PATHO - Digestive System Flashcards
The digestive system includes what components?
- GI tract
- Accessory organs of digestion
- salivary glands
- liver
- gall bladder
- exocrine pancreas
What movements of the digestive system are controlled by hormones and autonomic NS?
a) chewing
b) swallowing
c) defecation of solid wastes
d) peristalsis
d) peristalsis
Describe the general pathway of food from ingestion to elimination.
1) food breakdown starts in the mouth with chewing and continues in the stomach where it’s churned and mixed with acid, mucus, enzymes and other secretions
2) In stomach, fluid and partially digested food pass into small intestine where more biochemical agents and enzymes secreted by the intestinal cells, gallbladder, and exocrine pancrease break things down even more into components that can be absorbed (proteins, carbs, fats)
3) Nutrients pass through the walls of small intestine into blood vessels and lymphatics, they’re off for storage or further processing
4) Things that are not absorbed in small intestine pass into large intestine where fluid continues to be absorbed. Fluid wastes travel to kidneys for elimination via urine. solid wastes through rectum for defecation.
What components does the GI tract consist of?
- mouth
- esophagus
- stomach
- small intestine
- large intestine
- rectum
- anus
What digestive processes are carried out by the GI tract?
- Ingestion of food
- Propulsion of food and wastes from the mouth to the anus
- Secretion of mucus, water, and enzymes
- Mechanical & chemical digestion of food particles
- Absorption of digested food
- Elimination of waste products by defecation
- Immune and microbial protection against infection
Histology
study of microscope structure of tissues
What are the four layers of the GI tract, starting from inside out?
mucosa
submucosa
muscularis
serosa/adventitia
What is the enteric/intramural plexus and why is it important?
The enteric plexus is located within different layers of the GI walls and it a network of nerves that control mobility, secretion, sensation and blood flow within the GI tract.
This is all coordinated through through local and autonomic nervous system
How many permanent teeth are in an adult mouth? What is the importance of having teeht?
32
needed for speech and mastication
Function of mouth/tongue
- acts as a reservoir for chewing and mixing food with saliva
- food particles gets smaller and move around in the mouth where taste and buds and olfactory nerves are continuously stimulated to add to satisfaction of eating
- Tongue’s surfaces has thousands of chemoreceptors that can distinguish between salty, sour, bitter, sweet, and savoury (umami) tastes and these (along with food odors) help with initiating salivation and secretion of gastric juice in stomach
Describe the structures & substances involved with salivation and what functions saliva may have.
Structures involved: 3 pairs of salivary glands - submandibular, sublingual, parotid glands that collectively secrete ~1L of saliva/day
- Innervated by sympathetic and parasympathetic divisions to control salivation; not regulated by hormones (nervous system only)
- Gland stimulation: cholinergic parasympathetic fibers, β-Adrenergic stimulation from sympathetic fibers
- Gland inhibition: atropine (anticholinergic), makes mouth dry
Composition of Saliva: mostly water with mucus, sodium, bicarbonate, chloride, potassium, salivary α- amylase (ptyalin), an enzyme that initiates carbohydrate digestion in the mouth and stomach. Composition depends on rate of secretion.
Functions:
- pH ~7.4 to neutralize bacterial acids and prevent tooth decay
- also contains mucin, IgA and other antimicrobial substances to help prevent infection
- Mucin provides lubrication
- Exogenous fluoride (i.e. from drinking water) also secreted in saliva as additional protection against tooth decay
What structural components are involved with swallowing. Describe this process as if you were following a piece of food down to the stomach.
- once food passes the mouth, it enters the esophagus (hollow muscular tube ~25cm long that conducts food from oropharynx into stomach) and moves via peristalsis
- each end has a sphincter
- upper esophageal sphincter: keeps air from entering esophagus during respiration
- Lower esophageal sphincter (Cardiac sphincter): prevents regurgitation from stomach and caustic injury to esophagus. Normally constricted serving as a barrier between stomach and esophagus; relaxes with swallowing
- pharynx and upper 1/3 of the esophagus is striated muscle (voluntary) that is directly innervated by skeletal motor nueorns that control swallowing
- Lower 2/3s contain smooth muscle (involuntary) that is innervated by preganglionic cholinergic fibers from vague nerve
- fibers activated and coordinated by swallowing center in the medulla
What is peristalsis and when is it stimulated?
Definition: coordinated sequential contraction and relaxation of outer longitudinal and inner circular layers of muscles to move food throguh GI tract
How it works: stimualted when afferent fibers along the length of the esophagus sense changes in wall tension caused by food passing by and stretching the walls. The greater the tension, the greater the intensity of contraction. Intense contractions can cause pain similar to “heartburn” or angina
Swallowing is coordinated primarily by the swallowing center in the medulla. There are several phases that make up swallowing. Identify what the two phases are and describe what happens during each phase.
1) Oropharyngeal (voluntary) phase: takes <1 second
- Food is segmented into a bolus by the tongue and forced posteriorly toward the pharynx.
- The superior constrictor muscle of the pharynx contracts so the food cannot move into the nasopharynx.
- Respiration is inhibited, and the epiglottis slides down to prevent the food from entering the larynx and trachea.
2) Esophageal phase: takes 5-10 seconds, bolus moves 2-6cm/sec
- The bolus of food enters the esophagus.
- Waves of relaxation travel the esophagus, preparing for the movement of the bolus.
- Peristalsis, the sequential waves of muscular contractions that travel down the esophagus, transports the food to the lower esophageal sphincter, which is relaxed at that point.
- The bolus enters the stomach, and the sphincter muscles return to their resting tone.
Primary vs Secondary Peristalsis
primary peristalsis: peristalsis that immediately follows the oropharyngeal phase of swallowing
secondary peristalsis: if a bolus of food becomes stuck in the esophageal lumen, a wave of contraction and relaxation independent of voluntary swallowing occurs. This is a response to stretch receptor stimulation by increased wall tension which activates impulses from the swallowing centre of the brain.
Describe the structural components and functions of the stomach.
Structure: hollow, muscular organ below the diaphragm
- starts at the lower esophageal sphincter where food passes through the cardiac orifice at the gastroduodenal junction into the stomach
- other end: pyloric sphincter which relaxes as food is propelled through the pylorus/gastroduodenal junction into the duodenum
- innervated by sympathetic and parasympathetic divisions of ANS
- at rest, contains about 50ml of fluid and has no wall tension (everything is relaxed)
Function: stores food during eating, secretes and mixes food with digestive juices, propels partially digested food (chyme) into duodenum and small intestine
The functional areas of the stomach are:
fundus (upper portion)
body (middle portion)
antrum (lower portion)
What are the three layers of smooth muscle that make up the stomach?
1) outer longitudinal layer
2) middle circular layer
3) inner oblique layer (the most prominent)
these layers become progressively thicker in the body and antrum where food is mixed and pushed into duodenum
Describe the vasculature of the stomach
receives its blood supply from the celiac artery
abundant blood supply that ischemic changes will occur only after majority of the arterial vessels are blocked off
drains blood via small veins that empty into hepatic portal vein
What kind of effect does swallowing have on the stomach and what other hormones facilitate this process?
swallowing causes the fundus to relax (Receptive relaxation) to receive a bolus of food from the esophagus
relaxation coordinated by vagal fibers and facilitated by gastrin and cholecystokinin
Gastrin - describe its source of secretion, when it is stimulated, and what its action is.
Source: Stomach mucosa
Stimulus for secretion: presence of partially digested proteins in stomach
Action: stimulates gastric glands to secrete HCl, pepsinogen, histamine; growth of gastric mucosa
Cholecystokinin - describe its source of secretion, when it is stimulated, and what its action is.
Source: small intestine mucosa
Stimulus for secretion: presence of chyme (acid, partially digested proteins, fats) in duodenum
Action: Stimulates gallbladder to eject bile and pancreas to secrete alkaline fluid; decreases gastric motility; constricts pyloric sphincter; inhibits gastrin
What factors increase gastric motility/contractions?
- initiation of perstaltic waves (go from body to antrum) - rate ~3 contractions/min
- Gastrin, motilin, vagus nerve all increase rate of contraction by lowering threshold potential of muscle fibers
What factors decrease or inhibit gastric motility/contractions?
- sympathetic activity
- secretin
- both raise threshold potential
Motilin - describe its source of secretion, when it is stimulated, and what its action is.
Source: small intestine mucosa
Stimulus for secretion: presence of acid and fat in duodenum
Function: increases GI motility
Secretin - describe its source of secretion, when it is stimulated, and what its action is.
Source: small intestine mucosa
Stimulus for secretion: Presence of chyme (acid, partially digested proteins, fats) in duodenum
Function: Stimulates pancreas to secrete alkaline pancreatic juice and liver to secrete bile; decreases GI motility; inhibits gastrin and gastric acid secretion
Describe the process of gastric mixing and emptying - what is happening in the stomach at this point in time?
