Clinical Cases of Carbohydrates

Subsection: Clinical Conditions in Carbohydrate Metabolism

Case Scenario 1:

A male patient around 51 years of age came to the hospital with complaints of increased thirst, frequent urination, and unexplained weight loss over the past 3 months. He also reports fatigue and blurred vision.  On investigation, his blood sugar was 300 mg/dL, and HbA1c was found to be 8.2%.

1. Mention the disease and its type that the patient is suffering
2. Write down the differences between the two
3. Describe the metabolic changes occurring in the above case.

Answer:

1. 1. a) Disease and Its Type:
   • The patient is suffering from Diabetes Mellitus – Type 2.
   • It is characterized by insulin resistance and relative insulin deficiency.
   • Common in adults over 40 years and associated with obesity or sedentary lifestyle.

    

   1. b) Differences Between Type 1 and Type 2 Diabetes Mellitus:

   Feature	Type 1 Diabetes Mellitus	Type 2 Diabetes Mellitus
   Onset	Usually before 30 years	Usually after 40 years
   Cause	Autoimmune destruction of β-cells	Insulin resistance + β-cell dysfunction
   Insulin levels	Absent or very low	Normal or high (early); low (late)
   Body weight	Usually lean	Usually overweight or obese
   Ketosis	Common	Rare
   Treatment	Insulin essential	Lifestyle, oral drugs ± insulin

    

   1. c) Metabolic Changes in This Patient (Type 2 DM):

   Due to insulin resistance and deficiency, the following changes occur:

   1. Carbohydrate Metabolism:
      • ↓ Glucose uptake in muscles and adipose tissue
      • ↑ Hepatic gluconeogenesis → hyperglycemia
      • Glycosuria
   2. Fat Metabolism:
      • ↑ Lipolysis → ↑ Free fatty acids
      • Hypercholesterolemia, Hypertriglyceridemia
      • May lead to mild ketosis (rare in Type 2)
   3. Protein Metabolism:
      • ↑ Proteolysis → muscle wasting → weight loss

Case Scenario 2:

A 22 years old boy came to surgery OPD with history of recurrent constipation. From his dietary habits, surgeon noticed that the intake of vegetables & fruits is very less. He advised him to increase intake of dietary fibres.

1. Mention the deficient carbohydrate along with its
2. Enumerate four other carbohydrates belonging to the subclass of deficient
3. Explain why this deficient carbohydrate cannot be digested by
4. Write four functions of deficient

Answer

1. 1. a) Deficient Carbohydrate and Its Subclass:
   • Deficient carbohydrate: Cellulose
   • Subclass: Homopolysaccharide

    

   1. b) Four Other Carbohydrates in the Same Subclass (Dietary Fibers):
   1. Hemicellulose
   2. Pectin
   3. Lignin (non-carbohydrate fiber)
   4. Gums and mucilages

    

   1. c) Reason for Indigestibility in Humans:
   • Humans lack the enzyme cellulase, which is needed to break the β-1,4-glycosidic bonds in cellulose.
   • As a result, cellulose is not digested in the human gastrointestinal tract.

    

   1. d) Four Functions of Dietary Fiber (Deficient Carbohydrate):
   1. Increases stool bulk and promotes regular bowel movements (relieves constipation)
   2. Delays gastric emptying and slows glucose absorption, helping in blood sugar control
   3. Lowers blood cholesterol by binding bile acids
   4. Improves gut health by acting as a prebiotic and aiding beneficial bacteria

Case Scenario 3:

A 10 months old infant was brought by parents to pediatric OPD with history of passing loose watery stools and flatulence for one week. The baby was being fed diluted cow’s milk since last 15 days.

1. What is the most probable diagnosis? Mention the deficient
2. Explain the biochemical basis for watery stools and
3. Define and classify carbohydrate with suitable

Answer:

1. a) Most Probable Diagnosis and Deficient Enzyme:

• Diagnosis: Lactose intolerance (secondary or acquired)
• Deficient enzyme: Lactase (β-galactosidase)
  • Lactase is needed to digest lactose, the disaccharide present in milk.

