Diabetes + Endocrine Disorders Flashcards
Define diabetes mellitus
A chronic metabolic disease in which the body’s ability to produce or respond to the hormone insulin is impaired, resulting in abnormal metabolism of carbohydrates and hyperglycaemia
There are two main types of diabetes mellitus
Type 1 - Where the pancreas cannot produce insulin, this type is usually is diagnosed in childhood. Caused by either autoimmune or idiopathic B cell destruction
Type 2 - Develops due to prolonged hyperglycaemia in adults or adolescents, over time the bodies cells stop responding to insulin
Define diabetes insipidus
An endocrine disorder involving under secretion of ADH by hypothalamus, causing extreme thirst (polydipsia) and increased urination (polyuria)
What is the function of the pancreas?
Endocrine Function - Islets of langerhans cells secrete hormones (insulin and glucagon) into blood vessels to control blood glucose levels
Exocrine Function - Acinar cells secrete digestive enzymes into the pancreatic duct to help digest food (particularly protein)
Name some clinical features of type 1 diabetes mellitus
Sudden onset with severe symptoms of thirst and ketoacidosis.
Recent marked weight loss - Subject is usually lean.
Spontaneous ketosis
Requires insulin to sustain life
Absent c-peptide
Markers of auto-immunity present (e.g. islet cell antibodies)
Name some clinical features of type 2 diabetes mellitus
Usually insidious onset with associated fatigue, thirst, polyuria and nocturia.
Symptoms may be minimal and/or ignored by patient
No ketoacidosis
Usually overweight or obese with no associated weight loss.
Frequent infections e.g. urine, soft tissue, chest.
C-peptide detectable.
Other features of metabolic syndrome i.e. hypertension
What factors contribute to the development of type 2 diabetes?
Obesity
Hypertension
Hyperlipdemia
Smoking
Sedentary lifestyle
What is HbA1c a measure of?
The level of glucose adherence to haemoglobin over the last 3 months
What does a HbA1c result of 48 mmol/mol (6.5%) or greater mean?
A level of 48 mmol/mol or higher supports a diagnosis of diabetes
What is considered a normal HbA1c level for non-diabetic individual?
Below 42 mmol/mol (<6.0%)
What are the two main short term complications of type 1 diabetes?
Ketoacidosis and coma (Diabetic ketoacidosis or DKA)
Hypoglycaemia
What is DKA and why does it happen?
A state of severe uncontrolled diabetes caused by insulin deficiency, characterised by hyperglycaemia, hyperketonaemia (accumulation and elevation of circulating ketones) and metabolic acidosis (an increase in the hydrogen ion concentration that results in low serum bicarbonate levels)
The glucose in the blood stream of a type 1 diabetic goes largely unused since the absence of insulin means glucose cannot be transported into the cells for energy.
This condition means the body uses stored fat as an alternative means of energy.
This process produces acidic ketones, which then build up as ketones require insulin to break them down.
The presence of acidic ketones in the bloodstream causes the blood to more acidic than the body tissues, which creates a toxic condition.
What are some common DKA symptoms?
High blood sugar levels
Frequent urination (polyuria) and thirst
Fatigue and lethargy
Blurred vision
Vomiting & Nausea
Abdominal pain
Fruity odour to breath
Rapid, deep breathing
Muscle stiffness, aching or cramps
Coma (10% of cases)
What factors can precipitate DKA?
Infection
Insulin administration error or omission
Cardiovascular or cerebrovascular event (e.g MI or CVA)
Pancreatitis
Pulmonary embolism
Excessive alcohol consumption
Steroid use
What are the main 3 macro-vascular complications of diabetes mellitus?
Cardiovascular disease - MI, heart failure e.t.c
Cerebrovascular Disease - Stroke, cognitive impairment e.t.c
Peripheral Vascular Disease - Acute and chronic limb ischaemia, gangrene, amputation
What are the main 3 micro-vascular complications of diabetes mellitus?
Diabetic Retinopathy
Diabetic Nephropathy
Diabetic Neuropathy
What is the main pathological factor in the development of macro-vascular complications in diabetes?
Atherosclerosis - the formation of fatty plaques (atheroma) on the inner wall of an artery (tunica intima), the plaques harden over time and cause narrowing of the vessel (sclerosis)
What are the main pathological mechanisms involved in the development of micro-vascular diabetes complications?
