physiology Flashcards
what is filtration?
process in kidney that occurs at glomeruli to form filtrate protein free
GFR?
AND VALUE?
180L/DAY = 125mls/min
measure of kidney function to regulate eco volume and eliminate waste/toxins
reabsorption is?
substances reabsorbed into blood and not to be excreted into urine
secretion is?
secreting substances into tubule and want to be excreted into thru urine
why are kidneys at high risk of vascular disease?
as high % of cardiac output used here - so vulnerable
efferent arterioles lead to ?
efferent arterioles lead to peritubular capillaries and then to renal vein
what forces are filtration dependant on? 2
hydrostatic forces - causing filtration
oncotic pressure forces - against filtration - but favour reabsorption
what other factors affect filtration?
molecule size
charge
shape
describe the normal afferent and efferent arterioles?
afferent - short and wide = low resistance
efferent - long and narrow = high resistance
why does only filtration occur at glomerular capillaries?
as hydrostatic pressure always exceeds oncotic pressure
hydrostatic pressure in glomeruli (Pgc) dependant on?
afferent and efferent arteriole diameter and balance between them
if contract afferent/efferent arterioles impact on filtration?
afferent contracted = decreased flow - decreased filtration
efferent contracted = lack of flow out - pressure in capillary increase and increased filtration
auto regulation of kidneys means?
kidneys are indepednat of nerves and hormones - can regulate GFR and blood flow themselves - can see it still in a isolated perfused kidney
percentage of plasma that is filtered?
20%
percentage of filtrate reabsorbed and secreted ?
19% reabsorbed and 1% excreted
forces needed for reabsorption and where?
oncotic pressure highest and hydrostatic pressure falls favouring reabsorption
in peri-tubular capillaries
reabsorption occurs where mainly in tubule?
primary convoluted tubule
tm?
maximum transport capacity of reabsorption - due to saturation of carriers
what happens if tm exceed?
excess substrate enters the urine - excreted
glucose filtering how much?
how much is reabsorbed?
freely filtered - all filtered
10mmoles/L - will be reabsorbed
normal glucose level?
5mmol/l
What does it mean when tm is set way above?
it means to ensure all nutrient is normally reabsorbed and maintains normal plasma conc.
how are Na ions reabsorption?
where?
and what is the result of this?
not by Tm mechanism - active transport instead
in proximal tubule
establishes a conc. gradient across tubule wall for other solutes to pass passively & use of carrier mediated transports
through use of Na active pumps
what ions diffuse passively across proximal tubule?
Cl- - negative ions
what drags/reabsorbs the rest of the permeable solutes across membrane?
water moves by osmosis and creates ongoing conc gradients - as it concentrates all the substances left in the tubule - creates conc. gradient
rest travel across by diffusion
how much urea is reabsorbed?
50% - reminder stays and most excreted
proximal tubule membrane impermeable to?
inulin and mannitol
normal ECF K level?
4mmoles/L
what happens to K in kidney? 3 things and where
filtered at glomerulus and reabsorbed at proximal tubule and secretion occur in distal tubule
aldosterone does what?
controls K secretion
Aldosterone increases =
increases K secretion in distal tubule
increases Na reabsorption in distal tubule
proximal tubule what occurs here?
reabsorption
what is the type of fluid leaving the proximal tubule?
isosmotic - 300 mOmoles/l
where are the proximal and distal tubules in the kidney?
in the cortex
where are the loop of Henle’s?
in the medulla
what is the minimum H2o loss? and why
500mls
required bc important for excretion of waste products
loop of Henle act as?
counter-current multipliers
explain ascending limb and descending limb of henle?
ascending limb - actively transports Na/cl out of tubule - impermeable to water - DILUTES
descending limb - freely permeable to water 0 impermeable to NACL - CONCENTRATES
what is the result of the ascending limb of the loop of henle?
conc falls in tubule
interstitium rises
horizontal gradient of 200mOsm made
producing hypotonic urine into distal tubule
role of the vasa recta ? 2
provide oxygen to medulla without disturbing gradient between interstitium and tubule
and removes volume from the interstiitum
where is the site of water regulation? controlled by?
in collecting duct where permeability is controlled by ADH
ADH released where?
made by what?
from posterior pituitary gland
made by SO and PVN in hypothalamus
stored in posterior pituitary and then released
adh relationship with water in body?
adh increase when decrease water in body - to preserve water in body and higher osmolarity
makes you pee more conc urine
when dehyrdrated -
adh and tonicity or osmolarity relationship ?
