Urinary Flashcards
Name common exit point of resp, GI and urinary systems in developing embryo
Cloaca
Name the 3 kidney systems formed in embryonic development
Pronephros, mesonephros and metanephros
What does the urinary system form from?
Intermediate mesoderm
Where does the ureteric bud sprout from?
Mesonephric duct
What does the metanephric blastema become?
the adult kidney (the excretory portion)
What does the cloaca divide into?
The urogenital sinus and the primitive ano-rectal canal.
What separates the urogenital sinus and the ano-rectal canal?
The uro-rectal septum.
What are the 3 parts of the urogenital sinus?
The urinary bladder, pelvic part and phallic part.
What does the allantois become when its lumen is obliterated, and what does this then form in the adult?
Urachus
Median umbilical ligament
What do the mesonephric ducts eventually become in the male?
The ejaculatory ducts
What aids fluid reabsorption from the interstitium to the peritubular capillaries in the PCT region of the kidney?
- high interstitial hydrostatic pressure due to sheer volume of fluid entering interstitium.
- high oncotic pressure of peritubular capillaries due to presence of proteins to large to be filtered in glomerulus, which passed into the efferent arteriole and into the peritubular capillaries.
When do autoregulatory mechanisms (myogenic resoponse and tubuloglomerular feedback) not work to maintain GFR?
When systemic arterial pressure is not within physiological limits, so when pressure below 80mmHg or greater than 180mmHg.
What is released by macula densa cells to cause vasoconstriction of afferent arteriole?
Adenosine
What is released by macula densa cells to cause vasodilation of afferent arteriole?
Prostaglandins
Give an example of a loop diuretic and explain its mechanism of action in the thick ascending limb of loop of Henle.
Bumetanide and Furosemide
Inhibit Na+ uptake from tubular filtrate by inhibiting Na+-K+-2Cl- co-transporter. So Na+ left in urine, so less H20 reabsorbed in later parts of nephron, remains with Na+ increasing blood vol. lost, so decreases BP.
Describe glomerulotubular balance.
Mechanism of ensuring that Na+ and water excretion aren’t significantly impacted on by changes in GFR. Same proportion of Na+ reabsorbed in PT no matter GFR, so always 67%, hence a constant fraction is reabsorbed, limiting amount of change.
Occurs via 2 mechanisms:- hydrostatic and oncotic pressure differences between interstitial fluid and plasma in peritubular capillaries.
- increase in filtered load of glucose and aa.
What Na+ transporters are present on apical membrane of PCT cells in S1?
Na+-H+ exchanger
Na+ and organic solute co-transporters e.g. Na+-glucose symporters and Na+-aa symporter.
Na+-Pi channels
What apical transporters present in S2-S3 of PCT?
Na+-H+ exchanger
Cl-, base anti-porters
Name the 2 important apical transporters in thick ascending limb.
Na+-K+-2Cl- symporter
ROMK- renal outer medullary K+ channel
Name the transporters found in the early DCT
Apical: NCC, Ca2+ channels
Basolateral: Na+ pump, Cl- channels, NCX
What transporters are present in principal cells of late DCT and collecting duct?
-ENa+ channels
-K+ channels
Na+ pump on basolateral membrane.
What does the negative charge left in the lumen after Na+ reabsorption in the collecting duct drive?
Paracellular Cl- reabsorption
What diuretic inhibits ENaCs?
Amiloride
What do type B intercalated cells in the collecting duct do?
Use H+ATPase to generate a H+ gradient as Na+ gradient can’t be used for H+ excretion as most Na+ has been reabsorbed, and H+ gradient then used to reabsorb Cl- which is coupled to HCO3- secretion.
What are the 4 neurohumoral resonses controlling BP?
- RAAS
- SNS
- ADH
- ANP
Which 3 factors are important for stimulating renin secretion?
- reduced NaCl reaching distal tubule
- reduced perfusion pressure
- SNS stimulation to JGA
Where is angiotensinogen produced?
Liver
Where is renin produced?
By granular cells of JGA in kidney.
What are the actions of Ang II?
- arteriorlar vasoconstriction
- Stimulates SNS
- increase thirst via increasing ADH
- acts on kidney directly to increas NaCl reabsorption
- acts indirectly on kidney via stimulation of aldosterone release, which increase Na+ reabsorption
Describe the use of clearance rates as a measure of GFR?
If a substance is completely cleared from the plasma filtered i.e. all filtered is excreted, with no reabsorption or secretion, then its clearance rate is equal to GFR. Clearance rate= concentration of substance in urine x urine flow rate / concentration in plasma.
Inulin clearance rate can be used, aswell as creatinine, even though some creatinine is secreted by organic cation secretory system in PT, as there is also a 10% error in measuring creatinine conc. in plasma.
What is calcitonin?
a polypeptide hormone released by the parafollicular cells of the thyroid gland located in the base of the neck, anterior to the lower larynx and the upper trachea, which may help to preserve the maternal skeleton during pregnancy.
What is the renal threshold?
The plasma concentration of a substance at which the transport maximum is reached and the substance 1st starts to appear in the urine.
Define isosmotic reabsorption
Solute and water reabsorption are proportional to each other.
What do disorders of water balance cause?
