Urinary System Flashcards
What is the urinary system made up of?
Kidneys
Ureters
Urinary bladder
Urethra
Where are the kidneys located?
Retroperitoneal in the upper abdomen
What is posterior to the kidney?
The diaphragm
What is superior to the kidney?
Pleural cavity
Which kidney is lower?
Right
Where are the superior poles of the kidney?
Right: 11th intercostal space
Left: 11th rib
At what vertebral level are the kidneys?
L1
Which pole of the kidneys is angled inwards?
Superior
Under what ribs is the spleen located?
9 and 10
What muscles surround the kidney? Where
Posterior: Psoas major and Quadratus lumborum
Lateral: Transversus abdominis
Superior: Diaphragm
What fat surround the kidney? Why?
Perinephric fat
Protection- kidneys have a large blood supply
What organs surround the right kidney?
Liver
Hepatic flexure
Hilus
lies behind the second part of the duodenum
What organs surround the left kidney?
Stomach
Pancreas
Spleen
Splenic flexure
Where does the kidneys blood supply come from and drain to?
From abdominal aorta via the renal arteries
Renal veins drain into inferior vena cava
Which renal artery is is longer?
Right
Which renal vein is longer?
Left
Are the renal arteries or veins posterior?
Arteries
What is the renal pelvis?
The funnel-like start of the ureter where fluid drains
What structures does filtrate from the kidney flow through to enter the ureter?
Renal papilla Minor calix Major calix Renal pelvis Ureter
What structures are in the cortex of the kidney?
Glomerulus
Bowman’s capsule
Arcuate arteries and veins
Proximal and Distal convoluted tubules
What is located in the medulla of the kidney?
Loop of Henle
Collecting tubule
Are afferent or efferent arterioles larger in the kidney?
Afferent
More goes in than comes out
In what plane do the ureters run vertically down the posterior abdominal wall?
In the plane of the tips of the transverse processes of the lumbar vertebrae
Where do the ureters cross the pelvis brim?
Anterior to the sacroiliac joint and bifurcation of the common iliac arteries
At what level do the ureters enter the bladder?
The level of the ischial spine
Where do the ureters get their blood supply?
Renal artery
Testicular arteries
Common iliac arteries
(every major vessel is passes)
Where are the constriction points on the ureter?
1) Ureteropelvic junction
2) Pelvic inlet
3) Entrance to bladder
How is urine transported to the bladder?
Through the ureters by peristalsis in their smooth muscle walls
Where are the sites kidney stones occur in the ureters?
At the constriction points along the ureter
Where is the apex and base of the bladder?
Apex points anteriorly
Base points posteriorly
What epithelium lines the bladder? Describe it
Urothelium
Three layered epithelium with very slow cell turnover. Large luminal cells have highly specialised low-permeability luminal membrane.
Prevents dissipation of urine-plasma gradients
What ligament attaches to the apex of the baldder?
Median umbilical ligament
Why is there no ureter sphincter?
Ureters run obliquely so when full it puts pressure on them without the need for a sphincter. Prevents reflux
What separates the bladder and periuneum?
A diaphragm through which the urethra passes
Where do ejaculates enter the urethra in males?
At the back of the prostate
What sphincter in the bladder is under parasympathetic control?
Sphincter vesicae
What is sphincter vesicae? What causes it to open?
Internal sphincter- smooth muscle
At the neck of the bladder
Reflex opening in response to bladder wall tension
Controlled by parasympathetic NS
What sphincter in the bladder is under somatic control?
Sphincter urethrae
What is sphincter urethrae? What causes it to open?
External sphincter- striated muscle
In perineum
Tone maintained by somatic nerves in pudendal nerve (S2, 3, 4)
Opened by voluntary inhibition of nerves
What nerves innervate the sphincter urethrae?
S2, 3, 4
In a woman, what is the distance between parasympathetic and sympathetic sphincters?
∼5cm
In men, what is the distance between parasympathetic and sympathetic sphincters?
∼20cm
Why are females more prone to bladder infections?
Because the distance between their parasympathetic and sympathetic sphincters is much shorter
How is voluntary control stimulated when needing to empty the bladder?
