So these are kinda barebones because I have to fit inside a word limit but here are the sort of questions I have to answer for school 😭😭😭
List and define 5 different morphological reactions to persistent stress (e.g., atrophy, dysplasia). Are these adaptations reversible? Why is dysplasia considered to be a pre-neoplastic condition?
Atrophy is the decrease in cell (or organ) size or function. It is reversible in some cases. For example, atrophy from cell shrinkage can be reversed in the case of muscle atrophy, while atrophy from cell death in the brain is irreversible.
Hypertrophy is the increase in cell (or organ) size or function. It is reversible.
Hyperplasia is the increase in cell number with no impact on cell size. It can occur along with hypertrophy but the two reactions are considered distinct. Hyperplasia is reversible.
Metaplasia is the conversion of one differentiated cell type to another. It is reversible.
Dysplasia is a change in the way cells grow and mature. It can reverse but requires intervention to do so. Dysplasia is considered to be a pre-neoplastic condition because it is a necessary stage in the journey cells take to become cancerous. In the development of cancer, the accumulated mutations from dysplasia disrupt cell regulation and progress to neoplasia.
Discuss the role of granulation tissue in wound healing, and explain how disruption of normal healing can lead to pathologic processes.
Granulation tissue replaces the provisional matrix during wound repair. It’s highly vascular and rich in fluids which allows immunoglobulins, antibacterial peptides, and growth factors to be transported to the wound as it heals. Over time, as the wound heals, this granulation tissue is replaced with normal tissue and the wound is returned to its original state.
Wound healing can be disrupted in many ways. Poor blood supply impedes repair and can lead to edema and ulceration. Chronic inflammation can lead to the continuous and excessive deposition of matrix proteins, which leads to loss of function. If cells can’t be replaced, scarring can result.
My Cancer Genome is a Health Informatics web site that provides up-to-date information on cancer genes, biomarker-directed therapies, and clinical trials. Learning how to obtain information from this web site (and others) will help you in your continuing education and clinical practice. To get started, please follow these instructions and post your findings to our discussion:
- Open My Cancer Genome
- Of the choices, click “Diseases” to begin
- Choose one of the neoplastic diseases listed to the right (e.g. Breast Carcinoma or Melanoma), or type in another neoplastic disease in the “Search” engine
- Scroll down to see a histogram of “Most Commonly Altered Genes” - copy and post the top 5
- Continue to scroll down to see “Biomarker-Directed Therapies” and click the link on the right. Select two therapies, and post the drug name and its mechanism of action (“Drug Category”)
The most commonly altered genes in melanoma are: BRAF, CDKN2A, NRAS, TP53, and NF1.
Two of the biomarker-directed therapies for melanoma are: Imatinib, an ABL inhibitor and tyrosine kinase inhibitor; and atezolizumab, an anti-PD-L1 antibody.
Define mutagen, carcinogen, and teratogen. Explain the interaction of genetic and environmental factors in the pathogenesis of phenylketonuria (PKU).
A mutagen is a chemical, physical, or biological agent that causes irreversible change to the genetic makeup of a cell. Most, but not all, mutagens are carcinogenic.
A carcinogen is a chemical, physical, or biological agent that promotes the formation of cancer. This can happen by either damaging the genome (as a mutagen does) or by disrupting the cell’s metabolic processes.
A teratogen is a chemical, physical, or biological agent that causes developmental abnormalities. For example, the sedative thalidomide was found to cause developmental abnormalities in the fetus when taken by pregnant women, causing children to be born with incomplete limbs as well as other problems with the heart and ears.
Phenylketonuria is an autosomal heritable disorder of amino acid metabolism that causes a deficiency in the liver enzyme phenylalanine hydroxylase, which breaks down phenylalanine into tyrosine. This leads to high levels of phenylalanine in the blood, which is neurotoxic and can lead to irreversible brain damage if not treated. However, if the patient follows a strict diet with no phenylalanine for life, there is no hyperphenylalaninemia and they can lead a fairly normal life without intellectual disability, seizures, or premature death. Therefore the disease has a genetic component but its expression is dependent on diet.
