PATHOLOGY & BIOCHEMISTRY MODEL DEGREE EXAM QUESTIONS - Coursework Example

?PATHOLOGY & BIOCHEMISTRY MODEL DEGREE EXAM QUESTIONS PATHOLOGY PART Q1. Write a full of the differences between Malignant and Benign neoplasm (you should have between 14-15 differences). In your essay you should draw up a table SIMILAR to the one below (Do not use the exact wording as the table below) (write about 250 words) DIFFERENCES BETWEEN MALIGNANT AND BENIGN NEOPLASIA MALIGNANT BENIGN 1 Made up of undifferentiated, anaplastic cells Differentiated cells 2 Metastasize to other tissues such as lymph nodes Growth is limited within tissue of origin 3 Ill-defined borders Well-circumscribed growth 4 Needs adjunct therapy such as medical and/or radiation intervention Usually treated with surgery alone 5 Nomenclature: suffix either –carcinoma or –sarcoma Nomenclature: always with a suffix of –oma 6 Greater rate of mitosis than benign Mitosis rate not as much as malignant 7 Pleomorphic, in that the cancer cells vary in size and shape Isomorphic 8 Hyperchromatic nuclei, nucleus is big (1:1) and its shape irregular, Nucleus is 1:4 or 1:6, and normally spherical 9 Polarity absent. Growth Is isorganized Polarity still present. Thus, growth organized 10 Cellular function deranged Cellular function intact 11 Growth causes progressive infiltration, invasion and destruction of surrounding tissue Cohesive expansile mass 12 Mitosis products are mutated Mitosis products are normal 13 Macroscopically large Macroscopically small 14 With hemorrhage and necrosis Hemorrhage and necrosis absent 15 Poorer prognosis than benign Better prognosis than malignant The identifying characteristic of malignant neoplasms, with nomenclature of either carcinoma or sarcoma in their suffixes, is that they have ill-defined borders, and are able to infiltrate surrounding tissues and metastasize to other tissues of the body. Malignant tumors are also more prone to necrosis and hemorrhage, as compared to benign ones, growth named with an –oma attached at the end. As such, surgical treatment alone is not enough in treating the disease. Adjunct therapy may include radiation and chemotherapy. In contrast, benign neoplasms can be resolved through surgery because they are encapsulated and their growth is limited within the tissue of origin. Given these reasons, the prognosis of patients with malignant neoplasms is poorer than those with benign growths. Microscopic differences are also present. Malignant neoplasms are composed of cells with a higher mitotic activity compared to benign neoplasms. Thus, malignant tumors are typically larger than benign ones. They also look different from benign cells, which look like normal, differentiated cells, because they are undifferentiated and anaplastic, their nuclei are big and hyperchromatic and their shapes are irregular. The malignant cells of a tumor also vary in size and shape, as opposed to cells of a benign tumor which are isomorphic. Malignant cells also lose their polarity, resulting to disorganized growth. Benign tumor cells still have their polarity intact, thus they are still capable of organized growth. Cell derangement is not just limited to structure , but also to function. Malignant cells have an altered function already, as opposed to benign tumors that retain the function of the tissue of origin. Q2. Write about the sequence of events and processes of the pathogenesis of a typical carcinoma. You may use the flow diagram below as a guide: (write about 200 words) EVENTS AND PROCESSES IN THE DEVELOPMENT OF DUCTAL CARCINOMA IN BREASTS NORMAL Nonproliferative PROLIFERATIVE CHANGES Caused by loss of growth inhibitory signals, increase in pro-growth signals, or decreased apoptosis DNA INSTABILITY AND ATYPICAL HYPERPLASIA Nuclear enlargement, irregularity and hyperchromasia as cells continue to proliferate HIGH GRADE DUCTAL CARCINOMA IN SITU Solid sheets of pleomorphic cells with hyperchromatism and necrosis Abrogation of the basement membrane, angiogenesis, stromal invasion HIGH GRADE INVASIVE CARCINOMA Cell mass with ill-defined borders A stepwise process is needed in the development of invasive carcinoma of the breast. Similar cellular changes can also be observed in other types of malignancy. From a normal, non-proliferative ductal cell, it will transform into a highly proliferative one, This is caused by the loss of growth inhibitory signals, increase in pro-growth signals, and or decreased apoptosis. At this point the genetic material and the appearance of cell is still normal. However, the accumulation of DNA mutations due to increased mitosis results to DNA instability and atypical hyperplasia. This is characterized by nuclear enlargement, irregularity and hyperchromasia. Further development into malignant cancer result to high grade