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218 Cards in this Set
- Front
- Back
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List the 5 main functions of the kidney.
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Water and electrolyte homeostasis
Regulation of blood pressure via the RAA system Elimination of metabolic waste products Elimination of toxic or unwanted substances Regulation of erythrocyte production (erythropoietin) |
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Describe the structure of the kidney.
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Outer cortex, inner medulla
Medullary pyramids project into the renal pelvis The renal calyces lie between the pyramids There are 10-18 lobes and 10 to the 6 nephrons |
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What are the three components of a renal tubule?
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Proximal convoluted tubule, loop of Henle and the distal convoluted tubule.
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What is the pass of exudate from the kidney?
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From the distal convoluted tubule of each nephron, exudate drains into a collecting tubule, and then a collecting duct, these empty into the renal pelvis (at the apex of each pyramid).
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Where will you find the renal corpuscles?
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The renal corpuscles are the filtration elements of each nephron, and are found in the cortex.
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Where would you find the proximal and distal convoluted tubules?
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Cortex.
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Where might you find the loops of Henle and collecting ducts?
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Medulla.
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How does a renal corpuscle form?
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A bundle of capillaries invaginates into the blind end of a renal tubule to crate the glomerulus.
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What is Bowman's capsule?
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A layer of epithelium which surrounds the afferent and efferent bundled capillaries.
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What is the name for the space which lies between the glomerulus and the outer layer of epithelium of Bowman's capsule (parietal layer)?
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Bowman's space.
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Which cells on the inner layer of Bowman's capsule wrap themselves around the capillaries?
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The podocytes.
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What is the name of the secondary interdigitating foot processes on the cells around the capillaries?
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Pedicels.
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Which cells share a basal lamina?
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The podocytes share a common basal lamina with the fenestrated endothelium of the glomerula capillaries.
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Describe glomerula filtration mechanisms.
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The main mechanism is the common basal lamina, which excludes all molecules over 70kD
Filtration is assisted by a diaphragm between the pedicels. |
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What is the name of the thin diaphragm between the pedicels?
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Filtration slit diaphragms.
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How does the filtration slit diaphragm work?
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Hinders negatively charged molecules.
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What protein is contains in the filtration slit, and what condition arises if this protein is congenitally absent?
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Nephrin - absence leads to proteinurea as albumin is able to pass out of the blood and into the urine.
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What proportion of filtrate is reabsorbed in the proximal convoluted tubule?
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2/3rds of the 180L of filtrate produced each day is reabsorbed in the PCT aided by it's microvilli brush border
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Name a feature of PCT cells?
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Numerous microvilli along the infoldings.
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Why are there infoldings in the PCT?
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Increased surface area for Na+ pumps
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Why is Na+ pumped back out of the lumen?
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Creates an osmotic gradient for the recover of H2O and almost all the glucose and amino acids.
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The PCT descends into the medulla as what?
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The Loop and Henle.
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What is the function of the loop of Henle?
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To create a highly hypertonic environment in the medulla.
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The loop of Henle has thick and thin sections, which direction to they travel in?
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Thin limb descends, thick limb ascends.
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The thin limb of the loop of Henle is permeable to what?
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H2O.
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The thick limb pumps out what, and is highly impermeable to what?
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Pumps out NaCl, and is highly impermeable to H2O.
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What accompanies the loop of Henle to supply the medulla without disturbing the osmotic gradient?
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Vasa recta.
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What is the name of the portion of the nephron which returns back in the medulla?
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Distal convoluted tubule.
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How do the cells of the DCT compare to the PCT?
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DCT cells are smaller and lack the brush border - the lumen appears more open.
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What is the main purpose of the DCT and how is it controlled?
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The DCT reabsorbs the remaining Na+ and secretes K+ and H+. It is controlled by aldosterone.
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How does the DCT continue?
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As the collecting duct.
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What increases the permeability of the collecting duct and tubules?
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ADH (vasopressin) - Anti Diuretic Hormone.
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Where is the juxtaglomerular apparatus?
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Found where the DCT makes contact with the afferent arteriole of its own renal corpuscle.
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What are the three components of the juxtaglomerular apparatus?
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Juxtaglomerular cells, macular densa and lacis cells.
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What are juxtaglmoerular cells?
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Modified smooth muscle cells in the wall of the afferent arteriole.
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What is the macular densa?
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Modified epithelial cells of the DCT.
