Histology #6 (Digestive) Flashcards
Esophogus
Overall - Tube that moves food from the the pharynx and the stomach by peristalisis
Bolus food reaches the pharux –> upper esopheogeal spicter relaxes –> bolus enters the esophgus –> food goes to the distal region of the esophgus –> sphicter relaxes and allows food to go to the stomach
Layers of the esophogus
Mucosa (innermost layer) –> Submucosa –> Muscolaris Propria –> Adventitia
Different parts of teh GI tract have different structres and functions but the main layers reman the same
Esophogeal Mucosa
Three Layers:
1. Epithelium
2. Laminca Propiria (conective stiius eto support epithelum)
3. Muscularis Mucosa (smooth mucscle)
Made up of Stratified squamus non-keritonosized cells
Lower Esophogeal Spincter (not an anotomical sphicter it is a functional sphicter)
- When damaged = get stomach acid to esophogus
Image
Esophogeal Submucosa
Contains fibroblasts + elastin fibers + sparse galnglia (Meissner PLexus) + lymphatic chanels + blood vessels + submucosal glands
- Elastic fibers = alows te esophgus to expand when food passes through
Submucosal glands comprised of mucinous cells surrounding a central lumen that prdouce acid mucin
- Submucosal = scretes mucous to lurbricate the surface of the esophogus
Esphogeal Muscularis propria
Composed of straited skelatal muscle + smooth mucles
- Skeltal mucles = in the proximal (upper) esophogus –> allows volentray control
- Smooth mucles = in the distal esophogus
- In middle of esphogus = have combination of skelatal and smooth mucle
Inner layer orients circumferentially ; outter later orients longitudley –> orientation allows segmental contracts and preistalsis
Between the inner and outter layer there are Myenteric plexuses (nerves and ganglia) - allows for rythmic contract for parastalsis
Image - Red arrows shows the inner layer is circular and the outter layer is longitidinal
Defintion of skelatal vs. Smooth mucle
Define skelatal and smooth muscle by the straitions of the muscle
Esophogeal Adventitia
Outter most layer
Composed of Loose iregular tissue
Function - Connect esophogus toe xternal sturctures (connect to retroperitineal organs)
Bottom of the esophogus - Last 1-2 cm of the esophogus = Serosa
- Covered by serosa within teh abdominal cavity
- Serosa = Simple squamours epithelium or mesothelium
Other structure:
1. Lymphatic vessles
2. Adipocytes
3. Aretry
Image
Pits and Glands of the stomach (overall)
The cardiace, fundic, and pyloric regions of the stomach contain different arrangments of gastric pits/glands
- Different regions have different pits/gands
Perfertaions of the lining of the stomach = leads to gastric pits –> go to glands at the bottom
- Glands scerete mucous + digestive enzymes
- Columnar epithelial cells
Cardiac region of the stomach
Cardia is a narrw curcular region at the gastrointestinal junction
- Secretes aliline mucous = protects the esophogeal mucosa and prevenst stomach acid from going up
Histology - Thin layer of mucosa and reduced bumber of gastric pits/Glands
- Pits at the tome ; glands a the bottom
- Pits and glands are the same size
Fundic region of the stomach
Projects into a dome like stricture above the sophogus fomring the largest and central region of the stomach
Has glands that secrete digetsive ezumes and proteins that aid in digestion
Fundic region of the stomach histology
Pista re thick and short ; glands are larger
Pyloric region of the stomach
Funnel shape opening up into the pyloric sphicter
Contains long pits and mucous secreting glands
- Glands make pepsin to aid in digestion
Histology - Deeper pits (longer) and shorter glads
- Glands produce gastrin hormone
Fundic stomach Cells
- Findic surface mucousal cells
- Fundic neck mucous cells
- Parietalc ells
- Cheif cells
- Eneroendrocrone cells G cells)
Fundic tomach cells (Mucoousal cells)
Overall - mucosal cells provde a protective barrier