Changes in plasma osmolarity
What are the action of ADH (vasopressin)?
Primary action: increase permeability of CD to water, hence conserve water in the body by reducing loss in urine.
Further actions: - increase NaCL reabsorption at ATL, distal tubule and cortical part of CD.
-vasoconstriction at glomerulus reducing effective filtering SA.
-H20 reabsorption at late distal tubule
-K+ secretion in cortical CD
-Increases permeability of medullary CD to urea, which adds to corticopapillary gradient maintained by vasa recta.
Describe ADH receptors in basolateral membrane of CD and how they function.
Name- V2 receptors which are GPCRs on basolateral membrane- binding of ADH to receptor activated a G protein-Gs-heterotrimeric structure, splits apart into its 3 subunits as GDP-GTP exchange, adenylyl cyclase then activated, increasing cAMP, activates PKA, resulting in AQP-2 channels being inserted into apical membrane.
What is the hallmark of the ATL of loop of Henle?
Diluting segment- ions reabsorbed from filtrate without water reabsorption, so filtrate diluted.
Describe how the cortico-papillary osmotic gradient is not destroyed.
Blood flows in the opposite direction in the vasa recta, to the tubular fluid in the nephron, so the descending vasa recta passes down through the hyper-osmotic interstitium, causing the blood to become very concentrated and so this blood is able to reabsorb water as it leaves the thin descending limb, drawn out by the increasing concentration of the interstitium, and as blood flow through the ascending vasa recta is towards the cortex, the reabsorbed water from the DTL is taken away from the concentrated middle of the kidney, so concentration gradient preserved.
Define range of values of normal pH
7.38-7.42
What are the 4 basic types of simple acid-base disorders?
Respiratory acidosis and alkalosis- primary disorders of CO2 handling by lungs.
Metabolic acidosis and alkalosis- primary disorders of plasma HCO3- levels.
Before compensation, what limits acid-base changes?
Buffers e.g. protiens-Hb in red cells, and phosphates.
Prinicpal ECF buffer= HCO3-
Co2 is a volatile acid- has potential to generate H+ after hydration with H20. Describe effects on HCO3- levels and pH of an increase in volatile and non-volatile acid production.
Volatile: pH decreases eventhough plasma HCO3- increases as CO2 reacts with water.
Non-volatile: H+ buffered by HCO3-, so plasma HCO3- levels fall and pH falls.
How long does lung compensation take, and how long does kidney compensation take?
Lung- minutes
Kidney- days
What is the anion gap?
The difference between the sum of the measured concentrations of Na+ and K+ ions and sum of measured concentrations of Cl- and HCO3- ions.
Describe respiratory acidosis and list some causes
High pCO2 in arterial blood and low pH.
Usually caused by Hypoventilation but may result from CNS disorder- reducing ventilatory drive, air pump disorder- diseases affecting muscles of inspiration e.g. myasthenia gravis, processes that interfere with GE e.g. COPD.
Describe compensation of respiratory acidosis.
Kidneys compensate by increasing HCO3- concentration, achieved by secreting more H+ and NH3 production.
Describe respiratory alkalosis
Low pCO2 and high pH, always result of hyperventilation. This may occur with increased ventilatory drive or hypoxaemia.
Describe metabolic acidosis
Decrease [HCO3-] in plasma and low arterial pH. Can be compensated for by increase in ventilation to transfer volatile acid to atmosphere, and plasma HCO3- falls further.
Describe metabolic alkalosis
Elevated [HCO3-] and arterial pH. May be caused by vomiting or diuretics. Compensation by reducing ventilation but this could lead to hypoxia. If patient is alkalotic due to vomiting, you want to correct fluid and electrolyte imbalance, and then patient can correct their condition with increased [HCO3-] excretion.
Describe layers of kidney.
Kidney parenchyma: inner medulla and outer cortex. Cortex surrounded by fibrous capsule, perinephric fat, renal fascia, and paranephric fat. Anterior and post. parts of renal fascia don’t meet - clinical significance.
How might left renal vein entrapment occur?
Traction of SMA or abdominal aortic aneurysm.
How might you distinguish between ureter and uterine artery in a hysterectomy?
Ureter- white cord, if prodded- peristaltic movement rather than pulsatile.
Blood supply of ureters
Ascending and descending arteries from renal, gonadal, common iliac, vesicular and uterine.
What is the bladder trigone?
2 ureteral orifices at top of triangle and internal urethral meatus at bottom.
What comprises the juxtaglomerular apparatus?
Macula densa cells of DCT, granular cells in afferenct arteriole and extraglomerular mesangial cells which have a supportive function.
Where does counter current multiplication occur?
Loop of Henle
What is the filtered load?
Amount of solute filtered from arterial plasma into Bowman’s capsule per unit time (so plasma conc x GFR)
At what vertebral level do the renal arteries arise from the abdominal aorta?
L1
Describe the course of the ureters
Arise at pelviureteric junction and descend towards the bladder, passing over the transverse processes of the vertebrae and crossing the pelvic brim at the bifurcation of the common iliac arteries. They swing out laterally, before passing anteriorly and medially into the bladder. Retroperitoneal throughout their course.
Why are tight junctions essential in PT?
