N715 Exam 2 Review PDF

# N715 Exam 2 Review ## Genetics Week 5 Objectives: 1. **Describe the difference and relationship between Genetics, Genomics, and Epigenetics - Princess** | Genetics | Genomics...

# N715 Exam 2 Review ## Genetics Week 5 Objectives: 1. **Describe the difference and relationship between Genetics, Genomics, and Epigenetics - Princess** | Genetics | Genomics | Epigenetics | | :---------------------------------------- | :-------------------------------------------------------------------------------------------------------------------- | :------------------------------------------------------------------------------------------------------------------------------------------------------ | | The study of heredity and variations in hereditary characteristics | The study of the human genome (map) with application of technologies to determine the role specific sets of genes play in determining various human Genome mutations (MEIOSIS) ---Change in the number of chromosomes per cell characteristics | The connection between genotype and phenotype. The study of how environmental, developmental, and other factors relate to expression of the genetic code in the human organism | 2. **Synthesize the role that genetics, genomics, and epigenetics can play in providing holistic patient management - Kristen C** 3. **Differentiate between germline and somatic mutations - Carmelle** | Germline | Somatic | | :------------- | :------------- | | | | 4. **Understand the difference between genome (whole chromosome), chromosomal (section of the chromosome) and gene (individual trait) mutations - Catherine** 5. **Discuss the implications of X-linked genetic conditions - Kristin** ## Topics: ## Pulmonary Week 6 Objectives: 1. **Apply the concepts of ventilation and respiration when learning about specific pathological pulmonary conditions - Sabrina** 2. **Examine risk factors for select pathological conditions and the impact of access to ongoing primary care - Melanie** ### Risk Factors #### Asthma - Exposure to allergens: Pet dander, mold, dust - Outdoor air pollution - Viral respiratory infections during infanthood - Cigarette smoking - Obesity - Exercise induced ### Impact of primary care: - **Early Detection and Diagnosis:** Primary care providers can recognize early signs and symptoms, enabling timely diagnosis and reducing the likelihood of complications. - **Asthma Action Plans:** Access to care ensures patients receive personalized action plans that help manage symptoms, prevent exacerbations, and outline steps for emergencies. - **Regular Monitoring:** Asthma is a chronic, fluctuating condition. Primary care enables regular check-ups to monitor symptoms, adjust medications (inhalers, corticosteroids), and evaluate triggers. - **Education on Trigger Avoidance:** Ongoing care provides education about environmental and allergen triggers, empowering patients to modify their environment and prevent attacks. - **Preventing Hospitalization:** Without regular care, asthma attacks may become severe, requiring emergency care. Ongoing care helps reduce the frequency and intensity of exacerbations. #### COPD - Tobacco smoke (childhood/fetal exposure) - Vaping (including adolescent population at higher risk for serious lung disease) - Occupational exposure: dust/chemicals - Biomass fuel in poorly dwellings (cooking/heating) - Infection - Low socioeconomic status - Genetic abnormalities (alpha1-antitrypsin deficiency) ### Impact of primary care: - **Early Intervention:** Primary care allows for early screening, particularly in high-risk populations like smokers, enabling earlier diagnosis and slowing disease progression. - **Medication Management:** Continuous care ensures access to bronchodilators, inhaled corticosteroids, and other medications essential for managing symptoms and preventing exacerbations. - **Pulmonary Rehabilitation and Lifestyle Support:** Primary care helps coordinate smoking cessation programs, exercise regimens, and dietary changes that are critical for COPD patients. - **Exacerbation Prevention:** Ongoing care allows for regular monitoring, vaccination (e.g., influenza, pneumococcal), and prompt intervention during respiratory infections, which can prevent life-threatening exacerbations. - **Comorbidity Management:** Many COPD patients have other health conditions, like heart disease or diabetes. Regular care helps address these comorbidities, reducing overall health