Exam 5 Study Guide PDF

**Exam 5 Worksheet** With each disorder focus on understanding the pathophysiology, clinical manifestations, differentiating between disorders with similar presentations, and complications of these conditions. If fluid is involved in the patho- how and why is it shifting into locations it should be...

**Exam 5 Worksheet** With each disorder focus on understanding the pathophysiology, clinical manifestations, differentiating between disorders with similar presentations, and complications of these conditions. If fluid is involved in the patho- how and why is it shifting into locations it should be. **Gastrointestinal (GI) Topics** - Patho: Sudden, tight, twisting of the bowel impedes blood flow to the bowel - Risk Factors: Anomaly of rotation ingested foreign body or adhesion but cause cannot always be identified. - **S/S:** - Manifestations: Impeded blood flow leads to gangrene, necrosis and perforation which is life- threatening. - **Dx:** - Patho: Partial or complete blockage of small or large bowel. Mechanical d/t adhesions, hernia, impacted feces, volvulus, intussusception. Functional d/t conditions that inhibit peristalsis. Ogilvie syndromes is characterized by recurrent bouts of ileus (rare). - Risk factors: previous abdominal surgery with adhesions, congenital bowel abnormalities, metastatic carcinoma, particularly cancer of the intestinal tract or female reproductive organs, fluid gas water and electrolytes accumulates in the bowel. - s/s: depends on site and duration. Mechanical- increased bowel sounds initially, accompanied by abdominal pain, nausea, and vomiting. Functional- absence of bowel sounds. Upper jejunal area- vomiting, dehydration and electrolyte depletion. Distal portion of the small bowel or ileum- constipation may be an early manifestation. - Manifestations: may cause perforation or ischemia and necrosis leading to bowel gangrene, sepsis, peritonitis and shock - Dx: CT, Xray, Endoscopy - Patho: Familial or congenital disorder of the large intestine where the [autonomic ganglia are reduced or absent.] - Risk factors: infants, children, males - s/s: failure to pass meconium in the immediate postnatal, - Manifestations: functional obstructions of the colon due to failure of the ganglion cells to migrate to the wall of the colon resulting from a mutation in the receptor tyrosine kinase. Hypovolemic shock, intestinal perforation, megacolon d/t stool stasis, fecal stagnation causing bacterial overgrowth resulting in enterocolitis (see below) - Dx: s/s with CT/MRI - Patho: Telescoping/invagination of a portion of bowel into adjacent (usually distal) bowel causing intestinal obstruction - Risk Factors: Infants and males more than females - S/S: nausea, bilious vomiting, pulling legs to chest, abdominal pain - Manifestations: gangrene shock and perforation if sx treatment is delayed - Dx: US, Xray, CT - Patho: Defect in the diaphragm that allows a portion of the stomach to pas through the diaphragmatic opening in the thorax. 2 types being sliding (3-10x more common in women, both a portion of the stomach and the gastroesophageal junction is above the diaphragmatic opening). Paraesophageal (greater part of the curvature of the stomach rolls through the diaphragmatic opening). - Risk factors: Women, - s/s: N/V, heartburn, reflux, pain, dysphagia - Manifestations: GERD development predisposition. Cameron ulcers are a mechanical phenomenon related to the extrinsic compression of the diaphragm on the stomach in patients with large hiatal hernias. If the portion above the opening is incarcerated, it becomes life threatening. - Dx: xray, sometimes incidentally found. - Inflammatory bowel disease is a chronic condition resulting from complex interactions between intestinal microbiota and host immunity in genetically predisposed individuals that leads to inappropriate mucosal immune activation. It is separated into two categories. The distinction between ulcerative colitis and Crohn disease is primarily based on the distribution of affected sites and the morphologic expression of disease at those sites. Ulcerative colitis involves **only** the colon and rectum and is generally limited to the mucosa and submucosa. In contrast, Crohn disease, which has also been referred to as regional enteritis (because of frequent ileal involvement) may involve any area of the GI tract and is typically transmural. +-----------+-----------+-----------+-----------+-----------+-----------+ | | Patho | Risk | s/s | Clinical | Diagnosis | | | | | | Manifesta | | | | | | | tions | | +-----------+-----------+-----------+-----------+-----------+-----------+ | Ulcerativ | Chronic | Autoimmun | Lower | Bloody | Colonosco | | e | inflammat | e, | Abdominal | diarrhea | py | | Colitis | ory | Genetics, | pain | | and | | | disease | age | extending | Ulcerativ | biopsy. | | | of the | (15-30), | to rectum | e | Large | | | mucosa of | caucasian | | colitis | ulcers | | | the | , | | should | form in | | | rectum | eastern | | follow | the | | | and | european | | high | mucosal | | | colon. | jewish | | fiber, | layer of | | | | descent, | | low-resid | the colon | | | Begins as | diet and | | ue | and | | | inflammat | environme | | diet | rectum. | | | ion | ntal | | | As if | | | at the | are | | IE: | skip | | | base of | secondary | | vegetable | lesions | | | crypts of | effects | | s | are | | | Lieberküh | that | | (juice/co | combined | | | n; | cause | | oked/cann | | | | damage | flare ups | | ed), | Increased | | | results. | | | ground | cancer | | | | | | beef, | risk | | | Abscess | | | veal, | after | | | formation | | | pork, | 7-10 | | | in | | | lamb, | years of | | | crypts; | | | white | disease | | | [abscesse | | | rice, | | | | s | | | pasta | | | | begin to | | | | | | | coalesce] | | | | | | | {.underli | | | | | | | ne}, | | | | | | | and large | | | | | | | ulceratio | | | | | | | ns | | | | | | | develop | | | | | | | in the | | | | | | | epitheliu | | | | | | | m. | | | | | +-----------+-----------+-----------+-----------+-----------+-----------+ | Chron's | Affects | Autoimmun | Intermitt | Iron | Suggestiv | | Disease | the | e | ent | deficienc | e | | | proximal | triggered | bouts of | y | findings | | | portion | by | fever, | anemia | are | | | of the | foreign | diarrhea, | | ulceratio | | | colon or | invader, | if | Fibrosing | ns, | | | terminal | th1 | bloody, | stricture | stricture | | | ileum. | release | not as | s | s, | | | | cytokines | severe as | | fibrosis, | | | Chronic | and | ulcerativ | | and | | | inflammat | triggers | e | | fistulas | | | ion | unregulat | colitis; | | | | | of all | ed | constant, | | The | | | layers of | inflammat | chronic | | presence | | | the | ion. | RLQ pain | | of | | | intestina | Genetics, | (d/t | | multiple, | | | l | NOD2 | ileum), | | separate, | | | wall | gene. | may have | | sharply | | | resulting | Granuloma | RLQ mass, | | delineate | | | from | s | tendernes | | d | | | blockage | form d/t | s | | areas of | | | and | encapsula | | | disease, | | | inflammat | ted | | | resulting | | | ion | inflammat | | | in **skip | | | of | ory | | | lesions** | | | lymphatic | cells | | | , | | | vessels. | that | | | is | | | Transmura | degrade | | | character | | | l | into | | | istic, | | | from | ulcers | | | and when | | | mucosa to | | | | present, | | | serosa. | | | | different | | | | | | | iates | | | | | | | Crohn | | | | | | | disease | | | | | | | from | | | | | | | ulcerativ | | | | | | | e | | | | | | | colitis. | +-----------+-----------+-----------+-----------+-----------+-----------+ - Patho: The accumulation of fluid in the peritoneal cavity. 85% of cases are caused by cirrhosis (diffuse remodeling of the liver). Ascites usually becomes clinically detectable when at least 500 mL have accumulated. The fluid is generally serous. The fluid may contain a scant number of mesothelial cells and mononuclear leukocytes. The presence of neutrophils suggests infection, whereas the presence of red cells points to possible disseminated intra-abdominal cancer. With long-standing ascites, seepage of peritoneal fluid through trans-diaphragmatic lymphatics may produce hydrothorax, usually on the right side. - Risk Factors: Portal HTN, hypoalbuminemia, The pathogenesis of ascites is complex, involving sinusoidal hypertension, hypoalbuminemia, increased hepatic lymph flow, and splanchnic vasodilation and hyperdynamic circulation. - S/S: abd distention - Dx: US and paracentesis - Both are initiated by injuries that lead to autodigestion of the pancreas by its own enzymes. Most digestive enzymes are synthesized as inactive proenzymes (zymogens) and packaged within secretory granules. - Proenzymes are activated by trypsin, which itself is activated by duodenal enteropeptidase (enterokinase) in the small bowel - Acinar and ductal cells secrete trypsin inhibitors, including serine protease inhibitor Kazal type l (SPINK1), which further limit intrapancreatic trypsin activity. - Pancreatitis occurs when these protective mechanisms are disrupted or overwhelmed. +-----------+-----------+-----------+-----------+-----------+-----------+ | | **Patho** | **Risk | **S/S** | **Manifes | **Diagnos | | | | Factors** | | tations** | is** | +-----------+-----------+-----------+-----------+-----------+-----------+ | **Acute** | Mild and | Biliary | Steady, | Pain | Laborator | | | self | tract | boring | increases | y: | | | limited | disease, | pain in | in | **lipase* | | | ti life | hypertrig | epigastri | intensity | * | | | threateni | lyceridem | um | | preferred | | | ng. | ia, | or LUQ | Severe | test | | | Character | ETOH | | tendernes | | | | ized | abuse. | Pain | s | Increase | | | by | | associate | on | in | | | reversibl | many | d | palpation | amylase | | | e | causes, | with | | and | | | pancreati | including | pancreati | Radiates | lipase | | | c | toxic | tis | or | during | | | parenchym | exposures | is caused | penetrate | first 12 | | | al | (e.g., | by | s | hr | | | injury | alcohol), | digestive | to back | (indicati | | | and | pancreati | enzymes | | ve) | | | inflammat | c | being | Nausea | | | | ion. | duct | secreted | and | Elevated | | | Autodiges | obstructi | into the | vomiting | aminotran | | | tion | on | parenchym | | sferases, | | | of the | (e.g., | a | Abdominal | alkaline | | | pancreas | biliary | | distentio | phosphata | | | from | calculi), | | n | se, | | | enzyme | inherited | | | and | | | activatio | genetic | | Hypoactiv | bilirubin | | | n; | defects, | | e | | | | results | vascular | | bowel | Abdominal | | | from | injury, | | sounds | x-ray | | | inappropr | and | | | | | | iate | infection | | Low-grade | Ileus | | | release | s. | | fever | pattern; | | | and | | | | "sentinel | | | activatio | | | It has | loop": a | | | n | | | been | distended | | | of | | | proposed | loop of | | | pancreati | | | that | small | | | c | | | acute | bowel in | | | enzymes | | | pancreati | the area | | | that, in | | | tis | of the | | | turn, | | | initiates | pancreas | | | destroy | | | a | | | | pancreati | | | sequence | **CT of | | | c | | | of | the | | | tissue | | | perilobul | abdomen** | | | and | | | ar | | | | elicit an | | | fibrosis, | Gold | | | acute | | | duct | standard: | | | inflammat | | | distortio | allows | | | ory | | | n, | remarkabl | | | reaction. | | | and | e | | | | | | altered | detail | | | 3 | | | secretion | | | | pathways: | | | s | | | | **1** | | | that, as | | | | Obstructi | | | a result | | | | on | | | of | | | | of the | | | recurrent | | | | pancreati | | | injury, | | | | c | | | leads to | | | | duct by a | | | loss of | | | | stone or | | | exocrine | | | | other | | | parenchym | | | | unknown | | | a | | | | cause | | | and | | | | **2** | | | fibrosis. | | | | Acinar | | | Chronic | | | | cell | | | pancreati | | | | injury | | | tis | | | | **3** | | | often | | | | Defective | | | follows | | | | intracell | | | repeated | | | | ular | | | episodes | | | | transport | | | of acute. | | | | of | | | | | | | proenzyme | | | | | | | s | | | | | | | with | | | | | | | acinar | | | | | | | cells. | | | | | +-----------+-----------+-----------+-----------+-----------+-----------+ | **Chronic | Chronic | Long term | Weight | Bouts of | Same as | | ** | pancreati | ETOH | loss: | acute | acute | | | tis | consumpti | poor | pancreati | different | | | is | on, | intake | tis | iated | | | defined | idiopathi | related | with | by length | | | as | c, | to pain | progressi | of | | | prolonged | hereditar | | ve | progressi | | | inflammat | y, | Insidious | endocrine | on | | | ion | hyperpara | onset of | and | of | | | of the | thyroidis | steady, | exocrine | symptoms | | | pancreas | m | boring | pancreati | | | | associate | (hypercal | epigastri | c | | | | d | cemia), | c | dysfuncti | | | | with | trauma | pain | on | | | | irreversi | | radiating | | | | | ble | Can | to back | Diabetes: | | | | destructi | progress | (first | progressi | | | | on | even if | symptom) | ve | | | | of | alcohol | | loss of | | | | exocrine | consumpti | Nausea | pancreati | | | | parenchym | on | | c | | | | a, | is | | islets | | | | fibrosis, | stopped | | | | | | and, in | | | Malabsorp | | | | the late | Does not | | tion: | | | | stages, | increase | | fat and | | | | loss of | the risk | | vitamins | | | | endocrine | for | | A, D, E, | | | | parenchym | cancer | | and K | | | | a. | | | | | | | May lead | | | After | | | | to | | | about 5 | | | | permanent | | | years of | | | | loss of | | | continual | | | | pancreati | | | pain: | | | | c | | | decrease | | | | function. | | | in | | | | Presence | | | symptoms | | | | of | | | (pain | | | | chronic | | | "burns | | | | inflammat | | | out") | | | | ory | | | | | | | lesions | | | Chronic | | | | in the | | | pancreati | | | | pancreas | | | c | | | | | | | injury of | | | | Key | | | any cause | | | | element: | | | leads to | | | | necrosis | | | local | | | | of | | | productio | | | | exocrine | | | n | | | | parenchym | | | of | | | | a | | | inflammat | | | | followed | | | ory | | | | by | | | mediators | | | | fibrosis | | | that | | | | | | | promote | | | | Leads to | | | fibrosis | | | | calcifica | | | and | | | | tion---ob | | | acinar | | | | structed | | | cell | | | | flow of | | | loss. | | | | pancreati | | | While | | | | c | | | there is | | | | juices | | | overlap | | | | | | | between | | | | Persisten | | | the | | | | ce | | | cytokines | | | | of | | | released | | | | symptoms | | | during | | | | secondary | | | chronic | | | | to | | | and acute | | | | pancreati | | | pancreati | | | | c | | | tis, | | | | dysfuncti | | | fibrogeni | | | | on | | | c | | | | over | | | factors | | | | weeks and | | | tend to | | | | months | | | predomina | | | | | | | te | | | | | | | in | | | | | | | chronic | | | | | | | pancreati | | | | | | | tis. | | +-----------+-----------+-----------+-----------+-----------+-----------+ - Patho: Inflammation of the esophageal mucosa. Closure of the LES (lower esophageal sphincter) is adversely affected. - Risk factors: Transient LES relaxation is thought to be a major cause. Relaxation is mediated via Vagal pathways and can be triggered by gastric distention. Medications, fatty foods, caffeine, ETOH, smoking, sleep position, obesity and low acid. - s/s: Heartburn, regurg, chest pain and dysphagia - Manifestations:vSeverity dependent on frequency, duration, volume, and acidity of refluxed materials. Esophageal strictures, cough, asthma, laryngitis. Barretts Esophagus. - Dx: s/s - Patho: Chronic musicals ulceration affecting the duodenum or stomach. Gastric- due to the breakdown of the protective mucous layer that normally prevents diffusion of acids into gastric epithelia due to chronic irritations. Duodenal- Inappropriate excess of secretion of acid, increased basal activity of vagus nerve stimulates pyloric antrum cells to release gastrin to act on gastric parietal cells to release HCl resulting in high HCl levels. - Risk factors: ASA, Smoking, NSAIDS, Stress, genetics, COPD, illicit drug use, ETOH cirrhosis, viral infection (CMV, HSV) Bile acids, ETOH may impair the alkalinity of the mucosa. Hyperplasia of the parietal cells in the stomach leads to an increased hydrochloric acid release. - s/s: Epigastric pain normally on an empty stomach that is relieved by eating, especially dairy or antacids. Pain occurs 2-3 hours after a meal and is relieved by more food intake is typically duodenal - Manifestations: GI Bleed may occur with no warning and be life threatening - Dx: endoscopy with biopsy - Patho: a complication of chronic