I am a medical student. I have one friend who is persuing his MBBS degree in Taishan Medical UNiversity. I got these notes from him.
These notes are by Dr. Bikesh, He is a famous lecturer of TMU.
These notes have helped me a lot and i also watch his lecture videos , which are great; highly simple and huge content.
I am uploading with Renal physiology. If you want some other topics i would upload for you.
"Let the Knowledge be spread" Dr. Bikesh
Movements in the GIT( the guyton and hall physiology)Maryam Fida
movements in GIT
1. Propulsive Movements -------- Peristalsis
2. Mixing Movements
Moves food forward along GIT at an appropriate rate for digestion and absorption
A contractile ring appears around the gut and then moves forward
Stimulation at any point in the gut can cause a contractile ring to appear in the circular muscle, and this ring then spreads along the gut tube
Directional movement toward Anus
Can occur in either direction but normally occurs towards anus
Requires active myenteric plexus
Stimulus for intestinal peristalsis
Distention of the gut
Irritation
Parasympathetic nervous signals
Peristalsis is absent:
Congenital absence of myenteric plexus
Atropine (paralyzes cholinergic nerve endings)
Peristalsis also occurs in
Bile ducts
Glandular ducts
Ureters
Many other smooth muscle tubes of the body
Law of the Gut or Peristaltic Reflex or Myenteric reflex:
Peristaltic reflex plus anal direction of movement of peristalsis is called "law of the gut”
Contractile ring normally begins on orad side of distended segment
The gut sometimes relaxes several centimeters downstream toward the anus, called "receptive relaxation," thus allowing food to be propelled easily anally
Medical Physiology of the GIT:
Mucosa, principles of GIT function, afferent sensory innervation, GI reflexes, motility throughout the GI system, control of stomach emptying, coordination of motility, GI secretions, Gastric events following ingestion of a meal......
GASTROINTESTINAL PHYSIOLOGY (The Guyton and Hall Physiology)Maryam Fida
ANATOMY OF GASTROINTESTINAL TRACT
Consists of
Gastrointestinal (GI) tract
Accessory glandular organs
Anatomy and functions of the GI tract
GI tract
◦ mouth, pharynx, esophagus,
◦ stomach, small intestine,
◦ large intestine, anus
◦ Accessory Glandular Organs
salivary glands, liver, gallbladder, pancreas
Histology/organization of the Gut Wall
From esophagus to anus, GI tract has the same basic arrangement of tissues.
There are following layers from outer surface to inward.
Serosa
Longitudinal smooth muscle
Circular smooth muscle layer
Submucosa
Mucosa
Layers of Alimentary Canal
Gastrointestinal Smooth Muscle Functions as a syncytium
The individual smooth muscle fibers in the gastrointestinal tract are 200 to 500 micrometers in length and 2 to 10 micrometers in diameter, and they are arranged in bundles of as many as 100 parallel fibers.
In the LONGITUDINAL MUSCLE LAYER, the bundles extend longitudinally down the intestinal tract.
In the CIRCULAR MUSCLE Layer, they extend around the gut.
Within each bundle, the muscle fibers are electrically connected with one another through large numbers of GAP JUNCTION .
Because of these gap junction electrical signals that initiate muscle contractions can travel readily from one fiber to the next within each bundle but more rapidly along the length of the bundle than sideways.
Each muscle layer functions as a SYNCYTIUM . That is , when an action potential is elicited anywhere within the muscle mass, it generally travels in all directions in the muscle.
MAIN FUNCTIONS
1. Ingestion or consumption of food substances.
2. Breaking them in to small particles.
3. Transport of small particles to different areas of the digestive tract.
4. Secretion of necessary enzymes and other substances for digestion.
I am a medical student. I have one friend who is persuing his MBBS degree in Taishan Medical UNiversity. I got these notes from him.
These notes are by Dr. Bikesh, He is a famous lecturer of TMU.
These notes have helped me a lot and i also watch his lecture videos , which are great; highly simple and huge content.
I am uploading with Renal physiology. If you want some other topics i would upload for you.
"Let the Knowledge be spread" Dr. Bikesh
I am a medical student. I have one friend who is persuing his MBBS degree in Taishan Medical UNiversity. I got these notes from him.
These notes are by Dr. Bikesh, He is a famous lecturer of TMU.
These notes have helped me a lot and i also watch his lecture videos , which are great; highly simple and huge content.
I am uploading with Renal physiology. If you want some other topics i would upload for you.
"Let the Knowledge be spread" Dr. Bikesh
Movements in the GIT( the guyton and hall physiology)Maryam Fida
movements in GIT
1. Propulsive Movements -------- Peristalsis
2. Mixing Movements
Moves food forward along GIT at an appropriate rate for digestion and absorption
A contractile ring appears around the gut and then moves forward
Stimulation at any point in the gut can cause a contractile ring to appear in the circular muscle, and this ring then spreads along the gut tube
Directional movement toward Anus
Can occur in either direction but normally occurs towards anus
Requires active myenteric plexus
Stimulus for intestinal peristalsis
Distention of the gut
Irritation
Parasympathetic nervous signals
Peristalsis is absent:
Congenital absence of myenteric plexus
Atropine (paralyzes cholinergic nerve endings)
Peristalsis also occurs in
Bile ducts
Glandular ducts
Ureters
Many other smooth muscle tubes of the body
Law of the Gut or Peristaltic Reflex or Myenteric reflex:
Peristaltic reflex plus anal direction of movement of peristalsis is called "law of the gut”
Contractile ring normally begins on orad side of distended segment
The gut sometimes relaxes several centimeters downstream toward the anus, called "receptive relaxation," thus allowing food to be propelled easily anally
Medical Physiology of the GIT:
Mucosa, principles of GIT function, afferent sensory innervation, GI reflexes, motility throughout the GI system, control of stomach emptying, coordination of motility, GI secretions, Gastric events following ingestion of a meal......
