Anatomy, Physiology, Biochemistry Flashcards
SXMaxillary artery first part branches
MAAID
Middle meningeal (foramen spinosum) Accessory meningeal (foramen ovale) Anterior tympanic (petrotympanic fissure) Inferior alveolar (mandibular foramen) Deep auricular (external auditory meatus)
Maxillary artery second part branches
Buccal
Pterygoid
Masseteric
Deep temporal
Maxillary artery third part branches
DIPS
Descending palatine
Infraorbital
Posterior superior alveolar
Sphenopalatine
Infratemporal fossa contents
SPLMMM
Sphenomandibular ligament Pterygoid venous plexus Lateral Pterygoid muscle Medial Pterygoid muscle Maxillary artery Mandibular nerve
TMJ ligaments
1) Capsular ligament
2) extracapsular ligaments:
- Sphenomandibular
- stylomandibular
- lateral ligament
Muscles of mastication
Medial pterygoid
Lateral pterygoid
Temporalis
Masseter
Roof of infratemporal fossa
Infratemporal surface of greater wing of sphenoid bone and temporal bone
- foramen spinosum
- foramen ovale
- petrotympanic fissure
- opens to temporal fossa lateral to infratemporal crest
Infratemporal fossa anterior wall
Posterior surface of maxilla, maxillary tuberosuty
- alveolar foramina
- inferior orbital fissure (upper part)
Infratemporal fossa medial wall
Lateral pterygoid plate, lateral wall of pharynx, tensor and Lebanon veli palatini
- pterygomaxillary fissure
Infratemporal fossa lateral wall
Medial surface of mandibular ramus
- mandibular foramen
Level of bifurcation of common carotid artery
Superior border of thyroid cartilage (C4)
External carotid artery branches
Medial:
- ascending pharyngeal
Anterior:
- superior thyroid
- lingual
- facial
Posterior:
- occipital
- posterior auricular
Terminal:
- maxillary
- superficial temporal
Subclavian artery first branch
1) vertebral artery
2) thyrocervical trunk
- inferior thyroid
- ascending cervical
- transverse cervical
- suprascapular
Subclavian artery second part branches
1) Costocervical trunk
- deep cervical
- highest intercostal
Subclavian artery terminal branches
Axillary artery
Circle of Willis encircles what structure?
1) optic chiasma
2) infundibulum
3) mammillary body
Ophthalmic artery branches
Ocular:
1) central artery of the retina
2) anterior ciliary artery
3) posterior ciliary artery
Orbital:
4) Lacrimal artery
5) zygomaticofacial artery
6) zygomaticotemporal artery
7) supraorbital artery
8) supratrochlear artery
9) lacrimal artery
10) dorsal nasal artery
11) anterior ethmoidal artery
12) posterior ethmoidal artery
Lingual artery branches
Deep lingual
Dorsal lingual
Sublingual
Primary sensory cortex
Brodmann area 1,2,3a, 3b
Post central gyrus
Preliminary processing of contralateral somatosensory information
6 layers of neurons
Modality-specific columnar arrangements
Different cortical zones for propioception and mechanoception
Secondary somatosensory cortex
Upper band of lateral sulcus
Brodmann area 40
Process somatosensory information from both sides of body
Association somatosensory cortex
Posterior parietal lobe
Brodmann area 5,7
Relates sensory and motor processing
To construct abstract map of extra personal space essential for movement -> relate to PMA and SMA for grasping and reaching and tracking
Integrates somatic sensory modalities for perception
Trigrminal nerve divisions
V1 ophthalmic
V2 maxillary
V3 mandibular
V2 maxillary branches
Zygomatic nerve (-> zygomaticofacial and zygomaticotemporal)
Infraorbital nerve
Superior alveolar nerve
Palatine nerve
V1 ophthalmic branch divisions
Supratrochlear nerve Supraorbital nerve Infratrochlear nerve External nasal nerve Lacrimal nerve (SOF) Frontal nerve (SOF) Nasociliary nerve (SOF)
V3 Mandibular nerve divisions
1) Trunk branches
2) Anterior branches
3) Posterior branches
V3 trunk branches
Meningeal nerve
Nerve to medial pterygoid
V3 anterior branches
Masseteric
Deep temporal
Buccal
Nerve to lateral pterygoid
V3 posterior branches
Auriculotemporal
Inferior alveolar
Lingual
Facial nerve motor branches
Temporal Zygomatic Buccal Mandibular Cervical
End of spinal cord (level and name)
Conus medullaris (around vertebrae L1 and L2)
End of dural sac - level
S2
Arterial supply of spinal cord
Anterior spinal artery
Posterior spinal arteries *2
Radicular artery
Segmental medullary artery
Where can one find lateral horn of spinal cord
Spinal cord level T1 to L2
Major function of brain stem
1) allow passage of all ascending and descending pathways
2) contains many cranial nerve nuclei
3) contains reticular formation, which control essential life functions e.g heart beat, breathing, BP
Medulla oblongata structure
Fiber tracts
nuclei of CN V, IX-XII
Pyramid: anterior surface, descending nerve tract, decussation inferiorly
Olives: protrude from anterior surface; olivary nuclei help regulate balance, modulation of inner ear sound
Reticular formation (reticular nuclei - flexor)
Vestibular nuclei
Pons structure
Fiber tracts
Pontine nuclei: anterior portion, relay between cerebrum and cerebellum
Nuclei for CN V - IX; posterior portion
Reticular formation (reticular nucleus - extensor)
Sleep centre
Respiratory centre
Reticular formation function
1) autonomic regulation of vital organ system e.g heart beat, breathing
2) behaviour control
3) somatic motor activities
4) sleep cycle and alertness (ARAS)
6) pain modulation
Midbrain structure
Tracts:
- tegmentum
- corticospinal tract via cerebral peduncle
Nuclei:
- tectum aka corpora quadrigemina: 4 nuclei on dorsal surface; superior and inferior colliculi
- superior colliculi: visual reflex
- inferior colliculi: hearing
- red nucleus: rubrospinal tract (UL flexor)
- substantial nigra: connect with basal nuclei of cerebrum
- CN III - V
Ascending reticular activating system
1) locus ceruleus-norepinephrine system
2) raphe nucleus-serotonin system
3) pontine-acetylcholine system
4) substantia nigra-dopamine system
Function of thalamus
Major relay for all ascending sensory information except olfaction
Controls touch, temperature, pressure perception
Movement control
Diencephalon subunits
Epithalamion
Thalamus
Subthalamus
Hypothalamus
Epithalamus function
Pineal gland secretes melatonin
Subthalamus function
Connects subthalamic nuclei and basal ganglia
–> control movement and emotion
Hypothalamus function
TAN HATS thirst and osmoregulation Adenohypophysis Neurohypophysis (ADH, oxytocin) Hunger Autonomic regulation Thermoregulation Sex
Major Thalamic nuclei
VA (GP -> prefrontal)
VL (motor; BG -> sup MCor)
VPM (face sensation & taste; trigeminal and gustatory -> S1)
VPL (pain, temp, touch, pressure, proprio; spinothalamic trc & DC/ML -> S1)
LGN (vision; CN II -> visual cortex)
MGN (hearing; superior olive and inferior colliculi -> auditory cortex)
Broca’s area
Inferior frontal gyrus, dominant lobe
Assembles motor programs of speech and writing
Non-fluent aphasia
Intact comprehension
Area 44
Fibres of cerebral white matter
1) arcuate fasciculi (gyri within a lobe)
2) longitudinal fasciculi (frontal lobe with other lobes)
Wernicke’s area
Superior temporal gyrus
analysis and formulation of language content
Fluent aphasia
Non-comprehensible
Area 22
Meninges classes
Pachymeninx
- Dura mater (periosteal, meningeal)
Leptomeninx
- arachnoid mater
- pia mater
Molecular Layers of cerebral cortex
1) molecular layer
2) external granular layer
3) external pyramidal layer
4) internal granular layer
5) internal pyramidal layer
6) multiform layer
Choroid plexus component
1) pia mater invagination in ventricles
2) ependymal cells
3) blood capillaries
Composition of CSF
More Na Cl and H ions than plasma
Less Ca K ions, glucose and protein than plasma
CSF function
Nourish the brain
Fluid cushion to protect
Reduce brain weight by 97%
Cerebral artery-cortical distribution
Anterior cerebral - anteromedial surface
Middle cerebral - lateral surface
Posterior cerebral - posterior and inferior surface
Five cell types of cerebellar cortex
Purkinje cells (GABA; dual input; direct from cf; indirect from mf; only cortical output neuron) Granule cells (excitatory neurotransmitter; receive mf) Golgi cells (GABA) Basket cells (GABA) Stellate cells (GABA)
Limbic system components
Cingulate gyrus Mammillary body Amygdala Fornix Hippocampus
Major ascending tracts
Spinothalamic (anterolateral) pathway
Dorsal column-medial lemniscus pathway
Spinocerebellar pathway
Modality of spinothalamic pathway
Touch, pressure (anterior tract)
Pain, temperature (posterior tract)
DC/ML pathway modality
Discriminative touch and proprioceptive information
Spinothalamic pathway neurons
A delta fibre, C fibre
1) ipsilateral dorsal root ganglion
2) ipsilateral substantia gelatinosa; travels through central commisure to contralateral anterior or lateral spinal cord white, where they ascend to thalamus
3) VPL nucleus of contralateral thalamus
DC/LM pathway neurons
A alpha, A beta, A delta fibres
1) ipsilateral posterior root ganglion, do not synapse in spinal cord but pass into dorsal column white (fasiculus cuneatus or gracilis)
