Exam 4 Flashcards
1-major function of kidneys
2-Na content affecting extracellular fluid volume
1-regulate volume & composition of the extracellular fluid (ECF)
2-Pna= Total Body Na content (mEq)/ ECF volume
- Na and its anions (Cl, HCO3) are primary solutes in the extracellular fluids and are determinants of plasma osmolality
- if Na content inc, Total body water increases to compensate (via thirst)
- if Na content dec, total body water dec to keep plasma osmolality constant (kidney will excrete h20)
- –to maintain extracellular fluid volume, the kidneys must match daily output of Na w/ intake of Na
1-Na Balance
2-hyperaldosteronism
1-Balance: output= input
- neg Na balance (loss of body Na content)= dec in ECF (ECF contraction)
- pos Na balance (gain of body Na content)= inc in ECF (ECF expansion)
-problems w/ sodium balance typically manifest as altered extracellular fluid volume
2-elevated aldosterone release from adrenal cortex—> kidney reabsorbes excess amts of sodium—> plasma osmoallity inc slightly so H20 consumption (thirst) & H20 conservation at kidney inc—> ECF vol inc—> patient becomes hypertensive due to ECF expansion
1-transport mechanisms used by the kidney
types of facilitated diffusion in the kidney tubule
2-symport
3-antiport
4-imp role of Na/K ATPase in tubule cell
5-H20 movement
1-solute movememnt (electrolytes, glucose, proteins) may be passive or active)—(active=ATP)
-Diffusion: solute goes down its electrochemical gradient:
—transcellular= through cell membrane
—paracellular= between cells
Facilitated Diffusion= movement of solute depends on interaction w/ specific protein in the membrane
2-coupled transport of 2 solutes in the same direction. process= co-transport & protein called transporter or symport
3-couple transport of 2 or more solutes in opposite direction. processs= exchange & protein called exchanger or antiport
4-conc gradient for Na to move into cell from tubule lumen is maintained by active transport of Na out of the cell by Na/K ATPase
5-H20 movement is passive, dirven by osmotic pressure gradients caused by reabsorption of Na & other solutes
1- solvent drag
2-aquaporins
3-Tm Limited Transport
1-when reabsorbed, solutes dissolved in H20 are carried along
- how solutes can be reabsorbed by kidney via paracellular route
- H20 goes through transcellular & paracellular paths in tubular segments that are permeable to H20
2-transcellular movement of h20 in response to osmotic pressure in prox tubule= high bc of water channels
-Aquaporin 1= proximal tubule—present in collecting duct but those are called Aquaporin 2 and are controlled by vasopressin
3-when transported is involved in movign a solute theres a max rate of transport for that solute
—# of sites x’s rate of transport/site
Tm= transport max, expressed in mg/min
===secretion & reabsorption
1-Tm limited reabsorption
2-Tm limited secretion
3-clinical relevance
1-if reabsorption is Tm limited—if filtered load exceeds Tm the solute will appear in urine
—if filtered load is less than Tm, the urine will be devoid of solute
2-secretion= transfer from peritubular capillaries to the tubule fluid
-if delivery of solute to peritubular capillaries exceeds the Tm secretion rate, then some solute will be returned to circulation via renal vein
-if deliver of solute is less than Tm, then no solute will appear in renal venous blood
Ex= PAH, penicillin, bile acids, creatinine, urea —all are secreted by Tm limited mechanisms
3-co-admin of drugs that compete for the same transporter can inc plasma conc of both drugs…probenecid w/ penicillin will inc plasma half life of penicillin by competing for the same renal transporter
1-electrolyte reabsorption & secretion along nephron
1- Na transporters are site of diuretic action…esp in proximal tubulue, site of acid-base regulation
K secretion in principal cells = safe plasma K in blood
-most of filtered Na is reabsorped in proximal tubule, followed by loop of henle…distal tubule & collecting duct “fine tune” the excretion of Na while Cl is reabsorbed
-proximal tubulues reabsorb LOTS of solute, then the loop then small amounts in the distal tubule.
