Physiology Flashcards
What are the basic renal processes?
Filtration, reabsorption, secretion
How much blood flow do the kidneys receive?
1200mls/min
What is the renal plasma flow?
660mls/min
What is the GFR normally?
125mls/min
What is the filtration fraction?
19%
What is the glomerular filtration dependent on?
The balance between the hydrostatic forces favouring filtration and the onocotic pressure forces favouring reabsorption
Why is the glomerular capillary p[resssure (Pgc) higher than most capillaries in the body?
Because the afferent arteriolar is short and wide
In the kidney describe the afferent arteriolar
Short and wide
In the kidney describe the efferent arteriolar
Long and narrow
What does a long and narrow efferent arteriole offer?
High post-capillary resistance
At the glomerular capillaries does the hydrostatic presssure exceed the oncotic pressure?
Yes, and the hydrostatic pressure favours filtration
Where does filtration occur?
At the glomerular capillaries
What is the primary factor that controls GFR?
Glomerular capillary pressure
What effect do sympthetic vasoconstrictor nerves have on afferent and efferent arteriole a?
Constriction
What effect do circulating catecholamines have on afferent arteriole?
Constrict afferent
What effect does angiotensin II have on efferent and afferent arteriole
Constricts efferent at [low] and both afferent and efferent at [high]
What intrinsic factor has a control on renal vasculature?
Arterial BP
GFR and BF are maintained by intrinsic ability in what range of arterial BP?
60-130mmHg
If there is an increase in mean arterial pressure,. What effect is there is afferent arteriolar and subsequent glomerular PGC?
Increase in afferent arteriolar construction and thus presvention in rise of glomerular PGC
What capillary is responsible fro reabsorption?
The peritubular capillaries
What is the hydrostatic pressure in the peritubular capillaries and why?
15mmHG
Because the efferent arteriole creates resistance creating a large pressure drop and subsequent very low hydrostatic pressure in the peritubular capillaries
Is the osmotic pressure in the peritubular capillaries high or low? And why?
High because the blood remaining in th peritubular capillaries has a higher concentration of plasma proteins and thus a high osmotic pressure
What makes the peritubular capillaries favourable for reabsorption?
The low Ppc and the high osmotic pressure
Where does the majority of reabsorption from tubule to peritubular capillaries occur?
Proximal convoluted tubule`
What percentage of H2O, glucose, Na+ and urea filtered at the glomerulus is reabsorbed within the tubule?
99% H2O,
100% glucose,
99.5% Na+,
50% urea
What are the mechanisms of reabsorption from the tubules to peritubular capillaries?
Carrier mediated transport systems,tubular secretion, reabsorption of Na+ via active transport
What substances use carrier mediated transport systems?
Glucose, amino acids, organic acids, sulphate and phosphate ions
What is the maximum transport capacity of carriers called?
Tm
Define renal threshold
Plasma threshold at which saturation occurs
What is the Tm of glucose carriers?
10mmoles/l
What is glycosuria/
Glucose in urine
What is the Tm for amino acids?
It is set so high, so no urinary excretion occurs
What substances aren’t regulated by the Tm mechanism, but use the carrier system?
Sulphate and phosphate ions
How much Na+ absorption occurs in the proximal tubule?
65-75%
How many mmoles/ day of sodium is there?
25560 mmoles/ day
How is Na+ transported into interstitial fluid?
Activ Na+ pumps pump out Na into the interesting fluid
This decrease [Na+] in the epithelial cells, increasing the gradient for Na+ ions to move into the cells passively
How do Na+ transport allow Cl- to pass?
The Na+ transport creates an electrical gradient that causes negative ions to diffuse passively across the proximal tubular membrane
How does Na+ and Cl- move water out of the cells into interstitial fluid?
The active transport of Na+ and Cl- out creates an osmotic force which moves H2O out of the tubules
How does the movement of H2O into interstitial fluid affect the movement of other subrstancces?
It concentrates all the substances left in the tubule creating an outgoing concentration gradient for subvstances such as K+, Ca2+ and urea
What is the rate of reabsorption dependent on for non-actively reabsorbed solutes?
