Digestive System Pathophysiology

Learning Objectives:
 Know the function of each organ in the gastrointestinal tract
Digestive System
 Function
 Breaks down ingested food
 Prepares food for uptake by the body’s cells
 Provides the body with water
 Eliminates waste
 Components:
 Gastrointestinal tract
 Accessory Organs
Mouth
• Reservoir for chewing and mixing food with saliva
• Tastes (and food odor) help initiate salivation and secretion of gastric
juices
• Salivation:
• 3 pairs of glands
• Secrete 1 liter a day
• Mostly water
• Alpha-amylase to initiate carbohydrate digestion
• Lipase to initiate fat digestion
• Bicarbonate to maintain pH 7.4 to neutralize bacterial acids
Esophagus
• Hollow muscular tube that conducts material from mouth to stomach
• Approximately 25 cm long
• Swallowing:
• Voluntary phase in oropharynx
• Food broken into bolus by tongue
• Involuntary phase in esophagus
• Respiration inhibited
• Epiglottis prevents food from entering larynx and trachea
• Food bolus propelled to stomach via peristalsis on smooth
muscles
• 2 – 6 cm/second
Stomach
• Hollow muscular organ
• Function:
• Stores food during eating process
• Secretes digestive juices
• Mixes food with digestive juices
• Oscillating motion breaks down large food particles
• Propels chyme into duodenum
• Gastric emptying
 • 3-6 hours depending on chemical composition and volume of food
• Large amount of food takes longer
• Solids, fats and nonisotonic solutions take longer
• Stomach mucosa
• Impermeable to water
• Absorb alcohol and NSAIDS (aspirin, etc..)
• Protected by mucus, intercellular tight junctions, bicarbonate,
submucosal acid sensors
• Gastric glands:
• Parietal cells:
• Secrete hydrochloric acid (dissolves food, bactericide,
activate pepsinogen to pepsin)
• Intrinsic factor (intestinal absorption of Vit B12)
• Gastroferrin (intestinal absorption of iron)
• Chief cells: secrete pepsinogen
Small Intestine
• Duodenum
• Mixing food with digestive juices from liver and pancreas
• Jejunum
• Nutrient absorption
• Ileum
• Absorb Vit B12 and bile salts
• Villi
• Fingerlike projections
• Longest in the duodenum and shortest in the distal ileum
• Increase the absorptive area 10-fold
• Goblet cells that secrete mucin
• Become more prominent throughout the length of the small
intestine
• Crypts or crypts of Lieberkühn
• Each crypt is monoclonal and contains only one stem cell that divides
and differentiates into goblet cell, enterocyte cell (absorptive),
enteroendocrine (hormone) cell, or Paneth cells (antimicrobial
peptides)
• Microvilli
• Tiny projections of the plasma membrane that line the apical border
of the enterocyte
• Aids in nutrient absorption
• Increase the surface area of the intestine another 20-fold
• Release digestive enzymes nucleosidases, peptidases, and
disaccharidases
• Lamina propria
• Underlies the epithelium
• Rich vascular and lymphatic network
 • Absorbs the digestive products
• Peyer patches
• Specialized aggregates of lymphoid follicles in the lamina propria
• Monitor intestinal bacteria populations and preventing the growth of
pathogenic bacteria
• Most abundant in the ileum
Large Intestine
• Cecum – receive chyme from ileum
• Appendix – immune function?
• Colon
• Absorb water
• Eliminate fecal mass

 Describe the structure and cells in gastric mucosa and the intestinal tract

 Describe the location, chemistry and absorption of fat, carbohydrates, and protein by
the digestive system
 In your small intestine, the fat molecules mix with a substance called bile,
secreted from your gallbladder, that emulsifies the fat particles, or makes them
more water-soluble.
 Your pancreas secretes a digestive enzyme, called lipase, into your small
intestine, where it digests triglyceride into its three individual fatty acids plus a
glycerol molecule.
 These fat components are now small enough to undergo absorption.

