Kidney and bladder histology
Kidney, ureter and bladder histology
Each segment of the nephron has an epithelium built for its job, from the leaky filtration barrier to the brush-bordered proximal tubule and the hormone-controlled collecting duct, while the urinary passages are lined by a stretchy, impermeable urothelium. These structures explain obstetric renal problems such as acute tubular necrosis after haemorrhage, pre-eclampsia and the dilated ureters of pregnancy.
Glomerulus and filtration barrier
- Bowman's capsule: the parietal layer is simple squamous epithelium; the visceral layer is podocytes. Crescents in rapidly progressive glomerulonephritis form from parietal cells in Bowman's space.
- Barrier, from blood to urine: fenestrated endothelium, glomerular basement membrane (type IV collagen, negatively charged heparan sulphate), podocyte foot processes with slit diaphragms (nephrin, podocin).
- Foot process effacement gives proteinuria (minimal change disease, FSGS).
- Alport syndrome: defective type IV collagen alpha 3–5 chains (usually X-linked, COL4A5); the GBM is thinned and split; haematuria, deafness, eye lesions. Goodpasture antibodies attack the alpha 3 chain.
- Mesangial cells support the capillary loops, are contractile and phagocytic.
- Pre-eclampsia: glomerular endotheliosis, swollen endothelial cells occluding enlarged bloodless glomeruli, driven by excess sFlt-1 binding VEGF; it reverses after delivery and is not immune-complex disease.
Nephron segments
| Segment | Epithelium | Key features |
|---|---|---|
| Proximal convoluted tubule | Simple cuboidal with dense brush border | Many mitochondria, eosinophilic; reabsorbs about two-thirds of filtrate; longest segment (longer than the DCT) |
| Thin limbs | Simple squamous | Water (descending) and passive salt movement |
| Thick ascending limb | Cuboidal, no brush border | Na-K-2Cl transport; makes Tamm–Horsfall protein; impermeable to water |
| Distal convoluted tubule | Cuboidal, no brush border, clear lumen | Contains the macula densa |
| Collecting duct | Cuboidal to columnar, pale, clear cell borders | Principal and intercalated cells |
- Acute tubular necrosis after massive PPH with hypotension hits the proximal tubule and thick ascending limb (high oxygen demand); urine shows muddy brown granular casts. The most severe obstetric haemorrhage with DIC can cause bilateral renal cortical necrosis, which is often irreversible.
- Juxtamedullary nephrons have glomeruli near the medulla, long loops of Henle and vasa recta: they concentrate urine. Most nephrons are cortical with short loops.
Collecting duct cells
| Cell | Function | Disorder |
|---|---|---|
| Principal | Na reabsorption (ENaC), K secretion, water via aquaporin-2 under ADH | Lithium enters by ENaC and reduces aquaporin-2: nephrogenic diabetes insipidus, no response to desmopressin |
| Type A intercalated | Secrete H+ | Failure: distal (type 1) RTA, urine pH above 5.5, hypokalaemia, stones (for example Sjögren syndrome) |
| Type B intercalated | Secrete bicarbonate | Alkalosis handling |
Juxtaglomerular apparatus
| Component | Nature | Role |
|---|---|---|
| Juxtaglomerular (granular) cells | Modified smooth muscle of the afferent arteriole | Secrete renin |
| Macula densa | Tall crowded cells of the distal tubule where it touches its own glomerulus | Sense tubular NaCl; tubuloglomerular feedback |
| Extraglomerular mesangial (lacis) cells | Between the arterioles | Signal transfer |
- The juxtaglomerular apparatus is not the same as juxtamedullary nephrons.
Urothelium
- Transitional epithelium (urothelium) lines the renal pelvis, ureter, bladder and proximal urethra. Its dome-shaped umbrella cells change shape as the bladder fills.
- The apical membrane is an asymmetric unit membrane of rigid uroplakin plaques joined by hinges; in the empty bladder plaques fold into vesicles. It forms an impermeable barrier to urine, and uroplakin is a marker of urothelial origin in metastatic carcinoma.