risks. #### DVT/PE - Age > 40 years old - Female - Obesity - Major surgery/ hospitalization - Immobilization, sedentary lifestyle, sitting for long periods/sedentary occupation - Standing for long periods - Family history - DVT or previous hx VTE - Certain medication such as birth control/ hormone replacement ### Impact of Primary Care: - **Risk Factor Management:** Regular visits allow primary care providers to assess risk factors (immobility, obesity, history of blood clots) and implement preventive strategies (e.g., anticoagulant therapy, lifestyle changes). - **Early Detection of DVT:** Early identification of symptoms (leg pain, swelling) can prevent progression to more dangerous conditions like pulmonary embolism (PE). - **Anticoagulant Monitoring:** For patients on blood thinners (e.g., warfarin, rivaroxaban), ongoing primary care ensures proper monitoring of blood clotting factors and adjusts medication dosages to prevent complications. - **Education on Warning Signs:** Primary care offers critical education about recognizing signs of DVT or PE (e.g., leg swelling, chest pain, shortness of breath) and when to seek emergency care. - **Post-Thrombosis Care:** After DVT/PE, primary care plays an important role in ongoing anticoagulation management, lifestyle modifications, and ensuring long-term prevention of recurrences. ## 3. **Assimilate the cellular pathophysiology associated with select pulmonary conditions with clinical manifestations found on history and physical assessment - Lauren H.** ## Topics: ### Asthma: - Type 1 Hypersensitivity. - Eosinophilic asthma - IgE mediated - Type 1 Alveoli: gas exchange - Type 2 Alveoli: Surfactant - Airway endothelial cells are exposed to an antigen triggering an immune response - Mast cell degranulation releases inflammatory mediators - Antigen detected by APC bound to MHC2 receptor - APC presents antigen to Th2 cells thru TLRs activating production of cytokines IL 4,5,13,33 - Histamine acts quickly - More inflammatory mediators released by mast cells like leukotrienes, prostaglandins, and PAFs - Mediators attract other immune cells and complements 2-24 hours after exposure - Late response: - 4-8 hours after early response ### COPD - Chronic inflammation due to long term exposure- irritants lead to persistent lung inflammation driven by inflammatory cells like neutrophils, macrophages, and lymphocytes - Airway remodeling- Airway structural changes secondary to inflammation and thickening of walls and increased mucous. Fibroblasts deposit collage and there is narrowing of the airway leading to obstruction - Destruction of lung tissue- Chronic inflammation activates proteases like elastases and matrix metalloproteinases which degrade lung tissue proteins. - Alpha 1 anti-trypin deficiency can cause emphysema. Alpha 1 anti-trypsin is a antiprotease that normally balance the proteases but unable to with this deficiency - Proteases break down elastinwhich causes destruction of the alveolar walls and loss of elasticity - Mucus hypersenction (bronchitis) inflammation stimulates mucus producing glands which contributes to obstruction - Small airway collapse - 4 cell responders- Epithelial cells, macrophages, neutrophils, fibroblasts - Blue bloaters are Chronic Bronchitis - Pink Puffers of Emphysema ## PE/DVT ### General Risk Factors - Age > 40 years - Female gender - Obesity - Major surgery or hospitalization - Immobilization or a sedentary lifestyle - Long-duration travel by car or airplane - Extended periods of standing - Family history of VTE - History of DVT or VTE - Serious illness or certain medications - Specific occupations ### Virchow's Triad - **Stasis of Blood Flow:** Immobilization, polycythemia, heart failure, varicose veins can lead to blood flow stasis and clot formation. - **Endothelial Injury:** Trauma, surgery, smoking, hypertension, IV drug use, and certain medical procedures can cause endothelial damage. - **Hypercoagulability:** Factors like cancer, chemotherapy, pregnancy, obesity, hormonal replacement therapy, genetic mutations (e.g., Factor V Leiden), and protein C and S deficiency contribute to a hypercoagulable state. ### Normal Venous Structure: - **Three Layers of Veins** - **Tunica Adventitia:** The outer layer providing structure and shape to the vein. - **Tunica Media:** The middle layer composed of smooth muscle cells allowing for stretching and contraction. - **Tunica Intima:** The inner layer with smooth endothelial cells