ALTERATIONS OF

DIGESTIVE
FUNCTION
Learning Objectives
◦ Differentiate mechanisms and hormones of short-term regulation from intermediate
and long-term regulation of food intake.
◦ Differentiate visceral from subcutaneous fat.
◦ Define and list major causes of malnutrition and starvation.
◦ Compare causes and consequences of marasmus and kwashiorkor and the role of
the somatic compartment and the visceral compartment in each disorder.
◦ Describe the pathology of marasmus-kwashiorkor.
Feedback mechanisms for control
of food intake
◦ Signals that decrease appetite and feeding
◦ Leptin is a hormone produced by increasing
amounts of fat cells as they increase in size; it
inhibits food intake
◦ Stretch receptors in the stomach activate sensory
afferent vagal pathways that inhibit food intake.
◦ Glucagon-like peptide-1 (GLP-1), cholecystokinin
(CCK), and insulin are gastrointestinal hormones
that are released by the ingestion of food and
suppress further feeding.

◦ Signals that increase appetite and feeding.

◦ Ghrelin, which is released by the stomach and
small intestine, especially during fasting,
stimulates appetite.
Regulation
Short-term Intermediate and Long-term

◦ Oral receptors detect tasting, chewing, ◦ Increased blood glucose.

swallowing

◦ Adipose cells secrete hormones.

◦ GI tract secretes hormones
◦ CCK, glucagon-like peptide 1, ghrelin, insulin,
◦ Leptin
glucagon

◦ Increased blood ketoacids.

◦ Stomach stretches
 Hypothalamus satiety center
 Hypothalamus satiety center
 Feeling of “fullness”
 Feeling of “fullness”
Obesity
◦ Overweight (BMI ≥ 25) and obesity (BMI ≥ 30)
◦ Some drugs are lipophilic and exhibit increased distribution
in fat tissue
◦ Multi-factorial disease: genetics and environment

◦ Adipocytokines – bioactive peptides secreted by adipose

tissue
◦ Leptin
◦ Increases with increased adipose
◦ Involved in satiety and appetite

◦ Adiponectin
◦ Decreases with increased adipose
◦ Regulates insulin sensitivity
Upper Versus Lower Body
Obesity
A. Central, abdominal, or visceral

B. Peripheral or gluteal-femoral
Malnutrition
◦ Marasmus
◦ Too few calories and too little protein in diet
◦ Affects the somatic compartment more severely

◦ Kawashiorkor
◦ Adequate calories but too little protein in diet
◦ Affects the visceral compartment more severely

◦ Marasmus-kwashiorkor
◦ Advanced protein-calorie deficit together with increased protein requirement or
loss.
◦ Fatty degeneration of organs such as the heart and liver.
◦ Obvious edema and wasting and loss of organ mass.
◦ Cardiac dysfunction
◦ Asymptomatic infections because their immune systems fail to respond appropriately.
◦ Loss of subcutaneous fat
◦ Reduced capacity for temperature regulation and water storage.
◦ Easily dehydrated and hypothermic
Learning Objectives
◦ Describe the physiologic mechanism involved in anorexia, nausea, and vomiting
◦ Compare the effects of parasympathetic and sympathetic activity on the motility
and secretory function of the gastrointestinal tract
◦ Differentiate causes of dysphagia, achalasia, esophageal lacerations, and hiatal
hernia.
◦ Describe the causes, pathophysiology, and complications (including Barrett
esophagus) of gastroesophageal reflux disease.
◦ Differentiate causes, pathophysiology, and clinical manifestations of peptic ulcer
disease, Zollinger-Ellison syndrome, and stress ulcers.
Anorexia, nausea, and vomiting
◦ Anorexia –
◦ Loss of appetite

◦ Nausea
◦ Ill-defined and unpleasant subjective sensation
◦ Common cause is abdominal distention
◦ ANS manifestations such as watery salivation and vasoconstriction with pallor, sweating,
and tachycardia are common
Vomiting
◦ Vomiting Center can be activated by:
◦ Irritation from GI tract and other abdominal organs
◦ CNS stimulated by emotions, sights, or sounds
◦ Vestibular (ear) apparatus
◦ Chemoreceptor trigger zone, which activated by chemical agents
such as drugs or toxins

