L12 - Renal Physiology II Flashcards
describe the Na+ and H2O balance - urine concentration (and the counter-current system)
The counter-current multiplier system of the loop of Henle
- Descending limb: no Na+ and Cl- reabsorption - water diffusion driven by the hyper osmotic interstitial medullary fluid
- Ascending limb: active Na+ and Cl- reabsorption - water impermeable creating hyperosmotic interstitial medullary fluid
The large volume of water reabsorption driven by hypersomotic intestinal medullary fluid over the whole loop of Henle from descending to ascending limb results in hyper osmotic tubular fluid
- DCT: active Na+ and CL- reabsorption - slightly water impermeable - even more hyposmotic tubular fluid
- CD: under vasopressin influence water permeability is regulated - high vasopressin results in water reabsorption causing hyperosmotic duct fluid - concentrated urine
describe how diuretics target Na+ reabsorption (3 main ones and their overall mechanism)
Inhibit Na+ reabsorption - increasing solute Na+ (Cl-, HCO3-) excretion - water follows solutes - water reabsorption decreased - water excretion increased - more urine - less plasma volume - lower blood pressure
Three important diuretics:
1. loop diuretics (inhibit NKCC, Na+, K+ 2Cl- cotransporter)
2. thiazides (inhibit NCC, Na+, Cl- cotransporter)
3. amiloride (inhibits ENaC, epithelial Na+ channel)
describe the three main diuretics method of work
- loop diuretics (furosemide)
- inhibits NKCC in ascending limb of the loop of Henle
- controls 25% water re-absorption
NA-K-2CL cotranporter (NKCC) - Na+ gradient across the apical membrane, driven by Na+/K+ ATPase, allows Cl- nd K+ co transport out of tubular lumen - critical to maintain K+ gradient
Loop diuretics - inhibit NKCC - Na+ remains in tubular lumen - water will remain as well and will also lower K+ gradient (unwanted) - diuretics (thiazides):
- inhibits NCC controls 5% water re-absorption, mild diuresis, but no effect on K+ - diuretics (amiloride):
- inhibits ENaC, controls 3% water re-absorption very mild diuresis, but no effect on K+
what is the clinical relevence of diuretics
used against:
- hypertension to reduce blood volume
- oedema in the lungs or legs
- heart failure (reduce preload)
-> reduce body water volume (.. pee more)
describe the regulation of renal Na+ excretion
Na+ excreted = Na+ filtered (GFR) - Na+ reabsorption
Changes in total-body Na+ - changes in extracellular fluid volume - changes in plasma volume - changes in blood pressures - changes in Na+ filtered (GFR)
No specific Na+ receptors - Na+ excretion regulated by baroreceptors (and some sensors in the kidney)
Renin-Angiotensin system:
(renin [secreted from kidneys], angiotensin I, ACE, angiotensin II)
1. vasoconstriction, 2. aldosterone
Aldosterone (steroid hormone)
- stimulates Na+ reabsorption by synthesis of ion channels (ENaC) and pumps (Na/K-ATPase) in the cortical collecting duct - hormone acts slower
- increase plasma volume and BP rises
describe the regulation at low plasma volume (low BP)
Renin secretion:
- sympathetic nerves (linked to CVS baroreceptors)
- intrarenal baroreceptors (afferent arterioles, stretch)
- GFR drops - Macula densa (sensing of Na+)
Renin-Angiotensin system:
(renin, angiotensin I, ACE, angiotensin II)
- vasoconstriction - aldosterone
Aldosterone:
- stimulates Na+ reabsorption by synthesis of ion channels (ENaC) and pump (Na/K-ATPase) in the cortical collecting duct - hormone acts slower
- plasma volume and BP rises
describe regulation at high plasma volume
ANP secretion:
- atrial natriuretic peptien (ANP)
- lower aldosterone - less Na+ reabsorption
- dilate afferent and constrict efferent arterioles -> increase GFR