ductal carcinoma in situ (DCIS) that is made up of solid sheets of pleomorphic and hyperchromatic cells. Also present are changes in surrounding tissue such as abrogation of the basement membrane, increased blood vessel production through angiogenesis, and stromal invasion. These changes are needed to support the growing mass with increased space and increased supply of blood that brings in nutrients and oxygen. In the end, a high grade invasive carcinoma develops when the cell mass has ill-defined borders capable of invading surrounding tissue and spreading in other tissues. . Q3. Write about tumor invasion and include the three key processes (use the document provided) [write approx 150 words] For the tumor to invade, it must accomplish three processes. First, the basal membrane and extracellular matrix are degraded to allow the cells to migrate to other tissues. Tumor cells or recruited stromal cells, such as fibroblasts and inflammatory cells, secrete proteases like metalloproteinases to degrade these membranes. The byproducts of degradation, collagen and proteoglycans, also induce angiogenesis and growth of surrounding tissue, thus further promoting disease progression. Next, the tumor cells should be able to pass through these degraded membranes. To do this, tumor cells should attach and reattach onto the membrane components laminin and fibronection while contracting their intracellular actin in between. For this, several cytokines and growth factors are released. Finally, tumor should have blood access to get nutrients and excrete wastes. It also provides growth factors, such as PDGF, inducing the further enlargement of the tumor. As well, cancer cells, through relative hypoxia, activate transcription of pro-angiogenic VEGF and bFGF. Q4. Write about the events and mechanisms associated with metastasis (use the table provided for guidance on what should be included in essay) [write approx 200-250 words] Normal non-proliferating cells, through a carcinogenic insult, will turn into hghly proliferating cells. Specifically, transformation of proto-oncogene into oncogene will allow self-sufficiency in growth signals. These cells are also insensitive to growth inhibitory signals such as transforming growth factor B and cyclin-dependent kinase inhibitors. In addition, mutation of p53, causing its inactivation, results to evasion of apoptosis. The resulting clonal expansion is supported by angiogenesis and escape from immunity. The latter is expected as these cells, albeit abnormal, are host cells, thus the inflammatory response is not programmed to discriminate the cancer cells from normal cells. Angiogenesis, on the other hand, is induced by an increased production of angiogenic factors and or loss of angiogenic inhibitors. Again, the absence of p53, which stimulates the production of anti-angiogenic factors such as thrombospondin-1, plays a role in angiogenesis. New blood vessels, aside from providing nutrients and oxygen, also expose the tumor cells to growth factors that further promote increase in mass. Finally, invasion and metastasis allow the tumor cells to grow in secondary tissues. First, the malignant cells should dissociate from one another. This means that adhesion molecules such as adherins and catenins are down-regulated in preparation for invasion. Next, the basement membrane and interstitial connective tissue are degraded. To do this, tumor cells themselves or induced stromal cells produce proteolytic enzymes such as matrix metalloproteinases. Finally, tumor cells attach to extracellular membrane proteins allowing them to propel themselves to secondary sites, where they can develop cancer mass anew. Q5. Make half a page of notes on the common patterns of injury, include each of the following terms; Oedema, Hemorrhage, Thrombosis, Infarctions and embolisms. (100-150 words each) Cardiovascular diseases are the primary causes of mortality and morbidity among Westerners today. They usually arise from disorders of hemodynamics, such as edema, hemostasis, such as hemorrhage and thrombosis, as well as embolism and infarction. Edema results from an increased hydrostatic pressure due to pooling of venous blood, for example, reduced plasma osmotic pressure when albumin is lost, sodium and water retention, and lymphatic obstructions. Hemorrhage, on the other hand, or the pooling of blood in the extravascular space, happens when there is rupture to blood vessels. Thrombosis is the pathologic formation of blood clot onto the endothelial surface, leading to blockage of blood vessels. However, through embolism, a previously attached clot can be released to reach a more distant point with less vascular caliber. Thus, it will prevent blood flow to the tissues supplied by the artery, causing infarction, or necrosis (cell