This document provides an overview of gastric acid secretion physiology. It discusses the intricate balance of stimulatory and inhibitory pathways that control acid secretion, including the cephalic, gastric, and intestinal phases. The key players in acid secretion are histamine, gastrin, acetylcholine, and somatostatin. Histamine is the major paracrine stimulator, while somatostatin is the main inhibitor. Gastrin enhances acid secretion by stimulating histamine release from ECL cells. Acetylcholine increases gastrin release and stimulates parietal cells. Prostaglandins and other factors provide autocrine inhibition of acid secretion. Pepsin secretion is closely linked to acid levels in the stomach
Enterohepatic circulation and Hepatic Portal circulationjohnedward869
in these slides we discuss about enterohepatic circulation, especially of bile acid ,also the hepatic portal circulation of blood passing through the liver to wards the heart via inferior vena cava and the return of such blood to the liver, and Porta caval Anastomosis(portosystemic Anastomosis) is also discussed.
Enterohepatic circulation and Hepatic Portal circulationjohnedward869
in these slides we discuss about enterohepatic circulation, especially of bile acid ,also the hepatic portal circulation of blood passing through the liver to wards the heart via inferior vena cava and the return of such blood to the liver, and Porta caval Anastomosis(portosystemic Anastomosis) is also discussed.
Posterior Pituitary or Neurohypophysis composed mainly of glial-like cells called pituicytes.
The pituicytes do not secrete hormones.
They act simply as a supporting structure for large numbers
of terminal nerve fibers and terminal nerve endings from nerve tracts.
That originate in the supraoptic and paraventricular
nuclei of the hypothalamus.
Posterior Pituitary or Neurohypophysis composed mainly of glial-like cells called pituicytes.
The pituicytes do not secrete hormones.
They act simply as a supporting structure for large numbers
of terminal nerve fibers and terminal nerve endings from nerve tracts.
That originate in the supraoptic and paraventricular
nuclei of the hypothalamus.
Stomach ANATOMY, FUNCTIONS AND SECRETIONS (the guyton and hall physiology)Maryam Fida
ANATOMY, FUNCTIONS AND SECRETIONS
Anatomically, the stomach is usually divided in to two major parts:
1. Body 2. Antrum
Physiologically, the stomach is divided in to
1. the “ ORAD” portion, comprises of about first two thirds of the body.
2. the “CAUDAD” portion, comprises the remainder of the body plus the antrum.
The esophagus empties into the orad stomach.
primary function is to store food.
800 -1500 mL of food. Or 0.8 – 1.5 L
Little mixing occurs in the orad stomach because the contractions are weak and infrequent, so the ingested food remains in unmixed.
vagovagal reflex :
“initiated by swallowing or distention is define as,” A reflex that occurs from the stomach to the brain stem and then back to the stomach reduces the tone in the muscular wall of the body of the stomach so that the wall bulges progressively outward, accommodating greater and greater quantities of food up to a limit in the completely relaxed stomach”.
mixing
The digestive juices of the stomach are secreted by Gastric glands
|
Gastric glands are present in body of stomach except along a narrow strip on the lesser curvature of the stomach
|
As long as food is in the stomach. WEAK PERISTALIC CONSTRICTOR WAVES called Mixing waves begins in the mid portion of stomach and move towards antrum about once every 15 to 20 seconds.
|
These waves are initiated by the “BASIC ELECTRICAL RHYTHM”
|
Consisting of SLOW WAVES. That occurs from the body and providing powerful PERISTALIC ACTION POTENTIAL
|
Driven constrictor rings that force the antral contents towards pylorus.
Strong peristalsis in the body of stomach
after 12-24 hour of last meal sometimes last for 2-3 min
Reach its max. 3-4 days
Due to hypoglycemia
Gastrointestinal Hormones by Pandian M, Dept of Physiology DYPMCKOP, for MBBS...Pandian M
Classify GIT hormones
List the source and functions of different GI hormones
Explain the mechanism of action and regulation of secretion of different GI Hormones
Describe the role of GI hormones in regulation of GI functions
Explain the dysfunctions produced by alteration in secretion of GIT hormones
The human digestive system consists of two major component one is the accessory organ like liver pancreas gall bladder salivary gland and other is the Alimentary canal which is started from oral cavity and ends on anal cavity.
in this ppt all parts are described briefly for better understanding.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
2. INTRODUCTION
• An intricate balance of chemotransmitters
delivered to the gastric mucosa by several
pathways.
• Stimulatory and inhibitory mechanisms.
• Remarkable ability of normal gastro-duodenal
mucosa to defend itself against injury –
Several mechanisms.
• Neural, endocrine, paracrine, and autocrine
control pathways.
3. INTRODUCTION
• There is limited understanding of the actual
physiologic and pathophysiologic importance
of most of these pathways and
chemotransmitters.
