Week 1 Flashcards
what are the basic hormone subtypes
protein and peptide hromones, steroid hormoones and tyrosine derivatives
what are the hormones receptors
G-protein coupled receptors
Receptor Tyrosine Kinase (RTK) Families
Receptors associated with tyrosine kinase activity
Steroid hormone receptors
what are the major endocrine glands?
hypothalamus, PG, 4Parathyroid and thyroid, 2 adrenal glands and pancreas, ovaries/testes, adipose tissue
where do most clinical problems from endocrine come from?
hypo/hypersecretion
what are the principles of endocrine testing?
If too little hormone – try and stimulate it
If too much hormone – try and suppress it
what type of glands make up the endocrine system
ductless glands
how is communication (long distance between glands and other tissues) done in endocrine system?
via hormones in bloodstream
how are hormones are specific at signalling?(3 reasons)
- chemically distinct hormones
- specific receptor for each hormone
- distinct distribution of receptors across target cells
what is the chemical nature and deriviative of Adrenaline + thyroid hormones (T3 and T4)?
modifed Amino Acids (from tyrosine)
what is the chemical nature and derivative of Cortisol, progesterone, testosterone?
steroid (from cholesterol)
what is the chemical nature and derivative of Adrenocorticotropic hormone ACTH), antidiuretic hormone (ADH), oxytocin?
(insulin)
peptide (from larger precursor proteins)
proteins
what are the three ways of chemical signally hormones can do?
autocrine, paracrine, endocrine
autocrine signalling definition
cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell/INTRACELLULAR
paracrine signalling definition
signalling molecule affects surrounding target cells (diffusion in ECF)
endocrine definiton
signalling molecule enters circulation and affects cells at a different site.
not all hormones act in one way. Somatostatin acts via which two signalling methods?
paracrine and endocrine
one hormone can affect many targets and several H may act on one target. T or F?
T
why does a very small change in the concentration of H lead to changes?
due to specific receptors with high efficacy
how long does it take H to act? What can occur when H attaches to receptor?
seconds to days.
Amplification - cascade of events
how are H eliminated?
terminated by enzyme-mediated metabolic inactivation in the liver.
or at sites of action.
What two ways can hormones interact? (Give example of each)
complementary (together - adrenaline, glucagon and cortisol allow enhances physical activity and inc energy while preventing hypokalaemia and hypoglycaemia prophylactically)
antagonistically (in opposition - insulin and glucagon)
Amines: synthesis, storage, release and transport
pre-synthesised from tyrosine, storage in vesicle by adrenaline, release due to external factor causing inc extracellular Ca2+ - release on demand, always reserve.
as amines are small, soluble and hydrophilic they are transported ‘freely’ in bloodstream.
peptide H: synthesis, storage, release and transport
pre-synthesised by long processes (by CONVERTASES), storage in vesicles, release due to external factor causing inc extracellular Ca2+ - release on demand, always reserve.
peptide H are hydrophilic so they are transported/dissolve ‘freely’ in plasma
Steroid H: synthesis, storage, release and transport
synthesised and secreted on demand (no storage)
pathways irrelevant but all via PREGNENOLONE.
hydrophobic so transported by carrier proteins in plasma(CP)
what are the rate limiting steps in Steroid H synthesis? (what inc steroid H synthesis)
(high) conc of cholesterol
(high) rate of conversion of cholesterol into pregnenolone
when are steroid H biologically active?
when ‘free’/when not bound to plasma proteins
what H are relatively insoluble in plasma?
steroids, T3, T4
T3 is what?
Triiodothyronine
T4 is what?
Thyroxine
what is the function of CPs? (give 3)
inc conc of H in blood
provide reservoir of H
to extend the T1/2 of H
give examples of common CP
CBG - cortisol binding globulin (binds cortisol, some aldosterone)
TBG - binds T4, some T3.
SSBG - testosterone + oestradiol
what are two important general CP and what do they carry?
albumin – binds many steroids and thyroxine
transthyretin – binds thyroxine and some steroids
how does CP regulate levels of steroid H?
acts as both buffer and reservoir (equilibrium between CP bonded and non-bonded). If too much or too little steered body can cope.
what state do H have to be to cross capillary wall (and nuclear membrane?)
free (unbonded)
how is H plasma conc levels maintained?
negative feedback system (both short range and long range)
[note that nervous and endocrine systems work together]
what is plasma concentration determined by?
rate of secretion vs rate of elimination
neuroendocrine in negative feedback system?
Elicits a sudden burst in secretion in response to a specific stimulus
what is diurnal/circadian rhythm?
fluctuation thoughtout day [dependant on external factors e.g:night/day]
what are the two main route of H elimination?
excretion by kidneys
metabolism by liver
what are the half life (approx) of amines, peptides and steroid H?
amine - secs
peptides-min
steroid-hours/days
3 types of H receptors?
