Case Scenario 1:
A 40-year-old man is brought to the hospital in a comatose state. On examination, he was found to be dehydrated with a characteristic breathing pattern and a sweet smell on his breath. His laboratory investigation reveals: Random blood glucose: 380 mg/dl, Urinary Benedict’s test: Brick red (strong positive), Urinary Rothera’s test: Positive.
- State the probable diagnosis.
- What is the cause of the sweet smell when breathing?
- Describe the metabolism of ketone bodies with a note on its clinical significance.
Answer:
- Diabetic ketoacidosis
- Acetone exhaled in breath
- Ketogenesis, Ketone bodies utilisation, Ketosis
Case Scenario 2:
A 20-year-old medical student decides to fast for a religious ritual. After 3 days of only water intake, she presents with mild fatigue, nausea, and a fruity odour on her breath. Her vitals are stable. Blood glucose is slightly low, and urine test shows positive ketones.
Questions:
a) Explain the biochemical basis of ketone body formation during starvation.
b) Describe the physiological significance and potential consequences of ketosis in prolonged fasting.
c) How can starvation ketosis be differentiated from diabetic ketoacidosis?
Answer:
a) Biochemical Basis of Ketone Body Formation During Starvation:
- In fasting, glycogen stores are depleted within 24 hours.
- Lipolysis is activated, increasing free fatty acids (FFA) in the blood.
- The liver converts FFA to acetyl-CoA via β-oxidation.
- Due to limited oxaloacetate (diverted for gluconeogenesis), acetyl-CoA cannot enter the TCA cycle efficiently.
- Excess acetyl-CoA is converted into ketone bodies: acetoacetate, β-hydroxybutyrate, and acetone.
b) Physiological Significance and Consequences:
- Ketone bodies serve as an alternative energy source, especially for the brain, after 2–3 days of fasting.
- Mild ketosis is adaptive and non-harmful. However, prolonged ketosis can cause ketoacidosis, dehydration, and electrolyte imbalance, though this is rare in healthy individuals.
c) Differentiation from Diabetic Ketoacidosis (DKA):
| Feature | Starvation Ketosis | Diabetic Ketoacidosis (DKA) |
| Blood glucose | Normal or slightly low | Very high (>250 mg/dL) |
| Insulin levels | Low but present | Absent or severely deficient |
| Acid-base status | Mild acidosis or normal | Severe metabolic acidosis |
| Dehydration | Mild or absent | Severe |
| Ketone levels | Moderate | High |
Case Scenario 3:
A 14-year-old girl is brought to the emergency department with deep, gasping breathing. Her mother reports that over the past week, the girl has experienced decreased appetite, fatigue, headache, and abdominal pain, and since this morning, has developed difficulty in breathing. On examination, she appears dehydrated and her breath has a fruity odour.
Investigations reveal:
- Random Plasma Glucose: 346 mg/dL
- Urine test: Positive for reducing sugar and ketone bodies
a) Explain the biochemical mechanism underlying the development of diabetic ketoacidosis.
b) Describe the clinical features and laboratory findings typical of DKA.
c) Describe the management of DKA.
Answer:
a) Biochemical Mechanism of DKA:
- In Type 1 Diabetes Mellitus, absolute insulin deficiency occurs due to autoimmune destruction of pancreatic β-cells.
- Without insulin, glucose cannot enter cells, leading to hyperglycemia and cellular starvation.
- The body compensates by increasing lipolysis, raising free fatty acids (FFA) in blood.
- The liver converts FFA into acetyl-CoA, which is diverted to produce ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone) due to excess and lack of TCA cycle intermediates.
- Accumulation of ketone bodies causes metabolic acidosis (ketoacidosis).
b) Clinical Features and Lab Findings:
- Symptoms: Polyuria, polydipsia, nausea, vomiting, abdominal pain, fatigue, Kussmaul breathing (deep, labored), fruity odor in breath (acetone), altered sensorium.
