in the body - distinct subpopulations (either secrete H+ or HCO3-) - reabsorb HCO3- or K+

what substances get secreted?

- metabolic byproducts such as creatine and urea - certain drugs and drug metabolites - excess K+ - H+ and organic acids (can be secreted as needed to maintain pH of blood) - some substances that are synthesized in the tubule cells are also secreted

creatinine

- metabolite of creatinine phosphate, which is in large amounts in skeletal muscle where it stores energy to regenerate ATP

collecting duct: principal cells

- more numerous - have sparse, short microvilli - are responsible for maintaining the body's water and Na+ balance - each collecting duct receives filtrate from many nephrons - runs through the medullary pyramids, giving them their striped appearance - as the collecting ducts approach the renal pelvis, they become the papillary ducts, which fuse together to deliver urine into the minor calyces via papillae of the pyramids

principal cells of the collecting ducts and late DCT

- more numerous than intercalated cells - reabsorb Na+ and Cl- - secrete K+ - activity regulated by ADH and aldosterone

what characteristics of creatinine make it useful in determining clearance and GFR?

- more often used in clinical settings to determine GFR - a breakdown product of CP (creatinine phosphate) in skeletal muscle --> usually produced at a relatively constant rate at a level proportional to muscle mass - has pretty constant C value of 140 ml/min --> freely filtered but also secreted in small amounts - often used to give a quick estimate of GFR because does not have to be intravenously infused into the patient as inulin does

Na+ couples passive tubular reabsorption of water

- movement of Na+ and other solutes establishes a strong osmotic gradient, and water moves by osmosis into the peritubular capillaries - solutes follow the solvent --> explains passive reabsorption of a number of solutes present in filtrate, such as lipid-soluble substances, certain ions, and some urea

what is NFP?

- net filtration pressure; sum of hydrostatic and colloid osmotic pressures - outward pressures - inward pressures - 10 mmHg

under what conditions would the sympathetic division of the ANS override renal autoregulation and decrease GFR?

- neural renal controls serve the needs of the body as a whole -- sometimes to the detriment of the kidneys - when volume of ECF is normal and the SNS is at rest --> renal blood vessels are dilated and renal autoregulation mechanisms prevail - when ECF volume is extremely low (ex. in hypovolemic shock during severe hemorrhage), it is necessary to shunt blood to vital organs and neural controls may override auto regulatory mechanisms --> could reduce blood flow to the point of damaging the kidneys

paracellular reabsorption

- occurs mainly in PCT - movement of solutes and water through leaky tight junctions in the PCT - water moves between cells and carries small dissolved solutes with it --> *bulk flow* - movement of substances in the paracellular route (between cells) is limited by tight junctions connecting those cells; but in the proximal nephron, these tight junctions are leaky and allow water and some important ions Ca2+, Mg2+-, K+ and some Na+) to pass through the paracellular route - then the water and solutes move through the interstitial fluid and into the capillaries

describe the myogenic mechanism and tell how it promotes a stable GFR

- one mechanism of intrinsic renal autoregulation - reflects a property of vascular smooth muscle --> contracts when stretched and relaxes when not stretched - raising systemic blood pressure stretches vascular smooth muscle in arteriolar walls, causing afferent arterioles to constrict --> this constriction restricts blood flow into glomerulus and prevents glomerular blood pressure from rising to damaging levels - declining systemic blood pressure causes dilation of afferent arterioles and raises glomerular hydrostatic pressure - both responses help maintain normal NFP and GFR

juxtamedullary nephrons

- originate close to the cortex-medulla junction - play an important role in the kidneys' ability to produce concentrated urine - have long nephron loops that deeply invade the medulla - their ascending limbs have both thick and thin segments

describe the composition and osmolarity of glomerular filtrate

- osmolarity --> isotonic, 300 mosm/L - composed of everything found in blood plasma except plasma proteins and large protein molecules

which factors promote glomerular filtration?