- Origin: bladder epithelium is endoderm of the urogenital sinus; the trigone is first mesodermal (mesonephric ducts) and later covered by endoderm.
- Chronic irritation (long-term catheter, stones, infection, schistosomiasis) causes keratinising squamous metaplasia and risk of squamous cell carcinoma. Most bladder cancers, however, are urothelial, linked to smoking and aromatic amines in dye and rubber industries.
Ureter
- Small star-shaped lumen lined by urothelium; muscle is the reverse of the gut: inner longitudinal, outer circular in the upper two-thirds, with a third outer longitudinal layer in the lower third; outer adventitia. No muscularis mucosae and no submucosa.
- Peristalsis, not gravity, drives urine.
- Pregnancy: dilatation of the pelvis and ureter begins in the first trimester because progesterone relaxes ureteric smooth muscle; later the enlarged uterus compresses the ureter at the brim, more on the right. Stasis raises the risk of pyelonephritis.
Bladder and urethra
- Mucosa thrown into folds when empty, except the trigone, where mucosa is firmly bound to muscle and always smooth. Smooth mucosa elsewhere in an empty bladder may hide carcinoma in situ.
- Detrusor: interlacing smooth muscle bundles (often described as three layers), not separate sheets like the gut.
- Female urethra: urothelium proximally, non-keratinised stratified squamous distally and at the meatus; the lining is oestrogen sensitive. Distal urethral carcinoma is therefore usually squamous; a urethral caruncle is an inflamed vascular polyp at the meatus.
- Skene (paraurethral) glands open near the meatus.
Remember Brush border means proximal tubule; uroplakin plaques on umbrella cells mean urothelium; three muscle layers in a ureter mean its lower third.
Exam trap The parietal layer of Bowman's capsule is simple squamous; the visceral layer is podocytes.
Exam trap Ureteric muscle has longitudinal inside and circular outside, the reverse of the gut.
Test yourself on this topic
5 of the 16 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
At cystoscopy of an empty bladder, the mucosa is thrown into folds everywhere except for a smooth triangular area between the two ureteric openings and the internal urethral orifice. Why is this area smooth?
Answer: Mucosa is firmly bound to the muscle
In most of the bladder the mucosa lies on a loose lamina propria and submucosa, so it folds (rugae) when the bladder is empty. In the trigone the mucosa is firmly attached to the underlying muscle, so it stays smooth whether the bladder is full or empty. The trigone develops from the incorporated ends of the mesonephric ducts, though it is soon covered by urothelium from the urogenital sinus.
Trigone
- Between ureteric orifices and urethra
- Mucosa firmly adherent
- Stays smooth when empty
- Origin: mesonephric ducts
Remember The trigone never wrinkles.
Exam trap Smooth mucosa outside the trigone in an empty bladder is abnormal and may hide carcinoma in situ.
Why the other options are wrong
- It lacks a urothelial lining The trigone is lined by urothelium.
- It is covered by squamous epithelium Squamous metaplasia here is an occasional variant, not the reason.
- It contains no lamina propria vessels It has vessels like the rest of the mucosa.
- It is lined by columnar epithelium Not its normal lining.
A 34-year-old woman has a massive postpartum haemorrhage with hours of hypotension. Over the next days her urine output falls and creatinine rises; urine shows muddy brown granular casts. Which tubular segment, with tall cuboidal cells bearing a dense brush border and abundant mitochondria, is most damaged?
Answer: Proximal convoluted tubule
The proximal tubule, lined by cuboidal cells with a microvillous brush border and many mitochondria for active reabsorption, has very high oxygen demand. Together with the medullary thick ascending limb, it is the segment most vulnerable to ischaemia. Prolonged hypotension causes ischaemic acute tubular necrosis: cells lose their brush border and slough into the lumen, forming granular casts and blocking flow.
Ischaemic ATN
- Most hit: proximal tubule (and thick ascending limb)
- Brush border, many mitochondria
- High oxygen demand
- Muddy brown casts
Remember The hardest-working cells die first.
Exam trap Bilateral renal cortical necrosis, not ATN, follows the most severe obstetric haemorrhage with DIC.
