Biochemistry – CIMS Bwp

Module 3

CBL 11: ARDS

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CBL	11
SENARIO:
In August 1963, First Lady Jacqueline Bouvier Kennedy was hospitalized in her 34th week of pregnancy at the Otis Air Force Base Hospital. Her fetus was in distress, but labor did not progress. On August 7, she underwent a cesarean section to deliver Patrick Bouvier Kennedy, who weighed 4 pounds, 10.5 ounces (2,112 grams). After delivery, the baby developed difficulty breathing, which did not improve despite oxygen therapy. The baby was then rushed to Children’s Hospital Boston, a leading center in respiratory distress syndrome (RDS). Unfortunately, despite the best medical efforts, the baby died two days later. The death of the newborn baby devastated the First Family. In the weeks that followed the tragedy, the president and his mother-in-law, Janet Auchincloss, feared that Jacqueline would have a nervous breakdown, although it was reported that this adversity ultimately brought the president and his wife closer together.
Task:
1. The preterm neonate Patrick Bouvier Kennedy was a normal baby, what was wrong with his lungs that led to the development of ARDS 2. At cellular level, which cells of his lungs were not performing their job? 3. What therapy could have been given to his mother for lung maturity? 4. A liquid is missing in his lungs give its: a. Biochemical composition b. Role c. Site of action 5. Before cesarean how fetal lung maturity could have been gauged

CBL 10: Hypoketotic Hypoglycemia

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CBL	10
SENARIO:
A 23-month-old baby girl brought into resuscitation by an ambulance with a 24-hour history of being unwell, 18-hour history of persistent vomiting and progressively worsening lethargy. There was no history of diarrhea or fever. She had been an otherwise well child. On examination, she was very lethargic and peripherally shut down evidenced by marked cold extremities and hypothermia. Urgent capillary blood glucose was 1 mmol/L. Systemic examination revealed no significant finding. She was actively resuscitated. Blood glucose level minimally increased to 1.3 mmol/L following glucogel therapy before ultrasound-guided cannulation was achieved. Blood samples were taken for hypoglycemia screening and partial septic screening including renal, liver and bone profile. Urine dipstick test performed in the emergency room showed ketones and traces of protein. Subsequently she received two boluses of 2 mL/kg of 10% dextrose solution and was maintained on dextrose saline solution. Over the next several days, she stabilized although there was a documented hypoglycemia (2.8 mmol/L) while on intravenous fluids. Initial half hourly glucose checks were reduced to hourly checks. Her blood sugar level was in the range of 3.8–4.8 mmol/L while on intravenous fluids and oral feeds. She spent a total of 6 days on the ward before she was transferred to the metabolic unit. Acyl carnitine profile revealed free carnitine (40 (15.5–46.7)), and short to medium chain acyl carnitines. She was started on intravenous ceftriaxone but was discontinued after 48 hours following no evidence of infection on investigations. She needed up to 12.5% dextrose to maintain blood sugar within the range of 4 mmol/L The patient made a full recovery and has been doing quite well. She is being followed up by the metabolic team. Parents have been educated on type of diet with a home care plan during periods of illness. She is currently on daily oral carnitine. Her two older sisters were screened with acyl carnitine profile and urine organic acids; they appear not to have the disorder. Parents were not screened for the mutation as they declined despite genetic counselling.
Task:
1. Give the likely biochemical cause of hypoketotic hypoglycemia in this patient? 2. Give the likely diagnosis? 3. With the help of a flow chart draw the metabolic pathway likely to be affected in this patient? 4. Give the rationale for giving oral carnitine to this patient when the fatty acids less than 12 carbons can cross the inner mitochondrial membrane without the aid of carnitine or carnitine shuttle

Module 2

CBL 9:

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CBL	09
SENARIO:
A 26-year-old nulliparous woman is diagnosed with cervical intraepithelial neoplasia (CIN) stage III. She has been sexually active for 6 years and has had 4 lifetime sexual partners and takes oral contraceptive pills consistently. She had a plantar wart a few years ago but otherwise has no medical problems. She drinks 1-2 glasses of wine every night but does not use tobacco or illicit drugs. The patient’s mother has breast cancer at age 42.
Learning Issues:
Which virus most likely lead to cervical intraepithelial neoplasia in this patient? What is HPV and what are its different strains? What was the most significant risk factor in patient history that predisposed this patient to cervical abnormalities? What is the mechanism by which HPV leads to cervical cancer? What is the prevention and treatment of HPV progressing to cervical neoplasia?