- outward pressures promote filtration formation - glomerular hydrostatic pressure (~55 mmHg) - colloid osmotic pressure in capsular space

reabsorption: PASSIVE TRANSPORT OF WATER AND OTHER SOLUTES

- passive reabsorption occurs via diffusion, facilitated diffusion, and osmosis - often, reabsorption of Na+ creates an electrical gradient that favors the reabsorption of anions - Na+ reabsorption also establishes an osmotic gradient --> H2O reabsorption also establishes an osmotic gradient --> H2O reabsorption via osmosis - water transport uses aquaporins

functions of the urinary system

- produce urine - regulating the total volume of water in the body and the total concentration of solutes in that water (osmolarity) - regulating the concentrations of the various ions in the ECF (even small changes in the concentrations of some ions, such as K+ can be fatal) - ensuring long-term acid-base balance - excreting metabolic wastes and foreign substances such as drugs or toxins - producing erythropoietin and renin (important molecules for regulating red blood cell production and blood pressure, respectively) - converting/metabolizing vitamin D to its active form - carrying out gluconeogenesis during prolonged fasting

how does ADH regulate water reabsorption

- produced by neurosecretory cells in the supraoptic nucleus of the hypothalamus-- released from posterior pituitary when osmoreceptors in hypothalamus are activated - acts on principal cells to cause more aquaporin-2 channels to be inserted in the apical membrane --> increases water permeability in distal tubule, allowing us to reabsorb H2O along its osmotic gradient (facultative water reabsorption) --> decreases urine volume - inhibits urine output - amount of ADH determines number of aquaporins and thus amount of water that is reabsorbed there - when body is over hydrated, ECF osmolality decreases, decreasing ADH secretion by posterior pituitary and making collecting ducts relatively impermeable to water - ADH increases urea reabsorption by collecting ducts

why is active reabsorption of Na+ so important in overall process of tubular reabsorption?

- reabsorption of Na+ by primary active transport provides the energy and means for absorbing almost every other substance, including water - the reabsorption of Na creates an electrical gradient which favors reabsorption of anions (particularly Cl-) to restore electrical neutrality in filtrate and plasma - Na+ reabsorption also establishes an osmotic gradient -> H20 reabsorption via osmosis

how does the medullary osmotic gradient promote the formation of a concentrated urine when we are over-hydrated?

- regulated by ADH - decreased osmolarity of ECF --> decreased ADH release --> less aquaporins in collecting duct --> less water is reabsorbed --> large volume of dilute urine excreted - ADH production is decreased - osmolality of urine falls as low as 100 mOsm - if aldosterone is present, the DCT and collecting ducts can remove Na+ and selected other ions from filtrate, making the urine that enters the pelvis even more dilute - osmolality can become as low as 50 mOsm

how does the medullary osmotic gradient promote the formation of a concentrated urine when we are dehydrated?

- regulated by ADH - increase in osmolarity of ECF --> large amounts of ADH released --> more aquaporins in collecting duct --> increased water reabsorption from collecting duct --> small volume of concentrated urine is excreted - posterior pituitary releases large amounts of ADH and the solute concentration of urine can rise as high as 1200 mOsm, which is the same as the concentration of interstitial fluid in the deepest part of the medulla - with maximum ADH secretion, up to 99% of the water in the filtrate is reabsorbed and returned to the blood and only 1/2 liter per day of highly concentrated urine is excreted

effects of ADH on principal cells of collecting ducts and late DCT

- regulates water reabsorption - produced by neurosecretory cells in the supraoptic nucleus of the hypothalamus-- released from posterior pituitary when osmoreceptors in hypothalamus are activated - acts on principal cells to cause more aquaporin-2 channels to be inserted in the apical membrane

what is renal clearance?

- the volume of plasma from which the kidneys clear (completely remove) a certain substance in a given time, usually 1 min - typically reported in units of ml/min - renal clearance tests are done to determine GFR (index of GFR), which allows us to detect glomerular damage and follow the progress of kidney disease

what is the detrusor muscle? what does it do?

- thick muscular layer of urinary bladder wall (middle layer) - consists of intermingled smooth muscle fibers arranged in inner and outer longitudinal layers, and a middle circular layer - contracts during urination to propel urine - as urine accumulates, the bladder expands, becoming pear shaped and rises superiorly in the abdominal cavity --> detrusor muscle thins and stretches and then rugae disappear - internal urethral sphincter is a thickened cuff of the detrusor muscle

describe the osmotic gradient in the interstitial fluid of the renal cortex and medulla