Bladder fills
Stretch receptors signal the parasympathetic nervous system- bladder contracts and internal sphincter mechanically opens
At the same time stretch receptors signal motor neurons which suggests the need for voluntary control. External sphincter remains closed when motor neuron is stimulated
What are the different parts of a male urethra?
Internal urethral oriface (bladder neck, bladder outlet) Prostatic urethra Membranous urethra Bulbar urethra Penile urethra Navicular fossa External urethral meatus
How is water excreted from the body?
Exhalation
Urine
Sweat
What does the body get rid of in the urine?
H2O, Na+, K+, H+, urea
What are the functions of the kidney?
Production of urine: - Filtration of blood plasma - Selective reabsorption of contents to be retained - Tubular secretion of some components - Concentration of urine as necessary Endocrine funtion
What part of the kidney has the best blood supply?
The cortex
Which part of a kidney is most susceptible to ischaemia?
Papillae- fragments end up in the urine
What is the mechanism for urine production in the kidney?
Filtration of blood passing through the glomerulus (all componenets
How are the cells in the filtration barrier modified for their function?
Fenestrated epithelia
Specialised basement membrane (basal lamina)
Podocytes with filtration slits between foot processes, producing a very fine filter (
What is the fluid tonicity in Bowman’s capsule?
Isotonic
Where does fluid filtered in Bowman’s capsule go?
Into the proximal convoluted tubule
What are the components of the renal corpuscle?
Bowman’s capsule
Glomerulus consists of capillaries
Podocytes associated with glomerulus
What is the blood supply to the renal corpuscle?
From afferent arteriole
Exits efferent arteriole
Glomerular capillaries at high pressure
In what part of the renal corpuscle is the blood supply and drainage?
Blood supply at vascular pole
Drains to proximal convoluted tubule at urinary pole
What happens in the proximal convoluted tubule?
Reabsorption of ions, glucose, amino acids, small proteins and water
How is the proximal convoluted tubule modified for function?
Brush border
Lots of mitochondria
Lots of vesicles
What occurs in the loop of Henle?
Countercurrent mechanism to create hyperosmotic fluid
What is the structure of the descending loop of Henle?
Simple squamous epithelium
Passive osmotic equilibrium (aquaporins)
What is the structure of the ascending loop of Henle?
Very water impermeable (no aquaporins)
Cuboidal epithelium, few microvilli
Lots of mitochondria (high energy requirement)
What is the structure and function of the vasa recta?
Blood vessels arranged in a loop
Blood in equilibrium with ECF
Loop structure stabilises hyper-osmotic [Na+]
What occurs in the distal convoluted tubule?
Adjustment of the ion content of urine
Controls levels of Na+, K+, H+, NH4+
What is the structure of the distal convoluted tubule?
Cuboidal epithelium, few microvilli
Complex lateral membrane interdigitations with Na+ pumps
Lots of mitochondria
Where does the concentration of urine occur in the kidney?
In the collecting tubule
Moves water down osmotic gradient into ECF
What hormone controls the concentration of urine? What part of the kidney does it act on?
Vasopressin (ADH)
Works on the collecting tubule
What is the structure of the collecting tubule?
Lots of tight junctions
Can absorb water
How does the collecting tubule control water permeability?
Basolateral membrane (outside) has aquaporin-3 which is not under ADH control. Apex of cells has aquaporin-2 which is under ADH control
What are juxtaglomerular cells? Where are they found?
Endocrine cells found around the afferent arterioles before they enter Bowman’s capsule that attach to the macula densa (modified part of the distal convoluted tubule)
What are the function of the juxtaglomerular cells?
Can sense urine input and output due to their location. Can detect low BP in the afferent arteriole and release renin.
Can also inhibit renin release due to high NaCl
What is glomerular filtration?
The formation of an ultrafiltrate of plasma in the glomerulus
An abrupt fall in glomerular filtration is renal failure
What is the mechanism of glomerular filtration?
Fluid is drive through the semipermeable (fenestrated) walls of the glomerular capillaries into the Bowman’s capsule space by the hydrostatic pressure of the heart
What is the filtration barrier in glomerulus permeable to?
Fluids
Small solutes
What is the filtration barrier in the glomerulus impermeable to?
