A form of liver disease observed in middle-aged patients with abnormal liver biochemical test results and histologic evidence of alcoholic hepatitis but no history of alcohol abuse
Nonalcoholic Steatohepatitis (NASH)
The causes of NAFLD may be divided into two main categories. What are they?
Drugs & Toxins
Metabolic Abnormalities (aquired or congenital)
What condition is most often reported associated with NAFLD?
Obesity
In regard to obesity-related NAFLD development, which is more important, the distribution of body fat or the total adipose tissue mass in the patient?
Distribution of Body Fat (intraabdominal or viceral fat may be an important predictor of NAFLD)
What is the hallmark histologic feature of NAFLD?
Hepatic Steatosis
What are the two primary pathogenic factors in steatosis in most patients with NAFLD?
Insulin Resistance
Hyperinsulinemia
How does NAFLD usually present?
It is usually discovered incidentally bc of elevated liver biochemical test levels or hepatomegaly noted during an evaluation for an unrelated medical condition. Most patients are asymptomatic
What is the advanced form of NAFLD?
NASH
In contrast to NAFLD, this is a localized or patchy process that stimulates a space-occupying lesion in the liver on imaging studies
Focal Fatty Liver
What is the main contributer to the amino acid pool?
Dietary Protein
In a mature adult, the Nitrogen Balance should be....?
0
Anabolism = Catabolism
In what situations should there be a positive nitrogen balance (nitrogen intake > nitrogen excretion)?
Growing animal
Pregnancy
Recovery from starvation or a wasting disease
Any circumstance where building up muscle tissue
In what situations should a negative nitrogen balance (nitrogen intake < nitrogen excretion) exist?
Starving animal
Acute injury or infection
Senescent animal
Deficiency of one or more essential amino acids in diet
What are the essential amino acids?
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucin
Methionine
Histidine
Arginine
Leucine
Lysine
What are the nonessential amino acids?
Proline
Tyrosine
Alanine
Aspartate
Asparagine
What are the conditional non-essential acids, and what essential acid are they derived from?
Tyr (derived from Phe)
Cys (derived from Met)
Where does protein degradation begin, and what is the main protease involved?
Stomach
Pepsin
What activates the zymogen pepsinogen to form the active pepsin protease?
The low pH in the stomach (pH 2-3)
For protein degradation in the intestine, what enzyme is responsible for the activation of the zymogen Trypsinogen? Where is this enzyme derived from?
Enteropeptidase
Intestinal Enzyme
For protein degradation in the intestine, what enzyme is responsible for the activation of the zymogen Chymotrypsinogen? Where is this enzyme derived from?
Trypsin
Pancreatic Enzyme
For protein degradation in the intestine, what enzyme is responsible for the activation of the zymogen Procarboxypeptidase? Where is this enzyme derived from?
Trypsin
Pancreatic Enzyme
For protein degradation in the intestine, what enzyme is responsible for the activation of the zymogen Proelastase? Where is this enzyme derived from?
Trypsin
Pancreatic Enzyme
When trypsin becomes abnormally activated in the pancreas, what molecule is responsible for binding to and inhibiting the active trypsin?
Pancreatic Trypsin Inhibitor
Where does Trypsin cleave?
Arg
Lys
Where does Chymotrypsin cleave?
Tyr
Phe
Trp
Where does Elastase cleave?
Small Amino Acids
Where does Carboxypeptidase A cleave?
C-terminal Aromatics or Aliphatics
Where does Carboxypeptidase B cleave?
C-terminal Arg
C-terminal Lys
From what end of the small peptide particle does Aminopeptidase cleave?
N-terminal End
From what end of the small peptide particle does Carboxypeptidase cleave?
C-terminal End
What is the most common genetic disease of amino acid transport?
Cystinuria
This is an AR disease characterized by a defect in the absorption of basic amino acids in kidneys and liver
Cystinuria
What are the symptoms of Cystinuria?
Cystine Crystals: form under acidic conditions
Cystine Crystals: appearance of ground glass
What is the treatment for Cystinuria?
Increased Fluid Intake
Alkalinization of the Urine above pH
What are the four basic amino acids deficiently absorbed in Cystinuria?
Lysine
Arginine
Ornithine
Cystine
This disorder is an AR disease characterized by a defect in the absorption of neutral amino acids in kidneys and intestine (major mediator of tryptophan uptake)?
Hartnup Disorder
What are the symptoms of Hartnup Disorder?
Pellagra-like Skin Rash (scaly, red rash)
Neurologic Symptoms (seeing double, ataxia, etc)
What is the treatment for Hartnup Disorder?
Nicotinic Acid Supplementation
What cells secrete HCl?
Parietal Cells
HCl is required for Chief Cells to secrete what?
Pepsinogen
In the intestine, what absorbs the amino acids?
Intestinal Mucosa
What can impair the release of HCl into the stomach?
Gastric Bypass Surgeries
Some Gastric Carcinomas
What can cause a failure of pancreatic zymogen cleavage? What can this cause? How can it be treated?
A problem or deficiency in Enteropeptidase
Can cause Failure to Thrive due to an inability to absorb amino acids
Treat by supplementing diet with time-released pellets of active pancreatic proteases
True or False:
Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease.
True
What is the most common cause of abnormal liver tests in the developed world?
NAFLD (non-alcoholic fatty liver disease)
NAFLD and Non-Alcoholic Steatohepatitis (NASH) may be independent risk factors for what type of disease, which is classified as the main cause of death in these patients?
