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Physiology)Topics)for)the)Exam:)Review ) /)Pictures )

(Based'on'Doc.'Motoc’s'slides,'Guyton’s'Medical'Physiology ,'Wiki ' and'some'personal'extras) '

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N°1:)Digestion)in)the)oral)cavity )

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As'food'enters'the'oral'cavity'the'cheeks'and'the'closed'lips'hold'food' between ' the'teeth,'the'tongue'mixes'the'food'with'saliva'to'soften'it,' and'the'teeth'cut'and'grind'it'into'a'bolus. The'tongue'initiates'the' voluntary'phase'of'deglutition.'The'tip'of'the'tongue'is'place'on'the' hard'palate,'and'then'contracts'which'forces'the'bol us'into'the' oropharynx. '

*Salivary'solutes?'Get'a'list!'(Salivary'pH'='6,8) '

Salivary'amylase'(begins'starch'digestion,'works'at'neutral'pH,' is'inactivated'by'the'stomach’s'pH) '

Lingual'lipase'(inactive'at'neutral'pH,'activated'in'the'stomach)'

Mucus'(lubric ation'and'bindings'of'food'into'bolus) '

Lysozyme'(kills'bacteria) '

Ig'A'(inhibits'bacteria’s'growing) '

Electrolytes' ' ***further'infos'at'topic'n°10 '

N°2:))Motility)of)the)Stomach )

The'bolus'is'mixed'with'gastric'juice'to'form'chime. ' This'is'possible' because'o f'the'3'muscle'layers'of'the'stomach ' (longitudinal,'circular' and'oblique) ,'and'the'contraction'of'the'pyloric'sphincter.'

The'propulsion'phase: '

After'a'meal,'peristalsis'begins'near'the'cardiac'region'and'moves' toward'the'pyloric'sphincter.'The'intensity'of'the'movements'is'due' to'the'increase'in'the'number'of'muscle'layers'of'the'stomach.' The'

pyloric'region'holds'about'30'ml'of'chyme.'It'allows'only'liquids'and'

small'particles'of'chyme,'about'3'ml,'to'pass'through'the'valve'for'

each'peristaltic'wave.'The'contractions'of'the'pylorius'decrease'the' opening'of'the'valve.'This'results'in'the'remaining'chyme'being' remixed'again'and'again. ' The'rate'of'peristaltic'waves'is'constant'

3/min.,'however,'the'intensity'can'be'modified.'This'contractile'

rhythm'is'set'by't he'spontaneous'activity'of'pacemaker'cells'located'

in'the'longi tudinal'smooth'muscle'layer.'These'cells'establish' the' basic'electrical'rhythm'of'the'stomach. ' The'stomach'usually'empties'

completely'within'4'hours'after'a'meal.'The'rate'of'gastric'emptying'

d epends'on'the'contents'of'the'duodenum'as'on'what'is'happening'in'

the'stomach.'

N°3:))Gastrointestinal)smooth)muscle )

N°3:))Gastrointestinal)smooth)muscle ) '

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Several'different'layers'form'the'GI'tract'structures'(from'the'

internal'to'the'external'portion):'

Epithelium '

Lamin a'propria'(contains'lymph'nodes) '

Muscularis'mucosae '

Submucosa'(and'his'glands) '

Circular'layer '

Longitudinal'layer '

Serosa '

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Electric'Features: ' Resting'potential'is'^ 40'to' ^ 80'mV'(usually'near'the'lower'end'of'this' range) .' Electrogenic'Na/K ^ ATPase'may'contribu te'more'to'resting'

potential .' Slow%waves% (3'to'12'per'minute)'are'oscillations'of'resting' membrane'potential .' Action'potentials'are'slow'with'little'overshoot'

(L

^ type'Ca2+'channels'involved)'

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Interstitial'cells'of'Cajal'generate'slow'waves.'Their'amplitude ' (and' frequency)'is'influenced'by'nerves'and'hormones.'Contractions'may' occur'in'the'absence'of'action'potentials.' When'action'potentials' occur,'contraction'is'more'forceful'

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N°4:)Neurological)and)hormonal)control)of)the)stomach )