- renal cortex is isotonic at 300 mOsm/L - outer renal medulla is hypertonic at 600 mOsm/L - inner medulla is hypertonic at 1200 mOsm/L - kidneys keep solute concentration in body the same by regulating urine concentration and volume -gradient established and maintained through the two countercurrent mechanisms (countercurrent multiplier in LOH of juxtamedullary nephrons and countercurrent exchanger in vasa recta of juxtamedullary nephrons) - without this gradient, body would not be able to raise concentration of urine above 300 mOsm (aka you couldn't conserve water when dehydrated) -the long nephron loops of juxtamedullary nephrons create the gradient. They act as countercurrent multipliers -the vasa recta preserve the gradient. they act as countercurrent exchangers. -the collecting ducts of all nephrons use the gradient to adjust urine osmolarity **(Osmolarity can increase from 300 to 1200 mOsm b/c more water is reabsorbed in descending limb but solutes remain because this portion of tubule is impermeable to solutes.

identify the regions of the renal tubule and describe the basic histological characteristics of each: OVERVIEW

- renal tubule is about 3 cm long and has 3 major parts - leaves the glomerular capsule as the *proximal convoluted tubule*, drops into a hairpin loop called the *nephron loop/loop of Henle*, and then winds and twists again into the *distal convoluted tubule* before emptying into a collecting duct - proximal and distal refer to the relationship of the convoluted tubule to the renal corpuscle - meandering nature of the renal tubule increases its length - throughout their length, the renal tubule and collecting ducts consist of a single layer of epithelial cells on a basement membrane --> but each region has a unique histology (reflecting their roles in processing filtrate)

parietal layer of the glomerular capsule

- simple squamous epithelium - contributes to the capsule structure but plays no part in forming filtrate

structure of a ureter

- slender tubes that convert urine from kidneys to bladder - each begins at level of L2 as a continuation of the renal pelvis --> from there it descends behind the peritoneum and runs obliquely through the posterior bladder wall (this arrangement prevents back flow of urine because any increase in bladder pressure compresses and closes the distal ends of the ureters) - ureter wall has 3 layers (from inside to out): mucosa, musclaris, adventitia

pH of urine

- slightly acidic (around 6) - changes in body metabolism or diet can cause pH to vary from around 4.5-8.0 - predominately acidic diets that contain large amounts of protein and whole wheat products --> urine is more acidic - vegetarian (alkaline diet), prolonged vomiting, and bacterial infection of the urinary tract cause the urine to become more alkaline

structure of urinary bladder

- smooth, collapsible, muscular sac that stores urine temporarily - located retroperitonealy on pelvic floor, just below pubic symphysis - prostate lies inferior to bladder neck, which empties into urethra in males - in females, bladder is anterior to vagina and uterus - interior of bladder has openings for both ureters and the urethra - smooth, triangular region of the bladder base outlined by these 3 openings = trigone (where a lot of the bladder infections take place) - very distensible

aquaporins

- specialized channels in the membrane of tubule cells that facilitate water reabsorption - 2 main types: aquaporin-1 and aquaporin-2

what is the normal average range for urinary specific gravity in adults? if a patient is below the normal, what does it indicate? and if above normal?

- specific gravity of urine ranges from 1.001 - 1.035 depending on its solute concentration - increased specific gravity could be indicative of: dehydration, vomiting, emesis, glucosuria, heart failure, decreased blood flow to kidneys, shock - decreased specific gravity could be indicative of: excess fluid intake, diabetes, kidney failure, infection of kidneys

what are the effects of angiotensin II?

- stimulates adrenal cortex to secrete aldosterone, which enhances renal absorption of Na - prods posterior pituitary to release ADH, which promotes water reabsorption by the kidneys - triggers thirst sensation to restore BP and blood volume - vasoconstrictor --> increases BP by increasing peripheral resistance - NOTE: kidney also makes its own locally acting angiotensin II that reinforces the effects of hormonal angiotensin II

Na+ couples secondary active transport

- substances reabsorbed by secondary active transport (pushed from gradient created by Na+/K+ pump) include glucose, amino acids, some ions, and vitamins - apical carrier moves Na+ down its concentration gradient as it cotransports another solute - cotransported solutes move across basolateral membrane by facilitated diffusion via other transport proteins before moving into peritubular capillaries

location and function of peritubular capillaries

- surround the tubular portions of the nephron in the cortex - cling closely to adjacent renal tubules and empty into nearby venules - arise from the efferent arterioles, which have high resistance --> only experience low pressure - low pressure, porous capillaires - readily absorb solutes and water from the tubule cells as these substances are reclaimed from the filtrate - renal tubules are closely packed together, so the peritubular capillaries of each nephron absorb substances from several adjacent nephrons

external urethral sphincter

- surrounds urethra as it passes through urogenital diaphragm - formed of skeletal muscle - voluntarily controlled - levator ani fo pelvic floor also serves as a voluntary constrictor fo urtehra

what does the term renal autoregulation mean?

