Endocrinology (RE) Flashcards
When is peak incidence of T1DM?
6m-5y
What percentage of T1DMs wont have a FHx of DM?
85% have no family Hx
Which chromosome is strongly linked to T1DM?
Chr 6 - HLA DQ
Group of genes on chromosome 6 that encode the major histocompatibility complex, or MHC, which is a protein that’s extremely important in helping the immune system recognize foreign molecules, as well as maintaining self-tolerance.
MHC is like the serving platter that antigens are presented to the immune cells. Interestingly, people with type 1 diabetes often have specific HLA genes in common with each other, one called HLA-DR3 and another called HLA-DR4.
But this is just a genetic clue right? Because not everyone with HLA-DR3 and HLA-DR4 develops diabetes.
What do the following cells of the pancreas produce?
- Alpha cells
- Β cells
- Δ cells
- Γ cells
- Epsilon cells
Alpha = Glucagon
Βeta = Insulin
Δ = Somatostatin
Γ = Pancreatic polypeptide
Epsilon = Gherkin
What is the pathophysiology of T1DM?
AI destruction of β cells = unable to produce insulin.
Which ABs can be measured to test for T1DM?
GAD
IA2
Zn T8
What is the initial stage of T1DM?
Insulitis - AI destruction is happening but β cells that remain are still able to produce enough insulin. (Honeymoon phase - can be 2-5 years)
What is T1DM associated with clinically?
Other AI diseases = likely the P has more than 1.
What are the symptoms of T1DM?
Thirst
Polyuria
Lethargy
Unintentional weight loss
Recurrent candidiasis
How can you distinguish T1 and T2 DM?
Due to speed of symptom onset - onset if faster in T1 than in T2
What does insulin do?
Insulin promotes membrane trafficking of the glucose transporter GLUT4 from GLUT4 storage vesicles to the plasma membrane, thereby facilitating the uptake of glucose from the circulation.
If there is no insulin - GLUT4 do not bind to the plasma membrane = no uptake of glucose into cells and respiration cannot occur.
How are ketones produced in the body?
When the body doesn’t have enough glucose - it breaks down fat for energy instead - the byproduct of this is ketones.
How is C-Peptide used to diagnose insulin?
Proinsulin is broken into insulin and C-peptide. If you are producing sufficient insulin, you should have elevated C-peptide levels. If you are not producing insulin then there will be no measurable C-peptide.
Therefore C-peptide is low in T1D2 - although will be high in T2DM.
What is the Tx for T1DM?
Basal-bolus regime if 1st line (long acting = basal, bolus = quick-acting to cover meal).
Insulin - given parentally (S/C, inhaled or mucous membranes)
Who qualifies for an insulin pump?
NICE =
12 yr +. T1DM +
- attempts to reach target HbA1c with multiple daily injections = disabling hypoglycaemia
- HbA1c have remained high despite attempts to carefully manage.
What types of insulin are there?
Short (15-20 mins before meal)
Intermediate
Long-acting - single dose per day
Can get ultra strength - bit better for less compliant Ps (teenagers)
What is the process of managing fluctuating blood sugars called?
Dose Adjustment for Normal Eating (DAFNE)
Can also do carbohydrate counting
What is the normal insulin to carb ratio?
1 insulin : 10g carbs
What is the insulin sensitivity factor?
Measure of how much 1 unit of insulin brings the blood sugar down by. On average it is reduced by 3.
What are the S&S of hypoglycaemia?
Shaky / dizzy
Blurred vision
Sweaty
Weak or Tired
Upset or Nervous
Headache
Hungry
What are the S&S of hyperglycaemia?
Dry skin
Extreme thirst
Hunger
Freq urination
Blurred vision
Drowsy
Slow wound healing
When do you need to notify the DVLA if diagnosed with T1DM?
All Ps using insulin need to notify
Impaired awareness of hypoglycaemia or P with more than 1 episode of severe hypoglycaemia whilst awake in past 12m must not drive and need to notify the DVLA.
