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37 Cards in this Set
- Front
- Back
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Describe the distribution of solutes and H2O in body fluid compartments
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Na-plasma (P) and interstitial (I)
K-intracellular (C) Cl-P & I HCO3-low quantitiy in P & I large anions and proteins-low quantity in P; large quantity in C |
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What happens to solutes and H2O as they travel through the nephron?
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PCT-greatest area of reabsorption
LoH-greatest area of secretion DCT-smaller reabsorption CCT-continued reabsorption until excretion inulin-not filtered nor secreted (100% excreted) urea-greatly secreted in LoH; greatly reabsorbed in CCT H2O-not secreted in LoH (impermeable) |
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describe the reabsorption of Na as it travels through the nephron
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67% of filtered load is reabsorbed in PCT; 25% reabsorbed in TALH of LoH; 5% reabsorbed in distal nephron; 3% rabsorbed in MCD; <1% of filtered load is excreted (almost 100% is reabsorbed)
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describe how Na is tranported in the various regions of the nephron
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1. PCT
a. apical membrane-transporters allow sodium to enter the cell, down its electrochemical gradient, while driving the active transport of another solute b. basolateral Na/K ATPase keeps cellular [Na+] low enough to allow apical sodium entry. 2. TALH: a. apical-NKCC (Na, K, 2Cl co-transported); NHE (NA/H exchange) b. basolateral-Na/K ATPase 3. Distal nephron a. apical-NCC b. basolateral-Na/K ATPase 4. CCT a. apical-Na channel b. Na/K ATPase |
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describe how Cl is transported in the various regions of the nephron
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1. early PCT-paracellular reabsorption
2. late PCT a. apical-active transport b. basolateral-KCC (K/Cl cotransporter) 3. TALH a. apical-NKCC b. basolateral-Cl channel 4. distal nephron a. apical-NCC b. basolateral-Cl channel 5. CCT: principal cell-paracellular reabsorption |
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describe the tubular fluid (TF) to plasma (P) ratios along the proximal tubule
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TF=P: concentration of the solute (osmolality) same on both sides
TF<P: concentration of solute is reaborbed faster than H2O TF>P: concentration of H2O reabsorbed faster than solute note that the rate of Na and H2O is relatively the same |
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describe H2O transport throughout the nephron
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1. PCT: iso-osmotic (follows Na)
2. LoH a. descending limb-permeable to H2O; impermeable to NaCl b. ascending limb-impermeable to H2O; permeable to NaCl Note-The proximal tubule and tDLH show constant, non-hormonally regulated high water permeability due to the constitutive expression of apical and basolateral aquaporins (AQP1). The ALH, CCT and MCD have relatively low water permeabilities in the absence of ADH (antidiuretic hormone = arginine vasopressin, AVP) |
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explain the relative osmolarity of tubular fluid along the nephron
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1. PCT-TF/P=1
2. LoH a. descending limb: >1 as H2O is permeable but NaCl isn't b. ascending limb: decreases and drops <1 as H2O is impermeable and NaCl is permeable 3. distal nephron and further on-depends on H2O intake, presence/absence of ADH |
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Explain the role of ADH in the nephron
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AQP2 insertion into the apical membrane of the collecting duct epithelial cells is under the control of ADH (AVP). When ADH binds to its basolateral receptor (a GPCR), cAMP is produced that stimulates a phosphorylation cascade, leading to the insertion of vesicles containing AQP1 into the apical membrane, thus increasing water permeability (and therefore reabsorption).
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Explain the importance of potassium (K) balance
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Maintenance of ECF K+ homeostasis is critical for normal cell function, particularly for excitable cells
A disruption in ECF [K+] would affect: a. Membrane potential across cell membranes b. Acid/base balance Acute changes in extracellular K+ are buffered by shifting K+ in and out of the cellular compartment |
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Describe K handling along the nephron
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1. PCT-80% of filtered load of K+ is reabsorbed (primarily paracellular and passive)
Apical K+ channel involved in volume regulation 2. TALH-10% of filtered load of K+ is reabsorbed in TALH (paracellular and transcellular-NKCC processes) Apical K+ channel secretes K+ to recycle with the NKCC 3. CCT a. a-intercalated cells-K+ reabsorption via apical H+/K+ ATPase (Link between K+ balance and acid/base balance) b. Principal cells-K+ secretion via apical K+ channel and/or a K+-Cl- cotransporter (KCC); Under hormonal control by aldosterone |
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Explain the effect of dietary K intake on K handling
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10% of filtered load enters DCT
Depending on dietary intake, distal nephron and collecting tubules may show either a net secretion or reabsorption Low intake-An additional 2% of initial filtered load is reabsorbed; Used under conditions where need to conserve K+ (hypokalemia) normal/high-Initial collecting tubule (ICT), cortical collecting tubule and proximal outer medullary collecting duct (OMCD) are the distal K+ secretory system (secretes from 10% to 150% of the initial filtered load of K+) note-K+ reabsorption occurs across IMCD |
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what's the correlation b/t urine flow rate and urine osmolarity?
