Physiology Flashcards
what is osmolarity
concentration of osmotically active particles present in a solution
what is the units of osmolarity
osmol/l
mosmol/
what two factors are needed to calculate osmolarity
molar concentration of the solution
number of osmotically active particles present
what is another word for osmolarity
osmolality
what is the osmolarity of body fluids
around 300 mosmol/l
what is tonicity
the effect a solution has on cell volume
can be either hypo/hyper/iso tonic
what is the effect of an isotonic solution
no change in cell volume
what is the effect of an hypertonic solution
decrease in cell volume as the cell is losing water to extracellular environment
cell shrinks
what is the effect of an hypotonic solution
increase in cell volume as the cell gains water from the extracellular environment
cell hurts/lysis
what else is taken into consideration in tonicity
ability of a solute to cross the cell membrane
effect of urea on RBC
RBC very permeable to urea, all urea molecules enter the cell. Leaves behind water; osmotic gradient from outside to inside the cell. Cause cell to burst
Therefore must be hypotonic
effect of sucrose on RBS
RBC membrane impermeable to sucrose. Same osmolarity.
Therefore is isotonic
RBC cell membrane is more permeable to urea than sucrose
who has a greater total body water and why
Males
Females have more fat cells which hold less water
what are the 2 compartments of total body water and which has more water
Intracellular - has higher % of water
Extracellular
what does ECF contain
plasma
interstitial fluid (highest % of ECF)
lymph + transcellular fluid
what can we use to measure body fluids compartments
through tracers
- obtain the distribution volume of a tracer
what are the useful tracers
TBW: 3H2O
ECF: Inulin
Plasma: labelled albumin
how can we measure intracellular water
rearrange TBW = ECF + ICF
ICF = TBW - ECF
how can volume of distribution be measured
V (in litres) = Dose/sample concentration
how can the distribution volume of a tracer be measured
1 - Add a known quantity of tracer X (Qx; mol or mg) to the body
2 - Measure the equilibration volume of X in the body ([X])
3 - V = Qx /[X]
what is essential for water balance/homeostasis in the body
input=output
what is the ionic composition of ICF and ECF
ECF
- more sodium, chloride and HCO3
ICF
- more potassium and magnesium
- -ve charged proteins
what separates the ECF and ICF and helps to maintain the differences between these compartments
cell membrane
membrane transport mechanism
what is fluid shift
Movement of water between the ICF and ECF in response to an osmotic gradient.
what happens if the osmotic concentration of ECF increases
osmolarity increases in ECF
ICF becomes hypertonic
cell looses water and cell volume decreases
what effects fluid homeostasis
gain/loss of water
gain/loss of NaCl
gain/loss of isotonic fluid
what is the affect of NaCl gain/loss
ECF NaCl gain:ECF ↑ ICF ↓
ECF NaCl loss:ECF ↓ ICF ↑
what does change in isotonic fluid affect
only the ECF
what regulates ECF and why is it important to do so
Kidney alters composition & volume of ECF
Regulation of ECF volume is vital for long term regulation of blood-pressure
what is > 90% of osmotic concentration of ECF
Na+
therefore vital to regulate it
what does K+ play a key role in
establishing membrane potential
what can changes in K+ lead to
muscle weakness → paralysis
cardiac irregularities → cardiac arrest
how does salt imbalance manifest
changes in ECF volume
what is the functional unit of the kidney
the nephron
what is the function of the nephron
1 - filtration
2 - reabsorption
3 - secretion
what does the Juxtaglomerular apparatus secrete
rennin
what are the 2 types of nephron
Juxtaglomedullary (around 20%)
Cortical (around 80%)
what are podocytes
visceral epithelial cells
cells in the Bowman’s capsule that wrap around capillaries of the glomerulus
what arteriole takes blood into the bowmens capsule and what takes it out
afferent arteriole - in
efferent arteriole - out
what is urine
Modified filtrate of the blood
what is the renal tubule
‘conveyor belt’
substances are added/removed as urinary filtrate moves from proximal to distal end
how much of the plasma that enters the glomerulus is filtered
around 20%
the other 80% is not filtered and leaves through the efferent arteriole
what is the rule for any substance in regards to filtration
