Renal Flashcards
What are the functions of the kidney?
HOMEOSTASIS
Electrolyte homeostasis
Fluid balance
acid base homeostasis
regulation of arterial blood pressure
EXCRETION
excretion of waste - urea, drugs
ENDOCRINE
secretion and metabolism of hormones - Renin, EPO, vitamin D active form
METABOLISM
gluconeogenesis
describe the anatomy of the renal vasculature..
aorta - left and right renal arteries enter at hilum
divide into segmental and then interlobular arteries
eventually afferent arteriole –> glomerulus –> efferent arteriole
efferent arterioles give rise to vasa recta or peritubular capillaries.
the glomerulus is a high pressure capillary network
whereas the vasa recta/ peritubular capillaries are low pressure.
how much blood flows to kidneys?
20-25% of CO
1L/min
90% cortical, 10% medulla
what is the role of the vasa recta?
hairpin capillary system closely related to loop of henle
hairpin arrangment helps maintain ionic concentrations of medulla whilst still delivering O2 to collecting tubules and loop of henle.
what are the peritubular capilaries ?
supply O2 and reabsorb nutrients from PCT, DCT, parts of collecting ducts.
what is meant by autoregulation of renal blood flow?
many organs have an intrinsic mechanism to regulate flow to maintain a constant perfusion pressure to ensure O2 is being delivered and CO2 removed.
In the kidneys autoregulation has the additional role of maintaining GFR.
the main mechanism for this is known as the myogenic response
when MAP increases, causes muscle contaction - to maintain constant flow.
this autoregulation can function between 90-200mmHg
other mechanisms contributing to autoregulation include tubuloglomerular feedback
what factors affect renal blood flow and GFR?
autoregulation/ myogenic response
tubuloglomerular feedback
sympathetic NS
hormonal factors - ATII, catecholamines,
what is tubuloglomerular feedback?
this helps maintain a constant filtrate rate. relies on juxtaglomerular apparatus. the macula densa at DCT senses Na delivery. if this is increased due to high GFR, local metabolites are released which cause afferent arteriole vasoconstriction to reduce GFR.
metabolites invovled depending on if high or low include NO, enodthelin, prostaglandins
how does the sympathetic NS influence renal blood flow and GFR?
activation of sympathetic NS
causes vasoconstriction via a1
reduces blood flow and GFR
water retention
sympathetic NS also causes renin release via B1 receptors. this results in ATII which causes further vasoconstriction.
how does ATII affect renal blood flow and GFR
vasoconstiction of efferent more than afferent
maintains GFR
however also causes contraciton of mesangial cells to reduced filtration
reduces renal blood flow.
(whereas sympathetic afferent more than efferent so both reduced)
describe the strucutre of glomerulus and bowmans capsule?
glomerulus = capillary network of fenestrated capillaries
in close contact with bowmans capsule
so as high pressure blood is filtered, the filtrate enters bowmans capsule.
the barrier between the 2 makes up the filtration barrier and consists of fenetrasted endothelium of capillaries , BM, podocyte foot processes of bowmans
what molecules are filtered at the glomerulus?
depends on size and charge
under 7KDa = freely filtered
then the rate of filtration is proportional to size
above 70kDA = none filtered
slight negative charge of filtration barrier means positive are favoured over negative
give example e.g. small ions, glucose - freely filtered
large proteins - albumin - not filtered
what is meant by glomerular filtration rate?
the rate at which fluid enters the bowmans capsule from the glomerulus. (volume of plasma per min)
normally 125ml/min (180l/day)
what factors determine GFR?
starlings forces of filtration
pressure
* high pressure system within glomerulus, the pressure in both afferent and efferent are high so hydrostatic pressure is maintained across the length, helping to produce filtrate
oncotic pressure
* oncotic pressure of plasma has an opposing force drawing fluid back in, this is higher than in bowmans capsule (near 0)
reflection coefficient / permeability
* this is how leaky the capillaries are. there is high permeability due to fenestrations. however limited to >70Kda
S.A:
contaction of mesangial cells, reduces S.A to regulate fitlration. many humeral factors affect this e.g. ATII constricts them
how does starlings filtration forces differ in kidneys to other tissues?
in normal tissues the arterial end has a high pressure and then there is a big drop at venule end which draws fluid back in
in glomerulus, it is a high pressure system which is maintained across - hence net filtration out of capilaries, not reabsorbed at that point.
in normal tissue = 35mmHg to 10mmHg
in renals = remains at 45mmHg
oncotic pressure in both 25mmHg (slight rise by effrent end as fluid has left)
in bowman oncotic = 0mmHg
bowman pressure is 10mmHg
what is the equation for starlings filtration in kidneys
Kf = filtration coefficient = permeability x S.A
describe the different methods of tubular transport?
