Week 1 Flashcards
What are some common problems in insulin treatment?
Giving an incorrect dose
Omitting insulin (forgetting, if ill etc.)
Giving the wrong type of insulin
Which structure in the neck is the first complete cartilagenous ring (if travelling superiorly to inferiorly)?
The cricoid cartilage
The thyroid cartilage isn’t a complete ring!
How many ATP are produced per glucose molecule?`
36
The carotid sheaths blend inferiorly with which structure?
At what level does the common carotid bifurcate, and which branch remains within the carotid sheath?
Blends with the mediastinal fascia
Bifurcates at the level of C4, and the internal carotid artery remains within the carotid sheath
Very generally, how do Type I and Type II Diabetes Mellitus differ?
Type I - loss of most of the beta cells responsible for secreting insulin, resuling in high levels of blood Glucose
Type II - beta cells lose the ability to sense changes in blood Glucose due to hyperglycaemia taking Glucose concentrations outwith the Km of Glucokinase, the beta cells have “been worked very hard and are likely to be very stressed”
Can hormones bound to a carrier molecule cross capillary walls and activate receptors?
No - only ‘free’ (i.e. unbound) hormones can cross the capillary wall
Glucagon (lowers/raises) blood glucose.
How does it do this?
What other hormone is involved?
Glucagon raises blood glucose
It does this by stimulating hepatic glycogenolysis and gluconeogenesis
Unlike insulin, it does not affect the uptake of glucose into muscle and adipose tissue. However, adrenaline does inhibit this, resulting in an increased plasma glucose
How is control of Diabetes measured?
Home blood glucose monitoring - used in day-to-day diabetes management and allows for adjustments in insulin dose, but only provides a snapshot at one particular time point. Continuous glucose monitoring provides the whole picture
Urinalysis to measure ketones and glucose
HbA1c measurements
What are some of the functions that carrier proteins provide?
Allow for a reserve of hormones
Increase the amount of hormones transported in the blood
Extend the half-life of the hormone in circulation
Describe the synthesis and structure of insulin
Synthesised in the Rough ER of pancreatic Beta cells as a larger single chain prehormone - Preproinsulin
Preproinsulin is then cleaved to form Insulin
Insulin contains 2 polypeptide chains linked by disulphide bonds
What is the early clinical effect on vision of a pituitary gland tumour?
A pituitary tumour will initially result in midline compression of the optic chiasm
This results in disruption of the action potentials from the nasal retinas, meaning the patient loses the ability to see structures in the temporal side of the visual field, bilaterally
This is known as bilateral hemianopia
Insulin (lowers/raises) blood glucose.
How does it do this?
Insulin lowers blood glucose by inhibiting hepatic glycogenolysis and gluconeogenesis
It also stimulates uptake of glucose into muscle and adipose tissue
In embryological development, at what time does the thyroid gland reach its final position in relation to the larynx/trachea?
7th week of development
How does T1DM classically present?
Is there typically evidence of microvascular disease at the time of diagnosis?
Pre-school and peri-puberty, with a small secondary peak in late 30s
Usually lean
Acute onset and severe weight loss, thirst, polyuria
Weakness, fatigue, lethargy, blurred vision. Possibly presenting with thrush
Ketonuria +/- metabolic acidosis
Typically no signs of microvascular disease at the time of diagnosis
Name to surgical approaches to accessing the pituitary fossa
Transcranial - under the frontal lobe
Transsphenoidal - via the nasal cavities and sphenoid sinus
What is the name of the structure that connects the Hypothalamus to the Pituitary gland?
The infundibulum
What are the blood glucose targets in insulin treatment pre- and post meal?
3.9-7.2 mmol/L pre-meal
<10 mmol/L 1-2 hours following a meal
Insulin is a hormone of the ____ state.
What happens to Insulin upon feeding? What is it’s action?
FED state
Insuline is RELEASED from pancreatic beta cells in response to feeding. This results in a LOWERING of blood Glucose
To what group do the platysma muscles belong to? What is their nerve innervation?
The muscles of facial expression
The facial nerve (CNVII)
What structures lie near the Thyroid gland?
