6010 Exam 2 Study Guide

Understand general concept of oxygen transport.

Approximately 1000 ml (1 L) of oxygen is transported to the cells each minute. Oxygen is transported in the blood in two forms. A small amount dissolves in plasma, and the remainder binds to hemoglobin molecules. Without hemoglobin, oxygen would not reach the cells in amounts sufficient to maintain normal metabolic function. Diffusion Across the Alveolocapillary Membrane The alveolocapillary membrane is the ideal medium for oxygen diffusion, because it has a large total surface area and is very thin. In addition, the partial pressure of oxygen molecules (PO2) is much greater in alveolar gas than in capillary blood, a condition that promotes rapid diffusion down the concentration gradient from the alveolus into the capillary. The amount of oxygen in the alveoli (PAO2) depends on the amount of oxygen in the inspired air and on the amount of air that remains in the alveoli and tracheobronchial tree between breaths (physiologic dead space). Determinants of Arterial Oxygenation As oxygen diffuses across the alveolocapillary membrane, it dissolves in the plasma, where it exerts pressure (the partial pressure of oxygen in arterial blood, or PaO2). As the PaO2 increases, oxygen moves from the plasma into the red blood cells (erythrocytes) and binds with hemoglobin molecules. Oxygen continues to bind with hemoglobin until the hemoglobin binding sites are filled or saturated. Oxygen then continues to diffuse across the alveolocapillary membrane until the PaO2 and PAO2 equilibrate, eliminating the pressure gradient across the alveolocapillary membrane. At this point diffusion ceases. Because hemoglobin transports all but a small fraction of the oxygen carried in arterial blood, increases in hemoglobin concentration affect the oxygen content of the blood. Decreases in hemoglobin concentration below the normal value of 15 ml/dl of blood reduce oxygen content, and increases in hemoglobin concentration may minimize the effect of impaired gas exchange. In fact, an increase in hemoglobin concentration is a major compensatory mechanism in pulmonary diseases that impair gas exchange. For this reason, measurement of hemoglobin concentration is important in assessing individuals with pulmonary disease. If cardiovascular function is normal, the body's initial response to low oxygen content is to accelerate cardiac output. In individuals who also have cardiovascular disease, this compensatory mechanism does not work, making increased hemoglobin concentration an even more important compensatory mechanism.

Understand etiology and pathophysiology of bronchopulmonary dysplasia.

Chronic lung disease of prematurity Caused by premature birth, immature lungs, infections, genetics About 20% to 30% of very low and extremely low birth weight infants develop BPD Clinical manifestations includes the need for supplemental oxygen at 36 weeks of postmenstrual age (estimated time of conception to birth plus weeks since birth) and for at least 28 days after birth, with a graded severity dependent on required respiratory support at term (divided into mild, moderate, and severe based on oxygen requirements and ventilatory needs). Clinically, the infant exhibits hypoxemia caused by ventilation-perfusion mismatch and diffusion defects. Work of breathing is elevated, resulting in hypercapnia. The ability to feed may be impaired. Intermittent bronchospasm with wheezing, mucus plugging, and pulmonary hypertension characterizes the clinical course of the most severely affected babies. Evaluation and Treatment: Infants with severe BPD require prolonged, assisted ventilation with cautious weaning. Prevention of lung damage with "gentle ventilation" or early nasal CPAP, or both, is used in clinical situations when permitted. Diuretics are used to control pulmonary edema, bronchodilators reduce airway resistance, and inhaled corticosteroids improve the rate of extubation and reduce the time that mechanical ventilation is required. Caffeine citrate is used to prevent apnea and for neuroprotection. Supplementation with vitamin A provides antioxidant protection and stimulates lung growth and surfactant production. Careful nutritional and fluid and electrolyte support is routinely used and has resulted in improved outcomes.

Understand clubbing

Clubbing is the selective bulbous enlargement of the end (distal segment) of a digit (finger or toe) whose severity can be graded from 1 to 5 based on the extent of nail bed hypertrophy and the amount of changes in the nails themselves. It is usually painless. Clubbing is commonly associated with diseases that interfere with oxygenation, such as bronchiectasis, cystic fibrosis, pulmonary fibrosis, lung abscess, and congenital heart disease. It is rarely reversible with treatment of the underlying pulmonary condition. It can sometimes be seen in individuals with lung cancer even without hypoxemia, because of the effects of inflammatory cytokines and growth factors (hypertrophic osteoarthropathy).

Know and understand different causes of hypoxemia

Hypoxemia, or reduced oxygenation of arterial blood (reduced PaO2), is caused by respiratory alterations, whereas hypoxia, or reduced oxygenation of cells in tissues, may be caused by alterations of other systems as well. Hypoxemia results from problems with one or more of the major mechanisms of oxygenation: 1. Oxygen delivery to the alveoli a. Oxygen content of the inspired air (FiO2) 2. Ventilation of the alveoli 3. Diffusion of oxygen from the alveoli into the blood a. Balance between alveolar ventilation and perfusion (V/Q mismatch) b. Diffusion of oxygen across the alveolocapillary membrane 4. Perfusion of pulmonary capillaries Clinical manifestations of acute hypoxemia may include cyanosis, confusion, tachycardia, edema, and decreased renal output.

Understand pathophysiology including risk factors for reactivation of tuberculosis infection as well as clinical manifestations.

Infection caused by Mycobacterium tuberculosis, an acid-fast bacillus that usually affects the lungs, but may invade other body systems. TB is the leading cause of death from a curable infectious disease throughout the world. TB cases increased greatly during the mid-1990s because of AIDS. Individuals with AIDS are highly susceptible to respiratory tract infections, including multidrug-resistant TB. Pathophysiology TB is highly contagious and is transmitted from person-to-person in airborne droplets. Host susceptibility to infection is influenced by host and parasite genetic polymorphisms. In immunocompetent individuals, the microorganism usually is contained by the inflammatory and immune response systems, and latent TB infection (LTBI) develops with no clinical evidence of disease. Microorganisms lodge in the lung periphery, usually in the upper lobe. Once the bacilli are inspired into the lung, they multiply and cause nonspecific pneumonitis (lung inflammation). Some bacilli migrate through the lymphatics and become lodged in the lymph nodes, where they encounter lymphocytes and initiate the immune response. Inflammation in the lung causes neutrophils and macrophages to migrate to the area. These cells are phagocytes that engulf the bacilli and begin the process by which the body's defense mechanisms isolate the bacilli, preventing their spread. However, the bacterium is successful as a pathogen because it can survive within macrophages, resist lysosomal killing, multiply within the cell, form well-organized granulomas creating a confined environment, terminate its own central metabolism, stop replication, and transit into a stage of dormancy rendering itself extremely resistant to host defense and drug treatment. In defense, macrophages and lymphocytes release interferon, which inhibits the replication of the microorganisms and stimulates more macrophages to attack the bacterium. Apoptotic infected macrophages also can activate cytotoxic T cells (CD8). Neutrophils, lymphocytes, and macrophages seal off the colonies of bacilli, forming a granulomatous lesion called a tubercle. Infected tissues within the tubercle die, forming cheeselike material called caseation necrosis. Collagenous scar tissue then grows around the tubercle, completing isolation of the bacilli. The immune response is complete after about 10 days, preventing further multiplication of the bacilli. Once the bacilli are isolated in tubercles and immunity develops, TB may remain dormant for life. If the immune system is impaired, progressive active disease occurs and may spread through the blood and lymphatics to other organs. *Infection with human immunodeficiency virus (HIV) is the single greatest risk factor for reactivation of tuberculosis infection.* Cancer, immunosuppressive medications, poor nutritional status, renal failure, and other debilitating diseases can reactivate disease. Clinical Manifestations Latent TB infection is asymptomatic. Symptoms of active disease develop so gradually that they are not noticed until the disease is advanced. However, symptoms can appear in immunosuppressed individuals within weeks of exposure to the bacillus. Common clinical manifestations include fatigue, weight loss, lethargy, anorexia (loss of appetite), a low-grade fever that usually occurs in the afternoon, and night sweats. (These are common signs and symptoms of all chronic infections.) A cough that produces purulent sputum develops slowly and becomes more frequent over several weeks or months. Dyspnea, chest pain, and hemoptysis also may occur as the disease progresses. Extrapulmonary TB disease is common in HIV-infected individuals and may cause neurologic deficits, meningitis symptoms, bone pain, and urinary symptoms. Evaluation and Treatment TB is diagnosed by a positive tuberculin skin test (TST; purified protein derivative [PPD]), sputum culture, immunoassays, and chest radiographs. A positive tuberculin skin test indicates the need for yearly chest radiographs to detect active disease. The skin test does not differentiate between past, latent, or active forms of the disease. Chest radiographs of individuals with current or previous active disease demonstrate characteristic changes. Nodules, calcifications, cavities, and hilar enlargement (enlarged mediastinal lymph nodes) commonly are seen in the upper lobes. Prevention of tuberculosis infection is a complex challenge. Isolating individuals with active tuberculosis, limiting use of immunosuppressive medications, and treating underlying immunocompromising diseases, such as AIDS, are all critical steps. Development of an effective TB vaccine has been elusive and vaccines are currently in clinical development.

90% of water is absorbed where?

Small intestine

Understand the different types of inflammatory bowel disease

Ulcerative Colitis • Chronic inflammatory disease that causes ulceration of the colonic mucosa Sigmoid colon and rectum Suggested causes • Infectious, immunologic, dietary, genetic (supported by family studies and identical twin studies) • Young adults usually affected • More common in Caucasians Manifestations Frequent stools - water, mucus, blood, *weight loss* Crohn Disease • Granulomatous colitis, ileocolitis, or regional enteritis • Idiopathic inflammatory disorder; affects any part of the digestive tract, from mouth to anus • Causes "skip lesions" • Ulcerations can produce longitudinal and transverse inflammatory fissures that extend into the lymphatics • Anemia may result due to malabsorption of vitamin B12 and folic acid Manifestations: Weight loss, irritable bowel type symptoms, diarrhea, abdominal pain Treatment is similar to ulcerative colitis Smoking can lead to Crohn's but not colitis ---------- Ulcerative colitis and Crohn disease are chronic, relapsing inflammatory bowel diseases (IBDs) of unknown origin. Both diseases are associated with genetic factors, alterations in epithelial cell barrier functions, immunopathology related to abnormal T-cell reactions to commensal microflora and other luminal antigens, and varying phenotypes. Ulcerative Colitis Ulcerative colitis (UC) is a chronic inflammatory disease that causes ulceration of the colonic mucosa and extends proximally from the rectum into the colon. The lesions appear in susceptible individuals between 20 and 40 years of age. Risk factors include family history of disease or Jewish descent, and the disease is more prevalent among white populations and Northern Europeans. UC is less common in smokers. Although the cause of UC is unknown, dietary, infectious, genetic, and immunologic factors are all suggested causes. Inflammation may be caused by commensal or pathogenic enteric microorganisms with increased mucosal adherence and invasion and persistent activation of T cells. Pathophysiology The primary lesions of UC are continuous with no skip lesions, are limited to the mucosa, and are not transmural. The mucous layer is thinner than normal and there is impairment of the epithelial barrier. The rectum is almost always involved. Inflammation begins at the base of the crypt of Lieberkühn in the large intestine, primarily the left colon, with infiltration and release of inflammatory cytokines from neutrophils, lymphocytes, plasma cells, macrophages, eosinophils, and mast cells. Activated macrophages also contribute cytokines that cause fever and the acute phase response. The inflammation damages the epithelial mucosal barrier with leak of fluids into the gut. The disease is most severe in the rectum and sigmoid colon. With milder inflammation, the mucosa is hyperemic and edematous, and may appear dark red and velvety. In more severe inflammation, the mucosa becomes hemorrhagic, and small erosions form and coalesce into ulcers. Abscess formation occurs in the crypts. Necrosis and ragged ulceration of the mucosa ensue. Edema and thickening of the muscularis mucosae may narrow the lumen of the involved colon. In chronic disease, inflammatory polyps (pseudopolyps) develop in the colon from rapidly regenerating epithelium. Clinical Manifestations The course of UC consists of intermittent periods of remission and exacerbation. Clinical manifestations vary with the severity and extent of disease. Loss of the absorptive mucosal surface and decreased colonic transit time can cause large volumes of watery diarrhea. Mucosal destruction causes bleeding, cramping pain, and an urge to defecate. There is frequent bloody diarrhea with passage of purulent mucus. Mild UC involves less mucosa and may be limited to proctitis, so that frequency of bowel movements, bleeding, and pain is minimal. Severe forms may involve the entire colon (pancolitis) and are characterized by fever, elevated pulse rate, frequent diarrhea (10 to 20 movements per day), urgency, obviously bloody stools, and continuous crampy pain. Dehydration, weight loss, anemia, and fever result from fluid loss, bleeding, and inflammation. Complications include toxic megacolon, anal fissures, hemorrhoids, and perirectal abscess. Severe hemorrhage is rare, but chronic blood loss may precipitate hypotension and shock. Edema, strictures, or fibrosis can obstruct the colon. Perforation is an unusual but possible complication. The risk of left-sided colon cancer increases significantly after many years of ulcerative colitis and the presence of primary sclerosing cholangitis. Evaluation and Treatment Diagnosis of ulcerative colitis is based on the medical history, clinical manifestations, imaging procedures, and histologic criteria. Endoscopic evaluation shows an inflamed and hemorrhagic mucosa. Radiologic assessment may show loss of haustra, ulceration, and irregular mucosa. The laboratory data include low hemoglobin values, hypoalbuminemia, and low serum potassium levels. Infectious causes are ruled out by stool culture. The symptoms of ulcerative colitis can be very similar to those of Crohn disease, and serological markers may be used for differential diagnosis. First-line therapy is 5-aminosalicylic acid (mesalazine). Corticosteroids and salicylates suppress the inflammatory response and help alleviate the cramping pain. Immunosuppressive agents are used for chronic active disease. Broad-spectrum antibiotics may induce remission. For unknown reasons, nicotine may have a protective effect in ulcerative colitis but not in Crohn disease. Severe, unremitting disease can require hospital admission and administration of intravenous fluids. Extreme malnutrition may require intravenous hyperalimentation. Surgical resection of the colon or a colostomy may be performed if other forms of therapy are unsuccessful. Crohn Disease (granulomatous colitis, ileocolitis, or regional enteritis) is an idiopathic inflammatory disorder that affects any part of the gastrointestinal tract from the mouth to the anus. The distal small intestine and proximal large colon are most commonly affected by the disease. In a small percentage of cases, CD is difficult to differentiate from ulcerative colitis. Risk factors include family history, smoking, Jewish ethnicity, urban residency, age less than 40 years, and a slight predominance in women. The CARD15/NOD2 (nucleotide-binding-oligomerization-domains) gene mutations have the strongest association with CD (35% to 45% of cases) although many other genes have been identified. The CARD15 /NOD2 genes code for a protein (a Toll-like receptor) involved in the recognition of gram-negative and gram-positive bacteria. The pathogenesis of CD may be associated with an overly aggressive response to normal flora bacteria in genetically predisposed individuals. Th1-mediated inflammation with activation of leukocytes and cytokines causes injury. Recruited leukocytes release proinflammatory substances, including prostaglandins, leukotrienes, proteases, reactive oxygen species, and nitric oxide, which cause further injury and inflammation. Elevations in IgG levels are associated with severity of disease. Pathophysiology The inflammatory process of CD begins in the intestinal submucosa and spreads across the intestinal wall to involve the mucosa and serosa in areas overlying lymphoid tissue. Progression of the disease involves neutrophil infiltration of the crypts, resulting in abscess formation and crypt destruction. The most common site of the disease is the ileocolon, but both the large and small intestines may be involved. The inflammation can affect some haustral segments but not others, creating a pattern called skip lesions. One side of the intestinal wall may be affected but not the other. The ulcerations of CD produce longitudinal and transverse fissures that extend inflammation into lymphoid tissue. The typical chronic lesion is a granuloma having cobblestone projections of inflamed tissue surrounded by areas of ulceration. The lumen can narrow with inflammation, edema, and fibrotic strictures. Fistulae may form in the perianal area between loops of intestine or extend into the bladder. Clinical Manifestations Individuals with CD may have no specific symptoms other than an "irritable bowel" for several years. Symptoms vary and are associated with disease location. Abdominal pain and diarrhea are the most common signs (more than five stools per day), with passage of blood and mucus. Diarrhea can result from decreased colonic absorption, bypass fistulae, medications, bacterial overgrowth, and the presence of bile in the colon that inhibits water absorption. Other manifestations are related to the location and extent of intestinal involvement. Inflammation of the ileum, for example, causes tenderness in the lower right side of the abdomen. If the ileum is involved, the individual may be anemic as a result of malabsorption of vitamin B12. There also may be deficiencies in folic acid, vitamin D absorption, and calcium leading to bone disease. Proteins may be lost, leading to hypoalbuminemia. Weight loss is common. Anal manifestations occur in about 30% of cases, including anal fissure, perianal abscess, and fistula. Individuals with CD of long duration are also at risk for intestinal adenocarcinoma. Complications include obstruction, fistulae, abscess formation, and chronic blood loss. Extraintestinal manifestations are similar to those described for UC. Evaluation and Treatment The diagnosis and treatment of CD are similar to the diagnosis and treatment of ulcerative colitis. Treatment with immunomodulatory agents can be effective. TNF-α-blocking agents are used for treatment of fistulae and to maintain remission. Surgery is generally performed to manage complications such as strictures, fistulae, abscesses, and perforation, or to relieve obstruction. When treatment involves surgical resection of small intestinal segments, complications related to short bowel syndrome can occur, including malabsorption, diarrhea, and nutritional deficiencies. Symptoms are related to the extent and location of resection.

Tubuloglomerular feedback

(sodium chloride [NaCl] content) When sodium filtration increases, GFR needs to be decreased. Macula densa cells stimulate afferent arteriolar vasoconstriction. When sodium filtration decreases, the opposite is true — GFR needs to be increased. --- Tubuloglomerular feedback is a second mechanism for keeping renal blood flow and GFR constant and stable. As the GFR in an individual nephron increases or decreases, the macula densa cells in the distal tubule sense the increasing or decreasing amounts of filtered sodium. When sodium filtration increases, the macula densa cells stimulate afferent arteriolar vasoconstriction to decrease GFR. The opposite occurs with decreases in sodium filtration at the macula densa. --- When we have an increased delivery of sodium and water to the distal tubule (which can occur when increased arterial pressure causes a rise in GFR), the MACULA DENSA sends a chemical signal (ATP) causing constriction of the afferent arteriole. This reduces GFR so that less fluid enters the nephron tubules, a response that protects the late distal tubule and cortical collecting duct from being overloaded.

Intestines are colonized at what age?

3-4 weeks after birth Normally with e coli and Strep

Factors associated with Primary HTN

A combination of genetic and environmental factors is thought to be responsible for the development of primary hypertension. Genetic predisposition to hypertension is thought to be polygenic. The inherited defects are associated with renal sodium excretion, insulin and insulin sensitivity, activity of the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS), and cell membrane sodium or calcium transport. In blacks, variants of the apolipoprotein L1 (APOL1) gene are associated with hypertension and renal disease. *Risk factors associated with primary hypertension include*: 1. family history of hypertension 2. advancing age 3. gender (men older than 55 and women older than 70 years) 4. black race 5. high dietary sodium intake 6. glucose intolerance (diabetes mellitus) 7. cigarette smoking 8. obesity 9. heavy alcohol consumption 10. low dietary intake of potassium, calcium, and magnesium. Many of these factors are also risk factors for other cardiovascular disorders. In fact, hypertension, dyslipidemia, and glucose intolerance often are found together in a condition called *metabolic syndrome*. Although populations with high dietary sodium intake have long been shown to have an increased incidence of hypertension, recent studies indicate that low dietary potassium, calcium, and magnesium intakes are also risk factors because without their intake, sodium is retained. The nicotine in cigarette smoke is a vasoconstrictor that can elevate systolic and diastolic blood pressure acutely. In habitual smokers an individual cigarette may not raise blood pressure, yet habitual smoking is associated with a high incidence of severe hypertension, myocardial hypertrophy, and death resulting from coronary artery disease (CAD). The incidence of hypertension is higher among heavy drinkers of alcohol (more than three drinks per day) than among abstainers, but moderate drinkers (two to four drinks per week) appear to have the lowest average blood pressures and cardiovascular mortality. Obesity is recognized as an important risk factor for hypertension, even in children and adolescents.

