Overview
This lecture covers the microscopic anatomy of the liver and of the exocrine pancreas. The liver half builds up from the tissue’s blood supply and stroma, to the hepatocyte and its immediate neighbours (sinusoid, bile canaliculus, perisinusoidal space), to the two ways the parenchyma is divided up: the hepatic lobule as the structural unit and the hepatic acinus as the functional unit whose zonation explains where damage falls. The non-hepatocyte resident cells (stellate and Kupffer) and the lymphatic drainage then link the normal histology to fibrosis, cirrhosis and portal hypertension. The pancreas half separates the endocrine islets from the exocrine 98%, then details the acinar cell, its zymogen granules, the duct system that begins with centroacinar cells, and the pancreatic stellate cell, which shares a lineage with the liver’s Ito cell and drives chronic pancreatitis in the same way.
Liver blood supply and the direction of flow
- Portal circulation: arteries of the digestive tract supply the capillaries of the stomach, intestines, pancreas and spleen; these drain into the hepatic portal vein, which carries the blood to the capillaries (sinusoids) of the liver; blood leaves the liver in the hepatic vein, into the inferior vena cava and back to the heart.
- Second supply: the aorta gives rise to the hepatic artery, which also supplies the liver.
- The bile duct leaves the liver.
- Within the lobule, blood in the sinusoids flows from the peripheral portal triad (hepatic artery plus hepatic portal vein) towards the central vein.
- Bile runs the other way: bile canaliculi run between hepatocytes towards the bile duct of the portal triad.
Capsule and supporting stroma
- Glisson’s capsule is 50 to 100 microns thick and forms septa/trabeculae between liver tissues.
- Structural integrity of the liver is maintained by a mesh of reticular fibres. On the micrograph these fibres form a fine scaffold running between the plates of hepatocytes and supporting the parenchyma.
Hepatocytes, sinusoids and bile canaliculi
Hepatocyte
- Large polyhedral cell.
- Round nuclei, which can be binucleated.
- Strongly eosinophilic cytoplasm.
- Lots of mitochondria, free ribosomes and RER.
- Lipofuscin brown granules, which increase with age.
Sinusoids
- Pale-stained spaces between two plates of hepatocytes.
- Lined with flat endothelial lining cells with flat nuclei.
Bile canaliculi
- Lie between the plasma membranes of two hepatocytes.
Arrangement of the tissue: hepatic plates of hepatocytes radiate outwards from the central vein; sinusoids lined by endothelial cells lie between adjacent plates; bile canaliculi run as dark branching channels between hepatocytes within a plate.
The hepatocyte and its sinusoidal interface
A single hepatocyte sits between two sinusoids. Blood enters the sinusoid from the portal vein and hepatic artery and leaves towards the central vein.
- The sinusoid is lined by fenestrated endothelium.
- Between that endothelium and the hepatocyte surface is the perisinusoidal space (space of Disse), into which the hepatocyte projects microvilli. Collagen fibres lie in this space.
- The bile canaliculus runs between adjacent hepatocytes and is sealed by tight junctions; desmosomes lie along the lateral membrane below the tight junction.
- Hepatocyte organelles shown: mitochondria; RER; SER with Golgi; lipid droplets and peroxisomes; glycogen.
Synthetic functions (the three numbered arrows):
- Albumin, synthesised at the RER and directed towards the sinusoid.
- Bile, directed from the region near the SER towards the bile canaliculus.
- Glycogen, from the glycogen/RER region towards the sinusoid.
[the slide gives only the numbered list of the three products; it does not explain each arrow’s destination further]
The hepatic lobule: the structural unit
- The hepatic lobule is the structural unit of the liver.
- Hexagonal lobules form around a central venule (centrilobular venule).
- In humans, hepatic lobules are less distinct, and they have less functional and clinical significance.
- The six corners of the hexagon contain portal triads: portal vein, hepatic artery and bile duct.
- The triad is accompanied by lymphatics and autonomic nerves.
- The central venule (centrilobular venule, hepatic venule) is NOT part of the triad.
On the micrograph, the portal vein is the largest thin-walled lumen of the triad, with the hepatic arteriole and bile ductule beside it and a lymphatic nearby; the central venule sits alone in the parenchyma at the centre of the hexagon, with cords of hepatocytes and intervening sinusoids radiating from it.
The hepatic acinus: the functional subunit and zonation
- The hepatic acinus is the functional subunit, and it carries the physiological and clinical relevance.
- Shape: a diamond/lens-shaped territory spanning between two portal triads, centred on the vessels running along the shared border of two adjacent lobules, so it straddles parts of both lobules. Blood flows from that central axis outwards to the central veins.