-K is secreted from prinicpal cells whenever theres normal/elevated intake of K
- PTH enhances tubular Ca reabsoprtion
- PTH reduces Pi reabsorption by tubular cells
1-early proximal tubule & Na Linked Transport
2-why is Na/K atapase more imp in proximal tubule
3-Na-H antiport
4-Na-solute symport
1-proximal tubule, the reabsorption of every substance (even H20) is linked bc of Na-K ATPase pump
2-movemnt of solutes is linked to passive movememnt of Na into the tubule cell down its electrochemical gradient, the accum of solute in the interstitial space drives the passive movement of H20
3-secretion of H ion is imp renal mechanism for removing acid from blood
-results in bicard reabsorption in 1 for 1 exchange w/ H
4-Na-glucose—SGLT 1&2
- Na-amino acids
- Na other solutes (phosphate & lactate)
glucose & AA are cleared form tubule fluid by end of proximal tubule
1-late proximal tubule Na reabsorption
2-prox tubule summar
3-diuretics
4-natriuesis
5-kaliuresis
6-diuretics inhibiting Na reabsorption
1-little Cl was reabsorbed in early proximal tubule
- late proximal tubule, Cl is avidly reabsorbed due to passive diffusion of Na, Cl, via paracellular path
- operation of parallel Cl/Anion & Na/H antiporters reabsorb NaCl via transcellular route
2-Na is reabsorebed in prox tubule by
- –Na/H antiport, Na/solute symport, passive diffusion w/ Cl, solvent drag w/ H20
- all glucose + AA are reabsorebed here
- large amts of Ca & P are reabsorbed
- H20 reabsorbed
- by the end of the tubule, tubular fluid= isoosmotic to plasma bc of the osmotic movement of H20
3-inc excretion fo both Na & H20
4-inc in Na excretion
5-inc in K excretion
6-diuretics dec ECF volume…reduction initiates compensatory mechanisms that enchance Na reabsorption in tubules so the patient returns to Na balance of input=output, but at a lower level of total body Na & steadstate ECF
Diuretics & prox tubule
1-osmotic diuretics
2-carbonic anhydrase inhibition
1-osmotic diuretics are unresorbable solute that slows osmotic movement of H20 from lumen to the interstitial space
—dec in H20 reabsorption = less Na reasborption via paracellular solvent drag
—excess gluocse in prox tubule (filtere load> Tm) = diuretic…ppl w/ untreated diabetes= polyuria
(manitol= diuretic)
—osmotic diuretics arent ised in control of arterial hypertension= acute fluid overload
2-acetazolamide= inhibitor of enzyme carbonic anhydrase. inhibition of CA slows the Na-H exchanger= inc in Na & H20 excretion…H20 accompanies extra Na in lumen
- –Ca inhibitors arent used for hypertension
- –Ca inhibitors can alter acid base balance—make it more ifficult for body to excrete acid & easier to lose bicarb in urine…so CA inhibitors can be used to treat alkalotic condition= promote metabolic acidosis
Na reabsorption in the loop of henle
1-thick ascending limb
2-thin descending limb
3-thick ascending limb of the loop of henle TALH
1-Na reasborption occurs—25% of filtered load of Na
2-doesnt reabsorb that much—H20 reabsorbed bc of inc osmotic gradient
3-reabsorption of Na, K & Cl bc of basolateral Na/K ATPase—-apical transported called Na-K-2Cl symport
- blocked by diuretic furosemide—loop diuretic
- loop diuretic= powerful, treat acute pulm edema & to control edema in patients w/ congestive heart failure
- Na/H antiport= reabsorbs Na
- tubule segment is impermeable to H20
- positively charged lumen drives passive paracellular reabsorption of cations—Na, K, Ca, Mg…some K returns to tubular lumen via sep apical K channel, reasonw hy tubular lumen +3-10mV to peritubular fluid
- Na reabsorption in loop of henle occurs via paracellular route via facilitated diffusion
1-early distal tubule
2-late distal tubule & collecting duct
3-aldosterone & principal cell
1-Na-Cl symporter = reabsorb Na in early distal tubule