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By'the'way'slides'may'be'a'little'confused,'take'it'step'by'step'would'be'helpful:'
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1.
Cephalic)Phase: ' stage'in'which'the'stomach'responds'to'sight,'
smell,'taste'or'thought'of'food,'these'sensory'and'mental'inputs'
converge'on'hypothalamus'releasing'signals'to'th e'medulla'
oblongata.'From'this'point'signals'are'transmitted'to'the'
VAGUS'NERVE'stimulating'gastric'activity '
2. Gastric)phase:) a'period'in'which'swallowed'food'and'semi ^
digested'proteins'activate'gastric'activity,'2/3'of'gastric'
secretions'occur'in'this'phase ,'ingested'food'stimulates'gastric'
activity'in'2'ways,'by'stretching'the'stomach'and'by'raising'the'
pH'of'its'contents.'These'stretches'activate'2'reflexes,'a'short'
one'by'the'myenteric'nerve'plexus'and'a'long'one'by'the'vagus'
and'the'brain'stem.' *NOW)REVIEW)THE)GASTRIC)SECRECTIONS)
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3.
Intestinal)phase:) stage'in'which'the'duodenum'responds'to'
the'arriving'chime.'First'it'enhances'gastric'secretions'but'soon'
inhibits'it.' '
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MECHANICAL'DIGESTION,'PROPULSION : '
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1.'Pace ^ maker'cells ^^ interstitial'cells'of'Cajal'esta blish'intrinsic'
control. '
2.'Vagus'nerve — control'mechanical'digestion'extrinsically. '
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MECHANICAL'DIGESTION : '
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1. Gastrin ^^ stimulate'gastric'emptying '
2. Serotonin ^^ contraction'of'smooth'muscle' '
3. Somatostatin ^^ inhibits'motility'and'emptying' '
4. Secretin ^^ inhibits'gastric'motility '
5. Gastric'Inhibitory'Peptide ^^ inhibits'gastric'motility '
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PROPULSION : '
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1.'Gastrin ^^ stimulates'emptying '
2.'Somatostatin ^^ inhibits'gastric'motility'and'emptying '
3.'Secretin ^^ inhibits'gastric'motility'and'emptying '
4.' Gastric'Inhibitory'Peptide — inhibit s'gastric'motility'and'emptying '
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N°5)Physiological)events)in)the)small)intestine )

(I

f)you)get)this ) one ) your)luck)is)falling)down)apart) )

These'events'can'be'divided'in: '

1. Mechanical'digestion :'MOTILITY '

In'segmentation,'nonadjacent'segments'of'the'intestin e'alternately' contract'and'relax,'moving'the'chyme'forward'and'then'backward' resulting'through'mixing.'This'results'in'the'chyme'being'well'mixed' with'the'enzymes'from'the'liver'and'the'pancreas. In'addition,' segmentation'ensures'that'the'chyme'well'move't o'the'plasma' membrane'of'the'lining'cells'of'the'small'intestine.'These'simple' columnar'epithelial'cells'have'brush'border'enzymes'within'their'

plasma'membrane,'which'complete'the'chemical'digestion'of'the' chyme. ' One'by'one'we'can'read'below'these'key'feat ures: '

 

Contractions,'serves'to'mix'chime'with'intestinal'juice,'bile,' pancreatic'juice'and'neutralize'acid'in'order'to'digest'nutrients' more'effectively.'It'helps'to'bring'the'chime'in'contact'with'the' mucosa'for'nutrient'absorption'and'to'move'residues'to ward' the'intestine. '

Segmentation'is'a'movement'in'ring ^ like'constrictions,' common'of'several'places'of'the'intestine. '

Pacemaker'cells'of'muscolaris'externa'set'the'rhythm'of'

segmentations,'contracting'it'12'times'/'minute'in'duodenum'

and'8 ^ 9'times/minute'i n'ileum.'Segmentation'processes'slow' down'as'the'chime'progresses'toward'the'colon. '

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2. Chemical'digestion: ' (Good'Luck!) '

Carbohydrate,'firstly'by'salivary'amylase,'then'by'pancreatic' amylase'and'brush'border'enzymes.'( From ' starch'to' olig osaccharides,'from'this'one'to'maltose'and'finally'to' glucose'ready'to'be'absorbed) ' '

Proteins ,'hydrolyzed'by'pepsin,'trypsin'and'chymotrypsin.' (Breaking'all'peptide’s'bonds'we'have'to'underline'the'action' of'tree'more'enzymes:'Carboxypeptidase,'Aminopeptidse,' Dipeptidase) '

Lipids ,'mainly'by:'lipases'(lingual'and'pancreatic),'important' features'of'emulsification'and'reducing'droplets'into'smaller' ones'made'by'bile'components.'

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' ' 3. Absorption: ' • Carboh ydrates'are'mainly'absorbed'as'monosaccharides '

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3. Absorption: '

Carboh ydrates'are'mainly'absorbed'as'monosaccharides ' (80%glucose,'20%'galactose,'20%'fructose) .'Important'key ^ feature:' Sodium ^ Glucose'co'transport'membrane.' ' ***Attention:'absorption'of'monosaccharides'take'place'close'to'the' digestion'enzymes'and'transporters'= digestion ^ absorption'coupling. '

Most'proteins,'after'digestion,'are'absorbed'through'the'luminal' membranes'in'the'form'of'dipeptides,'tripeptides'and'few'free'amino' acids.'Similar'to'the'glucose'transport'they'are'absorbed'by'the'co ^ transport'of'the'AA'and' peptides. '