Left main coronary artery

Arises from left ostium and has 2 main branches 1. Anterior interventricular artery [Left anterior descending artery (LAD)]: Supplies interventricular septum and portions of the right and left ventricle 2. Circumflex artery: Supplies left atrium and left lateral wall of left ventricle. Travels in the coronary sulcus Occlusion of LCA or L Main will occlude septum and entire left ventricle Occlusion of the LAD will be an anteroseptal MI Occlusion of the L Circumflex will be a lateral MI (lateral edge of l ventricle, blood supply to L atrium as well)

Pathology of gastric, peptic and duodenal ulcers, how they are different and where they occur in the GI system

A peptic ulcer is a circumscribed area of mucosal inflammation and ulceration caused by excessive secretion of gastric acid, disruption of the protective mucosal barrier, or both. The three types of peptic ulcers are duodenal, gastric, and stress ulcers and they are usually caused by H. pylori infection or NSAIDs. Duodenal ulcers, the most common peptic ulcers, are associated with increased numbers of parietal (acid-secreting) cells in the stomach, elevated gastrin levels, and rapid gastric emptying. Pain occurs when the stomach is empty, and pain is relieved with food or antacids. Duodenal ulcers tend to heal spontaneously and recur frequently. - Pain up to 3 hours after eating, takes time to get down to the duodenum Gastric ulcers develop near parietal cells, generally in the antrum, and tend to become chronic. Gastric secretions may be normal or decreased, and pain may occur after eating (30 mins - 1hr). Zollinger-Ellison syndrome is associated with a gastrinoma, chronic secretion of gastric acid, and gastric and duodenal ulcers. Stress ulcer (stress-related mucosal disease) is an acute form of peptic ulcer associated with severe illness or extensive trauma. Ischemic stress ulcers develop suddenly after severe illness, systemic trauma, neural injury, or burns (Curling ulcer). Ulceration follows mucosal damage caused by ischemia (decreased blood flow to the gastric mucosa). Above falls under Peptic Ulcer Disease which is defined as: A break or ulceration in the protective mucosal lining of the lower esophagus, stomach, or duodenum • Causes - H. Pylori, NSAIDs • H. Pylori: Gram negative spiral bacteria, present in ~50% of the population, causes general inflammation and inhibits somatostatin (which would normally decrease stomach acid) • NSAIDS: Block prostaglandins which are responsible for building up mucosal barrier. Stomach is more vulnerable to acid • Can be acute or chronic ulcers • Superficial: Erosions • Deep (mucosa and submucosa): True ulcers

Portal HTN

Abnormally high blood pressure in the portal venous system due to resistance to portal blood flow Prehepatic: Portal thrombosis Intrahepatic: Cirrhosis or cancer Posthepatic: R ventricular failure Consequences Varices in LE, stomach, rectum Splenomegaly Ascites Hepatic encephalopathy: Liver is not able to filter ammonia out

3 things that stimulate acid secretion

Acetylcholine, histamine, and Gastrin

Right coronary artery

Arises from right sinus Right coronary artery follows the right atrioventricular groove Supplies the right atrium, right ventricle, bottom portion of both ventricles and back of the septum The sinoatrial and atrioventricular nodes are supplied by branches of the right coronary artery In 80-90% of individuals, the RCA supplies the posterior interventricular artery (aka posterior descending artery) -- supplies the posterior (aka posterior descending artery) and inferior walls of the left ventricle if "right dominant". Blockage of the RCA will impact the Right atrium, Right ventricle, SA nodes and AV nodes..

Understand how ischemia and nephrotoxins may induce acute tubular necrosis (ATN)

Acute tubular necrosis (ATN) caused by ischemia is the most common cause of intrarenal AKI. It occurs most often after surgery/CONTRAST DIES (40% to 50% of cases) but is also associated with severe sepsis; obstetric complications; and severe trauma, including severe burns; or small vessel vasculitis. A combination of events and predisposing factors leads to the greatest risk for acute renal failure. ATN is generally described as postischemic or nephrotoxic or it can be a combination of both. Postischemic ATN involves persistent hypotension, hypoperfusion, and hypoxemia, producing ischemia and reduced levels of ATP and generating toxic oxygen-free radicals with loss of antioxidant protection that causes cell swelling, injury, and necrosis. Activation of inflammatory cells (e.g., neutrophils, macrophages, and lymphocytes) and complement and release of inflammatory cytokines contribute to tubular injury. Transport of sodium and other molecules is disrupted with damage primarily to the proximal tubular epithelium and shedding of the brush border with the appearance of tubular granular casts in the urine. Ischemic necrosis tends to be patchy and may be distributed along any part of the nephron tubules. Injury is most severe in the outer medulla with scattered necrosis in the cortex and loss of cells along the tubular epithelium. Severe disease of the glomeruli (i.e., acute or rapidly progressive glomerulonephritis) or renal microvascular disorders can also cause intrinsic kidney injury. Oliguria is common (urine output less than 30 ml/hour).

Necrosis

After about 20 minutes of myocardial ischemia, irreversible hypoxic injury causes cellular death and tissue necrosis. Necrosis of myocardial tissue results in the release of certain intracellular enzymes through the damaged cell membranes into the interstitial spaces. The lymphatics pick up the enzymes and transport them into the bloodstream, where they can be detected by serologic tests. Recent evidence has found that along with necrosis myocardial tissue also is destroyed by the tightly controlled process of apoptosis.

The role of different hormones such as epinephrine and angiotensin II after a myocardial infarction

After an MI, Epinephrine and Norepinephrine are activated. RAAS system is activated. Angiotensin II is potent, vasoconstrictor of peripheral arteries and will remodel the vessels to get blood back to the heart. Could become permanent vascular resistance. Endothelial dysfunction and platelet aggregation can also occur. Called negative remodeling. Can reverse and create positive remodeling with drugs Epi- and Nore- will increase HR and contractility, hypertrophy will occur and could cause HF.

Types of liver cirrhosis

Alcoholic → most common Oxidation of alcohol damages hepatocytes Non-alcoholic liver disease NAFLD (non-alcoholic fatty liver disease), can progress to NASH (non-alcoholic steatohepatitis). Commonly occurs with obesity, so try to lower cholesterol/lose weight Biliary (bile canaliculi) - less common • Cirrhosis begins in canaliculi and ducts • Primary biliary cirrhosis (autoimmune) • Secondary biliary cirrhosis (obstruction) • Chronic pancreatitis Post-necrotic Consequence of chronic disease

Aneurysm types and differences between them

An aneurysm is a localized dilation or outpouching of a vessel wall or cardiac chamber. *True aneurysms* involve all three layers of the arterial wall and are best described as a weakening of the vessel wall. Most are: 1. fusiform 2. circumferential. *False aneurysm* is an extravascular hematoma that communicates with the intravascular space. A common cause of this type of lesion is a leak between a vascular graft and a natural artery. Saccular aneurysms are basically spherical. Arteriosclerosis and hypertension are found in more than half of all individuals with aneurysms. Chronic hypertension results in mechanical and shear forces that contribute to remodeling and weakening of the vessel wall. Atherosclerosis is a common cause of aneurysms because plaque formation erodes the vessel wall. Infections, such as syphilis, collagen disorders (such as Marfan syndrome), and traumatic injury to the chest or abdomen, also can cause aortic aneurysms. Genetic susceptibilities have been identified including gene polymorphisms for the production of growth factors, myosin, and proteases. Inflammation (with the production of toxic oxygen radicals) and changes in cytokines, such as TGF-β, activate matrix degrading proteins and smooth muscle cell apoptosis resulting in loss of medial elastic lamellae and thinning of the tunica media. Aneurysms most commonly occur in the thoracic or abdominal aorta. The aorta is particularly susceptible to aneurysm formation because of constant stress on the vessel wall and the absence of penetrating vasa vasorum in the media layer. The prevalence of abdominal aortic aneurysms 2.9 to 4.9 cm in diameter ranges from 1.3% in men 45 to 54 years of age to 12.5% in men 75 to 84 years of age. For women, the prevalence ranges from zero in the youngest to 5.2% in the oldest age group.5 The prevalence of aneurysms has decreased in men ages 65 years and older likely because of improvements in risk factor management. Formation of a ventricular wall aneurysm occurs when intraventricular tension stretches the noncontracting infarcted muscle. The stretching produces infarct expansion, a weak and thin layer of necrotic muscle, and fibrous tissue that bulges with each systole. With time the aneurysm becomes more fibrotic but continues to bulge with each systole, thus acting as a "reservoir" for some of the stroke volume. Clinical manifestations depend on where the aneurysm is located. Aneurysms in the heart present with dysrhythmias, heart failure, and embolism of clots to the brain or other vital organs. Aortic aneurysms often are asymptomatic until they rupture, when they become painful. Symptoms of dysphagia (difficulty in swallowing) and dyspnea (breathlessness) are caused by the pressure of a thoracic aneurysm on surrounding organs. An abdominal aneurysm can impair flow to an extremity and cause symptoms of ischemia. Aneurysms that occur elsewhere in the body have variable symptoms and signs related to the size of the aneurysm and the potential for rupture and hemorrhage. The diagnosis of an aneurysm is usually confirmed by ultrasonography, CT, MRI, or angiography. The goals of medical treatment of aneurysms are to maintain a low blood volume and low blood pressure to decrease mechanical forces thought to contribute to vessel wall dilation. Medical treatment is indicated for slow-growing aortic aneurysms, particularly in early stages, and includes smoking cessation, reducing blood pressure and blood volume, and β-adrenergic blockage. For those aneurysms that are dilating rapidly, surgical treatment often is indicated. Surgery or endovascular repair should be done when aortic aneurysms reach 5 cm in diameter. The risk for eventual rupture approaches 20% for abdominal aortic aneurysms greater than 5 cm, and greater than 50% for aneurysms more than 7 cm in diameter. New endovascular surgical techniques with placement of a stent make aneurysm repair possible even in those individuals with acute symptoms or complications. Aortic aneurysms can be complicated by the acute aortic syndromes that include aortic dissection, hemorrhage into the vessel wall, or vessel rupture. Aortic dissection is a devastating complication that can involve any part of the aorta (ascending, arch, or descending) and can disrupt flow through arterial branches, thus creating a surgical emergency. Dissection of the layers of the arterial wall occurs when there is a tear in the intima and blood enters the wall of the artery. This occurs most commonly when there is trauma to the aorta or when there is tissue ischemia and necrosis at the edge of an atherosclerotic plaque that weakens the intima. Persistent chronic hypertension and inflammation contribute to further degradation of the vessel wall with fibrotic obstruction of vessels that feed the arterial wall. Emergent evaluation and surgical intervention are indicated.

Stable angina

Angina pectoris is chest pain caused by myocardial ischemia. Stable angina is caused by gradual luminal narrowing and hardening of the arterial walls, so that affected vessels cannot dilate in response to increased myocardial demand associated with physical exertion or emotional stress. If demand is decreased, no necrosis of myocardial cells results. Angina pectoris is typically experienced as transient substernal chest discomfort, ranging from a sensation of heaviness or pressure to moderately severe pain. Individuals often describe the sensation by clenching a fist over the left sternal border. The discomfort may be mistaken for indigestion. The pain is caused by the buildup of lactic acid or abnormal stretching of the ischemic myocardium that irritates myocardial nerve fibers. These afferent sympathetic fibers enter the spinal cord from levels C3 to T4, accounting for the variety of locations and radiation patterns of anginal pain. Pain may radiate to the neck, lower jaw, left arm, and left shoulder or occasionally to the back or down the right arm. Pallor, diaphoresis, and dyspnea may be associated with the pain. The pain is usually relieved by rest and nitrates; *lack of relief indicates an individual may be developing infarction.* Myocardial ischemia in women may not present with typical anginal pain. Common symptoms in women include atypical chest pain, palpitations, sense of unease, and severe fatigue. Similarly, in individuals who have autonomic nervous system dysfunction, such as older adults or those with diabetes, angina may be mild, atypical, or even silent.

Most common cause of CAD

Atherosclerosis

The effects atherosclerosis has on the cardiovascular system and why

Atherosclerosis is a form of arteriosclerosis in which thickening and hardening of the vessel are caused by the accumulation of lipid-laden macrophages within the arterial wall, which leads to the formation of a lesion called a plaque. Atherosclerosis is not a single disease but rather a pathologic process that can affect vascular systems throughout the body, resulting in ischemic syndromes that can vary widely in their severity and clinical manifestations. It is the leading cause of coronary artery and cerebrovascular disease. Pathophysiology Atherosclerosis is an inflammatory disease that develops and proceeds in the presence of elevated plasma cholesterol levels. Both innate and adaptive immunity play a role in the development and progression of atherosclerotic lesions. Pathologically, the lesions progress from endothelial injury and dysfunction to fatty streak to fibrotic plaque to complicated lesion. Atherosclerosis begins with injury to the endothelial cells that line artery walls. Possible causes of endothelial injury include the common risk factors for atherosclerosis, such as smoking, hypertension, diabetes, increased levels of low-density lipoprotein (LDL), decreased levels of high-density lipoprotein (HDL), and autoimmunity. Other causes of endothelial injury include inflammatory factors that are being explored as nontraditional cardiovascular risk factors, such as elevated C-reactive protein (CRP), increased serum fibrinogen, infection, and periodontal disease. Once injury has occurred, endothelial dysfunction and inflammation lead to the following pathophysiologic events: 1. Injured endothelial cells become inflamed and cannot make normal amounts of antithrombotic and vasodilating cytokines. 2. Numerous inflammatory cytokines are released, including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-1 (IL-1), toxic oxygen radicals, CRP, and heat shock proteins. 3. Macrophages adhere to injured endothelium by way of adhesion molecules. 4. These macrophages then release enzymes and toxic oxygen radicals that create oxidative stress, oxidize LDL, and further injure the vessel wall. 5. Growth factors also are released, including angiotensin II, fibroblast growth factor, TGF-β, and platelet-derived growth factor, which stimulate smooth muscle cell proliferation in the affected vessel. LDL penetrates into the subintima of arterial walls, where it is trapped by proteoglycans. Inflammation, oxidative stress, and activation of macrophages cause the aggregated LDL to become oxidized. Diabetes, smoking, and hypertension (especially with increased levels of angiotensin II) contribute to increased LDL oxidation. Oxidized LDL is toxic to endothelial cells and causes smooth muscle proliferation. Oxidized LDL also increases endothelial adhesion molecule expression, which recruits more monocyte/macrophages that penetrate the vessel wall. Several types of receptors on these macrophages (Toll-like receptors [TLRs], LDL receptor-related protein [LRP]) enable detection and engulfment of the LDL, which contributes to activation of additional innate and adaptive immune responses. Macrophages filled with oxidized LDL are called foam cells. Once these lipid-laden foam cells accumulate in significant amounts, they form a lesion called a fatty streak. These lesions can be found in the walls of arteries of most people, even young children. Once formed, fatty streaks produce more toxic oxygen radicals and cause immunologic and inflammatory changes, resulting in progressive damage to the vessel wall. At this point, smooth muscle cells proliferate, produce collagen, and migrate over the fatty streak forming a fibrous plaque. This process is mediated by many inflammatory cytokines, including growth factors (e.g., TGF-β). The fibrous plaque may calcify, protrude into the vessel lumen, and obstruct blood flow to distal tissues, especially during exercise, which may cause symptoms (e.g., angina or intermittent claudication). Many plaques, however, are "unstable," meaning they are prone to rupture even before they affect blood flow and are clinically silent until they rupture. Plaque rupture occurs because of the inflammatory activation of proteinases (matrix metalloproteinases and cathepsins), apoptosis of cells within the plaque, and bleeding within the lesion (plaque hemorrhage). Plaques that have ruptured are called complicated plaques. Once rupture occurs, exposure of underlying tissue results in platelet adhesion, initiation of the clotting cascade, and rapid thrombus formation that may suddenly occlude the affected vessel, resulting in ischemia and infarction. Aspirin or other antithrombotic agents are used to prevent this complication of atherosclerotic disease. Clinical manifestations Atherosclerosis presents with symptoms and signs that result from inadequate tissue perfusion because of obstruction of the vessels that supply them. Partial vessel obstruction may lead to transient ischemic events, often associated with exercise or stress. Once the lesion becomes complicated, increasing obstruction with superimposed thrombosis may result in tissue infarction. CAD caused by atherosclerosis is the major cause of myocardial ischemia and is one of the most important health issues in the United States. Atherosclerotic obstruction of the vessels supplying the brain is the major cause of stroke. Similarly, any part of the body may become ischemic when its blood supply is compromised by atherosclerotic lesions. Often more than one vessel is involved with this disease process; consequently, an individual may present with symptoms from several ischemic tissues at the same time, and disease in one area may indicate that the individual is at risk for other ischemic complications elsewhere. Evaluation and treatment In evaluating individuals for the presence of atherosclerosis, a complete health history (including risk factors and symptoms of ischemia) is essential. Physical examination may reveal arterial bruits and evidence of decreased blood flow to tissues. Laboratory tests include measurement of lipids, blood glucose, and high sensitivity CRP (hs-CRP). Judicious use of x-ray films, electrocardiography, ultrasonography, nuclear scanning, CT, MRI, and angiography may be necessary to identify affected vessels, particularly coronary vessels. Current management of atherosclerosis is focused on detecting and treating preclinical lesions with drugs aimed at stabilizing and reversing plaques before they rupture. Once a lesion obstructs blood flow, the primary goal in managing atherosclerosis is to restore adequate blood flow to the affected tissues. If an individual has presented with acute ischemia (e.g., MI, stroke), interventions are specific to the diseased area. In situations in which the disease process does not require immediate intervention, management focuses on reducing risk factors, removing the initial causes of vessel damage, and preventing lesion progression. This includes exercise, smoking cessation, and control of hypertension and diabetes when appropriate while reducing LDL cholesterol by diet or medications or both.

Autonomic negative feedback response

Baroreceptors send constant signals to brainstem Increased BP causes rate of signals to rise, inhibits vasomotor center, decreased sympathetic tone, vasodilation causes BP decrease

Vascular and Hematologic Liver Functions

Blood storage Bacterial and foreign particle removal Synthesizes clotting factors Produces bile to absorb fat-soluble vitamins Metabolizes fats, proteins, and carbohydrates Metabolic detoxification Storage of minerals and vitamins Degrades old red blood cells (billirubin) Lipid and cholesterol synthesis Takes up, stores and releases glucose

Ischemia

CAD, myocardial ischemia, and MI form a pathophysiologic continuum that impairs the pumping ability of the heart by depriving the heart muscle of blood-borne oxygen and nutrients. The earliest lesions of the continuum are those of coronary artery disease (CAD) which occludes the coronary arteries. By far the most common cause of coronary artery obstruction is atherosclerosis. CAD can diminish the myocardial blood supply until deprivation impairs myocardial metabolism enough to cause ischemia, a local state in which the cells are temporarily deprived of blood supply. They remain alive but cannot function normally. Persistent ischemia or the complete occlusion of a coronary artery causes acute coronary syndrome. Infarction (irreversible myocardial injury) constitutes the often-fatal event known as a heart attack.

Understand pathophysiology and clinical manifestations of asthma including inflammatory process

Bronchial hyperresponsiveness Constriction of airways Variable airflow obstruction that is REVERSIBLE Half of all cases develop during childhood 24.6 million Americans, prevalence on the rise Risk factors Genetics, allergen exposure, urban residence, pollution, tobacco smoke, environmental tobacco smoke, recurrent Clinical manifestations Asymptomatic between attacks Pulmonary function tests are normal Early symptoms: Chest constriction, expiratory wheezes, dyspnea, nonproductive cough, prolonged expiration, tachycardia, tachypnea Late symptoms: Use of accessory muscles, wheezing on inspiration and expiration, pulsus paradoxus, Hypoxemia, status asthmaticus, acidosis

Mineral and vitamin absorption

Calcium - important for cellular function, bones. Increase absorption by taking vitamin D3 Magnesium - absorbed by active transport in small intestine Phosphate - absorbed by active transport in small intestine Iron - generally, the amount you absorb is the amount your body needs. Can still increase absorption by taking with vitamin C. Milk, tea, antacids bind to iron and inhibit absorption. Iron deficiency = most common cause of anemia worldwide. Breastfed babies have increased likelihood of iron deficiency - should be supplemented with iron Fat soluble vitamins (ADEK) - absorbed into fat and stored in liver. Don't necessarily need these in daily diet because body is able to store these. Water soluble vitamins (B complex, folate, biotin, pantothenic acid) - have to have steady intake, body can't store these.

