Understand 1st year medicine

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Skin & Glands

Cell membrane junctions

  1. Tight junction: Proteins present below the apical surface of cells, functions to BLOCK the:
    1. BLOCK movement of enzymes moving between the basolateral and apical surface of cells
    2. BLOCK passage of materials directly between cells


  2. Gap junction: Integral protein (connexin) present in intercellular channel to (HOLES)
    1. Allow molecules and ions to freely move between cells
    2. Action potential in cardiac muscle to allow rhythmic contraction
  1. Desmosome: Integral protein (cadherin) to (GLUES)
    1. Hold cells tightly together
    2. Skin
    3. Absence: Ability to metastasize

Skin

Layers: Epidermis, dermis, hypodermis


Epidermis: Stratified squamous keratinocytes

  1. Stratum corneum: Dead cells, no nucleus, laid with keratin
  2. Stratum lucidum: Present in thick skin only (one cell layer), white
  3. Stratum granulosum: Distinctively black (filled with keratohyalin)
  4. Stratum spinosum: ‘Spines’ made of desmosome (GLUES cells together), langerhan (Antigen presenting cells) present
  5. Stratum basale: Cuboidal cells, mitosis to produce keratinocytes in the upper layer, merkel cell (touch)
  6. Basement membrane
Mnemonic: Come Let's Get Sun Burnt, Baby!

 


Epidermal ridge
Dermal papillary

Dermis:
  1. Thin papillary layer: Thin fine CT (connective tissue)
    1. Dermal papillary: Meisnner corpuscle (touch)
  2. Thick reticular layer: Dense irregular CT

Hypodermis: Fat
  1. Pacinian corpuscle (pressure)

Difference between thick skin and thin skin
  1. Thick skin: Thick stratum corneum, no hair, stratum lucidum
    1. Wear and tear skin - e.g. palm, sole
  2. Thin skin: Thin stratum corneum, hair, no stratum lucidum
    1. i.e. all other skin

Keratinized: Dry surface (e.g. skin)
Non-keratinized: Wet surface (e.g. oesophagus)

Receptors present in skin
Receptor Location Function
(Unencapsulated) Free nerve ending
  • Fast adapting
  • Slow adapting
Epidermis
Thermo receptor
Meissner capsule (balloon-looking) Dermal papilla
Mechanoceptor
Merkel cellsStratum basale
Mechanoceptor
Pacinian corpuscle (onion-looking) HypodermisMechanoceptor: Touch, vibration (fast-adapting receptor)
Ruffini corpuscle (spindle shaped)HypodermisProprioception



 

Types of receptors

  1. Baroreceptor: Blood pressure (e.g. in carotid sinus)
  2. Chemoreceptor: Chemicals (e.g. in carotid body)
  3. Mechanoceptor: Mechanical stress (e.g. pressure, touch)
  4. Nociceptor: Pain
  5. Osmoreceptor: Osmolarity of fluid
  6. Proprioceptor: Position
  7. Thermoreceptor: Heat/cold

Adaptation of receptors: When a stimulus is continually present, less action potential fired
  • Impulse frequency highest when there is a change (i.e. the moment stimuli is presented / removed)
  • Prevents bombarding of insignificant matters (e.g. touch of our clothing)
  • Fast-adapting: Pacinian corpuscle (mechanoceptor)
  • Slow-adapting: Free nerve endings (thermoceptor)


Skin Appendage

  • Hair and hair follicle
  • Arrector pilli muscle (origin: dermal papilla)
  • Sweat gland: Simple coiled tubular
    • Sympathetic: Sweating (e.g. exercise)
    • Types of sweat glands
      • Apocrine (a** and axilla, Genital)
      • Eccrine (everywhere), watery secretions (thermoregulation)
  • Sebaceous gland: Simple branched acinar
    • Sebum to lubricate the hair
    • Holocrine secretion

Glands

  • Exocrine (duct glands): Stomach enzymes etc.
  • Endocrine (duct-LESS glands): Hormones
  • Paracrine: Neighbouring cells
  • Unicellular: Goblet cell
  • Multicellular

