Gastrointestinal and Renal Histology

Histology, Lecture 4. This lecture covers the microscopic structure of the gastrointestinal tract from oesophagus to large intestine, the liver and pancreas, and the kidney, with clinicopathological correlations.

GI TRACT GENERAL STRUCTURE

The gastrointestinal tract is a hollow tube with a consistent four-layer wall structure throughout its length. From lumen outward: (1) Mucosa: the innermost layer, comprising epithelium (varies by region), lamina propria (loose connective tissue containing blood capillaries, lymphatics, immune cells including plasma cells and lymphoid follicles), and muscularis mucosae (thin inner layer of smooth muscle whose contraction creates mucosal folds). (2) Submucosa: loose connective tissue with larger blood vessels, lymphatics, and the submucosal (Meissner's) nerve plexus, which regulates secretion. (3) Muscularis externa: two layers of smooth muscle — inner circular and outer longitudinal; the myenteric (Auerbach's) plexus lies between them, co-ordinating peristalsis. Loss of Auerbach's plexus neurons (as in Hirschsprung's disease — congenital aganglionosis) causes functional obstruction. (4) Serosa or adventitia: the outermost layer; serosa is a mesothelium-covered layer present where the gut is intraperitoneal (most of the small intestine, transverse colon); adventitia is loose connective tissue without mesothelium, present in retroperitoneal segments (oesophagus, duodenum, ascending and descending colon).

REGIONAL SPECIALISATION

Oesophagus: mucosa lined by stratified squamous non-keratinised epithelium throughout — adapted to withstand mechanical abrasion from food. The muscularis externa is unique: upper third is skeletal muscle, lower third is smooth muscle, middle third is mixed. The lower oesophageal sphincter is physiological (identifiable functionally but not as a distinct anatomical sphincter on histology). Oesophageal glands (mucous) are in the submucosa and lamina propria. Barrett's oesophagus: metaplastic replacement of squamous epithelium by columnar (intestinal-type) epithelium due to chronic acid reflux — visible as pink columnar mucosa on endoscopy; a premalignant condition.

Stomach: gastric pits open into the mucosa; gastric glands extend into the lamina propria. Cell types in fundic glands (body/fundus): (a) Parietal (oxyntic) cells — large, eosinophilic (abundant mitochondria and intracellular canaliculi), basally located; secrete HCl (via H+/K+-ATPase) and intrinsic factor (essential for vitamin B12 absorption); targeted by proton pump inhibitors. (b) Chief (peptic/zymogenic) cells — basophilic (abundant RER), located in the deeper gland; secrete pepsinogen (inactive zymogen, cleaved by HCl to pepsin); also secrete gastric lipase. (c) G cells — enteroendocrine cells in antral glands; secrete gastrin (stimulates parietal cells and gastric motility). (d) Mucous neck cells — secrete acidic mucus in the neck region of fundic glands. Surface mucous cells: line the gastric pits and surface; secrete alkaline mucus protecting the epithelium from HCl. Helicobacter pylori infection: colonises the mucous layer; produces urease; causes chronic active gastritis (neutrophilic infiltration of lamina propria and pits); predisposes to peptic ulcer disease and gastric adenocarcinoma.

Duodenum: villi (finger-like projections of mucosa into the lumen, increasing surface area) covered by columnar enterocytes with a brush border (microvilli — further amplifying surface area); crypts of Lieberkühn (intestinal glands between villi): contain Paneth cells (secretory granules containing defensins and lysozyme — antimicrobial), enteroendocrine cells (S cells secreting secretin; CCK cells secreting cholecystokinin), and stem cells (base of crypt). Distinctive feature: Brunner's glands (submucosal mucous glands, unique to duodenum) — secrete bicarbonate-rich alkaline mucus neutralising gastric acid entering the duodenum.

Jejunum: tallest villi of the entire GI tract (maximising absorptive surface); deepest crypts; large numbers of goblet cells; no Brunner's glands. The most active site of nutrient absorption.

Ileum: shorter villi than jejunum; increased numbers of goblet cells; Peyer's patches — large organised mucosal lymphoid aggregates (B-cell follicles with germinal centres + T-cell zones + specialised M cells overlying follicles that sample luminal antigens); unique role in immune surveillance. Ileum is the site of vitamin B12-intrinsic factor complex absorption (terminal ileum, via cubilin receptor) and bile acid reabsorption.

Large intestine (colon): no villi; no Paneth cells; no Brunner's glands. Features: abundant goblet cells (mucus production for lubrication); deep straight crypts (tubular glands) without villi; enteroendocrine cells. Taeniae coli: three thickened longitudinal bands of the outer muscular layer (the rest of the outer longitudinal muscle is thin between the taeniae). Haustra: sacculations caused by the taeniae being shorter than the tube between them. Appendix: abundant lymphoid follicles in the mucosa and submucosa (making it a lymphoid organ); crypts present; no villi.

LIVER HISTOLOGY

The liver is organised into hepatic lobules (hexagonal units visible on H&E) centred on a central vein (terminal hepatic venule), with portal triads at the corners of the hexagon. Each portal triad contains: a portal venule (branch of portal vein), a hepatic arteriole (branch of hepatic artery), and a bile duct (lined by cholangiocytes). Blood flows from portal triads → hepatic sinusoids → central vein → hepatic veins → inferior vena cava. Hepatic sinusoids are specialised sinusoidal capillaries lined by fenestrated endothelium (no continuous basal lamina, allowing direct contact between blood and hepatocytes via the Space of Disse).