Know different types of renal calculi and their prevalence

Calculi, or urinary stones (urolithiasis), are masses of crystals, protein, or other substances that are a common cause of urinary tract obstruction in adults. They can be located in the kidneys, ureters, and urinary bladder. The prevalence of stones in the United States is approximately 6% in women and 15% in men, and is more common in whites. The recurrence rate is approximately 30% to 50% within 5 years. The risk of urinary calculi formation is influenced by a number of factors, including age, gender, race, geographic location, seasonal factors, fluid intake, diet, occupation, genetic predisposition, and other conditions including urinary tract infection, hypertension, atherosclerosis, metabolic syndrome, obesity, and diabetes. Most persons develop their first stone before age 50 years. Geographic location influences the risk of stone formation because of indirect factors, including average temperature, humidity, and rainfall, and their influence on fluid and dietary patterns. Most kidney stones are unilateral and are a risk factor for chronic kidney disease and an increased risk for myocardial infarction. Urinary calculi can be classified according to the primary minerals (salts) that comprise the stones. The most common stone types include calcium oxalate or calcium phosphate (70% to 80%), struvite (magnesium, ammonium, and phosphate) (15%), and uric acid (7%). Cystine stones are rare, less than 1%. Less common stone elements include cystine, 2,8-dihydroxyadeninuria (a rare genetic disorder that increases risk of xanthine stones). Urinary calculi also can be classified according to location and size. Staghorn calculi are large and fill the minor and major calyces. Non-staghorn calculi are of variable size and are located in the calyces, in the renal pelvis, or at different sites along the ureter. Renal calculus formation is complex and related to: (1) supersaturation of one or more salts in the urine, (2) precipitation of the salts from a liquid to a solid state (crystals), (3) growth through crystallization or agglomeration (sometimes called aggregation), and (4) the presence or absence of stone inhibitors - Alkaline urine: Increases the risk of calcium phosphate stone formation. - Acidic urine: Increases the risk of a uric acid stone. - Potassium citrate, pyrophosphate, and magnesium: Prevent calcium stone formation The pH of the urine also influences the risk of precipitation and calculus formation. An alkaline urinary pH significantly increases the risk of calcium phosphate stone formation, whereas acidic urine increases the risk of a uric acid stone. Cystine and xanthine precipitate more readily in acidic urine. Stones smaller than 5 mm have about a 50% chance of spontaneous passage, whereas stones that are 1 cm have almost no chance of spontaneous passage. Nevertheless, the person with ureteral dilation from the previous passage of a stone may be able to excrete larger stones when compared with the person experiencing an initial obstructing calculus. Clinical Manifestations Renal colic, described as moderate to severe pain often originating in the posterior hypochondrium (flank) and radiating to the groin, usually indicates obstruction of the renal pelvis or proximal ureter. Colic that radiates to the lateral flank or lower abdomen typically indicates obstruction in the midureter, and bothersome lower urinary tract symptoms (urgency, frequent voiding, urge incontinence) indicate obstruction of the lower ureter or ureterovesical junction. The pain can be severe and incapacitating and may be accompanied by nausea and vomiting. Gross (visible blood in the urine) or microscopic hematuria (three or more red blood cells per high power microscopic field) may be present. Evaluation and Treatment Urinalysis (including pH) is obtained and a 24-hour urine is completed to identify calcium oxalate, citrate, and other significant constituents. In addition, every effort is made to retrieve and analyze calculi that are passed spontaneously or retrieved through aggressive intervention. The goals of treatment are to manage acute pain, promote stone passage, reduce the size of stones already formed, and prevent new stone formation.

Which cardiac enzymes are useful in determining myocardial function

Cardiac biomarkers: Enzymes and proteins released when myocardial tissue is INJURED Cardiac Troponin I (cTnI): most sensitive test; Detectable 2-4 hours after onset of symptoms, 100% specific to myocardial tissue Creatine phosphokinase - muscle and brain (CPKMB): Detectable 3-8 hours after onset of symptoms

Frank-Starling law

Cardiac muscle, like other muscle, increases its strength of contraction when it is stretched. The Frank-Starling law of the heart, or the length-tension relationship of cardiac muscle, relates resting sarcomere length, expressed as the volume of blood in the heart at the end of diastole (end-diastolic volume), to tension generation, described as development of left ventricular pressure. Thus the volume of blood in the heart at the end of diastole (the length of its muscle fibers) is directly related to the force of contraction during the next systole. The mechanical function of the heart is characterized by a number of length-tension curves. Factors that increase contractility (i.e., positive inotropic), such as sympathetic nerve stimulation, cause the heart to operate on a higher length-tension curve. A higher tension or increase in ventricular stroke volume is generated without a necessary change in left ventricular end-diastolic volume or fiber length. Heart failure is characterized by a lower length-tension curve. The Frank-Starling law of the heart may not apply to dilated or failing hearts because their fibers are already stretched beyond their optimal length. The failing heart responds to increased filling or stretch with a progressive decline in the force of contraction. Thus at the same left ventricular end-diastolic volume as curves A and B (see Figure 31-18), the force of contraction of stroke volume is decreased. The cross-bridge arrangement with the sarcomere partially accounts for the length-tension mechanism of cardiac muscle. According to the Frank-Starling law, the longer the initial resting length of the cardiac muscle fiber (optimal length is between 2.2 and 2.4 mm), the greater the strength of contraction. At 2.2 mm an optimal number of active cross-bridges exist between actin and myosin. However, if the fibers are stretched beyond 2.2 to 2.4 mm, the force of contraction decreases because actin and myosin become partially disengaged, disrupting many of the cross-bridges. Excessive stretching, to about 3.65 mm, causes actin and myosin to become completely disengaged so that tension (force of contraction) drops to zero. The relationship between stretch and contraction can be compared with that of a rubber band. Up to a certain point, the more the rubber band is stretched the farther it will fly when one end is released; beyond that point, however, the rubber band will break but, of course, the myocardium does not actually break!

Understand neurochemical control of ventilation, specifically how chemoreceptors regulate pH, PaCO2 and PaO2 of arterial blood.

Central receptors Stimulated by H+ in cerebrospinal fluid (pH); really sensitive to pH changes Reflected in PaC02 Peripheral receptors Aorta and carotid bodies Stimulated by hypoxemia (Pa02) Slower to respond, less sensitive --- The mechanisms that control respiration are very complex. Breathing is usually involuntary because homeostatic changes in the ventilatory rate and volume are adjusted automatically by the nervous system to maintain normal gas exchange. Voluntary breathing is necessary for talking, singing, laughing, and holding one's breath. The respiratory center in the brainstem controls respiration by transmitting impulses to the respiratory muscles, causing them to contract and relax. The respiratory center is composed of several groups of neurons located bilaterally in the brainstem. The basic automatic rhythm of respiration is set by the DRG, a cluster of inspiratory nerve cells located in the medulla that sends efferent impulses to the diaphragm and inspiratory intercostal muscles. The DRG also receives afferent impulses from peripheral chemoreceptors in the carotid and aortic bodies, which detect the PaCO2 and the amount of oxygen in the arterial blood (PaO2). In addition, several different types of receptors in the lungs stimulate the VRG through afferent nerves. The VRG, also located in the medulla, contains inspiratory and expiratory neurons. It is almost inactive during normal, quiet respiration, becoming active when increased ventilatory effort is required. The pneumotaxic center and apneustic center, situated in the pons, do not generate primary rhythm, but rather act as modifiers of the inspiratory depth and rate established by the medullary centers. Breathing can be modified by input from the cortex, the limbic system, and the hypothalamus, and the pattern of breathing can be influenced by emotion and by disease.

Understand definitions of and pathophysiology of chronic bronchitis and emphysema including common opportunistic pathogens and effects of smoking. Also know clinical manifestations of both chronic bronchitis and emphysema.

Chronic bronchitis is defined as hypersecretion of mucus and chronic productive cough that continues for at least 3 months of the year (usually the winter months) for at least 2 consecutive years. Inspired irritants (like SMOKING) increase mucus production and the size and number of mucus glands Impaired ciliary function, difficulty clearing mucus Eventual airway remodeling Clinical manifestations ↓ exercise tolerance, wheezing, SOB, productive cough, ↓ FEV1 Marked hypoxemia leads to polycythemia and cyanosis ------------ Emphysema is permanent enlargement of acini and destruction of alveolar walls without obvious fibrosis Loss of elastic recoil Air trapping causes hyper-expansion of chest Clinical manifestations Dyspnea on exertion that progresses Thin, tachypnea with prolonged expiration ↑ AP diameter ------------ Opportunistic infections: Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and possibly pathogens of atypical pneumonia ------------ Smoking: Smoking is the most important risk factor, and about 50% of smokers develop COPD.

Basics of liver cirrhosis

Chronic liver damage from a variety of causes leading to scarring and liver failure. Cirrhosis is the most common cause of ascites; ascites is the most common complication of cirrhosis. Ascites is the accumulation of fluid in the peritoneal cavity and is a complication of portal hypertension. Ascites traps body fluid in the peritoneal cavity from which it cannot escape. The effect reduces the amount of fluid available for normal physiologic functions. Other diseases associated with ascites include right heart failure, abdominal malignancies, nephrotic syndrome, and malnutrition. Twenty-five percent of individuals who develop ascites caused by cirrhosis die within 1 year. Continued heavy drinking of alcohol is associated with this mortality because of increased risk for cirrhosis

Understand general concept of obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is defined as a "preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is NOT fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases. COPD is the third leading cause of death in the United States and is the sixth leading cause of death worldwide. Overall mortality from COPD has increased in the United States over the past 30 years; however, mortality in women has increased more than twice that much. Risk factors for COPD include tobacco smoke (cigarette, pipe, cigar, and environmental tobacco smoke), occupational dusts and chemicals (vapors, irritants, and fumes), indoor air pollution from biomass fuel used for cooking and heating (in poorly vented dwellings), outdoor air pollution, and any factor that affects lung growth during gestation and childhood (low birth weight, respiratory tract infections). Genetic susceptibilities have been identified, including polymorphisms of genes that code for tumor necrosis factor, surfactant, proteases, antiproteases, and risks for lung cancer. The clinical phenotypes of COPD are chronic bronchitis and emphysema. An inherited mutation in the α1-antitrypsin gene results in the development of COPD (emphysema) at an early age, even in nonsmokers. The pathologic changes of COPD occur in large central airways, small peripheral airways, and the lung parenchyma, the dominant features of chronic bronchitis and emphysema. Chronic irritant exposure recruits macrophages, neutrophils, and lymphocytes to the lung, resulting in progressive damage from oxidative stress, inflammation, extracellular matrix proteolysis, and apoptotic and autophagic cell death. Systemic abnormalities, such as renal and hormonal abnormalities, malnutrition, muscle wasting, osteoporosis, and anemia, are associated with COPD.

Causes and pathophysiology of constipation

Constipation is difficult or infrequent defecation and is estimated to affect 2% to 28% of the population. Constipation must be individually defined because patterns of bowel evacuation differ greatly among individuals. Normal bowel habits range from two or three evacuations per day to one per week. Constipation is not significant until it causes health risks (e.g., severe abdominal distention or fecal impaction) or impairs quality of life. Pathophysiology Primary constipation is generally classified into three categories. 1. Normal transit (functional) constipation involves a normal rate of stool passage but there is difficulty with stool evacuation. Functional constipation is most common and is associated with low-residue diet (the habitual consumption of highly refined foods) or low fluid intake, which decreases the volume and number of stools and can contribute to constipation. Physical activity stimulates peristalsis; therefore, a sedentary lifestyle and lack of regular exercise are common causes of constipation. Lack of access to toilet facilities, consistent suppression of the urge to empty the bowel, and dehydration are other causes. Slow-transit constipation involves impaired colonic motor activity with infrequent bowel movements, straining to defecate, mild abdominal distention, and palpable stool in the sigmoid colon. Pelvic floor dysfunction (pelvic floor dyssynergia-anismus) is difficulty expelling stool because of failure of the pelvic floor muscles or anal sphincter to relax with defecation. 2. Secondary constipation can be caused by neurogenic disorders (e.g., stroke, Parkinson disease, spinal cord injury, multiple sclerosis) in which neurotransmitters are altered or neural pathways are diseased or degenerated, resulting in delayed colon transit time. Opiates, particularly codeine, antacids containing calcium carbonate or aluminum hydroxide; anticholinergics; iron; and bismuth tend to inhibit bowel motility. Endocrine or metabolic disorders associated with constipation include hypothyroidism, diabetes mellitus, hypokalemia, and hypercalcemia. Pelvic hiatal hernia (herniation of the bowel through the floor of the pelvis), diverticuli, irritable bowel syndrome-constipation predominant, and pregnancy also can be associated with constipation. Aging can result in constipation caused from decreased motility related to the degeneration of neurons in the myenteric plexus, decreased neurotransmitter function, use of medications, and comorbid medical conditions. Constipation as a notable change in bowel habits can be an indication of colorectal cancer. 3. Mechanical conditions can slow intestinal transit time. The abdominal muscles are normally used to create the intra-abdominal pressure required to evacuate the rectum. Weakness or pain can interfere with the generation of adequate intra-abdominal pressure. Lesions of the anus, such as inflamed hemorrhoids, fissures, or fistulae, make defecation painful because of stretching. With the urge to defecate, the sphincter becomes hypertonic and the stool is not eliminated. Depression often impairs bowel evacuation, partly because depressed individuals tend to be sedentary and lack the motivation to eat a healthy diet. The problem is made worse if antidepressant drugs (e.g., anticholinergics) are used to treat the depression. Clinical Manifestations Indicators of constipation include two of the following for at least 3 months: (1) straining with defecation at least 25% of the time, (2) lumpy or hard stools at least 25% of the time, (3) sensation of incomplete emptying at least 25% of the time, (4) manual maneuvers to facilitate stool evacuation for at least 25% of defecations, and (5) fewer than three bowel movements per week. Changes in bowel evacuation patterns, such as less frequent defecation, smaller stool volume, hard stools, difficulty passing stools (straining), or a feeling of bowel fullness and discomfort or blood in the stools, require investigation. Fecal impaction (hard, dry stool retained in the rectum) is associated with rectal bleeding, abdominal or cramping pain, nausea and vomiting, weight loss, and episodes of diarrhea. Straining to evacuate stool may cause engorgement of the hemorrhoidal veins and hemorrhoidal disease or thrombosis with rectal pain, bleeding, and itching. Passage of hard stools can cause painful anal fissures. Evaluation and Treatment The history, current use of medications, physical examination, and stool diaries provide precise clues regarding the nature of constipation. Sudden-onset constipation can accompany the development of colorectal cancer and requires careful evaluation. The individual's description of frequency, stool consistency, associated pain, and presence of blood or whether evacuation was stimulated by enemas or cathartics (laxatives) is significant. Cramping abdominal pain may be symptomatic of partial bowel obstruction. Palpation discloses colonic distention, masses, and tenderness. Blood may be caused by bleeding hemorrhoids or a neoplastic lesion of the colon. The treatment for constipation is to manage the underlying cause or disease for each individual. Management usually consists of bowel retraining, in which the individual establishes a satisfactory bowel evacuation routine without becoming preoccupied with bowel movements. Moderate exercise, increased fluid and fiber intake, stool softeners, and laxative agents are useful for some individuals. Enemas can be used to establish bowel routine, but they should not be used habitually.

Concentration and Dilution of Urine

Countercurrent multiplication in the kidneys is the process of using energy to generate an osmotic gradient that enables you to reabsorb water from the tubular fluid and produce concentrated urine. This mechanism prevents you from producing litres and litres of dilute urine every day, and is the reason why you don't need to be continually drinking in order to stay hydrated. Countercurrent exchange system: • Contributes to production of concentrated urine • Fluid flows in opposite direction through parallel tubes • Fluid moves up and down the parallel limbs of the loop of Henle • The longer the loop, the greater the concentration gradient

Know how the basic metabolic waste products (creatinine, urea) are produced by the body and how they are clinically useful

Creatinine, a substance produced by muscle, is measured in plasma and urine to calculate a commonly used clinical measurement of GFR (creatinine clearance). The clearance of creatinine, a natural substance produced by muscle and released into the blood at a relatively constant rate, is commonly used clinically. It is freely filtered at the glomerulus and is not reabsorbed by the renal tubules, but a small amount is secreted by the renal tubules. Therefore, creatinine clearance overestimates the GFR but within tolerable limits. Creatinine clearance provides a good estimate of GFR because only one blood sample is required in addition to a 24-hour volume of urine. - Most valuable for monitoring the progress of chronic rather than acute renal disease. - Measures progressive renal dysfunction. Urea is an end product of protein metabolism and is the major constituent of urine along with water. The glomerulus freely filters urea. Tubular reabsorption depends on urine flow rate with less reabsorption occurring at higher flow rates. Approximately 50% of urea is excreted in the urine, and 50% is recycled within the kidney. The recycling of urea from the tubules and collecting ducts contributes to the osmotic gradient within the medulla and is necessary for the concentration and dilution of urine. Because urea is an end product of protein metabolism, individuals with protein deprivation cannot maximally concentrate their urine. Blood Urea Nitrogen (BUN) - Not as reliable as creatinine - Varies as a result of altered protein intake and protein catabolism. - Poor measure of GFR. - Better indicator for hydration status. - Increases in dehydration and kidney failure BUN/Creatinine ratio greater than 21

Understand etiology, pathophysiology and clinical manifestations of acute laryngotracheobronchitis (croup).

Croup is an acute laryngotracheobronchitis and most commonly occurs in children from 6 months to 3 years of age, with peak incidence at 2 years of age. In 85% of cases, croup is caused by a virus, most commonly parainfluenza; however, other viruses such as influenza A virus, respiratory syncytial virus (RSV), rhinovirus, adenovirus, and rubella virus (measles) as well as the atypical bacterium Mycoplasma pneumoniae has been associated with causation. The incidence of croup is highest in late autumn and winter, corresponding to the parainfluenza and RSV seasons, respectively. Croup is more common in boys than girls. In a significant portion of affected children, croup is a recurrent problem during childhood, and there is a family history of croup in about 15% of cases. Pathophysiology The pathophysiology of viral croup is caused primarily by subglottic edema from the infection. The mucous membranes of the larynx are tightly adherent to the underlying cartilage, whereas those of the subglottic space are looser and thus allow accumulation of mucosal and submucosal edema. Furthermore, the cricoid cartilage is structurally the narrowest point of the airway, making edema in this area critical. Increased resistance to airflow leads to increased work of breathing, which generates more negative intrathoracic pressure, which in turn may exacerbate dynamic collapse of the upper airway. Clinical Manifestations Typically there is a prodrome of rhinorrhea, sore throat, and low-grade fever for a few days. The child then develops the characteristic harsh (seal-like) barking cough, hoarse voice, and inspiratory stridor. Most cases are mild and resolve spontaneously after several more days. Occasionally, however, UAO becomes severe and requires urgent management. Evaluation and Treatment The degree of symptoms determines the level of treatment. Most children have a barking cough and viral symptoms and may need no specific treatment. However, the presence of stridor (especially at rest), retractions, or agitation suggests a sicker child. Severity also is classified as mild, moderate, and severe. Most children with croup require no treatment. Inhalation of humidified air does not improve symptoms in mild to moderate croup. Glucocorticoids, either injected or oral (dexamethasone) or nebulized (budesonide), have been shown to improve symptoms within 6 hours. Less sleep is lost by children, less stress is experienced by parents, and fewer children have a need for return healthcare visits or hospitalization when corticosteroids are used. The use of nebulized racemic epinephrine improves outcomes with moderate to severe croup. Epinephrine stimulates α- and β-adrenergic receptors and is thought to decrease airway secretions and mucosal edema. It is a temporizing measure until concomitantly given corticosteroids begin to take effect. Thus children who are given nebulized epinephrine should be closely observed for 2 to 3 hours to ensure that they will remain stable. Oxygen also should be administered. Heliox (helium-oxygen mixture of 80:20 or 70:30) may be used for severe cases of croup, although there is lack of scientific evidence to establish use in routine clinical practice.

What physiologic conditions must be present for cyanosis to occur?

Cyanosis is a bluish discoloration of the skin caused by desaturation of hemoglobin, polycythemia (overproduction of erythrocytes), or peripheral vasoconstriction

Presentation of diarrhea and the differences between osmotic diarrhea and secretory diarrhea

Diarrhea in which the volume of feces is increased is called large-volume diarrhea. Large-volume diarrhea generally is caused by excessive amounts of water or secretions, or both, in the intestines. Small-volume diarrhea, in which the volume of feces is not increased, usually results from excessive intestinal motility. The three major mechanisms of diarrhea are osmotic, secretory, and motility. Osmotic diarrhea: • When there is too much water in the bowels. • Example: Maldigestion (celiac's disease), osmotic laxatives, lactose or fructose intolerance (these are left undigested in the bowel and water is pulled in to balance Nonabsorbable substance in the intestine draws water into the lumen by osmosis. The excess water and the nonabsorbable substance cause large-volume diarrhea. Large oral doses of poorly absorbed ions, such as magnesium, sulfate, and phosphate, can increase intraluminal osmotic pressure. Excessive ingestion of synthetic, nonabsorbable sugars (e.g., sorbitol); introduction of full-strength tube feeding formulas; and dumping syndrome associated with gastric resection draw water into the intestinal lumen. Osmotic diarrhea disappears when ingestion of the osmotic substance stops. Malabsorption related to lactase deficiency, pancreatic enzyme or bile salt deficiency, small intestine bacterial overgrowth, and celiac disease also cause diarrhea. Secretory diarrhea: Is an increase in active secretion of nutrients (or decrease in absorption of nutrients) without structural damage. Large-volume diarrhea caused by excessive mucosal secretion of chloride- or bicarbonate-rich fluid or inhibition of net sodium absorption. Infectious causes include viruses (e.g., rotavirus), bacterial enterotoxins (e.g., Escherichia coli and Vibrio cholerae), or exotoxins from overgrowth of Clostridium difficile following antibiotic therapy. These infections cause secretion of transmitters from enteroendocrine cells (e.g., 5-HT) and activation of afferent neurons that stimulate submucosal secretomotor neurons and altered sodium and chloride transport resulting in decreased water absorption. Neoplasms (such as gastrinoma or thyroid carcinoma) produce hormones that stimulate intestinal secretion causing diarrhea. Small-volume diarrhea usually is caused by an inflammatory disorder of the intestine, such as ulcerative colitis, Crohn disease, or microscopic colitis. Inflammation of the colon causes smooth muscle contraction, cramping pain, urgency, and frequency. Small-volume diarrhea also can be caused by fecal impaction, a severe form of constipation. This diarrhea consists of secretions (mucus and fluid) produced by the colon to lubricate the impacted feces and move it toward the anal canal. These secretions flow around the impaction and cause low-volume, secretory diarrhea. Motility diarrhea is caused by resection of the small intestine (short bowel syndrome), surgical bypass of an area of the intestine, fistula formation between loops of intestine, irritable bowel syndrome-diarrhea predominant, diabetic neuropathy, hyperthyroidism, and laxative abuse. Excessive motility decreases transit time, mucosal surface contact, and opportunities for fluid absorption, resulting in diarrhea.

