Physiology Flashcards
What is osmolarity? The unit of osmolarity is ____
The concentration of osmotically active particles present in a solution. Osmol/L
What is the osmolarity of 150mmol/L NaCl? Explain why
Concentration = 150mmol/L number of osmotically active particles = 2 (1xNa & 1xCl) 150 x 2 = 300mosmol/L
What is the osmolarity of 100mmol/L MgCl2? explain why.
Concentration = 100mmol/L number of osmotically active particles = 3 (1xMg & 2xCl) 100 x 3 = 300mosmol/L
The osmolarity of the human body is approximately ______
300mosmol/L
Define tonicity
Tonicity is the effect that a solution has on cell volume if a cell is placed in that solution.
Explain hypo/iso/hypertonic
isotonic - no change in cell volume, no net movement of water Hypotonic - increase in cell volume, water moves from outside to inside cell. Hypertonic - decrease in cell volume, water moves from inside cell to outside.
Using urea and sucrose with RBCs as examples, explain why membrane permeability must be taken into account when thinking about tonicity?
- Osmolarity of both is approximately 300mosmol/L. - Urea is much more permeable than sucrose so moves in RBCs immediately and change osmolarity - therefore water follows - Cell will lyse - Sucrose is isotonic - does not move into cells - no net changes in water volumes/cell volume as osmolarity inside and out is the same.
70% of male and female body weight is water - true/false?
false - 60% of males/50% of females
Females have a lower total body water percentage than males - true/false. If true, explain.
True Women have a higher body fat percentage (22-25% F/15-18%M) and fat cells contain very little water.
The two main fluid compartments in the body are ____ & _____, which are separated by _______.
Intracellular and extracellular, separated by the plasma membrane.
What proportion of the total body water is in each fluid compartment?
2/3rds (67%) intracellular 1/3rds (33%) extracellular
The extracellular fluid compartment can be split into what constituents? What percentage of fluid lies in each compartment?
Interstitial fluid - 80% Plasma - 20% Transcellular fluid (e.g. CSF and intrapleural fluid) - negligible Lymph - negligible
Which tracers are used to calculate each fluid compartment’s volume?
Total Body Water = 3H2O
Plasma = Albumin
inulin = ECF
If there is no direct way to measure intracellular fluid volume, how might we calculate it indirectly?
We can detect the volume of TBW and the volume of the ECF directly using the tracers (3H2O for TBW, Inulin for ECF) and then realise that TBW = ECF + ICF
therefore ICF = TBW - ECF.
Explain the dilution principle for measuring the fluid volumes of distribution in the body.
If you add a known amount of a tracer to an unknown volume, you can work out the volume by taking off a small, known volume and calculating the concentration of your tracer in that volume. Scale up for 1L and then use:
Volume = Dose/Concentration
where dose is the total amount of tracer used.
Approximately how much of our fluid intake comes from each of the following sources:
- Food
- Fluids
- Metabolism
What percentage of daily intake does that equate to?
- Food = 1200ml/day = 48%
- Fluid = 1000ml/day = 40%
- Metabolism = 300ml/day = 12%
total = 2500ml
What are insensible fluid losses?
What are sensible fluid losses?
Skin & lungs are insensible
Sweat, faeces and urine are sensible losses
How much fluid on average is lost each day from the following sources:
- Urine =
- Faeces =
- Sweat =
- Lungs =
- Skin =
What percentage of daily loss does each equate to?
- Urine = 1500ml/day = 60%
- Faeces = 200ml/day = 8%
- Sweat = 100ml/day = 4%
- Skin = 350ml/day = 14%
- Lungs = 350ml/day = 14%
Total = 2500ml/day
Sodium concentration is greater outside the cell than inside - true/false
True - think of it as we all evolved from sea creatures so our cells like to be surrounded in salt (sodium and chloride ions much higher concentration in ECF than ICF)
ICF is lower in potassium than ECF -true or false
False
Chloride and bicarb are of higher concentrations in the ICF than the ECF - true/false
False - higher in the ECF than the ICF
if the concentrations of solutes are different in the ICF and ECF, how does the cell regulate the concentrations in each?
the membrane is a selectively permeable membrane with transporter molecules specific for each ion - e.g. the sodium/potassium-ATPase pump which pumps sodium out of and potassium into cells.
There is a difference in osmolarity in the ECF and ICF due to the difference of sodium and potassium concentrations - true/false
False - the ECF and ICF have identical osmolarity as any changes in osmotic gradient cause a movement of water to change the osmolarity back to equilibrium.
Gain of loss of water from one fluid compartment will cause a compensatory shift in the other compartment - e.g. if water is lost from ECF, water will move from the ICF to the ECF to restore equilibrium - true/false
True
Gain of loss of isotonic fluids e.g. 0.9% saline will cause no change in osmolality but will cause an increase in the volume of the ECF and ICF - true/false
False - only increases ECF.
