Lectures 11-15 Flashcards
How many tests would you carry out for diabetes?
In the presence of symptoms, 1 is enough.
Without symptoms, 2 are required
In type 1 diabetes, what might low insulin levels cause?
High blood glucose levls
increased lipolysis (and hence DKA)
increased protein degradation
What are the types of insulin? What examples of them might there be?
Meal time insulin - aspart
Longer acting insulin - Zinc
What allows the body to produce more insulin at mealtimes?
The incretin effect
stimulates endocrine cells, GLP-1 release
What binds iodine to tyrosine residues in thyroglobulin molecules?
thyroperoxidase
What enzyme forms T3 from T4?
deiodinase
How does TSH increase T3 production?
It binds to the TSHR’s on the basolateral membrane of the thyrocytes, causing an increase in Na/I symporters on the membrane, increasing the iodine presence within the cell
How would you test for thryoid function?
TSH and T4/T3 levels
What are the 3 main causes of Hyperthyroidism?
Graves’
Toxic nodular goitre
Thyroiditis: inflammation
What causes Grave’s disease?
pathogenic antibodies bind to TSH receptors on thyrocytes
What causes neonatal hyperthyroidism?
How is it treated?
TSH-R antibodies cross the placenta.
Antithyroid drugs
Surgical removal of thyroid
radioiodine therapy
What is the main classification of antithyroid drugs?
Thioamides
they block iodine incorporation through inhibition of thyroperoxidases
What might be a complication of antithyroid drugs?
Argranulocytosis
Liver disease with propylthiouracil
What are the complications of a total thyroidectomy?
hypothyroidism
Hypoparathyroidism (- Ca levels)
Recurrent laryngeal nerve damage
What might cause hypothyroidism?
Hashimoto’s hypothyroidism (autoimmune)
iodine deficiency
silent thyroiditis
What is cretinism?
congenital hypothyroidism, causing stunted mental and physical growth
How would the presence of thryoid nodules be investigated?
Serum TSH, T3/T4
Assessment of thyroid size (imaging)
Assessment of thyroid pathology
How would an ultrasound scan be useful for investigating thyroid pathology?
differentiates between cystic and solid nodules
What are the phases of insulin release?
1 - within 2 minutes of food ingestion, lasts 10-15 minutes
2 - sustained until normoglycaemia restored
What are the subunits of the insulin receptor?
2 alpha (extracellular) 2 beta (transmembrane, tyrosine kinase)
How are pre-diabetic treated?
Nicotinamide (DNA repair)
Who would be prescribed Metformin?
diabetics with a BMI over 25
What are the 3 main dosal regimes of insulin?
Short acting (3x daily) + and intermmediate/long acting one pre-mixed short + intermmediate insulins 2x daily continuous infucion
What are the 3 main complications of insulin therapy?
Hypoglycaemia
Allergy
lipodystrophy
What is diabetes type 2 caused by?
A loss of 1st phase insulin secretion, and hence insulin resistance
How does Metformin work?
It is a hypoglycaemic agent. Reduces gluconeogenesis in the liver.
Activates AMP-activated protein kinase, decreasing gene expression.
Increases Glucose uptake in muscles.
How do sulphonoureas work?
They bind to SUR’s on B cells (a part of K(ATP) channels), causing the depolarisation of the membrane, increasing insulin secretion
Who shouldn’t be given sulphonoureas?
Pregnant or breastfeeding women
What do thiazolidinediones do?
bind to transcription factors, increasing lipogenesis, decreasing gluconeogenesis and increasing glucose uptake
What are the two forms of drugs based on the incretin effect?
Inhibitors of DP-4
GLP-1 agonists
How do SGLT2 inhibitors work?
increase glucose and Na+ loss in the proximal tubule
How does PTH increase calcium levels?
Stimulates osteoclasts to release calcium into plasma (and reabsorption in Distal CT)
Ultimately activates Vitamin D (via 1-alpha hydroxylase) which causes Ca2+ absorption in the GIT, and reabsorption in the proximal tubule
Where does Vitamin D come from?
UV light converts 7-dehydroxycholesterol in the skin to Vitamin D3, which is then converted into calcidiol in the liver, which is then converted to 1,25 dihydroxy VD3 in the kidney
Which of PTH or Calcitonin is more important?
PTH
What is FGF23?
It is produced by osteocytes, and responds negatively to phosphate, it increases renal excretion of phosphate and suppresses renal synthesis of 1,25D3
What are osteocytes?
Found in the calcified matrix, with long processes contacting other osteocyes and osteoblasts
What are osteoblasts?
bone forming cells
What are osteoclasts?
bone reabsorbing cells
attached to bone by integrins
They can sometimes dig the Howship’s Lacuna
What are the different forms of hyperparathyroidsm caused by?
primary - PT tumour
secondary - renal disease, decreased activation of Vitamin D
tertiary - PT hyperplasia
What is Rickets caused by?
Vitamin D/Calcium deficiency.
lack of mineralisaiton
osteoid at growth plates are weak, so the growth plate expands to compensate.
What is the difference between rickets and osteomalacia?
Rickets - affects growing bones
Osteomalacia - affects adult bones
Name 2 types of antithyroid drugs
What enzymes do they target?
Propylthiouracil - deiodinase
Carbimazole - thyroperoxidase
What is the active form of carbimazole?
Methimazole