- gastric contents at this time (chyme) can take several hours to be mixed and emptied out of stomach
- Mixing occurs as food is propelled towards antrum
- Peristaltic wave velocity increases as contents is pushed towards the pylorus BUT this actually causes retropulsion (pushing contents back toward body of stomach) to allow for effective mixing of food with digestive juices and breaking down foods
- With each peristaltic wave, small portion of chyme passes through the pylorus and into duodenum
-
Gastric emptying: gastric conentes moving into duodenum - rate depends on volume, osmotic pressure, chemical composition of chyme
- larger volumes increase emptying, solids/fats/nonisotonic solutions (like feeding tubes) delay emptying
- When digesting fat, cholecystokinin is secreted to reduce gastric motility and emptying so that fats aren’t emptied at a faster rate of bile and enzyme secretion
- Osmoreceptors in the duodenal wall are sensitive to contents coming in. When activated it causes delayed gastric emptying to facilitate formation of an isoosmotic duodenal environment (so rate of emptying is adjusted to duodenum’s ability to neuralize incoming acidity
Phases of gastric secretion
all phases promote secretion of acid by stomach
1) cephalic phase (stimulated by the thought, smell, and taste of food)
2) gastric phase (stimulated by distention of the stomach)
3) intestinal phase (stimulated by histamine and digested protein)
Gatric juices/secretions are secreted from where and made up of what components?
- Primary secretory units: gastric flands in the fundus and body of the stomach
- mucus, acid, enzymes, hormones, intrinsic factor, and gastroferrin
- IF: needed for intestinal absorption of vitamin B12
- Gastroferrin: facilitates small intestinal absorption of iron
What factors may affect the composition of gastric juice?
- volume, flow rate
- varies with time of day - lowest in the morning, highest in afternoon and evening
- K+ remains relatively constant levels, but secretion increases with decreased Na+ (see chart)
- Stimulated by: process of eating (gastric distention), gastrin and paracrine pathways (histamine, ghrelin), NT Ach, other chemicals (ethanol, coffeem protein)
-
Inihibited by:
- stomatostatin (inhibits GH)
- unpleasant odors and tastes
- rage, fear, pain
- sympathetic impulses
Describe how and where hydrochloric acid is formed, its functions, and how it is regulated.
Formation: produced by parietal cells via hydrolysis of water, requires H+ and Cl- transport from these cells to stomach lumen
Function: dissolve food fibers, act as bactericide against swallowed microorganisms, convert pepsinogen to pepsin
Regulation: acid secretion stimulated by vagus nerve (ACh is released with stimulates gastrin secretion which then stimulates histamine release from enterochromaffin cells). Histamine activates H2 receptors on parietal cells where HCl gets secreted.
- Stimulators: caffeine, calcium
- Inhibitors: somatostatin, secretin, other intestinal hormones
What is pepsin and how is it secreted, activated/inactivated?
- a proteolytic enzyme (breaks down protein and forms polypetides in the stomach)
- chief cells are stimulated by ACh, gastrin and secretin to release pepsinogen during eating
- Pepsinogen converted to pepsin in acidic gastri environment (pH 2 for optimal activation)
- Inactivated once chyme enters the duodenum due to alkaline environment
What functions does a mucosal barrier have in the stomach?
- protection from digestive actions of acid and pepsin (in conjunction with intercerllular tight junctions and gastric mucosal blood flow contributing to protection)
- Prostaglandins protect mucosal barrier by stimulating secretion of mucus and bicarbonate, and inhibit secretion of acid
- also impermeable to water but can absorb alcohol and aspirin
What factors/substances can cause a break in the protective mucosal barrier?
- ischemia
- H. pylori
- aspirin
- NSAIDs (inhibit prostaglandin synthesis)
- Ethanol
- Regurgitated bile
- Breaks cause inflammation and ulceration
Where is the small intestine located and how long is it?
coiled within peritoneal cavity
about 5-6 m long
What are the small intestine’s functional divisions?
1) Duodenum: begins at pylorus and ends where it joins jejunum at the Tretiz ligament; lies retroperitoneally and is attached to the posterior abdominal wall
- absorbs calcium, magnesium, iron
2) Jejunum: suspended in loose folds from posterior abdominal wall by the mesentery membrane
- Absorbs fat soluble vitamins, amino acids, fats, water (90%), carbohydrates, water soluble vitamins, alcohol (80% of total), sodium, potassium
3) Ileum: no anatomical barrier between end of jejunum and beginning of ileum; ^also suspended as above;
- absorbs Vitamin B12, bile
Function of the mesentery
facilitates intestinal motility and supports blood vessels, nerves, and lymphatics.
Describe the structural components of the peritoneum.
- a serous membrane surrounding abdominal and pelvic organs
- visceral peritoneum - lies on surface of organs
- parietal peritoneum - lines wall of the body cavity
- In between is the peritoneal cavity and contains juts enough fluid to lubricate the two layers and prevent friction during organ movement
Describe the innervation and regulation of the small intestine
- small intestine innervated by enteric nerves from both division of the ANS
- Parasympathetic stimulation (via vague nerve) - stimulates secretion, motility, pain sensation, and intestinal reflexes
- Sympathetic activity - inhibits motility and produces vasoconstriction
- Intrinsic reflexive activity mediated by myenteric (Auerbach) plexus & submucosal (Meissner) plexus
How are the smooth muscles in the small intestine arranged and what function does it serve?
longitudinal outer layer and thicker inner circular layer
Circular folds of the small intestine slow the passage of food, which allows more time for digestion and absorption; folds most numerous and prominent in jejunum and proximal ileum
Where does absorption occur and what structures are involved with it?
- Absorption occurs through villi (functional units of the intestine) which cover the circular folds of muscle
- Microvilli on the villi create a mucosal surface called brush border = greatly increase SA available for absoprtion
-
Structure of villus: absorptive columnar cells (enterocytes) held together via tight junctions and mucus-secreting goblet cells of mucosal epithelium; contains tiny projections called microvilli
- contains the lamina propia which is a connective tissue layer of mucous membrane beneath villi epithelial cells; has lymphocytes and plasma cells to produce Immunoglobulins
- within each villus, central arterioles ascend in and branch into capillary network. Drained via hepatic portal circulation
- also contains lacteals
- Function of villus: secretes some digestive enzymes and absorb nutrients
Lacteal
lymphatic capillary found within each villus that is needed for absoprtion and transport of fat molecules. Contents of the lacteals flow to regional nodes and channels that eventually drain into the thoracic duct
Crypts of Liberkühn - Structure & Function
- found between the bases of the villi and extends to submucosal layer
- Undifferentiated cells arise from stem cells at the base of the crypt and move toward the tip of the villus, maturing to become columnar epithelial secretory cells (water, electrolytes, and enzymes) and goblet cells (mucus)
- Once at tip of villus, they function for a few days and are then shed into intestinal lumen and digested (endogenous protein)
- Entire epithelial population replaced every 4-7 days; influenced by starvation, B12 deficiency, cytotoxic drugs or irradiation suppress cell division and shorten villi
Briefly describe the process of digestion and absorption beginning at the stomach.
- Digestion is initiated in the stomach via gastric HCl and pepsin
- Chyme that passes into the duodenum is a liquid with small particles of undigested food
- Digestion continues in the proximal portion of the small intestine via pancreatic & intestinal enzymes, and bile salts.
- In proximal small intestine, everything is broken down (carbs to surgars, proteins degraded to AA, fats emulsified to FAs). These nutrients & water, vitamins, and electrolytes, are absorbed across the intestinal mucosa by active transport, diffusion, or facilitated diffusion
- Products broken down move into villus capillaries and then to the liver through the hepatic portal vein. Digested fats move into the lacteals and eventually reach the liver through the systemic circulation.
- Intestinal motility exposes nutrients to a large mucosal surface area by mixing chyme and moving it through the lumen.
Digestion and absorption of all major nutrients and many drugs occr in which part of the GI tract? How is it stimulated?
small intestine - stimulated by chyme leaving the stomach into the duodenum (helps blend secretions from the liver, gallbladder, pancreas, and intestinal glands)
Intestional motility is affected by what two movements?
1) Haustral segmentation - Localized rhythmic contractions of circular smooth muscles divide and mix the chyme, enabling the chyme to have contact with digestive enzymes and the absorbent mucosal surface, and then propel it toward the large intestine.
2) Persistalsis - Waves of contraction along short segments of longitudinal smooth muscle allow time for digestion and absorption. The intestinal villi move with contractions of the muscularis mucosae, a thin layer of muscle separating the mucosa and submucosa, with absorption promoted by the swaying of the villi in the luminal contents.
Motility, digestion, and absoprtion is also facilitated by neural reflexes. What are these reflexes?
1) Ileogastric reflex - inhibits gastric motility when ileum becomes distentded to prevent continued movement of chyme into an already distended intestine
2) Intestinointestinal reflex - inhibits intestinal motility when one part of the intestine is overdistended.