2) ipsilateral nuclei gracialis or cuneatus on posterior medulla, leave medulla and cross to contralateral side before reaching thalamus
3) VPL nucleus of thalamus
Foramen ovale contents
OVALE
Otic ganglion V3 mandibular nerve Accessory meningeal artery Lesser petrosal nerve Emissary veins
Foramen spinosum
MMM
Middle meningeal artery
Middle meningeal vein
Meningeal branch of mandibular nerve
Oral cavity boundaries
Roof: Hard palate
Floor: mylohyoid muscle
Side wall: buccinator muscle
Inferior orbital fissure contents
ZIP
Zygomatic branch of maxillary nerve
Infraorbital vessels (inferior ophthalmic vein)
Pterygopalatine ganglion’s ascending branches
Precise origin of buccinator muscle
1) from maxilla
2) from pterygomaxillary ligament (from maxillary tuberosity to hamulus of medial pterygoid plate)
3) pterygomandibular raphe (interdigitates with superior constrictor of pharynx; ends just superior end of mylohyoid line
4) external oblique line of mandible up to first molar
Separation of oral cavity and orophaynx
Palatoglossal arch - aka anterior pillar of fauces
Nasopharynx level
Below the skull and extends down to the level of soft palate (C1)
Oropharynx level
C1 (soft palate) to C3 (epiglottis)
Laryngopharynx level
C3 (epiglottis) to C6 (cricoid cartilage)
Nasopharyngeal epithelium
Respiratory epithelium
Oropharynx epithelium
Stratified squamous epithelium
Laryngopharynx epithelium
Stratified squamous epithelium
Soft palatine muscles and inner cation
Tensor veli palatini (V3 nerve to medial pterygoid)
Levator veli palatini (pharyngeal plexus)
Palatopharyngeus (pharyngeal plexus)
Palatoglosus (pharyngeal plexus)
Musculus uvulae (pharyngeal plexus)
Pharyngeal plexus
Source: CN IX, CN X, CN XI, sympathetic branches from superior cervical ganglion
Sensory: CN IX
Motor: CN XI via CN X
Cartilaginous components of larynx
1 Cricoid cartilage (hyaline)
1 thyroid cartilage (hyaline)
1 epiglottic cartilage (yellow)
2 arytenoid cartilages (hyaline)
Pharyngeal muscles
Circular:
1) superior constrictor [ph plx]
2) middle constrictor (thyropharyngeus [ph plx] and cricopharyngeus [CN X])
3) inferior constrictor [ph plx]
Longitudinal:
1) salpingopharyngeus [ph plx]
2) palatopharyngeus [ph plx]
3) stylopharyngeus [CN IX]
Fibrous components of larynx
Thyrohyoid membrane
Cricothyroid membrane
Quandrangular membrane
Extrinsic vestibular muscles
Elevation: Digastric Stylohyoid Mylohyoid Geniohyoid Stylopharyngeus Salpingopharyngeus Palatopharyngeus
Depression:
Sternothyroid
Sternohyoid
Omohyoid
Intrinsic laryngeal muscles
1) aryepiglottic
2) oblique arytenoids
3) thyroepiglottic
4) posterior cricoarytenoid
5) lateral cricoarytenoid
6) transverse arytenoids
7) cricothyroid
8) thyroarytenoid
9) Vocalis
Sensory nerve of oral cavity
V2, V3
Roof: greater palatine; nasopalatine
Floor: lingual
Cheek: buccal
Hard palate bony component
Palatine process of maxilla
Horizontal plate of palatine bone
Premaxilla
Greater palatine foramen
Greater palatine artery
Anterior palatine nerve
(Between maxilla and palatine bone)
Lesser palatine foramen
Perforated palatine bone
Middle and posterior palatine nerves
Incisive foramen
Greater palatine artery pass up to nasal cavity
Anterior palatine nerve pass up
Nasopalatine nerve pass down
Intrinsic tongue muscle
Superior longitudinal fibres
Inferior longitudinal fibres (along genioglossus, medial to hyoglossus)
Transverse fibres
Vertical fibres
ACTION: change tongue shape:
- transverse: narrow and heap up dorsal into convexity
- transverse + vertical: narrow but dorsum convexity flattened, thus smaller cross section and elongate
- trans+vert+ genioglossus: protrusion
Extrinsic tongue muscles (+innervation)
Change tongue position:
Genioglossus XII -> protrusion
Hyoglossus XII -> draw sides down
Palatoglossus (phary plx) -> raise for swallowing
Styloglossus XII -> retract for swallowing
Tongue venous drainage
Ranine vein -> underside to common facial vein
Lingual vein -> internal jugular vein
Tongue nerve supply
Anterior 2/3
- sense: lingual - taste: chorda tympani - secretonotor: C T
Posterior 1/3
- sense: IX
- taste: IX
- secretomotor: IX
Motor
XII except palatoglossus (pharyngeal plexus)
Functions of saliva
1) fluid lubricant
2) ion reservoir/ remineralisation
3) buffer
4) cleansing
5) anti microbial
6) agglutination
7) pellicle formation
8) digestion
9) taste
10) excretion
11) water balance
Saliva stimulators factors
Chewing
Vomiting
Taste (esp sour)
Food
Levels of Control of salivary secretion
1) vascular
- sympathetic vasoconstriction -> decrease filtration pressure thus scanty secretion
- parasympathetic vasodilation -> increase filtration pressure thus copious secretion
2) myoepithelial cell
- Sympathetic constriction (alpha adrenoceptor -> expulsion of saliva)
- Parasympathetic constriction (muscarinic Ach receptor -> expulsion of saliva)
3) Secretory cell
- sympathetic (beta adrenoceptor) -> protein release and scanty viscous secretion
- parasympathetic (muscarinic Ach receptor -> electrolyte transport and copious watery secretion
Factors affecting saliva composition
1) Gland of secretion (at rest 65% submandibular 20% parotid; high flow rate 50% parotid)
2) Duration
3) Circadian rhythm (Na Cl peak in morning, K peak 12 hrs out of phase, Protein peak in late afternoon)
4) Flow rate (high flow rate -> more Na Cl HCO3, pH)
5) Nature of stimuli -> affects flow rate
Levels of Control of salivary secretion
1) vascular
- sympathetic vasoconstriction (alpha adrenoceptor) -> decrease filtration pressure thus scanty secretion
- parasympathetic vasodilation (Ach muscarinic receptor or VIP receptor) -> increase filtration pressure thus copious secretion
[NOTE: 1) Increase capillary blood flow, increase capillary hydrostatic pressure, increase fluid supply to acinar cells; 2) Increase Arteriovenous anastomotic blood flow, increase venous hydrostatic pressure, increase filtration pressure via back transmission on high venous pressure, increase fluid supply to acinar cells]
2) myoepithelial cell
- Sympathetic constriction (alpha adrenoceptor -> increase intraductal pressure -> expulsion of saliva)
- Parasympathetic constriction (muscarinic Ach receptor -> increase intraductal pressure -> expulsion of saliva)
3) Secretory cell
- sympathetic (beta adrenoceptor) -> protein release and scanty viscous secretion
- parasympathetic (muscarinic Ach receptor -> electrolyte transport and copious watery secretion
Roof of nasal cavity
Frontonasal, ethmoidal and sphenoidal bones
Nose components
Nasal bones
Nasal part of frontal bone
Frontal process of maxilla
Floor of nasal cavity
Palatine process of maxilla
Horizontal plate of palatine bone
How self tolerance is achieved
Clonal deletion Clinal anergy Activation induced self death Sequestration antigen Treg cells (CD4 cd25 foxp3) release TGFbeta IL10
Treg cells antigen and cytokines and function
CD3 CD4 CD25 foxp3
Releases TGF beta and IL 10
- Inhibit potentially harmful immune responses
- prevent autoimmune responses and allograft rejection
Th0 cell cytokines
Precursor of Th1 and Th2
Releases IL2,4,5,6,10,13 IFN gamma and TNF
T helper cells subsets
Th0, Th1, Th2
All expresses CD3 and CD4
Th1 cells nature
CD3 CD4
Induced by IL12 (produced by APC) by induction of IFN gamma
Inhibited by IL4 IL10 IL13
Secretes IL2 (autocrine), IFN gamma, TNF alpha
Activates macrophages
CMI
Lymphatic system components
Lymphatic capillaries
Lymphatic vessels
Lymphatic nodes
Lymphatic trunks
Lymphatic ducts
Lymphatic tissues
Th2 nature
CD3 CD4
Induced by IL4
Inhibited by IFN gamma
Secretes IL4, IL5 IL6 IL10 IL13
Recruits eosinophil
Promote B cells IgE production
Humoral immunity
Lymphatic trunks
Jugular
Subclavian
Bronchomediastinal
Intestinal
Lumbar
Lymphatic ducts
Right lymphatic duct (drains right side of head, right upper limb, right thorax)
Thoracic duct
Lymphatic cells
NK cell B cell -> plasma cell T cell Macrophage Dendritic cell Reticular cell
Diffuse lymphatic tissue location
Throughout the body under moist epithelial membrane ie gastrointestinal, respiratory, genitourinary tracts (eg Peyer’s patches in ileum)
MALT
GALT
BALT
Location of thymus
Superior mediastinum; posterior to sternum and anterior to heart great vessels
Tonsil subtypes and histology
Pharyngeal (roof of pharynx; respiratory epithelium))
Palatine (between palatoglossus and palatopharyngeus arches; stratified squamous)
Lingual (base of tongue, stratified squamous; not as deep tonsillar crypts)
T cell regulating factors released by thymus
Thymulin
Thymopoietin
Thymosin alpha 1 and beta 4
Thymus function
Development of immunocompetent T lymphocytes to produce Th and Tc
Proliferation of clones of mature naive T cell to supply circulating lymphocyte pool and peripheral tissues
Development of immunological self tolerance
Secretion of hormones and factors to regulate T cell maturation proliferation and function
Epithelioreticular cell types
Located in thymus - 6 types
I - boundary of cortex and capsule; serve to separate thymus parenchyma from connective tissue