Summarize clinicopathologic features of systemic lupus erythematosus, and explain how steroidal anti-inflammatory drugs might block, alter, or reverse the course of this autoimmune disease.
Systemic lupus erythematosus can affect almost any organ, but one of the suggestive signs of systemic lupus erythematosus is having a high blood titer of two antinuclear antibodies: the antibody to double-stranded DNA and a soluble nuclear antigen complex, Sm antigen (part of the spliceosome). Systemic lupus erythematosus can manifest through joint disease as polyarthralgia (usually without joint destruction as in rheumatoid arthritis), renal disease as glomerulonephritis, pleuritis and pleural effusions, respiratory disease and pneumonitis, Libman-Sacks endocarditis which is characterized by small nonbacterial lesions on the heart’s valves, and central nervous disease such as psychiatric disease or vasculitis-related hemorrhage or stroke. However, this is just a small range of the symptoms of systemic lupus erythematosus, since the circulating disordered immune complexes can deposit in nearly every tissue in the body.
Steroidal anti-inflammatory drugs are often used in the treatment of systemic lupus erythematosus because most of the injury from this disease is due to the deposition of immune complexes against the self-antigens characteristic of lupus. Steroidal anti-inflammatory drugs suppress immune response, which prevents these immune complexes from forming and therefore prevents them from depositing in the body and causing chronic inflammation and injury. However, prolonged use of steroidal anti-inflammatory drugs can also cause illness and injury.
Identify the etiology, pathogenesis, clinical manifestations (warning signs), and developmental considerations of melanoma.
Exposure to UV light and the mutations that arise from UV damage are considered the leading cause of melanoma.
Melanoma has several mutations implicated in its pathogenesis, especially BRAF and NRAS mutations that use the MAPK pathway, which regulates cell proliferation. Mutations in the tyrosine kinase receptor are often seen in acral, mucosal, and lentigo maligna melanoma. Mutations in PTEN, which suppresses a pathway that regulates cell survival, also can cause melanoma, as can mutations in CDKN2A, which encodes for tumor suppressor genes. Malignancy probably involves mutations in several of these genes at once.
The course of melanoma goes from the radial growth stage, in which a nevus becomes abnormal and proliferates along the surface of the skin, to the vertical growth stage, in which the cancer grows deeper into the dermis perpendicular to the radial growth stage. If the melanoma stays below 1mm thick, the risk of metastasis is lower.
Warning signs of melanoma include increased number of total nevi, large nevi, and dysplastic nevi. These proliferations of melanocytes may be benign, but when many of them appear or when they begin to grow abnormally, it is a large risk factor in developing melanoma.
Developmental considerations of melanoma include fair skin, susceptibility to burning and tanning, and the tendency to form increased numbers of nevi with sun exposure.
Assess usual clinical manifestations and determine appropriate treatments for patients with cardiogenic, hypovolemic, or anaphylactic shock.
Cardiogenic shock is caused by heart failure. This usually happens after a massive myocardial infarction but can also be caused by myocarditis. Other causes of reduced cardiac output include pulmonary embolisms, cardiac tamoponade (in which pericardial fluid rapidly accumulates, causing a decline in cardiac output), or an atrial myxoma (tumor on the heart). The symptoms of cardiogenic shock include hypotension, rapid breathing, fast pulse, clamminess, decreased urine output, and loss of consciousness. Because cardiogenic shock is usually preceded by myocardial infarction, the patient may also experience the symptoms of myocardial infarction along with those of shock. The treatment of cardiogenic shock varies depending on the cause of the shock but can include thrombolytic drugs to dissolve coronary artery clots, anticlotting agents to prevent new clots, drugs to increase the heart’s ability to pump blood (for example: epinephrine), bypass surgery to allow blood to flow around blocked or narrowed arteries, balloon angioplasty to open blocked coronary vessels, electrical shock to “reset” the heart, or the implantation of a pacemaker.
