Endocrinology (glucose metabolism and ketone bodies formation) Flashcards
What is the role of insulin in glucose metabolism
In a healthy patient, insulin and glucagon work together to maintain a stable glucose level that allows cells to perform functions essential for life
When blood glucose levels are high, the beta-cells of the islets of Langherans in the pancreas secrete insulin, which binds to insulin receptors on cell membranes
- This binding allows glucose to enter the cell, where it is converted into adenosine triphosphate (ATP) through cellular respiration
- ATP is the main energy source for cells
- Once cells’ energy needs are met, insulin stimulates conversion of excess glucose into glycogen that can be stored in the liver
Insulin also causes amino acids to be stored as protein and fatty acids to be stored in adipose tissue
What is the role of glucagon
If cells’ energy needs are not being met (e.g., during fasting), the alpha-cells of the islets of Langherans secrete glucagon
Glucagon is insulin’s opposite, it stimulates:
- Glycogenolysis (breakdown of glycogen into glucose)
- Proteolysis (breakdown of protein into amino acids)
- Lipolysis (breakdown of adipose tissue into fatty acids)
The body then uses the released glucose and other components to maintain consistent energy production
What is the renal glucose threshold and what is its importance in diabetus mellitus
Not all glucose can be immediately transported into cells or converted into glycogen
- Some remains in the bloodstream and travels to the kidneys, where, in a normal, healthy patient, the proximal convoluted tubule of the nephron reabsorbs it so it can reenter circulation
- There is a limit to how much glucose the tubules can reabsorb; this is referred to as the renal threshold and is normally 220-250 mg/dL in cats
As long as blood glucose is below this threshold, glucose should never be excreted into the urine
- It is all used for energy or stored as glycogen
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Describe the pathophysiology of diabetus mellitus
When there is a deficiency in insulin, diabetus mellitus develops
- Without adequate insulin, glucose in the bloodstream cannot enter cells at sufficient levels to meet energy needs, leading to cell starvation
In response, glucagon is secreted to increase the breakdown of glycogen, protein, and fat
- The result is a huge increase in glucose, but still little to none of it can enter the cells
- Blood glucose rises to surpass the renal threshold and excess glucose is secreted into the urine
Due to glucose’s high osmolality, more water is pulled into the urine, leading to polyuria
The resulting free water loss, along with the lack of cellular energy, stimulates the hunger and thirst control centers of the hypothalamus, causing polydipsia and polyphagia
- However, despite the patient eating more and appearing hungry more often, weight loss occurs as muscle and fat continue to be broken down in the ongoing absence of insulin
- Polyuria, polydipsia, polyphagia, and weight loss are the typical presenting concerns of clients with diabetic pets
How could you explain an inadequate amount of insulin leading to diabetus mellitus
There are two general reasons:
- Insulin deficiency (e.g., congenital hypoplasia, immune-mediated destruction of beta-cells, pancreatitis, prolonged insulin resistance)
- Insulin resistance (e.g., hyperadrenocorticism, renal insufficiency, obesity, chronic inflammation, administration of glucocorticoids or progestins)
What is the difference between insulin deficiency and insulin resistance
Insulin deficiency is the result of loss of functioning beta-cells, leading to a decrease in the overall amount of insulin in the body
Insulin resistance occurs when cells have reduced sensitivity to insulin and therefore do not use it in appropriate amounts
- In addition, beta-cells fail to compensate for this reduced sensitivity and do not increase insulin secretion (i.e. beta-cells exhaustion)
It is estimated that 80% to 90% of cats with diabetus mellitus are insulin resistant, which is why cats can go into remission
How would you explain the progression from diabetus mellitus to diabetic ketoacidosis
Patients can compensate for undiagnosed diabetus mellitus for weeks to months without severe consequences, as long as there is some circulating insulin
If another disease develops (e.g., pancreatitis, hepatic lipidosis, CKD), metabolic homeostasis becomes more difficult to achieve and compensatory mechanisms are quickly overwhelmed and begin to fail
Stress, such as concurrent illness, stimulates the release of catecholamines, cortisol, growth hormone, and glucagon referred to as diabetognic hormones
- These hormones increase blood glucose concentration through glycogenolysis, gluconeogenesis, lipolysis, and/or proteolysis
In a normal patient, these hormones help support the body during a stressful event by increasing the amount of glucose available to be converted into energy
In diabetic patients, the resulting level of hyperglycemia - added to the demands of an activated immune system and the effects of ongoing total body cell starvation, water loss, and breakdown of muscle and fat - leads to increasingly detrimental attempts to compensate
Explain ketone formation and acidemia
Lipolysis increases the level of free fatty acids, which are converted by the liver into acetyl coenzyme A (acetyl-CoA)
Normally, acetyl-CoA enters the citric acid (Kreb’s) cycle to form ATP, but in diabetic patients, due to depletion of other enzymes during gluconeogenesis, it is instead converted into beta-hydroxybutyrate, which is further broken down into acetoacetate, and acetone
Beta-hydroxybutyrate, acetoacetate, and acetone are all ketones, which are acidic
In DKA, the rising ketone concentration eventually leads to acidemia
- As ketones levels increase, the pH continues to decrease
Because cells only function within a very narrow pH range (7.35 to 7.45), the increasing acidemia can cause multiple metabolc disruptions
Metabolic acidosis is a hallmark of DKA
Explain the origin of hypovolemic shock in DKA
Excretion of ketones into the urine further exacerbates osmotic diuresis
- At this point, water loss dehydrates the patient to the point of hypovolemia
- Hypovolemia leads to low cardiac output because stroke volume is decreased, and hypotension occurs, compromising oxygen delivery to the tissues and resulting in poor perfusion to all vital organs
- The renin-angiotensin-aldosterone system is activated in attempt to increase cardiac output by decreasing water loss and incresaing systemic vascular resistance
- However, the degree of continued diuresis in DKA patients overwhelms this compensatory system, resulting in hypovolemic shock
Explain electrolytes imbalances accompanying DKA
Osmotic diuresis causes severe electrolyte disturbances resulting from excess secretion of sodium, potassium, magnesium, and phosphorus by the kidneys into the urine
The body compensates by shifting intracellular stores into the extracellular fluid (plasma), but a total body deficit of each electrolyte remains
- Sodium is particularly affected, as most sodium is stored in the extracellular fluid and has already been depleted due to water loss, therefore, hyponatremia cannot be compensated for in this way
Explain why urine strips are less sensitive than ketometers
Urine strips are less sensitive and accurate in showing the degree of ketosis because they do not detect beta-hydroxybutyrate