• Gastric acid is not essential for life.
• The benefits of gastric acid are to facilitate
digestion of proteins and the absorption of
calcium, iron, and vitamin B12.
4. INTRODUCTION
• Gastric acid suppresses growth of bacteria,
which can help prevent enteric infections and
small intestinal bacterial overgrowth.
6. Phases Of Gastric Secretion
• Three interrelated phases: cephalic, gastric,
and intestinal.
• Cephalic phase is activated by the thought,
taste, smell and sight of food, and swallowing,
mediated mostly by cholinergic/vagal
mechanisms.
• Gastric phase is due to the chemical effects of
food and distension of the stomach.
7. Phases Of Gastric Secretion
• Gastrin appears to be the major mediator
since the response to food is largely inhibited
by blocking gastrin action at its receptors.
• Intestinal phase accounts for only a small
proportion of the acid secretory response to a
meal; its mediators remain controversial.
12. Mechanism Of Acid Secretion
• The hydrogen ion concentration in parietal cell
secretions is roughly 3 million fold higher than
in blood.
• Chloride is secreted against both a
concentration and electric gradient.
• Ability of the parietal cell to secrete acid is
dependent on active transport.
• The key player in acid secretion is an H+/K+
ATPase or "proton pump" located in the
cannalicular membrane.
13. Mechanism Of Acid Secretion
• 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 catalyzed
by carbonic anhydrase.
• Bicarbonate is transported out of the
basolateral membrane in exchange for
chloride.
14. Mechanism Of Acid Secretion
• 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.
15. Mechanism Of Acid Secretion
• 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.
16. Mechanism Of Acid Secretion
• The resulting gastric juice is 155 mM HCl and
15 mM KCl with a small amount of NaCl.
19. Control Of Acid Secretion
• Parietal cells bear receptors for three
stimulators of acid secretion.
– Acetylcholine (muscarinic type receptor)
– Gastrin
– Histamine (H2 type receptor)
• When low levels of each i.e. Acetylcholine,
Gastrin & Histamine are present, acid
secretion is strongly forced.
20. Control Of Acid Secretion
• Additionally, pharmacologic antagonists of
each of these molecules can block acid
secretion.
• Histamine's effect on the parietal cell is to
activate adenylate cyclase, leading to
elevation of intracellular cyclic AMP
concentrations and activation of protein
kinase A (PKA).
21. Control Of Acid Secretion
• One effect of PKA activation is
phosphorylation of cytoskeletal proteins
involved in transport of the H+/K+ ATPase
from cytoplasm to plasma membrane.
• Binding of acetylcholine and gastrin both
result in elevation of intracellular calcium
concentrations.
24. The Parietal Cell
• In the resting state, parietal cells are filled
with secretory vesicles that coalesce with
stimulation to form channels (canaliculi) that
drain to the apical lumen.
• The secretory membrane lining these
structures contains the hydrogen-potassium-
ATPase acid-secreting pump.
25. The Parietal Cell
• This pump is always active, but exists in a
short-circuited state in resting vesicles
because the pathway necessary for
transporting potassium to the apical surface
for exchange with hydrogen is not present or
active.
• With stimulation, this pathway for potassium-
chloride cotransport becomes active, allowing
hydrogen-potassium exchange to occur.
26. The Parietal Cell
• Parietal cell activation involves an increase in
cytoplasmic calcium or generation of cyclic
AMP, followed by activation of a cAMP-
dependent protein kinase cascade that
triggers translocation of proton pump
containing membranes to the apical surface.
• The cessation of acid secretion is associated
with the re-internalization of the hydrogen-
potassium-ATPase pump.
29. Gastrin
• Gastrin is the major endocrine regulator of the
secretory response to a protein meal.
• It is released from gastrin-expressing cells (G
cells) localized to the antrum.
• Gastrin enhances gastric acid secretion from
parietal cells primarily by stimulating the
synthesis and release of histamine from
oxyntic mucosal enterochromaffin-like (ECL)
cells.
30. Gastrin
• However, gastrin also has direct actions on
parietal cells.
• Acid secretion is tightly controlled by a second
hormone, somatostatin, which is a potent
inhibitor of both gastrin and histamine
synthesis and release, and, therefore, of
gastric acid secretion.
• Gastrin is the best identified trophic regulator
of parietal cell mass in humans.
31. Gastrin Receptors
• Gastrin acts via activation of the
cholecystokinin CCK2 receptor (also known as
the CCK-B or gastrin receptor), which has
equal affinity for cholecystokinin (CCK) and
gastrin.
• These receptors have been localized to
parietal and ECL cells, but it is likely that the
ECL cell gastrin receptor is of greater
importance in regulating acid secretion.
32. Gastrin Receptors
• Gastrin "receptors" have also been found on
somatostatin-secreting D cells.
