Physiology 2 Flashcards
how much of the plasma is initially filtered by bowmans capsule
20%
how does the inital filtrate within bowmans capsule compare to the plasma
same minus plasma proteins
where does must reabsorption take place
within the proximal tubule
how much of what is filtered in reabsorbed
99% of fluid 99% of salt 100% of glucose 100% of amino acids 50% of urea 0% of creatinine
is reasborbtion of filtration specific
only reabsorbtion is specific (filtration relatively non specific)
what should glomerular filtrate not contain
RBCs, large plasma proteins
how mcuh fluid is reabsorbed in the proximal tubule
80 ml/min
how does the fluid reabsorbed within the proximal tubule compare to the filtrate
is iso-osmotic- no change in osmolarity between bowmans and end of proximal tubule
what is reabsorbed in the proximal tubule
sugars amino acids phosphate sulphate lactate
what is secreted in the proximal tubule
H+ hippurates neurotransmitters bile pigments uric acid drugs + drug metabolites (atropine, morphine, pencillin) toxins
what is the path of transcellular reabsorption
tubular lumen luminal membrane (into tubular epithelial cell) basolateral membrane (into interstitial fluid) endothlium
what is the path of paracellular reabsorption
through tight gap junctions inbetween the tubular epithelial cells
what is primary active transport
energy directly required to operate the carrier and move the substrate against its concentration gradient (energy from hydrolysis of ATP)
what is secondary active transport
when the molecule is transported coupled to the concentration gradient of an ion (usually sodium)
what is facilitated diffusion
passive carrier mediated transport of a substance down its concentration gradient
what is the sodium potassium pump
a primary active transporter
moves 3 Na out and 2 K in for every 1 ATP hydrolysed against their concentration gradients
what are the types of secondary active transporters
symporter- both molecules moving same direction
Anteporters - move in opposite directions
what are the different ways of getting into a cell
diffusion through lipid bi layer diffusion through channels facilitated diffusion primary active transport secondary active transport
where are Na+K+ATPase pumps alwats
on the basolateral membranes of cells
what is the Na+K+ATPase pump essential for
Na+ reabsorption
describe Na+ reabsorption in the proximal tubule
ISO-OSMOTIC
net movement of sodium from lumin to blood via transcellular route creates an electrical gradient
water follows this gradient via paracellular route (passive down NaCl osmotic gradient)
(Cl- also follows sodium)
what other than the NaCl osmotic gradient pulls water from the lumen into the capillary
oncotic drag of peritubular plasma- plasma proteins more concentrated within the blood pulls water into capillary (increased on= water in)
also follows the con gradient of glucose via a paracellular route
how much of glucose is reabsorbed in the proximal tubule
100%
what is glucose reabsorbed in the proximal tubule
co transport (in with Na+) ad luminal membrane facilitated diffusion at basolateral membrane
why is there no change in the osmolarity of the tubular fluid at either end of the proximal tubule
as solute and water reabsorbed in equal proportions
what is the transport maximum- why is it relevant
maximum rate at which we can reabsorb a particular substance that is dependent on the expression of specific membrane proteins
increasing plasma conc of a substance (e.g. glucose) saturates the transporters, that which cant be reabsorbed is excreted in the urine (diabetes)
what does PAH measure
renal plasma flow - completely filtered/ secreted
is there a secretion maximum
yes- secreting transporters can also be saturated
how much of salt and water are reabsorbed in the proximal tubule
67%
how much of glucose and amino acids are reabsorbed in the proximal tubule
100%
what drives Na+ reabsorption
the basolateral Na+ K+ ATPase
how does Cl- follow Na+
via paracellular pathway
how is water reabsorbed