Enable polarisation of epithelial cell- ion transporters remain on correct side of cell so that the luminal and basolateral membranes retain different properties.
How is HCO3- reabsorbed in PT?
- Na+pump- genrates Na+ gradient
- Gradient used by Na+-H+ exchanger to expel H+ against its conc gradient
- H+ reacts with HCO3- in lumen, producing H20 and CO2.
- CO2 diffuses into cell and reacts with H20, producing H+ and HCO3-.
- H+ recycled through Na+-H+ exchanger
- HCO3- exported across basolateral membrane via sodium bicarbonate symporters and Cl–HCO3- antiporters.
Why is 98% of our body K+ in ICF?
ICF has higher volume, and K+ are at a higher concentration here due to action of Na+ pump- moves 3 Na+ out of cell for every 2 K+ moved in
Mainly skeletal muscle, also liver, rbc and bone
When we measure K+, we are talking about ECF K+- normal concentration= 3.5-5.0 mmol/L
How is K+ responsible for our negative resting membrane potential of cells?
K+ at high concentration inside cells due to Na+-K+-ATPase. K+ can diffuse out of cells, down its concentration gradient, via K+ channels, but Cl- unable to follow as channels not present, so cell is -ve on the inside with respect to the outside
Why is cardiac membrane vulnerable to fibrillation with hyperkalemia?
Reduced K+ gradient across cell for K+ outward movement, so membrane depolarise, Na+ channels unable to be reprimed after inactivation, so membrane actually made less excitable.
How does insulin influence K+ movement across cell membrane?
Insulin promotes Na+/H+ exchange, so more Na+ brought into cell, increasing activity of Na+ pump so more K+ brought into cell.
Beta 2 agonists activate Na+ pump, so more K+ brought into cell, reducing plasma concentration. B blockage can therefore increase plasma potassium.
So plasma K+ tends to be higher in patients with diabetes.
How is pH associated with K+ levels
When H+ enters cells, it displaces K+, as all cell will move ions around to try and control their own pH, so H+ moved out of cell, raising plasma K+ levels.
How can thyroid hormones affect K+ levels?
Promote Na+ pump synthesis, and can therefore cause hypokalemia
Where is final K+ concentration in urine determined?
Cortical CD-ROMK channels present here, aswell as in ATL of loop of Henle
Why does enhanced Na+ delivery to DT increase K+ secretion into filtrate?
More Na+ results in increased activity of ENaC channels in CD, generating lumen -ve potential that drives K+ secretion via K+ channels (ROMK). ENaC Na+ reabsorption controlled by aldosterone.
What effect does diuretic amiloride have on K+ secretion?
Secretion reduced as ENaC channels inhibited, so less Na+ movement into CD cells, so less of a luminal -ve potential generated for K+ secretion. Also, less Na+ movement into cell will reduce activity of Na+ pump bringing K+ into cell.
How is K+ excretion increased when increased K+ in ECF?
Increased activity of Na+ pump on basolateral membrane, so more K+ brought into principal cells of CD, which can then be excreted across apical membrane via K+ channels
How does aldosterone control renal K+ excretion?
Aldosterone release stimulated when increased K+ levels detected in ECF of adrenal cortex.It promotes Na+ pump synthesis in cortical CD, and insertion of more Na+ pumps into basolateral membrane fpr K+ uptake into cell. Also stimulates Na+ and K+ channel activity, increasing Na+ reabsorption and K+ secretion.
How does increased pH promote K+ secretion?
Increases apical K+ channel activity and basolateral Na+ activity.
How can hypokalemia result from magnesium deficiency?
Mg blocks ROMK channels, reducing K+ secretion so if less Mg, inhibitory effect reduced, more K+ secreted and so K+ decreases.
What is general effect of diuretics of K+ excretion?
increased as urinary flow rates increased which reduce luminal K+ concentration, so enhance K+ secretion.
How does spironolactone reduce K+ secretion
antagonises effect of aldosterone
Why can stress lower plasma [K+] rapidly?
Stress- more catecholamines released- acts via B2 adrenergic receptors which in turn, stimulate Na+ pumps, which stimulates K+ uptake into cell.
How does exercise reduce K+ levels in cells?
Exercise- skeletal muscle contraction, so net release of K+ during recovery phase of AP, increasing plasma [K+] which is proportional to exercise intensity. Uptake of K+ by non-contracting tissues prevents hyperkalemia, inaddition to catecholamine release stimulated by exercise, which stimulates Na+ pump, so more K+ uptaken from plasma.
How does plasma K+ alter with cell lysis?
Hyperkalaemia. Severe trauma, rhabdomyolysis and chemotherapy can all destroy cells and so release K+ into plasma. Also occurs with IV haemolysis e.g. in G6PDD patients treated with primaquine- capacity to defend against ROS insufficient as NADPH defecit from PPP, so anti-oxidant lack and rebc subsequently destroyed.
How does plasma tonicity affect K+?
Increase in plasma and ECF tonicity e.g. diabetic ketoacidosis, means water moves into ECF from cells, so [K+] inside cells increases, and K+ leaves down its concentration gradient, into ECF.
How does acid base balance affect K+ concentration?