GASTROINTESTINAL PHYSIOLOGY (The Guyton and Hall Physiology)Maryam Fida
ANATOMY OF GASTROINTESTINAL TRACT
Consists of
Gastrointestinal (GI) tract
Accessory glandular organs
Anatomy and functions of the GI tract
GI tract
◦ mouth, pharynx, esophagus,
◦ stomach, small intestine,
◦ large intestine, anus
◦ Accessory Glandular Organs
salivary glands, liver, gallbladder, pancreas
Histology/organization of the Gut Wall
From esophagus to anus, GI tract has the same basic arrangement of tissues.
There are following layers from outer surface to inward.
Serosa
Longitudinal smooth muscle
Circular smooth muscle layer
Submucosa
Mucosa
Layers of Alimentary Canal
Gastrointestinal Smooth Muscle Functions as a syncytium
The individual smooth muscle fibers in the gastrointestinal tract are 200 to 500 micrometers in length and 2 to 10 micrometers in diameter, and they are arranged in bundles of as many as 100 parallel fibers.
In the LONGITUDINAL MUSCLE LAYER, the bundles extend longitudinally down the intestinal tract.
In the CIRCULAR MUSCLE Layer, they extend around the gut.
Within each bundle, the muscle fibers are electrically connected with one another through large numbers of GAP JUNCTION .
Because of these gap junction electrical signals that initiate muscle contractions can travel readily from one fiber to the next within each bundle but more rapidly along the length of the bundle than sideways.
Each muscle layer functions as a SYNCYTIUM . That is , when an action potential is elicited anywhere within the muscle mass, it generally travels in all directions in the muscle.
MAIN FUNCTIONS
1. Ingestion or consumption of food substances.
2. Breaking them in to small particles.
3. Transport of small particles to different areas of the digestive tract.
4. Secretion of necessary enzymes and other substances for digestion.
I am a medical student. I have one friend who is persuing his MBBS degree in Taishan Medical UNiversity. I got these notes from him.
These notes are by Dr. Bikesh, He is a famous lecturer of TMU.
These notes have helped me a lot and i also watch his lecture videos , which are great; highly simple and huge content.
I am uploading with Renal physiology. If you want some other topics i would upload for you.
"Let the Knowledge be spread" Dr. Bikesh
Reabsorption In Renal Tubule (The Guyton and Hall physiology)Maryam Fida
Features of PCTPCT have high capacity of active & passive re-absorption.
This is due to special cellular features of epithelial cells.
They have increased no. of mitochondria due to high metabolic activity.
brush border on luminal (apical) side.
Brush border contains protein carrier molecules to transport Na+ by co-transport mechanism with other substances (a.acids, glucose etc).
Additional sodium is transported by COUNTER-TRANSPORT that reabsorb sodium while secreting hydrogen.
About 65 % of filtered load of Na+ & water is reabsorbed in PCT.
A lower % age of Cl- is also absorbed.
In 1st half of PC tubules, Na+ is re-absorbed by co-transport along with glucose, a.acids and other solutes.
In 2nd half of PC tubules, mainly Na+ is reabsorbed with Cl- and some of glucose + a.acids remain un-absorbed.
2nd half of PCT has high conc of Cl- (140 mEq/L) as compared to 1st half (105 mEq/L).
This presentation is about the basic composition and functions of various digestive juices secreted by different organs of the Digestive tract which help out in digestion.
anatomy of large intestine, its section, ceacum, ascending colon, transverse colon, descending colon, sigmoid colon, functions of large intestine , relations of each components of large intestine, carddinal siggns of large intestine, iliocecal junstion, difference between large and small intestine. abdominal angina, superior mesenteric and inferior mesenteric artery, lymphatic drainage, colonoscophy,
Reabsorption In Renal Tubule (The Guyton and Hall physiology)Maryam Fida
Features of PCTPCT have high capacity of active & passive re-absorption.
This is due to special cellular features of epithelial cells.
They have increased no. of mitochondria due to high metabolic activity.
brush border on luminal (apical) side.
Brush border contains protein carrier molecules to transport Na+ by co-transport mechanism with other substances (a.acids, glucose etc).
Additional sodium is transported by COUNTER-TRANSPORT that reabsorb sodium while secreting hydrogen.
About 65 % of filtered load of Na+ & water is reabsorbed in PCT.
A lower % age of Cl- is also absorbed.
In 1st half of PC tubules, Na+ is re-absorbed by co-transport along with glucose, a.acids and other solutes.
In 2nd half of PC tubules, mainly Na+ is reabsorbed with Cl- and some of glucose + a.acids remain un-absorbed.
2nd half of PCT has high conc of Cl- (140 mEq/L) as compared to 1st half (105 mEq/L).
This presentation is about the basic composition and functions of various digestive juices secreted by different organs of the Digestive tract which help out in digestion.
anatomy of large intestine, its section, ceacum, ascending colon, transverse colon, descending colon, sigmoid colon, functions of large intestine , relations of each components of large intestine, carddinal siggns of large intestine, iliocecal junstion, difference between large and small intestine. abdominal angina, superior mesenteric and inferior mesenteric artery, lymphatic drainage, colonoscophy,
slides on emporiatrics for indian travellers,i was not able to find a decent slide so i compiled the epidemologicl data for various diseases hope u guys find it useful
This lecture talking about; Digestion hydrolysis of large and complex organic molecules of foodstuffs into smaller and preferably water-soluble molecules which can be easily absorbed by the GIT.