3) Gastroileal reflex - activated by an increase in gastric motility and secretion & stimulates increase in ileal motility and relaxation of the ileocecal valve/sphincter - empties the ileum and prepares it to receive more chyme
Ileocecal valve/sphincter - Structure, Function, and Regulation
Structure: marks the junction between terminal ileum and large intestine. Intrinsically regulated and normally closed.
Function: controls the flow of digested material from the ileum into the large intestine and prevents reflux into the small intestine.
Regulation:
- Open: Arrival of peristaltic waves fro last few cm of the ileum causes it to open and allow a small amoutn of chyme to pass; gastroileal reflex
- Close: distention of upper large intestin to prevent further distention or retrograde flow of intestinal contents
Descrribe the structure of the large intestine
- ~1.5m long
- consists of cecum, appendix, colon (ascending, transverse, descending, sigmoid), rectum, anal canal
Cecum & Vermiform appendix
Cecum: pouch that receives chyme from ileum; where chyme starts to enter the colon
Vermiform appendix: attached to cecum, is an appendage with little to no function
What are the two sphincters controlling flow of intestinal contents through the cecum and colon?
- ileocecal valve: admitting chyme from ileum to cecum
- rectosigmoid (O’Berine) sphinter: controls movement of wastes from sigmoid colon to rectum
Internal & External anal sphincter
Internal anal sphincter; thick (2.5-3cm) portiom of smooth muscle surrounding the anal canal
External anal sphincter: aka anus. Distal to ^ and is made of striated skeletal muscle
Describe the musculature and cellular make up of the cecum and colon (i.e. what type of muscles and cells and their respective functions).
Musculature:
- longitudinal muscle layer with 3 longitudinal bands (teniae coli) and are shorter than the length of the colon to give it a “gathered” appearance
- circular muscles of colon separate the gathers into outpuchings called haustra
Cellular structure:
- mucosal surface of the colon has rugae (folds) especially between the haustra and Liberkühn cryps but no villi
- Columnar epithelial cells and mucus-secreting goblet cells form the mucosa throughout large intestine ; absorbs fluid and electyolytes (columnar) and lubrate mucosa (goblet cells)
What innervation does the large intestine have?
Where does it receive its blood supply from?
Innervations:
- extrinsic parasympathetic innervation via vagus nerve, extends from cecum up to first part of transverse colon; increases rhythmic contraction of proximal colon
- extrinsic parasympathetic innervation reaches the distal colon through sacral parasympathetic splanchnic nerves
- Myenteric plexus provides the major innervation of the internal anal sphincter, but responds to sympathetic stimulation to maintain contraction and parasympathetic stimulation (via celiac and superior mesenteric ganglia and the sphincter nerve) that facilitates relaxation when the rectum is full
- External anal sphincter innervated by pudendal nerve arising from sacral levels of spinal cord
Blood supply: branches of the superior and inferior mesenteric arteries; drains via inferior mesenteric vein
What kind of movements (i.e. peristaltic, propulsive, etc.) occurs in the colon, and what benefits do these types of movements have in this region of the GI tract?
- Segmental: primary type of movement in colon. Circular muscles contract and relax at different sites which help shuttle contents bakc and forth between the haustra (most commonly during fasting); massages the contents (fecal mass at this point), to facilitate water absorption
- Propulsive: occurs with proximal-to-distal contraction of several haustral units; initiated by gastrocolic reflex
- Peristaltic: promote emptying of the colon
Gastrocolic reflex
- reflex that initiates propulsion in the entire colon (usually during or immediately after eating) when chyme enters from ileum
- causes fecal mass to pass radpily into sigmoid colon and rectum - stimulating defecation
- gastrin may also contribute to this reflex
- epinephrine inhibits contractily activity
Where does absorption occur in the large intestine and what substances are reabsorbed vs what substances remain in the colon to be eliminated?
- ~500-700 ml of chyme flows from ileum to cecum daily
- H2O: most of the water is absorbed in colon via diffusion and active transport
- Sodium: aldosterone also increases membrane permeability to Na (so Na uptake into the cell via diffusion and interstitial fluid via active transport)
- Macros: some FAs, but no monosaccharides and AA
- absorption occurs in cecum, ascending/transverse./descending colon; it becomes feces when it gets to the sigmoid colon (food residue, unabsorbed GI secretions, shed epithelial cells, and bacteria)
Defecation/Rectosphincteric reflex
- stimulated by movement of feces into the sigmoid colon and rectum
- rectal wall stretches and internal anal sphincter (smooth muscle with ANS control) relaxes which creates the urge to defecate
- can be overridden voluntarily by contraction of the external anal sphincter and muscles of the pelvic floor
- rectal wall gradually relaxes which reduces tension and urge to defecate passes
- reflex can be inhibited with pain or fear of pain (i.e. with hemorrhoids)
What techniques help with defecation?
- sitting/squatting as these positions straighten the angle between rectum and anal canal (increases efficiency of straining via increasing intra-abdominal pressure)
- Valsalva maneuver: increases intra-abdominal pressure (and intrathoracic) by inhaling and forcing the diaphragm & chest muscles against the closed glottis (pressure is transmitted to the rectum)
What kinds of immune defences is the GI tract equipped with?
- mucosa of intestine produces secretions that make antibodies (esp. IgA) and enzymes that provide defenses against microorganisms
- Paneth cells: found near base of crypts of Leiberkühn - produce defensins and antimicrobial peptides and lysozymes needed for mucosal immunity
- Peyer patches: lymph nodules with lymphocytes, plasma cells and macrophages - found mostly in the ileum and produce antimicrobial peptides and IgA as a component of gut-associated lymph tissue in small intestine; important for antigen processing and immune defence
What role doe the intestinal microbiome play, and what factors may change its composition?
Function:
- increasing number of bacteria from proximal to distal GI tract, highest number in colon
- no major digestive/absorptive functions but involved with metabolism of bile salts, estrogens, androgens, lipids, carbs, nitrogenous substances, and drugs
- produce antimicrobial peptides, hormones, NTs, anti-inflammatory metabolites, and vitamins
- destroys toxins & prevents pathogen colonization
- alerts immun system to protect against infection
Factors:
- genetics, diet, environmental pollution, personal hygiene, vaccination, antibiotics/drugs
- intestinal tract is sterile at birth, becomes colonized within a few hours
- Wtihin 3-4 weeks after birth, normal flora is establisehd
- # and diversity of bacteria decrease with aging
How much bacteria can be found in the GI tract?
- sparse in the stomach due to acid secretion that kills ingested pathogens or inhibits bacterial growth (wiht exception of H. pylori)
- Bile acid secretion, intestinal motility, and antibody production suppress bacterial growth in the duodenum
- Low aerobe concentration in duodenum and jejunum: primarily streptococci, lactobacilli, staphylocci, other enteric bacteria
- Anaerobes only found distal to ileocecal valve (make up ~95% of fecal flora and contribute to 1/3 of the solid bulk of feces)
- Bacteroides & Firmicutes are most common intestinal bacteria
What is the importance of splanchnic blood flow?
- provides blood to esophagus, stomach, small and large intestines, liver, gallbladder, pancreas and spleen
- blood flow regulated by cardiac ouput and blood volume, ANS, hormones, and local autoregulatory mechanisms
- serves as an important reservoir of blood volume to maintain circulation to heart and lungs when needed
How do the accesory organs of the GI system contribute to digestion?
1) Liver: produces bile which has salts in it that are necessary for fat digestion and absorption. Also receives nutrients absorbed by small intestine & metabolizes them into forms that can be absorbed by body’s cells (releases it into the blood stream or stores it for later use)
2) Gall bladder: Between meals, bile is stored in the gall bladder
2) Exocrine pancreas: produces 1) enzymes needed for complete digestion of carbs, proteins, and fats & 2) alkaline fluid that neutralizes the chyme and makes the pH of the duodenum appropriate for enzymatic action
Alls ecretions are delivered to duodenum through sphincter of Oddi at the major duodenal papilla (of Vater)
External structures of liver
- weighs 1200-1600g
- located under R diaphragm & divided into R and L lobes
- Larger R lobe further divided into caudate & quadrate lobes
- Falciform ligament: separates the R and L lobes and attaches the liver to the anterior abdominal wall
- Round ligament (ligamentum teres): extends along free edge of falciform (from umbilicus to inferior surface of liver)
- Coronary ligament: branches from falciform and extends over superior surface of R and L lobes (binds liver to inferior surface of the diaphragm)
- covered by the Glisson capsule - contains blood vessels, lymphatics, and nerves; becomes distended and causes pain when liver is diseased
Internal structures of the liver
- Liver lobules: further smaller units within the liver lobes, formed of cords/plates of hepatocytes
- hepatocytes: functional cells of the liver, can regenerate
-
Sinusoids: small capillaries that are located between the plates of hepatocytes & receive blood from venous and arterial blood from branches of the hepatic artery and portal vein
- blood from here drains to a central vein in the middle of each liver lobule which then drains into hepatic vein (then into IVC)
- sinusoids have highly permeable endothelium to allow nutrient transport from sinusoids into hepatocytes where they are metabolized
-
Bile canniculi: small channels that conduct bile (produced by hepatocytes) outwards to bile ducts, eventually drains into common bile duct
- Common bile duct then empties bile into ampulla of Vater, then into duodenum through major duodenal papillar (Sphincter of Oddi)
Blood supply of the liver
- receives blood from both arterial and venous sources
- Hepatic artery: branched from celiac artery, provides oxygenated blood ~400-500ml/min (~25% of cardiac output)
-
Hepatic portal vein: receives deoxygenated blood from mesenteric veins, splenic veins, gastric and esophageal veins, and delivers 1000-1500 ml/min to liver
- carries 70% of blood supply to the liver & is nutrient rich that is absorbed from intesitnal tract
What cells/structures within the liver are involved with immune functions?