- reduce tubular Na+ reabsorption and increase Na+ excretion
- increase supply (dilate afferent arteriole) and increase pressure (constrict efferent arteriole)
Natriuresis:
- increase in Na+ excretion due to osmotic diuresis
- plasma volume decrease, BP drops
describe how water excretion is controlled (look at diagrams on slides)
Water excited = water filtered (GFR) - water reabsorption
Tight link between regulation Na+ and water (vasopressin major regulator)
- baroreceptors sense low BP
- osmoreceptors sense blood osmolarity
Reduced VP:
- pain, fear
- drugs - ethanol inhibits VP, more urine
describe renal regulation of H+/acid-base balance (ways of losing or gaining H+)
Maintain pH homeostasis (plasma pH of 7.35 - 7.45 normal)
CO2 + H2O <=> H2CO3 <=> HCO3- + H+
Losing of body H+:
1. hyperventilation - increased removal of CO2
2. utilisation for metabolism (organic anions)
3. loss of H+ when vomiting
4. loss of H+ in urine
Gaining of body H+:
1. hypoventilation - more generated from CO2
2. non-volatile acids from metabolism (proteins)
3. loss of HCO3- from GI/gastric fluids (diarrhoea)
4. loss of HCO3- from urine
HCO3- excreted = HCO3- filtered (GFR) - HCO3- reabsorption
Lung ones are fast (minutes) whilst kidney ones can take hours/days
describe renal regulation of H+/acid-base balance (what is acidosis and alkalosis, how the lungs and kidney work together)
Acidosis: increase of arterial H+: arterial pH < 7.4
Alkalosis: decrease of arterial H+: arterial pH > 7.4
- respiratory acidosis
- respiratory alkalosis
- metabolic acidosis
- metabolic alkalosis
Lungs and kidneys work ‘together’ to maintain pH homeostasis
-> compensate each other’s function to maintain pH homeostasis
describe respiratory acidosis and alkalosis
- respiratory acidosis: increase of CO2 - hypoventilation (produce more CO2 than eliminated)
- compensation (kidney): increase of HCO3- re-absorption (to normalise excess blood H+ - mops up excess H+ to reduce H+ conc and restore pH) - respiratory alkalosis: decrease of CO2 - hyperventilation (eliminate more CO2 than produced)
- compensation (kidney): increase HCO3- secretion (to normalise lower blood H+)
- lack of HCO3- -> more H+ in plasma and restores pH
describe metabolic acidosis and alkalosis
- metabolic acidosis: diabetes, diarrhoea (loss of HCO3-), excessive lactic acid production
- compensation (lungs): increase of ventilation (to decrease PCO2 and lower blood H+)
- lung H+ and CO2 move opposites (compared to respiratory acidosis) - metabolic alkalosis: vomiting (loss of H+)
- compensation (lungs): decrease of ventilation (to increase PCO2 and increase blood H+)
- alternative: increase secretion of HCO3- (kidney)
describe urine composition (normal and pathological)
Pathological: glucose (glucosuria, diabetes), protein (proteinuria), blood (erythrocytes, haematuria), haemoglobin (haematoglobinurea), leucocytes, bacteria (infection)
Pathological:
- taste: sweet: glucose -> diabetes mellitus
- smell: fruity -> ketosis (fasting), diabetes, chronic alcohol abuse
rotten: infection (bacteria), tumour
describe analysing urine and dental care (mercury eg)
Murcury
- bound to carriers
- transporters move it our of lumen (reabsorption) or blood (secretion)
- accumulate in tubular cells
- nephrotoxicity - aging
Human exposure:
- dental amalgum
- consumption contaminated fish/seafood
- mining industry (used for gold mining)
- cosmetic products
- environmental pollution
The number of rdental amalgam restorations correlates positive with urinary mercury concentration
Clinical studies show no direct effect, but individual cases of: inflammation of mouth, neurological effects (tremor, anxiety), kidney failure