Diverticular disease including pathophysiology and causes

Diverticula: herniations or saclike outpouchings of mucosa through the muscle layers of the colon wall, especially the sigmoid colon Diverticulosis: asymptomatic diverticular disease. Diverticulitis: represents inflammation. The cause of diverticular disease is unknown but is associated with age greater than 60 years, decreased dietary fiber, increased intracolonic pressure, abnormal neuromuscular function, and alterations in intestinal motility. Pathophysiology Diverticula can occur anywhere in the gastrointestinal tract but the most common site is the left colon. They rarely occur in the small intestine. The diverticula form at weak points in the colon wall, usually where arteries penetrate the tunica muscularis to nourish the mucosal layer. The colonic mucosa herniates through the smooth muscle layers. A common associated finding is thickening of the circular and longitudinal (teniae coli) muscles surrounding the diverticula. Hypertrophy and contraction of these muscles increase intraluminal pressure and degree of herniation. Habitual consumption of a low-residue diet reduces fecal bulk, thus reducing the diameter of the colon. According to Laplace's law, wall pressure increases as the diameter of a cylindrical structure decrease. Therefore, the pressure within the narrow lumen can increase enough to rupture the diverticula. Insoluble dietary fiber deficiency also may change the intestinal microflora, decreasing the immune response and levels of inflammatory cytokines in the colon. Diverticulitis can cause abscess formation, fistula formation, peritonitis, or obstruction. Clinical Manifestations Symptoms of diverticular disease are usually vague or absent and about 30% of individuals develop specific symptoms. Cramping pain of the lower abdomen can accompany constriction of the hypertrophied colonic muscles. Diarrhea, constipation, distention, or flatulence may occur. Diverticula with an obstructed opening become inflamed or abscesses form, and the individual develops fever, leukocytosis (increased white blood cell count), and tenderness of the lower left quadrant. Right lower quadrant pain and severe complications, such as hemorrhage, perforation with peritonitis, bowel obstruction, and fistula formation, are rare. Evaluation and Treatment Diverticula are often discovered during diagnostic procedures performed for other problems. Ultrasound, sigmoidoscopy, or barium enema is used for diagnosis of uncomplicated diverticula. Abdominal computed tomography (CT) is used for complicated cases. An increase of dietary fiber intake increases stool weight, lowers colonic pressures, improves transit times, and often relieves symptoms. Uncomplicated diverticular disease is treated with bowel rest and antibiotics. Surgical resection may be required if there are severe complications, including hemorrhage, bowel stenosis, obstruction, abscesses, fistulae, bowel perforation, and peritonitis.

Understand the different types of dyspnea and their causes.

Dyspnea is a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity. It is often described as breathlessness, air hunger, shortness of breath, increased work of breathing, chest tightness, and preoccupation with breathing. Dyspnea may be the result of pulmonary disease or many other conditions, such as pain, heart disease, trauma, and anxiety. The severity of the experience of dyspnea may not directly correlate with the severity of underlying disease. Either diffuse or focal disturbances of ventilation, gas exchange, or ventilation-perfusion relationships can cause dyspnea, as can increased work of breathing or diseases that damage lung tissue (lung parenchyma). One proposed mechanism involves an impaired sense of effort where the perceived work of breathing is greater than the actual motor response generated. Stimulation of many receptors can contribute to the sensation of dyspnea including mechanoreceptors (the stretch receptors, irritant receptors, and J-receptors), upper airway receptors, and central and peripheral chemoreceptors that interact with the sensory and motor cortex. The more severe signs of dyspnea include flaring of the nostrils, use of accessory muscles of respiration, and retraction (pulling back) of the intercostal spaces. In dyspnea caused by parenchymal disease (e.g., pneumonia), retractions of tissue between the ribs (subcostal and intercostal retractions) are observed more often than supercostal retractions (retractions of tissues above the ribs), which predominate in upper airway obstruction. Retractions of any type are more commonly seen in children or in adults who are thin and have poorly developed thoracic musculature. Dyspnea can be quantified by the use of ordinal rating scales or visual analog scales. Dyspnea can occur transiently or can become chronic. The first episode commonly occurs with exercise and is called dyspnea on exertion. Orthopnea is dyspnea that occurs when an individual lies flat and is common in individuals with heart failure. The recumbent position redistributes body water, causes the abdominal contents to exert pressure on the diaphragm, and decreases the efficiency of the respiratory muscles. Sitting in a forward-leaning posture or supporting the upper body on several pillows generally relieves orthopnea. Paroxysmal nocturnal dyspnea (PND) occurs when individuals with heart failure or lung disease wake up at night gasping for air and must sit up or stand to relieve the dyspnea.

Nephron

Functional unit of the kidney. Superficial cortical nephrons: Make up 85% of all nephrons, which extend partially into the medulla. Midcortical nephrons: Have short or long loops. Juxtamedullary nephrons: Lie close to and extend deep into the medulla and are important for the process of concentrating urine; secrete renin. Each kidney contains 1.2 million nephrons

Different sources of emboli and their possible effects

Embolism is the obstruction of a vessel by an embolus—a bolus of matter that is circulating in the bloodstream. The embolus may consist of a dislodged thrombus; an air bubble; an aggregate of amniotic fluid; an aggregate of fat, bacteria, or cancer cells; or a foreign substance. An embolus travels in the bloodstream until it reaches a vessel through which it cannot fit. No matter how tiny it is, an embolus eventually will lodge in a systemic or pulmonary vessel. The source of the embolus determines whether the embolus will lodge in a vessel of the pulmonary or systemic circulation. Pulmonary emboli originate in the venous circulation (mostly from the deep veins of the legs) or in the right heart. Arterial emboli most commonly originate in the left heart and are associated with thrombi after MI, valvular disease, left heart failure, endocarditis, and dysrhythmias. Embolism causes ischemia or infarction in tissues distal to the obstruction. A limb that is ischemic because of arterial occlusion is characterized (1) by an almost waxy whiteness of the skin because the vasculature is devoid of erythrocytes, and (2) by numbness and pain resulting from neural ischemia. Embolism to a central organ causes organ dysfunction and pain. For example, pulmonary artery embolism causes chest pain and dyspnea; renal artery embolism causes abdominal pain and oliguria; and mesenteric artery embolism causes abdominal pain and a paralytic, ischemic bowel. In the coronary, cerebral, and peripheral arterial systems, embolism may occur as a result of rupture or mechanical disruption of an atherosclerotic plaque. This phenomenon is sometimes referred to as cholesterol embolization syndrome or atheroembolism. Embolism to a coronary or cerebral artery is an immediate threat to life if the embolus severely obstructs a major vessel. Occlusion of a coronary artery causes an MI, whereas occlusion of a cerebral artery causes a stroke.

Injury & vasoactive inflammatory cytokines

Endothelial injury and tissue ischemia result in the release of vasoactive inflammatory cytokines. Although many of these cytokines (e.g., histamine, prostaglandins) have vasodilatory actions in acute inflammatory injury, chronic inflammation contributes to vascular remodeling and smooth muscle contraction. Endothelial injury and dysfunction in primary hypertension is further characterized by decreased production of vasodilators, such as nitric oxide, and increased production of vasoconstrictors, such as endothelin.

Stomach anatomy

Fundus: top Bottom: antrum (where gastric ulcers tend to occur) • Pyloric sphincter controls movement of food from antrum → duodenum; Pylorus is essential for controlling rate that foods moves into duodenum Composed of 3 muscle layers: longitudinal (outermost) circular oblique (innermost) Stomach is lined with mucosal cells that play a large role in secretion of substances for digestion. Stomach uses mechanical breakdown (churning the food bolus that enters) and chemical breakdown. Only nutrients that are really digested in stomach are proteins via pepsin (although some breakdown of starches starts in mouth with salivary amylase).

Acinus

Gas exchange occurs in the acinus. Consists of: Respiratory bronchioles, alveolar ducts, and alveoli Alveoli: Primary gas exchange unit Pores of Kohn: Permit air to pass between alveoli to equalize pressures and oxygenation

What substances the stomach releases, from where and for what purpose

Gastric Secretion Stimulated by eating, the stomach produces large volumes of gastric secretions. Specialized cells located throughout the gastric mucosa produce mucus, acid, enzymes, hormones, intrinsic factor, and gastroferrin. Intrinsic factor is necessary for the intestinal absorption of vitamin B12 and gastroferrin facilitates small intestinal absorption of iron. The hormones are secreted into the blood and travel to target tissues in the bloodstream. The other gastric secretions are released directly into the stomach lumen under neural and hormonal regulation. Mucus covering the entire mucosa, intercellular tight junctions, bicarbonate secretion, and submucosal acid sensors form a protective barrier against acid and proteolytic enzymes, which otherwise would damage the gastric lining. In the fundus and body of the stomach, the gastric glands of the mucosa are the primary secretory units. Several of these glands (three to seven) empty into a common duct known as the gastric pit. The parietal cells within the glands secrete hydrochloric acid (HCl), intrinsic factor, and gastroferrin. The chief cells within the glands secrete pepsinogen, an enzyme precursor that is readily converted to pepsin (a proteolytic enzyme) in the gastric fluid by mixing with HCl. The pyloric gland mucosa in the antrum synthesizes and releases the hormone gastrin from G cells. Enterochromaffin-like cells secrete histamine (inhibits histamine and thus decreases the acidity of the stomach acid), and D cells secrete somatostatin (decreases production of acid). Acid The major functions of gastric hydrochloric acid are to dissolve food fibers, act as a bactericide against swallowed organisms, and convert pepsinogen to pepsin. The production of acid by the parietal cells requires the transport of hydrogen and chloride from the parietal cells to the stomach lumen. At a high rate of gastric secretion, bicarbonate moves into the plasma, producing an "alkaline tide" in the venous blood, which also may result in a more alkaline urine. Acid secretion by parietal cells is stimulated by acetylcholine (ACh) (a neurotransmitter), gastrin (a hormone), and histamine (a biochemical mediator). The vagus nerve releases ACh and stimulates the secretion of histamine and gastrin-releasing peptide (GRP), which stimulates the release of gastrin. Histamine secretion is also stimulated by gastrin. Histamine is stored in mast cells in the gastric mucosa. Histamine receptors in the gastric mucosa are H2 receptors (unlike those in the bronchial mucosa, which are H1 receptors). Gastric lipase is produced by glands in the fundus of the stomach and is most effective in an acidic environment. Caffeine stimulates acid secretion, as does calcium. Prostaglandins, enterogastrones (such as gastric inhibitory peptide), somatostatin, and secretin inhibit acid secretion. Pepsin Acetylcholine, through vagal stimulation during the cephalic and gastric phases, is the strongest stimulation for pepsin secretion. The precursor pepsinogen is quickly converted to pepsin at a pH of 2. Acid also stimulates a local cholinergic reflex and stimulates chief cells to secrete pepsin. HCl and Pepsin work together to dissolve protein. Once chyme has entered the duodenum, the alkaline environment of the duodenum inactivates pepsin. Mucus The gastric mucosa is protected from the digestive actions of acid and pepsin by a coating of mucus called the mucosal barrier. Gastric mucosal blood flow is important to maintaining mucosal barrier function. The quality and quantity of mucus and the tight junctions between epithelial cells make gastric mucosa relatively impermeable to acid. Prostaglandins and nitric oxide protect the mucosal barrier by stimulating the secretion of mucus and bicarbonate and by inhibiting the secretion of acid. A break in the protective barrier may occur because of exposure to aspirin or other nonsteroidal anti-inflammatory drugs, Helicobacter pylori, ethanol, regurgitated bile, or ischemia. Breaks cause inflammation and ulceration. Intrinsic factor (IF), a mucoprotein produced by parietal cells, combines with vitamin B12 in the stomach. It is required for the absorption of vitamin B12 by the ileum. Atrophic gastritis and failure to absorb vitamin B12 result in pernicious anemia.

Understand the basics of how GI system is innervated and how gastric secretion and gastric and intestinal motility is regulated

Except for chewing, swallowing, and defecation of solid wastes, the activities of the digestive system are controlled by hormones and the autonomic nervous system. As ingested substances move through the gastrointestinal tract, they trigger the release of hormones that stimulate or inhibit (1) the muscular contractions (gastrointestinal motility) that mix and propel food from the esophagus to the anus, and (2) the timely secretion of substances that aid in digestion. The autonomic innervation, sympathetic and parasympathetic, is controlled by centers in the brain and by local stimuli that are mediated by neural plexuses within the gastrointestinal walls. The gastrointestinal tract (alimentary canal) consists of the mouth, esophagus, stomach, small intestine, large intestine, rectum, and anus. It carries out the following digestive processes: 1. Ingestion of food 2. Propulsion of food and wastes from the mouth to the anus 3. Secretion of mucus, water, and enzymes 4. Mechanical digestion of food particles 5. Chemical digestion of food particles 6. Absorption of digested food 7. Elimination of waste products by defecation Histologically, the gastrointestinal tract consists of four layers. From the inside out, they are the mucosa, submucosa, muscularis, and serosa or adventitia (esophagus only). These concentric layers vary in thickness, and each layer has sublayers. Neurons forming the enteric nervous system are located solely within the gastrointestinal tract and are controlled by local and autonomic nervous system stimuli. The enteric nervous system comprises three nerve plexuses located in different layers of the gastrointestinal walls. The submucosal plexus (Meissner plexus) is located in the muscularis mucosae, the myenteric plexus (Auerbach plexus) between the inner circular and outer longitudinal muscle layers in the muscularis, and the subserosal plexus just beneath the serosa. The enteric (intramural) plexus neurons regulate motility reflexes, blood flow, absorption, secretions, and immune response. Histology • Mucosa: Most inner • Submucosa: ducts and glands • Muscularis: muscle layers that control peristalsis • Serosa or adventitia: The connective tissue layer, holds everything in place Enteric plexus (Enteric Nervous System): Controlled by local and autonomic nervous system stimuli • Submucosal plexus • Myenteric plexus • Subserosal plexus

Vitamin Absorption

Fat soluble vitamins (A, D3, E, K), stored in liver, dont need everyday because we store them. Water soluble vitamins (B complex, folate, biotin, pantothenic acid): Have to have a steady intake because our body doesn't store them.

Function, anatomy and physiology of the stomach and small intestine

Food is propelled through the gastrointestinal tract by peristalsis: waves of sequential relaxations and contractions of the muscularis. The lower esophageal sphincter opens to admit swallowed food into the stomach and then closes to prevent regurgitation of food back into the esophagus. The stomach is a baglike structure that secretes digestive juices, mixes and stores food, and propels partially digested food (chyme) into the duodenum. The smooth muscles of the stomach include the outer longitudinal, middle circular, and internal oblique. The vagus nerve stimulates gastric (stomach) secretion and motility. The hormones gastrin and motilin stimulate gastric emptying; the hormones secretin and cholecystokinin delay gastric emptying. Gastric glands in the fundus and body of the stomach secrete intrinsic factor, which is needed for vitamin B12 absorption, and hydrochloric acid, which dissolves food fibers, kills microorganisms, and activates the enzyme pepsin. Chief cells in the stomach secrete pepsinogen, which is converted to pepsin in the acidic environment created by hydrochloric acid. Acid secretion is stimulated by the vagus nerve, gastrin, and histamine and inhibited by sympathetic stimulation and cholecystokinin. Acetylcholine stimulates pepsin secretion. Mucus is secreted throughout the stomach and protects the stomach wall from acid and digestive enzymes. The three phases of acid secretion by the stomach are the cephalic phase (anticipation and swallowing), the gastric phase (food in the stomach), and the intestinal phase (chyme in the intestine). The small intestine is 5 m long and has three segments: the duodenum, jejunum, and ileum. Digestion and absorption of all major nutrients and most ingested water occur in the small intestine. The peritoneum is a double layer of membranous tissue. The visceral layer covers the abdominal organs, and the parietal layer extends along the abdominal wall. Blood flow to the small intestine is primarily provided by the superior mesenteric artery. The duodenum receives chyme from the stomach through the pyloric valve. The presence of chyme stimulates the liver and gallbladder to deliver bile and the pancreas to deliver digestive enzymes and alkaline secretions. Bile and enzymes flow through an opening guarded by the sphincter of Oddi. Bile is produced by the liver and is necessary for fat digestion and absorption. Bile's alkalinity helps neutralize chyme, thereby creating a pH that enables the pancreatic enzymes to digest proteins, carbohydrates, and sugars. Enzymes secreted by the small intestine (maltase, sucrase, lactase), pancreatic enzymes (proteases, amylase, and lipase), and bile salts act in the small intestine to digest proteins, carbohydrates, and fats. Digested substances are absorbed across the intestinal wall and then transported to the liver through the hepatic portal vein, where they are metabolized further. The ileocecal valve connects the small and large intestines and prevents reflux into the small intestine. Villi are small fingerlike projections that extend from the small intestinal mucosa and increase its absorptive surface area. Carbohydrates, amino acids, and fats are absorbed primarily by the duodenum and jejunum; bile salts and vitamin B12 are absorbed by the ileum. Vitamin B12 absorption requires the presence of intrinsic factor. Bile salts emulsify and hydrolyze fats and incorporate them into water-soluble micelles that transport them through the unstirred layer to the brush border of the intestinal mucosa. The fat content of the micelles readily diffuses through the epithelium into lacteals (lymphatic ducts) in the villi. From there fats flow into the lymphatics and into the systemic circulation, which delivers them to the liver. Minerals and water-soluble vitamins are absorbed by active and passive transport throughout the small intestine. Peristaltic movements created by longitudinal muscles propel the chyme along the intestinal tract, whereas contractions of the circular muscles (segmentation) mix the chyme and promote digestion. The ileogastric reflex inhibits gastric motility when the ileum is distended. The intestinointestinal reflex inhibits intestinal motility when one intestinal segment is overdistended. The gastroileal reflex increases intestinal motility when gastric motility increases.

Glomerulus anatomy

Glomerular filtration membrane filters selected blood components through its three layers. 1. Inner layer: Glomerular endothelium, small pores 2. Middle layer: Glomerular basement membrane (GBM); negative charge, doesn't allow albumin and other positively charged molecules/protein into tubules 3. Outer layer: Visceral epithelium (podocytes) that forms the inner layer of Bowman capsule; they interlock, looks kind of like a dendritic cell Supplied by the afferent arteriole and drained by the efferent arteriole Juxtaglomerular apparatus • Juxtaglomerular cells: These specialized cells are located around the afferent arteriole where the afferent arteriole enters the glomerulus. • *Macula densa: Portion of the distal convoluted tubule with specialized sodium and chloride-sensing cells is located between the afferent and efferent arterioles* • Control of renal blood flow (RBF), glomerular filtration, and renin secretion occurs at this site

Know structures in the juxtaglomerular apparatus (JGA), its function and how it carries out its function

Glomerular filtration occurs when plasma filtrate from the glomerulus passes through the three layers of the glomerular membrane into Bowman space to form the primary urine. The endothelium, basement membrane, and podocytes are covered with protein molecules bearing anionic (negative) charges that retard the filtration of anionic proteins and prevent proteinuria. The glomerulus is supplied by the afferent arteriole and drained by the efferent arteriole. A group of specialized cells known as juxtaglomerular cells are located around the afferent arteriole where it enters the glomerulus. Between the afferent and efferent arterioles is a portion of the distal convoluted tubule with specialized sodium- and chloride-sensing cells known as the macula densa. Together the juxtaglomerular cells and macula densa cells form the juxtaglomerular apparatus (JGA). Control of renal blood flow, glomerular filtration, and renin secretion occurs at this site. Renin is an enzyme secreted from the juxtaglomerular apparatus; it causes the generation of angiotensin I, which is converted to angiotensin II by the action of ACE. Angiotensin II is a potent vasoconstrictor and also stimulates release of aldosterone from the adrenal cortex. Thus the renin-angiotensin-aldosterone system is a regulator of renal blood flow and blood pressure

Know purpose of Glomerular Filtration Rate (GFR) clinically and what it represents

