Unit 11 — Digestive Glands · Question Bank

The liver weighs about 1.5 kg and runs the body's central biochemistry — plasma-protein synthesis, glycogen storage, detoxification of drugs and hormones, bile production and filtration of incoming gut blood. To accomplish all of that, its tissue is built from one repeating module: the classic hepatic lobule. The examiner is testing whether you can describe both its three-dimensional shape and the cell-level architecture that gives the liver its functions.

Overall shape

The classic lobule is a hexagonal prism, roughly 1–2 mm across, with a central vein running along its long axis and six portal triads embedded in connective tissue at the corners. In most species lobules are demarcated by interlobular connective tissue septa, but in human liver the septa are sparse and the boundaries are imaginary lines drawn between adjacent triads.

Hepatic plates and hepatocytes

From the central vein, one-cell-thick plates of polygonal hepatocytes radiate outward like spokes on a wheel, anastomosing freely as they go. Each hepatocyte is about 20 µm across with one or two large central nuclei (binucleate and polyploid cells are normal here because hepatocytes routinely double their genome to keep up with biosynthetic demand). The cytoplasm is acidophilic with scattered basophilic patches of rough ER, and is packed with smooth ER (detoxification, lipid metabolism), about 2000 mitochondria, peroxisomes, Golgi apparatus, glycogen rosettes and small lipid droplets.

Sinusoids, space of Disse and resident cells

Between every pair of hepatic plates runs a hepatic sinusoid — a wide, irregular, discontinuous capillary lined by fenestrated endothelium with essentially no basal lamina. The leaky design lets plasma pour out and bathe the hepatocyte microvilli directly. The thin gap between the endothelium and the hepatocyte surface is the perisinusoidal space of Disse, where the actual metabolic exchange happens. Two specialised cells live with the sinusoid: Kupffer cells, fixed macrophages sitting in the sinusoidal lumen that phagocytose old red cells and gut-derived bacteria, and hepatic stellate (Ito) cells in the space of Disse that store vitamin A in lipid droplets and, in chronic injury, transform into fibrogenic myofibroblasts — the cellular engine of cirrhosis.

Bile canaliculi

On the opposite face of each hepatocyte, the apposed lateral plasma membranes of two adjacent cells form a tiny groove sealed by tight junctions and lined by microvilli — the bile canaliculus. It has no wall of its own and is too small to see on routine H&E, but is classically demonstrated by silver impregnation. Bile flows along the canaliculi centrifugally — outward, away from the central vein — into the canals of Hering at the lobular edge and then into the interlobular bile duct of the portal triad.

Portal triads at the corners

Each portal triad contains a branch of the hepatic artery (oxygen), a branch of the portal vein (nutrients from the gut) and an interlobular bile duct (drainage), commonly with a lymphatic. The hepatic artery and portal vein feed the sinusoids; the bile duct collects the bile coming the other way.

Directions of flow — the opposite-currents rule

Blood and bile run in opposite directions. Blood flows centripetally: portal vein + hepatic artery → sinusoids → central vein → sublobular vein → hepatic vein → IVC. Bile flows centrifugally: bile canaliculi → canals of Hering → interlobular bile duct → hepatic ducts. Holding these directions in your head is the easiest way to keep the lobule oriented under the microscope.

Clinical anchor

The architecture explains the disease. Damage to bile canaliculi or ducts traps bile and produces conjugated jaundice with pale stools and dark urine. Chronic injury (viral hepatitis, alcohol, NASH) activates Ito cells, replaces the orderly cords with collagen nodules — cirrhosis — and distorts the vascular architecture to produce portal hypertension with varices, splenomegaly and ascites. Hepatocellular carcinoma typically arises on this cirrhotic background.

The liver is unique among solid organs in receiving a dual blood supply — oxygenated arterial blood from the hepatic artery and nutrient-rich venous blood from the portal vein — and in producing an exocrine secretion (bile) that flows in the opposite direction. Its histology is engineered around that traffic system. A complete answer must describe the building blocks, the vascular plumbing and the biliary plumbing in turn.