simple diffusion - O2, CO2, lipid soluble drugs
fasciliated diffusion - glucose, aa , ions in ion channels e.g. Na
active transport - Na/K ATPase, H+ secretion and H/K ATPase - often sets up gradients for 2nd AT
secondary AT - glucose and aa later in tubules against conc gradient using Na/glucose symporters
osmosis - water follows paracellular or AQUAporins
paracellular movemnet - between cells dragged with water
why is urine a different composition to filtrate?
reabsorption
secretion
what happens in PCT?
majority of substances are reabsorbed
in healthy kidneys, non pregnant
all of glucose
all of aa
60% of sodium , K , Cl
85% HCO3
60% water
occurs via a number of transport mechanisms.
also some secretion - e.g. penicillin, aspirin, histamine, catecholamines, morphine etc
draw a graph to show the filtrate:plasma conc as fluid moves down PCT
initially all equal as equilbrium reached with plasma so ratio is 1
as it moves down, glucose, amino acids and HCO3 are reabsorbed so ratio drops as plasma conc increases and filtrate conc drops.
although Na is reabsorbed, the concentration is unchanged with distance as water is also reabsorbed
inulin is secreted into the tubules so its ratio increases.
urea and creatinine would also increase as these are not reabsorbed but water is so their conc increases
describe how the structure of PCT relates to its function?
brush border - high S.A
many transport proteins
mitochondria - AT
describe the mechanism of glucose reabsorption at PCT…
basolateral membrane Na/K ATPase
luminal - SGLT - sodium glucose symporter
basolateral = glut 2
what is meant by T max?
the PCT has a max rate of reabsorption of molecules. beyond this point, the substance will appear in urine
e.g. for glucose this is 10mM
below this, as glucose conc increases, rate of reabsorption increases up to a max
if glucose conc exceeeds 10mM , the reabsorption pathways are saturated and the remaining glucose is excreted.
therefore Tmax = the max rate of reabsorption of a substance. for glucose this is 300mg/min (which equates to the rate at 10mM)
not all nephrons have the same Tmax value
how is sodium handled by PCT?
Na/K ATPase
Na/Glucose symptor
Na/aa symptors
Na/H antiporter - luminal membrane
how is chloride reabsored
as Na and HCO3 are reabsorbed and water follows, Cl conc increases
passively diffuses down conc gradient
also co-transporter
how is bicarb reabsorbed by the kidneys
carbonic anhydrase, combines H+ and bicarbonate to H2CO3 to make H20 and CO
these can diffuse across back into plasma
how is urea handled by the PCT?
50% is reabsorbed by passive diffusion due to other things being reabsorbed and conc rising
where is water reabsorbed by kidneys?
70% PCT
15% LoH
variable = collecting ducts
describe the structure of the LoH?
hair pin like structure with countercurrent mechanism
fluid flows down descending and up ascending
2 types of nephrons = juxtamedullary (15% to deep medulla) and cortical (85% - only junction of cortex and medulla)
descending = impermeable to solute, permeable to water.
thin ascending limb = impermeable to water, permeable to solule
TAL = permeable to ions and impermeable to water
this aids its mechanism in creating high osmoltic pressure in depths of medulla and hence water conservation.
describe the countercurrent mechanism in LoH…
active transport of solutes out of TAL - Na/K basolateral, Na/2Cl/K luminal, K+ channels basolateral etc
creates high osmotic pressure in interstium
water leaves the DL
as descending travels further down, less water to dilute and thus interstitial fluid increases in osmotic pressure
increases conc of solute within DL
this is fed back round to TAL which is impermeable to water and now has high conc solutes delivered for further AT
the hairpin arrangement creates a countercurrent mechanism which creates very high concs in depths of medulla. 1400mOSm /L at deepest point.
this allows for efficient water reabsorption by collecting duct in times of dehydration.
what is the fluid leaving LoH like?
TAL has pumped out fluid so dilute
100mOSmol/l enters DCT
what is the role of the vasa recta?
capillaries emerging from efferent arterioles
hairpin structure following LoH
this hairpin arrangement and low flow means solutes are not washed away as equilibrium is reached.
however O2 is still supplied
how does ATII affect vasarecta , what about other drugs
vasoconstriction of vasa recta, slows down flow
allowing time to equilbrate and hence maintaining medullary concentrations
hence aids fluid absorption
some drugs will oppose this e.g. ARBs, ACEi
what is the role of DCT?
further reabsorption of solute - Na/ HCO3, K
impermeable to water so delivers hypotonic solution to collection duct for control of water regulation
also contains macula densa - part of juxtamedullary apparatus and communicates with afferent arterioles.
what is the function of the collecting duct?
role in water reabsorption and homeostasis of osmotic pressure
And also in Na reabsorption
OSMOTIC HOMEOSTASIS:
Dilute fluid enters collecting duct
collecting duct passes through medulla
if aquaporins are present, reabsorption of water is allowed by the high osmotic gradient created by LoH
if aquaporins are not present, dilute urine is excreted
this is regulated by ADH
urea recycling also plays a role here.