- the kidneys ability to adjust its own resistance to blood flow --> allows kidney to maintain a constant GFR despite fluctuations in systemic arterial blood pressure - two types of controls regulate GFR: intrinsic controls (renal auto regulation) and extrinsic controls (by nervous and endocrine systems) - renal auto regulation uses 2 different mechanisms: myogenic mechanism, and tuboglomerular feedback mechanism

how does the nervous system help regulate renal function?

- the sympathetic vasomotor fibers of the renal plexus regulate renal blood flow by adjusting the diameter of renal arterioles and thus influencing the formation of urine by the nephron --> triggers vasoconstriction and reduces renal blood flow - parasympathetic nervous stimulation from the vagus nerve will trigger vasodilation and increased blood flow

compare and contrast male and female urethras: BOTH

- thin-walled muscular tube that drains urine from bladder and conveys it out of the body - epithelium of its mucosal lining is mostly pseudostratified columnar epithelium --> near bladder becomes transitional epithelium --> near external opening, changes to a protective stratified squamous epithelium - internal and external urethral sphincters - urethral mucosa is continuous with that of the rest of the urinary tract

what factors oppose glomerular filtration?

- two inward forces inhibit filtration forming by opposing the glomerular hydrostatic pressure - capsular hydrostatic pressure (~15 mmHg) - blood colloid osmotic pressure (~30 mmHg)

how is urine propelled through the ureter to the urinary bladder?

- ureter plays an active role in transporting urine - incoming urine distends the ureter and stimulates its muscularis to contract, propelling urine into the bladder - urine does not reach the bladder through gravity alone - strength and frequency of peristaltic waves are adjusted to the rate of urine formation - sympathetic and parasympathetic fibers innervate each ureter, but neural control of peristalsis is insignificant compared to the way that ureter smooth muscle responds to stretch

glomerular filtration membrane: FOOT PROCESSES OF PODOCYTES OF THE GLOMERULAR CAPSULE

- visceral layer of the glomerular capsule is made of podocytes that have filtration slits between their foot processes - if any macromolecules manage to make it through the membrane, slit diaphragms (thin membranes that extend across the filtration slits) prevent almost all of them from traveling further

reabsorption in descending limb of LOH

- water can leave descending limb via osmosis due to the presence of aquaporin-1s - but descending limb is virtually impermeable to solutes

how to macula densa respond to high levels of NaCl in filtrate?

- when GFR increases --> not enough time for reabsorption --> concentration of NaCl in filtrate remains high --> macula densa cells respond to high levels of NaCl in filtrate by releasing vasoconstrictor chemicals (ATP and others) that cause intense constriction of afferent arteriole --> reduces blood flow to glomerulus --> drop in blood flow decreases NFP and GFR --> flows the flow of filtrate and allows more time for filtrate processing (and NaCl reabsorption)

how does tubular secretion help control blood pH?

- when blood pH becomes lower (more acidic), renal tubule cells actively secrete more H+ into filtrate and generate more HCO3- (a base) --> blood pH rises and urine drains off excess H+ - when blood pH becomes higher (more alkaline), Cl- is reabsorbed instead of HCO3-, which is allowed to leave the body in urine

what happens when a solute in the filtrate exceeds its renal threshold?

- when concentration of a solute exceeds the renal threshold --> tubule cells do not completely reabsorb the solute --> solute will show up in urine - can interfere with reabsorption of other solutes - what happens to people with high blood sugar from diabetes (glucose ends up in urine even though renal tubules are still functioning normally because carriers are saturated)

how does bladder shape change with fullness?

