Physiology Flashcards
what is osmolarity?
concentration of osmotically active particles present in a solution
what are the units of osmolarity?
osmol/l or mosmol/l
what 2 factors are needed to calculate osmolarity?
- the molar concentration of the solution
- the number of osmotically active particles present
what are the units of osmolality?
osmol/kg water
when can the terms osmolarity and and osmolality be used interchangeably?
for weak salt solutions including body fluids
what is tonicity?
the effect a solution has on a cell volume
what affect does a hypertonic solution have on a cell?
fluid moves out of the cell- the cell shrinks
what affect does a isotonic solution have on a cell?
there is no change
what affect does a hypotonic solution have on a cell?
water moves into the cell, cell bursts
what are the 2 major components of total body water?
intra cellular fluid and extracellular fluid
why do males have 60% of body weight made up of water and woman only have 50%?
woman have more fat. fat cells dont contain a lot of water
what does extracellular fluid consist of?
plasma, interstitial fluid, other (negligible)
what are all body cells bathed in?
interstitial fluid
how can we measure body fluid compartments?
with ‘tracers’
what is insulin a useful tracer for?
ECF
what is a useful tracer of plasma?
labelled albumin
useful tracer of total body water?
3H20
how do you calculate the distribution volume (in litres)?
- add a known quantitty of tracer X (Qx: mol or mg) to the body
- measure the equilibration volume of X in the body ([X])
distribution of volume = Qx (mol) / [X] (mol/litre)
what is meant by insensible loss of water?
loss of water from somewhere when there is no physiological control over this water loss eg water loss from the skin, lungs
where is there sensible loss of water in the body?
- in sweat
- faeces
- urine
3 ways in which water can be put into the body?
- fluid intake
- food intake
- metabolism
what changes when there is water imbalance?
body fluid osmolarity
are sodium ions more abundant in ECF or ICF?
always more sodium on the outside of the cell in the ECF
where is chloride ions more abundant?
ECF
where are potassium ions more abundant?
in the cell (ICF)
what are the main ions in the ICF?
potassium, magnesium
what is the difference in osmotic concentrations of ECF and ICF?
they are identical
what is the osmotic concentration of the ECF and ICF?
around 300 mosmol/l
what is meant by fluid shift?
movement of water between the ICF and ECF in response to an osmotic gradient
if the ECF loses water, what will happen to its osmolarity?
it will go up
an increase in osmolarity in the ECF will cause what?
it to become hypertonic and cells are now in hyperotonic solution so they will begin to loss water from the ICF and water will go into ECF to restore volume and osmolarity
if there is a gain of NaCl in the ECF, what is the fluid shift response?
ECF goes up and ICF goes down
if there is a loss if NaCl from the ECF, what is the fluid shift response?
ECF goes down and ICF goes up
what affect does a gain or loss of isotonic fluid have?
- no change in fluid osmolarity
- change in ECF volume only
what gives rise to electrolyte balance?
when the rates of loss equal the rates of gain
what are the 2 reasons why electrolyte balance is important?
1- total electrolyte concentrations can directly affect water balance (via changes in osmolarity)
2. the concentrations of individual electrolytes can affect cell function
what is the balance of sodium and potassium particularly important?
- they are major contributors to the osmotic concentrations of the ECF and ICF, respectively
- they directly affect the functioning of all cells
the presence of what makes up >90% of the osmotic concentration of the ECF?
sodium salts
what do potassium ions play a key role in?
establishing the membrane potential
what percentage of the bodys potassium is intracellular?
> 95%
what are the 2 things that can happen if small leakages or increased cellular uptake of potassium occurs?
- muscle weakness — paralysis
2. cardiac irregularities — cardiac arrest
what does salt imbalance manifest as?
changes in ECF volume
what is bilirubin a breakdown of?
haemoglobin
what hormone stimulates the kidney to produce erythropoitin?
EPO
what does erythropoitin do?
increase red blood cell production
what percentage of the cardiac output does the kidneys receive?
20-25%
what kind of appearance does the medulla have?
granulated appearance
what kind of appearance does the cortex have?
striated
what does the afferent arteriole subdivide to form?
the glomerulus
where does blood from the glomerulus pass to?
the efferent arteriole
where does blood flow to from the efferent arteriole?
into the peritubular capillaries
following the peritubular capillaries, where does the blood go?
the renal vein
what are the 2 types of nephron?
juxtramedullary and cortical
what percentage of nephrons are juxtamedullary nephrons?
