REVISION

1. REVISION Define Hypertension. Outline the pathophysiology of Hypertension. Name two causes of cardiogenic shock. Name two causes of hypovolemic shock. Define Septic shock and name two pathophysiologic changes. In asthma, hyper-responsiveness of the airways and bronchospasms occur. However, how does an asthma attack progress. Name three pathophysiologic changes that occur during an asthma attack.

2. REVISION Name three causes of lung cancer. Outline three pathophysiologic changes in Lung Cancer. Outline the differences between bacterial and viral pneumonia. Compare the pathophysiologic changes of pneumothorax and pulmonary oedema. Compare the pathophysiology of Type I Hypersensitivity and Type II Hypersensitivity reactions. Compare the pathophysiology of Type III Hypersensitivity and Type IV Hypersensitivity reactions. Outline the pathophysiology of Idiopathic Thrombocytopenia.

3. REVISION Outline the pathophysiology of Pre-renal failure. Outline the pathophysiology of chronic renal failure. Outline 7 predisposing factors of renal calculi. Outline the pathophysiology of glomerulonephritis. What is the most accurate measurement of glomerular filtration. Define Hydronephrosis and outline the most common causes.

4. ALTERATIONS TO GASTROINTESTINAL FUNCTION

5. Gastrointestinal disorders are not cited as the leading cause of death in developed countries of the world, nor do they receive the same publicity as heart disease and cancer. However, digestive diseases rank high in the total burden of illness, resulting in considerable human suffering, personal expenditures for treatment, and lost working hours.

6. Pathophysiologic concepts Anorexia: Loss of appetite or lack of desire for food despite normal hunger stimulation. Can be caused by: slow gastric emptying or gastric stasis, high levels of neurotransmitters, excess cortisol levels. Diarrhoea: Increase in fluidity of faeces and frequency of defecation. Characterised by three main mechanisms: osmotic diarrhoea, secretory diarrhoea, motility diarrhoea. Jaundice: Yellow pigmentation of skin and sclera; Results when production of bilirubin exceeds metabolism and excretion and bilirubin accumulates in blood; Occurs when bilirubin levels exceed 2.0 to 2.5 mg/dl. Nausea: Feeling of urge to vomit; Marked by increased salivation, diminished functional activities of the stomach, and altered small intestinal motility. Vomiting: Forceful oral expulsion of gastric contents; Occurs when chemoreceptor trigger zone in medulla is stimulated.

7. Appendicitis Occurs when the appendix becomes inflamed. Most precisely, this disorder is an inflammation of the vermiform appendix, a small, finger-like projection attached to the cecum just below the ileocecal valve. Pathophysiology: It had previously been thought that appendicitis was thought to result from an obstruction by a faecal mass, a stricture, barium ingestion, or viral infection. Obstruction does sometimes occur, but mucosal ulceration usually happens first. After ulceration occurs, appendicitis progresses this way: Inflammation accompanies the ulceration and temporarily obstructs the appendix. Obstruction, if present, is usually caused by stool accumulation around vegetable fibres (fecalith). Mucous outflow is blocked, which distends the organ. Pressure within the appendix increases, and the appendix contracts. Bacteria multiply and inflammation and pressure continue to increase, affecting blood flow to the organ and causing severe abdominal pain.

8. Cholecystitis In cholecystitis the gallbladder becomes inflamed. Usually, a gallstone becomes lodged in the cystic duct, causing painful gallbladder distension. Pathophysiology: Cholecystitis is caused by the formation of calculi called gallstones. The exact cause of gallstone formation is unknown. Abnormal metabolism of cholesterol and bile salts play an important role. Acute cholecystitis may also result from poor or absent blood flow to the gallbladder.

9. Understanding Gallstone Formation Abnormal Metabolism of Cholesterol and Bile Salts Contracting Gallbladder Obstructing Gallstone Jaundice, Irritation and Inflammation Up the Biliary Tree Hendler, C.B. 2002. Pathophysiology made ridiculously easy, 2nd ed.