- early distal tubule reabsorbs Ca & Pi
- located in cortex, is impermeable to H20
- Na-CL symporter is blocked by thiazide diuretics…treat hypertension & congestive heart failure
2-principal cells & intercalated cells
- principal cells= reabsorbe Na & secrete K
- intercalated= secrete H or HCO2 & reabsorb K (imp for acid base)
3-aldosterone= adrenal mineralocorticoid—stimulates Na reabsorption in thick ascending limb TALH, early distal tubule & in principal cells of late distal tubule
- inc Na/K ATPase protein abundance
- Aldosterone also inc the amt of apical Na/K/2Cl symporters (TALH) and Na-CL symporters (early distal tubule)
- *-primary site of aldosterones action in principal cell in the late distal tubule & collecting duct= Na reabsorption & K secretion**
- alters protein synthesis by acting w/ nuclear DNA
- –release is stimulated by angiotensin 2, high plasma K, & plasma acidosis
1-epithelial Na channel (ENaC) for Na reabsorption in principal cell
2-aldosterone inc Na Reasborption by
3-aldosterone inc K secretion by
1-Na enters principal cell through epithelial channel that is blocked by diuretic amiloride.
- can be be slowed by aldosterone recep. antagonists
- tubule lumen is neg compared to peritubular fluid, lumen negativity helps K secretion down gradient
- Cl is reabsorbed via paracelullar pathway by lumen neg voltage
- Cl is reabsorbed via paracellular pathway, driven by lumen neg voltage
- H20 permeability is dependent on action of ADH (vasopressin)
2-inc permeability to Na by inc number of active ENaC’s by stimulating synthetsis & insertion of new ENaC’s into apical membrane
- inc activity & # of Na/K ATPases in basolateral membrane
- –principal cell= site of renal tubular K secreton
3-stimulating Na reabsorption
-inc number of open apical K channels
1-kidney & maintaining K homeostasis in the body
2-insulin
3-epinephrine
4-aldosterone
1-maintenance of plasma K w/in narrow limits is imperative. REnal excretion of K takes longer but is regulated…rapid movement of K into cells is regualted by 3 hormones
-hormones stimulate activity of Na/K ATPase, Na/K/2Cl symporter, and Na/Cl symporter in skeletal muscle liver, bone, & RBC
2-move K into cells w/in min. Insulin infused IV to rapidly correct hyperkalemia
3-stimulation of alpha adrenoceptors releases C from cells & stimulation of beta-2 adrenoceptors promotes uptake of K…w/in min
4-peripheral action to promote cell uptake of K= a hour. chronic elevation of aldosterone (adrenal tumor)= hypokalemia bc of inc excretion of K via kidney & via uptake of K into cells
1- K reabsorption along the nephron
1-major role in regulating K balance in body, unlike Na, K can also be secreted into the tubule—secretion & reabsorption of K can happen in late distal tubule/collecting
- secretion= principal cell, reabsorp=intercalated cell
- secrete K on a normal K intake
- high dietary intake, secretion inc greatly
- low dietary intake, reabsorption of K = reduce excretion to 1% filtered load
- –plasma K & aldosterone = physiologic regulators of K secretion, w/ aim of maintaing normal K balance
1-aldosterone & K secretion
2-plasma & K secretion
1-normal circulating levels of aldosterone regulate K loss via principal cells
- further inc in aldosterone further stimulate K secretion, hyperaldosteronism= hypokalemia
- lack of aldosterone = difficult to remove extra K from body…low aldosterone= hyperkalemia
- plasma K regulates aldosterone release
2-inc in plasma K= inc renal secretionof K
- dec in plasma K= dec renal secretion of K
- effects= direct effect of plasma K on principal cells & indirect effect = modulation of aldosterone release
1-K-sparing diuretics works at principal cells
1-principal cell= site of action for 2 diff types of diuretics
- first type is ENaC channel blockers= amiloride, block Na from using ENaC
