Dermatology and Endocrine Flashcards
Describe the progression from melanocytic naevi (mole) to nodular melanoma.
Melanocytic naevi -> dysplastic melanocytic naevi -> in situ melanoma -> superficial spreading melanoma -> nodular melanoma.
What is the main cause of all skin cancer?
SUN EXPOSURE - UV light.
What is the treatment for malignant melanoma?
Surgical excision.
Give 5 causes of generalised pruritus but no rash.
- AGEING.
- Chronic renal failure.
- Cholestasis e.g. PBC.
- Iron deficiency.
- Lymphoma.
- Polycythaemia.
- Hypothyroid.
- Drugs.
Give 3 causes of generalised pruritus with rash.
- Urticaria.
- Atopic eczema.
- Psoriasis.
- Scabies.
- Lichen planus.
What investigations might you do in someone with pruritus?
- FBC.
- Ferritin levels.
- U+E.
- LFT’s.
- TFT’s.
What cytokines are commonly targeted in the treatment of pruritus?
IL-4 and IL-13.
Why do transdermal drugs need to be lipophilic?
They need to be lipophilic in order to get through the lipid rich stratum corneum.
Give 2 essential properties of transdermal drugs.
- Lipophilic.
- High affinity for their targets.
Give 3 advantages of transdermal drug delivery.
- Avoids first pass effect, hardly metabolised.
- No pain.
- Controlled dosing.
What are emollients used for?
They hydrate the skin and reduce itching.
In what diseases would the use of emollients be indicated?
Dry skin, eczema.
What receptors do glucocorticoids target?
Cytoplasmic receptors.
How does hydrocortisone work?
Hydrocortisone targets cytoplasmic receptors. It leads to a reduction in pro-inflammatory cytokines and an increase in anti-inflammatories.
In what diseases would the use of hydrocortisone be indicated?
Eczema and contact dermatitis.
Give 3 potential side effects of glucocorticoids.
- Skin thinning.
- Oral candidiasis.
- Acne.
- Striae.
- Bruising.
What receptors do vitamin A analogues target?
Nuclear retinoic acid receptors.
Name a Vitamin D analogue.
Calcipotriol.
How does calcipotriol work in the treatment of psoriasis?
Calcipotriol is a vitamin D analogue. It has anti-proliferative and anti-inflammatory effects.
In what diseases would the use of calcipotriol be indicated?
Psoriasis.
Calcipotriol is a vitamin D analogue.
What receptors does tazarotene bind to?
Tazarotene is a Vitamin A analogue. It binds to nuclear retinoic acid receptors.
How does tazarotene work in the treatment of acne and psoriasis?
Tazarotene is a Vitamin A analogue. It binds to nuclear retinoic acid receptors and modifies gene expression and inhibits cell proliferation.
In what diseases would the use of tazarotene be indicated?
Psoriasis and acne.
Would you prescribe tazarotene to a pregnant lady?
NO! Tazarotene is highly teratogenic.
What class of drug is tacrolimus?
Calcineurin inhibitor.
When might you prescribe someone tacrolimus?
Tacrolimus is often used as a second line treatment for eczema.
(1st line = glucocorticoids e.g. hydrocortisone).
Name 3 drug induced dermatological reactions.
- Exanthematous reactions.
- Urticaria.
- Stephen Johnson syndrome.
Give 5 signs of eczema.
- Superficial skin redness/inflammation.
- Oozing.
- Scaling.
- Pruritus.
- Flexors typically affected e.g. at elbows.
Describe the aetiology of eczema.
- Genetic predisposition - loss of function mutations in filaggrin.
- Environmental triggers and irritants.
Describe the treatment for eczema.
- Avoid irritants and allergens.
- Use emollients liberally and frequently.
- First line - hydrocortisone.
- Second line - tacrolimus.
- Third line - sedative anti-histamines.
Briefly describe the pathophysiology of acne.
Seborrhea (increased sebum production) -> narrowed follicle blocks sebum, comedo formation -> sebum stagnates and p.acne colonises -> inflammation of pilosebaceous unit.
