What is osmolarity?
Units
Which two factors can be used to calculate it?
Concentration of osmotically active particles in a solution
osmol/L or mosmol/L
1) Molar concentration of solution
2) number of osmotically active particles present
e.g. 150mM NaCl
molar conc = 150mM
No.of osmotically active particles = 2
therefore, osmolarity = 2X150 =300 mosmol/L
Osmolality
Units of osmol/kg water
For weak salt solutions (i.e. the body), osmolality and osmolarity are interchangeable
Osmolarity of body fluids?
300 mosmol/L
Tonicity
effect a solution has on cell volume
Isotonic - effect on cell
No change in cell volume
Hypotonic
Increase in cell volume if a cell is exposed to a hypotonic environment
Hypertonic
Causes a decrease in cell volume
Cell is losing water to its environment to try and dilute it
300mM urea solution vs 300mM sucrose- effect on RBC
Hypotonic
Therefore the RBCs lyse and burst
Cell membrane is more permeable to urea than sucrose
Total Body water consists of?
Intracellular fluid (ICF) - 67% Extracellular fluid (ECF) - 33%
ECF can be broken down into?
Plasma (20% of ECF)
Interstitial fluid (~80%)
Lymph+ trans cellular fluid (negligible)
Purpose of a tracer?
Obtain the distribution of volume of a tracer and therefore the volume of the body fluid compartments
ECF tracer
Inulin
Plasma tracer
Labelled albumin
Total body water tracer
3H2O
How to measure distribution of volume of a tracer
- Add a known quantity of tracer X (Qx; mol or mg) to the body
- Measure the equilibration volume of X in the body [X]
- Distribution volume (litres) = Qx(mol)/X
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Largest contributor to water loss in the human body?
Urine
Why can we not “turn off” urine output - especially if we are dehydrated or are exercising intensely
The body still needs to excrete metabolic waste products.
Ionic composition of major fluid compartments (ICF, ECF)
of Na+, K+, Cl-, HCO3-
Na+ in ICF = 10mM
Na+ in ECF = 140mM
K+ in ICF = 140mM
K+ in ECF = 4.5mM
Cl- in ICF = 7
Cl- in ECF = 115
HCO3- in ICF = 10
HCO3- in ECF = 28
Concentrations of which ions are essentially the same in plasma and interstitial fluid?
Sodium and bicarbonate
as are chloride ions
Main ions in ECF are
Na+, Cl- , HCO3-
Main ions in ICF
K+, Mg2+, and positively charged proteins.
Osmotic concentrations of ECF and ICF are the same/different?
Same
~300mosmol/L
What is Fluid shift?
what would happen if:
a) the osmotic concentration of the ECF increases
b) If the osmotic concentration of the ECF decreases
Movement of water between the ICF and ECF in response to an osmotic gradient.
a) if osmotic concentration of ECF increases, water will move from ICF–> ECF in order to dilute and equilibrate the two compartments. (e.g. dehydration) ECF is hypertonic compared to ICF.
Fluid in ICF decreases, ECF increases.
b) Overhydration. Too much water but not enough salt, so ECF is hypotonic vs ICF.
Water therefore moves from ECF to ICF.
Fluid in ICF increases, ECF decreases
Water loss/gain if ECF gains/loses NaCl.
ECF NaCl gain: ECF ↑ ICF ↓
ECF NaCl loss: ECF ↓ ICF ↑
Gain or loss of isotonic fluid?
No change in fluid osmolarity
Change in ECF volume only.
Regulation of ECF volume is vital for?
Long term regulation of blood pressure.
Electrolyte balance
Why is it important? (2)
rates of gain = rates of loss
Important for two reasons:
1) Total electrolyte concentrations can directly affect water balance (via changes in osmolarity)
2) The concentrations of individual electrolytes can affect cell function
Na+ and K+ are particularly important
Where is Na+ mainly present?
Is this ion a major determinant of ECF volume?
ECF.
Therefore it is a major determinant of ECF volume (water follows salt)
Vital to regulate Na+
> 95% of which ion is intracellular?
