Flashcards in Physiology Deck (262):
what is osmolarity?
the concentration of osmotically active particles present in a solution
what 2 factors are needed to calculate osmolarity?
1. the molar concentration of the solution
2. the number of osmotically active particles present
what is tonicity?
the effect a solution has on cell volume
what will an isotonic solution do to cell volume?
what will a hypertonic solution do to cell volume?
decrease in cell volume
what will a hypotonic solution do to cell volume?
increase in cell volume
what does tonicity take into consideration that osmolarity doesnt?
the ability of the solute to cross the cell membrane
compare percentage of total body water to body weight in males and females?
males- 60% of body weight
females 50% of body weigh
what are the 2 major compartments that make up total body water? (and the percentage of each)
intracellular fluid 67%
extracellular fluid 33%
what are the main 2 compartments that make up the extracellular fluid? (and the percentage of each)
interstitial fluid 80%
what separates the extracellular fluid and the intracellular fluid?
how do we measure body fluid compartments clinically?
what tracer allows us to determine the total body water?
what tracer allows us to determine the volume of extracellular fluid?
what tracer allows us to determine the volume of plasma?
is sodium higher intracellularly or extracellularly?
is potassium higher intracellularly or extracellularly?
is chloride higher intracellularly or extracellularly?
what separates the plasma from the interstitial fluid?
what are the main ions in the ECF?
what are the main ions in the ICF?
negatively charged proteins
what is the osmotic concentration of the ECF?
roughly 300 mosmol/l
what is the osmotic concentration of the ICF?
roughly 300 mosmol/l
urea is the biproduct of the breakdown of what substance?
bilirubin is the biproduct of the breakdown of what substance?
what hormone is released by the kidney in response to hypoxia?
uric acid if the biproduce of the breakdown of what substances?
eg adenosine, guanine
what is the active form of vitamin D?
what is the function of calcitriol?
promotes Ca++ absorption in the GI tract
how many OH hydroxyl groups are added to vit D in order to convert it to calcitriol?
2 hydroxyl groups
where is the first hydroxyl group added to vitamin D? (a step in the conversion to calcitriol)
where is the second hydroxyl group added to vitamin D? ( a step in the conversion to calcitriol)
what percentage of cardiac output goes to the kidneys?
what are the 2 types of nephron? (and give percentages of each)
compare the loop of Henle's in the cortical and juxtamedullary nephrons?
juxtamedullary nephron loop of Henle is much longer and extends right down into the medulla, cortical nephron is shorter and only extends slightly into the medulla
compare the capillaries which surround the renal tubules of the cortical and juxtamedullary nephrons?
juxtamedullary nephron- efferent arteriole becomes a single capillary called the vasa recta
cortical nephron- efferent arteriole becomes a network of capillaries called the peritubular network
compare the diameter of the afferent and efferent arterioles?
afferent arteriole has a bigger diameter
how much plasma of the afferent arteriole is filtered into the bowman's capsule?
what cells is renin secreted from?
granular cells (juxtaglomerular cells) wichin the juxtaglomerular apparatus
how do you calculate the rate of filtration of a substance?
rate of filtration = plasma conc of substance x GFR
what is the normal GFR?
what happens to the rate of filtration of a substance as the concentration of the substance in plasma increase?
rate of filtration increases
how do you calculate the rate of excretion of a substance?
rate of excretion = urine conc of substance x urine flow rate
how do you calculate the rate of reabsorption of a substance?
rate of filtration - rate of excretion
what is the normal urine flow rate?
1ml per minute
0.001l per minute
(very variable depending on body conditions)
how do you calculate the rate of secretion of a substance?
rate of excretion - rate of filtration
collectively, what is the glomerular capillary endothelium, basement membrane and podocyte layer called?
what net charge does the basement membrane of the glomerular membrane have?
what is the function of the negatively changed basement membrane of the glomerular membrane?
repels large negatively charged proteins
what are the 4 starling forces that compromise net filtration pressure at the glomerulus?
glomerular capillary blood pressure
bowmans capsule hydrostatic pressure
capillary oncotic pressure
bowmans capsule oncotic pressure
which is the starling force which contributes most to the net filtration pressure at the glomerulus?
glomerular capillary blood pressure
how do you calculate the net filtration pressure of the glomerulus?