- when empty, collapses into its basic pyramidal shape and its walls are thick and thrown into folds (rug) - as urine accumulates the bladder expands, becomes pear-shaped, and rises superiorly in the abdominal cavity; the muscular wall stretches and thins, the rugae disappear --> these changes allow the bladder to store more urine without a significant rise in internal pressure - moderately full bladder is about 12 cm long and holds about 500 ml (1 pint) of urine --> can hold nearly double if necessary - when bladder tenses with urine, can be palpated well above pubic symphysis - maximum capacity of bladder is 800-1000 ml and when it is over distended, it may burst

calculations with inulin

- when inulin is infused such that its plasma concentration is 1 mg/ml (P = 1), then generally, U = 125 mg/ml and V = 1 ml/min --> renal clearance is C = 125 ml/min --> in one minute, kidneys have cleared all of the inulin present in 125 ml of plasma - amount filtered = amount excreted - amount filtered = GFR x [In]pi (plasma concentration of inulin) - amount excreted = [IN]ur (urine concentration of inulin) x V (volume of urine excreted/produced per minute) - therefore, GFR = [IN]ur x (V/[IN]pi) - normal clearance value for inulin is 125 ml/min

reabsorption in distal convoluted tubule (DCT)

- while reabsorption in PCT and nephron loop does not vary with body's needs, hormones fine-tune reabsorption in DCT and collecting duct - Na+ and Cl- via Na+-Cl- symporter - Ca2+ regulated by PTH - H2O

what is the transport maximum (Tm)?

- with any solute requiring a carrier for reabsorption, it is possible to saturate the carriers --> when the carriers are saturated, they are working at their fastest rate --> this rate limit is called the transport maximum (mg/min) - reflects the number of transport proteins in the renal tubules available to ferry a particular substance - in general there are plenty of transporters for substances such as glucose that need to be retained, and few or no transporters for substances of no use to the body - when transporters are all saturated (all bound to the substances they transport) the excess is excreted in urine

colloid osmotic pressure in capsular space

- would theoretically pull filtrate into tubule - but this pressure is basically zero because virtually no proteins enter the capsule

blood colloid osmotic pressure

- ~ 30 mmHg - pressure exerted by the proteins in the blood

capsular hydrostatic pressure

- ~15 mmHg - the pressure exerted by the filtrate in the glomerular capsule - is much higher than hydrostatic pressure surrounding most capillaries because the filtrate is confined in a small space with a narrow outlet

what is the minimum production of urine (mL/min) you expect to see in a healthy renal system?

0.5 mL/min (because normal urine output is 30 cc/hour)

steps of sodium reabsorption

1) at basolateral membrane, Na+ is pumped into interstitial space by Na+-K+-ATPase --> active Na+ transport creates concentration gradients that drive the following steps: 2) downhill Na+ entry at the apical membrane 3) reabsorption of organic nutrients and certain ions by cotransport at the apical membrane 4) reabsorption of water by osmosis through aquaporins; water reabsorption increases concentration of solutes that are left behind: these solutes can then be reabsorbed as they move down their gradients --> 5) lipid-soluble substances diffuse by transcellular route and 6) various ions (Cl-, Ca2+, K+, etc...) and urea diffuse via paracellular route

steps of creating the medullary osmotic gradient

1) filtrate entering the nephron loops is isosmotic to both plasma and cortical interstitial fluid 2) water moves out of the filtrate in the descending limb down its osmotic gradient --> this concentrates the filtrate 3) filtrate reaches its highest concentration (1200 mOsm) at the bend of the loop --> at 100 mOsm, it is hypo-osmotic to interstitial fluid

what are the 3 steps involved in urine formation?

1) glomerular filtration 2) tubular reabsorption 3) tubular secretion

glucose reabsorption steps

1) glucose and 2 Na+ use an Na+-glucose symporter to travel from the tubule lumen into the PCT 2) Na+ travels to the ICF via the Na+/K+ pump 3) glucose travels to the ICF via facilitated diffusion 4) glucose and Na+ diffuse into the peritubular capillary 5) active transport of Na+ makes a concentration gradient that fuels glucose reabsorption at luminal membrane

what are the 3 key players and their role in the countercurrent mechanism

1) the long nephron loops of juxtamedullary nephrons create the gradient. they act as countercurrent multipliers. 2) vasa recta preserves the gradients. acts as countercurrent exchanger. 3) collecting ducts of all nephrons use the gradient to adjust urine osmolarity.

osmolarity of filtrate in DCT

100 mOsm/L

osmolarity of urine at the beginning of the collecting tubule

100 mOsm/L

osmolarity of the filtrate in the deepest part of the LOH (juxtamedullary nephrons)

1200 mOsm/L

osmolarity of filtrate in ascending limb of LOH

1200 mOsm/L --> 100 mOsm/L (osmolarity decreases as the filtrate moves up)

collecting ducts (and late DCT)

2 main cell types in this region of the tubule: intercalated cells and principal cells (have separate roles)

what are the layers of the bladder wall?

