what is the horizontal gradient between levels of the loop of Henle
200 mOsmol
how do stretch receptors in the bladder control micturition (babies/ spinal injuries)
become distended as the bladder fills (300- 350mls) until their output is large enough to stimulate parasympathetic system and relax external sphincter by inhibiting somatic neurones
what effect does hyperkalaemia/ hypokalaemia have on the body cells
hyperkalaemia - >5.5 - lower r.m.p –> ventricular fibrilation
hypokalaemia - <3.5 - increase r.m.p –> hyper polarise cells –> cardiac arrythmias
when the renal artery constricts what hormone is released
Renin
what is the HCO3 in blood
24 mmoles/ L (22- 26)
what is the pH of blood and how many H ions are free
7.4 (7.37 - 7.43)
4 x 10-6 mmoles/L free H - contribute to pH
what is the henderson hassebalch equation for pH
pH = HCO3/ PCO2
if a substance has a lower clearance that inulin what will happen
filtered and reabsorbed
[Ux] lower, [Px] higher
how do changes in osmolarity affect osmoreceptors
increases osmolarity - water out the cells, cells shrink, increased neural discharge
decreased osmolarity - water in the cells, cells swell, decreased neural discharge
what is the anion gap
difference between the sum of principal cations (Na and K) and principle anions (Cl and HCO3) in the plasma
normally 14-18 mmoles/L
what is the filtration fraction of the kidneys
19%
GFR/ Renal plamsa flow (55% of BV) x 100 = 125/660 x 100
when the mean arterial blood pressure increases, what happens to the afferent arteriole?
constricts - prevent rise in glomerular pressure
describe the process of ammonium excretion
in renal tubule cells - deamination of glutamine by renal glutaminase enzyme produces NH3
NH3 moves out tubule to combine with secreted H (fro CO2 in blood)
NH4 is formed in lumen which combines with Cl and NH4Cl is excreted in distal tubule
how does a metabolic alkalosis occur
HCO3 increase
what is the minimum and maximum pH of urine
min - 4.5-5
max - 8
what is used to estimate GFR
creatinine clearance
eGFR = 1/ [PCr]
in antidiuresis, how is urea retained to save water
reabsorbed from collecting duct into interstitium where it reinforces the interstitial gradient in the loops of Henle
if molecules X has filtration < excretion what will be the renal handling of X
net secretion
how do osmoreceptors regulate ADH secretion
increased osmolarity increased neural discharge mediated by osmoreceptors in the anterior hypothalamus
what is the mechanism for reabsorption of HCO3
active H secretion from tubule cells coupled to passive Na reabsorption
filtered HCO3 reacts with H to form H2CO3
with carbonic anhydrase this is converted into CO2 and H20
CO2 freely permeable and enters the cell
within the cell CO2 forms H2CO3 which dissociates to H and HCO3
the HCO3 ions pass into the peritbular capillaries with Na
(1 for 1 - no net gain)
how does increased sympathetic nerve activity impact renin release
increase release (B1 effect)
why can a big blood transfusion cause a metabolic alkalosis
bank blood contains citrate to prevent coagulation which is converted to HCO3
in the absence of ADH, what happens to water in the collecting duct
impermeable to H20 so large volumes of dilute urine are lost (compensate for H20 excess)
where does the majority of respiratory acid get buffered
97% within cells
rest within plasma proteins
what is the function of ANP
promotes Na excretion
what is the kidney regulation of HCO3 dependent on
active H ion secretion from the tubule cells into the lumen
how does the body respond to a low ECF to reduce blood pressure
reduced; ECF –> plasma volume –> venous pressure –> venous return –> atria pressure –> end diastolic volume –> systolic volumes –> cardiac output –> BP –> carotid sinus baroreceptor that normally inputs sympathetic discharge
increased sympathetic discharge
why is the oncotic pressure in peritubular capillaries so high
very concentrated plasma proteins