facilitating smooth blood flow. - **Types of Veins** - **Deep Veins:** Responsible for carrying 90% of blood flow back to the heart. - **Superficial Veins:** Transport blood from surface tissues to deep veins. - **Perforating (Connecting) Veins:** Short veins connecting superficial veins to deep veins. - **Blood Flow Mechanism:** - Muscle movements, especially in the calf muscles, push blood through the veins. - Valves within the veins prevent backflow, ensuring unidirectional blood flow towards the heart. ### Abnormal Venous Structure - **Varicose Veins:** Develop due to incompetent valves resulting in leakage, retrograde flow, and pooling of blood in superficial veins. - Superficial veins are more prone to venous wall distension and tortuosity. - Manifest as bulging of the skin over affected veins with blood pooling behind valves. - **Contributing Factors:** - Inactivity, surgical damage, venous trauma, smoking, obesity, genetic predisposition, and previous blood clots can contribute to abnormal venous structures which increase VTE risk ### Pathophysiology - **Thrombus Formation** - **Initial Steps:** Venous valves are particularly susceptible to thrombus formation. - **Flow Disruption:** Immobility or heart failure leads to blood pooling; alterations lead to hypoxia and endothelial damage. - **Inflammatory Response:** Reactive oxygen species (ROS) buildup in endothelial cells triggers the release of transcription factors such as TF (Tissue Factor), IL-1, TNF, VEGF, and NO. - **Clotting Cascade:** Tissue factor activates the extrinsic clotting pathway. Neutrophils undergo NETosis, activating the intrinsic clotting pathway, and further leading to platelet activation and clot formation. ### Clinical Manifestations: - **Deep Vein Thrombosis (DVT):** - Symptoms include leg swelling, pain, tenderness, and erythema. - Post-thrombotic syndrome may occur as persistent symptoms in the lower extremities. - **Pulmonary Embolism (PE):** - Symptoms include dyspnea (difficulty breathing), tachycardia, tachypnea (rapid breathing), chest pain, anxiety, dizziness, hemoptysis (coughing up blood), and hypoxia (low oxygen levels). ### Summary: - Individuals developing a DVT are predisposed to chronic inflammation in the lower extremities, with a significant risk of progressing to a life-threatening PE. - Risk factors and circumstances influenced by Virchow's Triad (venous stasis, endothelial injury, and hypercoagulability) are pivotal in thrombus formation. - The pathophysiology of DVT and PE heavily involves both inflammatory and coagulative responses. - Awareness and early recognition of clinical signs and symptoms, including leg swelling, pain in DVT, and chest pain, shortness of breath in PE, are crucial for timely intervention. ## Tuberculosis: ### Pathophysiology: - TB is highly contagious and is transmitted from person to person in airborne droplets. In immunocompetent individuals, the M. tuberculosis is usually contained by the person's inflammatory and immune response systems. This results in latent TB infection (LTBI) and is associated with no clinical evidence of disease. - Results in a caseous necrosis- cavernous lesion on CXR ### MOA: - Once the bacilli are inspired, they lodge in the lung, usually in the upper lobe, and cause localized nonspecific inflammation to the lung tissue. - Some bacilli migrate through the lymphatics and become lodged in the lymph nodes, initiating an immune response. - Alveolar macrophages and neutrophils engulf and isolate the bacilli, preventing them from spreading. However, the bacterium can evade the person's defense mechanism within macrophages and resist lysosomal killing, forming a granulomatous lesion called a tubercle. - Infected tissues within the tubercle die, forming cheese-like material called caseation necrosis. - Collagenous scar tissue then grows around the tubercle, completing the isolation of bacilli. - The immune response is complete after about 10 days, preventing further multiplication of bacilli. - Once bacilli are isolated in tubercles, tuberculosis may remain latent (LTBI) for life. - If the immune system is impaired, reactivation with progressive disease can occur and may spread throughout the lung and through the blood and lymphatics to other organs, causing active pneumonia and extrapulmonary disease. - Cancer, immunosuppressive medications (e.g., corticosteroids), poor nutritional status, renal failure, and HIV can reactivate the disease. ## GI