The renal system

Question 1

renal and urinary system

Answer 1

kidneys, ureters, bladder, urethra

Question 2

renal functions

Answer 2

filtering, fluid and electrolyte exchange, endocrine

Question 3

functions of the kidneys

Answer 3

regulation of water and inorganic ion balance; regulation of extracellular fluid volume and composition, Na, K, Ca, Mg, HCO, H, phosphates, sulphates, water

removal of metabolic waste products from the blood and their excretion in the urine; urea from protein breakdown, creatine breakdown, breakdown products of Hb

removal of a range of compounds from the blood and their excretion in the urine; drugs, pesticides

gluconeogenesis; synthesis of glucose
besides the liver, the kidney is the only organ capable of generating sufficient glucose to release into circulation and is also responsible for filtration and subsequent reabsorption or excretion of glucose.

Question 4

endocrine functions of the kidneys

Answer 4

erthyopoetin (EPO) enhances erythrocyte production. anemia can occur in patients with renal disease. renin an enzyme which controls formation of angiotensin and influences BP and Na balance.
calcitriol influences calcium balance

Question 5

renal structure

Answer 5

the kidneys are paired organs lying in the posterior abdominal wall on either side if the vertebral column. covered in tough fibrous capsule.
kidneys are divided into an outer granular cortex and an inner striated medulla

Question 6

renal blood supply

Answer 6

comprise 0.5% of body weight, 20% of cardiac output

interlobular arteries enter cortex and divide into afferent arterioles>supply each nephron via compact bundle of capillaries forming the glomerulus>leaves via efferent arterioles> onto peritubular capillaries or descending vasa recta> interlobular vein ascending vasa recta arcuate vein

Question 7

nephron

Answer 7

the nephron is the basic unit of the kidney with around 2.5 million in the human kidney. each nephron consists of 2 functional components; tubular and vascular. kidney function depends on the relationship between these two components.

Question 8

cortical or superficial nephrons

Answer 8

around 80% of nephrons, glomeruli in outer cortex and their LoH barely penetrate the medulla, very limited contracting ability

Question 9

juxtamedullary nephrons

Answer 9

around 20%, glomeruli in cortex and long LoH which descend into medulla. significant urine concentration is achieved thanks to the hyperosmolar medulla set up by these structures. in juxtamedullary nephrons the capillaries form hairpin like loops, the vasa recta, which dip into the medulla in parallel with the loops of Henle. these capillaries ultimately drain into venules and veins and blood leaves the kidney in the renal vein

Question 10

functions of the nephron

Answer 10

filtrate leaves the blood supply to enter the tubule system, reabsorption NaCl and NaHCO3, osmosis, acid-base balance, nutrient reabsorption
water and electrolyte reabsorption, fine control of water and salt secretion

Question 11

renal tubule

Answer 11

a single layer of epithelial cells which differ in structure and function from portion to portion. starts in a blind sac the bowman’s capsule surrounding the glomerulus.

Question 12

renal corpuscle

Answer 12

glomerulus, bowman’s capsule, bowman’s space

Question 13

glomerulus

Answer 13

compact node of capillaries that protrude into bowman’s capsule.
glomerular capillaries; unique in the body as the vessels recombine to form another arteriole, the efferent arteriole, which then divides up again to form a second set of capillaries; peritubular capillaries for superficial glomeruli
vasa recta for juxtamedullary glomeruli

Question 14

glomerular endothelial cells

Answer 14

surrounded by basement membrane, podocytes and mesangial cells. large fenestrations that allow passage of water and solutes. limit cellular elements such as RBCs entering tubule

Question 15

basement membrane

Answer 15

located between the endothelium and podocytes. restricts intermediate to large sized solutes, negative favour filtration of positively charge solutes

Question 16

podocytes

Answer 16

feet like processes that cover the basement membrane, filtration slits with pores ranging from 4-14nm. podocytes are covered in glycoproteins with negative charges

Question 17

glycocalyx

Answer 17

fibrous layer of negatively charged glycoproteins

Question 18

renal tubule; structure-function

Answer 18

proximal convoluted tubule; large apical surface area for reabsorption
lots of mitochondria; high energy requirement

thick ascending limb of the LoH
complex cells with folds on baso lateral surface, vital role in sodium regulation and control of osmolality of urine.

distal convoluted tubule- starts at macula densa similar in structure to thick ascending limb

collecting tubule-intercalated cells secrete H?HC)3 and reabsorb K, principal ells reabsorb Na and Cl secrete K

medullary collecting duct- transport of water salt and urea

Question 19

juxta-glomerular apparatus

Answer 19

granular cells- juxtaglomerular cells, specialised smooth muscle on afferent arterioles, produce store and release renin

mesangial cells; contractile cells that secrete extracellular matrix support the glomerular capillary loops.

macula densa; specialised epithelial cells at ascending limb/distal tubule, junction of glomerulus and afferent/efferent arterioles.