G-protein coupled (GPCR)
Receptor kinases
Nuclear receptors
G-protein receptors: are found where, which H use them?
found on cell surface as hydrophilic H
amine H and some peptide H
receptor kinases: are found where, which H use them?
found on cell surface as hydrophilic H
activated by some protein/peptide H
nuclear receptors: classes, are found where, which H use them?
receptor on nucleus as lipophilic H (can diffuse across PM)
Class 1 - many steered H; located in cytoplasm and move to nucleus when activated Class 2 - mostly lipids; constitutively present in the nucleus Hybrid - activated by thyroid hormone (T3) and other substances; similar in function to class 1
what is the difference between type 1 and 2 diabetes?
1- absolute insulin deficiency
2-relative insulin deficiency
what is the definition of DM?
a group of metabolic diseases characterised by hyperglycemia resulting from defects in insulin secretion, insulin action, or both
how is diabetes diagnosed?
HbA1c > 48m/m/6.5% (type 2)
fasting glucose >7mmol/L
2hr glucose in OGTT > 11.1mmol/L (after 2hrs)
random glucose>11.1mmol/L (=symptoms)
[slightly lower values can indicate pre-diabetes /impaired function]
type 1 DM PC
Pre-school and peri-puberty Small peak in late 30’s Usually lean Acute Onset severe symptoms severe weight loss ketonuria metabolic acidosis no evidence of microvascular disease at diagnosis immediate and permanent requirement for insulin
what signs to look out for in type 1 DM?
4T’s
toilet, thirsty, tired, thinner
type 2 DM PC
middle-aged/elderly
usually obese
pre-diagnosis duration of probably 6-10 years
insidious onset over weeks to years
ketonuria minimal or absent
evidence of microvascular disease at diagnosis in 20 %
managed initially with diet/ lifestyle +tablets
risk factors for type 2 DM
Obesity (central) Family History Gestational Diabetes Age Ethnicity (Asian, African, Afro-Caribbean) PHx of MI/ Stroke Medications e.g. antipsychotics IGT/ IFG
what is mostly likely cause of DM in children under 1?
neonatal or genetic diabetes
rarely type 1 (even if looks like it)
type 1 DM is what kind of disease? what occurs? what does this allow to help in diagnosis?
AID, insulitis (lymphocytic inflitrate). Antibodies can be used to diagnoses as AID.
PC of type 2 DM
Thirst Polyuria Thrush Weakness Fatigue Blurred Vision Infections (Weight Loss) T2DM- Signs of complications- neuropathy, retinopathy
what are useful discriminatory tests (tell you which type of diabetes is present)?
GAD/ Anti-Islet Cell antibodies
Ketones
C-peptide (plasma)
what is LADA?
Latent autoimmune diabetes (type 1 occuring in adults).
lots of patients with LADA are assumed to have type 2 DM. how is LADA different?
ketosis = type 1 diabetes
type 3 diabetes causes are what?
pancreatic disease, endocrine disease, drug-induced, Abnormalities of insulin and its receptor,
Genetic diseases
what pancreatic conditions cause type 3 diabetes?
Chronic or recurrent pancreatitis (alcoholism mainly)
Haemochromatosis
Cystic Fibrosis
what endocrine conditions cause type 3 diabetes?
Cushing’s syndrome
Acromegaly
Phaechromocytoma
glucagonoma
what drugs
cause type 3 diabetes?
Glucocorticoids
Diuretics
B-blockers
what genetic disease cause type 3 diabetes?
Cystic fibrosis
Myotonic dystrophy
Turner’s syndrome
Down’s syndrome
what are signs of monogenic diabetes (not polygenic)?
Strong Family History Associated Features (renal cysts etc) Young Onset GAD-negative C-peptide positive
what is type 4 DM?
Gestational diabetes - Any degree of glucose intolerance arising or diagnosed during pregnancy
what is HbA1c? what is its use?
Glycated haemoglobin.
Provides a measure of glucose control over past 2-3 months.
complication of DM
Macro-vascular: Heart Disease and Stroke (70% of people with diabetes die from cardiovascular disease)
Micro-vascular: Retinopathy(blindness), Nephropathy (RF), Neuropathy,
Psychiatry/ Psychology
Peripheral vascular disease - ulcers/amputation
DKA
what is DAFNE?
dose adjustment for normal eating (type 1DM)
[educates people on estimating carbohydrate per meal and injecting the right does of insulin]
which DM has stronger genetic competent?
type 2 (twin studies and risk factor for type 2 development greater if parents have than type 1 - weird)- extra info
what is a normal blood glucose level?
5mmol/L
what are the cells of the pancreatic islets, watch percentage and what do they produce?
