Histology #6 (Digestive) Flashcards

(121 cards)

1
Q

Esophogus

A

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

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2
Q

Layers of the esophogus

A

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

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3
Q

Esophogeal Mucosa

A

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

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4
Q

Esophogeal Submucosa

A

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

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5
Q

Esphogeal Muscularis propria

A

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

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6
Q

Defintion of skelatal vs. Smooth mucle

A

Define skelatal and smooth muscle by the straitions of the muscle

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7
Q

Esophogeal Adventitia

A

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

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8
Q

Pits and Glands of the stomach (overall)

A

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

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9
Q

Cardiac region of the stomach

A

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

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10
Q

Fundic region of the stomach

A

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

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11
Q

Fundic region of the stomach histology

A

Pista re thick and short ; glands are larger

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12
Q

Pyloric region of the stomach

A

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

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13
Q

Fundic stomach Cells

A
  1. Findic surface mucousal cells
  2. Fundic neck mucous cells
  3. Parietalc ells
  4. Cheif cells
  5. Eneroendrocrone cells G cells)
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14
Q

Fundic tomach cells (Mucoousal cells)

A

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)

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15
Q

Fundic tomach cells (Pareital cells)

A

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

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16
Q

Fundic tomach cells (Pareital cells) - Histology

A

Image - shows where the pareital cells are located

Parteal cells = posses a “fred egg” appearnce – round cnetral nuceleus/medium sized cytoplasm + eosenphilic cytoplasm

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17
Q

Fundic tomach cells (Cheif cells)

A

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

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18
Q

Fundic tomach cells - Cheif cell vs. pareitalc ell histology

A

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

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19
Q

Enteroedocrne cells

A

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

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20
Q

G cell Histology

A

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)

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21
Q

Inner lining of the esophogus

A

Inner lining of the esophogus is mainly composed of squamous cels

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22
Q

Barret’s esophogus

A

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

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23
Q

Barret’s esophogus Pathophysiology

A

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

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24
Q

Barret’s esophogus Histology

A

Have intestinal type cells in the esophogus

See trasnitiion of starfied squamous to intestinal columnar (goblet cells)

