Clinical biochemistry case studies PDF

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Dr. Vinaya Sampath, case studies for whole semester...

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Week 1 1. A 1-week old newborn with difficulty feeding was evaluated at a hospital emergency room. The infant presented with mild jaundice, respiratory congestion and a possible upper respiratory tract infection. Admission screening assays demonstrated the following abnormal levels: AMINO ACID SCREEN Phenylalanine 20mg/dL (1210μM) Increased pH 7.20 Slightly Decreased pCO2 (arterial) 58 mmHg Increased pO2 (arterial) 50 mmHg Normal PLASMA PROTEINS Total Protein 5.7 g/dL Slightly Decreased Albumin 2.5 g/dL Decreased Haptoglobin 340 mg/dL Increased C3 129 mg/dL Slightly Increased C4 32 mg/dL Slightly Increased CRP 8.7 mg/dL Increased Answer the following questions: a. What is the probable reason for increased phenylalanine levels in the infant? In current times, what diagnostic method is likely to have been used for this test? The infant has absent or defective Phenylalanine Hydroxylase or cofactor tetrahydrobiopterin, which causes increased levels of Phenylalanine. HPLC or MS//MS can be used to determine how much Phenylalanine is present in the sample. b. What can be done to prevent any negative consequences of increased phenylalanine levels in the newborn? Replacement of phenylalanine strict diet can prevent any negative consequences. c. What is the probable cause for reduced albumin levels seen in the infant? What other clinical/diagnosis factors can be used to corroborate the reasoning? Albumin is a negative acute phase reactant, presence of inflammation due to respiratory infection causes albumin levels to drop. Another reason can be malnutrition, the infant was having difficulty with being fed and albumin levels drop when one doesn’t have enough amino acids in diet. d. How is the diagnosis of respiratory congestion and respiratory tract infection reflected in the clinical findings? The PCO2 levels have increased, probably due to infection which caused inflammation, therefore CO2 pressure increased not being able to exhale out properly. 2. a. What is different about the serum electrophoresis profile of the patient in comparison to the reference sample? Albumin protein is missing on the patient’s serum electrophoresis b. What are the likely effects of the observed change in the plasma protein composition? There is a possibility of inflammation which could cause decreased levels of albumin.

c. What could be a possible cause of the observed change? Liver disease, kidney disease or malnutrition can be the possible causes of decreased levels of albumin d. What other biochemical tests can be used to confirm this finding? Different serum electrophoresis can be performed to confirm the specific protein changes in patient’s blood 3. A 69 yr old woman experiencing fatigue, bone pain, loss of appetite in Jan 2006 was admitted to the nearest clinic. Serum protein electrophoresis (SPEP) and Immunofixation electrophoresis were ordered and results shown above . After diagnosis, she was put on therapy for her disease and a repeat of the tests were performed in Aug 2006.

a. What is the likely diagnosis for this patient based on the SPEP and Immunofixation electrophoresis done in Jan 2006? SPEP suggest Multiple myeloma and IEP shows increased IgA immunoglobulin b. How does Immunofixation electrophoresis allow clinical chemistry technicians to identify the exact plasma component that is increased/decreased in this patient? Using the IFE the separate immunoglobulin bands that are seen on the can help determine increase/decrease of specific immunoglobulin.

c. How does the SPEP and IFE performed in Aug 2006 confirm that the patient is in remission at that time? Jan 2006 IFE of we can see that the IgA levels have gone down to normal levels compared to IFE results from Jan 2006. Indicating IgA isn’t as high as it was in Jan 2006 d. Suppose the treatment makes the patient more susceptible to inflammation, how would the SPEP and immunofixation electrophoresis results change? SPEP would show increase in albumin and IFE would show increase in IgM 4. A 50 yr old male was brought into the hospital by ambulance, complaining of shortness of breath and dull chest pain that radiates to shoulders and arms present for the last three days. He has a history of Type II diabetes, hypertension, and being a smoker. The attending physician suspects the patient suffered a myocardial infarction (MI) three days ago. a. What biochemical tests would confirm the physician's suspicions? (restrict yourself to tests discussed in class to date). Explain why But Cardiac troponin levels can be checked for since it is a late marker and would confirm that the patient had suffered from MI. b. What biochemical tests usually associated with myocardial damage are unlikely to be informative in this case. Explain why The urine test would be normal after 3 days because the myoglobin levels are normal in urine now. c. How are the patient's BUN and creatinine levels likely to respond if he has had a recent MI? BUN and creatinine levels would increase because the kidney which is filtering isn’t functioning properly due to limited blood flow. d. How would you expect the Haptoglobin levels to change in this patient from when they were admitted to when they undergo treatment? Keep in mind that as patients recover from MI, they are likely to experience large scale hemolysis followed by inflammation due to MI damage. Haptoglobin levels will increase as it is a positive acute phase protein, increasing with inflammation. 5. A 20year old female presented to her doctor with swollen hands and feet. She had finished a course of topical antibiotics to treat a skin infection 10days. Her heart and respiratory function tests were mostly normal. Her physician suspects post-streptococcal glomerulonephritis (PSGN). PSGN is a result of type II hypersensitivity reactions that cause immune complexes of streptococcal antigen-IgG antibodies to deposit in glomeruli of kidneys. This triggers a complement driven immune reaction that results in swelling of glomerular endothelial membrane, increased capillary permeability and breakdown of glomerular function a. What will be the likely effect of PSGN on BUN and creatinine levels in serum? BUN and creatinine levels would be high since the GFR is low due to dysfunction in the glomerular.

