Pathophysiology of Digestive System

most common esophageal lacerations are ____________ which are caused by ________

mallory-weiss tears severe vomiting -> no relaxation of m

achalazia

motor disorder of esophageal smooth m, dilatation of esophageal structure

patho increase of inferior esophageal sphincter tonus and nervous degeneration is the pathogenesis of which disorder

achalazia

manifestations of achalazia

dysphagia, nocturnal regurgitations, retrosternal pain

complications of achalazia

malabsorption, lung infections, esophageal rupture

_________ is recurrent gastric content expulsion in inf esophagus w/ postprandial pyrosis

GERD

pathogenesis of GERD

primary dysfxn by - decreased basal tonus secondary dysfxn by - increased intrabd p, drugs, food

pyrosis

symptom of GERD, after meal, exacerbation at night, retrosternal pain

pyrosis is NOT correlated w severity of

mucosal lesions

complications of GERD

reflux esophagitis (-> anemia), reflux laryngitis (-> dysphonia) and Barrett's syndrome (premalignant)

hiatal hernia

protrusion thru diaphragm of stomach from abd inside thorax

classification of hiatal hernias

type 1 - axial (sliding) 2 - paraesophageal (rolling) 3- mixed 4 - entire stomach upside-down

which type of hiatal hernia is by congenital causes

type 1

Type 1 manifests as gerd, but what about type 2?

type 2 does not develop gerd as long as cardial sphincter is inside abd and is fxnal

which type of hiatal hernia manifests are gastritis and PUD

type 2

_________ hiatal hernia manifests as a combo of GERD and peptic ulcers, which is aggravated in type 4

type 3

traction esophageal vs epiphrenic diverticulum

traction from outside esophagus at tracheal bifurcation

epiphrenic is at sup diaphragm

zenker diverticulum

esophageal pulsion (high p) diverticulum on post part of cervical esophagus

esophageal varices

collateral circ in portal HTN of submucosal (superficial) v in lower esophagus, risk of rupture

esophageal cancer can be __________ which is most common, or _______ developing on Barrett's esophagus

squamous carcinoma adenocarcinoma

how is Hcl formed in stomach

bicarb exchanged into v blood for Cl + K+-, H+ pumped out

parietal cells secrete acid in response to 3 types of stimuli

histamine (H2-r), ach (M3-r) and gastrin (CCK2-r)

how does increased cAMP level affect stomach

increases acidity by increasing protein kinase A -> resorption k+ ions, secretion h+

effect of gastrin

increased His synthesis in ECL cells -> parietal cells activated -> acid

________ is located in delta cells in antrum, duod and pancreatic islets

somatostatin

effect of somatostatin

released -> portal v -> heart -> inhibits acid secretion

stomach is protected by

tight cell jxns, mucus layer and PGs

classification of gastritis

acute - erosive, stress lesions, infectious gastroenteritis chronic - type A (autoimmune), B (H.pylori), C (duudeno-biliary reflux, chemical)

pathophysio mechanism of acute gastritis

vasoconstriction in splanchnic area w/ mucosal hypoxia and surface erosions

complications of ________ are ulcers or chronicity

acute gastritis

how do NSAIDs cause gastritis

inhibit COX (primarily 1) -> PGs not synthesized

curling gastric ulcers

occur in prox duod and associated w/ trauma

_____ arise in patients w/ intracranial disease by acid hypersecretion by vagal nuclei

cushing ulcer

pathogenesis of stress-related gastric ulcer

local ischemia by vasoconstriction

______ is associated w/ autoatb against parietal cells

chronic fundic gastritis type A

what is seen in patients w/ chronic gastritis type A

achlorhydria and megaloblastic anemia

type B chronic gastritis is localized in

antrum

flagella, urease, adhesins and toxins are virulence factors for which bacteria

h pylori

PUD

lesions of gastric mucosa extending beyond m mucosae (at least 3 layers) from imbalance in aggressive/protective factors

increased Hcl (+pepsinogen), vasodilation and smooth m tonus is associated with which patho

peptic gastric ulcer

PU are commonly localized in _______ and in _______ patients

antrum + duodenum, one or all layers older male

manifestation of ______ is abd pain (midline epigastrium) especially when stomach empty

PU

Zollinger-Ellison's syndrome

multiple gastroduod ulcers by gastrin-secreting tumour, diarrhea from lipase modifications

Dumping syndrome

syndrome of gastrectomized patients (Bilroth or Roux surgeries)

early vs late dumping syndrome

early - premature evacuation of hypertonic gastric content, GIT symptoms + vasodilation late - absorption glucose -> hyperglycemia -> insulin -> hypoglycemia

carcinoid syndrome

vasoactive substances secreted by tumour causing flushing, sweating, bronchospasms, abd pain

manifestations of gastric adenocarcinoma

resembles chronic gastritis

celiac disease, gluten-induced enteropathy and non-tropical sprue

chronic disorders of proximal SI from gluten intolerance (gliadin), characterized by severe malabsorption

celiac disease pathogenesis

antibody rxn against transglutaminases + gliadin (which digest gluten) and endomysial -> kill enterocytes by cytokines + Ly -> increased movement gliadins -> deaminated by transglutaminases -> cycle repeats

maldigestion vs malabsorption

digestion flaws vs absorption impairment

pathophysiological mechanism of malabsorption syndromes

asynchronism bw stomach emptying and release of pancreatic juice or bile in duodenum, decreased CCK

reduced absorption b12 is seen in

malabsorption syndromes, atrophic gastritis, vegetarians, Crohn's (ileum lesions)

enterocyte defects cause malabsorption in what

disaccharides, lactose, lipids

defects of transporters of intestinal mucosa causing malabsorption

hartnup disease (impairment a-as), cystinuria (cysteine + a-as)

consequences of monosaccharide malabsorption

fermentation by bacterial flora -> gassy, diarrhea

diverticulosis

presence of multiple diverticula in the walls of the (primarily sigmoid) colon

causes of diverticulosis

structural abnormalities of intestinal wall or constipation

leading cause of UGIB

diverticulosis -> hemorrhage

genetics, autoimmune association, measles and psych problems are etiologies for which patho

