Liver/Pancreas Histology Flashcards
liver
-largest organ in the abdoment and also a gland since it secretes proteins and hormones the body needs
-divided into a larger right lobe and a smaller left lobe by the falciform ligament
-each lobe is further divided into 2 sectors by the right hepatic vein and left hepatic vein —> sectors are then divided into a total of eight hepatic segments which each have redundant functions but their own blood supply and biliary drainage
-within the hepatic segments are hepatic lobules, which have hexagonal structures centered around a central vein, surrounded by portal triads at the periphery
dual blood supply of liver
-hepatic artery brings in oxygen-rich blood from the heart (25% of blood supply)
-portal vein brings nutrient-rich but oxygen-poor blood from the GI tract (provides 75% of the blood supply)
liver function
-detoxification- all blood leaving the stomach and intestines passes through the liver —> it removes toxins, byproducts, bacteria, and old RBCs
-bile production- a fluid critical for digestion of fats and absorption of fat-soluble vitamins in the small intestine
-storage- stors a significant amount of vitamins, minerals, and glycogen
-blood clotting regulation
-immune system support
-produces albumin, which controls osmotic pressure by keeping the fluids in the bloodstream from diffusing into the surrounding tissues
liver lobule
-basic unit of the liver
-hexagonal shape with central vein at the center
-composed of hepatocytes arranged in plates
-portal triad located at each corner of the lobule
portal triad
-hepatic artery- supplied oxygen-rich blood
-portal vein- carries nutrient-rich blood from the digestive organs
-bile duct- transports bile produced by hepatocytes
-blood flow direction- toward the central vein
-bile flow- toward the bile duct
histology of portal triad
-portal vein has larger, thinner wall
-hepatic artery a thicker and smaller diameter
-bile duct is lined with cuboidal epithelium
central vein
-located at the center of each hepatic lobule and lined by a single layer of endothelial cells
-receives oxygen and nutrient rich blood at the sinusoids from the portal vein and hepatic artery
-coalesces into the hepatic vein, which carries deoxygenated blood back to the inferior vena cava
central vein histology
-wide lumen
-nearby sinusoids where the blood enters the portal triad —> goes through sinusoids —> heads toward CV
bile duct
-lined with simple cuboidal epithelium cells called cholangiocytes
-small bile ductules join together to form left and right hepatic ducts
-passes through the liver and collects bile as the liver produces it
-cholangiocytes modify bile composition and volume through secretion and absorption of water and electrolytes —> cells act as an access point for immune cells while acting as a barrier and help maintain homeostasis of the biliary system
space of disse
-space between the sinusoidal endothelium and hepatocytes
-important for the transport of lymphatic fluid to lymphatic capillaries in the portal triad
-essential for uptake of macromolecules, bile salts, nutrients, and ions
hepatocytes
-main functional cells of the liver
-polygonal shaped, arranged in interconnecting plates
-bile canaliculi between adjacent cells
-help with endocrine and exocrine secretion, synthesis of proteins and lipids, metabolism, detoxification, and activation of immune cells
kupffer cells
-macrophages located in the walls of the hepatic sinusoids
-variable and irregular shape with oval or indented nuclei
-cell surface has microvilli and long, slender projections
-remove pathogens and debris through phagocytosis
stellate or ito cells
-mesenchymal cells located in the space of disse
-star-shaped, containing multiple lipid vacuoles
-vitamin A storage, liver development and regeneration, and response to hepatic injury
endocrine vs exocrine pancreatic functions
-endocrine- hormones —> bloodstream
-exocrine- digestive enzymes —> small intestine
alpha cells
-produce glucagon in response to low blood glucose, fasting response, and after exercise
-make up 20% of islet cells
-H&E: stain pink due to the glucagon granules
glucagon function
-glycogenolysis- stimulates the liver to convert glycogen to glucose
-gluconeogenesis- stimulates liver to uptake amino acids from blood to glucose
-lipolysis- form of gluconeogenesis, which stimulates the liver and adipose tissue to covert triglycerides to free fatty acids and glycerol