Week 7 Objectives: 1. **Describe how regional development, structure, and function of the GI system relates to the clinical manifestations of specific conditions - Angela** ### Layers of the GI tract: - **Mucosa:** Epithelium, fiable, turn over and replace rapidly and constant injury; those cells are replicating fast and have more chance for cancer - **Lymph nodes:** Circulating IgG - **Submucosa:** Inner walls of the GI tract. Ulcerations get through to submucosal-vascular layer and huge nerve supply - **Muscularis:** Layers of muscle outside of the submucos= striated-somatic, smooth muscle(peristalsis) - **Serosa (adventitia):** Outlayer attaches to peritoneum ### Mouth: - Gi tract begins in mouth with mastication and saliva for breakdown of starches - **Digestions-food breakdown** - Saliva consists mostly of water with varying amounts of mucus, sodium, bicarbonate, chloride, potassium, and salivary a-amylase (ptyalin), an enzyme that initiates carbohydrate digestion in the mouth and stomach. - pH 7.4 sustained by Bicarb - Saliva also contains Mucin(provides lubrication), IgA - **Sympathetic and Parasympathetic ANS** both control salivation - **Hormones DO NOT** regulate salivary gland secretion but are found in saliva- cortisol, testosterone, estradiol ### Esophagus/Swallowing: - **Esophagus:** Thin layer of mucosa, more vascular than other areas, varicies from portal htn, life-threatening bleeding - **Mediated by** trigeminal muscles, nucleus tractus solitarus, and reticular formation of the brainstem and other brain areas -insula/claustrum and cerebellum - **2 phases swallowing** - **oropharyngeal-Voluntary phase** - **Esophageal-involuntary phase** - **Esophagus:** Transitions from striated (voluntary) to Smooth muscle (involuntary) in the lower esophagus., pH is neutral (7) when we have GERD pushes acid back up into the esophagus causing damage and scarring and increases risk for cancers - **UES** reduces risk of damage in the upper esophagus, where the glottis is - **Allows food bolus** to enter the esophagus and prevents air from entering esophagus during respiration - **LES:** Relaxes to allow food bolus to enter the stomach. Really important with GERD, if not tight, then reflux- Cholengeric vagal input and GASTRINincrease sphincter tone - **Noradregneric and noncholingeric vagal impulses** relax LES along with progesterone, secretin, and glucagon. Food passes through the Cardiac Orifice to the GE juntion - **Primary persistatlis:** Immediately follows the oropharygeal phase - **Secondary peristalsis:** Sequential contraction and relation in the mid and lower esophagus propelling food bolus into the GE junction ### Abdomen/Stomach: - **Mesentary:** - Double fold of the peritoneum with several contiguous segments, internal organ which all abdominal digestive organs develop and maintain these organs in a systemic continuity. - Provides a conduit for lymphatics, blood vessels, and nerves and is continuous from the esophago-gastric to anorectal junctions - **Functions:** - Supports embryonic development of abdominal organs of digestions by providing molecular and cellular signals(organogenesis) - Maintains abdominal digestive organs in positions and continuity with all other body systems - Reduces friction and supports free movement, prevents twisting, and dislocation into pelvic region - Stores fat, regulates glycemic and lipid metabolism and provides organs with rapid access to metabolic substrates - **Peritoneum:** - Major source of systemic CRP when there is intestinal inflammation - Contains Superior and inferior mesenteric arteries and veins which provide circulation, lymph nodes and vessels. - Serous membrane surrounding the organs of the abdomen and pelvic cavities - Functions to lubricate and prevent friction during organ movement - **Omentum:** - Intraabdominal organ composed of large flat layer of adipose tissue in 2 parts, greater and lesser omentums. - Functions include fat storage, protection of underlying organs, immune regulation (contains immune cells called “milky spots”, wound healing, tissue regenerations via activation of stemcells and neurovascularization - **Stomach:** - 3 layers of Smooth muscle: - Outer-longitudinal- absent on anterior and posterior surfaces - Middle- circular- most prominent - Inner-olique- least complete - Mucus, bicarb, prostaglandins Protective stomach lining from damage from acids - Mucosa lines the interior of stomach which sits