β cells - secrete insulin (70%)
α cells - secrete glucagon (15%)
δ cells - secrete somatostatin (5%)
PP cells - secrete pancreatic polypeptide (<1%)
how is insulin made? (?→?+?→?+?)
preproinsulin→ proinsulin +singalling petpide →insulin + C-peptide (cleaved to form insulin)
where is preproinsulin made?
Synthesized in the rough endoplasmic reticulum of pancreatic β cells [as a larger single chain preprohormone]
how fast can insulin preparations work?
ultra-short acting to ultra-long acting
ultra-short acting insulin called what? taken when?
lispro.
Injected within 15 minutes of beginning a meal
short duration of action- must be used in
combination with longer-acting preparation for Type 1 diabetes unless used for continuous infusion
(it is monomeric and not antigenic)
ultra-long acting insulin called what? when is it given?
glargine
Recombinant insulin analog that precipitates in the neutral environment of subcutaneous tissue
Peakless- prolonged action
Administered as single bedtime dose
how does glucose enter the Beta-cells?
GLUT2 glucose transporter
what happens to glucose once it enters the beta-cell?
it is phosphorylated by glucokinase (glucokinase is the glucose-sensor)
what can lead to dramatic change in glucokinase captivity?
(small) change in glucose conc
what is the process for excreting insulin?
inc metabolism of glucose→ inc intracelluar ATP conc →inhibition of ATP-sensitive K+ channels Katp → depolarisation of cell membrane → opening of voltage- gated Ca2+ channels → inc intracellular Ca2+ → fusion of secretory vesicles with the cell membrane and release of insulin
how many cells make and secrete insulin?
ONLY B-cells make and secrete
when should insulin be secreted?
ONLY once conc > 5mmol/L
What is the problem in Type 1DM, …type 2 DM?
B-cells are lost -1
cells lose ability to sense change in glucose. - 2
what is the release of insulin? Why?
biphasic → readily released pool (immediate ) and reserve pool (preparation reaction must occur)
what happens to the insulin secretion curve in Type 2 DM?
it flattens and weakens (due to down regulation of sensory process)
what drugs can mimic the action of ATP to depolarise beta cells?
sulphonylurea drugs [SUR’s]
what do Katp channels consist of which two proteins?
Kir6 (An inward rectifier subunit (Kir) - pore subunit )
SUR1 (A sulphonylurea receptor - regulatory subunit) - need both to form functional Katp channel
what is the structure of Katp channel?
octomeric structure
how to SUR’s work?
directly inhibit Katp
give some example of SUR’s, when can they be used?
tolbutamide or glibenclamide
2nd line for type 2 DM)
how is Katp regulated?
inhibited by SUR’s (stimulates insulin secretion)
stimulated by diazoxide (inhibits insulin secretion)
what mutation give neonatal diabetes?
Kir6.2 mutations
why does neonatal diabetes occur? treatment?
Due to constitutively activated KATP channels or an increase in KATP numbers
In some of these patients the β cells are usually responsive to SURs, such as tolbutamide; recover euglyceamia fairly quickly on SURs.
what does euglyceamia mean?
normal blood glucose (normoglycemia)
what mutations lead to congenital hyperinsulinism?
some Kir6.2 or SUR1 mutations
why does congenital hyperinsulinism occur? treatment?
trafficking or inhibiting mutations
diazoxide can help inhibit insulin secretion if channels are still getting to the membrane
MODY: what is it? who does it occur?
Maturity-onset diabetes of the young
Monogenic diabetes with genetic defect in β cell function; Familial form of early-onset type II diabetes, primary defects in insulin secretion
Mutations in at least 6 different genes can cause MODY
why is it important to differentiate MODY from type 1 DM? how is this done?
treatment with sulphonylurea rather than insulin (as MODY patients usually have some b-cell function available).
robust genetic screening
what occurs in type 1, 2 and MODY?
Type 1 Diabetes – Loss of insulin secreting beta cells.
what occurs in type 2 DM
Type 2 Diabetes- Initially hyperglycemia with hyperinsulinemia so primary problem is reduced insulin sensitivity in tissues
what occurs in MODY?
MODY- defective glucose sensing in the pancreas and/or loss of insulin secretion
what is insulin’s biological effect
anabolic
what does insulin promote?
- Amino acid uptake in muscle
- DNA synthesis
- Protein synthesis
- Growth responses
- Glucose uptake in muscle and adipose tissue
- Lipogenesis in adipose tissue and liver
- Glycogen synthesis in liver and muscle
what does insulin inhibit?
lipolysis
gluconeogenesis in liver
what receptor does insulin bind to?
receptor tyrosine kinases
what does insulin cause to happen at the tyrosine kinase receptor?
insulin binds to α subunits → β subunits to dimerise → β + phosphorylate themselves/autophosphorylation → activates catalytic activity of the receptor
how does glucose get transported into the cell?