- 2nd type= aldosterone receptor antagonist= spironolactone—block from interacting w/ intracellular
- K secretion from prinicpal cell dec when principal cell based diuretics are used…K sparing diuretics
- other diuretics–osmotic, loop, thiazides, all inc K excretion by the kidney—K losing diuretics…bc of enhanced delivery of Na to principal cells
K SECRETION DEC WHEN NA REABSORPTION SLOWS DOWN
1-water balance
2-sensed
3-sensor
4-effector
5-affected
6-clinical Dx
1-lose water via sweat glands, respiration, fecal route, urinary route, vomiting
- water intake= oral and is variable
- kidney regulates water loss via conc or dilution of urine
- kidney excrete urine that varies from 50-1200 mOsm/kg H20
- amt of H20 lost from body affects plasma osmolality
2-ECF vol= effective circulating volume
Plasma Osmolality=plasma osmolality
3-ECF vol= arterial & cardiac barorecptors
plasma osmolality= hypothalmic osmoreceptors
4-ECF Vol= ANg 2/aldosterone/SNS/ANP
plasma osmolality= ADH
5-ECF Vol= urine Na excretion
plasma osmolality= urine osmolality (H20 output) & thirst (H20 intake)
6-ECF vol= bedside Exam of ECF volume
plasma osmolality= lab test plasma osmolality
***problems w/ Total body water= altered plasma osmolality, reflected as alteration in plasma Na
***problems w/ total body Na= manifest as altered ECF vol
1-Antidiuretic hormone & control of renal H20 excretion
2-ADH
3-osmotic regulation of ADH
1-normal plasma osmolality= 275-295 mOsm/Kg H20
- diuresis= excretion of a large amt of urine
- antidiuresis= excretion of a small amt of urine
- during diuresis the urine = hypoosmolar or dilute(Uosm < Posm)
- during antidiuresis, urine is hyperosmotic or concentrated (Uosm>Posm)
2-same hormone as vasopressin or AVP
- release from posterior pituitary is inc or suppressed depending on neural signal from hypothalamic osmoreceptors or from signals arising from arterial & atrial baroreceptors
- ADH inc H20 reabsorption in late distal tubule & collecting duct, regualtes how much H20 leaves in urine
3-cells in hypothalamus sense changes in plasma osmolality
- osmoreceptors then send a signal to hypothalamic neuronal cells to either suppress or inc ADH release
- neural cells synthesize ADH & then secrete ADH from nerve terminals in posterior pituitary
- when osmolality is <280 or so, ADH secretion= zero
- sensitive to small inc in osmolality above this point
1-low plasma osmolality
2-high plasma osmolality
1-sensed by hypothalmic osmoreceptors (dec firing rate)
- reduced stimulation of vasopressin neurons, dec secretion of vasopressin
- dec plasma vasopresisn, reabsorption of H20 in collecting duct dec, amt of H20 in urin inc
- return of plasma osmolallity towards normal
2-sensed by hypothalmic osmoreceptors (inc firing rate)
- enhanced stimulation of vasopressin, inc secretion of vasopressin
- inc plasma vasopressin, reabsorption of H20 in collecting duct inc, amt of H20 in urine dec
- conservation of plasma H20…return to nromal plasma osmolality requires intake of fluid
1-ADH & aquaporins
2-overview of conc & dilution
3-conc & dilution occur bc
1-ADH inc H20 permeability in collecting duct, so ADH dec urine flow rate & inc urine osmolality
- in principal cells of kidney, ADH binds to vasopressin 2 receptor—V2 receptor inc cAMP levels that will trigger a cascade that causes insertion of aquaporins into apical membrane
- aquaporin channels are H20 channels & are selective…allow H20 but not electrolytes
- when ADH levels dec, the aquaporins zip back into interior of cell…dec H20 permeability in the cells
2-in prox tubule, water follows solute reabsorption= isoosmolar fluid by end of proximal tubule
- kidney is capable of disengaging H20 from solute reabsorption…only in this way can the kidney regulate H20 & solute balance separately