GERD, characterized by intestinal metaplasia withing the esophageal squamous mucosa and is associated with an increased risk of cancer. - Risk factors: Family hx, white men, 40-60 years old, chronic heartbrun/reflux, smoking (present or hx), obesity, increased risk for esophageal adenocarcinoma. - s/s: Heartburn, indigestions, horaseness, chronic cough, throat irritation - Manifestations: Cancer - Dx: endoscopic evidence of metaplastic columnar mucosa above the gastroesophageal junction. Microscopically intestinal-type metaplasia is seen as a replacement of the squamous esophageal epithelium with goblet cells. Goblet cells are diagnostic of Barretts esophagus. They have distinct mucous vacuoles that stain pale blue and impart the shape of a wine goblet to the remaining cytoplasm. +-----------+-----------+-----------+-----------+-----------+-----------+ | | Patho | Risk | S/S | Manifesta | Diagnosis | | | | | | tions | | +-----------+-----------+-----------+-----------+-----------+-----------+ | Cholecyst | Acute | Cholelith | Severe, | If | CT | | itis | inflammat | iasis | right | untreated | | | | ion | present | upper | , | | | | of the | in 90% of | abdominal | escalates | | | | gallbladd | patients | pain | ; | | | | er | | radiates | gangrene | | | | wall. | Obstructi | to back; | may occur | | | | Causes | on | abdominal | | | | | fibrosis | of cystic | tendernes | Rupture | | | | and | duct | s; | | | | | thickenin | present | fever and | Peritonit | | | | g | in almost | chills, | is | | | | | all | leukocyto | | | | | Related | patients: | sis, | Septic | | | | to the | related | mild | shock | | | | continued | to stasis | elevation | | | | | presence | of bile | s | Localized | | | | of | | of | abscess | | | | gallstone | Bacterial | bilirubin | (empyema) | | | | s | infection | and serum | | | | | | may be | transamin | Cholecyst | | | | 2 types | present | ases | oenteric | | | | | | | fistula | | | | Acute | | | (fistula | | | | | | | between | | | | Chronic | | | gallbladd | | | | | | | er | | | | Acalculou | | | and GI | | | | s | | | tract) | | | | cholecyst | | | | | | | itis | | | Chronic: | | | | | | | Chronic | | | | Occurs in | | | inflammat | | | | patients | | | ion | | | | without | | | of | | | | preexisti | | | gallbladd | | | | ng | | | er | | | | gallstone | | | wall | | | | s | | | | | | | | | | Related | | | | Males | | | to | | | | \>50 | | | persisten | | | | years | | | t | | | | | | | low-grade | | | | Tends to | | | irritatio | | | | occur in | | | n | | | | the | | | from | | | | setting | | | gallstone | | | | of major | | | s; | | | | surgery, | | | recurrent | | | | critical | | | attacks | | | | illness, | | | of acute | | | | trauma, | | | cholecyst | | | | burn-rela | | | itis | | | | ted | | | | | | | injury, | | | Predispos | | | | or TPN | | | ing | | | | | | | factors: | | | | Rapid | | | diabetes, | | | | developme | | | obesity | | | | nt | | | | | | | of | | | \- | | | | gangrene, | | | Asymptoma | | | | perforati | | | tic; | | | | on, | | | intermitt | | | | emphysema | | | ent | | | | tous | | | biliary | | | | cholecyst | | | colic or | | | | itis, | | | symptomat | | | | and | | | ic | | | | empyema | | | acute | | | | | | | attacks | | | | | | | | | | | | | | Leads to | | | | | | | complicat | | | | | | | ions | | | | | | | | | | | | | | Biliary | | | | | | | sepsis; | | | | | | | scarring/ | | | | | | | calcified | | | | | | | (porcelai | | | | | | | n | | | | | | | gallbladd | | | | | | | er): | | | | | | | higher | | | | | | | risk for | | | | | | | cancer | | +-----------+-----------+-----------+-----------+-----------+-----------+ | Cholelith | Gallstone | Prolonged | | Chronic: | CT | | iasis | formation | fasting | | Biliary | | | | : | or rapid | | colic | | | Gallstone | | weight | | | | | | Lecithin: | loss, | | Related | | | | helps | Pregnancy | | to | | | | keep | , | | intermitt | | | | cholester | Oral | | ent | | | | ol | contracep | | obstructi | | | | from | tives, | | on | | | | precipita | Obesity, | | of the | | | | ting | Age, Sex | | cystic | | | | into | | | duct | | | | crystals | Native | | | | | | in bile | Americans | | Precipita | | | | | \> | | ted | | | | Crystals | American | | by a meal | | | | of | Caucasian | | (infreque | | | | cholester | s | | nt | | | | ol | | | schedule) | | | | may | Women \> | | | | | | initiate | men (2:1) | | Persisten | | | | gallstone | | | t | | | | formation | | | epigastri | | | | | | | c | | | | Relative | | | or right | | | | concentra | | | upper | | | | tions | | | abdominal | | | | of | | | pain, | | | | cholester | | | often | | | | ol, | | | radiates | | | | lecithin, | | | to the | | | | and bile | | | back | | | | acids: | | | | | | | determine | | | Nausea, | | | | the | | | vomiting, | | | | likelihoo | | | sweating, | | | | d | | | flatus | | | | of | | | | | | | cholester | | | Increases | | | | ol | | | steadily | | | | gallstone | | | for \>15 | | | | formation | | | minutes, | | | | | | | lasts | | | | 3 phases: | | | several | | | | | | | hours, | | | | 1. Super | | | then | | | | saturatio | | | slowly | | | | n | | | decreases | | | | of | | | | | | | bile | | | Fatty | | | | with | | | food | | | | chole | | | intoleran | | | | sterol | | | ce, | | | | causi | | | belching, | | | | ng | | | bloating, | | | | preci | | | and | | | | pitation | | | epigastri | | | | of | | | c | | | | chole | | | burning | | | | sterol | | | | | | | | | | | | | | 2. Nucle | | | | | | | ation | | | | | | | of | | | | | | | cryst | | | | | | | als | | | | | | | | | | | | | | 3. Hypom | | | | | | | otility | | | | | | | (stas | | | | | | | is | | | | | | | of | | | | | | | bile) | | | | | | | allow | | | | | | | ing | | | | | | | stone | | | | | | | growt | | | | | | | h | | | | | +-----------+-----------+-----------+-----------+-----------+-----------+ - Patho: initiated by progressive increases in intraluminal pressure that compromise venous outflow causing Inflammation of the vermiform appendix. Overt luminal obstruction, usually caused by a small stone-like mass of stool, or fecalith, or, less commonly, a gallstone, tumor, or mass of worms - Risk Factors: - S/S: Periumbilical pain, RLQ pain ("McBurney's point" deep tenderness located two-thirds of the distance from the umbilicus to the right anterior superior iliac spine) (classic, but may be anywhere), nausea, vomiting, fever, diarrhea, RLQ tenderness, rebound tenderness, systemic signs of inflammation - Manifestations: sepsis and shock if ruptured - Diagnosis: clinical s/s, CT +-----------------+-----------------+-----------------+-----------------+ | | **ACUTE** | **CHRONIC** | **FAILURE** | +-----------------+-----------------+-----------------+-----------------+ | **PATHO** | - | - | **Inflammation* | | | | | * | | | | | | | | | | - | +-----------------+-----------------+-----------------+-----------------+ | **CLINICAL | - | - | | | MANIFESTATIONS* | | | | | * | | | | 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Colon polyps** **18. Portal Hypertension** **19. Pyloric stenosis** - **Defined as an increase in stool mass, frequency, or fluidity, typically greater than 200g per day** - **Typically does not require additional testing if no fever, chills, or blood present.** - **Diarrhea can be classified into 4 major categories:** 1. ***Secretory diarrhea* - isotonic stool and persists during fasting** 2. *Osmotic diarrhea* **- occurs with lactase deficiency, is due to excessive osmotic force exerted by unabsorbed luminal solutes. The diarrhea fluid is more than 50 mOsm more concentrated than plasma, and diarrhea abates with fasting.** 3. *Malabsorptive diarrhea* **follows the generalized failure of nutrient absorption, is associated with steatorrhea, and is relieved by fasting.** 4. *Exudative diarrhea* **due to inflammatory disease is characterized by purulent, often bloody stools that continue during fasting.** **Endocrine Topics** **4. Diabetes Type I vs Type II** ***\*\*\*LONG-TERM COMPLICATIONS OF TYPE II DIABETES MELLITUS\*\*\**** - The long-term complications of diabetes, while similar in both Type I and Type II, stem from prolonged periods of elevated blood glucose levels and involve several key pathological mechanisms: - **Formation of Advanced Glycation End Products (AGEs):** Elevated glucose levels lead to the formation of AGEs, which can cause damage to blood vessels and tissues. - **Activation of Protein Kinase C (PKC):** This pathway is implicated in various diabetic complications, affecting blood flow and inflammation. - **Disturbances in the Polyol Pathway:** *Increased glucose can lead to the conversion of glucose to sorbitol* via the enzyme aldose reductase, resulting in oxidative stress and damage to cells. - Sorbitol is toxic to tissue - **Hexosamine Pathway Overload:** Excess glucose can lead to an overload of the hexosamine pathway, further contributing to insulin resistance and vascular damage. - **Types of Complications:** - **Macroangiopathy (Large-Vessel Disease):** - Atherosclerosis - Ischemic heart disease - Lower extremity ischemia - **Microangiopathy (Small-Vessel Disease):** - **Retinopathy:** Damage to the blood vessels in the retina, leading to vision problems. - **Nephropathy:** Kidney damage, potentially resulting in kidney failure. - **Neuropathy:** Nerve damage, which can lead to pain, tingling, or loss of sensation, particularly in the extremities. Persistent hyperglycemia, also known as glucotoxicity, is a key factor contributing to the long-term complications of diabetes. The consequences of elevated blood sugar levels lead to several detrimental processes in the body. **1. Formation of Advanced Glycation End Products (AGEs)** - **Accelerated Formation:** The presence of high glucose levels accelerates the formation of AGEs. These are harmful compounds formed when sugar molecules bind to proteins or lipids. - **Interaction with Receptors:** AGEs bind to a specific receptor called RAGE (Receptor for Advanced Glycation End Products), which is found on various cells, including: - **Inflammatory Cells:** Such as macrophages and T cells - **Endothelial Cells:** The inner lining of blood vessels - **Vascular Smooth Muscle Cells:** Cells in the walls of blood vessels **2. Detrimental Effects of the AGE-RAGE Signaling Axis** - The binding of AGEs to RAGE triggers several harmful effects within the vascular system, including: - **Release of Cytokines and Growth Factors:** - **Transforming Growth Factor-β (TGF-β):** This factor promotes the deposition of excess material in the basement membrane, which can thicken blood vessel walls. - **Vascular Endothelial Growth Factor (VEGF):** Involved in the development of new blood vessels, this factor is notably linked to diabetic retinopathy, a common eye condition in diabetes. - **Generation of Reactive Oxygen Species (ROS):** - The interaction leads to the production of ROS in endothelial cells, which can cause oxidative stress and further damage to blood vessels. - **Increased Procoagulant Activity:** - Endothelial cells and macrophages exhibit increased procoagulant activity, making blood