REVISION

1. ADVANCED MEDICAL SCIENCE REVISION Define Anorexia. What can it be caused by? What are the 3 major mechanisms by which diarrhoea can be characterised? Briefly outline the pathophysiology of jaundice. Outline the pathophysiology of cirrhosis. How does colorectal cancer develop? Outline the pathophysiologic changes that can occur with colorectal cancer. Draw and explain the bowel changes that unfold with Crohn’s disease. How is non-viral hepatitis different from viral hepatitis. Outline the pathophysiology of Irritable bowel syndrome.

2. REVISION Distinguish between hyperplasia and hypertrophy. List the characteristics of cancerous tissue which differentiate it from normal tissue. Identify 1 cause and 1 pathophysiologic change for the genetic disorder, Haemophilia. Differentiate between autosomal disorders and Sex-linked disorders. Provide 1 example for each pathophysiologic concept. Define the term intracellular accumulations and outline how each category differs. Identify two outcomes of cell injury and outline their differences. Describe in detail the differences between a benign neoplasm and a malignant neoplasm. Outline the condition ALL and identify which chromosomal disorder it is most likely to develop in.

3. Diverticular Disease Characterised by bulging pouches (diverticula) in GI wall that pushes mucosal lining through surrounding muscle. Classified by two clinical forms: Diverticulosis (diverticula are present but do not cause symptoms) Diverticulitis (diverticula are inflamed; may cause potentially fatal obstruction, infection or haemorrhage) Pathophysiology: Diverticula probably result from high intraluminal pressure on an area of weakness in the GI wall, where blood vessels enter. In diverticulitis, retained undigested food and bacteria accumulate in the diverticular sac. This hard mass cuts off the blood supply to the thin walls of the sac, making them more susceptible to attack by colonic bacteria. Inflammation follows and may lead to perforation, abscess, peritonitis, obstruction or haemorrhage.

4. Diverticular Disease Causes: Diminished colonic motility and increased intraluminal pressure. Low-fibre diet Defects in colon wall strengthen. Pathophysiologic changes: Inflammation of the diverticula Trapping of bacteria-rich stool in diverticula: Often accompanied by low-grade fever. Rupture of diverticula and subsequent inflammation and infection. Sepsis Rupture of diverticula near vessel: Microscopic or massive haemorrhage. Intestinal obstruction.

5. Gastroesophageal Reflux Disease Backflow of gastric or duodenal contents (or both) into oesophagus and past lower oesophageal sphincter (LES), without associated belching or vomiting. Reflux of gastric contents causes acute epigastric pain, usually after meals. Pathophysiology: Hormonal fluctuations, mechanical stress, and the effects of certain foods and drugs can decrease LES pressure. When LES pressure falls and intra-abdominal or intragastric pressure rises, the normally contracted LES relaxes inappropriately and allows reflux of gastric acid or bile secretions into the lower oesophagus. There, the reflux irritates and inflames the oesophageal mucosa, causing pyrosis. Persistent inflammation can cause LES pressure to decrease further, possibly triggering a recurrent cycle of reflux and pyrosis.

6. Gastroesophageal Reflux Disease Causes: Weakened oesophageal sphincter Increased abdominal pressure Hiatal hernia Medications Food, alcohol or cigarettes Nasogastric intubation for more than 4 days Pathophysiologic changes: Increased abdominal pressure and oesophageal irritation.

7. ALTERATIONS TO ENDOCRINE FUNCTION

8. Addison’s Disease Addison's disease, also called adrenal hypofunction or adrenal insufficiency, occurs in two forms: primary and secondary. It is a relatively uncommon disorder that occurs in people of all ages and in both sexes. Either primary or secondary Addison’s disease can progress to adrenal crisis. The primary form of Addison’s disease originates within the adrenal glands. It is characterised by decreased mineralocorticoid, glucocorticoid, and androgen secretion. The secondary form of Addison’s disease is caused by a disorder outside the gland, such as a pituitary tumour with corticotrophin deficiency. In secondary forms of the disorder, aldosterone secretion may be affected.