Acidosis cause H+ uptake into cells, resulting in reciprocal shift of K+ out of cells causing hyperkalaemia. Similarly, if hyperkalaemia, K+ will be removed from ECF into cell, and H+ will them move out of cell, causing an acidosis.
What is key difference between Na+ and K+ renal handling?
K+ is secreted by DT and cortical CD cells (prinicipal cells) but Na+ is only reabsorbed by kidney, not secreted.
How is favourable electro-chemical gradient created by principal cells to secrete K+?
Chemical gradient- Na+ pump on basolateral membrane that brings K+ into cell, so favourable concentration gradient for secretion across apical membrane.
Electrical- ENaC channels on apical membrane bring Na+ into cell, creating lumen -ve potential, which attracts K+ to move out of cell.
Why is K+ secretion increased by principal cells when increased distal tubular flow rate?
K+ washed away more quickly so always a favourble concentration gradient for K+ to move out of cell and so be secreted.
How does acidosis reduce K+ secretion?
It inhibits Na+ pump which accumulate K+ inside cells, so more in plasma, and reduces K+ channel permeability.
How is K+ absorbed in DT and CD?
K+ absorbed actively by intercalated cells using H+-K+-ATPase in apical membrane.
Why does poor kidney perfusion cause hypokalemia?
RAAS activated, so increase aldosterone, which increases K+ excretion.
Why would hyperkalaemia occur with renal failure?
Renal excretion maintains our external balance of K+, so if this can’t occur due to renal failure, K+ in ECF will increase.
Why are UTIs more common in females?
Bacteria can ascend urethra between voiding, and as urethra shorter in females, infection is commoner.
Where can K+ be secreted when dietary K+ intake increases?
DT and CD- both determine overall rate of K+ excretion as variable magnitude and direction of K+ transport
What 3 major factors control rate of K+ secretion by DT and CD?
- Activity of basolateral Na+-K+-ATPase
- Electrochemical gradient (driving force) for movement across apical membrane
- Permeability of apical membrane to K+
How does ADH affect K+ secretion?
No net effect on K+ excretion. Decreases tubular flow as more water reabsorbed, so reduces K+ secretion as less of a concentration gradient for K+ diffusion across apical membrane. BUT, also stimulates electrochemical driving force for K+ exit across apical membrane of prinicpal cells as stimulates Na+ reabsoption by prinicpal cells, so urinary K+ excretion maintained constant when fluctuations in H2O excretion.
Why are aldosterone antagonsits e.g. spironolactone, the preferred drug for acsites and oedema in cirrhosis?
These drugs are K+ sparing drugs, as they inhibit action of aldosterone which normally increases K+ secretion by increasing expression of Na+ pumps on BL membrane, and Na+ and K+ channels on apical membrane. This is important as hypokalemia can potentiate hepatic encephalopathy which may occur with a cirrhosed liver as the conditon results from a reduced detoxification ability of the liver, resulting in, for example, increased NH3 in systemic circulation, which can go on to damage the brain, so K+ levels need to be maintained.
What is a diuretic?
It is a substance/drug that promotes a diuresis- increased formation of urine by the kidney, as a result of increased renal excretion of water and sodium, causing a reduction in ECF volume.
How do aldosterone antagonists work as diuretics?
Competitive inhibition of intra-cellular aldosterone receptors, resulting in reduced Na+ reabsorption via ENaC, so more Na+ retained in filtrate, along with H20?
How do carbonic anhydrase inhibitors work as diuretics?
Inhibit Na+ and HCO3- reabsorption at PT by inhibiting action of carbonic anhydrase, increased HCO3- levels in filtrate oppose H2O reabsorption.
Define hypokaleamia
A plasma [K+] of less than 3.5mmol/L
Where do carbonic anhydrase inhibitors e.g. acetazolamide act and why are they the least potent diuretic?
PCT
They inhibit NaHCO3 reabsorption, rather than NaCl reabsorption. There is less HCO3- in glomerular filtrate so reduced effect on Na+ reabsorption.
Plasma HCO3- levels reduce with chronic drug use as increased urinary excretion, further limiting diuretic potency.
When are carbonic anhydrase inhibitors still used and why?
Glaucoma
Reduce formation of aq humour.
Also used in some unusual types of infantile epilepsy.
Why might thiazides be used in treatment of hypocalcaemia/urinary calcium stones (calciuria)- high excretors?
They inhibit NCC transporters on apical membrane in DCT, so less Na+ reabsorbed, so less entering cell, so increased concentration gradient for Na+ entering via NCX on basolateral membrane, so NCX stimulated, so more Ca2+ removed from cell into ECF, so more Ca2+ reabsorbed from lumen, reducing calcium stone formation in filtrate.
Describe actions of Mannitol- an osmotic diuretic.
Filtered in glomerulus then not reasbsorbed, so remains in filtrate, and as H2O reabsorbed, osmolarity of filtrate increases until osmotic effect of mannitol opposes further water reabsorption, so sodium then reabsorbed without water. Na+ reabsorption eventually inhibited as gradient between filtrate and plasma increases to point at which Na+ leaks back into filtrate.
Mannitol used to dehydrate brain cells in cerebral oedema. Enhances RBF by increasing EC and IV volume and reducing rc vol. abd blood viscocsity. Urinary concentrating capacity reduced as enhanced blood flow reduces medullary interstitial osmolarity.