ONLY an increase in osmolarity that also increases tonicity is effective in causing an increase in ADH
toncitiy referring to solutes that are impermeable
is urea permeable?
yes - so doesn’t affect tonicity
the amount of urine to excrete depends on what? 2
adh
amount of solute to be excreted - as water needed to excrete it out !
how is the permeability of the collecting duct altered?
by incorporating water channels into the membrane - aquaporins - water pores in membrane
adh present means what type of urine?
what state is the body in then?
decrease volume of urine
increased conc of urine
dehydration
where is urea reabsorbed in cd ?
near medullary tips - permeable to urea here
adh and urea relationship?
adh makes medullary cd membrane more permeable to urea - so less urea in urine
anti-diuresis means?
dehydration state - to preserve water - reduced urine
ecf volume and adh relationship?
ecf volume of plasma in vessels goes up
adh down
ecf volume detected by what? 3
carotid and aortic baroreceptors
AND
atrial stretch receptor
what’s the most important role of the kidney?
regulation of volume
regulation of ecf means regulation of what too?
regulation of Na levels
affect of lowering ecf volume?
give examples of the above where it can happen
vomiting, diarrhoea
decreases in plasma volume - decreases in plasma pressure - leading to decrease in blood pressure - detected by atrial and carotid sinus baroreceptors - can restrict vessels AND INCREASE ADH
how does reabsorptive range in proximal tubule?
due to changes in reabsorptive forces -
oncotic pressure
and hydrostatic pressure
reabsorption during hypovalemia? DUE TO
is more than normal
ONCOTIC higher than normal
hydrostatic lower than normal
what is the forces in the proximal tubule in normovolaemia?
Ppc - is less
oncotic - larger
favours reabsorption in normal conditions
regulation of distal Na reabsorption is by?
aldosterone
juxtaglomerular cells explain what?
granule cells - smooth muscle around afferent arteriole - before entering glomerulus
macula densa?
loop of distal tubule
what is the juxtaglomerular apparatus?
JG cells + macula dense in distal tubule
JG cells make?
renin
how much angiotensin II available is relied on what?
on how much renin there is
angiotensin I role?
inactive and no role - mostly always converted to ANG II due to always present ACE enzyme
aldosterone secretion triggered by?
angiotensin II
what is the rate limiting step?
release of renin
sympathetic activity - how does it cause increase in renin release?
via beta1 effect
how does macula dense communicate with afferent arteriole? and result of it
when flow past the macula densa increases - is sends paracrine signalling TO afferent arteriole - it then constricts and pressure decreases in glomerulus - and GFR decreases
volume or osmolarity to fix - what does the body do?
volume considerations have more importance - and is more key to maintain -
ANP does what?
it promotes Na excretion -
works against aldosterone
aldosterone affect on weight and why?
aldosterone increases Na reabsorption and water retention
this leads to weight gain
ANP release triggered by? 3
leads to?
aldosterone leads to ANP release
also triggered by volume expansion and weight gain
and increase in blood volume and bp
natriuresis - Na loss and h2o in urine
still K depleted
uncontrolled Diabetes leads to ?
hyperglycaemia coma = osmotic diuresis
explain the mechanism of uncontrolled DM?
- glucose levels in plasma exceed the TM and stay in proximal tubule
=and exerts an osmotic effect to retain water in tubule too
- Na reabsorption is decreased and so therefore symport glucose reabsorption is further decreased
= resulting in fluid that is very dilute - very dilute fluid entering ascending limb
- gradient in ascending limb is much less and EVENTUALLY LOST
- higher volume of water deliver to distal tubule
- this increase is detected by the macula densa AND detects the high rate of delivery of NaCl
- renin secretion is reduced and Na reabsorption in distal tube is reduced
- due to wrecked gradient - loose ability to conc. the urine - ADH loses ability to conserve
- excrete 8L of ISOTONIC urine per day
ascending limb of the loop involves what ions to be reabsorbed?
via what?
NaCl and POTASSIUM
vis the NaK Cl co transporter
why must we regulate pH so much?
as enzymes reside here - so must keep highly regulated
What contributes to the pH level?
number of free H+ ions
2 types of acid?
respiritary acid and metabolic acid
respiratory acid meaning?
increase ventilation
decrease in co2
lead to increase in carbonic acid
increase in H+ ions
metabolic acids examples?
inorganic acids - phosphoric acids/amino acids
organic acids - fatty acids/lactic acids
major source of alkali?
organic anions - citrate
what is the role of buffer?
to minimize changes in pH when H+ ions are added or removed
what’s the most important buffer?
name other buffers
bicarbonate buffer
plasma proteins/dibasic phosphate
HCO3- regulated by?