Carbohydrates (also called carbs) are a type of macronutrient found in certain foods and drinks. Sugars, starches and fiber are carbohydrates. Other macronutrients include fat and protein. Your body needs these macronutrients to stay healthy.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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
Novas diretrizes da OMS para os cuidados perinatais de mais qualidade
Gastrointestinal Physiology
1. Gastrointestinal Physiology
DIGESTION & ABSORPTION
proteins, fats and complex CHO are broken down, digested, principally in the small intestine
the products of this digestion, plus the vitamins and minerals cross the mucosa and enter the
portal blood or lymph, absorption
orderly process, involving a large number of digestive enzymes, originating in the saliva, stomach,
SI and exocrine pancreas
the action of these enzymes is aided by the action of HCl in the stomach and by bile in the SI
the mucosa of the SI has a brush border made of numerous microvilli
this is covered by a layer of neutral and amino-sugars, the glycocalyx
the membranes of the mucosal cells contain glycoprotein enzymes which hydrolyze CHO and
peptides
the glycocalyx is made, in part, of the CHO portions of these glycoproteins which extend into the
intestinal lumen
next to the brush border and the glycocalyx is a 100-400 µm unstirred water layer (UWL)
the mucous coat overlying the mucosa is also a significant barrier to difusion
processes involved in the absorption of substances include,
a. diffusion
b. facilitated diffusion
c. solvent drag
d. active transport
e. secondary active transport
f. endocytosis
2. Gastrointestinal Physiology
Carbohydrates CHO
Digestion
the principal dietary CHO is composed of,
a. polysaccharides
b. monosaccharides
c. disaccharides
starches, polymers of glucose and their derivatives, are the only polysaccharides of importance to
humans
in glycogen, glucose molecules are joined by 1-4~ linkages, with some chain branching by 1-6α
linkages
amylopectin, which ~ 80-90% of dietary starch, is similar but has less branches
amylose possesses only 1-4~ linkages and is a straight chain
glycogen is found in animals, whereas the later two are of plant origin
the disaccharides lactose & sucrose are also ingested, along with the monosaccharides glucose &
fructose
starch is first degraded by ptyalin, the α-amylase of saliva
however, the optimal pH for this is 6.7 and activity is terminated by gastric acidity
once in the SI, pancreatic α-amylase is added
both of these attack the 1-4α linkages but spare,
a. the 1-6α linkages
b. the 1-4α linkages next to branch points
c. the terminal 1-4α linkages
thus, the end products of this digestion are,
a. the disaccharide maltose
b. the trisaccharide maltotriose
c. larger polymers of glucose with 1-4α linkages
branched polymers, ~ 8 units, the α-limit dextrins
d.
these are further digested by the oligosaccharidases located at the outer portion of the membrane
of the microvilli,
a. maltase
b. lactase
c. sucrase
α-limit dextrinase
d.
in many mammals and some races of humans, intestinal lactase activity is high at birth, declines to
low levels in childhood and remains low subsequently
3. Gastrointestinal Physiology
low levels being associated with intolerance of milk as lactose remains in the GIT and acts as an
osmotic agent prior to being broken down by bacteria in the colon
however, most Caucasians retain their lactase activity but most adult blacks are intolerant
Absorption
hexoses and pentoses are rapidly absorbed across the intestinal mucosa
these then enter the capillaries which drain to the portal vein
glucose and Na+ share the same symport, thus a high [Na] at the mucosal surface facilitates
glucose absorption
→
due to the action of the basal Na-K-pump secondary active transport
the same mechanism also transports galactose
fructose utilizes a different carrier, and its absorption is independent of luminal Na+
→ facilitated diffusion
insulin has minimal effect on the intestinal transport of sugars, as is the case for reabsorption in
the proximal nephron
both are essentially normal in diabetes but are depressed by the drug phlorhizin
the maximal rate of glucose absorption is ~ 120 g/h
4. Gastrointestinal Physiology
Proteins & Nucleic Acids
Protein Digestion
begins in the stomach, where pepsins cleave some of the peptide linkages
these are secreted in an inactive form, as pepsinogens, and are activated by the low luminal pH
there are a large number of these, however, they can be divided into two distinct
immunohistochemical groups,
a. pepsinogen I - found only is HCl secreting region
b. pepsinogen II - also found in the pyloric region
maximal acid secretion correlates with pepsinogen I levels, and patients with high circulating
levels have a 5 times higher incidence of ulceration
pepsins hydrolyse bonds between an aromatic AA, such as tyrosine or phenylalanine, and a
second AA
thus, the products of this digestion are diverse peptides
the optimum pH ~ 1.6-3.2, therefore action is terminated on exit from the stomach
the pH in the duodenal cap ~ 2.0-4.0, but the rest of the duodenum is ~ 6.5
in the SI, these smaller peptides are further fragmented by proteolytic enzymes of the pancreas,
which may be divided into the,
a. endopeptidases - trypsin, chymotrypsin & elastase
b. exopeptidases - carboxydipeptidases
and the aminopeptidases of the brush border
some di and tripeptides are absorbed and finally broken down by intracellular peptidases
thus, the final digestion of peptides occurs in three locations,
a. the lumen
b. the brush border
c. within the cell
Absorption
the l-AA's are absorbed more rapidly then their d-AA isomers and following a meal there is a
sharp transient rise in the nitrogen content of portal blood
the d-isomers are absorbed soley by passive diffusion
whereas, most of the l-isomers are actively transported from the lumen
there are 4 seperate systems,
a. neutral AA's
b. basic AA's
c. proline, hydroxyproline and glycine
d. dicarboxylic AA's - glutamic and aspartic acids
5. Gastrointestinal Physiology
there is a separate system for the di & tri-peptides