Why the other options are wrong
- Thin descending limb Thin, flat cells with low metabolic needs.
- Collecting duct Relatively resistant to ischaemia.
- Distal convoluted tubule Less vulnerable than the proximal tubule.
- Parietal Bowman capsule Not part of the tubule.
Electron microscopy of the luminal surface of bladder urothelium shows large surface cells whose apical membrane is unusually thick, stiff and arranged in rigid plaques joined by hinge regions. What gives the membrane this structure?
Answer: Uroplakin plaques
The umbrella (superficial) cells of the urothelium have an asymmetric unit membrane: rigid plaques made of uroplakin proteins separated by flexible hinge areas. The plaques form a permeability barrier against urine, and when the bladder fills they unfold from intracellular vesicles into the surface, increasing surface area. This explains the thick, darkly staining luminal membrane seen in light microscopy.
Umbrella cells
- Asymmetric unit membrane
- Made of uroplakin plaques
- Barrier to urine
- Plaques fold away into vesicles when empty
Remember Uroplakins make urothelium watertight.
Exam trap Uroplakins are a useful immunostain marker of urothelial origin in metastatic carcinoma.
Why the other options are wrong
- Keratin filaments Urothelium is not keratinised normally.
- Microvilli Characteristic of the proximal tubule brush border.
- Stereocilia Found in the epididymis, not the bladder.
- Glycogen granules Not responsible for the membrane plaques.
A 22-year-old woman has persistent microscopic haematuria and mild proteinuria. Her brother and maternal uncle needed dialysis in their thirties and are deaf. Electron microscopy of her renal biopsy shows thinning and splitting of the glomerular basement membrane. Which component of the membrane is defective?
Answer: Type IV collagen α3–α5 chains
This is Alport syndrome, usually X-linked, caused by mutations in the COL4A5 gene encoding the α5 chain of type IV collagen. The α3-α4-α5 network is needed in the glomerular basement membrane, the cochlea and the lens. Defects give a thin, split, basket-weave GBM, haematuria progressing to renal failure, sensorineural deafness and eye lesions. Female carriers usually have milder disease.
Alport syndrome
- Type IV collagen α3–α5
- Usually X-linked (COL4A5)
- GBM split, basket-weave
- Haematuria, deafness, eye lesions
Remember Kidney plus ears plus eyes: think type IV collagen.
Exam trap Goodpasture antibodies target the same collagen chain (α3), but as an autoimmune attack, not a mutation.
Why the other options are wrong
- Type I collagen Found in bone, skin and tendon, not the GBM network.
- Heparan sulphate proteoglycan Gives charge selectivity; not the Alport defect.
- Nephrin of podocyte slits Mutated in congenital nephrotic syndrome of Finnish type.
- Fibrillin-1 microfibrils Defective in Marfan syndrome.
A 30-year-old woman with bipolar disorder has taken lithium for years. She passes 5 litres of dilute urine daily, and urine osmolality does not rise after desmopressin. On which collecting duct cells does lithium act to cause this?
Answer: Principal cells
Principal cells of the collecting duct carry V2 receptors; ADH binding inserts aquaporin-2 channels into their apical membrane to reabsorb water. Lithium enters principal cells through epithelial sodium channels (ENaC), accumulates and interferes with V2 signalling and aquaporin-2 expression. The result is nephrogenic diabetes insipidus, which does not respond to desmopressin. Amiloride blocks ENaC and can reduce lithium entry.
Lithium nephrogenic DI
- Lithium enters via ENaC
- Acts on principal cells
- Less aquaporin-2
- No response to desmopressin
Remember Lithium sneaks into principal cells through ENaC.
Exam trap Failure to respond to desmopressin points to nephrogenic, not cranial, diabetes insipidus.
Why the other options are wrong
- Type A intercalated cells Secrete acid; not the site of ADH water handling.
- Macula densa cells Sense tubular chloride for feedback.
- Juxtaglomerular cells Secrete renin.
- Proximal tubule cells Not the target of lithium's water effect.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Histology, Kidney, ureter and bladder histology