(glomerulus capillary blood pressure + bowmans capsule oncotic pressure)
(bowmans capsule hydrostatic pressure + capillary oncotic pressure)
why, unlike most capillaries, is the glomerular capillary blood pressure constant from afferent arteriole to efferent arteriole?
because as you lose volume the diameter decreases
--> pressure is maintained
what solutes determine oncotic pressure?
since there should be no plasma proteins within the lumen of the bowman's capsule, what should the bowmans capsule oncotic pressure be?
what is the glomerular filtration rate?
the rate at which protein=free plasma is filtered from the glomeruli into the bowman's capsule per unit time
how do you calculate the gfr?
Kf x net filtration pressure
where Kf = filtration coefficient
what is the main determinant of GFR?
glomerular capillary blood pressure
what are the 2 main ways of glomerular filtration rate regulation?
which nervous system is involved in the extrinsic control of GFR and via what reflex?
sympathetic control via baroreceptor reflex
what are the 2 types of intrinsic autoregulation of GFR?
tubuloglomerular feedback mechanism
what does vasoconstriction of the afferent arteriole do to the GFR?
decreases the GFR
what does vasodilation of the afferent arteriole do to the GFR?
increases the GFR
explain why a fall in blood pressure might cause reduced GFR? (external regulation)
reduced BP detected by baroreceptors
sympathetic activity is increased
generalised arteriolar vasoconstriction (afferent arteriole)
reduced glomerular capillary BP so reduced GFR and urine volume
[helps to compensate for fluid loss]
broadly speaking, why do systemic arterial blood pressure changes not always causes changed in GFR?
intrinsic control of the GFR (autoregulation)
what is myogenic autoregulation of GFR?
if vascular smooth muscle is stretched (due to increased BP) it contracts thus constricting the afferent arteriole
what is tubuloglomerular feedback autoregulation of GFR?
If the NaCl increases (happens when GF is raised) within the juxtaglomerular apparatus raises, the macula densa sense it and cause the afferent arteriole to constrict
why might a kidney stone cause reduced GFR?
increased hydrostatic pressure which opposes filtration
why might severe diarrohea cause reduced GFR?
dehydration leads to increased plasma protein concentration (ie bigger capillary oncotic pressure which opposes filtration)
why might severely burned patients have an increased GFR?
plasma proteins are lost from site so leads to decreased plasma protein concentration (ie smaller capillary oncotic pressure)
why might kidney damage cause decreased GFR?
might decrease filtration coefficient leading to decreased GFR
what is plasma clearance?
the volume of plasma completely cleared of a particular substance per minute
what are the units of plasma clearance?
ml per min
how do you calculate clearance of a substance?
rate of excretion/ plasma concentration
what is the inulin clearance rate?
is inulin absorbed by the renal tubules?
is inulin secreted by the renal tubules?
the clearance of which substance is much more convenient to determine GFR from than inulin?
why is creatinine clearance not as accurate as inulin clearance as an indicator of GFR?
because some is secreted in the tubules
what is the rate of glucose clearance?
why might the clearance of a substance be 0?
1. filtered, all reabsorbed, no tubular secretion
2. not filtered no tubular secretion
is urea reabsorbed in the renal tubules?
is urea secreted in the renal tubules?
what is the range of values for clearance of a substance which is partly reabsorbed but not secreted?
Less than 125ml/min
what is the range of values for clearance of a substance which is secreted but not reabsorbed?
because clearance is bigger than GFR
is hydrogen reabsorbed in the renal tubules?
is hydrogen secreted in the renal tubules?
if the clearance of a substance is lower than the GFR, what does this indicate?
the substance is reabsorbed in the renal tubulres
if the clearance of a substance is the same as the GFR, what does this indicate?
the substance is neither reabsorbed or secreted
if the clearance of a substance is the higher than the GFR, what does this indicate?
the substance is secreted into the tubules
the clearance of what substance indicates the renal plasma flow?
clearance of para-amino hippuric acid (PAH)
why is clearance of PAH used to measure renal plasma flow?
filtered freely at glomerulue and is completely secreted in the renal tubules, none is reabsorbed
creatinine a biproduct of the breakdown of what?
what is the clearance of PAH?
what is the renal plasma flow?
how do you calculate the filtration fraction?