Cells
Proteins
Drugs etc carried bound to protein
If the concentration of a solute in the blood is 1mM and 20% is filtered what is the concentration of the solute in Bowman’s capsule?
1mM
What is the formula for net ultrafiltration pressure?
Puf = Pgc - Pt - 𝜋gc
What two factors affect the ultrafiltration coefficient?
Membrane permeability
Surface area
How do you calculate GFR?
GFR = Puf x Kf GFR = net ultrafiltration pressure x ultrafiltration coefficient
What is GFR?
The amount of fluid filtered from the glomeruli into the Bowman’s capsule per unt time (ml/min)
The index of kidney function
What is renal blood flow?
∼1L/min (1/5 of cardiac output)
What is renal plasma flow?
∼0.6L/min
What is the filtration fraction?
0.2
Ratio between RPF and amount of filtrate filtered by glomerulus, normally 20%
What is normal GFR?
120mL/min
What does the glomerular filtration rate depend on?
Glomerular capillary pressure (Pgc)
Plasma oncotic pressure (𝜋gc)
Tubular pressure (Pt)
Glomerular capillary surface area or permeability (Kf)
What would happen for your GFR if you start exercising?
It would not change as the body has mechanisms to regulate GFR (e.g. myogenic mechanism)
What is the myogenic mechanism?
Vascular smooth muscle constricts when stretched. Keeps GFR constant when blood pressure rises
Arterial pressure rises
Afferent arteriole stretched
Arteriole contracts (vessel resistance increases)
blood flow reduces
GFR remains constant
What is the tubuloglomerular feedback mechanism?
NaCl concentration in fluid sensed by macula densa in juxtaglomerular apparatus
Macula densa signals afferent arteriole and changes its resistance to maintain steady GFR
How does severe haemorrhage affect GFR?
It would fall
Due to drop in BP and CO
How does obstruction in nephron tubule affect GFR?
It would fall
Increasing opposing forces
How would reduced plasma protein concentration affect GFR?
It would increase
How would a small increase in blood pressure affect GFR?
It would not change GFR
What is renal clearance?
The extent to which a substance is removed from the blood.
Clearance is the number of litres of plasma that are completely cleared of the substance per unit time
What is the formula for renal clearance?
C=(U x V)/P
U = concentration of substance in urine
P = concentration of substance in plasma
V = Rate of urine production
Why is inulin used to predict GFR?
It is freely filtered and it is not reabsorbed or secreted.
It is measurable in the urine (stable, does not degrade) and is non toxic
What is used clinically to measure GFR? Why?
Creatinine
Waste product from creatine in muscle metabolism
Amount released is fairly constant so amount in urine is stable
Low values of creatinine clearance may indicate renal failure
High plasma creatinine may indicate renal failure
How does PAH have a clearance rate of 625ml/min?
Filtered and actively secreted in one pass of the kidney, so can be used to measure renal plasma flow.
How do you measure renal plasma flow?
Use a substance which is filtered and secreted which will be removed in one pass of the kidneys
What is the amount excreted from the kidney equal to?
Amount excreted = amount filtered - amount reabsorbed + amount secreted
What does it mean is a solute is “freely filtered”?
It has the same concentration in the plasma and the filtrate
Sodium is freely filtered, but the concentration of sodium in the tubule is lower than that os the plasma. Why is this?
Because it is reabsorbed
Is a substance has higher clearance than inulin what can you conclude?
That it is secreted
How much of the ultrafiltrate is reabsorbed?
∼99%
What is osmolarity?
A measure of the osmotic pressure exerted by a solution across a perfect semi-permeable membrane
It is dependent on the number of particles in a solution and NOT the nature of the particles
All the concentrations of the different colutes (in mmol/L) added together. Each ion is counted separately
What is normal plasma osmolarity?
285-295 mosmon/L
What is normal urine osmolarity?
50-1200 mosmol/L
What are the two types of reabsorption from one side of a cell to the other in the tubule?
Transcellular
Paracellular
What are the different types of transport in the tubules of the kidney?
Osmosis Active transport Passive transport Counter transport Co-transport Movement down electrochemical gradient
In protein dependent transport what type of molecules does this move? What is it dependent on?
Hydrophilic molecules
Dependent on the number of proteins
What types of transport of solutes across tubules have saturable kinetics?