Filtration (GF) + Secretion (TS) = Reabsorption (TR) + Excretion
Amount filtered = Amount excreted
how can the equation also be written so that ROExcretion is first
Rate of excretion = rate of filtration + rate of secretion - rate of reabsorption
how is movements of a substance within the kidney described as
in terms of concentration × flow
what is the equation for rate of filtration of a substance
Rate of filtration of X = mass of X filtered into the Bowman’s capsule per unit time
how does the equation for rate of filtration of a substance translate into for the body
Rate of filtration of X = [X]plasma × GFR
where GFR = glomerular filtration rate
what is the equation for rate of excretion of a substance
Rate of excretion of X = [X]urine × Vu
where Vu = urine flow rate
what is the equation for rate of reabsorption of a substance
Rate of reabsorption of X = rate of filtration of X – rate of excretion of X
how is rates of secretion of a substance calculated
Rate of secretion of X = rate of excretion of X – rate of filtration of X
what do rates of reabsorption and secretion reflect
tubular modification of filtrate
6 kidney functions
1- water balance
2 - salt balance
3 - acid-base balance
4 - Excretion of metabolic waste products
5 - Secretion of renin (control of arterial blood pressure)
6 - Secretion of erythropoietin (EPO; RBC production)
in glomerular filtration, what are the 3 filtration barriers in the lumen
(1) Glomerular Capillary Endothelium (barrier to RBC)
(2) Basement Membrane (basal lamina) (plasma protein barrier)
(3) Slit processes of podocytes (plasma protein barrier)
(Glomerular epithelium)
what are the forces that comprise net filtration pressure
Glomerular capillary blood pressure (BPcg)
Bowman’s Capsule hydrostatic (fluid) pressure (HPbc)
Capillary oncotic pressure
(COPgc)
Bowman’s Capsule oncotic pressure (COPbc)
what are the rough values of the 4 forces
BPgc - 55mmHg
HPbc - 15mmHg
COPgx - 30mmHg
COPbc - 0mmHg
what forces are going in what direction
BPgc and COPgc - into Bowmen’s
HPbc and COPbc - out of Bowmen’s
what is the Net Filtration Pressure
(55+0) - (15+30) = 10mmHg
going into Bowmen’s capsule
what are these forces also known as and what is there role
Starling Forces
the balance of hydrostatic pressure and osmotic forces
what is GFR
rate at which protein-free plasma is filtered from the glomeruli into the Bowman’s capsule per unit time.
how is the GFR calculated
GFR = Kf × net filtration pressure
where Kf = filtration coefficient
what is the normal value for GFR
125 ml/min
what is the major determinant of GFR
Glomerular capillary fluid (blood) pressure (BPgc)
what are the regulators of renal blood flow and GFR
- Extrinsic regulation of GFR
(a) Sympathetic control via baroreceptor reflex - Autoregulation of GFR (Intrinsic)
(a) Myogenic mechanism
(b) Tubuloglomerular feedback mechanism
what happens if BPgc falls
GFR decreases
how does GFR increase
1 - increased arterial BP 2 - increases blow flow into the glomerulus via afferent arteriole 3 - increases glomerular capillary BP 4 - increases net filtration pressure 5 - increases GFR
what would cause GFR to increase/decrease
increase - vasodilation
decrease - vasoconstriction
what helps compensate when there is a fall in blood volume
decrease urine volume
what is the role of autoregulation
prevents short term changes in systemic arterial pressure affecting GFR
what are the mechanisms of auto regulation in the kidneys
1 - myogenic i.e. If vascular smooth muscle is stretched (i.e. arterial pressure is increased), it contracts thus constricting the arteriole
2 - Tubuloglomerular feedback i.e. If GFR rises, more NaCl flows through the tubule leading to constriction of afferent arterioles
what cells of the Juxtaglomerular apparatus sense NaCl content of tubular fluid
macula densa cells
what diseases could affect GFR
↑ HPbc (e.g. kidney stone) = ↓ GFR
↑ COPgc (e.g. diarrhoea) = ↓ GFR
↓ COPgc (e.g. severly burned patients) = ↑ GFR
↓ Kf (change in surface area available for filtration) = ↓ GFR
what is plasma clearance
A measure of how effectively the kidneys can ‘clean’ the blood of a substance
Equals the volume of plasma completely cleared of a particular substance per minute
Each substance that is handled by the kidney will have it’s own specific plasma clearance value
what is the equation for clearance of substance
Clearance of substance X
= [X]urine x Vurine/[X]plasma