Small leakages, or increased cellular uptake of this ion may lead to?
K+
Important in cell membrane potential
Muscle weakness –> paralysis
Cardiact irregularities –> cardiac arrest.
Must be closely monitored
Salt imbalance is manifested as?
Changes in ECF volume.
Recommended maximum salt intake per day?
6g.
Primary function of the kidneys?
Regulate volume, composition and osmolarity of the body fluids.
Controlled excretion of ions/water/other substances.
Structure of the kidney
- Outer renal CORTEX - granulated appearance
- Inner renal MEDULLA - striated appearance
- Renal pyramid
- Minor and major calyces.
- Renal pelvis
- Ureter
Functional unit of the kidney
Nephrons
~ 1 million in each kidney
Functional mechanism of the nephrons
- Filtration
- Reabsorption
- Secretion
How much of cardiac output does the kidney receive?
~25%
Types of nephron (2)
- Cortical nephron (80%)
2. Juxtamedullary nephron (20%)
How thick are the tubes of the nephron?
1 cell thick.
Blood supply of the nephron
Renal artery –> Afferent arteriole –> glomerulus –> Efferent arteriole –> Peritubular capillaries
Through which blood vessels are substances reabsorbed or secreted?
Peritubular capillaries
Bowman’s capsule
Cup like sack at beginning of tubular component of a nephron.
Comes into close contact with glomerular capillary.
Plasma crosses to form tubular fluid.
–> proximal tubule –> loop of henge –> distal tubule –> collecting duct –> ureter
Initial fluid in the tubular component of the nephron is composed of?
After it enters the tubes, what is the fluid then known as?
Plasma.
Then known as TUBULAR FLUID
Differences between cortical (CO) and juxtamedullary (JM) nephron?
which produces a more concentrated urine?
- JM loop of henge is a lot longer
- JM don’t have peritubular capillaries
- JM have VASA RECTA
- JM produces more concentrated
- CO has a short loop of henge
- Possess peritubular capillaries
** Diameter of afferent arteriole is larger than the efferent arteriole’s. Why? **
Keeps glomerular capillary blood pressure constant due to the “back-dating” of blood in the capillaries.
Contraction of smooth muscle wall of afferent arteriole leads to
Narrow diameter –> reduce amount of blood going to glomerulus
Relaxation –> increased blood flow to capillary
Inner layer of Bowman’s capsule is composed of what cell?
Podocyte.
Wrap around capillaries of glomerulus.
“Foot-like” extensions.
Interdigitate with extensions from neighbouring cell.
Gaps formed between adjacent podocytes are known as filtration SLITS
Gaps formed between adjacent podocytes are known as?
Filtration Slits
Why is there more filtration in glomerulus compared to other sites in the body?
Gaps between endothelial cells in the glomerulus are a lot larger ==> more filtration.
Juxtaglomerular apparatus
What cells form the juxtaglomerular apparatus
Specialised structure formed by the distal convoluted tube and the glomerular afferent arteriole.
- Granular cells - secrete RENIN
- Macula densa - detect/respond to levels of NaCl in the tubule
What do granular/juxtaglomerular cells do?
Secrete Renin when blood pressure in arteriole falls.
Macula densa function
detect/respond to levels of NaCl in the tubule
In response to elevated sodium, the macula densa cells trigger contraction of the afferent arteriole, reducing flow of blood to the glomerulus and the glomerular filtration rate
Extraglomerular mesangial cells
Function remains unclear.
What is urine
Modified filtrate of the blood
Renal processes
- Glomerular filtration
- tubular reabsorption
- Tubilar secretion
20% of the plasma that enters the glomerulus is?
Filtered.
80% of the plasma that enters the glomerulus is not filtered and leaves through the efferent arteriole.
Renal tubule acts as a conveyor belt…
substances are added or removed as urinary filtrate moves from proximal to distal end.
