Lecture 4 -- Biochemistry of Glucose and Electrolytes

These flashcards cover essential concepts related to glucose metabolism, renal function, and electrolyte disturbances within the context of veterinary biochemistry.

Which organs are involved in glucose physiology?

• Intestine: 

  • Dietary carbohydrates are digested into glucose via amylase and absorbed in the small intestine.

• Pancreas:

  • High blood glucose → Uptake via GLUT2 in β-cells → Increased cellular respiration → Increased ATP → Closure of ATP-sensitive K⁺ channels → K+ remains inside the cells → Depolarisation → Ca²⁺ influx via voltage-gated calcium channel → Insulin secretion

  • Low blood glucose → Absent of ATP → → Closure of ATP-sensitive K⁺ channels → K+ remains inside the cells → Depolarisation → Ca²⁺ influx via voltage-gated calcium channel → Stimulation of α-cells → glucagon secretion

• Muscle and adipose tissue: 

  • Insulin promotes GLUT4 translocation to the cell membrane, increasing glucose uptake

  • Muscle stores glucose as glycogen

What regulates gluconeogenesis in the liver (Promotion and inhibition) ?

• Promoted by: Glucagon, cortisol

• Inhibited by: Insulin

What regulates glycogenolysis in the liver (Promotion and inhibition) ?

• Promoted by: Glucagon, catecholamines

• Inhibited by: Insulin

What regulates glycogenolysis in muscle (Promotion and inhibition)?

• Promoted by: Catecholamines, GH and glucagon

• Inhibited by: Insulin

What regulates glucose uptake in muscle (Promotion and inhibition)?

• Promoted by: Insulin

• Inhibited by: Catecholamines and cortisol

What are the causes of hyperglycaemia?

1. Physiological

   • Stress

   • Postprandial

2. Endocrine disease

   • Diabetes melltius

   • Hyperadrenocorticism

3. Drugs

   • Glucocoritcoid

What are the causes of hypoglycaemia?

1. Increased insulin secretion

   • Insulinoma

2. Decreased gluconeogensis or glycogenolysis

   • Hepatic insufficiency

   • Hypoadrenocoriticism

     • Since cortisol and catecholamines help promote glycogenolysis and gluconeogensis in the liver and inhibit glucose uptake by muscle

3. Increased glucose utilisation

   • Lactational hypoglycaemia

4. Drugs

   • Insulin

5. Other

   • Non-B cell neoplasm

   • Sepsis

How is persistent hyperglycaemia confirmed?

• Ketoamines

  • Fructosamine concentration

  • HbA1c

• Serial blood glucose curve (e.g. measurements every 2 hours)

What are ketoamines?

Glucose reacts with amino group on all protein (Albumin or Haemoglobin) non-enzymicatically → Produce glycated protein

Give examples of glycated proteins.

• Fructosamine: Glycated albumin

• HbA1c: Glycated haemoglobin

Why ketoamines are useful for diagnosing persistent hypoglycaemia?

Transient hyperglycaemia will have no effect on ketoamines

What time periods do fructosamine and HbA1c reflect blood glucose?

• Fructosamine: Approximately 2–3 weeks

• HbA1c: Approximately 2–3 months

What affects fructosamine concentration?

• Serum albumin concentration

• Thyroid status (Hyper and hypothyroidism)

What affects HbA1c concentration?

Haemoglobin concentration

What are the major electrolytes in extracellular and intracellular fluid?

• Extracellular fluid (ECF): Sodium (Na⁺), Chloride (Cl⁻)

• Intracellular fluid (ICF): Potassium (K⁺)

What are the causes of hyponatraemia?

1. Vomiting and diahorrea

2. Third space loss

3. Hypoadrenocorticism

   • ↓ Aldosterone → ↓ sodium reabsorption through DCT and CT → Sodium loss

4. Hyperglycaemia

   • Glucose is osmotically active → Water shifts into extracellular space → Dilution of sodium

5. Congestive heart failure:

   • Water retention → Dilutional hyponatraemia

6. Chronic kidney disease

What are the causes of hypernatraemia?

1. Central diabetes insipidus

   • ↓ Antidiuretic hormone (ADH) production → ↓ Water reabsorption in DCT = Relatively increased sodium level

2. Nephrotic diabetes insipidus

   • Normal ADH production but renal tubules are unresponsive → ↓ Water reabsorption in DCT = Relatively increased sodium level

3. Vomiting and diahorrea

4. Third space loss

5. Chronic kidney disease

6. Adrenal-dependent hyperadrenocorticism

Why does chloride (Cl⁻) follow sodium (Na⁺)?

To maintain electroneutrality in extracellular fluid

What does it mean if corrected Cl⁻ is within the reference interval?

What does it mean if corrected Cl⁻ is abnormal?

