Aspects of Renal Physiology

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From the 12/11/13 Human Physiology lecture.

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Question Answer
Kidneys are <1% body weight, but receive what percentage of cardiac output? ~25%
What is the functional unit of the kidney? How many are there? The functional unit of the kidney is the nephron, of which there are 2.5 million per kidney. These are lost on a daily basis and do not regenerate over life.
Roughly what size are nephrons? ~5 cm in length and ~5μm in diameter.
How many litres of plasma do the kidneys process per day? How much of this ends up as urine? ~180 L / day. ~1% of this ends up as urine.
Given how many nephrons each kidney consists of, what volume of the plasma filtered in a day is filtered by an individual nephron? ~1.5 drops
How much sodium is reabsorbed in a day? ~600g
List some roles of the kidney. Excretion of waste products (e.g. urea); excretion of foreign compounds (e.g. xenobiotics); control of erythrocyte number via erythropoietin; production of active form of vitamin D; regulation of plasma osmolarity; long term acid/base balance (short term = breathing) and excretion of non-volatile acids; long term control of blood pressure via regulation of H2O and ions.
Which two elements does a nephron consist of? Vascular and tubular.
What is the force that drives renal filtration of plasma? Ventricular systole pumps blood to the kidneys under high enough pressure that plasma is filtered into Bowman's capsule.
Describe the journey of plasma/solute that is filtered from the plasma. The blood enters the afferent arteriole and its diffuse capillary bed under pressure from each ventricular systole and each peristaltic movement, which is sufficient to cross the basement membrane of Bowman’s capsule. The filtered plasma travels through the glomerulus/capsule and the proximal convoluted tubule in the cortex, then the loop of Henle in the medulla, before returning to the distal convoluted tubule in the cortex, and emptying via collection ducts into collection tubules and eventually the renal pelvis, after much reabsorption and secretion of course.
Complete the equation regarding renal excretion. Excreted = ... filtered + secreted - reabsorbed
Urine osmolarity is the sum total of...? The solutes involved.
What does hypotonic urine require for its production? Hypotonic urine requires Na+ reabsorption independent of H2O, which is achieved via Na+-pumps in the distal convoluted tubule, which is impermeable to H2O.
What does hypertonic urine require for its production? Hypertonic urine, in which H2O reabsorption independent of Na+ occurs, is more difficult. Once filtered, the H2O is technically outside the body, so osmotic forces are required – a hypertonic area inside the body - to set up an H2O concentration gradient. This area is the medullary interstitium, maintained by the loop of Henle. There is a very low water concentration in the medulla (maintained by solutes pumped out) so the H2O concentration is higher in the tubule, forcing it to move out into the interstitium independently of solutes in the tubule.
How is urine composition controlled? Hormonally (via renin-angiotensin, aldosterone etc).
Which hormone is involved in the production of hypertonic urine? Anti-diuretic hormone (ADH).
Where is ADH released from? The posterior pituitary (neurohypophysis).
Which sensory cells are involved in the release of ADH? Osmoreceptors in the hypothalamus (specialised cells sensitive to H2O movement which swell or shrink in response to this and their activity is altered because they are nerve cells) and volume receptors in the right atrium.
How does ADH aid H2O reabsorption independent of Na+? It acts to make the tubules more permeable to H2O.
How does atrial natriuretic peptide (ANP) act to reduce blood pressure? When stretch receptors in the right atrium of the heart are activated by large volumes being returned to it, ANP is released from the atrium. It inhibits Na+ reabsorption, causing its excretion, which H2O follows down a concentration gradient, thus lowering the circulating volume and blood pressure.
Which hormone is involved in the production of hypotonic urine? How does it aid this? To generate hypotonic urine, in which Na+ is reabsorbed independent of H2O, aldosterone is released from the adrenal cortex, where it acts on the kidneys to stimulate Na+ reabsorption via channels. Its release is sensitive to the plasma osmolarity and to angiotensin.
Where is renin released from? The kidneys.