Cardiovascular Disease
What percentage of patients in developed countries have Fatty Liver or Non-Alcoholic Steatohepatitis (NASH)?
20% or more
Is ALT testing specific to the liver?
No; includes liver, heart, muscle, and kidney
What is the most common monosaccharide found in humans?
Glucose
How are monosaccharides classified?
According to the most oxidized functional group
Monosaccharides are classified according to the most oxidized functional group. If it is an aldehyde, what is it called?
Aldose
Monosaccharides are classified according to the most oxidized functional group. If it is a ketone, what is it called?
Ketose
Monosaccharides that have the same chemical formula, but different structures are called?
Isomers
A specialized type of isomer in which the structure is varied around a single carbon is called?
Epimer
If the single carbon that isomers are varied around happens to be the carbonyl carbon, then the two compounds are called?
Anomers
Anomers of glucose are in equilibrium so that in our bodies, glucose is 2/3 __________ anomer and 1/3 _________ anomer
Beta
Alpha
Monosaccharides that are mirror images of each other are called?
Enantiomers
An example of glucose enantiomers is D-glucose and L-glucose. Our cells can use __________ in metabolic pathways, but cannot use ________
D-glucose
L-glucose
What are monosaccharides linked by?
Glycosidic Bonds
True or False:
All monosaccharides are reducing agents
True, because the carbonyl carbon can be further oxidized to a carboxyl carbon
True or False:
All dissaccharides are reducing agents
False; they can be reducing sugars as long as the carbonyl carbon of one of the monosaccharides is not in a glycosidic linkage
What is an example of a reducing dissacharide?
Lactose
What is an example of a non-reducing dissarcharide?
Sucrose
Where does digestion of carbohydrates begin?
Oral Cavity
What enzyme begins digesting plant starches and animal glycogen in the oral cavity?
Salivary Alpha-Amylase
What are the major dietary complex carbohydrates?
Starch
Glycogen
What stops salivary alpha-amylase activity when it reaches the stomach?
Low pH; salivary alpha-amylase works at neutral pH
When the stomach contents enter the small intestine, the pH is neutralized by the secretion of what from what organ?
Bicarbonate
Pancreas
What enzyme is secreted into the small intestine to further digest the oligosaccharides?
Pancreatic Amylase
What does pancreatic amylase in the small intestine break the oligosaccharides down into?
Dissacharides
The final stage of dissacharide digestion occurs by the action of...?
Dissacharidases that are associated with the luminal side of the brush border membranes of the intestinal mucosal cells
What are the 5 major dissacharidases?
Isomaltase
Maltase
Lactase
Sucrase
Trehalase
What results from digestion of the dissacharides by dissacharidases in the intestinal mucosa?
Monosaccharides
The monosaccharides that result from digestion by the dissarcharidases are absorbed by....?
Intestinal cells of the duodenum and upper jejunum
What are the two mechanisms by which the monosaccharides that result from digestion of disaccharides in the small intestine absorbed by the intestinal cells of the duodenum and upper jejunum?
Active Transport
Facilitative Diffusion
What is the active transporter protein responsible in part for the absorption of monosaccharides into the duodenum and upper jejunum? What is it dependent on?
SGLT-1
Energy- and Sodium-Dependent
How are the monosaccharides absorbed by the small intestine transported during faciliated diffusion?
Down a concentration gradient
Glucose and Galactose are transported across the brush border in the duodenum and upper jejunum by which transport process?
Active Transport
Fructose is transported across the brush border in the duodenum and upper jejunum by which transport process?
Facilitative Diffusion
What is the facilitative diffusion transporter involved in the absorption of monosaccharides into the small intestine?
GLUT5
Abnormalities in the degradation of dissacharides can lead to digestive problems. What results from a deficiency of lactase? What are its symptoms? How can it be treated?
Lactose Intolerance
Bloating, Diarrhea, Dehydration
Treat by dietary change
Abnormalities in the degradation of dissacharides can lead to digestive problems. What deficiency results in an intolerance to sucrose? How can this be treated?
Sucrase-maltase deficiency
Supplementary digestive products can be given
Triacylglycerol degradation is carried out by ....?
Pancreatic Lipase
Pancreatic lipase can be inhibited by high concentrations of what?
Bile Salts
During triacylglycerol degradation, a second protein, _______, helps to anchor the pancreatic lipase to the lipid/aqueous interface facilitating enzymatic activity
Colipase
Cholesteryl ester degradation is carried out by _______ which removes the free fatty acid from the 3-hydroxyl group
Cholesteryl ester hydrolase
Cholesterylesterase is activated by the presence of what?
Bile Salts
Secretion of the digestive enzymes that degrade dietary lipids is under hormonal control. The mucosal cells in the duodenum and jejunum secrete the peptide _________, which is responsible for this digestion
Cholecystokinin (CCK)
What are the three main functions of CCK?
Signals the gallbladder to secrete bile
Signals the exocrine portion of the pancreas to secrete the digestive enzymes
Slows gastric motility
What hormone signals the liver and pancreas to secrete bicarbonate to neurtralize the gastric contents (chyme)?
Secretin
This consists of digested lipid products and bile salts to form an amphipathic particle. This particle has a hydrophilic outer surface and a hydrophobic core
Mixed Micelle
What part of the mixed micelle allows the digested lipid materials to be transported through the unstirred water layer that separates the mucosal membrane from the bulk fluid contents of the intestine?