What are the causes of decreased chloride (hypochloraemia)?

1. Vomiting (loss of HCl)

2. Chronic respiratory acidosis

What are the causes of increased chloride (hyperchloraemia)?

• Diarrhoea (loss of bicarbonate)

• Chronic respiratory alkalosis

What promotes the uptake of potassium (K⁺) into cells?

• Hyperkalaemia

  • Greater concentration gradient of K+ between extracellular and intracellular

• Insulin

• Epinephrine

Which foods are high in potassium?

• Bananas

• Tomatoes

What are the causes of hypokalaemia?

1. Prolonged anorexia

2. Insulin or IV glucose administration

3. Osmotic diuresis

4. Ketonuria

   • Ketone is anion → K+ is an cation so it follows ketone and loss via urine

5. Chronic kidney disease

What are the causes of hyperkalaemia?

1. Urinary obstruction → Oliguria

   • Because one of the major roles of kidney is potassium excretion

2. Acute kidney injury → Oliguria

   • Because one of the major roles of kidney is potassium excretion

3. Hypoadrenocorticism

   • ↓ aldosterone → ↓ K⁺ excretion

4. Metabolic acidosis

   • K+ is reabsorbed in exchange for H+ secretion via H+/K+ ATPase in type A intercalated cells

5. EDTA contamination

   • EDTA contains potassium → Should not use EDTA to measure K+

In what forms does calcium exist in the body?

• ~50% ionised (free, biologically active)

• ~40–45% protein-bound (mainly albumin)

• ~10% complexed with anions (e.g. citrate)

What are the major causes of hypercalcaemia?

1. Increased intestinal absorption

   • Vitamin D toxicity

2. Bone lesion

3. Decreased urinary excretion

   • Renal disease

4. Increased PTH

   • Primary hyperparathyroidism

   • Humoral hypercalcaemia of malignancy (PTH-related peptide)

5. Normal in cats

What are the causes of hypocalcaemia?

1. Inadequate absorption in intestine

   • Renal disease

   • Protein-losing enteropathy

2. Decreased PTH

   • Hypoparathyroidism

3. Hypoalbuminaemia

   • Since 50% of calcium binds to albumin

4. Contamination of EDTA, citrate or oxalate

5. Other

   • Ethylene glycol toxicosis

   • Acute pancreatitis

   • Critical illness

What are the causes of decreased phosphate (hypophosphataemia)?

1. Increased urinary excretion

   • Primary hyperparathyroidism

   • Humoral hypercalcaemia of malignancy

2. Decreased intestinal absorption (Unimportant)

3. Shift from ECF to ICF (Unimportant)

4. Defective mobilisation from bone (Unimportant)

What are the causes of increased phosphate (hyperphosphataemia)?

1. Decreased urinary excretion

   • Decreased GFR

   • UT obstruction

   • Primary hypoparathyroidism

2. Increased intestinal absorption (Not important)

3. Shift from ICF to ECF (Not important)

4. Other

   • Hyperthyroidism

   • Artifactual e.g. Haemolysis

What markers indicate renal dysfunction?

• Urea

• Creatinine

Which is more reliable for assessing renal function?

Creatinine

• Urea can be reabsorbed through descending limb of LOH

What is urea? How is it produced and excreted?

• Produced in the liver from ammonia via the urea cycle

• Excreted by the kidneys (50% reabsorbed; 50% excreted)

What causes decreased urea?

• Liver insufficiency

• Low protein intake

• Decreased urea cycle enzyme

• Polyuria

  • Less time for kidney to reabsorb urea

What causes increased urea?

• Azotaemia (pre-renal, renal, post-renal)

• High protein intake

• Increased proteolysis (Caused by infection or sepsis)

• Intestinal haemorrhage

What causes increased creatinine?

• Azotaemia (pre-renal, renal, post-renal)

• Increased muscle mass

What causes decreased creatinine?

• Reduced muscle mass

P.S. usually not clinically significant

What are the causes of pre-renal azotaemia?

Dehydration or hypovlaemia

Why is urea disproportionately increased compared to creatinine in pre-renal azotaemia?

Hypoevlaemia causes reduced renal blood flow → Sensed by the macula densa cells of ascending limb of LOH → Signal JG cell to produce renin and activate RASS → Activate posterior pituitary gland to release ADH → Enhance urea reabsorption BUT NOT creatinine reabsorption

What are the causes of renal azotaemia?

Renal disease

What are the causes of post-renal azotaemia?

• Urinary tract obstruction

• Urine leakage (e.g. trauma, rupture)

How can pre-renal and renal azotaemia be differentiated?

Urine specific gravity (USG):

• Pre-renal: Concentrated urine (high USG) since the body is trying to minimise the water loss

• Renal: Inadequately concentrated urine (low or isosthenuric USG)