Endocrinology (RE) Flashcards
(184 cards)
1
Q
When is peak incidence of T1DM?
A
6m-5y
2
Q
What percentage of T1DMs wont have a FHx of DM?
A
85% have no family Hx
3
Q
Which chromosome is strongly linked to T1DM?
A
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.
4
Q
What do the following cells of the pancreas produce?
- Alpha cells
- Β cells
- Δ cells
- Γ cells
- Epsilon cells
A
Alpha = Glucagon
Βeta = Insulin
Δ = Somatostatin
Γ = Pancreatic polypeptide
Epsilon = Gherkin
5
Q
What is the pathophysiology of T1DM?
A
AI destruction of β cells = unable to produce insulin.
6
Q
Which ABs can be measured to test for T1DM?
A
GAD
IA2
Zn T8
7
Q
What is the initial stage of T1DM?
A
Insulitis - AI destruction is happening but β cells that remain are still able to produce enough insulin. (Honeymoon phase - can be 2-5 years)
8
Q
What is T1DM associated with clinically?
A
Other AI diseases = likely the P has more than 1.
9
Q
What are the symptoms of T1DM?
A
Thirst
Polyuria
Lethargy
Unintentional weight loss
Recurrent candidiasis
10
Q
How can you distinguish T1 and T2 DM?
A
Due to speed of symptom onset - onset if faster in T1 than in T2
11
Q
What does insulin do?
A
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.
12
Q
How are ketones produced in the body?
A
When the body doesn’t have enough glucose - it breaks down fat for energy instead - the byproduct of this is ketones.
13
Q
How is C-Peptide used to diagnose insulin?
A
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.
14
Q
What is the Tx for T1DM?
Basal-bolus regime if 1st line (long acting = basal, bolus = quick-acting to cover meal).
A
Insulin - given parentally (S/C, inhaled or mucous membranes)
15
Q
Who qualifies for an insulin pump?
A
NICE =
12 yr +. T1DM +
- attempts to reach target HbA1c with multiple daily injections = disabling hypoglycaemia
- HbA1c have remained high despite attempts to carefully manage.
16
Q
What types of insulin are there?
A
Short (15-20 mins before meal)
Intermediate
Long-acting - single dose per day
Can get ultra strength - bit better for less compliant Ps (teenagers)
17
Q
What is the process of managing fluctuating blood sugars called?
A
Dose Adjustment for Normal Eating (DAFNE)
Can also do carbohydrate counting
18
Q
What is the normal insulin to carb ratio?
A
1 insulin : 10g carbs
19
Q
What is the insulin sensitivity factor?
A
Measure of how much 1 unit of insulin brings the blood sugar down by. On average it is reduced by 3.
20
Q
What are the S&S of hypoglycaemia?
A
Shaky / dizzy
Blurred vision
Sweaty
Weak or Tired
Upset or Nervous
Headache
Hungry
21
Q
What are the S&S of hyperglycaemia?
A
Dry skin
Extreme thirst
Hunger
Freq urination
Blurred vision
Drowsy
Slow wound healing
22
Q
When do you need to notify the DVLA if diagnosed with T1DM?
A
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
23
Q
What is the role of glucagon?
A
Glucagon is used to increased blood glucose levels - it makes the liver undergo gluconeogenesis.
24
Q
What type of respiration can be seen in DKA?
A
Kussmaul respiration
25
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.
26
How is DKA managed?
Aggressive fluids (help dehydration, insulin and lower BG levels)
Replacement of electrolytes to reduce the acidosis
27
How does adrenaline affect glucagon?
Stress = release of adrenaline = releases glucagon
28
What are the two types of complications of T2DM?
Microvascular (retinopathy, neuropathy, nephropathy)
Macrovascular (IHD, CVD, PVD)
29
What medical emergency is seen in Ps with T2DM?
Hyperosmolar Hyperglycaemic State (HHS)
30
What is the diagnostic criteria for T2DM?
31
What test can be done for T2DM?
Oral Glucose Tolerance Test
32
What is the pathophysiology of T2DM?
Pancreas - apoptosis β cells, dec insulin excretion
Hyperlipidaemia
Liver - inc hepatic glucose output
Muscle - insulin resistance
33
What are the RF for T2DM?
34
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.
35
What are high levels of ectopic fat linked to?
- Hypertension
- Atherogenic dyslipidemia
- T2DM
- Thrombosis
- Atherosclerosis
- Inflammation
36
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)
37
What are the benefits of exercise?