Rate of excretion for any substance =
Rate of filtration + rate of secretion + rate of reabsorption
Rate of filtration of X =
Mass of X filtered into Bowman’s capsule per unit time.
i.e. Rate of filtration of X = [X]plasma x GFR.
What is GFR
Normal value of GFR?
Glomerular filtration rate.
Rate at which protein-free plasma is filtered from the glomeruli into the bowman’s capsule per unit time.
GFR = Kf x net filtration pressure.
Kf is the filtration coefficient - how “holey” the glomerular membrane is.
125ml/minute
Rate of excretion of X =
[X]urine x Urine production rate
Rate of reabsorption o X =
Rate of filtration of X - rate of excretion of X
Rate of secretion of X =
Rate of excretion of X - rate of filtration of X
If rate of filtration is greater than rate of excretion, what has occurred?
Net secretion.
Rate of filtration > rate of excretion
net reabsorption has occurred
Rate of urine production?
1ml/min
Filtration barriers of the glomerulus (3)
- Glomerular capillary endothelium (barrier to RBC)
- Basement membrane (basal lamina) (plasma protein barrier)
- Slit processes of podocytes (plasma protein barrier)
Filtration Slits are formed between?
Adjacent podocytes’ interdigitating processes.
How many layers must the fluid pass through from the glomerulus to the Bowman’s capsule?
- Endothelial cell/pores
- Basement membrane (negatively charged)
- Podocyte slits
Electrical charge of the basement membrane of the glomerulus
Negative
Repels large plasma proteins.
Forces that comprise net filtration pressure (4)
Glomerular capillary blood pressure (BPGC) - 55mmHg
Capillary oncotic pressure
(COPGC) (i.e. proteins in the blood exerting a force) - 30mmHg
Bowman’s Capsule hydrostatic (fluid) pressure
(HPBC) - 15mmHg
Bowman’s Capsule oncotic pressure
(COPBC) - 0 mmHg
Net filtration = (55+0) - (15+30) = 10mmHg
Is filtration in the kidney active or passive?
Passive.
Largest/most important hydrostatic pressure? Main determinant of GFR.
Is it constant along the length of the capillary
Glomerular capillary blood pressure.
Remains constant along entire length of capillary
Why is oncotic pressure of bowman’s capsule 0?
There should not be any proteins in Bowman’s capsule.
Presence of plasma proteins (i.e. capillary oncotic pressure) does what
Tries to attract fluid from the Bowman’s capsule back into the capillary
Increased GFR leads to (plasma, urine)
Filtering more plasma
Producing more urine
Decreased GFR leads to (plasma, urine)
Filtering less plasma, producing less urine
Regulation of renal blood flow and GFR (2)
- Extrinsic regulation of GFR
- sympathetic control via baroreceptor reflex - Autoregulation of GFR (intrinsic)
- a) myogenic mechanism
- b) tubuloglomerular feedback mechanism
If arterial blood pressure increases thereby increasing…
Vasodilation
Blood flow to the glomerulus.
Increases glomerular capillary blood pressure
Increases net filtration pressure
Increases GFR
If arterial blood pressure falls, then…
Vasoconstriction
Glomerular capillary pressure decreases
Net filtration decreases
GFR decreases
Autoregulation in the kidneys prevents?
Short term changes in systemic arterial pressure affecting GFR
Renal Blood flow and GFR are protected from changes in MABP over wide range of MABP.
Can extrinsic control override intrinsic control?
Yes.
Myogenic autoregulation
If vascular smooth muscle is stretched (i.e. arterial pressure is increased), it contracts thus constricting the arteriole
Tubuloglomerular feedback
Involves the juxtaglomerular apparatus (mechanism remains unclear)
If GFR rises, more NaCl flows through the tubule leading to constriction of afferent arterioles
If there is increased salt in the blood, macula densa releases vasoactive chemical messengers, causing contraction of smooth muscle within wall of afferent arteriole and thus reducing GFR.
When would there be an increase in Bowman’s capsule fluid pressure?
Kidney stones.
Opposes net filtration, decreases GFR.