Fats'are'first'digested'to'form'monoglycerides'and'free'fatty'acids,' dissolved'in'the'central' lipid'portion'of'bile’s'micelles.'For'their ' absorption'micelles'work'as'“ferryboat”'to'bring'nutrients'to'the' epithelial'cell'membrane'and,'once'empty,'they'can'run'back'to'the' chime'to'function'once'again.' '

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4.'Propulsion :' Propulsion'is'the'result'of'peristalsis.'This'causes' adjacent'segments'to'alternately'contract'and'relax. '

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Peristalsis'begins'in'duodenum,'travels'10/70'cm'and'dies'out'to'be' followed' by'another'wave,'begins'a'little'further'down'than'the'first' one'did. '

N°6 ) Neurological)and)Hormonal)control)of)the)small)intestine )

Intrinsic'pacemaker'cells'in'longitudinal'smooth'muscle'layer'initiate' segmentation. ' Gastrin'stimulates'contraction'of'the' smooth'muscle'of' the'small'intestines. ' This'results'in'an'increase'in'segmentation. ' Perstalsis'is'stimulated'by'gastrin.'Also,'gastrin'relaxes'the'ileocecal' valve,'which'allow'chyme'into ' the'large'intestines. '

N°7)Regulation)of)GI)Secretions,)Generalitie s)(LOL!) )

There'are'several'types'of'stimulation'of'the'Alimentary'tract'glands: '

The'mechanical'presence'of'food'stimulate'glands'o f'that' region'to'secret'juices '

Hormonal'and'neural'stimuli'to'the'parasympathetic'nerves' rise'most'of'the'secretions '

The'symp athetic'nerves'stimulation'has'two'roles:'it'can' slightly'increase'the'secretions'when'run'alone'and'it'can'be' superimposed'to'the'parasympathetic'one'if'it'is'already' causing'copious'secretions'by'glands.'

Taking'a'further'look'for'the'motility'and'secret ion'regulation'it'is'

quite'better'to'talk'ab out'the'harmony'between'ENS,' CNS ' and'GI' peptides . '

Central'nervous'system'triggers'long'reflexes'to'the'GI'tract ,' cooperating'with'the'ESN,'external'stimuli'by'many'sensory' structures'and'emotional'statuses'(like ' “butterfly'in'the'

stomach”'feeling)' *mediated'by'Vagus'and'Brain'stem '

Enteric'nervous'system'head'the'short'reflexes'(this'system' standalone'from'the'brain'and'regulate'itself) ' *mediated'by'the'

myentric'nerve'plexus' '

For'completeness : ' the'GI'peptides' are' signal'molecules'that'are' released ' into'the'blood'by'the'GI'cells .'They'act'on'a'variety'of' tissues'including'the'brain,'digestive'accessory'organs,'and'the' GI'tract.'The'effects'range'from'excitatory'or'inhibitory'effects'

on'motility'and'secretion'to'feelings'of'satiety'or'hunger'when' acting'on'the'brain. '

' N°8)Types)of)GI)hormones)and)their)role ) ) Epithelial)cells)lining)the)lumen)of)the)stomach)and)small)
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N°8)Types)of)GI)hormones)and)their)role )
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Epithelial)cells)lining)the)lumen)of)the)stomach)and)small)
intestine)secrete)the)classical)GI)hormones.' These'hormone ^
se creting'cells'(endocrinocytes) ' are'intersp ersed'among'a'much'
larger'number'of'epithelial'cells'that'secrete'their'products'(acid,'
mucus,'etc.)'into'the'lumen'or'take'up'nutrients'from'the'lumen.'GI'
hormones'are'secreted'into'blood,'and'hence'circulate'systemically,'
where'they'affect'function'of'other'parts'of'the'digestive'tube,'liver,'
pancreas,'brain'and'a'variety'of'other'targets. '
There'are' a%bunch ' of'hormones,'neuropeptides'and'
neurotransmitters'that'affect'gastrointestinal'function.'Interestingly,'
a'number'of'the'classical'GI'hormones'are'also' synthesized'in'the'
brain,'and'sometimes'referred'to'as'"brain ^ gut'peptides".'The'
significance'of'this'pattern'of'expression'is'not'clear. '
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One)by)one)review: )
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Gastrin)is)a)major)physiological)regulator)of)gastric)acid) secretion. ' It'also'has'an'important' trophic'or'growth ^ promoting'influence'on'the'gastric'mucosa.'Gastrin'is' synthesized'in'G'cells,'which'are'located'in'gastric'pits,' primarily'in'the'antrum'region'of'the' stomach. The'primary' stimulus'for'secretion'of'gastrin'is'the'presence'of'certain' foods tuffs,'especially'peptides,'certain'amino'acids'and' calcium,'in'the'gastric'lumen. ' It'is'inhibited'by'a'low'pH. ' Its' main'feature'is'to'stimulate'gastric'acid'secretion'and'to' promote'mucosal'growth. '