Direct ATP dependent
Indirect ATP dependent
Protein dependent
How are proteins reabsorbed?
Binding them to low-affinity, high variability receptors on the cell surface, internalise into a vesicle and recycle the receptor
Why is glucose present in the urine in diabetes mellitus?
Glucose in the blood increases so amount of glucose being filtered increases
Amount being reabsorbed increases until transporters become saturated at which point no more glucose can be reabsorbed and it starts to be excreted
What is secretion in the kidneys?
Moving substances from the peritubular capillaries into the tubular lumen
How much of what goes into the kidney ends up in the tubule system?
20%
How much sodium is absorbed in the different parts of the kidney?
Proximal convoluted tubule: 65%
Loop of Henle: 25%
Distal convoluted tubule: 8%
Collecting duct:
Where is glucose reabsorbed in the kidney?
In the proximal convoluted tubule
What is most of the ATP used in resorption used for?
Pumping Na+ to generate a large concentration gradient
What is Na+ transport used for in reabsorption?
Reabsorbing Cl-, glucose and amino acids in the proximal convoluted tubule
Reabsorbing bicarbonate and to excrete protons
What occurs in the descending limb of the loop on Henle?
Water is passively reabsorbed through squamous epithelium which draws in Na+ and K+
What happens in the ascending limb of the loop of Henle?
Chloride is actively reabsorbed
Sodium is passively reabsorbed and with it bicarbonate is reabsorbed
Impermeable to water. High energy requirement
By now 85% water and 90% sodium and potassium have been reabsorbed
What is the osmolarity of the tubular fluid leaving the loop of Henle with respect to plasma?
Hypoosmolar
What cotransporter is present in the distal convoluted tubule?
Na⁺K⁺ATPase on the apical side
NA+Cl- on the basal (tubule) side
In the distal convoluted tubule and collecting tubule sodium reabsorption is dependent on what?
Aldosterone
Is the distal part of the nephron permeable to water?
No, unless there is ADH
What are the two cell types in the distal tubule and collecting duct?
Principle cell
Intercalated cell
What are the roles of principle cells in the distal tubule and collecting duct?
Important in sodium, potassium and water balance (mediated via Na/K ATP pump)
What is the role of intercalated cells in the distal tubule and collecting duct?
Important in acid-base balance (mediate via H-ATP pump)
What is renal tubule acidosis?
Single gene defect Hypercholermic metabolic acidosis Impaired growth Hyperkalemia Caused by an inability to excrete protons or extra protons leak out after being pumped out causing an acidosis Mutation in Na+H+ cotransporter
What is (Antenatal) Bartter syndrome?
Excessive electrolyte secretion Premature birth, polyhydraminos Severe salt loss Moderate metabolic alkalosis Hypokalemia Renin and aldosterone hypersecretion Mutation in Na+2Cl-K+ transport protein
What is Fanconi Syndrome?
Increased excretion of uric acid, glucose, phosphate, bicarbonate
Increased excretion of low MW protein
Disease of the proximal tubules associated with renal tubular acidosis
Proton pump won’t dissociate so can’t relocate transporter
What do the water balance and salt in the body determine?
Water balance regulates plasma osmolarity
Salt determines the ECF volume
What are the volumes of different compartments of body water?
Intracellular fluid: 25L (65%)
Extracellular fluid: 15L (35%) mainly interstitial fluid, also plasma, lymph and transcellular
What methods does the body use to get rid of water? How much is lost in this way? What are these methods affected by?
Sweat ∼450ml/day (fever, climate, activity)
Faeces ∼100ml/day (diarrhoea)
Respiration ∼350ml/day (activity)
Urine output ∼1500ml/day
Where is water absorbed in the kidneys?
Proximal convoluted tubule: 60-70%
Decending loop of Henle: ∼30%
Distal convoluted tubule: ∼20%
How much water do we excrete based on what we filter?
How do the kidneys produce hyperosmolar urine?
Using a countercurrent mechanism
1) Salt is pumped into the interstitium from the ascending limb creating a 200mmol gradient
2) Water flows out of descending limb to equilibrate the gradient
3) Flows round loop of Henle so the new fluid entering is of lower concentration
4) Salt again pumped out making 20mmol gradient which is even higher now
5) Water pumps out descending
Salt concentration continues to get lower as the gradient becomes larger.