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What is another name for lacis cells?
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Extra glomerular mesangial cells.
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What is the purpose of the juxtaglomerular apparatus?
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Monitor blood pressure and release Renin if BP drops in the afferent arteriole.
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What is Renin?
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A protease which acts to cleave Angiotensinogen to make Angiotensin I.
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What role do the macular dense cells perform?
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Monitor low Na+ in the DCT via chemoreceptors, and stimulate the juxtaglomerular cells to release Renin.
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The glomerular filtration rate is constant at what range of arterial BP?
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Around 90 - 200 mmHg.
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What is the term used to describe the constant rate of filtration in the glomerulus independent of BP?
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Autoregulation.
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How does autoregulation occur in the kidneys?
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Smooth muscles in the afferent arteriole constrict for two reasons - 1) direct effect of pressure, and 2) tubulo-glomerular feedback.
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List 3 endocrine kidney functions and explain them briefly.
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Renin - produced by juxtaglomerular cells, cleaves Angiotensinogen to Angiotensin 1, which is converted to angiotensin 2 (by ACE). Angiotensin 2 is a powerful vasoconstrictor, which also acts on kidney via Aldosterone to retain Na+.
Vitamin D active form, 1,25, produced in proximal tubule, important for Ca2+ absorption and bone mineralisation. Erythropoeitin - Produced by cortical cells in response to hypoxia, stimulates red cell formation in bone marrow. |
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Where might you find juxtaglomerular cells?
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On the walls of the afferent arteriole.
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How many capillary beds are there in the nephron and what do they surround?
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2. The glomerular, and the peritubular surrounding the proximal and distal convoluted tubules.
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List the three main renal functions.
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Filtration, absorption and secretion.
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What is a typical glomerular filtration rate.
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120ml/min (170L per day).
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What is reabsorption, and where does it occur?
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Transfer of filtered H2O and solutes from the lumen to the peritubular capillaries. Occurs throughout the nephron but most in the PCT.
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What is secretion and where does it occur?
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Transfer of solutes from the peritubular capillaries to the lumen, occurs in both PCT and DCT.
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How much of these common compounds are absorbed or secreted - H2O, Electrolytes, Urea, Glucose, Bicarbonate, PAH?
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H2O, electrolytes and urea - fully filtered, almost totally reabsorbed, very little in urine.
Glucose and bicarbonate - fully filtered and fully reabsorbed, none in urine normally. PAH - partially filtered, fully secreted, so none remains in the blood. |
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How much glucose (180D), inulin (5.5kD), myoglobin (17kD) and albumin (69kD) are filtered?
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Glucose and inulin, 100%, myoglobin, 80%, albumin, 0%.
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Does charge make a difference to filtration and how?
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Yes. Cationic dextrans are filtered better than neutral dextrans, and anionic dextrans are filtered the least.
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What drives fluid movement across a capillary wall?
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Balance between hydrostatic pressure driving fluid out of the capillary into the interstitium, and oncotic pressure drawing fluid in from the interstitium.
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What factors ensure that the fall in hydrostatic pressure along the glomerulus is kept low?
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High resistance in the efferent arteriole, and low resistance in the glomerular arteriole wall means the fall in pressure is low.
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What factors help raise and lower GFR?
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High efferent pressure increases hydrostatic pressure, and therefore GFR. High afferent pressure reduces hydrostatic pressure and therefore GFR.
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What two factors affect the filtration rate?
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Pressure difference (hydrostatic v oncotic) and resistance in the artery wall.
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How does the pressure difference change along the glomerular artery, and why?
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Starts around 16mmHg - net outward hydrostatic pressure greater than oncotic.
Ends around 0mmHg - net outward remains same, but oncotic pressure greater as H2O has been driven out. |
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How do hydrostatic and oncotic pressures aid filtration and reabsorption.
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High hydrostatic pressure facilitates filtration in the glomerulus, high oncotic pressure facilitates reabsorption in the peritubular capillaries.
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How much cardiac output is taken by kidneys?
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20%
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Are filtration, reabsorption and secretion active or passive?
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Filtration is passive, reabsorption and secretion is active.
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How does tubuloglomerular feedback allow a nephron to control its own GFR?
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Macula densa checks NaCl concentration in DCT, it releases adenosine, constricting the afferent arteriole in response to high NaCl, and reduces release of adenosine, relaxing the afferent arteriole in response to low NaCl. Adenosine constricts the afferent arteriole, so when NaCl is high, GFR is reduced, and when NaCl is low GFR is increased.