in folds called Ruggae - The stomach is impermeable to water - Can absorb Alcohol and Aspirin because they are fat soluable - Blood supply comes from Celiac artery - A series of small veins drain blood from the stomach toward the hepatic portal vein. - **Hepatic disorders** that increase pressure in the portal vein can cause gastric veins to dilate(VARICES) and bleed, ### Gastric Motility: - Swallowing causes fundus to relax (receptive relaxation) to receive food bolus - Relaxation is caused by 2 polypeptide hormones secreted by the GI mucosa= **Gastrin and Cholecystokinin** which protect the gastric mucosa during digestion and help maintain the integrity of the islet cells in the pancreas - Gastric motility increases with the initiation of peristaltic waves with a rate of 3 per min influenced by Gastrin, Motilin, and vagus nerve. - The rate of peristalsis is mediated by pacemaker cells that initiate a wave of depolarization which move from upper part of stomach down to pyloris - Motilin also impacts the brain-pancreas axis and influences insulin secretion during meals, Motilin helps with movement into duodenum with pulsations - Secretin and sympathetic activity are inhibitory and decrease gastric sectretions, activating pancreas to release pancreatic enzymes ### Gastric mixing of Chyme takes several hours. - Food is propelled into the antrum - Retropulsion mixes food with digestive juices ### Gastric emptying: - Movement of chyme into duodenum - Solids, fats, and non-isotonic solutions delay gastric emptying - Osmoreceptors in duodenum are sensitive to osmotic pressure - Rate of emptying is adjusted to duodenum's ability to neutralize the incoming acidity - Peristaltic activity in the stomach is also affected by blood sugar leves, hypoglycemia increase rate of emptying, and hyperglycemia decrease rate ### Gastric Secretion: - Specialized cells in the gastric mucosa secrete large volumes of acid, pepsinogen, mucus, enzymes, hormons, intrinsic factor and gastroferrin (prevents insoluble iron salt formation). - Acid converts inactive pepsinogen into Pepsin - Intrinsic factor facilitates absorption of B12 - Gastroferrin facilitates absorption of Iron in the small intestine ### Gastic Glands: - **Primary secretory units that contain:** - **Parietal cells:** secrete HCL, intrinsic factor and gastroferrin, gastric Hydrochloric acid dissolves food fibers, bactericide, and converts pepsinogen to pepsin, facilitates absorption of iron in duodenum - **Pepsin:** proteolytic enzyme -breaks down proteins and forms Polypeptides, once in duodenum, pepsin is deactivated by alkalinity - **Chief cells:** secrete pepsinogen during eating stimulated by ACh, gastrin, and secretin - **Pyloric gland in antrum** secretes Gastrin from G cells: - gastrin activates smooth muscle for movement into duodeum - **Enterochromaffin-like cells** secrete histamin - **D Cells** secrete somatostatin - **Empty into the common duct - Gastric pit** - **Gastric Lipase** is an acid lipase that doesn't require bile for activation, accounts for 30% of fat digesetion, less efficient than Alkaline Lipase - **Mucus:** Protected from acids and pepsin by tight junctions, the mucosal barrier, and gastric mucosal blood flow. Prostaglandins and Nitric Oxide protect the mucosal barrier by stimulating mucus and Bicarbonate - **A breakdown in the protective barrier** may occur d/t ischemia or H. Pylor, ASA, NSAIDS, Ethanol, or regurgitated bile causing breakdown and ulceration ### Three phases of gastric secretion: - **Cephalic:** sensory and anticipatory experiences, mediated by ACh via vagus nerves which stimulate parietal cells - **Gastric:** begins with arrival of food to stomach. Distention of stomach and presence of digested protein give a secretory effect - **Intestinal:** Movement of chyme to duodenum initiates this phase ## Small Intestines: - **2 layers:** - **Outer longitudinal layer** - **Inneer thicker circular layer** - **Three Segments:** Duodenum, Jejunum, Ileum - **Duodenum:** begins at pyloris - **Jejunum:** slightly larger than ileum - **Ileum** - **Ileocecal valve (sphincter):** controls flow of digested material from ileum into the cecum of large intestine and prevents reflux into small intestine. ### Absorption: - **Villi:** cover circular folds. A Villus is composed of absorptive columnar cells (enterocytes) and mucus secreting Goblet cells. - **Lamina propria:** connective tissue layer of mucous membrane lies beneath