Describe the order of contents in the Carotid Sheath
Thyroid gland is covered in pretracheal fascia
Trachea (anterior) and Oesophagus (posterior) lie in the centre line. In between these are the Recurrent Laryngeal Nerves
Either side of the Thyroid gland, outside the pretracheal fascia, are the carotid sheaths, and laterally to medially these go Internal Jugular Vein, Vagus Nerve, Carotid Artery
What common embryological variations are seen in the thyroid?
Pyramidal lobe - 28-55% prevalence, most commonly originating from the left lateral lobe
Incomplete/missing isthmus
What structures are found within the carotid sheath?
Vagus nerves
Carotid arteries - common then internal
Internal jugular vein
Deep cervical lymph nodes
In the transsphenoidal transnasal surgical approach to the pituitary, which sinuses of which bone need to be passed through?
This approach requires the surgical fracture of the nasal septum, as well as the floor and roof of the sphenoid sinuses, which are located in the sphenoid bone
Describe the secretion of Insulin
Glucose enters Beta cells through the GLUT2 glucose transporter and is phosphorylated by glucokinase
This increased metabolism of Glucose results in an increase in intracellular ATP, which inhibits the ATP-sensitive K+ channel, KATP
Inhibition of KATP = depolarisation of cell membrane = opening of voltage-gated Ca2+ channels
Opening of Ca2+ = fusion of secreteory vesicles with cell membrane = RELEASE OF INSULIN
Generally, what is the difference between the anterior and posterior lobes of the pituitary gland? What do they secrete?
Anterior Lobe
- more glandular than posterior lobe due to different embryological origin
- Secretes:
- Thyroid stimulating hormone (TSH)
- ACTH
- FSH and LH
- Growth Hormone (GH)
- Prolactin
- Endorphins
Posterior Lobe
- collection of nerve cells
- embryologically originates in the hypothalamus and migrates downwards
- Secretes:
- ADH (a.k.a. vasopressin)
- Oxytocin
What is an insulin pump?
medical device that acts as a continuous administrator of short-acting insulin
Delivers a background insulin dictated by basal rate
Delivers a manually activated bolus of insulin to cover meals
For each of the following, state whether they are pre-synthesised and stored or synthesised and released on demand
- Amines
- Peptides and proteins
- Steroids
Amines - pre-synthesised and stored in vesicles, then released in response to Ca2+-dependent exocytosis
Peptides and proteins - as with amines, pre-synthesised and stored in vesicles, then released in response to Ca2+-dependent exocytosis
Steroids - synthesised from cholesterol and secreted on demand
What is the definition of Type I DM?
A state of absolute insulin deficiency
“in all probability caused by an environmental trigger in a genetically susceptible individual mediated for the most part by an autoimmune process of varying degree of severity within the pancreatic beta cell
At the level of what cartilages does the isthmus lie?
Anterior to the 2nd and 3rd cartilages of the trachea
Briefly describe insulin physiology in the healthy individual
Insulin is secreted at a low basal rate, which accounts for approx 50% of total insulin production
Post-prandial insulin is secreted in response to post-meal surges in glucose
Briefly describe age of onset, family history and duration/severity of symptoms in the various types of Diabetes listed below:
- Type I
- Type II
- Monogenic
- Secondary
Type I
- Age - peaks <5 and between 10 and 14
- Family history - possible
- duration/severity - short, severe
Type II
- Age - unusual in under 25s
- Family history - frequent, 30%
- Duration/severity - months, usually mild
Monogenic
- Age - neonate to adulthood
- Family history - almost always
- Duration/severity - months, usually mild
Secondary
- Age - usually later in life
- Family history - rare
- Duration/severity - weeks/months, severity depends on cause
Cell types in the pancreatic islets - what do each secrete?
- Alpha cells
- Beta cells
- Delta cells
- PP cells
Alpha - GLUCAGON
Beta - INSULIN
Delta - SOMATOSTATIN
PP - PANCREATIC POLYPEPTIDE
What anatomical structure in the osteology of the skull does the pituitary gland sit in?
Pituitary gland is a midline structure in the pituitary fossa of the sphenoid bone
The pituitary fossa lies within the sella turcica (Turkish saddle)
Through what transporter does glucose enter beta cells?
How does a change in glucose conc. affect glucokinase activity?
