11. Uro-Genital System (TT) Flashcards

Question

Describe the basic underlying process by which absorption across epithelia occurs.

Answer 1

Ussing model: * The model relies of the asymmetrical expression of membrane transport proteins: * Basolateral membrane -\> High permeability to potassium ions + Presence of Na⁺/K⁺-ATPase * Apical membrane -\> High permeability to sodium * The driving force is the active movement of sodium out across the basolateral membrane by the Na⁺/K⁺-ATPase * This causes sodium to diffuse into the cell across the apical membrane * Potassium moved in by the Na⁺/K⁺-ATPase can easily diffuse out across the basolateral membrane * The unilateral movement of sodium is used to drive the movement of other solutes: * This depends on the selection of transport proteins (e.g. co-transporters) on the membranes * The composition of these proteins depends on the cell type

Answer 2

Basolateral membrane has the properties of a regular cell: * Na⁺/K⁺-ATPase * K⁺ leak channels (high permeability to potassium, P_K) * Low permeability to sodium (P_Na) * Ca²⁺-ATPase * Cl^- x OH^- exchanger * Hormone receptors Apical membrane on the other hand: * High P_Na * May also contain specialised transport systems adapted to the functions of specific tissues

Answer 3

* Apical -\> High P_Na * Basolateral -\> LowP_K

Answer 4

Tight: * Na+ channels Leaky: * Na⁺-glucose symport * Na⁺-amino acids symport * Na⁺/K⁺/2Cl^-symport (kidney) * Na⁺ x H⁺ antiport (kidney)

Answer 5

* Inhibited -\> By amiloride (a diuretic) * Regulated -\> By aldosterone

Answer 6

* Na⁺/K⁺-ATPase sets up sodium gradient across basolateral membrane and also across the apical membrane * Sodium can diffuse across the apical membrane into the cell * This is used by a sodium-linked glucose transporter (SLGT) to transport glucose into the cell by secondary active transport * The glucose can then diffuse across the basolateral membrane through GLUT transporters

Answer 7

* Tight epithelia have a very low water permeability becasue there is very little paracellular transport, so all transport must go through cells * In the collecting duct, there is the possibility of switching on water permeability by ADH, which causes insertion of aquaporins into the apical membrane * (Note: The basolateral membrane always contains aquaporins, so all control is at the apical membrane)

Answer 8

* Leaky epithelia have a very high water permeability: * Mainly due to lots of transcellular transport through aquaporin I and III channels, which there are lots of * There is also a lot of paracellular transport due to less complex tight junctions between cells * Permeability cannot be regulated

Answer 9

* In tight epithelia, the only channels are sodium channels, so the membrane potential is close to the Nernst potential for sodium ions * E_Na = nRT/F (log [Na]_mucosa/[Na]_cell) * In leaky epithelia, the situation is complicated by the presence of other transport proteins (such as co-transporters) and the shunt

Answer 10

* There are two electrogenic forces: * Na⁺/K⁺-ATPase * Leak of potassium out of the cell through channels * E_BLM= E_K + E_pump * Where EK = nRT/F (log [K]_serosa/[K]_cell) Note: The electrogenic effect of the ATPase is relatively small, so the membrane potential is approximated to the Nernst potential for potassium.

Answer 11

It is the sum of the apical and basolateral membrane potentials: E_T-E= E_AM + E_BLM This approximates to the Nernst equilibrium potential for sodium plus the Nernst equilibirium potential for potassium.

Answer 12

* Na⁺/K⁺-ATPase pumps sodium out of the cell at the basolateral membrane as per usual * The Na⁺/K⁺/2Cl^- symport utilises this gradient to move chloride ions into the cell at the basolateral membrane * Cl^- ions exit passively into the lumen down the chemical gradient via Cl^- channels * This sets up a negative p.d. in the lumen * K⁺ recycles across the basolateral membrane * Na⁺ ions move passively across the epithelium via the paracellular pathway, driven by the transepithelial p.d. * Together, the sodium and chloride draw water into the lumen down an osmotic gradient.

Answer 13

* The nephron is the microscopic structural and functional unit of the kidney. * It is composed of a renal corpuscle and a renal tubule. * The renal corpuscle consists of a tuft of capillaries called a glomerulus and an encompassing Bowman's capsule. * The renal tubule extends from the capsule.

Answer 14

* It is a capillary knot * It is supplied by an afferent capillary and drained by an efferent capillary

Answer 15

* The part of the nephron that wraps around the glomerulus and carries out filtration * It is connected to the PCT of the renal tubule Note: It is also known as the glomerular capsule.

Answer 16

* Blood flows through an afferent capillary into the glomerulus * Blood exits the glomerulus via an efferent capillary * Blood then returns to the renal vein via paratubular capillaries (that run alongside the renal tubule) and vasa recta (that wrap around it)

Answer 17

* It is a glomerulus along with the Bowman's capsule that surrounds it * It is the blood-filtering component of the kidney

Answer 18

The space within the Bowman's capsule, connected to the renal tubule.

Answer 19

There are 3 main processes: * First, the Bowman's capsule filters blood from the glomerulus -\> Blood cells and proteins remain in the blood * Next, there is reabsorption of solutes and water from the renal tubules into the blood * There is also secretion of solutes from the blood into the tubular fluid

Answer 20

The filtration of a clear fluid (free from blood cells and proteins) is filtered from the glomerulus into the Bowman's capsule.

Answer 21

* Bowman first described the microscopic structure of the glomerulus in 1842 * Ludwig proposed the theory of capillary ultrafiltration in 1844 * Wearn and Richards obtained the first samples from Bowman's space by micropuncture in 1921-\> Showed that the filtrate in the Bowman's space is identicle to plasma but lacks proteins

Answer 22

Note: In the diagram on the left you can see a part of the ascending limb of the loop of Henle, which passes close to the afferent arteriole.

Answer 23

* Podocytes -\> Modified epithelial cells that wrap around capillaries of the glomerulus. * Mesangial cels -\> Modified smooth muscle cells that are interwoven with the glomerulus Together they support the structure and function of the glomerulus (i.e. in filtration).

Answer 24

Ascending loop of Henle

Answer 25

Macula densa

Answer 26

* High permeability to water * Low permeability to proteins * Pressure is very high (45mmHg) and regulated by constriction of afferent and efferent arterioles

Answer 27

It is the juxtaglomerular apparatus: * AA - Afferent arteriole * EA - Efferent arteriole * M - Mesangial cells * P - Podocytes * FP - Foot processes (of podocytes) * PE - Epithelial cells of Bowman's capsule * BS - Bowman's space * PT - Proximal tubule * MD - Macula densa

Answer 28

* Capillary endothelial cells * Endothelial basement membrane * Foot processes of podocytes (epithelial cells)

Answer 29

Fenestrated (60nm holes)

Answer 30

It is rich in negatively-charged glycosaminoglycans.

Answer 31

* They are found wrapped around the capillaries in the glomerulus * They have foot processes that wrap around the capillary and end in pedicels that interdigitate, forming slit pores * They form the 3rd layer of filtration that solutes must get through in glomerular filtration

Answer 32

* They are smooth muscle cells are interwoven with the capillaries in the glomerulus * They can contract to modify the surface area of the capillaries, controlling the rate of glomerular filtration

Answer 33

* CL is the capillary lumen * The layer above it with gaps is the fenestrated capillary lumen * The dense band above that is the basement membrane * The triangular structures above that are the foot processes and pedicels -\> Arrows indicate pores * CB is the Bowman's capsule

Answer 34

* A negatively charged mesh of proteins called nephrins * The gaps between the nephrins create slit pores, which are the final filtration unit

Answer 35

* Size * Shape -\> Need to fit through slit pores (although of similar size, haemoglobin is better filtered than albumin) * Charge -\> Negative charge reduces filterability

Answer 36

* Molecular weight: ~68kDa * Molecular radius: ~4nm

Answer 37

* Negative charge reduces permeability * This is due to the: * Negative basement membrane (GAGs) * Negative nephrins between podocytes

Answer 38

* Endothelial layer -\> Only a barrier for cells * Basement membrane -\> Negative charges repel negatively-charged macromolecules such as albumin * Epithelial podocyte layer with filtration -\> Also negatively charged and contributes to the barrier

Answer 39

* Where damage to basement membrane occurs, and proteinuria results * This illustrates the importance of the basement membrane in filtering out proteins

Answer 40

Starling forces

Answer 41

Note: It is oncotic pressure, not osmotic. This is because it is dependent on the proteins, since all of the other solutes should be the same on each side of the filter.