the epithelial cells of the villi and contains lymphocytes and plasma cells that produce Immuoglobulin - **Central Lacteal:** Lymphatic capillary within the Villus that absorb and transport fat molecules and eventually drain back to thoracic duct. - **Crypts of Lieberkuhn:** at base of villi extending into the submucosal layer. Undifferentiated cells arise from stem cells at base of the crypt and move toward the tip of the villus maturing and becoming columnar epithelial secretory cells(water, electrolytes, enzymes) and goblet cells(mucus) - **Microvilli:** mucosal surface created by microvilli called the brush border increases surface area for absorption - **Nutrients absorption in the Small intestines:** - Water and electrolytes - Carbohydrates - Proteins - Fats - Minerals - Vitamins ## Large intestines - Consists of Cecum, appendix, Colon, rectum, anal canal - **Cecum:** pouch that recieves chyme from ileum - **Vermiform appendix:** attached to cecum, role in gut immunity - **Colon:** Chyme enters from Cecum. - Ascending colon - Transverse colon - Descending colon - Sigmoid colon - **Two Sphincters:** - Ileocecal: ileum to cecum - Rectosigmoid: sigmoid colon to rectum - **Colon and Cecum** muscle layer has 3 longitudinal bands called **TENIAE COLI** - **Circular layers** of the colon separate the gathered areas into outpoucings called **HAUSTRA** - **The mucosal surface** of the colon has **RUGAE** (folds) - **Golblet cells** form the mucosa - **The Primary type** of colonic movement is **SEGMENTAL** - **Water is abodrped** in the colon by diffusion and active transport - **Aldasterone increases** colon membrane permeability to sodium - **Colon does not absorb** monoasccharides and amino acids (some short chain free fatty acids do get abdorbed) ## Gl tract Immunity: - **GALT:** gut associated lymphoid tissue- immune defese killing pathogentic microorganism and preventing reaction to foreign proteins (dietary antigens), modulates the systemic adaptive immune system by the mucosa secreting IgA and enzymes that provide defecse - **Paneth cells:** located near base of cysts of lieberkhun produce defensins, antimicrobial peptides, and lysosomes. - **Peyers Patches:** lymph nodules containing lymphocytes, plasma cells, and macrophages, most abundant in ileum and produce antimicrobial peptides and IgA. ## Gut to Brain: - **Neurotransmitter Production:** The gut produces several neurotransmitters, including serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid (GABA). It also influences brain-derived neurotrophic factor (BDNF), which is crucial for memory and implicated in Alzheimer's disease. - **Intestinal Barrier Protection:** Gut microbiota help maintain the integrity of the intestinal barrier, preventing "leaky gut," which can lead to systemic inflammation and cognitive impairment. - **Vagus Nerve Modulation:** The Vagus nerve is a critical communication highway that transmits sensory information from the gut to the brain, affecting mood and stress responses. ## Brain to Gut: - **Mucus and Biofilm Production:** Stress and emotional states can alter gut mucus production, impacting microbial habitats. - **Intestinal Lumen and Motility:** Stress can change gut motility, influencing the speed at which content moves through the gastrointestinal tract. - **Leaky Gut and Immune Function:** The integrity of the gut lining can be compromised by stress, leading to immune dysfunction and systemic inflammation. ## Development of Microbiome in Infancy: ### Key Points: - Neonatal Microbiome: The fetus is exposed to microbes in the meconium, placenta, amniotic fluid, and umbilical cord, suggesting that microbiome development begins in utero. - **Microbiota in Preterm and Full-Term Infants** - **Preterm Infants:** The microbiota of preterm infants often includes Enterobacter, Staphylococcus, and Enterococcus due to prolonged stays in Neonatal Intensive Care Units (NICU) and antibiotic use, increasing the risk of Necrotizing Enterocolitis (NEC). - **Breastfed vs. Formula-fed Infants:** - **Breastfed:** Higher presence of Lactobacillus, Staphylococcus, Bifidobacterium. - **Formula-fed:** Higher presence of Roseburia, Clostridium, and Anaerostipes, which can lead to increased inflammation and a more adult-type microbial colonization early on. ## Autism Spectrum Disorder and Gut Microbiome: - Over 50% of children with ASD suffer from gastrointestinal disorders like constipation and diarrhea. These children also exhibit: - Reduced Presence of Carbohydrate-Degrading Bacteria - Decreased Microbiome Diversity - Overgrowths of Clostridium and Candida - Elevated IgA in Stool: Indicating immune abnormalities - Impairments in Blood-Brain and Intestinal Barriers: Known as "leaky gut," contributing to systemic immune activation and neuroinflammation. ## The Best Diet for the Gut Microbiome - Emeran A Mayer, a renowned gastroenterologist and neuroscientist, outlines several steps to enhance gut health: 1. Optimized Diet: Incorporating high-fiber, low-sugar, fermented foods and probiotics. 