Diarrhoea would cause an increase in
Capillary oncotic pressure
therefore a decrease in GFR.
Severely burned patients would lead to …
Decreased capillary oncotic pressure
Burn patients lose/leak plasma proteins at site of burn.
Increased GFR.
Decreased Kf (decreased filtration coefficient)
Decreased GFR.
Plasma clearance
Equation.
- 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
Clearance of substance X = rate of excretion of X ÷ plasma concentration of X
i.e.
= ([X]urine x Urine flow rate)/ [X]plasma
in ml/min.
Inulin clearance is equal to
GFR.
- Freely filtered at glomerulus.
- Neither absorbed nor secreted
- Not metabolised by kidney
- not toxic
- easily measured in urine and blood
125ml of inulin-free plasma is returned to the circulation per minute.
Which substance is used to determine GFR in patients?
Creatinine.
Clearance of a substance which is filtered, completely reabsorbed and not secreted?
(need a number)
example of a substance.
Clearance = 0
e.g. Glucose
Also applies to a substance that is not filtered and not secreted.
substances which are filtered, partly reabsorbed and not secreted
Clearance < GFR
e.g. Urea
For substances which are filtered, secreted but not reabsorbed
Clearance > GFR
e.g. H+ ions.
All of the filtered plasma is cleared of a substance, and the peritubular plasma from which the substance is secreted, is also cleared
How much of all urea is reabsorbed back into the bloodstream?
50%
Other 50% is excreted.
If clearance < GFR (inulin clearance) then substance is REABSORBED
If clearance = GFR then substance is neither reabsorbed nor secreted
If clearance > GFR then substance is SECRETED into tubule
–
What substance is used to clinically calculate Renal Plasma Flow (RPF)?
Why
Para-amino hipputric acid (PAH) - an exogenous organic anion.
PAH is
a) freely filtered at glomerulus
b) secreted into the tubule (not reabsorbed)
c) completely cleared from plasma
i. e. all PAH in the plasma that escapes filtration is secreted from the peritubular capillaries.
Normal value of renal plasma flow?
650ml/min
= PAH clearance
Clearance marker - GFR marker and RPF marker
What properties should they have?
- Non toxic
2) Inert - Easy to measure
a) A GFR marker should be filtered freely; NOT secreted or reabsorbed
b) An RPF marker should be filtered and completely secreted (i.e. no reabsorption)
Filtration fraction
Fraction of plasma flowing through the glomeruli that is filtered into the tubules.
= GFR/RPF
= 20% of plasma that enters the glomeruli is filtered.
Renal blood flow (RBP) equation
Renal plasma flow x (1/1-Haematocrit)
= 650 x 1.85
= ~1200ml/Min
roughly 24% of cardiac output.
Where does the vast majority of reabsorption occur in the nephron?
Proximal convoluted tubule
Roughly how many times is the plasma filtered per day?
65 times.
How much filtered fluid is reabsorbed in the proximal tubule per minute?
~80ml/min.
Meaning there is a 45ml.min flow into Loop of Henle
(125-80)
Is the fluid reabsorbed in the proximal tubule the same osmolarity as the filtrate?
Yes it is iso-osmotic
Substances reabsorbed and secreted in the proximal tubule
Reabsorbed
- sugars
- amino acids
- phosphate
- sulphate
- lactate
Secreted
- h+
- Hippurates
- Neurotransmitters
- Bile pigments
- Uric acid
- Drugs
- Toxins
Steps that constitute TRANSCELLULAR tubular reabsorption (5)
Substance has to
- Make it across the basal membrane
- Make it through the cell without being metabolised
- Make it past the apical membrane e
- make it through the lateral space/interstiital fluid
- make its way across endothelial wall of capillary
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
Na+ reabsorption in the proximal convoluted tubule is achieved by?
An energy dependent Na+K+ ATPase transport mechanism at the basolateral membrane
Iso-osmotic fluid reabsorption across leaky proximal tubule epithelium is due to?
1) Standing osmotic gradient
2) Oncotic pressure gradient
Sodium ions leave the cell at the basolateral membrane via the sodium potassium pump.