why is knowing GFR important in drug prescribing
if drug is excreted by the kidneys reduced GFR will increase drug concentration which may lead to toxicity
(adjust dose to appropriate renal function)
what factors affect serum creatinine
muscle mass
dietary intake
drugs
when is ANP released from he atria of the heart
response to expansion of ECF volume - causes natriuresis, loss of Na and H20 in urine
how do pudendal nerves control micturation
somatic motor neurones - innervate skeletal muscle of external sphincter, keeping it closed against strong bladder contractions (s2,3,4)
for micturition they must be inhibited by interneurones
how long do respiratory compensations take to occur
minutes
how does the kidney regulate HCO3
reabsorbing filtered HCO3
regenerating new HCO3
what blood pressure range is auto regulation effective in
60- 130 mmHg
filtration ceases <50 mmHg
how do juxtaglomerular cells act as renal baroreceptors
increase renin release when increased pressure in afferent arteriole
what can cause a metabolic alkalosis
- H ions lost in vomiting
- renal H lost in excess aldosterone/ liquorice (glycyrrhizic acid)
- excess HCO3 administration in renal impairment
- big blood transfusions
what is the equation for the buffer of plasma proteins
Pr + H –> HPr
what is the osomotic concentration of the fluid that leaves the proximal tubule
300 mOsmoles/ L - same as the plasma
what is used to measure renal plasma flow (RPF) and why
para-amino hippuric acid (PAH)
- freely filtered and actively secreted so plasma content is cleared of it
what is the net filtration pressure of the glomerulus
10 mmHg OUT
what is the vertical gradient of the loop of henle
300 -1200 mOsmol
what drug abolishes the the active transport of NaCl in the loop of henle
diuretics - furesmide
NaCLa nd H20 are no longer absorbed and concentration differences are lost - kidney produces a large amount of isotonic urine
what is oncotic pressure
osmotic force exerted on fluids by presence of proteins in the blood and tissue
where are the low and high pressure receptors
low - L and R atria and great veins
high - carotid and aortic baroreceptors
how does the body respond to a chronic metabolic acidosis
Renal correction increase H excretion and generate new HCO3 by ammonium excretion - need renal glutiminase (4-5 days)
how long does the kidney take to adapt to acid loads
4-5 days (chronic)
requires protein synthesis of renal glutiminase
how would the posterior pituitary respond to dehydration
increase ADH
what molecules share the same carrier molecule as Na
glucose, AA, HCO3
where is Angiotensin Converting Enzyme (ACE) found
throughout vascular endothelium
Where are the Na pumps in the proximal tubule
basolateral membrane
is the urea clearance higher or lower than inulin
lower - reabsorbed
which bladder sphincter is under voluntary control
external
how would low P receptors in atria respond to a reduction in ECF
decreased receptor discharge increases ADH released
In hypovolaemia, what affect does a reduction of atrial pressure have
Increases ADH secretion (low P receptors)
what is the normal decline of GFR
1ml/ min/ year after 30
how do pelvic nerves control micturation
parasymapthetic supply - increase contraction of detrusor muscle to increase pressure/ micturition (S2,3,4)
what would the ingestion of a hypertonic solution e.g seawater do to urine flow
Increase urine flow leading to dehydration
what 3 components on the glomerulus prevent solutes passing
fenestrations - RBC
basal lamina - larger proteins
still membrane between pedicles - medium sized proteins
what happens in the ascending limb of the loop of henle
fluid flows up
Na and Cl actively transported out of lumen into interstitium
impermeable to water
how does the body responf to metabolic acidosis
Increase PCO2 by decreasing ventilation
HCO3 lost in urine
If the pressure of the glomerular capillaries increases, what happens to filtration?