Question 20

neuronal regulation

Answer 20

symp ANS, NA and dopamine from symp nerves near smooth muscle cells

• vasoconstriction
• enhanced sodium reabsorption
• stimulates renin secretion

Question 21

renin innervation

Answer 21

symp ANS, sensory neurones
increased perfusion pressure stimulates renal baroreceptors (intralobular arteries and afferent arterioles\0
ischaemia and abnormal ion composition stimulate renal pelvis chemoreceptors (K and H)

Question 22

ureters

Answer 22

lined by endothelium, submucosal layer of connective tissue; contain inner longitudinal smooth muscle, circular outer smooth muscle

is unitary smooth muscle where gap junctions permit electrical activity to pass between cells.
mechanical or chemical stimuli, as well as depolarisation can trigger action potential
peristalsis originates from pacemakers in the proximal portion of the kidney pelvis

Question 23

the bladder-ureters

Answer 23

peristalsis can occur without innervation, but can be modulated by the ANS, p-symp enhances contractility via Muscarinic M3 receptors

symp - excitatory (alpha adrenoreceptors)
inhibitory (beta adrenoreceptors)

Question 24

the bladder

Answer 24

ureters enter the lower posterior portion of the bladder. two urethral orifices connected by ridge of tissue forms bladder trigone

flap like mucous membrane covers opening to prevent reflex during contraction of bladder.
distensible organ with folded muscular wall
detrusor muscle has 3 smooth muscle layers
thickening of urethral muscle forms internal sphincter. striated muscle forms external sphincter

Question 25

micturition

Answer 25

pontine micturition centre (PMC) coordinates the micturition reflex with cortical and suprapontine centres in the brain exert inhibitory influence on micturition reflex storage phase; stretch receptors in bladder send afferent info to brain via pelvic splanchnic nerves first urge around 150ml. dullness at 400-500ml until socially acceptable opportunity to void, efferent impulses from brain inhibit contractile p-symp actions on detrusor muscle (learned reflex)

Question 26

bladder tone

Answer 26

relationship between volume and internal pressure

Question 27

voiding phase of micturition

Answer 27

voluntary relaxation of internal/external sphincter, urine reaching urethra signals to cortex suprapontine/pontine centres in the brain no longer exert inhibitory influence on p-symp nerves- initiates micturition reflex cortical centres also inhibit external sphincter muscles, voluntary contraction of abdominal muscles also required to raise bladder pressure detrusor muscle contracts, further trains of sensory information from stretch receptors initiate a self0regenerating process

Question 28

sodium reabsorption

Answer 28

transcellular; two membrane model of transport; 1. passive entrance of Na into cell >low [Na] and favourable electrochemical gradient >combinations of co-transporters and exchangers 2. active transport of Na out of cell across basolateral membrane >Na-K pump helps to keep [Na] low (round 15mM) and [K] high (around 120mM) paracellular; trans-epithelial >electrochemical gradient drives Na transport >positive gradient favouring reabsorption in proximal tubule and thick ascending limb only.

Question 29

sodium reabsorption-proximal tubule

Answer 29

``` 1.electrogenic apical membrane co-transporters coupled to transport of other solutes; >glucose >amino acid >net positive charge into cell ``` 2.Na-H exchanger >electroneutral exchanger coupled to the transport of protos (H) 3. Na-K pump >basolateral membrane >contributes around 10mV to RMP

Question 30

sodium reabsorption- proximal tubule

Answer 30

Na flux-> to interstitial space (around 60% reabsorbed) water follows Na influx->fluid reabsorption water follows the Na by passive diffusion via paracellular and cellular pathways as this epithelium is very water permeable due to the presence of AQP1 channels in apical and baso-lateral membranes

Question 31

sodium reabsorption in thick ascending limb of Henle's loop

Answer 31

``` transcellular 1. Na/K/Cl co transporter (NKCC2) >electroneutral transport 2. Na-H exchanger >coupled to H transport 3. Na-K pump >basolateral membrane ``` paracellular >high density of apical K channels results in lumen positive PD >driving force for Na diffusion Na flux from lumen-> to interstitial space, around 15-20% Na reabsorbed energy requirement impermeable to water

Question 32

Counter current flow (Na reabsorption)

