1 Pathopharm II FINAL Exam SG Stress and Disease (4 Qs) Homeostasis: Constancy maintained by body during change; Steady Dynamic state of internal balance; Body uses adaptive responses that are efficient and effective; Not more than needed Feedback Mechanisms: Acts to restore the body’s homeostasis > Neg feedback [MUCH MORE COMMON]: Corrects deficit in system > Pos feedback [LESS COMMON]: Exaggerates original response; EX: Uterine Contractions Adaptation: Short-Term responses (GOOD) EX- Renin-angiotensin-aldosterone mechanism (to conserve water) & vasoconstriction…Long-term (BAD) EX- Cardiac remodeling, Hypertrophy or dilation of ventricles Selye’s General Adaptation Syndrome… 1. Alarm stage- Stimulation of SNS/HPA axis; Release of catecholamine’s (epinephrine/NE) & Cortisol (End result of this stage is the release of cortisol, because cortisol’s main job is to increase blood glucose levels) Locus ceruleus (in brain stem) causes release of norepinephrine (NE) and activation & regulation of SNS 2. Resistance- body selects most efficient and effective channel of defense; Body responds to stressor and attempts to return to homeostasis; Utilizes coping mechanisms… > Endocrine response: Increased levels of cortisol, glucagon, thyroid hormone, aldosterone; blood glucose > Immune system response: Immune suppression; Decreased T Lymphocytes; Makes susceptible to infection 3. Exhaustion (Or Recover: Exhaustion occurs if stressor is prolonged or overwhelms ability of body to defend itself; Resources depleted & Sx of systemic damage appear; Severe immunodeficiency; End-organ dysfunction (renal failure, heart failure); Onset of disease > Adaptive responses: blood glucose going up during stressful event > Maladaptive responses: weight gain, shortness of breath, psychological disturbances Disorders of Stress Response Acute stress: is time-limited; Sympathetic response; Headache, cold moist skin, stiff neck, increased heart rate; Increased alertness and cognition; Usually beneficial/lifesaving Chronic stress: Stress response not meant to be chronic; Failure of a component (hypothyroidism); Dysfunction of neural-hormone connections; Original stimulus prolonged or of overwhelming magnitude; Linked to many health disorders (diseases of CV, GI, immune, neuro, psych systems) Stress related disorders…Infections, Autoimmune, Neoplasia, HTN & CAD, Asthma, Renal failure, IBS, ulcers, Sleep disorders, depression, PTSD (differs from acute stress in that cortisol levels are decreased), RA, SLE Autonomic Nervous System (Patho 1 Q; Pharm 6 Qs) Sympathetic NS: Epinephrine & NE (Except for sweat glands & blood vessels, which use ACh); Various sphincters in urinary and GI system are contracted; Stimulates alpha (BVs, when binded they cause vasoconstriction, when bind w/ Ach, causes vasodilation)
2 beta (B1 found in heart, increase HR/CO when binded, B2 found in lungs, causes bronchodilation) Parasympathetic NS: Sphincters throughout body are relaxed, so food can move along alimentary canal; Increases smooth muscle tone (urinary bladder)!, so that digestive/elimination processes can take place. ADRENERGICS (Mimic Symp NS)…Avoid w/ pts who have/are: HTN (cause unsafe rise in BP [peripheral vasoconstriction]), Angina, Dysrhythmia, Narrow angle glaucoma (causes closure in filtration angle of eye), Pregnancy (b/c shunts blood flow to growing fetus), PVD…Are ONLY taken IV/IM/subQ not PO (b/c not absorbed in GI tract) Epinephrine- Nonspecific; Treats anaphylaxis, shock, cardiac arrest, bronchoconstriction to increase CO and blood flow, increase BP…AEs: dysrhythmias, HTN, excess CNS stimulation Norepinephrine (Levophed)- (IV drip) Stimulates alpha receptors (vasoconstriction and increase BP); Treats hypotension and shock…AE- severe decrease in blood flow to periphery, so need to check pulses in extremities & temp often Dopamine (Intropin): Low dose: increase renal blood…Medium dose: beta– increase heart rate & CO (positive inotropic)…High dose: alpha-vasoconstriction and increase in BP AEs: dysrhythmia, tachycardia, decreased blood flow periphery; If IV infiltrates tissue necrosis w/ extravasation (give Regitine (phentolamine) at site if IV infiltrates) ANTI-ADRENERGICS (SYMPATHOLYTICS)…Use: to treat hypertension… Prazosin (Minipress)- An Alpha-adrenergic antagonist; Occupy alpha-receptor sites on smooth muscle of BVs so