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25
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
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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
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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
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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
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Primary Intestinal Lymphangiectesia Symptoms
1. Nutrien definceycies because can't absorb fats and vitaments 2. Protein loss (albumin loss) --> decreases onctotic pressure leading to lage of lymhati vessels = lose albumin 3. Edema (primary in limbs) because less portein blocking = decrease oncotic pressure 4. Abdominal discomfert - swelling of the peracardium and fluid in the chest
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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)
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Lymphangiectesia Treatment
1. Long term low fat diet 2. Diuretics (help with edema) 3. Albumin infusion (increases onctotic pressire and reduces edema) 4. Removal of diseased protion of intestine if localized 5. adress the promary cause of lyphatic pbstruction IF have Secondary Intestinal Lymphangiectesia
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Colon
Function - absorb water + electrolytes + vitaments - Also produces mucus lubricating the intestinal surface Divided into 4 layers: Mucosa --> submucosa --> muscularis Priria --> serosa
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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
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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
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Hirschsprung Histology
Angaglionic segment - absence of submucosal and myteic ganglion cells + have submucosal and mysenteric nerve enlargment to over compensate (black arrows)
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Normal colon
See ganglion cells (black arrows) +submucosal nerves that are narrow (white arrows)
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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
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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)
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Colon Adenocarcinoma Symptoms
Symptomes: 1. Rectal bleed 2. Abdominal Pain 3. Anemia
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Colon Adenocarcinoma Diagnosis
1. Colonscopy --> AFTER do multiple biospies of the suspected lesion 2. Barium enema - barium passed into bowels + X-Ray 3. CT colonoscopy
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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
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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
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Colon Adenocarcinoma Histology
Healthy colon mucosa = have gladsn in regular pattern Adenocarcimao - fewer glands + irregular patterns Image - poorly differentared tumor (no glandular space)
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Colon Adenocarcinoma treatment
1. Sugery (used fro localized/earl stage) 2. Chemotherapy if advanced (Ex. 5-Floururicil) 3. Immunotherapy (ant PD1, anti-VEGF etx)
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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
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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
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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
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Liver Function
Liver = considered a gland that secreted proteins and hromones 1. Detoxification - removes toxins + bacteria + old RBCs (immunologic suveilnce) 2. Bile production - Bile is used for the breakdown of fats in SI 3. Storage of vitame s + mineral + glucose 4. Blood coagulates 5. Makes albumin - controsl oncotic pressure
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Key structires of the liver
1. Portal triad 2. Central Vein 3. Bile Duct 4. Space of Disse
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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
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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
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Liver Histology
See cetral vein
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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
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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
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Central Vein Histology
Left - see sinuisoidal a the bottom - blood goes through them to the Central vein Right - see pattern of hepatpcytes
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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
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Bile Duct Histology
See cholgiocytes lining the bile duct
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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
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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
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Specilized cells of the liver
1. Hepatocytes 2. Kupffer Cells 3. Stellate Cells
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Hepatocytes
Main functional cells of he liver Shape - Polygonal shapes + arranged in interconecting plates - Bile canaliculi between adjacent cells = allows bile to flow - Have microvili Involoved in Main function of the liver: 1. Endocrine and exocrine secretion 2. Synthesis of proteins and lipids 3. Metabolism 4. Detoxification 5. Activation of immune cells
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Hepatocytes Histology
Left - See arangment of hepatcytes with iterlated plate sbranching from cnetral vein Right - see have many mitocorndria + many ER + rpund central nucelus
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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
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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
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Stellate Cells
Overall - Mesenchymal cells located in the space of Disse Shape - Star hsaped contaning multiple lipid vacuoles in cytoplasm + irregular nuclei Functions: 1. Vitamen A storage 2. Liver development and regernations 3. Response to hepatic injury - If have toxins/pathigens = stellate cells make ECM and collegen (could lead to fibrosis)
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Stellate Cells Histology
Left - Identofy Stelate cells based on lipid vaculaues circule structure) Right - see vacule is lighter yellow + irregu;ar nuceli
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Pigments in hepatocytes
yellow color = lipfusion on Hepatocytes H ane E = older hepatpcytes ; can have also bile pigment o heptocytes
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Two main Pancreotic functions
1. Endocrine = hormones going to the blood stream 2. Exocrine = digestive enzymes going to the small intestine
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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
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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
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Glucogan Function
Overall - increases glucose in the body 1. Glycogenolysis - stimulates the liver to cnvert glycogen to gucose 2. Gluconogensis - Stimulates the liver to increase amino acid uptake from the blood to make glucose 3. Lipolysis (form of gluconeogensis) - stimulates the liver and adipose tissue to convert stores trglycerides to free fattery acids and glyceral to then make glycerol and then make glucose in the liver
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Beta cells
Produce inculin - When have food in inetstine --> hae release of gastrointestinal hormones --> leads to insulin production by beta cels - Secretion is stimulated by increase blood glucose 75% of islet cels (most numerous cell in islets) H/E = stain blue because of insulin granial Lose of function --> get tyoe 1 diabetes
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Insulin Function
Overall - decreases blood glucose - Inhibit the release wgen blood glucose decreases 1. Stimulates glycosis (get breakdown of Glucose to get ATP) 2. Stimulate glycogensis (Covert glucose to glycogen) 3. Inhibits glycogenolysis and gluconeogensos 4. Promotes triglyceride and protein syntehsis - creates a negative feedback loop to mkae sure blood surgar doesn't drop too low
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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
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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
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Delta Cells
Overall - Produce Somatostatin - Release is stimulated by increase in glucose + ghrelin in the stomach Cooridnates insulin + glucose secretion to maintain homeostasis 4% of islet cells
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Somatostatin Function
Overall - Inhibits release of glucogan + insulin Somatstin = activate somatostatsin receptors on alpha and beta cells coupled to inhibitory GPCR --> supresses electrical stimularion --> inhibits exicytosis of granualswith glucose or insulin
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Pancreatic Polypetde Cell
