Endocrine system

Endocrine system

1. Autocrine

   • Released then acts on self

2. Paracrine

   • Acts on nearby cells

3. Endocrine

   • Released into blood- distant cells

4. Neuroendocrine

   • Released by neurone into blood stream- distant cells

5. Hormones

   • Steroids
     • Steroidogenesis
       • Cholesterol
         • Mineral corticoids
           • Glucocorticoids
             • Androgen
               • Oestrogen
               • Zona reticularis
                 • Adrenal gland
                   • Medulla
                     • Epinephrine and norepinephrine
                       • Catecholamines= epinephrine, norepinephrine and dopamine 
                   • regulated by
                     • hypothalamus
                     • RAA system
                   • arterial supply
                     • Inferior phrenic
                       • Abdominal aorta
                     • Renal arteries
                   • Venous drainage
                     • Right suprarenal veins
                       • Drains direct into IVC
                     • Left suprarenal veins
                       • Renal veins first
                         • Then IVC
             • Cortisol
               • Breaks down protein into amino acids to make glucose, rises blood glucose levels. Also glycogenolysis 
               • Too much= cushings
                 • Weight gain
                 • Bruise easily
                 • Muscle/bone aches
                 • loss of labido
                 • Causes
                   • tumour in pituitary gland
                     • lots of ACTH
                     • uncommonly can develop in lungs and produce ACTH
                   • Current corticosteroid medication
             • Zona fasciculata
           • Progesterone
           • Zona glomerulosa
             • Adrenal gland
           • aldosterone
     • Lipid soluble
       • Pass through plasma membrane to bind with receptor in cell
   • Peptide/ protein hormones
     • Bind to cell surface receptor
       • G protein coupled receptor
         • inhibitory Gi
         • Adenylyl cyclase
           • Increase in cAMP
             • phospholipases
               • Increase in Ca2+
     • Tyrosine kinase receptor for large peptides
       • Two binding sites, when both bound are a dimer
         • Phosphates bind to tyrosines
   • Amino acid derived
     • From tyrosin-> dopamine-> norepinephrine
     • Water soluble
       • Cell-surface receptor
         • Signal transduction
   • Secretion
     • Episodic
     • Response to stimulus
     • Circadian
       • 24 hour cycle
   • Melatonin secreted from pineal gland
     • regulates circadian cycle
   • Growth hormone works by stimulating the liver to release IGF1
     • insulin like growth factor 1
   • Too much prolactin can be due to
     • adenoma of pituitary
       • adenoma= tumour of the gland Sarcoma= tumour of muscle
     • Dopamine receptor antagonist
       • Dopamine (released from hypothalamus) inhibits prolactin (released from ant. pituitary).  Somatostatin inhibits Growth hormone (same sites) 
     • Lesion blocking dopamine delievery

6. Corticotrophin releasing hormone CRH (hypothalamus)

   • Adrenocorticotrophic hormone ACTH (ant. pitutary)
     • Cortisol
     • Pituitary = hypophysis