II - within cortex; stellate with processes and desmosomes that join long cytoplasmic processes on adjacent cells; serve to compartmentise areas for developing T cell, and T cell education
III - between cortex and medulla; functional barrier
IV - in cortex and medulla; close to type III as barrier at corticomedullary junction
V - in medulla; stellate with processes joined by desmosomes
VI - thymic/ Hasall’s corpuscles; flattened nuclei; produces IL4 and 7
Tonsil lymphatics supply
No afferent lymphatic vessels bring lymph into tonsils: supply of tonsillar lymphoid cell is exclusively by blood
Hassall’s corpuscle
Aka thymic corpuscle, found in thymic medulla
Flattened epithelioreticular cell (type VI) wrapped around each other in lamellar fashion and vary in diameter; keratinised, and joined by desmosomes and contain keratohyalin granules
Blood-Thymus Barrier
Found in the thymic cortex:
Epithelial cells form a sheath around capillaries to prevent entry of antigenic materials into spaces between epithelial cells
Blood capillary endothelial cell are not fenestrated
Endothelial cell basal lamina
Thin perivascular connective tissue with pericytes and macrophages
Type I ERCs with basement membrane
–> prevent lymphocytes from premature differentiation
How is thymus different from other lymphoid tissues
1) immature lymphocyte predominates
2) no afferent lymphatics, few efferent lymphatics
3) mature lymphocytes leave and enter blood via postcapillary venules in medulla, never recirculate here
4) blood thymus barrier
5) ERCs with few fibres in medulla
6) Hassall’s corpuscle
7) no germinal centres
What is the largest lymphoid organ
Spleen
Spleen general organisation
Covered by perineum
Encapsulated by dense connective tissue - collagen elastic fibres and smooth muscle fibres
Branching trabeculae derived from the capsule enter the spleen parenchyma
Reticular fibres form spleen stroma
White pulp (splenic nodules) and red pulp (splenic sinusoids) and marginal zone between white and red
No cortex no medulla no afferent lymphatic vessels
Vascularisation of spleen
1) splenic artery in hilum -> trabecular arteries -> central arteries (follicular arterioles) -> continues and displaces eccentrically
2a) central arteries -> periarterial lymphatic sheath PALS and penetrates lymphatic nodule/ white pulp
2b) Central arteries -> displaces eccentrically to penicillar artery, and ends as macrophage sheathed capillaries (phagocytose RBCs)
3) terminal capillary drains to splenic sinusoids (close circulation) or terminates as open-end vessels with the red pulp (red pulp)
4) splenic sinusoids -> drained by pulp veins to trabecular vein -> splenic vein
Primary lymphoid organs
Thymus and bone marrow
-> provide microenvironment for development and maturation of lymphocyte
Location of spleen
Left superior corner of abdominal cavity
Secondary lymphoid organs
Spleen, lymph nodes and nodules, GALT, MALT, BALT, Peyer’s patches of ileum
-> provide environment for lymphocyte interaction with antigens and accessory cells
Splenic White pulp anatomy physiology
I.e. Splenic nodules for immune component
1) central artery leads to periarterial lymphatic sheath PALS (T cells), which follows along secondary lymphatic nodules (B cells)
2) randomly distributed among red pulp cords and sinuses
3) corona with B cells and APCs
4) Activated B cells migrate to germinal centres near central artery
5) Plasma cells migrate to red pulp and release antibody to sinuses
Splenic marginal zone anatomy physiology
Found between red and white pulp, peripheral to periarterial lymphatic sheath PALS around central artery
Receive radial arterioles from central artery
Consist of loose lymphatic tissue with phagocytic macrophage and APCs
Dendritic cells trap and present antigens to plasma cells
This is where blood contacts the splenic parenchyma (macrophage and APCs)
Splenic red pulp anatomy physiology
Supported by reticular fibres - reticular cells and macrophage
Splenic cords = plasma cells and Mac and blood cells supported by reticular stroma
Splenic sinusoids = discontinuous vascular spaces lined by rib shaped endothelial cells oriented parallel along sinusoid long axis
Ring like strands of basal lamina and reticular fibres, as well as macrophages, surround splenic sinusoids
Open circulation (blood vessels opening to red pulp spaces) and closed circulation (blood vessels leading to splenic sinusoids) ---------
Filter to remove ages and damaged RBCs and microorganisms from blood
Storage site for RBCs
Spleen function
Blood——
1) filters blood
2) remove and destroy old and abnormal RBCs; breakdown products, bilirubin and iron are transported to liver via splenic and portal veins
3) blood passes through red pulp before leaving spleen - macrophage remove foreign substances and worn out RBCs via phagocytosis
Immune——–
4) supply effector T and B cells in white pulp, which activated during infection or inflammation
5) immune response to blood borne antigen presented via APCs
6) produce antibodies via plasma cells
7) phagocytosis
Three superficial aggregation of lymph nodes
Inguinal - from lower limb
Axillary - from upper limb and chest
Cervical - from head and neck
Lymph node basic anatomy
1) capsule of dense connective tissue
2) cortex
- trabeculae
- lymphatic nodules with dark corona of B cell; and germinal centre with lymphoblasts and plasmablasts
- mantle zone for memory cell migration
3) paracortex (deep cortex)
- T cells
- HEV (for B and T cell entry)
4) medulla
- mature B cells in medullary cords
- cords separated by medullary sinus
- plasma cells secrete Ab into efferent LVs
- follicular DCs - APC
5) subcapsular sinus
Lymphatics and vasculature of lymph nodes
Afferent lymphatic vessels enter cortex, the postcapillary high endothelial venules HEV enters paracortex and allow lymphocyte entry
Medulla with medullary cords and sinusoids
Efferent vessels at hilum
—- unidirectional flow of lymph:
1) afferent lymphatic vessels and HEV
2) subscapulr sinus
3) Trabecular sinus
4) medullary sinus
5) efferent lymphatics
Functions of lymph nodes
1) defence against foreign substances and toxins
2) filter of lymphs via reticular processes that spans sinuses -> disturb and retard lymph flow to allow time for macrophage phagocytosis of antigens and debris, and allow dendritic cells or B cells to detect for antibody production
3) maintenance and production of immune effector cells
Primary and secondary lymphatic nodules
Primary; mostly small B cells
Secondary: formed in response to antigenic challenge
- follicular dendritic cells and macrophage stimulate B cells to enlarge and prepare for mitosis
- proliferate and for plasma cell formation, producing antibody
Cutaneous mechanoceptors classifications
1) structure
- Encapsulated (meissner’s corpuscle, pacinian corpuscle, ruffini corpuscle)
- Unencapsulated (free nerve endings, hair follicle receptor, Merkel disc)
2) rate of adaptation
- slowly adapting (merkel disc, ruffini corpuscle; skin indentation depth, intensity, form and texture)
- moderately rapid adapting (meissner’s, hair follicle; velocity, motion and flutter)
- rapidly adapting (pacinian; acceleration, vibration, rapid repetitive displacement of skin)
3) modality
Meissner’s - touch, motion and flutter
Pacinian - vibration
Ruffini - skin stretch
Merkel - touch, pressure and form
Hair follicle - direction and velocity of movement
Free nerve - temperature, pain, itch and tickle
Proprioception qualities
1) body position (static limb position and trunk orientation)
2) movement (velocity and direction of joint movement)
3) forces generated by muscle contractions
Proprioceptors
1) muscle spindle (annulospiral and flower spray endings, gamma motor neuron control; sense extension - static ie muscle length and stretch - and dynamic is velocity of stretch)
2) Golgi tendon organ (sense muscle tension ie contraction)
3) joint receptor (free nerve endings and corpuscular receptors; for dynamic response; group II II IV fibres, found in connective tissues capsule and ligament of joints)
4) cutaneous mechanoceptors help
How to test for propioception
Romberg test
Patient maintain balance while standing with feet together and eyes closed
Spatial perception source
Proprioceptors
Labyrinth receptor in inner ear
Visual input
Temperature sensation
I) Static temperature detection
- detection constant skin temperature
- cold and warmth receptors
- localisation only accurate when accompanied by tactile activation
- at temperature extremes adaptation won’t occur
II) dynamic temperature sensation
- detect change in skin temperature
- depends on:
i) initial skin temperature (threshold for warmth and cold)
ii) rate of temperature change (more rapid more easily sensed)
iii) area of activated skin (spatial facilitation)
Thermoreceptors
Central Thermoreceptors
- hypothalamus and spinal cord
- thermoregulation
Cutaneous Thermoreceptors
- cold and warmth receptors
- conscious sensation of temperature
- thermoregulation
Somatosensory information, after somatosensory cortices, will be conveyed to where?