More than 95% of the ECF osmolarity comes from sodium salts - true/false
False - more than 90% comes from sodium salts
How does sodium concentration influence volume of the ECF
- increases osmolarity in a fluid
- water follows sodium
- e.g. increased sodium in the plasma, water is drawn into plasma
- e.g. increased sodium in renal filtrate, water drawn into renal filtrate
Potassium ions form a key role in the establishment of which physiological process?
the formation of the membrane potential.
_____% of the body’s potassium is intracellular.
95%
The kidneys produce _____ml/min of urine
1ml/min of urine
the kidney secretes ______ and _______. It also converts vitamin D into its active/inactive form (________)
the kidney secretes renin and erythropoeitin. It also converts vitamin D into its active form (calcitriol)
Primary function of the Kidney is _______
To regulate the volume, composition and osmolarity of bodily fluids.
Collectively the kidneys recieve ______% of total cardiac output
20%
The cortex appears ______ while the medulla appears ________
The cortex appears granulated, the medulla appears striped.
Where do the peritubular capillaries run?
They run along the tubules very closely and are the capillaries both involved in the reabsorption/secretion of substances and supplying the nephron.
how many cells thick are the tubular walls?
1 cell thick
When does the filtrate become urine?
Only when it passes into the minor calyx as it doesn’t undergo any more changes after the collecting ducts.
The two types of nephron are _________ & ___________
the two types of nephron are Juxtamedullary and Cortical
What is the difference between the two types of nephrons?
Juxtamedullary:
- Longer loop of henlé
- single capillary called the vasa recta which follows loop of henlé
Cortical
- Shorter loop of henlé
- network of peritubular capillaries.
What is the purpose of a juxtamedullary nephron?
it allows us to produce very concentrated urine.
In the glomerulus the ______ arteriole is wider than the _______ arteriole.
Afferent arteriole is wider than the efferent arteriole
Compare the filtrate to blood
Exactly the same; minus large proteins and cells
What three processes happen in the nephron?
- Glomerular filtration
- Tubular Secretion
- Tubular Reabsorption
The renal tubule is described as like a conveyor belt; explain?
As the urine is passing through the tubules, things are added (secreted from the blood) and things are removed reabsorption
Filtration + _________ = Excretion + _________
Filtration + secretion = excretion + reabsorption
Rate of excretion = _______________
Rate of excretion = (Rate of filtration + secretion) - rate of absorption
Rate of filtration = __________
Rate of filtration of substance X = [Xplasma] x GFR
Rate of excretion of Substance X = ______________
Rate of excretion of substance x = [X]Urine x VU
What is VU?
Flow rate of Urine
Rate of reabsorption of substance X = ______________
Can this be measured directly?
Rate of absorption of substance X = rate of filtration of X - Rate of secretion of X
if Filtration is greater than secretion; this is net filtration
Rate of Secretion of substance X = _________________
Rate of Secretion of substance X = Rate of excretion - rate of filtration
If rate of excretion > rate of filtration, this is net secretion
For chloride, the following values are true. Calculate rate of filtration/excretion and decide if this is overall net secretion or reabsorption. What is the magnitude of the net effect?
- [Cl-]Plasma = 110mmol/L
- [Cl-]Urine = 200mmol/L
- GFR = 0.12L/min
- VU = 0.001L/min
- [Cl-]Plasma = 110mmol/L
- [Cl-]Urine = 200mmol/L
- GFR = 0.12L/min
- VU = 0.001L/min
Rate of filtration = [Cl-]Plasma X GFR = 110 x 0.12 = 13.2mmol/min
Rate of excretion = [Cl-]Urine X VU = 200 x 0.001 = 0.2mmol/min
Rate of filtration > rate of excretion
therefore; this is net reabsorption
Magnitude = filtration - secretion = 13.2 - 0.2 = 13mmol/min reabsorbed.
(sorry for all the BS on the card!!)
What are the three filtration barriers to glomerular filtration? What does each provide a barrier to?
Glomerular capillary endothelium - barrier to RBCs
basal Lamina (basal membrane) - barrier to plasma proteins
Slit process of podocytes - barrier to plasma proteins
The Endothelial cells have very large/small pores in them
The endothelial cells have very large pores in between them
How does the basement membrane prevent the entry of large proteins into the glomerular filtrate?
It is made up of no cells, but has lots of collagen and glycoproteins. this gives it a net negative charge. Plasma proteins have a net negative charge. therefore they repel each other.
What cells make up the basement membrane of the glomerulus?
trick question - no cells; made up of collagen and glycoproteins
The process of filtration is active - true/false
False - it is entirely passive
There are __ pressures which maintain filtration - name them and their approximate size (mm Hg)
4 pressure
Glomerular filtration pressure - 55mm Hg; favours filtration
Bowman’s capsule hydrostatic pressure - 15mm Hg; opposes
Capillary oncotic pressure - 30mm Hg; opposes
Bowman’s capsule oncotic pressure - 0mm Hg; favours
What is the glomerular filtration pressure?