Net movement of sodium sets up an electrchemcial gradient for the reabsorption of chloride (negative) paracellularly
Therefore we absorb NaCL
Water then follows the salt.
Water and salt enter peritubular capillary
How much glucose is reabsorbed by the proximal tubule?
100%
Glucose Leaves cell at basal membrane down its concentration gradient
It also sets up an osmotic gradient which water follows.
Renal threshold for glucose reabsorption?
10-12mmol/L
normally humans have 4-5mmol so this is not a problem. it is an issue in diabetics
Transport maximum (Tm) of glucose
2 mmol/min
Any glucose not being reabsorbed is excreted in the urine
Can secretory/reabsorption mechanisms become saturated?
Yes they can.
Percentage of all salt and water reabsorbed in the Proximal tubule?
Glucose and amino acids
~67%
100% of amino acids and glucose
How is Chloride reabsorbed in the proximal convoluted tubule? (which route)
Paracellularly
Na+ drives this reabsorption due to electrochemical gradient (negative chloride attracted by positive sodium ion)
Function of the Loop of Henle
Generates a cortico-medullary solute concentration gradient
This enables the formation of hypertonic (concentrated) urine
Fluid flow in the Loop of Henle is describe as?
Countercurrent flow
The loop functions as a countercurrent multiplier.
The loop and vasa rectae establish a hyper-osmotic medullary interstitial fluid.
Ascending Limb of the loop of henle
what is being absorbed?
what substance is this section of the loop of henge impermeable to?
> Na+ and Cl- are being reabsorbed along the entire length of the Ascending limb
- thick upper AL: this is achieved by active transport
- thin, lower AL: passive
> Impermeable to water
Descending Limb of the loop of henle
what is not reabsorbed?
Highly permeable to?
Does NOT reabsorb NaCl
Highly permeable to water
Na+ reabsorption in the thick ascending limb of the Loop of Henle.
What kind of transporter is present on the basal membrane?
What does this transporter transport?
Is there an electric gradient created?
Na+ and Cl- are reabsorbed in the thick ascending limb, but this region is impermeable to water.
Triple co-transporter is present on the basal membrane
Transports 1 Na+; 1 K+; 2 Cl- (2 positive and 2 negative charges = no current/electro gradient created)
Which drugs block the triple co-transporter?
Loop diuretics.
Potassium recycling in ascending limb
K comes in via triple co transporter, and moves down concentration gradient on apical membrane out of the cell.
Comes back into cell via Na+ K+ co transporter –> Na+ absorbed into interstitial fluid
Potassium joins chloride ions in a symport so that Cl- is also absorbed into interstitial fluid
Potassium recycled back into cell.
Triple co-transporter pumps solute from the thick ascending limb of Loop of Henle… 5 steps
shitty question I know
- 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
What kind of fluid moves on to the distal tubule? (hypo/hyper/iso)
Hypotonic.
Is there a decrease/increase of osmolality from beginning of loop of henge to the end of it?
There is a decrease in osmolality.
What 2 things are the main contributors to the corticomedullary concentration gradient?
Salt and urea
Distal tubule not permeable to urea.
Purpose of countercurrent multiplication?
Concentrate medullary interstitial fluid.
This enables the kidney to produce urine of different volume and concentration according to the amounts of circulating antidiuretic hormone (ADH = vasopressin)
Vasa rectae
Run alongside the long loop of henge of juxtamedullary nephrons.
Freely permeable to NaCl and water.
Capillary blood equilibrates with interstitial fluid cross the leaky endothelium
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 (water gained, solute lost)
Acts as a countercurrent exchanger.
Passive exchange across endothelium preserves medullary gradient - blood equilibrates at each layer.
Ensures that the solute is not washed away.
Essential blood flow through medulla tends to wash away NaCl and urea.
To minimise this problem (3)
- Vasa recta capillaries follow hairpin loops
- Vasa recta capillaries freely permeable to NaCl and water
- Blood flow to vasa recta is low (few juxtamedullary nephrons)
High medullary osmolarity in presence of ADH produces?
