The renal system Flashcards
renal and urinary system
kidneys, ureters, bladder, urethra
renal functions
filtering, fluid and electrolyte exchange, endocrine
functions of the kidneys
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.
endocrine functions of the kidneys
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
renal structure
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
renal blood supply
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
nephron
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.
cortical or superficial nephrons
around 80% of nephrons, glomeruli in outer cortex and their LoH barely penetrate the medulla, very limited contracting ability
juxtamedullary nephrons
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
functions of the nephron
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
renal tubule
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.
renal corpuscle
glomerulus, bowman’s capsule, bowman’s space
glomerulus
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
glomerular endothelial cells
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
basement membrane
located between the endothelium and podocytes. restricts intermediate to large sized solutes, negative favour filtration of positively charge solutes
podocytes
feet like processes that cover the basement membrane, filtration slits with pores ranging from 4-14nm. podocytes are covered in glycoproteins with negative charges
glycocalyx
fibrous layer of negatively charged glycoproteins
renal tubule; structure-function
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
juxta-glomerular apparatus
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.
neuronal regulation
symp ANS, NA and dopamine from symp nerves near smooth muscle cells
- vasoconstriction
- enhanced sodium reabsorption
- stimulates renin secretion
renin innervation
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)
ureters
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
the bladder-ureters
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)
the bladder
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
micturition
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)
bladder tone
relationship between volume and internal pressure
voiding phase of micturition
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
sodium reabsorption
transcellular;
two membrane model of transport;
- passive entrance of Na into cell
>low [Na] and favourable electrochemical gradient
>combinations of co-transporters and exchangers - 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.
sodium reabsorption-proximal tubule
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)
- Na-K pump
>basolateral membrane
>contributes around 10mV to RMP
sodium reabsorption- proximal tubule
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
sodium reabsorption in thick ascending limb of Henle’s loop
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
Counter current flow (Na reabsorption)
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
sodium reabsorption- distal convoluted tubule
transcellular-
1. electroneutral Na/Cl cotransporter
>same family as Na/K/Cl co transporter but K independent.
- Na/K pump
>basolateral membrane
sodium reabsorption - initial/cortical collecting tubules
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
medullary collecting tubules-sodium reabsorption
transcellular
>minimal Na reabsorption
>Na crosses the apical membrane by epithelial Na channels
>Na-K pump basolateral
water reabsorption in proximal tubule
> epithelium is very permeable to water
transcellular and paracellular
transcellular predominates due to the presence of AQP channels on apical ad basolateral membranes.
water reabsorption in LoH
> relatively low water permeability
water permeability can be upregulated by vasopressin
large osmotic gradient allows passive reabsorption when modulated by AVP
glucose reabsorption
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
urea absorption and secretion
thin descending limb
>urea transporter UT2 secretes urea
inner medullary collecting duct
>apical urea transporter UT1 reabsorbs urea
>basolateral; urea transporter UT4 transports urea
amino acid absorption
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
calcium absorption
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)
glomerular filtration
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
measurement of glomerular filtration rate
insulin, creatinine regulation of GFR 1. hydrostatic and oncotic pressure 2. tubulo-glomerular feedback 3. renin-angiotensin-aldosterone system
criteria for a substance to measure GFR
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
factors effecting glomerular filtration
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
control of renal blood flow and glomerular filtration
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
afferent and efferent arterioles
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)
control of renal blood flow and glomerular filtration
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
tubule-glomerular feedback
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)
- increases in luminal [Na] and [K] and [Cl]
Na/K/Cl transporter activity in MD cells
NKCC2 transporter in juxtaglomerular apparatus
NKCC2 transporter in macula densa cells alters local signalling and renin release further modifying renal blood flow and causing more general vasodilator effects
(control of renal blood flow and glomerular filtration)
chloride
- increased [Cl], followed by Cl efflux via basolateral Cl channel
>depolarisation
> [Ca] increase
increase in calcium will release pancrine factors
>ATP, adenosine, thromboxane
- 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
factors that modulate glomerular filtration
- 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 - 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 - prostaglandins
>local production buffers against excessive vasoconstriction - nitric oxide
>local production buffers against excessive vasoconstriction
>dilates afferent and efferent arterioles - 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
regulation of blood pressure and volume
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
osmolality of extracellular fluid (ECF)
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
sensors, efferent pathways, effector and what is affected with ECF (effective circulating volume)
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
sensors, efferent pathways, effector and what is affected with plasma osmolality
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
feedback regulation of osmolarity
thirst- increased water intake
vasopressin (AVP) or antidiuretic hormone (ADH)
AQP2 insertion in collecting duct
increased reabsorption of water
AVP or ADH
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
renin
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
renin-angiotensin system
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
factors stimulating renin release
- low effective circulating volume
- baroreceptors stimulate medullary control centres
- symp signal to juxtaglomerular apparatus to release renin - changes in renal tubule luminal [NaCl]
- changes in Na is detected by macula densa cells which modulate renin release - decreased renal pressure
- stretch receptors in granular cells in afferent arterioles
- amount of renin release dependant on degree of distension
actions of angiotensin 2
- ANG2 stimulates release of aldosterone from adrenal cortex, aldosterone increases sodium reabsorption in collecting tubules
- 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 - ANG2 enhances tubule glomerular feedback, raises sensitivity- Na has more pronounced decrease on GFR
- ANG2 enhances Na-H exchange
- stimulates exchangers in the proximal tubule and thick ascending limb
- Na reabsorption - simulates thirst
- acts on hypothalamus to stimulate thirst
- increase AVP(ADH) secretion
- increase in total body free water
R-A-A-S system
inactive angiotensin->renin->angiotensin 1->ACE-> active angiotensin 2->vasoconstriction, decreased GFR, increased Na absorption, increase in free water->aldosterone
aldosterone
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
factors stimulating aldosterone synthesis and secretion
angiotensin 2, increased plasma [K], ACTH (adrenocorticotrophin)
collecting tubules
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
aldosterone activation of receptors
in principle cells, results in the synthesis of new proteins, insertion of new Na and K channels
increased sodium absorption
mechanism of action for aldosterone
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
pathways regulating ECF
- rennal sympathetic nerve activity
- arginine vasopressin (ADH)
- atrial natriuretic peptide
sympathetic nerve regulation
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)
atrial natriuretic peptide
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
ECF vs osmolarity
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