Describe the treatment for acne.
Treatment is important to avoid scarring and psychological distress:
- Regular washing with acne soaps to remove grease.
- Benzoyl peroxide and topical clindamycin.
- 2nd line - topical retinoids e.g. tazarotene.
- 3rd line - low dose oral antibiotics e.g. doxycycline.
- Hormone treatment can also be used.
What is psoriasis?
A chronic hypo-proliferative disorder characterised by well demarcated silvery grey, scaly plaques over extensor surfaces such as elbows and knees and in the scalp.
What environmental factors can cause psoriasis in a genetically susceptible individual?
- Group A streptococcal infection.
- Lithium.
- UV light.
- Alcohol.
- Stress.
Describe the treatment for psoriasis.
- Emollients and reassurance.
- Vitamin D and A analogues e.g. calcipotriol and tazarotene.
- Phototherapy.
What is necrotising fasciitis?
Deep spreading infection of all layers of the skin -> necrosis.
Give 3 risk factors for necrotising fasciitis.
- IVDU.
- Diabetes mellitus.
- Homeless.
- Recent surgery.
What bacteria can cause necrotising fasciitis?
- Type 1: aerobic and anaerobic.
- Type 2: group A strep e.g. s.pyogenes.
What is the treatment for necrotising fasciitis?
- Surgical debridement.
- Aggressive IV benzylpenicillin and clindamycin.
What is cellulitis?
Inflammation of the SC layer of the skin.
What bacteria is the commonest causal organism of cellulitis?
S.pyogenes.
Give 5 signs of cellulitis.
- Inflammation.
- Swelling.
- Redness.
- Warmth.
- Pain.
- Unilateral.
What is the differential diagnosis in someone with the signs and symptoms of cellulitis?
DVT!
What is the treatment for cellulitis?
Penicillin and flucloxacillin.
Give an example of a water soluble hormone.
Peptides e.g. TRH, LH, FSH.
Are water soluble hormones stored in vesicles or synthesised on demand?
Water soluble hormones e.g. peptides are stored in vesicles.
How do water soluble hormones e.g. peptides get into a cell?
They bind to cell surface receptors.
Give an example of a fat soluble hormone.
Steroids e.g. cortisol.
Are fat soluble hormones stored in vesicles or synthesised on demand?
Fat soluble hormones e.g. steroids are synthesised on demand.
Give an example of an amine hormone.
Noradrenaline and adrenaline.
Describe the pathway for noradrenaline synthesis.
Phenylalanine -> L-tyrosine -> L-dopa -> dopamine -> NAd and Ad.
Name 2 enzymes that break down catecholamines.
MAO and COMT.
What are noradrenaline and adrenaline broken down into?
Normetadrenaline and metadrenaline.
Where in a cell are peptide cell receptors located?
Peptide cell receptors are located on the cell membrane.
Where in a cell are steroid cell receptors located?
Steroid cell receptors are located in the cytoplasm.
Where in a cell are thyroid/vitamin A and D cell receptors located?
Thyroid, vitamin A and D and oestrogen act on nuclear receptors.
Give 5 ways in which hormone action is controlled.
- Hormone metabolism.
- Hormone receptor induction.
- Hormone receptor down-regulation.
- Synergism e.g. glucagon and adrenaline.
- Antagonism e.g. glucagon and insulin.
What layer of the trilaminar disc is the anterior pituitary derived from?
Ectoderm (Rathke’s pouch).
Name 6 hormones that the anterior pituitary produces.
- TSH.
- FSH.
- LH.
- ACTH.
- Prolactin.
- GH.
What is the posterior pituitary derived form?
The floor of the ventricles.
Where are posterior pituitary hormones synthesised?
They are synthesised in the para-ventricular and supra-optic nuclei.
Name 2 hormones secreted from the posterior pituitary.
Oxytocin and ADH.
What is the function of ADH?
It acts on the collecting ducts of the nephron and increases insertion of aquaporin 2 channels -> there is H2O retention.
Give 2 functions of oxytocin.
- Milk secretion.
- Uterine contraction.