 

1. b) Biochemical Basis for Watery Stools and Flatulence:

• In the absence of lactase, lactose is not digested into glucose and galactose.
• Undigested lactose remains in the intestinal lumen, increasing osmotic pressure, leading to watery diarrhea.
• Colonic bacteria ferment lactose, producing gases (H₂, CO₂, methane), causing flatulence and bloating.

 

1. c) Definition and Classification of Carbohydrates (with examples):

Definition:

Carbohydrates are organic compounds made of carbon, hydrogen, and oxygen (C:H:O in 1:2:1 ratio). They are the main source of energy for the body.

Classification:

1. Monosaccharides (Simple sugars)
   • Cannot be hydrolyzed further
   • Examples: Glucose, Fructose, Galactose
2. Disaccharides
   • Composed of 2 monosaccharides
   • Examples: Sucrose (Glucose + Fructose)
     Lactose (Glucose + Galactose)
     Maltose (Glucose + Glucose)
3. Oligosaccharides
   • 3 to 10 monosaccharide units
   • Example: Raffinose
4. Polysaccharides
   • Long chains of monosaccharides
   • Examples:
     • Starch, Glycogen (storage polysaccharides)
     • Cellulose (structural, indigestible)

Case Scenario 4:

A 10 year old boy presented to gastroenterology clinic with complaints of abdominal pin, bloating and diarrhoea, after attending a birthday party. At the party, he had eaten cheese sandwich, yoghurt and coffee with milk. His abdominal cramps worsened after consuming the milk.

1. What is the most probable diagnosis? Mention the deficient enzyme.
2. Explain the biochemical basis for watery stools and diarrhoea.
3. What will you suggest the patient to relieve the symptoms?

Answer:

1. 1. a) Most Probable Diagnosis and Deficient Enzyme:
   • Diagnosis: Lactose intolerance (secondary or acquired)
   • Deficient enzyme: Lactase (β-galactosidase)
     • Lactase is needed to digest lactose, the disaccharide present in milk.

    

   1. b) Biochemical Basis for Watery Stools and Flatulence:
   • In the absence of lactase, lactose is not digested into glucose and galactose.
   • Undigested lactose remains in the intestinal lumen, increasing osmotic pressure, leading to watery diarrhea.
   • Colonic bacteria ferment lactose, producing gases (H₂, CO₂, methane), causing flatulence and bloating.

    

   1. c) Suggestions to Relieve Symptoms:

• Avoid lactose-containing foods (milk, soft cheese, ice cream).
• Use lactose-free milk or plant-based alternatives (e.g., almond, soy milk).
• Take lactase enzyme supplements before consuming dairy.
• Some may tolerate fermented dairy (like yoghurt) in small amounts.

• Case Scenario 5:

A 22-year-old male of Mediterranean descent presents to the emergency department with complaints of fatigue, dark-colored urine, and yellowing of the eyes after taking antimalarial medication (primaquine) 2 days ago. On examination, he is mildly jaundiced and has pallor. His laboratory tests reveal low hemoglobin, elevated reticulocyte count, and presence of Heinz bodies in red blood cells. Further tests confirm low activity of glucose-6-phosphate dehydrogenase (G6PD).

1. What is the role of G6PD in red blood cell metabolism?
2. Explain the pathophysiology of hemolysis in G6PD deficiency.
3. List common triggers of hemolytic episodes in G6PD-deficient individuals.
4. Mention the importance of the pentose phosphate pathway in red blood cells.

Answer:

1. a) Role of G6PD:

• G6PD is the first and rate-limiting enzyme of the pentose phosphate pathway (HMP shunt).
• It generates NADPH, which is essential for maintaining glutathione in its reduced form (GSH).
• Reduced glutathione protects RBCs from oxidative damage by neutralizing reactive oxygen species (ROS).

1. b) Pathophysiology in G6PD Deficiency:

• In G6PD-deficient individuals, NADPH production is impaired.
• This leads to inadequate levels of reduced glutathione, making red blood cells vulnerable to oxidative stress.
• Damaged RBCs are destroyed prematurely in the spleen (extravascular hemolysis) or lyse within circulation (intravascular hemolysis), leading to hemolytic anemia.