Funcic surface mucosal cells + Fundic neck mucous cells BOTh fucntion in protectsion
Surface cells = secrete Alkiline mucous
Neck cells (bottom cells) = Secret Acidic mucous
Image - Histoligy - reselble gblet cels (have pocket space + less nulceus to create more mucous to create a protective barrier)
Fundic tomach cells (Pareital cells)
Function - Facilitate digestion through sceretions
- Use protom pump to make HCl
- Secret Gastric Acid (HCl) –> rasies the acity of the stomach –> Actvates gastric enzymes and kills bacteria (creates unsuitable envirnment for pathigen replication ; acts as extension of immune)
- Functions in digestion + Absorption
- ALSO secretes intrinsic factr which is required for B12 absorption
Fundic tomach cells (Pareital cells) - Histology
Image - shows where the pareital cells are located
Parteal cells = posses a “fred egg” appearnce – round cnetral nuceleus/medium sized cytoplasm + eosenphilic cytoplasm
Fundic tomach cells (Cheif cells)
Function - Work together with parietal cells to induce digestive actuvity
- Make enzymes that need an acidic envirnment to function
Secrets:
1. Pepsinogen –> Actiavted by gastric acid to become pepsin
- Pepsin = proteolytic enzyme that cleaves proteins –> get peptodes that can be absorbed
2. Lipase –> Breaks down fats
3. Leptin –> communicates with the brain to control signlas for food intake and energy expenditure
- High leptin = no hunger ; lack leptin = need energy
Fundic tomach cells - Cheif cell vs. pareitalc ell histology
Pareital cells = more eosenphilic Vs. cheif cells will have blue/pruple cytoplasm
Cheof cells = have eccentric nuceli vs. parietal cells tend to have central nucelus
Enteroedocrne cells
Example - G Cells
G Cell Function - provide important role in controling digestion (stimulatiion and regulation of digestion)
- Works iwth the nervous system to make gastrin and intiate digestive actions
Seretes gastrin –> secretion induces HCl production in pareital cells
G cell Histology
Located near the base of glands in the stomach
- If have G-Cel hyperplasia = have more cells in the base
Hard to see with H and E ; commonly idetified with IHC (use anti-gastrin)
Inner lining of the esophogus
Inner lining of the esophogus is mainly composed of squamous cels
Barret’s esophogus
Damage of the inner lining of teh esophogus
No Symotomes
Associated with GERD (acid reflux to the esophogus causing heartburn + indigetion + nocterunal regurgitation)
Sigonised with endoscopy + biopsy
- Barets is supsected by salmon pink color (normal is white) and confirmed but microscopic examination of cells
Barret’s esophogus Pathophysiology
Acid goes from the stomach to the lower part of teh esophogus (GERD)
Acid damages the inner lining of the esophogus
Have Intestinal metaplasia - sequmous to columnar goblet cells (intestinal cells)
- Goblet cells are more resistent to stomach acid
Barret’s esophogus Histology
Have intestinal type cells in the esophogus
See trasnitiion of starfied squamous to intestinal columnar (goblet cells)
Barret’s esophogus vs. Chroic brinchitus
BOTH = indicated by metaplasia but different types
Barretts - intetsinal metaplasia (statified squamous to columnar intestinal epithelium)
Chronic mronchitus - sqamous metaplasia (psudostratfied columnar to squamous)
Image - see the metaplasia
Lacteals
Location - ONLY found in the small intestine
- Located centrally in teh villi within the lamina propria
- Function of SI = absorb Nutrietnst (does so because of the villi)
- lacteals = Lymphatic vessels in the Villi
Function - absorb dietary fats and fat soluble vitamens + affect gut immune repsone by facolitatiing the transport of antigen and antigen presenting cells
Lacteals + fat absorption
Once fat and nutrients enters the lacteal –> fat/nutrients will go through the lymphatic system –> fat/nuteints will enter the blood stream –> go to cells that need nutrients