GLUT 4 receptor (then glycogen synthesis occurs as does cell growth)
what is insulin resistance?
reduced ability to respond to ‘physiological’ insulin levels - due to reduced insulin sensing and/or signalling.
what is the effect of obesity/adipose tissue on insulin resistance?
direct correlation with obesity
[however complete absence of adipose also results in insulin resistance] (therefore adipose tissue is key mediator of insulin sensitivity)
what is leprechaunism/Donoghue syndrome? why does it occur?
Rare autosomal recessive condition, mutations in the gene for the insulin receptor causes severe insulin resistance. [defects in insulin binding or insulin receptor signalling]
what type of condition is type 2 DM? (genetically)
polygenic, [with a large input from environmental influence]
leprechaunism/Donoghue syndrome signs?
Developmental abnormalities (elfin facial appearance,
growth retardation,
absence of subcutaneous fat, decreased muscle mass) - death < 1yearold.
genetics of Rabson Mendenhall syndrome?
Rare autosomal recessive condition,
what is Rabson Mendenhall syndrome?
Severe insulin resistance, hyperglycemia and compensatory hyperinsulinemia
signs of Rabson Mendenhall syndrome
Developmental abnormalities
Acanthosis nigricans (hyperpigmentation)
Fasting hypoglycaemia (due to hyperinsulinemia)
DKA
DKA PC
Vomiting Dehydration abdo pain deep gasping breaths confusion/unconsciousness Increased heart rate Distinctive smell on breath
where are ketone bodies formed?
liver mitochondria. [then diffuse into bloodstream and to peripheral tissues]
what are ketone bodies derived from?
acetyl-CoA, which is from β oxidation of fats.
what are ketone bodies good for/used for by body?
Important molecules of energy metabolism for heart muscle and renal cortex (converted back to acetyl-CoA, which enters TCA cycle)
Emergency energy
supply for brain
during fasting
what inhibits lipolysis and prevents ketone body overload?
insulin (even small amounts)
when can DKA occur?
T1DM - if miss insulin supplementation
T2DM -rarer (as there is still inhibition of lipolysis); can occur as insulin resistance and deficiency increases, alongside increase in glucagon.
when is Acetyl CoA diverted to ketones in TCA cycle?
is supply of Oxaloacetate is limited.
what does fatty acid oxidation yield?
acetyl-CoA → enters the TCA cycle if fat and carbohydrate degradation are balanced.
why is Oxaloacetate consumed?
for gluconeogenesis
give examples of ketone bodies
Acetone
Acetoacetic acid
β-hydroxybutyric acid
when glucose is not available, what are oxidised to provide energy
fatty acids.
what happens to the excess acetyl-CoA in a low glucose environment?
Excess acetyl-CoA is converted to ketone bodies, blood levels increase.
what does the accumulation of ketone bodies in blood lead to?
acidosis (metabolic)
what does high glucose excretion cause?
dehydration, exacerbates acidosis
what is severe complication of DKA
coma, death
how is DKA treated?
insulin (and rehydration)
what conditions does ketosis occur?
glucose limiting conditions (starvation and diabetes).
what are the four parts of the brain?
cerebral hemispheres, cerebellum, brainstem, spinal cord
what makes up the Diencephalon
Thalamus (T) + Hypothalamus (H)
where is the diencephalon
onto of midbrain of brainstem.
how is the hypothalamus anatomically & functionally connected to the pituitary gland?
infundibulum or “pituitary stalk”
which bone does the pituitary fossa lie in?
sphenoid bone (within sella turcica)
what effect can a PG tumour have on the visual pathway? why
can cause Bitemporal hemianopia (loss of temporal field of view); because pitc chaism is impinged
what are the two way to surgically access the PG?
Transcranial approach (subfrontal – under the frontal lobe)
transphenoidal approach (via nasal cavities & sphenoid sinus)
what two concha contribute to the ethmoid bone? which is a bone in its own right
Inferior concha = bone on its own;
Sup and middle concha part of ethmoid bone
what are the paranasal sinuses? what types are there?
Air-filled spaces within the bones surrounding the nasal cavities
Frontal bone (frontal sinuses) Maxillae (maxillary sinuses) Ethmoid bone (ethmoidal air cells) - 3 groups Sphenoid bone (sphenoid sinuses)
- all R+L sinuses
possible function of paranasal sinuses
make mucus and drain it into nasal cavities, reduced weight of skull, add resonance to voice. (no real function?)
what are paranasal sinuses lined by?
mucous-secreting respiratory mucosa
which paranasal sinuses are important when concerned with PG?
sphenoid sinuses
what does a transphenoidal transnasal approach involve
surgical fracture of the nasal septum and the floor (septum) & roof of the sphenoid sinus(es)
what can be used by surgeons go gain access to PG in more complicated cases
Le Fort 1 Down-#
which CN can be damaged in PG surgery causing eye problems?