38
How can T2DM be reversed?
Through diet or inc exercise leading to weight changes
39
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.
40
How is T2DM managed?
41
What treatment can be given to prevent complications of T2DM?
Cholesterol lowering tx
Antihypertensives
Anti-platelet tx
42
What BMI qualifies for bariatric surgery?
BMI > 35
43
What is the MOA of biguanides?
Overall reduction in insulin resistance
44
Name a biguanide drug?
Metformin
45
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)
46
When is metformin contraindicated?
Acute metabolic acidosis - inc lactic acidosis & DKA
eGFR <30
Liver problems
47
Name a sulphonylurea drug.
Gliclazide
48
What is the MOA of sulphonylureas?
Blocks the K ATP channels within β cells of pancreas => stimulates insulin secretion
49
What are the SEs of sulphonylureas?
50
When are sulphonylureas contraindicated?
51
Name a DPP4 Inhibitor drug
Sitagliptin
Linagliptin
52
What is the mechanism of action of Gliptins (DPP4 inhibitors)?
Increases insulin levels and reduces insulin resistance
53
What are the side effects of gliptins?
54
When are gliptins contraindicated?
Ketoacidosis
Renal failure
55
Name an SGLT2 Inhibitor (Flozins)
Dapagliflozin
Canagliflozin
Empagliflozin
56
What is the MOA of SGLT2 Inhibitors?
Decrease renal tubular glucose absorption - therefore excretes glucose and lowers serum glucose without affecting insulin
Diuretic effect
57
What are the side effects of SGLT2 Inhibitors?
58
Name a GLP1 Agonist
Dulaglutide
Exanatide
Liraglutide
Semaglutide
59
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
60
What are the benefits of GLP1 Agonists?
Improved BP and lipid profile
Improve HbA1c
Decreased weight
No hypoglycaemia
61
What are the SEs of GLP1 agonists?
62
When are GLP1 agonists contraindicated?
63
What are the side effects of insulin?
64
What is a state of unrousable unresponsiveness?
Coma
65
What is obtundation?
Slowed thinking
66
What is interoception?
Awareness of the state of your body - e.g. sensing breathing, heart beat or internal pain
67
What is the definition of a coma?
Unrousable unconsciousness - lasting more than 6 hours
Fails to respond to painful stimuli, light or sound
68
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.
69
Can you describe the criteria for GCS?
70
What is the lowest GCS score a P can have?
3
71
What can an acute confusional state indicate?
Delirium
If it fluctuates - classic presentation of delirium
72
What is a transient loss of consciousness?
Syncope / Blackout
Must be less than 6 hours - otherwise coma
73
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.
74
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).
75
What are the four types of syncope?
Postural
Vasovagal
Cardiogenic
Neurological
76
Is there one area of the brain which is responsible for consciousness?
Not one area - lots of areas work together to achieve consciousness.
77
Which part of the brain is responsible for interception?
Von economo neurons
78
What area of the brain is suppressed by GA?
Intralaminar thalamic nuclei
79
Which part of the brain stem regulates sleep-wake cycles and behaviour?
Reticular activating system
80
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
81
What is wakefulness with absent awareness?
Vegetative state
82
What is loss of voluntary control of movement + normal wakefulness and awareness?
Locked in syndrome
83
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.
84
What are the functions of the following glial cells?
- Astrocytes
- Oligodendrocytes
- Ependymal
- Microglia
- Schwann cells (PNS)
- Satellite cells (PNS)
85
What is the brain protected by?
The BBB and 3 meninges
86
What are the three meninges of the brain and spinal cord?
Dura
Arachnoid
Pia
87
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)
88
What is a paraneoplastic syndrome?
Remote effect of a cancer - cancer can produce hormones which affect the body or the immune system can have an abnormal response to the cancer which begins fighting the brain - causing abnormal signalling & neuronal responses.
89
What is Lambert-Eaton syndrome?
A paraneoplastic syndrome of the PNS = neuromuscular junction disorder affecting communication between nerves and muscles. This intricate disorder can manifest due to a paraneoplastic syndrome or a primary autoimmune disorder. The majority of cases are associated with small-cell lung cancer.
90
What is an example of a paraneoplastic syndrome of the CNS?
NMDA encephalitis
Encephalitis is an uncommon but serious condition in which the brain becomes inflamed (swollen).
91
What is meningitis?