GFR/renal plasma flow
what is the filtration fraction?
what is haemocrit?
packed cell volume
--> volume percentage of red blood cells in blood
how doyou calculare renal blood flow?
renal plasma flow / (1-haemocrit)
what is the average renal blood flow?
compare transcellular and paracellular absorption?
transcellular- absorption across the cell of the tubular wall
paracelular- absorption across spaces in the cells of the tubular wall
what is required for primary active transport to occur?
what ion is secondary active transport usually coupled to the movement of?
Na+ down its conc gradient
what membrane (apical or basolateral) is the Na/K/ATPase pump exclusively found on?
the Na/K/ATPase requires the hydrolysis of what?
why is it important that the Na/K pump keeps pumping Na out of the cells lining the proximal convoluted tubule?
keeps intracellular conc of Na low which allows Na to diffuse from the lumen into the cell down a conc gradient
the secondary active transporter on the apical membrane of the cells in the proximal convoluted tubule transports what ion across the membrane into the lumen in replace for Na?
why does Cl- from the lumen of the proximal convoluted tubule follow Na+ into the interstitial fluid of the cells lining the tubule wall?
postively charged Na influx sets up an electrochemical gradient for negatively charged Cl- to follow
does Cl- get reabsorbed from the proximal convoluted tubule transcellularly or paracellularly?
why does H2O from the lumen of the proximal convoluted tubule follow NaCl into the interstitial fluid of the cells lining the tubal wall?
NaCl sets up an osmotic gradient for water to follow
does H2O get reabsorbed from the proximal convoluted tubule transcellularly or paracellularly?
why has the oncotic pressure of the vasa recta increased since the afferent arteriole?
same number of protiens as before but 20% of plasma has gone
--> increased conc of plasma proteins
how does glucose get reabsorbed over the apical membrane from the proximal convoluted tubule lumen?
how does glucose get across the basolateral membrane of the cells lininc the proximal convoluted tubule?
what happens when the glucose transporter mechanisms in the proximal convoluted tubule become saturated?
not all glucose can be reabsorbed
--> glucose in urine
why might there be more glucose present than space on the glucose transporter mechanisms?
high blood glucose eg diabetes mellitus
the tubular fluid is 'iso-osmotic' when it leaves the proximal convoluted tubule, why?
because both salt and water (in correlating amounts) have been reabsorbed
the tubular fluid is 'iso-osmotic' when it leaves the proximal convoluted tubule? what does this mean?
same osmolarity as the plasma
what is reabsorbed in the ascending limb of the loop of henle?
Na+ and Cl-
compare the thin ascending limb and thick ascending limb of the loop of henle in terms of how the salt is reabsorbed?
thick ascending limb: active transport
thin ascending limb: passive transport
what is reabsorbed in the descending limb of the loop of henle?
why is the ascending limb of the loop of henle impermeable to water?
very tight junctions so H2O can't follow osmotic gradient (remember it moves paracellularly)
what ions does the triple co-transporter found on the ascending limb of the loop of henle reabsorb?
what drug blocks the triple co-transporter found on the ascending limb of the loop of henle?
why does water reabsorb in the descending limb of the loop of henle?
follows the osmotic gradient created by the interstitial fluid
(originally created by the reabsorption of salt from ascending limb)
is the fluid leaving the ascending limb of the loop of henle hypo-osmotic, iso-osmotic or hyper-osmotic?
is urea actively or passively reabsorbed in the loop of henle?
what is countercurrent multiplication?
the reabsorption of NaCl and urea from the ascending loop of Henle followed by the reabsorption of water from the descending loop of Henle making the corticomedullatry gradient
what is the purpose of the countercurrent multiplication?
to enable the kidney to produce different volumes and concentrations of urine according to the amounts of ADH
what happens to the osmolairity of the vasa recta as it dips down into the medulla? and why?