20%
what are the 2 differences between juxtamedullary and cortical nephrons?
- juxtamedullary nephron has a very long loop of Henle compared to cortical nephron
- cortical nephron has a network of capillaries, whereas the juxtamedullary only has one vessel
what is the vessel in the juxtamedullary nephron called and what is its flow like?
vasa recta, sluggish flow
what is the function of the juxtamedullary nephrons?
enable us to make concentrated urine
if the smooth muscle of the afferent arteriole contracts, how will this affect the flow downstream to the glomerular capillary?
less blood will flow downstream
what percentage of plasma that flows through the capillary makes up the initial tubular fluid?
20%
how does the initial tubular fluid differ from the plasma?
almost identical except tubular fluid does not contain large proteins or red blood cells
what do the macula densa cells of the juxtaglomerular apparatus detect?
amount of salt in tubular fluid as it passes through this region of the nephron
for any substance: rate of excretion = ?
rate of filtration + rate of secretion - rate of reabsorption
for a freely filterable substance: rate of filtration = ?
rate of filtration of
X = [X]plamsa x GFR
GFR= glomerular filtration rate
what is the normal GFR in a healthy adult?
125 mil/min
how do you calculate rate of excretion?
rate of excretion of X:
X = [X]urine x Vu
Vu = urine flow rate
how do you calculate the rate of reabsorption?
Rate of reabsoption of X
= rate of filtration of X - rate of excretion of X
how do you calculate the rate of secretion of a substance?
Rate of secretion of X:
rate of excretion of X - rate of filtration of X
what does is mean if the rate of filtration of a substance exceeds the rate of excretion of that substance?
net reabsorption of the substance has occured
what are the 3 filtration barriers in glomerular filtration?
- glomerular capillary endothelium
- basement membrane (basal lamina)
- slit processes of podocytes
what is the glomerular capillary endothelium a barrier to?
to RBC
what is the basement membrane a barrier to?
plasma protein barrier
what is the slit processes of podocytes a barrier to?
plasma protein barrier
what charge does the basement membrane have and how is the useful?
has a net negative charge, this helps to repel negatively charged plasma proteins to prevent filtration of these
what 4 things contribute to net filtration pressure?
- glomerular capillary blood pressure
- capillary oncotic pressure
- Bowman’s capsule hydrostatic pressure
- Bowman’s capsule oncotic pressure
how is the net filtration pressure calculated?
(glomerular capillary BP + Bowman’s Capsule oncotic pressure) - (Bowman’s capsule hydrostatic pressure + capillary oncotic pressure)
what 2 forces that compromise net filtration favor filtration?
glomerular capillary BP and Bowmans capsule oncotic pressure
what 2 forces that compromise net filtration oppose filtration?
Bowman’s capsule hydrostatic pressure and capillary oncotic pressure
will a build up of fluid in the lumen of Bowman’s capsule act to oppose or promote filtration?
oppose filtration
what is another term for oncotic pressure?
colloid osmotic pressure
what are the 4 forces that compromise net filtration pressure often known as collectively?
Starling forces
why is the oncotic pressure of the Bowman’s capsule zero?
since there should be no plasma proteins within the lumen
is filtration at the glomerulus active or passive?
passive
what is the normal GFR?
125 ml/min
what is the major determinant of GFR?
glomerular capillary fluid (blood) pressure
what is the extrinsic regulation of GFR?
sympathetic control via baroreceptor reflex
other than extrinsic regulation of GFR, what else controls it?
autoregualtion (intrinsic) control
what are the 2 parts to the autoregulation (intrinsic) of GFR?
- myogenic mechanism
2. tubuloglomerular feedback mechanism
how does blood pressure affect GFR?
because it affects glomerular filtration pressure
what happen to GFR is there is vasoconstriction of the afferent arteriole?
reduced GFR
what affect does an increase in sympathetic activity have on the GFR and urine output?
causes constriction of afferent arterioles which causes a reduction in glomerular capillary fluid pressure which causes a fall in GFR and decreased urine volume
what prevents short term changes in systemic arterial pressure affecting GFR?
autoregulation
what happens in the myogenic response?
if vascular smooth muscle is stretched (ie arterial pressure increased), it contracts thus consticting the arteriole
what is the tubuloglomerular feedback mechanism? what does it do if GFR rises?