Angiotensin release is sensitive to what? Blood pressure and plasma osmolarity.
Which aspect of the nephron is the renin-angiotensin system based around? The juxtaglomerular apparatus.
Which cells is renin released from? Renin is released from granular juxtaglomerular cells on the afferent and efferent arterioles, smooth muscle cells which no longer stretch/contract but secrete renin.
What is renin release sensitive to? Stretch (physical pressure), sympathetic stimulation, and hormones in the blood.
Which nephron structures is the distal convoluted tubule located between? The glomerulus, and the afferent and efferent arterioles.
Where are the macula densa cells located? In the distal convoluted tubule.
What do the macula densa cells do? Feedback on the production and release of renin, with regard to the blood volume and pressure.
What is significant about the placing of the granular juxtaglomerular cells in the afferent and efferent arterioles and the macula densa cells in the distal convoluted tubule? Given their close proximity but very different functions, the macula densa cells can easily feedback on the effect of the renin release by the granular juxtaglomerular cells. The afferent arteriole possesses the majority of the granular juxtaglomerular cells, and responds to the stretch of the blood volume passing through. The renin release will increase Na+ reabsorption and therefore H2O reabsorption, restoring blood pressure. The macula densa cells can feedback to the granular juxtaglomerular cells as to how effective this has been, and whether the response should be prolonged or reduced.
What is the substrate of the renin-angiotensin system? Angiotensinogen.
Which signs of lowered blood pressure do the granular juxtaglomerular cells release renin in response to? Decreased renal perfusion pressure – baroreceptor, decreased Na+ at macula densa cells, and increased sympathetic nerve activity – β1.
What does renin do to angiotensinogen, which is present in the blood? It cleaves the last 10 amino acids from angiotensinogen to form angiotensin I.
Which enzyme converts angiotensin I to the octopeptide angiotensin II? Angiotensin converting enzyme (ACE).
Which enzyme converts angiotensin II to angiotensin III? Aminopeptidase.
List some physiological effects of angiotensin II which support blood pressure. Vasoconstriction; direct renal sodium retention; aldosterone secretion (H2O reabsorption following Na+ reabsorption); increased thirst; anti-diuretic hormone release; sympathetic activity facilitation to act on heart/vessels; increased cardiac contractility; and long-term cardiac and vascular hypertrophy.
Which hormones are released to support/raise blood pressure? Anti-diuretic hormone, aldosterone, renin/angiotensin, and adrenaline.
Which hormone helps to reduce blood pressure? Atrial natriuretic peptide (ANP).
What is renal clearance? The volume of plasma from which a substance is removed, per unit time (typically ml/min).
What is the renal clearance of urea? Curea = 60ml/min : every minute, 60ml of plasma is cleared of urea.
What are the assumptions made when calculating renal clearance? That all substances in the urine come from the plasma, that blood flow into the kidney is equal to blood flow out of the kidney (given that a tiny amount of plasma is lost), and that if a substance appears in the urine the kidneys must have reduced its plasma concentration (i.e. venous concentration < arterial concentration).
What does (U x V) / (P x T) stand for? What does it calculate? (urinary concentration of analyte x volume of urine) / (plasma concentration of analyte x time taken for urine to accumulate or be collected). This equation calculates the rate at which a volume of plasma has been cleard of the analyte.
How would you calculate the total amount of the analyte excreted? Urinary concentration of the analyte x urinary volume
How would you calculate the minimum volume of plasma that could have supplied the mass of excreted analyte? (urinary concentration x urinary volume) / plasma concentration
Creatinine is filtered but not secreted or reabsorbed. True or false? True!
If creatinine is filtered but not secreted or reabsorbed, what is its clearance equal to? The glomerular filtration rate.
What is the glomerular filtration rate? ~120 ml / min.
If a substance undergoes net reabsorption, how will its clearance relate to the glomerular filtration rate? Its clearance will be less than the glomerular filtration rate.
Why is urea, a waste product of protein degradation, reabsorbed? For the hypertonicity of the renal medulla.