osmosis (paracellular pathway)
describe the tubular fluid when it leaves the proximal tubule
iso-osmotic (i.e. 300 mosmol/l)
what is the function of the loop of henle
generates cortico-medullary solute concentration gradient (created by the interstitial fluid)
this enables the formation of hypetonic urine
acts as a countercurrent multiplier
what is fluid flow like within the loop of henle
countercurrent- opposing flow in the two limbs
what do the loop of henle and vasa recta establish together
a hyper osmotic medullary interstitial fluid
what is the role of the descending limb
highly permeable to water
does not reabsorb NaCl
what is the role of the ascending limb
Na+ and Cl- reabsorption
(thick upper= active transport, thin lower= passive)
relatively impermeable to water
what enables an osmotic gradient to be established within the medulla
selective permeabilities of the ascending and descending limbs
what three ions does the triple co transporter on the luminal membrane move into the cell
Na+
K+
Cl-
why is the ascending limb not permeable to water
gap junctions too tight
what do loop diuretics block
the triple co transporter within the ascending limb
in the ascending limb what allows NaCl to be absorbed into the interstitial fluid
K+ recycling (moving in and out of both luminal and basolateral membranes)
where is the triple co transporter
the thick ascending limb of the loop of henle
describe what happens to tubular fluid as it goes through the loop of henle
goes into descending limb
water removes- concentrated tubular fluid, increased omsolarity (300 to 400)
move into ascending limb where salt is removed- decreasing the osmolarity (400-200)
what type of fluid moves from the ascending tubule to the distal tubule
hypotonic
what is countercurrent multiplication
the process of using energy to generate an osmotic gradient that enables you to reabsorb water from the tubular fluid and produce concentrated urine
As the fluid continues to move through the loop of Henle, the horizontal gradient is multiplied into large vertical gradient, causing the osmotic gradient to steadily multiply until it reaches a steady state. The length of the loop of Henle determines the size of the gradient - the longer the loop, the greater the osmotic gradient
(progressive increase in interstitial fluid osmolarity)
what is the omsolarity of the kidney interstitial fluid
peripheries 300, increases to 1200 at centre (near hilum)
what creates the corticomedullary concentration gradient
the different interstitial fluid osmolarities of the kidney (isotonic at peripheral, hypertonic at centre)
made from urea and NaCl concentrations
what contributes 50% of medullary osmolarity
the urea cycle (adds solute to interstitium)
- urea diffuses passively into the loop
- collecting ducts absorb 50 urea
- distal tubule not permeable to urea
what is the purpose of countercurrent multiplications
to concentrate the medullary interstitial fluid
allows kidney to produce urine of different volume and concentration depending on the circulating antidiuretic hormone
what is normal Vu
1ml/min
what is the countercurrent exchanger
vasa recta- runs along side the loop of henle juxtamedullary nephrons
how does the countercurrent exchanger work
capillary blood equilibriates with interstitial fluid across the leaky endothelium
blood osmolarity rises as it dips down into the medulla (water loss, solute gained)
blood osmolarity falls as it rises back into the cortex (water gained, solute lost)
how does the countercurrent system (loop of henle + vasa recta) prevent essential blood flow washing away NaCl and urea
vasa recta capillaries follow hair pin bends (slow blood flow)
are freely permeable to NaCl and water
blood flow to vasa recta is low
what is the purpose of the vasa recta (countercurrent system)
prevents essential blood flow washing away NaCl and urea
(no net change in blood as it flows through and then passes into renal vein)
Passive exchange across the endothelium preserves medullary gradient - blood equilibrates at each layer.
