Liver and Kidney: Histology, Pathology, and Special Stains – Exam-Ready Study Notes

Liver: Normal Histology & Pathology

Overview of the Liver

• Largest organ and main glandular tissue mass in the body.

• Dual blood supply: ~75% from the hepatic portal vein (nutrient-rich, low O2), ~25% from the hepatic artery (O2-rich, low nutrients).

• Exocrine function: Produces bile for fat digestion and waste removal.

• Endocrine-like functions: Synthesis of albumin, coagulation factors, and insulin-like growth factor (IGF).

• Metabolic functions: Nutrient storage/distribution, iron storage, vitamin conversion, drug/toxin degradation.

• Regeneration: As little as 51% of the liver can regenerate to full size.

Structural Components of the Liver

• Parenchyma: Plates of hepatocytes (80% of liver cells) radiate from portal triads toward the central vein.

• Connective Tissue (Stroma): Collagen around portal areas; expands in fibrosis/cirrhosis.

• Hepatic Sinusoids: Irregular, fenestrated vascular channels between hepatocyte plates; allow fluid/protein passage but not blood cells.

• Space of Disse: Perisinusoidal space for exchange; contains stellate cells and hepatocyte microvilli.

Three Models of the Liver Unit

Model	Shape	Centre	Blood Flow Direction	Key Use
Classic Lobule	Hexagonal	Central vein	Portal triads → central vein	Anatomical/histological
Portal Lobule	Triangular	Portal triad (bile duct)	Inward from portal triad	Bile secretion model
Liver Acinus	Diamond	Portal triad branches	Zone 1 → 2 → 3 → central vein	Perfusion, metabolism, pathology

• Acinus Zones: Zone 1 (closest to portal supply, most O2/nutrients, first hit by toxins), Zone 3 (furthest, susceptible to paracetamol/alcohol damage), Zone 2 (intermediate).

• Centrilobular necrosis: Occurs in Zone 3.

The Portal Triad

• Located at the corners of the classic lobule; contains four structures:

Component	Description
Portal Vein	Nutrient-rich, low O2 blood from GI tract; thin wall, wide lumen
Hepatic Artery	O2-rich blood from aorta; thick wall
Bile Duct	Carries bile to duodenum; lined by cholangiocytes
Lymphatic Vessel	Difficult to see in light microscopy; visible in EM

Hepatocytes

• Large, polygonal, often binucleated cells with acidophilic cytoplasm (abundant sER, rER, mitochondria, peroxisomes, Golgi).

• Arranged in plates radiating toward the central vein.

• Basal surface: Faces sinusoids (space of Disse) for protein exchange.

• Apical surface: Forms bile canaliculus with adjacent hepatocyte; lined by microvilli.

• Bile flow: Canaliculi → Canals of Hering → Intrahepatic ductules → Interlobular bile ducts → R/L hepatic ducts → Common hepatic duct → Gallbladder → Bile duct → Duodenum.

• Canals of Hering: Partly hepatocytes, partly cholangiocytes; contain hepatic stem cells.

Non-Parenchymal Cells

Cell Type	Location/Function
Kupffer Cells	Sinusoidal macrophage-like; phagocytose old RBCs, recycle iron, monitor pathogens, produce cytokines
Hepatic Stellate Cells (Ito)	Space of Disse; store Vitamin A when quiescent; activated by injury/IL-1/toxin → myofibroblasts → collagen I → fibrosis
Sinusoidal Endothelial Cells	Discontinuous, highly fenestrated; allow fluid/protein passage, not blood cells

Bile Formation & Flow

• Bile: Waste products + bile salts for fat emulsification/digestion.

• Released into duodenum under cholecystokinin (CCK) stimulation.

• Flow is opposite to blood flow in sinusoids.

Liver Diseases & Pathology

• Hepatitis: Inflammation of the liver (e.g., viral, autoimmune, alcohol-induced); histology shows mononuclear infiltrate around portal veins.

• Cirrhosis: End-stage of chronic liver diseases; hallmarks: (1) Thick fibrous bands (collagen), (2) Nodules of regenerative hepatocytes. Macroscopically: shrunken, nodular, stiff liver.

• Hepatocellular Carcinoma (HCC): Most common primary liver tumour, usually in cirrhotic livers; liver is also the most common site for secondary (metastatic) tumours from the GI tract.