Cholecystokinin)plays)a)key)role)in)facilitating)digestio n) within)the)small)intestine. ' It'is'secreted'from'mucosal' epithelial'cells'in'the'first'segment'of'the'small'intestine' (duodenum),'and'stimulates'delivery'into'the'small'intestine'of' digestive'enzymes'from'the'pancreas'and'bile'from'the' gallbladder.'Cholec ystokinin'is'also'produced'by'neurons'in'the' enteric'nervous'system,'and'is'widely'and'abundantly' distributed'in'the'brain. The'most'potent'stimuli'for'secretion'

of'cholecystokinin'are'the'presence'of'partially' digested'fats' and'protei ns'in'the'lumen'of'th e'duodenum.'This'hormone'has' the'effect'of' triggering'the'release' digestive)enzymes)from) the)pancreas ' into'the'duodenum'and'to'trigger'c ontraction)of) the)gallbladder)to)deliver)bile' into'the'duodenum. '

A'flood'of'acid'from'the'stomach'periodically'assaults' the'small' intestine,'and'it'is'important'to'put'out'that'fire'in'a'hurry'to' avoid'acid'burns. ' This'role'is'taken'by' Secretin ,' with'a' principal'target'for ' the'pancreas,'which'responds'by'secreting' a'bicarbonate ^ rich'fluid,'which'flows'into'the'first'part'of ' the' intestine'through'the'pancreatic'duct.'Bicarbonate'ion'is'a'base' and'serves'to'neutralize'the'acid,'thus'preventing'acid'burns' and'establishing'a'pH'conducive'to'the'action'of'other'digestive' enzymes. As'acid'is'neutralized'by'bicarbonate,'the'intestinal' pH'rises'toward'neutrality,'and'secretion'of'secretin'is'turned' off. '

Gastric)inhibitory)peptide)(GIP) ' is'a'member'of'the'secretin' family'of'hormones. Like'secretin,'it'is'secreted'from'mucosal' epithelial'cells'in'the'first'part'of'the'small'intestine.' Another' activity'of'GIP'is'its'ability'to'enhance'the'release'of'insulin'in' response'to'infusions'of'glucose.'For'this'action,'it'has'also' been'referred'to'as' glucose 0 dependent%insulinotropic%peptide . ' For)completeness:)) '

Ghrelin: a ppears'to'be'a'strong'sti mulant'for'appetite'and' feeding;'also'a'potent'stimulator'of'growth'hormone'secretion.

Motilin: ' a pparently'involved'in'stimulatin g'patterns'of'motility ' in'the'stomach'and'small'intestine '

Serotonin:'increase'intestinal'motility '

Substance'P:'read'above '

Vasoa ctive'intestinal'peptide'(VIP):' neurotransmitter'for' intestinal'smooth'muscle'stimulates'secretion'of'water'and' ions '

Neurotensin: decreases'intestinal'motility'increases'blood'flow' to'ileum '

Histamine:'increase'HCl'secretion '

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N°9)Gastrin ' (Damn'I'should'have ' not'write'so'much'before…) '

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Don’t'loose'time'with'generalities;' gastrin'is'a'hormone'that' stimulates'secretion'of'gastric'acid'(HCl)'by'the'parietal'cells'of'the' stomach'and'aids'in'gastric'motility.'G'cells'in'the'stomach,' duodenum,'and'the'pancreas'rele ase'it.'Its'release'is'stimulated'by'

peptides'in'the'lumen'of'the'stomach . ' Loose'time'for'its'functions:'

The'presence'of'gastrin'stimulates'parietal'cells'of'the'stomach'to' secrete'hydrochloric'acid'(HCl)/gastric'acid.'This'is'done'both' directly'on'the'pa rietal'cell'and'indirectly'via'binding'onto'

CCK2/gastrin'receptors'on'ECL'cells'in'the'stomach,'which'then'

responds'by'releasing'histamine,'which'in'turn'acts'in'a'paracrine' manner'on'parietal'cells'stimulating'them'to'secrete'H+'ions.'This'is' the'major'st imulus'for'acid'secretion'by'parietal'cells.' Along'with'the'above mentioned'function,'gastrin'has'been'shown'to' have'additional'functions'as'well: '

Stimulates'parietal'cell'maturation'and'fundal'growth. '

Causes'chief'cells'to'secrete'pepsinogen,'the'zymogen' (inactive)'form'of'the'digestive'enzyme'pepsin. '

Increases'antral'muscle'mobility'and'promotes'stomach' contractions. '

Strengthens'antral'contractions'against'the'pylorus,'and' relaxes'the'pyloric'sphincter,'which'stimulates'gastric' emptying. '

Plays'a'role'in't he'relaxation'of'the'ileocecal'valve.[7] '

Induces'pancreatic'secretions'and'gallbladder'emptying.[8] '