1) amount of H2O removed as this will determine the extent of the concentration gradient
2) the permeability of the membrane to any particular solute
Give an example of substance that the tubular membrane is impermeable to
Insulin and mannitol
What reabsorption is Na+ reabsorption linked to?
Glucose, amino acids, HCO3-
What transporter does Na+ use to be able to pull glucose into proximal tubule cells?
SGLT (Sodium- dependent Glucose Transporter
What is tubular secretion?
Secretory mechanisms transport substances front he peritubular capillaries into the tubule lumen and provide a second route into the tubule
What type of substances is tubular secretion important for?
Protein-bound and harmful substances
What tubule does tubular secretion occur in?
Proximal convoluted tubule
What substances can be secreted using the same carrier mediated secretory transported as lactic and uric acid?
Penicillin, aspirin and PAH
What substances can be secreted using the same carrier mediated secretory transported as choline, creatinine?
Morphine and atropine
What is a normal ECF[K+]
4mmoles/l
What is classed as hyperkalaemia?
Greater that 5.5mmoles/l
What happens to resting membrane potentials of excitable cell in hyperkalaemia?
They are decreased causing more membrane to become excitable, leading to ventricular fibrillation and death
What is classed as hypokalaemia?
<3.5mmoles/l
What happens to the resting membrane potential of cells in hypokaelaemia?
It is increased, hyperpolarises muscles, leading to cardiac arrhythmias and eventually death
What effect does aldosterone have on K+ secretion?
It increases K+ secretion
What concentration is the fluid on leaving the proximal tubule?
Isosmotic with plasma, 300mosmoles/l
What is the maximum concentration of urine that can be produced by the human kidney?
1200-1400mOsmoles/l
What concentration of waste products must be excreted in a day and what is the minimum obligatory H2O loss needed for this?
600mOsmoles and 500mls of water loss is needed
What is the minimum [urine} that a human can produce?
30-50mOsmles/l
What system allows the kidney to produce urine of varying concentrations?
The counter-current multiplier system of the loops of Henle of juxtamedullary nephrons
What are the critical characteristics of the loops that makes them counter-current multipliers?
- the ascending loop actively co-transports Na+ and Cl- ions out of the tubule lumen into the interstitium. And is impermeable to H20
- the descending limb is freely permeable to H2O but relatively impermeable to NaCl
At any given horizontal level of the loop of Hemel what is the mOsmol gradient different between the ascending limb and interstitium?
200mOsmoles
What range does the vertical gradient in the interstitium go from/
300-1200mOsmols
How do diuretics work eg frusemide?
They stop the use of the NaCl channels in the acsending limb of loop of Henle which causes all concentration differences to be lost and the kidney to only produce isotonic urine
So what is the overall function of the countercurrent multiplier?
It concentrates the medullary interstitium and delivershypotonic fluid to the distal tubule
What is the vasa recta?
The specialised arrangement of peritubular capillaries of the juxtamedullary nephrons
What role do the vasa recta play in the countercurrent mechanism?
Countercurrent exchangers
What are the functions of the vasa recta?
They provide O2 for the medulla, remove volume from the interstitium and don’t disturb the interstitial gradient
What hormone controls water regulation?
Anti-diuretic hormone (ADH or vasopressin or arginine vasopressin (AVP))
Where is vasopressin synthesised?
The supraoptic (SO) and paraventricular (PVN) nuclei of the hypothalamus of the brain and contained in the posterior pituitary
What mechanism controls ADH secretion?
Plasma osmolarity, ECF volume
If there is an increase in osmolarity what happens?
There is an increase of H2O secretion from the cell, causing the cell to shrink and the stretch sensitive ion channel to be activated, this causes neural discharge and increase in ADH secretion
If there is a decrease in osmolarity what occurs?
H2O enters the cells causing them to swell, this cases a decreased neural discharge and decreased ADH secretion
What is the normal plasma osmolality?
280-290mOsm/kg H2O
Does it take a large or small change in osmolality to get a large increase in ADH?
A small change, there is a 10 times increase in [ADH] for a 2.5% increase in osmolality
Is there an increase in [ADH] if there is in an increase in osmorality but not tonicity
No, there must be a change in tonicity for an increase in [ADH]
Is there a change in [ADH] for a increase in urea?