◦ Hypoxia exerts a direct effect

◦ Decreased CO, shock, brain ischemia

◦ Neurotransmitters
◦ Dopamine – prochlorperazine (dopamine antagonist)
◦ Affects the CTZ
◦ Acetylcholine – anticholinergic drugs such as scopolamine
◦ Receptors in the vestibular center
◦ Serotonin (5HT) – ondansetron
◦ Cancer therapies
◦ Opioid receptors
Abdominal Pain
◦ Presenting symptom for a number of GI disorders
◦ Root of the problem:
◦ Mechanical – stretching and (rapid) distention
◦ Inflammatory – pain mediators, edema and vascular congestion,
◦ Ischemic
◦ Parietal, Viseral, or Referred
◦ Parietal (somatic) pain: In the peritoneum
◦ Lateralizes due to innervation, localized, sharp
◦ Visceral pain: In the organs themselves
◦ Usually around midline, diffuse and vague, dull
◦ Referred pain: Felt in another area, usually the back
Esophagus
◦ Disorders of Esophageal Structure and Function
◦ Swallowing Disorders
◦ Esophageal Diverticula
◦ Esophageal Lacerations
◦ Hiatal hernias

◦ Gastroesophageal reflux disease

◦ Cancer of the esophagus

Disorders of Esophageal Structure
and Function
◦ The Lower esophageal sphincter has a great deal tone

◦ Dysphagia –
◦ Mechanical or Functional
◦ Achalasia – failure to relax ~ incomplete relaxation

◦ Esophageal Laceration
◦ Mallory-Weiss syndrome
◦ Inadequate relaxation of the esophageal sphincter during vomiting,
Esophageal Concerns
◦ Hiatal Hernia
◦ Protrusion or herniation of stomach
through esophageal hiatus of the
diaphragm
◦ Sliding –
◦ Most common; Supine versus standing;
Associated w/ gastroesophageal reflux
(GERD); factors that increase intra-
abdominal pressure

◦ Paraesophageal -
◦ Stomach pouch slides out; Reflux is
uncommon; Congestion of blood leads to
edema and ischemia; Mechanical
strangulation is a major complication
Gastroesophageal
Reflux Disease (GERD)
◦ Reflex versus GERD

◦ Lower esophageal sphincter is weak/incompetent

◦ Refluxate  esophageal mucosa injury

◦ Treated with antacids, H2-receptor antagonists, proton

pump inhibitors

◦ Can lead to Barrett esophagus  adenocarcinoma

Cancer of the Esophagus
◦ Most common at the gastroesophageal junction

◦ The pathogenesis of esophageal carcinoma is facilitated by

◦ Chronic inflammation, metaplasia, and dysplasia caused by gastroesophageal reflux (Barrett
esophagus)
◦ Long-term exposure to irritants, such as alcohol and tobacco, that cause neoplastic
transformation

◦ Clinical manifestations
◦ Chest pain and dysphagia
◦ Occurs in individuals older than 60 years of age
Disorders of the Stomach
◦ Gastric Mucosal Barrier

◦ Gastritis

◦ Ulcerative Disorders

◦ Cancer of the Stomach

Patho and Pharm
Prostaglandins Stimulate Proton- Pump
HCl
secretion

Proton
pump
Gastritis
◦ Inflammatory disorder of the gastric mucosa
◦ Acute Gastritis
◦ Associated with H. pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), drugs, chemicals
◦ Chronic Gastritis
◦ 3 major types of chronic gastritis: Helicobacter pylori gastritis, autoimmune gastritis, and
chemical gastropathy.7
◦ Absence of grossly visible erosions and the presence of chronic inflammatory changes,
leads to atrophy of the glandular epithelium
◦ Loss of Chief cells and Parietal cells
◦ Leads to elevated levels of Gastrin
◦ Older adults, chronic inflammation and mucosal atrophy, and metaplasia
◦ H. pylori: Secrete urease and promote strong inflammatory response
 Peptic Ulcer Disease
◦ Break or ulceration in the protective mucosal lining of
the lower esophagus, stomach, or duodenum
◦ Acute versus chronic ulcers
◦ Superficial (erosions) versus deep
◦ Risk factors
◦ Genetic predisposition
◦ H. pylori infection
◦ Habitual use of NSAIDs
◦ Excessive use of alcohol, smoking, acute pancreatitis,
chronic obstructive pulmonary disease, obesity, cirrhosis,
and over 65 years of age
FEATURE Gastric Ulcers Duodenal Ulcers
(more common)
Location Stomach Duodenum
Risk Factors Frequent cause: H. pylori Increase in parietal cells
Back diffusion of HCl into High gastrin levels
mucosal layer→ release Rapid gastric emptying
of Histamine Increased acid production
Demographics ~ 55 – 65 Younger adults, Type O
Blood Group None Type O
Nourishment May be malnourished “Pain-food-relief”
Acid production Normal, reabsorbs H+ Hypersecretion
Pain Occurs ½ - 1 hour after a Occurs 1.5 – 3hr after a
meal meal
No nighttime issues Nighttime discomfort
Hemorrhage Hematemesis > melena Melena > Hematemesis
Malignancy Associated Rare
Peptic Ulcers
◦ Zollinger-Ellison Syndrome
◦ Associated with a gastrinoma ~ Chronic secretion of gastric acid
◦ Gastric and duodenal ulcers

