EAR (pituitary/ Thyroid) Flashcards
Where is insulin secreted
Islets of langerhans in the pancreas
What is lipolysis
Breakdown of triglycerides into free fatty acids and glycerol
Inhibited by insulin
Stimulated by glucagon, cortisol, GH and catecholamines
What is synergistic activity of hormones
Produce much greater enhanced response than sum of either hormones alone
What is permissive action of hormones
Presence of one hormone allows a second hormone to act
Eg cortisol on catecholamine activity
And prolactin to allow oxytocin action
What is antagonistic actions of hormones
When effects of hormones oppose each other
Eg PTH increases blood Ca2+ ; calcitonin decreases blood Ca2+
And insulin / glucagon in blood glucose
When is highest growth rate in humans
During foetal development and just after birth (pre natal and post natal)
What factors affect growth
Genetic
Socioeconomic and nutritional
Chronic disease and stress (cortisol causes anti growth activity by blocking actions of GH)
Endocrine hormones (mainly GH, also thyroid, insulin, glucocorticoids and sex hormones)
Where is GH synthesised
Somatotrophs in the anterior pituitary
Most abundant hormone secreted here
Actions of growth hormone (direct)
Increases lipolysis in the adipose tissue
Increases AA uptake and protein synthesis in skeletal muscle
Increases gluconeogenesis in liver
Indirect effects of GH
Stimulates release of growth factors such as IGF-I (insulin like growth factor 1) and IGF-II (somatomedins) from liver and other cell types
Action of IGF-I on cells
Stimulates protein synthesis, increase cell size (hypertrophy) - increase in lean body mass
Stimulates cell division (hyperplasia) increase in size of individual organs
Promotes skeletal growth- linear growth (increased height)
What is the role of thyroid hormones in growth
Action of GH on growth requires the presence of thyroid hormones
- permissive role on GH activity in promoting growth
- key role in CNS development (mental retardation in infants)
Role of insulin in growth
Important growth promoter (anabolic)
Important intra uterine growth factor
Role of sex hormones in growth
Dramatic rise in growth during puberty
- linear growth, muscle building and stop bone elongation by promoting epiphyseal plate closure (no more cartilage formation and remodelling into bone tissue and no more lengthening of the shaft)
What tissues do the anterior pituitary hormones have effects on
Prolactin - breast
LH, FSH (gonadotropins) - testes, ovaries
TSH (thyrotropin) - thyroid
ACTH (corticotropin) - adrenal cortex
What is GH regulated by
Hypothalamic releasing hormones (growth hormone releasing hormone (positive influence) and somatostatin(small negative influence)
What is the dual effect of glucocorticoids and GH
Initial synergism on metabolism
If chronic high levels of glucocorticoids this could inhibit GH release (eg Cushing’s syndrome, long term use of high dose steroids)
Particularly important in children as can cause growth retardation
Explain pituitary dwarfism
GH deficiency
Can be treated with hormone replacements in the pasts from human cadaver pituitaries. Now as recombinant human growth hormone
Licensed in uk to teat GH deficiency
GHD in adults symptoms
Psychological changes Malaise, tiredness, anxiety, depression Osteoporosis Poor muscle tone, decrease in lean body mass Increase in adipose tissue Impaired hair growth
What is hypothyroidism
Insufficient thyroid hormones for GH activity
What is cushings syndrome
Excess cortisol
Inhibits GH release
Inhibits linear bone growth
What is congenital adrenal hyperplasia and sexual precocity
Increased androgens result in early / rapid bone maturation (closure of epiphyseal growth plates)
What is gigantism
Tumour or excess GH in childhood
Often look much older than age
What is acromegaly