transport is linked to Na+ and is facilitated by an increase in luminal [Na], as for glucose
from the cells, diffusion of AA's into the portal blood is passive
absorption is rapid in the duodenum and the jejunum, but slow in the ileum
of the digested protein,
→
a. ingested food 50%
→
b. GIT secretions 25%
→
c. desquamated mucosal cells 25%
only ~ 2-5% of protein in the SI escapes in the stools, most of the protein found is due to bacteria
and cellular debris from the colon
in infants moderate amounts of undigested proteins are also absorbed
the IgG secreted in maternal milk enters the circulation by endocytosis, although this transfer is
relatively minor for humans
absorption of protein antigens takes place in large microfold cells (M cells), which are specialized
epithelial cells which overly aggragates of lymphoid tissue → Peyer's patches
these cells present the antigens to lymphoblasts, which are activated and enter the circulation
they eventually return to the mucosa, where they secrete secretory IgA in response to exposure
to the same antigen
Nucleic Acids
pancreatic nucleases split the nucleic acids to nucleotides
these are subsequently split in the nucleosides and phosphoric acid by enzymes at the brush
border
these are further broken down to their constituent sugars and purine and pyrimidine bases
the bases are absorbed by active transport
6. Gastrointestinal Physiology
Lipids
Fat Digestion
significant digestion begins in the duodenum with pancreatic lipase being the most important
this hydrolyses the 1 & 3 bonds of triglycerides (TG) with relative ease but the 2 bond at a slower
rate
the principal metabolites are FFA's and 2-monoglycerides
this acts on fats which have been emulsified, but cannot act without the protein colipase, which is
secreted by the pancreas
this binds to the surface of the droplet, displacing the emulsifying agents and anchoring the lipase
most of the dietary cholesterol is in the form of cholesterol esters, and pancreatic esterase
hydrolyses these in the lumen
fats are finely emulsified in the SI by the detergent action of the bile salts, lecithin, and
monoglycerides → particles 200-5000 nm
bile salts alone are relatively ineffective
when the [bile salts] is high, as after a meal and gallbladder contraction, lipids and bile salts
interact spontaneously to form micelles ~ 3-10 nm
these generally contain FFA's, monoglycerides and cholesterol
micellar formation further solubilizes the lipids and provides a mechanism for their transport to
the brush border, through the UWL by diffusion
lipids enter the cells by passive diffusion and are rapidly esterified, maintaining the concentration
gradient for diffusion
unlike the ileal mucosa the uptake of bile salts by the jejunum is low, and these diffuse back into
the intestinal lumen
thus, bile salt micelles solubilize lipids, transport them across the UWL, and maintain a saturated
concentration of lipids at the mucosal cell
pancreatectomized animals, or those with pancreatic insufficiency, suffer steatorrhoea, due to,
a. lipase deficiency
b. depressed micellar formation
due to low HCO3from the pancreas
the acid environment prevents incorporation of FFA's into micelles
this is also why patients with excess gastric acidity secrete fatty stools
Fat Absorption
monoglycerides, cholesterol and FFA's from micelles enter the mucosa by passive diffusion
the subsequent fate of FFA's depends upon their size,
→
a. FFA < 10-20C portal blood as FFA
→
b. FFA > 10-12C reesterified to TG
in addition, some of the absorbed cholesterol is esterified
the TG and cholesterol esters are covered by a layer of protein, cholesterol and phospholipid to
form chylomicrons, which enter the lymphatic circulation
7. Gastrointestinal Physiology
most of the TG is formed by acylation of absorbed 2-monoglycerides at the SER, though, some is
also formed from glycerophosphate from the glycolytic pathway
the acylation of glycerophosphate and the formation of lipoproteins occurs in the RER
CHO moeities are added to proteins in the golgi apparatus, and the conmplete chylomicrons are
released by exocytosis
the majority of absorption occurs in the proximal SI and on a normal diet less than 5% appears in
the stools, most of this coming from cellular debris
these processes are not fully mature at birth, and infants fail to absorb nearly 10-15% of their
dietary fat
Absorption Of Cholesterol And Sterols
cholesterol is readily absorbed if bile salts, FFA's and pancreatic juices are present
absorption is said to be limited to the distal SI
almost all of the absorbed cholesterol is incorporated into chylomicrons, which then enter the
lymphatics
closely related sterols of plant origin are poorly absorbed
some of these reduce the absorption of cholesterol, probably by competing with cholesterol for
esterification with FFA's
8. Gastrointestinal Physiology
Water & Electrolytes
Water, Sodium & Potassium
water balance in the GIT
1. Input: 9000 ml
i. Ingested: 2000 ml
ii. Endogenous secretions: 7000 ml
salivary glands 1500
stomach 2500
bile 500
pancreatic 1500
intestinal 1000
2. Reabsorption: 8800 ml
i. jejunum 5500
ii. ileum 2000
iii. colon 1300
3. Excretion in stools: 200 ml
thus, 98% of the fluid load is reabsorbed
only small amount s of water move across the gastric mucosa, however, water moves freely
across the SI in accordance with osmotic gradients
Na+ is actively transported from the lumen by pumps located in the baso-lateral cell membranes
in the ileum and jejunum, this is facilitated by aldosterone
luminal membrane transport is variably coupled to glucose, AA's or other substances
the absorption of sodium is facilitated by the presence of the cotransported solutes
→ the use of NaCl & glucose solutions in diarrhoeal illnesses
some E.coli and V.cholera produce a toxin which activates adenylate cyclase and increases cAMP
this increases Clsecretion from the mucosa, and inhibits the function of the mucosal carrier for
Na+, reducing NaCl reabsorption
however, the symport for glucose/Na+ is unaffected
duodenal contents may be hyper or hypo-osmotic, but the time the jejunum is reached the
contents are iso-osmotic