Which has a longer half life, triiodothyronine or thyroxine?
Thyroxine has a half life of 5-7 days whereas triiodothyronine has a half life of only 1 day.
Describe the thyroid axis.
Hypothalamus -> TRH -> AP -> TSH -> thyroid -> T3 and T4.
T3/4 have a negative feedback effect on the hypothalamus and the anterior pituitary.
What would be the effect on TSH if you had an under-active thyroid?
TSH would be raised as you have less T3/4 being produced and so no negative feedback.
What would a low TSH tell you about the action of the thyroid?
A low TSH indicates an over-active thyroid.
Lots of T4 and T3 is being produced and so there is more negative feedback on the pituitary and less TSH.
Describe the mechanism of ACTH.
Hypothalamus -> CRH -> AP -> ACTH -> adrenal cortex (zona fasciculata) -> glucocorticoid synthesis e.g. cortisol.
Cortisol has a negative feedback effect on the hypothalamus and the anterior pituitary.
Give 3 functions of thyroid hormones (T3/4).
- Food metabolism.
- Protein synthesis.
- Increased sympathetic action e.g. CO and HR.
- Heat production.
- Needed for growth and development.
Give 3 functions of cortisol in response to stress.
- Mobilises energy sources -> lipolysis, gluconeogenesis and protein break down.
- Vasoconstriction.
- Suppresses inflammatory and immune repsonses.
- Inhibits non-essential functions e.g. growth and reproduction.
Briefly describe the mechanism of LH and FSH.
Hypothalamus -> GnRH -> AP -> FSH/LH -> ovaries/testes.
FSH acts on granulosa cells to produce oestrogen and sertoli cells to stimulate spermatogenesis.
LH acts on theca cells to produce androgens or leydig cells to produce testosterone.
What cells does FSH act on?
- In the ovaries: granulosa cells.
- In the testes: sertoli cells.
What cells does LH act on?
- In the ovaries: theca cells.
- In the testes: leydig cells.
What is the function of theca cells?
Theca cells are stimulated by LH to produce androgens that diffuse into granulosa cells to be converted into oestrogen.
What is the function of granulosa cells?
Granulosa cells are stimulated by FSH to convert androgens into oestrogen using aromatase.
What is the function of sertoli cells?
Sertoli cells produce MIF (mullerian inhibiting factor) and inhibin and activin which acts on the pituitary gland to regulate FSH.
What is the function of leydig cells?
Leydig cells are stimulated by LH to produce testosterone.
Describe the GH/IGF-1 axis.
Hypothalamus -> GHRH (+) or SMS (-) -> AP -> GH -> Liver -> IGF-1.
What is the function of IGF-1?
It induces cell division, cartilage and skeletal growth and protein synthesis.
Briefly describe the mechanism of prolactin.
Hypothalamus -> dopamine (-) -> AP -> prolactin.
Prolactin acts on the mammary glands to produce milk.
What would happen to serum prolactin levels if something was to impact on the pituitary stalk and block dopamine release?
Prolactin levels would increase.
Give 3 potential consequences of a pituitary tumour.
- Pressure on local structures e.g. optic chiasm.
- Hypo-pituitary.
- Functioning tumour e.g. Cushing’s, gigantism, prolactinoma.
Give 2 causes of prolactinoma.
- Pituitary adenoma.
- Anti-dopaminergic drugs.
Give 5 signs of prolactinoma.
- Infertility.
- Golactorrhoea.
- Amenorrhoea.
- Loss of libido.
- Visual field defects and headaches due to local effect of tumour.
What investigation would you do on someone presenting with difficulty getting pregnant, golactorrhoea, amenorrhoea, loss of libido and headaches?
You would measure serum prolactin.
These are symptoms of prolactinoma.
Describe the treatment for prolactinoma.
Dopamine agonist e.g. cabergoline.
Describe growth hormone secretion from the anterior pituitary.
It is secreted in a pulsatile fashion and increases during deep sleep.
What can cause acromegaly?
A benign pituitary adenoma producing excess GH.
Give 5 symptoms of acromegaly.