Inflammation of the meninges of the brain and spinal cord. Presents with headache, nuchal rigidity and photophobia
92
What is inflammation of the leptomeninges (Pia & Arachnoid) usually caused by?
Infection
93
What is inflammation of the pachymeninges (Arachnoid & Dura) usually caused by?
Cancer or TB
94
What is encephalitis?
Inflammation of the brain leading to alternation in cognition / sensorium
95
Where about do you want to do a spinal tap?
Below L2 = preferably around L4-5-S1
96
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
97
What is the treatment for most viral encephalitis?
Most have no specific Tx - supportive Tx only
98
What is the choroid plexus?
A network of BVs in each ventricle which produce CSF
The innermost layer of the meninges, called the pia mater, forms evaginations in some parts of the ventricles. These vascularized evaginations, are lined by a plexus of specialised cells that produce our CSF. This plexus of cells is called the choroid plexus.
99
What are the following called?
Pia Mater + Arachnoid Mater
Arachnoid Mater + Dura Mater
(1). Leptomeninges
(2). Pachymeninges
100
What are the foramina of the brain?
Foramina of Lushka
Foramina of Magendie
101
What is a
- direct
- indirect
blunt force head trauma called?
Direct = coup
Indirect = contre-coup
102
How do concussion and contusion present?
Concussion - headache, drowsiness, concentration problems and amnesia (for months)
Contusion - confusion, altered cosnciousness and possible focal neurological deficits
103
How do acceleration-deceleration injuries affect the brain?
Shearing forces - cause axons to stretch - can lead to LOC or coma
104
What does the following indicate:
Headaches, meningism, vision changes, papilloedema, CN6 palsy, LOC
Increased cerebral pressure
105
What is papilloedema?
Papilledema is a disease entity that refers to the swelling of the optic disc due to elevated intracranial pressure (ICP).
106
What is Cushing's triad?
A sign of raised ICP - triad of high BP with widening pressures, reflexive bradycardia (baroreceptors) and irregular respirations
107
What can repetitive brain injuries cause?
Chronic Traumatic Encephalopathy (CTE) - get tauopathy and deposition as β-amyloid plaques
108
Name three types of primary headaches
Tension-type
Migraine
Cluster headache (trigeminal autonomic cephalalgias)
109
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
110
What is the most common primary headache?
Tension-type
111
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
112
What are the S&S of migraine?
PIN
Photophobia
Incapacity
Nausea
113
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
114
What is status migrainsous?
Migraine lasting longer than 72 hours
115
How do cluster headaches present?
Excruciating pain causing agitation + autonomic features
Rare - 0.1% of headaches
116
117
What can cause an anoxic brain injury?
Hypoxia
Ischaemia
118
What is a seizure?
Abnormal firing of the brain disturbing consciousness, behaviour, emotion, motor function or sensation
119
What is the definition of epilepsy?
2 or more unprovoked seizures separated by 24 hours
120
What is the correlation between abnormally developed brains and epilepsy?
Likelihood of having an irritative focus in abnormally developed brains is much high - therefore if an MRI shows abnormality - would treat as having epilepsy immediately
121
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
122
What is a seizure termed that lasts longer than 5 minutes?
Status epilepticus
Medical emergency - mortality of 10-15%
123
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
124
Is a daily occurrence of deja vu normal?
No - suspicious if every day - can be symptomatic of temporal lobe seizures
125
What do the following terms mean
- Prodrome
- Preictal / aura
- Ictal
- Post-ictal
1
126
What are the most common causes of seizures in adults and children
Adults = stroke, tumour, trauma, infection
Children = genetic / metabolic disorders, trauma, infection
127
How do we manage acute seizures?
Treat underlying cause
Benzodiazepines (IV lorazepam, buccal midazolam or rectal diazepam)
Antiseizure meds if risk of recurrence
128
What are the DDs for a seizure?
129
How do seizures appear on EEG?
Does a normal EEG rule out epilepsy?
Seizures appear as Epileptiform Discharges and you can get interictal epileptiform discharges in between seizures.
Normal EEG does not rule out epilepsy
130
When is the greatest risk of recurrence of a seizure after the first one?
Within the first 2 years
131
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
132
What is SUDEP?
Sudden Unexplained Death of Epilepsy
Happens more often in sleep - unsure of causative mechanism but could be cardio-respiratory arrest?
133
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
134
What is a trough level with medications?
It is the lowest blood concentration of the drug - taken just before the next dose is given
135
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.