Hypertonic urine?
Tubular fluid leaving the Loop of Henle entering the distal tubule is ____osmotic to plasma?
Hypo-osmotic (100 mosmol/L)
What does the distal tubule empty into?
Collecting duct
The collecting duct is bathed by progressively _________ concentrations of surrounding interstitial fluid as it descends through the medulla
Increasing concentrations (300-1200 mosmol/L)
Distal tubule and collecting ducts are major sites for?
Regulated by?
Regulation of ion and water balance
Regulated by hormones
Which hormones act in the distal tubules/collecting ducts? (4)
- ADH (incr. water reabsorption)
- Aldosterone (Na+ reabsorption; H+/K+ secretion)
- Atrial natriuretic hormone (decreased Na+ reabsorption)
- Parathyroid hormone (Ca2+ increased, decreased PO43- reabsorption)
Distal tubule has low permeability to?
Therefore?
Water and urea
Urea is concentrated in the tubular fluid (helps establish osmotic gradient in the medulla)
Distal tubule is made up of 2 sections - what are they referred to as?
“Early” and “late” distal tubule.
Early distal tubule transports and reabsorbs which ions?
Transport//
Na+
K+
2CL-
Reabsorption//
NaCl
Late distal tubule secretes/reabsorbs?
Reabsorption
Ca2+
Na+ (basal state)
K+ (basal state)
Secretion//
H+
K+ secretion when K+ secretory cells are activated.
Collecting duct is split into?
Early and late
Late collecting duct has (re ions; 2 things)
- low ion permeability
2. permeability to water and urea influenced by ADH
Where is ADH secreted from?
Posterior pituitary
Where is ADH synthesised?
Octapeptide synthesised by the supraoptic and paraventricular nuclei in hypothalamus.
Size of ADH peptide?
Octapeptide.
Effects of ADH on collecting duct?
Increases permeability of luminal embrace to H2O by inserting new water channels (aquaporins)
Water channels formed by ADH stimulation are known as?
Aquaporins
Direction of water movement in presence of maximal ADH?
Water moves from the collecting duct lumen along the osmotic gradient into the medullary interstitial fluid
-> hypertonic urine formation.
Tubular fluid equilibrates with interstitial via aquaporins
In presence of minimal ADH, the collecting duct is ________ to water?
Impermeable to water.
No water reabsorption
Large, volume of dilute urine
Most important stimulus for ADH release?
Other stimuli
Hypothalamic osmoreceptors
Activation of left atrial stretch receptors (decreased atrial pressure –> increased ADH release) – large changes in volume detected.
Stimulation of stretch receptors in upper GI tract exerts feed-forward inhibition of ADH
Nicotine stimulates ADH release
Alcohol inhibits ADH release
Effect of nicotine on ADH?
Stimulates ADH release.
Aldosterone - what kind of hormone is it?
Secreted from?
Steroid hormone.
Secreted by the adrenal cortex
When is aldosterone secreted? (2)
- In response to rising [K+] or falling [Na+] in the blood (juxtaglomerular apparatus)
- Activation of the RAA system.
Function of aldosterone
Stimulates Na+ reabsorption and K+ secretion
therefore na+ retention contributes to an increased blood volume and pressure
Where is majority of K+ is reabsorbed?
Proximal tubule
When aldosterone absent, rest is reabsorbed in the distal tubule.
Renin release control (3)
Released from granular cells in juxtaglomerular apparatus
- Reduced pressure in afferent arteriole
- - more renin released, more Na+ reabsorbed, blood volume increased, BP restored. - Macula densa cells sense the amount of NaCl in the distal tubule
- - if NaCl reduced, more renin released, more Na+ reabsorbed - Increased sympathetic activity as a result of reduced arterial BP
- - granular (renin secreting) cells directly innervated by sympathetic nervous system, causes renin release.
Where does aldosterone increase Na+ reabsorption?