• However, this receptor is a CCK1 or CCK-A
receptor that has much greater affinity for CCK
than for gastrin.
• This difference in receptor affinity may explain
why gastrin is so much more effective as a
stimulant of acid secretion, while CCK induces
greater release of the inhibitor somatostatin.
33. Gastrin Receptors
• CCK1 receptors exert inhibitory effects on acid
secretion in vivo, mediated by release of
endogenous somatostatin.
34. Regulation Of Gastrin secretion
• Complex mechanisms control gastrin release
from the antral G cells.
35. Regulation Of Gastrin secretion
• Two meal-related factors stimulate gastrin
secretion: gastric distention and amino acids.
• Low grade distention activates vasoactive
intestinal peptide neurons which stimulate
somatostatin release and therefore inhibit
gastrin secretion.
• Higher grade distention causes cholinergic
activation which reverses the pattern to one
of increased gastrin and reduced somatostatin
secretion.
36. Regulation Of Gastrin secretion
• Amino acids induce gastrin release; direct
actions on the G cell have been demonstrated
but amino acids also activate both cholinergic
neurons and bombesin neurons.
• The release of bombesin (also called gastrin-
releasing peptide) from mucosal nerves
directly stimulates the G cell.
• Somatostatin is the major inhibitory paracrine
regulator of gastrin release.
37. Regulation Of Gastrin secretion
• Gastrin itself contributes to this process by
enhancing the secretion of somatostatin.
• Cholinergic activation after gastric distention
or in response to a meal promotes acid
secretion by shifting the balance of
stimulatory and inhibitory mechanisms
toward the stimulatory side, directly activating
the parietal cell and stimulating gastrin
release while suppressing somatostatin
release.
40. Histamine
• Histamine is the major paracrine stimulator of
acid secretion.
• It is localized both in mucosal mast cells and in
endocrine cells, the latter called
enterochromaffin-like (ECL) cells because of
the silver-staining properties of their granules.
• The ECL cells are localized to the acid-
secreting oxyntic or body mucosa, in direct
proximity to the parietal cell.
41. Histamine
• Gastrin is the primary stimulus to histamine
release from ECL cells.
• ECL cells are also directly stimulated by
pituitary adenylate cyclase-activating
polypeptide (PACAP) and vasoactive intestinal
peptide (VIP).
• Somatostatin is a major direct inhibitor of
histamine release; calcitonin gene-related
peptide (CGRP), peptide YY, prostaglandins,
and galanin also inhibit release.
42. Histamine
• Stimulated ECL cells promptly degranulate,
with release of histamine and pancreastatin
from the vesicles; this is followed by an
increase in histamine synthesis.
• Although gastric mast cells outnumber ECL
cells, gastrin has only been demonstrated to
release histamine from ECL cells.
• Several lines of evidence indicate that ECL cell
histamine is the major physiological mediator
of acid secretion.
43. Histamine
• Inhibitors of the histamine-forming enzyme,
histidine decarboxylase (HDC), block the acid
secretory response to gastrin, but not to
histamine.
• The effects of histamine are largely mediated
by the H2 receptors, which explain the efficacy
of H2 receptor blockers in the treatment of
acid-peptic disease.
44. Histamine
• These drugs inhibit acid secretion in response
to gastrin, meal, and neural stimulation,
clearly establishing that histamine plays a role
as a universal mediator or modulator of the
acid secretory response.
• Histamine may also act at H3 receptors to
increase acid secretion via inhibition of
somatostatin release.
46. Somatostatin
• Somatostatin is a potent inhibitor of acid
secretion.
• It is released from D cells, which are present
throughout the gastric mucosa.
• Although somatostatin has some effects on
parietal cells, its major effects are exerted on
the inhibition of histamine release and to a
lesser extent on gastrin release.
47. Somatostatin
• The secretion of somatostatin is increased by
gastric acid and by gastrin itself, suggesting
that a major function of somatostatin is to
modulate the feedback inhibition of the acid
secretory response to gastrin.
• Somatostatin primarily acts by suppressing
gastrin-stimulated release of histamine from
ECL cells.
48. Somatostatin
• Somatostatin secretion is also affected by
neural inputs. It is suppressed by cholinergic
activation and increased by vasoactive
intestinal peptide activation.
50. Acetylcholine
• Neural input may serve as an important
integrator of secretory function.
• The mucosal nerves, containing acetylcholine,
bombesin, VIP, and PACAP mediate the
response to the cephalic phase of acid
secretion and to gastric distention and amino
acids.
• Acetylcholine is the major stimulatory
mediator.
51. Acetylcholine
• The major effects of muscarinic receptor
activation are to increase gastrin release,
stimulate parietal cells, and inhibit
somatostatin secretion.
• Vasoactive intestinal peptide release has a
dual effect: a weak transient increase in acid
secretion, possibly due to direct effects on ECL
cells; and a sustained reduction due to
enhanced release of somatostatin.