10. Cirrhosis Cirrhosis, a chronic liver disease, is characterised by widespread destruction of hepatic cells, which are replaced by fibrous cells. This process is called fibrotic regeneration. Pathophysiology: There are many types of cirrhosis, each with a different cause. The most common include: Portal Cirrhosis: stems from chronic alcoholism and malnutrition. It is most prevalent among malnourished alcoholic men and accounts for half of all cirrhosis cases. Post-necrotic Cirrhosis: is usually a complication of viral hepatitis, but it may also occur after exposure to liver toxins. Biliary Cirrhosis: results from prolonged bile duct obstruction or inflammation. Cardiac Cirrhosis: is caused by prolonged venous congestion in the liver from right-sided heart failure.

11. Cirrhosis Cirrhosis is characterised by irreversible chronic injury of the liver, extensive fibrosis, and nodular tissue growth. These changes result from: liver cell death, collapse of the liver’s supporting structure, distortion of the vascular bed and nodular regeneration of remaining liver tissue. When the liver begins to malfunction, blood clotting disorders, jaundice, oedema, and a variety of metabolic problems develop. Fibrosis and the distortion of blood vessels may impede blood flow in the capillary branches of the portal vein and hepatic artery, leading to portal hypertension.

12. Crohn’s Disease Crohn’s disease is one of two major types of inflammatory bowel disease. It may affect any part of the GI tract. Inflammation extends through all layers of the intestinal wall and may involve lymph nodes and supporting membrane in the area. Ulcers form as the inflammation extends into the peritoneum. Pathophysiology: Although researchers are still studying Crohn’s disease, possible causes include: Lymphatic obstruction: causes oedema, mucosal ulceration, fissures, abscesses and sometimes granulomas. Infection Allergies Immune Disorders e.g. Increased Suppressor T cell activity Genetic factors: Crohn’s disease sometimes occurs in identical twins, and 10 to 20 percent of patients with the disease have one or more affected relatives.

13. Crohn’s Disease As Crohn’s disease progresses, fibrosis thickens the bowel wall and narrows. Narrowing can occur in any part of the intestine and cause varying degrees of intestinal obstruction. At first, the mucosa appear normal, but as the disease progresses it takes on a cobblestone appearance. Complications: Anal Fistula Perianal abscess Fistula may develop to the bladder, vagina and skin. Intestinal obstruction Nutrient deficiencies Fluid Imbalances Peritonitis

14. Hiatal Hernia Hiatal hernia occurs when a defect in the diaphragm permits a portion of the stomach to pass through the diaphragmatic opening into the chest cavity. Some people remain unsymptomatic while others experience reflux, heartburn, and chest pain. It occurs more commonly in women than men. Pathophysiology: Usually hiatal hernia results from muscle weakening that is common with aging. It may also be secondary to oesophageal cancer, kyphoscoliosis, trauma and certain surgical procedures. It may also result from certain diaphragmatic malformations that may cause congenital weakness. In hiatal hernia, the muscular collar around the oesophageal and diaphragmatic junction loosens, permitting the lower portion of the oesophagus and the stomach to rise into the chest when intra-abdominal pressure increases.

15. Irritable Bowel Syndrome Irritable bowel syndrome is characterised by chronic symptoms of abdominal pain, alternating constipation and diarrhoea, and abdominal distension. Irritable bowel syndrome is generally associated with psychological stress; however, it may result from physical factors, such as diverticular disease, ingestion of irritants (coffee, raw vegetables or fruits), abuse of laxatives, food poisoning and colon cancer. Pathophysiology: Typically the patient with irritable bowel syndrome has a normal appearing GI tract. However, careful examination of the colon may reveal functional irritability- an abnormality in colonic smooth-muscle function marked by excessive peristalsis and spasms, even during remission.