Impacts'lower'esophageal'sphincter'(LES)'tone,'causing'it'to'

relax.[9]'Taking'this'into'consideration,'high'levels'of'gastrin'

may'play'a'role'in'the'develop ment'of'some'of'the'more' common'LES'disorders'such'as'acid'reflux'disease. '

Diesease'States:'Excessive'secretion'of'gastrin,'or'hypergastrinemia,'is'a'well ^ recognized'cause'of'a'severe'disease'known'as'Zollinger^ Ellison'syndrome,' which'is'seen'at'low'frequ ency'in'man'and'dogs.'The'hallmark'of'this'disease'is' gastric'and'duodenal'ulceration'due'to'excessive'and'unregulated'secretion'of' gastric'acid.'Most'commonly,'hypergastrinemia'is'the'result'of'gastrin ^ secreting' tumors'(gastrinomas),'which'develop'in'the' pancreas'or'duodenum.'

N°10)Composition)and)role)of)Saliva) (I’ll)be)fast)on)this)one) )

Key'features: '

Moistens'mouth '

Digests'a'little'part'of'starch'and'fat '

Cleanses'teeth'and'inhibits'bacterial'growth '

Dissolves'molecules'so'they'can'stimulate'taste'buds '

Moistens'foods'and'binds'particles'together'to'help'swallowing' process '

• It'is'an'hypotonic'solution'of'91'up'to'99.5%'of'water'and… '
• It'is'an'hypotonic'solution'of'91'up'to'99.5%'of'water'and…
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…'These'following'salivary'solutes: '
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• Salivary'amylase,'begins'starch'digestion '
• Lingual'lipase,'activated'by'stomach'acid'(yo u'know…) '
• Mucus,'binds'and'lubricates'the'food'mass '
• Lysozyme,'kills'bacteria '
• Ig ^ A,'inhibits'bacterial'growing '
• Electrolytes :'Na+,'K+,'HCo3 ^ ,'Cl ^ ,'Po4 ^ '
• Organic'substances:'urea,'uric'acids'residues… '
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For'completeness'saliva'is'divided'in'two'main'protein'secretion:
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a. A'serous'one,'that'contains'ptyalin'(an'α ^ amilase) '
b. A'mucus'kind'that'contains'mucin,'lubricating'and'surface'
protective'substance. '
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N°11)Secretion)of)Saliva )
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The'daily'secretion'is'around'1.5L,'while'the'basal'flow'can'be'of'0,5'
up'to'5'mL'per'minute. '
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It'is'made'by: '
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• Parotid'gland:'produce'wate ry'fluid'(serous)' '
• Submandibular'glands:'both'water'and'mucus '
• Sublingual:'mainly'mucus '
It'is'an'isotonic'(290 ^ 310'mOsm/L)'fluid'similar'to'the'plasmatic'
ultra ^ filtrate,'but'with'an'higher'concentration'of'K+'
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Saliva'is'produced'in'and'secreted'from'salivar y'glands.'The'basic' secretory'units'of'salivary'glands' are'clusters'of'cells'called' acini.' These'cells'secrete'a'fluid'th at'contains'water,'electrolytes,'mucus' and'enzymes,'all'of'which'flow'out'of'the'acinus'into'collecting'ducts. '

Within'the'ducts,'the'composition'of'the'secretion'is'altered.'Much'of' the'sodium'is'actively'reabsorbed,'potassium'is'secreted,'and'large' quantities'of'bicarbonate'ion'are'secreted.'Bicarbonate'secretion'is'of' tremendous'importance'to'ruminants'because'it,'along'with' phosphate,' provides'a'critical'buffer'that'neutralizes'the'massive'

quantities'of'acid'produced'in'the'forestomachs.'Small'collecting' ducts'within'salivary'glands'lead'into'larger'ducts,'eventually' forming'a'single'large'duct'that'empties'into'the'oral'cavity.' '

N°12) Regulation)of)salivary)secretion )

Secretion'of'saliva'is'under'control'of'the'autonomic'nervous'system,' which'controls'both'the'volume'and'type'of'saliva'secreted.' Potent' stimuli'for'increased'salivation'include'the'presence'of'food'or' irritating'substance s'in'the'mouth,'and'thoughts'of'or'the'smell'of' food.'Knowing'that'salivation'is'controlled'by'the'brain'will'also'help' explain'why'many'psychic'stimuli'also'induce'excessive'salivation'^ ' for'example,'why'some'dogs'salivate'all'over'the'house'when'it's' thu ndering . '

Autonomic'nervous'system ' control'its'regulation : '

Parasympathetic)(ACh,)VIP) :' '

High ' and'sustained'output' ' '

Synthesis ' and'secretion'of'amylase'and'mucins' '

Transport ' activity'of'ductular'epithelium' '

Vasodilation ' and'increased'blood'flow' '

Positive ' f eed'back'on'blood'supply'through'kallikrein ^ kininogen'system' '

Stimulation ' of'glandular'metabolism'and'growth ' Sympathetic :' '

Transient'increase'of'secretion' '