No because urea is freely permeable so is an ineffective osmole
Why can dehydration occur when you ingest hypertonic solutions?
Because there is an increase solute load that needs to be excreted and thus an increased urine flow and more H2O required for excretion
Where is the site of water regulation?
The collecting duct
How does ADH increase H2O reabsorption?
It binds to membrane receptors,
The receptor activated cAMP second messenger system,
The cell inserts AQP2 water pores into apical membrane,
Water is absorbed by osmosis into the blood
If youre deficit in water what is the likely concentration of your urine?
1200mOsm
If you have excess water what is your likely urine osmolarty?
30-50mOsm/L
What enhances the permeability of urea?
ADH
Where is there an increasing tendency for urea to move out of the collecting duct down its concentration gradient?
The medullary tips
In antidiuresis with high levels of ADH what does urea do when absorbed form the CD into the interstitium?
It acts to reinforce the interstitial gradient in the region of the thin ascending loops of Henle
What is it important that urea is reabsorbed?
Because if it remained in the tubule, it would exert an osmotic effect to hold H2O in the tubule and thus cause dehydration
What happens with regards to [ADH] if there is an increase in ECF volume
[ADH] will decrease
What happens with regards to [ADH] if there is a decrease in ECF volume
[ADH] levels will increase
Where are low pressure receptors located?
In the L and R atria and great veins
What are low pressure receptors also called and why?
“Volume receptors” because they monitor the return of blood to the heart and the “fullness” of circulation
Where do you find high pressure receptors?
Carotid and aortic arch baroreceptros
If there is a moderate decrease in ECF volume what detects it and what is its effect?
The atrial receptors detect and their receptor discharge is decreased which causes and increase in ADH release
If the ECF volume changes enough to affect MBP what receptors detect this and what is their response?
Carotid and aortic receptors which increase ADH release
What stimuli can increase ADH release?
Pain, emotion, stress, exercise, nicotine, morphine, traumatic surgery
What stimuli can decrease ADH release?
Alcohol
If the osmoratlity is greater that 280 mOsm what detects this change?
Hypothalamic osmoreceptors
What is diabetes insipidus ?
ADH deficiency
What are causes of central diabetes insipidus
ADH synthesising hypothalamic arease diseased due to tumours, Meningitis, surgery
What are peripheral causes of diabetes insipidus
Collecting duct insensitive to ADH
How is central diabetes insipidus treated?
ADH
What are typical causes of peripheral diabetes insipidus?
Hypercalcaemia or hypokalaemia
What is the ECF volume determined by?
The number of osmotically active particles in each compartment
What major osmoles determine the ECF volume?
Na+ and Cl-
What major osmole determines ICF volume?
K+ salts
What is the distribution of body water between the plasma, interstitial fluid and ICF?
Plasma- 3l, interstitial fluid 11l and ICF 28l
What is regulation of Na+ dependent on, considering the fact it can affect BP?
High and low pressure baroreceptos
How does the body respond to hypovolaemia?
Decreased pressure volume causing,
Decreased venous pressure,
Decreased venous return,
Decreased atrial pressure (which stimulates release of ADH)
Decreases EDV,
Decreased SV,
Decreased CO,
Decreased BP,
Decreased carotid sinus baroreceptor inhibition of sympathetic discharge causing
Increased sympathetic discharge- increased VC, increased TPR sand increased BP
What effect does increased sympathetic vasoconstriction have on the kidney?
It causes increased renal artery construction which stimulates the release of renin,
What effect does increased renin have on Na+ reabsorption and why?
It increases Na+ reabsorption from the proximal tubule as renin causes the release of angiotensin 2 which decreases peritubular capillary hydrostatic pressure and increases osmotic pressure causing increases Na+ reabsorption and
Angiotensin 2 causes the release of aldosterone which increases distal tubule Na+ reabsorption
In hypovolaemia why is peritubular pressure decreased?
Due to the efferent arteriolar constriction by angiotensin 2
In hypovolaemia why is osmotic pressure greater than normal?
Because of lost NaCl and H2O there is increased [plasma protein]
What regulates distal tubule Na+ reabsorption?
Aldosterone
Where do you find juxtaglomerular cells?
In the smooth muscle of the media of the afferent arteriole
What is the name of the histological specialised loop of the distal tubule?