more likely to clot. This can contribute to cardiovascular issues. - **Enhanced Proliferation of Vascular Smooth Muscle Cells:** - The signaling pathway promotes the growth of these muscle cells and the synthesis of extracellular matrix, which can narrow blood vessels and impede blood flow. +-----------------------+-----------------------+-----------------------+ | | **HASHIMOTO | **GRAVES' DISEASE** | | | THYROIDITIS** | | +-----------------------+-----------------------+-----------------------+ | **PATHO** | - Hashimoto | - **Autoimmune | | | thyroiditis is an | Mechanism**: | | | autoimmune | Graves\' disease | | | disorder | is an autoimmune | | | characterized by | disorder | | | the progressive | characterized by | | | destruction of | the production of | | | the thyroid | **autoantibodies* | | | gland, leading to | * | | | gradual thyroid | against multiple | | | failure. The | thyroid proteins, | | | condition arises | primarily | | | from a breakdown | targeting the | | | in the body's | **thyroid-stimula | | | self-tolerance to | ting | | | thyroid | hormone (TSH) | | | autoantigens, | receptor**. | | | which are | | | | proteins normally | - **Thyroid-Stimula | | | present in the | ting | | | thyroid. | Immunoglobulin | | | | (TSI)**: The most | | | - **Pathogenesis** | common antibody | | | | subtype, known as | | | - **Autoantibod | **thyroid-stimula | | | y | ting | | | Formation**: | immunoglobulin | | | In Hashimoto | (TSI)**, binds to | | | thyroiditis, | the TSH receptor, | | | the immune | mimicking the | | | system | action of TSH. | | | produces | This binding | | | autoantibodie | activates | | | s | adenylate | | | that target | cyclase, leading | | | specific | to increased | | | thyroid | intracellular | | | proteins, | cyclic AMP (cAMP) | | | notably | levels, which in | | | **thyroglobul | turn stimulates | | | in** | the synthesis and | | | and **thyroid | release of | | | peroxidase**. | thyroid hormones | | | These | (T3 and T4). | | | autoantibodie | | | | s | | | | interfere | | | | with normal | - The autoimmune | | | thyroid | nature of Graves' | | | function and | disease results | | | contribute to | in an overactive | | | gland damage. | thyroid and is | | | | often associated | | | - **Genetic | with other | | | Predispositio | autoimmune | | | n**: | disorders. | | | There is a | | | | strong | - Infiltrative | | | genetic | ophthalmopathy | | | component to | can lead to | | | Hashimoto | significant | | | thyroiditis, | visual impairment | | | indicating | and requires | | | that | careful | | | individuals | monitoring and | | | with a family | management. | | | history of | | | | autoimmune | - Laboratory | | | diseases are | findings include | | | at a higher | elevated free | | | risk for | T~4~ and T~3~ | | | developing | levels and | | | this | depressed TSH | | | condition. | levels. | | | | | | | - **Immune | | | | Response**: | | | | The | | | | destruction | | | | of thyroid | | | | tissue is | | | | mediated | | | | primarily by | | | | **CD8+ | | | | cytotoxic T | | | | cells**, | | | | which are a | | | | type of white | | | | blood cell. | | | | These cells | | | | attack and | | | | destroy | | | | thyroid | | | | follicular | | | | cells, | | | | leading to | | | | impaired | | | | hormone | | | | production. | | | | | | | | - Most prevalent | | | | between 45 and 65 | | | | years of age | | | | | | | | - More common | | | | in women than | | | | in men, with | | | | a female | | | | predominance | | | | of 10 : 1 to | | | | 20 : 1 | | +-----------------------+-----------------------+-----------------------+ | **CLINICAL | - **Fatigue**:Persi | - **Clinical | | MANIFESTATIONS** | stent | Presentation**: | | | tiredness and | The disease is | | | lack of energy. | characterized by | | | | a classic triad | | | - **Weight | of clinical | | | Gain**:Unexplaine | findings: | | | d | | | | increase in | - - - | | | weight despite no | | | | changes in diet | | | | or exercise. | | | | | | | | - **Cold | | | | Intolerance**:Inc | | | | reased | | | | sensitivity to | | | | cold | | | | temperatures. | | | | | | | | - **Dry Skin**:Skin | | | | may become rough, | | | | dry, and flaky. | | | | | | | | - **Hair | | | | Changes**:Thinnin | | | | g | | | | hair or hair | | | | loss; hair may | | | | become coarse and | | | | brittle. | | | | | | | | - **Constipation**: | | | | Decreased | | | | bowel movements | | | | and difficulty | | | | passing stool. | | | | | | | | - **Depression**:Fe | | | | elings | | | | of sadness, | | | | hopelessness, and | | | | mental | | | | sluggishness that | | | | may mimic | | | | depression. | | | | | | | | - **Cognitive | | | | Impairment**:Diff | | | | iculty | | | | concentrating, | | | | memory issues, | | | | and slowed | | | | thinking. | | | | | | | | - **Hoarseness**:Ch | | | | anges | | | | in voice, | | | | including a | | | | hoarse or deeper | | | | voice. | | | | | | | | - **Menstrual | | | | Irregularities**: | | | | Changes | | | | in menstrual | | | | cycle, including | | | | heavy or | | | | irregular | | | | periods. | | | | | | | | - **Goiter**: | | | | Enlargement of | | | | the thyroid | | | | gland, which may | | | | be visible or | | | | palpable in the | | | | neck. | | | | | | | | - **Joint | | | | Pain**:Aches and | | | | stiffness in | | | | joints, which may | | | | be mistaken for | | | | arthritis. | | | | | | | | - **Muscle | | | | Weakness**:Genera | | | | lized | | | | muscle weakness, | | | | particularly in | | | | the upper arms | | | | and