1) motor system - as continuous sensory feedback
2) limbic system eg hippocampus - for emotion and memory
3) polysensory association cortex in temporal lobe - for creation of abstract sensory map of external world
Pain definition
the subjective perception of aversion or unpleasant sensory and emotional experience associated with actual or potential tissue damage
Stimulus characteristics encoding
1) modalities
2) intensity coding
- stimulus converted to electrochemical energy
- amplitude of receptor potential and frequency of afferent fibres modulation
- population coding of recruitment
3) temporal coding
- duration of stimuli measured by discharge of receptors of different adapting speed (rapidly - onset and termination; slowly - duration)
4) spatial localisation
- receptive field
- dermatomes and sensory homunculus
- somatotopic projection
5) spatial acuity -> 2 point acuity
- size of receptive field
- innervation density
- lateral inhibition
- convergence
Nociception definition
the reception of signals in the CNS evoked by activation of nociceptors that provide information about tissue damage
Types of pain
A) Somatic pain
i) Superficial pain (skin; initial pain vs delayed pain)
ii) Deep pain (bones, joints, muscles)
B) Visceral Pain (viscera eg liver, kidney stones)
nociceptors
- Non-specialised free nerve endings
- high threshold
- non-adapting
- majority multimodal
- brain lacks nociceptor
- A-delta fibres or C fibres as afferent nerve fibres
Nociceptive afferent fibres
1) A-delta fibres
- finely myelinated
- larger diameter than C
- intense mechanical stimuli
- sharp, pricking sensation
- fast and first pain
2) C fibres
- unmyelinated
- smallest diameter
- multimodal stimuli
- burning sensation
- slow and second pain
Double Pain Physiology
A brief painful stimuli may give rise to two separate pain sensation to certain body surface as A-delta and C fibres produce different pain sensations
Pain stimuli
Associated with actual or potential tissue damage:
1) Mechanical
2) Thermal
3) Electrical
4) Chemical
Peripheral pain transduction
1) Direct from stimuli to nociceptors
2) Indirect via mediator release e.g. tissue damage releases damage byproducts and inflammatory cytokines that stimulate nociceptors; prostaglandin will sensitise nociception
Pain sensitization
A physiological process after an injury that helps healing by ensuring that contact with the injured tissue is minimised until repair is complete
tissue damage -> inflammation -> prostaglandins and bradykinin sensitise nociceptors, causing primary (at stimulation site) or secondary (site remote from original injury) hyperalgesia
Allodynia -> normally innocuous stimuli perceived as pain
Ascending pain pathways
Body and limbs -> A delta and C -> dorsal root ganglion -> substantia gelatinosa -> crosses ventral commissure -> ascent along Anterolateral system -> VPL of thalamus
Face and head -> A delta and C -> trigeminal nerve -> trigeminal nucleus -> cross midline via trigeminothalamic system through trigeminal lemniscus -> VPM of thalamus
At thalamus -> specific thalamocortical system (topographically represented) or non-specific thalamocortical system (emotional and affective aspects of pain)
Cortical projection to SI (discrimination, localisation and meaningful interpretation of pain), SII somatosensory cortex , anterior cingulate gyrus, and insula (affective components of pain)
Anterolateral system of ascending pain pathway
From body and limbs to VPL
1) Lateral spinothalamic tract
- specific thalamocortical system
- Specific thalamic nucleus to S1
- For localisation, and discrimination of pain
2) Spinoreticular tract
- to reticular formation (ARAS)
- non-specific thalamocortical system
- Intralaminar thalamic nuclei, diffuse projection to cerebral cortex in relation with limbic and hypothalamus
- for arousal, autonomic reflexes and emotional aspects of pain
3) Spinomesencephalic tract & spinotectal tract
- to midbrain and periaqueductal gray
- for affective and aversve behaviours associated with pain, initiates orienting responses, and descending pain modulation
Descending pain modulatory pathways
1) Frontal cortex and Periventricular area -> midbrain periaqueductal gray -> nucleus raphe magnus in medulla -> superficial layers of dorsal horn
2) parallel descending system from noradrenergic locus ceruleus in upper pons -> medulla -> dorsal horn
Neurotransmitters in pain pathway
Peraqueductal gray: serotonin, glutamate, opioid neuropeptides
Nucleus raphe magnus: serotonergic
Locus ceruleus: noradrenergic
Spinal cord dorsal horn: Enkephalin
Nociception characteristics
1) Modalities -> A delta and C afferent contribute to different nociceptive modalities (e.g. pricking vs burning)
2) Intensity Coding
- stimulus converted to electrochemical energy
- amplitude of receptor potential and frequency of afferent fibres modulation
- population coding of recruitment
- psychological factors
3) Temporal Coding
- little adaptation; protective
4) spatial localisation; poor because:
- low innervation density
- wide receptive field
- branching and convergent ascending fibres
- coarse topographical representation
- -> localisation aided by contribution from non-nociceptive modalities
Errors in localisation
Projected pain and referred pain
Projected pain (and examples)
Pain is incorrectly localised when ascending pathway is stimulated unnaturally
Pain sensation projected to receptive field of stimulated nerve
e.g. Spinal root compression
Ascending tract compression
Phantom Limb
Referred pain (presentation and examples)
Excitation of visceral nociceptors sensed as originating from superficial sites
Visceral pain referred to cutaneous dermatomes that share the same dorsal root (dermatomal rule)
Viscerotomes arranged according to original embryonic locations
e. g. myocardial infarction, angina; acute appendictitis, gall stone colic, renal colic, ureteric colic
Referred Pain mechanism theories
1) Axon reflex -> visceral nociception branch cause antidromic activation of cutaneous branch
2) Convergence-Projection: convergence of nociceptive cutaneous and visceral receptors onto same pool of second or higher order neutrons
3) Convergence-Facilitation: excitation of visceral afferent facilitates pain stimulus transmission from superficial pathways
4) Psychological
Body reaction to pain
1) Local reaction (triple response -> redness, swelling, warmth)
2) Reflex action
- Somatic reflex (cutaneous - flexion withdrawal; visceral - overlying muscle contraction eg peritonitis guarding)
- Autonomic reflexes (Sharp - increased sympathetic activities; Dull - decrease sympathetic activities, nausea)
3) Behavioural and emotional response
Two basic modes of muscle contraction
1) Phasic contraction
- discrete movements
- transient contraction
- rhythmic repetitive contraction e.g. walking
2) Tonic contraction
- stabilise joints eg postural maintenance
Types of movement
1) Reflex
2) voluntary movement
3) Autonomic/Rhythmic motor patterns
Motor Unit
motor neuron + muscle fibres that it innervates
Control of muscle contraction force
1) Frequency coding -> increase in frequency of firing of motor neurone allow summation of successive muscle twitches
2) population coding -> motor units recruited in fixed order from weakest to strongest
Features of reflex movement
Simple Rapid Stereotyped Involuntary Protective Controlled and elicited by stimulus
Features of automatic rhythmic movement
Repetitive movements e.g. walking running swallowing
Only the initiation and termination is voluntary; once initiated, sequence of movement is stereotyped, repetitive and automatic
Voluntary movement features
1) Complex, goal-directed (purposeful)
2) Learned (performance improve with practice -> greater practice will reduce needed conscious direction)
Nature of organization of motor control and its benefits
1) Hierarchical organization (3 level of cerebral cortex, brainstem and spinal cord)
- allow lower level to generate stereotyped movements, leaving higher centres free to generate motor commands without specifying details
2) Parallel organization
- permits higher centres to adjust spinal circuitry operation
- allows independent control of function
Motor cortex inputs
1) Sensory input:
- Somatosensory (e.g. joints, muscle spindle)
- Vestibular
- Visual
2) Corticocortical inputs
3) Subcortical inputs (via thalamus)
- Basal ganglion
- Cerebellum
Spinal cord level of motor control
Ventral horn contains lower motor neurons (final pathway for motor execution)
Somatotopically arranged with medial innervating axial muscles and lateral innervating distal muscles
Provides:
i) stereotyped response e.g. stretch reflex
ii) stereotyped motor coordination e.g. flexion reflex
iii) Rhythmic locomotor pattern e.g. walking swimming (can function with brain disconnection)