The macula densa
What do the juxtaglomerular cells and macula densa combine to form?
The juxtaglomerular apparatus
What do the juxtaglomerular cells produce?
Renin
What does renin do?
Converts angiotensinogen to angiotensin
What effect does angiotensin 2 have on the arterioles?
Causes them to vasoconstrict which increases blood pressure
What effect does angiotensin 2 have on the hypothalamus?
Increases ADH production and increases thirst, which in turn increases volume and maintain osmolarity and increases blood pressure
Wha5 effect does angiotensin 2 have on the adrenal cortex
It stimulates the release of aldosterone
What increases renin release?
When pressure in afferent arteriole at level of JG cells decreases,
When there is an increase in sympathetic activity,
When there is decreased delivery of NaCl at macula densa
what inhibits renin release?
Angiotensin 2 (via feedback) and ADH
How does the tubuloglomerular feedback contribute to GFR constancy?
If GFR increases the flow through the tubule increases and passses the macula densa, the paracrine from the macula densa to afferent arteriole causes the afferent arteriole to constrict and increase the resistance in the afferent arteriole, this causes pressure in the glomerulus to decrease and GFR to decrease
What has priority in severe diarrhoea ECF volume or ECF osmolarity?
ECF volume to save perfusion for the brain
What hormone promotes Na+ excretion?
ANP- Atrial Natriuretic Peptide
If there is increased blood volume causing increased atrial stretch, myocardial cells will stretch and release what?
Natriuretic peptides- ANP
What effect does ANP have on the hypothalamus?
Causes decreased ADH causing increased NaCl and H2O excretion
What effect does ANP have on the kidney?
Causes increased GFR and decreased renin causing less aldosterone production and c=increased NaCl and H2O excretion
What effect does ANP have on the adrenal cortex?
Causes less aldosterone production
What effect does ANP have on the medulla oblongata?
Causes decreased blood pressure
What does ANP act on?
Hypothalamus, kidney, adrenal cortex and medulla oblongata
What affect does uncontrolled DM have on the interstitial gradient?
It abolishes it as H20 NaCl are retained within the tubule
Will renin be produced in uncontrolled DM in response to a large volume of NaCl and H2O being delivered to the distal tubule?
No because the macula densa will detect th which rate of NaCl so renin secretion will be suppressed
What type of urine will be excreted in someone with uncontrolled DM?
Large volumes of nearly isotonic urine `
What effect will excreting large volumes of isotonic urine have on plasma volume?
It will decrease plasma volume
In someone with uncontrolled DM what effect will occur due to decreased plasma volume?
It will stimulate ADH release via baroreceptors however it wont be effective as the interstitial gradient has been worn down
How much urine can uncontrolled DM patients produce in a day?
6-8l/day
What is a hyperglycaemic coma?
A coma due to inadequate blood flow to yeh brain
What is a hypoglycaemic coma
A coma caused by inadequate glucose for the brain
What is classed as the upper urinary tract?
Kidneys and ureters
what is classed as the lower urinary tract?
Bladder, bladder outflow tract (bladder neck, prostate, external urethral sphincter, urethra, urethral meatus, foreskin)
What are common presentations of renal disease?
Pain, Pyrexia, haematuria, proteinuria, pyuria, mass on palpation and renal failure
What is the definition of proteinuria?
Urinary protein excretion >150mg/day
What is the definition of microscopic haematuria?
> /= to 3 red blood cells per high power field
Define oliguria?
Urine output <0.5ml/kg/hour
Define anuria?
Absolute anuria- no urine output
Relative anuria <100ml/24hours
Define polyuria?
Urine output >3L/24hours
Define nocturia?
Waking up at night >/=1 occasion to micturate
Define nocturnal polyuria?
: nocturnal urine output >1/3 of total urine output in 24 hours
How dies the body produce H+?
Via respiratory acid and metabolic acid
How does metabolic acid produce H+?
Via metabolism of inorganic acids (eg S-containing amino acids and phosphoric acid)
And organic acids (fatty acids, lactic acid)
In a normal diet what is the net gain to the body?
50-100 mmoles H+ per day
What is the major source of alkali in the body?