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Does tubuloglomerular feedback affect renin release?
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Yes, it causes release of Renin from lacis and granular cells, which increases BP.
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How does angiotensin 2 affect kidney arterioles?
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Angiotensin 2 affects the efferent arteriole, increasing GFR.
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In what two physiological circumstances are GFR said to vary?
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Exercise, GFR can reduce by as much as 50% as sympathetic stimulation constricts afferent arterioles.
After feeding, GFR increases by as much as 20%, mechanism unknown. |
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How does noradrenalin affect GFR/renal blood flow?
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Preferentially constricts efferent arterioles, which would put GFR up, but also constricts systemic arteries, and therefore causes afferent constriction also.
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How does angiotensin 2 affect GFR/renal blood flow?
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Constricts afferent and efferent arterioles, dominant on efferent so raises GFR. Angiotensin 2 blockers would therefore lower GFR.
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How do adenosine and endothelin affect GFR/renal blood flow?
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Affect both, so lower GFR.
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How do acetylcholine, bradykinin, histamine and PGE2 and PGI2 affect GFR/renal blood flow?
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Vasodilators, so they raise GFR.
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How can we estimate GFR?
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Clearance - measure urine flow, and the concentration of solutes in the urine and venous blood.
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How do you estimate clearance?
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Clearance = [urine] x amount of urine produced (ml/min) divided by [plasma]
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What two factors affect clearance?
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GFR and the rate of reabsorption/filtration of a given substance.
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How might GFR be estimated by measurement of clearance?
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The rate of clearance of a substance which is freely filtered and neither reabsorbed nor secreted will equal the GFR.
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What substance is used clinically to test clearance?
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Creatinine, a biproduct of muscle metabolism is a good indicator, although not perfect due to some secretion in the nephron.
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Why might creatinine clearance not be a good marker of kidney function in an elderly or sick patient?
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Reduced muscle mass (elderly) or inactivity (sick) will give a low plasma creatinine reading.
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What might a depressed GFR be an indicator of?
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Kidney failure.
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What is the most important substance secreted by the nephron?
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H+ ions.
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Are substances that demonstrate net absorption also secreted?
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Yes. E.g. K+
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Why might clearance of PAH be a useful indicator of renal plasma flow?
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Because at low concentrations it is entirely cleared by the kidney in one pass.
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What is normal renal blood flow?
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625ml/min
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What is normal renal plasma flow?
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625ml/min divided by 1-hematocrit. Hematocrit is blood volume occupied by cells, so 1-hematocrit = plasma. 625/0.55 = 1136 ml/min
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How does the kidney concentrate urine?
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Differential water permeability along the length of the nephron
Osmotic gradients in the interstitium created by countercurrent and active solute transport Regulation of permeability in DCT and collecting ducts by ADH |
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Describe activity in the PCT.
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PCT is highly permeable to H2O. Na+ is reabsorbed, and H2O follows. 65% of NaCl and H2O reabsorbed in PCT. Isotonic - so conc in tubule and out is the same.
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Describe activity in the thin descending limb.
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Highly permeable to H2O, H2O drawn out by osmotic gradient, so tubular fluid becomes hypertonic as it descends. 10% H2O reabsorbed here.
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Describe activity in the thin ascending limb.
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Impermeable to H2O, but permeable to NaCl and Urea. At this point NaCl will leave as interstitium is hypotonic.
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Describe activity in the thick ascending limb and early DCT.
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Impermeable to water and urea. NaCl is actively extruded, tubular fluid become hypotonic.
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Describe activity in the DCT and collecting ducts given the presence of absence of ADH.
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With ADH, permeability to H2O increases, urea transport increases and urine is concentrated.
Without ADH, permeability to H2O decreases, so urine becomes dilute (diuresis). |
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Why is fluid absorption in the PCT isotonic?
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Because permeability to H2O is high, so H2O follows Na+ extrusion.
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Describe the countercurrent mechanism.
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Thin descending limb permeable to H2O, H2O drawn out following NaCl pumped out.
Ascending limb impermeable to H2O so it cannot follow the solutes that leave at that point. Result is a dilute interstitium, drawing further solutes out in the thin ascending limb. This creates a gradient to draw more H2O out of the descending portion. The longer the loop, the greater the osmolality. |
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Where are the urea transporters, how do they work and what are they stimulated by?