Pressure that is constant along entire capillary; caused by the afferent arteriole being larger than efferent - back pressure
What causes the bowman’s capsule hydrostatic pressure?
Build up of fluid in the bowman’s capsule - opposes filtration
What is causing capillary oncotic pressure?
Think “plasma proteins” everytime you hear oncotic. Plasma protein concentration gradient causes a fluid shift to compensate.
What causes the bowman’s capsule oncotic pressure?
lack of plasma proteins - no pressure, water is drawn in
How is net filtration pressure calculated?
Calculate it using the typical values
Forces favouring filtration - forces opposing filtration
= (glomerular filtration pressure + Bowmans oncotic pressure) - (bowman’s hydrostatic + Capillary oncotic pressures)
= (55 + 0) - (30 +15) = 55 - 45 = 10mm Hg
Define GFR
The rate at which protein free plasma is filtered from the glomeruli in to the bowman’s capsule per unit time.
GFR = __________
Net filtration pressure x the filtration co-efficient (KF)
How is GFR regulated?
Extrinsically - sympathetic control through baroreceptor reflex
Autoregulation - via myogenic or tubuloglomerular feedback mechanisms
If arterial BP increases, blood flow to the glomerulus ______ and so GFR will ______
If arterial BP increases, blood flow to the glomerulus will increase and glomerular filtration rate will increase
If the afferent arteriole constricts then blood flow to the glomerulus will _____ and GFR will _____
If the afferent arteriole constricts then blood flow to the glomerulus will decrease and GFR will decrease
Urine volume is a direct marker of GFR - true/false
True
If mean arterial blood pressure falls, the baroreceptors cause a (constriction/dilation) of the afferent arterioles. this cause glomerular capillary blood pressure to (rise/fall) and therefore GFR to (rise/fall)
If mean arterial blood pressure falls, the baroreceptors cause a constriction of the afferent arterioles. this cause glomerular capillary blood pressure to fall and therefore GFR to fall.
Autoregulation relies on what two methods to control GFR?
Myogenic and tubuloglomerular
Describe the myogenic response and how it controls the GFR
Vascular smooth muscle is stretched, it will constrict to oppose the change and so there will be a reduced blood supply to the glomerulus leading to reduced filtrations
What is the mechanism of the tubuloglomerular feedback in controlling GFR?
It involves the juxtaglomerular apparatus but exact mechanism is unknown. If GFR rises, more NaCl is flowing through the tube. this is sensed by the macula densa and the juxtaglomerular apparatus secretes a vasoconstrictor mediator to reduce GFR again.
if hydrostatic pressure in the bowman’s capsule increases GFR _______
If oncotic pressure in the capillary increases, GFR ________
If oncotic pressure in the capillary decreases, GFR ________
if KF decreases, GFR __________
if hydrostatic pressure in the bowman’s capsule increases GFR decreases
If oncotic pressure in the capillary increases, GFR decreases
If oncotic pressure in the capillary decreases, GFR increases
if KF decreases, GFR decreases
What is plasma clearance?
A measure of how effectively kidneys can “clean” the body of a substance, measured in volume of plasma completely cleared per minute
What is inulin?
An exogenous compound, freely filtered at the glomerulus and neither absorbed or secreted. it is non-toxic, not metabolised and easy to measure in both blood and urine
Inulin clearance gives a reliable estimate of GFR - true/false
False - inulin clearance gives an exact measure of GFR.
Clearance of which substance is used to give an estimate of GFR?
Creatinine
an example of a substance that is filtered, completely reabsorbed and never secreted. Its clearance should be 0/min.
Glucose
This is filtered, partially reabsorbed and not secreted. Its clearance should be < GFR
Urea
Filtered, secreted and not reabsorbed. Clearance should be > GFR
H+ ions
Give the Equation for clearance
Clearance = ([X]urine x Vu)/[X]plasma
Inulin clearance is typically around what value?
125ml/min
State whether there is secretion, reabsorption or neither, If clearance of a substance is:
- > GFR
- = GFR
- < GFR
Clearance > GFR = Secretion
Clearance = GFR = neither excretion nor secretion
Clearance < GFR = reabsorption
Given the following values for sodium, decide if it is excreted, reabsorbed or neither.
- [Na]plasma = 140mmol/L
- [Na]urine = 70mmol/L
- VU = 1ml/L
- Inulin clearance = 125ml/min
[Na]urine x Vu = 70x10-3 = 0.07 x 1 = 0.07
70/[Na]plasma = 0.07/140x10-3 = 0.5ml/min
inulin rate = 125ml/min.
therefore sodium clearance < inulin clearance
therefore this is reabsorbed.