The hydrophilic outer surface
What is found in the interior of the mixed micelle?
Free Cholesterol (from the diet)
Fat-Soluble Vitamins (A, D, & K)
Free Fatty Acids
What occurs once the contents of the mixed micelle are taken up by the intestinal cell (enterocyte)?
Resynthesis of Triacylglycerol and Cholesterol Esters
What is the first step in the resynthesis process of triacylglycerol and cholesterol esters?
The activation of the long chain fatty acids to form fatty Acyl CoA molecules
What is used for the glycerol backbone for triacylglycerol synthesis?
2-monoacylglycerol
Malabsorption of lipids leads to increased fat content of fecal material. What is this called, and what can it cause?
Steatorrhea
Causes: defective secretion of bile salts from the gallbladder, defective secretion of pancreatic enzymes, or a defect in the intestinal mucosal cells
What are complex lipids formed in the enterocytes synthesized into?
Chylomicrons
Throughout the length of the GI tract, the wall of the gut can be divided into four layers. What are they?
Mucosa
Submucosa
Muscularis Externa
Serosa
What is the inner layer of the digestive tract?
Mucosa
The luminal surface of the gut is lined by a layer of epithelium that is moistened by glandular secretions. What lies deep to the epithelium?
Lamina Propria
This is a layer of loose connective tissue that is rich in blood vessels, nerves, and lymphatic ducts.
Lamina Propria
In most regions of the GI tract, lying in the outer region of the lamina propria (away from the lumen) is a thin layer of smooth muscle called the ...?
Muscularis Mucosa
Contractions of the muscularis mucosa affect the folding of the epithelial surface into ridges called ______ (stomach) and _______ (intestines)
Rugae
Pleicae
What cell type secrete various signaling molecules into the lamina propria where they can: 1) act as hormones by entering the blood stream; 2) activate neural reflexes by acting on nerves in the lamina propria; 3) act as paracrine compounds by acting on nearby cells in the epithelial layer and lamina propria; or 4) have an autocrine action by providing feed-back to each other
Enteroendocrine Cells
What is the double layer of smooth muscle (inner circular and outer longitudinal) that lies outside the submucosa?
Muscularis Externa
What are the sheets of smooth muscle of the Muscularis Externa necessary for?
Mechanical processing and propagation of luminal contents of the bowel
What ganglionated plexus lies between the longitudinal and circular muscle layers of the Muscularis Externa and regulates the actions of the smooth muscle layers?
Myenteric Plexus (Auerbach's)
What is the ganglionated plexus of nerves located in the Submucosa called?
Submucosal Plexus (Meissner's)
Within the peritoneal cavity, the structures of the digestive tract are covered with a sheet-like serous membrane comprised of a monolayer of mesothelial cells. What is this known as?
Serosa
A dense network of collagen fibers, referred to as ________, envelops GI structures that are retroperitoneal, as well as the upper regions of the GI tract from the oral cavity to the esophagus as it passes through the diaphragm. It attaches these regions of the digestive tract to adjacent structures.
Adventitia
What are the muscle layers of the small intestine?
Longitudinal Muscle Coat
Circular Muscle Layer
Muscularis Mucosa
The motor function of the longitudinal and circular muscle layers of the small intestine is coordinated by?
Myenteric Plexus
The motor function of the muscularis mucosa and epithelial function of the small intestine are regulated via the?
Submucosal Plexus
What is the primary function of the intestine?
The absorption of water, electrolyte and nutrient substances
This is most commonly caused by an adverse mucosal response to dietary gluten which is present in wheat- or rye-based foods. It results in a stunting of the villi and a decreased absorptive mucosal surface area.
Sprue
What is the primary site of nutrient absorption?
Jejunum
What is the primary function of the small intestine?
Absorption of water, electrolyte, and nutrients
Within the small intestine, what cell type tends to be absorptive?
Villous Cells
Secretion of fluids and electrolytes occurs in the small intestine. What cell type are responsible for secretion?
Crypt Cells
What are the two routes of epithelial transport in the small intestine?
Intercellular or Paracellular: through tight junctions
Intracellular or Transcellular: active or passive transport through the cell (across brush border)
The permeability of tight junctions varies depending on location in the GI tract. Are they tight or loose in the small intestine?
Relatively loose, or leaky
What are the four methods of sodium transport across enterocytes?
Electrogenic Transport: active transport, Na-K pump (basolateral side) rheogenic
Substrate-Coupled Transport: rheogenic
Electro-neutral Transport: Symport
Anti-Porter: with H ions
Water movement in the intestine is passive and relies on what three things?
Osmolality of Chyme
Rate of Solute Transport
Size of the Intercellular Spaces
Describe calcium transport across the enterocyte?
Actively absorbed in duodenum and jejunum by a membrane bound carrier, activated by 1,25-dihydroxycholecalciferol.
Diffuses into the enterocyte where it is bound to calcium binding protein
Is then actively transported across the basolateral membrane
There are at least two methods of Iron uptake, one for __________ and a second for __________
Heme Iron
Free Iron
Free iron is toxic when it enters the cell, so it binds to _______ to form __________
Apo-Ferritin
Ferritin
How does absorbed ferritin exit the enterocyte, and where does it go?
By the Ferroportin Transport Protein
Enters the Plasma
How is chloride secreted from crypt cells in the small and large intestine?
