Endocrine

Question 1

Describe the pathophysiology of diabetes mellitus

Answer 1

Diabetes mellitus is a disease in which there is a persistent state of hyperglycaemia and loss of glucose homeostasis.

To utilise glucose the cells require insulin, a hormone produced by the pancreatic islets.

In diabetes the effects of insulin are reduced due to:

• decrease in production
• cells have become resistant to its effect

Cells don’t take up adequate glucose, causing it to build up in the blood, overflow into the urine, and flow out of the body.
Cells are starved of glucose even though the blood contains large quantities of it.

These are the basis of distinction between Type 1 and Type 2 Diabetes Mellitus:

• Type 1 ( Hx known as IDDM/Juvenile ) - autoimmune disease. Lymphocytes attack antigens on the beta cells of the pancreatic islets, destroying them, and causing an absolute deficiency of insulin production. The disease becomes clinically apparent when production is decreased by at least 90%
• Type 2 ( Hx known as NIDDM/Adult-onset ) - cells do not respond normally to insulin, they are resistant to it’s effects, meaning they are not stimulated to take up glucose even though insulin is present. Glucose remains in the circulation, in response to persistent hyperglycaemia, the beta cells can increase insulin production, causing the islet cells to ‘burn out’ over time, resulting in insulin deficiency.

Question 2

Explain how diabetes can manifest as hyperosmolar hyperglycaemic state and diabetic ketoacidosis

Answer 2

Hyperglycaemia occurs when levels of sugar in the blood exceed normal ranges. Early signs include:

• frequent/excessive thirst
• frequent/excessive urination

It can be caused by:

• excessive food intake
• insufficient insulin dosages
• infection/illness
• injury
• surgery
• emotional stress

Onset may be:
- rapid(mins), eg. excessive food intake
or
- gradual(hrs-days), eg. infection/illness

Left untreated hyperglycaemia will progress to Diabetic Ketoacidosis(DKA) - life threatening condition caused certain acids accumulating in the body due to insulin not being available:

• deficiency of insulin prevents cells taking up extra glucose.
• cells send signal via sympathetic nervous system, causing the release of various stress hormones.
• as the body can’t use glucose, it turns to there sources of energy, mainly fat.
• the metabolism of fat generates acids and ketones as waste products.
• meanwhile glucose continues to accumulate in the blood, and as blood sugar rises a pt undergoes massive osmotic diuresis(passing large amounts of urine due to the high solute concentration of the blood).
• as glucose must be excreted in the urine in solution, the body loses excessive amounts of water and electrolytes(sodium and potassium), leading to disturbance of water and acid-base balance.
• together with vomiting, these events cause dehydration and even shock.

Signs/symptoms of DKA:

• Polyuria(excessive urine output) - due to osmotic diuresis
• Polydipsia(excessive thirst) - due to dehydration
• Polyphagia(excessive eating) - due to insufficient utilisation of nutrients
• nausea and vomiting - worsens dehydration
• tachycardia - due to dehydration
• deep, rapid respiration(Kussmaul respiration) - body attempts to compensate for acidosis by blowing off CO2
• warm, dry skin and dry mucous membranes - due to dehydration
• fruity odour of ketones on breath
• sometimes fever, abdominal pain, hypotension

Hyperosmolar Hyperglycaemic State(HHS)

• metabolic derangement occurring mainly in Type 2 diabetics, most pt diagnosed have known diabetic Hx
• characterised by hyperglycaemia, hyperosmolarity and an absence of significant ketosis
• most pt present with dehydration, and focal or global neurological deficits
• acute M.I. is frequently associated with HHS
• often develops in diabetics who have some secondary illness that leads to reduced fluid intake
• infection is most common cause(pneumonia, UTI), but many other conditions can cause altered mental state or dehydration
• in most cases, secondary illness is not identified
• hyperglycaemia and hyperosmolarity lead to osmotic diuresis and osmotic shift of fluid to intravascular space, causing further intracellular dehydration
• unlike DKA, pt with HHS does not develop ketoacidosis
• stress response to acute illness increases hormones that favour elevated glucose levels like cortisol, catecholamines(adrenaline/noradrenaline), glucagon, having effects that counteract those of insulin
• neurological changes may be found:
  
  • drowsiness
  • lethargy
  • delirium
  • coma
  • focal/generalised convulsions
  • visual disturbance
  • hemiparesis
  • sensory deficit

Question 3

Briefly describe the pathophysiology of Diabetes Insipidus and Gestational Diabetes

Answer 3

Diabetes Insipidus:

• destruction of posterior pituitary and/or hypothalamus leads to decreased release of vasopressin(antidiuretic hormone), resulting in failure of water reabsorption in the kidney
• the resultant excess urination leads to excess thirst
• as such the symptoms of diabetes insidious resemble diabetes mellitus
• rare condition caused by infiltrative processes such as neoplasms, infections like meningitis, head injury/surgery

Gestational Diabetes Mellitus(GDM):

• inability to process carbohydrates during pregnancy
• increased maternal insulin production results in increased placental production of human placental lactogen, leading to an imbalance between the supply of the mother’s insulin, and glucose production from fats, in order to be made readily available to the foetus
• pt’s may be asymptomatic or display same sign/symptoms as diabetes mellitus

Question 4

Briefly describe the pathophysiology of adrenal insufficiency

Answer 4

Adrenal insufficiency is classified as either Primary or Secondary.

Primary Adrenal Insufficiency:

• also known as Addison’s disease
• caused by atrophy or destruction of the adrenal glands, which leads to deficiency of all the steroid hormones produced by these glands
• rare disease, most frequently the result of idiopathic atrophy, an autoimmune process in which the immune system creates antibodies that attack the adrenal cortex, leading to its gradual destruction
• less commonly caused by tuberculosis, bacterial, viral or fungal infections, adrenal haemorrhage or cancer of the adrenal glands
• the body fails to achieve proper regulation of the amount of sodium, potassium and water in body fluids
• blood volume and pressure fall, along with sodium concentrations in the blood
• blood potassium rises
• blood volume may become so reduced that circulation can no longer be maintained efficiently
• frequently exhibit increased pigmentation of the skin, due to the increased secretion of hormones

Secondary Adrenal Insufficiency:

• relatively common
• defined as a lack of ACTH secretion from the pituitary gland
• ACTH, a pituitary messenger, stimulates the adrenal cortex to manufacture and secrete cortisol
• a pt who abruptly stops taking corticosteroids(eg. prednisolone) may experience secondary adrenal insufficiency
• corticosteroid treatments suppress natural cortisol production