BG monitoring = mandatory for insulin treated diabetes drivers
What is the role of glucagon?
Glucagon is used to increased blood glucose levels - it makes the liver undergo gluconeogenesis.
What type of respiration can be seen in DKA?
Kussmaul respiration
How is potassium affected in DKA?
Insulin stimulates Na-K ATPase transporters - enables potassium to get into the cells. Lack of insulin = more K+ in the blood.
Also - high levels of H+ from ketone breakdown stimulate H+/K+ pump to pull more H+ into cells and leaves K+ in the blood.
Both = hyperkalaemia. K+ is then excreted - so overall stores of K+ intracellularly start to run low.
How is DKA managed?
Aggressive fluids (help dehydration, insulin and lower BG levels)
Replacement of electrolytes to reduce the acidosis
How does adrenaline affect glucagon?
Stress = release of adrenaline = releases glucagon
What are the two types of complications of T2DM?
Microvascular (retinopathy, neuropathy, nephropathy)
Macrovascular (IHD, CVD, PVD)
What medical emergency is seen in Ps with T2DM?
Hyperosmolar Hyperglycaemic State (HHS)
What is the diagnostic criteria for T2DM?
What test can be done for T2DM?
Oral Glucose Tolerance Test
What is the pathophysiology of T2DM?
Pancreas - apoptosis β cells, dec insulin excretion
Hyperlipidaemia
Liver - inc hepatic glucose output
Muscle - insulin resistance
What are the RF for T2DM?
How does increased fat cause insulin resistance?
Increased fat = increased levels of inflammation (via macrophage activation)
Inflammation impairs oxidative capacity - leads to trigger of insulin resistance.
What are high levels of ectopic fat linked to?
- Hypertension
- Atherogenic dyslipidemia
- T2DM
- Thrombosis
- Atherosclerosis
- Inflammation
What is the definition of metabolic syndrome?
Central obesity
+ 2 of:
- Raised 3Gs (>150)
- Reduced HDL cholesterol (<40 M and <50 F)
- Raised BP (>130/85)
- Raised fasting plasma glucose (>5.6)
What are the benefits of exercise?
How can T2DM be reversed?
Through diet or inc exercise leading to weight changes
How does T2DM cause macrovascular complications?
Raises oxidative stress, inc PKC and AGEs - these damage endothelium - causing vasoconstriction, inflammation & thrombogeneis. This leads to increased atherogenesis.
How is T2DM managed?
What treatment can be given to prevent complications of T2DM?
Cholesterol lowering tx
Antihypertensives
Anti-platelet tx
What BMI qualifies for bariatric surgery?
BMI > 35
What is the MOA of biguanides?
Overall reduction in insulin resistance
Name a biguanide drug?
Metformin
What are the SEs of biguanides / metformin?
NB. Diabetic population are at risk of neuropathy and B12 deficiency can present in the same way (i.e. peripheral neuropathy)
When is metformin contraindicated?
Acute metabolic acidosis - inc lactic acidosis & DKA
eGFR <30
Liver problems
Name a sulphonylurea drug.
Gliclazide
What is the MOA of sulphonylureas?
Blocks the K ATP channels within β cells of pancreas => stimulates insulin secretion
What are the SEs of sulphonylureas?
When are sulphonylureas contraindicated?
Name a DPP4 Inhibitor drug
Sitagliptin
Linagliptin
What is the mechanism of action of Gliptins (DPP4 inhibitors)?
Increases insulin levels and reduces insulin resistance
What are the side effects of gliptins?
When are gliptins contraindicated?
Ketoacidosis
Renal failure
Name an SGLT2 Inhibitor (Flozins)
Dapagliflozin
Canagliflozin
Empagliflozin
What is the MOA of SGLT2 Inhibitors?
Decrease renal tubular glucose absorption - therefore excretes glucose and lowers serum glucose without affecting insulin
Diuretic effect
What are the side effects of SGLT2 Inhibitors?