Answer 42

Towards Bowman's space: * P_GC = hydrostatic pressure in capillary * Π_BS = oncotic pressure of filtrate in Bowman's space Towards glomerulus: * P_BS = hydrostatic pressure in Bowman's space * Π_GC = oncotic pressure of glomerular capillary plasma

Answer 43

* Π_BS (oncotic pressure of filtrate in Bowman's space) * It approximates to 0 because there should be almost no proteins that filter through to the glomerular space

Answer 44

Net filtration pressure (P_UF) = (P_GC + Π_BS) -(P_BS + Π_GC) Where: * P_GC = hydrostatic pressure in capillary * Π_BS = oncotic pressure of filtrate in Bowman's space * P_BS = hydrostatic pressure in Bowman's space * Π_GC = oncotic pressure of glomerular capillary plasma

Answer 45

* Glomerular filtration rate * It is the rate at which the glomerular filtrate is produced

Answer 46

Rate of formation of filtrate (GFR) = K_f x P_UF Where: * K_f= Filtration coefficient = Permeability x Surface area * P_UF= Net filtration pressure = (P_GC + Π_BS) - (P_BS+ Π_GC)

Answer 47

* High hydrostatic pressure in capillary * Drainage of the filtrate into the renal tubule This helps maintain a pressure gradient across the filter.

Answer 48

The efferent arteriole is more constricted than the afferent.

Answer 49

Ultrafiltration -\> This is where hydrostatic pressure forces a liquid against a semi-permeable membrane..

Answer 50

* The P_BS(hydrostatic pressure of the Bowman's space) is low and constant along the whole length of the capillary * The P_GC (hydrostatic pressure of glomerular capillary) is high and constant along the whole length of the capillary * The Π_BS(oncotic pressure of fluid in Bowman's space) approximates to 0 since very few proteins are in the glomerular filtrate * The Π_GC (oncotic pressure of plasma in glomerular capillaries) increases along the length because as fluid is filtered the remaining proteins become more concentrated * The P_UF (net filteration pressure) decreases along the length of the capillary because Π_GC increases along the length

Answer 51

Point of filtration pressure equilibrium

Answer 52

GFR = K_f x ((P_GC+ Π_BS) - (P_BS + Π_GC)) * P_GC is most important variable -\> Varies with blood pressure and resistance of afferent and efferent arterioles * P_BS may vary if the ureter is blocked (e.g. kidney stones) * K_f (filtration coefficient) -\> Mesangial cells can contract and vary the surface area, which is one of the two variables that K_f depends on

Answer 53

Resistance of afferent and efferent arterioles is regulated by sympathetic nervous system, angiotensin II and by tubuloglomerular feeback.

Answer 54

* Auto-regulation is the way in which renal blood flow and consequently GFR (glomerular filtration rate) remain constant over a relatively wide range of arterial blood pressures * This happens by two main mechanisms: * Myogenic regulation (Bayliss effect) * Tubulo-glomerular feedback

Answer 55

Thi happens by the Bayliss effect: * Increase in pressure stretch arteriole smooth muscle * This causes opening of stretch-mediated channels in the cell membranes -\> This leads to influx of cations and therefore depolarisation * This causes opening of VGCC and entry of calcium -\> This causes contraction of the smooth muscle * Therefore, the resistance increases and so blood flow decreases -\> This maintains the blood flow relatively constant over a range of arterial blood pressures

Answer 56

This is a flow-dependent mechanism: * Macula densa (part of the juxtaglomerular apparatus) in the ascending limb of the loop of Henle detect the flow rate in the loop of Henle (distal flow rate) * If distal flow rate increases (because GFR has increased), the macula densa cell release a signal (adenosine) onto the adjacent afferent arteriole * This causes constriction of the arteriole, which increases the resistance and decreases glomerular pressure, so GFR is reduced

Answer 57

* Clearance is the volume of plasma from which substance X is completely removed. * This is an idealised variable since plasma is not completely clearance of solutes -\> So you have to think about the minimum volume of plasma that would be contain the amount of the solute that was cleared * For example, 50% of glucose removed from 200ml in a minute of blood is a clearance of 100ml/min

Answer 58

The amount of X removed from the blood = The amount appearing in the urine. It is dependent on: * Freely filtered * Not reabsorbed from the nephron * Not secreted into the nephron * Not metabolised or synthesised by the kidney

Answer 59

ml/min (the same as GFR)

Answer 60

C = (U x V) / P Where: * C = Clearance (ml/min) * U = Concentration of solute in urine (mmol/ml) * V = Volume of urine produced per unit time (ml/min) * P = Concentration of X in the plasma (mmol/ml)

Answer 61

* Inulin and creatine * This is because they obey all of the rules underlying the assumption that the excretion rate of the marker is equal to the removal rate of the marker at the kidneys (e.g. they are not secreted into the nephron)

Answer 62

The concentration of it in the blood will be reduced (U), so the value for GFR will be too low.

Answer 63

* It is the fraction of the fluid reaching the kidneys that gets taken up into the Bowman's capsules * It is equal to the the ratio of the glomerular filtration rate (GFR) to the renal plasma flow (RPF). * It is normally about 20%.

Answer 64

* Bowman's capsule * Proximal tubule * Descending limb of loop of Henle * Ascending limb of loop of Henle * Distal tubule * Collecting duct

Answer 65

The proximal tubule is a leaky epithelium and then the epithelia become progressively tighter until at the collecting duct it is very tight. This means that further down the tubule is more subject to hormones like aldosterone and ADH.

Answer 66

* Bowman's capsule -\> Ultrafiltration of water and solutes from the plasma, leaving proteins and blood cells in the blood * Proximal tubule -\> Reabsorption of everything that is needed back into the interstital fluid (so it can go into the blood) * Rest of nephron further further down stream -\> Fine tuning of urine composition to maintain body homeostasis

Answer 67

No, it reabsorbs them into the interstital fluid, from which they can diffuse into the blood (CHECK THIS!)

Answer 68

* The second approach would require transporters for any solute that would need to be filtered out at any point -\> By using the "filter and reabsorb" method, everything can be filtered out and then only transporters for specific essential nutrients are required for reabsorption * Also, water cannot be moved out using a transporter, so the "filter and reabsorb" method uses that fact that water follows solutes that are filtered, and then only reabsorbes the water * Also, it is energetically advantageous, since many other solutes can be recovered in association with the reabsorption of Na⁺

Answer 69

Reabsorption into the blood via the interstitial fluid (where the basolateral side is on the side of the blood).