Ensures that the solute is not washed away
maintain corticomedullary concentration
what does high medullary osmolarity allow
the production of hypertonic urine in the presence of ADH
what is the omsolarity of the fluid leaving the loop of henle (distal tubular fluid)
hypo-osmotic (100 mosmol/L)
what is the osmolariy of the renal cortex
300 mosol/L
what is the osmolarity of the interstitial fluid surrounding the collecting duct
progressively increases from 300 to 1200 as descends through the medulla
what are the roles of the distal tubule and collecting duct
regulate ion and water balance
>95% of ions reabsorbed before they reach it but remaining 5% v important
what do all tubules empty into
the cortical collecting ducts
what mainly regulates fluid and NaCl regulation
hormones
where in nephrones do hormones affect
the cells of the distal tubule and the collecting duct (dont affect proximal tubule/ loop of henle)
what hormone increases water reabsorption
ADH (vasopressin)
what hormone causes reabsorption of Na+ and H+/K+ secretion
aldosterone
what hormone causes decreased sodium reabsorption
atrial natriuretic hormone (ANH)
what hormone causes increased Ca2+ reabsorption and decreased PO43- secretion
parathyroidhormone (PTH)
what is the distal tubule permeable to
low permeability to water and urea- but can by increased with high ADH circulating
why must urea be concentrated in the distal tubule fluid
as helps to establish osmotic gradient within the medulla
what are the two segments of the distal tubule and their role
early segment:
-Na+ K+ 2Cl triple co transporter (salt reabsorption)
the late distal tubule:
- Ca2+ reabsorption
- H+ secretion
- Na reabsorption
- K+ reabsorption ( K+ secretion if aldosterone there)
what cells are sensitive to aldosterone
later part of distal tubule
what is the late collecting duct permeable to
low ion permeability
permeable to water (and urea)
what is the collecting duct influenced by
ADH
what are the parts of the collecting duct
early and late
what is ADH and where is it made
(octa)peptide hormone
synthesised by the supraoptic and paraventricular nuclei in the hypothalamus
(is therefore and neuropeptide)
what is the path of ADH
transported down nerves to terminals where is stored in granules (vesicles within the terminals) in the posterior pituitary gland
released into blood when action potentials down the nerves lead to Ca2+ dependent exocytosis
what is the plasma half life of ADH
10-15 mins (short like all peptide hormones)
how does ADH affect water permeability of the collecting duct
when ADH binds it increases intracellular
cAMP
this initiates the insertion of aquamporins into the apical membrane of collecting duct epithelial cells
this increases the collecting ducts permeability to water
what happens to collecting duct when ADH decreases
the expression of water channels at apical membranes decreases (channels become internalised within vesicles)
what happens to water when there is high ADH
moves from the collecting lumen along to osmotic gradient into the meduallry interstitial fluid- enables hypertonic (concentrated) urine formation
what happens to water when there is low ADH
collecting ducts have low permaebility
enables the creation of hyptonic urine (<50mosmol/L)
what equilibrates when there is high ADH
the tubular fluid equilibrates with interstitium (via aquaporins) as water moves from into interstitium ad concentrated urine (to 1200 mosmol/L)
where is impermeable to water
the ascending loop of henle
AND
the collecting duct when there is minimal ADH (no water reabsorption)
does ADH conc have a direct/ inversely proportion affect on urine volume and osmolarity
direct with osmolarity
inversely proportionate with urine volume
how does increased plasma osmolarity affect ADH secretion
stimulates hypothalamic osmoreceptors these stimulate hypothalamic neurones increase thirst increases fluid intake decreases plasma osmolarity increases plasma volume/ABP
how does a decrease in ECF volume cause secretion of ADH
causes decrease in ABP (usually when large changes in plasma volume)
stimulates left artial volume receptors
stimulates hypothalamic neurones
increases ADH secretion
increases arteriolar vasoconstriction
also increases H20 permeability of distal and collecting tubules
increases H2O reabsorption
decreases urine output
increases plasma volume and decreases plasma osmolarity
what are the symptoms of diabetes insipidus
large volumes of dilute urine
constant thirst
what are the types of diabetes insipidus
central- failure to produce/secrete ADH from post pit
nephrogenic- unable to respond to ADH- defect in type II vasopressin receptor/ defect in cell response
what is the treatment for diabetes inspidus
central- ADH replacement
nephrogenic- dependent on cause (stop possible causative drugs, rehydrate etc)
what is the most important stimulus for ADH release
hypothalamic osmoreceptors (respond to changes in omsolarity of plasma)
also stimulated by activation of left atrial stretch receptors
decreased atrial pressure = increased/ decreased ADH release?