osmolairity increases as the fluid equilibrates with the corticomedullary gradient
what happens to the osmolarity of the vasa recta as it ascends back to the cortex? and why?
osmolarity decreases as the fluid equilibrates with the corticomedullary gradient
why is the vasa recta in a hairpin loop?
prevents the washing away of solutes
(as on its ascent it losses solutes and gains water)
compare the osmolairities of the blood entering and leaving the vasa recta?
what acts as the countercurrent exchanger?
the vasa recta
what makes up the countercurrent system?
countercurrent multiplier and countercurrent exchanger
ie loop of henle plus vasa recta
what is the osmolarity of the tubular fluid entering the distal tubule?
what parts of the nephron are within the corticomedullary gradient?
loop of henle
what parts of the nephron do hormone influence?
distal convoluted tubule
what does ADH cause the reabsorption/secretion of?
increased reabsorption of water
what does aldosterone cause the reasbsorption/secretion of?
increased reabsorption of Na
increased secretion of K
what does atrial natriureteric peptide cause the reabsorption/secretion of?
decreased reasborption of Na
what does parathyroid hormone cause the reabsorption/secretion of?
increased calcium reabsorption
decreased phosphate reabsorption
how do you calculate pH from [H+]?
pH = log (1/[H+])
what is the pH of arterial blood?
what is the pH of venous blood?
what is the average pH of blood?
what happens to the pH as [H+] increases?
compare acidosis and alkalosis in terms of what they do to the nervous system?
acidosis can lead to CNS depression
alkalosis can lead to PNS and CNS overexcitability
what does increased plasma [H+] do to the amount of K+ secreted in the renal tubules?
decreases K+ secretion
what are the 3 sources of H+ addition?
carbonic acid formation
inorganic acids produced from nutrient breakdown
organic acids produced from metabolism
what molecules form carbonic acid?
CO2 + H2O
what does carbonic acid dissociate into?
H+ + HCO3-
compare strong and weak acids in terms of dissociation in solution?
strong acids dissociate completely in solution
weak acids dissociate partially in solution
what is a buffer system?
a pair of substances, one can yield free H+ when the [H+] decreases, the other can take free H+ when the [H+] increases in order to maintain pH
what is the first line defence to any change in pH/acid status?
within the HA = H+ + A- buffer system, which molecule can yield free H+ when the [H+] decreases?
within the HA = H+ + A- buffer system, which molecule can mop up free H+ when the [H+] increases?
if H+ is added to the HA= H+ + A- system, what happens to the equilibrium and levels of each molecule?
equilibrium is shifted to the left
[H+] remains the same
if base (B-) is added to the HA = H+ + A- system, what happens to the equilibrium and the levels of each molecule?
equilibrium shifts to the right
[H+] remains the same
how do you calculate the dissociation constant of a weak acid?
K = ( [H+] [A-] )/ [HA]
how do you calculate pK using the dissociation constant (K)?
pK = -log K
what is pK?
the pH at which a particular chemical reaction will be at equilibrium
what does the henderson-hasselbalch equation calculate?
what is the henderson-hasselbalch equation?
pH = pK + log( [A-] / [HA] )
what is the most important physiological buffer system?
the CO2 - HCO3 buffer
what is the CO2 - HCO3 buffer?
CO2 + H2O = H2CO3 = H+ + HCO3-
formation of carbonic acid from carbon dioxide and water is catalysed by what enzyme?
what is the pK for carbonic acid?
pH at equilibrium (pK) = 6.1
what controls the [HCO3-] of plasma?
what controls the PCO2 of plasma?
why might the renal vain have a higher [HCO3-] than the renal artery?
because the kidneys can add new HCO3- to the blood
what does the reabsorption of filtered HCO3- and the addition of new HCO3- to the renal vein depend on?
H+ secretion into the renal tubule
how does reabsorption of HCO3- occur in the proximal tubule?