16. Pancreatitis Pancreatitis is an inflammation of the pancreas. It occurs in acute and chronic forms. In men, the disorder is commonly linked to alcoholism, trauma, or peptic ulcer; in women, to biliary tract disease. The prognosis is good when pancreatitis follows biliary tract disease but poor when it is a complication of alcoholism. Mortality reaches 60 percent when pancreatitis causes tissue destruction or haemorrhage. Pathophysiology: The most common causes of pancreatitis are biliary tract disease and alcoholism, but it can also result from: Abnormal organ structure Metabolic or endocrine disorders, such as high cholesterol or overactive thyroid. Pancreatic cysts or tumours Penetrating peptic ulcers Blunt trauma and surgical trauma

17. Pancreatitis Pathophysiology Continued: Drugs such as glucocorticoids, sulphonamides, thiazides and oral contraceptive. Kidney failure and transplantation Endoscopic examination of the bile duct and pancreas.

18. Chronic Pancreatitis Chronic pancreatitis is a persistent inflammation that produces irreversible changes in the structure and function of the pancreas. It sometimes follows an episode of acute pancreatitis. How it Happens: Protein precipitates block the pancreatic duct and eventually harden or calcify. Structural changes lead to fibrosis and atrophy of the glands. Growths called pseudocysts, containing pancreatic enzymes and tissue debris, form. An abscess results if the growths become infected.

19. Acute Pancreatitis Acute pancreatitis occurs in two forms: Oedematous, causing fluid accumulation and swelling. Necrotising, causing cell death and tissue damage. The inflammation that occurs with both types of is caused by premature activation of enzymes, which cause tissue damage. Normally the acini cells in the pancreas secrete enzymes in an inactive form. Two theorises explain why enzymes become prematurely activated: A toxic agent such as alcohol, alters the way the pancreas secretes enzymes. Alcohol may increase pancreatic secretion, alters the metabolism of the acinar cells, and encourages duct obstruction by causing pancreatic secretory proteins to precipitate. A reflux of duodenal contents containing activated enzymes enters the pancreatic duct, activating other enzymes and setting up a cycle of more pancreatic damage.

20. Peptic Ulcer Peptic ulcer is a circumscribed lesion in the mucosal membrane of the upper GI Tract. Peptic ulcers can develop in the lower oesophagus, stomach, duodenum or jejunum. Pathophysiology: The two major forms of peptic ulcer are:duodenal and gastric. Duodenal ulcers: affect the upper part of the small intestine. This type of ulcer accounts for about 80 percent of peptic ulcers. Duodenal ulcers occur mostly in men between the ages of 20 and 50. Gastric Ulcers: affect the stomach lining (mucosa). They are most common in middle-aged and elderly men, especially malnourished men. They commonly occur in chronic users of aspirin and alcohol.

21. Peptic Ulcer Pathophysiology Continued: There are three major causes of peptic ulcer: Bacterial infection with Helicobacter pylori is the cause of 70 percent to 80 percent of peptic ulcers. Use of NSAIDS Hypersecretory states such as Zollinger-Ellison Syndrome. Researchers are still discovering the exact mechanisms of ulcer formation. Predisposing factors include: Blood type A (common in people with gastric ulcers) Blood Type O (common in people with duodenal ulcers) Genetic factors Exposure to irritants Trauma Stress and anxiety Normal aging.

22. Peptic Ulcer In peptic ulcer due to H. pylori, acid adds to the effects of the bacterial infection. H. pylori releases a toxin that destroys the stomach’s mucous coat, reducing the epithelium’s resistance to acid digestion and causing gastritis and ulcer disease. A possible complication of severe ulceration is erosion of the mucosa. This can cause GI Haemorrhage, which can progress to hypovolemic shock, perforation, and obstruction. Obstruction of the pylorus may cause the stomach to distend with food and fluid, block blood flow and cause tissue damage. What to look for: Recent loss of weight or appetite Pain, heartburn or indigestion A feeling of abdominal fullness or distension. Pain triggered or aggravated by eating.