Classes of brainstem motor neurons
1) Somatic motor neurons (extraocular muscles and tongue intrinsic muscles via CN III, IV, VI, XII)
2) Special visceral motor neurons (striated muscle that control chewing, facial expression, larynx and pharynx; via CN V, VII, IX, X, XI)
3) General visceral motor neurons (parasympathetic preganglionic neurons innervating glands, blood vessels and smooth muscles)
Descending motor system for brainstem modulation
1) Lateral descending system
- rubrospinal tract
- terminates on dorsolateral spinal grey
- control of goal-directed movements, especially arms and hands (distal body parts)
2) Medial descending system
- vestibulospinal, reticulospinal and tectospinal tracts
- terminate on ventromedial spinal grey
- control of posture by axial and proximal muscles
Brainstem motor functions
1) provide motor innervation to head and neck
2) modulate spinal motor neuron and interneuron activities
3) controls posture by intergrating visual, vestibular with somatosensory information
4) Movement coordination and head and eyes
Sensory information’s importance to motor function
1) Highest level
- generate a mental image of body and its relationship with environment
2) Middle level
- tactile decisions based on memory of sensory information from past movements
3) Lowest level
- sensory feedback used to maintain posture, muscle length, tension before and after each voluntary movement
Primary motor cortex
Location: Brodmann area 4;
Precentral gyrus of frontal lobe from midsaggital sulcus to lateral sulcus
Input: receives input from PMA and SMA, direct projection from sensory area in parietal lobe and thalamus, indirect projection from cerebellum and basal ganglion
Output: terminate directly (corticospinal tract or corticobulbar tract) or indirectly (via thalamus) on spinal cord
To striatum, thalamus and pons; form elaborate neural loops through basal ganglia and cerebellum
Function: main generator/initiator of projecting signal to spinal cord; discharge frequency encodes the force of movement; direction-encoding by different populations
(note: fine digit control vai corticospinal tract)
~lowest stimulation threshold
Premotor cortex
Location: Brodmann area 6; immediately anterior to M1
Input: posterior parietal cortex (SA? for visual and somatosensory cues)
Output: medial descending system to brainstem and spinal cord to control proximal and axial muscles;
corticocortical projection to M1 for distal muscle control
Function: Sensory guidance
- proximal and axial muscles for initial phases of body and arm target orientation
- distal muscle control
~ highest stimulation threshold
Supplementary motor area
Location: Medial part of brodmann area 6; buried within the longitudinal fissure
Function: planning of movement (not directly with execution), sequence of movement, programming complex movement, coordinating bilateral movement
Efferent output from motor cortex
1) Corticospinal tract (pyramidal tract) - from middle and medial precentral gyrus
2) Corticobulbar tract - from lateral precentral gyrus
Corticobulbar tract
Origin: Motor cortex (lateral precentral gyrus - face areas)
Terminal: cranial motor nuclei (III-XII except VIII) in brainstem (all bilateral; except hypoglossal XII and lower half of facial nuclei VII which are contralateral)
Cerebellum peduncles
Superior peduncle
- output to midbrain
- ascending thalamocortical projection
Middle peduncle
- input from pons
- cortico-pontine-cerebellar circuit (pontine mossy fibres)
Inferior peduncle
- Mainly input from medulla
- spinocerebellar tract (mossy fibres)
- olivocerebellar tract (inferior olive - climbing fibres)
Cerebellum lobules
10 lobules
I to VIII lobule divided to 3 sagittal zones
IX and X are nodulus and flocculus
Cerebellum functional zones
Spinocerebellum (medial)
- vermal cortex (fastigial nucleus)
- intermediate cortex (emboliform, globose nuclei)
Cerebrocerebellum (lateral)
- hemispheric cortex (dentate nucleus)
Vestibulocerebellum (flocculonodulus)
Cerebellum input fibres
1) Mossy fibres (major afferent, e.g. spinocerebellar tract, cortico-pontine-cerebellum circuit)
- terminates at granule cells -> parallel fibres that terminates on the dendritic tree of parking cells
2) Climbing fibres (olivocerebellar tract)
- from inferior olive in medulla (with source from ruber)
- terminates <10 purkinje cells
Spinocerebellum function
Error-detector by comparing command signals (from cerebral cortex via cortico-pontine-cerebellar circuit) with the updated feedback of executed motor action via spinocerebellar tract –> moment to moment mistake correction
1) Medial corticonuclear zone (fastigial nucleus):
control postural and voluntary movement of axial and proximal muscles via
i) ventromedial descending system - vestibulospinal tract (deiters) and reticulospinal tract (ret form)
ii) ascending thalamocortical projection -> act on corticospinal component of ventromedial descending system (i.e. ventral corticospinal tract)
2) Intermediate corticonuclear zone (emboliform and globose):
coordinate voluntary movement of distal body parts via:
i) lateral descending system - rubrospinal trdact
ii) ascending thalamcortical projection -> act on corticospinal component of lateral descending system (i.e. lateral corticospinal tract)
Cerebrocerebellum function
1) Movement design (from association cortex) via cerebro-pontine-cerebellar tract reach dentate, are converted to movement programs and sent to premotor cortex via thalamocortical projection for subsequent execution of goal-directed voluntary movement (esp oculomotor control)
2) Cognitive processes
Vestibulocerebellum
1) Control of vestibulospinal reflex (postural movement via axial motor system)
- via lateral vestibulospinal tract and reticulospinal tract (ventromedial descending system)
2) Coordination of vestibule-ocular reflex
- controlled by flocculus
Vestibular nuclei
in medulla oblongata
Input: vestibular apparatus
Output: limb and trunk muscles -> extensor
Function: equilibrium and balance e.g. vestibulospinal reflexes
Red nucleus
in midbraine
Input: cerebral cortex and cerebellum
Output: rubrospinal tract -> UL flexor
Reticular nuclei
Medullary - flexor
Pontine - extensor
Central sulcus
division between frontal and parietal lobe
Sylvian fissure
divides temporal lobe from frontal and parietal lobe
Cerebral cortex input and output at molecular level
thalamus and other cortical region –> layer 4 (thickest in S1) –> spread to superficial and deep layers –> Layer 3 and 5 (thickest in M1) send output to other regions
Cerebral cortex pyramidal cell
conical cell body
apical and basal dendrites
Axon leaves base of cell to white matter
Cerebral cortex granule cells
small round cell body
interneurons that receive input from cortical afferent fibres
synapsing in output neuron
Frontal lobe function
- speaking and muscle movements
- making plans and judgements
Higher:
- problem-solving
- self-motivation
- planning
- mental tracking
- abstract thinking
- general motor control
Parietal Lobe function
- Somatoesthetic interpretation
- understanding speech
- formulate words for expression
- interpretation of shape and textures
Higher:
- space orientation
- complex movement
- recognition of self and world
- perception and integration of sensory data
Occipital lobe function
- opposite visual field’s visual information
- correlate visual image with previous experience
- integrate eye accommodation
Higher: visual and related info
Temporal lobe
- Contralateral auditory information
- Memory of auditory and visual experiences
Primary cortices
S1 and M1
Secondary cortices
PMA and SMA
S2
Tertiary cortices
Association cortex
Multimodal association
- from all sensory modalities
- handle complex function
Prefrontal association area
Works closely with motor cortices
- spatial coordinates of body
- effective motor planning
- circuitry for word formation (Broca’s)
- problem solving, self motivation, planning, abstract thinking, mental tracking
Parieto-occipito-temporal association area
Polymodal sensory high level analysis and interpretation of signals (visual, auditory and somatosensory inputs)
- memory
- spatial coordinates
- Language comprehension (Wernicke’s)
- Written words’ visual processing
- Naming of objects
Dominant hemisphere
Function: language, fine motor control
In 99% right handed, 50% left-handed -> dominant is left hemisphere
How to map brain activation
CT fMRI PET EEG MEG
Intelligence tests
IQ -> standardised test adjusted to a ge
Wechsler Adult intelligence Scale III
Folstein Mini Mental Status Examination (MMSE)
MMSE
Folstein Mini Mental Status Examination
Scale of 0-30: - Copying - Attention - Registration - Recall - Orientation - Language CARROL
Normal ageing neurological changes
