Exam 4 Flashcards
Alveolar-Capillary
Gas exchange in the lungs occurs
in air sacs, known as alveoli.
- Type I alveolar cells
- Type II alveolar cells (surfactant)
- Alveolar epithelium
- Epithelial basement membrane
- Capillary basement membrane
- Capillary lumen
- RBC
Gas exchange
A. Dalton’s law of partial pressures:
Partial pressure= Total pressure X Fractional gas concentration
In dry inspired air, PO2=160 mm Hg, PCO2=0 mm Hg
In humidified tracheal air at 37 C. (H2O) PO2=150 mmHg, PCO2=0 mmHg
Partial pressures of O2 and CO2 in inspired air, alveolar air, PAO2=100 mmHg, PACO2=40 mmHg (A=Alveolar)
In blood (Pulmonary a.) PO2=40 mmHg, PCO2=46 mmHg
In blood (Pulmonary v.) PO2=100 mmHg, PCO2=4o mmHg
Gas Laws
Diffusion of gases-Fick’s law
Transfer of gases across cell membranes or capillary walls occurs by simple diffusion, For gases, the rate of transfer by diffusion is directly proportional to the driving force, a diffusion coefficient, and the surface area available for diffusion, it is inversely proportional to the thickness of membrane barrier.
Gas Laws
Lung diffusing capacity (DL)
DL combines:* the diffusion coefficient of the gas, *the surface area of the membrane, and *the thickness of the membrane.
DL also takes into account the time required for the gas to combine with proteins in pulmonary capillary blood (e.g., binding of O2 to hemoglobin in red cells).
DL can be measured with carbon monoxide (CO) because CO transfer across the alveolar/pulmonary capillary barrier is limited exclusive by the diffusion process.
Lung diffusing capacity (DL)
In various diseases,
In various diseases, DL changes: in emphysema, DL deceases because destruction of alveoli results in a decreased surface area for gas exchange.
In fibrosis or pulmonary edema, DL decreases because the diffusion distance (membrane thickness or interstitial volume) increases.
In anemia, DL decreases because the amount of hemoglobin in red blood cells is reduced (recall that DL includes the protein-binding component of O2 exchange).
During exercise, DL increases because additional capillaries are perfused with blood, which increases the surface area for gas exchange.
Diffusion of gases such as O2 and CO2
The diffusion rates of O2 and CO2 depend on the partial pressure differences across the membrane and the area available for diffusion.
For example, the diffusion of O2 from alveolar air into the pulmonary capillary depends on the partial pressure difference for O2 between alveolar air and pulmonary capillary blood. Normally, capillary blood equilibrates with alveolar gas, when the partial pressures of O2 become equal, then there is no more net diffusion of O2.
Perfusion-limited and diffusion-limited gas exchange:
- Perfusion-limited exchange
In perfusion-limited exchange, the gas equilibrates early along the length of the pulmonary capillary. The partial pressure of the gas in arterial blood becomes equal to the partial pressure in alveolar air.
Thus, for a perfusion-limited process, diffusion of the gas can be increased only if blood flow increases.
- Diffusion-limited exchange *****
In fibrosis, the diffusion of O2 is restricted because thickening of the alveolar membrane increases diffusion distance.
In emphysema, the diffusion of O2 is decreased because the surface area for diffusion of gases is decreased.
Lung volumes
Tidal volume (TV)
is the volume inspired or expired with each normal breath.
Lung volumes
Inspiratory reserve volume (IRV)
- is the volume that can be inspired over and above the tidal volume.
- is used during exercise.
Lung volumes
Expiratory reserve volume (ERV)
is the volume that can be expired after the expiration of a tidal volume.
Lung volumes
Residual volume (RV)
is the volume that remains in the lungs after a maximal expiration.
Can not be measured by spirometry.
Lung volumes
Dead space
a. Anatomic dead space
- is the volume of the conducting airways.
- is normally approximately 150ml.
Lung volumes
Dead space
b. Physiologic dead space
- is a functional measurement.
- is defined as the volume of the lungs that does not participate in gas exchange.
- is approximately equal to the anatomic dead space in normal lungs.
- may be greater than the anatomic dead space in lung diseases in which there are ventilation/perfusion (V/Q) defects.
VD = dead space VT = tidal volume PaCO2 = partial pressure of carbon dioxide in arteries PECO2 = partial pressure of carbon dioxide in exhaled air
-In words, the equation states that physiologic dead space is tidal volume multiplied by a fraction. The fraction represents the dilution of alveolar Pco2 by dead-space air, which does not participate in gas exchange and does not therefore contribute CO2 to expired air.
VD = dead space VT = tidal volume PaCO2 = partial pressure of carbon dioxide in arteries PECO2 = partial pressure of carbon dioxide in exhaled air
-In words, the equation states that physiologic dead space is tidal volume multiplied by a fraction. The fraction represents the dilution of alveolar Pco2 by dead-space air, which does not participate in gas exchange and does not therefore contribute CO2 to expired air.
Ventilation rate
a. Minute ventilation is expressed as follows
:Minute ventilation=Tidal volume x Breath/min
b. Aveolar ventilation is expressed as follow:
Alveolar ventilation= (Tidal volume –Dead space) x Breath/min
Lung capacities
Inspiratory capacity
-is the sum of tidal volume and inspiratory reserve volume (IRV).
Lung capacities
Functional residual capacity (FRC)
-is the sum expiratory reserve volume (ERV) and residual volume (RV).
Is the volume remaining in the lungs after a tidal volume is expired.
-includes the residual volume, so it cannot be measured by spirometry.
Lung capacities
Vital capacity (VC) or forced vital capacity (FVC)
- is the sum of tidal volume, IRV, and ERV.
- is the volume of air that can be forcibly expired after a maximal inspiration.
Lung capacities
Total lung capacity (TLC)
- is the sum of all four lung volumes.
- is the volume in the lungs after a maximal inspiration.
- includes residual volume, so it cannot be measured by spirometry.
Forced expiratory volume (FEV1)
- is the volume of air that can be expired in the first second of a forced maximal expiration.