CN3-6
a Transcranial approach can lead to damage of what CN causing what?
Injury to CN1= reduced smell
what is the dura mater?
thick layer that is outermost of 3 layers of meninges; adheres to the internal aspects of all the bone of the cranial vault
what is the function of dural venous sinuses?
to drain blood from cranial cavity (inc brain) into the internal jugular veins. (not histologically veins but function like veins)
what are two types of dural venous sinuses?
cavernous(R/L) and intercanvernous (A/P)
what passes through the cavernous sinuses?
internal carotid artery
what is the function and function deficit of optic chasm?
Conducts APs bilaterally from the nasal retinae
bitemporal hemianopia
what is the function and function deficit of Oculomotor nerve
Motor to muscles that move the eyeball (globe)
Parasympathetic to the sphincter muscle of the iris
problems with several eye movements
a dilated pupil
what is the function and function deficit of Trochlear nerve
Motor to one muscle that moves the globe
problems with specific eye movements
what is the function and function deficit of Trigeminal nerve
Sensory to most of the face
Motor to the muscles of mastication
sensory symptoms on the face
difficulty chewing
what is the function and function deficit of Abducent nerve
Motor to one muscle that moves the globe
problems with specific eye movements
what is the function and function deficit of Cavernous sinus
Drains venous blood
venous haemorrage
what is the function and function deficit of internal carotid artery
Supplies arterial blood to brain & orbit (including globe)
catastrophic haemorrage
what is the function and function deficit of dura mater
Protects the structures of the cranial cavity
Cerebrospinal fluid (CSF) leak.
thyroid gland consists of what? (anatomically)
2 lateral lobes (right & left) and an isthmus (a narrow connecting band)
where do the lobes of the thyroid attach?
the lateral aspects of the thyroid & cricoid cartilages and to the trachea
where does the isthmus lie?
lies anterior to the 2nd & 3rd cartilages of the trachea
where are the 4 parathyroid glands located?
on the posterior surfaces of the thyroid gland’s lateral lobes (Sup and inf L+R)
what is the pyramidal lobe? how may people have one? Where dos it commonly originate from? Where does it attach/extent to? Why?
anatomical variation coming of the thyroid (posterior) in 44% of people;commonly originates from left lateral lobe.
Most attach superiorly to thyroid cartilage; May extend as far superiorly as the hyoid bone (occurs as in embryology thyroid gland begins at junction of 2/3rd of tongue and migrates down via thyroglossal duct)
what are the platysma muscles? what do they do? Nerve supply?
- Located immediately deep to the skin within the superficial fascia of the neck
- Belong to the group of muscles called “the muscles of facial expression”
- Nerve supply is cranial nerve VII (the facial nerve)
name the fascial compartments of the neck
pre-vertebral (deep), investing, 2 carotid sheaths, pre tracheal fascia.
what is in the investing fascia?
Encloses all the other neck fascial compartments encloses 2 pairs of muscles:
Trapezius
Sternocleidomastoid
what is in the prevertebra (deep) fascia?
Located posteriorly encloses:
Postural neck muscles
Cervical vertebrae
what is in the pre tracheal fascia?
Located anteriorly & encloses: Oesophagus Trachea Thyroid gland Strap muscles Recurrent laryngeal nerves
what is in the 2 carotid sheaths?
Located anterolaterally & encloses: Vagus nerves Deep cervical lymph nodes Carotid arteries Internal jugular vein
where does the SCM attach?
Sternal head: attaches to the manubrium of the sternum
Clavicular head: attaches to the medial end of the clavicle
Both heads pass superiorly to attach to the mastoid process of the temporal bone
what nerve supplies SCM & trapezius?
CNXI
where does the trapezius attach (descending part)
Attaches inferiorly to the spine of the scapula & the lateral end of the clavicle
where do the external and anterior jugular veins run?
within superficial fascia
Drain into subclavian and external jugular vein respectively
where are the carotid sheaths located?
-Deep to the investing fascia -located anterolaterally in the neck either side of the thyroid gland
(they are bilateral tubes of deep fascia)
what is enclosed within the carotid sheath?
IJV
Common + internal carotid arteries
Vagus nerve
Deep cervical lymph nodes
what does carotid sheath do superior/inferior
sup= attach to base of skull
inf = blend with mediastinal fascia (infection spread easy to mediastinum)
what is the arterial blood supply to the thyroid and parathyroid glands?