Na-K-Cl Triporter
Acetylcholine: by increasing intracellular Ca
VIP and Prostaglandins by elevating intracellular cAMP
What stimulates anion secretion? What mediates it?
Response to neuronal or hormonal influences
Bacterial toxins
May be mediated by a rise in intracellular cAMP or Ca
What stimulates fluid secretion? Where is this particularly important?
High luminal osmolality
Proximal duodenum
Increased interstitial hydrostatic pressure, also called secretory filtration, may accompany what?
Severe luminal distention
The small intestine is involved in the breakdown and assimilation of three important food components. What are they?
Carbohydrates
Proteins
Lipids
Emulsified fat products must first pass through two barriers:
The unstirred water layer lying above the brush border
The lipid membrane barrier
What are the components of the mixed micelle?
Bile Salts
Cholesterol
Lecithins
Monoglyceride
Free Fatty Acid
Efficient absorption of fat-soluble vitamins requires what?
Bile Salts
What happens to the intestine when longitudinal muscle contracts?
Becomes shorter
What happens to the intestine when circular muscle contracts?
Becomes occluded
What does postprandial mean?
Fed
When do interdigestive patterns occur?
Between meals (fasting)
What type of contractions promote forward movement of luminal contents in the small intestine?
Peristaltic Contractions
What type of contractions promote mixing with no net forward movement of luminal contents in the small intestine?
Segmental Contractions
What provides contact between smooth muscle cells and allows for coordinated contractions?
Gap Junctions
Circular smooth muscle cells in the small intestine are characterized by rhythmic episodes of spontaneous depolarization of 5-15 mV in amplitude lasting 1-5 sec. These are called what?
Slow Waves
What happens if slow waves reach threshold?
They generate action potentials
What are the action potentials or spikes of slow waves due to?
The inward movement of calcium
Is the strength of contractions in the small intestine determined by the number of spikes or their amplitude?
The number of spikes
Where do propagating slow waves originate in the small intestine?
In the Interstitial Cells of Cajal (ICCs)
What are the pacemakers of the gut?
Interstitial Cells of Cajal (ICCs)
Slow waves do not directly produce contractions and are propagated from cell to cell via _________
Gap Junctions
What is the primary neurotransmitter released from intrinsic nerves associated with the longitudinal muscle?
Acetylcholine
What is the primary neurotransmitter associated with circular smooth muscle?
VIP or NO
A large portion of the increase in intracellular calcium in smooth muscle is derived from an influx of __________ calcium. In contrast, in skeletal muscle calcium is mobilized from _________ stores.
Extracellular
Intracellular
The contractions of the small intestine serve to:
Mix chyme, facilitating its exposure to the absorptive surface
Move chyme towards the large intestine
The frequency of slow waves varies along the upper GI tract. What are the frequencies per minute in the stomach, duodenum, and ileum?
3/min Stomach
12/min Duodenum
8/min Ileum
This is a motor phenomenon that occurs in the small intestine during the interdigestive period
What are the three phases of the MMC, and what do they entail?
Phase I: period of relative quiescence
Phase II: characterized by intermittent motor activity
Phase III: is composed of regular, propagating contractile activity
What does phase III activity of the MMC do?
Clears the lumen of debris (sloughed epithelial cells, etc.)
What terminates the MMC?
Feeding
These type of contractions displace chyme in an oral and aboral direction. The forces for this are exerted by the circular muscle layer only.
Segmentation (mixing)
What is the most common type of contraction following a meal?
Segmentation (mixing)
This says that stimulation (e.g. distention by a bolus) at one locus of the small bowel induces contraction above and relaxation below the point of stimulation
Law of the Intestine or Peristaltic Reflex
The Law of the Intesine or Peristaltic Reflex is mediated by the?
Enteric Nervous System
This occurs when distension of one segment of small bowel reflexively inhibits the contractile activity of other segments
Intestino-Intestinal Reflex
This is a state of no muscle contractility. Electrical slow waves are present but there is little or no spike activity. This results from continuous activity of the intrinsic inhibitory neurons and is caused by peritoneal irritation
Ileus
This is the opposite of ileus in that there is no activity of the inhibitory neurons. The syncitial properties of the intestinal smooth muscle cells and their inherent contractility then produce maximal contractions
Spasm of the Circular Muscle
Name the Protozoan:
Disease: Amebiasis/Amebic Dysentery/Liver Abscesses
Epidemiology: Worldwide; male homos in US; trop and subtrop climates
Symptoms:
85-90% pts asymptomatic
2-21 day incubation period
Variable or chronic intestinal symptoms (GI upsets, including colitis & diarrhea) Very Severe Cases: ulcers; ameboma; perforation; hemorrhage; fulminant, bloody diarrhea; intestinal hemorrhages & dysentery; Amebic hepatitis = single abscess in right lobe (RUQ pain, fever, weight loss)
How is it transmitted?
How is it diagnosed, treated, and prevented?
Entamoeba Histolytica
Fecal-oral route through ingestion of cyst stage in contaminated food & water
Differential diagnosis: must exclude bacillary dysentery; finding trophozoites in loose stools or the cyst in formed stools; X-ray/US to detect ulcers and abscesses
Treatment: Metronidazole plus Iodoquinol
Prevention: Avoid contaminated water & food; practice good personal hygiene
What are the differences between Amebic and Bacillary Dysentery?