b. Why is the patient likely to show less albumin in serum and presence of albumin in urine? How does this help explain edema seen in this patient? Due to inflammation the albumin levels are low and increased permeability is causing them to be filtered in urea, hence albumin is present in urea. Less albumin in serum will not pull water out of tissue causing swelling in tissue called edema. c. Predict whether Complement C3 levels will increase or decrease in serum. Explain why. C3 complement will increase because of acute inflammatory disease in the glomerular. d. What is the likely effect of this condition on Glomerular Filtration rate (GFR)? How is GFR calculated from laboratory findings? GFR decreases due to infection. Levels of creatinine in urea can help us determine the GFR. Creatinine is inversely proportional to GFR.

Week 2 1. A pediatrician evaluated a 15-year-old male. The patient complained of sore muscles, had lost considerable weight over the last month and was always thirsty and had frequent nocturnal urination. The patient's mother reports that around the same time frame, the patient joined an elite tennis team and was in training five days a week for three hours a day. The results from clinical tests ordered by a pediatrician are shown below. BASIC SCREEN Creatinine Kinase (CK) 160 U/L (30-160) LDH 180 U/L (125-220U/L) LDH 5 10% LDH (6-16% LDH) Fasting Glucose 140 mg/dL (65-110) Ketones in urine Moderate a. What are the two possible diagnoses that the pediatrician is considering based on the patient's symptoms? Diabetes (hyperglycemia) and ketoacidosis b. Based on the test results, what is the most likely diagnosis? How do the results from clinical test/s help the pediatrician make the correct diagnosis? Diabetic ketoacidosis is most likely diagnosis, the fasting glucose is 140mg/dL which is high and ketones are found in moderate level in urine c. What other clinical tests could the physician have ordered to help confirm the diagnosis? Glycosylated hemoglobin levels and arterial blood gas could have been ordered to help confirm the diagnosis d. What physiological changes in the patient's body are likely the cause of the patient's disease? Since the patient started playing tennis had a lot of practice which caused electrolyte

imbalance and therefore an increase in urination. e. How would the test results above change if the other possible diagnosis had been true? The lab results would be same for ketoacidosis

2. Emergency personnel were called to the home of a 72 yr old man who had collapsed on

the floor of his home. His adult daughter who lived with him reported that her father complained of shortness of breath, radiating pain down his left shoulder shortly before collapsing. The attending physician at the hospital suspected a myocardial infarction and admitted the patient for analysis and treatment a. What enzymatic tests from the patient's serum should the physician order to confirm his suspicions? CK level and troponin level can be measured in serum to confirm myocardial infarction b. How would an isoenzyme profile of CK be informative in this case? Increase in CK-MB higher than 6% will indicate myocardial infarction c. How would an isoenzyme profile of LDH be informative in this case? LD1 greater than LD2 in a patient indicates MI d. What precautions should the clinical lab take in patient sample handling to get accurate results? The clinical lab should be careful and prevent hemolysis while collecting sample, since the LDH levels are high in erythrocytes e. What enzymatic activity does increase with AMI but is unlikely to be used in this case? Explain why? AST levels would increase with AMI but would not be useful due to wide tissue distribution. 3. A 38 year old woman with a BMI of 28 and active lifestyle is trying to conceive a child