Vasoconstriction ' leads'to'decrease'of'salivation '

N°13)Gastric)Juice )

The'stomach'is'famous'for'its ' secretion'of'acid,'but'acid'is'only'one'of' four'major'secretory'products'of'the'gastric'epithelium,'all'of'which' are'important'either'to'the'digestive'process'or'to'control'of'gastric' function: '

Mucus: ' The'most'abundant'epithelial'cells'are'mucous'cells,'w hich' cover'the'entire'lumenal'surface'and'extend'down'into'the' glands'as'"mucous'neck'cells".'These ' cells'secrete'a' bicarbonate ^ rich'mucus ' that'coats'and'lubricates'the'gastric' surface,'and'serves'an'important'role'in'protecting'the'

epithelium'from'acid'an d'other'chemical'insults. '

Acid: ' Hydrochloric'acid'is'secreted'from'parietal'cells'into'the' lumen'where'it'establishes'an'extremely'acidic'environment.' This'acid'is'important'for'activation'of'pepsinogen'and' inactivation'of'ingested'microorganisms'such'as'b acteria. '

Proteases: ' Pepsinogen,'an'inactive'zymogen,'is'secreted'into' gastric'juice'from'both'mucous'cells'and'chief'cells.'Once' secreted,'pepsinogen'is'activated'by'stomach'acid'into'the' active'protease'pepsin ,'which'is'largely'responsible'for'the' stomach 's'ability'to'initiate'digestion'of'proteins.'In'young' animals,'chief'cells'also'secrete' chymosin'(rennin),'a'protease' that'coagulates'milk'protein ' allowing'it'to'be'retained'more' than'briefly'in'the'stomach.'

Hormones: ' The'principal'hormone'secreted'from't he'gastric' epithelium'is' gastrin ,'a'peptide'that'is'important'in'control'of' acid'secretion'and'gastric'motility. ' Gastric'epithelial'cells'secrete'a'number'of'other'enzymes ,'including' a'lipase'and'gelatinase.'One'secretory'product'of'considerable' importance ' in'man'is' intrinsic'factor ,'a'glycoprotein'secreted'by' parietal'cells'that'is'necessary'for'intestinal'absorption'of'vitamin'B 12 . '

N°)14 ) Secretion)of)the)Stomach) (why?)Gastric)juice)wasn’t)enough??? ) DAMN ) )

1°)part:) Mechanism)of)Acid)Secretion )

The'hydrogen ' ion'concentration'in'parietal'cell'secretions'is'roughly'

3'million'fold'higher'than'in'blood,'and'chloride'is'secreted'against'

both'a'concentration'and'electric'gradient.'Thus,'the'ability'of'the' partietal'cell'to'secrete'acid'is'dependent'on'active'trans port. '

The'key'player'in'acid'secretion'is'a'H+/K+'ATPase'or'"proton'pump"' located'in'the'cannalicular'membrane.'This'ATPase'is'magnesium ^ dependent,'and'not'inhibitable'by'ouabain.'The'current'model'for' explaining'acid'secretion'is'as'follows:'

• Hydrogen'ions ' are'generated'within'the'parietal'cell'from' dissociation'of'water.'The'hydroxyl'ions'formed'in'this'process' rapidly'combine'with'carbon'dioxide'to'form'bicarbonate'ion,'a' reaction'cataylzed'by' carbonic)anhydrase . '

• Bicarbonate'is'transported'out'of'the'baso lateral'membrane'in' exchange'for'chloride.'The'outflow'of'bicarbonate'into'blood' results'in'a'slight'elevation'of'blood'pH'known'as'the'"alkaline' tide".'This'process'serves'to'maintain'intracellular'pH'in'the'

parietal'cell. '

• Chloride'and'potassium'ions'are' transported'into'the'lumen'of'the' cannaliculus'by'conductance'channels,'and'such'is'necessary' for'secretion'of'acid. '

• Hydrogen'ion'is'pumped'out'of'the'cell,'into'the'lumen,'in'exchange' for'potassium'through'the'action'of'the'proton'pump;' potassium'is'thus' effectively'recycled. '

• Accumulation'of'osmotically ^ active'hydrogen'ion'in'the' cannaliculus'generates'an'osmotic'gradient'across'the' membrane'that'results'in'outward'diffusion'of'water' ^ ' the'

resulting'gastric'juice'is'155'mM'HCl'and'15'mM'KCl'with'a'

small'am ount'of'NaCl. '

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Controlling'the'Acid:' Parietal'cells'bear'receptors'for'three' stimulators'of'acid'secretion,'reflecting'a'triumverate'of'neural,'

paracrine'and'endocrine'control: '

 

Acetylcholine ' (muscarinic'type'receptor) '

Gastrin '

Histamine ' (H2'type'receptor) '

2°)Part:)Pepsinogen)and)Pepsin )