-glycerol is then converted to glucose in the liver
beta cells
-produce insulin from the food in the intestine
-food is in the intestine —> release of gastrointestinal hormones (glucose-dependent insulinotropic peptide) —> insulin production by beta cells
-secretion is stimulated by increased blood glucose
-make up 75% of islet cells
-H&E: stain blue due to insulin granules
insulin function
-decreases blood glucose by stimulating glycolysis (glucose —> ATP) then stimulating glycogenesis (glucose —> glycogen)
-inhibits glycogenolysis and gluconeogenesis
-promotes tryglyceride and protein synthesis
-as blood glucose goes down, the release is inhibited
-facilitates glucose uptake- especially in skeletal muscle and adipose tissue but RBCs, brain, liver, kidneys, and small intestine do not need it
-mechanism is largely unknown (activates tyrosine kinases —> move glucose transporter GLUT4 storage vesicles to plasma membrane)
delta cells
-produce somatostatin, which is also released by the hypothalamus, stomach, and intestines and is stimulated by increased glucose and ghrelin
-coordinates insulin and glucagon secretion to maintain glucose homeostasis
-4% of islet cells
somatostatin function
-inhibits release of glucagon and insulin
-activates somatostatin receptors on alpha and beta cells coupled to inhibitory G protein —> suppresses electrical stimulation —> no exocytosis of granules
pancreatic polypeptide cell
-gamma or F cells
-produce pancreatic polypeptide hormone —> produced after eating and in response to fasting
-secretion is stimulated by intestinal hormones cholecystokinin, secretin, and gastrin
-1% of islet cells
pancreatic polypeptide function
-regulates appetite to reduce hunger levels by sending signals to the brain through vagus nerve
-slows digestion by reducing the rate of gastric emptying, pancreatic exocrine secretion, and gallbladder contraction
exocrine products of pancreas
-essential for breaking down food into constituent molecules for absorption
-produces pancreatic juice containing digestive enzymes, bicarbonate, and water
-products are released into the duodenum
acinar cells secrete digestive enzymes
-amylase- breaks down starches (carbs) into simple sugars
-protease- breaks down proteins into amino acids Ex. trypsin, chymotrypsin, and carboxypeptidase
-lipases- break down fats into fatty acids and glycerol
-nucleases- break down nucleic acids (DNA and RNA) into nucleotides
EM of acinar cell
-abundant ER for protein synthesis
-stores inactive enzymes in secretory vesicles called zymogen granules
-zymogen is an inactive enzyme precursor that releases via exocytosis when stimulated by CCK
intercalated ducts secrete bicarbonate and water
-bicarbonates are secreted into the duodenum and neutralize HCl
-secretin hormone, which is released when the acidic chyme is in the duodenum, stimulates bicarbonate release
histology of exocrine cells
-acinar cells have apical granules stained pink and pyramidal shape
-centroacinar cells are pale, low cuboidal cells and the first cells of the intercalated ducts
histology of endocrine cells
-arranged in islets with dense fenestrated capillaries
-endocrine products are delivered to the systemic circulation via the portal system
histology of pancreatic lobules
-formed by groups of acini and islets wrapped in a layer of connective tissue
-vasculature, nerves, and lymphatics run with the septa
ductal cells (exocrine) and classification of ducts
-epithelial ductal cells- transition to columnar cells along path to main pancreatic duct
-intercalated ducts are the most proximal part
-intralobular ducts join the acini within a lobule
-interlobular ducts connect lobules
secretion of centroacinar cells
-secretin hormone binds to secretin receptors on the acinar cells
-leads to GPCR signalling, which involves adenylate cyclase converting ATP to cAMP, a secondary messenger
-cAMP will stimulate the secretion of bicarbonate and water
secretion of intercalated ducts
-lined with centroacinar cells
-stimulated by the secretion of the centroacinar cells and move the products along to the main pancreatic duct
secretion of acinar cells
-CCK will directly and indirectly stimulate the release of digestive enzymes from the acinar cells
-directly by binding to CCK receptors on the acinar cells