Answer 70

* It is a bulk reabsorber of solutes into the interstital fluid (since it is a leaky epithelium * It uses carrier proteins in conjunction with an Na⁺ gradient to allow for this reabsorption Reabsorbed from filtrate into the interstitial fluid: * Using carriers -\> Na⁺, Cl^-, HCO₃^-, Ca²⁺, Glucose, Amino acids (+ maybe PO₃^- - Check this) * By osmosis (via paracellular pathway and aquaporins) -\> Water * By solvent drag (i.e. carried by the osmotic water) -\> K⁺, Ca²⁺, Mg²⁺ Secreted into the filtrate: * Organic anions and cations (endogenous and exogenous) -\> e.g. uric acid + penicillin (mentioned in spec)

Answer 71

* It is involved in the reabsorption of water and ion from the filtrate, as well as establishing an osmotic gradient in the interstitial fluid that is used to extract water from the collecting duct later along the nephron DESCENDING LIMB Reabsorbed from filtrate into interstitial fluid: * Through channels -\> Water ASCENDING LIMB: Reabsorbed from filtrate into interstitial fluid: * By carriers -\> Na⁺, Cl^-, HCO₃^- * Via paracellular route -\> Na⁺, K⁺, Ca²⁺, Mg²⁺

Answer 72

* The end of the nephron is involved in fine tuning the urine composition to maintain body homeostasis, including diluting the urine appropriately EARLY DISTAL TUBULE Reabsorbed from filtrate into the interstitial fluid: * Using carriers -\> Na⁺, Cl^- LATE DISTAL TUBULE AND COLLECTING DUCT Reabsorbed from filtrate into the interstitial fluid: * Through channels -\> Na⁺, Water * Using carriers -\> Urea Secreted into filtrate: * Using carriers -\> H⁺ * Through channels -\> K⁺

Answer 73

Descending has a higher water permeability.

Answer 74

* At first, they are mostly carriers, then they are mostly channels further along the nephron. * The paracellular route becomes less significant further down the nephron.

Answer 75

* All one cell type * Have brush-border microvilli * Form a leaky epithelium

Answer 76

* S1 + S2 -\> Convoluted tubule * S3 -\> Straight tubule

Answer 77

* High permeability to ions -\> Shunt leads to low potential difference * High permeability to water

Answer 78

* Reabsorbs all organic solutes (e.g. glucose) * Reabsorbs 2/3 of salt and water * It does this isotonically, meaning that at any point in the tubule you cannot detect an osmotic gradient

Answer 79

It works by the Ussing model: * Active Na⁺ transport out of the cell by Na⁺/K⁺-ATPase on basolateral membrane underlies transport * It creates a sodium gradient across the apical membrane * Na+ absorption is coupled to absorption of most organic solutes and anions, and to H₂O

Answer 80

First half of proximal tubule: * Na⁺ uptake coupled with: * Organic solutes (glucose, amino acids) * Phosphate * Bicarbonate Second half of proximal tubule: * Na⁺ uptake coupled with Cl^-

Answer 81

* SGLT (sodium-glucose linked transporter) with 2 isoforms: * SGLT2 -\> In S1 and S2 -\> 1 Na⁺ per 1 glucose * SGLT1 -\> In S3 -\> 2 Na⁺ per 1 glucose (greater power to go against concentration gradient Note: These are specific to D-glucose.

Answer 82

* T_m= Transport maximum -\> This is because glucose reabsorption is mediated by carrier proteins, so there is a maximum rate at which the glucose can be reabsorbed from the filtrate * If the plasma glucose is above the threshold, all of it will be filtered into the filtrate, but not all of it will be reabsorbed back into the blood, so some is excreted -\> This is the glucose overspill

Answer 83

200mg of glucose per 100ml of plasma

Answer 84

* It is the same process as with glucose (Ussing model), except for the use of different transporters on the apical membrane. * There are at least 4 distinct symporter types for: * Cationic (basic) amino acids (lys, arg, his, sys) * Anionic (acidic) amino acids (asp, glu) * Neutral amino acids (ala, val, leu, ser, thr) * Glycine and imino acids (gly, pro, hydroxypro * These are stereospecific for L-amino acids

Answer 85

* A defect in the cationic amino acid symporters on the apical membrane of the proximal tubule * Cystinuria predisposes to formation of kidney stones

Answer 86

It uses a slightly different mechanism to the typical Ussing model: * Hydrogen ions in the cell are transported into the tubule lumen by a sodium-hydrogen antiporter or H⁺-ATPase * Bicarbonate (HCO₃^-) in the tubule lumen reacts with the H⁺ ions to form carbonic acid (H₂CO₃) * Carbonic anhydrase on the apical membrane of the cells catalyses the breakdown of carbonic acid intoCO₂and H₂O, which can diffuse into the cell * Carbonic anhydrase now recombines CO₂ and H₂O into carbonic acid, which dissociates into bicarbonate and H⁺ * Carbonic acid now moves across the basolateral membrane by one of two ways: * Na⁺/3HCO₃^- symporter -\> This is unusual because it goes against the sodium gradient set up by the Na⁺/K⁺-ATPase, but it is down the gradient of the bicarbonate, so the 3:1 ratio allows this to happen * Cl^-/HCO₃^-antiporter

Answer 87

There are 2 pathways: * Paracellular * Via tight junctions and lateral intercellular space * Passive movement down electrochemical gradient, since the interstitial fluid is now positive from prior reabsorption of cations (electrical gradient) and there is also a chemical gradient due to prior osmotic movement of water concentrating the chloride * Transcellular * Hydrogen ions are moved out of cell across apical membrane by Na⁺/H⁺antiport * The hydrogen ions are used to move bicarbonate across (see other flashcard), but once they are all used up, the H⁺can react with anions (formate, HCOO^-) to form an uncharged complex * The uncharged complex can diffuse across the apical membrane into the cell, before splitting back into the H⁺ and anion * H⁺ ion recycles back into Na⁺/H⁺ antiport * Anion goes into anion/Cl^- antiport, moving the Cl^- into the cell * Note that the coupling of these two antiports means that essentially the sodium diffusion gradient is used to pump the chloride across the membrane, just like in the other transport processes, but indirectly. * Chloride moves across basolateral membrane through the K⁺/Cl^-symport

Answer 88

It is unusual because it does not rely on the sodium gradient established. It can move in one of two ways: * Paracellularly by solvent drag * Transcellularly * Diffuse across the apical membrane into the cell down its concentration gradient via channels (ECaC - Epithelial calcium channels) * Ca²⁺ moves across the cytosol bound to calcium-binding proteins * It moves across the basolateral membrane by two transporters: * Calcium ATPase * Ca²⁺/3Na⁺ antiporter *

Answer 89

* Proximal tubule, Ascending loop of Henle, Distal tubule * Stimulated by: Parathyroid hormone (PTH), Vitamin D

Answer 90

For example, PAH (para-amino hippurate): * Sodium gradient across the basolateral membrane (established by Na⁺/K⁺-ATPase) is used by a sodium/anion symport to accumulate the anion in the cell * This creates an outwards anion gradient across the basolateral membrane * The gradient is utilised by a PAH^-/anion antiport to move PAH^-into the cell * PAH^-is moved across the apical membrane into the renal tubule lumen by another PAH^-/anion antiport

Answer 91

* PAH secretion is a transporter-mediated process, so it can be saturated. * The maximum rate of secretion is the T_m. Clinically, clearance of PAH can be used to estimate RBF (renal blood flow): * Below the point when the secretion mechanism becomes saturated, all of the PAH that enters the kidneys ends up in the urine (1/5th by filtration and 4/5th by secretion) * Therefore, by calculating the clearance gives an estimate for the blood flowing through the kidneys (RBF)

Answer 92

* GFR (glomerular filtration rate) -\> The rate at which the glomerular filtrate is produced * RBF (renal blood flow) -\> The blood flow through the kidneys

Answer 93

* Filtration = 1/5th * Secretion = 4/5th

Answer 94

The y-axis is the ratio of the concentration of the solute in the TF to its concentration in the plasma.