Name a GLP1 Agonist
Dulaglutide
Exanatide
Liraglutide
Semaglutide
What is the mechanism of action of GLP1 Agonists?
Inc insulin resistance
Inc β cell replication in pancreas and prevents their death
Delayed gastric emptying
Decreased glucagon secretion
What are the benefits of GLP1 Agonists?
Improved BP and lipid profile
Improve HbA1c
Decreased weight
No hypoglycaemia
What are the SEs of GLP1 agonists?
When are GLP1 agonists contraindicated?
What are the side effects of insulin?
What is a state of unrousable unresponsiveness?
Coma
What is obtundation?
Slowed thinking
What is interoception?
Awareness of the state of your body - e.g. sensing breathing, heart beat or internal pain
What is the definition of a coma?
Unrousable unconsciousness - lasting more than 6 hours
Fails to respond to painful stimuli, light or sound
What is the doll’s head manoeuvre?
Typically the doll’s eyes reflex is elicited by turning the head of the unconscious patient while observing the eyes. The eyes will normally move as if the patient is fixating on a stationary object. If there is a negative doll’s eyes reflex then the eyes remain stationary with respect to the head.
Can you describe the criteria for GCS?
What is the lowest GCS score a P can have?
3
What can an acute confusional state indicate?
Delirium
If it fluctuates - classic presentation of delirium
What is a transient loss of consciousness?
Syncope / Blackout
Must be less than 6 hours - otherwise coma
When taking a Hx - what should you ask a P with syncope?
Do they remember falling - can determine whether LOC was due to syncope or hitting head on the floor.
What questions in a Hx about syncope should you ask about the event?
Did anyone see them fall?
How long were they unconscious?
Was there seizure activity?
Urinary incontinence?
Tongue biting?
How fast did they recover?
Is there residual neurological impairment? (Epileptic fits tends to have residual neurological impairment - post-ictal effect).
Is there one area of the brain which is responsible for consciousness?
Not one area - lots of areas work together to achieve consciousness.
Which part of the brain is responsible for interception?
Von economo neurons
What area of the brain is suppressed by GA?
Intralaminar thalamic nuclei
Which part of the brain stem regulates sleep-wake cycles and behaviour?
Reticular activating system
What is it called when a P is wakeful (has preserved sleep/wake cycle) but with minimal awareness - and has inconsistent but reproducible responses?
Minimally conscious state
What is wakefulness with absent awareness?
Vegetative state
What is loss of voluntary control of movement + normal wakefulness and awareness?
Locked in syndrome
How is brain stem death confirmed?
By the absence of brain stem reflexes - pupils, cornea, motor response, oculovestibular, gag and cough reflexes, and apnoea testing.
What are the functions of the following glial cells?
- Astrocytes
- Oligodendrocytes
- Ependymal
- Microglia
- Schwann cells (PNS)
- Satellite cells (PNS)
What is the brain protected by?
The BBB and 3 meninges
What are the three meninges of the brain and spinal cord?
Dura
Arachnoid
Pia
What happens to the brain in neuroinflammation?
Vascular dilation
Microglia become activated
Can get oedema
Astrocytes repair
Can get neural degeneration, demyelination of neurons and gliotic scars (possible epileptic foci)
What is meningitis?
Inflammation of the meninges of the brain and spinal cord. Presents with headache, nuchal rigidity and photophobia
What is inflammation of the leptomeninges (Pia & Arachnoid) usually caused by?
Infection
What is inflammation of the pachymeninges (Arachnoid & Dura) usually caused by?
Cancer or TB
How does meningoencephalitis present on spinal tap if caused by
- bacteria
- virus
- fungal/TB
Bacterial = turbid fluid, high protein, low glucose, Ns
Viral = clear, normal-high protein, normal glucose, Ls
Fungal / TB = fibrin web appearance, normal-high protein, normal/low glucose, Ls
What are the following called?
Pia Mater + Arachnoid Mater
Arachnoid Mater + Dura Mater
(1). Leptomeninges
(2). Pachymeninges
How do concussion and contusion present?