Excess GH in adults Coarsening of facial features Enlarged hands and feet Headaches, visual disturbances Sleep apnoea, general tiredness Hypertension, cardiomegaly Glucose intolerance (diabetes) Irregular or loss of periods (female); impotence (males)
Treatment of gigantism and acromegaly
Surgery or radiotherapy Somatostatin drugs (inhibit GH release)
Some tumours respond to dopamine receptors agonsits
What is hyperthyroidism
Excess THs promote GH activity
What is sexual precocity in accelerated growth
Initial accelerated bone growth (early growth spurt)
What is eunuchoidism
Hypogonadism
Low sex hormone levels result in extension of long bone growth (delayed bone maturation)
What does the hypothalamus control
Emotional state Homeostasis Body temp Hunger / thirst Circadian rhythm Sleep / wake Reproductive functions
What does the hypothalamus act with
Limbic system
Endocrine system
Autonomic nervous system
Where is the hypothalamus
Frontal and inferior to thalamus (and smaller)
- part of the diencephalon
What is the hypothalamus connected to in the limbic system
Hippocampus via fornix
Brain stem via medial forebrain bundle (from olfactory bulb)
Thalamus via mammillothalmic tract
What does the hypothalamus do through the limbic system
Deals with emotion regulation
Gets regulatory input for the ANS
What is homeostasis
Maintenance of a constant internal environment BP HR Water balance Food intake Metabolic rate Blood glucose level Used feedback loops and regulatory centres in hypothalamus and brain stem
Describe thermoregulation.
Too hot:
- anterior hypothalamus neurons
- peripheral vasodilation
- sweating
Too cold: - posterior hypothalamus neurons Peripheral vasoconstriction - piloerection - shivering - brown fat thermogenesis
What is brown fat thermogenesis
When brown fat burns it creates heat without shivering. The brown fat also burns calories.
What is rheostasis
Changes of the internal environment to counteract external changes
- circadian rhythms
- seasonal changes
What are circadian rhythms
Sleep wake cycle Heart rate / BP Body temp Organ function Hormones: vasopressin and cortisol Mental ability: attention and reaction time
What are circadian rhythms driven by
Suprachiasmatic nucleus
Evidence for this comes from lesion studies
Why do we need circadian rhythms
To anticipate changes in the external environment so our bodies can adapt
What are branchial (pharyngeal) arches
In the 4-5 week old embryonic pharynx
Arches- mesodermal proliferation - grow centrally - meet in midline -
Only 4 visible, 5th degenerates, 6th indistinct
Each arch contains:
Structural components (cartilage / bone / connective tissue)
An artery
A nerve
A muscle
And between the arches almost touching ; pouches internally lined with endoderm, grooves or clefts externally lined with ectoderm
Describe the nerves of the branchial arches
Each arch has its own nerve which innervates the associated muscle. If muscle migrates it takes its nerve with it
Describe the arteries of the branchial arches
Paired dorsal aortae connect to paired ventral aortae by branchial arch arteries - thus they surround the primitive gut. Gives rise to various arteries
What are the different arches
1st- meckels cartilage: incus, malleus, maxillary process, anterior ligament of malleus and sphenomandibular ligament
2nd- reicherts cartilage: stapes, styloid process, stylohyoid ligament, lesser Cornu and upper body of hyoid
3rd- greater Cornu and most of body of hyoid
4th- thyroid cartilage and some other laryngeal cartilages
6th arch - cricoid cartilage
What do the different arches form
1s - middle ear cavity and eustachiuan tube
2nd - tonsillar crypts
3rd- ventral wing descends into thorax to form hassall’s corpuscles and epithelial reticulum of thymus
4th- ventral wing forms ultimobranchial body which gives rise to C cells in thyroid
Dorsal wing gives rise to superior parathyroid
How does the tongue form
1st arch - lateral lingual swellings - anterior 2/3rds - median swelling
2/3/4 arch - hypobranchial eminence (copula) posterior 1/3rd