3 layers: mucosa-- containing transitional epithelium detrusor-- thick muscular layer; consists of intermingled smooth muscle fibers arranged in inner and outer longitudinal layers and a middle circular layer fibrous adventitia (except on superior surface, where it is covered by peritoneum)

what is the minimum hourly urine output required to maintain renal function in a young healthy person?

30 cc/hour

osmolarity in body fluids (blood and interstitial fluid) aka ECF

300 mOsm/L

osmolarity of filtrate in PCT

300 mOsm/L

osmolarity of glomerular filtrate

300 mOsm/L

osmolarity of filtrate in the descending limb of LOH

300 mOsm/L --> 1200 mOsm/L (osmolarity increases as the filtrate moves down)

erythropoietin

A hormone produced and released by the kidney that stimulates the production of red blood cells by the bone marrow

trace the tubular system of a nephron from Bowman's capsule to the renal pelvis

Bowman's capsule (ala glomerular capsule) --> PCT --> descending limb of LOH --> ascending limb of LOH --> DCT --> collecting duct --> papillary duct --> minor calyces --> major calyces --> renal pelvis (--> ureter)

if provided measures of plasma creatinine, urine concentration of creatinine and urine volume, how would you calculate GFR?

C = (urine concentration x urine volume) / concentration in plasma C = (1.25 mg/ml x 60 ml/60 min)/ 0.01 mg/ml = 125 mg/min

secretion in PCT

H+, NH4+, and some drugs

renal columns

Inward extensions of the cortex tissue separating the renal pyramids -- projecting inward towards the renal sinus

in what part of the tubule is the greatest amount of water reabsorbed?

PCT (65%)

antiporter

a carrier protein that transports two molecules acrss the plasma membrane in opposite directions.

perirenal fat capsule

a fatty mass that surrounds the kidney and cushions it against blows

fibrous capsule

a transparent capsule that prevents infections in surrounding regions from spreading to the kidneys

diuretic

administered to stimulate the kidneys to increase the secretion of urine to rid the body of excess sodium and water

name the vessel that carries blood into a glomerulus

afferent arteriole

renal fascia

an outer layer of dense fibrous connective tissue that anchors the kidney and the adrenal gland to surrounding structures

what is the end product of the renin-angiotensin cascade?

angiotensin II

what is the effect of angiotensin II on GFR?

angiotensin II increases GFR because it increases systemic blood pressure

trace the circulatory pathway of a kidney from the renal artery to the renal vein

aorta --> renal artery (branches off of the abdominal aorta) --> segmental arteries (in renal sinus) --> lobar arteries (in renal sinus) --> interlobar arteries (run between the pyramids, in the renal columns, to the cortex) --> arcuate arteries (form arches over the base of the pyramids) --> interlobular arteries/cortical radiate arteries --> afferent arteriole --> glomerulus (capillaries)--> efferent arteriole --> peritubular capillaries or vasa recta --> either: cortical radiate veins or arcuate veins --> if goes to cortical radiate veins, then goes from there to the arcuate veins --> interlobar vein --> renal veins --> inferior vena cava

trace the flow of urine from the collecting tubules to the point where it leaves the body

collecting duct --> papillary duct --> minor calyx --> major calyx --> renal pelvis --> ureter --> bladder --> urethra

what are the 2 types of nephrons?

cortical nephrons juxtamedullary nephrons

which type of nephron is most numerous?

cortical nephrons (account for 85% of the nephrons in the kidney)

which type of nephrons performs most of the reabsorptive and secretory functions of the kidney?

cortical neprhons

what are the 2 types of countercurrent mechanisms that act to determine urine concentration and volume?

countercurrent multiplier countercurrent exchanger

adventitia of ureter

covering the ureter's external surface is typical fibrous connective tissue

histology of thick descending limb of LOH

cuboidal cells

histology of the thick ascending limb of the LOH

cuboidal or even low columnar

name the vessel that carries blood out of a glomerulus

efferent arteriole

why is net filtration pressure (NFP) so much higher in the glomerulus than in the systemic capillaries?