- disengagement is found in processes of conc & dilution
3-parts of nephron are impermeable to H20 yet transport solute (loop of henle, early distal tubule)
- parts of nephron have a H20 permeability that is dependent on level of ADH (late distal & collecting)
- medullary interstitium is hyperosmotic, & level of tonicity can be altered
1-cortical & medullary osmolality
2-what creates medullary interstitial osmotic gradient
1-ADH alters the tubule permeability to H20
- H20 will only move when there is a conc difference between tubule fluid & interstitial fluid
- medullary interstitium has graded levels of hyperosmolality
- hyperosmlality is critical for formation of hyperosmotic (conc) urine
2-solutes that are reabsorbed by thick ascending limb & collecting ducts—particularly NaCL & urea provides osmoles for interstitial gradient
-unique anatomic arrangement of loop of henle + collecting—contributes to medullary interstitial gradient= countercurrent multiplication= porgressive inc in osmolality as loop dips deeper into medulla
1-overview of dilution of urine
2-dilution steps
1-dependent on thick ascending limb of loop of henle
- solutes are reabsorbed here w/o water
- impermeable to water—if you remove solute but not H20, tubule fluid= more dilute
- ADH must be low to keep tubular fluid dilute as collecting duct moves through the medullary interstitial osmotic gradient on way to papilla of kidney
2-iso-osmolar tubular fluid enters thin descending limb
- water is removed & tubular fluid= hyperosmotic at end of loop
- thin ascending limb, NaCl moves out but H20 cant leave…dilution starts
- thick ascending limb, Na-K-2Cl symport removes solute, but water cant elave, tubular fluid becomes hypo-osmolar
- distal tubule & cortical collecting duct continues to reabsorb NaCl…in absence of ADH, Water perm= low and tubular fluid osmolality is 100 water
- medullary collecting duct, some NaCl is reabsorbed…absence of ADH, H20 permeability is low…final urine can be hyp-osmolar as 50 w/ minimal amts of NaCl
1-concentration step by step
2-key pt
3-imp role of urea in medullar osmolality
1-same steps from proximal tubule through early distal tubule
- then if ADH is present, H20 perm inc in late distal tubule & collecting
- H20 leaves the tubule & the tubule fluid equilibrates w/ surrounding hyperosmotic medullary interstitial fluid
- end of collecting duct, urin has an osmolality of 1200 or whatever the level is in the medulla
2-transport of NaCl out of ascending thick limb= impaired, renal concentrating power will dec bc max medullary interstitial osmolality will be lower than usu
3-urea= byproduct of protein metabolism
- important solute in inner medulla interstitial fluid
- collecting duct = permeable to urea only in inner medulla & permability inc w/ ADH
- ADH does this by phsophorylating urea transporters in apical membrane of the inner medullary collecting duct cells
- chronic H20 restriction, ADH stimulate production of additional transporters
- urea moves out of tubule along its conc gradient & accumulates in interstitium
- antidiuresis is max about 600 of total medullary osmolality is attributabe to NaCl & about 600 is attributable to urea
1-when ADH levels are suppressed
2-key pt
1-urea perm in inner medulla dec
but theres still urea perm in absence of ADH
-some of urea will reenter the tubule & thin ascending limb through a urea transporter
-recycling of urea in kidney facilitates accum in interstitium
-permeability of loop of henle to urea= less than the permeability in inner medulla
2-accum of urea in the interstitium is necessary to reach max renal conc power
—animals w/ defect in renal ureal transporters= reduced urinary conc ability…low protein diet can cause a dec in urinary conc ability while a high protein diet can enhance max conc power