Answer 95

* The transepithelial p.d. changes sign along the length of the proximal tubule, as a result of reabsorptive processes: * In S1, the lumen is negative (-2mV) -\> Due to Na⁺reabsorption * In S2 and S3, the lumen is positive (+2mV) -\> Due to Cl^- reabsorption * In S2, the lumen positivity drives passive Na⁺ reabsorption via paracellular route (accounts for up to 30% of Na⁺ reabsorption)

Answer 96

* No, there is also a large amount (about 30%) of absorption by the paracellular route. * This is driven by the positivity of the lumen

Answer 97

* Water moves passively down its concentration gradient, which is set up by the prior movement of ions and other solutes into the transcellular space * This occurs via: * Paracellular route -\> Through the leaky tight junctions * Transcellular route -\> Cells express lots of aquaporins

Answer 98

* There is no discernible osmotic difference between the lumen and interstitial fluid, so absorption appears ‘isotonic’ * This is because the leaky epithelium is highly permeable to water (since it is leaky and has lots of aquaporins), so only a small osmotic gradient is required to drive water movement and any gradients are quickly minimised

Answer 99

* Aquaporin I * About 90% of water reabsorption in the proximal tubule occurs through these (other 10% is through paracellular route)

Answer 100

* Loop of Henles -\> Involved in concentrating the interstitial fluid near the distal tubule and collecting duct, so that there is an osmotic gradient for water reabsorption there if necessary. * Distal tubule + Collecting duct -\> Involved in concentrating the urine and control of ion content of the urine.

Answer 101

* The proximal tubule involves isoosmotic processes, so the osmolarity remains at 300mOsm/L, but there is removal of solutes and water, so the flow rate falls from 125ml/min to 45ml/min. * The descending limb of the loop of Henle removes water, causing the flow rate to decrease, and concentrates the filtrate to about 1200mOsm/L. * The ascending limb removes solutes, causing a reduction in the osmotic potential to around 100mOsm/L. The flow rate out of the LOH (due to removal of water in the descending limb) is around 25ml/min. * If ADH is present, water removal occurs in the distal tubule and collecting duct, so that the filtrate is more concentrated and the flow rate is lower. * If ADH in not present, the filtrate remains relatively unchanged.

Answer 102

Diluting segment

Answer 103

* Daily water intake = 2500ml * Loss in sweat, faeces and airways = 1000ml Therefore, around 1500ml per day are lost in the urine, although this value depends on changes to the intake and loss pathways.

Answer 104

30 - 1200mOsM

Answer 105

Dilute, because the daily intake typically greatly exceeds the daily loss.

Answer 106

* A countercurrent system in the loop of Henle concentrates the interstital fluid and creates an osmotic gradient for water movement out of the distal tubule and collecting duct * Regulation of the distal tubule and collecting duct then determines whether this gradient is used to reabsorb water from the filtrate

Answer 107

* The loop of Henle * Comparison of the length of loops between different species shows that the longer the loop, the more concentrated the urine

Answer 108

Where there is a hairpin, so that the flow in one limb is in the opposite direction to the other limb.

Answer 109

* Loop of Henle * This is a countercurrent MULTIPLIER * Which is a mechanism that expends energy to CREATE a concentration gradient. * Vasa recta * This is a countercurrent EXCHANGER * Which is a mechanism in which opposing flow MAINTAINS a concentration at all points along the exchanger.

Answer 110

* Diuresis = water loss * Large volume of dilute (hypotonic) urine * 20l/day, 50mOsm/l * Antidiuresis = water conservation * Small volume of concentrated (hypertonic) urine * 0.5l/day, 1200mosm/l

Answer 111

* Antidiuretic hormone (ADH) Also known as: * AVP * Vasopressin

Answer 112

A condition where your body is deficient in water.

Answer 113

* Principle cells of the collecting duct and distal tubule * It increases the permeability to water, so water moves from the filtrate back to the interstitial fluid (and then the blood) * This is done by the insertion of aquaporin II into the cell membranes of collecting duct cells

Answer 114

It is a 9 amino acid peptide.

Answer 115

* Synthesised in neuroendocrine cells in the (supraoptic and paraventricular nuclei of the) hypothalamus * Transported along the axons * Stored in the nerve terminals in the neurohypophysis (posterior pituitary) Hypothalamus neuroendocrine cells -\> Transported along axons -\> Stored in posterior pituitary

Answer 116

* AQP1 -\> Proximal tubule and descending limb cells. * AQP2 -\> Apical membrane of collecting duct principal cells subjected to ADH * AQP3 and AQP4 -\> Basolateral membranes of collecting duct principal cells

Answer 117

* Binding to a V₂ receptor on the basolateral membrane of principle collecting duct cells * This causes activation of adenylate cycle, which increases cAMP in the cell * This leads to activation of PKA, which phosphorylates several targets * One of the targets are parts of the cytoskeleton associated with the vesicles that contain aquaporins II -\> This phosphorylation causes fusion of the vesicles with the apical membrane, inserting the aquaporins into the membrane * This allows water molecules to enter the cell, after which they can exit via aquaporins III and IV in the basolateral membrane

Answer 118

* A condition characterised by the production of large volumes of dilute urine * Neurogenic diabetes insipidus -\> Failure of ADH release * Nephrogenic diabetes insipidus -\> Aquaporin insertion into the membrane, or a mutation in the aquaporin gene

Answer 119

* Thin ascending limb -\> The lower part of the ascending limb, with thin cells that lack mitochondria * Thick ascending limb -\> The upper part of the ascending limb, with thick cells that have mitochondria

Answer 120

* Descending loop of Henle * High permeability to water * Impermeable to Na⁺ * Low urea permeability * Thin ascending loop of Henle * Impermeable to water * High Na⁺ permeability * Low urea permeability * Thick ascending loop of Henle * Impermeable to water * Some Na⁺ permeability -\> Due to active transport of Na⁺ * Low urea permeability

Answer 121

* Distal tubule / Outer medullary collecting duct * Inner medullary collecting duct

Answer 122

Distal tubule/outer medullary collecting duct: * Water permeability increased by ADH * Low Na⁺ permeability -\> Due to active transport of Na⁺ * Impermeable to urea Inner medullary collecting duct: * Water permeability increased by ADH * Low Na⁺ permeability -\> Due to active transport of Na⁺ * Urea permeability increased

Answer 123

No, only the thick ascending limb of the loop of Henle (the upper part). This is because there is insufficient ATP production deep in the medulla.

Answer 124

Reabsorption of water in the descending limb of the loop of Henle concentrates the salt in the filtrate and provides a gradient for the passive reabsorption in the thin ascending limb.

Answer 125

* To establish a cortico-papillary interstitial osmotic gradient. * This gradient ensures that there is a concentration gradient between the collecting duct lumen and the interstitial fluid at all points along the collecting duct (for water reabsorption, if required)

Answer 126

* It is the osmotic gradient between the cortex and papilla (in the medulla) of the kidney * It is essentially a gradient from low to high osmolarity as you go from the outside to the inside of the kidney * It is set up by the counter-current multiplication in the loop of Henle

Answer 127

* NKCC co-transport * Urea concentration in the interstitial space

Answer 128

* The active absorption of sodium ions by the thick ascending loop of Henle. * It initiates a series of events that lead to counter-current multiplication

Answer 129

* Na⁺/K⁺-ATPase on the basolateral membrane creates a sodium gradient inwards across the apical membrane * This is used by an NKCC (a carrier that moves 1 sodium, 1 potassium and 2 chlorines) on the apical membrane * The potassium diffuses back out across the apical membrane trhough channels * The sodium is pumped out via the ATPase and chloride also exits on the basolateral side by diffusion through channels * The net result is the absorption of sodium and chloride into the interstitial fluid, so that there is hypertonicity that can be used to extract water from the descending limb

Answer 130

* A carrier that uses a sodium gradient to transport 1 Na⁺, 1 K⁺and 2 Cl^-into cells of the thick ascending loop of Henle across the apical membrane * It can be stimulated by ADH (via V₁ receptors on the basolateral membrane that are coupled to PLC -\> So that the IP₃ cascade leads to phosphorylation of NKCC) * It can be inhibited by loop diuretics, such as furosemide

Answer 131

1) Thick ascending loop of Henle * Active transport of sodium (and diffusion of chloride that follows it) out of thick ascending loop of Henle * Water does not follow because the thick ascending loop is impermeable to water (thus the name 'diluting segment' of the loop of Henle) 2) Descending loop of Henle * Water moves out of the descending loop of Henle due to the hypertonicity of the interstitial fluid created by the thick ascending loop * The filtrate becomes gradually more concentrated 3) Thin ascending loop of Henle * Sodium is able to passively diffuse into the interstitial space There is a snowball effect where this cycle self-reinforces. The resulting axial hypertonicity gradient in the medulla can be used to extract water from the collecting duct.