Glucose enters beta cells via GLUT2 glucose transporters and is phosphorylated by glucokinase
Change in glucose conc results in a dramatic change in glucokinase activity
Name the specific carrier molecules for the following steroids
- thyroxine (T4)
- cortisol
- sex steroids (testosterone and oestradiol)
What are some “general” carrier proteins that are worth knowing?
Thyroxine - thyroxine-binding globulin (TBG)
Cortisol - cortisol-binding globulin (CBG)
Sex steroids - sex steroid-binding globulin (SSBG)
Albumin and Transthyretin bind both steroids and thyroxine
Describe the phasic pattern of Insulin release.
Why does this occur?
Biphasic - 1st initial larger spike, followed by a 2nd phase
5% of insulin granules are immediately available for release (RRP - readily releasable pool)
The ‘Reserve Pool’ must undergo preparatory reactions to become mobilised before it is available for release
What structures are found within the pretracheal fascia?
(Located anteriorly)
Oesophagus
Trachea
Thyroid gland
Strap muscles
Recurrent laryngeal nerves
What two courses on Diabetes management are made available to everyone diagnosed?
DAFNE (dose adjustment for normal eating) and TIM (Tayside insulin management)
Name some Short Acting and Rapid Acting forms of Insulin
Short Acting
- Humulin S
- Actrapid
- Insuman Rapid
Rapid Acting
- Humalog
- NovoRapid
- Apidra
Where is the precursor to insulin formed, and what is it cleaved into?
Large, single prehormone called preproinsulin is formed in the rough ER of pancreatic beta cells
Cleaved to form insulin and C-peptide
Describe the two layers of Strap Muscles
Superficial Layer
- Sternohyoid - travels from the Hyoid bone to the body of the sternum
- Omohyoid - has 2 bellies - superior and inferior, with a fascial sling attaching the intermediate tendon between the two bellies to the clavicle
Inferior Layer
- Thyrohyoid - attaches the Hyoid to the Thyroid
- Sternothyroid - attaches the Thyroid to the Sternum
What are some of the environmental triggers of T1DM?
viral factors
maternal factors
weight gain
What pattern of insulin administration is the Gold Standard for mimicking normal insulin release?
Basal bolus - take a long-acting dose once a day (in the evening) and a bolus of rapid-acting insulin before each meal
What is glycated haemoglobin?
HbA1c
Formed by non-enzymatic glycation of haemoglobin on exposure to glucose
Increases in a predictable way in response to glucose
Used as a measure of average blood glucose over a prolonged period of time (e.g. a couple of months)
Describe the visual pathway of the optic nerves through the skull, and how signals travel down this pathway in response to light hitting the temporal and nasal retinas
The left and right optic nerves (CNII) form the optic chiasm, which lies directly superiorly to the pituitary gland.
From the optic chiasm, the optic tracts pass posteriorly
After synapsing in the thalamus, the next axons in the chain pass via the optic radiation to the visual cortex in the visual lobe.
Light hitting the temporal retina travels on the same side of the visual pathway
Light hitting the nasal retina travels on the opposite side of the visual pathway
What structures are found within the investing fascia?
Encloses all other neck fascial compartments
Also encloses 2 pairs of muscles:
- Trapezius
- Sternocleidomastoid
Give some of the biological effects of insulin
Increases uptake of amino acids into muscle
Increases DNA synthesis
Increases protein synthesis
Growth responses
Increases glucose uptake into muscle and adipose tissue
Lipogenesis in adipose tissue and liver
Glycogen synthesis in liver and muscle
What are the two options of prandial insulin available? How long do they last, when do they peak, and what are some examples?
Insulin analogue (majority of T1DM patients)
- NovoRapid, Humalog and Apidra
- Onset 10-15 mins
- Lasts 4-5 hours, with peak action at 60-90 mins
Soluble Insulins
- Actrapid, Humulin S
- Onset 30-60 mins
- Lasts 5-8 hours, with peak action at 2-4 hours
Describe venous drainage in the skull
What venous drainage surrounds the pituitary gland?
Venous channels are made via folds in the Dura mater - these Dural Venous Sinuses drain venous blood, but aren’t actually veins
The pituitary gland is surrounded by the cavernous and intercavernous sinuses
1 unit of insulin equals how many grams of carbohydrate?
10 grams
How does the activity of Glucokinase change in response to Glucose?