CBL 8: Nucleic Acids (ADA Deficiency)

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CBL	08
SENARIO:
A little girl aged 11 months was brought by her parents to a children’s hospital. She had a number of attacks of pneumonia and thrush (oral infection usually due to a fungus Candida albicans) since birth. The major findings of a thorough workup were very low levels of circulating lymphocytes (i.e. severe lymphopenia) and low levels of circulating immunoglobulins. The attending pediatrician suspected SCID. Analysis of a sample of red blood Cells revealed a low activity of ADA and very high level (about 50 times normal) of dATP. This confirmed the diagnosis of SCID due to deficiency of ADA, the enzyme that converts adenosine to inosine. The deficiency of ADA is inherited as autosomal recessive and accounts for almost 15% cases of SCID. T lymphocytes express high activity of enzyme normally. Lack of ADA activity leads to accumulation of adenosine and dATP which is toxic to T cells. Secondarily B lymphocytes are also affected and lead to impaired humoral immunity. Defective immune system allows different opportunistic infection to occur and recur. An example of acquired immunodeficiency is AIDS. Such conditions can be treated by, antibiotics, fortifying immune system by immunoglobulins and treating the root cause.
Learning Issues:
1. Ingestion and fate of nucleotides in human body 2. Role of Nucleotides in DNA synthesis 3. The biochemical basis of various clinical features
Reference Books:
1. Harper’s text book of Biochemistry. (Page 616) 2. Davidson’s Practice of Medicine. 3. Lippincott’s textbook of Biochemistry.

CBL 7:

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CBL	07
SENARIO:
A 46-year-old man presents to the orthopedics clinic complaining of knee pain he has been having after playing basketball. He denies any trauma to his knees and any fevers, redness, or swelling of his knees. On examination he has full range of motion without resistance, along with some mild crepitus on flexion/extension. He is sent home with a prescription for ibuprofen. Two months later he returns after an obvious tear of his right anterior cruciate ligament. During preoperative evaluation for an arthroscopic repair of the injury, the laboratory calls to report that his urine is unusually dark in color, but is negative for blood. In the operating room the surgeons are surprised to find that the cartilage in his knee is also black.
Learning Issues:
What is the most likely diagnosis in this patient? A defect in which enzyme is the underlying cause of the patient’s condition? Draw the pathway showing the process involving that enzyme. This patient ‘s abnormal enzyme is involved in the metabolism of which amino acid? Name other organs/structures that can be involved in this patient? What is the biochemical basis of Dark Urine in this patient? What is the biochemical basis of black knee cartilage in this patient? What is the biochemical basis of ligament tear in this patient? What treatment can be given to this patient?

CBL 6:

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CBL	06
SENARIO:
A 4-month-old boy is brought to the office for his first visit since arriving in the United States. The patient was recently adopted, and his adopted mother says the boy is tremulous compared to her biological children. Over the past week, the boy has also had episodes of upward eye deviation and bilateral arm and leg shaking for approximately 2 minutes at a time. Biological family history is not available. His temperature is 36.7 C (98.1 F), blood pressure is 90/40 mm Hg, pulse is 120/min, and respiration are 30/min. Examination shows a fair- skinned infant with blue eyes and a musty body odor.
Learning Issues:
What is the most diagnosis in this patient? The underlying condition responsible for this patient’s health is most likely caused by a deficiency of which enzyme? Which amino acid is most likely essential in this patient now?
SENARIO:
The parents are extensively counseled on the child’s condition, including the necessary dietary restrictions and the adequate supplements that this child must adhere to. Several months later, the laboratory tests indicate that the infant has a normal serum phenylalanine level; however, after careful examination, the physician observes some neurological abnormalities. Further workup includes a serum prolactin level, which is elevated.
Learning Issues:
Which cofactor is most likely deficient in this patient that is leading to the treatment failure? What is the reason for elevation of prolactin in this patient?
SENARIO:
2 years later, assessment of his developmental milestones shows severe intellectual disability. He dies 6 months later from refractory seizures resulting in respiratory failure. Autopsy shows pallor of the substantia nigra, locus ceruleus and vagal nucleus dorsalis.
Learning Issues:
What was the reason of pallor in this location(s) in this patient? What was the biochemical basis of intellectual disability in this patient? What was the biochemical basis of musty body odor in this patient? What is the most appropriate treatment for the condition that infant most likely had?