What is PAH? What is it used for?
it is an exogenous organic ion which is non-toxic, not reabsorbed, completely cleared by plasma as any that is not filtered is secreted into the filtrate
It is used to measure renal plasma flow.
What is the excretion rate for PAH?
What is this equal to?
650ml/min
Equal to Renal plasma flow
What is the filtration fraction? How is calculated?
It is the fraction of plasma which flows through the glomeruli which is filtered into the tubules.
Calculated as the GFR/renal plasma flow.
Using the typical values for GFR and Renal plasma flow, calculate the filtration fraction.
GFR = 125ml/min
RPF = 650ml/min
Filtration fraction = GFR/RPF
= 125/650 = 0.19 = 19%.
Where is the majority of reabsorption in the nephron occuring?
The proximal tubule
Reabsorption is necessary because the kidneys would otherwise filter all of our blood volume out in an hour otherwise - true/false
True
The kidneys filter approximately 200L of plasma per day - true/false
False - approximately 180L/day
The kidneys filter our blood approximately __X per day
65x per day.
What percentage of the following substances is reabsorbed by the kidneys?
- Fluid
- Salt
- Glucose
- Amino acids
- Urea
- Creatine
- Fluid = 99%
- Salt = 99%
- Glucose= 100%
- Amino acids = 100%
- Urea = 50%
- Creatine = 0%
Filtration and reabsorption are both passive processes - true/false
False - filtration is passive, reabsorption is active
Water and salt are reabsorbed in equal proportions in the proximal tubule and this is why we have no change in osmolarity in the proximal tubule - true/false
True.
What solutes are reabsorbed in the proximal tubules?
Sugar
Amino Acids
Phosphates
Sulphates
Lactate
What substances are secreted into the proximal tubules?
H+
Hippurates
Neurotransmitters
Bile pigments
Uric Acids
Drugs
Toxins
50% of glucose is absorbed in the PCT; the other 50% is absorbed in the remainder of the nephron - true/false
False - it all is absorbed in the PCT - no glucose is reabsorbed beyond this point.
Sodium is reabsorbed transcellularly - true/false
True
The sodium potassium pump is found on which membrane of the tubule cells?
What does it do?
How many potassium/sodium ions does it move each turn?
It is located on the basolateral membrane
It Moves sodium out of and potassium into cells
It is an antiporter which moves out 3 sodium/in 2 potassium for every ATP hydrolsed - pumping sodium into the interstitium
How does the sodium potassium ATP-ase pump aid the reclamation of sodium from urinary filtrate?
It maintains a sodium gradient from the filtrate to the cell.
Sodium glucose co-transporters do what?
they move sodium and glucose into the cell together
Sodium amino acid co-transporters do what?
they move sodium into the cell along with amino acids
Sodium hydrogen antiporters pump sodium out of and hydrogen into the cells at the luminal membrane - true/false
False - sodium in/hydrogen out to the filtrate
Presence of sodium in the interstitium causes reclamation of chloride and water - how?
There is an electrochemical gradient which draws chloride out due to opposing charges through the paracellular route. this in turn causes an osmolarity gradient to be set up which then draws water out via the paracellular route (water follows salt)
What causes water to be drawn back into the blood from the interstitium after it is removed from the filtrate?
Oncotic pressure of the capillary draws water back in.
Glucose is reabsorbed through the potassium glucose anti-porter pump - true/false?
False - reabsorbed via the sodium-glucose co-transporter
Glucose passes out of the cell into the interstitium from the basolateral membrane through which transporter?
Glucose transporter via facilitated diffusion.
Sodium and chloride are reabsorbed in both limbs of the loop of henlé - true/false
False - absorbed in the ascending limb but not the descending limb.
Both limbs of the loop of henlé are permeable to water - true/false
False - ascending is very impermeable, descending is very permeable
In the thick upper ascending limb, salt reabsorption is (active/passive) while in the thin, lower ascending limb, salt reabsorption is (active/passive)
In the thick upper ascending limb, salt reabsorption is active while in the thin, lower ascending limb, salt reabsorption is passive.
The cells in the ascendling limb contain which transporter on their luminal membrane?
Triple co-transporter to pump sodium/potassium/chloride into the cell
In the ascending limb, the basolateral membrane contains two pumps:
- _____________
- _____________
Explain how together these recycle potassium at the basolateral membrane.
- Sodium/potassium anti-porter
- Potassium/chloride co-transporter
Sodium/potassium anti-porter pumps sodium into the interstitium and potassium into the cell while the potassium/chloride co-transporter moves potassium and chloride into the interstitium.
No water follows salt into the interstitium from the ascending limb of the loop of henlé - true/false
true
Tubular fluid leaing the loop of henlé and entering the distal convoluted tubule is hypo/hyperosmotic to the plasma
Hypo-osmotic in reference to the plasma
It is hypotonic
It will cause cells to increase in volume if placed into it.