- Decline in speed of central processing
- Decline on timed task performance
- Decline in recent memory retrieval
- Decline in new learning
- Decline in performance IQ
- presbyopia
- Decline in muscle bulk and strength
- Gait becomes wider based, smaller steps
- Poor balance
- Loss of ankle jerk
Motivation and its source
Definition: Needs or desire that direct behaviour
Sources (+/–):
1) Drives - internal states that pushes behaviour
2) Incentives - external stimuli that pulls behaviour
Reward stimuli
Triggers release of dopamine in striatum –> feeling “high”
Ventral striatum
i.e. Nucleus Accumbens
- responsible for incentive motivation processes
- Dopamine received from Ventral Tegmental Area (VTA)
Dorsal striatum
Caudate and Putamen
- concerned with regulation of movement and cognition
- Dopamine received from substantial nigra
Associative learning
PALOVIAN CONDITIONING
- Learning predictive relationships
- neutral cue precedes reliably a reinforcer - an unconditioned stimulus (e.g. food)
- the neutral cue acquires motivational value per se - conditioned stimulus
- Anticipatory response –> Consummatory response
INSTRUMENTAL CONDITIONING
- learning that an action leads to delivery of reward ->reinforcing an instrumental response
- Basolateral amygdala has extensive sensory cortical input that forms CS-US association
- Central nucleus of amygdala critical for CS-response outcome learning
- Amygdala connected to striatum and prefrontal cortex (palovian information linked with decision making system)
- Ventral striatum (Nuc Ac) gives motivational drive amplified via dopamine -> promote rewarding actions
- Prefrontal cortex provide info on choices and inhibitory control
Descending pathways
1) Lateral pathway
i) Lateral corticospinal tract
ii) rubrospinal tract
2) Ventromedial pathway
i) Ventral corticospinal tract
ii) Reticulospinal tract
iii) Vestibulospinal tract
iv) Tectospinal tract
Lateral descending pathway
i) Lateral corticospinal tract
ii) rubrospinal tract
Motor cortex and red nucleus -> posterior limb of internal capsule -> decussate at lower medulla (pyramid) -> lateral funiculus of spinal cord -> terminates contralaterally at interneurons (small number), or lateral ventral horn’s motor neurons
- Innervates limbs, especially distal muscles
- All terminations are unilateral and contralateral
- Terminal branch gives off few collaterals
Ventromedial descending pathway
i) Ventral corticospinal tract
ii) Reticulospinal tract
iii) Vestibulospinal tract
iv) Tectospinal tract
Origin -> posterior limb of internal capsule -> does not decussate -> ventral funiculus of spinal cord -> terminates ipsilaterally at interneurons (many), or medial ventral horn’s motor neurons -> many collaterals leading to bilateral terminations
- innervates axial and proximal muscles
- Many bilateral terminations
- terminal branch gives off many collaterals
Lateral pathway vs ventromedial pathway
1) Component tract difference
2) Lateral funiculus vs ventral funiculus
3) Terminal branch few collaterals vs many collaterals
4) Small number interneuron termination vs many
5) Lateral ventral horn vs medial ventral horn
6) All unilateral vs many bilateral
7) Innervates distal muscles vs axial and proximal
Thyroid gland embryology
midline caudal to the median tongue bud, an endodermal thickening at foramen caecum.
forms a bilobed structure and migrates ventral to the laryngotracheal tube to reach its definitive position (7th week)
During migration, thyroid remains connected to the tongue by the thyroglossal duct. This duct later disappears
Ultimobranchial body forms the C cells/ parafollicular cells of thyroid
Parathyroid gland embryology
Dorsal recess of the 3rd pharyngeal pouch becomes solid by proliferation, forming the inferior parathyroid glands
Dorsal recess of the 4th pharyngeal pouch becomes solid by proliferation, forming the superior parathyroid glands
Migrate caudally with the thymus and and become intimately associated with the dorsal aspect of the thyroid gland
Parathyroid gland location
embedded between the posterior border and the capsule of the thyroid
usually 4, but may vary from 2 to 6
Vasculature of the thyroid gland
Superior thyroid artery (from external carotid artery)
Inferior thyroid artery (from thyrocervical trunk of 1st part of subclavian artery)
Superior and middle thyroid vein (to internal jugular veins)
Inferior thyroid vein (to brachiocephalic vein or internal jugular vein)
Thyroid anatomy
Bilobed lying on either side of the trachea and the larynx
Lobes connected by isthmus at level of 2nd - 4th tracheal cartilage
50% has appendix from isthmus towards hyoid cartilage
Encapsulated by a tough fibrous capsule
pretracheal fascia binds the gland in front and at the back of the trachea
Between the gland capsule and the fibrous capsule posteriorly are the parathyroid glands
sternothyroid, sternohyoid muscles and cervical fascia lie in front
Nerves closely associated with the thyroid glands
1) External laryngeal nerve (branch of the superior laryngeal nerve; supply the cricothyroid muscle)
2) Recurrent laryngeal nerve (in the tracheo-oesophageal groove posterior to the inferior thyroid artery, 50% in pretracheal fascia; supply all laryngeal muscle except cricothyroid
Histology of the thyroid gland
Vesicular follicles formed by follicular cells (T3 T4), which are lined with simple cuboidal to squamous epithelium (will become columnar when active)
Follicular lumen filled with homogenous colloid, thyroglobulin, with many tyrosine residues (colloid will shrink when active)
Light staining parafollicular cells or C cells (Calcitonin) lies between follicles or embedded within the follicle
Histology of the parathyroid
two kinds of epithelial cells:
1) Principal cells - parathyroid hormone (PTH)
2) Oxyphil cells - eosinophilic cells; function unknown.
Thyroid innervations
Adrenergic innervation from there cervical ganglia
Cholinergic innervation from the vagus nerves.
Hormones that increase cAMP
FLAT CHAMP GG
FSH
LH
ACTH
TSH
CRH hCG ADH (V2) MSH PTH
Glucagon
GHRH
Hormones that increase IP3
GOAT HAG
GnRH
Oxytocin
ADH (v1)
TRH
H2
Gastrin
Hormones that act via steroid receptor
VETTT CAP
Vit D Estrogen Testosterone T4 T3
Cortisol
Aldosterone
Progesterone
Hormones that act via JAK/STAT pathway
PIG
Prolactin
GH
Immunomodulin
Hormones that act via tyrosine kinase pathway
inslun, IGF-1
TSH effect
Binds to thyroid follicular cells, increase cAMP level, which will stimulate:
1) thyroglobulin production
2) NI symporter
3) TH exocytosis
Thyroid hormone form
Tetraiodothyronine (T4; usually called thyroxine) Triiodothyronine (T3)
Derived from the modification of tyrosine
Difference between T3 and T4
Less T3 (~10%) released by thyroid gland than T4 (~90%)
T3 has greater biological activity (faster onset) than T4 (slower onset)
99.5% bound to plasma proteins vs 99.95%
Small pool vs large pool
Mainly intracellular vs mainly circulating
Short half life (fast turnover) vs long half life (slow turnover)
Thyroglobulin biosynthesis
Thyroglobulin (TG) is a large polypeptide which is synthesized in ribosomes of thyroid follicle cells in response to TSH/cAMP
The TG colloid is incorporated into exocytotic vesicles and extruded into follicular antrum.
Biosynthesis of TH
1) Iodide trapping
2) Oxidation
3) Iodination/Organification
4) Coupling
- ——
1) iodide is taken up actively by Na-I symporter (activated by TSH/cAMP)
2) iodide is oxidized by thyroidal peroxidase to iodine in thyroglobulin
3) tyrosine residue in thyroglobulin is iodinated and forms MIT (monoiodotyrosine) & DIT (diiodotyrosine).
4) iodotyrosines (MIT & DIT) are coupled together to form T3 & T4 [MIT+DIT=T3; DIT+DIT=T4]
Secretion of TH
When thyroid gland is stimulated (e.g. TSH/cAMP), vigorous endocytosis of colloid occurs.
Endocytotic vesicles fuse with lysosomes inside the follicular cell. T3 & T4 are hydrolyzed from the thyroglobulin and released into the circulation via exocytosis.
Transport form of TH
TH is lipid-soluble but insoluble in water, therefore usually associated with binding proteins in plasma:
1) Thyroid Hormone-Binding Globulin (~70%)
2) Pre-albumin (transthyretin) (~15%)
3) Albumin (~15%)
4) Free (<1%)
Biological active form of TH
Free or albumin bound
Activation & inactivation of TH
Deiodination reactions in the peripheral tissues activate and inactivate TH
25% of T4 is deiodinated (outer ring, by D1 or D2) to T3 in peripheral tissues. Deiodination (inner ring, by D1 and D3) may form an equal amount of reverse T3 which has no biological activity.
T3 (and rT3) may then be inactivated by further deiodination (inner ring and outer ring respectively) to form T2
Enzymes for deiodination of thyroid hormones
Deiodinase type 1 (D1) located in the liver, kidney and thyroid gland.