9. Addison’s Disease Pathophysiology: In primary Addison’s disease, more than 90 percent of both adrenal glands are destroyed. Massive destruction usually results from an autoimmune process whereby circulating antibodies attack adrenal tissue. Destruction of the gland may also be idiopathic. Other causes of primary Addison’s disease include: Tuberculosis Removal of both adrenal glands Haemorrhage into the adrenal gland Neoplasms Infections, such as HIV, histoplasmosis, meningococcal pneumonia, and cytomegalovirus. In rare cases, a familial tendency. Pathophysiology: Secondary Addison’s disease may result from: Hypopituitarism Removal of a non-endocrine corticotrophin-secreting tumour Disorders of hypothalamic-pituitary function that diminish the production of corticotrophin.

10. Understanding Adrenal Crisis

11. Cushing’s Syndrome Cushing's syndrome is a cluster of physical abnormalities caused when the adrenal glands secrete excess glucocorticoids. It may also be caused by excessive androgen secretion. When glucocorticoid excess is due to pituitary-dependent conditions, its is called Cushing’s syndrome. Pathophysiology: Cushing’s syndrome appears in 3 forms: Primary: caused by a disease of the adrenal cortex. Secondary: caused by hyperfunction of corticotrophin-secreting cells of the anterior pituitary gland. Tertiary: caused by hypothalamic dysfunction or injury. In about 70 percent of patients, Cushing’s syndrome results from an excess of corticotrophin. This leads to hyperplasia of the adrenal cortex. Corticotrophin overproduction may stem from: Pituitary hypersecretion A corticotrophin producing tumour in another organ Administration of synthetic glucocorticoids

12. Cushing’s Syndrome Complications associated with Cushing’s syndrome are caused by the effects of cortisol, the principal glucocorticoid. These complications may include: Osteoporosis and pathologic fractures Peptic ulcer Lipdosis Impaired glucose tolerance Frequent infections or slow wound healing due to decreased lymphocyte production and suppressed antibody formation may occur. Suppressed inflammatory response may mask infection. Hypertension due to sodium and water retention is common in Cushing's syndrome. It may lead to ischemic heart disease and heart failure. Menstrual disturbances and sexual dysfunction also occur because of increased adrenal androgen secretion. Decreased ability to handle stress may result in psychiatric problems ranging from mood swings to psychosis.

13. Diabetes Insipidus Diabetes insipidus is a disorder of water metabolism caused by a deficiency of ADH. The absence of ADH allows filtered water to be excreted in the urine instead of reabsorbed. The disease causes excessive urination and excessive thirst and fluid intake. It may first appear in childhood or early adulthood and is more common in men than in women. Pathophysiology: Some drugs as well as injury to the posterior pituitary gland can cause abnormalities in ADH secretion. A less common cause is a failure of the kidneys to respond to ADH. Lesions of the hypothalamus, infundibular stem, and posterior pituitary gland can also interfere with ADH synthesis, transport or release. Lesions may be caused by brain tumour, removal of the pituitary gland, aneurysm, thrombus, immunologic disorder or infection. Normally ADH is synthesised in the hypothalamus and then stored in the PPG. Once it is released into the general circulation, ADH increases the water permeability of the distal and collecting tubules of the kidneys, causing water reabsorption.

14. Diabetes Insipidus What to look for: Abrupt onset of extreme polyuria (usually 4 to 16L/day of dilute urine, but sometimes as much as 30 L/day. Polydipsia and consumption of extraordinarily large volumes of fluid. In severe cases, fatigue occurs because sleep is interrupted by the need to void and drink fluids. Children often have enuresis, sleep disturbances, irritability, anorexia, and decreased weight gain and linear growth. Weight loss Dizziness Weakness Constipation Increased serum sodium and osmolality

15. Diabetes Mellitus Diabetes mellitus is a disease in which the body does not produce or properly use insulin, leading to hyperglycaemia. The disease occurs in two primary forms: Type 1 Type 2 Several secondary forms also exist, caused by conditions such as pancreatic disease, pregnancy, hormonal or genetic problems, and certain drugs or chemicals. Pathophysiology: In Type I diabetes, the beta cells in the pancreas are destroyed or suppressed. Type I diabetes is subdivided into idiopathic and immune-mediated types. A local or organ specific deficit may induce an autoimmune attack on beta cells. This attack, in turn, causes an inflammatory response in the pancreas called insulitis. By the time the disease becomes apparent, 80 percent of the beta cells are disabled.