Glomerulus is freely permeable to water and relatively impermeable to large colloids such as plasma proteins. Size and electrical charge are important factors that affect permeability. • Positive-charged particles permeate the membrane more readily than neutral- or negative-charged particles. *Net filtration pressure: The combined effect of forces favoring and forces opposing filtration. • Favoring forces: Capillary hydrostatic pressure • Opposing forces: Oncotic pressure in the capillary and hydrostatic pressure in Bowman capsule* ---- The fluid filtered by the glomerular capillary filtration membrane is protein free but contains electrolytes such as sodium, chloride, and potassium and organic molecules such as creatinine, urea, and glucose in the same concentrations as in plasma. Like other capillary membranes, the glomerulus is freely permeable to water and relatively impermeable to large colloids such as plasma proteins. The size of the molecules and their electrical charge are important factors affecting the permeability of substances crossing the glomerulus. The small size of the filtration slits in the glomerular epithelium restricts the passage of proteins and other macromolecules. The negative charge along the filtration membrane further impedes the passage of negatively charged macromolecules (because like forces repel each other). Positively charged macromolecules, therefore permeate the membrane more readily than neutrally charged particles. Capillary pressures also affect glomerular filtration. The hydrostatic pressure within the capillary is the major force for inducing water and solute movement across the filtration membrane into Bowman capsule. This pressure is determined by the systemic arterial pressure and the resistance to blood flow in the afferent and efferent arterioles. Two forces oppose the filtration effects of the glomerular capillary hydrostatic pressure (PGC): (1) the hydrostatic pressure in Bowman space (PBC), and (2) the effective oncotic pressure of the glomerular capillary blood (πGC). Hydrostatic pressure is a pushing force in relation to water, and oncotic pressure is a pulling force. Because the fluid in Bowman space normally contains only minute amounts of protein, it usually does not have an oncotic influence on the plasma of the glomerular capillary. As the protein-free fluid is filtered into Bowman capsule, the plasma oncotic pressure increases and the hydrostatic pressure decreases. The increase in glomerular capillary oncotic pressure is great enough to reduce the net filtration pressure to zero at the efferent end of the capillary and to stop the filtration process effectively. The low hydrostatic pressure and increased oncotic pressure in the efferent arteriole then are transferred to the peritubular capillaries and facilitate reabsorption of fluid from the proximal convoluted tubules. Filtration Rate The total volume of fluid filtered by the glomeruli averages 180 L/day, or approximately 120 ml/minute, a phenomenal amount considering the size of the kidneys. Because only 1 to 2 L of urine is excreted per day, 99% of the filtrate is reabsorbed into the peritubular capillaries and thus is returned to the blood. Obstruction to the outflow of urine (caused by strictures, stones, or tumors along the urinary tract) can cause a retrograde increase in pressure at Bowman capsule and a decrease in GFR. Low levels of plasma protein in the blood from severe malnutrition or liver disease result in a decrease in πGC, which increases GFR. Excessive loss of protein-free fluid from vomiting, diarrhea, use of diuretics, or excessive sweating can increase glomerular capillary oncotic pressure and decrease the GFR. Renal disease also can cause changes in pressure relationships by altering capillary permeability and the surface area available for filtration. ---- The GFR is the BEST estimate of kidney function. Lost or damaged nephrons lead to corresponding decline in GFR. Clinically determined by calculating creatinine clearance GFR will decrease with age (Creatinine is the product of muscle metabolism)

How fats, carbohydrates and proteins are digested including where in the GI system digestion begins and/or occur and what enzymes are necessary to digest the particular substance

Hydrochloric acid: Breaks down carbohydrates in stomach and intestines. Has pH of about 4 → very acidic! Pepsin: Breaks down proteins Pancreatic enzymes: Two main ones are amylase and lipase - helpful for breaking down carbs and fats, Generally very alkaline Intestinal enzymes: Help with breaking down sugar, proteins Bile : Essential for breaking down fats, Found mostly in liver, Very alkaline Carbs → monosaccharides (the only form we can absorb) Proteins → amino acids Fats → fatty acids Carbohydrates Enzymes: salivary amylase, pancreatic amylase, brush border enzymes Location: mouth, small intestine Fats Enzymes: emulsifying agents (bile), pancreatic lipases Location: small intestine Proteins Enzymes: pepsin, pancreatic enzymes, brush border enzymes Location: stomach, small intestine

Digestion and Absorption

Hydrochloric acid: Mainly in stomach, Breaks down carbs, pH of 3-4 Pepsin: breaks down proteins Pancreatic enzymes: various enzymes. 2 important ones are amylase and lipase, helpful for breakdown of carbs and fats. Generally alkaline Intestinal enzymes Bile: breaks down fat, formed mostly in the liver, very alkaline (due to bicarb). Made up of bile salts, cholesterol, bicarbonate, and electrolytes and water. 90% of water is absorbed in the small intestine

Know the function and role of the following hormones: renin, ADH and aldosterone in regulating urine and plasma volume

Hormonal factors and many mediators can alter the resistance of the renal vasculature by stimulating vasodilation or vasoconstriction. A major hormonal regulator of renal blood flow is the renin-angiotensin-aldosterone system (RAAS), which can increase systemic arterial pressure and increase sodium reabsorption. Renin is an enzyme formed and stored in granular cells of the afferent arterioles of the JGA. The release of renin is principally triggered by decreased blood pressure in the afferent arterioles, which reduces stretch of the juxtaglomerular cells; decreased sodium chloride concentrations in the distal convoluted tubule; sympathetic nerve stimulation of β-adrenergic receptors on the juxtaglomerular cells; and release of prostaglandins. When renin is released, it cleaves an α-globulin (angiotensinogen produced by liver hepatocytes) in the plasma to form angiotensin I, which is physiologically inactive. In the presence of angiotensin-converting enzyme (ACE) produced from the pulmonary and renal endothelium, angiotensin I is converted to angiotensin II. Angiotensin II stimulates secretion of aldosterone by the adrenal cortex, *is a potent vasoconstrictor*, and stimulates antidiuretic hormone (ADH) secretion and thirst. Numerous physiologic effects of the RAAS serve the purpose of stabilizing systemic blood pressure and preserving the extracellular fluid volume during hypotension or hypovolemia, including sodium reabsorption, potassium excretion, systemic vasoconstriction, sympathetic nerve stimulation, thirst stimulation, and drinking. ACE inhibitors are a class of drugs that reduce blood pressure by inhibiting the formation of angiotensin II and aldosterone. Natriuretic peptides are a group of peptide hormones, including atrial natriuretic peptide (ANP), secreted from myocardial cells in the atria and brain natriuretic peptide (BNP) secreted from myocardial cells in the cardiac ventricles. When the heart dilates during volume expansion or heart failure, ANP and BNP inhibit sodium and water absorption by kidney tubules, inhibit secretion of renin and aldosterone, vasodilate the afferent arterioles, and constrict the efferent arterioles. The result is increased urine formation leading to decreased blood volume and blood pressure. C-type natriuretic peptide is secreted from vascular endothelium and in the nephron and causes vasodilation. Urodilatin is secreted by the distal convoluted tubules and collecting ducts and causes vasodilation and natriuretic and diuretic effects.

Mechanisms that cause the different types of hypertension

Hypertension is consistent elevation of systemic arterial blood pressure. Hypertension is the most common primary diagnosis in the United States—approximately 1 in 3 adults greater than 20 years of age has hypertension; this increases to nearly two thirds in those older than age 60. The prevalence of hypertension is nearly equal between men and women. Black adults have among the highest rates of hypertension in the world (44%). Approximately 80% of hypertensive adults are aware of their condition, 71% are using antihypertensive medication, but only 48% of those have their hypertension controlled. Hypertension is defined in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) as a sustained systolic blood pressure of 140 mmHg or greater or a diastolic pressure of 90 mmHg or greater. Normal blood pressure is associated with the lowest cardiovascular risk, whereas those who fall into the prehypertension category (which includes between 25% and 37% of the U.S. population) are at risk for developing hypertension and many associated cardiovascular complications unless lifestyle modification and treatment are instituted. Some individuals with hypertensive disease have isolated systolic hypertension. *Isolated systolic hypertension (ISH)* is elevated systolic blood pressure accompanied by normal diastolic blood pressure (less than 90 mmHg). ISH is becoming more prevalent in all age groups and is strongly associated with cardiovascular and cerebrovascular events. Approximately 95% of cases of hypertension have no known cause and therefore are diagnosed as *primary hypertension*. *Secondary hypertension* accounts for 5% of cases and is caused by altered hemodynamics associated with an underlying primary disease. Hypertension is a complex disorder that affects the entire cardiovascular system, and all types and stages of hypertension are associated with increased risk for target organ disease events, such as myocardial infarction (MI), kidney disease, and stroke.

Hypertension and CAD

Hypertension is responsible for a two- to threefold increased risk of atherosclerotic cardiovascular disease including MI. It contributes to endothelial injury, a key step in atherogenesis, and causes myocardial hypertrophy, which increases myocardial demand for coronary flow. The overactivity of the SNS and RAAS commonly found in hypertension also contributes to the genesis of coronary artery disease

Understand alterations in children including hypospadias, epispadias and bladder exstrophy and their differences

Hypospadias is a congenital condition in which the urethral meatus is located on the ventral side or undersurface of the penis. The meatus can be located anywhere on the glans, the penile shaft, the base of the penis, the penoscrotal junction, or the perineum. This is the most common anomaly of the penis and occurs in about 1 in 125 infant boys. The etiology is multifactorial and related to disruptions in male hormones, including testosterone biosynthesis defects, steroid 5α-reductase type 2 mutations, genes associated with penile and urethral development, hormones administered for in vitro fertilization, advanced maternal age, and other environmental factors. Chordee, or penile torsion, may accompany hypospadias. In chordee a shortage of skin on the ventral surface causes the penis to bend or to "bow" ventrally. Penile torsion is a counterclockwise twist of the penile shaft. Partial absence of the foreskin, inguinal hernia, and cryptorchidism are associated with the anomaly. The goals for corrective surgery on the child with hypospadias are: (1) a straight penis when erect to facilitate sexual intercourse as an adult, (2) a uniform urethra of adequate caliber to prevent spraying during urinations, (3) a cosmetic appearance satisfactory to the individual, and (4) repair completed in as few procedures as possible. Formerly performed in two or more stages, hypospadias repairs are now done in one stage. Improvements in microsurgical techniques have enhanced outcomes and decreased complications and the need for follow-up surgery. Surgery is usually performed between 4 and 12 months of age. Epispadias and exstrophy of the bladder are the same congenital defect but expressed to a different degree. The dorsal urethra is not fused in epispadias and has failed to form into a tube. In male epispadias the urethral opening is on the dorsal surface of the penis. In females a cleft along the ventral urethra usually extends to the bladder neck. The incidence of epispadias is about 1 in 40,000 to 118,000 births. About twice as many boys as girls present with this defect. In boys the urethral opening may be small and situated behind the glans (anterior epispadias), or a fissure may extend the entire length of the penis and into the bladder neck (posterior epispadias). The majority of children with epispadias can achieve urinary continence, although surgical intervention may be necessary. Exstrophy of the bladder is a rare extensive congenital anomaly of herniation of the bladder through the abdominal wall with failure of the abdominal muscles, pelvic ring, and pelvic floor musculature to fuse in the midline. The posterior portion of the bladder mucosa is exposed and appears bright red. The prevalence of exstrophy of the bladder is about 2.07 in 100,000 live births. Boys are predominant with a ratio of about 2:1 and this complication is more common in whites. Exstrophy of the bladder is caused by intrauterine failure of the abdominal wall and the mesoderm of the anterior bladder to fuse. Urine seeps onto the abdominal wall from the ureters, causing a constant odor of urine and excoriation of the surrounding skin. The rectus muscles below the umbilicus are separated, and the pubic rami (bony projections of the pubic bone) are not joined. The clitoris in girls is divided into two halves with the urethra between them. The penis in boys is epispadic. In addition, the posterior aspect of the pelvis is externally rotated, which retroverts the acetabula and causes external rotation of the feet. This causes a waddling gait when the child first learns to walk, but most children quickly learn to compensate. Surgical intervention may be required. Because the exposed bladder mucosa becomes hyperemic and edematous, it bleeds easily and is painful. It should be covered with Silastic or a plastic dressing (e.g., kitchen plastic wrap) for protection from diaper irritation while permitting urine drainage. Ideally the bladder and pubic defect should be closed before the infant is 72 hours old. Surgical reconstruction is usually performed within the first year either as a complete primary repair or as staged procedures. Staged procedures may include bladder augmentation and bladder neck and epispadias repair.

Understand physiologic effects of hypoventilation and hyperventilation.

Hypoventilation Hypercapnia can lead to respiratory acidosis Hyperventilation Hypocapnia can lead to respiratory alkalosis

Understand pathophysiology and clinical manifestations of pulmonary hypertension.

If alveolar hypoxia affects all segments of the lung, vasoconstriction occurs throughout the pulmonary vasculature, and pulmonary hypertension (elevated pulmonary artery pressure) can result. The pulmonary vasoconstriction caused by low PAO2 is reversible if the PAO2 is corrected. Chronic alveolar hypoxia can result in permanent pulmonary artery hypertension, which eventually leads to cor pulmonale and heart failure. Acidemia also causes pulmonary artery constriction. If the acidemia is corrected, the vasoconstriction is reversed. It is important to note that an elevated PaCO2 without a drop in pH does not cause pulmonary artery constriction. Other biochemical factors that affect the caliber of vessels in pulmonary circulation are histamine, prostaglandins, endothelin, serotonin, nitric oxide, and bradykinin.

Know the relationships between bowel obstruction and states of acidosis and alkalosis

If the obstruction is at the pylorus or high in the small intestine, metabolic alkalosis develops initially as a result of excessive loss of hydrogen ions that normally would be reabsorbed from the gastric juice. With prolonged obstruction or obstruction lower in the intestine, metabolic acidosis is more likely to occur because bicarbonate from pancreatic secretions and bile cannot be reabsorbed. Hypokalemia from vomiting and decreased potassium absorption can be extreme, promoting acidosis and atony of the intestinal wall. Metabolic acidosis also may be accentuated by ketosis, the result of declining carbohydrate stores caused by starvation. Lack of circulation permits the buildup of significant amounts of lactic acid, which worsen the metabolic acidosis.

Understand the different causative agents for acute glomerulonephritis and which are the most common. Also know what portions of the kidney are affected and how it is clinically manifested

Immune Mechanisms - Formation of immune complexes (antigen/antibody) in the circulation with subsequent deposition in glomerulus - Antibodies produced against the organism that cross-react with the glomerular endothelial cells; ex: *post-strep* - Activation of complement - Recruitment and activation of immune cells and mediators Nonimmune Mechanisms - Ischemia - Toxin exposure - Drugs Decreased glomerular filtration rate (GFR) - Decreased glomerular perfusion (glomerular blood flow) as a result of inflammation - Glomerular sclerosis (scarring) - Thickening of the glomerular basement membrane, but increased permeability to proteins and red blood cells Types 1. Immunoglobulin A (IgA) nephropathy (Berger disease) - Binding of abnormal IgA to mesangial cells in the glomerulus, resulting in injury and mesangial proliferation - *Most common form of acute glomerulonephritis, twice as common in males, young males* - Hematuria, happens quickly after an infection 2. Membraneous nephropathy - Complement-mediated glomerular injury with increased glomerular permeability and glomerulosclerosis 3. Rapidly progressive crescentic glomerulonephritis - Injury that results in the proliferation of glomerular capillary endothelial cells with a rapid loss of renal function - Casts are formed as cells slough off - Poor prognosis if not caught early - Proteinuria 4. Mesangial proliferative glomerulonephritis - Immune complex in the mesangium with mesangial cell proliferation 5. Membranoproliferative glomerulonephritis - Involves mesangial cell proliferation, complement deposition, and crescent formation Clinical manifestations - Hematuria with red blood cell casts - Smoky, brown-tinged urine - Proteinuria including loss of albumin - Low serum albumin (because of loss of neg charge and physical openings) - Edema - htn Severe or progressive glomerular disease: Eventual oliguria Oliguria: Urine output <30 ml/hr or <400 ml/day Nephrotic Sediment Clinical manifestations: Contains massive amounts of protein (≥3 grams/day of protein into the urine) and lipids and either a microscopic amount of blood or no blood. Nephritic Sediment Clinical manifestations: Blood is present in the urine with red cell casts, white cell casts, and varying degrees of protein, which is not usually severe.

Causes and pathophysiology of pancreatitis

Inflammation of the pancreas Enzymes cause auto-digestion of pancreatic tissue and leak into bloodstream to cause injury to blood vessels and organs (when we eat, our bodies signal the pancreatic enzymes to secrete and activate for digestion. However, if they can't get out of the pancreas, they are activated within it) Usually have to go on NPO diet and rest pancreas so it stops producing enzymes Associated with several clinical disorders - Most common = alcohol intake - Second most common = cholecystitis (inflammation of gallbladder) Symptoms Epigastric pain radiating to the back, worsened after eating Fever and leukocytosis Hypotension and hypovolemia (enzymes increase vascular permeability) Increase in serum amylase level Chronic pancreatitis - related to alcohol abuse ---- Pancreatitis, or inflammation of the pancreas, is a relatively rare (about 17 cases per 100,000 people in the United States) and a potentially serious disorder. Incidence is about equal in men and women and is more common between 50 and 60 years of age. Risk factors include: alcoholism, obstructive biliary tract disease (particularly cholelithiasis), peptic ulcers, abdominal trauma, hyperlipidemia, certain drugs, and genetic factors (hereditary pancreatitis, cystic fibrosis). The cause is unknown in 15% to 25% of cases. Acute Pancreatitis Acute pancreatitis is usually a mild disease and resolves spontaneously, but about 20% of those with the disease develop a severe acute pancreatitis requiring hospitalization. Pancreatitis develops because of obstruction to the outflow of pancreatic digestive enzymes caused by bile duct or pancreatic duct obstruction (e.g., gallstones). Chronic alcohol use may also cause spasm of the sphincter of Oddi and formation of protein plugs in pancreatic ducts, resulting in obstruction. Acute pancreatitis can also result from direct cellular injury from drugs or viral infection. Pathophysiology In obstructive disease, the backup of pancreatic secretions causes activation and release of enzymes (activated trypsin activates chymotrypsin, lipase, and elastase) within the pancreatic acinar cells. The activated enzymes cause autodigestion (e.g., proteolysis, lipolysis) of pancreatic cells and tissues, resulting in inflammation. The autodigestion causes vascular damage, coagulative necrosis, fat necrosis, and formation of pseudocysts (walled-off collections of pancreatic secretions). Edema within the pancreatic capsule leads to ischemia and can contribute to necrosis. Systemic effects are associated with severe acute pancreatitis. Proinflammatory cytokines (e.g., interleukin-6, tumor necrosis factor-alpha, transforming growth factor-beta, and platelet-activating factor) and vasoactive peptides are released into the bloodstream. Activation of leukocytes, injury to vessel walls, and coagulation abnormalities with development of vasodilation, hypotension, and shock occur. These systemic effects can lead to acute respiratory distress syndrome (ARDS), heart failure, renal failure, coagulopathies, and the systemic inflammatory response syndrome (SIRS). Translocation of intestinal bacteria to the bloodstream may cause peritonitis or sepsis. Anti-inflammatory cytokines and specific cytokine inhibitors are produced in response to the systemic inflammatory response and may increase risk of infection. As the pancreatitis progresses, pancreatic stellate cells become activated, causing pancreatic fibrosis, strictures, and duct obstruction and leading to chronic pancreatitis. Clinical Manifestations Epigastric or midabdominal pain is the cardinal symptom of acute pancreatitis. The pain may radiate to the back because of the retroperitoneal location of the pancreas. The pain is caused by edema, which distends the pancreatic ducts and capsule; chemical irritation and inflammation of the peritoneum; and irritation or obstruction of the biliary tract. Fever and leukocytosis accompany the inflammatory response. Nausea and vomiting are caused by hypermotility or paralytic ileus secondary to the pancreatitis or peritonitis. Abdominal distention accompanies bowel hypermotility or paralytic ileus and the accumulation of fluids in the peritoneal cavity (ascites). Hypotension and shock occur with hypovolemia and SIRS. Tachypnea and hypoxemia are indicative of ascites, diaphragmatic irritation, or respiratory complications. In severe cases, hypovolemia decreases renal blood flow sufficiently to impair renal function. Transient hyperglycemia also can occur if glucagon is released from damaged A cells in the pancreatic islets. SIRS and multiple organ failure account for most deaths with severe pancreatitis. In severe acute pancreatitis, some individuals develop flank or periumbilical ecchymosis, a sign of poor prognosis. Evaluation and Treatment Serum lipase levels increase within 4 to 8 hours of clinical symptom onset and decrease within 8 to 14 days. Serum amylase level is elevated but is not diagnostic of severity or specificity of disease. Acute pancreatitis is difficult to diagnose because several other disorders can cause similar clinical and laboratory findings (e.g., perforating duodenal ulcer, acute cholecystitis, and kidney stones). There is no specific treatment for acute pancreatitis. The goal of treatment is to stop the process of autodigestion and prevent systemic complications. Hemodynamic monitoring and parenteral fluids are essential to restore blood volume and prevent hypotension and shock, particularly in the first 24 hours. Narcotic medications may be needed to relieve pain. Meperidine hydrochloride (Demerol) is used instead of morphine because it causes less spasm of the sphincter of Oddi than morphine. Nasogastric suction may not be necessary with mild pancreatitis but may help relieve pain and prevent paralytic ileus in individuals who are nauseated and vomiting. Feeding is usually initiated within 24 to 48 hours if ileus is not present. In severe acute pancreatitis, enteral nutrition with use of jejunal tube feeding is usually well tolerated and may decrease pancreatic enzyme secretion, prevent gut bacterial overgrowth, and maintain gut barrier function. Parenteral hyperalimentation should be initiated only when enteral feeding is not tolerated. Drugs that decrease gastric acid production (e.g., H2 receptor antagonists) can decrease stimulation of the pancreas by secretin. Necrotizing pancreatitis requires surgical resection, and antibiotics may control infection. The risk of mortality increases significantly with the development of pulmonary, cardiac, and renal complications. Chronic Pancreatitis Chronic alcohol abuse is the most common cause of chronic pancreatitis because repeated exacerbations of acute pancreatitis can lead to chronic changes. Obstruction from gallstones, autoimmune disease, gene mutations, smoking, occupational chemical exposure, and obesity are associated with chronic pancreatitis. The disease is idiopathic in about 25% of cases. Toxic metabolites and chronic release of inflammatory cytokines contribute to the destruction of acinar cells and islets of Langerhans. The pancreatic parenchyma is destroyed and replaced by fibrous tissues, strictures, calcification, ductal obstruction, and pancreatic cysts. The cysts are walled-off areas or pockets of pancreatic juice, necrotic debris, or blood within or adjacent to the pancreas. Continuous or intermittent abdominal pain is the classic symptom. Pain is associated with increased intraductal pressure, increased tissue pressure, ischemia, neuritis, ongoing injury, and changes in central pain perception. Weight loss and, less commonly, steatorrhea and diabetes mellitus accompany disease progression and require treatment with oral lipase and insulin. Autoimmune chronic pancreatitis is treated with corticosteroids. Preventing disease progression includes lifestyle modification to stop alcohol use and smoking. Pain management is complex with use of analgesics, endoscopic therapy, nerve block, and surgical drainage of cysts or partial resection of the pancreas. Chronic pancreatitis is a risk factor for pancreatic cancer.

