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36 Cards in this Set
- Front
- Back
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Summarise the effects of the Renin - Angiotensin - Aldosterine system?
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Fall in tubular [Na+]
Causes fall in pressure Causes sympathetic in afferent arteriole Stimulates granular cells Release of renin - causes Angiotensinogen to activate to Angiotensin 1 Angiotensin 1 converted to angiotensin 2 by ACE angiotensin 2 --> Aldosterone Aldosterone = mineralocorticoid steroid from adrenal cortex affects Na+ and K+ handling in distal nephron |
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Briefly summarise the reabsorption of salt in the nephron?
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-65% of salt (and water) reabsorbed in PCT
-active reabsorption of salts in the thick ascending loop of Henle, DCT, and early collecting duct (Usually 98-99% of filtered NaCl is reabsorbed in nephron) |
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Describe Na+ transport in the Thick Ascending Loop of Henle?
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1. Electroneutral Na+:K+:2Cl- cotransporter at luminal surface
Inhibited by loop diuretics eg. furosemide 2. Na+ removed by 3Na+:2K+ pump and Na+:HCO3- transporter 3.Cl- diffuses via channels 4. K+ diffuses into LUMEN via apical channels, causes lumen to become +ve Some K+ diffuse to blood via basolateral channels also 5. Tight junctions are impermeable to water but allow diffusion of cations driven by +ve potential |
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Describe Na+ transport in the Early DCT?
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1. Electroneutral Na+:Cl- transporter at apical membrane transports 1 Na and 1 Cl into the cell from the lumen.
Inhibited by thiazide diuretics 2. Na+:K+ pump at basal surface removes Na+ 3. Cl- diffuse out through channels 4. K+ diffuses out via channels 5. Cell junctions impermeable to water -->luminal fluid become hypotonic (conc) |
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Describe Na+ transport in the Late DCT and collecting duct?
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=Principal Cells involved in transport of Na+
1/ Na+ entry from lumen via ENaC Inhibited by amiloride and atrial natriuretic hormone (ANP) 2. Na+ pump exchanges 3Na for 2K+ 3. Na+ entry from lumen causes -ve potential in lumen promotes: K+ diffusion via ROMK into lumen (K+ secretion) 5. Aldosterone increases transcription of ENaC, ROMK and Na+K+ pump |
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Regulation of Ca2+
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bone turnover and gut absoption
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Regulation of Mg2+
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renal mecanisms
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Regulation of PO42-
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bone turnover, gut absoption, renal mechanisms
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What hormones control regulation of Ca2+, Mg2+ & Po42-
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Parathyroid Hormone (PTH)
vit D Calcitonin |
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Where are Ca2+, Mg2+ and PO42- reabsorbed in the nephron ( give %)
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PCT
Ca2+ = 70% Mg2+ = 30% PO42- = 80% thinLoH - Impermeable to all thick ascending LoH Ca2+ = 20% Mg2+ = 65% DCT Ca2+ = 10% Mg2+ = 5% PO42- = 10% CD PO42- = 3% |
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How is Ca2+ and Mg2+ absorbed in the Thick ascending limb of Loop of Henle
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passive and paracellular (between the tight junctions between cells)
driven b +ve charge in lumen due to transport of K+ into the lumen by ROMK =20% of Ca2+ 60% of Mg2+ |
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Major and minor Mg2+ regulatory pathway in TAL LoH?
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Major
calcitonin and PTH by increasing Mg2+ permeability pf paracellular path Minor basolateral Ca-Mg sensor low plasma [ca] or [mg] leads to increased activity of na-2cl-k receptor and ROMK therefore driving force for paracellular pathway increases |
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Describe the pathway for Ca2+ absorption in the distal tubule?
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Ca2+ enters cell from lumen
via PTH activated channel Binds to calbindin (limits rise in Ca2+) removed by Ca2+ atpase transporter and 3Na+ in 1 Ca2+ out exchanger Vit. D can also increase amount of calbindins 10% |
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Describe the pathway for Mg2+ absorption in the distal tubule?
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enters cell down electrochemical grad. via TRPM6 channels
removed by Mg2+ atpase channel 5% |
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Describe the pathway for PO42- absorption in the distal tubule?
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reabsorbed by transporter as in PCT
Inhbited by PTH 10% |
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Why is K+ regulation very important
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[K+] ratio across cell membrane determines membrane potential and excitability
Disturbances have serious effects on nerves, muscle and heart |
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What factors is the [k+] ratio dependent on?
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1. pH
increased [H+] bind to -vely charged cystolic proteins Cancelling -ve charge so K+ moves out of th cell 2. Insulin and B adrenergic agonists (eg. adrenaline) stimulate Na+ pump and therefore K+ into cell |
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how much K+ do we intake in the diet?