 Discuss the role of the microbiome in digestion and function of the GI tract
GI Microbiome
 Consists of about 1014 bacteria
 Mainly located in the large intestine
 Functions:
 Prevents colonization by pathogenic microorganisms
 Provides energy for the gut wall from undigested food
 Regulates the mucosal immune system
 Educating the naive infant immune system
 Important source of immune stimulators throughout life
 Contributes to the maintenance of an intact GI barrier

 Describe the clinical signs of GI dysfunction including anorexia, vomiting, constipation,

diarrhea, abdominal pain, and GI bleeding
Anorexia:
 Lack of desire to eat despite physiologic stimuli that would normally
produce hunger
 Often associated with nausea, abdominal pain, diarrhea, and
phychological distress
  Side effect of drugs and disorders of other organ systems (cancer, heart
disease, renal disease)
Vomiting:
 Forceful emptying of stomach and intestinal contents through the mouth
 Stimulation of vomiting center either direct (ex: irritants) or indirect (ex:
motion sickness or pain)
 Stimulated by serotonin from the enterochromaffin cells of the intestines
 Consequence: Fluid, electrolyte, and acid base disturbance
 Nausea: Hypersalivation and tachycardia
 Retching: Muscular events of vomiting without expulsion of vomitus
Constipation:
 Difficult or infrequent defecation
 “Normal” rate is a range
 Normal transit (functional) – normal rate but difficulty with evacuation
 Low-residual diet, low fiber, low fluid intake
 Slow-transit – impaired colonic motor activity
 Pelvic floor dysfunction – failure of muscles to relax
 Secondary causes
 Neurogenic disorders
 Opiate usage
 Endocrine disorders
Diarrhea:
 Increase in the frequency of defecation and the fluid content, volume,
and weight of feces
 Large-volume: excessive amounts of water and/or secretions from
intestines
 Small-volume: excessive motility
 Osmotic: non absorbable substance in intestine draws water into the
lumen
 Secretory: Excessive mucosal secretion of chloride- or bicarbonate-rich
fluid
 Infectious causes: rotavirus, bacterial enterotoxins from E. Coli,
Clostridium difficile overgrowth
 Cancers produce hormones that stimulate intestinal secretion
 Inflammation from ulcerative colitis or Crohn’s
 Motility: resection of small bowel, bypass, fistula, laxative
 Decreased transit time decreases ability for fluid absorption
Abdominal Pain:
 Biochemical mediators of inflammation: histamine, bradykinin, and
serotonin
 Stretching from edema and vascular congestion
 Parietal pain – localized and intense pain arising from peritoneum
 Visceral pain – stimulus acting directly on organ
 Referred pain – visceral pain felt at some distance from affected organ
 Upper GI bleeding:
 Esophagus, stomach, or duodenum
 Bright red bleeding in emesis or dark digested blood in stool
Lower GI bleeding:
 Jejunum, ileum, colon, or rectum
 Undigested blood in stool
Occult bleeding – slow chronic blood loss that can lead to anemia
Severe GI bleeding can be life threatening

 Describe the clinical signs and pathogenesis of:

 Hiatal hernia
 Protrusion (herniation) of upper stomach through diaphragm into thorax
 Most common is Sliding
 Through esophageal hiatus
 Weakening of diaphragmatic muscles
 Exacerbated by increased intra-abdominal pressure
 Coughing, bending, obesity, pregnancy

 GERD
 Esophagitis cause by the reflux of acid and pepsin from the stomach
 HEARTBURN!
 Upper abdominal pain that worsens when prone
 May experience chest pain
 Risk factors: obesity, hiatal hernia, agents that relax the lower esophageal
sphincter (LES) like nicotine
 May trigger asthma and chronic cough
 Caused by a delayed gastric emptying
 Inflammatory response in esophageal wall
 Edema, erosion, ulceration