2. Gut-Brain Connection Optimization: Through mindful eating and managing stress. 3. Understanding Food Cravings: Recognizing the influence of gut bacteria on dietary choices. 4. Supporting Beneficial Microbes: Facilitating the growth of good bacteria while inhibiting ## Embryologic Development of the Digestive System: ### Formation of the Primordial Gut: - Initial Development: Formation begins in the 4th week with the folding of the embryo and the formation of the gut tube. - The primordial gut is closed at the cranial end by the oropharyngeal membrane and at the caudal end by the cloacal membrane. - Most of the gut arises from the endoderm, while the epithelium at the cranial and caudal ends is derived from the ectoderm of the stomodeum and proctodeum. ### Foregut Development: - **Components and Blood Supply:** - The foregut develops into the esophagus, stomach, duodenum, liver, biliary apparatus, and pancreas. - The celiac artery supplies blood to these structures. - **Esophagus:** - Develops immediately caudal to the pharynx. - Initially short but elongates rapidly to reach final length by the 7th week. - Epithelium proliferates and obliterates the lumen, with recanalization by the end of the 8th week. - **Anomalies:** - **Esophageal Stenosis/Atresia:** Failure of recanalization, potentially associated with tracheoesophageal fistula. - **Congenital Hiatal Hernia:** Failure of esophagus elongation, pulling the stomach into the esophageal hiatus. - **Stomach:** - Formed by the dilation of the tubular foregut in the 4th week. - Rotates 90 degrees clockwise causing the left side to move ventrally and the right side dorsally. - **Anomalies:** - **Pyloric Stenosis:** Overproliferation of the smooth muscle of the pyloric sphincter, leading to projectile vomiting in infants. ### Midgut Development: - **Components:** - Small intestine (including the duodenum distal to the bile duct opening), cecum, appendix, ascending colon, and right half to two-thirds of the transverse colon. - Blood supply from the superior mesenteric artery. - **Development Processes:** - **Elongation and Herniation:** Midgut elongates forming a U-shaped loop that herniates into the umbilical cord at the 6th week, retracting by the 10th week. - **Rotation and Fixation:** Rotates 90 degrees counterclockwise during herniation and further 180 degrees upon retraction, with the mesentery of the ascending colon fusing to the parietal peritoneum. - **Anomalies:** - **Omphalacele:** Persistent herniation into the umbilical cord due to defective growth of mesenchyme. - **Gastroschisis:** Incomplete closure of the lateral folds causing visceral protrusion into the amniotic cavity, often detected via elevated alpha-fetoprotein or ultrasound. - **Umbilical Hernia:** Incomplete closure of the umbilical ring, typically resolving by age 3. - **Rotational Defects:** Include nonrotation, mixed rotation, and reversed rotation of the midgut. ### Clinical Conditions Related to Gut Development: - **Necrotizing Enterocolitis (NEC)** - **Pathogenesis:** - Mucosal injury leading to bacterial proliferation, intramural gas, transmural necrosis, and possible perforation. - Etiology: Multifactorial, including hypoxic insult, enteral feedings, sepsis, and inflammatory mediators. - **Risk Factors:** Premature birth, congenital heart disease, gastrointestinal anomalies. - **Signs & Symptoms:** - **Enteric:** Bloody stools, abdominal distension and tenderness, emesis, ileus, erythema, and ascites. - **Systemic:** Respiratory distress, apnea, bradycardia, lethargy, temperature instability, and hypotension. - **Gluten-Sensitive Enteropathy (Celiac Disease)** - **Description:** - T-cell mediated autoimmune disease affecting the small intestinal villous epithelium upon gluten ingestion. - **Associated Disorders:** Type 1 diabetes mellitus, autoimmune thyroiditis, and Addison's