• Obstructive Jaundice (Icterus): Blocked bile duct leads to bile accumulation in liver; histology shows bile pigment in ducts, possible hepatocyte necrosis.

• Causes of Liver Disease: Infection (e.g., hepatitis viruses, TB), immune (autoimmune hepatitis), genetic (haemochromatosis, Wilson disease), cancer, alcohol, NAFLD, drugs.

• Haemochromatosis vs Haemosiderosis: Haemochromatosis is genetic (HFE mutation, parenchymal iron overload); haemosiderosis is secondary/acquired (iron in macrophages/Kupffer cells).

Laboratory Investigations — Liver

• Liver Function Tests (LFTs): ALT/AST (hepatocyte damage), bilirubin (jaundice/haemolysis), ALP (biliary obstruction), albumin (liver failure).

Stain	What It Shows	Clinical Use
H&E	Nuclei (blue/purple), cytoplasm (pink)	General architecture, inflammation, necrosis
Perls' Prussian Blue	Iron (blue)	Haemochromatosis, haemosiderosis
Reticulin (Silver)	Reticular fibres (black)	Cirrhosis/fibrosis, lobular architecture
Van Gieson / Masson Trichrome	Collagen (blue/green), bile (yellow/green)	Cirrhosis, obstructive jaundice
PAS	Glycogen (magenta/purple)	Glycogen storage diseases
PASD	PAS after diastase (removes glycogen)	Alpha-1 antitrypsin deficiency
Oil Red O / Sudan Black	Lipid/fat droplets (red/black)	Fatty liver (requires frozen section)

Principle of H&E Staining

• Haematoxylin: Basic dye, binds acidic (basophilic) structures (nuclei) → blue/purple.

• Eosin: Acidic dye, binds basic (acidophilic) structures (cytoplasm/proteins) → pink/red.

• Gold standard for tissue examination; differentiates nucleus from cytoplasm, identifies cell types, tissue architecture, inflammation, necrosis, tumour cells.

Kidney: Normal Histology & Pathology

Overview of the Kidney & Urinary System

• Components: 2 kidneys, 2 ureters, bladder, urethra.

• Urine production: 180 L filtrate/24 h → ~1.5 L urine (via reabsorption/secretion).

• Functions: Waste elimination, acid-base balance, fluid/electrolyte conservation, blood pressure regulation.

• Endocrine: Erythropoietin (EPO) for RBC production, renin for blood pressure (RAAS).

Gross Structure of the Kidney

• Retroperitoneal, bean-shaped; hilum faces medially.

• Capsule: Dense irregular collagenous CT.

• Cortex: Contains glomeruli, PCT, DCT, cortical collecting tubules, medullary rays.

• Medulla: Renal pyramids (loop of Henle, collecting ducts); tip = renal papilla.

• Renal pelvis/calyces: Minor calyx (7–13) → major calyx (2–4) → pelvis → ureter → bladder.

• Arcuate arteries/veins: At corticomedullary junction (histological landmark).

The Nephron — Functional Unit

• Juxtamedullary nephrons: Long loop, deep into medulla; concentrate urine.

• Cortical nephrons: Shorter loop, less significant for concentration.

• Filtrate pathway: Renal corpuscle → PCT → thick descending limb → thin loop of Henle → thick ascending limb → DCT → collecting tubules/ducts → papillary duct (duct of Bellini) → area cribrosa → minor calyx.

Segment	Epithelium	Key Features	Function
PCT / Thick Descending	Simple cuboidal	Intensely eosinophilic, brush border (narrow lumen)	Active reabsorption (glucose, amino acids, Na+, water)
Thin Loop of Henle	Simple squamous	Nuclei bulge into lumen, thin walls	Passive water/ion movement
DCT / Thick Ascending	Simple cuboidal	Pale, low brush border (wide lumen)	Active ion transport, macula densa present
Collecting Tubules/Ducts	Simple cuboidal	Pale cytoplasm, prominent cell boundaries	Urine transport, ADH-regulated water reabsorption

Renal Corpuscle — Glomerulus & Bowman's Capsule

• Glomerulus: Ball of fenestrated capillaries; afferent arteriole enters, efferent exits.