- involved the juxtaglomerular apparatus
- if GFR rises, more NaCl flows through the tubule leading to constriction of afferent arterioles
give an example when extrinsic control to the kidneys can override intrinsic control?
haemorrhage
what part of the juxtaglomerular apparatus senses NaCl content of tubular fluid?
macula densa
how does a kidney stone decrease GFR?
blockage increases hydrostatic fluid pressure in Bowman’s capsule which opposes filtration and decreases GFR
what affect does severe diarrhoea have on GFR?
decreases it
how does severe diarhhoea decrease GFR?
dehydration which increases plasma protein concentration which increases capillary oncotic pressure which opposes filtration: decreased GFR
what affect does severe burns have on GFR?
increases GFR
how do severe burns increase GFR?
lose plasma proteins from site of burns, decreases plasma protein conc, decreases capillary oncotic pressure which normally would oppose filatration but since it is decreased GFR goes up
how does damage to the kidneys lead to a decreased GFR?
makes glomerular membrane less permeable which leads to reduced GFR
what is plasma clearance a measure of?
of how effectively the kidneys can ‘clean’ the blood of a substance
what is the plasma clearance equal to?
the volume of plasma completely cleared of a particular substance per minute
what are the units of plasma clearance?
ml/min
how do you calculate clearance of a substance?
clearance of substance X =
(conc of X in urine) x (rate of urine flow) divided by plasma conc of X
why does inulin clearnance = GFR?
it is freely filtered at glomerulus and is neither absorbed nor secreted and not metabolised by kidney
what can measurements of inulin clearance be used to determine?
GFR
what is inulin?
exogenous compound- a polysaccharide
what else other than inulin can be used as a rough determinant of GFR?
creatinine clearance
why is creatine clearance not as reliable as inulin clearnace in determining GFR?
undergoes some tubular secretion
what should the clearance of glucose be?
should be zero, should be no glucose in urine
how is urea handled in the kidney?
filtered, partly reabsorbed and not secreted
should the clearance of urea be higher or lower than GFR?
clearance of urea should be lower than GFR
what percentage of filtered urea is reabsorbed?
50%
for a substance that is filtered, secreted but not reabsorbed, is its clearance more or less than GFR?
more than GFR
what is used clinically to calculate renal plasma flow (RPF)?
para-amino hippuric acid (PAH)
what is para-amino hippuric acid?
an exogenous organic anion
how is para-amino hippuric acid dealt with in the kidney?
freely filterated at glomerulus, secreted into the tubule, not reabsorbed and completely cleared from the plasma
what should the renal plasma flow of a healthy individual be?
650 ml/min
critea for a GFR marker?
should be filtered freely, not secreted or reabsobed
critea for a RPF marker?
should be filtered and completely secreted
what is filtration fraction?
is the fraction of plasma flowing through the glomeruli that is filtered into the tubules
how do you calculate filtration fraction?
GFR divided by renal plasma flow
what is the normal filtration fraction?
20%
how do you calculate renal blood flow?
renal plasma flow x (1/1-Hct)
where Hct = haematocritt
what percentage of CO does the kidneys receieve?
around 24%
approximately how many times a day is plasma filtered?
65 times per day
how much of filtered fluid is reabsorbed in the proximal tubule per minute?
80ml/min
is the fluid that is reabsorbed in the proximal tubule hypo/hyper or iso-osmotic with filtrate?
iso-osmotic
what is meant by iso-osmotic?
salt and water reabsorption is equal
what substances are reabsorbed in the proximal tubule?
sugars, amino acids, phosphate, sulphate, lactate
what is secreted in the proximal tubule?
hydrogen ions, hippurates, neurotransmitters, bile pigments, uric acid, drugs, toxins
what are the 2 types of reabsorption that can take place in the nephron?
transcellular and paracellular
when does paracellular reabsorption occur?
if the cells dont have such tight junctions
what do substances from the filtrate need to go through to get into the peritubular capillary?
luminal membrane then tubular epithelial cells then interstitial fluid then the capillary wall (endothelia)
what are the 3 types of carrier-mediated membrane transport?