- Kupffer cells (tissue macrophages): part of mononuclear phagocye system (MPS); important for healing of liver injury, are bactericidal, & important for bilirubin production and lipid metabolism
- Stellates cells: contain retinoids (vit A), are contractile in liver injury, regulate sinusoidal blood flow, may proliferate into myofibroblasts, participate in liver fibrosis, produce EPO, act as APCs, trap bacteria, and remove foreign substances from blood
- NK cells (pit cells): found in sinusoidal lumen; produce interferon-γ and are important in tumor defense
- Disse space: between endothelial lining of sinusoid and hepatocytes & drains interstitial fluid into hepatic lymph system
What is bile and how much is secreted daily?
- an alkaline, bitter-tasting, yellow-green fluid that contains bile salts (conjugated bile acids), cholesterol, bilirubin, electrolytes, and water
- formed by hepatocytes and secreted into the bile cannuculi
- Bile salts: needed for intestinal emulsification and absoprtion of fats; become actively absorbed into the terminal ileum when emulsifying fat and gets returned to the liver via portal circulation to be resecreted (pathway known as enterohepatic circulation)
- 700-1200ml of bile daily
Describe the enterohepatic circulation of bile salts
- bile has two fractional components: acid-dependent and acid-independent fraction
- hepatocytes secrete acid-dependent fraction - bile acids, cholesterol, lecithin (phospholipid), bilirubin
- Acid-independent: secreted by hepatocytes and epithelial cells of bile canaliculi (bicarb-rich aq fluid that contributes to alkaline pH of bile)
- Acids are synthesized into primary bile acids from cholesterol in hepatocytes & then conjugated by two AA (taurine and glycine) into bile salts
- bile salts either get stored in gallbladder or go to small intestine to emulsify fats
- Bile salts are then excreted via rectum (15-35%) or transported across intenstinal lume and deconjugated by bacteria into secondary bile acids
- Secondary bile acids diffuse passively into portal blood (65-85% of bile salts) and are transported back to hepatocytes in liver
What is a cholerectic agent?
- a substance that stimulates bile secretion (choleresis)
- Stimulants:
- high [bile salts]
- cholecystokinin
- vagal stimulation
- secretin
Describe the steps in metabolizing bilirubin
- Bilirubin - a byproduct of aged RBC destruction & creates that greenish black colour in bile and the yellow tinge in jaundice
- When RBCs get degraded, they create heme and globin components
- heme is converted to biliverdin by cleaving iron
- iron is transported back to liver/bone marrow for new RBCs
- biliverdin is converted to bilirubin in Kupffer cells and then released into plasma to bind with albumin (aka unconjugated/free bilirubin) which is lipid soluble (May have a role as an antioxidant and provide cytoprotection)
- In liver, unconjugated bilirubin moves from plasma in sinusoids to hepatocytes
- In hepatocytes: unconjugated bilirubin joins with glucuronic acid to form conjugated bilirubin (water soluble and secreted in the bile)
- Once it reaches distal ileum and colon, it is deconjugated by bacteria and converted into urobilinogen (then reabsorbed in intestine and excreted in the urine as urobilin)
- Small amount excreted in feces (stercobilin) which contributes to poop’s brown colour
What vascular and hematologic functions does the liver have?
- has extensive vascular network and can store a large volume of blood (amount stored depends on pressures in arteries and veins)
- can also release blood to maintain circulatory volume if needed (i.e. hemorrhage)
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Hemostatic function:
- synthesizes most clotting factors
- the bile that is secreted by liver helps with vitamin K absorption which is neede for synthesis of clotting factors
How does the liver contribute to metabolism of fats, proteins and carbohydrates?
Fats: absorbed by lacteals in intestinal villi then goes into liver via lymphatics as triglycerides. Hydrolyzed and then used to produce ATP or released into bloodstream as lipoproteins (to go to adipose cells for storage). Also makes phospholipids and cholesterol that are used in bile salt production, steroid hormones, etc.
Proteins: In hepatocytes, AA converted to keto acids via deamination (removing NH3). NH3 converted to urea by liver and passes into blood for excretion via kidneys. Liver synthesizes plasma proteins (albumins, globulins) that contribute to maintaining plasma oncotic pressure.
Carbohydrates: liver contributes to stability of BGL by glucose release during hypoglycemia and absorbing glucose during hyperglycemia. Stores it as glycogen or converts it to fat. IF all glycogen stores are used, can also convert AA and glycerol to glucose (gluconeogenesis).
How does the liver accomplish metabolic detoxification?
- aka biotransformation
- alters exogenous/endogenous chemicals like drugs, foreign molecules,s and hormones to make them less toxic or less biologically active
- Diminiahses the intestinal or renal tubular reabsorption of potentially toxic substances and facilitates their intestinal and renal excretion
- helps with preventing excessive accumulation and adverse effects from things like EtoH, barbituates, amphetamines, steroids and hormones
- detoxification is usually protective, but the end products sometimes become toxins or active metabolites.
What kinds of minerals and vitamins are stored in the liver
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Minerals: iron and copper (in times of excessive intake)
- iron stored as ferritin (released as needed for RBC production)
- Vitamins: B12 and D (several months); vitamin A (several years), E and K
Structure and Function of gallbladder
Structure: saclike organ on inferior surface of liver
Function: store and concentrate bile between meals
- between digestive periods, bile flows from liver (via R or L hepatic duct) into common hepatic duct and meets resistance the closed sphincter of Oddi (duodenal papilla) which controls flow into duodenum and prevents backflow
- Bile then flows through cystic duct into gall bladder for concentration and storage
- Gallbladder mucosa readily absorbs water and electrolytes which leaves a high concentration of bile salts, pigments, and cholesterol
- holds ~90ml of bile
How does bile get released from the gallbladder?
- Within 30 min after eating, gallbladder begins to contract which forces stored bile through the cystic duct and into common bile duct
- Sphincter of Oddi relaxes and allows bile to flow into duodenum via major duodenal papilla
- Gallbladder contraction mediated by vagus nerve & cholecystokinin
- Relaxation stimulated by vasoactive intestinal peptide, pancreatic polypeptide, SNS stimulation
Structure of the pancreas
- ~20cm long, head tucked into curve of duodenum and tail touching the spleen
- lies deep in the abdomen behind the stomach
- has endocrine and exocrine functions
- receives blood via celiac and superior mesenteric arteries, and drains into portal vein (body and tail drains through splenic vein
- innervation from parasympathetic neurons of the vagus nerve (which stimulate enzymatic and hormone secretion); sympathetic innervation causes vasoconstriction and inhibits pancreatic secretion
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Structure and Function of exocrine pancreas
- composed of acinar cells that secrete enzymes and networks of ducts that secrete alkaline fluid (both for digestion)
- Acinar cells are organized in lobes around small secretory ducts where secretions drain into the pancreatic duct (Wirsung duct) which empties into common bile duct at the ampulla of vater then into the duodenum
- Aq solution secreted: isotonic and contains K, Na, HCO3-, Cl (neutralizes acidic chyme when entering the duodenum to allow for enzymes to digest and fat absorption)
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What enzymes are released from the pancreas?
