Case Study

Case 1

  1. Discuss the immunological mechanisms that might contribute to the pathology of ulcerative colitis.


Ulcerative colitis is a form of inflammatory bowel disease characterized chronic and relapsing inflammation of the colon, generally starting from the cecum up to the rectum. A distinguishing feature of ulcerative colitis that differentiates it from other inflammatory bowel diseases is that it is only confined to the large intestine and the affected areas are distributed evenly on the top layer of the affected part of the colon. General symptoms include abdominal pain, diarrhea and bloody stools. Other signs and symptoms may be present depending on the location of the inflammation. For instance, anaemia is also generally observed depending on the onset and duration of the disease and the amount of blood loss during defecation.

The exact of cause of inflammatory bowel disease is still unknown but an abnormalities in a person’s immunological response is considered to be a probable reason behind inflammatory bowel diseases. This includes any abnormal behavior involving the phagocytic activities of phagocytes or abnormalities in how an immune response is triggered that results to release of cytokines in the gut. These abnormalities can result into negative changes on normal gut flora that can result into an increased number in harmful gut pathogens that causes inflammation.

In normal patients, normal gut flora thrives in the colon forming a symbiotic relationship with its host. Normal gut flora acquires nutrients from undigested food and then provides essential vitamins to its host. Under normal conditions, these bacteria are tolerated and spared by our immune response because of the intestinal mucosa that limits contact between these bacteria with epithelial cells of the large intestine. The intestinal mucosa has two layers: the outer layer and an inner layer that is closer to the epithelial cells. In between these layers lies MUC2 mucin that forms a mesh-like layer between the two mucosal layers. While, the inner layer is dense enough to prevent the entry of bacteria, the MUC2 is an integral component because this area serves as attachment points for normal gut bacteria. These placement sites limits the exposure of gut bacteria to the immune response of the body and also makes it difficult for foreign, generally harmful bacteria, to proliferate as the attached normal gut bacteria prevents their spread in the mucosal layer. Furthermore, the number of normal bacteria is maintained by the immune response of the person that includes antibacterial proteins, IgA, T-cells and phagocytes. The activity of these cells are normally regulated to maintain gut bacteria with normal levels.

Based on this arrangement, any abnormality in the MUC2 and involved immune mechanisms can reduce the number of normal gut bacteria in the mucosal layer. Increased sensitivity of antibacterial proteins, IgA, T-cells and phagocytes and reduce the number of normal bacteria beyond normal levels, making it easier for foreign bacteria to attach themselves to the mucosal layer and spread infection. Likewise, decreased sensitivity can abnormally increase the number of gut bacteria. In both cases, inflation occurs within the mucosal layer and surrounding areas that may help cause ulcerative colitis.

 

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  1. Discuss how the blood cell indices can be used to determine the underlying cause of the anaemia (low haemoglobin concentration), i.e. whether it’s likely to be blood loss, suppression of red cell production or impaired iron handling.


Anaemia is a condition characterized by either a deficiency of hemoglobin or a deficiency of red blood cells (RBC) that results into poor oxygen concentration in the patient’s blood stream. Diagnosis of anaemeia is made using a complete blood test that measures specific blood cell indices. In the case, anemia was diagnosed based on four blood cell indices. These are Hct or the Hematocrit level, RBC count, Hb or hemoglobin and MCV or Mean Corpuscular Volume.

Hemoglobin is the protein found in red blood cells that allows it to carry and distribute oxygen during circulation. Hematocrit is the percentage of red blood cells in the patient’s blood stream and is generally as a ratio between red blood cells and the other blood cells during circulation. Both of these parameters are considered to be important measures that reflect the body’s capability to circulate oxygen as there should be enough red blood cells in circulation to ensure that the body is getting its oxygen needs. The RBC count is determines the number of red blood cells in circulation. The MCV or Mean Corpuscular Volume refers to the average volume of red blood cells and is often related to their size and is an indicator of the overall health of the red blood cells in circulation.

Low levels of both hematocrit and hemoglobin are generally needed to diagnose anaemia like in the case. But these two measures alone do not directly determine what causes the anaemia so other information are required to determine its cause, especially if the other blood measures are normal. For instance, some diseases such as colon cancer, kidney diseases or ulcers can cause chronic bleeding that may lower hematrocrit levels and RBC count. Accidents such as trauma and burns can lower these indices as well resulting into anaemia that will only be resolved once the injuries has been healed.