1. c) Common Triggers of Hemolysis (2 marks)
2. Certain drugs – e.g., antimalarials (primaquine), sulfonamides, nitrofurantoin.
3. Infections – e.g., bacterial or viral infections that increase oxidative stress.
4. Foods – particularly fava beans (favism).

1. d) Production of NADPH & Pentose Sugar

Case Scenario 6:

A 9-month-old infant is brought to the paediatric clinic with complaints of poor feeding, lethargy, and a distended abdomen. On examination, the baby is found to have hepatomegaly. Laboratory tests show severe hypoglycaemia, lactic acidosis, hyperlipidaemia, and hyperuricemia. Genetic testing reveals a deficiency of the enzyme glucose-6-phosphatase in the liver.

1. a) State the probable diagnosis.
2. b) What are the typical biochemical findings in this disorder?

Answer:

1. Von Gierke’s disease is Glycogen Storage Disease Type I, a genetic metabolic disorder due to deficiency of the enzyme glucose-6-phosphatase.
2. Metabolic Consequences:

• Inability to convert G6P to glucose leads to severe fasting hypoglycemia.
• Accumulation of G6P diverts metabolism to:
  • Increased glycolysis → results in lactic acidosis
  • Increased lipogenesis → causes hyperlipidemia
  • Excess ribose-5-phosphate production → increases nucleotide degradation → hyperuricemia
• Glycogen accumulates in the liver → hepatomegaly

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Case Scenario 7:

A 7-day-old neonate is brought to the pediatric emergency with complaints of vomiting, jaundice, lethargy, and poor feeding. The mother reports that symptoms began after breastfeeding started. Physical examination reveals hepatomegaly and cataracts. Blood tests show hypoglycemia, hyperbilirubinemia, and a positive test for reducing sugars in urine, but glucose oxidase test is negative. Further investigations confirm a deficiency of galactose-1-phosphate uridyltransferase (GALT).

1. State the most probable diagnosis? Explain the biochemical basis of the disorder
2. List the clinical features, complications, and the basis for dietary management in this disorder

Answer:

1. a) Galactosemia – Definition, Biochemical Basis, and Types (3 marks)
   • Biochemical Basis: Due to enzyme deficiency, galactose or its metabolites accumulate, particularly galactose-1-phosphate, which is toxic to liver, brain, kidneys, and lens of the eye.
2. b) Clinical Features, Complications, and Dietary Management (3 marks)

Clinical Features:

• • Neonatal jaundice
  • Vomiting and diarrhea after milk intake
  • Hepatomegaly
  • Hypoglycemia
  • Cataracts (early onset due to accumulation of galactitol in the lens)
  • Lethargy, irritability, and failure to thrive

Complications:

• • Liver dysfunction → cirrhosis
  • Developmental delay or intellectual disability
  • Renal tubular dysfunction

Dietary Management:

• • Immediate and lifelong elimination of lactose and galactose from the diet (e.g., switch to lactose-free formula like soy-based milk)

 

Subsection: Gluconeogenesis

Case Scenario 8:

A 60-year-old female suffering from a terminal illness has exhausted her liver glycogen stores due to prolonged fasting (10–18 hours). To maintain normal blood glucose levels, her body now relies on the synthesis of glucose from non-carbohydrate sources.

1. What is the biochemical term for the process that synthesizes glucose from non-carbohydrate sources? Mention any two such substrates.
2. Describe the irreversible steps of this process, including key enzymes involved.
3. What is the significance of this process during fasting or illness?

Answer:

1. Gluconeogenesis; Substrates- Lactate, Pyruvate, Glycerol, Glucogenic Amino acids
2. Irreversible Steps:

• Pyruvate to Phosphoenolpyruvate (PEP)
• Fructose-1,6-bisphosphate to Fructose-6-phosphate
• Glucose-6-phosphate to Glucose

1. Significance: Maintains blood glucose levels during prolonged fasting, starvation, or illness. Essential for glucose-dependent tissues like the brain, RBCs, and renal medulla.

 

Subsection: Kreb’s Cycle

Case Scenario 9:

A 20-year-old male presents with symptoms of muscle weakness, fatigue, and exercise intolerance. Blood lactate levels are elevated, and further investigations reveal a deficiency of alpha-ketoglutarate dehydrogenase, He is advised to consume a diet rich in thiamine.