- is normally 80% of the forced vital capacity, which is expressed as:
FEV1/FVC=0.8
- In obstructive lung disease, such as asthma, FEV1 is reduced more than FVC so that FEV1/FVC is decreased.
- In restrictive lung disease, such as fibrosis, both FEV1 and FVC are reduced.
Mechanics of Breathing
Muscles of inspiration
- Diaphragm
- is the most important muscle for inspiration.
-When the diaphragm contracts, the abdominal contents are pushed downward, and the ribs are lifted upward and outward, increasing the volume of the thoracic cavity.
- External intercostals and accessory muscles
- are not used for inspiration during normal quiet breathing.
- are used during exercise.
Mechanics of Breathing
Muscles of Expiration
- Expiration is normally passive.
- Because the lung-chest wall system is elastic, it returns to its resting position after inspiration.
- Expiratory muscles are used during exercise or when airway resistance is increased because of disease (e.g., asthma).
- Abdominal muscles
- compress the abdominal cavity, push the diaphragm up, and push air out of the lungs. - Internal intercostal muscles
- pull the ribs downward and inward.
Surface tension of alveoli and surfactant
Surface tension of alveoli
- results from the attractive forces between molecules of liquid lining the alveoli.
- creates a collapsing pressure that is directly proportional to surface tension and inversely proportional to alveolar radius (Laplace’s law), as shown in the following equation:
P=2xT/r
P=collapsing pressure on alveolus (or pressure required to keep alveolus open)
T= surface tension
r= radius of alveolus (cm)
a. Large alveoli have low collapsing pressures and are easy to keep open.
b. Small alveoli have high collapsing pressures and are more difficult to keep open.
- In the absence of surfactant, the small alveoli have a tendency to collapse (atelectasis).
Surface tension of alveoli and surfactant
Surfactant
- lines the alveoli.
- reduces surface tension by disrupting the intermolecular forces between molecules of liquid. This reduction is surface tension prevents small alveoli from collapsing and increases compliance.
- is synthesized by type II alveolar cells and consists primarily of the phospholipid dipalmitoryl phosphatidylcholine (DPPC).
- In the fetus, surfactant synthesis is variable. Surfactant may be present as early as gestational week 24 and is almost always present by gestational week 35.
- Neonatal respiratory distress syndrome can occur in premature infants because of the lack of surfactant. The infant exhibits atelectasis (lung collapse), difficulty reinflating the lungs (as a result of decreased compliance), and hypoxemia because of the V/Q defect.(Glucocorticoid)
Relationships between pressure, airflow, and resistance
Airflow
- is driven by, and is directly proportional to, the pressure difference between the mouth (or nose) and the alveoli.
- is inversely proportional to airway resistance; thus the higher the airway resistance, the lower the airflow. This inverse relationship is:
Q=delta P/R
Q- airflow (ml/min or L/min)
delta P= pressure gradient (cm H2O)
R=airway resistance (cm H2O/L/sec)
Relationships between pressure, airflow, and resistance
Factors that change airway resistance
- The major site of airway resistance is the medium-sized bronchi.
- The smallest airways would seem to offer the highest resistance, but they don’t because of their parallel arrangement.
a. Contraction or relaxation of bronchial smooth muscle-changes airway resistance by altering the radius of the airways.
1. Parasympathetic stimulation, irritants, and the slow-reacting substance of anaphylaxis (asthma) constrict the airways, decrease the radius, and increases the resistance to airflow.
2. Sympathetic stimulation and sympathetic agonists (isoproterenol) dilate the airways via beta receptors, increase the radius, and decrease the resistance to airflow.
b. Lung volume
- alters airway resistance because of the radial traction exerted on the airways by surrounding lung tissue.
c. Viscosity or density of inspired gas
-changes the resistance to airflow
During a deep-sea dive, both air density and resistance to airflow are increased.
Breathing a low-density gas, such as helium, reduces the resistance to airflow.
Breathing cycle
At rest (before inspiration begins)
a. Alveolar pressure equals atmospheric pressure.
B. Intrapleural pressure is negative.
C. Lung volume is the functional residual capacity (FRC: Functional Residual Capacity is the volume of air present in the lungs at the end of passive expiration).
Breathing cycle
During inspiration
a. The inspiratory muscles contract and cause the volume of the thorax to increase.
As lung volume increases, alveolar pressure decreases to less than atmospheric pressure.
The pressure gradient between the atmosphere and the alveoli now causes air to flow into the lungs; airflow will continue until the pressure gradient dissipates.
b. Intrapleural pressure becomes more negative.
Because lung volume increases during inspiration, the elastic recoil strength of the lungs also increases. As a result, intrapleural pressure becomes even more negative than it was rest.
Breathing cycle
C. Lung volume increases by one Tidal volume (TV).
C. Lung volume increases by one Tidal volume (TV).
During expiration
a. Alveolar pressure becomes greater than atmospheric pressure.
b. Intrapleural pressure returns to its resting value during a normal (passive) expiration.
C. Lung volume returns to Functional Residual Capacity (FRC).
Asthma
Asthma is a chronic illness involving the respiratory system in which the airway occasionally constricts, becomes inflamed, and is lined with excessive amounts of mucus, often in response to one or more triggers.
These episodes may be triggered by such things as exposure to an environmental stimulant (or allergen) such as cold air, warm air, moist air, or exertion, or emotional stress.
In children, the most common triggers are viral illnesses such as those that cause the common cold. This airway narrowing causes symptoms such as wheezing, shortness of breath, chest tightness, and coughing. The airway constriction responds to bronchodilators.
- is an obstructive disease in which expiration is impaired.
- is characterized by decreased FVC (forced vital capacity), decreased FEV1, and decreased FEV1/FVC.
- Air that should have been expired is not, leading to air trapping and increased functional residual capacity (FRC).
- FVC : (Sum of Tv, FEv, FIv).This is the total amount of air that you can forcibly blow out after full inspiration, measured in liters.
COPD (Chronic obstructive pulmonary disease )
- is a combination of chorionic bronchitis and emphysema.
- is an obstructive disease with increased lung compliance in which expiration is impaired.
- is characterized by decreased FVC, decreased FEV1, and decreased FEV1/FVC.