The kidneys, retina and vascular endothelium are insulin independent tissues, meaning glucose moves freely across the cell membrane of these tissues regardless of the action of insulin - in diabetes this causes intracellular hyperglycaemia
Which causes…
Increased production of vascular endothelial growth hormone (VEGF)
Oxidative stress
Excessive sorbitol production (over-activation of the polyol pathway)
The non-enzymatic formation of advanced glycated end products (AGEs)
These mechanisms are thought to induce microvascular endothelial dysfunction - causing diabetic nephropathy, neuropathy and retinopathy
What pathological mechanisms contribute to the development of atherosclerosis in diabetes?
Hyperglycaemia
Hypertension
Dyslipidemia - Imbalance of lipids (low density lipoprotein cholesterol, triglycerides and high density lipoproteins)
Advanced Glycoslated Endproduct (AGE) production
Increased oxidative stress
Inflammation
Why is the risk of cardiovascular and cerebrovascular disease higher in patients with type 2 diabetes?
Type 2 diabetes usually occurs in the setting of metabolic syndrome: Abdominal obesity, hypertension, hyperlipidemia, increased coagulability and insulin resistance
These factors are all associated with the development of atherosclerosis, a major contributing factor to conditions such as coronary artery disease, myocardial infarction, TIA, CVA e.t.c
How are the macro-vascular complications of diabetes managed?
Lifestyle Modification - Recommend diet adjustment, exercise and smoking cessation if applicable
Management of Hyperglycaemia - Type 1 = Insulin, Type 2 = Metformin
Management of Hypertension - ACE inhibitors (Ramipril, Lisinopril), ARBs (Candesartan, Irbesartan), Calcium channel blockers (Amlodipine, nifedipine)
Management of Dislipidemia - Statins/ HMG-CoA reductase inhibitors (Atorvastatin, Fluvastatin)
What is the polyol pathway?
A metabolic pathway that converts glucose into glucose alcohol (sorbitol). This is also known as the sorbitol-aldose reductase pathway (aldose reductase is the inital enzyme in the intracellular polyol pathway)
This pathway is only triggered when there is high levels of glucose in the body: as in a hyperglycaemic state the affinity of aldose reductase for glucose rises, which causes the accumulation of sorbitol
How is the polyol pathway involved in diabetic micro-vascular complications?
Chronic hyperglycaemia leads to excessive activation of the polyol pathway - increasing intra and extra cellular sorbitol and fructose
Which causes changes in vascular permeability, cell proliferation and capillary structure via stimulation of the protein kinase C and transforming growth factor-beta
This process also results in…
Intracellular oedema and osmotic stress - which results in electrolyte imbalances and membrane damage
Oxidative stress - due to decreased levels of NADPH
Formation of AGEs - due to increased phosphorylation of fructose
How does oxidative stress contribute to the development of micro-vascular diabetes complications?
High glucose levels can stimulate the production of free radicals and formation reactive oxygen species (ROS), which causes oxidative stress, leading to vascular dysfunction
How does the formation of AGEs and vascular endothelial growth factor contribute to the development of micro-vascular complications in diabetes
Hyperglycaemia promotes the non-enzymatic formation of advanced glycated end products (AGEs) - which is associated with pericyte (cells present in the walls of capillaries, small arterioles and venules - they regulate blood flow) loss, tissue injury and inflammation
Production of endothelial growth factor (VEGF), growth hormone and transforming growth factor beta is increased in diabetic retinopathy and is thought to be a response to retinal hypoxia
What is the most common micro-vascular complication of diabetes?
Diabetic retinopathy
What are the 3 stages of diabetic retinopathy?
Stage 1 - Background Retinopathy: Micro-aneurysms and ‘dot’ haemorrhages appear within inner layer of the retina, sight not yet affected
Stage 2 - Pre-Proliferative Retinopathy: More severe changes including retinal haemorrhage and oedema, high risk of developing vision loss
Stage 3 - Proliferative Retinopathy: Neovascularisations (new blood vessels) form on retina, significant bleeding occurs. Potential for retinal detachment and very high risk of vision loss
What is diabetic nephropathy and how does it progress?
Progressive deterioration of renal function caused by the micro-vascular damage associated with diabetes mellitus.
Prolonged hyperglycaemia causes renal hypertrophy (kidneys increase in size - approximately 25%) and an increased glomerular filtration rate
Renal function begins to decline, causing persistant microalbminuria and proteinuria (elevation of albumin and presence of protein in urine) and decreased glomerular filtration rate
This progresses to overt diabetic nephropathy with massive microalbuminuria, will progress to ENRF within 8 years if not treated
Finally, GFR declines to <10ml/min - end stage renal failure, dialysis or transplantation necessary
What is the most common form of neuropathy in diabetes?
Chronic sensorimotor distal symmetrical polyneuropathy - otherwise known as ‘stocking and glove’ neuropathy
How does diabetes cause neuropathy?