Image - shows lacteal
Primary Intestinal Lymphangiectesia
Overall - dysfuction in lacteal
aka Waldmann disease
Congetical disorder with no known cause
Diagnosed before 3 YO
Charetized by Pitting Edema
- Have enlarged lacteals leading to disrputed absorption of nuetrients
- Dilated lacteals = Lymph fluid leaks back into the small intestine
Primary Intestinal Lymphangiectesia Symptoms
- Nutrien definceycies because can’t absorb fats and vitaments
- Protein loss (albumin loss) –> decreases onctotic pressure leading to lage of lymhati vessels = lose albumin
- Edema (primary in limbs) because less portein blocking = decrease oncotic pressure
- Abdominal discomfert - swelling of the peracardium and fluid in the chest
Secondary Intestinal Lymphangiectesia
Due to an underlying condiion that block or damage lymphatic vessels in the intestines
- Get dilation of the villi
Caused by:
1. Tumors
2. Inflamatory disease (ex. chrons)
3. Traima or lymphatic infections (Ex. Whipple’s disease + TB)
Lymphangiectesia Treatment
- Long term low fat diet
- Diuretics (help with edema)
- Albumin infusion (increases onctotic pressire and reduces edema)
- Removal of diseased protion of intestine if localized
- adress the promary cause of lyphatic pbstruction IF have Secondary Intestinal Lymphangiectesia
Colon
Function - absorb water + electrolytes + vitaments
- Also produces mucus lubricating the intestinal surface
Divided into 4 layers: Mucosa –> submucosa –> muscularis Priria –> serosa
Hirschsprung disease
Overall - motor disorder of the colon
Have missing nevre cells in colon = problems with passing stool
Mainly affects newborns
- No bowl movment in 48 hours + green/brown vomit + swolen Abdomen
Diagnosis - use a rectal biopsy
Untreated = can lead to constipation + bowl obstrcution
Hirschsprung Pathophysiology
Colon Aganglionosis - no entertic ganglion cells in the submucosal/ no myenteric nerve plesxus of colon
Motor disorder of colon = caused by falure of nueral crest cells to migrate during intestinal developmet
- Agalionic segemnt of teh colon fails to relax = causes functional obstruction
- Intestinal contents build up ebhind the obstruction
Hirschsprung Histology
Angaglionic segment - absence of submucosal and myteic ganglion cells + have submucosal and mysenteric nerve enlargment to over compensate (black arrows)
Normal colon
See ganglion cells (black arrows) +submucosal nerves that are narrow (white arrows)
Hirschsprung Histology IHC
Use actylcholineestrase IHC
- Can diagnosis with IHC
Normal = Actylchontersatse highlighst sparse thin nerves vs. Hirschsprung it hiughlights abdendet course nerves (shows never enlargment)
Image - Hirschsprung Histology
- Nomrla = less brown
Colon Adenocarcinoma
Overall - cancer of the epithelial cells from colonic mucosa
Risk factors:
1. Age
2. Family history
3. Genetc predispotion
4. Illness (Ex. IBD)
5. Envirnment/lifestyle (Ex. Alchol + smoking)
Colon Adenocarcinoma Symptoms
Symptomes:
1. Rectal bleed
2. Abdominal Pain
3. Anemia
Colon Adenocarcinoma Diagnosis
- Colonscopy –> AFTER do multiple biospies of the suspected lesion
- Barium enema - barium passed into bowels + X-Ray
- CT colonoscopy
Colon Adenocarcinoma Pathophysiology
Accumilation of multiple geneic mutations over time
Three major pathways:
1. Chromosomal Insatbility (CIN)
- APC (tumor supressore) mutations
- Intiated by mutations in tumor supressor gene
2. Mircosailite insability
- Muations in Mismatch repair mutations
3. CpH Island methylaion (CIMP)
- BRAF muations (mutation in oncogene)
- Leads to serrated Polyps
Colon Adenocarcinoma types
Mustaions are largley aqured sporatically (70% of pateints)
3-5% have well defined inherited mutations
- Ex. Lynch syndrome –> gemrinline mutations in MMR genes
- Family adenomatous polyposis (FAP) –> germiline mutaion in APC
25% have family history but no well defined mutation
Colon Adenocarcinoma Histology