- Air that should have been expired is not, leading to air trapping, increased FRC, and a barrel-shaped chest.
A. Pink puffers (primarily emphysema) have mild hypoxemia and, because they maintain alveolar ventilation, normocapnia (normal Pco2).
B. Blue bloaters (primarily bronchitis) have serve hypoxemia with cyanosis and because they do not maintain alveolar ventilation, hypercapnia (increased Pco2). They have right ventricular failure and systemic edema.
- FRC: Functional Residual Capacity is the volume of air present in the lungs at the end of passive expiration).
Fibrosis
- is a restrictive disease with decreased lung compliance in which inspiration is impaired.
- is characterized by a decrease in all lung volume. Because FEV1 is decreased less than FVC, FEV1/FVC is **increased ( or may be normal).
- FVC (forced vital capacity ): This is the total amount of air that you can forcibly blow out after full inspiration, measured in liters.
Forms of gases in solution
Dissolved gas
In alveolar air, there is one form of gas, which is expressed as partial pressure. However, in solutions such as blood, gases are carried in additional forms.
Henry’s law gives the relationship between the partial pressure of a gas and its concentration in solution: for a given partial pressure, the higher the solubility of the gas, the higher the concentration of gas in solution.
Of the gases found in inspired air, nitrogen (N2) is the only one that is carried only in dissolved form, and it is never bound or chemically modified.
Forms of gases in solution
Bound gas
In alveolar air, there is one form of gas, which is expressed as partial pressure. However, in solutions such as blood, gases are carried in additional forms.
O2, CO2 and carbon monoxide (CO) are bound to proteins in blood. O2 and CO2 bind to hemoglobin inside red blood cells and carried in this form.CO2 binds to hemoglobin in red blood cells and to plasma proteins.
Forms of gases in solution
Chemically modified gas
In alveolar air, there is one form of gas, which is expressed as partial pressure. However, in solutions such as blood, gases are carried in additional forms.
The most significant example of a chemically modified gas is the conversion of CO2 to bicarbonate (HCO3-) in red blood cells by action of carbonic anhydrase. In fact, most CO2 is carried in blood as HCO3-, rather than as dissolved CO2 or as bound CO2.
Oxygen Transport
- O2 is carried in blood in two forms: dissolved or bound to hemoglobin
- Hemoglobin, at its normal concentration, increases the O2-carring capacity of blood seventyfold.
Oxygen Transport
Hemoglobin
- Characteristics-globular protein of four subunits
- Each subunit contains a hem moiety, which is iron –containing porphyrin.
- The iron is the ferrous state (Fe2+), which binds O2.
- Each subunit has a polypeptide chain. Two of the subunits have alpha chains and two of the subunits have beta chains; thus, normal adult hemoglobin is called alpha2 beta2.
Oxygen Transport
Hemoglobin
- Fetal hemoglobin, the beta chains are replaced by gama chains;
thus fetal hemoglobin is called alpha2 gama2.
- The O2 affinity of fetal hemoglobin is higher than the O2 affinity of adult hemoglobin because 2,3-diphosphoglycerate (DPG) binds less avidly.
- Because the O2 affinity of fetal hemoglobin is higher than the O2 affinity of adult hemoglobin, O2 movement from mother to fetus is facilitated.
- 2,3-BPG is present in human red blood cells (RBC; erythrocyte) at approximately 5 mmol/L. It binds with greater affinity to deoxygenated hemoglobin (e.g. when the red cell is near respiring tissue) than it does to oxygenated hemoglobin (e.g. in the lungs). thus enhancing the ability of RBCs to release oxygen near tissues that need it most.
Oxygen Transport
Hemoglobin
- O2 capacity
- is the maximum amount of O2 that can be bound to hemoglobin.
- is dependent on the hemoglobin concentration in blood.
- is measured at 100% saturation.
Oxygen Transport
Hemoglobin
- O2 content
- is the total amount of O2 carried in blood, including bound and dissolved O2.
- depends on the hemoglobin concentration.
Oxygen Transport
Hemoglobin-O2 dissociation curve
- Hemoglobin combines rapidly and reversibly with O2 to form oxyhemoglobin.
- The hemoglobin-O2 dissociation curve is a plot of percent saturation of hemoglobin as a function of Po2.
- The sigmoid shape of the curve is the result of a change in the affinity of hemoglobin as each successive O2 molecule binds to a heme site.
- Binding of the first O2 molecule increases the affinity for the second O2 molecule, and so forth.
- The affinity for the fourth O2 molecule is the highest.
This change in affinity facilitates the loading of O2 in the lungs (flat portion of the curve) and the unloading of O2 at the tissues.
In the lungs
- Alveolar gas has a Po2 (Partial pressure of O2) of 100mmHg.
- Pulmonary capillary blood is arterialized by the diffusions of O2 from alveolar gas into blood, so that the Po2 of pulmonary capillary blood also becomes 100 mmHg.
In the peripheral tissues
- O2 diffuses from arterial blood to the cells.
- The gradient for O2 diffusion is maintained because the cells consume O2 for aerobic metabolism, keeping the tissue PO2 low.
CO2 Transport
A. Forms of CO2
- CO2 is produced in the tissues and carried to the lungs in the venous blood in three forms.
1. Dissolved CO2 (small amount), which is free in solution
2. Carbaminohemoglobin (small amount), which is CO2 bound to hemoglobin.
3. HCO3- (from hydration of CO2 in the red blood cells (RBCs), which is the major form (90%)
CO2 Transport
B. Transport of CO2 as HCO3-
- CO2 is generated in the tissues and diffuses freely into the venous plasma and then into the RBCs.
- In the RBCs, CO2 combines with H2O to form H2CO3, a reaction that iscatalyzed by carbonic anhydrase. H2CO3 (carbonic acid) dissociates into H+ and HCO3-.
- HCO3- leaves the RBCs in exchange for CL- (chloride shift) and is transported to the lungs in the plasma. HCO3- is the major form in which CO2 is transported to the lungs.
- H+ is buffered inside the RBCs by deoxyhemoglobin. Because deoxyhemoglobin is a better buffer for H+ than is oxyhemoglobin, it is advantageous that hemoglobin has been deoxygenated by the time blood reaches the venous end of the capillaries.