death) due to hypoxia. Q6. Write about cell death (only necrosis and apoptosis), include each type of necrosis (coagulative, colliquative, caseous, gangrenes -including dry, wet and gas gangrene), fat necrosis and fibrinoid. In your introduction you include: the definition, key features and morphological indicators of cell necrosis. (About 50-60 words each) Cell death may be physiologic, through the programmed apoptosis, or as a culmination of cell injury, in which case it is called necrosis. There are many patterns of tissue necrosis, Coagulative necrosis has a preserved architecture of dead tissues due to the denaturation of proteases, together with structural proteins. As such, eosinophilic and anucleate cells persist for at least some days. However, necrotic cells will ultimately be degraded by the circulating leukocytes that digest dead cells through their lysosomal enzymes. Colliquative necrosis is characterized by a liquid viscous mass, and thus is called a wet gangrene, as opposed to coagulative necrosis, aptly called the dry gangrene. It is seen in focal infection, which stimulates leukocyte migration and accumulation even before tissue necrosis. The early presence of these inflammatory cells resulted to the viscous nature of the tissue. Once the leukocytes have completely digested the dead cells, an empty space among the living tissue is produced. This is called a gas gangrene. Gangrenous necrosis is more of a clinical than a pathologic description of a necrotic limb. It can either be coagulative, or colliquative, especially when there is secondary infection of the necrotic tissue. Casseous necrosis, on the other hand, is a characteristic of a tissue suffering from tuberculosis infection. It is made up of lysed cells and amorpous granular debris within an inflammatory border. Q7. Write notes on the following adaptive changes: atrophy, hyperplasia, hypertrophy, metaplasia, dysplasia, desmoplasia, neoplasia and disordered storage (i.e. accumulations inside cells in abnormal amounts). You are encouraged to include relevant diagrams or tables). (About 50 words each) The highly adaptive characteristic of organisms makes obvious the adaptations of cells in molecular level. Hypertrophy is an increase of size of cells, as manifested by an increase in organ size. This is a result of the increased production of structural proteins. Tissues that have a limited mitotic capacity can respond to increased metabolic demands by hypertrophy. On the other hand, hyperplasia is an increase in the number of cells, similarly increasing the size of the organ. This happens when an increased functional capacity is needed, or when the organ needs to compensate for a resected section. This can be pathologic, as it can result to abnormally high levels of endogenous substances such as hormones Atrophy, as opposed to hypertrophy and hyperplasia, is a decrease in cell size and number, resulting to a reduced organ size. Physiologic atrophy is seen in some embryonic structures such as the notochord. But, disuse, lack of chemical and nerve stimulation, inadequate nutrition, and pressure can cause atrophy as well. Metaplasia is a much more complicated type of adaptation as a differentiated cell type is replaced by another, which is much more suitable to respond to such change in environment. For example, when a columnar cell tissue is chronically exposed to irritants, it will be replaced with squamous tissue, although secretory and ciliary functions are lost. Dysplasia, which literally means disordered growth, often occurs in metaplastic epithelial cells. Dysplastic cells are pleomorphic and exhibit a large hyperchromatic nuclei and high nuclear to cytoplasmic ratio. Subsequently, dysplastic tissue has a characteristic loss of uniformity among its cells and loss of architectural orientation. Sometimes, metaplasia leads to neoplasia. It is the continuation of an increased mitotic activity despite the absence of a stimulus. This happens because of genetic alterations that allow excessive and unregulated proliferation. When large enough, it demands nutrients and oxygen from the body, thus depleting the supply to other more functional tissues of the body. Neoplastic cells also cause changes to the surrounding normal tissues. For example, it may induce stromal cells to produce more collagen and other stromal connective tissue to provide the structural stability needed during neoplastic growth. This abundance of collagenous stroma is referred to as desmoplasia. Another adaptation to change is disordered storage, or the presence of intracellular accumulation due to metabolic derangements. This happens when the production is increased, or metabolism is decreased. The usual molecules stored are lipids, cholesterols, proteins, hyaline, glycogen, and pigments. Thus, they