thighs. | | | | | | | | - **Elevated | | | | Cholesterol | | | | Levels**: | | | | Increased total | | | | cholesterol and | | | | LDL levels due to | | | | altered lipid | | | | metabolism. | | | | | | | | - **Puffy Face**: | | | | Swelling of the | | | | face, | | | | particularly | | | | around the eyes, | | | | may occur. | | +-----------------------+-----------------------+-----------------------+ PARATHYROID GLANDS - The four parathyroid glands are composed of two cell types: chief cells and oxyphil cells. - *Chief cells* have secretory granules containing ***parathyroid hormone (PTH)***. - The main function of the parathyroid glands is to maintain calcium homeostasis by producing parathyroid hormone (PTH), which regulates calcium, phosphorus, and magnesium levels in the body. - PTH is critical for proper functioning of the nervous and muscular systems and plays a role in bone health. - Increased renal tubular reabsorption of calcium, thereby conserving free calcium - Increased conversion of vitamin D to its active dihydroxy form in the kidneys, which, in turn, augments gastrointestinal calcium absorption - Increased urinary phosphate excretion, thereby lowering serum phosphate levels and further increasing calcium (since phosphate binds to ionized calcium) - Enhanced osteoclastic activity (i.e., bone resorption, thus releasing ionized calcium), by promoting the differentiation of osteoclast progenitor cells into mature osteoclasts - The net result of these activities is to elevate the level of free calcium, which, in turn, inhibits further PTH secretion in a classic feedback loop. PTH ACTIONS - **Bone**: PTH stimulates osteoclast activity, leading to the release of calcium and phosphate from the bone into the bloodstream, which increases serum calcium levels. - **Kidneys**: PTH increases calcium reabsorption and phosphate excretion, helping to retain calcium and excrete phosphate in the urine. It also stimulates the kidneys to convert vitamin D to its active form (calcitriol), which enhances calcium absorption in the intestines. - **Intestines**: Through the action of calcitriol, PTH indirectly increases calcium absorption from the gastrointestinal tract. - **Feedback Regulation**: The secretion of PTH is regulated by serum calcium levels through a negative feedback loop. Low blood calcium stimulates PTH release, while high calcium levels inhibit it, ensuring calcium balance is maintained. - **Clinical Significance**: - **Hypoparathyroidism**: Low PTH levels lead to hypocalcemia, causing muscle spasms, tingling, and even life-threatening tetany. - **Hyperparathyroidism**: Excess PTH results in hypercalcemia, which can cause osteoporosis, kidney stones, and neuromuscular issues. ***THE ONLY THING ABOUT HYPERCALCEMIA IS HYPERPARATHYROIDISM BUT I THINK MAYBE HOW PTH HAS AN EFFECT ON HYPERCALCEMIA? (LOOK AT \#12)*** +-----------------------+-----------------------+-----------------------+ | | **TYPE 1 DM** | **TYPE 2 DM** | +-----------------------+-----------------------+-----------------------+ | | - Onset: Usually | - Onset: Usually | | | childhood and | adult; ↑ | | | adolescence; | incidence in | | | abrupt | childhood and | | | | adolescence | | | - Normal weight or | | | | weight loss | - Majority are | | | before diagnosis. | obese (80%) | | | | | | | - Progressive | - ↑ blood insulin | | | decreases in | (early); normal | | | insulin levels. | or moderate | | | | decrease in | | | - Circulating islet | insulin (late) | | | autoantibodies | | | | (anti-insulin, | - No islet | | | anti-GAD, | autoantibodies | | | anti-ICA512) | | | | | - Nonketotic | | | - DKA in absence of | hyperosmolar coma | | | insulin therapy. | more common | +-----------------------+-----------------------+-----------------------+ | GENETICS | Major linkage to MHC | No HLA linkage | | | class II genes | | +-----------------------+-----------------------+-----------------------+ | PATHOGENESIS | Dysfunction in T-cell | Insulin resistance in | | | selection and | peripheral tissues, | | | regulation leading to | failure to | | | breakdown in | compensation by 𝛽 | | | self-tolerance to | cells | | | islet autoantigens | | +-----------------------+-----------------------+-----------------------+ | PATHOLOGY | Insulitis | No insulitis; amyloid | | | (inflammatory | deposition in islets. | | | infiltrate of T cells | | | | and macrophages) 𝛽 - | Mild 𝛽 - cell | | | cell depletion, islet | depletion | | | atrophy | | +-----------------------+-----------------------+-----------------------+ - Type I diabetes is an autoimmune disorder where the body's immune system mistakenly targets and destroys insulin-producing β-cells in the pancreas. This destruction occurs through a gradual process often influenced by both genetic predispositions and environmental triggers (e.g., viral infections). - The key stages in Type I diabetes development include: 1. **Genetic Susceptibility**: Individuals with certain HLA genotypes are more susceptible to autoimmune reactions that target β-cells. 2. **Autoimmune Activation**: Environmental triggers, such as infections, can activate the immune response, leading to the production of autoantibodies against β-cell antigens, including insulin and glutamic acid decarboxylase (GAD). 3. **Progressive β-Cell Destruction**: Activated CD8+ T cells and cytokines further attack β-cells, gradually reducing insulin production. This process can take months to years, ultimately leading to insulin deficiency. 4. **Clinical Onset**: Symptoms appear only after approximately 80-90% of β-cell mass is destroyed, causing hyperglycemia, ketosis, and other signs of insulin deficiency. 