in the colon, Na+ is actively pumped into the lumen and water follows
9. Gastrointestinal Physiology
for the majority, the movement of K+ is by passive diffusion
the net movement being determined by the potential difference between the lumen and intestinal
capillaries, leading to,
[K+] ~ 6 mmol/l
a. jejunum -5 mV
[K+] ~ 13 mmol/l
b. ileum -25 mV
[K+] ~ 30 mmol/l
c. colon -50 mV
with the lumen negative and concentration being in the lumen
thus, the loss of ileal of colonic fluids by diarrhoea leads to severe hypokalaemia
Chloride & Bicarbonate
in the ileum and colon, Clis actively reabsorbed in exchange for HCO3--
this results in the intestinal contents becoming more alkaline
Vitamins & Minerals
Vitamins
absorption of the water soluble vitamins is rapid and efficient
the fat soluble vitamins, A, D, E, & K require normal fat absorption
a deficiency of either bile salts or pancreatic juices will result in deficient absorption
most are absorbed in the proximal SI, though, B12 is absorbed in the ileum
along with intrinsic factor secreted by the stomach
Calcium
absorption ranges from 30-80% and occurs mainly in the proximal SI
some absorption is by passive diffusion, though, active transport is stimulated by Vit. D3
this stimulates the formation of Ca++ binding protein in the mucosal cells
the exact relationship of these proteins to increased Ca++ absorption is unsettled
this is under feedback control and GIT absorption is one of the main regulators of the plasma
Ca++ levels
absorption is also facilitated by lactose and protein
it is inhibited by phosphates & oxalates, as these form insoluble salts
10. Gastrointestinal Physiology
Iron
1. average daily losses
i. men ~ 0.6 mg
ii. women ~ 1.2 mg
losses for females vary considerably
2. average intake ~ 20 mg
but absorption is equal only to daily losses
3. absorption ~ 2-3%
4. normal plasma iron
i. men ~ 130 µg/dl
ii. women ~ 110 µg/dl
more readily absorbed in the ferrous (Fe++) state
however, most dietary iron is in the ferric form (Fe+++)
gastric secretions dissolve the iron and enable reduction to the ferrous state
this is the reason iron deficiency anaemia follows gastrectomy
ascorbic acid is another reducing agent in the diet which favors the conversion of the ferric the
ferrous ion
haem is also absorbed and the attached Fe++ is released by the mucosal cells
absorption is an active process occurring mainly in the proximal SI
mucosal transferrin binds iron in the lumen and transfers it across the brush border
most of this is then transferred directly to the blood stream, but a significant amount is bound to
apoferritin in the mucosal cells
this iron is lost when the cells desquamate
this protein combines with iron to form ferritin
each ferritin molecule may contain as many as 4500 molecules or iron, which exist in a micelle of
ferric-hydroxyphosphate, contained within the protein
ferritin molecules in lysosomal membranes may aggregate in deposits of > 50% iron
→ haemosiderin
approximate distribution in the body,
a. haemoglobin ~ 70%
b. myoglobin ~ 3%
c. ferretin ~ 27%
ferritin is also found in the plasma, but most iron is bound to transferrin
this polypeptide has 2 binding sites and total saturation is usually ~ 35%
in iron deficiency, the amount of ferritin is decreased and a greater fraction enters the plasma
in overload, ferritin stores are large and absorption from the intestine is decreased → mucosal
block
11. Gastrointestinal Physiology
REGULATION OF GASTROINTESTINAL FUNCTION
Functional Anatomy
there is some local variation, however, in general there are 3 layers of smooth muscle, 2
longitudinal & 1 circular
the wall is lined by mucosa and , except in the case of the oesophagus, is covered by a serosa
the serosa continues into the mesentry, which carries the nerves, blood vessels, and lymphatics
Innervation
there are two major networks of nerve fibres which are intrinsic to the GIT, the,
a. myenteric plexus of Auerbach
between the outer lonitudinal and middle circular layers of muscle
b. submucous plexus of Meissner
between the middle circular layer and the mucosa
these plexuses are interconnected and they contain nerves with processes which originate from
receptors, either in the wall of the gut or the mucosa
there are also an enormous number of interneurons
the mucosal receptors include,
a. mechanoreceptors, sensitive to stretch
b. chemoreceptors, sensitive to changes in the contents of the lumen
neurons innervate all of the muscular layers of the gut wall, other neurons innervate hormone
secreting cells
these constitute a complex enteric nervous system, which some authorities include as a third
division of the autonomic system
there are a total of ~ 106 neurons
the secreted neurotransmitters include,
i. ACh
ii. enkephalins
iii. VIP
iv. CCK
v. NA
vi. gastrin releasing peptide GRP
vii. Substance P
viii. neurotensin
12. Gastrointestinal Physiology
coordinated motor activity of the gut occurs in total absence of extrinsic innervation
extrinsic innervation is from both the PNS & SNS
the preganglionic PNS fibres consist of ~ 2000 vagal efferents plus efferents from the sacral
nerves
they generally end on cholinergic nerves in either of the intrinsic systems
the SNS fibres are postganglionic, but many of them end on postganglionic cholinergic neurons,
where they inhibit ACh secretion
others innervate blood vessels, producing vasoconstriction, while others end directly on intestinal
smooth muscle
Circulation
see CVS notes on special circulations
Gastrointestinal Hormones
there are a large number concerned with the regulation of GIT motility and secretion
when given in large doses their functions frequently overlap, however, in physiological levels
their actions appears discrete
many of these fall into one of 2 families,
a. gastrin family - gastrin 34
- CCK 39
b. secretin family - secretin
- GIP
- glucagon
- VIP
- glicentin
c. others - motilin
- substance P
- somatostatin 14
- GRP
Gastrin
produced by G cells of the lateral walls of the gastric antral mucosa
receptors mediating gastrin responses to changes in the luminal contents are present in the
microvilli