Know what common organisms infect the urinary tract; know the common risk factors for developing a UTI and how to distinguish pyelonephritis from cystitis

Inflammation of the urinary epithelium after invasion and colonization by some pathogen in the urinary tract Retrograde movement of bacteria into the urethra and bladder Classification: Location or complicating factors Cystitis: Bladder inflammation Pyelonephritis: Inflammation of upper urinary tract Most common pathogens Escherichia coli (80-85%) Staphylococcus saprophyticus (10%) Other microorganisms (≈5%): Psuedomonas, viruses, etc. Host defenses: washout phenomena, protective mucin layer, local immune responses, peristaltic movement of ureters Elderly and post menopausal produce less mucin making them more susceptible to UTIs Cystitis: is an inflammation of the bladder Manifestations: Frequency, dysuria, urgency, and lower abdominal and/or suprapubic pain, Possible confusion in elderly (>80) Treatment: Antimicrobial therapy for 3-7 days, increased fluid intake, avoidance of bladder irritants, and urinary analgesics Pyelonephritis Acute pyelonephritis: Acute infection of the ureter, renal pelvis, and/or renal parenchyma Clinical manifestations Flank pain Fever, chills Costovertebral tenderness Evaluation - White blood cell casts, indicating pyelonephritis - Urine culture Treatment Antibiotic administration for 2-3 weeks Chronic pyelonephritis Persistent or recurrent infection of the kidneys, leading to scarring of the kidneys Inflammation and fibrosis, located in the interstitial spaces between the tubules, leading to chronic kidney failure NSAID overuse, ischemia, autoimmune disorders like Lupus Treatment Treat underlying cause Prolonged antibiotics for recurrent infections Relieve obstruction

Pathophysiology of appendicitis as well as signs and symptom and clinical manifestations

Inflammation of the vermiform appendix Possible causes - exact cause no understood Obstruction (often with fecal matter) Ischemia Increased intraluminal pressure Infection Ulceration Symptoms • Epigastric and right lower quadrant pain (usually starts epigastric, then moves RLQ) • Rebound tenderness • Nausea, vomiting • Fever, leukocytosis Clinical manifestations Acute appendicitis (non-ruptured): can be removed, can go home from hospital in a couple hours Ruptured appendicitis: will be in hospital for a few days Chronic appendicitis: never get to acute phase, but still have symptoms

What are the clinical manifestations and evaluation & treatment of intestinal obstruction and ileus?

Intestinal obstruction can be caused by any condition that prevents the normal flow of chyme through the intestinal lumen or failure of normal intestinal motility in the absence of an obstructing lesion (ileus). The small intestine is more commonly obstructed because of its narrower lumen. Mechanical obstructions: Due to either problems with the esophageal wall or obstructions outside the wall, such as a tumor, stricture, or herniations, pushing in on the lumen Functional obstructions: results from neural or muscular disorders that interfere with voluntary movement or peristalsis. Causes include dermatomyositis, neurologic impairments caused by stroke, multiple sclerosis, Parkinson disease, and achalasia Achalasia Denervation of smooth muscle in the esophagus and failure of the lower esophageal sphincter to relax Food gets stuck in the esophagus Acute obstructions usually have mechanical causes, such as adhesions or hernias. Chronic or partial obstructions are more often associated with tumors or inflammatory disorders, particularly of the large intestine. Intussusception is rare in adults compared with the more frequent occurrence in infants. The most common causes of large bowel obstruction are colorectal cancer, volvulus (twisting), and strictures related to diverticulitis. Pathophysiology The consequences of intestinal obstruction are related to its onset and location, the length of intestinal tract proximal to the obstruction, and the presence and severity of ischemia. Postoperative paralytic ileus results from inhibitory neural reflexes associated with inflammatory mediators, and the influence of exogenous (meperidine) and endogenous opioids (endorphins) that affect the entire GI tract, including the stomach. Small intestine obstruction leads to accumulation of fluid and gas inside the lumen proximal to the obstruction. Fluids accumulate from impaired water and electrolyte absorption and enhanced secretion with net movement of fluid from the vascular space to the intestinal lumen. Gas from swallowed air, and to a lesser extent from bacterial overgrowth, contributes to the distention. Distention begins almost immediately, as gases and fluids accumulate proximal to the obstruction. Distention decreases the intestine's ability to absorb water and electrolytes and increases the net secretion of these substances into the lumen. Within 24 hours, up to 8 L of fluid and electrolytes enters the lumen in the form of saliva, gastric juice, bile, pancreatic juice, and intestinal secretions. Copious vomiting or sequestration of fluids in the intestinal lumen prevents their reabsorption and produces severe fluid and electrolyte disturbances. Extracellular fluid volume and plasma volume decrease, causing dehydration. Hemoconcentration (decreased plasma volume) elevates hematocrit level and causes hypotension and tachycardia. Severe dehydration leads to hypovolemic shock. If the obstruction is at the pylorus or high in the small intestine, metabolic alkalosis develops initially as a result of excessive loss of hydrogen ions that normally would be reabsorbed from the gastric juice. With prolonged obstruction or obstruction lower in the intestine, metabolic acidosis is more likely to occur because bicarbonate from pancreatic secretions and bile cannot be reabsorbed. Hypokalemia from vomiting and decreased potassium absorption can be extreme, promoting acidosis and atony of the intestinal wall. Metabolic acidosis also may be accentuated by ketosis, the result of declining carbohydrate stores caused by starvation. Lack of circulation permits the buildup of significant amounts of lactic acid, which worsen the metabolic acidosis. If pressure from the distention is severe enough, it occludes the arterial circulation and causes ischemia, necrosis, perforation, and peritonitis. Fever and leukocytosis are often associated with overgrowth of bacteria, ischemia, and bowel necrosis. Bacterial proliferation and translocation across the mucosa to the mesenteric lymph nodes or systemic circulation cause sepsis. The release of inflammatory mediators into the circulation causes remote organ failure. Consequences of large bowel obstruction are related to the competence of the ileocecal valve, which normally prevents reflux of colonic contents into the small intestine. When the ileocecal valve is competent, the cecum cannot decompress into the small intestine, resulting in distention. Ischemia occurs when the intraluminal pressure exceeds the capillary pressure in the lumen. Clinical Manifestations Colicky pains caused by intestinal distention followed by nausea and vomiting are the cardinal symptoms. Typically the pain occurs intermittently. Pain intensifies for seconds or minutes as a peristaltic wave of muscle contraction meets the obstruction. The passing of the wave is followed by a pain-free interval. Pain may be continuous with severe distention and then diminish in intensity. If ischemia occurs, the pain loses its colicky character, becoming more constant and severe. Sweating and tachycardia occur as a sympathetic nervous system response to hypotension. Fever, severe leukocytosis, abdominal distention, and rebound tenderness develop as ischemia progresses to necrosis, perforation, and peritonitis. Vomiting and abdominal distention vary, depending on the level and completion of the obstruction. Obstruction at the pylorus causes early, profuse vomiting of clear gastric fluid. Obstruction in the proximal small intestine causes mild distention and vomiting of bile-stained fluid. Obstruction in the distal small intestine causes more pronounced distention because a greater length of intestine is proximal to the obstruction. In this case, vomiting may not occur or may occur later and contain fecal material. Partial obstruction can cause diarrhea or constipation, but complete obstruction usually causes constipation only. Complete obstruction increases the number of bowel sounds, which may be tinkly and accompanied by peristaltic rushes and crampy, abdominal pain. Signs of hypovolemia and metabolic acidosis may be observed as early as 24 hours after the occurrence of complete obstruction. Distention may be severe enough to push against the diaphragm and decrease lung volume. This can lead to atelectasis and pneumonia, particularly in debilitated individuals. Large intestine obstruction usually presents with hypogastric pain and abdominal distention. Pain can vary from vague to excruciating, depending on the degree of ischemia and the development of peritonitis. Evaluation and Treatment Evaluation is based on clinical manifestations and includes ultrasound and radiography. Successful management requires early identification of the site and type of obstruction. Replacement of fluid and electrolytes and decompression of the lumen with gastric or intestinal suction are essential forms of therapy. Laparoscopic procedures can release adhesions. Immediate surgical intervention is required for strangulation and complete obstruction. Neostigmine, a parasympathomimetic, is used for colonic pseudo-obstruction and colonoscopic decompression may be required.

Differences between right and left heart failure including etiology and symptoms

Most causes of heart failure result in dysfunction of the left ventricle (systolic and diastolic heart failure). The right ventricle also may be dysfunctional, especially in pulmonary disease (right ventricular failure). *LEFT HF* 1. Systolic heart failure: Inability of the heart, specifically the left ventricle, to generate adequate cardiac output to perfuse tissues Catecholamine activation: can be toxic to the myocytes if chronic Activation of RAAS: Angiotensin II and aldosterone Inflammatory cytokines: Endothelial hormones, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) Insulin resistance and diabetes Clinical manifestations • Dyspnea, orthopnea, cough of frothy sputum • Fatigue • Decreased urine output and edema Treatment • Apply oxygen • Diuretics, ACE inhibitors, aldosterone blockers, and/or beta-blockers • Increase contractility • Reduce preload and afterload 2. Diastolic heart failure Heart failure with preserved ejection fraction Decreased compliance of the left ventricle and abnormal diastolic relaxation Clinical manifestations: Dyspnea on exertion and fatigue Treatment • Physical training (aerobic and weight training); Improves endurance and quality of life • Beta-blockers, ACE inhibitors, ARBs, and aldosterone blockers *RIGHT HF* Inability of the right ventricle to provide adequate blood flow into the pulmonary circulation. Clinical manifestations • Jugular venous distension, peripheral edema, hepatosplenomegaly Treatment: Same as left heart failure

Small Intestine anatomy

Muscle layers 1. Outer - longitudinal 2. Inner - circular Mucosal folds (plica) 1. Villi: functional unit of intestine; Surface of mucosal folds of villus have tight cell junctions - cells are right up next to each other. Makes it impermeable to water - water doesn't just leak through, it's absorbed where it needs to be. 2. Microvilli: on top of villi 3. Brush border: on top of microvilli Main function of villi/microvilli → to increase surface area for better absorption of water, nutrients, electrolytes Water absorption: mainly in small intestine Stomach generally more acidic, intestines more alkaline.

Myogenic mechanism and tubuloglomerular feedback

Myogenic mechanism (stretch) As arterial pressure declines, stretch on the afferent arteriolar smooth muscle decreases, the afferent arteriole relaxes and glomerular perfusion increases. An increase in arteriolar pressure causes the afferent arteriole smooth muscle to contract and decreases glomerular perfusion. -- As arterial pressure declines, the stretch on the afferent arteriolar smooth muscle decreases and the arteriole relaxes, causing an increase in glomerular perfusion; an increase in arteriolar pressure causes the arteriole smooth muscle to contract and decreases glomerular perfusion.

Nephrotic vs. Nephritic Syndrome

Nephrotic Syndrome - Excretion of 3.0 g or more of protein in urine - Protein excretion as a result of glomerular injury - Clinical manifestations: Hypoalbuminemia. Peripheral edema, Prone to infection Nephrotic syndrome is urinary excretion of > 3 g of protein/day and is more common among children and has both primary and secondary causes. Glomerular disorders associated with primary nephrotic syndrome include minimal change disease, focal segmental glomerulosclerosis, and membranous glomerulonephritis. Secondary causes account for < 10% of childhood cases but > 50% of adult cases, most commonly caused by diabetic nephropathy, amyloidosis, SLE, and certain drug reactions. In the nephrotic syndrome, protein loss is due to glomerular proteinuria, characterized by increased filtration of macromolecules across the glomerular capillary wall. The podocytes (foot processes) and glomerular basement membrane are the major targets of injury in nephrotic syndrome including loss of the negative charge and foot process effacement or slit diaphragm disruption. Primary causes Minimal change glomerulonephritis Focal segmental glomerulosclerosis Membranous glomerulonephritis Secondary causes SLE Hep B and C HIV Diabetes mellitus Malignancy -------------- Nephritic Syndrome: Hematuria (usually microscopic) and red blood cell casts are present in the urine in addition to proteinuria, which is not severe. - Advanced stages: Hypertension, uremia, and oliguria - Caused by increased permeability of the glomerular filtration membrane - Pore sizes enlarge. - Red blood cells and protein pass through. Glomerular disorders associated with nephritic syndrome include acute postinfectious glomerulonephritis (majority are streptococcal), crescentic GN, IgA nephropathy (Berger disease) and systemic lupus erythematosus (SLE). In nephritic syndrome, symptoms and signs range from asymptomatic hematuria (in about 50%) and mild proteinuria to full-blown nephritis with microscopic or gross hematuria (cola-colored, brown, smoky, or frankly bloody urine), proteinuria, oliguria, edema, hypertension, and renal insufficiency. Immune complex injury of the glomerular capillary endothelium causes hematuria. Meanwhile, widespread damaged glomerular vessel walls will activate degranulation of the platelets and lead to thrombotic blockade of the vessels and a resulting drop in the GFR and oliguria. Drop in the GFR will aggressively activate the renin-angiotensin system, and this leads to hypertension. *One clinical tip to note is that hematuria of glomerular origin presents with red blood cell casts, whereas the hematuria that originates after the renal pelvis does not present with casts.* Also, RBCs that pass through injured fenestrations of the glomerular capillaries are damaged and assume dysmorphic shapes. On a urinalysis, *the presence of RBC casts and dysmorphic RBCs will indicate glomerular damage.* Associated Diseases: - Post-streptococcal glomerulonephritis - appears weeks after upper respiratory tract infection (URTI) - IgA nephropathy - appears within a day or two after a URTI - Rapidly progressive glomerulonephritis (crescentic glomerulonephritis) - Goodpasture's syndrome - anti-GBM antibodies against basal membrane antigens - Vasculitic disorder - Wegener's granulomatosis / - Microscopic Polyangiitis / Churg Strauss disease - Membranoproliferative glomerulonephritis - primary or secondary to SLE / Hepatitis B/C - Henoch-Schönlein purpura - systemic vasculitis - deposition of IgA in the skin and kidneys

Understand nephrotic syndrome in children including causes and clinical manifestations

Nephrotic syndrome is a term used to describe a symptom complex characterized by: 1. proteinuria, 2. hypoalbuminemia, 3. hyperlipidemia, 4. and edema. The syndrome is more common in children than adults. When no identifiable cause is found, the condition is termed primary (idiopathic) nephrotic syndrome. If it results from a systemic disease or other causes (e.g., drugs, toxins, diabetes mellitus, lupus nephritis) it is called secondary nephrotic syndrome. Primary nephrotic syndrome is usually described by histopathologic results (i.e., minimal change nephropathy [MCN], focal segmental glomerulosclerosis [FSGS], membranous nephropathy [MN], or membranoproliferative glomerulonephritis [MPGN]): Can only see damage on tests, no obvious explanation why Secondary nephrotic syndrome has the same patterns of histopathology but is associated with an underlying cause. Approximately 95% of cases of nephrotic syndrome in children occur in the absence of systemic or preexisting renal disease. Primary nephrotic syndrome is found predominantly in preschool children, with a peak incidence of onset between 2 and 3 years of age. Onset is rare after 8 years of age. Boys are affected more often than girls. The cause of nephrotic syndrome in children is usually idiopathic and includes minimal change nephropathy Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome in children and adolescents, as well as a leading cause of kidney failure in adults. It is also known as "focal glomerular sclerosis" or "focal nodular glomerulosclerosis". It accounts for about a sixth of the cases of nephrotic syndrome. Edema is the classic symptom of nephrotic syndrome. Several factors contribute to edema formation with hypoalbuminemia (decreased plasma oncotic pressure) and sodium retention as major contributors. The movement of fluid from the vascular to the interstitial space can decrease blood volume and increase the activity of aldosterone and antidiuretic hormone (vasopressin), and decrease atrial natriuretic peptide concentration, all of which promote fluid retention. Clinical Manifestations Onset of nephrotic syndrome is often insidious, with periorbital edema as the first sign. The edema is most noticeable in the morning but subsides during the day as fluid shifts to the abdomen and lower extremities. Parents may notice diminished, frothy, or foamy urine output; when edema becomes pronounced with ascites, respiratory difficulty from pleural effusion and labial or scrotal swelling may develop. Edema of the intestinal mucosa may cause diarrhea, anorexia, and poor absorption. Edema often masks the malnutrition caused by malabsorption and protein loss. Because of protein deficiency, changes in the quality of hair indicate a malnourished state. Pallor, with shiny skin and prominent veins, may be present. Blood pressure is usually normal. The child has an increased susceptibility to infection, especially pneumonia, peritonitis, cellulitis, and septicemia. Irritability, fatigue, and lethargy are common. Infants born with congenital nephrotic syndrome have large fontanels and separated cranial sutures. Evaluation and Treatment The diagnosis of nephrotic syndrome is evident from the clinical presentation and findings of proteinuria, hyperlipidemia, and edema. Several diagnostic tests, including kidney biopsy, may be required to determine whether the cause is an intrinsic renal disease or a consequence of systemic disease. The goals of treatment are to reduce the excretion of protein and to maintain protein-free urine. Prevention or treatment of infection, control of edema, establishment of a balanced nutritional state, and restoration of normal metabolic processes also are important in managing the disorder and avoiding adverse aspects of treatment. Basic management of nephrotic syndrome includes administering glucocorticosteroids (prednisone); adhering to a low-sodium, well-balanced diet; performing good skin care; and, if edema becomes problematic, administering diuretics (furosemide, metolazone). Angiotensin-converting enzyme (ACE) inhibitors inhibit formation of angiotensin II and aldosterone, resulting in decreased blood pressure and decreased renal sodium reabsorption. Nephrotic syndrome is often described by the response to steroid therapy. Steroid-sensitive nephrotic syndrome usually results in complete remission without serious adverse effects. Steroid-resistant nephrotic syndrome is described for children (usually infants 3 to 12 months of age or adolescents) who fail to respond to prednisone within 8 weeks. They may be treated with noncorticosteroid immunosuppressive agents (i.e., cyclophosphamide) or combinations of corticosteroids and noncorticosteroid immunosuppressives to prolong remission. Children with minimal change disease tend to have a very favorable prognosis, whereas those with other conditions, such as FSGS, may develop end-stage kidney disease.

Lung Cancer Histology

Non-small cell lung cancer (85%) 1. Squamous cell carcinoma (30%) - Strongest association with smoking - Tend to be more centrally located, in the bronchi - Localized, metastasized late (you have time to treat) 2. Adenocarcinoma (35‐40%) - Arising from glands, more peripheral - More frequent in women, nonsmokers and Asians Large cell carcinoma (undifferentiated) - Bronchogenic with rapid growth rate - Diagnosed through process of exclusion Neuroendocrine lung tumors - Small cell carcinoma (14%) - Almost exclusively occurs in smokers - Rapid growth, early metastasis - Tumor derived hormone production; hyponatremia, cushing's syndrome, gynecomastia Bronchial carcinoid tumors (1%) - Unrelated to smoking - Slow growing, low metastasis, encapsulated Mesothelioma - Rare tumors associated with asbestos - Symptom onset 20‐40 years - Cancer of the pleura, have to remove the pleura and lung

Risk factors for CAD

Nonmodifiable risk factors: Advanced age; family history Male gender or women after menopause Modifiable risk factors: Dyslipidemia Hypertension Endothelial injury, increase in myocardial demand Cigarette smoking Vasoconstriction and increase in LDL, decrease in high-density lipoproteins (HDL) Diabetes mellitus and insulin resistance Endothelial damage, thickening of the vessel wall Obesity and/or sedentary lifestyle Obesity, dyslipidemia, and hypertension: Metabolic syndrome

Understand abnormal breathing patterns including Kussmaul and Cheyne-Stokes respirations.