- Signs: Dehydration, tachycardia, hypotension, signs of shock in severe cases.
- Lab findings:
- Hyperglycemia (>250 mg/dL)
- Metabolic acidosis (low pH, low bicarbonate)
- High anion gap
- Positive urine/serum ketones
- Electrolyte imbalances, especially low potassium
c) Management and Differentiation from Starvation Ketosis:
- Management includes:
- Fluid resuscitation (IV normal saline)
- Insulin therapy (regular insulin IV)
- Electrolyte correction, especially potassium
- Monitor blood glucose, ketones, and acid-base status regularly
Case Scenario 4:
A 24-year-old woman who had gained weight after childbirth was advised by her physician to reduce her calorie intake. Eager to lose weight quickly, she completely stopped consuming fats and oils. Although she lost the excess weight, after a few months she developed dry, scaly skin lesions on the posterior and lateral aspects of her limbs and buttocks.
Questions:
a) What is the most likely diagnosis in this case?
b) Name two examples of the deficient molecule involved.
c) Mention the dietary sources and functions of these molecules.
d) Explain why humans cannot synthesize these molecules.
Model Answers:
a) The most likely diagnosis is Essential Fatty Acid (EFA) deficiency- Phrynoderma/ Toad Skin
b) Examples of EFAs:
-
- Linoleic acid (Omega-6 fatty acid)
- α-Linolenic acid (Omega-3 fatty acid)
c) Dietary Sources: Sunflower oil, safflower oil, corn oil, soybean oil
Functions:
- Essential for membrane structure and fluidity
- Precursors for eicosanoids (prostaglandins, thromboxanes, leukotrienes)
- Important for skin integrity, wound healing, and immune function
- Required for growth and development, especially neural and retinal development
- Help in reducing inflammation and promoting cardiovascular health
d) Why Humans Cannot Synthesize EFAs:
- Humans lack the enzymes (Δ12 and Δ15 desaturases) required to introduce double bonds beyond the 9th carbon from the carboxyl end of fatty acids.
Case Scenario 5:
A 45-year-old man visits the outpatient clinic for a routine check-up. He has a family history of heart disease and is overweight. He reports no specific complaints. His lipid profile reveals:
- Total Cholesterol: 260 mg/dL
- LDL-C: 180 mg/dL
- HDL-C: 32 mg/dL
- Triglycerides: 220 mg/dL
His blood pressure and fasting glucose are within normal limits.
a) Define dyslipidemia and classify its types.
b) Explain the biochemical basis and risk factors contributing to this patient’s lipid profile.
c) Describe dietary and lifestyle interventions used to manage dyslipidemia.
Answer:
a) Definition and Classification of Dyslipidemia:
Dyslipidemia refers to abnormal levels of lipids in the blood, including cholesterol and triglycerides.
Types:
- Hypercholesterolemia – Elevated total cholesterol and LDL-C
- Hypertriglyceridemia – Elevated triglycerides
- Mixed dyslipidemia – Elevated cholesterol and triglycerides
- Low HDL cholesterol – Often seen with other abnormalities
b) Biochemical Basis and Risk Factors:
- Elevated LDL-C: Suggests increased cholesterol synthesis or decreased clearance
- Low HDL-C: Indicates reduced reverse cholesterol transport.
- Elevated Triglycerides: May be due to increased VLDL production or impaired lipoprotein lipase activity.