Out of all the glucose that is filtered by the glomerulus, how much would appear in the urine if the Na+ pumps on the BL membrane of tubular cells were inhibited?
All of it!
Na+ pump necessary for tubular reabsorption as generates a Na+ gradient for apical transporters.
Why can loop diuretics be used in hypercalcaemia?
They inhibit the Na+-K+-2Cl- co-transporter in apical membrane of ATL cells. Transporter normally results in lumen +ve potential as 1 Na+ reabsorbed with 2 Cl-, which stimualtes Ca2+ reabsorption. As this effect is inhibited, less Ca2+ is reabsorbed from filtrate, so more excreted.
Describe 3 mechanisms by which loop and thiazide diuretics may cause hypokalaemia
- inhibit Na+ and H20 reabsorption, so increase flow rate of filtrate in lumen, so K+ secreted into lumen washed away faster, maintaining favourable gradient for K+ secretion so more lost.
- reduced reabsorption means more Na+ in lumen in late DT and CD, so more Na+ reabsorbed by ENaC, creating lumen -ve potential for K+ secretion.
- reduction in ECF vol. stimulates RAAS as reduced perfusion pressure of kidney, so increased aldosterone secretion, which increases Na+ reabsorption and K+ secretion.
Define an antiporter
A co-transporter that uses secondary AT to transport 2 different ions across PM in opposite directions
Why might repeat specimens be required when investigating UTI?
If low bacterial counts, evidence of contamination or sterile pyuria.
Causes of sterile pyuria
prior antibiotic fastidious organisms urethritis urinary TB appendicitis chemical inflammation vaginal infection/inflammation
Treatment for uncomplicated UTI?
3 day course of trimethoprim or nitrofurantoin
Treatment for complicated UTI?
5 day course of trimethoprim, nitrofurantoin or cephalexin
Treatment for pyelonephritis or septicaemia?
14 day course of co-amoxiclav, ciprofloxacin or gentamicin
Prophylaxis for UTI?
If 3 or more episodes in 1 yr with no treatable underlying condition. Trimethoprim or nitrofurantoin- single nightly dose.
Why does reducing ECF volume with diuretics lower body weight?
1 L of ECF weighs 1 kg
Why do all diuretics increase K+ excretion, apart from K+-sparing diuretics?
They increase delivery of tubular fluid to K+ secretory portion of nephron, and increased aldosterone and ADH secondary to diuretic-induced decrease in ECF vol.
How might a thiazide diuretic decrease BP?
Inhibits Na+-Cl- co-transporter in apical membrane of cells lining early part of distal tubule. So more Na+ and H2O excreted in urine, reducing ECF volume, blood volume and CO.
Why might a thiazide diuretic cause hypokalaemia?
Acts proximal to K+ secretory sites of nephron, increases tubular fluid flow rate to K+-secretory site, so K+ washed away more readily, maintaining concentration gradient for K+ secretion, so more secreted. Also, stimulation of aldosterone and ADH release.
Treatment of hypokalaemia in patient on thiazide diuretics?
Administer K+ sparing diuretic alongside thiazide.
Increase K+ intake in diet or with KCL tablets.
Main causes of hypercalcaemia
primary hyperparathyroidism- typically adenomas
haematological and non-haematological malignancies
Symptoms of hypercalcemia
Kidney stones, depression, abdominal pain, nausea, constipation, anorexia, hypertension, enhanced sensitivity to digoxin, polyuria and polydipsia.
Distinguishing between hypercalcaemia of malignancy, and primary hyperparathyroidism?
Plasma PTH
Plasma calcitriol
Bone formation
Why can PTHrP exert same biological effect as PTH?
As amino acid homology with N-terminal of PTH-active portion of PTH
Management of acute hypercalcaemia
Hydration Loop diuretic e.g. furosemide Bisphophonates Calcitonin Treat underlying condition
When is haematuria more suggestive of renal stone?
When abdominal pain. If painless, more likely to me malignancy
Why might urate stones form?
Chemotherapy- increases uric acid formation due to killing lots of cells
Alcohol- competes with urate for excretion by kidney
What are the most common renal stones made from?
Calcium (70-80% of stones)
Factors involved in calcium oxalate stone formation?
Hypercalcuria- high Ca2+ in urine
Reduced urine volume
Low urine pH (<5.47)
Process involves urine supersaturation with respect to calcium oxalate
Conservative medical management of renal stones?
Increase fluid itnake- urine output >2L daily, dietary restriction of oxalate and sodium, consider Ca2+ dietary restricition and animal proteins.
How does PTH affect Pi urinary excretion?
Inhibits PT Pi reabsorption, where 80 % Pi reabsorbed, and rest usually excreted, so PTH increases Pi excretion. PTH stimulates endocytic removal of apical transporters.
How does ECF vol affect Pi excretion?
Increased ECF vol increases excretion as increased GFR and hence filtered load, reducing Na+-Pi coupled reabsorption and reduces plasma Ca2+ so PTH increased which increases excretion.
Acid base affect Pi excretion?
Acidosis increases excretion- Pi reabsorption inhibited by PT as glucocorticoid secretion. DT and CD can then secrete more H+ as titratable acid and generate more HCO3- as Pi is an important urinary buffer.