Deiodinase type 2 (D2) located in skeleton muscle, CNS, pituitary gland and placenta. Can only deiodinate outer ring.
Deiodinase type 3 (D3) found in fetal tissue and placenta; also present throughout brain, except in the pituitary. Can only deiodinate inner ring.
Mechanism of TH action
- Cells take up free TH from blood.
- Once inside the cell, T4 is deiodinated to T3
which enters the nucleus and binds to TH receptor (TR). - TR with bound T3 forms a complex with another nuclear receptor called retinoid X receptor (RxR) to initiate transcription of thyroid hormone response elements (TRE)
- TR can also complex with other coactivators or corepressors to regulation protein production.
Physiological effects of TH
BBBB
1) Bone growth and growth
2) Brain maturation and CNS effect
3) Basal metabolic rate and thermogenesis
4) Beta-adrenergic effects and enhance heart contraction
5) Biphasic Metabolism modulation
6) Permissive effect on other hormones
1) Stimulates endochondral ossification for skeletal maturation (more cartilage to bone)
1) Biphasic effect on protein by increase proteolysis increase protein production
1) Increase growth hormone secretion and its effects
1) Stimulation of cell growth directly
1) Normal response to parathormone and calcitonin
2) Critical for brain development (deficiency → permanent mental retardation)
2) Behaviour control through expression of beta-adernoceptors to potentiate response to catecholamine (increased excitability)
3) Increase N+/K+-ATPase, which increases oxidative phosphorylation and ATP production from ADP and the basal metabolic rate; heat is generated as a result
4) Direct effect by increasing the expression of contractile proteins
4) Expression of beta-adernoceptors enhances response to adrenaline/noradrenaline (sympathetic nervous system)
4) Metabolic effect of enhanced thermogenesis and oxidative phosphorylation leads to vasodilation, ↑blood vol. → ↑ venous return → ↑ cardiac output
5) Biphasic control on glucose (increase glycolysis, increase gluconeogenesis, increase glycogenesis, increase glycogenolysis, increase GI glucose absorption [hyperglycaemia]
5) Biphasic effect on protein by increase proteolysis increase protein synthesis; [increase protein; too high -> skeletal muscle proteolysis]
5) Biphasic effect on lipid, increase lipolysis and lipid synthesis; [decrease in serum cholesterol]
Permissive action of thyroid hormone
1) By inhibiting phosphodiesterase (prevents cAMP breakdown)
2) By increasing the synthesis of adenyl cyclase
3) By increasing receptors for another hormone e.g. T4 on beta-adrenoceptor.
TH secretion regulation
- Hypothalamic-pituitary thyroid axis: TRH -> TSH -> T3/T4 (somatostatin released by hypothalamus inhibits TSH secretion)
- Negative feedback: circulation T3/T4 inhibit TRH & TSH secretion
- Environmental factors: Cold, trauma, stress
- Excessive iodide (anti-TSH): ↓ synthesis & release of TH
Neck lymph node levels
6 levels
Level Ia submental
Level Ib submandibular
Level II upper jugular
Level III mid jugular
Level IV lower jugular
Level V posterior triangle
Level VI pretracheal
Supraclavicular fossa - lower nodes of IV and V
Structure of Neck lymph node level Ia
Submental
- lower lip
- anterior oral floor
- tongue tip
- mandibular incisors
Structure of Neck lymph node level Ib
Submandibular
- oral cavity
- tongue
- anterior nasal cavity
- submandibular gland
Structure of Neck lymph node level II
Upper jugular
- nasal cavity and sinuses
- oral cavity
- orophaynx
- nasopharynx
- supraglottic larynx
- hypopharynx
- parotid and submandibular glands
Structure of Neck lymph node level III
Mid jugular
- oral cavity
- oropharynx
- larynx
- hypopharynx
Structure of Neck lymph node level IV
Lower jugular
- hypopharynx
- larynx
- thyroid
- cervical oesophagus
Structure of Neck lymph node level V
Posterior triangle
- nasopharynx
- oropharynx
- posterior neck and scalp
Structure of supraclavicular fossa LN
Drainage from neck above or below clavicle
Right side - infra-clavicle lesion
Left side - infra-clavicle lesion of infra-diaphragmatic lesion (via thoracic duct) aka Virchow’s node
Electrical synaptic transmission
1) An action potential reaches the presynaptic terminal
2) ions flow through gap junction changes formed by connexons and depolarise post-synaptic membrane
3) Generation of action potential
Chemical synaptic transmission
1) Neurotransmitter synthesised in presynaptic terminal and stored in vesicle
2) Action potential reaches presynaptic terminal
3) Presynaptic voltage gated calcium channels open to allow calcium influx
4) Calcium influx causes fusion of vesicle and membrane that allows exocytosis of neurotransmitter vesicles
5) Neurotransmitters diffuse through synaptic cleft to reach postsynaptic membrane and bind with receptor
6) Ligand-gated postsynaptic ion channel open/close
7) Generation of EPSP or IPSP
8) Retrieval of vesicular membrane from plasma membrane
Electrical synapse vs chemical synapse
Faster response in electrical synapse (no lag phase between presynaptic and postsynaptic)
Miniature End Plate Potential (MEPP)
- Fixed size of 0.5mV
- Spontaneous in absence of stimulation
- Increased frequency with depolarisation
- Neurotransmitter release
Quantal nature of neurotransmitter release
- Higher extracellular calcium level and calcium influx will increase the probability of fusion of synaptic neurotransmitter vesicles with plasma membrane and the release of neurotransmitters (0.5mV = one unit MEPP = one vesicle)
- summation of MEPP
SNARE definition
SNAP receptor
Form complexes to pull membranes closer together for future fusion
synaptic vesicle SNARE
synaptobrevin
plasma membrane SNARE
syntaxin and SNAP-25
Synaptic vesicle fusion with plasma membrane biochemistry
1) Vesicle docking
2) Formation of SNARE complexes between synaptic vesicle synaptobrevin and plasma membrane SNAP-25 and syntaxin -> pull membranes closer together
3) Influxed calcium binds to synaptotagmin -> catalyse membrane fusion
Proteins required for endocytotic budding of plasma membrane to form vesicles
Clathrin
Dynamin (pinching off)
Protein that helps to maintain synaptic vesicle in reserve pool
synapsin
synapsin function
Reversibly bind to synaptic vesicles for cross-linking -> tether them to stay in reserve pool for future neurotransmitter release
NSF function
NEM-sensitive fusion protein
Vesicle and golgi membrane fusion
Priming synaptic vesicles for fusion
Regulate SNARE assembly
SNAP function
soluble NSF attachment protein
Vesicle and golgi membrane fusion
Priming synaptic vesicles for fusion
Regulate SNARE assembly
Monoamine neurotransmitters
Norepinephrine
Dopamine
Histamine
Serotonin
Purine neurotransmitter
ATP
Adenosine
Amino acid neurotransmitter
Glutamate
Glycine
GABA
Peptide neurotransmitters
Endorphin
Enkaphalin
Substance P
Small molecule neurotransmitter vs peptide neurotransmitter synthesis and release
Small molecule vs peptide
1) Cell body synthesise enzyme VS synthesise pre-propeptide and enzyme
2) Slow axonal transport of enzymes to axon terminal VS fast axonal transport of nascent peptide and enzyme in vesicles along microtubule tract
3) at axonal terminal, synthesis and packaging of neurotransmitter with enzyme and precursor VS enzymatic processing of nascent peptide into mature peptide
4) Release and diffusion (identical)
Acetylcholine receptor
1) Nicotinic receptor
- ligand-gated Na and K channel
2) Muscarinic receptor
- GPCR
Glutamate receptor
AMPA, NMDA, Kainate
Ionotropic glutamate receptor
AMPA - ligand-gated NA channel (Na influx)
NMDA - Mg blocks NMDA; Na influx will displace Mg, activate channel; ligand-gated Na and Ca channel -> Ca as secondary messenger
EPSP definition
A reverse potential that is more positive than action potential threshold
IPSP definition
A reverse potential that is more negative than action potential threshold
Ionotropic GABA receptor
Pentamer, ligand-gated Cl- channel
Spatial summation of post-synaptic potential
Occurs when several excitatory postsynaptic potential arrives at axon hillock simultaneously
Temporal summation of post-synaptic potential
Postsynaptic potentials created at the same synapse in rapid succession are summed
Ionotropic GABA receptor is activated by:
GABA
Benzodiazepine
Barbiturates
Neurosteroids
Ethanol
Synaptic memory
High frequency stimulation (e.g. via electrodes) of synapse can cause a long-lasting increased sensitivity to the stimulation
aka long term potentiation
Heme structure
macrocyclic compound made up of four pyrrole subunits; carries Fe2+
Metabolic functions of Heme