This creates a low concentration fluid at the end of the ascending limb and a high concentration filtrate at the end of the descending limb
What part of the nephron is permeable to urea?
The bottom of the collecting duct and the bottom of the loop of Henle
How does urea increase the concentration of urine?
As the filtrate travels along the collecting duct water is reabsorbed into the interstitium. This part is impermeable to urea so the concentration increases. When in the permeable area urea moves out into the interstitium down the concentration gradient.
Urea then moves down the concentration gradient into the loop of Henle back into the filrates and recirculates
This continues creating very highly concentrated filtrate
What are the urea transporters? Where are they located?
UT-A2 in the thin descending limb of the loop of Henle
UT-A1 and UT-A3 in the inner medullary collecting duct
UT-B1 in the vasa recta
How is the vasa recta specialised for function?
Follows the same path as the loop of Henle. Permeable to water and solutes
Descending limb: Water diffuses out and solutes diffuse in
Ascending limb: Water diffuses in and solutes diffuse out
What is vasopressin? Where is it synthesised and where does it work?
Peptide hormone
Synthesised in the hypothalamus and packages into granules
Secreted from the posterior pituitary (neurohypophysis)
Binds to specific receptors on basolateral membrane of principle cells in the collecting ducts
What is the mechanism of action of vasopressin?
Causes insertion of aquaporins into the cells membrane (predominantly AQP2 into the luminal membrane)
Also stimultes urea transport from IMCD into thin ascending limb of loop of Henle and interstitial tissue by increasing membrane localisation of UTA1 in the inner medullary collecting duct
What triggers ADH release?
Plasma osmolarity >300mOs regulated by osmoreceptors
Also stimulated by a marked fall in blood volume or pressure (monitored by baroreceptors or stretch receptors)
Ethanol inhibits ADH release, which leads to dehydration as urine volume increases
What is the response mechanism to low plasma osmolarity?
↓ Plasma osmolarity (Hypothalamic receptors) ↓ ADH release ↓ Collecting duct water permeability ↑ Urine flow rate Increased fluid loss will raise plasma osmolarity
What is the response mechanism to high plasma osmolarity?
↑ Plasma osmolarity
(Hypothalamic receptors)
↑ ADH release
↑ Collecting duct water permeability
↓ Urine flow rate
Decreased fluid loss will lower plasma osmolarity
Hypothalamus also stimulates thirst centre- increased water intake will lower plasma osmolarity
What different disorders of water balance can you have?
1) No/insufficient production of ADH
2) No detection of ADH (mutant ADH receptor)
3) No response to ADH signal (mutant aquaporn)
What is diabetes insipidus?
Excretion of large amounts of watery urine (as much as 30 litres each day)
Unremitting thirst
Due to a disorder with ADH
What four components of the nephron allow the generation of a hyperosmolar environment?
1) Counter current mechanism
2) Descending loop impermeable to salt but permeable to water
3) Ascending loop impermeable to water but ‘permeable’ to salt
4) Urea permeability of the bottom of the loop and collecting duct
How does dietary sodium affect blood pressure?
Increased dietary sodium
Increased osmolarity
Increased ECF volume
Increased blood volume and pressure
What happens to sodium reabsorption if you increase GFR?
↑ Na reabsorption
What happens to sodium reabsorption if you decrease GFR?
↓ Na reabsorption
How does the sympathetic nervous system increase sodium retention?
- Causes vasoconstriction of the kidney tubular blood vessels predominantly the afferent arteriole (decreasing pressure gradient across glomerulus goes down)
- Increase sodium uptake mechanisms in the proximal convoluted tubule
- Stimulates juxtaglomerular cells to release renin and produce angiotensin
If you want to increase Na retention what mechanism does this?
Increase sympathetic activity
Decrease GFR
What stimulates juxtaglomerular cells to release renin?
1) Sympathetic nervous system
2) Low tubular Na
How is sodium reabsorption decreased?
Atrial naturitic peptide decreases absorption of sodium in the proximal convoluted tubule and the collecting duct and also decreases stimulation of juxtaglomerular cells
What is the renin-angiotensin-aldosterone system?