• Bowman's Capsule: Parietal layer (simple squamous, outer), visceral layer (podocytes, inner).

• Bowman's/Urinary Space: Between layers; filtrate collects here before entering PCT.

Filtration Barrier Layer	Structure	Function
Fenestrated Endothelium	Large pores	Allows fluid/small molecules; blocks blood cells
Glomerular Basement Membrane (GBM)	Negatively charged glycoprotein	Blocks large/negatively charged proteins
Podocyte Filtration Slits	Foot processes with slit diaphragms	Final molecular sieve; damage → proteinuria

• Vascular pole: Entry/exit of arterioles; site of juxtaglomerular apparatus (JGA).

• Urinary pole: Exit to PCT.

Juxtaglomerular Apparatus (JGA) — Blood Pressure Control

• JG Cells: Modified smooth muscle in afferent arteriole wall; secrete renin in response to low BP/Na+.

• Macula Densa: Specialised DCT cells at vascular pole; sense low salt, signal JG cells to release renin.

• Renin-Angiotensin-Aldosterone System (RAAS):

$\text{Renin} \rightarrow \text{Angiotensinogen} \rightarrow \text{Angiotensin I} \rightarrow \text{ACE (lungs)} \rightarrow \text{Angiotensin II} \rightarrow \text{Aldosterone} \rightarrow \uparrow \text{Na}^+ \text{ reabsorption} \rightarrow \uparrow \text{BP}$

Identifying Cortex vs Medulla in Histology

• Cortex: Glomeruli, medullary rays (PCT + DCT), arcuate arteries at base.

• Medulla: No glomeruli; thin loop of Henle segments, collecting ducts, vasa recta.

• Area cribrosa: End of collecting ducts at renal papilla; urine exits into minor calyx (lined by transitional epithelium).

• Transitional epithelium (urothelium): Lines calyces, pelvis, ureters, bladder; allows stretching.

Blood Supply of the Kidney

• Arterial: Renal artery → segmental → lobar → interlobar → arcuate (corticomedullary junction) → interlobular → afferent arterioles → glomerular capillaries → efferent arterioles.

• Venous (cortex): Stellate veins → interlobular veins → arcuate veins.

Kidney Diseases & Pathology

• Nephritis: General inflammation of the kidney.

• Acute Glomerulonephritis: Inflammation of glomeruli; haematuria, proteinuria, oedema.

• Congenital: Polycystic kidney disease.

• Diagnosis uses paraffin sections (special stains), immunofluorescence (IF), and electron microscopy (EM).

Stain/Technique	What It Shows	Clinical Use
H&E	General structure, thickening of glomerular BM	First-line assessment
PAS	Basement membrane, brush border of PCT	Glomerulonephritis (BM thickening)
PA Silver	Spikes, serrations, deposits in BM	Membranous nephropathy
MSB	Fibrin/connective tissue/clots	Thrombosis, fibrin in glomeruli
Sirius Red / Congo Red	Amyloid deposits (apple-green birefringence under polarised light)	Amyloidosis
Immunofluorescence (IF)	IgG, IgA, IgM, C3, C4, fibrinogen deposits (granular fluorescence)	Autoimmune diseases (immune complex deposition)
Electron Microscopy (EM)	Dense deposits in/on GBM, podocyte changes	Membranous nephropathy, podocyte disease

Quick-Reference Summary

Liver Key Numbers	Kidney Key Numbers
80% hepatocytes	180 L filtrate/24 h → 1.5 L urine
75% portal vein / 25% hepatic artery	7–13 minor calyces, 2–4 major calyces
51% minimum for regeneration	3-layer glomerular filtration barrier
3 unit models	JGA at vascular pole of glomerulus
4 portal triad components	Arcuate arteries at corticomedullary junction

Example Applications

• Paracetamol overdose: Causes centrilobular (Zone 3) necrosis in the liver acinus.

• Alpha-1 antitrypsin deficiency: PASD-positive globules in hepatocytes; reticulin stain shows lobular architecture changes.

• Membranous nephropathy: PA silver stain shows spikes/serrations in glomerular BM; EM shows dense deposits.

Additional info: This guide integrates histological, pathological, and laboratory diagnostic features for the liver and kidney, focusing on high-yield exam content for cellular and transfusion science students.