with her partner. She goes in for pre-natal testing to rule out any health problems. Among the many tests ordered by her physician were the following results: Fasting Plasma glucose: 104 mg/dL Plasma Glucose 2hr in Oral Glucose tolerance test: 160mg/dL Ketones in urine: Negative. a. What diagnosis can be made from these results? Pre-diabetic b. What risk factors are likely to explain this diagnosis? What symptoms is she likely

to exhibit in this condition? Age, overweight and genetics are the risk factors explaining this diagnosis. Excessive hunger, thirst and frequent urination are some of the symptoms she is likely to exhibit in this condition c. If the woman were to get pregnant, what condition should she be monitored for during her pregnancy? She should monitor her glucose intolerance, for possible gestational diabetes d. How is this diagnosis likely to be manifested when she reaches her 50s? She will develop type 2 diabetes e. What additional tests are likely to be recommended for the patient from now on? HbA1c test 4. A 70 yr old man is seen by his urologist because the patient complains of blood in urine, weak urine flow and frequent urination. His urologist performs a digital rectal exam and notes an enlarged prostate with possible masses. The urologist suspects prostate cancer in the patient and orders clinical tests. a. What clinical test would the physician order if this case was occurring in 1980? ACP (acid phosphatase) b. What level on the test in Q. a would be considered diagnostic for prostate cancer? Metastasized prostate cancer can be detected using the ACP test, however nonmetastasized prostate cancer will not be detected. c. What assay conditions would need to be maintained during the clinical testing? We need to make sure that labelled antigen are constant and limited. d. If this case were occurring in current time, what clinical test would be ordered by the urologist? PSA (prostate specific antigen) e. Explain why the newer diagnostic test is preferred in current time? Because it can also detect non-metastasized prostate cancer

Week 5 and 6 1. A 50 yr old, overweight man was admitted to the hospital with complaints of chest pain, radiating pain from his shoulder through his upper arm for the past three days. He was a pack a day smoker for 3 decades before quitting recently. He was previously diagnosed with high blood pressure and was on medication to control it. He doesn’t know his family history of heart disease as he was adopted at birth. The attending physician suspects that the patient had a recent myocardial infarction and ordered a lipid panel and

enzymatic assays. Here are the results: Patient

Reference

Total Cholesterol

280mg/dL

140-200mg/dL

HDL

35 mg/dL

40-75 mg/dL

Triglycerides

200 mg/dL

60-150 mg/dL

CK

110 U/L

30-60 U/L

CK-MB

8%

LDH2

a. Yes. High levels of CK-MB in results and LD1 greater than LD2 indicate MI in the patient b. Total cholesterol = 280mg/dL, HDL = 35mg/dL, Triglyceride = 200mg/dL LDL = 280 - 35 - (200/5) = 205mg/dL c. Risk factors are increased triglyceride and decreased levels of HDL. Overweight and smoking is how his heart is influenced by it d. High LDL is due to his smoking, BP and overweight e. Knowing his family history would help confirm if he is a FH or not 2. A 75 yr old man is recovering from a stroke for the last week and has been making steady improvements in regaining his mobility and physical capabilities. However, over the last few days, he has been complaining of malaise, nausea, headaches and lethargy. Infections were ruled out as a cause based on microbiological testing. His physician recommends tests for electrolytes to check if the patient has acquired SIADH (Syndrome of Inappropriate Antidiuretic Hormone release) due to neurological changes caused by the stroke. Here are the results from the tests: Patient

Reference

Na+

125 mmol/L

135-145 mmol/L

K+

4 mmol/L

3.5-5.5 mmol/L

HCO3-

28 mmol/L

22-29mmol/L

BUN

10

7-18

Creatinine

1

0.6-1.2 mg/dL

Osmolality

256

275-295 mOsm/kg

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What is the patient’s blood volume status-hypovolemic, hypervolemic or euvolemic? Explain your answer using the test results above. Hypovolemic - low osmolality and low Na+ ● What test results confirm the physician’s suspicion of SIADH secondary to stroke? Explain your reasoning Decreased levels of sodium causes more water retention which is due to SIADH ● How can you explain the patient’s current symptoms of neurological dysfunction based on these test results? SIADH causes dehydration and therefore neurological dysfunction is caused ● Predict the Cl- ions levels of the patient. Normal reference range is 96-106 mmol/L. Explain your reasoning. Cl- ions level would be around 86mmol/L, decrease in Na+ ions would decrease Cl- ions as well. Antiduretic hormone promotes Cl- ion reabsorption. ● Why are some electrolytes not affected by this condition? Since there is no gastrointestinal loss - K+ and HCO3- levels are not affected.