6th arch - tracheo-bronchial groove (laryngeal opening)
Formation of thyroid
Pouch of epithelium grows down from foramen caecum (between 1st and 2nd arches) to thyroid cartilage thus forming
- thyroglossal duct
In adults may form:
Cysts
Ectopic thyroid tissue
Pyramidal lobe
Development of face
Face develops from 5 elevations
- the fronto-nasal process
- paired maxillary processes
- paired mandibular processes
How does the face develop
Ectoderm all thickening gives rise to nasa placodes which then form nasal pits with medial and Lateral nasal elevations
How does the palate develop
Free communication between oral and nasal cavity
Palate makes these separate except in the oro and naso pharynx at posterior
Primary palate - intermaxillary segment
Palatine shelves - maxillary processes - vertical
How does cleft lip form
Failure to fuse anterior to incisive foramen
How does cleft palate form
Failure to fuse posterior to incisive foramen produces cleft palate
Tongue abnormalities
Cleft
Macroglossia
Microglossia
Any of these can cause speech defects
Nose abnormalities
Microstomia
Bifid
Facial abnormalities caused by fetal alcohol syndrome
Mid line facial abnormalities and effects on behaviour
Wide nose
Lack of philltrum
Heavy epicanthic folds and flattened nose
What is Graves’ disease
Hyperthyroidism Fast HR Weight loss Wasting Heat sensitive Goitre
What happens in Graves’ disease
Antibodies that stimulate TSH receptors
To shut down production of TSH, suppressing further thyroid and hormone synthesis. Thyroid hormones shut down TSH production but have no effect on autoantibody production which continues to cause excessive thyroid hormone problems
What happens in a preganant person with graves fisease
Patient with Graves’ disease makes anti TSHR antibodies
Transfer of antibodies across placenta into the foetus
Newborn infant also suffers from Graves’ disease
Plasmapheresis removes maternal anti- TSHR antibodies and cures the disease
What is pre tibial myxoedema
Thickening and coarsening of skin seen in Graves’ disease
What is Hashimoto’s thyroiditis
Hypothyroidism Low BMR Weight gain Pain, numbness Slow responses Goitre (swelling of thyroid gland that produces a lump at neck) Cold sensitive
Mechanism of B12 malabsorption in pernicious anaemia
Antibodies that block the binding of B12 to the plasma cell or antibodies that bind in the place of the B12
Type 1 diabetes mellitus
The B cell specific T cells recognise peptides from insulin or glutamic acid decarboxylase
Islets of langerhans contain several cell types secreting different hormones. Each cell expresses different tissue specific proteins
Effector T cell recognises peptides from a B cell and kills the B cell
So insulin cannot be made
What is myasthenia gravis
Autoantibodies that inhibit acetylcholine receptors
Acetylcholine receptors internalised and degraded so no Na+ influx and no muscle contraction
Tx: inject acetylcholinesterase which maintains the stimulation to the muscles for longer - makes person able to open eyes but is not a long term fix
What is goodpastures disease (type II hypersensitivity)
Autoantibodies bind directly to glomerular basement membranes giving ‘smooth’ staining pattern
Can lead to kidney failure
Takes time to build up so not obvious when autoantibodies are first generated
What is pemphigus vulgaris
Autoantibodies to epidermal cadherin
What are the subdivisions of the larynx
Nasopharynx: end of nasal cavity
Oropharynx: area of the mouth
Laryngopharynx: opening of larynx into tube
Oesophagus: runs through pharynx
What makes up the cranium
Neurocranium
Bony case of the brain
Viscerocranium
Made up of facial bones
What makes up the neurocranium
8 bones - 4 singular bones at midline 1. Frontal 2. Ethmoid 3. Sphenoid 4. Occipital 4 bilateral pairs: - temporal - parietal
What makes up the viscerocranium
14 bones - 2 singular bones at midline
- Mandible
- Vomer
- 12 bilateral pairs - Maxilla