Pepsins'are'the'principal'proteases'in'gastric'secretions'of'adult' mammals.'They'are'members'of'the'family'of'aspartic'proteases,'and' closely'related'to'chymosin,'another'gastric'protease'expressed' particularly'in'young'anim als.'These'enzymes'are'synthesized'and' secreted'predominantly'by'chief'cells'in'the'gastric'mucosa. '

Pepsins'are'synthesized'as'inactive'pre ^ proenzymes,'consisting'of'a' signal'peptide,'activation'peptide'and'active'enzyme.'The'signal' peptide'is'cleaved'as' the'protein'is'inserted'into'endoplasmic' reticulum'and'the'resulting'proenzyme' ^ ' pepsinogen' ^ ' is'transported' to'the'Golgi'and'condensed'into'secretory'granules.'

Pepsinogens'are'secreted'in'a'form'such'that'the'activation'peptide' assumes'a'compact'structure ' that'occludes'the'active'site.'On' exposure'to'an'acidic'(pH'Structurally,'the'active'site'is'located'in'a' deep'cleft'within'the'molecule.'Optimal'activity'of'pepsins'is'at'pH'of'

1.8'to'3.5,'depending'on'the'isoform.'They'are'reversibly'inactivated'

at'abou t'pH'5'and'irreversibly'inactivated'at'pH'7'to'8.'

In'general,'secretion'of'pepsinogens'is'coupled'to'secretion'of'acid' from'the'parietal'cell.'In'vitro'studies'have'demonstrated'that'agents' that'stimulate'either'of'two'conditions'effectively'stimulate' secr etion: '

Elevated'intracellular'levels'of'cyclic'AMP:'examples'include' secretin,'vasoactive'intestinal'peptide'and'epinephrine. '

Elevated'intracellular'calcium:'the'principal'mediators'investigated' include'acetylcholine'and'peptides'of'the' gastrin/cholecystok inin'family '

3°)Part:)Intrinsic)Factor )

Intrinsic'factor'is'a'glycoprotein'secreted'by'parietal'(humans)'or' chief'(rodents)'cells'of'the'gastric'mucosa.'In'humans,'it'has'an'

important'role'in'the'absorption'of'vitamin'B12'(cobalamin)'in'the'

intestine,'and' failure'to'produce'or'utilize'intrinsic'factor'results'in' the'condition'pernicious'anemia. '

Dietary'vitamin'B 12 ' is'released'from'ingested'proteins'in'the'stomach' through'the'action'of'pepsin'and'acid.'It'is'rapidly'bound'by'one'of' two'vitamin'B 12 ^ binding'pr oteins'that'are'present'in'gastric'juice;'at' acid'pH,'these'binding'proteins'have'a'greater'affinity'for'the'vitamin' than'does'intrinsic'factor.'In'the'small'intestine,'pancreatic'proteases' digest'the'binding'proteins,'releasing'vitamin' B 12 ,'which ' then' bec omes'bound'to'intrinsic'factor.'Finally,'there'are'receptors'for' intrinsic'factor'on'the'ileal'mucosa,'which ' bind'the'complex,'allowing' vitamin'B 12 ' to'be'absorbed'into'portal'blood.'

4°Part:)Chymosin)(Renin) )

Chymosin,'known'also'as'rennin,'is'a'proteolytic'enzyme'synthesized' by'chief'cells'in'the'stomach.'Its'role'in'digestion'is'to'curdle'or' coagulate'milk'in'the'stomach,'a'process'of'considerable'importance' in'the'very'young'animal.'If'milk'were'not'coagulated,'it'would' rapidly'flow'through'the'stomach'a nd'miss'the'opportunity'for'initial' digestion'of'its'proteins. '

Chymosin'efficiently'converts'liquid'milk'to'a'semisolid'like'cottage' cheese,'allowing'it'to'be'retained'for'longer'periods'in'the'stomach.' Chymosin'secretion'is'maximal'during'the'first'few'da ys'after'birth,' and'declines'thereafter,'replaced'in'effect'by'secretion'of'pepsin'as'

the'major'gastric'protease.'

Chymosin'is'secreted'as'an'inactive'proenzyme'called'prochymosin' that,'like'pepsin,'is'activated'on'exposure'to'acid.'Chymosin'is'also' similar ' to'pepsin'in'being'most'active'in'acidic'environments,'which' makes'sense'considering'its'mission.