What is the osmolarity of the surrounding interstitial fluid of the cortex around the distal convoluted tubule?
300mosmol/L
The collecting duct is bathed in progressively increasing/decreasing osmolarities as it descends through the medulla
What is the range of the osmolarities?
Increasing osmolarity as you descend through the medulla.
Ranges from 300mosmol/L - 1200mosmol/L
____% of filtered ions are reabsorbed before they enter the distal tubule.
>95% of filtered ions are reabsorbed before they enter the distal tubule.
The residual load of NaCl is the amount left in the filtrate when it reaches the distal tubule - true/false
What is the magnitude of the residual load?
True
700-1000mmol/cay of sodium chloride.
The residual load is very important for ______
the residual load is very important for salt balance.
In the distal tubule and collecting ducts, fluid and salt retention is largely dependent on what?
Hormones e.g. ADH/Aldosterone/ANP/PTH
What is ADH?
Anti-diuretic hormone
Produced in the hypothalamus and secreted by the posterior pituitary in response to increased osmolarity of the blood. Causes aquaporin expression to be increased allowing water to pass through the relatively impermeable distal convoluted and collecting tubules to be reabsorbed. Also known as vasopressin due to a slight vasoconstrictor activity.
Fluid entering the distal tubule is hypo/hypertonic to plasma (____mosmol/L)
hypotonic - 100mosmol/L
Select true or false for the following statements:
- The distal convoluted tubule is normally very impermeable to water but permeable to urea.
- permeability of both water and urea can be affected by ADH
- The distal convoluted tubules express a co-transporter which transport sodium and chloride across the apical membrane but not potassium.
- False - Normally very impermeable to both water and urea
- True - Permeability of water and urea is affected by ADH
- false - they express the triple co-transporter and so move sodium, potassium and chloride into the cells
The triple co-transporter in the distal tubule is secreted in its early/late part
Early
The cells in Which part, early or late, of the distal tubule reabsorb calcium?
late part cells
Where in the distal tubule does aldosterone have its effect?
The late part
The collecting duct is split into _____ and ______. Describe them both
Early; very like the late stage of the distal convoluted tubule
Late; low ion permeability and a permeability to water and urea influenced by ADH.
What kind of molecule is ADH?
octapeptide
Where exactly is ADH synthesised, what is it transported through and where exactly is it stored?
Synthesised: Supraoptic and paraventricular nuclei in the hypothalamus.
Passes: Down nerves to terminals in the posterior pituitary.
Stored: in granules in the posterior pituitary gland.
When is ADH released into the blood?
When action potentials cause calcium dependent exocytosis.
What is the half life of ADH once it has been secreted?
10-15mins (short half life)
What type of receptor does ADH bind to?
G-protein coupled receptor called a type 2 vasopressin receptor.
What happens when ADH is bound to the type 2 Vasopressin receptors?
ATP is converted to cyclic AMP and this increase causes increased expression of aquaporins to increase absorption of water into the cells.
Our ADH levels only change at one extreme or the other (i.e. dehyrdrated and overhydrated)
true/false
False! We are constantly adjusting our ADH levels to maintain a negative feedback loop.
Aquaporins in the basolateral membrane of the collecting ducts & distal tubules are ADH dependent/independent.
ADH independent - they are always there
ADH Does/Does not have any effect on the reabsorption of salt.
Does not - water only effected.
What is the main stimulant for vasopressin secretion?
Plasma osmolarity
increased will stimulate secretion of vasopressin, decreased will suppress vasopressin.
What detects changes in plasma osmolarity?
Osmoreceptors in the hypothalamus.
Explain what happens when osmoreceptors are stimulated in the hypothalamus.
The osmoreceptors are stimulated and in turn stimulate hypothalamic neurons which increase thirst and cause release of ADH from the posterior pituitary gland.
How does ADH/vasopressin cause a decrease in osmolarity of the plasma?
it causes the distal convoluted tubules and collecting ducts to increase their expressions of aquaporins and so more water will be reabsorbed into the interstitium and subsequently into the blood. the thirst response also increases water intake which, balance with the reduced water output, should dilute the blood to reduce the osmolarity.
How does reduced ECF volume and reduced arterial blood pressure affect vasopressin?
Increases secretion.
activation of left atrial volume receptors in very large changes of volume/arterial pressure. this stimulates hypothalamic neurons and ADH is secreted. this causes slight vasoconstriction and causes the increased reabsorption of fluid and both of these actions boost BP.
How do nicotine and alcohol affect ADH?
Nicotine will stimulate the secretion of ADH.
Alcohol will suppress the secretion of ADH.
Diabetes insipidus can be defined as one of two types
Central DI
Nephrogenic DI
Central Diabetes Insipidus is ________
A lack of ADH.
nephrogenic Diabetes Insipidus is
A problem where the nephron become resistant to the effects of ADH but ADH is secreted normally.