Liver releases angiotensinogen JGA release renin Converts angiotensinogen to angiotensin I ACE (lungs) converts to angiotensin II Stimulates the release of aldosterone
What stimulates the release of renin?
↓ Blood pressure
↓ Fluid volume
↑ β1-Sympathetic
What inhibits the release of renin?
↑ Blood pressure
↑ Fluid volume
↓ β1-Sympathetic
Production of ANP (atrial naturitic peptide)
What are the effects of angiotensin II?
1) Proximal tubule, ↑ Na uptake, ↑ water reabsorption, ↑ ECF, ↑ BP
2) Vascular system, vasoconstriction, ↑ BP
3) Adrenal gland, aldosterone synthesis
What is aldosterone? Why is it released? What does it do?
Steroid hormone synthesised and released from the adrenal cortex
Released in response to angiotensin II due to a decrease in blood pressure (via baroreceptors) or decreased osmolarity of ultrafiltrate.
Stimulates:
- ↑ Na reabsorption
- ↑ K+ secretion
- ↑ H+ secretion
What is caused by excess aldosterone?
Leads to hypokalaemic alkalosis
How does aldosterone work?
1) Enters cell and binds to steroid hormone receptor in the cytoplasm (which is bound to inhibitory protein)
2) When aldosterone binds to receptor the inhibitory protein is released
3) Steroid hormone receptors dimerises and translocates to the nucleus and drives transcription
4) Increases expression of Na channel in the collecting duct and induces formation of Na-K-ATPase pumps
What is hypoaldosteronism?
Reabsorption of sodium in the distal nephron is reduced Increased urinary loss of sodium ECF volume falls Increased renin, angiotensin II and ADH Causes: Dizziness Low BP Salt craving Palpitations
What is hyperaldosteronism?
Reabsorption of sodium in the distal nephron is increased Reduced urinary loss of sodium ECF volume increases (hypertension) Reduced renin, angiotensin II and ADH Increased ANP and BNP Causes: High BP Muscle weakness Polyuria Thirst
What is Liddle’s syndrome?
An inherited disease of high blood pressure
- mutation in the aldosterone activated sodium channel
- channel is always ‘on’
- results in sodium retention leading to hypertension
Where are the baroreceptors that detect low blood pressure?
In the atria and some in the right ventricle
In pulmonary vasculature
Where are the baroreceptors that detect high blood pressure?
Carotid sinus
Aortic arch
Juxtaglomerular apparatus
What happens in the low pressure baroreceptors when they detect low blood pressure?
Signal through afferent fibres to the brainstem
Stimulates sympathetic activity and ADH release
What happens in the low pressure baroreceptors when they detect high blood pressure?
Atrial stretch
Stimulates ANP, BNP release
What happens in the high pressure baroreceptors when they detect low blood pressure?
Signals through afferent fibres to the brainstem
Stimulates sympathetic activity and ADH release
Stimulates JGA cells which stimulates renin release
What is ANP? What does it do?
Atrial natriuretic peptide
Small peptide made in the atria (also make BNP)
Release in response to atrial stretch (i.e. high blood pressure)
Causes:
- Vasodilation of renal (and other systemic) blood vessels
- Inhibition of sodium reabsorption in proximal tubule and in the collecting ducts
- Inhibits release of renin and aldosterone
- Reduces blood pressure
What are the different types of diuretic?
1) Osmotic diuretics
2) Carbonic anhydrase inhibitors
3) Loop diuretics
4) Thiazides
5) K+ sparing diuretics
How do osmotic diuretics work? Where do they work in the nephron?
Glucose as in diabetes mellitus or mannitol
In the proximal convoluted tubule
How do loop diuretics work? Give an example
Blocks triple co-transporter (Na+Cl-K+)
e.g. furosemide
How to thiazides work? Where do they work in the nephron?
Block Na/Cl co-transport
In the distal convoluted tubule
Give two examples of K+ sparing diuretics and how they work? Where do they work in the nephron?
1) Amiloride- block Na channels
2) Spironolactone- aldosterone antagonist
They work in the distal convoluted tubule and into the collecting duct
Where do carbonic anhydrase inhibitors work in the nephron? How do they work?