what do the factors of the plasma clearance equation stand for
[X]urine = Urine concentration of substance X Vurine = urine flow rate [X]plasma = Plasma conc. of substance X
what are the units for the clearance of substance equation
ml/min
what can be measured clinically to determine GFR and why
Inulin clearance = GFR
what is inulin
NOT insulin freely filtered at glomerulus enters the urine via filtration alone neither absorbed nor secreted not metabolised by kidney not toxic easily measured in urine and blood
what clearance can be used instead of inulin
creatinine clearance
when does clearance = 0
For substances which are filtered, completely reabsorbed and not secreted (e.g. glucose)
when does Clearance
For substances which are filtered, partly reabsorbed and not secreted (e.g. urea)
when does Clearance > GFR
For substances which are filtered, secreted but not reabsorbed (e.g. H+)
what are the general rules to determine if it is tubular reabsorption of secretion
If clearance GFR then substance is SECRETED into tubule
what can be used to calculate the renal plasma flow (RPF)
using the para-amino hippuric acid (PAH) value (=650 ml/min)
what is PAH
exogenous organic anion
freely filtered at glomerulus,
secreted into the tubule (not reabsorbed)
completely cleared from the plasma i.e. all the PAH in the plasma that escapes filtration is secreted from the peritubular capillaries
what properties should any substance used as a clearance marker
(1) Non-toxic
(2) Inert (i.e. not metabolised)
(3) Easy to measure
what properties should a GFR marker have
should be filtered freely; NOT secreted or reabsorbed
what properties should a RPF marker have
should be filtered and completely secreted
what is the filtration factor
the fraction of plasma flowing through the glomeruli that is filtered into the tubules
how can FF be calculated
GFR/Renal Plasma Flow
125/650 = 0/19 = 20%
where does the remaining 80% of plasma that is not filtered move to
the peritubular capillaries
what is the average values for GFR, RPF and RBF
GFR = 125ml/min, 180litres/day
RPF = 650ml/min
RBF = 1200ml/min
where is substances reabsorbed
GFR = 125ml/min
80ml is in the Proximal tubule
45ml is in the Loop of Henle
what is the fluid reabsorbed in the proximal tubule state
iso-osmotic with filtrate
what is reabsorbed in the PT
sugars amino acids phosphate sulphate lactate
what is secreted in the PT
H+ Hippurates Neurotransmitters Bile pigments Uric acid Drugs Toxins
what are the 3 types of carrier-mediated membrane transport
primary active transport
secondary active transport
facilitated diffusion
what is primary active transport
Energy is directly required to operate the carrier and move the substrate against its concentration gradient
e.g. energy-dependent Na+-K+ ATPase transport mechanism
what is secondary active transport
The carrier molecule is transported coupled to the concentration gradient of an ion (usually Na+)
what is facilitated diffusion
Passive carrier-mediated transport of a substance down its concentration gradient
what is essential for sodium reabsorption
An energy-dependent Na+-K+ ATPase transport mechanism at the basolateral membrane
why does Isoosmotic fluid reabsorption across proximal tubule epithelium happen
Standing Osmotic Gradient
Oncotic Pressure Gradient
what is the function of the loop of Henle
Generates a cortico-medullary solute concentration gradient
Enables the formation of hypertonic urine
what is countercurrent flow
Opposing flow in the two limbs
Entire loop of Henle functions as a countercurrent multiplier
what establishes a hyper-osmotic medullary interstitial fluid
loop of Henle and vasa recta
which limb of Henle does not reabsorb NaCl and is highly permeable to water
Descending Limb (DL)
what is the features of the Ascending Limb of Henle
Na+ & Cl- are being reabsorbed
relatively impermeable to water
little or no water follows salt reabsorption
is the triple co-transporter
Na-K-Cl cotransporter (NKCC) is a protein that aids in the active transport of sodium, potassium, and chloride into and out of cells
what blocks the triple co-transporter
loop diuretics
what ensures NaCl is absorbed into the interstitial fluid
K+ recycling
what is the pathway of reabsorption in the loop of Henle
- Solute removed from lumen of ascending limb (water cannot follow)
- Tubular fluid is diluted and osmolality of interstitial fluid is raised