 

Method of secretion
Apocrine: Bud apical portion of cell (e.g. fat droplet in mammary gland)
Holocrine: Rupture whole cell to release its content (e.g. sebaceous gland)
Eccrine/merocrine: Exocytosis from vesicle


Secretions

  • Serous: Proteins e.g. enzymes secreted by red/pinkish chief cell
    • Gastric chief cells (zymogenic): Produces pepsinogen (ENZYMES are proteins)
    • Parathyroid chief cells: Parathyroid hormone (PTH)... HORMONES are proteins
    • Parotid gland
  • Mixed: Serous and mucous
    • Submandibular gland
  • Mucous: Carbohydrates (viscous mucin), transparent
    • Sublingual gland


Multicellular exocrine glands

  • Duct system [green is duct, red is secretory]
    • Simple (non-ramified) i.e. one duct only
  • Compound (ramified) i.e. multiple ducts
  • Secretory system
    • Tubular (MUCOUS)
      • E.g. Colon, Brunner’s and Submandibular
    • Alveolar/acinar (SEROUS): Bag
      • Chief cells in stomach and parathyroid
      • Parotid gland
    • Tubuloalveolar: Mixed
      • I.e. seromucous glands sublingual
      • Serous demilunes, mucous acinus, myoepithelium

Mucous acinus: Mucin flattens nuclei to the base


Serous acinus: Pink, round central nuclei


Examples

  • Simple straight tubular: Colon

  • Simple coiled tubular: Sweat gland
  • Simple branched tubular: Stomach
  • Compound tubular: Brunner’s (submucosal) gland

 


Pancreatic lobules
Intralobular: Secretions go from.... Acini → Intercalated → Striated

  • Secretory acini (secretory portion)
  • Centroacinar (terminal portion of intercalated duct in secretory acini)
    • Secrete HCO3- (bicarbonate)
      • Stimulation from  secretin (duodenal hormone)
  • Intercalated duct: CUBOIDAL - links to striated duct
  • Striated duct: COLUMNAR
    • Striated in basal side: Ion pump for bicarbonate

 

2) Interlobular

  • Interlobular duct + connective tissue

Secretory products flow from: Acinus/centroacinar cells -> Intercalated duct (cuboidal) -> Striated duct (columnar) -> Interlobular duct

Muscle

 

Smooth Muscle (involuntary muscle)Cardiac Muscle
(heart muscle)
Skeletal muscle
(voluntary muscle)
Single nuclei
Cigar-shaped nuclei
No t-tubule
Non-striated
Single large nuclei
Central nuclei
T-tubule Branched

Semi-striated
Intercalated disk
Multinucleated
Peripheral nuclei
T-tubule
Striated (orderly actin and myosin arrangement)



Myosin:Actin ratio
1:4 in heart > 1:6 in skeletal > 1:10 in smooth muscle

Smooth muscle has a low myosin:actin ratio thus low ATPase activity and slow squeeze (contraction) - peristalsis and sphincter

 

 


Skeletal muscle (cross section): Peripheral nuclei

Smooth muscle (cross section): Round nuclei 




Layers of Muscle


Muscle (Wrapped by epimysium)
Fascicle (Wrapped by perimysium)
Muscle fiber/cell (Wrapped by endomysium)
Muscle fibre contains actin and myosin

Contraction (needs calcium)
*
Short
No plateau phase: Ca2+ is actively transported via Ca2+-ATPase back to SR as soon as it is released
*

Long
Plateau phase: Ca2+ influx = K+ efflux (Ca2+ still enters cell to allow its binding to troponin, hence, contraction)

Coordination
Independent of one another

-70 to +30mV (threshold at -55mV)
Function synctium
  • Gap junction to allow ion passage through cells

Nodal: -60mV to 0mV
Contractile: -60mV to +20mV
Refractory period (time required for cell to return to its resting potential and prepare to initiate action potentialShort so Tetanus/spasms can easily occur
Long

 

Neurons and Skeletal muscle:


Triad in skeletal muscle = Terminal cisternae – T-tubule – Terminal cisternae

T-tubule: Invagination of sarcolemma into sarcoplasm
Terminal cisternae: Enlarged sarcoplasmic recticulum (Store and release Ca2+ -> Contraction)

Triad

  • Terminal cisternae x 2
  • T-tubule


Neuromuscular junction of muscle fiber: Nerve x Muscle

Neuromuscular junction / Motor end plate: Same principles!