16. Diabetes Mellitus With the idiopathic form, patients have a permanent insulin deficiency and are prone to ketoacidosis. However, there is no evidence of autoimmunity. Type 2 diabetes may be caused by the following: Resistance to insulin action in target tissues Abnormal insulin secretion Inappropriate hepatic gluconeogenesis (overproduction of glucose) Type 2 diabetes may also develop as a consequence of obesity and a sedentary lifestyle. The pancreas produces some insulin, but it is either too little or ineffective. The following factors contribute to its development: Impaired insulin secretion Inappropriate hepatic glucose production Peripheral insulin receptor insensitivity

17. Diabetes Mellitus Pathophysiologic Changes: High serum osmolality caused by high serum glucose levels: polyuria, polydipsia. Depleted cellular storage of CHO, Protein and Fat (polyphagia). Prevention of normal metabolism of CHO, Fat and Protein caused by impaired or absent insulin function. Low intracellular glucose levels: Headache, fatigue, lethargy, reduced energy levels. Electrolyte imbalances: muscle cramps, irritability, and emotional lability. Glucose induced swelling: Vision changes (blurring). Neural tissue damage: numbness and tingling. Hyperglycaemia: Slowly healing skin infections or wounds; skin itching.

18. Goitre A goitre is an enlargement of the thyroid gland. It is not caused by inflammation or neoplasm and not initially associated with hyperthyroidism or hypothyroidism. This condition is commonly referred to as non-toxic goitre. It is classified in two ways: endemic, caused by a lack of iodine in the diet. Sporadic, related to ingestion of certain drugs or food and occurring randomly. Non-toxic goitre is most common in females, especially during adolescence, pregnancy, and menopause. At these times, the demand for thyroid hormone increases. Toxic goitre arises from long-standing non-toxic goitre and occurs in the elderly. The enlarged thyroid gland develops small rounded masses and secretes excess thyroid hormone.

19. Goitre Pathophysiology: Non-toxic goitre occurs when the thyroid gland cannot secrete enough thyroid hormone to meet metabolic needs. As a result, the thyroid mass increases to compensate. This usually overcomes mild to moderate hormonal impairment. TSH levels in non-toxic goitre are generally normal. Enlargement of the gland probably results from impaired hormone production in the thyroid and depleted iodine, which increases the thyroid gland’s reaction to TSH. Endemic goitre usually results from inadequate dietary intake of iodine, which leads to inadequate synthesis of thyroid hormone. In Japan, goitre resulting from iodine excess from excessive ingestion of seaweed has been found. Sporadic goitre commonly results from ingestion of large amounts of goitrogenic foods or use of goitrogenic drugs.

20. Hyperthyroidism When thyroid hormone is overproduced, it creates a metabolic imbalance called hyperthyroidism. Excess thyroid hormone can cause various thyroid disorders; Grave’s disease is the most common. Pathophysiology: In Grave’s disease, thyroid stimulating antibodies bind to and stimulate the TSH receptors of the thyroid gland. The trigger for this autoimmune response is unclear, it may have several causes. Genetic factors may play a part; the disease tends to occur in identical twins. Immunologic factors may also be the culprit; the disease occasionally coexists with other autoimmune endocrine abnormalities, such as Type I diabetes mellitus, thyroiditis and hyperparathyroidism. Grave’s disease is also associated with the production of several autoantibodies formed because of a defect in suppressor T lymphocyte function.

21. Hyperthyroidism 3. What to look for: An enlarged thyroid Exophthalmos Nervousness Heat intolerance Weight loss, despite increased appetite Excessive sweating Diarrhoea Tremors palpitations

22. Hypothyroidism In thyroid hormone deficiency in adults, metabolic processes slow down. This is due to a deficit in T3 and T4, which regulate metabolism. The disorder is most prevalent in woman and people with Down Syndrome. Hypothyroidism is classified as primary or secondary. The primary form stems from a disorder of the thyroid gland itself. The secondary form stems from a failure to stimulate normal thyroid function. Pathophysiology: Primary hypothyroidism has several possible causes: Thyroidectomy Inflammation from radiation therapy Amyloidosis and Sarcoidosis Hashimoto’s thyroiditis Secondary hypothyroidism is caused by a failure to stimulate normal thyroid function.

23. Hypothyroidism What to look for: Energy loss Fatigue Forgetfulness Sensitivity to cold Unexplained weight gain Constipation As the disease progresses: anorexia, decreased libido, menorrhagia, paraesthesia, joint stiffness, muscle cramping. CNS Integumentary System Cardiovascular System GI Symptoms Reproductive System