Distal tubule and collecting duct
Abnormal increase in RAA system can cause?
Hypertension
Fluid retention associated with congestive heart failure
Treatment of abnormal increase in RAA system?
Low salt diet
Diuretics (loop diuretics)
Atrial Natriuretic Peptide (ANP) - produced by?
released when
Cardiac cells, stored in atrial muscle cells.
released when these cells are mechanically stretched due to an increase in circulating plasma volume
What does ANP promote?
Excretion of Na+ and diuresis
Decreases plasma volume
Lowers blood pressure
Micturition is governed by 2 mechanisms - what are they
- Micturition reflex
– urinary bladder can accommodate up to 250-400ml of urine before stretch receptors within its wall initiate the micturition reflex. -
– Causes INVOLUNTARY emptying.
– simultaneous bladder contraction and opening of both internal and external urethral sphincters
- voluntary control
– micturition can be VOLUNTARILY prevented by deliberate tightening of the external sphincter and surrounding pelvic diaphragm
Regulation of erythropoiesis
Kidney produces erythropoietin –> stimulates stem cells in bone marrow –> produces RBCs –> increases 02 supply in tissues
if too low –> kidney produces erythropoietin
Is venous blood more acidic or alkaline than arterial blood?
More acidic
presence of Co2
Average pH of blood?
7.4
Fluctuations in [H+] can… (3)
Alter nerve, enzyme and K+ activity.
- alter nerve activity. Acidosis can lead to depression of the CNS. Alkalosis can lead to overexcitability of the peripheral NS and later than CNS
- [H+] exerts a marked influence on enzyme activity
- Changes in [H+] influence K+ levels in the body
H+ is added from 3 sources (3)
- Carbonic acid formation
- Inoragnic acids produced during breakdown of nutrients
- Organic acids resulting from metabolism
Input must equal output to maintain a constant H+ in body fluids
Strong acids dissociate ______ in solution
Completely dissociate
Weak acids dissociate ______ in solution
Partially dissociate
If acid [H+] is added to this system, equilibrium shifts towards…
the left
Protons are mopped up by A-, leading to formation of more HA
If a base is added to the system, equilibrium shifts to
The right
Base is tied up by combining with H+, allowing more HA to dissociate.
HA falls, A- rises.
the rise in pH (fall in [H+]) has been limited (buffered) by further dissociation of HA
Most important physiological buffer?
CO2-HCO3 buffer.
HCO3- concentration is controlled by which organ?
The kidneys
PCO2 is controlled by the?
Lungs
Normal arterial PCO2?
0.03
Normal HCO3- concentration in plasma?
24 mmol/L
Role of kidney in control of [HCO3-] plasma (2)
- Variable reabsorption of filtered HCO3-
- Kidneys can add “new” HCO3- to the blood
i. e. [HCO3-] in renal vein > [HCO3-] renal artery
Mechanism of [HCO3-] reabsorption in the proximal tubule
HCO3- disappears from the tubular fluid and appears in the interstitial fluid.
However, the same HCO3- ion does not cross the epithelium. (it is broken down into CO2 and H2O/converted into carbonic acid in the cell, and then reformed and exits the epithelial cell into the interstitial fluid)
When concentration of HCO3 in tubular fluid is low (reabsorption), secreted H+ combines with?
Phosphate
Therefore there is a net gain of HCO3- as the hydrogen phosphate (HPO4^2-_ basic) has mopped up the hydrogen ions and excreted it. therefore there is HCO3 “free”, and it then becomes new.
How can amount of H+ be measured?
Titratable acid.
Measure amount fo strong base (NaOH) added to titrate the urine pH back to 7.4.
Max amount of titratable acid in a day?
40mmol
If 40mmol/day is added as titratable acid, how much “new” HCO3- has been gained?
40mmol (1 for 1)
What other substance acts as a buffer?
Ammonia
Combines with H+ to form ammonium ion.
H+ secretion by tubule does 3 things
A. Drives reabsorption of HCO3-
B. Forms “acid phosphate”
C. Forms ammonium ion