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curve is a reverse parabola
high ADH-high osmolarity, low flow rate (H2O retention) low ADH-low osmolarity, high flow rate (H2O excretion) |
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explain free H2O (CH2O) and osmolar clearance (Cosm)
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Urine volume (V) has two components:
1. Volume necessary to dissolve all excreted solutes to a concentration iso-osmotic to plasma= Cosm (osmolar clearance) 2. Volume of “pure” water added/removed to account for total urinary volume= CH2O (free water) V (L/day) = Cosm + CH2O Concentrated urine-Must reabsorb/reclaim free water without salt; Must have osmotic gradient to reabsorb water; Requires ADH Dilute urine-Reabsorb solute while lumenal epithelium is impermeable to water; Generate free water |
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explain how the corticomedullary osmotic gradients works
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The solute concentration in the LoH and the interstitial fluid ranges from 300 mOsm in the cortex (iso-osmotic to plasma) to 1200 mOsm in the inner medulla
This gradient is produced by the interaction between the flow of filtrate through the LoH (countercurrent multiplier) and collecting ducts and is maintained by the flow of blood through the vasa recta blood vessels (countercurrent exchanger) |
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explain how the corticomedullary concentration gradient works
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[NaCl]-increases in the cortex and through the medulla to level off at 300 mM each (or approx. 600 mOsm combined) in the inner medulla.
[Urea]-begins low and steeply rises as it moves through the medulla toward the renal papilla (600mOsm). Thus the highest osmolality, in the innermost medulla, is approx. 1300 mOsm (325mOsm + 325mOsm + 650mOsm for Na, Cl and urea, respectively) |
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how do counter current systems work?
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counter current multiplication-development of the corticomedullary osmotic gradient by LoH and the Collecting Duct system; requires active processes to establish a gradient (here, NaCl transport by the TALH and the DCT)
counter current exchange-as blood flows into and out of the medulla through a hairpin loop, H2O will leave and solute will enter along the entire descending vessel and part of the ascending vessel. Along the rest of the ascending vessel, the fluxes of water and solute are reversed. The net effect is that the blood exiting the medulla is less hypertonic than that in a straight tube vessel, so the kidney better preserves the osmotic gradient in the medulla. |
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How is Na reabsorption regulated?
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1. Glomerulotubular (GT) balance
2. Maintenance of effective circulating volume (whole body Na+ content) a. renin-angiotensin-aldosterone axis b. sympathetic nervous system activity c. antidiuretic hormone (arginine vasopressin) d. atrial natriuretic peptide |
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explain glomerulotubular (GT) balance
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As GFR increases, the filtered load of Na increases linearly. As filtered load increases:
A. flow of Na across the tubule wall (i.e., reabsorption) increases linearly. B. increase in the quantity of Na leaving the proximal tubule Note-both the quantity reabsorbed and the quantity remaining increase with filtered load but both do so linearly, showing that a constant fraction (%) of the filtered sodium was reabsorbed. |
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explain GT balance in the lumen
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An increase in GFR increases the flow rate of filtrate past the cells of the PCT:
1. In the early PCT, faster flow rate means less time to reabsorb various solutes (e.g., glucose) that are usually coupled with Na+ reabsorption 2. Therefore, more solutes are left in the lumen further down the PCT 3. Normally, reabsorption of these solutes is so efficient that glucose, etc, limits the rate of Na+ reabsorption further down the PCT 4. But with increased GFR, more of these solutes present downstream allows more Na+ reabsorption |
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explain peritubular mechanisms of GT balance
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Starling forces influence the rate fluids and solutes are reabsorbed across the PCT
1. With an increase in GFR, there will be a greater fraction of the plasma filtered across the glomerulus (increase in FF) 2. This decreases peritubular capillary hydrostatic pressure and increases oncotic pressure 3. Both promote greater net reabsorption from the lateral intracellular spaces (LIS) towards the capillary, reducing back flux through the tight juntions |
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list the effectors that work in parallel to regulate Na reabsorption in order to maintain extracellular fluid volume
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1. Renin-angiotensin-aldosterone system (RAAS)
2. Sympathetic innervation of the kidneys 3. Antidiuretic hormone (ADH) 4. Atrial natriuretic peptide(ANP)-this decreases reabsorption note-Factors that stimulate the 1st three systems also inhibit ANP secretion, leading to an increase in net Na+ reabsorption |
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describe how the RAAS works to increase Na reabsorption
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A. Angiotensin II (AngII)
1. Stimulates apical Na+/H+ (NHE3) activity in both the PCT and TALH 2. Increases Na+ reabsorption via the ENaC channel in ICT B. Aldosterone 1. Stimulates Na+ reabsorption and K+ secretion in the principal cells of the collecting duct system (ICT, CCT and OMCD) 2. Regulates the reabsorption of 2-3% of the filtered Na+ load 3. Aldosterone induced proteins include ENaC; SGK1; Na/K pump; TCA cycle enzymes |
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Describe aldosterone and mineralcorticoid receptors
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A. aldosterone-steroid hormone (mineralocorticoid); secreted by the adrenal cortex
B. aldosterone receptor (mineralocorticoid receptor-MR)-a cytoplasmic receptor C. Binding of aldosterone with its receptor stimulates gene transcription of proteins involved in Na+ reabsorption |
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How do the mineralcorticoid receptors (MR) work?