Hypovolemic shock is caused by large decreases in blood or plasma volume. This can be from hemorrhage or fluid loss from severe burns diarrhea, excessive urine formation, excessive perspiration, or trauma. Symptoms of hypovolemic shock include cold or clammy skin, rapid breathing, rapid heart rate, decreased urine output, a weak pulse, confusion, weakness, blue lips and fingernails, and loss of consciousness. The signs of hemorrhage include visible bleeding from area of injury, abdominal pain, blood in stool, black, tarry stool, blood in urine, vomiting blood, abdominal swelling, and chest pain. The treatment of hypovolemic shock should control the loss of fluid and blood through fluid resuscitation and blood transfusion, administering medications to increase heart rate and blood pressure like epinephrine, and treating the cause of the shock in the first place so that further fluids are not lost. This depends on the cause of the shock.
Anaphylactic shock is caused by a systemic immune hypersensitivity reaction to an allergen, which causes systemic vasodilation and therefore reduces cardiac output. Signs and symptoms of anaphylactic shock include itchiness, slurred speech, confusion, difficulty breathing, low blood pressure, weakness, rapid pulse, wheezing, hives, respiratory arrest, and unconsciousness. The first step in treating anaphylactic shock is administering epinephrine (for example: with an “epi-pen”), which allows the heart to pump blood more efficiently and reduces inflammation which would otherwise make breathing impossible. After this, steroids and antihistamines may be administered to reduce the allergic response.
In all cases of shock the patient should be monitored afterwards to treat any complications that arose from being in shock.
Assess usual clinical manifestations and determine appropriate treatments for patients with coronary artery disease.
Coronary artery disease is often caused by the buildup of plaque in the coronary arteries, limiting blood flow to the heart and causing infarction. Coronary artery disease may have no symptoms at all, but when there are symptoms, they are usually either chest pain on the middle or left side of the chest or shortness of breath and fatigue. The symptoms of myocardial infarction, the sequela of coronary artery disease, includes crushing pain in the chest, pain in the shoulder or arm, shortness of breath, sweating, and more atypical signs such as jaw pain, fatigue, and nausea. Coronary artery disease can be managed through lifestyle changes like managing blood pressure, stopping smoking, increasing physical activity, changing one’s diet, losing weight if the patient is overweight or obese, and reducing blood cholesterol levels. Drug interventions include statins to reduce LDL cholesterol levels, aspirin to reduce clotting in the blood, beta blockers to reduce heart rate and lower high blood pressure, and nitroglycerin to dilate the coronary arteries and reduce chest pain. Procedures to restore or improve blood flow include placing a stent to widen the coronary arteries and coronary artery bypass surgery to allow blood to flow around the blocked coronary artery.
Assess usual clinical manifestations and determine appropriate treatments for patients with bacterial or viral pneumonia.
The symptoms of viral and bacterial pneumonia are very similar: both are characterized by a cough with thick yellow, green, or bloody phlegm, stabbing chest pain, chills, fever, blueness of the lips, fatigue, sweating, and other flulike symptoms. Viral pneumonia can be differentiated from bacterial pneumonia by culturing the sputum to check for bacteria. Bacterial pneumonia is treated with antibiotics and respiratory therapy to prevent damage to the lungs. Intravenous fluids may be given to prevent dehydration. The treatment of viral pneumonia usually falls under symptom management, so fluids may be given to treat dehydration and cough suppressant medications given to manage the cough. In certain cases, such as in the elderly or immunocompromised, antiviral drugs might be administered to treat the infection directly. Most of the time viral pneumonia will run its course on its own, but sometimes it may progress to bacterial infection, which is then treated accordingly.
Respiratory Distress Syndrome
Discuss clinicopathologic features of diffuse alveolar damage (DAD) in patients with respiratory distress syndrome.