Answer 32

nephron differentially permeable to Na ions and water. combined with the counter- current flow in the loop of Henle. this results in hyper osmotic area with a strong osmotic gradient within the renal medulla allows for the production of dilute urine and when necessary via action of ADH concentrated urine

Question 33

sodium reabsorption- distal convoluted tubule

Answer 33

transcellular- 1. electroneutral Na/Cl cotransporter >same family as Na/K/Cl co transporter but K independent. 2. Na/K pump >basolateral membrane

Question 34

sodium reabsorption - initial/cortical collecting tubules

Answer 34

``` transcellular >principal cells (amiloride diuretic) >Na crosses the apical membrane by epithelial Na channels (distinct to neuronal channels) >Na-K pump >basolateral membrane >driving force for apical Na entry ```

Question 35

medullary collecting tubules-sodium reabsorption

Answer 35

transcellular >minimal Na reabsorption >Na crosses the apical membrane by epithelial Na channels >Na-K pump basolateral

Question 36

water reabsorption in proximal tubule

Answer 36

>epithelium is very permeable to water >transcellular and paracellular >transcellular predominates due to the presence of AQP channels on apical ad basolateral membranes.

Question 37

water reabsorption in LoH

Answer 37

>relatively low water permeability >water permeability can be upregulated by vasopressin >large osmotic gradient allows passive reabsorption when modulated by AVP

Question 38

glucose reabsorption

Answer 38

kidneys filter glucose at glomerulus then reabsorb in tubule normally only trace amounts in urine transcellular >Na/glucose transporter >electrochemical gradient of Na drives transport of glucose apical glucose uptake >early proximal SGLT2 >late proximal SGLT1 basolateral transport >early proximal GLUT2 >late proximal GLUT1 basolateral Na-K pump

Question 39

urea absorption and secretion

Answer 39

thin descending limb >urea transporter UT2 secretes urea inner medullary collecting duct >apical urea transporter UT1 reabsorbs urea >basolateral; urea transporter UT4 transports urea

Question 40

amino acid absorption

Answer 40

90% reabsorbed in proximal tubule apical membrane >Na dependent cotransporters >Na independent facilitated diffusion basolateral membrane >facilitated diffusion >Na dependent cotransport into cell for metabolism/nutrition 0% of filtered load is excreted in urine

Question 41

calcium absorption

Answer 41

4% bound to plasma proteins (60% filterable) proximal tubule- 80% paracellular (high calcium permeability)/solvent drag 20% transcellular thick ascending limb 50% transcellular]50% paracellular (lumen positive voltage)

Question 42

glomerular filtration

Answer 42

under normal conditions; 125ml/min> 180l/day exposes the entire extracellular fluid to filtration around 10 times each day high turnover essential to clear blood should a toxic or waste material build up in blood

Question 43

measurement of glomerular filtration rate

Answer 43

``` insulin, creatinine regulation of GFR 1. hydrostatic and oncotic pressure 2. tubulo-glomerular feedback 3. renin-angiotensin-aldosterone system ```

Question 44

criteria for a substance to measure GFR

Answer 44

filtered in glomeruli neither reabsorbed, secreted, metabolised or synthesised by kidney, physiologically inert ``` inulin> starch like fructose polymer plasma levels match levels in bowman's capsule> readily filtered reliable requires IV administration determination of levels is demanding unsuitable for routine use ``` creatinine>clearance is reasonable estimate of GFR in humans no need to inject patients, venous blood and urine analysed and calculation performed however, tubules secrete creatinine, the method overestimates plasma creatinine, these two errors cancel each other out >results comparable to inulin test

Question 45

factors effecting glomerular filtration

Answer 45

hydrostatic pressure in glomerular capillary favours ultrafiltration hydrostatic pressure in capillaries (blood pressure) forces fluid out of capillary oncotic pressure in capillary and hydrostatic pressure in Bowman's space oppose ultrafiltration >oncotic pressure is exerted by plasma proteins to draw fluid into capillaries >hydrostatic pressure within the bowman's capsule opposing filtration into the renal tubule

Question 46

control of renal blood flow and glomerular filtration

Answer 46

autoregulation >need to keep blood flow and GFR within narrow limits >arterial pressure can be variable >perfusion must be preserved in emergency situations (hypotensive shock) >protects fragile glomerular capillaries from increase in blood pressure that could lead to structural damage >regulation is independent of renal nerves and circulating hormones 1. myogenic response 2. tubulo-glomerular feedback