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The mineralocorticoid receptor binds both aldosterone and cortisol, but cortisol much more avidly
Aldosterone responsive cells have 11-b-hydroxysteroid dehydrogenase which converts cortisol to cortisone; Cortisone does not bind to aldosterone receptor, allowing cell to only respond to aldosterone |
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describe sympathetic innervation of the kidney and how it regulates Na reabsorption
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A. Sympathetic innervation of the kidney includes:
1. Portions of the renal nephron 2. Afferent/efferent arteriolar smooth muscle B. Norepinephrine(Nor) is the neurotransmitter-induces an increase in Na+ reabsorption by binding to a-adrenergic receptors: 1. PCT-stimulates apical NHE3 and basolateral Na/K ATPase activity 2. arteriolar smooth muscle-decreases renal blood flow-->reduces GFR-->decreases total Na+ excreted (via GT balance) 3. On the granular cells of the JGA, indirectly leading to an increase in aldosterone secretion |
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explain the role of ADH in Na regulating Na reabsorption
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ADH (AVP)-secreted from the posterior pituitary gland in response to increased ECF osmolality and decreased circulating volume
stimulates Na+ reabsorption-Acts on the TALH and the principal cells of the ICT and CCT |
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explain the role of atrial natriuretic peptide (ANP) in Na reabsorption
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A. ANP-peptide hormone secreted from atrial myocytes in response to stretch; rate of secretion is reduced when there is a decrease in effective circulating volume
B. ANP stimulates urinary Na+ excretion (natriuresis) 1. Increases RBF-leads to increase in GFR, leading to an increased filtered load and Na+ excretion via GT balance 2. Increased medullary blood flow also washes out medullary osmotic gradient, decrease passive Na+ reabsorption in tALH C. ANP also acts on IMCD to inhibit Na+ reabsorption |
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list the factors involved in regulating K secretion
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A. peritubular factors
1. stimulators-increased K intake; increased concentration of K; increased pH; aldosterone 2. inhibitors-decreased pH; epinephrine B. luminal factors 1. stimulators-increased flow rate; increased concentration of Na; decreased concentration of Cl; negative luminal voltage 2. inhibitors-increased concentration of K; increased concentration of Cl; Ba; amiloride |
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describe the effect of tubular flow rate on K secretion
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In the distal nephron, rate of net K+ secretion is dependent upon flow rate through the nephron at all levels of dietary K+ ingestion
Low flow rate-increased lumenal [K+] High flow rate-[K+] doesn’t increase as much, maintains high gradient for passive secretion |
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describe the features of the principal cells of the distal neuron
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A. Apical membrane
1. Na channel (reabsorb) 2. K channel (secretion) B. Basolateral membrane 1. Na pump 2. K+ channel note-the faster the flow rate, the less K+ builds up adjacent to the cells, keeping the gradient high and promoting K secretion |
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Explain the feedback control of effective circulating volume
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Kidneys increase Na+ excretion in response to an increase in ECF volume, not [Na+]
Note-the main sensors are all baroreceptors (the two central low pressure baro-receptors are the most important) |
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Describe the control of Renin secretion
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1. Decreased systemic blood pressure-sympathetic innervation of the JGA (Beta)
2. Decreased renal perfusion pressure-stretch receptors in the JGA granular cells of the afferent arterioles 3. Decreases [NaCl] in the tubular fluid-via the macula densa of the JGA, due to decreased GFR |
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describe the hemodynamic actions of Angiotensin II (ANG II) on Na reabsorption
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Angiotensin II induces vasoconstriction-Greater effect on efferent arterioles, leading to increases GFR
Overall reduction in renal blood flow, thus flow to vasa recta also decreases Net effect-increased Na reabsorption, decreased Na and H2O excretion |
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decribe the regulation of total body water
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Plasma osmolality is the primary parameter that is sensed and under physiologic control:
A. Sensor = hypothalamic osmoreceptors (ADH receptors); Osmoreceptors shrink or swell in response to a change in ECF osmolality B. Regulate both inflow and outflow of water 1. Thirst-regulates rate of water intake 2. Renal urinary excretion-regulates urine volume flow |
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explain the dependence of ADH secretion on plasma (ECF) osmolality
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Under normal conditions, the hypothalamus does not secrete ADH/AVP unless the plasma osmolality exceeds 280 mOsm
However, the sensitivity/threshold of the hypothalamus/posterior pituitary to stimuli inducing ADH secretion changes with effective circulating volume. A. large loss of volume-set point to induce ADH secretion falls below 280 mOsm and there is a greater amount of ADH secreted with smaller increases in plasma osmolality B. volume expansion-opposite is true (changes occur above 280 osm) |
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How do you calculate osmolar clearance (Cosm) and free H2O (Ch2o)?
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Cosm=(Uosm * V) / Posm (same as regular clearance)
Ch2o=V-Cosm |