- The acinus is subdivided into three zones:
- Zone 1: periportal (closest to the portal triad axis)
- Zone 2: intermediate
- Zone 3: pericentral (closest to the central vein)
Periportal zone 1, compared with zone 3, has:
- High level of oxygenation
- High intracellular organelle concentration
- High rate of metabolic activity
- High regenerative capacity
Pericentral zone 3:
- Is initially affected in hepatic fibrosis
- Contains more wear-and-tear pigment (lipofuscin) [the bracket is left unclosed on the slide]
Other resident liver cells
Hepatic stellate (Ito) cells
- Found in the perisinusoidal space (of Disse).
- Secrete collagen III (reticulin).
- Contain lipid droplets in which fat-soluble vitamin A is stored.
- Are a source of growth factors, for liver homeostasis and regeneration.
- Role in cirrhosis: they replace damaged hepatocytes with collagenous scar tissue, and this fibrosis can progress to irreversible cirrhosis.
Hepatic macrophage (Kupffer) cells
- Reside in the sinusoidal lumen, attached to the endothelial surface.
- Long cell processes extend into the sinusoidal lumen.
- Remove debris from blood and secrete cytokines for defence.
- Remove aged and damaged red blood cells post splenectomy.
- Secrete hepatic cytokines.
Important
The stellate cell is the pivot between normal histology and disease: normally a vitamin A store and growth factor source, but on activation the source of the collagenous scar that becomes irreversible cirrhosis.
Hepatic lymphatics, the canal of Hering, and cirrhosis
- Lymphatics run in the space of Disse and the space of Mall.
- Lymph drains from the space of Disse along the plates towards the space of Mall at the portal tract, where a lymphatic vessel lies.
- Orientation on the same diagram: zone 3 lies next to the central vein, zone 1 next to the portal tract (portal vein, hepatic artery and bile duct).
- The canal of Hering, at the junction between the hepatocyte plate and the bile duct, contains stem cells (cholangiocytes).
- In cirrhosis, the tissue is distorted; portal hypertension is directed away from the cirrhotic region, and lymph escapes as transcapsular lymphatic weeping across the liver capsule.
Pancreas: endocrine and exocrine parts
Endocrine part
- An epithelial cell mass embedded in the exocrine part.
- The islets of Langerhans (alpha and beta cells).
- They secrete insulin and glucagon.
- Surrounded by a dense vascular plexus.
Exocrine part
- Forms 98% of the glandular tissue.
- A true exocrine gland: it has acini, ducts and a capsule.
- The terminal duct joins the common bile duct (CBD) before opening into the duodenum.
The exocrine pancreatic acinus
- Acini have an appearance similar to serous salivary acini.
- Each acinus is a spherical mass of secretory cells.
- The cells are pyramidal with a basal nucleus.
- The base of the cell contains rER and is therefore basophilic.
- The apical region contains zymogen granules and is therefore eosinophilic.
- Acini secrete digestive proenzymes and bicarbonate.
On electron microscopy: a central acinar lumen (L) surrounded by pyramidal secretory cells, each with a basally placed nucleus (Nu), abundant adjacent rough endoplasmic reticulum (rER), a Golgi apparatus (G), and numerous dense round zymogen granules (Z1, Z2) concentrated in the apical cytoplasm towards the lumen.
Warning
Transcript flag (slide 16): individual letters on the electron micrograph are small and only partly legible at the rendered resolution, and further letters appear in the image (including one near “Coll” at the lower right and one at the top left) that the slide’s key box does not explain.
Pancreatic ducts and pancreatic stellate cells
“The duct is the backbone of the pancreas.”
Pancreatic duct cells
- The lumen of the acinus is surrounded by centroacinar cells.
- The ducts are lined by cuboidal cells.
- Arrangement: the acinar lumen is occupied by centroacinar cells, which are continuous with the intercalated duct cells, and the intercalated duct drains into larger ducts.
Pancreatic stellate cells
- Myofibroblast-like cells in the periacinar space.
- Long processes encircle the base of the acini and ducts.
- Usually quiescent; when activated they are involved in the pathogenesis of chronic pancreatitis and of cancer.
- Hepatic stellate (Ito) cells are from the same lineage and, when activated, contribute to liver fibrosis.
Warning
Transcript flag (slide 17): the right-hand electron micrograph on this slide carries no labels or caption, so the structures it is meant to show are not stated.