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Collecting duct, work via facilitated diffusion and are stimulated by ADH.
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What affect would a more concentrated fluid in the collecting duct have on urea?
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Urea would diffuse more into the interstitium.
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Is the thin ascending limb permeable to urea?
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Yes.
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What is the effect of urea diffusing into the ascending tubule as NaCl diffuses out?
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The osmolality of the tubule contents becomes more dependent on [urea]
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Are the thick ascending limb, distal tubule and upper collecting duct permeable to urea?
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No, so urea is trapped in.
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Is urea recycled?
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Yes. It augments the countercurrent mechanism.
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How much does recycling of urea contribute to the osmotic gradient?
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50%.
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What prevents water reduces the osmotic gradient?
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It is removed by the vasa recta.
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How many nephrons penetrate the deep medulla?
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12%.
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How many collecting ducts penetrate the deep medulla and what consequence does this have for the concentration of urine?
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100% - so urine osmolarity cannot be greater than that in the deep medulla (1400mOsM)
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Which hormone controls urine concentration and via what receptors on which cells?
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ADH, via V2 receptors on principal cells.
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In what proportion are Na+ and K+ reabsorbed compared to water in the PCT?
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Equal so their concentration remains constant, but the content falls.
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In what proportion is bicarbonate reabsorbed compared to water in the PCT?
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Greater, so the concentration of bicarbonate falls in the PCT.
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What effect does the drop in bicarbonate concentration have on the reabsorption of Cl- in the PCT?
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Less Cl- is reabsorbed to maintain charge balance, so concentration of Cl- actually rises.
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What affect does the reabsorption of water have on the concentration of a non-reabsorbed solute like creatinine?
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It increases threefold in the PCT.
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How much glucose, phosphate, calcium and magnesium are reabsorbed in the PCT?
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Glucose, 100%, Pi, 80%, Ca2+, 70%, Mg2+, 30%.
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Is there a maximum amount of reabsorption for solutes?
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Yes, reabsorption relies on transporters, they have a tubular transport maximum which if it is exceeded can result in appearance of solute in the urine. E.g. renal threshold of 11mM for glucose.
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What is the renal threshold for the reabsorption of glucose?
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11mM.
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What is splay?
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Splay is the difference between a substances maximum renal absorption and its appearance in the urine
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What is osmotic diuresis?
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Osmotic diuresis occurs when substances are filtered but not reabsorbed at all, or where reabsorption excess the tubular maximum (e.g. diabetes), in this instance, the presence of the substance in the tubular fluid draws H2O back in, leading to copious, dilute urine.
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What is the clearance range for most amino acids?
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6% of GFR for histidine, 0.1% for valine.
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Where does reabsorption of most amino acids take place?
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PCT, but can also be loop of Henle during loading.
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Why is cystine unique in reabsorption?
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It has only one transporter, RBAT, whilst other AAs have 2. Deficiency in RBAT can cause cystineuria.
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What is proteinuria and why might it be significant?
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Glomerular damage can lead to proteinuria, so it is a marker for kidney disease. This is especially prevalent in diabetes.
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What is nephrotic syndrome?
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Considerable protein loss in urine, mostly albumin.
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By what mechanism are most proteins absorbed in the PCT?
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Endocytosis.
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What are the 3 causes of proteinuria?
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Glomerular proteinuria - disease leading to bigger pore size
Tubular proteinuria - disease affecting the PCT reabsorption Overload proteinuria - various causes depending on disease, e.g. lysozyme in leukaemia |
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Describe the mechanisms for the reabsorption of key ions, compounds and H2O in the PCT.
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Most related to the uptake of Na+ - which is either exchanged for H+, or co-transported with glucose, AAs, Pi etc
H2O, K+, Ca2+, Pi, glucose and AA all taken up with Na+ K+, Cl- and urea also via paracellular pathways HCO3- is created in cells from H+ ions mixed with CO2 which diffuses into kidney PCT cells. Na+ is actively pumped into blood by an Na+K+ ATP-ase |
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What is the typical [K+] in and out of cells?
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4mM in plasma, 120-150mM in cells.
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Why is [K+] ratio important clinically?
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[K+] determines membrane potential, excitability and therefore has serious effects on muscles, nerves and heart.
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What effects might free H+ ions, insulin and B-agonists have on [K+]?