Small change can result is a dramatic change in Glucokinase activity
What is the name of the thick adherent material that covers all of the internal aspects of the cranial vault?
What is the name given to the “tenting” of this structure over the cerebellum?
What is the name given to the area where this structure covers the pituitary fossa?
The Dura Mater
The Tentorium cerebelli
The Diaphragm sellae
How is diabetes diagnosed? (3 different ways)
- Symptoms of hyperglycaemia (polyuria, polydipsia, unexplained weight loss, visual blurring, genital thrush, lethargy) AND Raised venous glucose detected once - fasting of 7mmol/L and above or random of 11.1mmol/L and above
- Raised venous glucose on 2 separate occasions - fasting of 7mmol/L and above or random of 11.1mmol/L and above or oral glucose tolerance test (OGTT) - 2hour value of 11.1mmol/L and above
- HbA1c of 48mmol/L and above, but below doesn’t exclude DM
What level of blood glucose should Insulin be released in response to?
Above 5 mM
Briefly describe the possible complications at presentation, ketone levels and weight loss in the following types of Diabetes:
- Type I
- Type II
- Monogenic
- Secondary
Type I
- Complications - never(?)
- Ketones - +++
- Weight loss - usually seen
Type II
- Complications - up to 30%
- Ketones - usually none
- Weight loss - not usually
Monogenic
- Complications - unusual
- Ketones - usually none
- Weight loss - not usually
Secondary
- Complications - unusual
- Ketones - ++/-
- Weight loss - depends on the primary cause
What hormones does the anterior pituitary secrete? Bonus points for what hormone they are triggered by (6)
ACTH - (corticotropin-releasing hormone)
LH/FSH - (Gonadotrophin-releasing hormone)
TSH - (thyrotropin releasing hormone)
GH - (growth hormone-releasing hormone)
PRL - (dopamine)
What are the clinical features of Bardet-Biedl Syndrome (hint: Diabetes is one of them!)
often very obese
polydactyly (extra fingers)
hypogonadal
visual and hearing impairment
mental retardation
diabetes
What 4 key checks should be done prior to giving a patient insulin?
- verify the type and amount of insulin with the patient if possible BEFORE ADMINISTRATION
- Only use specific insulin syringes for administration
- ALWAYS ensure a second independent check of insulin doses prior to administration
- Glucose should be used for all IV insulin infusions, except in cases of DKA
- (never give more than 6 syringes at any one time, and avoid abbreviations when documenting doses etc.)
What two components make up the diencephalon?
The Thalamus and the Hypothalamus
In normal function, at what threshold of blood glucose do beta cells secrete insulin?
What pattern of release is seen?
Above 5 mM
A biphasic release is seen in insulin resistance, with a large initial peak and a secondary smaller peak
What 2 proteins does the KATP channel consist of?
What class of drugs directly inhibits KATP, and therefore increases Insulin release?
What drug stimulates KATP, and therefore inhibits Insulin release?
Kir6 - inward rectifier subunit - pore subunit
SUR1 - a sulphonylurea receptor - regulatory subunit
Directly inhibited by the sulphonylurea class of drugs e.g. tolbutamide, glibenclamide
Diazoxide stimulates KATP, and therefore inhibits Insulin release
What structures pass through the cavernous sinuses?
Where do the dural venous sinuses drain into?
The internal carotid artery passes through the cavernous sinuses, as do Cranial Nerves III, IV, V1 and V2
The dural venous sinuses drain into the internal jugular veins at the jugular foraminae,
What structures are found within the prevertebral (deep) fascial compartment?
Postural neck muscles
Cervical vertebrae
What two forms of insulin are included in mixed administrations? Give some examples
Mixed insulin is made up of either Short or Rapid Acting and Intermediate
Rapid Acting/Intermediate mix
- Humalog Mix25/Mix50
- NovoMix30
Short Acting/Intermediate mix
- Humulin M3
- Insuman Comb 15, 25, 50
From Superior to Inferior, what are the three parts that make up the brainstem?
Midbrain
Pons
Medulla (oblongata)
What arteries supply the brain?
The left and right vertebral arteries come together to form the Basilar artery which flows into the Circle of Willis
The left and right internal carotid arteries also feed into the Circle of Willis
What surgical fracture of the skull can be used to access the pituitary gland in more complicated cases?