Diffuse alveolar damage can be caused by a variety of injuries, such as infection, aspiration of fluids, shock, fat embolism, heroin use, radiation, toxic gas inhalation, and cytotoxic drugs. Injuries to the endothelial cells allow fluid to leak from alveolar capillaries into the interstitial space, creating hyaline membranes on the alveolar walls. Edema within the alveolus follows, type II pneumocytes multiply to line the alveolar surface which becomes inflamed, and fibroblasts proliferate which may either lead to healing or fibrosis within the lungs which greatly reduces lung function. At first, this manifests no symptoms for a few hours after the injury. The first symptoms to occur are rapid breathing and difficulty breathing. As respiratory distress syndrome progresses, it becomes more difficult to breathe and the patient turns a blueish color. Even if increased oxygen concentration is administered, the damage to the alveoli makes it such that blood oxygenation does not increase, and mechanical ventilation is required.
Discuss the role of Helicobacter pylori infection in the pathogenesis of peptic ulcer disease and gastric cancer.
Helicobacter pylori normally inhabits the mucoid lining of the stomach near the duodenum and produces chemicals that, while they make the local environment more hospitable for the bacteria, are toxic to human epithelial cells. This leads to chronic inflammation (gastritis) which allows stomach acid to damage the stomach and duodenal linings, creating ulcers. The chronic inflammation and injury can lead to metaplasia, which increases the risk of gastric cancer. Inflammation in the stomach lining is proposed to alter epithelial cell adhesion and lead to the migration of mutated cells (which there is an increased rate of, due to the enhanced production of free radicals near the infection) and therefore metastasis.
Explain how screening colonoscopy reduces the risk of malignant neoplams of the large intestine.
Screening colonoscopy is associated with a 67% lower risk of death from colorectal cancer overall. It allows doctors to detect precancerous growths, colon polyps, and other neoplasms in the colon before they become malignant, and thus they can be treated early enough to not pose a risk to the patient.
Explain how chronic liver injury, regeneration, and repair leads to hepatic cirrhosis. List complications of hepatic cirrhosis.
Liver injury leads to inflammation and the death of liver cells, which triggers its regeneration and repair. In acute liver injury, liver regeneration is favored, while in chronic injury, the balance is tipped towards fibrosis. The repair process occurs simultaneously with inflammation during chronic liver injury, which induces fibrosis. A cytokine secreted from damaged hepatocytes stimulates a cascade in immune cells mediating inflammation that eventually leads to the activation of hepatic stellate cells which promote collagen formation and thus the scar tissue of cirrhosis.
Complications of hepatic cirrhosis include:
- portal hypertension
- edema in the legs and ascites in the abdomen (due to portal hypertension)
- bacterial peritonitis
- enlargement of the spleen and decreased white blood cell count as a result
- bleeding due to increased blood pressure
- hepatic encephalopathy
- multiorgan failure
Identify the etiology, pathogenesis, and clinical manifestation of gallstones (cholelithiasis)
In industrialized countries, 75% of gallstones are made up of cholesterol. Increased hepatic secretion of cholesterol and decreased production of bile salts can lead to the buildup of cholesterol in the gallbladder, creating these stones. Increased age, obesity, a high-calorie and high-cholesterol diet, metabolic disorders such as diabetes and hyperlipoprotenemia, ethnicity, and family predisposition are all factors associated with increased cholesterol secretion and therefore increased risk of cholesterol gallstones. Decreased secretion of bile salts is associated with pancreatic insufficiency. Decreased gallbladder motility is associated with being a premenopausal woman, especially those using oral contraceptives containing progesterone or who have gone through multiple pregnancies.
The other 25% of gallstones are made up of calcium bilirubinate and other calcium salts. Small black pigment stones are sometimes associated with cirrhosis and other liver damage, but often have no known etiology. Spongy, laminated brown pigment stones are uncommon in Western countries but are sometimes found in Asia, where they are almost entirely associated with parasitic worms infesting the biliary tract. In non-parasitic cases, they are associated with chronic obstruction of the biliary tract, such as in the presence of a catheter in the bile duct.