- In the lungs, all of the above reactions occur in reverse. HCO3 enters the RBCs in exchange for Cl-. HCO3 recombines with H+ to form H2CO3, which decomposes into CO2 and H2O. Thus, CO2, originally generated in the tissues, is expired.
Pulmonary Circulation
A. Pressures and cardiac output in the pulmonary circulation
- Pressures-are much lower in the pulmonary circulation than in the systemic circulation.
- For example, pulmonary arterial pressure is 15 mmHg (compared with aortic pressure of 100 mmHg). - Resistance
- is also much lower in the pulmonary circulation than in the systemic circulation. - Cardiac output of the right ventricle
- is pulmonary blood flow.
- is equal to cardiac output of the left ventricle.
- Although pressures in the pulmonary circulation are low, they are sufficient to pump the cardiac output because resistance of the pulmonary circulation is proportionately low.
Pulmonary Circulation
B. Distribution of pulmonary blood flow
- When a person is supine, blood flow is nearly uniform throughout the lung.
- When a person is standing, blood flow is unevenly distributed because of the effect of gravity. Blood flow is lowest at the apex of the lung (zone 1) and highest at the base of the lung (zone 3).
- Zone 1-blood flow is lowest.
- Alveolar pressure > arterial pressure > venous pressure.
- The high alveolar pressure may compress the capillaries and reduce blood flow in zone 1. This situation can occur if arterial blood pressure is decreased as a result of hemorrhage or if alveolar pressure is increased because of positive pressure ventilation. - Zone 2-blood flow is medium.
- Arterial pressure > alveolar pressure > venous pressure.
- Moving down the lung, arterial pressure progressively increases because of gravitational effects on hydrostatic pressure.
- Arterial pressure is greater than alveolar pressure in zone 2, and blood flow is driven by the difference between arterial pressure and alveolar pressure. - Zone 3 - blood flow is highest.
- Arterial pressure> venous pressure > alveolar pressure.
- Moving down toward the base of the lung, arterial pressure is highest because of gravitional effects, and venous pressure finally increases to the point where it exceeds alveolar pressure.
- In zone 3, blood flow is deriven by the difference between arterial and venous pressures, as in most vascular beds.
Regulation of pulmonary blood flow-hypoxic vasconstriction
- In the lungs, hypoxia causes vasconstriction.
- This response is the opposite of that in other organs, where hypoxia causes vasodilatation.
- Physiologically, this effect is important because local vasoconstriction redirects blood away from poorly ventilated, hypoxic regions of the lung and toward well-ventilated regions.
- Fetal pulmonary vascular resistance is very high because of generalized hypoxic vasoconstriction; as a result, blood flow through the fetal lungs is low. With the first breath, the alveoli of the neonate are oxygenated, pulmonary vascular resistance decreases, and pulmonary blood flow increases and becomes equal to cardiac output (as occurs in the adult).
Control of Breathing
Chemoreceptor for CO2, H+, and O2:
- Central chemoreceptors in the medulla
- Peripheral chemoreceptors in the carotid and aortic bodies
a. Decreases in arterial Po2
b. Increases in arterial Pco2
c. Increases in arterial H+
Other type of receptors for control of breathing
- Lung stretch receptors
- Irritant receptors
- J (juxtacapillary) receptors
- Joint and muscle receptors
Control of Breathing
- Sensory information (Pco2, lung stretch, irritants, tendons, and joints) is coordinated in the brain stem.
- The output of the brain stem controls the respiratory muscles and the breathing cycle.
Control of Breathing
- Sensory information (Pco2, lung stretch, irritants, tendons, and joints) is coordinated in the brain stem.
- The output of the brain stem controls the respiratory muscles and the breathing cycle.
Control of Breathing
A. Central control of breathing (brain stem and cerebral cortex)
- Medullary respiratory center
- is located in the reticular formation.
-Input to the dorsal respiratory group comes from the vagus and glossopharyngeal nerves.
The vagus nerve relays information from peripheral chemoreceptors and mechanoreceptors in the lung. The glossopharyngeal nerve relays information from peripheral chemoreceptors.
-Output from the dorsal respiratory group travels, via the phrenic nerve, to the diaphragm.
Control of Breathing
B. Ventral respiratory group
- is primarily responsible for expiration.
- is not active during normal, quiet breathing, when expiration is passive.
- is activated, for example, during exercise, when expiration becomes an active process.
- Apneustic center
- is located in the lower pons.
- stimulates inspiration, producing a deep and prolonged inspiratory gasp (apneusis). - Pneumotaxic center
- is located in the upper pons.
- inhibits inspiration and, therefore, regulates inspiratory volume and respiratory rate. - Breathing can be under voluntary control; therefore, a person can voluntarily hyperventilate or hypoventilate.
- Hypoventilation (breath-holding) is limited by the resulting increase in Pco2 and decrease Po2. A previous period of hyperventilation extends the period of breath-holding.
Physiology of the GI tract
Requires the following activities:
GI tract is designed to provide the body with nutrition.
Requires the following activities:
- Movement of food through GI tract
- Secretion of digestive juices and digestion of the food
- Absorption of the digestive products, water and electrolytes
- Circulation of blood through the GI organs to carry away the absorbed substances
- Control of these functions by nervous and hormonal systems
Physiology of the GI tract
The alimentary tract
Oral cavity – first breakdown of food
Esophagus – passage of food
Stomach – storage, second breakdown of food
liver, pancreas, gall bladder, small and Large intestine – digestion, absorption
Physiology of the GI tract
Principles of GI motility
GI wall – major and minor muscle layers, valves
Electrical activity
Structures and innervation of the GI tract:
1- Mucus membrane: is composed of specialized
epithelial cells for secretion or absorption
2- Muscularis mucosa: is the wide spread muscle fiber
layer beneath the lamina propria, its contraction causes
a change in the surface area for secretion/absorption.
3- Muscle layer: composed of inner circular and outer longitudinal muscle layers:
Circular muscle: contraction decreases the diameter of the lumen of the GI tract
Longitudinal muscle: contraction causes shortening of a segment of the GI tract
4- Serosa (adventitia): is the external peritoneal covering layer.