- inferior nasal concha (turbinate) - Zygomatic
- Palatine
- Nasal
- Lacrimal
What are sutures
Areas where the cranial bones have jointed together
- fibrous or synarthoridal joints
- cant move
What is the zygomatic bone
Cheek bone
Easily palpated inferolateral to eye
Borders: maxilla, frontal bone, temporal none
Layers of the scalp
Skin
- thin layer except occipital region
- dense connective tissue
- thick layer, well supplied by aa/vv/nn
- epicranial aponeurosis
- rigid tendon outs sheet that covers top part of skull (calavaria)
- loose connective tissue
- spongy layer that can distend with fluid, allows movement over calvaria
- pericranium
- dense layer of connective tissue over bone
Which layer of the scalp is most susceptible to infection
Loose connective tissue because emissary veins provide pathway to intracranial space
What are the attachments of the scalp
Pericranium tightly adhered to calvaria
- covers neurocranium from occipital to frontal bone
- lateral: extends over temporal fascia to zygomatic arches
- blood supply contained by pericranium
- pericranium can be stripped from calvaria
Osteology of the mandible
Lower jaw acts as receptacle for teeth
- articulates with temporal bone
Temporomandibular joint
- has horizontal body and 2 vertical rami
Anatomical structure of the body of the mandible
2 borders:
- superior: alveolar border (has sockets to hold lower teeth)
- inferior: base (site of attachment for digastric mm medially)
- mandibular symphysis (small ridge of bone at midline, encloses mental protuberance - chin)
- mental foramen (passageway for inferior alveolar nn / aa)
What is the anatomical structure of the rami of the mandible
- 2 of them
- each has: head, neck, coronoid process, mandibular foramen (internal surface)
- head: posterior articulates w temporal bone forming TMJ
- neck: attachment site of lateral pterygoid mm
- Coronoid process: attachment site of temporalis mm
What is the temporomandibular joint
Mandible + temporal bone
Anterior to tragus of ear (lateral)
- articulations b/w mandibular fossa, articular tubercle of temporal none, head of mandible
- articular bones separated by articular disk therefore never in contact
- splits joints into 2 synovial joint cavities (sup / inf)
- articular surfaces of bones covered by fibrocartilage
Movements at the TMJ
Produced by mm of mastication and hyoid mm
- protrusion (chin)
- retrusion / retraction (chin)
- elevation ( close mouth)
- depression (open mouth)
- lateral movements (grinding / chewing)
What happens in TMJ dislocation
Blunt force to side of face / large bite / yawning
- head of mandible slips out of fossa and pulled anteriorly
Pt cant close mouth
Risk: damage to facial, auriculotemporal nn
What are the muscles of mastication
Masseter
Temporalis
Medial pterygoid
Lateral pterygoid
Action of the masseter
Elevates mandible, closes mouth
Attachment of the masseter
Superficial - maxillary process of zygomatic bone
Deep- zygomatic arch of temporal bone
-> ramus of mandible
Innervation of the muscles of mastication.
Mandibular nerve (branch of trigeminal nerve)
Action of the temporalis
Elevates mandible, closes mouth
Retracts mandible, pulls jaw posteriorly
Attachment of the temporalis
Temporal fossa -> coronoid process of mandible
Action of the medial pterygoid
Elevates mandible, closes mouth
Attachment of medial pterygoid
Superficial- maxillary tuberosity and pyramidal process of palatine bone
Deep - tuberosity of maxilla
-> ramus of mandible
Action of lateral pterygoid
Bilateral: protracted mandible, pushes jaw forwards
Unilateral: side to side movement of jaw
Attachment of lateral pterygoid
Superior - greater wing of sphenoid
Inferior - lateral pterygoid plate of sphenoid
- > neck of mandible
Motor innervation of the tongue
All mm (except palatoglossus) -> hypoglossal nn Palatoglossus mm -> vagus nn
What is the facial artery
Origin: external carotid aa