- Change in appearance.
- Increase in size of hands and feet.
- Excessive sweating.
- Headache.
- Tiredness.
- Weight gain.
- Amenorrhoea.
- Deep voice.
- Goitre.
Give 5 signs of acromegaly.
- Prognathism - jaw protrusion.
- Interdental separation.
- Large tongue.
- Spade like hands and feet.
- Tight rings.
- Bi-temporal hemianopia.
What co-morbidities are associated with acromegaly?
- Arthritis.
- Cerebrovascular events.
- Hypertension and heart disease.
- Sleep apnea.
- T2 DM.
What investigations might you do on someone who you suspect has acromegaly?
- Plasma GH levels can exclude acromegaly - not diagnostic!
- Serum IGF-1 levels raised.
- Oral glucose tolerance test - diagnostic!
- MRI of pituitary.
What test is diagnostic for acromegaly?
Oral glucose tolerance test - failure of glucose to suppress serum GH.
Describe the treatment for acromegaly.
- Trans-sphenoidal surgical resection.
- Radiotherapy.
- Medical therapy: somatostatin analogues, dopamine agonists e.g. cabergoline.
Give 3 potential complications of trans-sphenoidal surgical resection for the treatment of acromegaly.
- Hypopituitarism.
- Diabetes insipidus.
- Haemorrhage.
- CNS injury.
- Meningitis.
Give 3 advantages of using dopamine agonists in the treatment of acromegaly.
- No hypopituitarism.
- Oral administration.
- Rapid onset.
Give 2 disadvantages of using dopamine agonists in the treatment of acromegaly.
- Can be ineffective.
- Risk of side effects.
Name a dopamine agonist that can be used in the treatment of acromegaly.
Cabergoline.
Give 5 causes of hypothyroidism.
- Autoimmune thyroiditis e.g. Hashimoto’s and atrophic thyroiditis.
- Post-partum thyroiditis.
- Iatrogenic - thyroidectomy.
- Drug induced e.g. carbimazole, amiodarone, lithium.
- Iodine deficiency.
Hypothyroidism: name 3 anti-bodies that may be present in the serum in someone with autoimmune thyroiditis.
- TPO (thyroid peroxidase).
- Thyroglobulin.
- TSH receptor.
Give an example of a transient cause of hypothyroidism.
Post-partum thyroiditis.
Give 2 examples of iatrogenic causes of hypothyroidism.
- Thyroidectomy.
- Radioiodine therapy.
Name 3 drugs that can cause hypothyroidism.
- Carbimazole (used to treat hyperthyroidism).
- Amiodarone.
- Lithium.
Why can amiodarone cause hypo/hyperthyroidism?
Because it is iodine rich.
Give 5 symptoms of hypothyroidism.
- Menorrhagia – heavy bleeding.
- Obesity/weight gain.
- Malar flush.
- Tiredness.
- Intolerance to cold.
- Energy levels fall/eyebrow loss.
- Depression/dry skin and hair.
- GOITRE!
Give 5 signs of hypothyroidism.
- Mental slowness.
- Dry thin hair.
- Bradycardia.
- Anaemia.
- Hypertension.
- Loss of eyebrows.
- Cold peripheries.
- Carpal tunnel syndrome.
What investigations might you do in someone who you suspect has hypothyroidism?
- TFT’s - serum TSH will be raised and T3/T4 will be low.
- Thyroid antibodies.
Describe the management for hypothyroidism.
Levothyroxine.
Give 5 causes of thyrotoxicosis.
Thyrotoxicosis - excess thyroid hormone due to any cause:
1. Increased production e.g. Grave’s, toxic adenoma.
2. Leakage of T3/4 due to follicular damage.
3. Ingestion.
4. Thyroiditis.
5. Drug induced.
Give 3 causes of hyperthyroidism.
- Grave’s disease.
- Toxic adenoma.
- Toxic Multinodular Goitre (TMG)
Briefly describe the pathophysiology of Grave’s disease.
Autoimmune disease. TSH receptor antibodies stimulate thyroid hormone production -> hyperthyroidism.