Pco2 - regulated by?
renal regulated -
respiratory regulated - ventilation
movement of H+ in and out of cells explain?
this can lead to what?
must be accompanied by Cl- in red cells or exchanged for a cation K+
in acidosis leading to hyperkalaemia/electrolyte disturbances
pH remains in normal range as long as?
as long as kidney and lungs are working normally
what does kidney regulate and how?
regulate HCO3-
- by reabsorbing filtered HCO3-
- by generating new HCO3-
both depend on active H ion secretion from tube cells on lumen
titratable acidity meaning?
explain what happens in process?
buffered by HPO4-
the amount of NaOH needed to titrate urine pH back to neutral for urine sample
generates new HCO3-
and excretes H+ ions
WHEN ACID LOAD ONLY
in distal tubule
distal tubule titratable acidity occurs leads to what?
generation of new HCO3- and excretion of H+
resulting in increased conc of P04-
what is ammonium excretion?
major adaptive response to an acid load - pH down
generates new HCO3-
excretes H+ ions
carbonic anhydrase does what?
enzyme that catalyses conversion from carbonic acid dissociation into its ions - H+ AND BICARBONATE
RENAL GLUTAMINASE does what?
enzyme that catalyses the conversion of glutamine AA into glutamate AND DURING PROCESS FORMS NH3
AMMONIUM excretion occurs where? 2
and difference between 2 locations
occurs in distal tubule and proximal tubule cell
distal - NH4+ forms outside tubule cell
proximal - use of NH4+/nA+ EXCHANGER - where NH4+ forms within cells and pass out into lumen
renal glutamine is what dependant?
explain relationship
pH dependant
pH falls AND RG increases in activity
how long does it take for ammonium excretion to have its effect? and why?
takes 4-5 days to reach max effect - as requires an increase in protein synthesis of renal glutamine
and takes time to switch off too! for opposite situation - increased alkali
respiratory acidosis results from?
response?
reduced ventilation and retention of CO2
increases Pco2
to allow pH to fall
to increase HCO3-
causes of respiratory acidosis?
drugs that depress respiratory centres in brain
obstruction of airways -copd/bronchitis/asthma
respiratory alkalosis results from?
response?
increased ventilation and co2 blow off
decreases pco2
to allow pH increases
to decrease HCO3-
causes of respiratory alkalosis? 2
hyperventilation
altitude
metabolic acidosis?
response?
ph fall and due to HCO3 fallen
need to decrease pCO2
how is metabolic acidosis corrected?
explain process and referred as?
increasing ventilation - to decrease PCO2
increase in depth not rate
called KUSSMAUL BREATHING
CAUSES OF METABOLIC ACIDOSIS? 3
increase H+ production - DKA
failure to excrete H+ - renal failure
loss of HCO3- - failure to reabsorb
resp correction vs renal correction?
respiratory compensation - takes mins
renal compensation - longer and delayed as RG synthesis - 4-5days to reach max
metabolic alkalosis?
response?
ph increase and H+ decrease
increase in HCO3-
response is to increase pCO2
causes of metabolic alkalosis?
increase in H+ ion loss - vomit
increase in renal H+ loss
excess adminstration of HCO3-
big blood transfusion - contains chemical which converts into HCO3-
an increase in PCo2 - difference in changes in pH in chronic/acute resp acidosis ?
AND WHY
smaller decrease in Ph in chronic respiratory acidosis then acute respiratory acidosis
due to it takes time for NH2 production to switch on and have affect
why is it important to measure GFR? 2
if renal disease - need to see nephron destruction and function
if drugs - see if renal function - and excretion of drug occurring - or else toxicity!
clearance means?
vol of plasma cleared out
what is used for measuring clearance? and why
inulin - as freely filtered but neither reabsorbed or secreted
only measures filtration !
normal gfr? 2
125mls/min
100mls/min/1.73m squared
what substance is currently used for clearance/gfr measuring?
and what’s the formula
what type of measurement does this give?
creatinine
eGFR - 1/Pcr
it gives us a estimated GFR - not calculated/exact
what factors affect creatinine in body? 3
muscle mass - more muscle more creatinine
dietary intake - vegetarians have less C
drugs
glucose clearance is?