H+ is secreted into tubule, this binds with HCO3- to form carbonic acid which forms carbon dioxide and water. This readily diffuses across the apical membrane into the cell.
what happens to the carbon dioxide and water which enters the tubular cell? (formed from H+ and HCO3- in the renal tubule)
forms carbonic acid and then dissociates into HCO3- and H+
where in the nephron is HCO3- reabsorbed?
how does HCO3- leave the basolateral membrane of the tubular cell?
how doe H+ leave the apical membrane of the tubular cell in the proximal tubule in order to bind with HCO3-?
what drives the secretion of H+ through the apical membrane of the tubular cell? in order to bind with HCO3-
CO2 partial pressure
what happens to the H+ that is transported across the apical membrane into the tubular fluid when all the HCO3- has already been absorbed?
binds to phosphate to form acid phosphate and is excreted
if even more H+
binds to ammonia to form ammonium and is excreted
what 2 ways does titratable acid and ammonium excretion increase the pH of the plasma?
loss of H+ ions
gain of HCO3-
(simultaneously rids body of acid and regenerates buffer stores)
what is the maximum amount of titratable acid that can be excreted and therefore the maximum amount of new HCO3- that can be gained through this way?
40mmol/day titratable acid
40mmol/day new HCO3-
ammonia is formed from the breakdown of what in the tubular cells?
what enzyme breaks glutamine down to ammonia?
how is ammonia transported across the apical membrane into the tubular fluid?
for every H+ excreted as acid phospate, how many new HCO3- have been formed?
for every H+ excreted as ammonium, how many new HCO3- have been formed?
in what pH state will titratable acid and ammonium be excretion be increased?
what is the normal range of [HCO3-] of the plasma? (and the usual value?)
what is the normal range of PCO3 of the plasma? (and the usual value?)
compare compensation and correction of acid base disturbances?
compensation: restoration of pH irresepctive of what happens to [HCO3- ]and PCO2
correction: restoration of pH, [HCO3-] and PCO2
why can buffer stores not always completely compensate for acid base disturbances?
stores become depleted
what organ has a role in restoring free bicarbonates invovled in buffering?
respiratory acidosis drives the carbonic equlibrium to which side?
to the right
what happens to the [H+] and [HCO3-] in respiratory acidosis?
what indicates uncompensated respiratory acidosis?
pH below 7.35 and CO2 above 45mmHg
why is more HCO3- reabsorbed/made in the kidneys in respiratoy acidosis?
high PCO2 drives H+ secretion into the tubular fluid which drives HCO3- reabsorption/production
how does the kidney compensate for respiratory acidosis?
increases [HCO3-] of plasma
what mechanism corrects respiratory acidosis?
restoration of normal ventilation
in respiratory acidosis, what does the renal compensatory system do to [H+] and [HCO3-]?
[HCO3-] increases further
what is respiratory alkalosis?
excess removal of CO2 from the body
what is respiratory acidosis?
retention of CO2
what does hyperventilation do to PCO2?
what does respiratory alkalosis do to the carbonic acid equilibrium?
shifts it to the left
what happens to [H+] and [HCO3-] in respiratory alkalosis?
they both fall
when is uncompensated respiratory alkalosis indicated?
pH above 7.45 and PCO2 below 35mmHg
what does respiratory alkalosis do to the rate of H+ secretion from the kidney tubules?
what does respiratory alkalosis do to the rate of HCO3- reabsorption/new production?
no new HCO3- is generated
in respiratory alkalosis, what does the renal compensatory system do to [H+] and [HCO3-]?
[H+] is increased
[HCO3-] is decreased further
how does correction of respiratory alkalosis occur?
restoration of normal ventilation
what does the renal compensatory system do to the pH in respiratory alkalosis?
(due to reducing HCO3- and therefore increasing H+ through buffer system)
what is the most common of the 4 major acid base disturbances?
in metabolic acidosis, what happens to the levels of [H+] and [HCO3-]?
what is uncompensated metabolic acidosis indicated by?
pH below 7.35 and [HCO3-] is low
how does the respiratory system compensate for metabolic acidosis?
ventilation increases to blow off more CO2
in respiratory compensation of metabolic acidosis, what happens to the [H+] and the [HCO3-]?