Intrinsic (enteric) innervation
of the digestive tract:
Digestive system is supplied by 2 different plexuses (parasympathetic):
1- Submucosal plexus of Meissner
2- Myenteric plexus of Auerbach
They integrate and coordinate the
motility and secretory and endocrine
functions of the GI tract.
Sympathetic fibers are interspersed
between the two mentioned plexus.
Extrinsic innervation of the GI tract:
Sympathetic and Parasympathetic
Efferent fibers: carry information from the brainstem and spinal cord to the GI tract
Afferent fibers: carry sensory information (chemoreceptors, mechanoreceptors) from
the GI tract back to the brainstem and spinal cord.
Sympathetic and Parasympathetic
Efferent fibers: carry information from the brainstem and spinal cord to the GI tract
Afferent fibers: carry sensory information (chemoreceptors, mechanoreceptors) from
the GI tract back to the brainstem and spinal cord.
Extrinsic innervation of the GI tract:
Parasympathetic:
Vagus N. and pelvic splanchnic N.
Excitatotry on GI function.
Preganglionic fibers synapse in the
Myenteric and submucosal plexuses.
Vagus (CNX): sends information to
the esophagus, stomach, pancreas,
intestine down to the upper parts of
the large intestine.
Pelvic splanchnic nerve (S2-4):
Carries information to the lower
parts of the large intestine and
pelvic organs.
Extrinsic innervation of the GI tract:
Sympathetic:
Originate from spinal cord.
coming via abdominal splanchnic
nerves (T5- L2).
Preganglionic cholinergic fibers
synapse in prevertebral ganglia.
Postganglionic adrenergic fibers
leave the prevertebral ganglia
and synapse in the myenteric
and submucosal plexuses.
They inhibit peristalsis and
gastric secretion and cause
pyloric contraction.
They also convey pain (in stomach).
Direct postganglionic adrenergic innervation of blood
vessels and some smooth muscle cells also occurs.
Gastrointestinal Motility:
Contractile tissue of the GI tract is unitary smooth muscle.
Exceptions: pharynx, upper 1/3 of the esophagus, and the external anal sphincter, all
of which are striated muscle.
Contraction of the circular muscle: leads to a decrease in diameter of that segment
of the GI tract.
Contraction of the longitudinal muscle: leads to a decrease in length of that segment
of the GI tract.
Phasic contraction: are found in esophagus, gastric antrum, and small intestine which
contract and relax periodically.
Tonic contraction: are found in lower esophageal sphincter, the orad stomach, and the
ileocecal and internal anal sphincters
Physiology of the GI tract
Slow waves
- are oscillating membrane potentials inherent to the smooth muscle cells of some parts of the GI tract.
- They occur spontaneously
- They originate in the interstitial cells of Cajal, which serve as the pacemaker for GI smooth muscle.
- They are not action potentials, although they determine the pattern of action potentials and, therefore, the pattern of contraction.
Mechanism of slow wave production:
is the cycle of activation and deactivation of the cell membrane.
Depolarization ( Ca2+ inward) during each slow wave brings the membrane potential of smooth muscle cells closer to threshold and, therefore, increases the probability that action potentials will occur.
Action potentials are produced on the top of the background of slow waves, which then initiates contraction of the smooth muscle cells.
The repolarizing phase of slow wave is K+ outward.
Frequency of slow waves:
*Varies along the GI tract, but is constant in each part.
*Is not influenced by neuronal or hormonal input. However, the
frequency of the action potentials that occur on the top of the slow
waves is modified by neural and hormonal influences.
- Lowest in stomach and highest in duodenum.
- 3-12/minute varying by place:
Stomach at 3, duodenum at 12, ileum at 9/minute.
Physiology of the GI tract
Spike potentials
They are the action potentials
Triggered at -40 mV. Resting membrane potential floats between -50 to -60 mV.
The number of spikes triggered is proportional to the rise above threshold and time above threshold. (i.e., bursts of 1-10)
The AP of GI muscle is 10-40 times as long as that in the large nerve fiber. (10-20 ms).
Caused by the calcium-sodium channels
Physiology of the GI tract
Resting Membrane Voltages
Normal is an average (50-60) of -56 mV
Depolarization: Stretching Acetylcholine Parasympathetic stimulation Specific gastrointestinal hormones
Hyperpolarization:
Norepinephrine/epinephrine
Sympathetic stimulation
Physiology of the GI tract
Calcium Ions and muscle contraction:
Acts through calmodulin not troponin C as the calcium regulator to coordinate the myosin/actin filament binding
Physiology of the GI tract
Tonic contraction of GI smooth muscle:
In GI smooth muscle, even sub-threshold slow waves produce a weak contraction. Thus, even without the occurrence of action potential, the smooth muscle is not completely relaxed, but exhibits basal contraction, or tonic contraction.
It is under a baseline contraction that is controlled by
1) nervous (non-slow wave associated spikes)
2) hormonal input
3) to an unknown extent by calcium entry with the variable resting membrane potential
Peristalsis happens relative to this tone.
Hormonal control of GI motility
Cholecystokinin
from mucosa of jejunum in response to fats, increases contractility of gallbladder to release bile and concomittantly decreases stomach contractilty (hold fats still for digestion)
Hormonal control of GI motility
Secretin
from mucosa of duodenum in response to acid, has a mildly inhibitory effect on GI motility to moderate acid load to small intestine
Hormonal control of GI motility
Gastric inhibitory peptide
from mucosa of upper small intestine in response to fats (lesser to carbs) to decrease motor function (peristalsis) when the upper small intestine is already full!
Functional Types of movement in GI tract
Propulsive – peristalsis, “forward flow”
Mixing – movement within the biomass of the digesting contents themselves
Propulsive – peristalsis, “forward flow”
Stimulation is primarily distension (only 2-3 cm is required). Coordinated contraction of circular and longitudinal muscles.
Functional Types of movement in GI tract
Propulsive
Propulsive – peristalsis, “forward flow”
Stimulation is primarily distension (only 2-3 cm is required). Coordinated contraction of circular and longitudinal muscles.
Functional Types of movement in GI tract
Mixing
Mixing – movement within the biomass of the digesting contents themselves
Mixing movements are very regional.