5. **Absolute Insulin Deficiency**: With insufficient insulin, glucose uptake is impaired, resulting in high blood glucose levels. This imbalance affects metabolism, leading to ***polyuria, polydipsia, polyphagia,*** and eventual complications like ketoacidosis if untreated. TYPE 1 DM CLINICAL MANIFESTATIONS - Symptoms develop due to the body's inability to produce insulin, a hormone essential for regulating blood glucose levels. Without insulin, cells cannot take in glucose from the blood, leading to hyperglycemia and a variety of systemic effects: - **Hyperglycemia**: Since glucose cannot enter cells without insulin, it accumulates in the blood. The high blood glucose levels lead to: - **Polyuria (Frequent Urination)**: The kidneys work to excrete the excess glucose, which pulls water with it, causing frequent urination. - **Polydipsia (Increased Thirst)**: The frequent urination causes dehydration, leading to excessive thirst as the body attempts to rehydrate. - **Lack of Cellular Glucose**: Despite high blood glucose levels, cells are deprived of energy because they cannot take in glucose without insulin. This results in: - **Polyphagia (Increased Hunger)**: The cells signal for more energy, driving a constant feeling of hunger. - **Weight Loss**: The body begins breaking down fat and muscle for energy, leading to weight loss even if the person is eating more. - **Fatigue**: With inadequate cellular glucose and energy, fatigue and general weakness are common as the body lacks a readily available energy source. - **Fat and Muscle Breakdown**: In the absence of glucose, the body shifts to breaking down fats for fuel, which produces ketones as a byproduct. This can lead to: - **Ketosis and Diabetic Ketoacidosis (DKA)**: If ketones build up in the blood, they cause acidosis, which can result in nausea, vomiting, abdominal pain, and, if untreated, life-threatening diabetic ketoacidosis (DKA). +-----------------------+-----------------------+-----------------------+ | | | | +-----------------------+-----------------------+-----------------------+ | ***[LACTOTROPH | - Prolactin-secreti | - ↑serum levels of | | ADENOMA]* | ng | prolactin | | ** | lactotroph | (*prolactinemia)* | | | adenomas are the | causes | | | most common type | amenorrhea, | | | of | ***[galactorrhea] | | | hyperfunctioning | ***, | | | pituitary adenoma | loss of libido, | | | | and infertility. | | | - Accounting for | | | | about 30% of | - Dx of adenoma is | | | cases | made more in | | | | women than in | | | | men, especially | | | | between 20-40 yrs | | | | of age, because | | | | hyperprolactinemi | | | | a | | | | disrupts the | | | | menstrual cycle. | +-----------------------+-----------------------+-----------------------+ | **SOMATOTROPH | - Growth hormone | - Persistently | | ADENOMA** | (GH)-secreting | elevated levels | | | somatotroph | of GH stimulate | | | adenomas are the | the hepatic | | | 2nd most common | secretion of | | | type of | insulin-like | | | functioning | growth factor-1 | | | pituitary adenoma | (IGF-1), which | | | | causes many of | | | - Causes gigantism | the clinical | | | in children and | manifestations*.* | | | acromegaly in | | | | adults. | | +-----------------------+-----------------------+-----------------------+ | **CORTICOTROPH | - Excess production | - Symptoms | | ADENOMA** | of ACTH by | discussed in | | | functioning | adrenal section | | | corticotroph | | | | adenomas leads to | - Nelson syndrome | | | adrenal | | | | hypersecretion of | - Mass effects (20% | | | cortisol and the | are hormonally | | | development of | silent) | | | hypercortisolism | | | | (***Cushing | | | | syndrome***) | | | | | | | | - Hypercortisolism | | | | due to excessive | | | | production of | | | | ACTH by the | | | | pituitary-***Cush | | | | ing | | | | disease*.** | | +-----------------------+-----------------------+-----------------------+ | **THYROTROPH | TSH | Hyperthyroidism | | ADENOMA** | | | +-----------------------+-----------------------+-----------------------+ | **GONADOTROPH | FSH, LH | Mass effects and | | ADENOMA** | | hypopituitarism (most | | | | are hormonally | | | | silent) | +-----------------------+-----------------------+-----------------------+ GROWTH HORMONE EXCESS - **Etiology and Pathogenesis** - **Cause**: Often due to an uncontrolled GH-producing benign somatotropic tumor in the pituitary. - **Mechanism**: - GH stimulates the liver to produce **IGF-1**, leading to the growth of soft tissues and bones. - Can cause **persistent hyperglycemia** and increased insulin production (GH is a diabetogenic hormone). +-----------------------------------+-----------------------------------+ | **ACROMEGALY** | **GIGANTISM** | +-----------------------------------+-----------------------------------+ | **Acromegaly** (in Adults) | **Pituitary Gigantism** (in | | | Children) | | - **Physical Changes**: | | | | - **Occurs Before Epiphyses | | - Enlarged hands and feet | Close**: Leads to excessive | | (ring or shoe size | height and growth velocity | | increases). | (\>95th percentile on growth | | | chart). | | - **Frontal Sinus | | | Enlargement**: Causes | - **Untreated Outcome**: Height | | prominent brow. | may exceed 8 feet, with | | | increased risk of | | - **Mandible Growth**: | **cardiomegaly** and **heart | | Leads to progressive | failure**. | | underbite (prognathism). | | | |  | | - Coarse facial features | | | (squaring of their jaw), | | | **skin tags**, and