cause vasodilatation; HTN med to Decrease BP; AEs: 1st dose effect: decrease BP & syncope due to orthostatic hypotension (give at bedtime; monitor BP; flushing) Propranolol (Inderal)- “Beta-Blockers”; Used to treat HF, HTN; Decreases BP and force of heart contraction; AEs: hypotension, bradycardia, bronchoconstriction (esp. for pts w/ asthma); Teach: Might be initial fatigue; Check pulse often CHOLINERGICS…Contraindications: Urinary/GI tract obstruction (b/c increase smooth muscle tone), Asthma (b/c or bronchoconstriction), PUD or IBD (b/c stimulates GI tract), Hyperthyroidism, Pregnancy (b/c increase smooth muscle (uterus) tone, affect fetus) Bethanecol (Urecholine)- Direct-stimulating (stimulate cholinergic receptors); Treats urinary retention and paralytic ileus; AE: n/v/d, bronchoconstriction, increased resp and oral secretions, bradycardia, decreased LOC (coma), pupil constriction (miosis) Neostigmine, Tensilon Mestinon, Physostigmine Indirect-acting [block acetylcholinesterase] drugs; These block the action of acetycholineasterase (which breaks down ACh in the synapse), increase the amount of ACh in the synapse b/c block the enzyme that breaks it down; Used in the treatment of Myasthenia Gravis (MG) ANTCHOLINERGICS…
3 Used for treating urinary incontinence (does this by decreasing bladder smooth muscle spasms); Used to treat bronchoconstriction, given inhalation (b/c has a bronchodilating effect, mostly for people w/ asthma, COPD); Treating s&s of Parkinson’s (tremors, salivation, tremors); Also used to treat motion sickness Atropine- to increase HR in symptomatic bradycardia and heart block; Used in emergency situations AE’s of Anticholinergic’s “Can’t see, pee, shit, spit”; Blurry vision, urinary incontinence, constipation, decreased sweating (can cause people to overheat, so wear cool clothing), dry mouth, cardiac issues CHOLINERGIC ANTIDOTE Atropine, and anticholinergic drug ANTCHOLINERGIC ANTIDOTEPhysostigmine, acts indirectly by blocking anticholinesterase (cholinergic) Myasthenic Crises Cholinergic crises Cause Exacerbation of MG due to Excessive anticholinesterase insufficient anticholinesterase meds in system (Toxicity ) meds or to stress or trauma overstimulation of PNS Common S&S Profound weakness, difficulty Same swallowing and with respirations Differences in Improve with Tensilon; Pupil No improvement with Tensilon symptoms dilation Pupil constriction * Will actually make it worse b/c will gives you more ACh in synapse) Treatment Increase anticholinesterase Stop anticholinesterase drugs drugs; resp support with and give Atropine as antidote; ventilator as needed resp support with vent as needed GI system (Patho: 6 Qs; Pharm: 6 Qs) Disorders of upper GI… GERD: Reflux in esophagus Gastritis: Inflamm of gastric mucosa…Acute gastritis (Transient, local irritant (ASA, NSAID, alcohol, MOs)self-limiting; Chronic gastritis (chronic epithelial changes); H. pylori Gastritis (US and international implications) H. pylori infection: Major cause of chronic gastritis worldwide; Treat w/ antibiotics & PPI or H2RA Peptic Ulcer Disease: Esophageal (least common), Gastric, and Duodenal ulcers (most common) > Stress ulcers- major physiologic stress response > Curling ulcers- Major trauma/severe illness; Increased cortisol levels > Cushing ulcers- Increased intracranial pressure, increased gastric acids (vagus stimulation) * ALL critically ill pts should be on prophylactic anti-ulcer med (for prevention of formation)
4 Mechanisms of nausea/vomiting: Stimuli from various sources cause stimulation of vomiting center in medulla Disorders of lower GI… IBS: unknown etiology, has emotional factor (treat w/ antidepressants as well as GI drugs); Relieved by defecation IBD (Crohn’s & UC): > Crohn’s- Granulomas; Submucosal; Affects all areas (targets ileum); Onset 20-30; Skip lesions, no blood diarrhea > UC- Mucosa, Rectal & Colon; High ESR; NO skip lesions; Starts teens, peaks 30’s; Risk for colon cancer Diverticulosis: High pressure, low fiber, sedentary, ignoring urge; Usually asymptomatic Diverticulitis: Inflamm of diverticula; Pain in LLQ; Can lead to perforation peritonitis Appendicitis: inflamm appendix, common age 5-30; Risk for peritonitis Intestinal obstruction: Caused by post-op adhesion, strictures, tumors, intussusception, volvulus, paralytic ileus Peritonitis: Acute inflamm of