like many other cells of the GIT secreting hormones, these contain amines related to NA & 5HT
and are of neural crest origin → APUD cells
there is a second type of gastrin secreting cell found throughout the GIT, the TG cell
this contains G34 but lacks G17
gastrin is also found in the pancreatic islets in foetal life and gastrin secreting tumors occur in the
pancreas
it is also found in the CNS, where it appears to act as a central neurotransmitter
displays both macroheterogeneity & microheterogeneity
13. Gastrointestinal Physiology
the former referring to differences in peptide length, the later to differences in molecular structure
due to differing AA's
three main forms are found, G34, G17, & G14 gastrins
all possess the same C-terminal tetrapeptide, which in itself has gastrin activity (~ 10% of G17)
the G17 form is the principal agent in the regulation of gastric acid secretion
the two smaller peptides have half lives of 2-3 mins, whereas the larger G34 up to 15 mins
inactivation is primarily in the kidney and SI
the physiological effects include,
a. gastric acid secretion
b. pepsin secretion
c. increased gastric motility
d. ? increased tone of the gastro-oesophageal sphincter
e. stimulates insulin & glucagon secretion after a protein meal
NB: atropine does not inhibit the response,
the transmitter probably being gastrin releasing peptide GRP
also direct stimulation from the products of protein digestion, ie. AA's
acid in the antrum inhibits secretion, providing a negative feedback loop
Cholecystokinin
secreted by the cells of the upper SI
results in both
a. increased secretion from the pancreas, and
b. contraction of the gallbladder
like gastrin, it displays both macroheterogeneity & microheterogeneity
prepro-CCK is processed into many fragments, from CCK4 to CCK58
the major active fragments secreted by the duodenum & jejunum are probably CCK8 & CCK12
the half life is ~ 5 mins, but little is known about its metabolism
it is also found in cells in the ileum and colon, in parts of the CNS, and in nerves in many parts of
the body
other actions of the hormone include,
a. augmentation of the action of secretin
b. inhibits gastric emptying
c. increases the secretion of enterokinase
d. has a trophic effect on the pancreas
e. may enhance the motility of the SI and colon
both CCK and gastrin stimulate the secretion of glucagon from the pancreas in response to a
protein meal, and may be the quot;gut factorquot; responsible in vivo
the action on the gallbladder may be mediated by cGMP
14. Gastrointestinal Physiology
secretion from the proximal GIT is stimulated by peptides, AA's and FFA's of more than 10 C
length
as bile increases digestion, a positive feedback loop exists, secretion being terminated by the
passage of contents distally
Secretin
first demonstrated by Bayliss and Starling in 1902, that the excitatory effect of duodenal
stimulation on pancreatic secretion was due to a blood-borne factor
subsequent research led to the discovery of secretin
from this research, Starling introduced the term hormone to characterise chemical messengers
secreted by cells located deep within the glands of the proximal SI
the AA sequence is very similar to that of glucagon, VIP & GIP
its half life is ~ 5 mins, little is known about its metabolism
secretin increases the formation of bicarbonate by the duct cells of the pancreas and biliary tract
thus, it causes a watery, alkaline pancreatic secretion
its action is mediated by cAMP
other effects include,
a. augments the action of CCK in stimulating pancreatic secretion of digestive enzymes
b. decreases gastric acid secretion
c. increases pyloric tone
secretion of secretin is increased by the presence of the products of protein digestion and by acid
in the proximal duodenum
the increased alkaline secretion acts to neutralize the acid products entering the upper SI
GIP
GIP is a 43 AA peptide found in the mucosa of the duodenum and jejunum
its secretion is stimulated by the presence of glucose and fat
it also stimulates the release of insulin, and evidence is accumulating that this is the GIT factor in
physiological β-cell stimulation
VIP
a 28 AA peptide found in many of the nerves of the GIT
also found in the blood but the half life is only 2 mins
it markedly stimulates intestinal secretion of water and electrolytes
other actions include,
a. inhibition of gastric acid secretion
b. dilatation of peripheral blood vessels
it is also found in neurons of the CNS, where it coexists with ACh
in many tissues it potentiates the action of ACh
15. Gastrointestinal Physiology
THE STOMACH
Functional Anatomy
in the pyloric and cardiac regions of the stomach the glands secrete mucus
in the body, including the fundus, the glands contain
→ HCl & intrinsic factor
a. parietal cells (oxyntic)
chief cells (zymogen, peptic) → pepsinogens
b.
these mix in the necks of the glands with mucus
several of the glands open into a common chamber, a gastric pit
the blood vessel and lymphatic supply is extensive
the PNS innervation comes from the vagi
the SNS innervation comes from the coeliac plexus
Gastric Secretion
the average daily secretion of gastric juice ~ 2500 ml
the hydrochloric acid secreted by the stomach has a number of functions,
a. kills many bacteria
b. aids protein digestion
c. provides the necessary pH for the activity of pepsin
d. stimulates the flow of bile and pancreatic juices
also contains mucus, which protects the mucosal lining against potential tissue damage
this is secreted by cells in the necks of the glands and from the surface
each glycoprotein molecule is made up of 4 subunits joined by disulphide bridges and the mucus
forms a flexible gel that coats the mucosa
the mucosa also secretes bicarbonate into the mucus, forming an unstirred layer with pH ~ 7.0
the unstirred layer, plus the surface membranes of the mucosal cells and the tight junctions
between them, form the mucosal bicarbonate barrier which is responsible for the protection of the
stomach
substances which tend to disrupt the barrier include,
a. ethanol
b. bile acids
c. aspirin and other NSAIDs
prostaglandins stimulate mucus secretion, and their synthesis is inhibited by the NSAIDs