Healthy colon mucosa = have gladsn in regular pattern
Adenocarcimao - fewer glands + irregular patterns
Image - poorly differentared tumor (no glandular space)
Colon Adenocarcinoma treatment
- Sugery (used fro localized/earl stage)
- Chemotherapy if advanced (Ex. 5-Floururicil)
- Immunotherapy (ant PD1, anti-VEGF etx)
Grades of Colon Adenocarcinoma
Colon Adenocarcinoma is typically graded by level of glandular formation
Well diferentation (95% of tumor gland fomring) vs modertaly differentites (>50%) vs. Poor differentated (<50%)
Image - Well differentated tumor - has lots of glandular looking space but different shapes + some empty and some have cells
Liver structure
Have the right and left lobe - seperated by a ligament
Lobes are divived by the haptic veins –> divsions ate furtehr dvided into 8 segments that house the hepatic lobules
- All 8 segments have same functiion but different blood supply
Blood supply of the liver
Liver has dual blood supply
75% of the blood comes from the protal vein (deoxgynated blood) –> liver filters the blood
Liver Function
Liver = considered a gland that secreted proteins and hromones
- Detoxification - removes toxins + bacteria + old RBCs (immunologic suveilnce)
- Bile production - Bile is used for the breakdown of fats in SI
- Storage of vitame s + mineral + glucose
- Blood coagulates
- Makes albumin - controsl oncotic pressure
Liver Lobule
Overall - Basic fucnational unit of liver structure
Functiion - maintains metabolsim + detoxification
Hexoganal shape with central vein at the center
Composed of Hepatocytes arranged in plates
- Hepatocytes have a radial pattern
- Radial pattern = Ensures proper blood flow and niterinet absorption
Portal traid located at the corner of the hexoginal lobule
Poetal Triad
Composed of:
1. Hepatic artery - supplies oxygen-rich blood from the heart
2. Portal vein - carries nuterint rich blood from the digestive organs
3. Bile duct - transports bile produced by hepatpcytes
Blood and bile flow in opposite directions - Blood flow towards the cebtral vein ; bile flows towards the bile duct
- Direction of flow = important for liver function –> ensures porper porcessing of nutreints and waste
Liver Histology
See cetral vein
Portal Triad Histology
See Potal vein + Hepatic artery + Bile duct
Portal vein and hepatic arteru = made up of endothlial cells BUT can distiguish between them because the veins are larger in diamter/thinner and the arteries are thicker
- Bile duct = cuoidal epithelial cells
Central vein
Location - At the cnter of each hepatic lobule and lined with a single layer of endothelial cells
- Central vein = surroinded by the protal traid
Function - central vein receives oxygen and nucetrint rich blood at the sinusoids from the portal vein and hepatic artery
Central vein coeleces into the hepatic vein –> hepatic vein carries deoxygeated blood back to the IVC
Image - See central vein at the bottom and protal traid at the top
Central Vein Histology
Left - see sinuisoidal a the bottom - blood goes through them to the Central vein
Right - see pattern of hepatpcytes
Bile Duct
Lined with Cholangiocytes - simple cuboidal epithelum cells
Emerge from canacals of hering –> get larger in diamater –> branch to the irght and left hepatic duct –> go to the common hepatic duct –> goes to others in GI
Function - stores and passes bile
Small bile ductules join together to form left and irght hepatic ducts
Passes through the liver and collects bile as liver produces it
Chalangiocytes have many functions in bile modoification
- Chalangiocytes = chnage the bile composition through secretion and reabsorption of water and electrocytes + immine cells. barrier for bile
Bile Duct Histology
See cholgiocytes lining the bile duct
Space of Disse
Overall - Space between the sinusoidal endotheluum and hepatcytes
Function - Trasnport of lymphatic fluid to lymphatic capilaiers in the protal traid