Give 5 symptoms of Grave’s disease that don’t include opthalmopathy signs.
- Weight loss.
- Increased appetite.
- Irritable.
- Tremor.
- Palpitations.
- Goitre.
- Diarrhoea.
- Heat intolerance.
- Malaise.
- Vomiting.
Give 5 signs of Grave’s disease that don’t include opthalmopathy signs.
- Tachycardia.
- Arrhythmias e.g. AF.
- Warm peripheries.
- Muscle spasm.
- Pre-tibial myxoedema (raised purple lesions over the shins).
- Thyroid acropachy (clubbing and swollen fingers).
With what disease would you associated pre-tibial myxoedema and thyroid acropachy?
Grave’s disease.
Give 5 Grave’s opthlmopathy signs.
- Exophthalmos (bulging eyes).
- Lid lag stare.
- Redness.
- Conjuctivitis.
- Pre-orbital oedema.
- Bilateral.
- Extra-ocular muscle swelling.
What investigations might you do in someone who you suspect has hypothyroidism?
TFT’s - serum TSH is suppressed and T3/4 are elevated.
What would you see histologically in someone with Grave’s disease?
Lymphocyte infiltration and thyroid follicle destruction.
Describe the treatment for Grave’s disease.
- Anti-thyroid drugs e.g. carbimazole.
- Radioiodine drugs.
- Surgery - partial thyroidectomy.
How does carbimazole work in treating Grave’s disease?
It targets thyroid peroxidase and so prevents the formation of T3/4.
Give a potential serious side effect of taking carbimazole to treat Grave’s disease.
Agranulocytosis.
Patient’s are advised to seek medical attention if they develop an unexplained sore throat or fever.
How do radioiodine drugs work in treating Grave’s disease?
Radioiodine drugs emit beta particles that destroy thyroid follicles and so thyroid hormone production is decreased.
Give 3 potential complications of a partial thyroidectomy.
- Bleeding.
- Hypocalcaemia.
- Hypothyroidism.
- Recurrent laryngeal nerve palsy.
What disease would you treat with Carbimazole?
Grave’s disease.
What disease would you treat with levothyroxine?
Hypothyroidism.
Give 5 metabolic changes that occur in pregnancy.
- Increased EPO, cortisol and NAd.
- High CO.
- High cholesterol and triglycerides.
- Pro thrombotic and inflammatory state.
- Insulin resistance.
Give 5 gestational syndromes.
- Pre-eclampsia.
- Gestational diabetes.
- Obstetric cholestasis.
- Gestational thyrotoxicosis.
- Postnatal depression.
- Post partum thyroiditis.
At what week are foetal thyroid follicles and T4 synthesised?
Week 10.
Why can hCG activate TSH receptors and cause hyperthyroidism?
HCG and TSH are glycoprotein hormones with very similar structures. HCG can therefore activate TSH receptors.
Is hypothyroidism or thyrotoxicosis more common in pregnancy?
Hypothyroidism is more common in pregnancy.
How can you differentiate between Grave’s disease and gestational thyrotoxicosis?
- Grave’s: symptoms predate pregnancy; symptoms are severe during pregnancy; goitre and TSH-R antibodies present.
- Gestational thyrotoxicosis: symptoms do not predate pregnancy; lots of N/V - hyperemesis gravidarum associated. No goitre or TSH-R antibodies.
Give 3 potential consequences of untreated hypothyroidism in pregnancy.
- Gestational hypertension.
- Placental abruption.
- Post partum haemorrhage,
- Low birth weight.
- Neonatal goitre.
Give 3 potential consequences of untreated hyperthyroidism in pregnancy.
- Intra-uterine growth restriction.
- Low birth weight.
- Pre-eclampsia.
- Risk of still birth/miscarriage.
What disease is described as being a ‘disorder of carbohydrate metabolism characterised by hyperglycaemia’?
Diabetes mellitus.
What are the 4 cells to make up the islets of langerhans?
- Beta cells (70%).
- Alpha cells (20%).
- Delta cells (8%).
- Polypeptide secreting cells.