3. A. The blood pH of a patient is slightly acidic, as indicated in the table its 7.1 and the normal range of pH in human is 7.35-7.45 B. Anion gap =(Na+ + K+) - (Cl- - HCO3-) = (143 + 3.2) - (102 + 10) = 34.2mmol/L Decreased levels of bicarbonate ions in blood is what makes the blood pH acidic the anion gap is high as indicated in the calculation C. Ethylene glycol metabolized forms glycolaldehyde, which than is converted into glycolic acid, causing the blood to be more acidic D. The HCO3- levels decrease due to excess H+ ions causing the pH of blood to drop. Body compensating by conserving the HCO3 and releasing H+ ions E. Calcium oxalate accumulated in the kidney causes dehydration and therefore inhibiting ion reabsorption

4. A. HPLC can be performed to confirm diagnosis, the type of hemoglobin present in it would be shown in the results. B. Reduced oxygen carrying capacity is what causes the shape of the blood cell to be sickled. C. Sickle is produced by reduced oxygen tension, therefore only some RBCs are sickle shaped. Normal RBCs oxygen carrying capacity is not affected. D. The sickle cell would pile up on blood vessels causing the vasoocclusive disease. Which would restrict the flow and cause swelling in hands and feet. E. Sickle cells would be hemolyzed which increases bilirubin level causing the Jaundice. Increased levels of bilirubin can be detected in the blood and urine analysis

Week 7 and 8 A 17 yr old female is brought to her gynecologist as having never experienced a menses before. Examination shows that patient is completely feminine with well-developed breasts, female external genitalia, sparse auxiliary and pubic hair development. An internal examination shows presence of undescended testes and lack of any uterus, fallopian tubes or ovaries. The patient is advised to have a gonadectomy to remove the undescended testes as it can frequently become malignant. ● What is the likely diagnosis for this patient? What is the biochemical cause of this diagnosis? Production of androgen is what made her internal genetial to be male, no testosterone and DHT production from leydig cells of testes. Testicular feminization syndromeHypergonadotropic hypogonadism ● Using some numbers, predict what will be the patient’s level of LH, FSH, Estrogen and Testosterone in this patient. Explain why you chose those numbers. High LH - 40IU/L and FSH - 30IU/L, low testosterone - 100ng/dL and high estrogen levels - 500pg/mL. Since there is no negative feedback, the hormones caused inhibition of the LH and FSH. Testosterone levels are similarly high in females, and it coverts to Estrogen, which would also increase. ● What is the likely karyotype for this individual? How would that correlate with the symptoms seen in this patient? XY karyotype - undescended testes which secrete androgen, but due to resistance in this hormone it is not active which converts it all into estrogen which caused the breast enlargement ● Explain how the gonadectomy would affect the patient’s levels of testosterone and estrogen. Gonadectomy would help decrease levels of testosterone and estrogen. A 30 yr old female reports to her ob-gyn that she is experiencing irregular menstruation and is having trouble getting pregnant with her partner with a normal sperm count. Doctors evaluating her note that the patient has a high BMI (>30) and showing signs of excess hair growth on lip, chin and sideburn areas that could not be explained by her ethnic origin. An internal examination showed the presence of an intact female reproductive system. Endocrine tests showed the following results: Testosterone: 135 ng/dL (20-80ng/dL) Prolactin: 18 ng/ml (2-30ng/ml) TSH: 2.6 uIU/ml (0.4-3.8 uIU/ml) LH: 18 IU/L (5-20IU/L for Follicular phase) FSH: 6 IU/L (5-20 IU/L) LH:FSH ratio: 3 (1.5-2 for adults) ● What is the diagnosis for this patient? Diagnosis for this patient is PCOS and hirsutism ● How do the clinical symptoms, test results allow you to reach this diagnosis? Excess testosterone is due to high estrogen production. Body hair, irregular menses,

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unable to get pregnant and high BMI are all symptoms of PCOS What would be a finding from an ultrasound examination of her ovaries? The ultrasound examination would multiple small cyst on ovaries (pcos) What is the biochemical cause of hirsutism exhibited by this patient? Increased androgen which is converted into testosterone is the cause of hirsutism.

A 46 yr old woman presents to her physician with fatigue, weight gain, hoarseness in voice, dry skin, constipation. She has a family history of auto-immune disease. On examination, her physician notes an increased abdominal distension and an enlarged thyroid gland and suspects s...