If a substance undergoes net secretion, how will its clearance relate to the glomerular filtration rate? Its clearance will be more than the glomerular filtration rate.
What is para-aminohippurate (PAH) used for? PAH is filtered and fully secreted but not reabsorbed, and so its clearance is equal to the renal plasma flow, which it is used to asses, as well as to calculate renal blood flow.
What is the equation used to calculate renal blood flow? Renal blood flow = renal plasma flow / (100 – packed cell volume) * 100
What must be known in order to calculate renal blood flow? Renal plasma flow (established by measuring the clearance of PAH), the volume of erythrocytes in the blood, and the proportion of blood volume taken up by erythrocytes, the packed cell volume or PCV).
What is an osmole? A mole of particles, whatever they are (different compounds).
Roughly, what is the normal osmolarity of the plasma? ~300 mOsm (milli osmoles / L)
What does the osmolarity of plasma reflect? What does it determine? It reflects the concentration of all solutes dissolved in it, and this determines the water concentration and water movement by osmosis.
Why are osmoles used instead of the molarities of glucose and NaCl? Because both are present and both have different molarities, and both have a similar effect on water, so they must be considered together, equally, which is best done by using the non-discriminatory measurements of osmoles.
What can be used to calculate the osmolarity of urine and plasma? What is the principle behind this? A Freezing Point Depression Osmometer can be used to establish the osmolarity of these fluids. Each solute lowers the freezing point of water in a known and constant way, and so the difference between the fluid and the normal freezing point of water is telling of its osmolarity.
What is osmolar clearance? The volume of plasma completely cleared of solutes in a given time.
Having established the osmolarity of urine and plasma, what other information would be needed to calculate the osmolar clearance? According to (U x V) / (P x T), the volume of the urine and the time taken to accumulate/collect it is necessary to calculate the rate of clearance.
If you produce 100ml of 300 mOsm (isotonic) urine, what is the minimum volume of plasma that must have been cleared? 100ml (because it is isotonic).
If you produce 100ml of hypotonic urine (~125 mOsm), what is the minimum volume of plasma cleared? What is the free water clearance? If you produce 100ml of hypotonic urine (e.g. 150 mOsm), then the osmolar clearance is 50 ml/hour (the smallest volume of plasma required to account for all the solutes in that 100ml of hypotonic urine is 50ml). The other 50ml is ‘free’ water – it is positive free water clearance. You can see that the kidneys are ‘dumping’ water, because only 50ml of the urine was required for the solutes, the other 50ml is ‘free’ and so may have been ‘dumped’ if blood pressure was too high, for example.
If you produce 100ml of hypertonic urine (~600 mOsm), what is the minimum volume of plasma cleared? What is the free water clearance? If you produce 100ml of hypertonic urine (e.g. 600 mOsm) per hour, then the osmolar clearance is 200ml/hour. The urine is twice as ‘strong’ as the isotonic plasma, so twice the volume of plasma would be required to supply those solutes. Given that 200ml has been cleared, but only 100ml has been excreted, the remaining 100ml is ‘free’ water – but this is negative free water clearance, as it is retained in the body.
What is the equation for calculating free water clearance? free water clearance = urine production rate - osmolar clearance
Generally, are we in positive or negative free water states? Why? We are mainly in positive free water states, because we are well hydrated so water is excreted rather than retained.
What is the filtration fraction? The filtration fraction is the proportion of the plasma that is filtered when it flows through the glomerular capillaries. This is ~20%.
What isn't all plasma filtered at the kidneys, rather than just the filtration fraction? The full amount can’t be filtered, or only the erythrocytes would be left in the vessels and blood would be too viscous to flow. ~80% is unfiltered, and serves to dilute the erythrocytes.
Why is urine 'naturally' acidic? Because we produce acids all the time, many are non-volatile, and urine is their primary mechanism of excretion, so many are present in urine.
What is titratable acidity? Titratable acidity is the amount of alkali required to bring urine pH back to 7.4 (the more acid excreted, the more base required to return urine to pH 7.4).
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