[HCO3-] further decreases
why is respiratory compensation for metabolic acidosis? essential when metabolic correction through the kidneys can occur?
respiratory compensation is needed to compensate pH immediately
renal system would take too long to correct
how do you correct for metabolic acidosis?
kidneys lose H+ and gain HCO3-
what happens to the [H+] and [HCO3-] in metabolic alkalosis?
what is uncompensated metabolic alkalosis indicated by?
pH above 7.45 and [HCO3-] is high
how does the respiratory system compensate for metabolic alkalosis?
ventilation is slowed
how do pH changes signal to change lung ventilation?
through peripheral chemoreceptors
what happens to the [H+] and [HCO3-] in respiratory compensation of metabolic alkalosis?
[HCO3-] further increases
how do you correct for metabolic alkalosis?
HCO3- is excreted
(this also increases [H+] due to buffer system)
compare correction of resp acidosis/alkalosis to metabolic acidosis/alkalosis?
resp: restoration of normal respiratory function
metabolic: mediated by renal system
compare compensation of resp acidosis/alkalosis to metabolic acidosis/alkalosis?
resp: renal system compensates
metabolic: resp system compensates
why is respiratory acidosis harder to compenate for than metabolic acidosis?
because renal compensation (for respiratory acidosis) takes far longer than respiratory compensation (for metabolic acidosis)
which parts of the nephron are the triple cotransporters found on?
thick ascending limb of the loop of henle
early distal tubule
compare the ion permeability of the early and late collecting duct?
late collecting duct has a lower ion permeability
what is the half life of ADH?
what receptors within the cells of the collecting duct does ADH bind to?
type 2 vasopressin receptors
what membrane of the cells lining the collecting duct are type 2 vasopressin receptors found on?
what does the binding of ADH to the type 2 vasopressing receptors do?
increases expression of aquaporins on the apical membrane
where are the aquaporins stored when they are not on the apical membrane?
internalised within vesicles and stored in the cytoplasm
what does high plasma ADH concentrations do to the tonicity of the urine?
makes it hypertonic
what does low plasma ADH concentrations do to the tonicity of the urine?
makes it hypotonic
why does opening more aquaporins increase urine osmolarity?
because the fluid within the collecting duct equalises with the corticomedullary gradient meaning lots of water is reabsorbed
as ADH concentration within the plasma increases what happens to the urine volume?
as ADH concentration within the plasma decreases what happens to the urine volume?
as ADH concnetration within the plasma increases what happens to the total solute excretion?
remains the same
what are the 2 main functions of ADH?
what are the 2 stimulators of the hypothalamus to release ADH?
left atrial volume receptors
what is the main form of treatment for central diabetes insipidus?
what long term drug side effect can cause diabetes insipidus?
what is the main stimulator of the hypothalamus to release ADH?
what causes the feed-forward inhibition of ADH?
stimulation of stretch receptors in the upper GI tract
what does nicotine do to ADH release?
what does MDMA do to ADH release?
what does alcohol do to ADH release?
what directly stimulates release of aldosterone from the adrenal cortex?
what indirectly stimulates the release of aldosterone from the adrenal cortex?
decreased Na+ through RAS
how much K+ is usually excreted in the urine in the absence of aldosterone and why?
none because it is all reabsorbed
from what organ is ACE produced?
what are the 4 functions of angiotensin II?
promote ADH secretion
what are the 3 stimulatory factors for renin release from the granular cells in the juxtaglomerular apparatus?
1. reduced pressure in the afferent arteriole
2. reduced NaCl sensed by the macula densa
3. increased sympathetic activity (due to low BP)
how does aldosterone increase reabsorption of Na?
increases expression of apical Na channels
increases number/activity of basolateral Na/K ATPase
(both in distal and colelcting tubules)
where is atrial natriureteric peptide secreted?
atrial muscle cells
what stimulates the secretion of ANP?
mechanical stretching of the atrium
what are the 2 mechanisms which govern micturation?
1. micturation reflex
2. voluntary control
what stimulates the micturation reflex?
stretch in the walls of the urinary bladder
what is the earliest expression of diabetic nephropathy?
what is the most common reason for proteinuria? (broad)