- hydrolyzes proteins, fats, and carbs
- trypsin, chymotrypsin, carboxypeptidase, elastase (but all secreted in their inactive forms to protect the pancreas from its digestive effects)
- Once in duodenum, they are activated by enterokinase (secreted from duodenal mucosa)
- trypsinogen is activated first which stimulates conversion of chymotrypsinogen and procarboxypeptidase
- Once the enzymes are activated in the small intestine, they inhibit the release of more cholecystokinin (that stimulated their release in the first place) to inhibit secretion of any more pancreative exocrine secretion
Geriatric changes to the GI system
- Mouth: teeth decay, everything decreases in terms of senses and function
- Stomach: everything slows down (motility, blood flow, gastric emptying) & mucosal barriers decrease
- Intestines: change in microbiome, decreased immunity, decline in overall health nutritional status, absorption declines, fecal making changes
- Liver: decrease in regrowth, detox abilities, bloow flow (thus drug metabolism)
- Pancreas and Gallbladder: fibrosis, fatty deposits; decreased digestive enzyme secretion; increased risk of gall stones and inflammation
Anorexia
Definition: lack of desire to eat despite physiological stimuli that would normalyl produce hunger
- often associated with nausea, abdo pain, diarrhea, stress
- may also be from side effects of drugs or disorders (cancer, heart/renal disease)
Vomiting - Definition and Types
Vomiting (emesis): forceful emptying of stomach and intestinal constents via mouth. Vomiting center in medulla oblongata and stimulated with:
- severe pain; stomach/duodenum distension; presence of ipecac/copper salts in duodenum
- motion sickness (CN 8 stimulation of vestibular system)
- drugs
- trauma to genitourinary structures
- activaiton of chemoreceptor trigger zone (CTZ) in medulla
Nausea: usually precedes vomiting. Is a subjective experience. Often associated with hypersalivation and tachycardia; can be brought on by things like abnormal pain and spinning movements
Retching: muscular event of vomiting without anything coming out
Projectile Vomiting: spontaneous vomiting not prceded by nausea or retching. Caused by direct stimulation of vomiting center by neuro lesions (IICP, tumors, aneurysms) involving brainstem or a symptom of GI obstruction (pyloric stenosis)
What physiological changes/mechanisms occur during the process of vomiting?
- begins with deep inspiration; hlottis closes, intrathoracic pressure falls, and esophagus becomes distended. Simultaneously abdominal muscles contract creating a pressure gradient from abdomen to thorax
- Lower esophageal sphincter (LES) and body of the stomach relax, but the duodenum and antrum of the stomach spasm
- The reverse peristalsis and pressure gradient force chyme from the stomach and duodenum up into the esophagus but upper esophageal sphincter is closed so chyme does not enter the mouth
- As the abdominal muscles relax, esophageal contents drop back into the stomach & process may be repeated several times before vomiting occurs
- when vomiting does occur, diaphragm is forced high into the thoracic cavity by strong contractions of the abdominal muscles and causes the UES to open and chyme expelled from the mouth
- Then the stomach relaxes and the upper part of the esophagus contracts, forcing the remaining chyme back into the stomach. The LES then closes & cycle repeats if more vomiting needs to occur
- A diffuse sympathetic discharge causes the tachycardia, tachypnea, and diaphoresis that accompany retching and vomiting. Parasympathetic system mediates copious salivation, increased gastric motility, and relaxation of UES and LES
Constipation
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: difficult or infrequent defecation. Common among elderly. (normal bowel habits can be 1-3/day to 1/week)
Pathophysiology: primary or secondary condition
Primary:
- Normal transit (functional) constipation: normal rate of stool passage but difficulty with evacuation
- Functional constipation: associated with sedentary lifestyle, low-residue diet (highly refined foods) or low fluid intake
- Slow-transit constipation: involves impaired colon motor activity with infrequent bowel movements, straining to defecate, mild abdominal distention, palpable stool in sigmoid colon
- Pelvic floor/outlet dysfunction: inability/difficulty expelling stooling due to dysfunction of pelvic floor muscles/anal sphincter
Secondary: can be caused by diet, meds, neurogenic disorders (CVA, Parkinson’s SCI, MS) where neural pathways or NTs are altered and colon transit time is delayed.
- Drugs: opiates, antacids with CaCO or AlOH, anticholinergics, iron, bismuth inhibit bowerl motility
- Endocrine disorders (hypothyroidism, DM, hypokalemia, hypercalcemia)
- Abdo: pelvic hiatal hernia (herniation of bowel through floor of pelvis), diverticuli, IBS, pregnancy
- Aging
Clinical Manifestations: 2 of the following for at least 3 months
- (1) straining with defecation at least 25% of the time
- (2) lumpy or hard stools at least 25% of the time
- (3) sensation of incomplete emptying at least 25% of the time;
- (4) manual maneuvers to facilitate stool evacuation for at least 25% of defecations;
- (5) fewer than three bowel movements per week
Look for changes in bowel evacuation patterns (less pooping, smaller stool volume, hard stools, straining, feeling bowel fullness and discomfort). Fecal impaction (hard dry stool retained in rectum) leads to rectal bleeding, abdominal cramps, N/C, weight loss, diarrhea. Passage of hard stools may cause hemorrhoidal disease and painful anal fissures.
Diagnosis: History, meds, physical exam, stool diaries
Treatment: Manage underlying cause or disease. Bowel retraining, moderate exercise, increasing fluids and fiber intake. Laxatives/stool softeners for some. Last resort would be surgery.
What physiological responses occur with GI bleeding?
- changes in BP and HR
- Early stages: peripheral arteries and arterioles constrict to shunt blood to vital organs (brain)
- Signs of large volume blood loss: postural hypotension, lightheadedness, loss of vision, tachycardia as compensatory
- eventually hypovolemic shock
- Decreased UP and potentially oliguria (due to decreased blood flow to kidneys), tubular necrosis, and renal failure
Achalasia
Definition, Pathophysiology, Clinical Manifestations, Treatment
Definition: rare form of dysphagia related to loss of inhibitory neurons in the myenteric plexus & smooth muscle atrophy in the middle and lower portions of esophagus.
Pathophysiology; Myenteric neurons attacked by cell-mediated and anti-body mediated immune response against an unknown antigen. Leads to altered esophageal peristalsis and failure of LES to relax causing functional obstruction of the lower esophagus with varying severity. Food accumulates above the obstruction, distends the esophagus, and causes dysphagia. As hydrostatic pressure increases, food is slowly forced past obstruction and into the stomach.
Clinical Manifestations: Coughing, aspiration. Similar to dysphagia symptoms (pain when eating/drinking, pain after swallowing, vomiting, weight loss, etc.)
Treatment: Mechanical dilation or surgical myotomy (cutting muscular layer) of LES
Hiatal Hernia
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: type of diaphragmatic hernia. Protusion of upper part of stomach through the diaphragm and into thorax
Pathophysiology: several types:
Sliding hiatal hernia (Type 1): most common. Proximal portion of stomach moves into thoracic cavity via esophageal hiatus (opening in diaphragm for esophagus and vagus nerves). Causes: congenitally short esophagus, fibrosis or excessive vagal nerve stim., weakening of diaphragmatic muscles at gastroesophageal junction. Often associated with GERD and made worse with coughing, bending, tight clothing, ascites, obesity, pregnancy.
Paraesophageal hiatal hernia (Type 2): herniation of greater curvature of the stomach through a secondary opening in diaphragm alongside esophagus. Causes congestion of mucosal blood flow, leading to gastritis and ulcers. Major complication is strangulation of hernia, presenting with vomiting and epigastric pain.
Mixed hiatal hernia (Type 3): less common; a combination of sliding and paraesophageal hiatal hernias. Tends to occur in conjunction with several other diseases (reflux esophagitis, peptic ulcer, cholecystitis, cholelithiasis, chronic pancreatitis, diverticulosis
Clinical Manifestations: often asymptomatic. Wide variety of Sx developing later in life related to GI disorders. Heartburn, regurgitation, dysphagia, epigastric pain. Ischemia from hernia strangulation causes acute, severe chest or epigastric pain, N/V and GI bleeding.
Diagnosis: radiology (barium swallow), endoscopy, high resolution manometry. Chest X ray
Treatment: conservative. Eat small frequent meals and avoid laying down after eating. Avoid abdominal supports and tight clothing. Weight control. Antacids. Elevation of the head of bed 6 inchs. Surgery (fundoplication) if other Ix fail.
Intestinal Obstruction and Functional Obstruciton (Paralytic Ileus)
Definition, Causes, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: any condition that prevents normal flow of chyme through intestinal lumen (small or large intestine but small usually more obstructed due to narrower lumen). Classified as:
- Simple obstruction: mechanical blockage of lumen by a lesion; most common type
- Functional obstruction (paralytic ileus): failure of intestinal motility often after intestinal/abdo surgery, acute pancreatitis, or hypokalemia
Causes: hernia, intussusception (intestine telescoping into another), Torson (volvulus; intestinal twisting), diverticulosis (inflamed diverticuli ), tumor, paralytic ileus (loss of peristaltic motor activity), fibrous adhesions (peritoneal irritation from surgery, trauma, Chron disease leading to fibrosis)
- Small bowel obstruction: adhesions (2’ to abdo surgery, most common), hernia, tumors, mesenteric ischemia, Crohn disease
- Large bowel obstruction: colon/rectal cancer (most common), volvulus, diverticular disease
Pathophyisiology: Paralytic ileus 2’ to surgery is due to inhibitory neural reflexes associated with inflammatory mediators and opioids that affect entire GI tract. Small bowel obstruction (SBO) caused by post-op adhesions, tumors, Crohn disease, and hernias & leads to distention caused by impaired absoprtion and increased secretion of fluid and gas. Distention decreases the ability to absorb water and electrolytes, on top of that with copious vomiting as well causes severe fluid electrolyte disturbances. ECF and plasma volume decrease (causing dehydration increased Hct, hypotension, and tachycardia; eventually hypovolemic shock).