Comparison exercise
The lecture includes a “spot the differences” pair of H&E micrographs of glandular tissue. Left: densely packed acini throughout, with a yellow circle around a rounded, paler-staining, more loosely arranged cluster of cells within the acinar tissue, and a small vessel/duct profile at the upper right. Right: acini separated by broader pale bands of connective tissue running between the lobules, with a small duct profile near the upper left and no circled area.
Warning
Transcript flag (slide 14): the slide gives no answer text and neither micrograph is labelled, so the tissue, the identity of the circled structure and the intended differences are not stated on the slide.
Self-test
- Trace the path of blood from the capillaries of the intestine to the heart, naming each vessel.
- State the two blood supplies of the liver and where their blood mixes.
- Describe the direction of bile flow within a lobule relative to the direction of blood flow, and explain why the two differ.
- Give the thickness of Glisson’s capsule and state what it forms within the liver.
- What maintains the structural integrity of the liver parenchyma?
- List the histological features of a hepatocyte.
- Which hepatocyte pigment accumulates with age, and in which acinar zone is it most abundant?
- Describe the sinusoid: what lies between the plates of hepatocytes, and what lines it?
- Where exactly does a bile canaliculus lie, and what seals it?
- Name the space between the fenestrated endothelium and the hepatocyte surface, and describe what the hepatocyte does at that surface.
- List the three synthetic products indicated on the hepatocyte diagram and state where each is directed.
- Define the hepatic lobule and name the structure at its centre.
- List the three components of the portal triad, name the two additional structures that accompany it, and state which vessel is explicitly not part of it.
- Explain why hepatic lobules are given less weight than acini in humans.
- Describe the shape and position of the hepatic acinus relative to the lobules.
- Name the three acinar zones and state four ways zone 1 differs from zone 3.
- Explain why zone 3 is the first region affected in hepatic fibrosis, using the zonation described.
- Distinguish hepatic stellate (Ito) cells from Kupffer cells by location and function.
- Describe the role of the stellate cell in cirrhosis.
- State two functions of Kupffer cells relating to blood.
- Describe the route of lymph from the space of Disse to the portal tract, and what happens to lymph drainage in cirrhosis.
- What is the canal of Hering and what does it contain?
- Distinguish the endocrine from the exocrine pancreas by proportion, structure and secretions.
- Explain why the basal cytoplasm of a pancreatic acinar cell is basophilic and the apical cytoplasm eosinophilic.
- Describe the cells lining the pancreatic acinar lumen and the duct continuing from it.
- A patient with chronic alcohol use develops both progressive liver fibrosis and chronic pancreatitis. Name the cell type common to both processes and describe its behaviour in each organ.
- A liver biopsy shows collagenous scar tissue and loss of hepatocytes beginning around the central veins, with lymph weeping from the capsule surface. Explain each finding using the acinar zonation and the lymphatic anatomy described.
- Integrative: starting at the portal triad and ending at the central vein, describe what a red blood cell passes and what a hepatocyte along that route does, incorporating oxygenation, metabolic activity and the resident cells encountered.
Answers
Reveal answers
- Digestive tract arteries supply the capillaries of the stomach, intestines, pancreas and spleen; these drain into the hepatic portal vein, which carries blood to the capillaries (sinusoids) of the liver; blood leaves via the hepatic vein into the inferior vena cava and returns to the heart.
- The hepatic portal vein (from the digestive tract capillaries) and the hepatic artery (from the aorta). Both enter at the portal triad and their blood flows through the sinusoids towards the central vein.
- Blood flows from the peripheral portal triad inwards to the central vein; bile flows in the bile canaliculi between hepatocytes outwards towards the bile duct of the portal triad. They differ because bile is collected in canaliculi that drain to the bile duct component of the triad, while blood drains centrally to the hepatic venous system.
- Glisson’s capsule is 50 to 100 microns thick and forms septa/trabeculae between liver tissues.
- A mesh of reticular fibres, forming a fine scaffold between the plates of hepatocytes.
- Large polyhedral cell; round nuclei that can be binucleated; strongly eosinophilic cytoplasm; abundant mitochondria, free ribosomes and RER; brown lipofuscin granules.
- Lipofuscin, the wear-and-tear pigment; it is most abundant in pericentral zone 3.
- Sinusoids are the pale-stained spaces between two plates of hepatocytes, lined by flat endothelial lining cells with flat nuclei; on the ultrastructural diagram this lining is fenestrated.
- Between the plasma membranes of two adjacent hepatocytes within a plate, sealed by tight junctions, with desmosomes along the lateral membrane below.
- The perisinusoidal space (space of Disse). The hepatocyte projects microvilli into it; collagen fibres and stellate cells also lie in this space.