can be seen microscopically as unusual intracellular vacuoles. Q8. Write about the differences between acute and chronic inflammation (write 200 words) Inflammation is either acute or chronic depending on the nature of stimulating agent and the effectiveness of the body’s initial immune response. Acute inflammation, such as that observed during an insect bite, is rapid in onset, usually within minutes after exposure to the agent. However, it is short in duration, resolving after hours or a few days after exposure to the injuring agent. It has a characteristic edematous formation and abundance of fast-acting immune cells such asbneutrophils. Normally, these immune cells should eliminate the agent, but if not it can progress to a chronic phase. However, chronic inflammation can be insidious in onset. The presenting symptoms of edema and immune cell emigration last longer in duration. However, the neutrophils are already replaced with lymphocytes and macrophages. Angiogenesis is stimulated, blood vessels become more abundant around the inflamed tissue, fibrosis ensues, and both normal and abnormal tissues become destructed by immune cells, incapable of discriminating between normal and abnormal cells. Thus, because of the amount of changes chronic inflammation causes, it is probable that it can explain the natural history of some chronic diseases. Indeed, chronic inflammation underlies common chronic conditions such as rheumatoid arthritis, atherosclerosis, type 2 diabetes, Alzheimer’s disease, cancer, and lung fibrosis. Q9. Write about changes in hypothetical cancer cell that are routinely used in histopathological and cytopathological laboratories in diagnosis – consider cellular changes that may form the basis of future diagnostic techniques.(write about 200 words) After biopsy, samples taken are processed and are examined through the microscope to look for cellular changes that definitively show cancerous growth. Cancer cells are anaplastic in nature, which means they are pleomorphic, and they have hyperchromatic nuclei. As well, surface proteins unique to cancer cells can be detected using immunohistochemistry. This is useful especially in identifying the origin of an undifferentiated tumor mass. Determining the cellular origin of such mass is important in dictating the steps of treating the disease. For example, the presence of cytokeratin means that the origin is epithelium (carcinoma). On the other hand, detection of desmin establishes the origin of tumor to be muscular. More specifically, the identification of prostate-specific antigen and thyroglobulin in the sample points to carcinomas of prostate and thyroid, respectively. As well, flow cytometry can help classify the neoplasm. Detection of oncogene-activating transformations in hematopoietic neoplasms can be done through cytogenetic analysis or FISH technique. Polymerase chain reaction, or PCR, can also help detect genetic transformation, especially from samples that are difficult to distinguish among the others on the basis of morphology. Q10. Write about the events and processes that occur in acute inflammation. Include: the three conceptual phases (i.e. initiation, amplification and termination), include the typical time course and effector pattern, cardinal signs (i.e. calor, rubor, tumor, dolor and loss/decline in functional capacity –Virchow). Write in detail about the micro vascular and cellular phase. Also include 4-5 cellular mediators in depth. You can include diagrams/tables flow diagram etc. (About 250-300 words) The acute inflammation is characterized by the three phases, specifically the initiation, or the triggering of inflammatory reaction by an agent, amplification, or the mechanisms involved in allowing the recruitment of more immune cells toward the injury site through the release of cytokines, and termination, which happens when the injurious material is eradicated from the body, and the edema recedes. This happens within minutes of exposure to agent and lasts for around days to weeks. Initiating stimuli may include infections, necrotic tissue, and foreign bodies. Virchow aptly describes the events of acute inflammation through calor and rubor, or heat and redness due to increased blood flow that permits leukocyte migration, tumor, caused by edema that is a secondary response to endothelial contraction and subsequent leaky vessel walls, and dolor, the pain caused by the prostaglandin released by immune cells. Many substances come into play during acute inflammation. Vasodilation is caused by the action of histamine and nitric oxide to vascular smooth muscle. VEGF also induces vascular leakage by stimulating the production of ion and water channels. Histamine and thrombin result to the endothelial production of P-selectin, which transiently