Answer 132

At the bottom -\> This is the cortico-papillary interstitial gradient.

Answer 133

* ADH increases the permeability of the collecting duct to both urea and water * Urea is responsible for up to 50% of the osmolarity of the inner medullary interstitial fluid * Movement of urea into the interstitial space of the inner medulla near the collecting duct draws water out of the collecting duct, helping concentrate the urine

Answer 134

Animals on low protein diets tend to produce more dilute urine.

Answer 135

* It occurs via facilitated diffusion proteins called UT * This is upregulated by ADH

Answer 136

* The loop of Henle has a low permeability to urea, so the urea can be passively reabsorbed into the renal tubule * This ensures that the urea doesn't pass back into the blood

Answer 137

* NKCC -\> Involved in beginning the snowball effect that concentrates the interstitial fluid with salt * Urea -\> Further concentrates the interstitial space depending on release from the collecting duct (upregulated by ADH)

Answer 138

Both limbs have the same permeability, which is why they are a counter-current exchanger, not a counter-current multiplier.

Answer 139

* Deliver nutrients to the medulla * Remove reabsorbed water

Answer 140

It helps minimise the washing away of solutes in the interstitial fluid by the blood. This helps maintain the gradient for the reabsorption of water from the collecting duct if necessary.

Answer 141

* In the descending limb, the water moves out of the vessel due to the surrounding hypertonic interstitial fluid * Solutes also diffuse into the vessel down their concentration gradient * The gradually makes the blood more concentrated, so after it turns the hairpin loop, solutes diffuse out of the blood into the interstitial fluid and water diffuses back in * This keeps the solutes trapped in the interstitial fluid (which is important), while water is reabsorbed * ADH can slow blood flow, so there is more time for these equilibritive processes to occur

Answer 142

1. Insertion of aquaporins II in collecting duct principle cells 2. Activation of NKCC in thick ascending loop of Henle 3. Activation of urea transporters in the inner medullary collecting duct principle cells 4. Slowing of the blood flow through the vasa recta

Answer 143

* The capacity to separate water absorption from solute absorption * This goes against the natural tendency of water to follow solutes

Answer 144

Water: * ADH -\> Increases water retention Salt: * Angiotensin/Aldosterone -\> Increase sodium retention * ANP (Atrial natriuretic peptide) -\> Decrease sodium retention

Answer 145

* When there is increased intake of sodium, there is increased concentration and osmolarity of body fluid * ADH increases water retention, so concentration falls but volume increases * ANP increases salt excretion (while angiotensin-aldosterone system increases sodium retention, so it is downregulated) * Increased salt excretion leads to lower osmolarity, so ADH is down-regulated and water is not retained * This means that the volume also falls back to normal In this way, the two mechanisms allow maintenance of osmolarity and volume.

Answer 146

* Generally, it remains constant in response to blood pressure, at around 125ml/min, due to the Bayliss effect and tubuloglomerular feedback * However, it CAN change independently of blood pressure -\> For example, if renal plasma flow is reduced

Answer 147

* Yes, the functional activity of each nephron segment depends on what happened in previous segments * There is intrinsic and extrinsic regulation

Answer 148

* Across epithelium into interstitial fluid -\> Active Na⁺ transport provides primary driving force for isotonic fluid movement of solutes and water across epithelium * From interstitial fluid into blood -\> Fluid and solute uptake into peritubular capillaries is driven by Starling forces

Answer 149

* Glomerulotubular balance (DO NOT confuse with tubuloglomerular feedback) * Hormones * Angiotensin II (+ Acidosis) * Parathyroid hormone * Sympathetic nervous system

Answer 150

* The phenomenon whereby a constant fraction of the filtered load of the nephron is resorbed across a range of Glomerular Filtration Rates (GFR) * In other words, if the GFR spontaneously increases, the rate of water and solute resorption in the tubule proportionally increases, thus maintaining the same fraction the filtered load being resorbed.

Answer 151

* The graph shows how delivery to the distal tubule changes as GFR changes * Line 1 is if no reabsorption occured * Line 2 is if reabsorption was always constant * Line 3 is with glomerulotubular balance (reabsorption proportional to GFR)

Answer 152

There are two main mechanisms: * Increased GFR causes greater rate of transport by symports (e.g. Na⁺-glucose) * Starling forces determine balance of uptake into capillaries vs paracellular backflux into tubule lumen

Answer 153

No, some backflux occurs into the lumen of the tubule (shown by arrow 3). This is typically much less than the reabsorption into the blood (arrow 2).

Answer 154

* Efferent arteriole dilation reduces GFR, but increases hydrostatic pressure in the efferent arteriole * This means that the Starling forces are altered and there is less reuptake into the blood and more backflux into the lumen of the proximal tubule * As a result, the drop in GFR does not cause such a large drop in the flow of filtrate into the distal tubule (i.e. a roughly constant delivery of filtrate to the distal tubule occurs at all GFR values)

Answer 155

About 2/3rds

Answer 156

Na⁺/H⁺ exchanger on the basolateral membrane: * Stimulated by angiotensin II, acidosis and sympathetic nerves (by activation of adenylate cyclase) * Inhibited by parathyroid hormone (by inhibition of adenylate cyclase) The exchanger is involved in the reuptake of bicarbonate and then chloride ions from the tubule lumen. The parathyroid hormone is involved in increasing calcium reuptake in times of hypocalcaemia. Sympathetic stimulation is important in raising blood pressure (e.g. in response to haemorrhage).

Answer 157

* Na⁺/H⁺ exchanger on the basolateral membrane is stimulated by sympathetic activity, increasing sodium reuptake. * This is important to raise blood pressure (since water follows the Stimulated by angiotensin II and acidosis (by activation of adenylate cyclase) Inhibited by parathyroid hormone (by inhibition of adenylate cyclase) The exchanger is involved in the reuptake of bicarbonate and then chloride ions from the tubule lumen.

Answer 158

* Load-dependent absorption * Hormones * ADH * Aldosterone * Glucocorticoids

Answer 159

NKCC transport protein is stimulated by: * ADH * Aldosterone * Glucocorticoids These therefore increase sodium reabsorption.

Answer 160

The reabsorption is essentially dependent on the flow rate: * If the flow rate is increased, there is less time for passive sodium reabsorption in the thin ascending loop of Henle * So more sodium reaches the thick ascending loop of Henle * However, this extra sodium load is dealt with by increased activity of the NKCC ('mopping up') * Increased salt delivery to the macula densa also triggers tubuloglomerular feedback These processes help to ensure that a constant sodium load is delivered to the distal tubule.

Answer 161

It decreases renin release from granular cells in the afferent arteriole wall.