- Albumin (from the RER, directed towards the sinusoid), bile (from near the SER, directed towards the bile canaliculus) and glycogen (from the glycogen/RER region towards the sinusoid). The slide does not elaborate beyond the numbered list.
- The hepatic lobule is the structural unit of the liver, a hexagonal unit formed around a central venule (centrilobular venule).
- Portal vein, hepatic artery and bile duct; accompanied by lymphatics and autonomic nerves; the central venule/centrilobular venule/hepatic venule is not part of the triad.
- In humans the lobules are less distinct, and they carry less functional and clinical significance than the acinus, which is the functional subunit with physiological and clinical relevance.
- The acinus is a diamond or lens-shaped territory spanning between two portal triads, centred on the vessels running along the shared border of two adjacent lobules, so it straddles parts of both lobules; blood flows from that axis outwards to the central veins.
- Zone 1 periportal, zone 2 intermediate, zone 3 pericentral. Compared with zone 3, zone 1 has a high level of oxygenation, high intracellular organelle concentration, a high rate of metabolic activity and high regenerative capacity.
- Zone 3 lies furthest along the flow axis, next to the central vein, so it is the least oxygenated and the least metabolically and regeneratively equipped compared with zone 1; the slides state it is initially affected in hepatic fibrosis and accumulates more lipofuscin.
- Stellate (Ito) cells lie in the perisinusoidal space of Disse; they secrete collagen III (reticulin), store fat-soluble vitamin A in lipid droplets, and are a source of growth factors for homeostasis and regeneration. Kupffer cells lie in the sinusoidal lumen attached to the endothelial surface, with processes extending into the lumen; they remove debris from blood, secrete cytokines for defence, and remove aged and damaged red cells post splenectomy.
- They replace damaged hepatocytes with collagenous scar tissue, and this fibrosis can progress to irreversible cirrhosis.
- Removal of debris from the blood and removal of aged and damaged red blood cells post splenectomy; they also secrete cytokines for defence.
- Lymph drains from the space of Disse along the hepatocyte plates towards the space of Mall at the portal tract, where a lymphatic vessel lies. In cirrhosis the tissue is distorted, portal hypertension develops, and lymph escapes as transcapsular lymphatic weeping across the liver capsule.
- A region at the junction between the hepatocyte plate and the bile duct; it contains stem cells (cholangiocytes).
- Endocrine: an epithelial cell mass embedded within the exocrine tissue, the islets of Langerhans (alpha and beta cells), secreting insulin and glucagon, surrounded by a dense vascular plexus. Exocrine: 98% of the glandular tissue, organised as acini, ducts and a capsule, secreting digestive proenzymes and bicarbonate, with the terminal duct joining the common bile duct before opening into the duodenum.
- The base of the cell is packed with rough endoplasmic reticulum, which is basophilic; the apical region is packed with zymogen granules, which are eosinophilic.
- The acinar lumen is surrounded by (occupied by) centroacinar cells, which are continuous with the intercalated duct cells; the ducts are lined by cuboidal cells and the intercalated duct drains into larger ducts.
- The stellate cell. Pancreatic stellate cells are myofibroblast-like cells of the periacinar space whose processes encircle the base of acini and ducts; usually quiescent, on activation they contribute to the pathogenesis of chronic pancreatitis and cancer. Hepatic stellate (Ito) cells are from the same lineage and, on activation, replace damaged hepatocytes with collagenous scar tissue, producing fibrosis that can progress to irreversible cirrhosis.
- Scarring and hepatocyte loss around the central veins correspond to pericentral zone 3, which is initially affected in hepatic fibrosis and is the least oxygenated and least regenerative zone; the scar tissue is collagen laid down by activated stellate cells. Capsular weeping is transcapsular lymphatic weeping, which occurs when lymph normally draining from the space of Disse to the space of Mall is obstructed by the distorted cirrhotic tissue and the accompanying portal hypertension.
- The cell enters at the portal triad from the hepatic artery and portal vein, passes into a sinusoid lined by fenestrated endothelium, travelling through zone 1 (well oxygenated, organelle-rich, metabolically active, highly regenerative), then zone 2, then zone 3 (least oxygenated, lipofuscin-rich, first affected in fibrosis), before leaving via the central vein. Along the way it passes Kupffer cells in the lumen, which remove debris and damaged red cells, while across the fenestrated endothelium the space of Disse holds stellate cells, collagen fibres and hepatocyte microvilli. The hepatocytes it passes secrete albumin and glycogen towards the sinusoid and bile in the opposite direction into the canaliculi, which drain back towards the bile duct of the portal triad.