CBL 5:

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CBL	05
SENARIO:
A 4-month-old boy is brought to the office for his first visit since arriving in the United States. The patient was recently adopted, and his adopted mother says the boy is tremulous compared to her biological children. Over the past week, the boy has also had episodes of upward eye deviation and bilateral arm and leg shaking for approximately 2 minutes at a time. Biological family history is not available. His temperature is 36.7 C (98.1 F), blood pressure is 90/40 mm Hg, pulse is 120/min, and respirations are 30/min. Examination shows a fair- skinned infant with blue eyes and a musty body odor.
Learning Issues:
What is the most diagnosis in this patient? The underlying condition responsible for this patient’s health is most likely caused by a deficiency of which enzyme? Which amino acid is most likely essential in this patient now?
SENARIO:
The parents are extensively counseled on the child’s condition, including the necessary dietary restrictions and the adequate supplements that this child must adhere to. Several months later, the laboratory tests indicate that the infant has a normal serum phenylalanine level; however, after careful examination, the physician observes some neurological abnormalities. Further workup includes a serum prolactin level, which is elevated.
Learning Issues:
Which cofactor is most likely deficient in this patient that is leading to the treatment failure? What is the reason for elevation of prolactin in this patient?
SENARIO:
2 years later, assessment of his developmental milestones shows severe intellectual disability. He dies 6 months later from refractory seizures resulting in respiratory failure. Autopsy shows pallor of the substantia nigra, locus ceruleus and vagal nucleus dorsalis.
Learning Issues:
What was the reason of pallor in this location(s) in this patient? What was the biochemical basis of intellectual disability in this patient? What was the biochemical basis of musty body odor in this patient? What is the most appropriate treatment for the condition that infant most likely had?

Module 1

CBL 4:

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CBL	04
SENARIO:
A 50-year-old surgeon presents to his primary care physician with a 2-3 week history of fatigue and right upper quadrant discomfort. During the past week, he has noticed yellowing of his eyes. He was previously health and has no chronic medical problems. Several months ago, while supervising a new intern on a trauma case he was accidentally stuck with a needle. He did mot seek medical care at that time due to the patient’s critical condition but thinks that the patient may have been a drug user. His physical exam is notable for jaundice, hepatomegaly, and right upper quadrant tenderness. His labs include: Bilirubin : 8.9 mg/dl AST: 1398 U/L AST: 2200 U/L Alkaline phosphatase: 290 U/L INR: 1.2 HbsAg, HBeAg, HBV DNA:positive Anti-HBs, anti-HBE: negative
Learning Issues:
What is the most likely diagnosis? What are the signs and symptoms associated with this condition? What is the biochemical basis for appearance of jaundice? What is the biochemical basis for the elevation of amino transferases in this patient? What reactions were being catalyzed by ALT and AST in this patient? What laboratory tests could be used to confirm the diagnosis?

CBL 3:Carbohydrate metabolism & maintenance of blood glucose levels

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CBL

SENARIO:

A 6-year-old previously healthy girl presented to emergency department in comatose state. She had a 3-day history of progressive epigastric abdominal pain, polydipsia and nocturnal enuresis and a 2-week history of weight loss of 5 kg. Her initial assessment revealed tachypnea with Kussmaul’s respiration, tachycardia and moderate dehydration. Urinalysis revealed ketonuria and glucosuria. After admission, appropriate fluid resuscitation and insulin treatment were started.