◦ Stress Ulcers
◦ Is a peptic ulcer related to a severe illness, multisystem organ failure, or major trauma
◦ Curling ~ related to burn injuries, trauma, ARDS, Sepsis
◦ Result from ischemia, tissue acidosis, and bile salts entering the stomach in critically ill persons
with decreased gastrointestinal tract motility
◦ Cushing ~ related to head trauma
◦ Thought to be the result of hypersecretion of gastric acid due to overstimulation of vagus nerve
Cancer of the Stomach
◦ Environmental risk factors
◦ Infection with Helicobacter pylori that carries the CagA gene product, cytotoxin-associated
antigen A (80% of cases)
◦ Dietary factors
◦ High salt intake
◦ Food additives (nitrates) in pickled or salted foods (bacon)
◦ Low intake of fruits and vegetables
◦ Atrophic gastritis
◦ Lifestyle, alcohol consumption, cigarette smoking
◦ Begins in the glands of the stomach mucosa
◦ Clinical manifestations
◦ Symptoms do not usually occur until the tumor has metastasized: Weight loss, upper
abdominal pain, vomiting, hematemesis, anemia
Learning Objectives
◦ Compare and contrast Crohns and Ulcerative Colitis
◦ Be able to discuss the etiology and pathology of disorders concerning GI motility
◦ Be able to discuss the signs and symptoms of small bowel obstruction as it relates
to location and severity
◦ Compare and contrast malabsorption syndromes and their unique presentation
◦ Identify various types of GI bleeding
Disorders of the Small and Large
Intestines
◦ Inflammatory Bowel Disease
◦ Infectious Enterocolitis
◦ Appendicitis
◦ Disorders of Motility
◦ Peritonitis
◦ Disorders of Intestinal Absorption
◦ Colorectal Neoplasms
Inflammatory Bowel Diseases
◦ Chronic, relapsing inflammatory bowel disorders of unknown origin
◦ Genetics
◦ Environmental factors: Gut flora, smoking
◦ Alterations of epithelial barrier functions
◦ Immune reactions to intestinal flora
◦ Abnormal T-cell responses
◦ Examples
◦ Ulcerative colitis
◦ Crohn disease
Inflammatory Bowel Disease
◦ Ulcerative Colitis
◦ Is common in those 20 to 40 years of age or of
Jewish descent.
◦ Clinical manifestations
◦ Diarrhea (10 to 20 bowel movements per day),
bloody stools, cramps
◦ Remission and exacerbations
◦ Increased risk for colon cancer is demonstrated.

◦ Crohns Disease
◦ Clinical manifestations
◦ Abdominal pain and diarrhea are the most common
signs; more than five stools per day.
◦ Anemia may develop as a result of malabsorption
of vitamin B12 and folic acid.
 Ulcerative Colitis Crohn Disease
Location of lesions Colon and rectum; no “skip” lesions All of GI tract—mouth to anus; “skip”
lesions common

Area affected Mucosal layer Entire intestinal wall

Type of inflammation Ulcerative and exudative Granulomatous

Abdominal pain Occasional Common

Bloody stools Common Less common

Steatorrhea Rare Common
Fistulas Rare Common
Strictures Rare Common
Development of Relatively common Uncommon
Cancer
Infectious Enterocolitis
◦ Viral Infections
◦ Rotavirus (kids), Norovirus (all ages), Enteric Adenoviruses (kids)
◦ Bacterial Infections
◦ Ingestion, infection
◦ More severe than viral infections: dehydration, sepsis, and perforation
◦ Two particularly serious forms
◦ C. difficile
◦ E. coli O157:H7
Colitis
Clostridium difficile E. coli O157:H7