Zero as - ALL REABSORBED
UREA CLEARANCE?
LESS THAN INULIN
as 50% is reabsorbed
PAH CLEARANCE MEANS?
measure of all plasma flowing through kidney in given time - RENAL PLASMA FLOW
how is PAH CLEARANCE TESTED? e.g.
e.g - pencilling used
freely filtered and then remaining in plasma is actively secreted into tubule again
clearance larger than inulin
how do ureters enter bladder? and why
at oblique angle - prevent reflux of urine
what type of muscle in bladder?
detrusor muscle - 3 bundles of muscle
internal and external sphincter explain control and type of muscle?
internal - not true - smooth muscle - not self uncontrolled
external - true - voluntary controlled - skeletal muscle
urethral vs ureter obstruction?
urethral - bilateral renal problems
ureter - unilateral renal problems
urine production varies between what?
750ml - 2500mls
micturition reflex means?
release of urine - peeing after bladder fills and then empties
EUS relaxes means?
external sphincter opens - to allow pee out
how to delay peeing? (hold it in)
done by descending pathway from brain - established by potty training
what happens after urination in males and females?
males - all urine in urethra expelled by contractions of bulbocavernosus muscle
females - urine empties by gravity
osmolarity?
conc. of solute in solution
adh released in response to? 3
dehydration and increased osmolarity and decreased ECF volume
PTH secretion stimulated by?
and actions?2
low plasma calcium levels - so then its increases calcium ion reabsorption to increases CA plasma conc.
increases phosphate excretion in urine - by decreasing phosphate reabsorption
what determines ADH release?
changes in tonicity
prolonged vomiting leads to what state?
metabolic alkalosis - loss of HCl from stomach
hyperventilation and hypoventilation leads to what acid/base state?
hyper - respiratory alkalosis - breathing off co2
hypo - leads to respiratory acidosis - keeps co2 in blood
altitude affect on acid/base state?
respiratory alkalosis - increased ventilation
normal values of acid/base values? 3
ph - 7.4
bicarbonate - 24
PCO2 - 40mmHg / 5.3kPa
narrowed afferent arteriole leads to?
less blood flow
less pressure in glomeruli
less gfr
VICE VERSA
percentages of what is filtered/excreted/reabsorbed?
100 % enters afferent arteriole
20% filtered
more than 19% reabsorbed
less than 1% excreted
pressures at glomeruli and RESULT?
hydrostatic MORE THAN oncotic
favours filtration
pressures at peritublar capillaries and RESULT FAVOURS?
oncotic MORE THAN hydrostatic
favours reabsorption
how do inuline and mannitol go over proximal tubule membrane?
impermeable
what type of fluid is delivered to distal tubule?
hypotonic fluid - 100mOsmol/L
role of adh?
stimulated when low level of h2o in the body AND HIGH OSMOLARITY/TONICTY
used to
aim to RESERVE H20 and preserve it in blood
anti-diaeresis/
dehydration -
Na REABSORPTION IN PROXIMAL AND dISTAL tubule controlled by?
reasons for this?
aldosterone
in hypervolaemia/hypovolaemia
3 ways to increase in renin release?
2 ways to decrease renin release?
HYPOVOLAEMIA
increase in sympathetic activity
decrease in JG cells stretch
decrease of NaCl delivery to macula densa
angiotensin II negative feedback
increase ADH
Aldosterone does what to Na and K?
increases K secretion in distal tubule
increase Na reabsorption in distal tubule
hypoproteinemia affect on glomerular filtrate produced?
osmotic pressure exerted by plasma proteins is lower than normal - so filtration pressure increases and filtrate increased
haematocrit?
ratio of rbc to total blood volume - % of rbc in blood
does gfr change a lot based on arterial pressure?
NO DUE TO pressure auto regulation
PTH effect on excretion proximal tubule?
increases phosphate excretion in urine and decreases the reabsorption of phosphate too
HCO3 elevated as result to situation already means?
suggests disturbance has been going long enough for kidneys to compensate
what drug can produce diuresis?
explain mechanism?
furosemide
block NacL removal out of ascending loop of henle
- removing gradient - producing LOTS OF isotonic urine
diuresis mean?
lots of urine produced
ANG II does what?
constrict of smooth muscle
constrict efferent vessel of glomerulus
insulin and glucagon does what to secretion of somatostatin?
insulin decreases it
glucagon increases it
what detects changes in NaCl and changes gfr based on that?
macula densa