NA REABSORPTION
collecting duct also plays a role in sodium homeostasis under influence of aldosterone.
how does the body achieve homeostasis of plasma osmolality?
sensors - control centre - effectors
with the hypothalamus and collecting ducts of the kidneys playing a central role in this
Sensors
* paraventricular and supraoptic nucleus of anterior hypothalamus
* detect changes to osmotic pressure
Control centre
* hypothalamus sends impulses to posterior pituitary and ADH is secreted, also sends impulses to initiate thirst
Effector
* ADH travels in blood
* receptors V2 on collecting ducts
* GPCR - Gs - cause vesicles containing aquaporin to fuse with luminal membrane
* (Aquporin channels already on BL membrane)
* now water can flow down osmotic gradient into the renal interstitium and absorbed by capillaries
what is the normal osmotic pressure of the blood?
280-290mOsm/Kg H20
where is ADH produced and stored
produced in hypothalamus (supraoptic)
travels down by axonic transport
stored in vesicles of posterior pituitary
what stimuli can cause ADH release and inhibit it?
stimulus = high osmolarity , ATII (volume depletion), sympathetic NS, opioid receptors, emotions (pain, stress), other drugs nicotine
which drug inhibits ADH
alcohol
what are the roles of ADH?
osmolarity homeostasis - collecting duct
vasoconstriction - helps with volume depletion
role in clotting (desmopressin releases vWF), platelet aggregation
neurotransmitter - release of ACTH
why is homeostasis of osmolarity important?
human cells are subject to osmotic pressure. in hypotonic solutions, water will enter cells and they can burst and in hypertonic they can shrink/ dehydrate
in the brain oedema in a constricted space can result in increase ICP and reduced perfusion and ischeamia
what is the role of urea in osmoregulation
urea is an active osmole
ADH causes urea channels on collecting duct
urea leaves collecting ducts, increases osmolarity of interstitium further, aiding further water reabsorption in times of dehydration
it is recycled by descending limb
what disorders of osmolarity do you know
excess ADH
* SiADH - lung tumours, traumatic brain injury
* low plasma osmolarity, concentrated urine. hyponatraemia
no ADH
* neurogenic diabetes insipidus
* dilute urine 23L/day
* high osmolarity, high sodium plasma conc
* caused by traumatic brain injury, SAH, brain tumour
insensitivity to ADH
* nephrogenic diabetes insipidus e.g. lithium, congential , CKD
* dilute urine 23L/day
* high osmolarity, high sodium plasma conc
how is SiADH diagnosed and treated?
diagnosis = low osmolarity (less than 280) , low sodium ( less than 135), euvolaemic
treatment - lithium, demeclocycline , fluid restriction
how is diabetes inspidus diagnosed and treated
urine production > 3L/day (usually much more)
sodium >145
osmolarity >305
desmopressin and fluids
how is extracellular fluid volume regulated?
since sodium is the main osmotically active solute, mostly via chnages to Na conc
Neuronal
sympathetic NS / baroreceptors
Hormonal:
RAAS
ANP/ BNP
osmolarity and ADH
other:
direct passive influence - more ECF, more GFR, higher excretion rate. more ECF, less reabsorption via peritubular capillaries
psychological and social factors -e.g. diet, fluid intake
how is GFR measured?
tindirect
* clearance of inulin - inulin is a polysaccharide that is freely filtered and not bound by plasma proteins, not reabsorbed or secreted or metabolised
* it is infused into a patient and clearance of it is measured
* this is accurate however time consuming and impractical
indirect / estimation
* using creatinine and cockcroft and gault equation which takes into account age, weight and gender to estimate GFR
* there is also the modification of diet in renal disease (MDRD) equation and the CKD EPI equation
* this is easier as creatinine is a natural byproduct of muscles so no need for an infusion however creatinine is secreted so not completely accurate and will over estimate GFR.
what properties of a substance make it ideal in measuring GFR?
freely filtered
not metabolised
not reabsorbed
not secreted
inert
doesnt influence GFR itself
what are the problems of using creatinine to estimate GFR?
some is secreted so overestimation of GFR
amount produced depends on body muscle amount - so can vary from gender to race to individual.