For the case, since the patient has ulcerative colitis and adenocarcinoma, it is possible that her anaemia is caused by these two conditions.  The low MCV results confirms this diagnosis as a low MCV indicates small-sized red blood cells. Four types of anaemia are associated with microcytic or small-zed red blood cells. These are iron deficiency anaemia, anaemia caused by chronic diseases, thalassemia, and anaemia related to bone marrow disorders. Based on the information available on the case, it is reasonable to link the anemia of the patient with her chronic diseases and should be resolved once her cancer and ulcerative colitis are managed.

  1. Discuss the role of histological investigations in supporting a diagnosis and decisions on treatment for this patient


Histological examinations are generally only done when other diagnostic test results show some possible signs that it is needed, especially if cancer is suspected, and are usually essential components of some diagnostic examinations such as biopsy. In cases where it is required, histological investigations are used to gather specific information about affected tissues samples to determine the proper course of action to take to manage the case of a patient. Cancer cases are the most common application of histological testing as it can help classify cancer growth, the type of cell proliferation, staging of cancer and metastasis.

In the case, histological examination only took place because of the abnormal CEA result. CEA is carcinoembryonic antigen test that is only conducted when there is a need to verify the presence or absence or cancer growth in the large intestine. It should be noted that ulcerative colitis increases the risk of developing cancer in most patients. The link between cancer and ulcerative colitis was the most likely reason why CEA was included in the blood tests and only a positive result, such as with the case, would require further testing using histological methods to verify the results of the CEA test as no other details in the case before the blood exam indicated the need to do.

The positive CEA result now requires further testing to verify the result and also identify the location of the detected abnormality. In the case, colonoscopy was conducted which helped revealed the exact location of the tumor. This information makes it easier to obtain the proper samples needed for a biopsy to begin as the possible cancer location has been located.

The result of histological test helps determine the proper course of treatment depending on the condition of the patient.  First, a biopsy can determine if the observed mass is either malignant or benign. These two conditions have different intervention options that patients and physicians can choose from. For instance, there are cases where in surgical removal of a tumor is possible in benign cases, but may not be appropriate for malignant tumors. Second, in malignant cases, histological testing is used to identify the stage of the cancer and also the presence or absence of metastasis. The different cancer stages each have different treatment options and surgical procedures that patients can have. Stages that involves metastasis requires different care plans to help manage cancer spreading. In the case, the confirmed staging and invasion sights helps determine the sequence of intervention, starting from removing the tumor and then the chemotherapy.

Case 2

1.a The case study states that a pure culture of Escherichia coli was obtained from a urine sample given by the patient.  Explain the predisposing factors for urinary tract infection with this organism particularly in patients with diabetes. 

Urinary tract infection is an infection in either the kidneys, urinary bladder, the ureters or the urethra. The cause of infection is generally bacteria that typically found in the colon finds its way into the urinary tract usually through the urethra. Because the urethra of females are shorter than males, they have a higher risk of getting urinary tract infection as the path needed by the bacteria to travel to is shorter in females compared to males. Furthermore, the proximity of the female urethra is closer to the anus compared to males, further making it easier for bacteria to reach the female urethra.

Escherichia coli is a common bacteria is one of the most common causes of urinary tract infection just like in the case. The presence of bacteria in a urine sample is one way of diagnosing urinary tract infection together with the presence of leucocytes in the urine and increase in white blood. The infection that caused the urinary tract infection is also determined to be the cause of DKA or diabetic ketoacidosis. Diabetic ketoacidosis is a complication in diabetic patients where in the patient’s body produces of high levels of acids known as ketones caused when the patient’s body cannot metabolize glucose due to insufficient insulin production. As a result, the body burns fat instead of glucose for energy. At this time, the patient had no knowledge that she has diabetes and was only confirmed when the diagnosis of diabetic ketoacidosis was confirmed.