Risk Factors:
- Obesity and physical inactivity
- Diet high in saturated fats and refined carbohydrates
- Genetic predisposition (e.g., familial combined hyperlipidemia)
- Alcohol use (can increase VLDL and triglycerides)
- Secondary causes: Hypothyroidism, nephrotic syndrome, certain medications
c) Management – Dietary and Lifestyle Interventions:
Dietary Changes:
- Reduce intake of saturated fats, trans fats, and cholesterol
- Increase soluble fiber (e.g., oats, legumes), which helps lower LDL
- Include omega-3 fatty acids (e.g., fish, flaxseed) to lower triglycerides
- Limit simple sugars and alcohol
Lifestyle Modifications:
- Regular aerobic exercise: Increases HDL, reduces triglycerides
- Weight reduction: Improves all lipid parameters
- Smoking cessation: Increases HDL and reduces cardiovascular risk
- Stress management. Bottom of Form
Case Scenario 6:
A 7-year-old boy is brought to the outpatient department with firm, whitish nodular eruptions over his right elbow, which have been present since he was 2 years old. These lesions are identified as subcutaneous xanthomas. His mother reports a family history of similar findings, and that the child’s father died of a heart attack at the age of 32.
Laboratory investigations reveal:
- Fasting Blood Sugar (FBS): 84 mg/dL (normal)
- LDL Cholesterol (LDL-C): 418 mg/dL (markedly elevated)
- Serum Triglycerides (TG): 118 mg/dL (normal)
- What is the most probable diagnosis?
- Describe the biochemical basis of this disorder.
- Explain the mechanism of xanthoma formation.
Answer:
- a) The most likely diagnosis is Familial Hypercholesterolemia (Type IIa Hyperlipoproteinemia), an autosomal dominant genetic disorder characterized by isolated elevated LDL-C levels.
2.b) Biochemical Basis of the Disorder:
- Familial hypercholesterolemia is caused by mutations in the LDL receptor (LDLR) gene, leading to reduced or absent LDL receptor function on hepatocytes.
- As a result, LDL particles are not cleared from the blood, leading to markedly elevated plasma LDL-C.
- Since LDL contains mostly cholesterol and little triglyceride, only LDL-C is elevated, while triglycerides and HDL may be normal.
- The high plasma LDL-C leads to cholesterol deposition in tissues and arteries, increasing the risk of premature atherosclerosis and coronary artery disease.
3.c) Cause of Xanthoma Formation:
- Xanthomas are cholesterol-rich deposits in skin and tendons.
- When plasma LDL-C levels are persistently high, macrophages in subcutaneous tissue phagocytose LDL particles, becoming foam cells.
- These foam cells accumulate to form visible xanthomas, especially in areas of mechanical stress like elbows, knees, Achilles tendon, and buttocks.
- Xanthomas are diagnostic clues to underlying lipid metabolism disorders.
Case Scenario 7:
A 45-year-old man with a history of chronic alcohol consumption presents with nausea, abdominal pain, and abdominal distension. On examination, he has hepatomegaly and jaundice. A liver biopsy shows fat accumulation within hepatocytes.
- What is the most probable diagnosis?
- Enumerate the common causes of this condition.
- What are lipotropic factors? Explain their role in hepatic fat metabolism
Answers:
- The most probable diagnosis is Fatty liver (Hepatic steatosis), likely due to alcoholic liver disease.
- Causes of Fatty Liver:
-
- Alcoholism – Most common cause
- Obesity and metabolic syndrome
- Type 2 Diabetes Mellitus
- Malnutrition or protein deficiency (e.g., Kwashiorkor)
- Drugs and toxins (e.g., methotrexate, amiodarone)
- Inborn errors of metabolism (e.g., abetalipoproteinemia)
- Rapid weight loss or starvation
3.Lipotropic Factors:
Lipotropic factors are substances that promote the export of fat from the liver and prevent its accumulation.
Major lipotropic factors include:
-
- Choline
- Methionine
- Inositol
- Folic acid
- Vitamin B12
Case Scenario 8:
A 53-year-old male accountant working in the Income Tax Department reports chest pain and breathlessness, especially during periods of high work stress, such as around the annual tax filing deadline.
He has a history of acute chest pain and shortness of breath two months ago.
At that time, his ECG was abnormal, and a coronary arteriogram showed 90% occlusion of the left main coronary artery.
- What is the medical term used for the narrowing of arteries?
- List the major risk factors associated with this condition.
- Why is the prevalence of heart disease generally higher in males than in females?