What do beta cells produce?
Insulin.
What do alpha cells produce?
Glucagon.
What do delta cells produce?
Somatostatin.
What is the importance of the alpha and beta cells being located next to each other in the islets of langerhans?
This enables them to ‘cross talk’ - insulin and glucagon show reciprocal action.
Describe the mechanism of insulin secretion from beta cells.
Glucose binds to beta cells -> glucose-6-phosphate -> ADP -> ATP -> K+ channels close -> membrane depolarisation -> Ca2+ channels open, influx -> insulin release.
Describe the physiological processes that occur in the fasting state in response to low blood glucose.
Low blood glucose = high glucagon and low insulin.
- Glycogenolysis and gluconeogenesis.
- Reduced peripheral glucose uptake.
- Stimulates the release of gluconeogenic precursors.
- Lipolysis and muscle breakdown.
Describe the effect on insulin and glucagon secretion in the fasting state.
Fasting state = low blood glucose.
Raised glucagon and low insulin.
How many carbon precursors are needed for gluconeogenesis?
3.
Describe the physiological processes that occur after feeding in response to high blood glucose.
High blood glucose = high insulin and low glucagon.
- Glycogenolysis and gluconeogenesis are suppressed.
- Glucose is taken up by peripheral muscle and fat cells.
- Lipolysis and muscle breakdown suppressed.
Describe the effect on insulin and glucagon secretion after feeding.
Insulin is high and glucagon is low.
A diagnosis of diabetes can be made by measuring plasma glucose levels. What would a persons fasting plasma glucose be if they were diabetic?
Fasting plasma glucose >7mmol/L.
A diagnosis of diabetes can be made by measuring plasma glucose levels. What would a persons random plasma glucose be if they were diabetic?
Random plasma glucose >11mmol/L.
A diagnosis of diabetes can be made by measuring plasma glucose levels. What would the results of the oral glucose tolerance test be if someone was diabetic?
Fasting plasma glucose >7mmol/L and 2-hour value >11mmol/L.
What might someone’s HbA1c be if they have diabetes?
> 48mmol/mol.
What is the affect of cortisol on insulin and glucagon?
Cortisol inhibits insulin and activates glucagon.
Describe the aetiology of type 1 diabetes mellitus.
Beta cells express HLA antigens (HLA DR3/DR4). Autoimmune destruction -> beta cell loss -> impaired insulin secretion.
Is type 1 diabetes characterised by a problem with insulin secretion, insulin resistance or both?
Type 1 diabetes is characterised by impaired insulin secretion - there is severe insulin deficiency.
At what age do people with T1DM present?
Often people with Type 1 diabetes will present in childhood.
Give 2 potential consequences of T1DM.
- Hyperglycaemia.
- Raised plasma ketones -> ketoacidosis.
Describe the natural history of T1DM.
Genetic predisposition + trigger -> insulitis, beta cell injury -> pre-diabetes -> diabetes.
T1DM is characterised by impaired insulin secretion. Describe the pathophysiological consequence of this.
Severe insulin deficiency -> glycogenolysis/gluconeogensis/lipolysis all not suppressed AND reduced peripheral glucose uptake -> hyperglycaemia and glycosuria.
Perceived stress -> cortisol and Ad secretion -> catabolic state -> increased plasma ketones.
Give 3 symptoms of T1DM.
- Weight loss.
- Thirst (fluid and electrolyte losses).
- Polyuria (due to osmotic diuresis).
Would you associate ketoacidosis with T1 or T2 DM?
TYPE 1.
Occurs due to the absence of insulin.
Describe the pathophysiology of diabetic ketoacidosis.
No insulin -> lipolysis -> FFA’s -> oxidised in liver -> ketone bodies -> ketoacidosis.
Name 3 ketone bodies.
- acetoacetate.
- acetone.
- beta hydroxybutyrate.
Where does ketogenesis occur?
In the liver.
Give 4 signs of diabetic ketoacidosis.
- Hypotension.
- Tachycardia.
- Kussmaul’s respiration.
- Breath smells of ketones.
- Dehydration.