Hepatocytes: the functional cells of the liver; polyhedral, acidophilic (pink, abundant mitochondria and RER); may be binucleate (polyploid — normal); contain glycogen granules (PAS-positive); smooth ER prominent for lipid metabolism and drug detoxification. Hepatocyte plates (one-two cells thick) radiate from central vein to portal triads.

Specialised cells in sinusoids: Kupffer cells — resident hepatic macrophages lining sinusoids; phagocytose bacteria, debris, and aged red cells. Hepatic stellate cells (Ito cells, perisinusoidal cells) — located in the Space of Disse; in normal liver, store vitamin A (retinoid) as lipid droplets; activated by chronic injury → transdifferentiate into myofibroblasts → synthesise collagen → hepatic fibrosis and cirrhosis.

Hepatic acinus (Rappaport's functional unit): an oval unit organised around the terminal portal arteriole and venule, comprising cells from adjacent lobules. Divided into three zones by proximity to blood supply: Zone 1 (periportal) — receives blood first, richest in O2 and nutrients, first to regenerate after injury, first to show features of toxic injury from portal blood (e.g., phosphorus, iron poisoning affect zone 1); Zone 2 (mid-zone); Zone 3 (pericentral/centrilobular) — receives blood last, lowest O2 tension, highest concentration of drug-metabolising enzymes (CYP450 — toxicity from activated toxic metabolites), most susceptible to ischaemia and hypoxic injury (e.g., right heart failure, shock → centrilobular (zone 3) necrosis), and is the site of fatty change in alcoholic liver disease.

PANCREAS

Exocrine pancreas (approximately 99% of pancreatic mass): acinar cells — pyramid-shaped, intensely basophilic (abundant RER for enzyme synthesis), with apical eosinophilic zymogen granules (contain inactive zymogens — trypsinogen, chymotrypsinogen, proelastase, prophospholipase, prolipase, amylase). Intercalated ducts drain acini; centroacinar cells (pale cells within acini at the origin of intercalated ducts) secrete bicarbonate. Acute pancreatitis: acinar cell injury releases activated proteases → auto-digestion; haemorrhagic pancreatitis shows fat necrosis (saponification — calcium soap deposits, chalky white areas) and haemorrhage on gross examination; histologically: acinar cell necrosis, interstitial oedema, inflammatory infiltrate.

Endocrine pancreas — islets of Langerhans: compact clusters of pale-staining cells scattered throughout the exocrine pancreas (approximately 1-2% of pancreatic mass). Four main cell types: alpha (A) cells — glucagon secretion; beta (B) cells — insulin secretion (most abundant, in centre of islet); delta (D) cells — somatostatin (inhibits both alpha and beta cells); PP (pancreatic polypeptide) cells. On immunohistochemistry these cell types are identified by specific antibodies. In type 1 diabetes: autoimmune destruction of beta cells; islets show insulitis (lymphocytic infiltration) in early disease, eventual ghost islets with reduced cell mass. Type 2 diabetes: islet amyloid polypeptide (IAPP) deposition, amyloid replacing beta cells.

RENAL HISTOLOGY

Renal cortex: contains renal corpuscles (glomeruli), proximal convoluted tubules (PCTs), distal convoluted tubules (DCTs), and peritubular capillaries. Renal medulla: contains loops of Henle (thin descending and ascending limbs, thick ascending limb) and collecting ducts converging toward the renal papilla. Renal columns (of Bertin) are cortical tissue projecting between medullary pyramids.

Glomerulus: the filtration unit. Components of the glomerular filtration barrier: (1) Fenestrated glomerular capillary endothelium — large fenestrae (70-100 nm) without diaphragms; first barrier to cells. (2) Glomerular basement membrane (GBM) — thick (approximately 300-350 nm in adults), composed of type IV collagen, laminin, and negatively charged proteoglycans (heparan sulphate) that repel negatively charged proteins (albumin). Thickened in diabetic nephropathy. (3) Podocytes (visceral epithelial cells) — highly specialised cells with long cytoplasmic extensions (primary processes) branching into secondary foot processes that wrap around the capillaries; foot processes from adjacent podocytes interdigitate, separated by slit pores bridged by the slit diaphragm (composed of nephrin, podocin — mutations cause congenital nephrotic syndrome). Mesangial cells: stellate-shaped cells in the centre of the glomerular tuft, not part of the filtration barrier; provide structural support; phagocytose immune complexes; contract in response to vasoactive agents.

Juxtaglomerular apparatus (JGA): a specialised structure at the vascular pole of the glomerulus. Macula densa: a plaque of densely packed DCT cells that sense tubular NaCl concentration and signal to the JGA. Juxtaglomerular (JG) cells: modified smooth muscle cells in the wall of the afferent arteriole; contain renin-secreting granules; release renin in response to reduced renal perfusion pressure (sensed by baroreceptors in the afferent arteriole wall) or macula densa signalling (low NaCl). Extraglomerular mesangial cells (Lacis cells) are also present.

Renal pathology: diabetic nephropathy — early: thickening of the GBM, mesangial expansion (increased matrix); advanced: Kimmelstiel-Wilson nodules (nodular glomerulosclerosis — PAS-positive acellular deposits in mesangium, named after the first describers); eventually diffuse glomerulosclerosis. Minimal change disease (MCD): the most common cause of nephrotic syndrome in children; light microscopy shows normal-appearing glomeruli; electron microscopy shows diffuse effacement (fusion) of podocyte foot processes — the diagnostic hallmark; caused by T-cell dysregulation affecting slit diaphragm integrity; responds well to corticosteroids.