also increases
what are the main symptoms of diabetes insidious
polydipsia and polyuria (very large volumes of very dilute uric - >10 L day)
what is the maximum concentration of urine produced by the kidneys
1200- 1400 mOsmoles/L
what is the renal threshold for glucose
10 mmoles/l
way above plasma level of 5 mmoles/L - all is reabsorbed
how does a hyperglycaemic coma occur
- glucose remains in tubule retaining water with it
- decreased Na concentration in lumen as it is more diluted
- reduced glucose and Na reabsorption (symport)
- reduced movement of water in DESCENDING loop of henle (retain water)
- fluid delivered to ascending limb is less concentrated
- lower medullary interstitial gradient
- macula densa detects high NaCl delivery so inhibits renin
- ADH has no function can’t conserve H20
- large volume of isotonic urine lost
- inadequate brain flow of blood
in a drastic ECF volume change that affects MBP which receptors contribute to ADH secretion
carotid and aortic
how does ADH control the permeability of the collecting duct to water
aquaporins on the luminal membrane
cAMP secondary messenger system tell cells to insert pores into membrane
what happens to urea in the collecting duct in the presence of ADH
becomes more concentrated due to the removal of water
what does the activity of renal glutaminase depend on
pH - if pH falls, activity increases - more NH4 formed and excreted
what is a major source of alkali
oxidation of organic anions such as citrate
which receptors do moderate decreases in ECF affect
low P receptors in atria
what blood vessels are responsible for reabsorption
peritubular capillaries
what percentage of the filtrate is removed by the loop of henle
15-20% - up to 36L
what is the equation of the plasma clearance of X
Cx = [Ux} x V / [Px] in mls/ min
what causes urine to flow from kidneys to ureters
peristaltic contraction
what is the function of ACE
converts angiotensin I into angiotensin II
what is renal threshold
plasma threshold at which saturation occurs
what are the differences between central and peripheral diabetes insidious (ADH deficiency)
central - hypothalamic area is diseased from tumour, meningitis etc, treat with ADH
peripheral - collecting duct insensitive to ADH
how can acidosis lead to ventricular fibrillation and death
K is moved out of cells with H, leading to hyperkalaemia
if you increase the blood pressure of the glomerular capillaries, what happens to filtration
increases
what is the respiratory source of H
CO2 + H20 –> H2CO3 –> H + HCO3
ie formation of carbonic acid - in a healthy person this will be adjusted by an increase in ventilation
what fraction of the concentration of H in comparison to Na
one millionth
what allows the kidney to produce urine of varying concentrations
counter current multipliers of juxtamedullary nephrons
describe the efferent arterioles of the glomerulus
long and narrow, increasing friction and resistance for fluid (causing a build up of pressure in the glomerulus and inhibiting free outflow of blood)
in hypovolaemia what happens to the hydrostatic pressure in peritubular capillaries
reduced - efferent arteriole constriction by angiotensin II
what is the equation for the buffer dibasic phsophate
HPO4 + H –> H2PO4 (monobasic)
once urien has left the kidneys, does its composition change
no
what can cause a metabolic acidosis
- increased H production eg DKA, lactic acidosis, acetoacetic acid
- failure to excrete normal load of H eg renal failure
- loss of HCO3 eg diarrhoea
in hypovolaemia what happens to the oncotic pressure in peritubular capillaries
increased - loss of salt and water increases the concentration of plasma proteins
where is the hypertonic medullary gradient established
loop of henle in the medulla
which hormone does the increase in renin increase production of
angiotensin II
why is there no change in anion gap when HCO3 is lost from the gut in metabolic acidosis
compensated by increase in Cl
what are the main functions of the proximal tubule
65-75% NaCl & H20 reabsorbed
all important substances reabsorbed - glucose, AA, FAs
major site of tubular secretion
what is the plasma concentration of Na
142 mmoles/L
how much urine is excreted every day
1-2 L
what 2 things cause and acidosis to occur (metabolic/ respiratory)
respiratory - Increase in PCO2
metabolic - Decrease in HCO3
how does the body cope with an acute metabolic acidosis
stimulates ventilation so that PCO2 falls (can reach 30L/ min when pH falls to 7)
what is responsible for creating the interstitial gradient in the loop of henle
active transport of NaCl of ascending limb
if ADH is present, what happens to water in the collecting duct
leaves it so less urine is lost and more is added to ECF
which of the starlings forces favour filtrations
hydrostatic pressure (fluid out a vessel)
what are the 2 main physiological processes in the renal response to a low ECF
reduced atrial pressure
Increased sympathetic discharge (carotid baroreceptors stop inhibition)
what is the pressure of the glomerular capillaries dependent on
afferent and efferent arteriole diameter and the balance of resistance between them
where is K primarily reabsorbed
proximal tubule
in hypovolaemia, what effect does a reduction in carotid sinus baroreceptor inhibition of sympathetic discharge have
increases vasoconstriction
Increased total peripheral resistance
Increases BP
where does the majority of metabolic acid get buffered
43% in plasma (with HCO3)
57% in cells
what does the quantity of carbonic acid in the blood depend on
amount of CO2 dissolved in plasma (solubility of CO2 and PCO2)
what vessels absorb water from the medullary interstitum
vasa recta
what 3 factors determine filterability of solutes across the glomerular filtration barrier
molecular size, electrical charge, shape
how do people live with a chronic respiratory acidosis
kidney produces HCO3 to protect pH
acidic conditions stimulate RG formation
how long does it take for the entire blood volume to pass through the kidneys
<5 mins
How does a change in ECF affect ADH secretion
increased ECF reduced ADH - more diuresis and reduced reabsorption
what is the function of renin
cuts angiotensinogen into angiotensin I
if you constrict the efferent arteriole, what happens to filtration?