- primary active transport
- secondary active transport
- facilitated diffusion
primary active transport?
energy is directly required to operate the carrier and move the substrate against its concentration gradient
secondary active transport?
the carrier molecule is transported coupled to the concentration gradient of an ion (usually Na+)
facilitated diffusion?
passive carrier-mediated transport of a substance down its concentration gradient
how does oxygen and carbon dioxide move into/out of the cell?
diffusion through the lipid bilayer
how does sodium enter the cell?
diffusion through channels
how does glucose enter the cell?
facilitated diffusion
what type of transport occurs at a sodium/potassium pump?
primary active transport
what type of transport occurs at a sodium/glucose pump?
secondary active transport
if one ATP is hydrolysed, what affect does this have in the sodium/potassium pump?
3 Na are kicked out of the cell and 2 potassium are taken in
what is the isoosmotic fluid reabsorption across ‘leaky’ PT epithelium due to?
- standing osmotic gradient
2. oncotic pressure gradient
what percentage of filtrate glucose is reabsorbed at the PT?
usually 100%
over what membrane can glucose easily pass down its gradient?
over basolateral membrane
what membrane can glucose not easily diffuse across, what does it need ti help?
the cell membrane - needs co-transporter or facilitated diffusion
why is there a transport maximum for glucose?
co-transport requires conformational changes in the proteins and therefore only so many molecules can be moved per unit time
what causes glucose in the urine in DM?
high glucose concentration in the plasma leads to high amount of glucose filtered and the transport mechanisms become saturated so not all glucose can be reabsorbed.
what is the renal threhold for plasma glucose concentration?
10-12 mmol/l
what percentage of all salt and water is reabsorbed in the PT?
67%
what is Na+ reabsorption driven by?
the basolateral Na+ - K+- ATPase
what does sodium reabsorption drive?
chloride reabsorption through the paracellular pathway
how is water reabsorbed?
by osmosis
what is the function of the loop of Henle and what does this enable?
- generates a cortico-medullary solute concentration gradient
- enables the formation of hypertonic urine
what is opposing flow in the 2 limbs of loop of Henle referred to as?
countercurrent flow
what does the loop of Henle work with to establish a hyper-osmotic medullary interstitial fluid?
vasa recta
what is being reabsorbed the entire length of the ascending limb of loop of henle?
sodium and chloride
how is sodium and chloride reabsorbed in the thick (upper) ascending limb?
active transport
how is sodium and chloride reabsorbed in the thin (lower) acending limb?
passive
why does little or no water follow salt reabsorption in the ascending limb?
it is relatively impermeabel to water
what does the descending limb of loop of Henle absorb?
does not reabsorb NaCl and it highly permeable to water
what does the selective permeabilities of the ascending and descending limbs of the loop of Henle enable?
an osmotic gradient to be established in the medulla
what do loop diuretics block?
the triple co-transporter
what happens at the triple co-transporter?
recycling of potassium and NaCl is absorbed into the interstitial fluid
where does the triple co-transporter pump solute from?
the thick ascending limb of loop of Henle
as you move further into the medulla, what happens to the concentration of interstitial fluid?
it increases
what happens to the concentration of the tubular fluid as it moves down the descending limb and then up the ascending limb?
increasingly concentrated as it moves down the descending limb and becomes increasingly dilute as it ascends the ascending limb
the tubular fluid is iso osmotic as it leaves the PT, what is it when it enters the DT?
hypo osmotic
what contributes to approx half of the medullary osmolality?
the urea cycle
how does urea enter the loop of Henle?
diffuses passively
what does urea add to the interstitium?
adds solute
is the distal tubule permeable to urea?
no
what is the purpose of countercurrent multiplication?
to concentrate the medullary interstitial fluid
why does a concentrated medullary interstitial fluid enable the kidney to do?
to produce urine of different volume and concentration according to the amounts of circulating ADH
essential blood flow through the medulla tends to wash NaCl and urea away. what features of the vasa recta minimise this?
- vasa recta capillaries follow hairpin loops
- vasa recta capillaries are freely permeable to NaCl and water
- blood flow in vasa recta is low
what preserves the medullary gradient?
passive exchange across the endothelium
what does preservation of the medullary gradient ensure?
that the solute is not washed away
what does the high medullary osmolarity allow in the presence of ADH?
production of hypertonic urine
what is the osmolarity of the tubular fluid leaving the Loop of Henle?
hypo-osmotic, 100 mosmol/l
what causes the osmotic gradient at the end of the loop of Henle/start of distal tubule?
tubular fluid is 100 mosmol/l and the surrounding interstitial fluid of the renal cortex is 300 mosmol/l.
what is the collecting duct bathed in?
progressively increasing concentrations (300-1200 mosmol/l) of surrounding interstitial fluid
what is the distal tubule and collecting duct a major site for?
the regualtion of ion and water balance
what percentage of filtered ions are left by the time it gets to distal tubule?
less than 5%
what is fluid and NaCl regualtion mainly influenced by?
hormomes
what parts of the nephron are affected by hormones?
only the distal tubule and collecting duct
what are the 4 hormones that influence the distal tubules and collecting duct in the regulation of ion and water balance?