1) Electron carrier and ATP synthesis (cytochrome)
2) Detoxification (cytochrome P450)
3) Carrier of oxygen (haemoglobin, myoglobin)
4) Decomposition of oxidative species (catalase)
First reaction in heme synthesis pathway
Glycine + succinyl Co-A –> delta-aminolevulinic acid (ALA)
Enzyme: ALA synthase
In mitochondria
ALA synthase isoforms
ALA-S1
- chromosome 3
- ubiquitously expressed
- regulated by heme
- low abundance, high rate of protein turnover
ALA-S2
- chromosome X
- expressed in erythroid cells
- regulated by iron-dependent mRNA translation
Bone marrow-produced heme fate
Haemoglobin formation
Liver-produced heme fate
60% - microsomal cytochrome P450
15% - catalase
some for mitochondrial cytochromes
Regulation of liver heme metabolism
ALA-S1 which is regulated by heme pool
Increased heme will inhibit:
1) DNA transcription to ALA-S1 mRNA
2) mRNA translation to ALA-S1
3) translocation of ALA-S1 to mitochondria
4) directly ALA-S1
Regulation of erythroid cell heme metabolism
ALA-S1 and ALA-S2
ALA-S2 mRNA translation is inhibited when Fe-transferrin level is low (e.g. when heme is high)
Increased heme may also inhibit:
1) DNA transcription to ALA-S1 mRNA
2) mRNA translation to ALA-S1
3) translocation of ALA-S1 to mitochondria
4) Directly ALA-S1
Heme degradation
Reticuloendothelial system of spleen:
1) Haemoglobin -> verdoglobin; Oxidation of methane bridge in porphyrin ring (heme oxygenase)
2) Cleavage of methane bridge to tetrapyrrole –> biliverdin
3) Globin is degraded by proteases while Iron returns to iron pool
4) Reduction of methane bridge –> bilirubin (biliverdin reductase)
Blood:
5) Bilirubin carried by albumin from spleen to liver
Liver:
6) Bilirubin conjugated with UDP-glucuronide (udp glucuronosyltransferase) -> bilirubin diglucuronide
7) Removed from liver via bile
Intestine:
8) Urobilinogen -> stercobilin
Kidney:
9) Urobilinogen from intestine -> urobilin
Heme synthesis sites
Synthesis in almost all cells, especially liver and erythroid tissue (RBM in adults)
(not haematopoiesis site, which is erythroid tissue only)
Metabolic roles for irons
1) Involved in redox reaction
- oxygen uptake (haemoglobin)
- redox reaction for electron transport or detoxification or oxidative species (cytochrome, CYP, catalase)
- activation of oxygen (oxidase, oxygenate)
- activation of nitrogen in plants (nitrogenase)
2) Essential for cell proliferation
2) Cell proliferation
Iron uptake in diet
- Bioavailability of food iron is more important than amount of iron in diet
- Heme iron more easily absorbed than non-heme
- mostly in form of ferric iron Fe3+
Inhibitors of non-heme iron absorption
Calcium salts Phosphoprotein in egg yolk Phytates in Bran Tannates in Tea Polyphenols in vegetables
Iron uptake biochemistry
Gastroferrin (stomach glyocprotein) forms complex with ingested Ferric iron (3+)
Iron crosses brush border of intestinal mucosal cells as Ferrous iron (2+)
Carrier protein in mucosal cells binds to ferrous and distribute it to rest of the body
Proteins for transport of iron
Transferrin (less blood iron -> increase in transferrin)
Protein for storage of iron
Ferritin: storage as mobile fraction (more blood iron -> increase in ferritin)
Hemosiderin: storage as aggregate
Ferritin structure
- Apoferritin made up of 24 subunits forming a sphere
- A core of polynuclear hydrated ferric oxide phosphate
- Hold 4500 ferric ions
- 8 hydrophilic channels for communication with exterior
Ferritin function
- Store iron as mobile fraction
- detoxification
Ferritin level regulation
When chelatable iron level rises, IRP-1 (IRE repressor protein-1) or IRP-2? will dissociate will dissociate from ferritin mRNA at IRE (iron-response element) -> increase translation of ferritin
Transferrin function
- iron transport (binds iron from donor cells and delivers it via plasma to specific receptors on recipient cells)
- distribution of iron
Transferrin structure
Single polypeptide chain that binds two ferric ions tightly but reversibly
Examples of transferrin
Serotransferrin
Ovotransferrin
Lactotransferrin
Transferrin receptor structure
a glycoprotein
Transferrin receptor synthesis regulation
- transferrin receptor mRNA contains 5 IREs
- Low iron concentration, IRP-1 will bind to IRE, which increases the ability of mRNA and protects it from degradation -> increased translation
Transferrin synthesis regulation
- Iron deficiency stimulates liver transferrin gene
- increased storage iron gives negative feedback on transferrin synthesis
Iron transport biochemistry
1) Iron is stored as ferric (3+) in ferritin and will be converted to ferrous (2+) for transfer in blood
2) Ferritin reductase will transfer iron to transferrin (ferric -> ferrous) in presence of FAD and NADH2
3) ferrous -> ferric by a ferroxidase, ceruloplasmin, in transferrin before transport
4) Ferric-transferin may bind to reticulocytes for transport
Haber-Weiss reaction
Ferrous + H2O2 => Ferric + OH* + OH-
O2-* (superoxide) + Ferric => O2 + OH- + OH*
Pentose phosphate pathway features
1) Anaerobic
2) Primary source of reduced NADP - for fatty acid and cholesterol synthesis
3) Supply source of pentose (ribose) - for nucleotide and nucleus acid synthesis
4) 1 G6P produce 12 NADPH and 6 CO2
Pentose phosphate pathway Phases
Phase I (oxidation)
- G6P to 6 phosphogluconate 6PG via G6PD
- 6PG to D-ribulose 5-phosphate via 6PGD
Phase II (decarboxylation-isomerization) - forms D-ribose 5P and D-xylulose 5P
Phase III
- 5,5 -> 7,3 (2 carbon shift)
- 7,3 -> 6,4 (3 carbon shift)
- 5,4 -> 6,3 (2 carbon shift)
- forming D-fructose 6P, D-glyceraldehyde 3P
G6PD gene
- Xq28 (long arm)
G6PD deficiency not caused by single mutation, large insertion or deletion; heterogenous in nature
G6PD function
- rate limiting step in pentose phosphate pathway (G6P -> 6PG)
- Generate NADPH that protects RBC membrane from reactive oxidative species (NADPH reduce glutathione via glutathione reductase to form reduced glutathione, that reacts with reactive oxidative species via glutathione peroxidase)
Glutathione structure
A tripeptide made up of glutamate, cysteine, glycine
Glutathione reductase function
Oxidised glutathione to reduced glutathione (NADPH -> NADP); disulphide form to sulfhydryl form
Glutathione peroxidase
reduce oxidative species such as peroxides by covering reduced glutathione to disulphide oxidised form
SOD1 gene function
(mutation leads to ALS)
- binds to Cu++ and Zn++
- regulate disputation of superoxide ion into hydrogen peroxide
Anterograde transport
From cell body to neuronal end; kinesin
Retrograde transport
From neuronal end back to cell body; dynein, dynactin
PARK2 gene
Parkin (E3 ubiquitin ligase)
mutation leads to parkinson’s
attachment of polyubiquitin chains to protein targeted for proteasome proteolysis
Cleavage site for coagulation factor activation
Arginine indicates peptide bond position that require cleaving for activation
Two ends of coagulation factor
COOH end: serine protease
NH2 end: Gamma-carboxy glutamic acid (for localising coagulation
Tissue factor nature
Extrinsic pathway
- localised in tissue adventitia
- expressed in most cells except resting endothelial cells
- transmembrane protein
- exposed to intravascular space after vascular damage
- does not require proteolytic activation
Factor VII
Extrinsic pathway
- single chain zymogen
- low intrinsic enzymic activity
- highly active when bound to tissue factor
GpIb
platelet-VWF adhesion (VWF binds to subendothelial surface)
GpIIb/IIIa
platelet-platelet aggregation (binds to fibrinogen)
Role of platelet in coagulation cascade
1) Adhesion -> binds VWF via GpIb at site of injury
2) Release reaction -> release Ca and ADP (for coagulation cascade; ADP also helps platelet to adhere on endothelial surface and GpIIb/IIIa expression on platelet surface)
3) Prostaglandin relase (TXA2 -> pro-aggregation)
4) membrane vesiculation
Phospholipid in coagulation cascade
Phospholipid in plasma membrane catalysed by floppase to express greater on outer cell surface -> localised coagulation by binding to gamma-carboxy glutamic acid of coagulation factors in the presence of Ca++
Thrombomodulin
Complex with thrombin to Activate protein C for anticoagulation
Protein C function
Activated by thrombomodulin (with thrombin)
direcrly cleaves, with protein S, membrane bound factor Va and VIIIa
mediate cleavage of factor Va to Vac, which then forms complex with Protein C and Protein S, to inactivate factor VIIIa
Inhibitors of platelet response
PGI2 and NO released by normal endothelial cells
Fetal haemoglobin
HbF (α2γ2)