Aka Gamma cells/F cells Produce Pancreotic Polypeptide - Produces after eating+ in response to fasting - Sceretion stimulated by intestinal hormones cholecystoknin + secrtin + gastron 1% of islaet cells Use Immunoflourence to see
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Pancreatic Polypetde Cell Function
Regulates appetitie to reduce hunger levels - Singals to the brain through the vegas nerve to decrease hunger levels after eating and slow digestion Slows digestion - Decreases the rate of gastric emptying - Decreases pancreati exocrine secretion - Decreases Gallblader contracton
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Histology of alpha cells, Beta Cells, Delta ells
see immunostains for different sections Alpha cells stain for glucogon Beta cells = stain for insuline
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Exocrine products of the pancreus
Function - Used for breaking down food into constutent molecules for absorbption - Pancreatis makes many products that we need to digets things Produces pancreitic juice that conatins digetsive enzymes + biocarbinate + water - Products are released into the duadenum of teh SI Exocrine = uses Acinar Cells
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Acinar Cells
Secrete digestive enzymes - Take complex biomilciles and breaks them down into end products we can absrobs Secrete: 1. Amylase - breask down starches into simple surgars 2. Protease - breaks down proteins into amino acids (Ex. Trypsin) 3. Lipases - break donw fats to fatty acids and lycerol 4. Nucelases - Break donw nucleic acids into nucleotides
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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
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Interclated Duct cells
Sceret Biocarbinate and Water Bicarbinated is scerted into the diadenum to nuertilzie HCl in acidic chyme - When acidic chyme is in the dusenum scertrin homrone is released which stimultae bicrabinate release - Bicarbinate protects the small intestone from stomach acid + maks H more aklinine to optomize pH for digestive zymes to function - Controled by secrtin hromone
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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
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Mucles in pancreus
There is no muscle in the pancreus to put fluid into teh SI --> center of the acinar and endothlialc els make water to push fluid put
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Exocrine cell organization - HItsoligy
Acinar cells = have apical granals (stains pinked) + pyrimidal shaped Centracinar Cells = pale + Low cuboidal cells
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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)
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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)
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Ductual cells and classifcation of ducts
Ductal cells = exicrine cells Veins + arteries + nerves + lymphatics = ofte fowllow connective tissue in pancreus 1. 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 2. Interclated Ducts - most proximal part - start as cuboidal and trasnition to columnar cells along path to main pancreatic duct 3. Intralobular ducts (D in image) - Join acini within a lobule 4. Interlobule ducts - Connect lobules
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Centroacinar Cells
Sectrein is produced in the duodenum in presnece of acids --> secrtin binds to secrtin recpetors on memebrane of centroacinar cells --> binding leads to GPCR signaling --> get secretion of biocrabinate and water from centroacinar cells
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Interclated Ducts
Centeroacinar Cells line the interclated ducts Stimulation of the centroacinar cells stiulates the intercalted ducts Centeroaconar cels --> intercladed ducts --> Pancreatic ductal system
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Acinar Cells
Cholecytoskinin (CCK) = prduced by the duodenum - Seretion of acinar cells = stimulated by CCK CCK has a direct and indirect effect on the secretion of acinar cells - Direct - CCK binds to CCK receptors on acinar cells (CCK recpetors may or may not be found in humans) - Indirect - CCK --> affects through vegal afferent fibers --> get actylcholine --> stimulates acinar cells to release digestive enzymes
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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
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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
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Pancreus + glucose metaolism
Pancreus regulates glucose metabolism - Produces digetsive enzymes and hromones important for glucose and lipid metabolism High blood suar = pancreus releases insulin -- release will bring glucose into cells and convert glucose to glycogen in the liver - Insulin lowers blood sugar levels
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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)
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Type 1 Diabetes
Autoimmune disease Cause = unknonw but has envirnmental and genetic components Have loss or inactivity of beta cells - Immune system attacks beta cells that produce insulin --> detsroyes beta cells --> pancreus can't make insulin --> results in high blood glucose level because glucose is no longer being brought into the cells
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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)
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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)
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Acute Pancreatitus Pathogensis
Have premature activation of Tyrsinogne to trypsin in acinar cells in the pancreus (activation should occur in teh duadenmum) - Trypisn activates several pancreatc enzymes --> leads to autog=digestion of the pancreus End = have self digestion of the pancreus
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Acute Pancreatitus Pathogensis proteins
1. Serine proteae inhibitore (SPINK1) - normally inhibites the convesion of trypsinogen to trypsin ; kazal type 1 - Muation or absense of function of SPINK1 = get prmeature activation of tyrpin - Mutation alone will not cause ALSO need genetic modifcation or envirnmental trigger to cause 2. Cytsic fibrosis trasnmemrane conductase regulator - ATP gated ion chanle that meduaes passive dffusion of Cl- and HCO3- - Mutation/dysfunction chanel = get abnormal secretion of digestive enzymes = failure to wash away active trypsin to pancreatic duct = get inflamation - One mutation in chanel won't cuase ALSO need other genetic modifcation
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Acute Pancreatitus
Acute inflamation of the pancreus - pancreus is swollen for short period of time Leading cuase of gastrointestinal related hspilization in the US Mortality rate is 3%-20% Causes: 1. Gallstones + Achol Use + hypertiglyceridemia - glyceride = lipid that prpvides energy -> too much in blood causes acute pancreatitus
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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
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Acute Pancreatitus Histology
Top = Normal Other 2 images - see intestinal damage in acuate pacreatitise - Have leukocyte invasion + edema
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Acute Pancreatitus Histology #2
More svere - have cells with nerosis + hemorage
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PDAC overall
Form of pancreatic cancer involved in the organ's exocrine cells that release digestive enzymes Risk factors: 1. Chonic pancreatitus 2. Diabetes 3. Inherited DNA mutaions 4. Obesity 5. Smoking Causes 90% of all pancreus cancer 13% 5 year survival rate (bad prognosis because detected late) 19% of tumors are detected at late stage >50% of tumoes have systemic metastses
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Lesions tyoes of PDAC
1. PanLN 2. IPMN 3. MCN
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PDAC histology
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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)
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PanIN
Pancreatoc intraepithelial neoplasia Microscopic size (Small) Found in intralobular ducts Causes 90% of PDAc cases Commonly found in the head of the pancreus
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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
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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)
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Histology of different types of neoplasms
Goes from normal --> low grade lesions --> high grade --> PDAC
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PDAC treatment - surgery
Whipple - remice head of pnacreus + duadenum + bile duct + gall bladder + part of stomach Distal pancreatectomy - remove body of pacreaus + tail of pancreus + spleen Total pancreatcomy - remove pancres + spleen + gallbladder + common bile duct + some of SI + some the stomach - Patients are given artifical hormones and digetsive enzymes
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PDAC treatment - readition
1. Extermal Beam Radaitio therapy 2. Intesity-modulated radiation therapy (IMRT) 3. Stereotactic Body radiation theapry (SBRT)
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PDAC treatment - Drugs
Can give chemothearapy drugs Examples: 1. Gemcitabime 2. 5-flourouracil 3. Irontecan 3. Alubimin bound pcitaxel 4. Cisplatin 5. Paclitaxel
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LOOK AT OWN PRESENTATION
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