- Metabolic alkalosis initially develops due to excess loss of H+ but then metabolic acidosis kicks in due to prolonged obstruction in intestine as HCO3- from pancreatic secretions and bile cannot be reabsorbed
- Metabolic acidosis also may be accentuated by ketosis, the result of declining carbohydrate stores caused by starvation. Buildup of lactic acid due to lack of circulation also increases acidosis
- If pressure from the distention is severe enough, it occludes the arterial circulation (causing ischemia, necrosis, perforation, and peritonitis).
- Fever and leukocytosis are often associated with overgrowth of bacteria, ischemia, and bowel necrosis. Bacterial proliferation and translocation across the mucosa to the systemic circulation cause peritonitis or sepsis. The release of inflammatory mediators into the circulation causes remote organ failure.
- Large Bowel Obstruction (LBO): less common, often related to cancer
- Acute colonic pseudo-obstruction (Oglivie syndrome): rare but massive dilation of large bowel related to excessive sympathetic motor input or decreases parasympathetic motor input with absence of mechanical obstrucition. Primarily in critically ill or immobilized older adults
Clinical Manifestations:
- SBO: colicky pain (from intestinal distention) followed by N/V. Pain intesnsifies for seconds or minutes as a peristaltic wave of muscle contraction meets the obstruction. If ischemia occurs, pain becomes more constant and severe. Hypotension, increased HR, diaphoresis, fever, ++leukocytosis, abdominal distention, rebound tenderness.
- Obstruction at pylorus: early, profuse vomiting
- Partial obstruction: diarrhea and constipation
- Complete obstruction: constipation only; increased bowel sounds, hypovolemia, metabolic acidosis. Distention may push against diaphragm leading to decreased lung volume, atelectasis and pneumonia
- Large Intestine obstruction: hypogastric pain, abdominal distention. Variable pain. Vomiting occurs later in obstructive process.
Diagnosis: Clinical presentation and imaging studies.
Treatment: early identification of site and type of obstruction. Fluid and electrolyte replacement, decompression of lume with suctioning. Laparoscopic procedures can release adhesions. Immediate surgery for strangulation, complete obstruction, or perforation
Peptic ulcers
What are they, how do they develop, what are the risk factors, and types of ulcers.
Definition: break or ulcertaion in the protective mucosal lining of the lower esophagus, stomach, or duodenum. They develop when mucosal protective factors are overcome by erosive factors (commonly caused by NSAIDs and H. pylori infection)
- can be single, multiple, acute or chronic, and superficial or deep
- Erosions: superficial ulcerations - erode mucosa but do not penetrate muscularis layer
- True ulcers: extend through muscularis mucosa and damage blood vessels leading to hemorrhage, or perforate GI wall
Risk factors: psych stress, H. pylori infeciton, chronic use of NSAIDs, alcohol, smoking, age, chronic disease, type O blood
Types: duodenal, gastric, and stress ulcers
Duodenal Ulcers
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: occur more commonly than other types & commonly due to H. pylori infection and NSAID use. Idiopathic ulcers are rare & associated with altered mucosal defenses, rapid gastric emptying, elevated serum gastrin levels, acid production 2’ to smoking.
Pathophysiology: Acid and pepsin in duodenum penetrate the mucosal barrier and cause ulceration. T and B lymphocytes activated in response to H. pylori infection, neutrophils infiltrated. Inflammatory cytokines released and damages gastric epithelium. H. pylroi causes apoptosis of gastric epithelial cells and promotes inflammation
Clinical Manifestations: **chronic intermittent pain in epigastric region**. Pain starts 2-3 hr after eating when stomach is empty. Can also occur at night and disappear in the morning; relieved rapidly by infestion of food or antacids (pain-food-relief pattern). Some may be asymptomatic and then have their first symptom as hemorrhaging or performation (esp with NSAID/anticoagulant use).
- Complications: bleeding, perforation, obstruction of duodenum or outlet of the stomach. Bleeding most common cause of mortality in elderly.
- Perforation occurs with destruction of all layers of the duodenal wall, causes sudden severe epigastric pain
- Obstruction may be from edema (inflammation) or scarring from chronic injury
- Exacerbations tend to develop in spring and fall
Diagnosis: endoscopies to visualize lesions, biopsy. Urea breath test to detect H. pylori
Treatment: often heal spontaneously but recur within months without tx. Pain relief allows healing. Treatment: relive causes and effects of hyperacidity and preventing complications. Antacids neutralize gastric contents and relieve pain. H2 receptor antagonists to inhibit acid secretion. PPIs to inhibit acid production. Antibiotics for H. pylori. Surgery for bleeding or perforations.
Gastric ulcers
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: ulcers of the stomach. Occurs equally in M and W usually between 55-65. Tend to develop in the antral region next to the acid-secreting mucosa of the body.
Pathophysiology: primary defect - an abnormality that increases the mucosal’s barrier permeability to H+. Gastric secretion is normal or less than normal, and there may be decreased pass of parietal cells. Contributing factors:
- Chronic gastritis - due to limiting mucosa’s ability to secrete a protective layer of mucus, which contributes to gastric ulcer formation
- Decreased mucosal synthesis of prostaglandins
- Duodenal reflux of bile and pancreative enzymes damaging the mucosal membrane
- Use of NSAIDs (decreased prostaglandin synthesis)
- H. pylori infection
Break in mucosal barrier allows H+ to diffuse into the mucosa which disrupts permeability and cell structure. Vicious cycle of: damaged mucosa → liberates histamine →increased acid and pepsinogen production, blood flow, capillary permeability → edema, bye bye plasma proteins → more bleeding and release of more histamine
Clinical Manifestations: similar to duodenal ulcers (upper abdo pain, intermittent, pain-antacid-relief pattern). Pain occurs immediately after eating. Tends to be chronic rather than remission-exacerbation. Causes more anorexia, vomiting, and weight loss than duodenal ulcers
Diagnosis and Treatment: similar to duodenal ulcers. Endoscopy for visualization. Antacids, H2 receptor antagonists, PPIs. Antibiotics for H. pylori. Surgery for bleeding or perforations.
Pathophysiology of obesity
- Involves interaction of peripheral and central pathways and numerous cytokines, hormones, and neurotransmitters
- Peripheral: fat cells store triglycerides and increase in size and number. Adipocytes secrete hormones and adipocytokines.
- Central/visceral white fat accumulation causes dysfunction in the regulation and interaction of these cytokines and hormones
- Peripheral sources of mediators act on hypothalamus & brainstem to regulate hunger/satiety, which include insulin from the beta cells of the pancreas; ghrelin from the stomach; peptide YY from the intestines; glucagon- like peptide-1 from intestinal endocrine cells; and the adipokines leptin, adiponectin, and resistin
- Obesity associated with increased levels of leptin, insulin, resistin, and ghrelin; decreased adiponectin and peptide YY
- Enlarged adipocytes increased lipolysis and secrete proinflammatory adipokines from T lymphocytes and activated macrophages - results in low-grade systemic inflammation
- Inflammation and accelerated lipolysis contribute to insulin resistance and metabolic syndrome
Ascites
Definition, Cause, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: fluid accumulation in peritoneal cavity. Fluid is trapped and cannot escape, so there’s less actual fluid available for normal physiological function.
Cause: _Most common cause - c_irrhosis. Others: HF, constructive pericarditis, abdominal malignancies, nephrotic syndrome, malnutrition. If it’s cirrhosis-related, 25% die within 1 year
Pathophysiology: several contributing factors - portal hypertension, decreased synthesis of albumin by the liver, splanchnic arterial vasodilation, & renal sodium and water retention.
- Portal hypertension & reduced albumin: causes capillary hydrostatic pressure to exceed capillary osmotic pressure which pushes water into the peritoneal cavity. Portal HTN also increased production of hepatic lymph which “weep” into peritoneal cavity.
- Splanchnic arterial vasodilation: due to increased NO produced by disease liver. Can decrease effective circulating blood colume which activates aldosterone and ADH and promote renal sodium and water retention and further portal HTN.
- Bacterial translocation and endotoxin release can cause peritonitis and increased capillary permeability and fluid shift into peritoneal cavity
Clinical Manifestations: abdominal distention, increased abdominal girth and weight gain. Fluid displaces the diaphragm and causes dyspnea by decreasing lung capacity. RR increases and person takes Semi-Fowler position to relieve it. Some peripheral edema. 10% of cases develop bacterial peritonitis (fever, chills, abdo pain, decreased bowel sounds, cloudy ascitic fluid).