Oxidation of organic anions such as citrate
What is the role of buffers
To minimise change in pH when H+ ions are added or removed
What is the most important extracellular buffer?
Bicarbonate buffer system
What is the ratio of bicarbonate to carbonate in the blood?
20:1
What does the quantity of H2CO3 depend on in the plasma?
The amount of CO2 dissolved in the plasma, which depends on the solubility of CO2 and Pco2
What is the solubility of CO2 in blood at 37oc?
0.03mmoles/l/mmHg Pco2
At normal PCO2 of 40mmHg what is the level of [H2CO3-]?
1.2mmoles/l
What is the normal pH range?
7.37-7.43
What is the pH range compatible with life?
7.0-7.6
What is the normal pH range?
36-44mmHg
4.8-5.9kPa
Normal [HCO3-] range?
22-26mmoles/l
What is the simplified Henderson-Hasselbalch equation?
PH(weird symbol, part of a sideways 8) [HCO3-]/PCO2
What is the bicarbonate buffer system equation?
H+ + HCO3- = H2CO3 = H2O + CO2
What happens if there is an increase in ECF H+ to the bicarbonate buffer system?
It is shifted to the right and ventilation is increased to greater increase the buffering capacity of the bicarbonate
Is {HCO3-] regulated by the kidneys or the respiratory system?
Renal
Is Pco2 regulated by the kidneys or the respiratory system?
Respiratory
What other buffers are used in the ECF?
Plasma proteins Pr- + H+ = HPr
Dibasic phosphate HPO4(2-) + H+ = H2PO4-
What are the primary intracellular buffers?
Proteins, organic and inorganic phosphates and in the erythrocytes- haemoglobin
Why does buffering of H+ ions by ICF buffers cause changes in plasma electrolytes?
Because to maintain electrochemical neutrality movement of H= must be accompanied by Cl- or K+
In acidosis, the movement of K+ out of the cells can cause what?
Hyperkalaemia:
Depolarisation of excitable tissues
Ventricular fibrillation and death
How does the kidney regulate [HCO3-]?
Reabsorbing filtered [HCO3-] and by generating new HCO3-
What is the kidneys regulation of [HCO3-] dependent on?
Active H+ secretion
What enzyme converts H2CO3 into CO2 and H2O
And then reverse?
Carbonic anhydrase
At the proximal tubule cells is H+ secreted?
No there is reabsorption of HCO3- but no excretion of H+
What is the minimum urine pH?
4.5-5.0
Max= 8.0
What is titratable acidity?
Weak acids and bases acting as buffers in the urine
Why is titratable acidicity important?
Generates new HCO3- and excretes H+
What tubule does titratable acidity occur in?
Principally in the distal tubule
Look at diagram on titratable acidicity
Diagram on PowerPoint/ book
Why is the distal tubule the site of formation of titratable acidity?
Because un-reabsorbed dibasic phosphate becomes highly concentrated by the removal of volume of filtrate
What is the basis of the mechanis, of ammonium excretion?
NH3 is lipid soluble and NH4+ is not
How is NH3 produced in the renal tubule cells?
By deamination of amino acids (mainly glutamine) by action of renal glutaminase
How is NH4+ production different in the proximal tubule compared to the distal tubule?
In the proximal tubule there is an NH4+/Na+ exchanger in the renal tubule cells so NH4+ ions formed within the cells pass out into the lumen
What is activity of renal glutaminase dependent on?
PH
When intracellular pH falls what happens to renal glutaminase activity?
There is an increase in renal glutaminase activity and therefore more NH4+ produced and excreted
How long does the kidney take to augment NH4+ production in response to acid loads?
4-5 days
How much NH4+ is lost in a day and what is the max in sever acidosis?
30-50mmoles H+ per day
But can increase to 250mmoles/l in response to severe acidosis
what is respiratory acidosis?
PH has fallen and is due to a respiratory change, so Pco2 must have increased. It results from reduced ventilation and thus retention of CO2
Acute causes of respiratory acidosis?
Drugs which depress the medullary respiratory centres, such as barbiturates and opiates,
And obstructions of major airways
What are the causes of chronic respiratory acidosis/
Lung disease eg bronchitis, emphysema, asthma
Wat is the body’s response to respiratory acidosis?