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40-120mmole/daily
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What is K+ excretion regulated by?
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kidney - control occurs in the late DCT and collecting duct by reg. of secretion
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K+ filtered per day and how much reabsorbed and by what mechanisms?
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880mmole/day
95% reabsorbed by 1. diffusion through tight junctions (paracellular) 2. Na+:K+:2Cl- transporter in Thick ascending loop of henle |
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summarise renal K+ handling?
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1. PCT - 65%
Passive reabsorption following Na+ and water via paracellular route 2. Thick Ascending LoH 30% Active via Na+:K+:2Cl- transport 3. Principal cells of late DCT and CD Regulation of K+ via Secretion 4. Modulation of K+ excretion by acid base in intercalated cells of late DCT and CD |
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Describe K+ handling in the Thick Ascending Limb of the Loop of Henle?
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1. Electroneutral Na+:K+:Cl- cotransporter at lumina surface (inhibited by loop diuretics therefore = K wasting)
2. K+ diffuses via ROMK channels at apical surface - making lumen =ve, (some also absorbed by basolateral channels) 3. Tight junctions impermeable to H20 but allows K+ diffusion driven by +ve potential 4. =30% |
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Describe K+ transport in the late distal tubule and collecting duct?
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Secretion
1. Principal cells = K+ secretion 2. Na+/K+ pump on basolateral surface 3. K+ diffuse into lumen via ROMK (assisted by -ve potential in lumen created by ENaC) and K+:Cl- cotransporter (K+ secretion) 4. increased tubular flow increases K+ secretion by diluting [K+] in lumen and increasing gradient 5. Aldosterone increases expression of Na+K+ pumps and ROMK = major method of K+ reg. REABSORPTION 1. Intercalated cells (Type A) 2. H+/K+ ATPase pumps K+ into cell in exchange for H+ out 3. K+ diffuses into interstitium via K+ channels NB. Intercalated Type A cells contain other processes related to H+ secretion Also note reciprocal relationship between K+ and H+ and therefore pH |
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Describe the factors affecting K+ secretion?
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1. Driving force for K+ secretion is -ve potential in lumen created by ENaC so factors affecting this affect K+ secretion eg. inhibited by amiloride
2. Tubular flow increases secretion of K+ as prevents build up of K+ therefore osmotic gradient not dissipated 3. Acidosis prevents K+ secretion and alkalosis enhances (part. due to disruptive -ve potential in lumen) 5. Aldosterone is the main regulator of K+ secretion as increases transcription of ROMK, Na+ pump and ENaC |
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aldosterone and the regulation of K+
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Increases plasma K+ directly stimulates prodn of aldosterone from adrenal cortex
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At what point does is there a steep relationship for excretion of K+ and plama [K+]?
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4-5mM [K+]
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When is K+ regulation impaired
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Hyperalosteronism (Conn's) and Hypoaldosteronism (Addison's)
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What is hypokalemia?
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Plama [K+] <3mM
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Causes of hypokalemia?
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1. increased renal excretion of K+
(loop/thiazide diuretics, osmotic diuresis, increased aldosterone) 2. GI loss of K+ (vomiting/ diarrhoea) 3. temp. shift of K+ into cells (metabolic alkalosis, B- adrenergic agonists, insulin) |
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Effects of hypokalemia?
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decreased neuromuscular excitability
muscle weakness and paralysis cardiac arrhythmias and conduction defects alkalosis ECG = ST depression flatted T appearance of U |
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Treatment of hypokalemia?
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Administration of KCl
Correction of alkalosis Use of K+ sparing diuretics (eg. spironolactone, amiloride) |
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What is hyperkalemia?
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plama [K+] > 5.5mM
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Causes of hyperkalemia?
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1. Failure to excrete K+
(renal failue, drugs eg. spironolactone, ACE inhibitors, hyperaldosteronism) 2. Shift of K+ out of cells (acidosis exacerbated by lack of insulin in metabolic ketoacidosis) 3. Tissue damage (eg. trauma and surgery, incorrect blood type with red cell lysis) |
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Effects of hyperkalemia?
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Depolarisation of excitable cells with muuscle weakness, cardiac arrhythmias, danger of fibrilation and cardiac arrest
ECG = tall peaked T wave loss of P wave widening of QRS complex |
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Treatment of hyperkalemia?
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Ca2+ gluconate to stabalise cardiac cells
insulin + glucose to shift K+ into cells Longer term - treat with loop/thiazide diuretics/ treat for renal failure |
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Give a summary of K+ homeostasis?
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-Regulation of K+ excretion confined to Late distal tubule and collecting duct - elsewhere secondary to other factors (Nb. Aldosterone is key)
-K+ excretion is strongly influenced by acid-base status -Some diuretics have a detrimental effect on plama [K+],others do not |