increases - reduce blood flow out
what is the vasa recta
specialised arrangement of peritubular capillaries of the juxtamedullary nephrons (hair pin loops)
which type of neurones control sensory innervation of the bladder
interneurones (pathways to sensory cortex –> sensation of fullness)
why is the blood flow through he vasa recta very slow
gives time to equilibrate with the interstiitum
is the glucose clearance higher or lower than inulin
clearance = 0 - all reabsorbed
what reflex is used by paraplegic patients to train themselves to initiate voiding
mild mass reflex
e.g pinch skin/ stroke thighs
what are 3 basic renal processes
filtration
reabsorption
secretion
why is GFR useful in measuring renal disease
progression of destruction of nephron function decreases GFR (total GFR = sum of all filtration by functioning nephrons)
what is the normal plasma osmolarity
280-290 mOsm/ kg H20
why is the hydrostatic pressure in the peritubular capillaries so low
due to hydrostatic pressure overcoming frictional resistance from efferent arterioles
in what situation is auto regulation of glomerular capillaries overridden and by what
when BP/ blood volume is under serious compromise e.g. haemorrhage
sympathetic vasoconstriction and angiotensin II
(this frees up blood for other organs - up to 800mls/ min)
where does the filtrate pass after the glomerulus
bowman’s capsule
how do hypogastric nerves control micturation
sympathetic supply - inhibit bladder contraction
main function is to prevent reflux of semen into bladder during ejaculation (L1-L3
Why does the oncotic pressure of the glomerulus increase throughout
Become more concentrate when everything but the proteins are filtered out (30 mmHg)
which arterioles does angiotensin II constrict at low and high pressures
low - efferent
high - both
in hypovolaemia, what can cause a hyperglycaemic coma
osmotic diuresis
what percentage of the filtrate can be reabsorbed in the proximal tubule during a volume deficit
75% - increased oncotic pressure
what do starling forces favour in the vasa recta
reabsorption - high oncontic pressure due to high concentration of particles and tight renal capsule which drives fluid into capillaries
how does alcohol affect ADH secretion
suppress release from pituitary - absorb less fluid and pee out more (leading to dehydration)
What is the function of a buffer
minimise changes in pH when H ions are added or removed
what is the osmolarity concentration of the distal tubule
100 mOsmol (more dilute than the plasma)
what does angiotensin II do in the body response to hypovolaemia (4)
- stimulates aldosterone to increase NaCl and H20 reabsorption
- vasoconstrictor (increases TPR)
- acts on hypothalamus to stimulate ADH secretion
- stimulates this mechanism and salt appetite
what 2 things cause and alkalosis to occur (metabolic/ respiratory)
respiratory - decrease in PCO2
metabolic - increase in HCO3
what molecules are regulated by Tm / carrier mediated transport
glucose, amino acids, organic acids, PO4, SO4
what is the major adaptive response to an acid load and what does it do
ammonium excretion
generates new HCO3 and excretes H
what percentages of H20, glucose, Na and urea are reabsorbed within the tubules
H20 - 99%
glucose - 100%
Na - 99.5%
urea - 50%
which of starlings forces is greater at the glomerular capillaries
hydrostatic pressure (Pgc > pie) only filtration occurs
what are the 3 mechanisms of reabsorption
carrier mediated transport system
Active transport of Na
tubular secretion
how does aldosterone affect K secretion
increases at distal tubule (K lost)
what pathways are set up during potty training
voluntary initiation pathways
what must a solute be to impact ADH secretion
an affective osmole - Na etc
urea, glucose etc are ineffective
what is the net production of H per day
50-100 mmoles per day
What substances are removed from the body by secretion
harmful - drug metabolites, K, H,
protein bound
How is Cl reabsorbed in the proximal tubule
diffuse passively down electrochemical gradient established by Na active transport
What constituents fo plasma flow are not filtered
RBCs
Proteins bigger than albumin
what is the average hydrostatic pressure fo the glomerulus
55 mmHg
what is a metabolic acidosis due to
decreased HCO3 from increased H buffering or direct loss of HCO3
what 2 things inhibit renin release
angiotensin II feedback
ADH
what is the minimum concentration of urine produce by the kidneys
30-50 mOsmoles/ L
what is the metabolic source of H
inorganic - S containing amino acids and phoshpholipids
organic - fatty acids, lactic acid (approx 50-100 mmoles H a day)
how does the renal tubule respond to an increase in K concentration
increase K secretion to decrease intracellular K
where is ADH synthesised
supraoptic (SO) and paraventricular (PVN) nuclei of the hypothalamus of the brain
describe the afferent arterioles of the glomerulus
wide and short with little resistance to flow
lots of blood pushed into the glomerulus at a high hydrostatic pressure
what is the pCO2 in blood
40 mmHg (36- 44)
what is the primary control of ADH secretion
increase in plasma osmolarity
if you constrict the afferent arteriole, what happens to filtration?
