Ureters
A 25-30 cm muscular tube that pushes urine to the bladder in waves, is narrow at three points, and reports essentially only stretch — so most of what goes wrong with it is either something blocking it or urine heading the wrong way.
What it normally does
The renal pelvis has its own pacemaker cells. They fire spontaneously about every 10-30 seconds (roughly 2-6 waves a minute) and send a squeezing wave down the ureter (peristalsis). The wave spreads muscle cell to muscle cell through gap junctions, each contraction driven by calcium entering through L-type calcium channels, and it is turned up by noradrenaline acting on alpha-1 adrenoceptors (alpha-1A and alpha-1D), which are densest in the lower third. At ordinary urine flows the bladder receives boluses rather than a continuous stream; in a large diuresis the ureter fills and flow becomes more continuous.
Explains why obstruction hurts in waves, why a segment that cannot conduct the wave obstructs, and why relaxing the lower ureter with an alpha-1 blocker can help a stone through.
The tube is narrow at three points: where the renal pelvis funnels into it (pelviureteric junction), where it crosses the pelvic brim over the iliac vessels, and where it tunnels obliquely through the bladder wall (vesicoureteric junction, a few millimetres across and the tightest of the three). In women it runs within about 2 cm of the cervix, passing under the uterine artery.
Explains where stones lodge, and where pelvic tumours and pelvic surgery catch the ureter.
The last 1-2 cm runs at a slant between the bladder muscle and its lining. There is no true anatomical sphincter here — the pressure of a filling or contracting bladder squashes that tunnel flat against the muscle. It is a one-way flap valve made mostly of geometry.
Explains how infected urine gets driven back up to the kidney when the tunnel is too short.
The ureter reports essentially only stretch (and the chemical mediators released when it is stretched). Its sensory fibres run back with the sympathetics into the spinal cord at T11-L2 — the same segments that supply the flank, groin, scrotum and labium — so the brain refers the pain there (visceral referred pain), and the patient cannot localise it precisely.
Explains loin-to-groin pain that migrates as the stone descends, and why the patient cannot find a position that helps.
What goes wrong
- Ureteric stone (renal colic)← from “The ureter reports essentially only stretch (a…”
A stone formed in the kidney drops into the ureter and jams at one of the three narrowings. Urine keeps being made, so pressure builds behind it: the pelvis and ureter distend and the muscle contracts harder against a closed tube. In the first hour or two prostaglandins released by the stretched wall dilate the afferent arteriole, so filtration keeps pouring into a system that cannot empty and the distension gets worse (renal blood flow falls again later in sustained obstruction). Stretched receptors fire into T11-L2 and the pain is referred to flank and groin. The pain is pressure, not scratching — which is why it comes in waves and why dropping the pressure stops it.
About 1 in 10 Australians form a stone in their lifetime, peaking in summer and in outdoor workers in the north — heat and low urine volume. Stones under 5 mm pass spontaneously roughly 70-80% of the time; stones over 10 mm usually will not, and generally need intervention.
You would find: Sudden severe one-sided loin-to-groin pain, often waking the patient, with vomiting and sweating, and a patient who rolls around and cannot get comfortable. Dipstick shows non-visible haematuria in roughly 80-90% — so a clean dipstick does not exclude a stone. Non-contrast CT KUB is the diagnostic test of choice in adults; ultrasound comes first in pregnancy and in children. When the stone reaches the vesicoureteric junction the pain moves into the groin or testis and brings frequency and urgency.
- Obstructed infected kidney (infected obstructed system, pyonephrosis)← from “The renal pelvis has its own pacemaker cells. …”
Peristalsis normally keeps the upper tract flushed and sterile. Block it and the urine above the stone becomes a stagnant closed space under pressure. Bacteria multiply, pus fills the collecting system, and the pressure collapses the surrounding capillaries so white cells and antibiotics reach it poorly. Bacteria and endotoxin are instead squeezed back into the venous blood (pyelovenous backflow) and the patient can become septic within hours.
Fever plus obstruction equals drainage. Treating an obstructed infected kidney with antibiotics alone is the classic fatal error.
You would find: Colic plus fever, rigors, tachycardia and falling blood pressure. Ultrasound shows hydronephrosis with a stone; pyuria, raised CRP and lactate. This is a urological emergency: percutaneous nephrostomy or retrograde stent within hours, with antibiotics as support, not as the treatment.