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Free H+ ions in cell bind to negative proteins in cytosol, neutralising their charge. K+ leaves cells to maintain an equilibrium causing [K+] to change (hyperkalaemia), alkalosis causes hypokalaemia.
Insulin and B-agonists stimulate the Na+ pump, drawing 2 K+ in for 3 Na+ out - hypokalaemia. |
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How is K+ reabsorbed in the PCT and how much?
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65% of filtered K+ reabsorbed in PCT passively following Na+ and paracellularly with H2O
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How is K+ reabsorbed in the thick ascending limb and how much, and how might this provide a useful site for drugs?
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30% of filtered K+ reabsorbed in the thick ascending limb by active transport with an Na+:K+:2Cl- co-transporter. Blocked by loop diuretics e.g. Furosemide.
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Which channel allows diffusion of reabsorbed K+ back into the lumen?
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ROMK.
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Where does K+ secretion take place and by what cells?
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Principal cells in the DCT and collecting ducts.
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What might cause increased K+ secretion and how does it work?
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Increased tubular flow causes increased K+ secretion, because the gradient is reduced.
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What is the effect of aldosterone?
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Increases expression of ROMK and Na+ channels (ENaC) in the DCT and collecting duct.
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What role do intercalating cells play in the reabsorption of K+?
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Minor one. Are in DCT and collecting duct, have an ATP-ase which swaps an H+ for a K+.
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How does Na+ affect K+ secretion?
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Na+ reabsorption creates a negative charge in the lumen, which aids K+ secretion, so anything which influences Na+ reabsorption (e.g. amiloride or aldosterone) will affect K+ secretion.
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Hyperkalaemia is associated with what? and Hypokalaemia?
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Hyperkalaemic acidosis, hypokalaemic alkalosis.
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How does the body use aldosterone to control [K+]?
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The body responds to low plasma [K+] by inhibiting release of Aldosterone from the adrenal cortex. If plasma [K+] is high, it stimulates the adrenal cortex to release aldosterone.
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Describe hypokalaemia, its causes, effects and treatment.
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Hypokalaemia = plasma [K+] <3mM
Caused by diuretics, osmotic diuresis, GI (vomiting, diarrhoea), or drugs (insulin, B-agonists) Effects include flaccid paralysis, sluggishness, polyurea, polydipsia, ECG changes Treat with K+Cl-, give alternative diuretics (K+ sparing). |
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Describe hyperkalaemia, its causes, effects and treatment.
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Hyperkalaemia = plasma [K+] >5.5mM
Caused by failure to excrete K+ - kidney failure, drugs, ACE inhibitors, ARBs, Addison's disease Effects include muscle weakness, ECG changes, danger of AF Treatment with Ca2+ IV, insulin and glucose, maybe diuretics. |
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Describe the difference in ECG changes in hypo and hyperkalaemia.
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Hypokalaemia - long PR, QT, ST depression, T-wave flat
Hyperkalaemia - long PR, QT, ST depression, T wave peak |
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Where are H+ ions secreted and why?
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Nephrons secrete H+ in the PCT, DCT and collecting duct in response to high PaCO2.
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How is bicarbonate almost all reabsorbed?
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Tubular H+ ions combined to bincarbonate to make carbonic acid, which dissociates to H2O and CO2 for reabsorption.
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In the presence of significant quanitites of H+ ions, how is urine maintained only a slightly acidic pH?
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Free H+ ions are buffered with phosphate (H2PO4) or Nitrogen (as ammonia), this keeps urine pH around 5-7, which is where it needs to be, any more acidic and H+ secretion channels would not work.
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What important enzyme facilitates the buffering of free H+ ions with bicarbonate in the PCT?
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Carbonic anhydrase.
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How is bicarbionate reabsorbed in the PCT?
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As CO2 and H2O, resulting in uptake of 1 Na+ with 1 HCO3-. No net movement of H+ ions.
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How is ammonia produced in the PCT?
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NH3+ can diffuse into lumen, where it combines with H+ ions to make ammonia, NH4+. This cannot diffuse back. Each NH4+ can buffer one H+ ion.
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Can some NH4+ be reabsorbed and how?
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Yes, it can be substituted for K+ at the Na+:K+:2Cl- co-transporter in the thick ascending loop.
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How does the liver excretion of amino acid metabolites help to regulate H+ excretion?
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The liver metabolises excess amino acids, yielding NH4+ and HCO3-. It then secretes these metabolites via two different pathways depending on the plasma pH.