-indirectly by stimulating the vagus nerve to release acetylcholine, which will stimulate the release of digestive enzymes by the acinar cells
pancreas anatomy
-composed of a tail, body, neck, and head (nestled into the duodenum of the small intestine)
-main duct running through it with branches coming off
exocrine pancreas
-acinar cells that release digestive enzymes
-ductal cells that release HCO3
endocrine pancreas
-alpha cells that release glucagon
-beta cells that release insulin
-delta cells that release somatostatin
pancreas + glucose metabolism
-produces digestive enzymes and hormones important for glucose and lipid metabolism
-high blood sugar —> pancreas releasing insulin —> helps glucose to enter cells and convert glucose to glycogen
-insulin lowers blood sugar levels
diabetes overview
-chronic disruption of insulin signalling
-hyperglycemia- high blood glucose levels
symptoms of diabetes
-excessive thirst or urination
-fatigue
-weight loss
-blurred vision
untreated diabetes
-circulatory disorders
-renal failure
-blindness
-gangrene
-stroke
-heart attack
type I diabetes
-autoimmune disease with unknown causes
-complete loss or inactivity of beta cells
-immune system attacks beta cells that produce insulin —> beta cells are destroyed and the pancreas can’t produce insulin —> high glucose levels in the blood
type II diabetes
-metabolic disorder that can be caused by lifestyle factors and genetic predisposition
-decrease in insulin secretion
-tissues fail to respond to insulin- insulin binds to receptors —> signalling can’t activate GLUT4 transporter —> glucose can’t enter the cell —> high glucose levels in the blood (amyloid deposits)
acute pancreatitis
-acute inflammation of the pancreas
-leading cause of GI-related hospitalizations in the US
-common causes include gallstones, alcohol use, and hypertriglyceridemia
pathogenesis of acute pancreatitis
-premature activation of the enzyme trypsinogen to trypsin in acinar cells of the pancreas instead of the duodenum
-once activated, trypsin activates several pancreatic enzymes and leads to self digestion
-protein 1- serine protease inhibitor, kazal type 1 (SPINK1) and in pancreatitis, there is a mutation or absence of function of SPINK1
-protein 2- cystic fibrosis transmembrane conductance regulator (CFTR), an ATP-gated ion channel that mediates the passive diffusion of Cl and HCO3 —> in pancreatitis, you have a loss or disfunction of CFTR which leads to an abnormal secretion of digestive enzymes
physiological condition of acute pancreatitis
increased intraductal pressure (gallstone) —> high intracellular Ca2+ level (alcohol use, hypertriglyceridemia)
pancreatic ductal adenocarcinoma
-type of pancreatic cancer involving the organ’s exocrine cells (those releasing digestive enzymes)
-risk factors include chronic pancreatitis, diabetes, inherited DNA mutations, obesity, and smoking
-causes about 90% of all pancreas cancers
-3 lesion types: PanIn, IPMN, and MCN
PanIN
-pancreatic intraepithelial neoplasia
-microscopic size (<5 mm)
-found in small intralobular ducts
-columnar or cuboidal cell type
-causes ~90% of PDAC cases
-commonly found in head of the pancreas
IPMN
-intraductal papillary mucinous neoplasm
-characterized as growths of ductal epithelium
-columnar cell type
-macroscopic size (>= 1 cm)
-account for <10% of PDACs
-commonly found in the head and neck of the pancreas
MCN
-mucinous cystic neoplasm
-does not involve pancreas ductal system
-characterized by ovarian-type stroma
-macroscopic size (avg. 10 cm)
-account for <3% of PDACs
-commonly found in the pancreas body and tail
whipple procedure
surgeons remove the head of the pancreas, most or all of the duodenum, portion of bile duct, gallbladder with lymph nodes, and sometimes part of the stomach
distal pancreatectomy
surgeons remove the body of the pancreas, tail of pancreas, and spleen
total pancreatectomy
surgeons remove the entire pancreas, spleen, gallbladder, common bile duct, portion of the small intestine, and portion of the stomach
external beam radiation therapy
machine directs radiation through skin to encounter tumors (neoadjuvant) or tumor sites (adjuvant)
intensity-mediated radiation therapy
transmits targeted radiation to tumors by changing radiation beam strength via computer control
stereotactic body radiation therapy
-provides targeted high doses of radiation in 5 treatments or fewer
-can treat tumors and neighboring tissue