- Important for the uptake of macromolecules + bile salts + nuetrients + ions
Blood goes from the portal triad to the central vein –> sinuisoids have fenestartes (open space that allow macromolcules to go to the space of disse)
Space of Disse = face the basolaternal surface of hepatcytes = allows hepatpcytes to uptake macromolecules
Space of Disse Histology
Seen in EM
See endothelial cells + hepatocytes ; space between is the space of Disse
In space = have Dentrotic cells + reticular fibers + liver stem cells + Stelate cells
Hepatocytes Histology
Left - See arangment of hepatcytes with iterlated plate sbranching from cnetral vein
Right - see have many mitocorndria + many ER + rpund central nucelus
Kupffer Cells
Overall - Macrophages located in the walls of hepatic sinuisoids
Shape - irregular and varibale shape + oval/indented
Cell surface conatins microvilli + slender projections that extend in all directons
Function - removes pathogens, compounds, and debris through phagocytosis
Kupffer cells Histology
Traid blie = taken up by the phagcytic Kupffer cells = can be used to idetfy them
Rigt - see iregular shape + proejctsiing coming from kupfer cells to the sinusoid space
Stellate Cells Histology
Left - Identofy Stelate cells based on lipid vaculaues circule structure)
Right - see vacule is lighter yellow + irregu;ar nuceli
Two main Pancreotic functions
- Endocrine = hormones going to the blood stream
- Exocrine = digestive enzymes going to the small intestine
Endocrine Function
Endocrone function = localizes at the islates of langerhands
Islets are composed of:
Alpaha cells - secrete glucagon
Beta Cells - Secrete Insulin
Delta Cells - Secrete somatostatin
F Cells - Secrete Pancreyotc polypeptides
Alpha cells
Function - Prodice Glucogan in reponse to low blood glucose
- fasting response + respond after excersize
Make up 20% of islet cels
H/E - stain pink due to glucogan granuales
Insulin Function Mechansim
Facilitates glucose uptake
- Occurs in skelatal mucles + Adipose tissue
Mechaism is largkey unknown
- Insulin activates tyrosin kinase –> kinase move glucose trasnprter GLUT4 from storage vesicles in the cytoplasm to the plasma membrane to take in glucose from the envirnment
H and P stain of beta cells
Alpha cells = in the periphery (pink cels) ; beta cells are on the inside of the sphere under the pink layer
Histology of alpha cells, Beta Cells, Delta ells
see immunostains for different sections
Alpha cells stain for glucogon
Beta cells = stain for insuline
EM of Acinar Cell
Have many ER for protein synthesis
- Acinar cells = main cells that make digetsive zymes = protein factpries = have many ER (light blue in image)
Acinar makes the enzymes in inactive form –> Stores inactive enzmes in Zymogen granuaals (purple in image)
- Zymogen has inactive enzyme precursory –> precursor is released via excocytosis when stimulated by CCK to the duadenum
Arrangment of Pancreatic cells + tissues
Uses Acinar Cells + epithelial cells + centracinar cells
Glandular tissue = tubular acinar function
Acinar cells = oretneted regu;larley around the lumen in glands ; centroacinar cells are the first cells in interclated ducts
Exocrine cell organization - HItsoligy
Acinar cells = have apical granals (stains pinked) + pyrimidal shaped
Centracinar Cells = pale + Low cuboidal cells
Endocrine organization
Shows the islets + blood flow in the islets
- Blood flows form the center of the islet to the periphery (drains to the portal vein)
- Capilaries put hormones throughout the body (focus on capilaries)
Capilaries - see fenetratsed capilaried running rthough the endocrine tissue + running hrough the islets
Acinar cells = darer purpel cells ; stain protein products rain ; pyrimindal shape
Centroacinar cells = more pale + cuboidal + first ductal cell in the system (form interclated ducts)
Pancreatic lobules Spatial + Strctural division