What GF regulates Pi excretion?
Fibroblast GF 23
How is the histology of the ureters relevant to their function?
Lined by transitional epithelium which is able to stretch without tearing to accomodate intraluminal volume increases.
Inner longitudinal, middle circular, and outer longitudinal smooth muscle layer in wall which contract to increase intraluminal pressure locally and convey urine to the bladder by peristalsis- wave propagation aided by gap juntions electrically coupling SMCs.
How is urine prevented from refluxing back up to the kidneys via the ureters when it enters the bladder?
Ureters enter bladder at an oblique angle, creating a valve that prevents ureteral reflux.
How is internal sphincter of bladder formed?
In neck of bladder by detrusor muscle and elastic tissue. Controlled by ANS (involuntary)
What is the external sphincter of the bladder composed of?
Skeletal muscle (voluntary) Only part of urinary system under voluntary control
Innervation of external urethral sphincter?
Pudenal nerve (S2-S4)
Where to sympathetic efferents to UT originate?
SC T11-L2 segements and travel to UT via hypogastric nerve or descend in paravertebral chain and then travel in pelvic nerve.
Which adrenergic receptors are present in the bladder and what do agonists of these receptors stimulate?
B2 adrenergic
Relaxation of detrusor muscle, so urine can be stored and isn’t emptied.
Other than relaxation of detrusor muscle, what else does sympathetic innervation to lower UT result in?
Constriction of bladder neck and urethra
Describe PSNS to lower UT
PSNerves originate from S2-S4 sacral spinal segements, and travel in pelvic nerve to pelvic plexus and bladder wall.
Stimulates detrusor muscle contraction, hence voiding, and relaxation of urethra and internal sphincter
Name given to folds formed by detrusor muscle which allows bladder to accomodate increasing volumes of urine?
Rugae
Where is ROMK found in kidney?
All nephron segements except PT
Where is K+ secreted and reabsorbed in collecting tubule and ducts?
Secretion by prinicipal cells, reabsorption by intercalated cells
Why can hyperkalaemia be expected to occur in renal failure?
As external balance (controlling whole body K+) is maintained by renal excretion.
Pharmacologic treatment in urge urinary incontinence? and side effects?
Anticholinergics- acts on M2 and M3 muscarinic receptors.
Can cause a dry mouth-xerostomia- reduced salivary flow, and constipation- intestinal smooth muscle M3 receptors.
Example of anticholinergic drug for urge urinary incontinence
Oxybutynin
How does urinary continence (urine storage by bladder) appear to be commanded?
Cerebral cortex, to pontine continence or storage centre (L-region- in dorsal part), to sympathetic nuclei in cord, to detrusor muscle and external urethral sphincter motorneurones in sacral cord.
How is micturition phase controlled?
Voiding circuits which arise from:
cerebral cortex, Pons (M-region), sacral levels of parasympathetic outflow, detrusor muscle contracts, and external urethral sphincter relaxes.
How is water moved for reabsorption along nephron?
By altering osmolarity across a semi-permeable barrier
How are glomeruli formed?
By capillaries invaginating developing tubules
What is hypospadias?
Hypospadias occurs when the urethra opens onto the surface of the inferior penis. It is caused by failure of the urethral folds to fuse properly
What is dysuria?
Difficulty with micturition, mainly pain
Where is pain common with urinary tract stones?
Loin
The pain is caused by obstruction to urine flow and subsequent distension and sometimes spasm of the ureters and collecting system upstream of the obstruction
How might a UT obstruction be detected?
Urinary tract obstruction is detected by ultrasound scanning which can visualise the distension of the collecting system upstream of the obstruction
What is the main function of kidney tubules?
To alter the volume and composition of filtered fluid
Why is the concentration of Na+ in the initial filtrate the same as the plasma and why is reabsorption in the PT termed isosmotic?
As Na+ is freely filtered. The proportion of Na+ reabsorbed is the same as the proportion of water reabsorbed in the PT, so the osmolarity of the filtrate doesn’t change and remains the same as the osmolarity of the plasma, with the osmolarity of the fluid being reabsorbed being equal to the osmolarity of the filtrate, so osmolarity doesn’t change, but the volume of filtrate is reduced.
Why do proteins have the ability to act as buffers?
Some proteins have aa side chains that are weak acids or bases
What is the only blood supply to the renal medulla?
Vasa recta
What are the main predisposing factors to renal stone formation?
infection, obstruction or other causes of urinary stasis and metabolic disorders causing high urine levels of stone forming substances or low levels of stone inhibiting substances e.g. citrate
Abdominal retroperitoneal organs?
SAD PUCKER
suprarenal glands, aorta/IVC, duodenum (2nd and 3rd parts), pancreas, ureters, colon (ascending and descending), kidneys, oesophagus, rectum
Vertebral level of upper pole of L kidney?
T11
Vertebral level of upper pole of R kidney?
T12
Length of male and female urethras
Male- 20 cm
female- 4 cm
Anatomical location of male urethra?
Pre-prostatic= between bladder and prostate Prostatic= passes through prostate Membranous= passes through deep perineal pouch Penile/spongy= passes through corpus spongiosum
Where is the opening of the female urethra?