Amebic: gradual onset of symptoms; no fever, chills, or pus; less prostration; chronic course
Bacillary: sudden onset; fever, chills, and pus; more prostration; acute course
Identify the Protozoan:
Epidemiology: Worldwide; common in hikers who drink unfiltered water
Symptoms:
Organism is non-invasive, but destroys epithelial microvilli Acute Infections: 2-21 day incubation period; severe diarrhea, but no dysentery; greasy, fatty, foul-smelling stools; abdominal distension w N&V Chronic Infections: Low antibody titers; diarrhea, weight loss, and intestinal malabsorption; flatulence
How is it transmitted?
How is it diagnosed, treated, and prevented?
Giardia Lamblia
Tranmission: Fecal-oral route through ingestion of cysts in contaminated water or food; anal sex
Diagnosis: Finding trophozoites or cysts in feces
Treatment: Metronidazole
Prevention: Avoid contaminated water; practice good personal hygiene
Identify the Protozoan: Disease: Cryptosporidiosis Epidemiology: Worldwide; outbreaks in US due to inadequate water purification Symptoms: Abdominal cramping with watery, non-bloody stool Opportunistic Infection: chronic diarrhea, severe fluid loss, malnutrition, can be fatal
How is it transmitted?
How is it diagnosed, treated, and prevented?
Cryptosporidium Parvum
Diagnosis: Finding oocytes in feces
Treatment: No current drugs or vaccines available; fluid replacement and supportive therapy
Prevention: water filtration; boil water that is suspected of contamination
Identify the Protozoans: Disease: Coccidiosis Epidemiology: Worldwide; outbreaks in US due to inadequate water purification Symptoms: Mild to severe diarrhea with varying degrees of abdominal cramping, gas, fever, nausea, and vomiting
Prevention: Boiling and filtering water; washing fruit and veggies
Identify the Helminth: Epidemiology: Worldwide, mostly southern US Symptoms: Largely asymptomatic; weakness and diarrhea
How is it transmitted?
How is it diagnosed, treated, and prevented?
Hymenolepis nana (dwarf tapeworm)
Transmission: Ingesting beetles containing cysticerci which develop into adult worms in the host's intestine
Diagnosis: Identification of eggs in stools
Treatment: Prazinquantal
Prevention: Hygiene and Sanitation
Identify the Helminth: Disease: common tapeworm in pets that can be passed to humans Epidemiology: worldwide Symptoms: Mostly asymptomatic; diarrhea & pruritis
How is it transmitted?
How is it diagnosed and treated?
Dipylidium caninum (dog tapeworm)
Transmission: Ingesting fleas containing cysticerci which develop into adult worms in the host's intestines
Diagnosis: Identification of proglottids (rice-like beads) in stool
Treatment: Niclosamide
Identify the Helminth: Epidemiology: Worldwide; predominantly tropics; 2.2 mil cases/yr in US Symptoms: Mostly asymptomatic; Abdominal pain; Diarrhea; Rectal Prolapse
How is it transmitted?
How is it diagnosed, treated, and prevented?
Trichuris trichiura (whipworm)
Transmission: Digestion of eggs from contaminated soil or food/water
Diagnosis: Identification of eggs in stool; Adult worms can sometimes be identified in rectal mucosa by proctoscopy
Treatment: Mebendazole
Prevention: Proper disposal of feces
Identify the Helminth: Epidemiology: Worldwide; most common human helminth infection Symptoms:
Acute infections are asymptomatic
Moderate to heavy infections can cause abdominal pain and intestinal obstruction
Adult worms may cause bile tract obstruction
Migrating worms can cause pulmonary problems including eosinophilia, pneumonia, and cough Malnutrition in children in developing countries
How is it transmitted?
How is it diagnosed, treated, and prevented?
Ascaris lumbricoides
Transmission: Digestion of eggs from contaminated soil, food, or water
Diagnosis: Identification of eggs in stool; Occasionally, worms can migrate out of the body via the rectum or mouth
Treatment: Mebendazole
Prevention: Proper disposal of feces
What is the most common human helminth infection?
Ascaris lumbricoides
Identify the Helminth: Epidemiology: worldwide; tropics, southern US Symptoms: 1/3 cases are asymptomatic
Skin penetration may cause a pruritic papular erythematous rash ("ground itch")
Pulmonary complications during lung migration (Loffler's syndrome)
Burning or colicky abdominal pain, diarrhea with passage of mucosa.
Nausea, vomiting, and weight loss Immunocompromised patients are more likely to suffer from autoinfection.
Presents with abdominal pain, distension, shock, pulmonary and neurologic complications and septicemia.
Can be fatal
How is it transmitted?
How is it diagnosed, treated, and prevented?
Strongyloides stercoralis
Transmission: filariform larvae in contaminated soil can penetrate skin; autoinfection
Diagnosis: Identification of larvae in stool or duodenal fluid; Larvae may be detected in sputum from patients with disseminated strongyloidiasis
Treatment: Ivermectin or Thiabendazole
Prevention: Wear shoes and proper disposal of feces
Identify the Helminths: Disease: Hookworm disease Epidemiology: Africa, Asia, Americas; Americas and Australia Symptoms:
Skin penetration may cause a pruritic papular erythematous rash ("ground itch")
Iron deficiency anemia and other nutritional disorders caused by worm attachment to intestine
Abdominal pain, diarrhea, weight loss due to adults residing in small intestine where they attach and feed on blood
Pulmonary eosinophilia during lung migration (Loffler's Syndrome)
How is it transmitted?