Question 47

afferent and efferent arterioles

Answer 47

afferent> direction of blood flow>efferent afferent arteriole (relaxation) increased blood flow into glomerular capillaries>increase GFR (prostaglandins, NO, atrial natriuretic peptide (ANP)) efferent arterioles (constriction) increased hydrostatic pressure within the glomerulus capillaries, increase GFR (angiotensin 2, adenosine, NA, endothelin's, leukotrienes) afferent arteriole (constriction) less blood flow into glomerular capillaries, decrease GFR, (angiotensin 2, adenosine, NA, endothelin's, leukotrienes) efferent arteriole (relaxation) decreased hydrostatic pressure within the glomerular capillaries, decrease GFR (prostaglandins, NA, ANP)

Question 48

control of renal blood flow and glomerular filtration

Answer 48

myogenic response; afferent arterioles can respond to changes in vessel wall tension >blood vessels can contract or relax 1. an increase n vessel diameter> 2. opening of stretch-activated cation channels> 3.depolarsation of smooth muscle cells> 4. influx of calcium stimulates contraction

Question 49

tubule-glomerular feedback

Answer 49

macula densa cells in the thick ascending limb can sense GFR via NKCC2 transporter activity 1. increase in arterial pressure =increase in glomerular capillary pressure =increase u renal plasma flow =increase In glomerular filtrate rate 1.increased GFR >increased NA and Cl (and fluid) into the distal tubule (macula densa) 1. increases in luminal [Na] and [K] and [Cl] Na/K/Cl transporter activity in MD cells

Question 50

NKCC2 transporter in juxtaglomerular apparatus

Answer 50

NKCC2 transporter in macula densa cells alters local signalling and renin release further modifying renal blood flow and causing more general vasodilator effects

Question 51

(control of renal blood flow and glomerular filtration) | chloride

Answer 51

1. increased [Cl], followed by Cl efflux via basolateral Cl channel >depolarisation > [Ca] increase increase in calcium will release pancrine factors >ATP, adenosine, thromboxane 1. triggers contraction in vascular smooth muscle cells >increase in afferent arteriolar pressure >decreases GFR outcome; modulation of afferent arteriole counteracts the increase in GFR due to increased blood pressure

Question 52

factors that modulate glomerular filtration

Answer 52

1. Renin-angiotensin-aldosterone axis >angiotensin 2- overall reduction blood flow and GFR >constricts renal artery >afferent and efferent arterioles >increases sensitivity of tubule glomerular feedback 2. symp NS >nerve terminals release NA >increase in afferent and efferent arteriole resistance >decrease in renal blood flow and GFR >release of renin from granular cells, thereby raising levels of angiotensin 3. prostaglandins >local production buffers against excessive vasoconstriction 4. nitric oxide >local production buffers against excessive vasoconstriction >dilates afferent and efferent arterioles 5. atrial natriuretic peptide >released from cardiac myocytes in response to increased atrial pressure >dilates afferent and efferent arterioles increasing blood flow >lowers tubule glomerular sensitivity >inhibits secretion of renin

Question 53

regulation of blood pressure and volume

Answer 53

extracellular fluid (ECF) volume is an important determinant of blood pressure ECF volume: rapidly regulated; ANS and CV responses slowly and sustained; changes in Na and water excretion extracellular osmolarity; hypotonic/hypertonic osmolarity can change cell volume and alter function regulation of volume and osmolarity use different sensors, hormonal transducers and different effectors but with some overlap

Question 54

osmolality of extracellular fluid (ECF)

Answer 54

regulation of osmolality of ECF by kidney is important to maintain cell volume. deviations of 15% can lead to CNS dysfunction ECF osmolality is regulated by controlling and adjusting body water content Na, HCO3 and Cl are important determinants of osmolality, water follows movement of Na Na load is monitored by hypothalamic receptors which signal thirst response and AVP (ADH) secretion which regulates water excretion Na excretion is response to high ECF volume

Question 55

sensors, efferent pathways, effector and what is affected with ECF (effective circulating volume)

Answer 55

sensors; carotid sinus, aortic arch, renal afferent arteriole, cardiac atria efferent pathways; R-A-S, sympathetic NS, AVP/ANP effector; short term- heart and blood vessel, long term- kidney what is affected; short term- BP, long term-Na secretion

Question 56

sensors, efferent pathways, effector and what is affected with plasma osmolality

Answer 56

sensors; osmoreceptors efferent pathways; AVP and thirst effector; short term; CNS, long term; kidney what is affected; sort term; water intake, long term; water reabsorption

Question 57

feedback regulation of osmolarity

Answer 57

thirst- increased water intake vasopressin (AVP) or antidiuretic hormone (ADH) AQP2 insertion in collecting duct increased reabsorption of water