The building block: classic hepatic lobule

The repeating unit is a hexagonal prism centred on a central vein, with portal triads at the corners. From the central vein, one-cell-thick plates of polygonal hepatocytes radiate outward, anastomosing as they go. Each hepatocyte carries one or two central nuclei (often polyploid), an acidophilic cytoplasm dotted with basophilic RER patches, extensive smooth ER for detoxification, around 2000 mitochondria, peroxisomes, Golgi, PAS-positive glycogen rosettes and small lipid droplets.

The sinusoidal compartment

Between adjacent plates run hepatic sinusoids — wide, discontinuous, fenestrated capillaries with essentially no basal lamina on the hepatocyte side. The thin gap between endothelium and hepatocyte microvilli is the perisinusoidal space of Disse, which holds plasma and the Ito (stellate) cells that store vitamin A and turn fibrogenic in chronic injury. Inside the sinusoidal lumen sit Kupffer cells — fixed macrophages that filter gut-derived bacteria, endotoxin and senescent red cells from portal blood.

Blood flow — centripetal

Oxygenated arterial blood from a branch of the hepatic artery and nutrient-rich venous blood from a branch of the portal vein enter at the portal triad, mix as they enter the sinusoids and flow inward through the plates to the central vein. From there blood drains into sublobular veins, then larger hepatic veins, and finally into the inferior vena cava. The dual supply means hepatocytes near the triad enjoy the highest oxygen and substrate concentration — the basis of acinar zonation discussed below.

Bile flow — centrifugal, opposite to blood

Hepatocytes secrete bile into the bile canaliculi, tiny grooves between the apposed lateral membranes of two adjacent hepatocytes, sealed by tight junctions and lined by microvilli (silver impregnation reveals them best). Bile flows outward from each canaliculus to the lobular edge, drains through the short cuboidal-lined canal of Hering, then enters the interlobular bile duct of the portal triad. Successive ducts merge into right and left hepatic ducts, then the common hepatic duct.

Functional unit — Rappaport's acinus and zonation

If you switch from the structural lobule to the functional acinus, the same tissue divides into three concentric zones around a terminal portal venule. Zone 1 (periportal) is best oxygenated and handles oxidative metabolism and gluconeogenesis. Zone 3 (centrilobular) is least oxygenated and rich in CYP450; it dies first in shock and right-heart failure and produces NAPQI from paracetamol — hence centrilobular necrosis in overdose.

Clinical anchor

The opposite-currents architecture is what allows obstruction of biliary outflow to produce jaundice without immediately killing hepatocytes, and what makes congestive hepatopathy specifically damage zone 3. Cirrhosis distorts vascular architecture and produces portal hypertension.

The pancreas is two organs sharing one capsule — a vast serous exocrine gland that supplies the duodenum with digestive enzymes, and microscopic endocrine islands sprinkled through it that run blood-glucose homeostasis. A good answer treats each compartment in turn, then closes with a comparison and a clinical anchor.

Exocrine pancreas — serous acini

The exocrine bulk is built from purely serous acini. Each acinar cell is pyramidal, with a deeply basophilic basal cytoplasm crammed with rough ER (hence the basophilia) and an apical pole filled with zymogen granules that hold inactive digestive proenzymes: trypsinogen, chymotrypsinogen, lipase, amylase, ribonuclease. Storing them inactive is a safety mechanism — activation only happens in the duodenum after enterokinase fires trypsin. Premature intra-pancreatic activation causes acute pancreatitis.

Duct system and centroacinar cells

A histological fingerprint of the pancreas is the centroacinar cell — pale cuboidal duct cells that have been pushed back into the centre of each acinus. They are the most proximal cells of the intercalated duct. The duct hierarchy continues intercalated → intralobular → interlobular → main pancreatic duct (of Wirsung). Crucially, the pancreas has no striated ducts; instead, duct cells secrete the alkaline, bicarbonate-rich watery fluid that neutralises gastric acid in the duodenum. CFTR mutations (cystic fibrosis) cripple this bicarbonate secretion and lead to duct obstruction and exocrine failure.