 Barrett Esophagus
• Long term consequence of GERD
• Tissue of the esophagus is replaced by tissue normally found in stomach
• Stratified squamous epithelium lining of the esophagus is replaced by
simple columnar epithelium with goblet cells
• Adaptation to chronic acid exposure
• Symptoms:
• Frequent and longstanding heartburn
• Trouble swallowing (dysphagia)
• Vomiting blood (hematemesis)
• Pain under the sternum where the esophagus meets the stomach
• Unintentional weight loss because eating is painful (odynophagia)
 Gastritis
 Inflammation of the gastric mucosa
 Symptoms: upper belly pain, nausea, and vomiting
 Acute: Injury to protective mucosal barrier
 NSAIDS (aspirin, ibuprofen) inhibit prostaglandins which normally
stimulate mucus secretion
 Helicobacter pylori (gram negative bacterium) induces
inflammation
 Chronic:
 Pernicious anemia from decreased Vit B12 absorption due to low intrinsic
factor
 Peptic ulcer disease: erosion and ulceration of mucosal lining

 Ulcerative colitis
 Chronic inflammatory disease of the colonic mucosa
 Extends proximally from the rectum to colon
 Peak incidence in 20 – 40 yo
 Risk factors: Family history, Jewish descent, white population, Northern
Europeans
 Less common in smokers
 Commensal or pathogenic enteric microorganism
 Persistent activation of T cells
 Plasma cells in inflamed colon
 Loss of absorptive mucosal surface leads to large amounts of watery
diarrhea
 Intermittent periods of remission and exacerbation
 Lesions are continuous
 Limited to mucosa
 Mucous layer thinner
 Most severe in rectum and sigmoid colon
 Edema, strictures, and fibrosis may cause obstruction

 Crohn disease
 Chronic inflammatory disease that affects GI mucosa from mouth to anus
 Distal small intestine and proximal colon most affected
-Risk factors: family history, smoking, Jewish decent, urban residency,
ageless than 40 yo, slight predominance in woman
 Strong association with mutations in CARD15/NOD2
 Gene involved in recognition of bacteria
 Overly aggressive immune response to normal flora
 Lesion begins in submucosa and spreads through intestinal wall
 Skip lesions – one side of intestinal wall affected but other not
 Ulcerations may produce fissures
  Stomach cancer
 Rates declining in US but still high world-wide
 Risk factors: family history, blood group A, alcohol consumption
 H. pylori infection - inflammation
 Salt and nitrates in food – conversation to carcinogenic
nitrosamines
 Cigarette smoking – decreases production of prostaglandins which
maintain gastric mucosal integrity
 Pathogenesis:
 Insufficient acid secretion by inflamed mucosa creates alkaline
environment
 Bacteria work on nitrates and increase nitrosamines and damage
to cellular DNA

 Colorectal cancer
 3rd most common cause of death in US

 Know the role of H. Pylori in GI pathologies

 May be present in more than 50% people world wide
 Positive patients have a 10 to 20% lifetime risk of developing ulcer
disease and a 1 to 2% risk of developing distal gastric cancer
 Transmitted fecal-oral route, during childhood
 Most infections asymptomatic
 Barry Marshall and Robin Warren isolation and culture H. pylori from the human
stomach
 Self-ingestion experiments demonstrated that these bacteria can colonize
the human stomach and induce inflammation of the gastric mucosa

 Know the function of each accessory organ in the digestive system

 Liver
 Largest solid organ in body
 Metabolic functions require large amounts of blood
 Hepatic portal vein carries 70% of blood supply to liver
 Rich in nutrients from digestive tract
 Can release blood to maintain circularly volume in hemorrhage
 Liver lobules
 Hepatocytes
 Secrete electrolytes, lipids, bile acids, cholesterol into canaliculi
 Secrete plasma proteins into blood
 Sinusoids
 Between hepatocytes
 Mixture of venous and arterial blood
 Permeable endothelium lends to absorption of nutrients
 Also lines with phagocytic (Kupffer) cells
  Secretion of Bile:
 Bile salts
 Conjugated bile acids (with AA so more water soluble)
 Intestinal emulsification and absorption of fat
 Cholesterol
 Bilirubin
 Byproduct of hemoglobin degradation when RBC
destroyed
 “Free” – unconjugated and lipid soluble
 “Conjugated” to glucuroin acid in hepatocytes, now water
soluble

 Pancreas
 Secrete digestive enzymes
 Proteases – trypsin, chymotrypsin, carboxypeptidase, elastase
 Amylases
 Lipases
 Secrete alkaline fluids
 Neutralize acidic chime entering duodenum from stomach
 Alkaline environment required for fat absorption by intestines