Pacreus = divided into lobules
Lobules = cluster f acinar and islets in connective tossue capsule (Blue in image)
Lobules often seoprate during processing (see on irght image)
Ductual cells and classifcation of ducts
Ductal cells = exicrine cells
Veins + arteries + nerves + lymphatics = ofte fowllow connective tissue in pancreus
- Epithelial ductual cells - start as cuboidal and trasnition to columnar cells along path to main pancreatic duct
- Also have more connective tossie as go tpwards main duct - Interclated Ducts - most proximal part
- start as cuboidal and trasnition to columnar cells along path to main pancreatic duct - Intralobular ducts (D in image) - Join acini within a lobule
- Interlobule ducts - Connect lobules
Pancreus Anatomy
Have head then neck then body then tail
Have the main duct thabranches and goes through the pancreaus to faclitate movement of pancreotic juices to teh SI
Pancreus physiology
Exocrine - digetive zbymes relased by acinar cels + ductual cells relased HCO3-
- Acinar cell - Digetsive enzymes
- Ductal cells - HCO3-
Endocrone - isle cells that have alpha + beta+ delta cells
- Hormone cells - Glycagon + insulin + Somatostatin
Image - see exocrine vs. endocrine pancreus
Diabetes
Chronic disrpuiion of insulin sugnlaing + chronic hyperglycemia
Get hyperglycemia - high blood glucose levels
Symptmes - Thirst + fatigure + weight loss + blurred vision
Untreated diabetes leads to - circulatpry disorders + renal failire + blindness + gangrene + stroke + heart attack
Tteatments - diet change + insulin (ex. pills)
Type 1 Diabetes Histology
Top image = helathy (have islets + beta cells)
Left - dark blue circles are lymphocytes influtrating islates = detroy beta cells
Right - more scere case of diabetes - immune cells took ove (no more beta cells)
Type 2 Diabetes
Metabolic disorder
Caused by Lifestyle factors + genetic predisposition
Have decrease in insulin secretion OR tissues fail to respond to insulin
- Insuoin binds to receptors but can’t activate GLUT4 –> glucose can’t enter the cell –> glucose builds up outside the cell –> reulst with high blood glucose levels
histology - charcterized by amyloid deposits (uildup of plaues in the pancreus because of misfolded proteins)
Acute Pancreatitus Pathogensis Physiological conditions
Condition 1 - increase intraductal pressure
- Caused by Gall stones
Condition 2 - High intrcelllular Ca2+ levels –> facilitaties activation of trypsin
- Caused by Alchol use + hypertriglyceridemia = get disrupts calcium homeostasis
Acute Pancreatitus Histology
Top = Normal
Other 2 images - see intestinal damage in acuate pacreatitise
- Have leukocyte invasion + edema
Acute Pancreatitus Histology #2
More svere - have cells with nerosis + hemorage
PDAC histology
PDAC progression
Two teir grading system for precursors (low and high grade dysplasia)
PANIN and Cyt=stic = transition from columnar cells with basolary orineted nuceli to irregular shape cells with displased nuceli (have cytologic and morphologic chnages)
PanIN
Pancreatoc intraepithelial neoplasia
Microscopic size (Small)
Found in intralobular ducts
Causes 90% of PDAc cases
Commonly found in the head of the pancreus
IPMN
Intraductal papilary mucinous neoplasm
Characterized as growths of the ductal epithelium
Columnar cell tye
Macroscopic size
<10% of PDAC
Comonlu found in head and neck fo pancreus
MCN
Mucinous cystic neoplasm
Does NOT invove panreus dctal system (not in communcation with pancreotic ducts)
Charcterized by ovarian type stroma (maybe due to estrogen receptors on origin cells)
Macroscopic size
<3% of PDAC
Commonly found in pancreus body and tail (distal regions)
Histology of different types of neoplasms
Goes from normal –> low grade lesions –> high grade –> PDAC
PDAC treatment - readition
- Extermal Beam Radaitio therapy
- Intesity-modulated radiation therapy (IMRT)
- Stereotactic Body radiation theapry (SBRT)