Le Fort I fracture
What issue may occur at the injection site when administering insulin? How is this avoided?
Lipohypertrophy can occur - build up of fat at injection site, preventing the absorption of the insulin injection
This is prevented by ensuring that the patient is rotating their injection sites
Ask to look at the patient’s injection site to assess
What antibodies are present in T1DM?
Usually characterised by the presence of anti-GAD/anti-islet cell antibodies
What are the typical presenting symptom of T1DM?
Classic Triad
- polyuria
- polydipsia
- weight loss
Fatigue
Blurred vision
Candidal infection
Ketoacidosis
What are the two options of basal insulin available? Again, give examples of each, duration and peaks
Isophane basal insulins
- Insulatard, Humulin I
- Duration of 12 hours, with peak of activity 4-6 hours
Analogue basal insulins
- Lantus, Levemir
- Longer duration of activity than the above, but less of a peak seen (flatter profile)
What are the aims of therapy in treating T1DM?
Prevent hyperglycaemia
- thirst, tiredness, blurred vision, weight loss, polyuria, nocturia, fungal infections
- cognitive effects, mood state, information processing, memory
- Potential risk of DKA
Avoid hypoglycaemia
- pallor, sweating, tremor, palpitations, confusion, nausea, hunger
- tense-tiredness, poor information processing and working memory, coma
Reduce chronic complications
- avoidance of micro/macrovascular disease
- avoidance of acute metabolic complications
Of the three nasal concha, which is the only one that exists as a bone it it’s own right?
The inferior nasal concha is the only concha to exist as a bone in it’s own right
The superior nasal concha and middle nasal concha are both parts of the ethmoid bone
Which HLA types are associated with T1DM?
HLA-DR3 and HLA-DR4
What is the name of the bridging section between the right and left lobes of the thyroid gland?
The isthmus
Describe the route of the Vagus Nerve (CNX), superiorly to inferiorly
Branches from the medulla oblongata, then exits the skull through the jugular foramen and travels within the carotid sheath
Descends through the chest and splits:
- Right - lateral to the trachea
- Left - left side of the aortic arch
- Both - posterior to the lung hilum and on the oesophagus
Both Vagus Nerves pass through the diaphragm with the oesophagus
Divide into their terminal branches on the surface of the stomach and supply the abdominal organs with parasympathetic axons to the distal midgut
What caution must be taken when administering insulin to ensure the patient is receiving the correct dose?
That the right type of insulin is being given and with an appropriate syringe…
Insulin syringes deliver 1 unit of insulin, and using a non-insulin syringe can lead to gross inaccuracies in insulin amount
How much of a steroid is biologically active at any one time?
Only 10%!
Steroids are hydrophobic and have to be transported bound to plasma proteins. In this form, they are not active i.e. only unbound steroids are biologically active
What antibody is associated with Coeliac disease?
Anti-TTG antibodies
Define Latent Onset Diabetes in Adulthood (LADA)
When would you suspect it?
presence of elevated pancreatic auto-antibodies in patients with ‘recently diagnosed’ diabetes who do not initially require insulin
Suspect when…
- age 25-40
- male preponderance
- usually non-obese
- auto-antibody positive
- associated autoimmune conditions
- non-insulin requiring at diagnosis
What non-insulin adjunct therapies can be used in the treatment of T1DM?
Metformin
Leptin
GLP-1
SGLT-2
(all of these protect beta cells, maybe not Metformin?)
What structures do the left and right Recurrent Laryngeal Nerves pass under?
How might injury to the Recurrent Laryngeal Nerves present?
Left RL Nerve passes under the arch of the aorta
Right RL Nerve passes under the right subclavian artery
Injury to the RL Nerves can affect phonation i.e. ability to make noise with the larynx, as seen in hoarseness causes by metastatic throat cancer
Name the four fascial compartments found in the neck
Prevertebral (deep) fascia
Investing fascia
Carotid sheaths (x2)
Pretracheal fasica
What is the downside of the twice daily insulin injection regimen?
Individuals need to eat at the correct time or risk hypoglycaemia
What are some of the risk factors and disease markers for clinical diabetes?