 Gallbladder
 Store and concentrate bile between meals

 Know the role of the liver in metabolism of fat, carbohydrates, and protein
Fat metabolism:
 Ingested fat from intestine
 Triglycerides converted to glycerol and free fatty acids
 Used to produce metabolic energy or transported to adipose for storage
Protein metabolism:
 Deamination: amino acids converted to carbohydrates by removal of ammonia
 Ammonia converted to urea for excretion by kidney
Carbohydrate metabolism:
 Maintain blood glucose levels by maintaining glycogen stores
 Metabolic Detoxification
 Makes chemicals less toxic
 Alcohol, barbiturates, amphetamines, steroids, and hormones
 Byproducts of alcohol metabolism are acetaldehyde and hydrogen
 Acetaldehyde damages mitochondria
 Hydrogen promotes fat accumulation

 Describe the clinical signs of Liver dysfunction including portal hypertension, ascites,
and jaundice
 Portal Hypertension
• Abnormally high blood pressure in the portal venous system
• Intrahepatic: inflammation, thrombosis, fibrosis from cirrhosis, viral
hepatitis, schistosomiasis
• Posthepatic: right-sided heart failure
• Clinically presents with vomiting blood
• Esophageal varices (distended collateral veins) form from prolonged
elevation of pressure
• Also splenomegaly from increased pressure of splenic vein
• Tributary of hepatic vein

Ascites
• Accumulation of fluid in the peritoneal cavity
• 10 – 20 LITERS
• Abdominal distention
• Can displace the diaphragm and cause dyspnea
• Complication of cirrhosis, heart failure, abdominal malignancy, nephrotic
syndrome, malnutrition

Jaundice
• Yellow or greenish pigmentation of skin caused by hyperbilirubinemia
• Causes: obstruction of bile flow (gallstones), intrahepatic obstruction
(cirrhosis or hepatitis), excessive hemolysis of RBC
Newborns: impaired bilirubin uptake and conjugation so not excreted in

 Discuss the etiologic agents causing hepatitis

Hepatitis A:
 Fecal-oral transmission from contaminated food or water
 45% of adults in urban areas have HAV antibodies
 Incubation period 4 – 6 weeks
 VACCINE available
Hepatitis B:
 Transmitted via blood or sexual contact
 Mother to fetal transmission if mother infected in 3rd trimester
 Chronic infection in 15% - 30% of those with acute infection
 Causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma
 Incubation period 6 – 8 weeks
 VACCINE available
Hepatitis C:
 Transmitted via blood or sexual contact
 40% cases involve IV drug use
 Chronic liver disease in 80% of those infected
 Causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma
 Greater risk if HIV co-infected
  No VACCINE available
 Antiviral medication now available to clear Hep C
 Interferes with the reproduction of the virus's genetic material
 8 – 12 weeks
 About $100,000

 Know the pathogenesis of cirrhosis

 Irreversible inflammatory, fibrotic liver disease
 12th leading cause of death in US
 Most common causes: viral hepatitis and alcohol abuse
 Fibrosis obstructs biliary channels and blood flow
 Jaundice and portal hypertension
 Distorts the architecture of the parenchyma
 Cobbled appearance
 Describe the clinical signs and pathogenesis of:
 Acute Liver failure
 Severe impairment or necrosis of liver cells without preexisting liver
disease
 Acetaminophen overdose
 HBV infection

 Hepatocellular carcinoma
 Hepatocyte
 Caused by:
 Chronic Hep C or Hep B infection
 Cirrhosis
 Chronic inflammation and cell repair leads to DNA damage

 Cholangiocellular carcinoma
 Bile ducts
 Caused by:
 Liver fluke infestation in SE Asia
 Chronic Hep C or Hep B infection
 Cirrhosis

 Describe the clinical signs and pathogenesis of:

 Gallstones
 Present in 10% - 15% of individuals in developed countries
 Risk factors: obesity, rapid weight loss in obese people, middle
age, female, American Indian ancestry, low LDL and
hypertriglyceridemia
 Cholesterol stones: form in bile that is supersaturated with
cholesterol made in the liver
 Grow and lodge in cystic or common duct
  Pigmented stones:
 Black (hard) associated with hyperbilirubinbilia
 Brown (soft) associated with bacterial infections of bile
ducts

 Pancreatitis
 Acute:
 Usually mild but 20% require hospitalization
 Risk factors: alcoholism, gallstones, peptic ulcers, trauma
 Obstruction of outflow of pancreatic digestive enzymes
 Enzymes active inside acinar cells
 Autodigestion leads to inflammation
 Chronic:
 Repeated acute pancreatitis
 Chronic alcohol abuse
 Fibrous changes lead to strictures and ductal obstruction

 Pancreatic cancer
 Mortality is about 95%
 Usually at advanced stage before detection
 Risk factors:
 Cigarette smoking, alcohol abuse, chronic pancreatitis
 Can occur throughout pancreas
 Tumors in head of pancreas cause biliary obstruction
 May be detected earlier
 Tumors in body and tail generally asymptomatic until
advanced

Pathophysiology of the Integument

Learning Objectives:

 Know the structure and function of the integumentary system including the skin and
the accessory structures
 Skin
 Largest organ
 20% of body weight
-Epidermis
 Outer layer
 Varies in thickness from 0.3 mm (eyelids) to 3 mm (palms of
hands and feet)
 Continually renews through shedding of superficial layer –
stratum corneum
  New keratinocytes form in basal layer and move up and
differentiate
 Cells enlarge and flatten and then stack
 Melanocytes synthesize melanin in response to UV radiation
 Langerhans cells are skin specific immune cells
 Merkel cells are touch receptors
-Dermis:
 Deeper layer
 Composed of connective tissue secreted by fibroblasts
 Hair follicles, sebaceous glands, sweat glands, blood vessels,
lymphatics, and nerves
 Also contains:
 Mast cells – release histamines
 Macrophages – phagocytic immune cells
-Subcutaneous layer:
 Adipose tissue

 Accessary structures: hair, nails, glands

-Nails
• Protective keratinized plates
-Hair Follicles & Sebaceous Glands
• Integrated units
• Hair arise from bulb in dermis
• Erector pilli muscle causes hair to stand
• Sebaceous gland secretes sebum (lipid) to prevent drying
-Sweat Glands
• Eccrine sweat glands
• Distributed throughout body
• Thermoregulation
• Apocrine sweat glands
• Fewer in number
• Located an axillae, scalp, face, abdomen, genitals

 Functions
 Barrier against microorganisms, UV radiation, fluid loss, stress of
mechanical forces
 Regulate body temperature

 Describe the layers of the skin including the epidermis, dermis, and subcutaneous
layer
-Epidermis
 Outer layer
 Varies in thickness from 0.3 mm (eyelids) to 3 mm (palms of
hands and feet)
  Continually renews through shedding of superficial layer –
stratum corneum
 New keratinocytes form in basal layer and move up and
differentiate
 Cells enlarge and flatten and then stack
 Melanocytes synthesize melanin in response to UV radiation
 Langerhans cells are skin specific immune cells
 Merkel cells are touch receptors
-Dermis:
 Deeper layer
 Composed of connective tissue secreted by fibroblasts
 Hair follicles, sebaceous glands, sweat glands, blood vessels,
lymphatics, and nerves
 Also contains:
 Mast cells – release histamines
 Macrophages – phagocytic immune cells
-Subcutaneous layer:
 Adipose tissue
 Know the types, description, and examples of the primary and secondary skin lesions

 Understand the development and prevention of pressure ulcers

 Pressure Ulcers
 Ischemic ulcers resulting from unrelieved pressure, shearing forces, friction, and
moisture
 Interrupts blood flow to and from skin
 Develop over bony prominences
 Prevention: repositioning, pressure reduction surfaces, decrease moisture, and
maintain fluid, protein, and caloric intake

 Know the pathogenesis of allegoric contact dermatitis and how patch tests work
Allergic Contact Dermatitis
 T-cell mediated (delayed) hypersensitivity (type IV)
 Allergens form sensitizing agents