decreases - lower pressure in glomerulus
what can be given in a high acidosis to prevent hyperkalaemia
Ca gluconate
what feature of renal vasculature keeps BF and GFR constant
autoregulation - intrinsic ability to adjust resistance in response to changes in a retrial BP
where in the nephron does ionic regulation occur
distal tubule
what is the half life of ADH and why is this
10 minutes - can rapidly adjust to the body needs for water conservation
what is different about ammonium excretion in the distal and proximal tubules
proximal - Na/ NH4 exchanger - NH4 is formed within the cell
why is the anion gap increased in a lactic /diabetic metabolic acidoses
reduction in HCO3 is replaced by other anions like lactate etc.
are carrier mediated secretory mechanisms specific
no
eg. lactic/ uric acid, penicillin, aspirin, PAH same
choline, creatinine, morphine atropine same
what is the biggest factor that affects GFR
Pressure of the glomerular capillaries (Pgc)
what is kussmaul breathing
hyperventilation in response to metabolic acidosis
what creates the osmotic force in the proximal tubules that drives H20 out
active transport of Na and Cl out
increases concentration of solutes inside tubules - glucose, urea
why does an increase in H in the ECF increase ventilation
drive equation to the right - increased carbonic acid formation and water and CO2
ventilation is then increased to blow off the extra CO2
what are causes of an acute respiratory acidosis
obstruction of major airways
drugs which depress medullary respiratory centres - opiates/ barbiturates
when using dibasic phosphate as a buffer, what is the source of the new HCO3
CO2 indirectly from blood
process depends on PCO2
what are the 2 main affects of angiotensin II on the tubules
- increases aldosterone production which increases NaCl and H20 reabsorption in DISTAL tubule
- increases NaCl and H20 reabsorption in PROXIMAL tubule
what is the gold standard for measuring plasma clearance and why
inulin clearance - freely filtered/ no kidney metabolism
IV loading dose and sample plasma / urine
which of the starlings forces favours reapsorption
oncotic pressure
what is the function of ADH/ vasopressin
control how concentrated the urine is
what is the total body water distribution in the body (42 L)
1/3 ECF (14L) - Plasma (3L), Interstitial fluid (11L)
2/3 ICF - intracellular fluid (28L)
what its the average daily GFR
180 L/ day
what is the ratio of bicarbonate (HCO3) to carbonic acid (H2CO3)
20 : 1
what is the relationship between the rate of ADH secretion and rate of discharge from stretch receptor afferents
inverse
What does a decreased delivery of NaCl to the macula densa do to renin release
increase renin release
what is the site of water regulation
collecting duct
what determines body water between cells and ECF
osmotically active particles - Na and Cl (major ECF osmoles)
what cells produce the hormone renin and where are they found
juxtaglomerular cells
smooth muscle cells of the media of the afferent arteriole
what are causes of an acute respiratory alkalosis
voluntary hyperventilation
aspirin
first ascent to altitude
why does volume consideration take primacy over osmolarity if ECF is compromised
save perfusion to the brain
how is urine removed form the male and female urethra
male - contractions of the bulbocavernous muscle
female - gravity
what percentage of Na reabsorption occurs in the proximal tubule
65-75%
active transport establishes a gradient for Na across wall
which tubule is dibasic phosphate used as a buffer and what does it produce
distal
generates new HCO3 and excretes H
if a substance has a higher clearance that inulin what will happen
filtered and secreted
[Ux] higher, [Px] lower
why does aldosterone cause a weight gain
retention of H20 and water
volume expands until ANP causes natural diuresis
which 3 nerves control motor innervation of micturition
pelvic - parasympathetic