Increase of [HCO3-]
Will also stimulate renal glutaminase
What is respiratory alkalosis?
Alkalosis of respiratory origin so due to falll in Pco2, which can occur through increased ventilation and CO2 blow-off
Acute causes of respiratory alkalosis?
Voluntary hyperventilation, aspirin, firs ascent to altitude
Chronic causes of respiratory alkalosis?
Long term residence at altitude- it causes decreased PO2 which stimulates peripheral chemoreceptors to increase ventilation
What is the body’s response to respiratory alkalosis
HCO3- is filtered out and excreted
What is metabolic acidosis?
An acidosis of metabolic origin due to a decrease in [HCO3]-
What is the body’s response to metabolic acidosis?
Pco2 must be decreased
Causes of metabolic acidosis?
diabetic ketoacidosis, lactic acidosis (increased H+ production) Renal failure (Failure to excrete the normal H+ load) Diarrhoea (loss of HCO3- as there is failure to reabsorbed intestinal HCO3-)
What type of breathing does acidosis cause?
Kussmaul breathing
Increased depth rather than rate
What comes first respiratory or renal correction of pH?
Respiratory compensation, respiratory compensation delays renal correction but protects the pH
What is metabolic alkalosis?
[HCO3-) must have increased and Pco2 needs to increase to protect pH
Causes of metabolic alkalosis
Vomiting (loss of gastric secretions causing loss of H+)
Aldosterone excesss eg liquorice ingestion (causing increased renal H+ loss)
Excess administration of HCO3- in someone with renal function impairment
8units of blood transfusions (due to citrate in blood being converted to HCO3-)
Difference between acute and chronic respiratory acidosis?
There a smaller pH decrease in chronic respiratory acidosis compared to acute
Why is there a smaller decrease in pH in chronic respiratory acidosis comapred to acute
Because can only raise [HCO3-] by titratable acid to begin with as NH3 production tales 4-5 days
How to treat the hyperkalaemia of a patien with respiratory and metabolic acidosis?
Insulin (stimulates cellular uptake of K+) Calcium resinous (exchanges Ca2+ ions for K+ ions) Ca gluconate (IV)(decreases excitability of heart)
What does the body sort first if someone has hypovolaemia and metabolic alkalosis?
The hypovolaemia by stimulating production of aldosterone, but the aldosterone will worsening the metabolic acidosis
Why does stimulation of aldosterone in someone with severe vomiting worsen metabolic alkalosis?
Because the Cl- is decreased due to loss of NaCl and HCl so the only remaining ion that can be exchanged for Na+ is H+, so aldosterone production increases Na+ reabsorption and increases loss of H+
If there is a patient who has lost ECF volume and has become alkalolitic, what kind of alkalosis are they called?
Contraction alkalosis
Due to the increase in aldosterone worsening the situation
Why can liquorice cause metabolic alkalosis?
Because liquorice contains glycyrrhizic acid that is similar to aldosterone
What is the anion gap?
The difference between the sum of principal cations (Na+ and K+) and the principal anions in the plasma (Cl- and HCO3-)
What is the normal range of the anion gap?
14-18mmoles/l
In what condition is it useful to measure the aniongp?
In metabolic acidosis
If someone is metabolic acidosis due to diarrhoea will there be a change in the anion gap?
No as there will be a compensation by increased chloride
If someone is metabolic acidosis due to diabetic ketoacidosis or lactic acidosis will there be a change in the anion gap?
Yes there will be an increase because the reduction of bicarbonate is made up by anions such as lactate, acetoacetate, b-OH
Why is important to be able to measure GFR?
Progression of people with renal disease, adjusting dosage incase of drug intoxication (eg from digitalis and antibiotics)
Equation for measurement of plasma clearance of x?
Cx= [Ux] V/[Px]
Ux= Urine concentration of X
V= Urine outflow rate
Px=plasma concentration of X
What do plasma clearance tats used for?
To measure renal function, and measure the ability of the kidney to clear the plasma of various substances,
The gold standard to use is inulin clearance
Why is inulin used to measure plasma clearance?
Because inulin is freely filtered at the glomerulus and is not reabsorbed or secreted
Substances that are a filtered and reabsorbed, do they have a lower or higher clearance than inulin?