What are the symptoms of diabetes insipidus?
Extreme thirst
Very large volumes of dilute urine (up to 20L)
What drugs are used to treat central diabetes insipidus?
ADH replacement drugs
What drugs are used to treat nephrogenic diabetes insipidus?
Drugs designed to reduce production of urine.
Where is aldosterone secreted from? In response to what, is aldosterone secreted?
The adrenal cortex - in response to rising potassium or falling sodium in the blood or by the activation of the RAAS.
What percentage of potassium is reabsorbed prior to the distal tubule normally?
90% - remainder absorbed in the distal tubule in the absence of aldosterone.
It is normal to have some potassium in urine - true/false
False - all potassium should be reabsorbed unless there is an excess in the blood.
Increased K+/Na+ in the plasma will directly stimulate secretion of aldosterone.
Increased K+/Na+ in the plasma will indirectly stimulate secretion of aldosterone.
Increased K+ in the plasma will directly stimulate secretion of aldosterone.
Increased Na+ in the plasma will indirectly stimulate secretion of aldosterone.
What causes indirect secretion of aldosterone in decreased sodium plasma concentration?
Occurs via the Juxtaglomerular apparatus.
What cells secrete renin?
Granular cells in the juxtaglomerular apparatus.
What stimulates release of renin?
Decreased NaCl/ECF volume/BP
Describe the action of the RAAS system.
Renin secreted from the granular cells of the juxtaglomerular apparatus acts on angiotensinogen produced by the liver to cleave it to angiotensin I.
Angiotensin I is converted to angiotensin II by angiotensin converting enzyme, secreted by the lungs.
Angiotensin II is a potent vasoconstrictor and increases blood pressure by constriction. Also stimulates release of aldosterone to allow increased water and salt retention and stimulates vasopressin secretion to increase water retention and (minor) vasoconstriction.
What three factors control renin release?
- Reduced afferent arteriolar pressure - more renin released and more sodium reabsorbed to increase blood volume/restore blood pressures
- Macula densa cells - monitor salt in distal tubule. Salt levels decrease, decreased filtration of salt. Macula densa stimulate renin to increase retention of salt
- Increase sympathetic activity - direct innervation by sympathetic nerve fibres stimulate renin secretions.
give the two ways aldosterone exerts its effect.
- Increases number expressed and rate of action, of Na/K antiporters at the basolateral membrane
- Increases number of sodium channels in the apical membrane
leads to increased reabsorption due to increased permeability to sodium and a constant concentration gradient into the cell, maintained by Na/K antiporter.
Abnormal increase in the RAAS causes ________ & ________
Some cases of hypertension and can cause difficulty for patients with congestive heart failure.
Briefly explain why patients with congestive heart failure can be exacerbated by their RAAS system.
heart failure - decreased cardiac output and therefore MABP.
Decrease MABP stimulates RAAS to try to correct balance. Increased salt retention, BP goes up. Heart works harder to pump higher pressures which exacerbates heart failure.
What is the treatment for heart failure exacerbated by abnormal RAAS function?
Low salt diet and loop diuretics.
ACEI can stop fluid and salt retention and arteriolar constriction.
What is atrial natriuretic peptide?
ANP is produced by the heart, stored in atrial muscle cells. released by cells under mechanical stretch. Promotes sodium secretion and diuresis to decrease plasma volume and lowers BP.
Also exerts a cardiovascular effect to lower BP.
Urine is transferred between the kidney and bladder in what structures? By what kind of process?
From the kidneys to the bladder in the ureter.
Peristaltic process.
What is micturition?
Fancy, clinical name for urination.
How much fluid can the bladder tolerate before the micturition reflex is initiated?
250ml-400ml.
What cells are stimulated by a full bladder and begin the micturition response?
Stretch receptors within the bladder wall.
How is voluntary control of micturition obtained?
Deliberate tightening of the external sphincter
Deliberate contraction of the pelvic diaphragm.
An inhibitory signal descending from the cortex.
Give the equation for pH
pH = -log[H+]
pH is a measure of total hydrogen concentration in the blood - true/false
False - only measures free hydrogen ions in the blood.
What is the average pH of the following:
Stomach acid =
Blood =
Stomach acid = 2
Blood = 7.35 - 7.45
If blood pH is less than ______ the patient has an acidosis.
If blood pH is more than _____ the patient has an alkalosis.
If blood pH is less than 7.35 the patient has an acidosis
If blood pH is more than 7.45 the patient has an alkalosis.
The ECF pH is very tightly controlled at ______
What is the equivalent hydrogen ion concentration?
7.4
40nM
Small changes in pH are caused by small/large changes in [H+]
Small changes in pH; large change in [H+]
what do acidosis and alkalosis do to the CNS?
Acidosis - suppresses it; coma.