Answer:
- The condition is called Atherosclerosis, which refers to the chronic, progressive narrowing and hardening of arteries due to plaque buildup (composed of lipids, cholesterol, calcium, and cellular debris) in the intimal layer of the arterial wall.
- Risk Factors for Atherosclerosis / Coronary Artery Disease:
Modifiable risk factors:
-
- Smoking
- Hypertension
- Diabetes mellitus
- Dyslipidemia (↑ LDL, ↓ HDL, ↑ triglycerides)
- Obesity and sedentary lifestyle
- Chronic stress
- Unhealthy diet (rich in saturated fats and processed foods)
Non-modifiable risk factors:
-
- Age (risk increases with age)
- Male gender
- Family history of premature heart disease
- Genetic predisposition
3.Why Heart Disease is More Common in Males:
Estrogen, the primary female sex hormone, has a protective effect on the cardiovascular system. It improves lipid profiles by:
-
- Increasing HDL (good cholesterol)
- Decreasing LDL (bad cholesterol)
Pre-menopausal women are less likely to develop atherosclerosis due to this hormonal protection. After menopause, as estrogen levels fall, the risk in females increases and begins to approach that of males.
Case Scenario 9:
A 29-year-old multigravida woman delivers a premature female infant weighing 1.5 kg. Soon after birth, the baby develops respiratory distress with a respiratory rate > 60/min, nasal flaring, and chest retractions.
- Which biomolecule is primarily responsible for the respiratory distress in this neonate?
- Explain the biochemical mechanism by which this biomolecule prevents respiratory distress.
Answers:
- Biomolecule is Pulmonary Surfactant- Dipalmitoyl lecithin
- Its major component is dipalmitoyl phosphatidylcholine (DPPC), along with other phospholipids and surfactant proteins (SP-A, SP-B, SP-C, SP-D).
Functions:
Surfactant reduces surface tension at the air-liquid interface within the alveoli. By lowering surface tension, it prevents alveolar collapse (atelectasis) during exhalation. It allows alveoli to remain open and promotes efficient gas exchange.
In Premature Infants: Surfactant synthesis begins around 28–32 weeks of gestation, and becomes sufficient by 34–36 weeks. Premature infants often have insufficient surfactant, leading to Respiratory Distress Syndrome (RDS),
Case Scenario 10:
A previously healthy 2-month-old male infant was found unresponsive in his crib early in the morning. The baby had no history of illness, and routine check-ups were normal. On autopsy, no definite cause of death could be determined. The baby was found sleeping on his stomach with loose bedding around him. There was no sign of infection, trauma, or congenital abnormality.
a) What is the most probable diagnosis in this case?
b) Mention the deficient enzyme.
Answer:
- Sudden Infant Death Syndrome
- Medium chain acyl CoA Dehydrogenase
Case Scenario 11:
A 6-year-old child from a rural area is brought to the hospital with repeated episodes of severe vomiting, weakness, and confusion. The mother reports that the child ate unripe ackee fruit earlier that day. On examination, the child is dehydrated and has low blood sugar. Laboratory tests show hypoglycemia and presence of organic acids in the urine.
Questions:
a) What is the probable diagnosis?
b) Explain the biochemical basis and toxic mechanism of this condition.
Answer:
a) Probable Diagnosis:
-
- The likely diagnosis is Jamaican Vomiting Sickness, caused by toxicity from unripe ackee fruit ingestion.
b) Biochemical Basis and Toxic Mechanism:
-
- The unripe ackee fruit contains hypoglycin A, a toxin metabolized into MCPA (methylenecyclopropylacetic acid).
- MCPA inhibits acyl-CoA dehydrogenases, enzymes essential for β-oxidation of fatty acids in mitochondria.
- This inhibition prevents fatty acid breakdown, leading to decreased gluconeogenesis and hypoglycemia.
- Accumulation of fatty acids and organic acids causes metabolic acidosis and systemic toxicity.