- Interstitial solute cannot enter the descending limb
- Water leaves the descending limb by osmosis
- Fluid in the descending limb is concentrated
how does flow occur in the loop of Henle
1 - Fluid enters the descending limb
2 - Fluid that has been concentrated in the descending limb moves onto the ascending limb
3 - Hypotonic fluid moves onto the distal tubule
how does pumping resumes in the loop of Henle
1 - Solute pumped out of the ascending limb
2 - Osmolality of the interstitial fluid rises
3 - Passive water efflux from the descending limb
4 - Flow occurs moving everything on as before
what is the state of the fluid in the loop of Henle
Leaving the PT - iso-osmotic
Entering the DT - hypo-osmotic
what contributes to half of the medullary osmolality
The urea cycle
what tubule is not permeable to urea
distal tubule
what is the purpose of countercurrent multiplication
To concentrate the medullary interstitial fluid
why do we need countercurrent multiplication
To enable the kidney to produce urine of different volume and concentration according to the amounts of circulating antidiuretic hormone (ADH = vasopressin)
where are vasa recta
run alongside the long loop of Henle of juxtamedullary nephrons
what is the countercurrent exchanger
Blood osmolality rises as it dips down into the medulla (i.e. water loss, solute gained)
Blood osmolality falls as it rises back up into the cortex (i.e. water gained, solute lost)
why is vasa recta needed
blood flow through medulla tends to wash away NaCl and urea
how does vasa recta minimise this problem
1 - Vasa recta capillaries follow hairpin loops
2 - Vasa recta capillaries freely permeable to NaCl and water
3 - Blood flow to vasa recta is low (few juxtamedullary nephrons)
what does the kidney not reabsorb
creatinine
how much urea does the kidney reabsorb
50%
what is reabsorbed in the PT of the kidney
Sugars Amino acids Phosphate Sulphate Lactate
what is secreted in the PT
H+ Hippurates Neurotransmitters Bile pigments Uric acid Drugs Toxins
what is the renal threshold for glucose
10-12 mmol/l
what is transport maximum
point at which increases in concentration do not result in an increase in movement of a substance across a membrane
how can the amount of substance filtered be calculated
plasma concentration of substance x GFR
how can excretion be determined
(filtration + secretion) - reabsorption
what is Na+ reabsorption driven by in the proximal tubule
by the basolateral Na+-K+-ATPase
what does Na+ reabsorption drive and through which pathway
Cl- reabsorption through the paracellular pathway
what is being absorbed in the ascending limb of the loop of Henle and not the Descending limb
Na+
Cl-
which limb of the loop of Henle is highly permeable to water and what is not
descending limb - very permeable
ascending limb - impermeable
what does the difference of water permeability in the loop of henle cause
an osmotic gradient to be established in the medulla
what hormones regulate the distal tubule and collecting ducts ion and water balance
ADH/Vasopressin
Aldosterone
Atrial Natriuretic hormones (ANH)
Parathyroid hormone (PTH)
what does ADH do
Increases water reabsorption
what does Aldosterone do
Na+ reabsorption ↑
H+ / K+ secretion ↑
what does Atrial natriuretic hormone do
Na+ reabsorption ↓
what does PTH do
Ca2+ reabsorption ↑
PO43- reabsorption ↓
where is urea concentrated and why
in the tubular fluid
distal tubule has low permeability to water and urea
what is responsible for the synthesis of octapeptide of ADH
supraoptic and paraventricular nuclei in the hypothalamus
where is the octapeptide stored for ADH
posterior pituitary
when is ADH released
Released into blood when action potentials down the nerves lead to Ca2+-dependent exocytosis
what is the action of ADH on the collecting ducts
Increases permeability of
luminal membrane to H2O
by inserting new
water channels (aquaporins)
what happens in the presence of ADH in the collecting duct
water moves from collecting duct into the medullary interstitial fluid
enables hypertonic urine formation
summary - what is the physiological state when there is high/low ADH
High [ADH]
= high water permeability
= hypertonic urine
i.e. Small volume, Concentrated urine
Low [ADH]
= low water permeability
= hypotonic urine
i.e. Large volume, dilute urine
how does the tubular fluid escape to equilibrate with interstitium
via aquaporins