peritoneum, caused by bac (organ rupture, or wound) or chemical irritation Disorders of Gallbladder and Pancreatic function … Cholelithiasis- Gallstones, FAT, FAIR, FORTY, FEMALE; May have no S&S; S&S occur when stones obstruct bile flow Cholecystitis: Inflamm of gallbladder; R/T obstruction of GB outlet from gallstones; Surgical correction > Acute cholecystisis- Caused by stones blockage, Abrupt onset of pain; requires quick medical treatment > Chronic cholecystisis- repeated, unresolved episodes; S&S vague (intolerance of fatty foods, colicky pain) >> Blocked duct S&S= Jaundice, clay colored stools; Dark colored urine; Pruritus; Steatoherra, Bleeding issues Pancreatitis: Blockage/stenosis/tumor of pancreatic duct causes pancreatic enzymes to be activated in pancreas (autodigestion) and damage/destroy its tissue); Can lead to… Calcium deposits in pancreas…Hypovolemia…SIDS…Acute resp distress syndrome (watch 02 sat) Disorders of Hepatic Function… Chronic Hepatitis: Lasts > 6mos; increased LFTs; Caused by HBV, HCV; Main cause of liver cancer/cirrhosis Hepatitis A (HAV): Benign; Self-limited (no carrier or chronic states); Fecal-oral transmission; Common in kids Hepatitis B (HBV): Serious infection; Blood/bodily fluid transmission; Vaccine available (For hep A also) Hepatitis C (HCV): Serious; Most common cause of chronic hep, carrier, cancer, cirrhosis; Blood bodily fluid trans; 60-70% asymptomatic, but can transmit; No vaccine available Hepatitis D: Requires co-infection with Hep B (Increases severity of Hep B)
5 Hepatitis E: Serious acute; Fecal-oral transmission; Rare in US; 20% mortality in preg women=fulminant hepatitis Chronic Viral Hepatitis: Caused by Hep B, C, D; Principal cause of chronic liver disease, cirrhosis, and hepatocellular (liver) cancer in the world; Chief reason for liver transplantation in adults Autoimmune Hepatitis: Chronic/progressive; Multifactorial (elevated serum Igs, genetic, environmental factors) Liver Failure… Acute: lasts 26 wks (6mos) or less; mortality up to 80%; Predisposes to chronic liver failure; Massive necrosis; Enlarged during initial inflammatory phase and later atrophies Causes: MOST COMMON= Acetaminophen toxicity (intentional and non-intentional); Idiosyncratic drug reactions; Viruses: Hepatitis, Herpes simplex, Epstein-Barr, CMV; Ischemia, malignancies (liver cancer) Manifestations: Fatigue/weakness, anorexia, malaise, Jaundice, dark urine, lightcolored stools, Itching, RUQ abd pain, Bloating…Later s/s: Hyperventilation w/ resp. failure; Hepatic encephalopathy; Coagulopathies; Hypoglycemia; Hepatorenal syndrome Fatty liver disease – 1st stage…accum. of fat in hepatocytes (steatosis) Alcoholic hepatitis: Intermediate stage between fatty changes and cirrhosis; Seen after abrupt increase in alcohol consumption; Anorexia, pain, fever, jaundice, ascites; Progression & severity is directly r/t severity of liver injury Alcoholic cirrhosis- End stage liver failure Nonalcoholic Fatty Liver Disease (NAFLD): Accumulation of fat in the hepatocytes inflammation w/ liver degeneration/fibrosis; Can be r/t fat, hormonal…Associated with= Obesity, Type 2 diabetes, dyslipidemia, rapid weight loss…Tx: Moderate pace wt. loss, correct underlying conditions Cirrhosis: End stage of chronic liver disease; liver tissue is replaced by fibrous tissue; Often no sympts until disease is advanced; Caused= chronic alcoholism, hepatitis, biliary obstruction, hemochromatosis (iron overload) Liver Disease Complications… Portal Hypertension: Increase pressure in BVs that flow to liver associated w/ cirrhosis; Back up of blood causes…engorgement spleen & veins in esophagus (varices) & stomach (ascites); Rx: beta-blockers, diuretics, paracentesis Ascites: Incr. fluid in peritoneal cavity; Caused by… Portal HTN, Decreased protein production, Hypovolemia Hepatic Encephalopathy: liver’s loss of ability to detoxify blood; Ammonia accumulates in blood and brain cells; Flapping tremors (asterixis); Treat w/ low protein diet and Cephulac (Lactulose) Esophageal Varices: : Increased pressure causes collateral channels to develop with veins Risk for rupturemassive hemorrhage; Replace clotting factors, Beta-blockers; TIPS (shunt/stent) GI drugs ACID BLOCKERS… Antacids: Local action; aluminum hydroxide (Mylanta)- Alum= Adverse Constipation; Give 1-2 hrs before or after other meds (binds)