Normal breathing (eupnea) is rhythmic and effortless. Ventilatory rate is 8 to 16 breaths per minute, and tidal volume ranges from 400 to 800 ml. A short expiratory pause occurs with each breath, and the individual takes an occasional deeper breath or sigh. Sigh breaths, which help maintain normal lung function, are usually 1.5 to 2 times the normal tidal volume and occur approximately 10 to 12 times per hour. The rate, depth, regularity, and effort of breathing undergo characteristic alterations in response to physiologic and pathophysiologic conditions. Patterns of breathing automatically adjust to minimize the work of respiratory muscles. Strenuous exercise or metabolic acidosis induces Kussmaul respirations (hyperpnea). Kussmaul respirations are characterized by a slightly increased ventilatory rate, very large tidal volume, and no expiratory pause. Labored breathing occurs whenever there is an increased work of breathing, especially if the airways are obstructed, as in chronic obstructive pulmonary disease (COPD). If the large airways are obstructed, a slow ventilatory rate, increased effort, prolonged inspiration or expiration, and stridor (high-pitched sounds made during inspiration) or audible wheezing (whistling sounds on expiration) are typical. In small airway obstruction, like that seen in asthma and chronic obstructive pulmonary disease, a rapid ventilatory rate, small tidal volume, increased effort, prolonged expiration, and wheezing are often present. Restricted breathing is commonly caused by disorders such as pulmonary fibrosis that stiffen the lungs or chest wall and decrease compliance. Restricted breathing is characterized by small tidal volumes and rapid ventilatory rate (tachypnea). Shock and severe cerebral hypoxia (insufficient oxygen in the brain) contribute to gasping respirations that consist of irregular, quick inspirations with an expiratory pause. Anxiety can cause sighing respirations that consist of irregular breathing characterized by frequent, deep sighing inspirations. Cheyne-Stokes respirations are characterized by alternating periods of deep and shallow breathing. Apnea lasting 15 to 60 seconds is followed by ventilations that increase in volume until a peak is reached, after which ventilation (tidal volume) decreases again to apnea. Cheyne-Stokes respirations result from any condition that slows the blood flow to the brainstem, which in turn slows impulses sending information to the respiratory centers of the brainstem. Neurologic impairment above the brainstem is also a contributing factor.

Inflammatory risk factors for coronary disease

Numerous markers of inflammation that have been linked to an increase in CAD risk: • hs-CRP: Explored in greatest depth • fibrinogen • protein C • plasminogen activator inhibitor *Highly sensitive C-reactive protein (hs-CRP)* is an acute phase reactant or protein mostly synthesized in the liver and is an indirect measure of atherosclerotic plaque-related inflammation. Elevated levels of hs-CRP are associated with numerous other CAD risk factors including smoking, obesity, and diabetes, and have been found to be an independent risk factor for coronary disease. A recent study demonstrated that hs-CRP levels can be used to better assign individuals into cardiovascular risk categories that aid in decision-making about pharmacologic interventions for individuals with other risk factors for coronary disease. Other markers of inflammation associated with CAD include: • erythrocyte sedimentation rate • von Willebrand factor concentration • uric acid • IL-6 • IL-18 • TNF-α • fibrinogen • YKL-40 (a 40 kDa (mass) glycoprotein produced by inflammatory cells, cancer cells, and stem cells)

Starvation

Poverty, chronic diseases, malabsorption syndromes, infection, cancer Increased dependence on ketone bodies as cellular energy source. Breaking down of adipose tissue, ketosis

Primary Hypertension pathophysiology

Primary hypertension is the result of a complicated interaction between genetics and the environment that increase vascular tone (increased peripheral resistance) and blood volume, thus causing sustained increases in blood pressure. Multiple pathophysiologic mechanisms mediate these effects including the sympathetic nervous system (SNS), the RAAS, and natriuretic peptides. Inflammation, endothelial dysfunction, obesity-related hormones, and insulin resistance also contribute to both increased peripheral resistance and increased blood volume. Increased vascular volume is related to a decrease in renal excretion of salt, often referred to as a shift in the pressure-natriuresis relationship. This means that for a given blood pressure, individuals with hypertension tend to secrete less salt in their urine. The pathophysiology of primary hypertension is summarized in Figure 32-3. The SNS contributes to the pathogenesis of hypertension in many people. In the healthy individual the SNS contributes to the maintenance of adequate blood pressure and tissue perfusion by promoting cardiac contractility and heart rate (maintenance of adequate cardiac output) and by inducing arteriolar vasoconstriction (maintenance of adequate peripheral resistance). In individuals with hypertension, overactivity of the SNS can result from increased production of catecholamines (epinephrine and norepinephrine) or from increased receptor reactivity involving these neurotransmitters. Increased SNS activity causes increased heart rate and systemic vasoconstriction, thus raising the blood pressure. Efferent sympathetic outflow stimulates renin release, increases tubular sodium reabsorption, and reduces renal blood flow. Additional mechanisms of SNS-induced hypertension include structural changes in blood vessels (vascular remodeling), insulin resistance, increased renin and angiotensin levels, and procoagulant effects. The SNS is implicated in the cardiovascular and renal complications of hypertension, and new techniques such as renal denervation are being explored to treat hypertension.

Prinzmetal angina

Prinzmetal angina (also called variant angina) is chest pain attributable to transient ischemia of the myocardium that occurs unpredictably and almost exclusively at rest. Pain is caused by vasospasm of one or more major coronary arteries with or without associated atherosclerosis. The angina may result from decreased vagal activity, hyperactivity of the sympathetic nervous system, and decreased nitric oxide activity. Other causes include altered calcium channel function in arterial smooth muscle and endothelial dysfunction with release of inflammatory mediators, such as serotonin, histamine, endothelin, or thromboxane. Serum markers of inflammation, such as CRP and IL-6, may be elevated in individuals with this form of angina. The pain often occurs at night during rapid eye movement sleep and may have a cyclic pattern of occurrence. If the spasm persists long enough, infarction or serious dysrhythmias may occur. However, most individuals are successfully treated with vasodilators and overall prognosis is good.

Autoregulation of the kidneys

Protects kidneys from HTN Constant GFR when arterial pressure between 80 to 180 mmHg. As the systemic blood pressure increases, afferent arterioles constrict, preventing an increase in filtration pressure. Prevents wide fluctuations in the systemic arterial pressure from being transmitted to the glomerular capillaries. Solute and water excretion is constantly maintained, despite arterial pressure changes

Hilus

Pulmonary artery divides and enter the lungs at the hilus Each bronchus and bronchiole has artery or arteriole

Secondary Hypertension pathophysiology

Secondary hypertension is caused by an underlying disease process that raises peripheral vascular resistance or cardiac output. If the cause is identified and removed before permanent structural changes occur, blood pressure returns to normal. In addition, medications are an important and often unrecognized cause of secondary hypertension.

Different kinds of angina and how they are different from each other

Stable angina Chronic coronary obstruction Recurrent predictable chest pain Vasospastic angina (Prinzmetal angina) Abnormal vasospasm Unpredictable chest pain Can lead to MI Silent ischemia Ischemia with no pain Not fully understood, occurs more in women May be fatigued, feel uneasy Acute coronary syndromes Sudden coronary obstruction because of thrombus formation over a ruptured atherosclerotic plaque Examples - Unstable angina - MI

Different congenital defects discussed in class including direction of shunt (if any), signs and symptoms, assessment findings, cyanotic/acyanotic, seriousness of defect (some cover the continuum from asymptomatic to non-life sustaining), treatment options (wait and see to immediate surgery required) and prognosis.

Starts on pg. 39 of google doc: https://docs.google.com/document/d/1EoJMUpC7PyvKBLZajcGqONbIlJqcqSV9ldnHg1cI25M Treatment & Prog PDA: closure in asymptomatic children with a murmur is recommended by 2 years of age because of the risk of subacute bacterial endocarditis. No treatment is recommended for small PDA in the absence of a murmur or other cardiac conditions. ASD: closure, generally before the child reaches school age, results in improved health later in life. If left unrepaired, right ventricular compliance decreases with age, and pulmonary hypertension and right ventricular hypertrophy may occur, placing the person at risk for the development of HF, atrial dysrhythmias, or embolic events later in life. Surgical closure is one method of closure and involves a pericardial patch or suture closure of the defect, depending on the size of the opening. VSD: Most muscular VSDs are hemodynamically insignificant and require no medical or surgical treatment. Many VSDs spontaneously close during the first year of life.2 Infants with symptoms of HF and poor weight gain despite medical management should have their VSD corrected as soon as possible. Left-to-right shunting with a pulmonary flow/systemic flow (Qp/Qs) ratio of greater than 2:1 or evidence of elevated pulmonary vascular resistance are indications for closure. Closure of the VSD at this time is to prevent the development of pulmonary vascular obstructive disease. TOF: The current practice is to repair TOF before 1 year of age. Triggers for repair include increasing cyanosis and hypercyanotic spells. Palliative procedures include the placement of a pulmonary-to-systemic artery shunt known as the Blalock-Taussig shunt to increase pulmonary blood flow or a modification of the shunt using prosthetic graft material placed from either the subclavian or the innominate artery to the PA. These shunts may cause PA distortion but may be necessary in a very small symptomatic child. Corrective repair involves patch closure of the VSD, resection of infundibular or valvular stenosis, and patch augmentation of the RV outflow tract. The procedure is done through a median sternotomy while the child is on cardiopulmonary bypass. The operative mortality is less than 5%. Complications include dysrhythmias and occasionally heart block. Many children require further surgery to relieve recurrent pulmonary stenosis or treat severe pulmonary insufficiency. CoA: The first step in treatment of the symptomatic infant is stabilization, which may require prostaglandin administration, mechanical ventilation, and inotropic support to maintain adequate cardiac output. Once this is achieved, surgical intervention is indicated. Surgical repair for infants younger than 1 year consists of either a subclavian flap aortoplasty technique to enlarge the constricted area or a resection with end-to-end anastomosis of the arch segments. Depending on the arch morphology, a modification of this procedure enlarges the aorta beyond the area of constriction. For children older than 1 year, surgical repair consists of resection with end-to-end anastomosis. Postoperative complications include recoarctation and paradoxical postoperative hypertension. Residual permanent hypertension requiring continued medical therapy is related to age at repair; therefore, surgical intervention is recommended at the time of diagnosis. Operative mortality for infants is less than 5%, and for children older than 1 year, it is less than 1%. Balloon dilation angioplasty in newborns has been successfully performed. However, aortic aneurysm formation and restenosis have been noted; therefore, surgical repair remains the correction of choice for the newborn. TGA: Surgical repair during the newborn period involves the arterial switch operation that moves the great arteries. The coronary arteries are removed from the aorta before the arterial switch is performed and reimplanted without torsion or kinking into the aorta. This establishes normal blood flow with the LV as the systemic pump. Results are approaching 100% survival. Complications include narrowing at the sites of the great artery anastomoses and, rarely, coronary insufficiency

Erythopoietin and the Kidney

Stimulates bone marrow to produce RBC's Stimulus to release Erythropoietin is a decreased oxygen delivery to kidneys Currently produced commercially: Epogen

Understand risk factors for SIDS as well as when it most commonly occurs.

Sudden death of infant under 1 year of age which remains unexplained even after investigation Peaks at 2‐4 months of age Occurs during nighttime sleep, seasonal variation Risk groups: preterm, low birth weight, multiple births, maternal smoking, young maternal age (<20), less prenatal care, poverty Etiology Combination of predisposing factors, vulnerable infant, environmental stressors, critical developmental period for homeostatic control, altered cardiorespiratory arousal Prevention: Fan in the room, being in the same room, back to sleep, breastfeeding, no extra bedding

Understand function of surfactant

Surfactant is a lipid-protein mix that is produced by type II alveolar cells and is critical for maintaining alveolar expansion (thus allowing normal gas exchange). It lines alveoli and reduces surface tension, preventing alveolar collapse at the end of each exhalation. Without surfactant, the alveoli tend to stay closed, demanding greater inspiratory force and work of breathing to re-expand on the next breath. Deficiency of surfactant is often seen in premature infants and causes respiratory distress syndrome (RDS), also known as hyaline membrane disease. Surfactant is produced by 20 to 24 weeks of gestation and is secreted into the fetal airways by 30 weeks. The more premature the infant, the higher the risk of RDS.

What regions of the heart a certain coronary artery supplies

The major coronary arteries are the right coronary artery (RCA) and the left coronary artery (LCA) These arteries traverse the epicardium and branch several times. The right coronary artery has greater flow than the left in 70% of individuals, the left greater than the right in 10%, and equal flow in each is found in 20% of individuals. The left coronary artery arises from a single ostium (opening) behind the left cusp of the aortic semilunar valve. This artery ranges from a few millimeters to a few centimeters in length. It passes between the left atrial appendage and the pulmonary artery and generally divides into two branches—the left anterior descending artery and the circumflex artery. Other branches of the left main coronary artery are distributed diagonally across the free wall of the left ventricle. The left anterior descending (LAD) artery delivers blood to portions of the left and right ventricles and much of the interventricular septum. The left anterior descending artery initially travels in a groove between the left and right ventricles down the anterior surface of the interventricular septum toward the apex of the heart. The circumflex artery travels in a groove called the coronary sulcus, which separates the left atrium from the left ventricle, to the left border of the heart. It supplies blood to the left atrium and the lateral wall of the left ventricle. The circumflex artery often branches to the posterior surfaces of the left atrium and left ventricle. The right coronary artery originates from an ostium behind the right aortic cusp, travels behind the pulmonary artery, and extends around the right heart to the heart's posterior surface, where it branches to the right atrium and ventricle. The three major branches of the right coronary artery include the conus, which supplies blood to the upper right ventricle; the right marginal branch, which traverses the right ventricle to the apex; and the posterior descending branch, which lies in the posterior interventricular sulcus and supplies smaller branches to both ventricles.

Production and flow of bile and the pathways for including the hepatic and gallbladder bile pathways and structures

The duodenum receives chyme from the stomach through the pyloric valve. The presence of chyme stimulates the liver and gallbladder to deliver bile and the pancreas to deliver digestive enzymes and alkaline secretions. Bile is produced by the liver and is necessary for fat digestion and absorption. Bile's alkalinity helps neutralize chyme, thereby creating a pH that enables the pancreatic enzymes to digest proteins, carbohydrates, and sugars. The gallbladder is a saclike organ that lies on the inferior surface of the liver. The primary function of the gallbladder is to store and concentrate bile between meals. During the interdigestive period, bile flows from the liver through the right or left hepatic duct into the common bile duct and meets resistance at the closed sphincter of Oddi, which controls flow into the duodenum and prevents reflux of duodenal contents into the pancreatobiliary system. Bile then flows into the gallbladder through the cystic duct where it is concentrated and stored. The mucosa of the gallbladder wall readily absorbs water and electrolytes, leaving a high concentration of bile salts, bile pigments, and cholesterol. The gallbladder holds about 90 ml of bile. Within 30 minutes after eating, the gallbladder begins to contract, forcing stored bile through the cystic duct and into the common bile duct. The sphincter of Oddi relaxes, and bile flows into the duodenum through the major duodenal papilla. During the cephalic and gastric phases of digestion, gallbladder contraction is mediated by cholinergic branches of the vagus nerve. Hormonal regulation of gallbladder contraction is derived primarily from the release of cholecystokinin secreted by the duodenal and jejunal mucosa in the presence of fat. Vasoactive intestinal peptide, pancreatic polypeptide, and sympathetic nerve stimulation relax the gallbladder Obstruction of the bile ducts from stones, tumors, or inflammation prevents the flow of bile from the liver and gallbladder from reaching the gastrointestinal tract. Both the conjugated and total serum bilirubin values are elevated, urine urobilinogen level is increased, stools are clay colored, and jaundice develops. Fat absorption can be impaired and the prothrombin time prolonged if vitamin K is not absorbed. With inflammation of the gallbladder, the white cell count is elevated.

Know what determines the severity of a urinary tract obstruction

The severity of an obstructive uropathy is determined by: (1) the location of the obstructive lesion, (2) the involvement of one or both upper urinary tracts (ureters and renal pelvis), (3) the completeness of the obstruction, (4) the duration of the obstruction, and (5) the nature of the obstructive lesion. Obstructions may be relieved or partially alleviated by correction of the obstruction, although permanent impairments occur if a complete or partial obstruction persists over weeks to months or longer.

Basic path of blood flow through heart including when each of the valves are opened and closed (including what mechanisms cause the valves to open and close)

The pumping action of the heart consists of contraction and relaxation of the heart muscle or myocardium. Each ventricular contraction and the relaxation that follows it constitute one cardiac cycle. During the period of relaxation, termed diastole, blood fills the ventricles. The contraction that follows, termed systole, propels the blood out of the ventricles and into the pulmonary and systemic circulations. Contraction of the left ventricle occurs slightly earlier than contraction of the right ventricle. During ventricular systole, blood from the veins of the systemic circulation enters the thin-walled right atrium from the superior and inferior venae cavae. Venous blood from the coronary circulation enters the right atrium through the coronary sinus. The right atrium fills, which, along with the falling right ventricular pressures, allows the right AV (tricuspid) valve to open and fill the right ventricle during ventricular diastole. The same sequence of events occurs a split second earlier in the left heart. The four pulmonary veins, two from the right lung and two from the left lung, carry blood from the pulmonary circulation to the left atrium. As the left atrium fills and left ventricular pressure falls, the mitral valve opens and blood flows into the left ventricle. Left atrial contraction, termed "atrial kick," provides significant increases in the volume of blood entering the left ventricle at the end of diastole. Filling of the right and left ventricles occurs during one period of diastole. Five phases of the cardiac cycle: Phase 1: Ventricular diastole begins with opening of the mitral and tricuspid valves and then ventricular filling from the atria occurs. The ventricles fill rapidly in early diastole and again in late diastole when the atria contract. Phase 2: Ventricular systole begins with "isovolumetric contraction," so-called because ventricular volume is constant since both the AV and the semilunar valves are closed. The first detectable rise in ventricular pressure occurs during isovolumetric contraction. This contraction pushes the AV valves shut. Their cusps bulge slightly into the atria but are prevented from opening back into the atria by their anchors, the chordae tendineae. Phase 3: When ventricular pressure reaches and then slightly exceeds that of the pulmonary artery and aorta, the semilunar valves open and ventricular ejection occurs. Intraventricular pressure and ventricular volume decrease rapidly. Phase 4: With ventricular relaxation and decreased ventricular pressure, the aortic valve closes and "isovolumetric relaxation" occurs. Again, both the AV and the semilunar valves are closed during this phase. Phase 5: When left ventricular pressure falls below atrial pressure, the mitral and tricuspid valves open and passive ventricular filling occurs.

Pathophysiology of GERD

The resting tone of the LES tends to be lower than normal from either transient relaxation or weakness of the sphincter in those who develop GERD. Vomiting, coughing, lifting, bending, or obesity increases abdominal pressure, contributing to the development of reflux esophagitis. Delayed gastric emptying contributes to reflux esophagitis by: (1) lengthening the period during which reflux is possible and (2) increasing the acid content of chyme. Disorders that delay emptying include gastric or duodenal ulcers, which can cause pyloric edema; strictures that narrow the pylorus; and hiatal hernia, which can weaken the LES. GERD causes inflammatory responses in the esophageal wall resulting in hyperemia, edema, tissue fragility, erosion, and ulcerations. Severity of inflammation is related to composition of gastric contents and length of exposure time. Fibrosis, basal cell hyperplasia, and elongation of papillae are common. Clinical Manifestations The clinical manifestations of reflux esophagitis are heartburn from acid regurgitation, chronic cough, asthma attacks, and laryngitis. Upper abdominal pain usually occurs within 1 hour of eating and can be relapsing and remitting. Symptoms can worsen if the individual lies down or if intra-abdominal pressure increases (e.g., as a result of coughing, vomiting, or straining at stool). Symptoms may be present when no acid is in the esophagus. Heartburn also may be experienced as chest pain, which requires ruling out cardiac ischemia. Edema, fibrosis (strictures), esophageal spasm, or decreased esophageal motility may result in dysphagia. Alcohol or acid-containing foods, such as citrus fruits, can cause discomfort during swallowing. Evaluation and Treatment Diagnosis of reflux esophagitis is based on the history and clinical manifestations. Esophageal endoscopy shows hyperemia, edema, erosion, and strictures. Dysplastic changes (Barrett esophagus) can be identified by tissue biopsy. Impedance/pH monitoring measures the movement of stomach contents upward into the esophagus and the acidity of the refluxate. Proton pump inhibitors are the most effective monotherapy. Other therapies include histamine-2 (H2) receptor antagonists, prokinetics, and antacids. Pain medication may be used in resistant cases. Elevation of the head of the bed 6 inches prevents reflux. Weight reduction and cessation of smoking also help to alleviate symptoms. Laparoscopic fundoplication is the most common surgical intervention when medical treatment fails. Eosinophilic esophagitis is a rare, idiopathic inflammatory disease of the esophagus characterized by esophageal infiltration of eosinophils associated with atopic disease, including asthma and food allergies. It occurs in adults and children. Dysphagia, food impaction, vomiting, and weight loss are common symptoms. Endoscopy with biopsy identifies the eosinophilc infiltration and differentiation from GERD. Treatment is symptomatic including elimination diets, proton pump inhibitors, and immunosuppression.

Know the function, anatomy and physiology of salivary glands, saliva and salivary amylase.