Concussion - headache, drowsiness, concentration problems and amnesia (for months)
Contusion - confusion, altered cosnciousness and possible focal neurological deficits
How do acceleration-deceleration injuries affect the brain?
Shearing forces - cause axons to stretch - can lead to LOC or coma
What can repetitive brain injuries cause?
Chronic Traumatic Encephalopathy (CTE) - get tauopathy and deposition as β-amyloid plaques
Name three types of primary headaches
Tension-type
Migraine
Cluster headache (trigeminal autonomic cephalalgias)
What are the red flags for headache?
Wakens from sleep
Worsens with Valsava
Change in character
Age of onset
Sudden onset - thunderclap
Focal neurological deficits
Constitutional sx
What is the most common primary headache?
Tension-type
When are headaches classified as frequent and as chronic?
Frequent - If 10 episodes occur on 1-14 days of the month for average of >3months
Chronic - >15 days of the month for >3m
What are the S&S of migraine?
PIN
Photophobia
Incapacity
Nausea
When are migraines classified as frequent?
When they occur on 15 + days per month for >3m - having headache features for at least 8 days per month
What is a seizure?
Abnormal firing of the brain disturbing consciousness, behaviour, emotion, motor function or sensation
What part of the brain causes most seizures?
60% occur from temporal lobe
Frontal next common
Rare to have seizures from parietal or occipital lobes
What is a seizure termed that lasts longer than 5 minutes?
Status epilepticus
Medical emergency - mortality of 10-15%
What types of seizures are there?
Focal (irritative focus that then spreads across the brain) - old name petit Mal
- Motor and visual features
- Aware / impaired awareness
Generalised - no focus - generalised misfiring of the brain in both hemispheres - old name grand Mal
- Loss of awareness
- Synchronous movements
- Eyes open
What do the following terms mean
- Prodrome
- Preictal / aura
- Ictal
- Post-ictal
1
What are the most common causes of seizures in adults and children
Adults = stroke, tumour, trauma, infection
Children = genetic / metabolic disorders, trauma, infection
What are the DDs for a seizure?
When is the greatest risk of recurrence of a seizure after the first one?
Within the first 2 years
What are the precautions a P who has had a seizure should take?
Can’t drive for 6m after 1st seizure, or 1 year if 2 seizures
What is SUDEP?
Sudden Unexplained Death of Epilepsy
Happens more often in sleep - unsure of causative mechanism but could be cardio-respiratory arrest?
How do anti-seizure drugs work?
Several modes of action. Can:
- Enhance GABA action (Diazepam, valproate)
- Inhibit Na channel function (Carbamazepine, Phenytoin, Valproate)
- Inhibit Ca channel function - Gabapentin, Valproate
Why is phenytoin a complex drug to give?
Is 90% protein bound - therefore alterations in proteins impact on the free (active) drug. Means there is a difference between individuals in terms of the level of saturation.
What do thyroid hormones control?
Basal metabolic rate
What element does the thyroid need in order to function?
Iodine
What hormones are made by the thyroid gland?
T4 (Thyroxine)
T3 (Tri-iodothyronine)
C cells in thyroid also make Calcitonin
Which thyroid hormone is the precursor to the other - T3 or T4?
T4 is a precursor to T3 - converted by removing one iodine molecule via deiodinase (needs selenium to do this)
What protein is made by the thyroid gland that is a precursor to T3 and T4?
Thyroglobulin
Which enzymes catalyse the oxidation of iodide ions to atoms and their subsequent binding to thyroglobulin to make T3 and T4?
TPO - thyroid peroxidase
Pendrin
What regulates thyroid hormone secretion?
Hypothalamus + Pituitary Gland
Hypothalamus produces TRH (Thyrotropin releasing hormone)
TRH stimulates pituitary to release TSH
High levels of T4 and T3 in the blood decrease secretion of TSH & TRH = negative feedback
What environment factors can stimulate thyroid hormone release?