Answer 162

* Distal convoluted tubule -\> Sodium-chloride co-transport reabsorption * Short connecting tubule -\> Calcium reabsorption * Connecting tubule -\> Tight epithelium for Na⁺, Cl^-, K⁺and H⁺ fine tuning * Collecting duct -\> Tight epithelium for Na⁺, Cl^-, K⁺ and H⁺ fine tuning The epithelia along the distal nephron become gradually tighter, so that the transport processes become simpler.

Answer 163

* It continues the reabsorption of the NaCl from the filtrate * It does this using a Na⁺-Cl^-co-transporter on the apical membrane (working in conjunction with the Na⁺/K⁺-ATPase on the basolateral membrane) * It is stimulated by angiotensin II and aldosterone * It is inhibited by thiazides Since the process is carrier mediated, reuptake is proportional to the load.

Answer 164

* Reabsorption of calcium by a similar process to the one in the proximal tubule * It can be upregulated by parathyroid hormone

Answer 165

* Fine tune the composition of the urine by: * Reabsorption of Na⁺ and Cl^-(and sometimes water) * Secretion of K⁺ and H⁺

Answer 166

Principal cells: * Reabsorb about 5% Na⁺ through amiloride-sensitive channels * Reabsorb H₂O (through regulated aquaporin channels) * Secrete K⁺ through channels Intercalated cells: * Passive Cl^- absorption * Active H⁺ secretion

Answer 167

Through amiloride-sensitive sodium channels.

Answer 168

* Reabsorb of Na⁺ through amiloride-sensitive channels * Reabsorb H₂O through regulated aquaporin channels * Secrete K⁺ through channels

Answer 169

Intercalated cells: * Passive Cl^-reabsorption * Active H⁺ secretion (H+ absorption in alkalosis)

Answer 170

* It acts to conserve sodium. * It has the opposite function of ANP.

Answer 171

* Causing a reduction in expanded extracellular fluid volume by increasing renal sodium excretion. * It has the opposite role to aldosterone.

Answer 172

Atrial natriuretic peptide

Answer 173

The hydrogen ions serve to regenerate bicarbonate ions that have been consumed by buffering non-volatile acid.

Answer 174

Effects on the principle cells: * Aldosterone stimulates sodium reabsorption from the tubular fluid * It also stimulates potassium secretion into the tubular fluid, since potassium secretion is proportional to sodium reabsorption (due to the Na⁺/K⁺-ATPase) Effects on the intercalated cells: * Aldosterone stimulates hydrogen secretion from the tubular fluid

Answer 175

* ENaC -\> Epithelial sodium channel * A mutation in ENaC leads to constitutive activation * The pseudohyperaldosteronism which results is called Liddle's disease

Answer 176

A drop blood pressure and fluid volume causes granular cells in the afferent arteriole walls in the kidney to release renin.

Answer 177

Converts angiotensinogen to angiotensin I.

Answer 178

In the liver.

Answer 179

ACE (angiotensin converting enzyme).

Answer 180

In the lungs.

Answer 181

* Causes vasoconstriction * Causes release of aldosterone Other actions: * Stimulates sodium reabsorption at several renal tubular sites * Stimulates ADH release from the posterior pituitary * Stimulates thirst centers within the brain * Enhaces sympathetic activity * Stimulates cardiac hypertrophy and vascular hypertrophy

Answer 182

* Stimulates Na⁺/H⁺ exchangers located on the apical membranes of cells in the proximal tubule and thick ascending limb of the loop of Henle * Stimulates apical Na⁺ channels in the collecting duct

Answer 183

* It is a steroid hormone * Released from the adrenal cortex

Answer 184

It binds to AT1 (angiotensin receptors) on the adrenal cortex.

Answer 185

Principle cells of the collecting duct.

Answer 186

* It binds to a receptor in the cytoplasm * This causes translocation of the receptor to the nucleus * This induces the transcription of proteins that are involved in the reabsorption of sodium from the lumen of the collecting duct: * Epithelial sodium channel (ENaC) * Basolateral Na⁺/K⁺-ATPase * Proteins involved in ATP production * Aldosterone also have must faster effects by increasing the activity of the channels by protein kinases that phosphorylate the transport proteins

Answer 187

* Renin -\> Inhibited by enalkiren * ACE -\> Inhibited by captopril * AT1 receptor -\> Inhibited by saralasin

Answer 188

Spirolactone

Answer 189

* Loss of sodium in the urine * It is stimulated by ANP (atrial natriuretic peptide)

Answer 190

Atria of the heart, when they are stretched.

Answer 191

* It antagonises the renin-angiotensin-aldosterone system, so that blood pressure falls and salt retention is decreased * It does this by raising intracellular cGMP levels

Answer 192

* Afferent arteriole dilation and efferent arteriole constriction -\> Increased GFR * Reduces renin release * Reduces aldosterone release * Inhibits angiotensin II actions in PT and systemic circulation * Reduces ADH release and inhibits ADH actions * Inhibits aldosterone action Overall this results in increased filtration but reduced sodium reabsorption, so salt is lost in the urine.

Answer 193

* Increased osmolarity of the blood. * It can also be affected by changes in blood volume, but much greater changes are required for this to happen.

Answer 194

* Loop diuretics * Thiazide diuretics * Osmotic diuretics * Potassium-sparing diuretics * Carbonic ahydrase inhibitors

Answer 195

* Treatment of heart failure and hypertension (i.e. when a rapid diuresis is needed in emergencies) * Can also be used in the longer term when weaker diuretics (thiazides) are found to be insufficient. * They are also used occasionally to correct some electrolyte disturbances, particularly hypercalcaemia. This is because of a short half-life in the plasma since they are actively excreted in the proximal tubule as well as being filtered at the glomerulus. For chronic conditions, they can be given orally.

Answer 196

Furosemide

Answer 197

* Inhibit the NKCC (Na/K/2Cl transporter) in the thick ascending limb of the loop of Henle -\> This is a site of significant sodium absorption, so sodium reabsorption into the interstitial fluid is reduced * So more sodium remains in the tubule and less is the interstitial fluid, so there is less of an osmotic gradient for water reabsorption in the collecting duct

Answer 198

They are vasodilators of: * Systemic resistance arterioles -\> Useful in lowering arterial pressure in hypertension and in reducing peripheral resistance in cardiac failure * Renal resistance arterioles -\> Useful in increasing GFR and so potentially increasing diuresis * Vasa recta of the renal medulla -\> Resulting in a "washout" of the accumulated osmotically active substances of the medullary interstitium, and so further reducing the osmotic potential there and increasing the potency of the diuresis

Answer 199

* Hypokalaemia * Hypovolemia Both of these are classic diuretic side effects that are discussed on later flashcards. Loop diuretics also result in calcium and magnesium loss, which relates to the loss of the charge gradient normally generated by the NKCC2 pump, as shown in the diagram.

Answer 200

* Uses -\> Heart failure and hypertension (acutely and chronically if needed), Correcting electrolyte balances * Common example -\> Furosemide * Mechanism of action -\> Inhibition of NKCC in thick ascending loop of Henle * Side-effects -\> Hypokalaemia, Hypovolemia, Calcium and magnesium loss

Answer 201

* Treatment of heart failure and hypertension, just like loop diuretics. * Thiazides are less potent than loop diuretics, and are usually used as a first attempt at diuretic therapy, with a switch to loop diuretics if the thiazide's effect is not strong enough.

Answer 202

Bendroflumethiazide

Answer 203

* Inhibit the sodium-chloride symporter (NCC) on the luminal (apical) surface of the distal convoluted tubule. * More sodium therefore remains in the lumen, which causes more water to remain in the lumen, increasing the volume of urine produced.