Three pairs of salivary glands 1. Submandibular 2. Sublingual 3. Parotid glands Salivary glands secrete about 1 L of saliva per day. Saliva consists mostly of water that contains varying amounts of mucus, sodium, bicarbonate, chloride, potassium, and *salivary α-amylase (ptyalin), an enzyme that initiates carbohydrate digestion in the mouth and stomach and provides lubrication.* The sympathetic and parasympathetic divisions of the autonomic nervous system control salivation. Because cholinergic parasympathetic fibers stimulate the salivary glands, atropine (an anticholinergic agent) inhibits salivation and makes the mouth dry. β-Adrenergic stimulation from sympathetic fibers also increases salivary secretion. The salivary glands are not regulated by hormones, although hormones are found in saliva The composition of saliva depends on the rate of secretion. Aldosterone can decrease the rate of secretion by increasing an exchange of sodium for potassium. Sodium and water are conserved and potassium is excreted. The bicarbonate concentration of saliva sustains a pH of about 7.4, which neutralizes bacterial acids and prevents tooth decay. Saliva also contains immunoglobulin A (IgA), which helps prevent infection. Exogenous fluoride (e.g., fluoride in drinking water) is absorbed and then secreted in the saliva, providing additional protection against tooth decay.

Most common valvular diseases including prevalence, signs and symptoms and assessment findings

Two primary types: Stenosis: failure of affected valves to open properly, causing an abnormal pressure gradient across the valve and increasing the pressure work of the heart Regurgitation: Regurgitant valves allow blood to flow backwards across the valve and results in increased work for the heart. Mitral Valve Prolapse Most Common Valve Disorder Most prevalent in young adult females Genetic Influence If symptomatic - palpitations, anxiety, lightheadedness, dyspnea, chest pain PE - Mid-systolic click, murmur; usually asymptomatic Disorders of the endocardium, the innermost lining of the heart wall, all damage the heart valves, which are made up of endocardial tissue. Endocardial damage can be either congenital or acquired. The acquired forms cause inflammatory, ischemic, traumatic, degenerative, or infectious alterations of valvular structure and function. Structural alterations of the heart valves lead to stenosis, incompetence, or both. Although all four heart valves may be affected, those of the left heart (mitral and aortic semilunar valves) are more commonly affected than those of the right heart (tricuspid and pulmonic semilunar valves). In valvular stenosis the valve orifice is constricted and narrowed, impeding the forward flow of blood and increasing the workload of the cardiac chamber proximal to the diseased valve. Intraventricular or atrial pressure increases in the chamber to overcome resistance to flow through the valve. Increased pressure causes the myocardium to work harder, causing myocardial hypertrophy. In valvular regurgitation (also called insufficiency or incompetence) the valve leaflets, or cusps, fail to shut completely, permitting blood flow to continue even when the valve is supposed to be closed. During systole or diastole some blood leaks back into the chamber proximal to the incompetent valve. Valvular regurgitation increases the volume of blood the heart must pump and increases the workload of the affected heart chamber. Increased volume leads to chamber dilation, and increased workload leads to hypertrophy. Valvular dysfunction stimulates chamber dilation and/or myocardial hypertrophy, both of which are compensatory mechanisms intended to increase the pumping capability of the heart. Eventually, myocardial contractility is diminished, the ejection fraction is reduced, diastolic pressure increases, and the affected heart chamber fails from overwork. Depending on the severity of the valvular dysfunction and the capacity of the heart to compensate, valvular alterations cause a range of symptoms and some degree of incapacitation. Look at pg. 1168

Different types of gastrointestinal bleeding terms and definitions

Upper GI bleeding = esophagus, stomach, duodenum (first part of small intestine) Lower GI bleeding = jejunum, ileum, colon or rectum - Below the ligament of Trietz (aka below the duodenum) - Ligament of Treitz stabilizes the duodenum and jejunum where they meet Hematemesis = blood in vomit Hematochezia = bright red blood in stool (coming from lower colon/rectum) Melena = black and tarry/coffee ground blood in stool (coming from upper GI) Occult bleeding = blood that is not seen, test with hemoccult cards. --- Upper gastrointestinal (GI) bleeding is bleeding in the esophagus, stomach, or duodenum and is characterized by frank, bright red bleeding in emesis or dark, grainy digested blood ("coffee grounds") in stool. Upper GI bleeding is caused by esophageal or gastric varices, a Mallory-Weiss tear at the esophageal-gastric junction from severe retching, cancer, angiodysplasias, or peptic ulcers. Lower gastrointestinal (GI) bleeding, bleeding from the small intestine (jejunum or ileum), colon, or rectum, can be caused by polyps, inflammatory bowel disease, diverticulosis, cancer, vascular ectasias, or hemorrhoids. Occult bleeding is usually caused by slow, chronic blood loss that is not obvious and results in iron deficiency anemia as iron stores in the bone marrow are slowly depleted. Acute, severe GI bleeding is life-threatening depending on the volume and rate of blood loss, associated disease, age, and effectiveness of treatment. Physiologic response to gastrointestinal bleeding depends on the amount and rate of the loss. Changes in blood pressure and heart rate are the best indicators of massive blood loss in the gastrointestinal tract. Blood losses of 1000 ml or more over a short time cause a decrease in blood pressure and a corresponding increase in heart rate. During the early stages of blood volume depletion, the peripheral arteries and arterioles constrict to shunt blood to vital organs, including the brain. Signs of large-volume blood loss are postural hypotension, lightheadedness, and loss of vision. If blood loss continues, hypovolemic shock develops. Diminished blood flow to the kidneys causes decreased urine output and may lead to oliguria (low urine output), tubular necrosis, and renal failure. Ultimately, insufficient cerebral and coronary blood flow causes irreversible anoxia and death. The accumulation of blood in the gastrointestinal tract is irritating and increases peristalsis, causing vomiting (hematemesis) or diarrhea, or both. If bleeding is from the lower GI tract, the diarrhea is frankly bloody. Bleeding from the upper GI tract also can be rapid enough to produce bright red stools (hematochezia), but generally, some digestion of the blood components will have occurred, producing melena, black or tarry stools that are sticky and have a characteristic foul odor. The digestion of blood proteins originating from massive upper GI bleeding is reflected by an increase in blood urea nitrogen (BUN) levels. The hematocrit and hemoglobin values are not the best indicators of acute gastrointestinal bleeding because plasma and red cell volume are lost proportionately. As the plasma volume is replaced, the hematocrit and hemoglobin values begin to reflect the extent of blood loss. The interpretation of these values is modified to account for exogenous replacement of fluids and the hydration status of the tissues. Anemia associated with chronic GI bleeding is caused by iron depletion. Evaluation and treatment involves identifying and treating the source of the bleeding and replacing iron losses.

Differentiate different types of hepatitis based on transmission routes, sources of infection, co-infections

Viral Hepatitis Viral hepatitis is a relatively common systemic disease that affects primarily the liver. Different strains of viruses cause different types of hepatitis: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis D virus (HDV) associated with HBV, hepatitis C virus (HCV), and hepatitis E virus (HEV) Hepatitis A was previously known as infectious hepatitis, and hepatitis B as serum hepatitis. Coinfection of HBV, HCV, HDV, and HIV occurs because these viruses share the same routes of transmission (contact between infected body fluids, broken skin or mucous membranes, or intravenously). Progression of liver disease is more rapid in these cases. Hepatitis A Virus (HAV): can be recovered from the feces, bile, and sera of infected individuals. The usual mode of transmission is the fecal-oral route (contaminated food or water), but the virus can be spread also by the transfusion of infected blood. Approximately 45% of adults in urban areas have HAV antibodies in their blood. The disease spreads readily in crowded, unsanitary conditions, usually through contaminated food or water. Person-to-person spread is more likely to occur in institutional care settings where there is contact between clients and caregivers who are not vaccinated. The incubation period for HAV is 4 to 6 weeks. Fecal shedding of the virus is greatest for 10 to 14 days before the onset of symptoms and during the first week of symptoms and up to 3 months after onset of symptoms. The disease is most contagious during this time. Antibodies to HAV (anti-HAV) develop about 4 weeks after infection. The administration of immunoglobulin before exposure or early in the incubation period can prevent hepatitis A. HAV vaccine and combined HAV and HBV vaccines are available and effective in preventing the disease and confer long-term immunity. Transmission of HAV is prevented by handwashing and use of gloves when disposing of fecal matter. Hepatitis B Virus (HBV): is transmitted through blood-blood contact and the sexual route. People who are immunosuppressed; receive hemodialysis, multiple blood transfusions, or immunosuppressive drugs; have multiple sex partners; or share needles, syringes, or other drug equipment or infants born to infected mothers have a greater risk of exposure or less resistance to HBV coinfection with HCV, HDV. HIV is common because these viruses share the same routes of transmission. Mother-infant transmission of HBV occurs if the mother becomes infected during the third trimester of pregnancy. In women who are seropositive for both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), vertical transmission is approximately 90%. Transmission among homosexual men may be by oral or genital contact with bleeding lesions in the rectal mucosa. Up to 400 million people worldwide carry the hepatitis B surface antigen (HBsAg) marker for active HBV. HBV is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV has an incubation period of 6 to 8 weeks. Chronic infection develops in 15% to 30% of those with acute infection. HBV DNA measures viral load and the efficacy of drug treatment. Persistent liver cell injury and deregulation of cellular growth control genes lead to increased risk for cirrhosis and hepatocellular carcinoma. Antiviral and immunomodulatory treatment for chronic hepatitis B includes monotherapy, combination therapy, and prevention of drug resistance. Vaccine prevents transmission of hepatitis B, the development of acute or chronic hepatitis B, and reduction of hepatocellular carcinoma, particularly in high-risk populations. Hepatitis B immunoglobulin provides postexposure prophylaxis against HBV after contact with blood or body fluids of individuals infected with hepatitis B. HBV vaccine or a combined vaccine for HAV and HBV provides protective immunity. Hepatitis C Virus (HCV): HCV (previously known as non-A, non-B hepatitis) is a parenterally transmitted flavivirus with six genotypes. About 40% of HCV cases involve intravenous drug users, who also have a high incidence of HIV infection. Coinfection with HBV also is prevalent. Approximately 80% of cases develop chronic liver disease. HCV is diagnosed through detection of anti-HCV IgG. Persistent infection with recurring acute symptoms and elevated aminotransferase levels represent the clinical presentation. Antiviral drug therapy is available. Progression of disease to cirrhosis or hepatocellular carcinoma is greatest among individuals with HIV or coexisting liver disease. The variants of HCV make vaccine development difficult and resistance to drug therapy is common. There is no vaccine for HCV. The Centers for Disease Control and Prevention have recommended that all persons born from 1945 through 1965 be screened for HCV infection. Hepatitis D Virus (HDV): occurs in individuals with hepatitis B. The delta virus depends on the HBV for its replication because the viral coat consists of HBsAg molecules that are on the surface of HBV. Hepatitis D has been shown to suppress replication of HBV. Parenteral drug users have a high incidence of HDV infection. HDV symptoms can be mild or severe with progression to fulminant liver failure. HDV is diagnosed by the presence of antibodies directed against HDAg (anti-HD) and HDV RNA in serum. Treatment for chronic HDV includes pegylated interferon alpha and it is effective in about 25% of individuals. Hepatitis E Virus (HEV): HEV is most common in Asian and African countries and is transmitted by the fecal-oral route, usually by way of contaminated water or uncooked meat. It is also found in developed countries and must be differentiated from drug-induced liver injury. Animal reservoirs of HEV include domestic pigs, wild boars, deer, and rodents. It is more prevalent among adults and has the highest mortality in pregnant women. Clinically, it resembles HAV and is diagnosed based on detection of anti-HEV IgM. A vaccine for HEV has been approved in China but not in other countries. Pathophysiology The pathologic lesions of hepatitis are similar to those caused by other viral infection. Hepatic cell necrosis, scarring, Kupffer cell hyperplasia, and infiltration by mononuclear phagocytes occur with varying severity. Cellular injury is promoted by cell-mediated immune mechanisms (i.e., cytotoxic T cells, T regulatory cells, and natural killer cells). Regeneration of hepatic cells begins within 48 hours of injury. The inflammatory process can damage and obstruct bile canaliculi, leading to cholestasis and obstructive jaundice. In milder cases, the liver parenchyma is not damaged. Damage tends to be most severe in cases of hepatitis B and hepatitis C. Hepatitis B is also associated with acute fulminating hepatitis, a rare form of the disease that is characterized by massive hepatic necrosis. Acute fulminating hepatitis causes severe encephalopathy, which is manifested as confusion, stupor, and coma. Liver failure can occur, leading to GI bleeding, cardiorespiratory insufficiency, and hepatorenal syndrome. Mortality is high, but recovery can be complete. Clinical Manifestations The clinical manifestations of the various types of hepatitis are very similar. The spectrum of manifestations ranges from absence of symptoms to fulminating hepatitis, with rapid onset of liver failure and coma. Acute viral hepatitis causes abnormal liver function test results. The serum aminotransferase values, aspartate transaminase (AST) and alanine transaminase (ALT), are elevated, but their elevation may not be consistent with the extent of cellular damage. The clinical course of hepatitis usually consists of four phases: incubation, prodromal, icteric, and recovery phases. The incubation phase and manifestations vary depending on the virus. A + E is about 15 days B + D is about 3 months C 6 months Prodromal Phase The prodromal (preicteric) phase of hepatitis begins about 2 weeks after exposure and ends with the appearance of jaundice. Fatigue, anorexia, malaise, nausea, vomiting, headache, hyperalgia, cough, and low-grade fever are prodromal symptoms that precede the onset of jaundice. About 10% of individuals may develop extrahepatic symptoms including rash, arthralgias, and purpura. HBV and HCV may cause nephritis related to glomerular immune complex deposition. Infection with HCV may have no symptoms. Right upper abdominal pain is common, and a weight loss of 2 to 4 kg is not unusual. The infection is highly transmissible during this phase. Icteric Phase (Jaundice) The icteric phase begins about 1 to 2 weeks after the prodromal phase and lasts 2 to 6 weeks. Individuals who develop chronic HBV infection do not become jaundiced and may not be diagnosed. Hepatocellular destruction and intrahepatic bile stasis cause jaundice (icterus). The urine may be dark and the stools clay-colored before the onset of jaundice from conjugated hyperbilirubinemia. The icteric phase is the actual phase of illness. The liver is enlarged, smooth, and tender, and percussion over the liver causes pain. During the icteric phase, gastrointestinal and respiratory symptoms subside, but fatigue and abdominal pain may persist or become more severe. The stools may be lighter in color as a result of cholestasis. Serum bilirubin levels range from 5 to 10 mg/dl, with conjugated bilirubin fraction increasing. The jaundice may last 2 to 6 weeks or longer. Mild and transient itching often accompanies jaundice. The prothrombin time may be prolonged in individuals with more serious forms of the disease. Recovery Phase The posticteric or recovery phase begins with resolution of jaundice, about 6 to 8 weeks after exposure. Although the liver may still be enlarged and tender, symptoms diminish. In most cases, liver function test results return to normal within 2 to 12 weeks after the onset of jaundice. Chronic hepatitis may begin at this point and is associated with HBV, HCV, and HDV infection. Chronic active hepatitis is the persistence of clinical manifestations and liver inflammation after the acute stages. Liver function tests remain abnormal for longer than 6 months, and HBsAg persists. Chronic, active HBV and HBC is a predisposition to cirrhosis and primary hepatocellular carcinoma. Chronic active hepatitis constitutes a carrier state, and HBV and HCV can be transmitted from mothers to infants. Evaluation and Treatment Physical activity may be restricted. A low-fat, high-carbohydrate diet is beneficial if bile flow is obstructed. There should be no direct contact with blood or body fluids of individuals with hepatitis B or hepatitis C. A combined vaccine for HAV and HBV is available. Hepatitis B immunoglobulin provides passive prophylactic immunity against HBV. Prophylaxis is recommended for healthcare workers, liver transplant recipients, and others who are at risk for contact with infected body fluids.

Vitamin D and the Kidney

Vitamin D: activated in the kidney. Starts in the sun, skin converts to inactivated, to liver, then to kidney where it activates Hydroxylation occurs first in the liver and then in the kidneys. Renal hydroxylation is stimulated by parathyroid hormone Necessary for absorption of calcium and phosphate absorption in small intestine Clinical significance: Patients with renal disease manifest disturbed calcium and phosphate balance

Infarction

When there is sudden coronary obstruction caused by thrombus formation over a ruptured or ulcerated atherosclerotic plaque, acute coronary syndromes result. Unstable angina is the result of reversible myocardial ischemia and is a harbinger of impending infarction. Myocardial infarction (MI) results when prolonged ischemia causes irreversible damage to the heart muscle. Sudden cardiac death can occur as a result of any of the acute coronary syndromes. An atherosclerotic plaque that is prone to rupture is called "unstable" and has a core that is especially rich in deposited oxidized LDL and a thin fibrous cap. These unstable plaques may not extend into the lumen of the vessel and may be clinically silent until they rupture. Plaque disruption (ulceration or rupture) occurs because of shear forces, inflammation with release of multiple inflammatory mediators, secretion of macrophage-derived degradative enzymes, and apoptosis of cells at the edges of the lesions. Exposure of the plaque substrate activates the clotting cascade. In addition, platelet activation results in the release of coagulants and exposure of platelet glycoprotein IIb/IIIa surface receptors, resulting in further platelet aggregation and adherence. The resulting thrombus can form very quickly. Vessel obstruction is further exacerbated by the release of vasoconstrictors, such as thromboxane A2 and endothelin. The thrombus may break up before permanent myocyte damage has occurred (unstable angina) or it may cause prolonged ischemia with infarction of the heart muscle (myocardial infarction). Diagnostic tests aimed at identifying unstable plaques before they rupture include intravascular ultrasound or MRI, angioscopy, and spectroscopy. Medications such as statins, ACE inhibitors, and beta-blockers can help stabilize plaques and prevent rupture. Enzymes and proteins released when myocardial tissue is INJURED Cardiac Troponin I (cTnI): most sensitive test; Detectable 2-4 hours after onset of symptoms, 100% specific to myocardial tissue Creatine phosphokinase - muscle and brain (but primary source is from the heart) (CPKMB): Detectable 3-8, reliable 12-24 hours after onset of symptoms

Know basics of Wilm's Tumor including prevalence, survival rates and clinical manifestations

Wilms tumor is an embryonal tumor of the kidney arising from epigenetic and genetic changes that lead to abnormal proliferation of renal stem cells (metanephric blastema). It is also known by the histologic name of nephroblastoma and is the most common solid tumor occurring in children. The incidence of Wilms tumor remains constant in the United States, with approximately 650 children diagnosed each year. Most children are between 1 and 5 years of age when they are diagnosed. The peak incidence occurs between 2 and 3 years of age. Wilms tumor is slightly more common in females and in black than in white children, and is less common in Asian children. Microscopically, Wilms tumor is composed of three cellular components: stromal, epithelial, and blastemic. This occurs because blastemic cells, which are primitive and undifferentiated, may have partially developed into epithelial or stromal tissue. With each of these three cellular components, varying stages of differentiation may be evident within the tumor. Pathogenesis Wilms tumor (nephroblastoma) has sporadic and inherited origins. The sporadic form occurs in children with no known genetic predisposition. Inherited cases, which are relatively rare (1% to 2% of cases), are transmitted in an autosomal dominant fashion. Clinical Manifestations Most Wilms tumors (90%) present as an enlarging asymptomatic upper abdominal mass in a healthy, thriving child. Other presenting complaints include vague abdominal pain, hematuria, fever, and hypertension. Evaluation and Treatment On physical examination, the tumor feels firm, non-tender, and smooth, and generally is a solitary mass of varying size confined to one side of the abdomen. Diagnostic imaging demonstrates a solid intrarenal mass. Diagnosis is based on surgical biopsy. Additional laboratory and radiologic studies are used to evaluate the presence or absence of metastasis. The most common sites of metastasis are regional lymph nodes and the lungs and less commonly liver, brain, and bone. Primary treatment is usually (1) surgical exploration and resection, or (2) chemotherapy followed by surgical resection. In bilateral disease, surgical intervention may include heminephrectomy of the less involved kidney and nephrectomy of the other. Radiation therapy has been found to be most effective if begun 1 to 3 days after surgery for stages III and IV disease and metastases. Chemotherapy is specific to histologic presentation and stage of disease. The overall cure rate is as high as 95% for children with stage I through stage III disease. Prognosis is improving for children with metastases, and this is one of the few tumors for which lung metastases have been cured. Recurrent disease is treated aggressively in children with favorable histologic results.

Bile

breaks down fat, formed mostly in the liver, very alkaline (due to bicarb). Made up of bile salts, cholesterol, bicarbonate, and electrolytes and water One of the key functions of the liver Functions • Assimilation of dietary lipid • Excrete hydrophobic molecules • Neutralizing gastric acid Enterohepatic pathway: Travels from the liver to the intestines and then back to the liver

Stages of liver disease

healthy liver → fibrotic liver → cirrhotic liver → liver cancer

Heart Failure

is defined as the pathophysiologic condition in which the heart is unable to generate an adequate cardiac output such that there is inadequate perfusion of tissues or increased diastolic filling pressure of the left ventricle, or both, so that pulmonary capillary pressures are increased. It is estimated that nearly 10% of Americans older than age 65 have symptomatic heart failure and approximately 20% of asymptomatic individuals older than age 40 have some evidence of myocardial dysfunction. Ischemic heart disease and hypertension are the most important predisposing risk factors. Other risk factors include age, obesity, diabetes, renal failure, valvular heart disease, cardiomyopathies, myocarditis, congenital heart disease, and excessive alcohol use.