◦ Gram-positive spore-forming bacillus ◦ Enterohemorrhagic

◦ Normal flora that takes advantage of ◦ Found in feces and contaminated milk
disruption of microflora environment of healthy dairy/beef cattle
◦ Shigella-toxins that attach and
◦ Pseudomembranous colitis ~ life damage the mucosal lining
threatening form of the disease ◦ Gain access to circulatory system and
initiate platelet activation
◦ Muscle tone in colon can be lost, at risk
◦ Hemolytic uremic syndrome
for perforation
◦ Thrombotic thrombocytopenic purpura
Diverticular Disease of the
Colon
◦ Diverticulosis
◦ Asymptomatic diverticular disease. Diverticula are herniation
of mucosa through the muscle layers of the colon wall
◦ Diverticulitis
◦ Inflammatory stage of diverticulosis.
◦ Pain in the lower left quadrant, accompanied by nausea and
vomiting, tenderness in the lower left quadrant, a slight fever, and
an elevated white blood cell count.

◦ Possible causes
◦ Almost nonexistent in many African nations and
underdeveloped countries
◦ This suggests that factors such as lack of fiber in the diet, a
decrease in physical activity, and poor bowel habits, along with
effects of aging, contribute
Disorders of Intestinal Motility
◦ Diarrhea

◦ Constipation

◦ Acute Intestinal Obstruction

Diarrhea
◦ Acute or Chronic

◦ Inflammatory (small-volume) versus Non-inflammatory (large-volume)

◦ Inflammatory ~ presence of fever and bloody diarrhea
◦ Non-inflammatory ~ large-volume watery and nonbloody stools, periumbilical cramps

◦ Types
◦ Osmotic
◦ Secretory
 Diarrhea
TYPE Description Causes
Non-absorbable substances draw
• Mg, Sulfates, and phosphates
water into the lumen
• Lactase deficiency
Osmotic Excessive motility decreases transit
• Celiac disease
time, mucosal surface contact and
• Short bowel syndrome
opportunities for fluid absorption
Large volume
• Bacterial endotoxins
Caused by excessive mucosal • Neoplasms
Secretory
secretion of Cl or HCO3-
Small volume
• Fecal Impaction
Constipation
◦ Defecation (discharge of feces from the rectum) is controlled by the action of two
sphincters, the internal and external anal sphincters.
◦ Internal sphincter is a several-centimeters-long, circular thickening of smooth muscle that lies inside
the anus.
◦ External sphincter – Under voluntary control.
◦ Defecation reflexes.
◦ Intrinsic myenteric reflex – Initiated by distention of the rectal wall
◦ Parasympathetic reflex –
◦ Signals are transmitted first to the sacral cord and then reflexively back to the descending colon, sigmoid colon,
rectum, and anus by the pelvic nerves.
◦ Increase peristaltic movements as well as relax the internal sphincter.

◦ To prevent involuntary defecation from occurring, the external anal sphincter is under the
conscious control of the cortex.
◦ Afferent impulses in this reflex loop fatigue easily, and the urge to defecate soon ceases.
Constipation
◦ NORMAL BOWEL HABITS RANGE FROM 2-3 TIMES A DAY TO 1X A WEEK

◦ Primary constipation
◦ Normal transit
◦ Low-residual diet or low fluid intake
◦ Slow-transit
◦ Alterations in intestinal innervatoin
◦ Pelvic floor dysfunction
◦ Secondary constipation
◦ Result of neurologic disorders, drugs, metabolic disorders
Intestinal Obstructions
◦ Any condition that prevents the flow of chyme through the intestinal lumen
◦ Can be mechanical or functional
◦ Mechanical
◦ Adhesions or hernias (inguinal, femoral, and umbilical)
◦ Functional
◦ Results from neurogenic or muscular impairment of peristalsis
◦ Ileus – Loss of peristaltic motor activity