In vaginal vestibule between anterior ends of labia minora and clitoris
What type of infarction does a kidney exhibit and why?
White infarct
Renal arteries= functional end arteries- supply sole source of blood to a particular area of kidney so occlusion to a particular artery means insufficient anastomoses to supply blood to the area normally supplied by that artery, hence the blood supply is cut off completely.
Which muscles lie posterior to the kidneys which the kidneys hence lie on?
Psoas major, quadratus lumborum, transversus abdominis
Phenylketonuria is an example of which aminoaciduria?
Why do infants with this condition have severly retarded brain development?
Specific overflow aminoaciduria
Phenylalanine unable to undergo metabolism to produce tyrosine as defective phenylalanine hydroxylase enzyme- autosomal recessive condition. Phenylalanine therefore undergoes metabolism via other pathways, producing phenylpyruvate which inhibits pyruvate uptake by the brain, necessary for energy production.
Describe the 2 normal functions of the bladder
- temporary storage of urine (filling phase)- compliance- receptive relaxation (stress-relaxation phenomenon), sensation of bladder filling- sensory afferents in SM, no detrusor contraction
- voiding- voluntary initiation via relaxation of external urethral sphincter, and complete emptying of bladder as mass contractor so once starts contracting, contracts all the way.
Define urinary incontinence
Complaint of any involuntary leakage of urine
When does urinary incontinence occur (general description)?
When bladder pressure is greater than urethral sphincter pressure- detrusor pressure is high, or sphincter pressure low
Pharmacologic management in stress UI?
Duloxetine- combined NA and serotonin uptake inhibitor
Which ribs do the kidneys lie deep to?
11th and 12th
Why is a left kidney more like to be transplanted?
As left renal vein longer than right, so something to do with anastomosis?
Where does the left gonadal vein run into?
The left renal vein
Where does the right gonadal vein run into?
IVC
Define nephrotic syndrome
More than 3 and a half g of protein lost in urine in a 24 hr period. Characterised by high protein content of urine=proteinuria, hyeprcholesterolaemia, oedema and hypoalbuminaemia.
When might prostate specific antigen be raised?
UT infection, inflammation, benign prostatic hypertrophy, prostate cancer
What is the usual reason for a palpable kidney?
Polycystic kidney disease
Common metastasis of prostate cancer?
Bone- sclerotic (osteoblastic) metastases- visualised as hot spots on a bone scan (isotopic bone scans) or X-rays
Describe hormonal treatment for metastatic prostate cancer
Use of LHRH (luteinizing hormone releasing hormone/ GRH-gonadotropin releasing hormone) agonists. These are injected, and as an agonsit, mimic the action of LHRH which is released from the hypothalamus, and acts on the anterior pituitary to result in LH release, which then acts on the zona reticularis of the adrenal cortex to stimulate testosterone release, and testosterone drives the growth of prostate cancer. So initally (in the 1st week), giving the agonist means LHRH is present all of the time, so more LH and testosterone produced, but then the anterior pituitary becomes worn out from being overly stimulated, so LH and testosterone become reduced.
May require combination with an anti-androgen
What’s found at the vascular pole of the kidney?
Afferent and efferent arterioles, with granular cells, macula densa cells and extra-mesangial cells
What grading system is used in prostate cancer?
Gleason grading- low magnification
Staging of prostate cancer?
TNM staging of digital rectal exam- tumour size, extent of regional node metastasis and distant metastases. T1/T2- localised, T3- locally advanced, T4- advanced
Where does blood in the efferent arteriole carry on through in cortical and juxtamedullary nephrons?
Cortical- peritubular capillaries
JM- vasa recta
Where is the glomerular damage in nephrotic syndrome?
Podocyte- abnormal foot processes/subepithelial
Why is there generalised swelling of patients with nephrotic syndrome?
Hypoalbuminaemia- decrease oncotic pressure of blood, so fluid moves out of capillaries into tissues, causing oedema.
Associated Na+ and water retention, increasing hydrostatic pressure in capillaries, causing oedema.
3 physical forces in blood filtration?
Glomerular capillary hydrostatic pressure, hydrostatic pressure in Bowman’s capsule, osmotic pressure difference between capillary and tubular lumen
Most common cause of nephrotic syndrome in children?
Minimal change glomerulnephritis- generalised oedema, usually no progression to renal failure, no scarring, responsive to steroids but may recur.
Describe focal segmental glomerulosclerosis
Nephrotic syndrome seen in adults, less responsive to steroids, focal (less than 50% of glomeruli) and segmental (involving part of glomerular tuft) scarring seen, as damage resulted in collagen depostion, scars contain Ig and complement. Circulating factor causing podocyte damage. Progression to renal failure. Disease can recur after renal transplantation.
Describe membranous glomerulonephritis
Most common cause of nephrotic syndrome in adults. Immune complex (antibody-antigen complexes) deposition on outside of BM (sub-epithelial). Most primary causes AI, may be secondary e.g. lymphoma. Minority develop end-stage renal disease.