In this case, the urinary tract infection may have triggered DKA. Infections can cause diabetic ketoacidosis as levels of specific hormones in circulation such as cortisol and adrenaline are often higher during periods of illness or infection that counters the effect of insulin, thereby making it harder for the body to metabolize glucose, as cortisol and adrenaline are known to increase glucose circulation. Having type 1 diabetes can also increase the risk for developing urinary tract infection as high glucose levels has a negative effective on neutrophil function and also has been determined to inhibit the production of actin, an integral component involved in phagocytosis. These relationships demonstrate that patients with diabetes are more likely to have an infection and experience complications due to uncontrolled sugar levels in circulation as it has negative effects on the immune system.

1.b How could bacterial organisms that could cause urinary tract infections be differentiated in the laboratory? How would this vary depending on the organism if a different pathogen was suspected?

Differentiating different pathogen is an important aspect of laboratory testing as correctly identifying the type of bacterial organism will make it easier to determine the most appropriate form of intervention to manage the infection. Identification of bacteria involves specific steps. These are staining, microscopy, culture, and identifying morphology and characteristics. Staining and microscopy are related process where in the former is the process of increasing the visibility of the bacteria while the latter is using a microscope to study the shape and identify the morphological structures of the bacteria. The staining process also helps prepare the bacteria for analysis as it can remove contaminants and highlight specific parts of the bacteria making it easier to study under a microscope. Gram staining, a process that uses specific stains that reacts differently for each type of bacteria, remains a dependable staining process that has been used to differentiate two types of bacteria (gram-positive and gram-negative) that has also led to the creation of antibiotics that works for each type characteristics.

Microbial cultures are used to grow different types of bacteria in controlled environments (Kumar 2012). The primary reason of using cultures is growing a number of bacteria makes study and comparison of the different types easier by comparing and studying their morphology. This method is also considered to be the most efficient means of identifying multiple bacteria from a single source as any observed difference between the growth cultures can easily be identified once they are grown.  Morphology refers to the distinct shape, parts, and cultural growth patterns that are generally linked with specific species or groups of bacteria as different morphology respond to different aspects such as oxidation, antimicrobial activity, nutrient limitation and DNA damage. Each of these approaches can be used to treat bacteria and difference in morphology helps determine which of these approaches is the most appropriate.

These differences can be observed either through direct observation of the culture or through a microscope. Key components that should be studied are the cytoskeleton, septum, and the cell division process used in these bacteria. Comparing the difference within these components makes it easier for laboratory technicians to determine the cause of infection so that the right type of antibiotics are prescribed. Most of these information are readily available to allow for accurate matchmaking between known groups so that the appropriate treatment can be selected.

  1. Biochemistry questions


2.1 Explain the abbreviation DKA. Outline the biochemical processes leading from insulin deficiency in type 1 diabetes to DKA.

As mentioned earlier, DKA stands for diabetic ketoacidosis and is a complication of diabetes when the patient’s body is forced to metabolize fat instead of sugar for energy in the absence of insulin or when insulin levels are not enough to metabolize the glucose in the bloodstream. DKA is more common in Type 1 diabetes which is characterized by the inability of the pancreas to produce insulin either because of genetics or damage of the cells that produce insulin because of an infection.

In situation where insulin is absent such as in patients with Type 1 diabetes, the body is forced to metabolize fat and proteins for energy instead of glucose. This process results into a steady increase of glycerol and free fatty acids (FFAs) in the bloodstream. In some cases, amino acid levels may also rise as muscles are metabolized for energy. As the glucose in the blood remains unused, the glycerol and FFA are then converted into ketones that is then later on converted to acetone. This is the source of the fruity smell that is often seen in patients experiencing DKA. These ketones are strong acids that results into metabolic acidosis as glycerol, FFA and protein accumulate in the bloodstream together with the unused glucose.

The metabolic acidosis together with the increased blood-glucose level leads to an osmotic effect that diverts water from tissues into the blood stream that is now saturated in glucose and FFA. This results into increased urination that often includes significant loses to fluids and electrolytes. The most significant among these electrolytes are sodium and potassium wherein abnormally low levels can develop into life threatening cardiac complications that may be fatal for the patient.

2.b Why was C-peptide measured and what does the low level indicate?  What may be deduced about the duration of the patient’s diabetes from the HbA1c measurement?