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What two pathways for excretion of amino acid metabolites can the liver use to which help regulate H+ excretion?
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A) Excretion of urea = 2 HCO3- and 2NH4+, or
B_ Excretion of Glutamine, which is an ammonia with a Glutamate. |
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Which liver pathway for regulation of H+ excretion predominates in acidosis and which in alkalosis?
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Urea excretion in alkalosis, because urea consumes HCO3-.
Glutamine in acidosis, as any HCO3- is returned to the blood. |
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Define respiratory acidosis.
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Insufficient ventilation (e.g. lung disease), look for a low pH, with a high PaCO2.
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Define respiratory alkalosis.
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Hyperventilation, usually due to hypoxia, altitude, VQ mismatch, look for a high pH and a low PaCO2.
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Define metabolic acidosis.
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Ingestion of acids, or metabolic production e.g. lactate, ketoacids in starvation or diabetes, or renal failure. Look for low pH and low [HCO3-]
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Define metabolic alkalosis.
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Ingestion of HCO3-, loss of acid e.g. vomiting, high aldosterone, hypokalaemia. Look for high pH and high [HCO3-].
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How would your kidney help compensate for respiratory acidosis?
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Absorption of more HCO3- to create normal pH.
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How would your kidney help compensate for respiratory alkalosis?
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Reduce absorption of HCO3-.
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What system might help compensate for metabolic acidosis/alkalosis?
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Respiratory, either hyperventilating to blow off CO2, or trying to slow breathing to maintain CO2 levels.
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What is the anion gap?
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Measure of 'unmeasured ions' - such as proteins, organic acids - can be clinically useful.
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How is the anion gap used clinically?
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Can help to define metabolic acidosis. If the acidosis is because HCO3- is being lost, then Cl- will replace HCO3-, and the anion gap will be normal. If it is due to presence of an acid whose anion is not Cl- (e.g. lactic acidosis, or ketoacidosis) then the anion gap is raised.
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What are the two mnemonics for the raised anion gap?
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KULT - Ketoacidosis, Uremia, Lactic Acidosis, Toxicity
MUDPILE - Methanol, Uremia, Diabetic Ketoacidosis, Paraldehyde, Isoniazid, Lactic Acidosis, Ethylene Glycol. |
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Why do we drink?
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To replace water lost through the skin and in our breath. We do lose H2O in urine but it is concentrated so not very much.
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How do we regulate plasma osmolality and why is that important?
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We regulate by drinking and urinating, and it is important because plasma osmolality drives osmolality in the rest of our tissues.
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Describe the effect of drinking a litre of water (a large amount) on plasma osmolality and urine production over a few hours.
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Water rapidly absorbed in gut, and as it enters plasma the osmolality drops. This is detected by osmoreceptors which signal the reduction in ADH release. Low ADH inhibits renal reabsorption of H2O in the DCT and collecting ducts, result is a rapid increase in urine production.
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Where are the osmoreceptors and where is ADH released from.
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Osmoreceptors are in the hypothalamus (and elsewhere). ADH is produced in the hypothalamus, and released from the posterior pituitary.
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How does ADH work in the DCT/collecting duct?
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Activates V2 receptors which release vesicles containing aquaporins. These insert onto the luminal membrane increasing reabsorption of H2O.
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What are the limits of urine osmolality and how are they set?
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In the absence of ADH you would not reabsorb H2O in the collecting duct, so osmolality would equal late DCT ~60-80mOsM.
With maximum ADH H2O is reabsorbed until the tubular fluid equals osmolality of the deep renal medulla, ~1400mOsM. |
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Other than osmolality, what other factors might affect the release of ADH from the posterior pituitary?
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Low blood pressure, and low blood volume. Alcohol and stress inhibit ADH release, and nausea stimulates it.
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What is the primary factor determining blood volume and therefore osmolality?
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Body Na+ content.
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Describe the physiological mechanisms which help regualte blood volume in response to increased blood volume.
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Detected by atrial stretch receptors, and arterial baroreceptors.
Result: Decreased sympathetic outflow to heart + vasculature, causing immediate reduction in BP Inhibition of ADH secretion, leading to diuresis Decreased stimulation of renal sympathetics, lowering output of Renin (RAAS) Increased release of Atrial-Natriuretic Peptide (ANP) - causing Natriuresis |
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Which system is activated by a fall in arterial BP or tubular [Na+]?