If a sphincter is present then peristalsis creates churning but little absorption is done around sphincters so little other dynamics of movement are important.
Local constrictive contractions occur under submucosal plexus control every few centimeters creating chopping and churning to increase contact between the biomass and the gut wall.
Defects in Meissner’s plexus lead to malabsorption.
Chewing, swallowing, and esophageal peristalsis:
Chewing
*Lubricates food by mixing it with saliva.
*Decreases the size of food particles to facilitate swallowing and to begin the
digestive process.
Chewing, swallowing, and esophageal peristalsis:
Swallowing
*The swallowing reflex is coordinated in the medulla (by CNIX and CNX).
Events involved in swallowing:
1- the nasopharynx closes and breathing is inhibited.
2- laryngeal muscles contract: glottis closes and larynx is elevated.
3- peristalsis begins in the pharynx, upper esophageal sphincter relaxes
(to propel the food towards and into the esophagus).
Chewing, swallowing, and esophageal peristalsis:
Esophagus & esophageal motility:
- 25- 30 cm long, propels food into the stomach
- It is about 40cm from the incisor teeth.
*It has 3 narrowings:
1- upper sphincter (prevents air entering esophagus)
2- Aortic narrowing (crossed by aortic arch)
3- Diaphragmatic narrowing (in the E. hiatus)
*Starts at the level of C6 vertebra (cricoid cartilage)
*It lies on the vertebral column
*accompanied by R&L vagus nerves
*passes through esophageal hiatus of diaphragm
at the level of T10.
(Aorta at T12 and IVC at T8 levels pass through
the diaphragm).
*Ends below the diaphragm
*Distal part of the esophagus may act as
a sphincter preventing gastric acid to enter
into the esophagus.
*Cardia: where esophagus enters the stomach
Innervation:
Sympathetic & parasympathetic (vagus)
Chewing, swallowing, and esophageal peristalsis:
Esophagus & esophageal motility:
Intraesophageal pressure and motility
Intraesophageal pressure:
*Because the esophagus is located in the thorax, intraesophageal pressure
equals thoracic pressure, which is lower than atmospheric pressure.
*A balloon catheter placed in the esophagus can measure intrathoracic pressure.
Esophageal motility:
The following sequence of events occurs when food moves down the esophagus:
1- upper esophageal sphincter relaxes to permit food to enter the esophagus.
2- upper esophageal sphincter then contracts to prevent food reflux into pharynx.
3- a primary peristaltic contraction creates an area of high pressure behind the
food. The peristaltic contraction moves down and gravity accelerates movement.
4- a secondary peristaltic contraction clears the esophagus of any remaining food.
5- relaxation of lower esophageal sphincter mediated by VIP through vagus N.
6- receptive relaxation of the orad region of the stomach to allow the food bolus
into the stomach.
Clinical tips:
Gastric Reflux
may occur if the tone of the lower esophageal sphincter is decreased and gastric contents reflux into the esophagus. This may cause heart burn.
Clinical tips:
Achalasia(cardiospasm):
retrosternal pain, neuromotor disorder of the lower
esophageal sphincter (LES). Decreased cells in the myentric plexus (analogous to
Hirschsprung’s disease), dysphagia for solid and liquid.
Dilated proximal esophagus and aperistalsis, increased LES pressure.
Dorsal view of the esophagus:
Esophagus is the continuation of Pharynx.
13- superior
14- middle
15- inferior constrictor muscles of the pharynx.
1- cervical portion of the esophagus
10- Vagus nerve
Esophagus
***Pathology:
Esophageal atresia
when distal end of the
esophagus is closed.
Esophagus
***Pathology:
Tracheoesophageal fistula
when there is a hole
(connection) between esophagus and the trachea.
Milk from the newborn esophagus finds its way into the
respiratory tract causing severe respiratory problems.
Esophagus
***Pathology:
Malignancy
frequently at transition between epithelia.
Esophagus
***Pathology:
Esophageal Cancers
Low in North America.
High in Iran and China (irritation of the mucosa
e.g.: hot tea, Opium, etc…)
Hiatal hernia:
protrusion of part of the stomach into the mediastinum
through the esophageal hiatus of the diaphragm. Often painful and mixed with
other chest pains including the cardiac ischemia
2 main types: sliding and paraesophageal types.
Sliding hiatus hernia (A): when abdominal part of the esophagus and cardia and even
part of the fundus slide up through the esophageal hiatus. *Regurgitation and heart burn
Paraesophageal hiatus hernia (B): Cardia doesn’t move but part of the fundus and
peritoneum passes through the esophageal hiatus. *Usually no regurgitation
Surgery:
Surgery reinforces the barrier to reflux that the lower esophageal valve normally provides.
In most cases, the operation performed to correct gastroesophageal reflux is a procedure called
“fundoplication.” The upper portion of the stomach (the fundus) is wrapped (plicated)
around the lower portion of the esophagus and anchored securely below the diaphragm.
Radiofrequency Treatment
Using an endoscope supplied by electrodes: the radiofrequency energy causes tiny burns at
G-E junction that heal and form scar tissue. The scar tissue actually tightens the weak valve.
Stomach:
Stomach is the most dilated part of
the alimentary tract between the
esophagus and the lesser intestine.
It has a “J” shape and lies in the
upper left quadrant of the abdomen.
But, Its shape and position varies in
different individuals.
It is an intraperitoneal organ.
It has anterior and posterior surfaces
and right and left borders.
Function:
It is a food reservoir and is involved
in enzymatic digestion.
**Parts of stomach:
Stomach has 4 parts and 2 curvatures: Parts of stomach: Cardia (1) Fundus (3) Body (5) Pyloric part (6) (its wide part, the pyloric antrum leads into the pyloric canal). Pylorus ends as a thickened structure, called: Pyloric sphincter (7).
8- Lesser curvature of the stomach
9- Angular notch
10- Greater curvature of the stomach
4- Cardiac notch.
Orad region: includes the fundus and the
proximal body, receives the ingested food.
Caudad region: includes the antrum and
distal body, mixes the food and propels
it into the duodenum.