binds to leukocytes after margination. Tumor necrosis factor (TNF) and interleukin-1 (IL-1), from endothelial cells and immune cells, induce the production of endothelial adhesion molecules that strongly binds to the leukocytes rolling on the vessel wall. Chemokines bind to leukocytes to modify the rearrangement of integrins to facilitate its binding with endothelial receptors. Q11. Write about the steps of neutrophil polymorph emigration (include: margination, adhesion, emigration and diapedesis). (Write about 150 words) Neutrophil polymorph emigration, or extravasation, starts with margination, in which a slower blood flow causes white cells to travel closer to the vascular walls. As such, they can undergo adhesion to complementary adhesion molecules expressed by endothelial cells. The expression of these receptors is induced by cytokines, such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), which is secreted by tissue macrophages, mast cells and endothelial cells in response to the presence of foreign, non-self, material. After which, leukocyte migration through the endothelium, or diapedesis occurs. After traversing the endothelium, leukocytes secrete collagenases to pierce the membrane. They emigrate toward the site of injury through chemotaxis, or locomotion oriented along a chemical gradient. Both exogenous and endogenous substances can act onto the leukocytes as chemoattractant. Q12. Write about types and mechanisms of cell and tissue injury (include hypoxic, ischemic and free radical induced injury- include reversible and irreversible injury. You should also include the most common mechanisms e.g. mechanical disruption, DNA damage or loss, membrane damage and blockage of metabolic pathways). Also mention homeostasis, adaptive capacity and compensatory mechanisms. You may include the diagram below: (write approx 250 -300 words) It is inevitable that cells are exposed to changes in its living conditions. Fortunately, they have repair mechanisms that allow mild and transient cell injury to be reversible to return the cell back to its normal state. However, severe, progressive presence of injurious material results to irreversible injury resulting to cell death. This injury usually results from the presence of free radicals, which are produced by chemical and radiation injury, cellular aging, and antimicrobial activity. Free radicals are chemical species that have an unpaired, highly reactive electron in its outer orbit. Upon reaction with other biomolecules like proteins, lipids and nucleic acids, these essential substances are denatured, structurally and functionally destroying the cell, and producing more free radicals as well. Specifically, it causes lipid peroxidation, destroying the plasma and organelle membranes. This is highly pathologic as reaction of free radical with one phospholipid induces destruction of all the phospholipids in the membrane are destroyed as well. Ischemia, or depletion of oxygen, also causes cell injury by decreasing the generation of ATP. This results to cytoskeleton denaturation and subsequent loss of ultrastructural features such as microvilli. In addition, there is no energy to power regulating mechanisms. For example, volume control through gated ion channels is dysfunctional, causing the mitochondria, lysosomes endoplasmic reticulum and other membranous organelles to swell up. Myelin figures are also present due to degenerating membranes in the cytoplasm. BIOCHEMISTRY PART Q1. Write brief notes on: a) the major functions of the kidney (150 words) The most commonly known kidney function is the controlled excretion of substances. The rates of filtration vary depending on the needs of the body. These substances include urea, a byproduct of protein metabolism, creatinine, which is used to measure kidney function, from the muscle creatine, uric acid from nucleic acid metabolism, bilirubin, and metabolites of various hormones. The substances that are still needed by the body, including water and solutes, are returned back to the circulation through ultrafiltration, thus ultimately producing hyperosmotic urine, and preventing dehydration and electrolyte imbalance. Water movement is driven by the ion concentration difference within and outside the ducts, as regulated by the ion, like potassium and hydrogen, channels along the tubules. In addition, kidneys produce regulatory substances. Erythropoietin is produced to induce the red blood cell production, calcitrol regulates calcium levels, and renin activates angiotensinogen and aldosterone production in response to increasing blood pressure levels. b) Metabolic alkalosis (150 words) c) In maintaining the pH, as defined by the equation pH = [pCO2] / [HCO3+], of the body to normal levels (neutral), the respiratory mechanism controls