Gallstones often do not present symptoms for many years until they obstruct the cystis or bile ducts. When this happens, it may cause inflammation of the bile duct system, inflammation of the gallbladder, inflammation of the pancreas, and obstructive jaundice. On top of this, the obstruction of the bile duct itself causes intense pain in the upper right quadrant of the abdomen, often accompanied by nausea and vomiting.
Identify the etiology, pathogenesis, and clinical manifestations of nephritic vs nephrotic syndromes.
Both nephritis and nephrotis are secondary responses to injury affecting the kidneys.
Nephritic syndrome is characterized by inflammation in the kidney, hematuria, hypertension, decreased urine output, pyuria, and mild to moderate amounts of protein in the urine. It often occurs in the glomerulus, where the glomerular basement membrane becomes inflamed and thins, while small pores form in the Bowman’s capsules podocytes, which allows both protein and red blood cells to pass into the urine. Nephritic syndrome is caused by inflammatory damage to capillaries in the glomerulus, which can be caused by infection (as in post-streptococcal glomerulonephritis and IgA nephropathy), autoimmunity (as in systemic lupus erythematosus or goodpasture syndrome), or thrombosis (as in infective endocarditis).
Nephrotic syndrome is characterized by high amounts of protein in the urine, hyperlipidemia, and edema. In nephrotic syndrome, hematuria and oliguria are uncommon. The most common cause of nephrotic syndrome in children is minimal change disease, which is limited to the kidney. MCD is considered idiopathic and involves the loss of podocyte function, which allows for proteins to be lost in the urine. The podocytes appear normal under a light microscope, but the disordered podocyte foot processes can be seen under an elecron microscope. In adults, primary nephrotic syndrome is often caused by focal segmental glomerulosclerosis, in which parts of certain glomeruli develop scarring. The causes for damage to the podocytes are not always known, but in many cases, a toxin or stressor that was hyperfiltered through the glomerulus is the reason for the cell damage. Either way, immune complexes are absent and inflammation is not the cause for the cell damage.
Assess the usual clinical manifestations and determine appropriate treatment options for patients with nodular prostatic hyperplasia.
Nodular prostatic hyperplasia is clinically characterized by obstruction of urinary outflow, leading to decreased flow of the urinary stream and increased urinary frequency. Other symptoms include inablity to urinate, loss of bladder control, and difficulty initiating urination. This is because the enlarged prostate compresses the urethra. Extended urinary obstruction can lead to dilation of the ureter, swelling of the kidney due to a buildup of urine, and eventually kidney failure and death. Other complications of nodular prostatic hyperplasia include bladder stones and urinary tract infections.
Treatment of nodular prostate hyperplasia can be either pharmaceutical or surgical. Pharmaceutical treatment includes drugs that block the enzyme 5α-reductase, such as finasteride or dutasteride, which reduces the size of the prostate in men with nodular prostate hyperplasia. Selective α1-adrenergic blockers can also enhance urine flow by relaxing muscles in the neck of the bladder and the prostate. Surgical intervention can be performed with transurethral resection of the prostate, prostate laser surgery, or simple prostatectomy. Castration before puberty prevents nodular prostatic hyperplasia altogether as well as preventing prostate cancer, but is not commonly performed in modern times.
Discuss the etiology, pathogenesis, clinical manifestations, and developmental considerations of breast cancer.
There are many risk factors for breast cancer, including mutations in the BRCA gene, age in general, age at menarche, age at menopause, breast density, use of hormone replacement therapy (excluding birth control), older age at first pregnancy, smoking, lower levels of physical activity, and exposure to radiation. In general, cumulative lifetime exposure to estrogen increases risk of breast cancer, since most breast cancers are stimulated by estrogen.
Mutations in the tumor-suppressing BRCA1 gene often leads to ductal carcinomas which are negative for estrogen receptors, progesterone receptors, and human epidermal growth factor 2. Mutations in the tumor-suppressing BRCA2 gene can lead to high-grade ductal tumors that are positive for estrogen and progesterone receptors. Mutations in BRCA2 also increase lifetime risk for ovarian cancer, pancreatic cancer, biliary tract cancer, skin melanomas, and uveal cancer.