Answer 204

* Loop diuretics increase calcium excretion * Thiazide diuretics reduce calcium excretion -\> This can be used in treatment of conditions such as stone formation in the urinary tract

Answer 205

* Hypokalaemia * Hypovolemia These are the classic side-effects of diuretics, including loop diuretics.

Answer 206

* Both act by reducing the reabsorption of salt from the renal tubule * However, loop diuretics act on the thick ascending loop of Henle NKCC, while thiazide diuretics act on the distal tubule NaCl transporter * Loop diuretics are more potent and involve a greater loss of potassium

Answer 207

* Uses -\> Heart failure and hypertension, Occasionally in treatment of stone formation in the urinary tract * Common example -\> Bendroflumethiazide * Mechanism of action -\> Inhibition of NaCl transporter in the distal tubule * Side-effects -\> Hypokalaemia, Hypovolemia

Answer 208

Loop diuretics and thiazide diuretics

Answer 209

Directly: * Diuretics cause an increased amount of sodium to remain in the renal tubule (e.g. by inhibition of the NKCC or NaCl transporter) * This means that there is greater reuptake of sodium in the distal convoluted tubule and collecting duct, which requires the Na⁺/K⁺-ATPase that pumps potassium into the urine Secondary effect: * The effects of the diuretic drug activate the juxtaglomerular apparatus, which responds by releasing renin * This leads to the eventual release of aldosterone, which: * Increases activity of the Na⁺/K⁺-ATPase in the distal nephron (a rapid response) * Causes the transcription of more ion channels and transporters (for the luminal surface) and of more Na⁺/K⁺-ATPases (for the basolateral surface) Overall, the increased reuptake of sodium in the distal tubule and collecting duct means that there is a stronger electrochemical gradient for potassium and hydrogen secretion into the urine.

Answer 210

* It increases reuptake of sodium in the distal tubule and collecting duct by various methods (see flashcard) * This means that there is a stronger electrochemical gradient for potassium and hydrogen secretion into the urine.

Answer 211

Secondary hyperaldosteronism

Answer 212

* A disease in which the adrenal glands make too much aldosterone * This leads to hypertension (high blood pressure) and low blood potassium levels.

Answer 213

Loop, because they stimulate greater sodium uptake from the tubular fluid.

Answer 214

A potassium supplement

Answer 215

Alkalaemia (due to increase H⁺ secretion into the urine).

Answer 216

They are used when: * Aldosterone levels are too high in disease, such as: * Cardiac failure * Hypertension * Aldosterone levels are too high as a natural response to diuretic therapy (sinc aldosterone conserves water indirectly by conserving salt)

Answer 217

They block the actions of aldosterone (a sodium-conserving hormone) by: * Antagonising aldosterone receptors * Inhibit the epithelial Na⁺channel in the collecting duct (so that less sodium is reabsorbed from the urine in the collecting duct)

Answer 218

* Aldosterone antagonists * Inhibitors of the epithelial Na⁺ channel in the collecting duct

Answer 219

* Aldosterone antagonists -\> Spironolactone * Inhibitors of the epithelial Na⁺ channel in the collecting duct -\> Amiloride

Answer 220

* In cardiac failure -\> Aldosterone levels are elevated because of: * Reduced renal perfusion * Increased sympathetic drive to the kidney (due to the baroreceptor reflex, responding to a fall in arterial blood pressure) * In hypertension -\> Some patients have elevated plasma renin and aldosterone levels, possibly reflecting a primary disease process in the kidney

Answer 221

* Diuresis activates the juxtaglomerular apparatus, which releases renin and causes the production of aldosterone. * Potassium-sparing diuretics may be used in these cases.

Answer 222

* Hyperaldosteronism * This is a nuisance because it increases sodium reabsorption in the distal tubule (so reducing the effects of the primary diuretic drug) and in increasing sodium reabsorption it causes the loss of potassium ions and protons at the same site.

Answer 223

Potassium-sparing diuretics are sometimes added to loop diuretics or (less commonly) thiazides to reduce the risk of hypokalaemia.

Answer 224

They do not typically have many side-effects unless too much is given, in which case they can result in hyperkalaemia.

Answer 225

* Uses -\> Treating hyperaldosteronism in heart failure and hypertension, Used alongside other diuretics * Common examples -\> Spironolactone, Amiloride * Mechanism of action -\> Antagonist of aldosterone receptors (spironolactone), Blocker of sodium channels in collecting duct (amiloride) * Side-effects -\> Potential hyperkalaemia

Answer 226

* Osmotic diuretics are used rarely, because they are difficult to control without causing side-effects * But they are useful when retained fluid must be removed quickly -\> e.g. Cerebral oedema.

Answer 227

In treating oedema: * Osmotic diuretic is infused into the blood (through a venous cannula); * Osmotic diuretic increases the osmotic pressure of the plasma, causing water to move out of the inflamed area and into the blood In the nephron: * Osmotic diuretic is easily filtered at the glomerulus and so it moves from the blood into the urine readily * This increases the osmotic potential of the fluid in the tubule, so that there is less fluid reabsorption into the interstitial fluid

Answer 228

* If the osmotic diuretic is given too quickly, water will be drawn out of the inflamed area more quickly than it can be filtered: in this case, the effective circulating volume increases and there is a risk of overloading the heart, causing heart failure. * Dehydration can also occur if the osmotic diuretic is given for too long

Answer 229

* Diabetes mellitus -\> Glucose acts as the diuretic * Glomerulonephritis -\> Protein acts as the diuretic Both of these situations can lead to quite rapid dehydration of the patient, indicating the potency of the osmotic diuretic mechanism.

Answer 230

They are very rarely used clinically as a diuretic, but the diuretic effect is a notable side-effect when they are used to treat other conditions.

Answer 231

Acetazolamide

Answer 232

* Carbonic anhydrase important in the metabolism of bicarbonate in the kidney. * Inhibition of this enzyme results in a weak diuresis driven partly by excretion of sodium bicarbonate. * The loss of bicarbonate leaves the patient with an acidaemia, and so the diuresis is self-limiting (because the amount of bicarbonate being filtered falls as the patient becomes more acidaemic). * In the proximal tubule, carbonic anhydrase also indirectly influences chloride absorption (through its effects on bicarbonate), and so diuresis induced by acetazolamide is a mixture of sodium bicarbonate and sodium chloride.

Answer 233

* ADH antagonists * ANP agonists * Angiotensin antagonists

Answer 234

* Loop diuretics -\> Furosemide * Thiazide diuretics -\> Bendroflumethiazide * Osmotic diuretics -\> Mannitol * Potassium-sparing diuretics -\> Sprinolactone + Amiloride * Carbonic anhydrase inhibitors -\> Acetazolamide

Answer 235

* Loop diuretics -\> Inhibit NKCC in thick ascending loop of Henle * Thiazide diuretics -\> Inhbit NaCl transporter in distal tubule * Osmotic diuretics -\> Increase osmotic potential of the tubular fluid * Potassium-sparing diuretics -\> Antagonists of aldosterone or Inhibit sodium channels in the collecting duct * Carbonic anhydrase inhibitors -\> Inhibit bicarbonate reabsorption in the proximal tubule

Answer 236

Loop diuretics are actively secreted into the proximal convoluted tubule as well as being filtered at the glomerulus, and so their plasma half-life is less than that of the thiazides (which are filtered but not secreted).

Answer 237

Loop diuretics and thiazides

Answer 238

* Drinking water changes the osmolarity of the body fluids, so less ADH is released and so aquaporins are removed from the collecting duct membrane, which causes rapid water excretion * Drinking isotonic saline does not change the osmolarity of the body fluids, so there is no immediate change in ADH. However, naturiesis is preferred over sodium conservation, so salt is lost, diluting the urine and gradually increasing water loss due to this In other words, with the saline you have to wait for the sodium excretion to drive water excretion, so it takes longer to return to the lower blood volume.