glomerular capillaries are drained by high-resistance efferent arterioles whose diameter is smaller than the afferent arteriole that feeds them --> allows filtration to occur along the entire length of the glomerular capillary and reabsorption doesn't occur the same way

effect of high blood pressure on urine volume

high blood pressure --> decrease in ADH --> decrease in aquaporin-2 channels in the late DCT and collecting duct --> decrease in water reabsorption --> more water excreted in urine --> larger urine volume and urine is more dilute

if a patient is producing less than the normal minimum urinary output, what might it indicate? what would you include in your nursing assessment?

if < 30 cc/hour --> UTI, dehydration, kidney infection, renal failure, blockage, solute and electrolyte imbalance nursing assessment: skin turgor, skin dry?, are they confused?, vitals, abdominal assessment, edema, strict Is and Os NOTE: if patient prescribed diuretics, give them these meds in morning, so doesn't interrupt their sleep

functions of juxtaglomerular apparatus (JGA)

important regulatory functions: secretes renin, secretes EPO (erythropoietin), regulate blood flow through the renal BV

in what segment of the tubule is urea reabsorbed?

in the deep medullary region of the collecting duct into the interstitial fluid of the medulla

where are the macula densa cells located?

in the walls of the ascending limb of LOH

incontinence

inability to control bladder and/or bowels; involuntary discharge of urine or feces

renal medulla

inner region of the kidney

what 2 substances are useful in determining renal clearance and GFR?

inulin and creatinine

which type of nephron plays the most important role in regulating urine concentration?

juxtamedullary nephrons

in what part of the tubules is water reabsorption regulated by ADH?

late distal convoluted tubule and the collecting duct

how do macula densa cells respond to low levels of NaCl in filtrate?

low NaCl concentration of slowly flowing filtrate --> inhibits ATP release from macula densa cells --> causes vasodilation of afferent arterioles --> allows more blood to flow into the glomerulus --> increases NFP and GFR

effect of low blood pressure on urine volume

low blood pressure --> increase in ADH --> increase in aquaporin-2 channels in late DCT and collecting duct --> increase in water reabsorption --> less water excreted in urine --> smaller urine volume and urine is more concentrated

secretion in loop of Henle

none

renal cortex

outer region of the kidney

renal threshold

plasma concentration at which a substance exceeds the transport maximum

how to calculate renal clearance rate of any substance

renal clearance rate (C) of any substance, in ml/min, is calculated from the equation: *C = UV/P* U = concentration of the substance in urine (mg/ml) V = flow rate of urine formation (ml/min) P = concentration of the substance in plasma (mg/ml)

identify the 3 layers of tissue that surround the kidney

renal fascia perineal fat capsule fibrous capsule

describe the steps in the reaction cascade triggered by renin

renin-angiotensin-aldosterone system low systemic blood pressure causes the JG cells to secrete renin --> renin enzymatically cleaves angiotensinogen, converting it to angiotensin I --> angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II --> angiotensin II increases aldosterone secretion by adrenal cortex --> increases Na reabsorption by kidney tubules and water follows --> increases blood volume --> increases systemic blood pressure NOTE: angiotensin II also causes vasoconstriction of systemic arterioles, which increases peripheral resistance --> increases systemic blood pressure

histology of the thin ascending limb of the LOH

simple squamous epithelial

histology of the the thin descending limb of the LOH

simple squamous epithelium

trigone

the smooth triangular area on the inner surface of the bladder located between the openings of the ureter and urethra, in which the ureters enter and the urethra exits

symporter

transporter that carries two different ions or small molecules, both in the same direction

renal pyramids

triangular-shaped areas in the medulla of the kidney

osmolarity of urine at the end of the collecting tubule

usually 300 mOsm/L but can be anywhere from 100 mOsm/L to 1200 mOsm/L depending on the concentration of ADH and aquaporin-2s

effect of GFR on vasoconstriction

vasoconstriction of afferent arterioles --> decrease GFR vasodilation of afferent arterioles --> increase GFR vasoconstriction of efferent arterioles --> increase GFR vasodilation of efferent arterioles --> decrease GFR