the electrolyte content varies with the rate of acid secretion
at low rates of secretion the [Na] is high, but as the rate of acid secretion increases the [Na] falls
and [HCl] rises
16. Gastrointestinal Physiology
Pepsinogen Secretion
these are secreted by the chief cells as inactive precursors, the pepsinogens
Hcl Secretion
transport of H+ from the cytoplasm to the lumen of the canaliculi is by an active H+-K+-ATPase in
the membrane of parietal cells
there is evidence that the pump is synthesized in tubulovesicular structures at rest, and is then
inserted into the membrane during stimulation of acid secretion
it is difficult to obtain pure samples, however, secretion may be an isotonic solution of essentially
pure HCL, with a pH as low as 0.87
the cytoplasm is similar to other cells, being around pH ~ 7.0, the H+ being pumped against an
enormous concentration gradient
the primary source of the secreted H+ ion is from the ionization of water, being immediately
extruded in exchange for K+
external K+ ions are not required for secretion, K+ readily diffusing across the membrane
the presence of the H-K-pump is almost entirely limited to the parietal cells
Cl- is also actively transported into the gastric juice
for each H+ secreted an OH- ion is neutralized by another H+ supplied from the dissociation of
carbonic acid
the HCO3formed is secreted into the interstitium in exchange for Cl-
the mucosa contains an abundance of carbonic anhydrase
the stomach has a negative respiratory quotient → the venous blood has a lower PCO2 than the
arterial blood
acid secretion is stimulated by,
→
a. H2 histamine receptors cAMP
→ Ca++
b. M1 muscarinic receptors
→ Ca++
c. gastrin receptors
the intracellular events interact, such that activation of one receptor type potentiates the response
to another
histamine comes from cells resembling mast cells, ACh from PNS endings and gastrin via the
circulation
Gastric Motility & Emptying
when food enters the stomach the organ expands = receptive relaxation
followed by well developed peristaltic contractions, most marked in the distal half, occurring at ~
3/min
the pyloric sphincter has only limited function in the rate of emptying of the stomach
this appears to be normal even if the pylorus is resected
apparently the antrum, pylorus and upper duodenum function as a unit, coordinating the rate of
emptying
the peristaltic contractions of the stomach are coordinated by the gastric slow wave
17. Gastrointestinal Physiology
a wave of depolarization of smooth muscle cells spreads from the circular muscle of the fundus to
the pylorus every 20 seconds
this is also termed the basic electrical rhythm
Regulation Of Gastric Emptying And Secretion
regulation is by both neural and humoral mechanisms
the neural components are local autonomic reflexes, involving cholinergic neurons, plus impulses
from the CNS via the vagus
vagal stimulation results in,
a. release of gastrin-releasing peptide
b. release of gastrin
c. secretion of acid & pepsin, via ACh
regulation of secretion of acid is usually divided into cephalic, gastric, and intestinal influences,
though these overlap
the cephalic influences are primarily mediated through the vagus,
a. food in the mouth
b. conditioned responses - smell, sight, thoughts
c. emotional responses
→ diencephalon and limbic systems
the gastric influences are mediated by local reflex mechanisms and responses to gastrin,
a. food in the stomach
b. stretch and chemical stimuli, mainly AA's, on the mucosa
→ receptors entering Meissner's plexus
→ postganglionic parasympathetic neurons
→ parietal cells which secrete acid
the reflex arc is totally within the wall of the stomach
these neurons are the same as those which mediate the cephalic phases of secretion
the products of protein digestion also bring about an increased secretion of gastrin
the intestinal influences are mediated by reflex and hormonal feedback mechanisms from the
mucosa of the small intestine
fats, CHO and acid in the duodenum inhibit the secretion of gastric acid, gastric motility and
pepsin secretion
these effects are probably brought about by the secretion of GIP & secretin
gastric acid secretion is increased following removal of large amounts of the small intestine, in a
roughly proportional manner
18. Gastrointestinal Physiology
hypoglycaemia acts via the CNS and vagal efferents to stimulate acid and pepsin secretion
the stimulation produced by insulin is the result of hypoglycaemia
other stimulants include,
a. caffeine
b. alcohol
Regulation of Gastric Emptying and Secretion
CHO leaves the stomach within a few hours
protein rich foods leave more slowly, and emptying is slowest for fat rich meals
the rate of emptying is determined by the osmolality of the contents reaching the duodenum
hyperosmolality is sensed by duodenal osmoreceptors which initiate a decrease in the rate of
emptying
products of protein digestion and acid initiate a neurally mediated decrease in gastric motility, the
enterogastric reflex
this is also produced by distention of the duodenum
Peptic Ulcer
related to a breakdown of the barrier which normally protects the mucosa from autodigestion
in patients with duodenal and prepyloric ulcers, excessive acid secretion also plays a role
however, this is not the case for other gastric ulcers
there is a correlation between the levels of pepsinogen I, maximal acid secretion and the incidence
of peptic ulceration
resting gastrin levels do not appear to be elevated, but their gastrin responses to stimulation are
greater than normal
their parietal cells are also hyperresponsive to gastrin stimulation
acid secretion is clearly involved in Zollinger-Ellison syndrome, where gastrinomas, usually in the
pancreas, result in continued acid hypersecretion
treatment is aimed at a reduction in the secretion of acid and enhancing the mucosal barrier
1. gastric H2 receptors can be blocked with cimetidine or ranitidine
2. cholinergic M1 receptors can be blocked with atropine or the more specific antagonist
pirenzipine
alternatively the H+-K+-ATP'ase can be inhibited by omperazole
3.