increased
how does the GI tract affect ADH secretion
stretch receptors in upper GI tract exerts feed-forward inhibition of ADH (stops secretion of ADH before food as fluid about to be absorbed in meals)
what ‘drugs’ stimulates/ inhibit ADH release
nicotine stimulates release
alcohol inhibits release
summaries the omsolarity of tubular fluid throughout the nephron
Tubular fluid at the start of the nephron flows along the proximal tubule (absorption of all filtered water and fluid- in equal proportions so stays same osmolarity) (flow rate reduces as so much absorbed)
When enters descending limb it loses water and osmolarity increases
When enters ascending limb loses salt so osmolarity decreases (when leaves has osmolarity of 100)
Depending on level of ADH when it enters distal tubule and collecting duct will increase in osmolarity (ADH high) or decreases (ADH low)
what is aldosterone and where is it made
steroid hormone secreted the adrenal cortex (zona glomerulosa)
when is aldosterone secreted
in response to rising K+ or falling Na+ in the blood
due to activation of the renin-angiotensin system
what does aldosterone do
stimulates Na+ reabsorption and K+ secretion
what does Na+ retention cause
increased blood volume and pressure (water follows sodium)
where is potassium K+ absorbed
90% in the early regions of the nephron (proximal tubules)
when aldosterone is absent the rest is reabsorbed in the distal tubule (no K+ excreted in the urine)
what does an increase in K+ conc directly stimulate
the adrenal cortex
how does sodium affect secretion of aldosterone
a decrease in plasma Na promotes the indirect secretion of aldosterone via the juxtaglomerular apparatus (macula densa cells) (activates RAAS system)
where does aldosterone affect
the cells of the distal and collecting tubule
what secretes renin
granular cells in the JGA
what secretes angiotensin
liver
what secretes ACE
lungs
where does angiotensin II stimulate
adrenal cortex
how does aldosterone affect Cl levels
Cl- follows Na+ passively (aldosterone increases Na reabsorption so Cl also increases)
what are the affects of angiotensin II (not on the kidney)
arteriolar vasconstriction increased thirst increased vasopressin (ADH)
what causes the release of renin
decreased: NaCl/ ECF volume/ ABP
reduced pressure in efferent arteriole
increased sympathetic activity as a result of reduced arterial blood pressure
what innervates the granular (renin secreting cells)
sympathetic nervous system (increased firing in decreased ABP causes renin release)
what senses a decrease in NaCl in the distal tubule
macula densa cells in the JGA (decreased NaCl = more renin released)
how does aldosterone increase Na+ reabsorption
increase number of Na channels in apical membrane
increase number and activity of channels of transporters at the basolateral membranes
why do the effects of aldosterone take longer
as steroid hormones (alter gene transcription and proteins, have longer half life)
how does heart failure cause fluid retention
as decreased CO and BP
low BP stimulates RAA system
increased salt and water retention
what is the treatment for heart failure
low salt diet loop duiretics (target to triple co transporter) ACE inhibitor (stop fluid and salt retention and ateriolar constriction)
what produces ANP
the heart- stored in atrial muscle cells
when is ANP released
when atrial muscle cells are mechanically stretched due to an increase in the circulating plasma volume
what does ANP do
promotes excretion of Na+ and duiresis (decreases plasma volume)
afferent arteriolar vasodilation
decreased sympathetic stim= decreased CO and total peripheral resistance
(decreased arterial BP)
what controls micturation
the mitcuration reflex (involuntary emptying by simultaneous bladder contraction and opening of sphincters) voluntary control (tightening of ecternal sphinter and surrounding pelvic diaphragm)
describe the steps of the micturition relfex
bladder fills stretch receptors increases parasym bladder contracts sphintcers open
how much can the bladder hold
250-400mls
what is water diuresis
increased urine flow but not increased solute excretion
what is osmotic diuresis
increased urine floe as a result of primary increase in salt excretion
what is the difference between water and osmotic diuresis
Any loss of solute in the urine must be accompanied by water loss (osmotic diuresis), but the reverse is not true; water diuresis is not necessarily accompanied by equivalent solute loss.