23. Ulcerative Colitis This inflammatory disease causes ulcerations of the mucosa in the colon. It commonly occurs as a chronic condition. Pathophysiology: Although the cause of ulcerative colitis is unknown, it may be related to an abnormal immune response in the GI tract, possibly associated with genetic factors. Stress does not cause the disorder, but it can increase the severity of the attack. Although no specific organism has been linked to ulcerative colitis, infection has not been ruled out. Ulcerative colitis damages the large intestines mucosal and submucosal layers. How does it progress: Usually, the disease originates in the rectum and lower colon. Then it spreads to the entire colon. The mucosa develops diffuse ulceration, with haemorrhage, congestion, oedema, and exudative inflammation. Unlike Crohn’s disease, ulcerations are continuous. Abscesses formed in the mucosa drain purulent pus, become necrotic, and ulcerate. Sloughing occurs, causing bloody, mucous filled stools.

24. Ulcerative Colitis As ulcerative colitis progresses, the colon undergoes changes: Initially, the colon’s mucosal surface becomes dark, red and velvety. Abscesses form and coalesce into ulcers. Necrosis of the mucosa occurs. As abscesses heal, scarring and thickening may appear in the bowels inner muscle layer. As granulation tissue replaces the muscle layer, the colon narrows, shortens, and loses its characteristic pouches.

25. Viral Hepatitis Viral hepatitis is a common infection of the liver. In most patients, damaged liver cells eventually regenerate with little or no permanent damage. However, old age and serious underlying disorders make complications more likely. Pathophysiology: Viral hepatitis is marked by liver cell destruction, tissue death (necrosis), and self destruction of cells. It leads to anorexia, jaundice, and hepatomegaly. Five types of viral hepatitis are recognised, each caused by a different virus: Type A: is transmitted almost exclusively by the faecal oral route, and outbreaks are common in areas of overcrowding and poor sanitation. Type B: Blood-borne; parental route, sexual, maternal neonatal, virus is shed in all body fluids. Type C: Blood Borne; parenteral route. Type D: Parenteral route. Type E: Primarily Faecal Oral Route.

26. Viral Hepatitis What to look for: Prodromal Stage: fatigue, anorexia, mild weight loss, generalised malaise, depression, headache, weakness, joint pain, muscle pain, intolerance , nausea, vomiting, changes in the sense of taste and smell, fever, right up per quadrant tenderness, dark coloured urine and clay coloured stools (1 to 5 days before the onset of the clinical jaundice stage). Clinical Stage: Begins 1 to 2 weeks after the prodromal stage. It is the phase of acute illness. Signs and symptoms include: itching, abdominal pain or tenderness, indigestion, appetite loss and jaundice. Jaundice lasts for 1 to 2 weeks and indicates that the damaged liver cannot remove bilirubin from the blood. Recovery Stage: Begins with the resolution of jaundice and lasts 2 to 6 weeks in uncomplicated cases. The prognosis is poor if oedema and hepatic encephalopathy develop.

27. Colorectal Cancer Slow-growing cancer that usually starts in the inner layer of the intestinal tract. Commonly begins as a polyp Signs and symptoms depend on the location of the tumour. Potentially curable if diagnosed early. How it develops: Most lesions of the large bowel are moderately differentiated adenocarcinomas. These tumours tend to grow slowly and remain asymptomatic for long periods. Tumours in the rectum and sigmoid and descending colon grow circumferentially and constrict the intestinal lumen. Tumours in the ascending colon are usually large and palpable. Risk factors: Inherited gene mutations, family or personal history of colorectal cancer, history of intestinal polyps, history of chronic inflammatory bowel disease, aging, high-fat diet, obesity and physical inactivity, diabetes, smoking, heavy alcohol intake.

28. Pathophysiologic Changes Early signs: Right side of Colon Gastrointestinal bleeding Bowel irritation Late Signs: Right side of Colon Anaemia Intestinal obstruction Early Signs: Left side of Colon GI bleeding Intestinal obstruction Late Signs: Left side of the Colon Intestinal obstruction GI Bleeding