How is it diagnosed, treated, and prevented?
Ancylostoma Duodenale; Necator Americanus
Transmission: Filariform penetrate skin
Diagnosis: Detection of eggs in fecal smear
Treatment: Mebendazole; treat severe anemia with ferrous sulfate
Prevention: wear shoes and proper disposal of feces
Identify the Helminth: Disease: pinworm, seatworm, enterobiasis Epidemiology: worldwide; most common helminth infection in US Symptoms: Children are most often infected but infection is typically asymptomatic
Perianal pruritis (nightime) leading to excoriations and bacterial infections.
Anorexia, irritiability, and abdominal pain
In rare cases causes peritoneal granulomas and vulvovaginitis (bacterial, Trichomonas, and Candida)
How is it transmitted?
How is it diagnosed, treated, and prevented?
Enterobius vermicularis (pinworm)
Transmission: ingestion of eggs; retroinfection occurs when eggs hatch and juvenile worms crawl back into anus
Diagnosis: Eggs detected in perianal region by using Scotch Tape; must be performed in morning before defecation and washing; cannot detect
eggs in feces
Treatment: Pyrantel pamoate (treat all family members bc of ease of infection
Prevention: personal hygiene and washing all bedding and clothes
What are the three primary functions of the large intestine?
To store fecal material, which consists of indigestible food products
To extract water from the luminal contents
To move fecal material towards the rectum
What digestive enzymes are secreted from the colon, and where does nutrient absorption take place in this organ?
TRICK QUESTION!!
None, and it doesn't
The longitudinal muscle of the colon is concentrated into three bands. What are these called? Due to this, the circular muscle has the appearance of bulging outwards in sacculations called what?
Tenia Coli
Haustra
Why is transit time so much slower in the colon than in the small intestine?
Because it has a storage function
What are the most common motility patterns in the colon, and where do they occur?
Mixing Movements
Proximal Colon
In the colon, ______ migration results in a net movement of chyme in an aboral direction. In this case slow waves are associated with long bursts of spike activity.
Haustral Migration
The _______ anal sphincter is composed of smooth muscle which is tonically contracted. Activation of the parasympathetic nerves relaxes it via the release of VIP while activation of sympathetic nerves causes it to contract.
Internal Anal Sphincter
The ________ anal sphincter is composed of skeletal muscle and receives excitatory innervation from the pudendal nerve. It is under voluntary control.
External Anal Sphincter
Defecation is initiated by mild distension which activates the __________ reflex which relaxes the internal anal sphincter and elicits the urge to defecate.
Rectosphincteric Reflex
During defection, mild distension of the rectum induces a reflexive contraction of the external anal sphincter, termed __________.
Continence
Defecation is facilitated by voluntary contraction of the abdominal muscles. What is this termed?
Valsalva Maneuver
The intrinsic innervation of the colon produces a net ________ influence on the muscular layers.
Inhibitory
The proximal colon receives extrinsic ________ innervation from both the vagus and the pelvic nerves. _______ stimulation causes segmental contractions; _______ nerve stimulation causes propulsive activity in the distal colon.
Parasympathetic
Vagal
Pelvic
Sympathetic innervation to the proximal colon is via the _______ nerves. In the distal colon it is the _________ colonic nerves, although these fibers are associated with the entire colon.
Splanchnic
Lumbar
The large intestine absorbs ____, _____, and _______ and secretes _______ and _______.
Na
Cl
Water
K
HCO3
Are the intercellular spaces smaller or larger in the colon compared to the small intestine?
Smaller; generates a significant electron gradient
How does the colon absorb Na?
Against a concentration gradient
Two or more of the following for 3 months or more is classification for what?
Straining more than 25% of the time
Hard stools more than 25% of the time
Incomplete evacuation more than 25% of the time
Two or fewer bowel movements in one week
Constipation
What are some of the common constipating drugs (4)?
What is an important aspect of the physical exam for constipation? What other screening methods are used?
Digital Rectal Exam
Endoscopy & Radiology
What are the treament options for constipation (general)?
Increase fiber to 20-40 g/day
Increase fluid intake
Laxatives
What type of diarrhea persists with fasting and has no osmotic "gap"?
Secretory
Which type of diarrhea disappears with fasting and is characterized by nonabsorbed ions?
Osmotic
Which diarrhea type is characterized by:
Stool (Na) > 90 and
Osmotic Gap of < 50
Secretory
Which diarrhea type is characterized by:
Stool (Na) < 60 and
Osmotic Gap >100
Osmotic
What is the single most common cause of Osmotic Diarrhea? What are some other possible causes?
Lactose MalabsorptionAntacids
Dietetic Foods/Drugs
Miscellaneous Drugs
Enteral Feeding
What are some common causes of Secretory Diarrhea?
Laxatives
Medications
Toxins
Bile Acids
Hormone Producing Tumors (rare)
What is the typical duration of an acute diarrhea? Acute diarrheas are usually infectious. What is the most common culprit?
Less than 2-3 weeks
E. Coli (Rotavirus most common in regard to viral issues)
What are the danger signs associated with acute diarrheas (7)?
High Fever (>38.5 or 101.3)
Systemic Illness
Tenesmus (crampy abdominal pain)
Dysentery
Prolonged Course (>2 weeks)
Dehydration
Elderly or Immunocompromised
When treating acute diarrheas with antibiotics for a suspected parasite, we dont typically wait for the culture to come back. Instead, what are the first through 4th lines of treatment often used?