- Antidiuretic hormone (ADH)
- Aldosterone
- Atrial natriuretic hormone
- Parathyroid hormone (PTH)
what affect does ADH have on the regulation of water?
causes increased water reabsorption
what affect does aldosterone have on ion regulation?
increased sodium reabsorption and and increased potassium and hydrogen excretion
what affect does atrial natriuretic hormone have on ion regulation?
decreased sodium reabsorption
what affect does PTH have on ion regulation?
increased calcium reabsorption and decreased phosphate ion reabsorption
what 2 segments can the distal tubule be split into?
the early and late
what is the function of the early distal tubule?
NaCl reabsorption
what does the early distal tubule contain that allows it to undertake NaCl reabsorption?
the triple co-transporters
Na+-K+-2Cl- transport
what is the late distal tubule responsible for?
- calcium reabsorption
- H+ secretion
- sodium reabsorption and potassium reabsorption in the basal state but in presence of aldosterone potassium secretion
what hormones is the late distal tubule sensitive to?
PTH, aldosterone
what is the early collecting duct similar to?
the late distal tubule
what are the properties of the late collecting duct and what is it influenced by?
a low ion permeability and permeability to water (and urea). influenced by ADH
Where is ADH secreted from?
posterior pituitary
what kind of peptide is ADH?
an octapeptide
where is ADH synthesied?
by the supraoptic and paraventricular nuclei in the hypothalmus
how is ADH transported from the hypothalmus to posterior pituitary and how is it stored?
down nerves to terminals where it is sorted in granules in posterior pituitary
what triggers the release of ADH?
when action potentials down the nerves lead to calcium dependent exocytosis
what is the plasma half-life of ADH?
10-15 minutes
what effect does increased ADH have on the water permeability of the collecting duct?
increased water permeability
what does ADH bind to in the tubule/collecting duct?
type 2 vasopressin receptor
where do you find the type 2 vasopressin receptor?
basolateral membrane
what type of receptor is a type 2 vasopressin receptor?
G-protein coupled receptor
what does binding of ADH to type 2 vasopressin receptor cause an increase in?
in cyclic AMP
what does the increase in cyclic AMP cause?
increased permeability of the luminal membrane
how does the luminal membrane increase its permeability to water?
by inserting new water channels (aqauporins)
what happens to the aquaporins on the luminal membrane when we are over-hydrated?
the become internalized back into vesicles and stored in the cytoplasm
how do the aquaporins on the basolateral membrane differ from those on the luminal membrane?
the ones of the basolateral membrane are always present (do not internalize) and they are not influenced by ADH
in the presence of high ADH, what type of urine is produced?
small amounts if hypertonic (concentrated) urine
what is the main stimuli for the release of ADH?
an increase in plasma osmolarity
what senses an increase in osmolarity?
hypothalamic osmoreceptors
where does the hypothalmic osmoreceptors send signals to and what does the lead to?
the hypothalamic neurons, leads to an increased thirst which increases fluid and decreases plasma osmolarity
a significant decrease in what can also activate hypothalamic neurons?
decrease in ECF
what senses a significant drop in ECF ?
left atrial volume receptors
if the left atrial volume receptors activates the hypothalamic neurons, what does this cause?
an increase in ADH, water reabsortion and decreased urine output so increased plasma volume
what are the 2 types of diabetes insipidus?
central diabetes insipidus and nephrogenic diabetes insipidus
main symptoms of DI?
- large volumes of dilute urine
- constant thirst
what is the problem in central DI?
posterior pituitary unable to produce or secrete ADH
what is the problem in nephrogenic DI?
ADH production is normal but it does not exert its affects on tubules - problem with the receptors
treatment for central DI?