19. Gastrointestinal Physiology
Other Functions of the Stomach
HCL kills many of the ingested bacteria
parietal cells secrete intrinsic factor, necessary for the absorption of cyanocobalamin
this cobalt containing vitamin is necessary for normal erythropoeisis, deficiency resulting in
megaloblastic anaemia
in pernicious anaemia, deficiency of intrinsic factor is due to idiopathic atrophy of the gastric
mucosa
intrinsic factor is a glycoprotein, MW = 45,000, the complex binding to specific receptors in the
terminal ileum
trypsin is required for this proces to be efficient, thus deficiency can also occur in pancreatic
insufficiency
in the blood stream, B12 is bound to transcobalamin II
20. Gastrointestinal Physiology
THE EXOCRINE PANCREAS
Functional Anatomy
compound alveolar gland resembling the salivary glands
granules containing the digestive enzymes, zymogen granules, are formed in the cells and
discharged by exocytosis
the small duct radicals coalesce to form a single duct, of Wirsung, which usually joins the
common bile duct at the ampulla of Vater
the ampulla opens through the duodenal papilla, and is surrounded by the sphincter of Oddi
there may be an accessory duct, of Santorini, entering more proximally
Composition of Secretion
juice is highly alkaline, with a high [HCO3--]
dialy secretion ~ 1500 ml
bile and intestinal juices are also alkaline or neutral, and these three secretions neutralize
duodenal contents, raising the pH to ~ 6.0-7.0
the powerful proteolytic enzymes are secreted as inactive proenzymes
trypsinogen is converted to trypsin by enterokinase / enteropeptidase, secreted by the duodenal
mocosa
secretion is increased by the hormone CCK
trypsin then converts other inactive enzymes to their active forms,
→
a. chymotrypsinogens chymotrypsin
→
b. proelastase elastase
→
c. procarboxypeptidase carboxypeptidase
→
d. trypsinogen trypsin
*(d) forming a (+)'ve feedback
deficiency of enterokinase leads to protein malnutrition
the pancreas normally also contains a trypsin inhibitor, to protect againt autodigestion
phospholipase A is activated by trypsin, splitting a fatty acid from lecithin, forming lysolecithin
the later product damages cell membranes and its formation from lecithin in bile is involved in
acute pancreatitis
a small amount of α-amylase normall leaks into the circulation
Regulation Of Secretion
primarily under hormonal control
secretin causes copious secretion of very alkaline pancreatic juice, relatively poor in enzyme
precursors
it acts on the epithelial cells of the small duct radicals, which secrete HCO3--, rather than the
acinar cells
as the rate of secretion increases, [Cl-] falls and [HCO3--] rises in a reciprocal fashion
secretin also stimulates bile secretion
21. Gastrointestinal Physiology
CCK results in secretion of juice rich in proenzymes, acting on acinar cells
with the release of zymogen granules
vagal stimulation also causes a smaller but similar increase in secretion
both act via an increase in intracellular [Ca++]
22. Gastrointestinal Physiology
LIVER & BILARY SYSTEM
Functional Anatomy
organised into lobules
within which, blood flows from branches of the portal vein to a central vein, through sinusoids
lined with hepatic cells
the sinusoidal capillaries have large fenestrations, allowing plasma close contact with the cells
generally, there is only one layer of cells per sinusoid, creating a large area of contact
blood from the hepatic artery also enters the sinusoids
the central veins coalesce to form hepatic veins which drain to the IVC
the average transit time for portal blood is ~ 8.5 s
there are a large number of tissue macrophages, Kupffer cells, which are anchored to the
endothelium
each hepatocyte is adjacent several bile canaliculi, which coalesce to form the right and left
hepatic ducts
these join outside the liver to form the common hepatic duct
the cystic duct drains the gallbladder to for the common bile duct
the mucous membranes of the cystic duct form the spiral vales of Heister
Functions of the Liver
the liver is the largest gland in the body
functions include,
1. formation of bile
2. CHO and intermediary metabolism
3. AA and ammonia metabolism
4. protein/glycoprotein synthesis and degradation
5. lipid metabolism - FFA's, TG and cholesterol
6. hormone synthesis & metabolism
7. detoxification of drugs and toxins
8. immune defence against agents entering the portal circulation
23. Gastrointestinal Physiology
Compositon Of Bile
bile is made up of,
a. bile pigments
b. bile salts
c. other substances - lecithin, FFA's, cholesterol
d. alkaline electrolyte solution - similar to pancreas
average daily secretion ~ 500 ml
some components are reabsorbed in the terminal ileum → enterohepatic circulation
the bile pigments are the glucuronides of bilirubin & biliverdin, and are responsible for the
golden yellow color
the bile salts are the sodium and potassium salts of bile acids conjugated to glycine or taurine
the acids are based on the cyclopentanoperhydrophenanthrene nucleus
there are two principal, or primary bile acids, formed by the liver,
1. cholic acid
2. chenodeoxycholic acid
95% of these are reabsorbed in the terminal ileum, the remaining 5% entering the colon
these are acted upon by bacteria forming the secondary bile acids,
1. deoxycholic acid - most of this is absorbed
2. lithocholic acid - insoluble and mostly excreted in the stools ~ 99%
average daily synthesis ~ 0.2-0.4 g
the total bile salt pool ~ 3.5 g
this recycles 6-8 times/day and 2 times/meal
these salts have a number of important actions,
→
a. combine with lipids to form micelles hydrotropic effect
→
b. with monoglycerides and phospholipids emulsify fats
c. activate lipases in the SI
in the absence of bile salts, ~ 25% of ingested fat appears in the feces, and there is severe
malabsorption of the fat soluble vitamins
24. Gastrointestinal Physiology
Bilirubin Metabolism & Excretion
bilirubin is formed in the RES by the breakdown of haemoglobin
the globin moiety is split-off and returned for re-use
the haem group converted to biliverdin and most of this is then converted to bilirubin
this is then transferred to the liver via the circulation, bound to plasma albumin
free bilirubin enters the hepatocytes where it is bound to cytoplasmic proteins, allowing continued
diffusion
conjugation to glucuronic acid is catalysed by glucuronyl transferase, located primarily on the
SER
each bilirubin binds 2 glucuronide molecules, which are derived from uridine
diphosphoglucuronic acid (UDPGA)
this is then transported against a concentration gradient into the bile canaliculi
some of this escapes into the bloodstream where it is excreted by the kidney
the intestinal mucosa is relatively impermeable to bilirubin glucuronide
however, it is permeable to unconjugated bilirubin and urobilinogens, a series of colorless
derivatives formed in the GIT by bacterial action
consequently, there is some reabsorption, most of which enters the bile again but some of which
is excreted in the urine
Jaundice
normal plasma bilirubin ~ 3.5-17.0 umol/l
clinical jaundice is seen when the plasma bilirubin ~ 34 umol/l (2 mg/dl)
hyperbilirubinaemia may result from,
1. excess production- haemolytic anaemia
2. decreased hepatic uptake
3. altered intracellular binding or conjugation
4. decreased secretion into the bile
5. intra, or extrahepatic biliary obstruction
NB: (a-d) → predominantly unconjugated bilirubinaemia
(e) → mixed bilirubinaemia