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Renin-Angiotensin-Aldosterone
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Describe the RAAS system.
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Renin, produced by the juxtaglomerular cells in the kidney, circulates and as a enzyme converts angiotensinogen to angiotensin 1. This is converted in the lungs by ACE to angiotensin 2. Angiotensin 2 is a potent vasoconstrictor, stimulates release of ADH and thirst, and also stimulates the adrenal glands to release Aldosterone.
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Where is aldosterone secreted, and in response to what 2 stimulators?
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In the zona glomerulosa of the adrenal cortex, responding to angiotensin 2 and hyperkalaemia.
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What effects does aldosterone have in the kidney?
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Increases gene transcription of ENaC & ROMK, which enhances K+ secretion and Na+ reabsorption.
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Where is Atrial-Natriuretic Peptide secreted and in response to what stimulation?
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Atrial muscle cells in response to stretch.
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What effect does ANP have on the kidney?
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Inhibits expression of ENaC, dilates afferent arteriole, so increasing GFR, this inhibits Renin release and promotes natreuresis.
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Which pump is inhibited by loop diuretics like Furosemide?
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The Na+:2Cl-:K+ cotransporter.
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How is Na+ removed from cells in the thick ascending loop?
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Na+ K+ ATP-ase and an Na+-HCO3- co-transporter.
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Which ions move across transcellular pathways?
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Na+, K+, Ca2+, Mg2+ and NH4-
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How is Na+ absorbed in the early DCT and which diuretics target this transport?
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An Na+ Cl- cotransport. Thiazides.
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What are the two types of cell in the late DCT and collecting duct?
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Principal cells, for Na+ transport, and Intercalated cells for H+ transport.
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Which transport in the late DCT reabsorbs Na+ and which diuretics target this?
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ENaC, targetted by Amiloride and ANP.
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What regulates uptake of Ca2+, Mg2+ and PO42-?
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Ca2+ = Bone turnover and formation, gut absorption
Mg2+ = Renal mechanisms PO42- = All three |
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How are Ca2+ and Mg2+ reabsorbed in the thick ascending limb?
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Passive, paracellular diffusion driven by positive charge in lumen created by secretion of K+ via ROMK.
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How much Ca2+ and Mg2+ are reabsorbed in the TAL?
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20% of Ca2+ and 65% of Mg2+.
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What is the major regulatory pathway for the reuptake of Mg2+?
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Calcitonin and PTH increase permeability to Mg2+.
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How does the Ca2+ Mg2+ sensor drive paracellular reabsorption?
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By increasing expression of Na:K:Cl transporter and ROMK, driving +ive lumen and reuptake of Ca2+ and Mg2+.
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How does PTH affect reuptake of Ca2+ in the DCT?
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Activates a Ca2+ reuptake channel.
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What prevents uptake of Ca2+ from raising [Ca2+]?
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Binds to calbindins.
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What 2 substances control the removal of Ca2+ by the Ca2+ATP-ase?
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PTH and Vitamin D.
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How does vitamin D affect calbindins?
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Increases amount of them in the cell.
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How is PO42- reabsorbed?
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Via a cotransporter with 2 x Na+
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Why do diuretics have such a large effect on urine production?
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99% of Na+ and H2O is normally reabsorbed, so a small reduction in this will have a big effect on urine output.
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Name three oedematous conditions and which type of diuretic you might use to treat them?
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Heart failure - low cardiac output causing increased venous pressure
Renal disease - protein lost so [protein] in plasma falls Hepatic disease - less albumin, plasma [protein] falls Treat with loop diuretics combined with K+ sparing |
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Which type of diuretic might you use to treat hypertension and why use a diuretic at all?
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Thiazide type - they lower blood volume and therefore cardiac output.
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Which diuretics work where?
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Proximal tubule - 65% Na+ reaborption - no diuretics here
TAL - 25% Na+ reabsorbed - loop diuretics block the Na:K:2Cl symport DCT - <10% Na+ reabsorbed - thiazides block the Na+Cl- symport Collecting tubule - <5% Na+ reabsorbed - K+-sparing diuretics work here by blocking Na+K+ exchanger |
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Give examples of loop diuretics.
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Furosemide, torasemide, etacrynic acid.
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How do loop diuretics work?
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Block the Na+:K+:2Cl- co-transporter in the TAL, causes a powerful diuresis, as the hypertonic medullary interstititum is lost.