136
What things affect the available proteins for drug binding in the blood?
Liver failure
Kidney failure
Pregnancy
137
When is a P considered to have drug-resistant epilepsy?
What are their tx options?
Considered drug-resistant if they have failed to respond to 2 different appropriate antiseizure meds
Options = surgery, neurostimulator devices, ketogenic diet
138
What is the largest endocrine gland in the body?
Thyroid
139
What do thyroid hormones control?
Basal metabolic rate
140
What element does the thyroid need in order to function?
Iodine
141
What hormones are made by the thyroid gland?
T4 (Thyroxine)
T3 (Tri-iodothyronine)
C cells in thyroid also make Calcitonin
142
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)
143
What protein is made by the thyroid gland that is a precursor to T3 and T4?
Thyroglobulin
144
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
145
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
146
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
147
How are T4 and T3 transported in the body?
Are bound to plasma proteins (T3 binds less strongly than T4 so quicker release)
148
What effects do released T3 have on cells?
Make them work faster and harder = more respiration takes place = inc metabolic rate
149
What effect do thyroid hormones have on the body?
150
When can the thyroid gland be physiologically enlarged?
Adolescence and pregnancy
151
What is the preferred choice of imaging for the thyroid gland?
USS
152
What does thyroid agenesis cause?
Congenital hypothyroidism - 1 in 3.5-5k - screened for in heel prick test.
153
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
154
How long does it take for TSH to reflect changes to T4 levels if taken orally?
Slow - about 6 weeks to reflect changes made
155
What are the normal ranges of
= TSH
= FT4
= FT3
TSH - 0.3 - 3.5
T4 - 10 - 25
T3 - 3.5 - 7.5
156
Which thyroid antibodies do we need to be aware of?
Do we routinely test for these?
TPO Ab = Tyroid Peroxidase AB
Antithyroglobulin ABs
TSH Receptor Ab
Don't routinely test because they don't indicate how well the P is doing. Only time you would test is TSH R AB for Graves
157
Which thyroid antibody is found to be in large quantities in Graves disease?
TSH Receptor Antibody
158
Is hypothyroidism more common in M or F?
F x10 > M
159
What are the signs and symptoms of hypothyroidism?
Cold intolerance
Facial puffiness
Dry skin
Hair loss
Hoarseness
Heavy periods
Bradycardia
160
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
161
What is the problem in primary hypothryoidism?
The thyroid gland is not producing sufficient T3 or T4
162
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
163
What is Sheehan syndrome?
After delivering baby = mother can suffer postpartum haemorrhage which infarcts the pituitary gland = causing hypopituitarism
164
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.
165
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.
166
Who suffers from hyperthyroidism more - M or F?
F x 10 > M
167
What are the S&S of hyperthyroidism?
168
What is hyperthyroidism also known as?
Thyrotoxicosis
169
What are the causes of thyrotoxicosis?
170
Which drugs can induce thyrotoxicosis?
Lithium
Amiodorone
171
What biochemical changes in the blood can you see from thyrotoxicosis?
Liver - high AST, ALP and ALT
Bone - high ALP
Hypercalcaemia
Pancytopenia or Neutropenia
172
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
173
How does hyperthyroidism appear on radio iodine uptake scans?
Uniformly inflamed and metabolising excess glucose
174
How does hyperthyroidism affect the eyes?
TED
Inflammation
Itchy
Dry
Prominent
175
What are 2 other causes of thyrotoxicosis apart from Grave's disease?
Toxic adenoma (one mass)
Toxic multi-nodular goitre (multiple masses)
176
What is inflammation of the thyroid gland called?
What is it caused by?
Thyroiditis
Infection - Bacterial / Viral
Postpartum AI
Drug
Radiation
177
What are the risks to the P if thyrotoxicosis goes untreated?
Escalation of Sx
AF
Osteoporosis
178
How is thyrotoxicosis treated?
Symptoms - can be controlled by β blocker
Tx - Carbimazole or Propylthiouracil
Can also use radioiodine or surgery to permanently treat
179
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
180
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
181
How is thyroid storm managed?
182
What is enlargement of the thyroid called?
Goitre
183
What can cause goitre?
184
How should goitre be investigated?
Are there any functional symptoms - hypo/hyper thyroid indications?
FHx
Extremes of age? <20 or >60
Male
Radiation Exposure Hx?
Any pressure Sx - cough / speech / swallowing difficulties?