Muscle layer of the stomach:
Muscle layer, tunica muscularis, is the motor of
the stomach and consists of bundles of smooth
muscle fibers.
Like that of the intestine, it has inner circular
(AB1) and an outer longitudinal (A2, 3) fibers.
*In addition, stomach has a 3rd layer, oblique (4)
fibers (in pyloric and lesser curvature it is missing).
C, D and E are 3 main types of stomach
configuration.
Motor functions of the Stomach
Three main functions
Storage (volume)
Chyme (mechanical digestion in the presence of gastric acid)
Controlled rate of passage and quality of digestion of food to duodenum
***Gastric mucosa (A1):
Has numerous gastric folds and pits (2). Gastric glands
(3) open into the pits. The mucosa and pits are covered
by columnar epithelium (4). Epithelial cells produce mucus
which protects the epithelium against auto-digestion.
**Glands in the body and the fundus
are elongated and contain 3 types of cells: Mucoid cells (6), Chief cells (7) in body/fundus, produce pepsinogen and Parietal cells (8) in body/fundus, produce HCl and the intrinsic factor for VitB12 absorption in the ileum.
*Gastrin
is produced by G cells mainly in pyloric antrum
stimulate acid secretion and growth of parietal cells.
**Zollinger-Ellison syndrome: gastrin secretion by
non-beta cells of the pancreas (multiple ulcers in stomach).
*Secretin by duodenum inhibits HCl secretion
- pepsinogen
is a protein-splitting enzyme activated
by HCl of the stomach into pepsin to break the food.
*Endocrine cells
of mucous membrane (1.2% of all)
mainly in antrum, produce: histamine, somatostatin,
gastrin, serotonin.
Secretion of gastric juice: 2 phases:
Nervous secretion: by vagus nerve, activated by
taste, smell and sight (even if stomach is empty).
Gastric (digestive) phase secretion:
stimulated by food ingestion.
HCl required for conversion of pepsinogen into pepsin
HCl required for conversion of pepsinogen into pepsin
Clinical point
deficiency of HCl leads to deficiency of pepsin which impacts the protein digestion and absorption
IF = intrinsic factor
carries vitamin B12 to ileum for absorption
Clinical point
deficiency of HCl leads to deficiency of pepsin which impacts the protein digestion and absorption
IF = intrinsic factor
carries vitamin B12 to ileum for absorption
Clinical point
deficiency or destruction of parietal cell leads to anemia
Clinical point
deficiency or destruction of parietal cell leads to anemia
Goblet cell
secretes mucus for formation of chyme
Goblet cell
secretes mucus for formation of chyme
Chyme is mixing of food content with enzymes
Chyme is mixing of food content with enzymes
Pepsinogen is inactive form
Pepsinogen is inactive form
G cell secretes gastrin
gastrin has direct effect on parietal cell which stimulates the HCl secretion
G cell secretes gastrin
gastrin has direct effect on parietal cell which stimulates the HCl secretion
Clinical point
over secretion of HCl inhibits gastric secretion
Clinical point
over secretion of HCl inhibits gastric secretion
Paracrine
when first hormone controls second hormone secretion
example: histamine increases HCl secretion
example: serotonin controls HCl secretion
example: somatostallin inhibits other gastric hormone secretion
Paracrine
when first hormone controls second hormone secretion
example: histamine increases HCl secretion
example: serotonin controls HCl secretion
example: somatostallin inhibits other gastric hormone secretion
Clinical point
over secretion of histamine may lead to gastritis or gastric ulcer
receptor: H2(histamine receptor)
treatment: H2 blocker to reduce histamine effect to control the HCl secretion
Clinical point
over secretion of histamine may lead to gastritis or gastric ulcer
receptor: H2(histamine receptor)
treatment: H2 blocker to reduce histamine effect to control the HCl secretion
I cell and CCK
CCK functions:
contraction of gall bladder for bile secretion into common bile duct
relaxes sphincter of oddi AKA ampulla of Vater(located in second part of duodenum) which releases bile and pancreatic enzymes
increases pancreatic enzymes and bicarbonate secretion into second part of duodenum
(very important)prevents/inhibits early gastric emptying when the chyme(food) has fat in duodenum
fatty foods need longer time to absorb and digest
I cell and CCK
CCK functions:
contraction of gall bladder for bile secretion into common bile duct
relaxes sphincter of oddi AKA ampulla of Vater(located in second part of duodenum) which releases bile and pancreatic enzymes
increases pancreatic enzymes and bicarbonate secretion into second part of duodenum
(very important)prevents/inhibits early gastric emptying when the chyme(food) has fat in duodenum
fatty foods need longer time to absorb and digest
S cell secretes secretin
secretin decreases gastric acid secretion and increases bicarbonate which exist in bile and also increases pancreatic bicarbonate secretion
pancreatic bicarbonate which is released into duodenum is to neutralize the acidic media
S cell secretes secretin
secretin decreases gastric acid secretion and increases bicarbonate which exist in bile and also increases pancreatic bicarbonate secretion
pancreatic bicarbonate which is released into duodenum is to neutralize the acidic media
GIP(below #3 in picture)
sensitive to oral glucose
GIP secretion stimulates beta cell in pancreas for secretion of insulin
decreases gastric acid secretion
GIP(below #3 in picture)
sensitive to oral glucose
GIP secretion stimulates beta cell in pancreas for secretion of insulin
decreases gastric acid secretion
Clinical Point
Zollinger-Ellison syndrome is a tumor in pancreas(non beta cell tumor of pancreas)
secretes a substance similar to gastrin which increases the gastrin level
gastrin increases HCl
tumor of pancreas and gastritis in stomach
Clinical Point
Zollinger-Ellison syndrome is a tumor in pancreas(non beta cell tumor of pancreas)
secretes a substance similar to gastrin which increases the gastrin level
gastrin increases HCl
tumor of pancreas and gastritis in stomach
VIP vaso intestinal peptide secreted by neurons function is to relax smooth muscle of GI and increases intestinal, pancreatic, gastric secretions increases gastric hormones
VIP vaso intestinal peptide secreted by neurons function is to relax smooth muscle of GI and increases intestinal, pancreatic, gastric secretions increases gastric hormones
GRP gastrin releasing peptide act as neurohormone secreted by neurons function is to increase gastrin hormone secretion
GRP gastrin releasing peptide act as neurohormone secreted by neurons function is to increase gastrin hormone secretion
Enkephalin
act as neurohormone
from neurons
function to contract smooth muscle and decreases intestinal secretion(hormones and enzymes)
Enkephalin
act as neurohormone
from neurons
function to contract smooth muscle and decreases intestinal secretion(hormones and enzymes)
Neuropeptide Y
act as neurohormone
relaxes smooth muscle
decreases intestinal secretion
Neuropeptide Y
act as neurohormone
relaxes smooth muscle
decreases intestinal secretion
Substance P
acts as neurohormone
co-secreted with ACH(acetylcholine)
contraction of smooth muscle and increases salivary secretion
Substance P
acts as neurohormone
co-secreted with ACH(acetylcholine)
contraction of smooth muscle and increases salivary secretion
Gastric glands contain several types of cells that secrete different products:
- Goblet cells, which secrete mucus
- Parietal cells, which secrete hydrochloric acid (HCl)
- Chief (or zymogenic) cells, which secrete pepsinogen, an inactive form of the protein-digesting enzyme pepsin
- Enterochromaffin-like (ECL) cells, found in the stomach and intestine, which secrete histamine and 5-hydrooxytryptamine (serotonin) as paracrine regulators of the GI tract
- G cells, which secrete the hormone gastrin into the blood
- D cells, which secrete the hormone somatostatinIn addition’ intrinsic factor.The exocrine secretions of the gastric cells, together with a large amount of water (2 to 4 L/day), form a highly acidic solution known as gastric juice.