Risk factors (accelerating factors)
- infection
- insulin resistance
- puberty
- diet/weight
- stress
Disease markers
- raised glucose
- ketones
- low insulin
- low beta cell mass
- low C-peptide
Name some Intermediate Acting forms of Insulin
Insulatard
Humulin I
Insuman Basal
Describe the arterial blood supply to the thyroid and parathyroid glands, along with the vessels they originate from.
What anatomical variation exists in quite a large proportion of people and must be kept in consideration when performing a tracheotomy?
TWO IN
Thyroid and Parathyroid are supplied by the Superior and Inferior Thyroid arteries (parathyroid is mostly done by inferior)
Superior Thyroid artery is a branch of the External Carotid artery
Inferior Thyroid is a branch of the Subclavian artery
The Thyroid Ima artery is a common variation, and branches from the Right Common Carotid artery, running up the midline to supply the Thyroid gland at the Isthmus
Describe the anatomy of the sternocleidomastoid muscle, including attachments, nerve innervation, and close venous anatomical relations.
Where are these veins located and where do they drain to?
2 heads
- Sternal head - attaches to the manubrium of the sternum (inferiorly), and the mastoid process of the temporal bone (superiorly)
- Clavicular head - attaches to the medial end of the clavicle, and the mastoid process of the temporal bone (superiorly)
Innervation
- Spinal accessory nerve (CNXI), also supplies the Trapezius
Close anatomical relations
- External jugular vein - runs within the superficial fascia, drains into the subclavian vein
- Anterior jugular vein - runs within the superficial fascia, and drains into the external jugular vein
What fascial compartment does the platysma sit in?
In the superficial fascia of the neck
Describe the venous drainage to the Thyroid and Parathyroid glands, along with the vessels they drain to.
THREE OUT
Superior Thyroid vein - drains to the internal jugular vein
Middle Thyroid vein - drains to the internal jugular vein
Inferior Thyroid vein - both left and right drain to the left brachiocephalic vein
At what ages do the various types of diabetes mellitus typically present?
Neonatal - just after birth
T1DM - at any point between 1 year old and up to 30s. Peaks seen around 10-15 and again at late 30s
MODY - early teens to 30s, strong family history component
LADA - basically T1DM diagnosed later on, early 20s and above
T2DM - late teens and above
In a young patient presenting with symptoms of diabetes, a strong family history of diabetes, associated features (e.g. renal cysts) but GAD -ve and C-peptide +ve (produced whenever a molecule of insulin is produced), what might the diagnosis be?
Monogenic diabetes (rare cause of diabetes in which the genetic defect is in only a single gene)
How do sulphonylureas work?
Give some examples of this class of drug
Directly inhibit KATP by binding to SUR1, increasing insulin secretion
Examples - tolbutamide, glibenclamide
At what vertebral level is the thyroid gland?
C5-T1
Classify the following types of Diabetes based on the age of patient in which they may present:
- neonatal diabetes
- T1DM
- T2DM
- MODY
- LADA
- Secondary diabetes (brought about by another condition e.g. cystic fibrosis)
Neonatal - from birth to 1 years old
T1DM - birth to 30s
T2DM - 10 years old onwards
MODY - early teens to 30s
LADA - early 20s to 30s
Secondary diabetes - late teens onwards
Describe the lymph drainage of the Thyroid and Parathyroid glands
The Internal Jugular vein has on its surface the Superior (deep) cervical lymph nodes and the Inferior (deep) cervical lymph nodes
On the RIGHT SIDE, lymph drains into the Right lymphatic duct and then into the Right Venous Angle
On the LEFT SIDE, lymph drains into the Thoracic duct and then into the Left Venous Angle
Further lymph nodes are also present on the trachea, these being the Pretracheal lymph nodes and the Paratracheal lymph nodes
How is diabetes diagnosed?
How is the type of diabetes diagnosed?
- fasting glucose greater than 7 mmol/L
- random blood glucose of greater than 11.1 mmol/L
- and symptoms, OR on repeat of a test
Diagnosing the type of diabetes
- type I is often diagnosed on the history and presentation (e.g. DKA) alone
- if in doubt, GAD/IA2 antibodies and C-peptide may help
What do the lobes of the thyroid gland attach to?
Lateral aspects of the thyroid and cricoid cartilages, and the trachea
What are some of the risk factors and disease markers for pre-diabetes?