Quinolones (Ciprofloxacin, Levofloxacin)
Sulfa-Trimethoprim
Metronidazole
Azithromycin, Clarithromycin, or Erythromycin
What is the first line of defense for C. Diff? Due to resistance, what is the second line of defense that is more costly, but has no known resistance?
Metronidazole
Vancomycin
How long does it typically take C. Diff patients to respond to antibiotics?
5-6 days
What is the most common type of Chronic Diarrhea?
Watery Diarrhea
What are the treatment options for Nonspecific Chronic Diarrhea?
What is the most common cause of severe diarrhea among young children worldwide?
Rotavirus
What is the mode of transmission of Rotavirus?
Feces or Fecal-contaminated Water
What is the diagnosis?
These are non-enveloped, triple-layer viruses, segmented dsRNA (11 segments), RNA genome. They cause viral gastroenteritis, and typically infect the intestines in children of age 6 months-3 years. The diarrhea results in fluid loss and severe dehydration.
Associated Symptoms:
Watery stools and vomiting after a 1-2 day incubation period in young children
Vomiting is common and may be prolonged
High, urine-specific gravity and metabolic acidosis
Usually no blood or fecal leukocytes
Rotavirus
True or False:
Natural rotavirus infection efficiently protects against severe disease associated with re-infection.
True
These are single stranded, positive sense RNA. Naked.
Major cause of non-bacterial diarrhea in children (> 2 years) and adults.
Most common cause of epidemics of viral gastroenteritis Associated Symptoms:
Watery Diarrhea
Nausea
Projectile Vomiting
Cramps
Fever
Headache
Malaise
What is the diagnosis?
Noroviruses (Caliciviruses): Norwalk and Norwalk-like
What is the most common cause of epidemics of viral gastroenteritis in schools, camps, cruise ships, etc?
Noroviruses (Caliciviruses): Norwalk
Do noroviruses have long term protection, or is re-infection possible?
No long term protection
These are ss, + sense RNA viruses, naked, icosahedral capsid.
Most commonly affect children under 2, but also elderly and immunocompromised.
Transmission appears to be person to person, fecal-oral.
Symptoms manifest 2-3 days post-infection
Disease usually lasts only a few days.
Symptoms very similar to rotavirus but not as severe.
Astrovirus
Crohn's Disease has been associated with polymorphisms in what three genes, which contribute to the function of the innate immune system and the process of autophagy?
NOD2
ATG16L1
IRGM
Patients with Crohn's Disease are more likely to have anitbodies to (3)?
ASCA
Cbir
OmpC,12
50-80% of Ulcerative Colitis patients have what antibodies?
pANCA
What is the diagnosis?:
A chronic, recurrent, usually focal, asymmetric and transmural inflammation of the GI tract, which may effect any portion of tract but most commonly small bowel and colon.
Symptoms/Complications: diarrhea, pain, weight loss, malabsorption, fistula and strictures, abscesses, and anemia
Crohn's Disease
If a Crohn's patient has this symptom, it means that the disease will be hard to treat. What is the symptom?
Perianal Pain
What is the diagnosis?:
Chronic inflammatory condition of the colon characterized by inflammation of the mucosa resulting in ulceration, characterized by abdominal pain and diarrhea (usually bloody). Proctitis may result in tenesmus, bleeding. Has a contiguous spread.
Symptoms: bloody diarrhea, abdominal pain, tenesmus, and, in severe disease, tachycardia, fever, and anemia.
Ulcerative Colitis
What two extraintestinal manifestations of inflammatory bowel disease have a course that follows the course of the disease?
Erythema Nodosum
Peripheral Arthritis
What extraintestinal manifestation of inflammatory bowel disease, characterized by bile duct inflammation resulting in fibrosis, is associated with an increased risk of colon cancer and choangiocarcinoma?
Primary Sclerosing Cholangitis
What are the two goals of treatment for inflammatory bowel disease?
Induce Remission
Maintain Remission
What is the main non-surgical treatment for Ulcerative Colitis?
Mesalamine (oral and rectal)
What is the best non-surgical treatment for Crohn's Disease?
Methotrexate
What is this characteristic of?
Perceived disturbance in GI function without structural or biochemical abnormalities by objective testing.
Sensorineural motor dysfunction
Low level inflammation without end organ damage
Functional Bowel Disease
What type of probiotics are used for IBS?
Lactobacillus
Bifidobacterial
E. Coli
Saccharomyces Boulardii
What is the most common cause of food poisoning in the US?
Staphylococcal Aureus
What is the diagnosis: Gram-positive coccobacillus
Typically transmitted through food that requires hand preparation
Virulence factors are several toxins which are produced by the organism that induce projectile vomiting
Typically occurs within hours of eating contaminated food Diarrhea almost never occurs
Toxins are heat stable and directly cause release of serotonin in the intestine that results in vomiting
Staphylococcal Aureus
How can Staph Aureus be differentiated from Norwalk virus?
Norwalk often causes diarrhea, whereas staph aureus doesn't
What is the diagnosis?:
Gram positive rod
Two types of food poisoning Type I: often a quick onset (2-3hrs), typically after ingesting starchy food. Causes vomiting through a heat-stable toxin Type II: caused by ingestion of contaminated meat or veggies and the organism produces a heat-labile toxin that causes diarrhea in 10-12 hours after ingestion
Virulence factors are several toxins which are produced by the organism that induce vomiting, often projectile.