◦ Major effects of intestinal obstruction

◦ Accumulation of gases, abdominal distention, loss of fluids and electrolytes
◦ May lead to strangulation, gangrenous changes, and potentially perforation
Intestinal Obstruction
◦ Mechanical
◦ Severe, colicky pain
◦ Borborygmus
◦ Audible, high-pitched peristalsis; peristaltic rushes
◦ Awareness of intestinal movements
◦ Paralytic
◦ Continuous pain
◦ Silent abdomen
Results of Obstruction
◦ Vomiting  fluid and electrolyte loss.
◦ Pylorus - Early, profuse vomiting of clear gastric fluid
◦ Proximal - vomiting of bile-stained fluid
◦ Distal – Greater distention but vomiting may not
occur or may occur later and contain fecal material
◦ Fluids move into intestinal contents.
◦ Gas accumulates.
◦ Distension of the bowel.
◦ Pain
◦ Small bowel: Colicky pains
◦ Large bowel: Hypogastric pain

◦ Compartment syndrome  ischemia, necrosis.

◦ Anaerobic bacteria produce endotoxin  toxemia.
Peritonitis
◦ Inflammatory response of the serous membrane that lines the abdominal cavity.
◦ It can be caused by bacterial invasion or chemical irritant
◦ Leading cause of death following abdominal surgery

◦ Characteristics that make it vulnerable to effects of peritonitis

◦ Large, unbroken space that favors dissemination of contaminants
◦ Allows rapid absorption of contaminants
◦ Uniquely adept at producing an inflammatory response as a means of controlling infection
◦ Fibrinous exudate to facilitate walling off infection
◦ Significant increase in capillary permability
◦ Diminished or absent peristalsis
Malabsorption Syndromes
◦ Interfere with nutrient absorption
◦ Maldigestion
◦ Failure of the chemical processes of digestion
◦ Malabsorption
◦ Failure of the intestinal mucosa to absorb (transport) the digested nutrients
◦ Fat-soluble vitamin deficiencies
◦ Vitamin A
◦ Night blindness
◦ Vitamin D
◦ Decreased calcium absorption, bone pain, osteoporosis, fractures
◦ Vitamin K
◦ Prolonged prothrombin time, purpura, and petechiae
◦ Vitamin E
◦ Testicular atrophy
◦ Neurologic defects in children
 Malabsorption Syndromes
Concern Symptoms Causative factor
Pancreatic Insufficient pancreatic enzyme Fatty stools Pancreatitis,
Insufficiency production ( Lipase, amylase, trypsin, (steatorrhea); pancreatic CA,
or chymotrypsin) weight loss pancreatic resection,
and cystic fibrosis
Bile-salts Conjugated bile salts are needed to Fatty stools, Liver disease or bile
Insufficiency emulsify and absorb fats and are diarrhea, and obstruction
synthesized from cholesterol in the loss of fat-
liver. soluble
Poor intestinal absorption of lipids vitamins (A, D,
E, K).
Lactase Inability to break down lactose into gas (cramping Genetic
Insufficiency monosaccharides and thus prevent pain,
lactose digestion and monosaccharide flatulence) and
absorption osmotic
diarrhea
Colorectal Neoplasms
◦ Adenomatous Polyps
◦ Benign neoplasms arise from the mucosal epithelium of the intestine

◦ Colorectal Cancer
◦ Adenocarcinoma of the colon is the most common malignancy of the gastrointestinal tract
and is the major cause of morbidity and mortality worldwide
Cancer of the Small Intestine
◦ Is rare.
◦ Adenocarcinoma: Is the most common.
◦ Occurs more frequently in familial adenomatous polyposis and with Crohn disease.
◦ Long-term management includes frequent screening and endoscopic surveillance.
Cancer of the Colon and Rectum
◦ Is the third most common cause of cancer death in the United States for men and
women.
◦ Most develop from adenomatous polyps (a mass or fingerlike projection arising from
the intestinal mucosal epithelium).
◦ Rectal carcinoma
◦ Is located up to 15 cm from the opening of the anus.
◦ Tumor spreads transmurally to the vagina in women or to the prostate in men.
Hemorrhage
◦ Above the stomach  frank hematemesis
◦ Into the stomach with partial digestion of blood  coffee-ground vomitus
◦ In the intestine with blood mixing into stools  occult blood
◦ Into the intestines with large volumes of blood  melena
◦ Rapid active bleeding in lower intestines (upper too)
◦ In the rectum  red blood coating stools