LV → arch of aorta → subclavian and common carotid → inferior and superior thyroid artery arise respectively. (have L+R inf and sup thyroid arteries).
also thyroid ima artery is anatomical variation what goes up cartilage to supply (may be nicked in emergency tracheostomy)
what is the venous blood drainage from the thyroid and parathyroid glands?
have sup, middle and inf thyroid veins.
sup and middle → IJV → brachiocephalic veins →SVC
inferior right drains into mainly right brachiocephalic vein but sometimes left. Left always to left
why is there a venous plexus around thyroid?
allows release of thyroid hormones
lymphatics of thyroid/paratyhroid glands
superior deep cervical LN, inferior deep cervical LN, tracheal lymph nodes (Pretracheal node +
Paratracheal nodes)
ON RIGHT:Lymph is returned via the Right lymphatic duct to the Right venous angle
ON LEFT:Lymph is returned via the Thoracic duct
to the Left venous angle
detail the vagus nerves (CNX) route through neck, throat to abdomen (wandering nerve)
Branch from the medulla oblongata Exit the skull via the jugular foramen Descend through in carotid sheath Descends through the chest: Right CNX – Lateral to trachea Left CNX – Left side of aortic arch Both – Posterior to the lung hilum and on the oesophagus Both vagus nerves pass through the diaphragm with the oesophagus
Then divide into their terminal branches on the surface of the stomach supply the abdominal organs with parasympathetic axons to the distal midgut
what is the route of the left recurrent laryngeal nerve?
recurs (turns back in opposite direction) under the arch of the aorta (comes of L vagus)
what is the route of the right recurrent laryngeal nerve?
recurs under the subclavian artery (comes of R vagus)
what happens if recurrent laryngeal nerve damaged?
cannot move vocal cords so Lose abiity to produce acurrate sound/speak
what are the 4 strap muscles? what are their fustiness
Superficial (omohyoid and sternohyoid )and deep (thyrohyoid, sternothryroid).
Move hyoid and thryoid up and down in swallowing
which strap muscle has superior an inferior belly? why?
Omohyoid
Fascial sling attaching the intermediate tendon of omohyoid to the clavicle
what are the surgical approaches to the thyroid gland?
Classical thyroidectomy (similar approach to tracheostomy) - open Endoscopically assisted thyroidectomy - keyhole Endoscopic trans-axillary approach (armpit) Endoscopic trans-breast approach (breast)
what is the medical name for adam’s apple?
Laryngeal Prominence [of the Thyroid Cartilage]
neck surface anatomy has two 4 key areas, what are they? (order from midline)- for right side of neck
right anterior triangle of the neck; SCM (with sternal + clavicular heads), right posterior triangle of the neck, trapezius
where is the poster triangle of the neck located?
between SCM and trapezium
where in anterior triangle of the neck?
between midline and SCM border - many important structures (carotid sheath, strap muscles)
how is a Classical Thyroidectomy incision performed
Incision should be just superior to the clavicles & jugular notch; made through skin & platysma
“collar” incision made in natural ski crease or in direction of Langer’s lines
what can easily be damaged in Thyroidectomy? how?
recurrent laryngeal nerve. Berry’s ligament needs cut (as attached thyroid to cartilage and RLN runs very close to berry’s ligament)
what does the recurrent laryngeal nerve do?
provides somatic motor supply to most of the skeletal muscles that move the right vocal cord (the intrinsic muscles of the larynx)
what does unilateral injury of recurrent laryngeal nerve cause?
“hoarseness” or weakness of the voice & a weak cough
what does bilateral injury of recurrent laryngeal nerve cause?
aphonia (inability to produce sound)
inability to close the rima glottidis (opening between vocal cords) to prevent aspiration (inhalation of foreign body into the lungs) or to produce a good cough (requires closure of the rima glottidis)
what is the rima glottidis
a space between the vocal cords
what is berry’s ligament function?
attaches thyroid to cartilage
what are the causes of death from DM?
coma, sepsis, vascular disease.
what is the peak age of T1DM diagnosis?
9-12, also small peak early 30’s
what is the aetiology and pathophysiology of Type 1 and 2? (what happens to the islet cells?)
lymphocytes infiltrate causing insulitis = type1
amyloid deposits cause fibrosis = type 2
what genes cause type 1 DM
HLA and non-HLA (many types) can increase risk
in which months in DM diagnosis rate raised?
Dec-Jan
what antibodies are used for diagnoses type1DM
islet cell autoantibodies (ICA)
what are the ICA antibodies?