  1. Action potential reaches axon terminal of the pre-synaptic neuron
  2. Voltage-gated Ca2+ channels open -> Ca2+ diffuse in
  3. Ca2+ influx stimulates vesicles containing ACh to be released across the synaptic cleft
  4. ACh binds to the ligand-gated Na+ channels in the post-synaptic neuron
  5. Na+ influx into muscle membrane/post-synatpaptic neuron
  6. Action potential propogates into transverse tubule (membrane) -> Calcium release from SR -> Contraction / Threshold potential reached -> Action potential in post-synaptic neurone axon hillock

Excitation-contraction coupling in muscles (actin and myosin)

    1. Action potential from motor endplate membrane spread to T-tubule
  1. Trigger Ca2+ to be released in the SR/terminal cisternae
  2. Ca2+ diffuses and binds to troponin C
  3. To dislodge tropomyosin
  4. To expose myosin binding sites on actin
  5. Myosin head binds to myosin binding site on actin - sliding filament theory for contraction
  6. When calcium reaches a certain level, Ca2+ is active transported back to SR via Ca2+ ATPase
    1. Tropomyosin blocks myosin head binding site (actin)
      1. Myosin head no longer can bind to actin



Sliding filament theory (
BRCPA: Biceps really catch people’s attention)
  1. Bound: Myosin head still firmly ATTACHED to actin
  2. Released: The binding of ATP to myosin head releases myosin from actin
  3. Cocked: Hydrolysis of the ATP using ATPase (-> Pi and ADP + Energy) in myosin head cocks the myosin head into high energy conformation (chemical -> mechanical energy)
    1. Weak actin affinity
  4. Pi is released -> Strong actin affinity -> Powerstroke to move actin filament
  5. ADP is released

 


A band: Dark band
I band: Light band

Muscle contraction

Plateau phase: Calcium enters cell via L-type voltage-gated (aka Dihydropyridine receptor DHPR) in  sarcoelmma -> Calcium-induced calcium release -> Calcium released from sarcolemma to cytosol


 

Motor Unit Summation - the degree of contraction of a skeletal muscle is influenced by the number of motor units being stimulated (with a motor unit being a motor neuron plus all of the muscle fibers it innervates; see diagram below). Skeletal muscles consist of numerous motor units and, therefore, stimulating more motor units creates a stronger contraction.

Wave Summation - an increase in the frequency with which a muscle is stimulated increases the strength of contraction. This is illustrated in (b). With rapid stimulation (so rapid that a muscle does not completely relax between successive stimulations), a muscle fiber is re-stimulated while there is still some contractile activity. As a result, there is a 'summation' of the contractile force. In addition, with rapid stimulation there isn't enough time between successive stimulations to remove all the calcium from the sarcoplasm. So, with several stimulations in rapid succession, calcium levels in the sarcoplasm increase. More calcium means more active cross-bridges and, therefore, a stronger contraction.

If a muscle fiber is stimulated so rapidly that it does not relax at all between stimuli, a smooth, sustained contraction called tetanus occurs (illustrated by the straight line in c diagram below).