In the proximal convoluted tubule
If you block carbonic anhydrase the protons cannot be pumped into the cell which then prevent Na from being pumped into the cell using a co-transporter
What does high potassium cause?
Depolarises membranes and action potentials
Causes heart arrhythmias
What does low potassium cause?
Heart arrythmias
What is the intracellular and extracellular K+ concentration?
Intracellular: 150mmol/L
Extracellular: 3-5mmol/L
What happens to K+ when you ingest it in a meal?
K+ aborption
↑ plasma K+
Tissue uptake (stimulated by insulin, aldosterone and adrenaline)
Pumped into cells via Na⁺K⁺ATPase
What is K+ secretion stimulated by?
↑ plasma [K+]
↑ aldosterone
↑ tubular flow rate
↑ plasma pH
How much of the K+ from the filtrate is secreted?
1-80%
What cell is responsible for potassium secretion? How does it do it?
Principle cells
Moves K+ into cell through Na⁺K⁺ATPase then into tubule through K+ channels
How does aldosterone stimulate K+ secretion?
Stimulates Na⁺K⁺ATPase pump and also stimulates Na+ channels (Na from tubule into cell) and K+ channels (K from cell into tubule)
How does flow stimulate the secretion of K+?
1) Flow stimulates the primary cilium which activates PDK1.
2) PDK1 activation causes an increase in intracellular calcium
3) Ca2+ stimulates the activity of the K+ channels
What are the most common electrolyte imbalances?
Hypokalaemia
Hyperkalaemia
What are the symptoms of hypokalaemia? What causes it?
Causes: Diuretics due to increased tubular flow rate Surreptitious vomitting Diarrhoea Genetic (Gitelman's syndrome)
What is Gitelman’s syndrome?
Mutation in the Na/Cl transporter in the distal nephron
Causes hypokalaemia
What is hyperkalaemia?
Seen in response to K+ sparing diuretics
ACE inhibitors
Elderly
When ADH is high is renin secretion increased?
No
When ADH is high are the principle cells permeable to water?
Yes
When ADH is high are aquaporins relocated to the plasma membrane of the principle cells?
Yes
In the loop of Henle does the ascending limb reabsorb K+?
Yes
In the loop of Henle is Na+ reabsorption required for the uptake of glucose?
No
None left all reabsorbed in the proximal convoluted tubule
Are body sodium levels used to regulate osmolarity?
No water levels are
What is the mechanism of maintaining acid base balance if you hyperventilate?
↑ ventilation CO2 'blown off' ↑ pH (↓H+) Respiratory alkalosis Compensatory change in renal function H+ gain / HCO3- loss ↓ pH (↑H+)
What is the mechanism of maintaining acid base balance if you hypoventilate?
↓ ventilation CO2 retention ↓ pH (↑H+) Respiratory acidosis Compensatory change in renal function H+ loss / HCO3- gain ↑ pH (↓H+)
What is the mechanism of acid base homeostasis when a change in GI/renal function results in H+ gain or HCO3- loss?
↓ pH (↑ H+) Metabolic acidosis Compensatory change in lung function ↑ ventilation CO2 'blown off' ↑ pH (↓ H+)
What is the mechanism of acid base homeostasis when a change in GI/renal function results in H+ loss or HCO3- gain?
↑ pH (↓ H+) Metabolic alkalosis Compensatory change in lung function ↓ ventilation CO2 retention ↓ pH (↑ H+)
Where is bicarbonate reabsorbed in the nephron?
Proximal CT: 80%
Loop of Henle (↑): 10%
Distal CT: 6%
Collecting duct: 4%
In the Henderson-Hasselcalch equation what is pK?
The ratio of whether bicarbonate is in carbonic acid form or bicarbonate and protons
What type of cells line the proximal convoluted tubule?
Cuboidal epithelial cells
How is bicarbonate reabsorbed in the proximal convoluted tubule?
1) H+ moved into filtrate via H+ATPase
2) H+ binds to HCO3- using carbonic anhydrase (in the membrane) to form (H2CO3 then) CO2 and H2O
3) CO2 diffuses across the membrane
4) Carbonic anhydrase catalyses CO2 + H2O to produce (H2CO3 then) H+ and HCO3-
5) H+ pumped back into the filtrate by H+ATPase and Sodium proton antiporter (loop)
6) HCO3- pumped into the interstitium by chloride bicarbonate exchanger and sodium bicarbonate cotransporter
7) Sodium potassium ATPase pumps Na into the interstitium
How is acid secreted in the collecting duct?