Diagnosis/Treatment: clinical presentation and identification of liver disease. Dietary salt restriction and use of potassium-sparing diuretics. Albumin administration. Paracentesis to aspirate fluid for culture. Goal of treatment to relieve discomfort & try to restore liver function. Removal of too much fluid via paracentesis relieves pressure on blood vessels and potential risk of hypotension, shock, death. If pt has ascites x portal HTN, best tx is liver transplant
Jaundice
Definition, Causes, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: aka icterus. Yellow/greenish colour of skin caused by hyperbilirubinemia
Causes: 1) extrahepatic (posthepatic) obstruction to bile flow; 2) intrahepatic obstruction (ex. bil canaliculi); 3) prehepatic obstruction of unconjugated bilirubin (excessive hemolysis of RBCs)
Pathophysiology:
Obstructive (posthepatic) Jaundice: due to extra-/intra-hepatic osbtruction. Extrahepatic develops if common bile duct occludes (gallstone, tumor, inflammation). Bilirubin conjugated by hepatocytes cannot flow through obstructed common bile duct into duodenum so it accumulates in the liver and enters bloodstream causing hyperbilirubinemia
Hemolytic (prehepatic) Jaundice: due to excess destruction of RBCs. Increased unconjugated bilirubin formed through metabolism of heme component of destroyed RBCs. Too much to handle by the liver causing bilirubin levels to rise in the blood.
Clinical Manifestations: darkened urine several days before onset of jaundice. Light coloured stools if complete obstruction of bile flow from liver to duodenum. Normal stool colour and bilirubin present in urine for partial obstructions. Fever, chills, pain with jaundice is likely viral or bacterial inflammation. Jaundice may start in sclera of eye and then progress to skin as bilirubin attaches to elastic fibers. Itching often accompanies jaundice due to bilirubin accumulating in the skin.
Diagnosis: bloodwork to look at elevated levels of bilirubin. Hx, physical exam to identiffy underlying disorders.
Treatment: correct underlying cause
Alcohol Liver Disease
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: Coexisting liver disease x alcohol toxic effects. Includes alcoholic fatty liver, alcoholic steatohepatitis, and alcohol cirrhosis
Pathophysiology:
- Alcholic fatty liver (steatosis): mildest form of alcohol liver disease. Can be casued by small amounts of alcohol and be asymptomatic. Reversible with stopping drinking. Fat deposits in liver is mainly due to increased lipogenesis, cholesterol synthesis, decreased fatty acid oxidation by hepatocytes
- Alcohol Steatohepatitis (alcoholic hepatitis): precursor of cirrhosis. Increased hepatic fat storage, inflammation, and degeneration and necrosis of hepatocytes with infiltration of neutrophils and lymphocytes. Fibrosis is characteristic of cirrhosis.
- Alcohol cirrhosis: caused by toxic effects of alcohol metabolism on liver, inflammatory cytokines, oxidative stress, and malnutrition. Alcohol is transformed to acetaldehyde and ++amounts alter hepatocyte function and activate stellate cells that are involved in fibrosis. Alcoholic cirrhosis impair the hepatocytes ability to oxidize fatty acids, synthesize enzymes and proteins, degrade hormones and clear portal blood of ammonia and toxins. The inflammatory response includes excessive collagen formation, fibrosis and scarring, which obstruct bile canaliculi and sinusoids. Bile obstruction causes jaundice. Vascular obstruction causes portal hypertension, shunting and varices.
Clinical Manifestations: Anorexia, nausea, jaundice, and edema develop with advanced fatty infiltration or the onset of alcoholic steatohepatitis. S/S of alcoholic steatopatitis can be mild or severe. Non-specific sx: fatigue, weight loss, anoreaxia. Manifestations of acute illness: nausea, anorexia, fever, abdo pain, jaundice. Cirrhosis is a multi-system disease (enlarged spleen, liver, ascites, portal HTN, GI bleeding, hepatic encephalopathy, esophageal varices).
Diagnosis: enlarged liver and hx of continuous alcohol intake within previous weeks/months. Hx and presentation. Serology - elevates serum enzymes and bilirubin, decreased albumin, prolonged prothrombin time. Liver biopsy
Treatment: No specific tx for alcoholic steatohepatitis or cirrhosis - Rest, vitamin supplements, nutritious diet, corticosteroids, antioxidants, drugs that slow fibrosis, and managing complications will slow disease progression. Cessation of alcohol. Liver transplant.
Acute Pancreatitis
Definition, PAthophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: mild form and resolves spontaneously but 20% of ppl will develop severe acute form requiring hospitaliztion. Develops due to obstruction to the outflow of pancreatic digestive enzymes caused by bile and pancreatic duct obstruction (eg. gallstones). Other causes - cell injury from EtOH, durgs, viral infection.
Pathophysiology: Pancreatic secretion and activation + release of enzymes is backed up within the acinar cells BUT because the enzymes are activated it causes autodigestion of pancreatic cells and tissues which leads to inflammation. Autodigestion also causes vascular damage, coagulation necrosis and fat necrosis. Pseudocysts occur (wall-off clumps of pancreatic secretions). Edema within the pancreatic capsule occurs which leads to ischemia and more necrosis.
With EtOH abuse, acinar cells metabolize ethanol and create toxic metabolis that accumulation and injure the acinar cells causing release od activated enzymes. Chronic alcohol use may also cause formation of protein plugs in the pancreatic ducts ans sphincter of ODdi spasm leading to obstruction (and more release of enzymes, autodigestion, inflammation, pancreatitis).
Systemic effects: proinflammatory cytokines released into bloodstream, injruy to vessel walls, coagulation shit with vasodilation, hypotension, shock. ARDS, HF, renal failure, intra-abdominal HTN, SIRS. Paralytic ileus and GI bleeding. Bacteria can also translocate and cause sepsis. Recurrent inflammation leads to fibrosis, stricutres and further duct obstruction that turns into chronic pancreatitis.
Clinical Manifestations: Cardinal signs - epigastric/midabdominal constant pain (mild to severe; may radiate to the back). Pain caused by edema (causing distension), chemical irritaiton and inflammation of peritoneum, irritation/obstruction of biliary tract, and inflammatoin of nerves.
- Fever, leukocytosis, N/V (from paralytic ileus), jaundice (from duct obstruction)
- Abdominal distention with decreased bowel motility & fluid accumulation in peritoneal cavity
- hypovolemia, hypotension, tachycardia, myocardial insufficiency, shock due to lost plasma volume with inflammatory mediators vasodilating
- Tachypnea and hypoxemia develop secondary to ascites, pulmonary edema, atelectasis, or pleural effusions
- Shock; multiple organ failure & SIRS accounr for most deaths with this
Diagnosis: Clinical presentation, lab studies, imaging, identifying associated disorders. Elevated lipase levels in serum is primary diagnostic marker
Treatment: stop process of autodigestion and prevent systemic complication - Narcotics for pain, oral foods and fluids withheld initially and gastric suction to provide relief to pancreas. Feeding after 24-48 h. Parenteral fluids to restore blodo volume and prevent hypotension and shock.
Colorectal Cancer (CRC)
Definition, Risk factors, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: THIRD MOST common cause of cancer and cancer death. Tends to occur in those 50+, rare in children.
Risk Factors: advanced age, high fat (esp. egg consumption), red and processed meats, low fiber. Alcohol, smoking, obesity, family hx, low exercise, IBD, T2DM
Pathophysiology: most are sporadic (acquired) or associated with family hx. Caused by gene alterations and environment. Both below are family-linked autosome dominal inheritance traits.
- Familial adenomatous polyposis (FAP) - mutation of APC gene & most common hereditary cause of colorectal cancer
- Hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome, is associated with several DNA mismatch repair
Sporadic ones are due to loss of function or mutation of tumor-suppressing genes. CRC begins with formation of adenoma (“tumor initiation”) and then progresses to carcinoma (“tumor progression”) over the course of 8-10 years.
Colorectal polyps closely associated with cancer development (Polyp - projection from mucosal epithelium). Most polyps are benign but neoplastic ones are premalignant. The larger the polyp, the greater risk for colorectal cancer. These tumors have a long preinvasive phase and when they invade, they tend to grow slowly. Lesions start in epithelial stem cells at the base of the intestinal crypts, creep into the layesr and then to the bloodstream and lymphatics where they metastasize.
Clinical Manifestations: Sx depends on location, size, shape of lesion and are silent in early stages. Liver metastasis is common.
- Tumors on ascending (proximal) colon are polypoid and extend along one wlal of cecum and ascending colon. Silent tumors that turn into painful, palpable masses in RLQ, anemia, fatigue, dark red blood in stool. These can become larger and bulky with necrosis and ulceration leading to continusous beleding and anemia. More common in women
- Tumors on descending (distal) colon are small elevated masses that grow circumferentially (encircles entire bowel wall) and eventually ulcerates in the middle, which penetrates blood supply. Obstruction is common but slow. Stools become more narrow and pencil shaped. Progressive abdomina distention, pain, vomiting, constipation, need for laxatives, cramps, bright red blood on stool surface. More common in men
Diagnosis: those with hereditary polyps should begin screening at early age and removal of polayps if found.
Treatment: Vitamind D, calcium, fiber, folate, diet modifications, weight control, exercise decreases risk of colorectal cancer. Tx for all stages is surgery.
Cleft lift (CL) & Cleft Palate (CP)
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: congenital orofacial anaomalies affecting the mouth. Can be unilaterla or bilateral, partial or complete.