LAB INVESTIGATIONS:

Test Name	Result	Normal Values
Glucose	581mg/dl(43.4mmol/l)	70-99(3.9-5.5)
3-hydroxybutyrate	350mg/dl	0-3
HCO₃^–	10 mmol/l	22-28
pH	7.13	7.35-7.45
pCO₂	26 mm Hg	35 – 45
pO₂	97 mm Hg	80 – 100

Tasks:

1. Give reference range for fasting blood glucose

2. Enumerate main players involved in blood glucose maintenance

3. Briefly describe intermediate states of hyperglycemia?

4. Give diagnostic criteria for:

a. Impaired fasting glucose

b. Impaired glucose tolerance

c. Diabetes mellitus

5. Give the likely precipitating factor for diabetic ketoacidosis, in this patient?

6. Give renal threshold for blood glucose?

7. Explain the biochemical basis of osmotic diuresis?

8. Explain the biochemical basis of polydipsia?

9. Convert mg/dL glucose to mmol/L

10. Give dietary modifications for diabetics

11. Give biochemical basis for acidic pH in this patient?

Learning Objectives:

At the end of the CBL session, the students should be able to:

1. Explain the Regulation of blood glucose

2. Interpret blood glucose report

3. Explain the ethical issues related to getting an informed consent from a patient, for examination, investigations and treatment purposes.

CBL 2 : CARBOHYDRATE METABOLISM

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CBL	02
SENARIO:
Rafiq is a 4-month-old boy whose mother is concerned about the ‘twitching’ movements he makes just before feedings. She tells the pediatrician that the movements started about 1 week ago and are most apparent in morning, and disappear shortly after eating. On physical examination Rafiq appears sleepy and feels clammy to touch. His respiratory rate is elevated. His temperature is normal. His abdomen Is protuberant and nontender. His liver is palpable 4cm below the costal margin and is smooth. His kidneys are enlarged and assymetrical. Labs results: Glucose: Low Lactate: High Urate: High Total cholesterol: High Triglycerides: High pH: Low HCO3- : Low Ultrasound reveals hepatosplenomegaly. Liver biopsy shows distended hepatocytes, staining reveals large amount of lipid and carbohydrate. Liver glycogen is elevated in amount and normal in structure. Enzyme assay reveals decreased activity of glucose-6-phosphatase.
Learning Issues:
1. Give the likely diagnosis? 2. Why is Rafiq hypoglycemic? 3. Give biochemical reason for hepatosplenomegaly? 4. What is the likely reason for Rafiq’s twitching movements? 5. Why triacylglycerol and cholesterol is elevated?

CBL 1: Pyruvate Kinase Deficiency

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CBL		01 (a)
SENARIO:
A 55 year old alcoholic was brought to the emergency department by his friends. During their usual nightly gathering at the local bar,he had passed out and they had been unable to revive him. The physician ordered an injection of thiamine followed by overnight parenteral glucose. The next morning the patient was alert and coherant, serum thiamine was normal and blood glucose was 73 mg/dL (4mM). The IV line was removed and he was taken home.
TASK	Which of the following enzymes is thiamine- dependant and essential for glucose oxidation in the brain? A.Transketolase B.Transaldolase C.Succinyl- CoA thiokinase D.Acetyl-CoA carboxylase E.Pyruvate dehydrogenase
Learning Issues:
Is there any biochemical connection between this condition and alcohol? Explain the relevant biochemical Metabolism that takes place in this condition when thiamine deficiency was corrected?

CBL		01 (b)
SENARIO:
A two year old girl was referred to hematologist after her pediatrician found her to be severely anemic with splenomegaly and jaundice. Her mother gave a possible history of “blood problem” in her family but did not know for sure. Her complete blood count revealed normal hemoglobin with normocytic anemia. The platelet and white cell count was normal. On the peripheral smear there were many bizarre erythrocytes including speculated cells. A diagnosis of pyruvate Kinase deficiency was made.

Learning Issues:
On what basis was the diagnosis of pyruvate kinase deficiency made? What is the normal appearance of RBCs on the peripheral smear? What appearance of RBCs would you expect on peripheral smear in this case? What is / are the function(s) of pyruvate kinase? What was / were the reason(s) for a) Anamia b) Bizarre shaped RBCs c) Jaundice d) Splenomegaly. Give the biochemical reasons for these abnormalities?