Prolonged hyperglycaemia leads to microvascular damage of the vessels supplying nerves, this causes necrosis of the nerve fibres leading to potential sensory, motor and autonomic peripheral neuropathy.
What is the function of the thyroid gland?
To regulate the body’s overall metabolism by secreting thyroid hormones: Thyroxine (T4) and Triiodothyronine (T3)
What are the two common types of hyperthyroidism?
Grave’s Disease & Toxic Multinodular Goitre
What are the common signs and symptoms of hyperparathyroidsm?
Heat intolerance - sweating and irritability
Weight loss
Tremor
Palpitations
Exophthalmos - protruding eyes
Muscle wastage
Tachycardia
Diarrhoea
Restlessness
Osteoporosis - accelerated bone remodelling, can also cause hypercalciuria and hypercalcaemia
What is Grave’s disease?
An autoimmune disorder that involves over activity of the thyroid gland, associated with typical symptoms of hyperthyroidism (exophthalmos, heat intolerance, weight loss e.t.c), an enlarged thyroid, pre-tibial myxedema (infiltrative dermopathy characterised by oedema and a waxy orange peel appearance of affected area) and pernicious anemia (lack of red blood cell production due to vitamin b12 deficiency)
How is hyperthyroidism treated?
Medication to reduce thyroid hormone production - Carbimazole and Propylthiouracil
Radioactive Iodine Therapy to destroy cells in the thyroid gland
Surgical excision of all or part of the thyroid gland
What are some signs and symptoms of hypothyroidism?
Weight gain
Intolerance to cold
Fatigue and lethargy
Muscle cramping
Slow reflexes
Dry pale skin and brittle hair
Hoarse voice
Constipation
Dementia or psychosis
Bradycardia
Hypertension
Heart enlargement (late stages)
How is hypothyroidism treated?
Synthetic Thyroid Hormone - Levothyroxine
What is the function of the parathyroid gland?
To control and regulate the levels of calcium within the body - does this by secreting parathyroid hormone
What are some signs and symptoms of hyperparathryoidism?
Fatigue
Muscle weakness
Nausea & loss of appetite
Confusion & depression
Hypercalaemia (High levels of calcium in the blood)
Renal calculi/ kidney stones
Peptic ulcers
Pancreatitis
Hypertension
Bone or joint pain
Irregular heartbeat
What are some signs and symptoms of hypoparathyroidism?
Tingling (Paraesthesia) of the fingers, toes and lips
Facial twitch/ fasiculations
Muscle cramping , especially in legs, feet and abdomen
Anhidrotic skin
Coarse hair
Hypocalcaemia
Hyperphosphatemia - high levels of phosphate in the blood
What is the function of the adrenal glands?
Maintain and regulate sodium levels, blood pressure, renal function and overall fluid levels in the body - does this by secreting adrenaline, aldosterone and cortisol
What is Cushing’s disease?
A condition characterised by the over-production of cortisol. This can cause…
Hyperglycaemia
Osteoporosis
Abdominal obesity with slim arms and legs
Thin skin
GI distress
‘Moon face’ - puffy rounded appearance of face
Redness of the cheeks
Deposition of fat on the back of the neck and shoulders
What is Addison’s disease?
Also known as primary adrenal insufficiency or hypoadrenalism, is a disorder in which the adrenal glands do not produce enough cortisol or aldosterone. This can cause:
Hypoglycaemia
Postural hypotension
Weight loss
Bronze pigmentation of the skin
Muscle weakness
Adrenal crisis - Profound fatigue, dehydration, vascular compromise, reduce BP, reduced serum NA and increased serum K
What is the function of the pituitary gland?
To control the activity of many other endocrine glands. It releases:
TSH - Thyroid stimulating hormone
ACTH - Adrenocortictropic hormone to regulate adrenal glands
FSH - Follicle stimulating hormone to regulate ovaries and testes
Prolactin - To stimulate breast milk production in women
Growth Hormone - to stimulate growth metabolism
ADH - Anti-diuretic hormone (produces by hypothalamus but stored in the pituitary)
Oxytocin - To contract the uterus in childbirth
What is acromegaly?
A rare condition characterised by the over-production of growth hormone by the pituitary gland, often caused by a pituitary adenoma. This can cause:
Abnormally large hands and feet
Hypertrophy of the sweat and sebaceous gland - oily skin and hyperhydrosis
Large, prominent facial features (I.E a prominent suborbital ridge)
Coarse, thickened skin
Headaches
Sexual dysfunction
Hypertension
Blurred vision
Joint pain
Cardiomyopathy