- Vesicoureteric reflux and reflux nephropathy← from “The last 1-2 cm runs at a slant between the bl…”
If the intramural tunnel is too short, or its opening sits too far laterally, the flap valve does not close when the bladder contracts. Urine — and whatever bacteria are in it — is driven back up to the renal pelvis, and at the gaping compound papillae of the poles it can track into the collecting ducts (intrarenal reflux). Repeated infected reflux scars the kidney. Scarred kidneys release renin and the lost nephrons cannot be replaced, so hypertension and chronic kidney disease can appear decades later.
Most mild reflux resolves by itself as the child grows and the tunnel lengthens. Kidney failure needing dialysis is several times more common in Aboriginal and Torres Strait Islander Australians, and higher again in remote communities — take a febrile UTI in a child seriously, and check the blood pressure and urine of the adult.
You would find: Recurrent febrile UTI in an infant or young child. Ultrasound shows dilated ureters, MCUG grades the reflux, DMSA shows the scars. Years on it presents as hypertension or proteinuria in a young adult with small scarred kidneys.
- Pelviureteric junction obstruction← from “The renal pelvis has its own pacemaker cells. …”
A short segment at the pelviureteric junction has too little muscle and too few gap junctions, or is kinked by a crossing lower-pole artery, so the peristaltic wave dies there. Urine only trickles through. The pelvis balloons while the ureter below stays normal calibre. At ordinary urine flows it may be silent; produce a big diuresis and the pelvis cannot empty fast enough, so pressure and pain spike.
Dilated pelvis with a normal ureter means the block is at the top. Dilated pelvis with a dilated ureter means the block is at the bottom.
You would find: Intermittent loin pain and vomiting an hour or two after a large drink, beer or coffee, relieved by a big void (Dietl crisis). Ultrasound shows a dilated pelvis with a normal ureter. A MAG3 diuresis renogram shows tracer sitting in the pelvis and failing to clear after frusemide. It is also the commonest obstructive cause of hydronephrosis found on antenatal ultrasound, though most antenatal pelvic dilatation is transient and never obstructs.
- Extrinsic obstruction and obstructive acute kidney injury← from “The tube is narrow at three points: where the …”
Because the ureter crosses the pelvic brim and runs through the retroperitoneum beside the cervix, disease outside it compresses it: cervical, prostate, bladder and colorectal cancer, enlarged nodes, retroperitoneal fibrosis, or a ligature at hysterectomy. The squeeze is gradual, so the wall stretches instead of spasming and there is usually no colic. If both ureters are caught the patient can become anuric and uraemic with little or no pain. After decompression the retained sodium and urea drag out a large diuresis (post-obstructive diuresis) and pressure-damaged tubules cannot concentrate urine.
Painless anuria with bilateral hydronephrosis on ultrasound is obstruction until proven otherwise. Any acute kidney injury without an obvious cause gets a renal tract ultrasound, because this is the cause you can reverse in an afternoon.
You would find: Rising creatinine with little or no urine, no pain, and bilateral hydronephrosis on ultrasound. After stenting or nephrostomy, watch for litres of dilute urine with salt and water depletion, hypovolaemia and falling potassium and magnesium.
What we give, and how it works
Open a drug to see what it binds, what that does to the cell, and what you then see in the patient.
- Binds
- Cyclo-oxygenase (COX-1 and COX-2) inside the cell.
- Which does
- Blocks conversion of arachidonic acid to prostaglandins, so PGE2 production in the kidney and in the ureteric wall falls.
- So you see
- The afferent arteriole loses its prostaglandin-driven dilatation, so renal blood flow and filtration into the obstructed system fall and the pressure behind the stone drops. Less PGE2 also means less ureteric contractile activity and less sensitisation of the stretch afferents. The pain settles without sedating the patient.
- And the same mechanism causes
- Those same prostaglandins are what hold the afferent arteriole open when renal perfusion is threatened. In a vomiting, dehydrated patient with an already obstructed kidney, removing them drops GFR — the drug that fixes the pain can precipitate acute kidney injury.
- Handling
- If pain persists despite an adequate NSAID, suspect unrelieved obstruction or infection rather than undertreated pain.