GAD65(glutamic acid decarboxylase),
IA-2 (protein tyrosine phosphatase),
IAA(antibodies to insulin),
ZnT8 (zinc)
what is Erythema ab igne
skin condition caused by long-term exposure to heat
what is the trigger for AID type 1DM?
viral (weight and puberty then accelerate it)
what are the disease markers in type 1 clinical diabetes
raised glucose, ketones are main signs
what are the disease markers in type 1 pre-diabetes
Gad65, IA2 are main antibodies
typical PC symptoms
Classic triad: -Polyuria [Enuresis in children], Polydipsia, Weight loss
Fatigue and somnolence
Blurred vision
Candidal infection: -Pruritis vulvae, Balanitis
keto-acidosis
when do you hospitalise a new case of diabetes?
DKA, vomiting, significant ketonaemia
what needs considered in social Hx
- school, college or university?
- employment
- Does the individual drive?
management of newly diagnoses Type 1DM
Blood glucose + ketone monitoring.
Insulin: usually basal [once daily] bolus [with meals] regimen + Carbohydrate estimation
Regular DSN and Dietitian contact
Appropriate medical clinic review: Weight, BP,
Bloods: HbA1c, Renal Function and Lipid; Retinal screening, Foot risk assessment
Record severe hypoglycaemic episodes or admission with diabetic ketoacidosis
what are the complications of poor diabetes control?
Retinopathy
Nephropathy
Neuropathy
(HbA1c is good predictor)
when is type 1 mot commonly diagnosed?
1-30
when is type 2 most commonly diagnosed?
young adult-elderly
when is MODY most commonly diagnosed?
13-30
when is LADA most commonly diagnosed?
20-30’s
when is secondary diabetes most commonly diagnosed
20+
what is the pattern of normal insulin secretion?
Biphasic secretion in response to meal
- Rapid phase of pre-formed insulin lasts 5 to 10 mins
- Slow phase over 1 to 2 hours
where is insulin secreted?
into portal vein
what percentage of people with CF develop sedentary diabetes?
20%
what is the likelihood of FHx for each type of diabetes? (1, 2, monogenic, secondary) in descending order of likelihood
Monogenic, 2, 1 ,secondary
what is the likelihood of ketourea at presentation for each type of diabetes? (1, 2, monogenic, secondary)
type 1 +++, sceondary +, type2/monogenic = usually none
what is the likelihood of weight loss at presentation for each type of diabetes? (1, 2, monogenic, secondary)
type 1 -usual, type2/monogenic-not usually, secondary = depends of cause
what is the likelihood of complications at presentation for each type of diabetes? (1, 2, monogenic, secondary)
type 1 - never, type 2 - up to 30%
monogenic/secondary - unusual
what is the typical age range of presentation for each type of diabetes? (1, 2, monogenic, secondary)
type1 - <5 and 10-14.
type2 - >25
monogenic - neonate to adulthood.
secondary - usually later in life
what is the duration of symptoms pre-presentation for each type of diabetes? (1, 2, monogenic, secondary)
Type1 - short, severe
type2 - months, mild
monogneic - months, mild
secondary - weeks, depends on cause
how to tell between type 1 + 2 DM?
age, BMI, symptoms, FHx of DM, ketones on urinalysis, glucose at presentation (>25 = type 1),
when are you likely to suspect neonatal (monogenic) diabetes rather than type 1 DM
Children diagnosed under the age of six months are much more likely to have Monogenic rather than Type 1 Diabetes
what does LADA stand for?
LAtent onset Diabetes of Adulthood (lowly progressing type 1/type1.5 DM).
when to suspect LADA?
non-obese Male, 25-40
Auto-antibody positive, Associated auto-immune conditions
Non-insulin requiring at diagnosis, Sub-optimal control on oral agents
patient with CF (random facts)
diabetes common, usually found in ‘severe’ mutations, i.e. ∆508, Prone to complications,
Insulin therapy preferred,
Screening with OGTT from age 10 years recommended.
what does DIDMOAD ( or Wolfram Syndrome ) stand for?
diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (also neurological anomalies)
Bardet-Biedl Syndrome signs
Often very obese Polydactyly Hypogonadal Visual impairment Hearing impairment Mental retardation Diabetes
Consanguineous parents
distinguishing feature in type 1 DM diagnosis
Short/severe
Ketones+++
Abs POS
distinguishing feature in type 2 DM diagnosis
Long/mild
Ketones 0
Abs NEG
Overweight
distinguishing feature in MODY diagnosis
Variable
Ketones 0/+
Abs NEG
Inheritanc
distinguishing feature in LADA diagnosis
Longer/variable
Ketones 0/++
Abs POS
Insulin delayed
what are some relatively commonly associated AID’s with diabetes?
Thyroid disease Coeliac disease Pernicious Anaemia Addison’s disease IgA deficiency PolyglandularEndocrinopathy
coeliac’s disease:PC + tests
Often asymptomatic
Bloating/diarrhoea
Malabsorption
Anaemia Low albumin Low calcium Anti TTG Antibodies NB IgA deficiency Duodenal Biopsy
thyroid disease: PC and tests
Many asymptomatic, Family History, Weight change, Deterioration in HbA1c, Hypoglycaemia
TSH
Consider Thyroid Abs
what needs to be screened for in diabetics?
weight, BP, retinal scan, foot risk
what test is used to regularly screen control of diabetes?