Cold exposure - ins production and release of TRH = inc metabolic rate
Fasting - reduces hormone release = reduced metabolic rate
Emotional reactions - stimulates SS = decrease of TSH
How are T4 and T3 transported in the body?
Are bound to plasma proteins (T3 binds less strongly than T4 so quicker release)
What effects do released T3 have on cells?
Make them work faster and harder = more respiration takes place = inc metabolic rate
What effect do thyroid hormones have on the body?
When can the thyroid gland be physiologically enlarged?
Adolescence and pregnancy
What is the preferred choice of imaging for the thyroid gland?
USS
What does thyroid agenesis cause?
Congenital hypothyroidism - 1 in 3.5-5k - screened for in heel prick test.
What thyroid blood tests can you do?
How do these present in
- Hypothyroidism
- Hyperthyroidism
TSH
FT4 = Free T4
FT3
Hypothyroid = T3&T4 low, TSH high
Hyperthyroid = T3 & T4 high, TSH low
How long does it take for TSH to reflect changes to T4 levels if taken orally?
Slow - about 6 weeks to reflect changes made
Is hypothyroidism more common in M or F?
F x10 > M
What are the signs and symptoms of hypothyroidism?
Cold intolerance
Facial puffiness
Dry skin
Hair loss
Hoarseness
Heavy periods
Bradycardia
What are the RF for hypothyroidism?
Other AI diseases (T1DM, Coeliac) - AI = commonest cause!
FHx
Immune therapy for cancer
Postpartum
- Also post surgery / radiotherapy for thyrotoxicosis
What is the problem in secondary hypothyroidism?
Disease of the pituitary or the hypothalamus - means they can’t produce hormones to stimulate the thyroid gland.
RARE
How is hypothyroidism treated?
Levothyroxine (T4) - taken on empty stomach.
T3 is not really used in the UK as v expensive. Only used for Ps with allergy to T4 or those who are refractory to it.
What is the severe presentation of hypothyroidism?
Myxoedema
Decreased awareness, hypothermia, bradycardia, hypotension, hypoglycaemia, peripheral oedema in face.
Often precipitated by infection, stroke, HF - inc basal requirements but body cannot provide.
Who suffers from hyperthyroidism more - M or F?
F x 10 > M
What are the S&S of hyperthyroidism?
What are the causes of thyrotoxicosis?
What biochemical changes in the blood can you see from thyrotoxicosis?
Liver - high AST, ALP and ALT
Bone - high ALP
Hypercalcaemia
Pancytopenia or Neutropenia
What is Grave’s disease caused by?
Ig AB binds to TSH receptors - mimics the action of TSH and stimulates them to produce T3 and T4
How does hyperthyroidism appear on radio iodine uptake scans?
Uniformly inflamed and metabolising excess glucose
How does hyperthyroidism affect the eyes?
TED
Inflammation
Itchy
Dry
Prominent
What are 2 other causes of thyrotoxicosis apart from Grave’s disease?
Toxic adenoma (one mass)
Toxic multi-nodular goitre (multiple masses)
What is inflammation of the thyroid gland called?
What is it caused by?
Thyroiditis
Infection - Bacterial / Viral
Postpartum AI
Drug
Radiation
What are the risks to the P if thyrotoxicosis goes untreated?
Escalation of Sx
AF
Osteoporosis
How is thyrotoxicosis treated?
Symptoms - can be controlled by β blocker
Tx - Carbimazole or Propylthiouracil
Can also use radioiodine or surgery to permanently treat
What is the mode of action of carbimazole or propylthiouracil?
What SE of these medications do you need to be aware of?
Inhibit TPO = reduction in production of T3 and T4
SE = Possible agranulocytosis - drop in WBCC
What is a possible (rare) complication of Grave’s disease?
Thyroid storm - extreme symptoms = hyperpyrexic, tachycardia >140, arrhythmia, HF, low GCS, agitation, delirium, N&V, deranged LFTs
How is thyroid storm managed?
What can cause goitre?