Risk factors (autoimmune trigger factors)
- viral infection
- vitamin D deficiency
- dietary factors
- environmental toxins
Disease markers
- Autoantibodies (GAD65, IA2)
- Candidate antigens
- Insulitis
What are the general HbA1c targets for diabetic individuals?
Differs based on the individual (i.e. age etc.), but generally aiming for between 48 mmol/L and 53 mmol/L
Describe the location of the parathyroid glands
Located on the surface of the thyroid gland.
Usually 4 with 2 on each lobe, but anatomical variation is seen - can be 3 on each side, 3 on one and 1 on the other etc.
Glucagon is a hormone of the ____ state.
What happens to Glucagon upon fasting? What is it’s action?
STARVED state
Glucagon is RELEASED from pancreatic alpha cells in response to increased hepatic glucose output, and this RAISES blood glucose
What respiratory condition is Diabetes commonly associated with?
Cystic fibrosis - >25% at 20 years
usually found in ‘severe’ mutations e.g. delta508
prone to complications
Insulin therapy is preferred
What is HbA1c useful for assessing? What % reduction in complications associated with diabetes does a 1% in HbA1c correspond to?
HbA1c is useful for measuring longer-term control of blood glucose
1% drop in HbA1c = 22% drop in likelihood of complications
What is the HLA association with T1DM? What are the highest risk genotypes?
HLA genes represent more than 50% of familial T1DM risk
Highest risk genotypes are DR3-DQ2 and DR4-DQ8, which confer a 19 fold increase in risk
95% of those diagnosed with T1DM under the age of 30 have one or both of these genotypes
Checklist for the newly presenting Diabetic patient
Has diabetes been confirmed?
If so, what type is it? - antibody testing
Is hospitalisation required? - DKA, ketonaemia, significant vomiting
Is he/she at school/college/university?
Are they employed?
Do they drive?
What are some of the causes of type III DM? (think pancreatic diseases, endocrine diseases and drug-induced causes)
Pancreatic disease - chronic/recurrent pancreatitis, haemachromatosis, cystic fibrosis
Endocrine disease - Cushing’s, Acromegaly, Phaeochromocytoma, glucagonoma
Drug-induced - glucocorticoids, diuretics, beta-blockers
Briefly describe how Insulin is normally secreted
Biphasic release in response to meals
- initial rapid phase of pre-formed insulin that lasts 5-10 mins
- slower phase released over 1-2 hours
Insulin is secreted into the portal vein, and is in response to multiple factors
List some of the endocrine glands
- Cranial cavity
- hypothalamus
- pituitary
- Neck
- 4 parathyroid glands (some anatomical variation)
- thyroid gland
- Abdomen
- 2 andrenal glands
- pancreas
- Pelvis (female)
- ovaries
- Perineum (male)
- testes
What type of receptor do the following act on…
- Insulin
- Growth Hormone
- Calcium
Insulin - receptor kinases, binding of insulin causes autophosphorylation
Growth Hormone - JAK2 kinase receptor
Calcium - GPCR
Name some Long Acting forms of Insulin
Lantus
Levemir
What are some of the Autoimmune conditions associated with Diabetes?
Common
- Thyroid disease
- Coeliac disease
- Pernicious anaemia
- Addison’s disease
- IgA deficiency
Rare/V.rare
- autoimmune polyglandular syndromes
- AIRE mutations
- IPEX syndrome
What is the name of the ligament that attaches the Thyroid gland to the trachea?
Cutting this ligament during surgery can risk damage to which nerve?
How might damage to this nerve present?
Berry’s Ligament
The Right Recurrent Laryngeal Nerve runs in very close proximity to Berry’s ligament and surgery here can risk cutting the nerve
Injury to this nerve presents as paralysis of the vocal cords which can be either unilateral (hoarseness/weakness of the voice & weak cough) or bilateral (aphonia, the complete inability to produce sound, and the inability to close the rima glottidis, prevent aspiration or produce a good cough)
What pattern of release does cortisol normally exhibit?
When are they at their highest and lowest?
Diurnal (circadian rhythm) due to external cues e.g. night and day
Highest levels are about noon, and lowest levels are seen overnight. This is important when considering suppression/stimulation testing