Alkalosis - increased excitability and nerve stimualtion. Pins and needles, muscle twitch, spasm including in severe cases resp muscle spasm.
How does a change in pH effect enzymes?
Changes the way it folds; alters its secondary structure; changes ability to work.
Changes in hydrogen ions have a knock on effect on potassium/sodium levels. Explain why
Changes in hydrogen ions have a knock on effect of potassium concentration.
This is because increased hydrogen secretion into the tubules means decreased potassium secretion and therefore secretion.
There are ____ sources of hydrogen ions. What are they?
3
Carbonic acid formation
Increased levels fof inorganic acids from nutrients e.g. meat protein breakdown into sulphur and phosphate to form acid
Organic acids from metabolism e.g. free fatty acid.
In Diabetes Mellitus, how is acid produced that isnt normally produced?
Uncontrolled DM leads to inability to respire glucose. Body carries out lipolysis for energy and forms keto-acids.
What is pKa a measure of?
inverse log of the dissociation constant.
It is the pH at which the dissociation is at equilibrium.
pKa = ___________
pKa = - log([H+][A-]/[HA])
Give the equation used to calculate pH using pKa.
pH = pKa + log ([HA]/[A-])
What is the most important buffer in the body?
Give its equation.
the CO2 - HCO3 Buffer
CO2 + H2O <–> H2CO3 <–> H+ + HCO3-
How is the CO2 - HCO3 maintained?
Both via the respiratory system (CO2) and the renal system (HCO3-)
How do the kidneys control HCO3-?
The selectively reabsorb and can add bicarbonate to the blood stream.
What does adding new bicarbonate to the plasma mean?
It means that the concentration in the renal vein is greater than the renal artery.
Both reabsorption of bicarbonate and generation of new bicarbonate rely on which process?
the secretion of hydrogen ions into the tubular filtrate.
How much bicarb is secreted per day?
Filtration rate = GFR x [X]plasma = 180L/day x 24mmol/L = 4320
Hydrogen ions are pumped out of the apical membrane of the tubular cells via which method?
Na+/H+ antiporter - sodium in, hydrogen out.
Hydrogen pumps from the cell binds to what substance? What does it form?
Binds to bicarbonate to form carbonic acid. this dissociates into carbon dioxide and water.
Carbonic acid is converted into _______ and _______ and then moves across the membrane where it rejoins to give _________
The enzyme which catalyses the conversion of carbon dioxide and water to carbonic acid and vice versa is ______
Carbonic anhydrase
Carbon dioxide leaves the cell through the basolateral membrane via a transporter - true/false?
False - moves by simple diffusion.
Intracellular H2CO3 becomes _____
Hydrogen and bicarbonate ions.
The bicarbonate in the tubular epithelial cells leaves via a transporter - what is it?
Sodium/bicarbonate co-transporter.
The CO2 in the cell and the tubule which binds with H2O is gathered from where?
The interstitium through the basolateral membrane.
When the concentration of bicarb in the tubule is low, the hydrogen ions can bind to the next best buffer which is _____
Phosphate ions (HPO42-)
Phosphate is reabsorbed in the renal tubules via a sodium/phosphate co-transporter on the apical membrane. true/false
False - it is not reabsorbed. it binds with hydrogen and is excreted as acid.
How does phosphate buffering allow the regeneration of bicarbonate?
Carbon dioxide and water intracellularly are able to bind via carbonic anhydrase to allow formation of H2CO3 which then dissociates and the hydrogen is secreted into the tubular fluid, where it binds with phosphate and the HCO3- is secreted into the interstitium via the sodium/bicarbonate co-transporter.
For every hydrogen ion bound to HPO42- how many bicarbonate are regenerated and released into the blood?
1 acid phosphate excreted = 1 bicarbonate generated.
What is the titratable acid? How is it measured?
The amount of H+ excreted as H2PO4- measured by titrating back to pH 7.4 using NaOH.
What is the maximum amount of titratable acid per day?
40mmol/day
What is the maximum “new” bicarb that can be generated per day from titratable acid?
40mmol/day
What compound is degraded to ammonia? What enzyme carries this out?
Glutamine by glutaminase.
Ammonia leaves the renal tubules via facilitate diffusion - true/false
False - simple diffusion.
The ammonia binds with what in the tubule? What is formed?
With hydrogen ion to give an ammonium ion (NH4+)
Ammonium ions are excreted in urine - true/false
True.
How does ammonium ion secretion cause regeneration of bicarb?
it allows the carbon dioxide and water in the cell to form carbonic acid in the cell instead of in the tubule and so the bicarbonate formed by the dissociation of the carbonic acid in the cell passes into the interstitium and into the plasma.
Ammonium ion excretion can be measured in titratable acid - true/false
False
What is normal ammonium ion excretion? What can it range to during acidosis?