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N°15 ) Hydrochloric)acid)secretion) (for)the)mechanism)read)above) ! ) )

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The'best ^ known'component'of'gastric'juice'is'hydrochloric'acid,'the' secretory'produc t'of'the'parietal,'or'oxyntic'cell.'It'is'known'that'the' capacity'of'the'stomach'to'secrete'HCl'is'almost'linearly'related'to' parietal'cell'numbers. '

When'stimulated,'parietal'cells'secrete'HCl'at'a'concentration'of' roughly'160'mM'(equivalent'to'a'pH'of'0.8 ).'The'acid'is'secreted'into' large'cannaliculi,'deep'invaginations'of'the'plasma'membrane'which' are'continuous'with'the'lumen'of'the'stomach. '

When'acid'secretion'is'stimulated'there'is'a'dramatic'change'in'the' morphology'of'the'membranes'of'the'parietal'ce ll.'Cytoplasmic' tubulovesicular'membranes,'which'are'abundant'in'the'resting'cell'

virtually,'disappear'in'concert'with'a'large'increase'in'the' cannalicular'membrane.'It'appears'that'the'proton'pump'as'well'as' potassium'and'chloride'conductance'channels'ini tially'reside'on' intracellular'membranes'and'are'transported'to'and'fused'into'the' cannalicular'membrane'just'prior'to'acid'secretion. '

The'epithelium'of'the'stomach'is'intrinsically'resistant'to'the' damaging'effects'of'gastric'acid'and'other'insults.'Nonet heless,' excessive'secretion'of'gastric'acid'is'a'major'problem'in'human'and,' to'a'lesser'extent,'animal'populations,'leading'to'gastritis,'gastric' ulcers'and'peptic'acid'disease.'As'a'consequence,'the'parietal'cell'and' the'mechanisms'it'uses'to'secrete'aci d'have'been'studied'extensively,' leading'to'development'of'several'drugs'useful'for'suppressing'acid' secretion. '

' N°)16)Protective)mechanism)of)the)stomach) ( Quite)so!) ) )
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N°)16)Protective)mechanism)of)the)stomach) ( Quite)so!) )
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The'gastrointestinal'mucosa'forms'a'barrier'between'the'body'and'a'
luminal'environment,' which'not'only'contains'nutrients,'but'is'laden'
with'potentially'hostile'microorganisms'and'toxins.'The'challenge'is'
to'allow'efficient'transport'of'nutrients'across'the'epithelium'while'
rigorously'excluding'passage'of'harmful'molecules'and'organisms'
into' the'animal.'The'exclusionary'properties'of'the'gastric'and'
intestinal'mucosa'are'referred'to'as'the'"gastrointestinal'barrier".'
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The'gastrointestinal'barrier'is'often'discussed'as'having'two' components: '

• The' intrinsic)barrier ' is'composed'of'the'epithelial'c ells'lining'the' digestive'tube'and'the'tight'junctions'that'tie'them'together.' '

• The' extrinsic)barrier ' consists'of'secretions'and'other'influences' that'are'not'physically'part'of'the'epithelium,'but'which'affect' the'epithelial'cells'and'maintain'their'barrier'function. ' The'gastric'mucosal'barrier'is'the'property'of'the'stomach'that' allows'it'to'contain'acid. ' If'the'barrier'is'broken,'as'by'acetylsalicylic'acid'(ASS,'aspirin)'in'acid' solution,'acid'diffuses'back'into'the'mucosa'where'it'can'cause' damage'to'th e'stomach'itself.' The'barrier'consists'of ' three'protective'components. ' These'provide' the'additional'resistance'for'the'mucosal'surface'of'the'stomach: ' A'compact'epithelial'cell'lining ,'tight'junctions'that'repel'harsh' fluids'that'may'injure'the'stomach'lin ing'bind'cells'in'the'

epithelium'of'the'stomach . '

A'special'mucus'covering :'t he'mucus'covering'is'derived'from' mucus'secreted'by'surface'epithelial'cells'and'mucosal'neck' cells.'This'insoluble'mucus'forms'a'protective'gel ^ like'coating' over'the'entire'surfac e'of'the'gastric'mucosa.'The'mucus' protects'the'gastric'mucosa'from'autodigestion'by'e.g.'pepsin' and'from'erosion'by'acids'and'other'caustic'materials'that'are' ingested. '

Bicarbonate'ions ,' secreted'by'the'surface'epithelial'cells.'The' bicarbonate'ions'act'to'neutralize'harsh'acids.'

' N°17)Regulation)of)gastric)secretions) (are)we)joking???) ) )
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N°17)Regulation)of)gastric)secretions) (are)we)joking???) )
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READ'SOME'OF'THE'ABOVEMENTIONED'POINTS!!!'(4,5,7) '
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N°18)Cholecystokinin) (Name!) ) ==>) READ)N°8 )
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N°19)Secr etin ) ==>) READ)N°8 )
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N°20) I’ m)too)sleepy … ) let ’ s)review)it)on)the) second) document!!! )
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That ’ s)all)for)today)folks,)tomorrow)I ) would)like)to)start)from)
here)and)finish)with)the)respiratory ) system ) (or)at)least) I ) hope)
so … ) )
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Hope)it)will)be) useful; ) if) I ) missed)something)or) I ) wrote) hogwash )
please)tell)me)so) I ’ d)fix)everything … )
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Your)Beloved)colleague,)Alessandro)Motta))

“ May % the%force%be%with%you ” %