Answer 239

1L of saline, since the there is no reduction in ADH immediately.

Answer 240

* Osmoreceptors (of hypothalamus) -\> Increase in osmolarity triggers ADH release * Baroreceptors -\> Decrease in blood volume triggers ADH release Detection by these receptors can also stimulate thirst.

Answer 241

Stimulate vasoconstriction, increasing blood pressure.

Answer 242

* Increased blood osmolarity (osmoreceptors) * Only a 2% change in osmolarity required to trigger significant ADH release * Decreased blood volume (baroreceptors) * Over 15% change in BP required to trigger significant ADH release The sensitivity of osmoreceptors to blood osmolarity is increased when blood volume drops.

Answer 243

Cardiovascular (result in changes to sympathetic nervous discharge): * Baroreceptors -\> Carotid sinus + aortic arch * Stretch receptors -\> Atria + pulmonary circulation * Pressure receptors -\> Renal afferent arterioles Renal (result in renin release from afferent arteriole): * Macula densa -\> Senses Na⁺, Cl^-reabsorption, which depends on GFR, which depends on ECV Overall, increased sympathetic nervous system discharge and decreased distal flow (of NaCl) to the macula densa cause increased renin release.

Answer 244

Granular cells of the afferent arteriole

Answer 245

* Sodium retention * Volume expansion * Vasoconstriction

Answer 246

* When the flow rate and NaCl reabsorption is increased, it is a marker of increased GFR and therefore high blood pressure and blood salts * Therefore, the macula densa releases ATP, which acts on the afferent arteriole and has 2 effects * ATP causes constriction of the afferent arteriole, decreasing GFR * Adenosine (a metabolite of ATP) also inhibits the release of renin, so salt retention is reduced and systemic vasodilation occurs

Answer 247

Stimulated by: * Sympathetic nerve activity and circulating catecholamines * Prostagladins Inhibited by: * Increased NaCl reabsorption across the macula densa * Angiotensin II * ADH * Increased stretch of juxtaglomerular cells

Answer 248

* Increased plasma K⁺, since sodium reabsorption involves the sodium-potassium pump that causes the opposite flux of potassium. * This means that hyperkalaemia can be resolved by aldosterone.

Answer 249

* Efferent * This is because this maintains higher peritubular pressure, so GFR remains high Check this - Do the Starling forces balance this change?

Answer 250

* Angiotensin II -\> Proximal tubule * Aldosterone -\> Collecting duct

Answer 251

* It increases the sensitivity of TG feedback in response to changes in distal flow rate * This is due to a change in the affinity of the carriers that are transporting chloride across the macula densa cells

Answer 252

* Internal -\> Smooth muscle * External -\> Striated muscle

Answer 253

It is between the internal and external sphincter

Answer 254

Detrusor muscle

Answer 255

Prevents penetration of urine into the detrusor muscle (due to its many tight junctions).

Answer 256

Has a role in sensing the filling of the bladder.

Answer 257

* Parasympathetic * Pelvic nerve (S2-S3) -\> Acts on bladder * Sympathetic * Hypogastric nerve (L2) -\> Acts on bladder and internal sphincter * Somatic * Pudendal nerve (S2-S4) -\> Acts on external sphincter

Answer 258

* Pelvic nerve (S2-S3) * Acts on M3 receptors

Answer 259

* Hypogastric nerve (L2) * Acts on β₃ receptors

Answer 260

* Hypogastric nerve (L2) * Acts on α₁ receptors

Answer 261

* Pudendal nerve (S2-S4) * Acts on nicotinic receptors

Answer 262

* Parasympathetic stimulation leads to: * Contraction of the bladder * Sympathetic stimulation * Relaxation of the bladder * Contraction of the internal sphincter

Answer 263

* Pelvic nerves of the parasympathetic nervous system * Detect the extent of stretch in the walls of the bladder

Answer 264

It causes it to contract (via nicotinic receptors).

Answer 265

* The lack of stretch of the bladder is detected by sensory pelvic nerve fibres (parasympathetic), feeding back to the sacral spinal cord * This low level of firing ACTIVATES the a fibre that causes firing of the hypogastric nerve (sympathetic) at the lumbar level * This causes relaxation of the bladder detrusor muscle and contraction of the internal sphincter * The brain/pons are also aware of the lack of sensory firing from the bladder, so they stimulate the hypogastric nerve and the pudendal nerve, while inhibiting the pelvic nerve

Answer 266

The act of urinating.

Answer 267

* The stretch of the bladder is detected by sensory pelvic nerve fibres (parasympathetic), feeding back to the sacral spinal cord * This high level of firing ACTIVATES a fibre that feeds directly back to a micturition centre in the brain * The brain/pons inhibit the hypogastric nerve and the pudendal nerve, while stimulating the pelvic nerve * There is also stimulation of interneurons that supply the thalamus and cerebral cortex, so you become aware of the sensation of needing to urinate

Answer 268

The nervous reflex that allows for urination to continue.

Answer 269

* The stretch of the bladder is detected by sensory pelvic nerve fibres (parasympathetic), feeding back to the sacral spinal cord * This activates interneurons that activate the pelvic nerve (parasympathetic) * This allows for mictrurition to continue NOTE: This is reflex arc, but it can also be influenced by the micturition centres in the brain (as described in a previous flashcard).

Answer 270

* The micturition reflex starts when the bladder is filled with around 200ml of urine -\> It is a reflex, but the brain has conscious control over it, and can over-power it. * If the external sphincter does not relax, the bladder progressively relaxes. An additional increase in bladder volume reinitiates the cycle. * If the volume of urine exceeds 500ml, the internal sphincter may be forced to open -\> This also leads to a reflexive relaxation of the external sphincter.

Answer 271

Less than 10ml

Answer 272

The required cortico-spinal connections not yet established.

Answer 273

* Incontinence * Urine retention

Answer 274

* UTIs * Pelvic floor injury * Elderly individuals * Nerve damage * Atonic bladder * Automatic bladder * Uninhibited neurogenic bladder

Answer 275

Chemical stimuli increase bladder activity and hence the urge to void.

Answer 276

* Generic loss of muscle tone * Detrusor overactivity leading to overactive bladder

Answer 277

* Caused by damage to sensory nerve fibers (e.g. crush injury to the sacral region) * Associated with overflow incontinence

Answer 278

* Caused by spinal cord damage above sacral region * Micturition reflex intact, but control by the brain is impaired

Answer 279

* Caused by lack of inhibitory signals from the brain (due to partial damage of spinal cord or brain stem that interferes with most of the inhibitory signals) * Frequent and poorly controlled micturition

Answer 280

* Enlargement of the prostate gland (constricts the urethra) * Kidney stones

Answer 281

Using an α₁antagonist, such as Tamsulosin.

Answer 282

Where an individual experiences frequent and uncontrolled need to urinate.

Answer 283

* Increased afferent activity (from the parasympathetic pelvic nerve that innervates the bladder muscle) * Decreased inhibitory control in the CNS * Increased detrusor sensitivity to efferent stimulation

Answer 284

To reduce bladder overactivity without interfering with normal micturition and without affecting other systems.

Answer 285

* Antimuscarinic drugs (e.g. oxybutynin) * Side effects: dry mouth and constipation (M3 receptors in salivary glands and gut) * Botulinum toxin * Administration is difficult * Resiniferatoxin and capsaicin (target sensory nerves)

Answer 286

* β₃ adrenoreceptor agonists * Phosphodiesterase type 5 inhibitors

Answer 287

* Incontinence -\> Muscarinic antagonists * Outflow obstruction -\> Alpha-1 antagonists

11. Uro-Genital System (TT) Flashcards

(341 cards)