52. Acetylcholine
• Vasoactive intestinal peptide release has a
dual effect: a weak transient increase in acid
secretion, possibly due to direct effects on ECL
cells; and a sustained reduction due to
enhanced release of somatostatin.
• Orexin, nitric oxide, and galanin may also
contribute to the neural regulation of acid
secretion.
55. Prostaglandins
• Prostaglandins are autocrine factors that
inhibit acid secretion, histamine-stimulated
parietal cell function, and gastrin-stimulated
histamine release.
• The effect on gastrin release is less clear as
both inhibitory and stimulatory mechanisms
have been described.
• They are generated from cells in the
epithelium and lamina propria.
56. Prostaglandins
• Macrophages and capillary endothelial cells
appear to be the primary source.
• The mechanisms regulating their release in
vivo are not well-understood.
58. Other Secretory Regulators
• Transforming growth factor-alpha (TGF-alpha)
is an autocrine factor that is present in
parietal cells and inhibits gastric acid
secretion.
• Peptide YY (PYY) is released postprandially
from cells in the ileum and colon and inhibits
the cephalic and gastric phases of acid
secretion via central and peripheral effects.
• PYY binds to receptors on ECL cells and
inhibits gastrin-stimulated histamine release.
60. Pepsin
• Acid plus pepsin is much more ulcerogenic
than acid alone, leaving little question that the
"peptic" label appropriately reflects the
critical role in ulcer formation of the
proteolytic activity in gastric juice.
• The potentiating effect of pepsin may be due
in part to its mucolytic activity.
• Peptic activity is closely linked to acid
secretion and gastric pH.
61. Pepsin
• This relation is partly due to peptic digests of
dietary protein (primarily amino acids), which
are potent stimulants of gastrin release and
acid secretion.
• In addition, pepsinogen is converted to the
active protease pepsin at low gastric pH; on
the other hand, pepsin is inactivated when the
pH is increased above 4.
62. Pepsin
• This pH dependence probably accounts for the
requirement for elevating the intraluminal pH
above 4 to heal refractory ulcers.
• Pepsinogen secretion is enhanced by
acetylcholine and peptides of the CCK/
gastrin family.
• In addition, agents that raise cyclic AMP, such
as secretin and vasoactive intestinal peptide,
increase pepsinogen secretion in vitro.
64. In Human
• Aspiration of gastric contents via a nasogastric
tube is the easiest method of measuring acid
secretion, if collections are complete.
• Basal acid secretion can also be reliably
measured through an endoscope during a 15-
minute collection period.
• Alternatively, intragastric titration allows the
actual level of acid secretion to be measured
by the quantity of base required to hold the
gastric pH at a predetermined level.
65. In Human
• Placement of a gastric pH probe allows
hydrogen ion concentration to be measured
over a 24-hour period, but measuring
hydrogen ion concentration provides only an
indirect indicator of the rate of acid secretion.
• Basal acid output (BAO) is the level of acid
secretion when the subject is unstimulated;
measurements are widely variable among
individuals.
66. In Human
• Physiologic factors enhancing secretion are
vagal activation, food (particularly amino
acids), and gastric distention.
• Histamine release from enterochromaffin-like
(ECL) cells plays a major role since the acid
secretory in response to food, gastrin, and
vagal stimulation is inhibited by H2 receptor
antagonists.
• In contrast, carbohydrates and fat inhibit acid
secretion.
67. In Human
• Intestinal exposure is required for the
carbohydrate effect, but the mechanisms are
uncertain.
• Fat stimulates the release of cholecystokinin
(CCK), which is a potent inhibitor of acid
secretion; fat also releases other potential
mediators and it activates neural responses.
69. H. Pylori
• Acute H. pylori infection induces a short
period of hypochlorhydria.
• In contrast, chronic infection can lead to
increases in basal and stimulated acid output,
particularly in patients who develop duodenal
ulcer.
• H. pylori eradication reduces basal and
stimulated acid output by 50 percent at one
month, and to normal levels by one year.
70. H. Pylori
• One mechanism by which H. pylori may
enhance gastric acid secretion is via increased
release of gastrin.
• Patients with H. pylori infection have elevated
basal and stimulated concentrations of serum
gastrin, and a decreased concentration of
somatostatin.
72. Hypersecretion
• Gastric acid hypersecretion (characterized by a
basal acid output >15 mEq/hour) is observed
in approximately 30 percent of patients with
duodenal ulcers.
• H. pylori infection is a contributing factor, but
some patients have acid hypersecretion
independent of H. pylori.
73. Hypersecretion
• Other uncommon conditions associated with
acid hypersecretion include the Zollinger-
Ellison syndrome (due to a gastrinoma),
mastocytosis, and a retained antrum following
partial gastrectomy.