 Describe the pathogenesis of psoriasis

 Characterized by papules, scales, plaques, and erythema
Psoriasis:
 Chronic, relapsing, proliferative, inflammation of skin and nails
 T-helper cell mediated autoimmune disease
 Turnover of dermis goes from normal 26-30 days to 3-4 days
 No time for keratinocyte maturation and keratinization
 Thickened epidermis and plaque formation

 Describe the presentations, etiologic agents involved in bacterial, viral, and fungal
infections of the skin
Bacterial Infections:
• Folliculitis: infection of hair follicle
• Usually Staphylococcus aureus
• Furuncle: “Boil”
• Inflammation of hair follicle developing from folliculitis
• Methicillin-resistant S. aureus (MRSA)
• Carbuncle: collection of infected hair follicles
• Cellulitis: infection of dermis and subcutaneous tissue
• Extension of furuncle or carbuncle
Viral Infections:
• Herpes Simplex Virus I and 2
• Oral and genital infections
• Transmitted through saliva and genital secretions
• Virus infects epithelial cells then moves by retrograde axonal
transport to dorsal root ganglion
 • Latent infection until reactive when virus moves down
peripheral nerve
• Can infect eyes
• Antivirals acyclovir, famciclovir, and valaciclovir
• Herpes Varicella-Zoster
• Cause chicken pox and can reactive to cause shingles
• Human Papillomavirus (HPV)
• Warts
• Infect stratifies epithelium of skin and mucosal membranes
Fungal Infections
• Superficial skin infections
• Thrive on keratin
• Tinea unguium – infection of nail
• Tinea pedis – infection of foot
• Tinea corporis – ringworm
• Tinea capitis – infection of scalp

• Candidiasis: yeast like fungus Candida albicans

• Normally found on mucus membranes, skin, GI tract, and
vagina
• Overgrowth in immunocompromised or ill people
• Thin-walled pustule that may burn or itch
• Accumulation of inflammatory cells and scale produces white
substance over lesion
• Spread until reach dry skin

 Understand vascular disorders of the skin and their pathogenesis

Cutaneous Vasculitis: inflammation of blood vessels in skin
 Triggered by infection, decreased blood flow, drugs, or autoimmune
disorders
 Immune complexes deposit in small blood vessels
Urticaria: HIVES!
 Pruritic (itchy!) circumscribed area of raised erythema with central pallor
in superficial dermis
 Erythema blanches under pressure
 Type I hypersensitivity reactions
 IgE-stimulated release of histamines and bradykinins from mast
cells or basophils
 Endothelium in blood vessels contracts
 Fluid leaks from vessels into tissue

 Describe nevi and cancers of the skin

Nevi (moles)
  Benign pigmented (or nonpigmented) lesions
 Begin forming at age 3-5
 Melanocytes accumulate at the junction of the dermis and epidermis
 Over time the cells move into the dermis
 May undergo malignant transformation to melanoma

Basal Cell Carcinoma

• Surface epithelial tumor of the skin
• Originate from undifferentiated basal cells
• Exposure to UV radiation
• Lesion usually has a depressed center with small surface blood vessels
(telangiectasias)
• Metastasis is rare since they do not invade blood vessels or lymphatics

Squamous Cell Carcinoma (SCC)

• Second most common human cancer
• Most often on head and neck (75%) and hands (15%)
• Risk factors:
• UV light exposure – sun or tanning beds
• Arsenic in water
• Immunosuppression
• Arise from Epidermal cells
• Invasive SCC grows faster than Basal cell and can spread to regional
lymph nodes

Cutaneous Melanoma
• Arise from melanocytes – make pigment melanin
• Risk factors: Exposure to UV radiation, nevi, family history, fair hair and
light skin, history of sun burns
• When to biopsy nevi? – ABCDE rule
• Asymmetric
• Border irregularity
• Color variation
• Diameter larger than 6 mm
• Evolution – change in size and shape
• Prognosis determined by thickness, ulceration, mitotic (replication) rate,
metastasis to lymph nodes and other organs
• Localized melanoma generally has favorable outcome
• Patients with distant metastasis 5 year survival rate is less than
5%