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When would you use a loop diuretic?
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In heart failure, hepatic or renal disease.
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What are the side affects of loop diuretics?
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Hypokalaemia, metabolic alkalosis, low plasma Ca2+ and Mg2+, hypovolaemia
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Give examples of thiazide diuretics.
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Hydrochlorathiazide, Benzoflumethiazide, Metolazone.
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How do thiazide diuretics work?
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Block the Na+:2Cl- co-transporter in the DCT, lower renal plasma volume, reduce venous return and therefore CO.
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When would you use a thiazide diuretic?
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Hypertensives.
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What are the side affects of thiazide diuretics?
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Hypokalaemia, hyperglycaemia, hyperuricaemia.
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Why does hypokalaemia cause hyperglycaemia?
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Hypokalaemia causes a reduction in insulin output, leading to high blood sugar levels.
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How do thiazide diuretics lower BP?
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Initially a decrease in CO caused by lower blood volume, but they also cause a reduction in TPR by an unknown mechanism.
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Give examples of K+ sparing diuretics.
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Amiloride, triamterene and spironolactone.
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How do K+ sparing diuretics work?
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Variously. Amiloride and triamterene block ENaC in principal cells of the DCT. This reduces Na+ reuptake, and reduces K+ secretion as these are linked.
Spironolactone antagonises Aldosterone, this upregulates ENaC and ROMK. |
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When would you use a K+ sparing diuretic?
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Not often used alone as they have a negligable diuretic effect and tend to cause hyperkalaemia.
Instead combined with a better diuretic. |
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What are the side affects of K+ sparing diuretics?
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Hyperkalaemia.
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Why are K+ sparing diuretics important?
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K+ loss in diuresis can cause hypokalaemia, alkalosis, arrhythmias etc.
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What are osmotic diuretics?
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Mannitol and Isosorbide. Given by IV, work by increasing osmolarity of the blood, this raises blood volume, increases GFR and reduces H2O reabsorption in the descending loop. Used in acute renal failure when tubular necrosis impairs kidney function.
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Define kidney failure.
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A sustained rise in serum creatinine and urea due to a decline in GFR leading to loss of normal H2O/solute homeostasis and life threatening metabolic sequelae
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What are the symptoms of acute kidney failure?
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Decline in GFR, oliguria (reduced urine) or anuria (urine output <50ml/day)
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Is acute kidney failure reversible?
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Yes.
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Is chronic kidney failure reversible?
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No.
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Describe the mechanism to maintain RBF if it drops.
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Prostaglandins dilate the afferent arteriole, and angiotensin 2 constricts the efferent arteriole.
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Describe three types of Acute Kidney Injury.
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Pre-renal, including hypovolaemia, hypotension, low kidney blood flow, oedema
Intrinsic, including glomerulonephritis, acute tubular necrosis, interstitial nephritis and vascular disease Post-renal, including stones and clots, or masses in prostate, pelvis etc |
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What is chronic kidney disease?
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Progressive loss of nephrons ranging from dysfunction to kidney failure, end stage kidney disease - dialysis dependency.
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What causes chronic kidney disease?
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Glomerulonephritis, diabetes, some hereditary diseases, hypertension, uropathy.
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Describe the symptoms of chronic kidney disease.
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Poor appetite, nausea and vomiting, tiredness, oedematous, itchy, cramping or restless legs... but can be asymptomatic.
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Why do patients with chronic kidney failure develop nocturia?
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Urine concentration is normally highest in the morning due to lack of drinking overnight. In CKF you lose the ability to concentrate urine a little, so you have to get up in the night to urinate.
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Why do patients with chronic kidney failure develop anaemia?
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Reduced kidney function affects kidneys ability to produce erythropoeitin, the hormone which stimulates production of red blood cells.
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How does plasma [Na+] differ between afferent and efferent arterioles?
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It doesn't. Na+ is reabsorbed in the same amount as H2O, so the [Na+] is the same.
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How does the plasma [protein] differ between afferent and efferent arterioles?
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Protein is not filtered. The RBF = 625ml/min, and GFR around 125ml/min, so for every 625ml in, 500 comes out. Protein amount will remain constant, so the [protein] increases by 625/500 = 125%.
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Why does the medulla have a low PO2?
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The blood diffuses across in the vasa recta so PO2 in the medulla is less than in the cortex.
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