7. Blood glucose

   • glycaemic index
     • how quickly a food triggers rise in blood sugar
     • 50-100
   • Controlled in pancreas
     • acini
       • exocrine function
         • digestive enzymes for GI
           • Emptied into ampulla of vater
             • sphincter of oddi controls the release
     • islets of Langerhans
       • insulin
         • released when too high
         • beta cells
       • glucogon
         • released when too low
         • alpha cells
       • Somatostatin
         • delta cells
         • Stops both insulin and glucagon
           • by paracrine
     • Anatomy
       • Body
       • Head
         • Cancer most common here
           • Presents with jaundice or pancreatitis
       • Uncinate process
         • Bit that curves round
     • Hypoglycaemia
       • Treat with beta blockers
         • In type 2 diabetes
           • Decrease in insulin produced
   • Diabetes
     • Type 1
       • no insulin produced
       • Complication
         • Diabetic ketoacidosis
           • No insulin
             • So cells have no glucose
               • So break down fat instead
                 • Producing ketones
     • Diabetic annual review
       • Purpose
         • Screen for complications
         • Check education
         • Identify risk factors
       • Before appointment
         • HbA1c
           • looking at glycated haemoglobin i.e. Hb with glucose attached, which is directly proportional to the amount of glucose in the blood
         • Cholesterol
           • HDL, LDL, ratio between them, total cholesterol, triglycerides
         • Creatine, U&Es
         • EMU for microalbumin/creatine ratio
           • EMU= early morning urine
         • BP
         • BMI
         • Waist/Hip ratio
         • Urinalyis
           • For blood, protein, ketones, glucose
         • Visual acuity
       • At appointment
         • Discuss results
         • General wellbeing
         • Examination
           • Feet- deformation, innervation, blood supply, ulcers BP
           • Foot examination
             • Use tuning fork
             • Inspection
               • between toes as well
             • Palpate
               • Foot pulses
             • Monofilament
               • pointy thing
                 • start with big toe, then metatarsals
         • Identify risk factors
           • hypoglycaemia frequency and occurrence  Diet Weight Exercise
         • Assess educational needs
           • Diet, exercise, self-administering medicine, self-monitoring, understanding risk and tx targets 
         • Issues/questions from patient
         • Agree tx plan
           • Targets for next year Review if poor control Refer for educational needs
         • Complications screen
     • Insulin
       • Kept in a fridge
       • Inject SC
         • don't withdraw needle
       • Hold for 6 secs
   • hypoglycaemia
     • hungry, headache, sweating, tired, seizures, coma, nausea, palpitations, pallor
     • Blood glucose <3mmol/L
       • Pathological <2.5mmol/L
     • Diagnosis
       • Low blood glucose
       • Symptoms of hypoglycaemia
       • Symptoms resolve after tx
     • Causes
       • Diabetic
         • To much insulin
         • Alcohol, illness, injecting into scarred site, exercise
       • Not diabetic
         • Endocrine disorders
           • CAH, Addison's disease,&nbsp;
         • liver/gut disease
           • Liver failure Alcohol abuse
         • Other
           • Malignancy, hypothermia, malaria
     • Treatment
       • Quick acting carb
         • 10-20g glucose
           • 2 teaspoons of sugar
             • Glucogel
               • 20% glucose
                 • 1mg glucagon IM
       • Long acting carb
     • Hyperglycaemia
       • Diabeteic ketoacidosis
       • Hypoosmolic Hyperglycaemia State
   • Monitoring
     • Finger prick test
       • Clean with alcohol wipe
       • Patient wash hand with soap and water
       • Insert test strip
       • Use single use lancet device in side of patient's finger
       • Wait 10 seconds then put on test strip
   • Glucose control
     • Stays between 4-6mmol/L
     • Glycogenolysis
       • Glycogen broken down into glucose-6-phosphate
       • After meals peaks then drops quickly
     • Gluconeogenesis
       • Makes glucose from lactate and amino acids
         • Protein breaking down
       • Last thing at night
     • Diet
       • Food raises blood glucose
     • How to decrease blood glucose
       • Insulin
         • Anabolic
           • building things up using energy
         • Lipogenesis
           • triglyceride
         • Glycogenesis
           • Glycogen
         • Protein synthesis
           • Protein
     • How to increase blood glucose
       • Glucagon
         • From a cells in pancreas Increased between meals (i.e. when blood glucose is lower) Short half life
         • catabolic
           • breaking things down and producing energy
       • Cortisol
         • Twice a day Chronically elevated in stress
       • GH
       • Adrenaline
         • Acute stress Prolonged exercise
       • Lipolysis
         • Free fatty acids
           • Ketone bodies
             • Brain can use these
       • Glycogenolysis
       • Gluconeogenesis
   • postprandial= mild dip in blood glucose after a meal