- branches 4 cervical + 4 facial
What is the facial vein
Origin: angular vv
Branches: cervical and facial
What is the facial nerve
Important for facial expression
Origin: pons of brain stem
Mixed nn fibres
Motor, sensory and parasympathetic fields of innervation
What is the parotid gland
Paired salivary gland
Superficial and deep lobes
Innervation: glossopharyngeal and auriculotemporal nn
How do yo test the facial nerve
Assess asymmetry at rest As pt to: - raise eyebrows - close eyes tightly - blow out cheeks - smile - add resistance
What are the muscles of facial expression
Orbital Nasal Oral Auricular Occipitofrontalis
What is the trigeminal nerve
Sensory: innervate skin, mucous membranes and sinuses of face
Motor: only mandibular branch, innervates mm of mastication
What is the anatomical course of the trigeminal nerve
Originates from 3 sensory nuclei and 1 motor nucleus
Midbrain -> medulla
Pons: sensory nuclei merge to form sensory root, motor nucleus continues to form motor root
- middle cranial fossa: sensory root expands to trigeminal ganglion, lateral to trigeminal cave
- motor root passes inferiorly to sensory and travels along floor of trigeminal cave (motor fibres only go to mandibular division)
Divisions of trigeminal nerve
Opthalmic division (V1) Maxillary division (V2) Mandibular division (V3)
How do the divisions of the trigeminal nerve exit the cranium
Opthalmic: via superior orbital fissure
Maxillary via foramen rotundum
Mandibular via foramen ovale
What is the buccal nerve
Sensory innervation to buccal membrane of mouth and 2nd / 3rd molar
What is the lingual nerve
Acts as conduit for fibres belonging to chords tympani
Innervates anterior 2/3 of tongue and submandibular sublingual glands
Sensory functions of the mandibular nerve
O facial skin in the lower third of the face, chin and lower liv
Oinferior row of teeth and gingiva
O anterior 2/3 of tongue
Motor functions of mandibular never
Olnervates the muscles of mastication
Olnervates the mylohyoid and anterior belly of digastric
Olnervates the tensor tympani and tensor veil palatini
What is the tensor tympani
Dampens sounds created by chewing by stabilising the malleus bone of the ear
What is the tensor veil palatini
Elevates the soft palate to prevent regurgitation of food and liquid into the nasopharynx
What is satiation
Feeling of fullness that terminates meal
What is satiety
Feeling of depletion that inhibits further meals
What is ghrelin
A hormone released from the GI tract that stimulates appetite
Secreted on anticipation of food
- acts centrally at ARC or brain stem to stimulate food intake through NPY and AgRP
What is leptin
Peptide hormone secreted from adipose tissue
Decreased food intake leads to decreased leptin levels (reversed by refeeding or insulin)
- production of leptin correlates with amount of adipose tissue ie energy stores
- mutations causing absence of leptin leads to severe obesity
What is PYY
Secreted from distal GIT dependent on nutrient intake (eg protein > fat or CHO)
Also stimulated by CCK, gastric acid and bile
Inhibits food intake possibly through vagal inputs
PYY levels stay elevated for 12 hours post meal
Decreases food intake in lean and obese - useful target for treatment of appetite in obese patients
How is appetite linked to reward processes in the brain
Eg opiod receptors (endorphins)
Cannabinoid receptors
Dopamine - feeding is associated with dopamine release in the dorsal striatum
What is bupropion
Dopamine reuptake inhibitor
Weight loss
What is orlistat
Inhibits gastric and pancreatic lipase
Minimal absorption
Needs to be taken before each meal
About 30% inhibition of lipases at normal therapeutic doses (lose 200kcal per day)
Needs to be combined with a low fat diet - reinforces the need to restrict fat intake
Side effects:
Steatorrhea- fatty foul smelling faeces, may help reduce fat intake
Need to monitor fat soluble vitamin status - supplements?