Lower clearance, eg urea
Substances that are a filtered and secreted, do they have a lower or higher clearance than inulin?
Lower eg penicillin
What is a normal GFR?
In a man about 125mls/min
10% lower in women
And GFR declines by 1ml/min/year after 30
In clinical practice what is now used in stead on inulin?
51Cr-EDTA
What is 51Cr-EDTA?
A radioactive substance that is handled by the kidney in the same way as inulin
What is used to routinely to estimate the GFR
Creatine clearance
Why can plasma creatinine be used to estimate GFR?
GFR (8 with bit missing on side symbol) 1/ [Pcr]
Why cant you juts use 1/PCr to work out the GFR?
Because there isn’t a linear relationship, so there are formulae using serum creatinine value which can take into account confounding variables
What are factors affecting serum creatinine?
Muscle mass, dietary intake, drugs
What is the normal GFR approximately?
100mls/min/1.73m2
What is used to measure Real Plasma Flow (RPF)
Organic anion para-amino-hippuric acid
Why is PAH used to mesasure real plasma flow?
PAH is freely filtered at th glomerulus and all remaining PAH in the plasma is actively secreted into the tubule,
Therefore the PAH clearance is a measure of all the plasma flowing through the kidneys in a given time
What is a normal renal plasma flow?
660mls/min
How does urine flow into the bladder?
From the kidneys to the ureters via peristaltic contraction of smooth muscle of the ureters, they then enter the bladder at an oblique angle
How is smooth muscle arranged in the bladder?
Arranged in spiral, longitudinal and circular bundles
If there is urethral obstructions what kind of renal problems can occur?
Bilateral renal problems
If there is ureter obstruction what kind of renal problems can occur?
Unilateral renal problems
Describe the pressure-volume curve of the bladder
There is a long flat segment as the initial increments of urine enter the bladder, there is then a sudden sharp rise of intravesical pressure as the micturition reflex is triggered
What does the parasympathetic nerves control in micturition?
From pelvic nerves,
Cause an increase in activity, increasing contraction of the detrusor muscle, which causes an increased pressure within the bladdder S2-S4
What does the sympathetic nerves control in micturition?
Hypogastric nerves
Inhibit bladder contraction and close the internal urethral sphincter
Prevent reflux of semen into the bladder during ejactulation L1-L3
What does the somatic mononeurones control in micturition?
Pudendal nerves
Inner are the skeletal muscle that forms the external urethral sphincter
Keeps the sphincter closed, even against strong bladder contractions
Where is the sensory innervatiuon from in micturition?
From stretch receptor afferents in the bladder wall
As the bladder fills, there is an increase discharge in afferent nerves to the spinal cord via interneurons
What effect does an increased discharge of afferent nerves from stretch receptors from bladder wall cause?
Excitation of parasympathetic outflow,
Inhibition of sympathetic outflow,
Inhibition of somatic motoneurones to external sphincter,
Pathways to sensory cortex- sensation of fullness
In an adult what is the volume of urine in the bladder required to initiate the spinal reflex?
300-350mls
What brain centres can delay passing urine and how?
Cortex, brainstem by inhibiting parasympathetic and stimulate the somatic nerves to the external sphincter
What is one of the initial events in voluntary urination?
Relaxation of muscles of the pelvic floor that may cause sufficient downward tug on the detrusor muscle to initiate contraction
Why can perineal muscles and external sphincter be contracted voluntarily?
So you can prevent urine flowing down the urethra or interrupt the flow once urination begins
After urination, how does the female urethra empty?
By gravity
How is urine remaining in the male urethra expelled?
By contractions of the bulbocavernosus muscle
What are the 3 major types of abnormalities of micturition due to neural lesions?
Interruption of afferent nerves, interruption of both afferent and efferent nerves, interruption of facilitatory and inhibitory descending pathways from the brain
How can paraplegic patients train themselves to initiate voiding of bladder or rectum?
By pinching or stroking thighs- causing a mild mass reflex as after a spinal section afferent stimul irradiate from one reflex centre to another.
So when a relatively minor noxious stimulus is applied to the skin it may irradiate to autonomic centres and evoke bladder or rectal voiding
What is normal creatine clearance
25mls/min