1) Hydrogen potassium ATPase move H+ inot the filtrate and K+ into cell
2) Carbonic anhydrase converts H+ and HCO3- to H2O and CO2
3) CO2 diffuses into cell and carbonic anhydrase converts CO2 + H2O to H+ and HCO3-
4) H+ATPase and Hydrogen potassium ATPase pumps H+ into the filtrate
5) AE1 (Chloride bicarbonate exchanger) pumps HCO3- into the interstitium in exchange for Cl-
How is bicarbonate secreted in the collecting duct
1) Carbonic anhydrase in the intercalated cell converts CO2 + H2O to HCO3- + H+
2) HCO3- exchanged with Cl- in the filtrate using a chloride bicarbonate exchanger
3) H+ inside the cell is pumped into the interstitium
How is HCO₃⁻ generated in the proximal convoluted tubule using carbonic anhydrase?
1) Carbonic anhydrase converts CO₂ + H₂O to H⁺ + HCO₃⁻
2) HCO₃⁻ pumped into interstitium via chloride bicarbonate exchanger (AE1) in exchange for Cl⁻
3) H+ pumped into filtrate via H+ATPase
4) Binds to phosphate (HPO₄²⁻) to form H₂PO₄
How can HCO₃⁻ be generated in the proximal convoluted tubule using glutamine?
1) Glutamine split into 2NH₄⁺ and 2HCO₃⁻
2) NH₄⁺ pumped into the filtrate in exchange for Na⁺
3) HCO₃⁻ pumped into the interstitium via a chloride bicarbonate exchanger (AE1)
4) Na⁺K⁺ATPase pumps Na⁺ into the interstitium and K⁺ into cell
What happens when the kidney stops working?
1) Loss of excretory function
- Accumulation of waste products
2) Loss of homeostatic function
- Disturbance of electrolyte balance
- Loss of acid-base control
- Inability to control volume homeostasis
3) Loss of endocrine function
- Loss of erythropoietin production
- Failure to 1α-hydroxylase vitamin D
4) Abnormality of glucose homeostasis
- Decreased gluconeogenesis
What are the most common symptoms that patients with chronic kidney disease (renal dysfunction) present with?
Hypertension
Oedema
Pulmonary oedema
(Fluid overload)
In chronic kidney disease which has particularly affected the medulla what can patients present with? Why is this?
Salt and water loss in patients with tubulointerstitial disorders which damage the concentrating mechanism
What would show on an ECG in a patient with hyperkalaemia
1) T wave peaks
2) P wave disappears
3) Frankles sign (bradycardia)
4) Broadening of the QRS
What are the implications of hyperkalaemia?
Caused by failure of distal tubule to secrete potassium
Exacerbated by acidosis- causes shift of potassium from intracellular to extracellular space
Can cause cardiac arrythmias (usually initial loss of p waves and bradycardia) and arrest
Can effect neural and muscualr activity
Clinical features of hyperkalaemia are dependent on the chronicity of the hyperkalaemia
What are the consequences of chronic renal failure?
Phosphate retention
Low levels of calcitriol
Hypocalcaemia
Hyperparathyroidism
In kidney failure there is decreased erythropoietin production. What does this cause?
Anaemia
In kidney failure you have low 1-25 vitamin D. What does this cause?
Poor intestinal calcium absorption
Hypocalcaemia (short term)
Hyperparathyroidism (longer term)
What is the major outcome of patients with chronic kidney disease?
Cardiovascular disease
How do you distinguish between acute and chronic kidney disease?
Renal size in chronic is usually reduced
Check previous creatinine (if previously abnormal it is chronic)
Chronic uraemic symptoms (nocturia)
What is the initial management of a patient with chronic renal failure?
IV saline to correct fluid depletion
IV sodium bicarbonate to correct acidosis
IV insulin and dextrose to lower plasma potassium (drives K⁺ ions back into cells)
Dialysis
How do you estimate GFR?
MDRD equation