the amount of carbon dioxide [pCO2] in the body, while the metabolic mechanism controls [HCO3+]. Thus, metabolic alkalosis is caused by an increase in bicarbonate concentration in the blood, resulting to a decrease in hydrogen ion concentration and an increase in pH levels. Such condition may result from vomiting, which decreases the amount of acid within the body, thus increasing the pH levels. In such a situation, the respiratory mechanism may partially compensate by slower breathing to increase [pCO2]. A full compensation may necessitate both the lowering of [HCO3+] and increase in [pCO2]. Thus, both the lungs and the kidneys must work together to bring the pH to physiologic levels. Q2. Write brief notes on: a) Type 2 diabetes mellitus (150 words) Type 2 diabetes mellitus is a condition of hypergylcemia due to insulin resistance, impaired insulin secretion and increased glucose production/intake. It is differentiated from type 1 diabetes caused by near-total insulin deficiency. Previous classification are insulin-dependent and non-insulin dependent DM, but this has been modified because both types will eventually need insulin treatment upon progression of disease. Type 1 DM results from the auto-immune destruction of insulin-producing beta cells. Thus, hyperglycemia manifests usually before the age of 30. Initially, type 2 DM is seen among older patients, but currently there are more reports of type 2 DM among younger patients. Genes contribute to both, although family history is a greater risk factor in type 2. Still, the progression of DM is dependent upon the eating habits of the patient. An increased caloric intake elevates the levels of blood glucose. Additionally, factors like smoking increases the morbidity vasculopathy, a DM complication. b) The lab assessment of kidney function (150 words) The rate at which substances are cleared can be used to assess the effectiveness by which the kidney excretes various substances. When impaired, glomerular filtration rate (GFR) decreases, which can be measured by creatinine clearance test. This test compares the creatinine levels in the urine and those in the blood. Normal levels of creatinine are 97 to 137 ml/min for males, while 88 to 128 ml/min for females. Lower than these values may indicate acute tubular necrosis of congestive heart dailure. Urine output is also a means to detect renal diseases such as acute renal failure, which is characterized by a significant slowing or stopping of urine output. The normal range of urine output is 800 to 2000 milliliters per day, assuming an intake of 2 liters per day. Another kidney function test is urine urea nitrogen, which measures protein breakdown of the body. The normal range is 12 to 20 grams per 24 hours. Lower than these values may indicate kidney problems, as protein metabolites are not cleared from the body effectively. Q3. a) Explain the following terms and suggest a cause for each condition: HYPERKALAEMIA and HYPOGLYCAEMIA( 120 words in total) Hyperkalemia is the increase in the extracellular potassium ion levels. This may be caused by insulin deficiency during diabetes mellitus, during Addison’s disease of the adrenal glands due to the deficiency of aldosterone that causes cellular uptake of potassium, blockade of B-adrenergic receptors, which upon activation decreases extracellular potassium, acidosis and cell lysis by causing loss of potassium from the cell, strenuous exercise when skeletal muscle releases potassium, and increased extracellular osmolarity. Hypoglycemia, or decreased blood sugar levels can develop from insulinoma or hyperinsulinism, starvation, decreased glucagon secretion, adrenal gland atrophy that decreases epinephrine and cortisol that signal release of glucose from the liver, hypopituitarism, which decreases growth hormone levels that signal glucose release as well. b)Write short notes on: 1- alkaline phosphate (ALP) and 2. alanine aminotransferase.(ALT) (120 words in total) Alkaline phosphate and alanine aminotransferase are enzymes used in laboratories to assess liver function, although they are produced in other tissues such as heart and kidneys. In liver diseases, shock, cholestasis or cancer, there is an abnormally elevated levels of ALT and ALP. However, elevated levels of ALP and ALT happen in physiologic conditions. High ALT levels occur after a strenuous exercise, as skeletal muscles also produce ALT, and the breaks in the tissues during exertion causes the release of the enzyme. High ALP are also observed among pregnant women, especially those in their third trimester, because the placenta also produces Children also have elevated ALP levels because of they need its activity in rapid bone growth. As well, low levels of ALP are pathological, possibly signaling Celiac disease. Read More