Describe IgA nephropathy (Berger’s disease)
Most common primary (only kidneys affected) glomerular disease. Mesangial damage causes inflammation as IgA deposited there. IgA able to enter mesangium easily as doesn’t have to pass through the BM. Classic presentation= young man who develops macroscopic haematuria 1-2 days after an upper RT infection. IgA= protects against mucosal infection, so when an infection, more IgA produced, so more deposited in mesangium, so patient may experience haematuria when they have a cold. Causes renal failure. Give supportive treatment.
Relationship of ureters to bifurcation of common iliac artery?
Ureters cross pelvic brim at this point. Area of ureteric constriction- susceptible to renal stones
Describe classification of glomerular pathology in terms of glomeruli affected
A focal glomerulonephritis affects some (<50%) but not all the glomeruli, a diffuse glomerulonephritis affects all the glomeruli. A segmental glomerulonephritis affects just a portion within the affected glomeruli (part f glomerular capillary tuft), a global glomerulonephritis affects all portions of affected glomeruli.
Why is goodpasture’s syndrome associated with haemoptysis aswell as haematuria?
Autoantibodies to collagen IV bind to the glomerular BM and destroy it so filtration is blocked. Glomerular BM very similar to alveolar BM, so autoantibodies also target the lung BM, causing pulmonary haemorrage and haemoptysis.
Presentation of a patient with prostate cancer?
Typically asymptomatic
Lower urinary tract symptoms
of obstruction
Less common=symptoms of metastatic spread e.g. back pain, anaemia or weight loss.
What are the problems of treating well people for prostate cancer?
Urinary incontinence
Erectile dysfunction
How do we diagnose prostate cancer?
Raised prostate specific antigen in serum, digital rectal exam, transrectal ultrasound-guided needle biospy- histological apperance gives Gleason score, also staged using TNM
What role does somatic NS have in urinary voiding?
Reduced activity, resulting in reduced muscle tone of external urethral sphincter. As intravesical pressure increases, this can overcome tone of sphincter, hence urine is voided.
Why might a patient be more susceptible to an upper UTI during pregnancy?
In pregnancy, the tone of the ureters is lowered and they may become dilated. This makes it more common for infection to ascend to the upper tract from the bladder during pregnancy
What are the 4 renal cortical compartments?
Glomerular
Vascular
Tubular
Interstitial
What is usually the 1st part of the kidney that goes wrong when there is a problem with the kidney?
PCT- as this is a region of very high metabolic activity
Function of the mesangium?
Maintains glomerulus and glomerular BM, provides nutrients to glomerulus, supports the glomerular capillaries
How is the lamina densa, a part of the glomerular BM, specialised for selective filtration?
It gives charge as electron dense layer, so repels proteins with the same charge.
How do the lamina rara interna and externa contribute to selective filtration of glomerular BM?
They have lots of interdigitating processes, forming a net
How is the nephron a functional unit?
Blood supply leaving glomerulus goes on to supply rest of nephron, and anything abnormally filtered by the glomerulus goes on through the nephron, e.g. lots of protein- directly toxic to rest of nephron.
Minimal change nephritis is associated with atopy in children, what is atopy and give 3 examples
A genetic predisposition to develop allergic reactions (hypersensitivity reactions) to common environmental antigens.
Examples: asthma, eczema, hayfever
Why is diabetes mellitus a secondary cause of proteinuria?
Damage to microvasculature. Abnormal material deposited in glomerular BM itself, and mesangium, causing mesangial sclerosis, forming nodules, so its function to maintain the BM and podocytes is impaired, so filter leak, proteins enter urine.
Thickened BM as material depos. here, so electron density disrupted, less able to repel proteins?
Describe the use of ACE inhibitors in the treatment of hypertension
Inhibit Ang II production, hence reduce intraglomerular pressure by dilating efferent arterioles more than afferent arterioles, reducing proteinuria and glomerulosclerosis. May cause hyperkalaemia as reduced aldosterone prodcution so less K+ excreted, and renal impairment if renal artery stenosis present. Also, ACE degrades bradykinin, so ACIs result in high bradykinin, which can cause a cough.
What is oilguria?
Less than 500ml of urine per day, or less than 20 ml per hour
What is anuria?
no urine, defined as less than 100 ml of urine per day.
usually indicates a blockage of urine flow
What are red cell casts in the urine diagnostic of?
glomerular disease
If pre-renal kidney injury, what is the fractional excretion on Na+?
<1%
How are calcium levels affected by change in acid-base status?
If acidosis, H+ binds to proteins so there is an increase in free Ca2+ with less bound Ca2+. Opposite in alkalosis where Ca2+ bound to plasma proteins and taken up by bone, causing hypocalcaemia which can cause life-threatening tetany, espec. if respiratory muscle affected.
Which part of the kidney is most vulnerable to ischaemia and why?
Medulla
Only receives its blood supply from vasa recta which descend from cortex into medulla
Which cells are damaged in acute tubular necrosis?
The epithelial cells lining the tubules
What does small renal size on ultrasound suggest?
Chronic kidney failure
Major immediate complications of acute renal failure?
Hyperkalaemia
Acidosis
Pulmonary oedema
Arise from loss of normal renal capacity to excrete K+, H+ and water
Main features distinguishing acute from chronic renal failure?
Chronic- decrease in GFR over mnths to yrs, rather than days.
Chronic RF complications e.g.bone disease
Size of kidneys- normal in acute, small in chronic