disease. - **Result:** Mucosal destruction leading to malabsorption due to villi flattening. - **Hormones and Neurotransmitters of the Digestive system:** - Gastrin, Histamine, Somatostatin, Acetylcholine, Gastrin-releasing peptide, Ghrelin, Motilin, Secretin, Serotonin, Cholecystokinin, enteroglucagon, Gastric inhibitory peptide, Peptide, YY, Pancreatic polypeptide, Vasoactive intestinal peptide | Source | Hormone/Neurotransmitter | Stimulus for Secretion | Action | | :-------------------- | :------------------------ | :------------------------------------------------------------------------ | :---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Mucosa of the stomach | Gastrin | Presence of partially digested proteins in the stomach | Stimulates gastric glands to secrete hydrochloric acid, pepsinogen, and histamine; growth of gastric mucosa | | | Histamine | Acid in stomach | Stimulates acid secretion | | | Somatostatin | Vagus and local nerves in stomach | Inhibits acid, pepsinogen, and histamine secretion and release of gastrin | | | Acetylcholine | Vagus and local nerves in stomach | Stimulates release of pepsinogen and acid secretion | | | Gastrin-releasing peptide | Vagus and local nerves in stomach | Stimulates gastrin and release of pepsinogen and acid secretion | | | Ghrelin | High during fasting | Stimulates growth hormone secretion and hypothalamus to increase appetite | | Mucosa of the small | Motilin | Presence of acid and fat in the duodenum | Increases gastrointestinal motility | | intestine | Secretin | Presence of chyme (acid, partially digested proteins, fats) in duodenum | Stimulates pancreas to secrete alkaline pancreatic juice and liver to secrete bile; decreases gastrointestinal motility; inhibits gastrin and gastric acid secretion | | | Serotonin (5- | Intestinal distention; vagal stimulation; presence of acids, amino acids, or hypertonic fluids; released from enterochromaffin cells throughout intestine | Stimulates intestinal secretion, motility and sensation (i.e., pain and nausea), vasodilation; activates gut immune responses | | | hydroxytryptamine) | | | | | Cholecystokinin | Presence of chyme (acid, partially digested proteins, fats) in duodenum | Stimulates gallbladder to eject bile and pancreas to secrete alkaline fluid; decreases gastric motility; constricts pyloric sphincter; inhibits gastrin | | | Enteroglucagon | Intraluminal fats and carbohydrates | Weakly inhibits gastric and pancreatic secretion and enhances insulin release, lipolysis, ketogenesis, and glycogenolysis | | | Gastric inhibitory peptide | Fat and glucose in the small intestine | Inhibits gastric secretion and emptying; stimulates insulin release | | | Peptide YY | Intraluminal fat and bile acids | Inhibits postprandial gastric acid and pancreatic secretion and delays gastric and small bowel emptying | | | Pancreatic polypeptide | Protein, fat, and glucose in the small intestine | Decreases pancreatic bicarbonate and enzyme secretion | | | Vasoactive intestinal | Intestinal mucosa and muscle | Relaxes intestinal smooth muscle | | | peptide | | | 2. **Examine the role of Inflammation, Infection, and Cellular Injury in the clinical manifestation of gastrointestinal disorders -- Carmelle** 3. **Explore the relationship between genetic variants, human development, and select GI conditions - Melanie** 4. **Assimilate the relationship between hepatic fibrosis and systemic complications of liver disease - Lauren B.** ## Topics: ## Intussusception: - **Description:** - Telescoping of the intestine, commonly at the ileocolic valve, leading to venous stasis, edema, necrosis, and perforation. - Symptoms: Sudden severe intermittent abdominal pain, vomiting, "currant jelly" stool, and possibly a "sausage-shaped" abdominal mass. - Recurrence: Occurs in approximately 10-13% of cases - **Pathophysiology** - **Mechanism:** Generally involves the small bowel ileum entering the cecum and colon, ascending to transvers - Peristalsis, the rhythmic movement of the intestine, pulls the proximal segment into the distal segment - Reduced blood supply to the trapped segment can lead to ischemia - "Red currant jelly" stool, which occurs due to mucosal sloughing off in response to ischemia, is a hallmark but occurs in a minority of cases - **Key Points:** - Peristalsis: Contraction and relaxation of intestinal muscles facilitating movement - Ischemia: Reduced blood flow to tissues causing tissue damage - Mucosal Slough