1. a) Mention the pathway with Outline the steps highlighting the step involving the deficient enzyme in this case.
2. b) Explain the role of this pathway in energy production and the importance of coenzymes involved.
3. c) Describe the biochemical consequences of alpha-ketoglutarate dehydrogenase deficiency and explain why thiamine is recommended.

Answer:

1. a) Steps of the Krebs Cycle and Role of Alpha-Ketoglutarate Dehydrogenase
2. b) Role in Energy Production and Coenzymes Involved (3 marks)

Total: 10 ATP per acetyl-CoA

Essential Coenzymes:

1. 1. NAD⁺ (derived from niacin)
   2. FAD (derived from riboflavin)
   3. Coenzyme A (CoA) (from pantothenic acid)
   4. TPP (Thiamine pyrophosphate) – required by α-ketoglutarate dehydrogenase
   5. Lipoic acid – also part of the enzyme complex

1. 1. c) Consequences of Enzyme Deficiency and Role of Thiamine

Consequences:

• • Block in the Krebs cycle at the α-ketoglutarate dehydrogenase step leads to:
    • Decreased ATP production → fatigue, muscle weakness
    • Accumulation of α-ketoglutarate and upstream metabolites
    • Increased pyruvate and lactate levels → leads to lactic acidosis

Role of Thiamine:

• • Thiamine is a precursor for TPP (thiamine pyrophosphate), a key coenzyme for α-ketoglutarate dehydrogenase.
  • Supplementing thiamine can improve enzyme activity and reduce symptoms in thiamine-responsive cases.

Subsection: Rapaport-Leubering Cycle

Case Scenario 10:

A 25-year-old mountain climber ascends to a high altitude and begins experiencing mild breathlessness and fatigue. After a few days, his symptoms improve without medication. Blood tests show an increased level of 2,3-bisphosphoglycerate (2,3-BPG) in red blood cells. His hemoglobin-oxygen dissociation curve is found to be shifted to the right, facilitating better oxygen delivery to tissues.

1. Mention the pathway where 2,3 BPG is synthesized? Describe its steps.
2. Explain how 2,3-BPG affects oxygen delivery and why its production increases at high altitude.

Answer:

1. a) Rapaport-Leubering Cycle – Steps
2. b) Effect of 2,3-BPG on Oxygen Delivery & High Altitude Response (3 marks)

Effect on Oxygen Binding:

• • 2,3-BPG binds to deoxyhemoglobin, stabilizing it and reducing hemoglobin’s affinity for oxygen.
  • This shifts the oxygen-hemoglobin dissociation curve to the right, facilitating oxygen release to tissues.

Why it Increases at High Altitude:

• • At high altitude, there is hypoxia (low oxygen availability).
  • RBCs respond by increasing 2,3-BPG synthesis via the Rapaport-Leubering shunt.
  • This adaptation improves oxygen unloading in peripheral tissues, helping compensate for lower atmospheric oxygen.

 

Subsection: Glycolysis

Case Scenario 11:

A 40-year-old laboratory worker accidentally inhales a chemical substance while working with experimental compounds. Soon after, he experiences shortness of breath, confusion, and weakness. Blood tests reveal elevated lactate levels, metabolic acidosis, and signs of tissue hypoxia, despite normal oxygen saturation. The substance is later identified as sodium fluoride, a known glycolytic inhibitor.

1. Sodium fluoride is inhibitor of which enzyme in glycolysis?
2. Describe the normal glycolytic pathway and mention the key regulatory enzymes.
3. Explain how sodium fluoride and other glycolytic inhibitors interfere with glycolysis.

Answer:

1. Enzyme Enolase
2. Pathway of Glycolysis and Key Regulatory Enzymes
3. Glycolytic Inhibitors and Their Mechanisms

Sodium Fluoride (NaF):

• • Inhibits enolase, an enzyme that converts 2-phosphoglycerate to phosphoenolpyruvate.
  • This blocks glycolysis at a late stage, halting ATP production from glucose.

Other Glycolytic Inhibitors:

1. 1. Iodoacetate – inhibits glyceraldehyde-3-phosphate dehydrogenase
   2. Arsenate – interferes with substrate-level phosphorylation by mimicking phosphate