when is there high ADH
when there is a water deficit
what are symptoms of Diabetes insipidus and what is the Tx
Large volumes of dilute urine Constant thirst
ADH replacement
what is the most important stimulus for ADH release and what is also a factor
Hypothalamic osmoreceptors - most important
Left atrial stretch receptors - also important
what does a decrease in atrial pressure cause
increased ADH release
what other chemicals can influence ADH
Nicotine stimulates ADH release
Alcohol inhibits ADH release
what is aldosterone
Steroid hormone secreted by the adrenal cortex
when is aldosterone secreted
- In response to rising [K+] or falling [Na+] in the blood
2. activation of the renin-angiotensin system
what does aldosterone do
Stimulates Na+ reabsorption and K+ secretion
what does sodium retention contribute to
increased blood volume and pressure
how does aldosterone work
- normally, 90% of K+ reabsorbed in PT
- when aldosterone ABSENT, rest is reabsorbed in distal tubule
- an increase in K+ directly stimulate adrenal cortex
- Aldosterone stimulates SECRETION of K+
- increase Na+ reabsorption in the distal and collecting tubule
what does a decrease in plasma Na+ promote
indirect secretion of aldosterone by means of the juxtaglomerular apparatus
what factors control the release of renin
- reduced pressure in afferent arteriole
- Macula densa cells sense the amount of NaCl in the distal tubule
- Increased sympathetic activity as a result of reduced arterial blood pressure
where is renin released from
granular cells in JGA
what does reduced pressure in afferent arteriole cause
More renin released, more Na+ reabsorbed, blood vol. increased, blood pressure restored.
why does Increased sympathetic activity cause renin release
Granular (renin-secreting) cells directly innervated by sympathetic nervous system
how is the RAAS system responsible of fluid retention associated with congestive heart failure
Failing heart»_space; Decreased CO & BP»_space; Low BP stimulates RAAS»_space; Increased salt + water retention»_space; failing heart
Tx of fluid retention
low salt diet
Diuretics (loop diuretics)
ACE inhibitors
where is ANP produced and where is it stored
the heart and is stored in atrial muscle cells
when is ANP released and what does is promote
when atrial cells are mechanically stretched due to an increase in the circulating plasma volume
promotes excretion of Na+ and diuresis, thus decreasing plasma volume
what is the process that empties urine from the bladder
micturition a.k.a urination
what two mechanisms govern urination
The micturation reflex Voluntary control (external sphincter and pelvic diaphragm)
what is the micturition reflex
involuntary emptying of the bladder by simultaneous bladder contraction and opening of both the internal and external urethral sphincters
what monitors ECF osmolarity
Hypothalamic osmoreceptors
what is water diuresis
an increased urine flow but not an increased solute excretion
what is osmotic diuresis
increased urine flow is as a result of a primary increase in salt excretion.
what can cause osmotic diuresis
failure of normal Na+ reabsorption causes both increased sodium and increased water excretion
what is Erythropoiesis
making RBC
how does an increase in [H+] cause
reduced pH
what are sources of [H+] in the body
Carbonic acid formation
Inorganic acids produced during breakdown of nutrients
Organic acids resulting from metabolism
how do strong/weak acids dissociate in solution
strong - dissociate completely in the solution
weak - dissociate partially in solution
what is the equilibrium equation
HA H+ + A-
HA undissociated acid
H+ proton
A- base
what cause the equilibrium to shift to the left and what does it cause
if acid (H+) is added
[HA] rises, [A-] falls
as protons are ‘mopped up’ by A- making more HA
what happens when a base is added to the system
equilibrium shifts to the right
[HA] falls, [A-] rises
Base is “tied-up” by combining with H+, allowing more HA to dissociate
what is the buffer in these equations
HA - either its formation or dissociation
at equilibrium what does the dissociation constant equal
K = [H+][A-] / [HA]
what is the log notation for K (the dissociation constant)
pK = -logK
what is the Henderson-Hasselbalch equation (used to calculate pH)
pH = pK + log ([A-] // [HA] )
what is the most important physiological buffer system
CO2 - HCO3 buffer
what is the buffer equation
CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO3-
what enzyme catalyse converting CO2 and water in to Carbonic acid (H2CO3)
Carbonic anhydrase (CA)
what controls [HCO3-]
the kidneys
what control Pco2
the lungs
what is normal plasma pH
7.4
what is the role of the kidney in control of [HCO3-]p
Variable reabsorption of filtered HCO3-
Kidneys can add “new” HCO3- to the blood
what is the control of [HCO3-] in the kidneys dependant on
upon H+ secretion into the tubule
how can the kidneys form ‘new’ HCO3-
secreted H+ combines with phosphate
what does H+ secretion by the tubule do
- drives reabsorption of HCO3-
- forms acid phosphate
- forms ammonium ion
what is titratable acid
way to measure amount of H+ excreted
how can the amount of acid phosphate made by H+ secretion be calculated
Measure the concentration of titratable acid (TA) in the urine ([TA]u
how can the amount of ammonium ion made by H+ secretion be calculated
Measure [NH4+]u
what rids the body of acid load and what else does this process do
Excretion of TA and NH4+ simultaneously
regenerate buffer stores
what is the normal [HCO3-] range
23-27
what is compensation
normal acid-base balance is disrupted, the first priority is to restore pH to 7.4
i.e. restoration of pH irrespective of what happens to [HCO3-]p and PCO2
what is correction
restoration of pH and [HCO3-]p and PCO2 to normal
what is the Davenport diagram used for
describe blood bicarbonate concentrations and blood pH following a respiratory and/or metabolic acid-base disturbance
what is respiratory acidosis and what can cause it
retention of CO2 by the body
e.g chronic bronchitis, chronic emphysema, airway restriction (bronchial asthma, tumour), chest injuries
how does CO2 retention cause acidosis
drives equilibrium to the right
[H+]p and [HCO3-]p rise
Increased [H+]p results in acidosis
what values would indicate uncompensated respiratory acidosis
pH 45 mmHg
what drives H+ secretion by the kidney and what does CO2 retention therefore stimulate
Pco2
H+ secretion into the filtrate
how does renal compensation for resp acidosis work
H+ secretion is stimulated
All filtered HCO3- is reabsorbed (i.e. no HCO3- excretion)
H+ continues to be secreted and generates titratable acid (TA) and NH4+
Acid is excreted and “new” HCO3- is added to the blood
what is respiratory alkalosis and what can cause it
Excessive removal of CO2 by the body
e.g. hyperventilation
how does hyperventilation cause respiratory alkalosis and what does this cause
Excessive CO2 removal drives equilibrium to the left
[H+]p and [HCO3-]p fall
The decreased [H+]p results in alkalosis
what values indicate uncompensated respiratory alkalosis
pH > 7.45 and PCO2
how does excessive removal o CO2 affect H+ secretion
reduces H+ secretion into the tubule
how does the kidneys compensate for respiratory alkalosis
H+ secretion is insufficient to reabsorb the filtered HCO3-
HCO3- is excreted and urine is alkaline
No titratable acid (TA) and NH4+ is formed, so no “new” HCO3- is generated
Renal compensation further lowers [HCO3-]p
what is metabolic acidosis and what can cause it
Excess H+ from any source other than CO2
e.g. Excessive metabolic production of H+ (DKA)
Excessive loss of base from the body (e.g. diarrhoea)
what values indicate metabolic acidosis
pH
how does the respiratory system compensate for metabolic acidosis
decrease in plasma pH stimulates peripheral chemoreceptors
Ventilation is quickly increased and more CO2 is blown off
how is metabolic acidosis corrected
Filtered HCO3- is very low and very readily reabsorbed
H+ secretion continues and produces TA & NH4+ to generate more “new” HCO3-
The acid load is excreted (urine is acidic) and [HCO3-]p is restored
what is metabolic alkalosis and what can cause it
Excessive loss of H+ from the body
e.g. Loss of HCl from the stomach (vomiting)
what happens in metabolic alkalosis
result of loss of H+ or addition of base, [HCO3-]p rises
what values indicate metabolic alkalosis
pH > 7.45
[HCO3-]p is high
how does the resp system compensate for metabolic alkalosis
slows ventilation
CO2 retained, PCO2 rises
[H+]p rises, lowering pH
[HCO3-]p also rises further
how is metabolic alkalosis corrected
Filtered HCO3- load is so large compared to normal that not all of the filtered HCO3- is reabsorbed
No TA or NH4+ is generated
HCO3- is excreted (urine is alkaline)
[HCO3-]p falls back towards normal