IBD

NOD2

susceptibility gene in Crohn, it encodes protein binding to peptidoglycans -> ineffective against intestinal bacteria fighting

pathogenesis of IBD

bacterial flora + defense mechanisms imbalanced, inflammatory rxn (cytokines, Ly, TNF, IL)

cytokines activated by IBD

TNF-a - apoptosis of mucosal cells IL-1 - inflammatory rxn + fibrosis IL-8 - activation of neutrophils - ulcers

defects of T cells + IL-10 is recognized in which patho

crohn's

localization of crohn's vs UC

crohn is along whole GIT UC is usually rectal, colon

manifestation of Crohn's vs UC

crohn - gradual onset watery diarrhea UC - sudden onset, bloody diarrhea often

complications of Crohn's vs UC

crohn - stenosis, fistual, hemorrhage UC - megacolon, renal lithiasis

extraintestinal manifestations of Crohn

uveitis, polyarthritis, ankylosing spondylitis, clubbing

primary sclerosing cholangitis and colonic adenocarcinoma are respectively more common in which IBD

UC Crohn's

ischemic colitis cause

atherosclerosis

diagnostic criteria for IBS

improvement w/ defecation, onset associated w/ change in frequency or appearance of stool

acute pancreatitis

acute inflammation of pancreas by autodigestion w/ necrosis, from activation of trypsin -> other pancreatic enzymes

mild vs severe forms of acute pancreatitis

mild is edematous severe is necrotic-hemorrhagic

causes of acute pancreatitis

gallstones, alcohol, hep, trauma

pathophysio mechanisms of acute pancreatitis

increased p (gallstone) or patency (alcohol) of pancreatic ducts, duodeno-pancreatic reflux (duod obstruction) or intracell activation of enzymes

pancreatic trypsin activates :

other enzymes, coag factors, bradykinin hormone and complement

how does high fat + protein diet cause acute pancreatitis

CCK stimulated to release -> enzyme secretion (trypsinogen + zymogen cascade)

how does alcohol cause acute pancreatitis

stimulates gastrin + causes Oddi sphincter spasm, sensitizes acinar cells to CCK

effects of pancreatic enzyme activation in acute pancreatitis

inflammation edema, proteolysis, fat necrosis, hemorrhage (elastase), cytokine release

MICROCIRCULATORY IMPAIRMENT in acute pancreatitis

constriction vessels + neutrophil stasis ischemia -> release enzymes = decreased vasc perfusion + blood stasis -> coag + fibrin deposits

hypocalcemia, hypomagnesemia, ca salts and hyperglycemia occurs in which patho

acute pancreatitis

complications of acute pancreatitis

pseudocysts, circulatory shock, hypoxia, ARDS, acute renal failure, DIC

"great abd drama" is in which patho

acute pancreatitis (sudden abd belt pain), "pancreatic position" is knee-pectoral

diagnosis of acute pancreatitis

amylase + lipase increased

chronic pancreatitis

Chronic inflammatory process that destroys both components of the pancreas (exocrine and endocrine) and ultimately leads to fibrosis of the entire gland

forms of chronic pancreatitis

1. w/ calcification -> from alcohol

2. obstructive -> occlusion by stenosis, dilation of the rest

3. Idiopathic or by hypercalcemia in hyperparathyroidism

pancreatic insufficiency in chronic pancreatitis manifests initially as

exocrine -> endocrine fxn

tumours of pancreas or papilla of Vater

usually on head, from mechanical jaundice, Courvoisier sign (enlarged gallbladder)

causes of acute hep

HAv + HEV, alcohol, drugs

which hep is cause for hepatocell carcinoma + occurs w/o cirrhosis

HBV

pathogenesis of acute viral hep

hepatocyte necrosis, inflammatory infiltrate from Ly mechanisms -> hepatic regeneration after viral aggression

phases of acute hep

1. incubation

2. prodromal (fatigue, nausea, headache, cough)

3. jaundice/sick (1-2w after prodromal, hepatomegaly)

4. recovering - 6-8w after

acute liver failure

liver disease that produces hepatic encephalopathy within 6m of initial diagnosis, from drugs or hepatitis -> massive hepatic necrosis

clinical features of acute liver failure

jaundice, vomiting, high transaminases, coagulopathy and encephalopathy develop

acute vs chronic hepatitis time period

6m is chronic

chronic hep causes

acute hep, alcohol, NASH, drugs, immune, genetic

3 forms of alcohol-induced liver injury

steatosis, alcoholic steato-hepatitis, fibrosis -> cirrhosis

pathogenesis of alcoholic liver disease

hepatotoxicity, cyP-450 -> ROS + TNF-a, increased intestinal permeability

NAFLD (nonalcoholic fatty liver disease)

NAFL -> steatosis NASH -> steatosis + inflammation in patients w/ obesity + insulin resistance

autoimmune hepatitis (AIH) histo findings

hepatic inflammation w/ preponderance of plasma cells + fibrosis

types of AIH

1 - classic, hypergammaglobulinemia, ANA atb 2. anti-liver/kidney microsomal atb