Ductal carcinoma in situ is often seen together with invasive carcinoma, and usually share grading with one another. Low-grade carcinoma cells are uniform and small, with infrequent mitosis and micropapillary or cribriform growth. High-grade carcinoma cells are large, pleiomorphic, proliferate rapidly, and often feature ductal necrosis throughout. Ductal carcinomas in situ are usually seen in imaging as calcifications in the breast. Invasive breast carcinoma often presents as an irregular, dense mass in imaging. Invasive lobular carcinoma forms sheets or nests of cancerous cells as opposed to ducts.
Symptoms of breast cancer include erythema or eczymatous inflammation of the nipple and areola, nipple retraction, palpable masses in the breast, change in shape or texture of the breast, and abnormal nipple discharge.
Breast cancer is almost always treated with surgery to remove the tumor. Depending on the molecular subtype of breast cancer, treatment and prognosis vary. Luminal A tumors are often low-grade and have good prognosis. They are typically managed with hormonal therapy. Luminal B tumors are similar and have intermediate prognosis. They are usally higher grade and respond better to chemotherapy. Tumors that overexpress HER2 have a poor prognosis and behave aggressively, but antibody treatment shows hope in increasing patient longevity. Basal-like cancers, constituting 10% of invasive breast carcinomas, are high-grade, aggressive, and have poor prognosis. They are treated with chemotherapy.
Discuss the benefits and risks associated with postmenopausal hormone therapy.
After menopause, many women have unpleasant symptoms such as hot flashes, vaginal atrophy, skin aging, decreased muscle mass, sexual dysfunction, and osteoporosis. This is largely due to the decreased levels of sex hormones after menopause. Postmenopausal hormone therapy can be used to provide short-term relief from these symptoms and prevent osteoporosis and its associated injuries. Postmenopausal hormone replacement therapy is also indicated in lowering blood cholesterol levels and decreased levels of coronary heart disease if started less than ten years after menopause, but increased risk of stroke if started more than ten years after menopause. Estrogen alone also increases the risk of blood clot formation and gallbladder disease. While hormone therapy can decrease the risk of endometrial cancer in postmenopausal women, it increases the chance of uterine fibroids. Hormone replacement therapy with synthetic progesterone is associated with increased risk of breast cancer, especially in women with a BMI below 25. It is also associated with an increased risk of ovarian cancer.
Discuss the pathology, pathogenesis, and usual clinical manifestations of patients with either Addison disease or Conn syndrome.
Addison disease is a fatal disorder caused by either the destruction or insufficiency of the adrenal glands. In Western societies, this is usually autoimmune in origin, although the disease was first described in the context of tuberculosis infection. Other causes of Addison disease include carcinoma, buildup of abnormal amyloid proteins in the body, congenital adrenal hypoplasia, fungal infection, defective ACTH receptors, and sarcoidosis. In order to show symptoms, 90% of the adrenal glands must be destroyed or otherwise rendered unable to produce androgens, cortisol, or aldosterone. Initial symptoms of Addison disease are often nonspecific, including severe weakness, weight loss, low blood pressure, hyperpigmentation of the skin, muscle pain, and electrolyte imbalance, and gastrointestinal symptoms like nausea, diarrhea, vomiting, constipation and abdominal pain. The patient may crave salt because of the electrolyte imbalance. Acute adrenal failure comes on quickly; symptoms of an adrenal crisis include severe weakness, pain in the lower back or legs, delirium, and shock. Without treatment to restore the missing hormones, Addison disease is fatal, but patients can live a normal life if they receive treatment.
Compare and contrast diabetes mellitus type I and type II. What is diabetes insipidus?
Both type I and type II diabetes mellitus are characterized by an imbalance of blood glucose and insulin, leading to hyperglycemia. Hyperglycemia in both type I and type II diabetes mellitus can cause extensive systemic cell damage, especially in the kidneys, heart, and eyes. The high blood sugar of diabetes mellitus leads to polyuria (hence the name diabetes) and glycosuria (hence the name mellitus). However, type I and type II diabetes mellitus are differentiated by their underlying pathophysiologies, affected populations, and recommended clinical managements.