Question 58

AVP or ADH

Answer 58

released from posterior pituitary in response to signals from; osmoreceptors- detect increase in plasma osmolality (primary stimulus) baroreceptors- detect decrease in circulating blood volume > acts via AVPR2 receptor to increase expression of AQP in distal tubule cells >water retention

Question 59

renin

Answer 59

renin- protease synthesised in renal juxtaglomerular granular cells, released in response to low renal perfusion and pressure, pressure detected by systemic baroreceptors and renal afferent arterioles, renin activates the RA system

Question 60

renin-angiotensin system

Answer 60

angiotensin is synthesised by liver and released into systemic circulation renin converts angiotensin to angiotensin 1 (physiologically inactive) angiotensin converting enzyme (ACE) present in endothelia throughout the body ACE converts angiotensin 1 to angiotensin 2

Question 61

factors stimulating renin release

Answer 61

1. low effective circulating volume - baroreceptors stimulate medullary control centres - symp signal to juxtaglomerular apparatus to release renin 2. changes in renal tubule luminal [NaCl] - changes in Na is detected by macula densa cells which modulate renin release 3. decreased renal pressure - stretch receptors in granular cells in afferent arterioles - amount of renin release dependant on degree of distension

Question 62

actions of angiotensin 2

Answer 62

1. ANG2 stimulates release of aldosterone from adrenal cortex, aldosterone increases sodium reabsorption in collecting tubules 2. ANG2 stimulates constriction of blood vessels increases sodium absorbed by - potentially constricts the afferent arteriole thereby reducing hydrostatic pressure - blood flow in vasa recta is slowed favouring sodium reabsorption and water retention due to changes 3. ANG2 enhances tubule glomerular feedback, raises sensitivity- Na has more pronounced decrease on GFR 4. ANG2 enhances Na-H exchange - stimulates exchangers in the proximal tubule and thick ascending limb - Na reabsorption 5. simulates thirst - acts on hypothalamus to stimulate thirst - increase AVP(ADH) secretion - increase in total body free water

Question 63

R-A-A-S system

Answer 63

inactive angiotensin->renin->angiotensin 1->ACE-> active angiotensin 2->vasoconstriction, decreased GFR, increased Na absorption, increase in free water->aldosterone

Question 64

aldosterone

Answer 64

regulates salt balance and ECV is a mineralocorticoid, exclusively synthesised in glomerulosa cells in adrenal cortex, synthesised from cholesterol no pre-synthesised aldosterone stored in glomerulosa cell >synthesised in response to ANG2 (and ACTH) 30% of circulating aldosterone free in plasma acts on receptors in kidney, colon. salivary and sweat glands >increased transcription of transport proteins

Question 65

factors stimulating aldosterone synthesis and secretion

Answer 65

angiotensin 2, increased plasma [K], ACTH (adrenocorticotrophin)

Question 66

collecting tubules

Answer 66

apical membrane; Na crosses via epithelial Na channels (distinct to neuronal channels) |K channels for secretion of K ions basolateral membrane; Na-K pump provides driving force for apical sodium entry

Question 67

aldosterone activation of receptors

Answer 67

in principle cells, results in the synthesis of new proteins, insertion of new Na and K channels increased sodium absorption

Question 68

mechanism of action for aldosterone

Answer 68

aldosterone increases number of apical ENaC channels and Na/Cl co-transporters in distal tubule and collecting duct (Na reabsorption) aldosterone increases transcription of Na-K pump in distal tubule - distal Na reabsorption - K excretion leading to; increased BP, increased ECF, increased extracellular fluid volume

Question 69

pathways regulating ECF

Answer 69

1. rennal sympathetic nerve activity 2. arginine vasopressin (ADH) 3. atrial natriuretic peptide

Question 70

sympathetic nerve regulation

Answer 70

renal nerve stimulation 1)increased vascular resistance 2)enhanced renin secretion from granular cells 3)increased tubular absorption of Na under normal conditions, influence of symp NS in kidney is limited important role in; challenges to homeostasis, haemorrhage (preserve ECF volume)

Question 71

atrial natriuretic peptide

Answer 71

synthesised in cardiac atria - secreted in response to atrial stretch and increased ventricular volume - promotes Na excretion (water follows by osmosis) effective as renal dilator - blood flow to the cortex and medulla - GFR increased medullary blood flow - reduces medullary hypertonicity - osmolarity=Na reabsorption - decreases circulating volume - decreases BP

Question 72

ECF vs osmolarity

Answer 72

under physiological conditions; volume and osmolarity are regulated independently under pathophysiological conditions; body defends volume at the expense of osmolarity, will tolerate hypo-osmolarity to expand volume