HbA1c, or glycerated haemoglobin
treatment of type 1 DM
insulin, educate, DAFNE,
aims of treatment of type 1 DM
prevent hyperglycaemia, avoid hyperglycaemia, reduced chronic complications
hypergylcaemia signs/symptoms
Thirst, tiredness, blurred vision, weight loss, polyuria, nocturia, fungal infections
Cognitive, mood state, information processing, working memory
Potential risk of diabetic ketoacidosis (“DKA”)
hypoglycaemia signs/symptoms
Pallor, sweating, tremor, palpitations, confusion, nausea, hunger.
Cognitive: tense-tiredness, information processing, working memory, coma
chronic complications of DM
microvascular disease
macrovascular disease
Avoidance of acute metabolic complications – DKA, SHG
Reduced psychosocial morbidity
what does a 1% reduction in HbA1c do?
lowers complications by 75%
what does the basal bolus regime consist of?
basal - long-acting insulin
bolus - before meals insulin
(can add in more/alter if necessary)
what is the twice daily regime
insulin taken twice a day (for elderly/non-compliant)
what needs to be taken into account when administering insulin dose?
carbohydrate intake
exercise
alcohol
pre-meal glucose
when is the one daily long-acting insulin does used?
severe type 2 DM
most people with Type 1 treated in what two ways?
MDI (x3-4 injections per day) or CSII (continuous subcutaneous insulin infusion/insulin pump)
what is the rule of thumb for starting insulin dosage?
0.3 units/kg body weight per day
how are diabetics managed in hospital?
they control their own blood sugar/insulin therapy
why are insulin regimes different from perosn to person
no one is the same - insulin rate of absorption differs,
route of administration preference, type of inulin/dosage variable
how is control of diabetes measured? (at home and clinic)
home blood glucose monitoring (newer continuous glucose monitor)
HbA1c
(rarely use urine testing for glucose/ketones anymore)
what is the advantage of continuous glucose monitoring over home glucose fingerstick tests?
“Fingerstick tests are like watching only a few scenes; CGM is like watching an entire movie. You get the full story.”
what is the largest component of the glycated hemoglobins
HbA1c
how is glycerinated haemoglobin formed?
non-enzymatic glycation of haemoglobin on exposure to glucose (predictable nature allows average blood glucose over prolonged time to be measured (6-8weeks) )
what is the target HbA1c?
48 -58 mmol/mmol or 6.5%-7.5% (aim low for younger)
what are factors affecting insulin absorption?
Temperature Injection site Injection depth Exercise pen accuracy leakage
what can occur if too many injections to same site? what is advised?
lipohypertrophy
stop injecting there (as reduced absorption)
insulin is a dangerous drug, what are some common errors made?
WRONG DOSE
INSULIN OMMISSION
WRONG INUSLIN TYPE
how to avoid giving wrong insulin dose?
Right patient Right medicine Right dose (use insulin syringe) Right route Right time
Additionally, insulin prescribing requires
Right documentation
Right monitoring
Right storage
what is taken account of when prescribing insulin?
Patient’s usual regimen and dose Blood glucose monitoring Ketone monitoring Sepsis/acute illness Steroid therapy Age / lifestyle if undergoing GA soon
what must you not do even when patient is hypo?
Do not omit insulin if hypoglycaemic, treat hypo and administer insulin as usual (can reduce dose but don’t omit)
when does alcohol affect insulin levels the most?
12-16 hours after (highest risk of hypo)
what to do with insulin administration concerning exercise
reduce short acting dose by 20% + reduce long acting dose that night.
what may be the future of insulin administration?
oral or inhaled insulin
what to do if diabetic is sick?
follow sick day rules/guidelines
when is IV insulin used?
Diabetic Ketoacidosis (DKA)
role in Hyperosmolar Hyperglycaemic State (HHS)
Acute illness
Fasting patients who are unable to tolerate oral intake
IV insulin management/ monitoring key things to do?
Hourly blood glucose (BG) monitoring
Aim for BG 5 -12 mmol/L
Free of hypoglycaemia
Check ketones if BG > 12 mmol/L
Check U & E’s at least daily
Safe transition from IV to SC insulin
what are the two types of pancreas transplant people can undergo?
Kidney-Pancreas Autotransplantation
Islet Autotransplantation
when are transplants indicated?
Imminent or ESRD due to receive or with kidney transplant
Severe hypoglycemia/ metabolic complications
Incapacitating clinical or emotional problems