ADH replacement
what drug has a 25% risk of giving the patient DI?
long term lithium
what is the most important stimuli for ADH release?
hypothalamic osmoreceptors
what affect does decreased atrial pressure have on ADH release?
increased ADH release
what affect does stimulation of stretch receptors in upper GI tract have on ADH release?
feed-forward inhibition of ADH
what affect does nictotine and alcohol have on ADH release?
nicotine stimulates ADH release and alcohol inhibits ADH release
most reabsoption happens at proximal tubule so why is there not a change is osmolarity?
salt and water is reabsorbed in equal proportions
what is aldosterone released in response to?
-to rising potassium or falling sodium conc in the blood
what system activates aldosterone release?
rennin-angiotensis system
what does aldosterone cause?
stimulates sodium reabsorption and potassium secretion
most of potassium is reabsorbed in the proximal tubule, when aldosterone is absent what happens to the rest of it?
it is reabsorbed in the distal tubule, no potassium is excreted in urine
a change in what ion directly stimulates the adrenal cortex?
an increase in potassium
how does a decrease in plasma sodium cause aldosterone secretion?
promotes indirect secretion of aldosterone by means of the juxtaglomerular apparatus
what are the 3 ways in which rennin release can be stimulated?
- reduced pressure in afferent arteriole
- macula densa cells sense the amount of NaCl in distal tubule
- increased sympathetic activity as a result of reduced arterial BP
what affect does reduced pressure in the afferent arteriole have on renin release and what affect does this have on blood volume?
more renin released, more sodium reabsorbed, increased blood volume, BP restored
what affect does a reduced NaCl conc in the distal tubule have on renin release?
more renin release so more NaCl is reabsorbed
what can abnormal increases in the R-A-A system cause?
hypertension
what do loop diuretics target and inhibit?
the triple co-transporter found in the ascending limb of loop of Henle
where is atrial natriuretic peptide/hormone produced and stored?
produced by the heart and stored in atrial muscle cells
when is ANP released?
when the atrial muscle cells are mechanically stretched due to an increase in the circulating plasma volume
what does ANP promote?
excretion of sodium and diuresis, decreasing plasma volume
what affect does ANP have on smooth muscle of afferent arteriole?
vasodilation
what affect does ANP have on sympathetic system?
decreases sympathetic activity
what affect does ANP have on kidney tubules?
decreased sodium reabsorption
what 2 mechanisms governs urination?
- the micturation reflex
2. voluntary control
how much urine can the bladder accommodate before stretch receptors within its walls initiates micturation reflex?
250-400 ml
what happens in the micturation reflex?
involuntary emptying of the bladder by simultaneous bladder contraction and opening of both internal and external urethral sphincters
how is mictruation reflex over-ridden?
by voluntarily tightening the external sphincter and surrounding pelvic diaphragm
what is the normal pH of arterial blood?
7.45
what is the normal pH of venous blood?
7.35
average pH of blood?
7.40
what is a pH of 7 in terms of nmol/l?
100 nmol/l
what is a pH of 7.8 in terms of nmol/l?
16 nmol/l
what do small changes in pH reflect?
large changes in hydrogen ion concentration
what affect can acidosis have on the CNS?
can lead to depression of the CNS
changes in what can influence potassium levels in the body?
changes in Hydrogen ions
what affect does an increase in hydrogen ions have on potassium ions and where does this happen?
renal tubule increase hydrogen ion secretion and have a decrease in potassium ion secretion and this can lead to potassium ion retention
hydrogen ions are continually added to the body fluids by what 3 sources?
- carbonic acid formation
- inorganic acids produced during breakdown of nutrients
- organic acids resulting from metabolism
how do strong acids dissociate in solution?
dissociate completely
how do weak acids dissociate in solution?
partially dissociate
what do buffer systems consist of?
a pair of substances- one can yield free hydrogen ions as the hydrgen ion concentration decreases and the other can bind free hydrogen ions when the hydrogen increases
at arterial PCO2 of 40mmHg what is the solubility coefficient?
0.03
what is the Henderson-Hasselbalch equation?
pH = pK + log [A-]/[HA]
what is the normal pK?
6.1
what is the normal bicarbonate?
24 mmol/l
how do you work out the rate of filtration of bicarbonate ions?
GFR x [HCO3-]plasma
what is the normal filtration rate of bicarbonate ions?