hypogastric - sympahtetic
pudendal - somatic motor neurones
How is the electrocehmical gradietn for Na reabsorption established
Na/K ase - 3 Na for 2 K - gradient drives Na out the cell
what is respiratory alkalosis a result of
fall in PCO2 from increased ventilation and CO2 blow off
what creates the fluid pressure of the glomerulus (hydrostatic)
pressure created by fluid in Bowman’s capsule
where in the loop of henle is the fluid most concentrated
at the bottom, in between descending and ascending limbs
where does the bulk of HCO3 reabsorption occur
proximal tubule
what is Tm
the max capacity of a carrier mediated transport system
what 4 factors affect GFR
pressure of glomerular capillaries
sympathetic vasoconstriction nerves
circulating catecholamines (constrict mostly afferent)
Angiotensin II
how does the body respond to severe vomiting (hypovolaemia and metabolic acidosis)
stimulate aldosterone to increase distal tubule Na reabsorption (H ion exchange as Cl is lost)
Increase PCO2 to drive H secretion
- this exacerbates the metabolic acidosis but restoring volume is more important
how does the kidney respond to chronic respiratory alkalosis
reduces HCO3 by reabsorptive mechanism - lost in urine
Why is glomerular capillary pressure higher than in most other capillaries fo the body
Afferent arterioles have a high hydrostatic pressure and efferent arterioles cause a build up of pressure in glomerulus
what is the golden rule of circulation
if you have a high resistance, hydrostatic pressure upstream is increased, while the pressure downstream is decreased
Where does the majority of reabsorption occur
distal and proximal tubule
what is the titratable acidity
measure of the amount of NaOH needed to titrate urine back to a pH of 7.4 for a 24 hour sample
why does buffering of H by intracellular buffers cause a change in electrolytes
in RBC - accompanied by Cl
exchanged for K
What is the plasma concentration of K
4 mmoles/L
what are causes of a chronic respiratory alkalosis
long term residence at altitude
low PO2 <60 mmHg - peripheral chemoreceptors increase ventilation
how much HCO3 if filtered per day
4320 mmoles - all reabsorbed
180 x 24
what is the average GFR
125 mls/min
what is the rate limiting step int eh production of angiotensin II
release of renin (angiotensinogen is always present in plasma)
is the penicillin clearance higher or lower than inulin
higher - filtered and secreted
what makes the border of the proximal tubule have a higher permeability to Na ions
enormous surface area from microvilli
large number of Na ion channels
which input responses increase ADH secretion
pain, emotion, stress, exercise, nicotine, morphine, traumatic surgery TO RETAIN FLUID
what is respiratory acidosis a result of
reduced ventilation - retention of CO2
if molecules X has filtration > excretion what will be the renal handling of X
net reabsorption
what is the normal GFR in a 1.73m^2
100 mls/ min
which hormone controls distal tubule Na reabsorption
aldosterone
what happens int he descending limb of the loop of henle
fluid flows down
relatively impermeable to NaCl
what are causes of a chronic respiratory acidosis
lung disease - bronchitis, emphysema, asthma
what hormone regulates K secretion
aldosterone
what are the main intracellular buffers
Proteins, organic and inorganic phosphates, haemoglobin in erythrocytes
what is the minimum obligatory loss of H20 each day and why
500 mls - urea, SO4, PO4, ammonia, non waste ions (Na and K)
what are the functions of the vasa recta
provide oxygen for medulla
don’t disturb interstitial gradient
remove volume from the interstitial
if blood pressure drops, what happens to Na active transport
reduces
where is ADH release from
posterior pituitary
what is the average blood flow to the kidneys
1200 mls/ min (20-25% of CO)
what happens to a substrate if it is present in concentrations higher than Tm
excreted in the urine