Endocrine pancreas — islets of Langerhans

Scattered through the exocrine tissue, especially in the tail, lie pale spherical clusters of cells — the islets of Langerhans. They look pale on H&E because their cells release hormones straight into capillaries rather than stockpiling granules. Each islet is surrounded by a delicate reticular capsule and pierced by fenestrated capillaries. Special stains identify four main cell types: β cells (~70%, concentrated centrally) secrete insulin; α cells (~20%, peripheral) secrete glucagon; δ cells (~5%) secrete somatostatin, which damps both insulin and glucagon; PP cells secrete pancreatic polypeptide. Rare ε cells produce ghrelin.

Contrast with salivary glands

It is worth highlighting how the pancreas differs from the morphologically similar serous salivary glands. The pancreas has centroacinar cells and islets; salivary glands have neither. The pancreas has no striated ducts; salivary glands rely on them for electrolyte modification. And the pancreas is purely serous — no mucous acini, no demilunes.

Clinical anchor

Premature trypsinogen activation drives acute pancreatitis (gallstone obstruction, alcohol, hypertriglyceridaemia), with serum amylase and lipase rising rapidly. Repeated attacks burn the gland into fibrotic chronic pancreatitis with eventual exocrine and endocrine failure. Type 1 diabetes is autoimmune destruction of β cells; type 2 is insulin resistance with later β-cell exhaustion. Ductal adenocarcinoma arises from duct epithelium and carries a grim prognosis. Insulinomas and gastrinomas (Zollinger–Ellison) are functional islet tumours.

The three paired major salivary glands — parotid, submandibular and sublingual — produce around a litre of saliva each day. They share the same compound exocrine plan (acini + branching duct tree + myoepithelial cells) but differ in the ratio of serous to mucous cells and in the prominence of the various duct segments. The examiner is checking whether you can compare them on those axes and link the morphology to function and pathology.

Shared architecture

All three are compound tubulo-acinar glands wrapped in a fibrous capsule that sends septa inward dividing the gland into lobules. Each lobule contains acini draining into intercalated → striated → excretory ducts. Myoepithelial cells — star-shaped contractile cells with actin and myosin — sit between acinar cells and the basement membrane, and continue along intercalated ducts. They squeeze the acinus on autonomic stimulation. Two acinar cell types exist throughout the system: serous cells (basal RER, apical zymogen granules, round central nucleus, dark basophilic basal cytoplasm) and mucous cells (clear bubbly cytoplasm, basal flattened nucleus, mucinogen content). Crescent caps of serous cells sitting on mucous acini are called serous demilunes.

Parotid — purely serous

The parotid is the largest and is composed exclusively of serous acini producing watery, amylase-rich saliva. A useful identification clue is the scattering of adipocytes between acini, leaving clear holes on H&E that you do not see in the other two glands. Striated ducts are abundant and conspicuous. The parotid secretes via Stensen's duct opposite the upper second molar. Clinically it is the site of mumps (paramyxovirus parotitis), pleomorphic adenoma (commonest salivary tumour) and Warthin tumour.

Submandibular — mixed, predominantly serous

The submandibular is mixed but mostly serous, with serous demilunes conspicuously capping the few mucous acini — this is the gland on which demilunes are classically described. Striated ducts are well developed. The submandibular contributes the majority of resting saliva and drains via Wharton's duct into the floor of the mouth. The thicker secretion and the upward course of the duct make this the classic site for sialolithiasis (salivary stones).

Sublingual — mixed, predominantly mucous

The sublingual is the smallest and is mixed but predominantly mucous, with sparse serous demilunes. Intercalated and striated ducts are short and less prominent because mucous acini do not need much ionic modification. It drains via several small ducts (Rivinus) plus the larger Bartholin duct.