20mmol/day
5-600mmol/day
Calculate how much bicarb is reabsorbed per day
GFR = 125ml/min = 180L/day & [bicarb]plasma = 24mmol/L
Filtered = 180 x 24 = 4320mmol/day
VU = 1L/day & [bicarb]urine = 20mmol/day
Excreted = 1 x 20 = 20
Reabsorbed = 4320 - 20 = 4320mmol/day
How much titratable acid is produced per day normally?
20mmol/day
How much ammonium is excreted each day normally?
40mmol/day
How much new bicarbonate is generated per day?
TA + NH4- = Amount of new bicarb = 20 + 40 = 60mmol/day
A person is in normal acid base balance if ______
pH, bicarb and pCO2 are all in normal ranges
What is the first thing that happens when there is an acid base disturbance?
Compensation; body alters to restore normal ASAP, regardless of cause
What is correction?
This is when, after the compensation has occured and pH is normal, the body restores normal ranges for bicarb and pCO2.
What are the two major classifications of acid base disturbances?
Respiratory
Non-respiratory (AKA metabolic)
What is each type of disturbance (respiratory and non-respiratory) further divided into?
Acidosis and alkalosis.
Increased pCO2 causes ________
Respiratory acidosis
Give 5 causes of CO2 retention.
Chronic bronchitis
Emphysema
Airway restriction
Chest injuries
Respiratory depression e.g. general anaesthesia
CO2 retention causes both H+ and bicarb to rise. Why does pH go down?
Hydrogen ion concentration = nanomolar
Bicarb concentration = millimolar
Overall increase in hydrogen is greater overall and so pH goes down
Outline respiratory acidosis compensation.
Kidneys must compensate; lungs are problem.
Increase pCO2 increases H+ secretion into the tubules. HCO3- will be completely reabsorbed and titratable acid and ammonia are formed. New HCO3- is formed. Bicarbonate in blood will be increased.
What is the correction for respiratory acidosis?
Correction - lower PCO2 by restoring normal ventilations.
Respiratory alkalosis is caused by ______
Excess removal of CO2 from the body
Give 4 causes of excess CO2 removal.
All are hyperventilations
- Decreased inspired pO2 at high altitude causes hyperventilation by stimulation of peripheral chemoreceptors and so loss of CO2
- Fever causing hyperventilation
- Brainstem damage causing hyperventilation
- Hysterical hyperventilation.
Hydrogen ion concentration and bicarbonate concentration will go down in a respiratory alkalosis - true/false
true
What happens in correction of a respiratory alkalosis?
Carbon dioxide is low; less secrtion of acid into the tubular fluid and therefore less HCO3- resorption. Bicarb lost in urine. Bicarb concentration decreases further. No titratable acid due to low H+ secretion. Bicarb further decreases to correct the alkalosis. (Equilibrium equation moves to replace the bicarbonate and therefore increases [H+] - maybe; checking with Dr. Christie - will be updated when he replies).
Correction of respiratory alkalosis is due to:
Correcting the reason for the excess CO2 loss i.e. restoring normal ventilation instead of hyperventilation.
Metabolic acidosis is defined as _________
An excess of hydrogen ions that is due to any reason other than CO2 retention
Give examples of causes of metabolic acidosis
Drinking acid
Acid producing foods
Excessive metabolic H+ production (e.g. DKA)
Excessive base loss from the body (e.g. diarrhoea)
Uncompensated metabolic acidosis is ________
pH < 7.35
decreased plasma concentration of bicarbonate
How is metabolic acidosis compensated for?
Respiratory system must compensate
decreased pH stimulates peripheral chemoreceptors and hyperventilation occurs to blow off excess CO2.
Hydrogen ion concentration falls and the bicarbonate also falls slightly.
How is a metabolic acidosis corrected?
lost bicarb through ventilation and buffering. Very low bicarb to be filtered. Those filtered very easily reabsorbed. Secretion of titratable acid to produce new bicarbonate. Ventilation can then be normalized.
Why is respiratory compensation so important in metabolic acidosis?
Correction is slow; acid load cannot be excreted immediately as titratable acid. Therefore respiratory compensation is essential until the slow correction occurs.
Metabolic acidosis is ________
Excessive loss of hydrogen ions/addition of base in the body causing pH and bicarbonate to rise.
Uncompensated metabolic acidosis will have _______
pH > 7.45
High bicarb
Normal pCO2
Metabolic alkalosis is compensated via ______
Peripheral chemoreceptors slow ventilation so pCO2 rises. Hydrogen ion concentration increases, lowering pH and bicarbonate rises further.
Correction of a metabolic alkalosis happens as:
Tubular cells cannot reabsorb all of the bicarbonate filtered, some released as urine. No titratable acid/new bicarb is produced. Alkaline urine, bicarbonate falls, renal corrects. But remember that renal correction is slow; respiratory compensation is essential.
Which of the four types of acid - base disturbance is most common?
Metabolic acidosis.