C-peptide is a substance produce in the pancreas that is formed together with insulin. Because of their association, c-peptide is often used as a marker that helps identify if the pancreas is still producing insulin. Because of its relationship with insulin, c-peptide testing is usually only done in newly diagnosed diabetes patient such as in the case, to determine if their pancreas is still producing insulin and how much of it is still present in circulation. A low c-peptide level generally means that production of insulin is diminished or compromised. C-peptide testing is also conducted to investigate hypoglycemic symptoms in the presence of high glucose levels in the blood, high lipid levels and hypertension, symptoms that are associated with complications such as diabetic ketoacidosis. In the case, results of the C-peptide test shows low levels of C-peptide indicating that the patient’s pancreas is still producing insulin but below normal levels.

HbA1c refers to glycated haemoglobin and its measurement is another test parameter used to determine the extent or duration of a patient’s diabetes. This measure is unique because it can provide information about the average glucose level of the patient form prolonged periods. In comparison, testing for fasting blood sugar or FBS only tests glucose levels while the results of HbA1c can represent the average blood-glucose concentration for 2-3 months. The higher the HbA1c, the longer the duration that the patient is suffering from elevated glucose levels and the higher the risk of developing complications associated with diabetes. In the case, the HbA1c is at 13.8% which is associated with prolonged high glucose levels that is consistent with type 1 diabetes. This finding is consistent with the cases as the diagnosis of type 1 diabetes was only made when the DKA occurred, implying that the patient has not been taking the proper amount of insulin before the diagnosis.

 

 

 

 

 

References

Baumgart, D.C. ed., 2012. Crohn's disease and ulcerative colitis: from epidemiology and immunobiology to a rational diagnostic and therapeutic approach. Springer Science & Business Media.

Bressler, B., Marshall, J.K., Bernstein, C.N., Bitton, A., Jones, J., Leontiadis, G.I., Panaccione, R., Steinhart, A.H., Tse, F., Feagan, B. and Group, T.U.C.C., 2015. Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus.Gastroenterology148(5), pp.1035-1058.

Chen, H.S., Su, L.T., Lin, S.Z., Sung, F.C., Ko, M.C. and Li, C.Y., 2012. Increased risk of urinary tract calculi among patients with diabetes mellitus—a population-based cohort study. Urology79(1), pp.86-92.

Gough, S., Manley, S. and Stratton, I. eds., 2010. HbA1C in diabetes: case studies using IFCC units. John Wiley & Sons.

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Jaqua, N.T., Stratton, A., Yaccobe, L., Tahir, U., Kenny, P. and Kerns, T., 2013. A review of the literature on three extraintestinal complications of ulcerative colitis: an ulcerative colitis flare complicated by Budd-Chiari syndrome, cerebral venous thrombosis and idiopathic thrombocytopenia.Acta gastro-enterologica Belgica76(3), pp.311-316.

Kumar, S., 2012. Textbook of microbiology. JP Medical Ltd.

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Mnif, M.F., Kamoun, M., Kacem, F.H., Bouaziz, Z., Charfi, N., Mnif, F., Naceur, B.B., Rekik, N. and Abid, M., 2013. Complicated urinary tract infections associated with diabetes mellitus: Pathogenesis, diagnosis and management. Indian journal of endocrinology and metabolism17(3), p.442.

Nyenwe, E.A. and Kitabchi, A.E., 2016. The evolution of diabetic ketoacidosis: An update of its etiology, pathogenesis and management.Metabolism65(4), pp.507-521.

Sahami, S., Kooij, I.A., Meijer, S.L., Van den Brink, G.R., Buskens, C.J. and Te Velde, A.A., 2016. The Link between the Appendix and Ulcerative Colitis: Clinical Relevance and Potential Immunological Mechanisms. The American journal of gastroenterology111(2), pp.163-169.

Sima, A.A. ed., 2011. Diabetes & C-peptide: Scientific and Clinical Aspects. Springer Science & Business Media.

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Stachs, A., Hartmann, S., Stubert, J., Dieterich, M., Martin, A., Kundt, G., Reimer, T. and Gerber, B., 2013. Differentiating between malignant and benign breast masses: factors limiting sonoelastographic strain ratio.Ultraschall in der Medizin-European Journal of Ultrasound34(02), pp.131-136.

Suchwalko, A., Buzalewicz, I. and Podbielska, H., 2013. Identification of bacteria species by using morphological and textural properties of bacterial colonies diffraction patterns. In Proceedings of SPIE (pp. 87911M-1

 

 

 

 

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