- Syndromic CLP: when CL and CP occurs with other chromosomal, mendelian or teratogenic (substances that cause malformations) syndromes
- Nonsyndromic/isolated CLP: CL or CP that occurs in isolation; more common in females
- CL +/- CP is more common in males
- Prevention: Vit B, folate, folic acid and reduced tobacco and alcohol
Pathophysiology: embryonic developmental anomalies that vary in severity. Epigenetic influences: maternal smoking, alcohol, steroid or statin use, folate or vit B deficiency, disordered metabolism. Causes reduced amount of neural crest mesenchyme (tissue) that migrate into the area that develops into the face eventually.
Cleft lip: caused by incomplete fusion of the nasomedial or intermaxillary process starting at 4th week of embryonic development (rapid development period). Cleft causes structures of the face and mouth to develop without normal restraints of encircling lip muscles. May also affect nose, nasla cartilages, nasal septum, and alveolar processes. Cleft usually just beneath the center of one nostril. Defect may be bilateral, symmetrical or asymmetrical. The greater the cleft lip, the more the teeth will be missing/malformed.
Cleft palate: May affect only the uvula and soft palate or may extend forward to the nostril and involve the hard palate and the maxillary alveolar ridge. Unilateral or bilateral with cleft occupying midline posteriorly and as far forward as alveolar process where it deviates to the involved side. If facial bones are involved then nasal cavity may freely communicate with oral cavity. Teeth in that area may be missing/deformed. Increased risk for middle ear infections.
Clinical Manifestations: easily recognized on facial structure. Feeding difficulty is the most significant clinical manifestation due to oronasal communication and inability to generate -ve pressure needed for normal sucking. Potential swallowing difficulties.
Diagnosis: Prenatal ultrasound, postnatal imaging.
Treatment: Surgery. Feeding specialist if CP and specialized equipment. Education for family and referral to more specific services (SLP, plastic surgeon, etc.).
Esophageal Atresia (EA)
Definition, Risk Factors, Pathophysiology, Clinical Manifestations, Dx, Treatment
Definition: most common congenital atresia (closed passage) of esophagus where the esophagus ends in a blind pouch. Usually accompanied by a fistula between esophagus and trachea (tracheoesophageal fistula [EA/TEF])
Risk Factors: Maternal exposure to methimazole, exogenous sex hormones, infectious diseases, alcohol, smoking; materal diabetes, advanced maternal age, maternal employment in agriculture.
Pathophysiology: unknown. Defective growth of endodermal cells and impaired enbryonic development of trachea and esophagus.
Clinical Manifestations: Diagnosed by noting increased amount of amniotic fluid (polyhydramnios). Fetus normally swallows amniotic fluid in utero and it is absorbed into the placental circulation. If the fetus can’t swallow, amniotic fluid accumulates in the uterus. EA will be diagnosed at birth on the basis of drooling, inability to swallow secretions or choking with feeding, and respiratory distress. Confirmed by trying to put a gastric tube into the stomach and can’t. If fistula connects trachea with distal esophagus, abdomen fills with air and become distended possibly interferes with breathing. Intermittent cyanosis may occur.
Pulmonary complications occur due to reflux of air and gastric secretions into the tracheobronchial tree via fistula. Severe chemical irritation. Those without fistula will have scaphoid (boat-shaped) gas-less abdomens. Those with fistula but no atresia will have recurrent aspiration, pneumonia, atelectasis.
Diagnosis: as above^. Evaluated with ultrasound, echocardiogram and x-rays.
Treatment: continuous suction to decrease risk of aspiration. Slight elevation of head of bed to assist draining of upper pouch. No PO feeding. Surgical repair. 95% survival rate.
Hirschsprung Disease
Definition, Pathophysiology, Clinical Manifestations, Diagnosis, Treatment
Definition: aka aganglionic megacolon - functional obstruction of the colon. The most common cause of colon obstruction _(_1/3 of all GI obstructions in infants). Mostly in males.
Pathophysiology: characterized by absence of parasympathetic intrinsic ganglion cells in the submucosal & myenteric plexuses & absence of peristaltic movement in bowels. Mostly only affects rectal end of sigmoid colon (80%), rare but can affect entire colon. This abnormal innervation impairs fecal movements which causes proximal colon to become distended (megacolon)
Clinical Manifestations: typically asymptomatic during first 24-72 hr after birth with delayed passage of meconium. Mild-severe constipation with poor feeding, poor weight gain, and progressive abdominal distention. First sign may be diarrhea because only water can travel around impacted feces.
- Most serious complication: enterocolitis - related to fecal impaction. Bowel dilation stretches and partly occludes vessels which lead to edema, ischemia, infarction, and ++outflow of fluid into the bowel lumen. Copious liquid stools result
- Infarction and destruction of mucosa allow enteric microorganisms to penetrate bowel wall leading to gram-ve sepsis with fever and vomiting
- Can cause severe fluid and electrolyte changes that lead to hypovolemia, septic shock or death
Diagnosis: radiocontrast enema. Definitive dx is a rectal biopsy that shows absence of ganglion cells in submucosa of colon
Treatment: Surgery for all cases. May need bowel retraining and have some LT constipation/fecal incontinence
Anorectal Malformations (ARMs)
Definition, Diagnosis, Treatment
Definition: a spectrum of anomalies of the anus and rectum. Include: anorectal stenosis, imperforate anus, anorectal atresia, and rectal atresia
- Persistent cloaca is the most severe type of anorectal malformation, occurs exclusively in girls (a defect in which the rectum, vagina and urinary tract are connected into a single common channel)
- ~40% of infants with ARMs have other developmental anomalies ‘
Diagnosis: most are identified in routine physical exam during neonatal period.
Treatment: depends on type of malformation & child’s health status. Dilations (for anals stenosis) and surgical corrections (for the other malformations)
Intussusception
Definition: telescoping of proximal segment of the intestine into a distal segment causing an obstruction. The most common cause of small bowel obstruction in children.
Demographics: most cases occur between 5 and 7 mos. More common in males. Can occur in children with polyps, tumors, CF, Meckel diverticulum, intestinal adhesions, or immediately post-op abdo surgery.
Pathophysiology: The most common scenario is the ileum telescopes into the cecum and part of the ascending colon by collapsing through the ileocecal valve. Also drags is mesentery into the enveloping lumen. Initially, mesentery is constricted which obstructs venous return. Within hours it turns to venous stais, engorgement, edema, exudation, and further vascular compression. The tension of the mesentary on the proximal part that’s telescoped in to arch the bowel in a curve. Edem and compression obstruct blood flow of chyme through intestine. If untreated, ischemia and necrosis occur.
Clinical Manifestations: Classic signs are colicky abdo pain, irritability, fetal position, abdominal mass, vomiting, bloody (currant jelly) stools
Diagnosis: clinical manifestations, onset of symptoms, and imaging studies.
Treatment: Enema reduction to avoid progression to ischemia and perforation (large bowel intussusception). Laparotomy for small bowel intussusception. Untreated is nearly always fatal. Most will recover if treated within 24 hours.
Celiac Disease (CD)
Definition: autoimmune disease that damages small intestinal villous epithelium when there is ingestion of gluten (protein component in cereal grains - wheat, rye, barley, malt)
- common multiorgan disease with strong genetic predisposition associated with human leukocyte antigen (HLA) DQ2 and DQ8.
Factors: CD presents more frequently in children with T1DM, autoimmune thyroid/liver disease, Downs, Turner syndrome, Williams syndrome, selective IgA deficiency, Addision disease, and 1st-degree relatives with CD.
Pathophysiology: genetics and immunological factors. Environmental factors: early infections, gut microbiota in infants, feeding patterns, timing and amount of gluten. Major characteristics is T-cell mediated autoimmune injury to small intestinal epithelial cells. Villi atrophy and flatten, crypt hyperplasia in upper small intestine, malabsorption of most nutrients when there is gluten.
Mucosa of duodenum and jejunum also get damaged which exacerbates malabsorption. Intestinal hormone secretion is diminished and thus pancreatic enzymes. Inflammation from the damage occurs, and water & electrolytes are secreted leading to watery diarrhea. K+ loss leads to muscle weakness. Magnesium and calcium malabsorption cause seizures and tentany. Fat malabsorption causes fatty stools. Vitamin deficiencies.
Clinical Manifestations: onset depends on age of infant when gluten was added to diet. 50% has onset that usually occurs by 18 months. Diarrhea, abdo pain and distension, vomiting, anorexia, constipation. Others: fatigue, weight loss, growth failure, delayed puberty.
- Celiac crisis: unusual complication in infants characterized by severe diarrhea, dehydration, hypoproteinemia due to malabsorption and protein loss.
Diagnosis: Serology autoantibody measurements again IgA. Screening for HLA
Treatment: lifelong adherence to gluten-free diet. Lactose intolerance may also be present due to villi damage so no milk either. Vit D, iron, and folic acid supplements to treat deficiences.