When would you prescribe orlistat
BMI >30 kg/m2 or BMI >28 kg/m2 if other risk factors eg type 2 diabetes, hypercholesterlaemia, hypertension
Should only be continued after 12 weeks if weight loss exceeds 5%
Treatment >12 months should only be done after discussion potential benefits and risks with patient
What is Alli
Reduced dose orlistat (OTC) Max 6 months Reduced dose Combined with reduced fat diet BMI >28 Dietary approaches and physical activity should be tried before Review after 12 weeks
What is saxenda
GLP1 agonist
Liraglutide is a glucagon like peptide 1 receptor agonist
Sc injection
Appetite suppression - increased secretion of POMC / CART anorexigenic neurons
GLP1 can also reduce high fat food intake by suppressing dopamine signalling - effect on reward pathways
What is mysimba
Combination of naltrexone and bupropion
Effects on reward pathway
Similar efficacy as orlistat
Not recommended by NICE as cost effectiveness isn’t clear (orlistat is much cheaper)
What is Sibutramine
Combined Noradrenaline and 5HT uptake inhibitor
Cf antidepressants
Appetite suppressant
No longer used - increase bp and hr
Define obesity
Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health
What comoribid conditions is obesity associated with
Depression Stroke Coronary disease (dyslipideamia, hypertension, LVH, CHF) T2 diabetes, prediabetes Gynae abnormalities Infertility GI diseases Non alcoholic fatty liver disease Pulmonary disease Sleep apnoea
What is a VLCD
Very low calorie diet
700-900 calories consumed each day for 10 weeks
What does GLP 1 do
Activates areas of the brain involved in appetite regulation
The postprandial GLP-1 response is associated with activation of areas of the human implicated in regulation of appetite and food intake
Peak postprandial increases in plasma GLP-1 concentration are correlated with increases in regional cerebral blood flor in the left dorsolateral prefrontal cortex and the hypothalamus
Types of intercellular messengers in the body
Endocrine
Autocrine and paracrine
Neuroendocrine
Neurotransmitter
What is a paracrine molecule
Relating to or denoting a hormone that has effect only in the vincinity of the gland secreting it
What is an autocrine molecule
A chemical signal that binds to and affects the cells that makes it
What is a neuroendocrine molecule
A nerve cell that makes the hormone and secretes it into the blood where it travels to target cells
What is preprohormone
‘Pre’: hydrophobic signal peptide - informs cells needs further processing and packaging because going to be exported out of cell
- large, inactive precursor
How are hormones synthesised
No gene involved
Enzymatic conversation of cholesterol
- lipophilic: lipid soluble -> readily pass over phospholipid bilayer so cant be stored
- released by simple diffusion
- bound to plasma carrier proteins in blood because aqueous
Difference in regulation of peptide vs steroid hormones
Peptide: regulation of release is control of exocytosis (presynthesised, stored hormone)
Steroid: regulation of release is regulation of synthesis
What is the endocrine axis
Interactions between hypothalamus, pituitary and peripheral endocrine glands, showing feedback regulation
General principles of treatment
Hormone deficiency: hormone replacement
Hormone excess: drugs to block production
Decreased target cell responsiveness: drugs to enhance cellular response to hormone
If tumour: radiotherapy / surgery
What are chromophobes
Immature with only a few hormones
Recently released most of their hormones
Waiting in reserve so don’t have many hormones
What are chromophils
Actively secreting cells
What are pituitary tumours
Adenoma
Common, usually benign, don’t spread
Can cause bilateral hemianopia (loss of peripheral vision) because of proximity to optic chiasm
What happens if there is damage to the pituitary stalk
Anterior pituitary hormones regulated by hypothalamic releasing factors which go down portal vessels
Hormone levels go down (other than prolactin which increases)
Posterior pituitary hormones: decrease ADP and oxytocin
How does surgical removal of pituitary tumours work
1) craniotomy - through skull above eye
2) trans - sphenoidal - through nose (most common)
What is the development of self concept
5-7 year olds can give description on range of dimensions but not relative to others
7-8 year olds can compare themselves to others - self esteem increases
Presentation of depression in adolescence
Reduced school / professional performance Social isolation Aggressive, violent behaviour Repeat consultations for ill defined complaints Family conflict Sleep disturbances Apathy Poor concentration Low self esteem