Bacillus Cereus
What is the diagnosis?:
Gram-positive rod
Causes abdominal cramping and watery diarrhea within 8-12 hours of ingesting infected food
Produces heat resistant spores that are not killed by cooking.
Virulence factors is an enterotoxin
The diagnosis is usually suspected when a local outbreak of the disease has occurred.
Clostridium Perfringens
What is the diagnosis?:
Gram-positive rod
Mostly found in people that have ingested improperly home-canned veggies or sausage Very rare Causes death in ~30% of infected individuals
Virulence factor is a toxin that takes 1-2 days after ingestion for symptoms to occur, because the toxin must spread from the intestine to the nerve synapses Only food borne disease that takes more than 12 hours from ingestion to symptom onset
Symptoms are severe and include blurred vision followed by bilateral descending, flaccid paralysis
Death is typically caused by respiratory failure
Clostridium Botulinum
What is the only food borne disease that takes more than 12 hours from ingestion to symptom onset?
Clostridium Botulinum
Which two forms of Escherichia coli cause "traveler's diarrhea"?
ETEC
EAEC
Which form of Escherichia coli causes a heat-labile and heat-stable toxin which causes watery diarrhea? Disease lasts ~ 24 hours.
ETEC
Which form of Escherichia coli causes disease by binding the mucosal cells of the intestine and then killing the cells, which leads to watery diarrhea. Disease does not typically resolve for several days.
EAEC
Which form of Escherichia coli does not produce a toxin, but rather injects proteins into the mucosal epithelial cells that leads to watery diarrhea. This causes a mild form of the disease and seems to be restricted typically to children 6 months of age or less
EPEC
What is the diagnosis?:
Typed using O antigen (139 serogroups): serogroup O1 (classical or El Tor; casuses pandemics); Non-O1 (cause less severe disease); recent Bangledesh outbreak (O139 "Bengal")
Non-inflammatory, enterotoxic disease
Causes massive efflux of fluid (up to 20 L/day)
Symptoms are due to dehydration
Primary virulence factor: 2-component toxin (AB toxin)
Incubation time: 7-14 days
Then, sudden onset of massive diarrhea ("rice water stool"); contains large numbers of organisms. Dehydration and shock can follow. Mucosa remains intact, no invasion.
Vibrio Cholera
What is the diagnosis?:
Thin, Gram-negative rod; non-motile
Serogroups: S. flexneri; S. sonnei
Symptoms: causes bacillary dysentery, invasive (gets into cells of large intestine), abdominal pain
Route of transmission: fecal-oral
Most cases are children < 5 yrs; outbreaks are long lasting
Virulence factor is Shiga Toxin
Shigella
What is the diagnosis?:
Causes self-limiting gastroenteritis
Dysentery type mechanism
Symptoms last from 2 days to a week and resolve spontaneously
Can be transferred to humans by reptiles, such as turtles
Salmonella Enterica
What bacterial agent is motile by peritrichous flagella?
Humans are sole carriers
Route of transmission is by ingestion of contaminated food and water
Incubation time is about 10-14 days
Symptoms, Week 1: Lethargy, fever, malaise, general aches and pains, constipation
Symptoms, Week 2: severely ill, sustained temp of 104, Diarrhea, Rose Spots
Diagnosis requires isolation from blood, two vaccines are available, and antimicrobial therapy is necessary
Salmonella typhi
What is the diagnosis?:
Causes acute enteritis
Common cause of human bacterial gastroenteritis
Zoonotic disease: most infections are due to ingestion of contaminated food and water, esp. chicken and turkey
Affects young children
Causes illness in all ages
Incubation time: 3-5 days
Low infective dose
Severe abdominal pain with fever, can mimic acute appendicitis, dysentery, usually self-limiting
Incubates at 42 degrees celcius
Anti-microbial therapy is used for treatment
Campylobacter Jejuni
EHEC can cause a severe life-threatening illness that most commonly strikes children under 5 and the elderly. It destroys RBCs, causing acute kidney failure. Treatment is blood transfusion. What is the illness?
Hemolytic Uremic Syndrome (HUS)
Other than HUS, what other life-threatening illness can be caused by E. coli?
Disease of the CNS: in adults, seizures and coma; after effects, blood clots in brain, death
What form of E. coli can cause severe life-threatening illnesses, such as HUS and CNS problems, as well as the non life-threatening dysentery. This form is linked to the powerful Shiga toxin, causing severe abdominal cramps, dysentery, vomiting, and nausea. However, there is NO FEVER present. Incubation time is 4-8 days, and duration of illness is 5-10 days.
EHEC
What is the most common cause of pseudomembranous colitis?
C. diff
What is the diagnosis?:
Gram-positive rod
Can survive at low temps, and often transmitted in soft cheeses, processed meats, even when properly refrigerated
Symptoms include fever, muscle aches, nausea, and diarrhea
Organism is an intracellular pathogen and can travel to the nervous system where symptoms include HA, stiff neck, loss of balance, confusion, and convulsions
The bacteria release toxins and other proteins in the intracellular niche they reside and use these invaded cells to help them traffic to other parts of the body.
Treatable with antibiotics
Listeria monocytogenes
Jaundice is not usually seen until bilirubin exceeds ___mg/dL