what regulates erythtopoiesis
kidney produce erythropoietin if O2 in tissues too low
erythropoietin stimulates stem cells in bone marrow to produce RBCs which increase O2 supply in tissues
what is pH
measure of the unbound H+ conc
what is a normal pH
7.35-7.45
which blood is more acidic
arterial- 7.45
venous- 7.35
(averages 7.4)
what do small changes in pH show
big changes in H+ conc
what is the pH of ECF
7.4 (tightly controlled)
what does acidosis cause
depression of the CNS (coma)
enzyme activity affected
potassium retention
what does alkanosis cause
overexcitability of the peripheral NS and central NS (pins and needles, muscle spasms)
affects enzymes
what ads to H+ in the body
carbonic acid formation
inorganic acids (produced during breakdown of nutrients- e.g. meat proteins)
organic acids resulting from metabolism (fatty, lactic or keto acids)
how does DM affect body pH
the metabolism of fat produces keto acids= acidosis= DKA
what are strong and weak acids
Strong acids dissociate completely in solution
Weak acids dissociate partially in solution
what makes up a buffer system
pair of substances
- one can yield free H+ of they decrease
- one can bind free H+ if the H+ increases
HA (undissociated acid) = H+ (proton) + A- (base)
what happens if H+ is added to HA = H+ + A-
equilibrium shifts to the left as protons are mopped up by A- causing more HA to be made (HA rises, A- falls)
what happens if B- is added to HA = H+ + A-
base is tidied up by combining with H+ allowing more HA to dissociate
equilibrium shifts to the right (HA falls A- rises)
what is the dissociation constant
K= ([H+] x [A-]) / [HA]
shows much much an acid will dissociate
what is pK
the pH at which the reaction will be at equilibrium
how do you calculate [H+]
what forms carbonic acid
CO2 and water, catlyzed by carbonic anhydrase
what is the carbonic acid buffer system
CO2 + H20 = (carbonic anhydrase) = carbonic acid (H2CO3) = H+ + HCO3- (bicarb)
what controlls HCO3-
the kidneys
what controls PCO2
the lungs
what controls the normal plasma pH at 7.4
HCO3- (24mmol/l) from kidneys
PCO2 (40mmHg x 0.03) from lungs
what is the role of the kidney in HCO3- concentration
variable reabsorption of filtered HCO3-
kidneys can add new HCO3- to the blood
(both these dependent on H+ secretion into the tubule)
what drives the reabsorption and secretion of bicarb from the kidneys (HCO3-)
H+ secretion
how is HCO3- reabsorbed in to the proximal tubule
combines with H+ to make carbonic acid which dissociates to make CO2 and water
these move into epithelial cells where via carbonic anhydrase they form carbonic acid again then split into H+ and bicarb
the H+ goes back to apical membrane to join the HCO3- in lumen again, the HCO3- moves out of basolateral membrane with Na+ to get into the interstitial fluid
what drives hydrogen ion secretion
CO2- CO2 retention will cause H+ ion secretion
how does the kidney make new HCO3-
(e.g. in order to regenerate buffer stores depleted by an acid load)
when [HCO3-] in tubular fluid is low, secreted H+ combines with phosphate (a waste product of protein metabolism) which forms and acid an is excreted in the urine = net gain of HCO3- and excretion of acid
what is titratable acid
the amount of H+ excreted as largely H2PO4-
max that can be excreted is 40 mmol/day
how else can acid be excrete (other than binding to phosphate)
break down glutamine (from liver) to form ammonia - this goes into tubular fluid and forms ammonium ion (NH4+) which is excreted in urine
(generates new HCO3- aswell)
this is done in severe acidosis
what does H+ secretion by the tubule do
drives reabsorption of HCO3- (to prevent acidosis)
forms acid phosphate (to excrete)
forms ammonium ion (to excrete)
alkanises the body and regenerates buffer stores