8. Thyoid

   • Arterial supply
     • Superior
       • External carotid
     • Inferior
       • Thyrocervical
         • Subclavian
   • Venous supply
     • Inferior
       • Brachiocephalic
     • Middle and Superior
       • Internal jugular
   • Embryology
     • Foramen Cecum
       • Tongue base
       • Thyroglossal duct
         • Thyroid
         • Should close
           • if doesn't close in adulthood= abnormal
             • Midline swelling
   • Produces calcitonin
     • Reduces calcium levels
       • blood calcium
       • hypocalcaemia mostly caused by vitamin D
     • Opposite of parathyroid hormone
       • Hypercalcaemia in hyperparathyroidism
         • Abdo pain, polydipsia, polyuria, dehydration
   • Goitre
     • Swelling of thyroid
       • Hyperthyroidism
         • aka thyrotoxicosis&nbsp;
         • Causes
           • Grave's disease
             • CD4 cells stimulate B cells to make TSI antibodies which stimulate thyoid
             • Autoimmune
             • thyroid stimulating immunoglobulins
         • Symptoms
           • Anxiety
           • Hyperactivity
           • Weight loss
           • Muscle weakness
           • Dry skin
         • Tx
           • thionamides
           • Anti-thyroid drugs
             • Carbimazole
         • decreased TSH, increased T4
         • Secondary
           • Increased TSH increased T4
         • Complication
           • thyrotoxic storm
             • tx: beta blocker
       • Hypothyroidism
         • reduced thyroxine
         • Causes
           • Iodine defiency
           • Hashimoto's disease
             • CD4 cells recruit B cells to make antibodies against thyroid and CD8 cells to destroy thyroid.
             • Auto-immune
             • Thyroid peroxidase antibodies present
               • in Graves as well
         • Symptoms
           • Cold
           • Weight gain
           • Tired
           • Brittle hair and nails
           • Depressed
           • Constipated
           • Slow reflexes
         • Increase TSH
         • Can lead to anaemia
         • Secondary= low TSH= low T4
       • Lack of iodine
   • Thyrotropin releasing hormone TRH
     • Thyrotropin (thyroid stimulating hormone) TSH
       • Normal levels: 0.4-3mlU/L. Also causes hyperproliferation of thyroid cells TSI= antibodies which mimic TSH
       • Thyroxine (T4)
         • normal levels: 0.8-2 T3 and T4 are formed from tyrosine -&gt; thyroglobin-&gt; thyroxineT4 converted to T3 (active) via iodinase
         • Thyroid hormone receptor
           • TRa1,2 TRb 1,2 TRa2 (T3 only) Receptors are in the nucleus
         • Bound to protein
           • Thyroxine binding globule TBG Transthyretin TTR Albumin&nbsp;
       • T3 triiodothyronine
         • Normal free levels: 2.4-4.2
         • Active thyroxine
           • 20% released directly from thyroid. Rest is converted by kidneys and liver from thyroxine.&nbsp;
       • Need iodine
         • Iodine is now in salt
   • Thyroid autoimmune disorders associated with type 1 diabetes
     • Lots of T3/4 promotes hyperlycaemia
       • Makes more glucose absorbed More glycogenolysis and gluconeogenesis Increases insulin clearance

9. Terms

   • permissiveness
     • one hormone influences another
     • not enough GF nother enough T3
     • T3 increases number of binding sites for epinephrine
   • Synergism
     • More hormones are better than one to create an affect
       • FSH and testosterone
   • Antagonism
     • one hormone prevents the other from working
       • Somatostatin prevents glucagon and insulin
   • Tropic gland
     • Gland which releases a hormone to affect another gland
   • Endocrine disorders
     • Primary
       • Peripheral gland
     • Secondary
       • Tropic gland

10. Investigations of pituitary disease

    • Urine and electrolyte sample
    • Blood sample
    • Renal function
    • MRI of pituitary/ hypothalamus
      • CT
        • calcium deposit in cancer
    • Lateral skull XR
      • enlarged pituitary fossa