Catches people out: A poor choice where renal perfusion is already prostaglandin-dependent: existing kidney impairment, hypovolaemia, or a single functioning kidney. The same COX-1 block strips gastric mucosal prostaglandins and can cause ulcers and bleeding. An opioid is the usual second-line add-on; pethidine is not recommended in Australia because its metabolite norpethidine accumulates and can cause seizures.
- Binds
- Alpha-1A (and alpha-1D) adrenoceptors on ureteric smooth muscle, densest in the distal third.
- Which does
- Blocks noradrenaline at a Gq-coupled receptor, so phospholipase C is not activated, IP3 falls, less calcium is released from the sarcoplasmic reticulum, and the muscle relaxes.
- So you see
- Resting tone and contraction force in the distal ureter fall while peristalsis above keeps pushing. The lumen around the stone widens, so it is more likely to pass and passes with less pain.
- And the same mechanism causes
- Alpha-1 receptors also hold tone in arteriolar smooth muscle (mostly the alpha-1B subtype) and at the bladder neck. Subtype-selective drugs cause less postural hypotension than non-selective ones, but dizziness on standing still happens. Ejaculatory dysfunction is common: with alpha-1A blockade the ejaculate is reduced or absent, mostly because seminal emission from the vas and seminal vesicles fails rather than because semen truly flows back into the bladder.
- Handling
- Alpha-1A also drives the iris dilator — the ophthalmologist needs to know before cataract surgery (intraoperative floppy iris syndrome).
Catches people out: Be honest about the size of the benefit: it is modest and largely confined to larger distal stones. The large SUSPEND trial found no overall benefit for stones up to 10 mm, and trials show little for stones under 5 mm, which usually pass on their own. Non-selective alpha-1 blockers such as prazosin are not the drugs used for this — they block alpha-1B in resistance vessels as well and can drop the blood pressure of an already vomiting, dehydrated patient.
- Binds
- The bacterial 30S ribosomal subunit; the useful spectrum is aerobic gram-negative organisms.
- Which does
- Binds essentially irreversibly and makes the ribosome misread mRNA, producing faulty membrane proteins. Getting into the bacterium needs oxygen and a membrane potential, so it works poorly in the acidic, anaerobic pus of an obstructed collecting system.
- So you see
- Fast, concentration-dependent bactericidal clearance of gram-negative bacteraemia, which buys time — but the obstructed kidney keeps seeding the blood until it is drained by nephrostomy or stent.
- And the same mechanism causes
- The same drug is taken up into proximal tubular cells by megalin-mediated endocytosis and into cochlear and vestibular hair cells, where it accumulates and kills them: non-oliguric acute kidney injury (usually reversible) and deafness or unsteadiness that often is not.
Catches people out: This is a nephrotoxin in a patient who already has an obstructed kidney — short courses with monitored levels, and the obstruction relieved.
- Binds
- Bacterial dihydrofolate reductase.
- Which does
- Blocks reduction of dihydrofolate to tetrahydrofolate, so the bacterium cannot make thymidylate and stops dividing (bacteriostatic). The drug is concentrated in urine, which is exactly where it is needed.
- So you see
- Fewer febrile UTIs while the child grows, the intramural tunnel lengthens and the flap valve becomes competent on its own. Fewer recurrences is the demonstrated benefit — not fewer scars.
- And the same mechanism causes
- Trimethoprim is structurally like amiloride and blocks the same ENaC sodium channel in the distal nephron. Sodium stays in the lumen, the electrical gradient driving potassium secretion collapses, and potassium rises. It also blocks OCT2, a transporter that secretes creatinine, so serum creatinine climbs with no change in GFR.
- Handling
- A creatinine that rises within days of starting trimethoprim and falls on stopping is usually a transporter effect rather than kidney injury.
Catches people out: The hyperkalaemia bites in adults on an ACE inhibitor or spironolactone far more than in a well child. Agent choice depends on age — cefalexin is the usual option in the first months of life, where trimethoprim and nitrofurantoin are avoided — and any prophylaxis selects for resistant organisms.
A patient who writhes typically has colic; a patient who lies dead still is more likely to have peritonitis. And colic plus fever means decompress — pus behind a stone behaves like a closed abscess that antibiotics alone will not clear.
Now test whether it stuck
Reading this through is not the same as being able to reconstruct it. Every question in the bank is free, with a full debrief on each option.