Describe the treatment for T1DM.
- EDUCATION - make sure the patient understands the benefits of good glycaemic control.
- Healthy diet - low in sugar, high in carbohydrates.
- Regular activity, healthy BMI.
- BP and hyperlipidaemia control.
- Insulin.
How is insulin administered in someone with T1DM?
Injected into SC fat.
Other than SC injections, how else can insulin be administered?
Insulin pump.
Give 4 potential complications of insulin therapy.
- Hypoglycaemia.
- Lipohypertrophy at ejection site.
- Insulin resistance.
- Weight gain.
- Interference with life style.
Is type 2 diabetes characterised by a problem with insulin secretion, insulin resistance or both?
Type 2 DM is characterised by impaired insulin secretion AND insulin resistance.
Describe the aetiology of T2DM.
Genetic predisposition and environmental factors e.g. obesity and lack of exercise.
Why is insulin secretion impaired in T2DM?
Impaired insulin secretion is thought to be due to lipid deposition in the pancreatic islets.
Describe the pathophysiology of T2DM.
Impaired insulin secretion and resistance -> IGT -> T2DM -> hyperglycaemia and high FFA’s.
Is insulin secretion or insulin resistance the driving force of hyperglycaemia in T2DM?
Hepatic insulin resistance is the driving force of hyperglycaemia.
Give 3 risk factors for insulin resistance in T2DM.
- Obesity.
- Physical inactivity.
- Family history.
What happens to insulin resistance, insulin secretion and glucose levels in T2DM?
- Insulin resistance increases.
- Insulin secretion decreases.
- Fasting and post-prandial glucose increase.
Why do you rarely see diabetic ketoacidosis in T2DM?
Insulin secretion is impaired but there are still low levels of plasma insulin. Even low levels of insulin can prevent muscle catabolism and ketogenesis.
Describe the treatment pathway for T2DM.
- Lifestyle changes: lose weight, exercise, healthy diet.
- Metformin.
- Metformin + sulfonylurea.
- Metformin + sulfonylurea + insulin.
- Increase insulin dose as required.
How does metformin work in treating T2DM?
Metformin increases insulin sensitivity and inhibits glucose production.
How does sulfonylurea work in treating T2DM?
Sulfonylurea stimulates insulin release.
Give a potential consequence of taking Sulfonylurea for the treatment of T2DM.
Hypoglycaemia.
(Sulfonylurea stimulates insulin release).
Give 3 microvascular complications of diabetes mellitus.
- Diabetic retinopathy.
- Diabetic nephropathy.
- Diabetic peripheral neuropathy.
Give a macrovascular complication of diabetes mellitus.
CV disease and stroke.
What is the main risk factor for diabetic complications?
Poor glycaemic control!
Give a potential consequence of acute hyperglycaemia?
Diabetic ketoacidosis and hyperosmolar coma.
Give a potential consequence of chronic hyperglycaemia?
Micro/macrovascular tissue complications e.g. diabetic reinopathy, nephropathy, neuropathy, CV disease etc.
What is the commonest form of diabetic neuropathy?
Distal symmetrical polyneuropathy.
Give 3 major clinical consequences of diabetic neuropathy.
- Pain.
- Autonomic neuropathy.
- Insensitivity.
Describe the pain associated with diabetic neuropathy.
- Burning.
- Paraesthesia.
- Nocturnal exacerbation.
Diabetic neuropathy clinical consequences: what is autonomic neuropathy?
Autonomic neuropathy - damage to the nerves that supply body structures that regulate functions such as BP, HR, bowel/bladder emptying.
Diabetic neuropathy: give 5 signs of autonomic neuropathy.
- Hypotension.
- HR affected.
- Diarrhoea/constipation.
- Incontinence.
- Erectile dysfunction.
- Dry skin.
What are the consequences of insensitivity as a result of diabetic neuropathy?
Insensitivity -> foot ulceration -> infection -> amputation.
Describe the distribution of insensitivity as a result of diabetic neuropathy?
Insensitivity starts in the toes and moves proximally. Glove and stocking distribution.