4320 mmol/day
when the concentration of bicarbonate ions is low in tubular fluid, what does secreted hydrogen ions combine with?
phosphate
what is tritratable acid?
the amount of hydrogen ions excreted as (largely) hydrogen phosphate
is ammonia a measurement of titratable acid?
no - separate ammonium determination is necessary
what can increase ammonium excretion in urine?
acidosis
what 3 things does secretion of hydrogen ions by the tubules do?
- drives reabsorption of bicarbonate ions
- Forms acid phosphate
- forms ammonium ion
how much hydrogen ions need to be secreted to accomplish a reaborption of 4320 mmol/day of bicarbonate ions?
4300 mmol/day H+ secretion
how much titratable acid is secreted a day?
20 mmol/day
how much ammonium is secreted per day?
40 mmol/day
how much titratable acid is excreted each day?
20 mmol/day
how much ammonium ions are excreted per day?
40 mmol/day
what is the amount of hydrogen ion excretion equal to?
amount of “new” bicarbonate generated
what is the vast majority of hydrogen ion secretions used for and why?
for bicarbonate ion reabsorption to prevent generation of acidosis
what is the difference between compensation and correction of acid-base balance?
compensation is the restoration of pH irrespective of what happens to bicarbonate ions and Pco2.
correction of acid-base disturbance is restoration of pH and bicarb and Pco2 to normal
what things can cause Co2 retention?
-chronic bronchitits, chronic empyhsema, airway restriction, chest injuries, respiratory depression
what does co2 retention cause?
respiratory acidosis
what causes the acidosis in CO2 retention?
increased CO2 drives equilibrium to the right and there is an increase in hydrogen ions
what values indicates uncompensated respiratory acidosis?
pH 45 mmHg
have affect does CO2 retention have on the renal tubules?
stimulates them to secrete hydrogen ions into filtrate
in respiratory acidosis what happens to the bicarb ions in the renal tubules?
they are all reabsorbed
what does correction of respiratory acidosis require?
lowering PCO2 by restoration of normal ventilation
what causes respiratory alkalosis and when can this happen?
excessive removal of CO2 by the body
- low inspired P02 at altitude
- hyperventilation
pH is only a measure of what?
free hydrogen ions
why does excessive CO2 removal cause an alkalosis?
drives equilibrium to the left and there is an fall in hydrogen ions and bicarb ions (pH is only a measurement of free [H+]
what values indicate a respiratory alkalosis?
ph > 7.5 and
PCO2
how does the kidney compensate for resp alkalosis?
reduces H+ secretion into the tubule
what affect does renal compensation for resp alkalosis have on bicarb concentration?
further lowers it
what causes metabolic acidosis?
excess H+ from any source other than CO2
examples of things that can cause an increase in H+?
- ingestion of acids or acid-producing foodstuffs
- excessive metabolic production of H+ (lactic acid)
- excessive loss of base from the body (e.g diarrhoea)
values that indicate metabolic acidosis?
ph
what does a decrease in plasma pH stimulate?
peripheral chemoreceptors
how does the respiratory system compensate for metabolic acidosis?
ventilation is increased and more CO2 is blown off, [H+]p is lowered raising pH to normal (bicarb ions are also lowered)
how does the renal system correct metabolic acidosis?
- filtered bicarb ions are very low and very readily reabsorbed
- H+ secretion continues and produces TA and NH4+, to generate more “new” bicarb ions
why is respiratory compensation essential in metabolic acidosis?
acid load cannot be excreted immediately, can take hours/days and even weeks to normalise
what causes metabolic alkalosis?
excessive loss of H+ from the body
in what ways can there be an excessive loss of H+?
- loss of HCl from the stomach (vomiting)
- ingestion of alkali
- aldosterone hypersecretion
how can aldosterone hypersecretion cause excessive loss of H+?
causes stimulation of Na+/H+ exchange at the apical membrane of the tubule: acid secretion
what values indicate metabolic alkalosis?
ph > 7.45
bicarb ions high
in respiratory acidosis is the bicarb high or low?
high
in metabolic alkalosis is the bicarb high or low?
high
in metabolic acidosis, is the bicarb low or high?
low
in respiratory alkalosis , is the bicarb low or high?
low
what affect does increased pH have on breathing?
slows ventilation
what is the correction of metabolic alkalosis?
- filtered bicarb load is so large so not all of it is reabsorped
- bicarb excreted in urine
- no TA or NH4+ is generated