Muscle relaxation
- Less intracellular calcium levels

  • Ca2+ ATPase in SR (organelle): Pump calcium back from cytosol to SR
  • Ca2+(out)/3Na+ (in)exchanger in sarcolemma (muscle membrane)


http://www.cvphysiology.com/Cardiac%20Function/CF023%20ion%20pumps.gif

 

Skeletal muscle fiber types

Slow oxidative (e.g. postural muscles): Type I

Intermediate

Fast glycolytic (e.g. arm muscles): Type II
  • Small diameter (few   myofibril) - great Surface area for gas exchange from capillary
  • slow and weak contraction - (slow twitch e.g. soleus)
  • Red (dark)
    • Many myoglobin
  • Presence of succinate  (Kreb’s cycle)
  • Produce many ATP from aerobic respiration
    • Few glycogen
    • respire using fat
  • Many mitochondria
  • Many capillaries
  • Low myosin ATPase
  • Large diameter (many myofibril)
  • fast twitch and strong contraction (many cross-bridges b/c diameter) e.g. occular muscle
  • White (light)
  • Absence of succinate (Kreb’s cycle)
  • Rely on glycolysis from anaerobic respiration
    • Many glycogen
  • Few mitochondria for oxidative phosphorylation
  • Few myoglobin (so appear white - chicken’s breast)
  • Few capillaries
  • Rich in myosin ATPase

 


Source of energy for muscle contraction is ATP!


ATP can be derived from
  • Creatinine phosphate -> Creatinine + Pi for ADP
  • Glycolysis: 8 ATP made/glucose
    • -2 ATP per glucose due to phosphorylation of Glucose and F6P
    • 4 ATP made per glucose from substrate level phosphorylation  so net +2 ATP made
    • 2 NADH made per glucose → 6 ATP made per glucose
  • Oxidative phosphorylation: 30 ATP made/glucose
    • Link reaction: Oxidative decarboxylation
      • 2 NADH made per glucose → 6 ATP made per glucose
    • Krebs cycle: 6 NADH (18ATP), 2 FADH2 (4 ATP), 2 GTP (GTP transfers Pi to ADP, so 2 ATP) per glucose
    • ETC electron transport chain:
      • 1 NADH makes 3 ATPs
      • 1 FADH2 makes 2 ATPs

Total ATP made: 8+30 = 38

 

 

Nerve





Action Potential

  • Heart: nodes: -60 to 0mV (phases 4, 0, 3, 4), Contractile: -60 to +20mV (phases 4, 0, 1, 2, 3, 4)
  • Neurones: add or minus 10 to contractile ... i.e. -70mV to +30; threshold potential -55mV

  1. Resting -70mV
    1. na/k pump  (3 na out 2 k+ in)
    2. negative proteins [can’t move out due to large size]
    3. closed activation (outside) sodium gate, opened inactivation sodium gate - like gravity....
  2. Depol. stimuli →  some Na+ channels open →  threshold potential reached (-55mV) →  voltage gated na+ channel (activation gates open while inactivation remain open) - massive  na+ influx
  3. Repolarization
    1. na+ inactivation gate close
    2. voltage-gated k+ channel open -> K+ efflux)
  4. Undershoot! (more K+ open than during membrane's resting state)
  5. Return to resting potential via na+k+ pump


Sodium Pump (aka sodium-potassium exchange pump)

  1. ATP binds to its binding site
  2. ATP is hydrolyzed -> ADP (goes away) and Pi (remain)
  3. 3Na+ binds to pump from inside
  4. The phosphorylation causes conformational change, to allow the 3Na+ to diffuse out
  5. 2K+ binds to pump from outside
  6. Bound Pi dissociates, allowing the pump to revert back to its original conformation
  7. 2K+ diffuse out

 






Nerve conduction

Unmyelinated axons - Action potential conduction

  1. Na+ entry from axon hillock action potential attracted to the relatively negative (local current flow) adjacent sections of the axon
  2. When threshold is reached, action potential in the adjacent sections is initiated -> Influx of Na+ through voltage-gated open activation gate of axon
  3. The previous depolarized section becomes a refractory region



Meylinated axons (Myelin formation for CNS: Oligodendrocytes, PNS: Schwann cell)
  • Saltatory conduction: Action potential jumps to where Na+ channels are present (nodes of ranvier where myelin is absent)
  • Action potential (Na+ influx) at one node creates JUST ENOUGH receptor potential to reach threshold of the next. Thus AP JUMPS between nodes, allowing faster propogation of the impulse.