Type I diabetes mellitus is usually caused by autoimmune destruction of the insulin-producing beta cells in the pancreatic islets of Langerhans, has an early and abrupt onset, and is characterized by an absolute insulin deficiency that can lead to hyperglycemia, diabetic ketoacidosis, extreme dehydration, coma and death. Type I diabetes mellitus can be managed with regular administration of exogenous insulin to replace the missing pancreatic functioning.
Type II diabetes mellitus has a slower onset and often affects older overweight people. Rather than an absolute insulin insufficiency, type II diabetes mellitus is characterized by reduced tissue sensitivity to insulin, which increases blood sugar and insulin secretion; however, the increased insulin secretion cannot be maintained by the pancreas and eventually the islets of Langerhans degenerate and the output of insulin decreases. The course of type II diabetes mellitus can be reversed in early stages before beta cell dysfunction with weight loss, exercise, and insulin sensitizers. After beta cell dysfunction sets in, type II diabetes mellitus can be managed with insulin secretagogues, incretins which increase insulin and decrease glucagon secretion, exogenous insulin, and bariatric surgery.
Diabetes insipidus shares the first word of its name with diabetes mellitus, but they are completely unrelated save for the fact that diabetes insipidus also causes increased thirst and polyuria. The glucose levels in people with diabetes insipidus are normal, but damage to the thirst-regulating parts of the hypothalamus or the pituitary cause a deficiency in antidiuretic hormone which leads to disrupted fluid homeostasis and the symptoms of increased thirst and increased urination. Diabetes insipidus can also be caused by impaired renal response to antidiuretic hormone, which is referred to as renal diabetes insipidus.
Discuss the pathogenesis and clinical manifestations of Alzheimer disease. Are there any recent studies that provide hope for early diagnosis and treatment?
Alzheimer disease is the most common cause of dementia in the elderly, starting with loss of memory and cognitive dysfunction and ultimately progressing to dementia, difficulty with language, and changes in behavior. It occurs when β-amyloid and tau proteins accumulate in the brain, causing cortical atrophy and hydrocephalus. Upon microscopic examination, plaques of extracellular abnormal β-amyloid proteins and intracellular tangles of tau proteins can be found. Unfortunately, the accumulation of plaques and tangles evolves over a period of years or decades and may remain asymptomatic for a long time before severe symptoms of Alzheimer disease become apparent.
Recent studies have shown that visinin-like protein I and neurogranin in cerebrospinal fluid may serve as good markers of disease progression, which can catch neuron loss and help diagnose early states of Alzheimer disease before symptoms of the disease become apparent.
Assess usual clinical manifestations and determine appropriate treatments for patients with multiple sclerosis.
Multiple sclerosis is a demyelinating disease which primarily targets the central nervous system. Many small demyelinated plaques accumulate in the brain and spinal cord, mostly invading the white matter. This can lead to paralysis, ataxia, weakness, loss of vision, incontinence, and dementia, depending on which parts of the nervous system are most affected. Patients with multiple sclerosis often have periods of time where symptoms of the disease progress rapidly, known as an attack, followed by a stable plateau of no new symptoms. However, the damage done to the nervous system accumulates over the patient’s lifetime. Additionally, the disease is still progressing despite the laxk of new symptoms. It is believed that multiple sclerosis is an autoimmune disorder where the immune system targets the nervous system; because of this one of the treatments to suppress the progress of the disease is to suppress the inappropriate action of the immune system with β-interferon to reduce inflammation in the brain, monoclonal antibodies that target human immune cells to prevent them from destroying the patient’s nervous tissue, and other immunomodulators to alter immune behavior. Cognitive behavioral therapy and other psychological therapies are somewhat effective to improve some cognitive symptoms of multiple sclerosis, while physical therapy, occupational therapy, and exercise can help improve some of the symptoms of physical disability after an acute attack.