Duct modification of saliva

Across all three glands, the acini produce an isotonic primary secretion. The striated duct then reshapes it — its tall columnar cells with basal mitochondria-packed infoldings actively reabsorb Na⁺, secrete K⁺ and HCO₃^-, producing the final hypotonic, slightly alkaline saliva that you swallow. The excretory duct only carries the finished product and is not involved in ionic editing.

Clinical anchor

Sjögren syndrome is autoimmune destruction of all three glands (and the lacrimals) producing dry mouth and dry eyes. Mucoepidermoid carcinoma is the commonest malignant salivary tumour and tends to arise in the parotid. Stones favour the submandibular duct because of its thicker secretion and uphill course.

The gallbladder is a pear-shaped musculomembranous sac that hangs from the visceral surface of the liver and connects to the duodenum through the cystic and common bile ducts. Its job is to hold the bile the liver produces between meals, concentrate it five- to ten-fold by absorbing water and ions, and squirt the concentrate into the duodenum on CCK stimulation when a fatty meal arrives. The whole biliary passage from canaliculus to ampulla of Vater should be described as a continuous drainage tree.

Wall layers — a non-standard plan

The gallbladder wall is unusual: it has no muscularis mucosae and no submucosa. From lumen out the layers are mucosa → muscularis → perimuscular connective tissue → adventitia/serosa. The mucosa is folded into low villus-like ridges when the bladder is empty and flattens out when full.

Mucosal epithelium — built to concentrate bile

The lining is a simple columnar epithelium covered in apical microvilli (a brush border), supported by mitochondria-rich cytoplasm. Those mitochondria power Na⁺/K⁺-ATPase pumps along the lateral membranes; sodium is pumped into the lateral intercellular space, water follows by osmosis, and the bile left in the lumen is concentrated five- to ten-fold. The epithelium has no goblet cells and no glands — the gallbladder is purely absorptive. Beneath sits a thin lamina propria of loose connective tissue with capillaries and a few lymphocytes.

Rokitansky–Aschoff sinuses

A feature unique to the gallbladder is the Rokitansky–Aschoff sinus — a mucosal diverticulum that punches through the lamina propria and dives into the muscularis. A few are present normally; they multiply and deepen in chronic cholecystitis, where they become little pockets that can trap bile, bacteria and even small stones.

Muscularis and outer layers

The muscularis is composed of interlacing smooth muscle bundles arranged in oblique, longitudinal and circular directions without forming distinct layers. It contracts in response to cholecystokinin released from duodenal I cells when fat enters the gut. Beyond the muscle is a perimuscular connective tissue layer, and the outermost coat is serosa (peritoneum) on the free surface but adventitia where the gallbladder is attached to the liver bed.

The biliary passages — canaliculus to duodenum

Bile leaves hepatocytes through the bile canaliculi — grooves between adjacent hepatocyte membranes sealed by tight junctions. It drains through the cuboidal-lined canals of Hering at the lobular edge into the interlobular bile duct of the portal triad. Successive ducts merge into right and left hepatic ducts that exit the liver and unite as the common hepatic duct. This joins the cystic duct from the gallbladder to form the common bile duct, which descends behind the duodenum, fuses with the main pancreatic duct at the ampulla of Vater, and opens into the second part of the duodenum through the sphincter of Oddi. Larger ducts are lined by simple columnar epithelium with mucous glands in the wall.

Clinical anchor

Cholelithiasis comes in cholesterol stones (the classic 4Fs — fat, female, fertile, forty) and pigment stones (black in haemolysis, brown in infection). Stone impaction at the cystic duct triggers acute cholecystitis with a positive Murphy sign. Chronic disease deepens the Rokitansky–Aschoff sinuses and can end in porcelain gallbladder — wall calcification with raised carcinoma risk. Migration of a stone into the common bile duct causes obstructive jaundice with pale stools and dark urine; impaction at the ampulla can trigger gallstone pancreatitis.