Gastric motility
- receptive relaxation:
*is a vagovagal reflex that is initiated by distention of the stomach and is
abolished by vagotomy
- the orad region of the stomach relaxes to accommodate the ingested meal
- CCK mediates receptive relaxation
Gastric motility
- mixing and digestion:
*the caudad region of the stomach contracts to break and mix the food with gastric
secretions and begins the process of digestion
A- slow waves in caudad stomach (3-5/min) depolarize the smooth muscle cells
B- Action potential and contraction follows if threshold is reached during slow waves.
C- Retropulsion: A wave of contraction closes the distal antrum, thus, as the caudad
stomach contracts, food is propelled back into the stomach to be mixed.
D- Vagal stimulation (Parasym.) increases the gastric contraction and sympathetic
decreases it.
Migrating myoelectric complex: are contractions that occur at 90-minute intervals
to clear the stomach of residual food (even during fasting). Motilin mediates these
Contractions.
Vagovagal reflex
afferent and efferent fibers are from vagus nerve
afferent to CNS
Efferent from CNS to GI tract
Vagovagal reflex
afferent and efferent fibers are from vagus nerve
afferent to CNS
Efferent from CNS to GI tract
Clinical point
in severe cases of gastritis where medication does not work then surgery
Vagotomy is surgery to cut to remove a few branches of vagus nerve that innervate the fundus of stomach
don’t cut the whole vagus nerve but cut the branches to parietal cells to reduce HCl secretion
Clinical point
in severe cases of gastritis where medication does not work then surgery
Vagotomy is surgery to cut to remove a few branches of vagus nerve that innervate the fundus of stomach
don’t cut the whole vagus nerve but cut the branches to parietal cells to reduce HCl secretion
Peristalsis is under control of Vagus nerve(parasympathetic)
Peristalsis is under control of Vagus nerve(parasympathetic)
Migrating myoelectric complex
goal is the clear residual food from stomach
Migrating myoelectric complex
goal is the clear residual food from stomach
CCK is extremely important
prevents the gastric emptying when chyme contains fat or acidic
CCK is extremely important
prevents the gastric emptying when chyme contains fat or acidic
Gastric emptying:
The caudad region of the stomach contracts to propel food into the duodenum
The rate of gastric emptying is fastest when the stomach contents are isotonic.
Fat inhibits gastric emptying (increases gastric emptying time) by release of CCK.
H+ in the duodenum also inhibits gastric emptying via direct neural reflexes
(H+ receptors in the duodenum relay information to the gastric smooth muscle
through interneurons in the GI plexus).
*The peristaltic waves create a gradient of food in the stomach selecting the most
digested chyme to the antrum. The more intense waves (movement as mixing) are
50-70 cm H2O (6X mixing constrictor waves) which can force chyme through the
pylorus in waves or jets. This is called the “peristaltic pump” as chyme is sent in
bursts into the duodenum.
**Innervation of the stomach:
Parasympathetic:
are the ant and post vagus trunks, giving the anterior and posterior gastric (Latarget) nerves. Motor to longitudinal muscles Secretomotor to the glands Sensory for gastric reflexes. Increases the blood flow in GI.
*Vagotomy is used for treating
the gastric ulcers not responding
to drug therapy.
**Innervation of the stomach:
Sympathetic:
Mostly coming from splanchnic nerves (also from upper lumbar) which synapse in the Celiac ganglion. Postganglionic fibers innervate the stomach.
They inhibit peristalsis and
gastric secretion and cause
pyloric contraction. They also convey pain.
Stimulation of Alimentary tract glands
Autonomic nervous system (ANS):
Parasympathetic: +ve effect to drive digestion.
Cranial nerves- to salivary glands
Vagus nerve- to upper GI tract, pancreas etc.
Pelvic splanchnic nerve- to distal large intestine.
Secretion in rest of small and large intestine:
is mainly driven by segmental neural and
hormonal stimuli
Sympathetic: mixed effect on digestion
Stimulation to increase gland secretion is offset
by arteriole constriction.
Regulatory substances in the Gastrointestinal (GI) tract:
GI hormones
These hormones are released from endocrine cells in the GI mucosa into the portal
circulation, enter the general circulation, and have physiologic action on target cells.
-Four substances meet the requirements to be considered “official” GI hormones.
Others are considered “candidate” hormones.
Official hormones: gastrin, cholecystokinin (CCK), secretin, gastrin inhibitory peptide
Regulatory substances in the Gastrointestinal (GI) tract:
GI hormones
Gastrin
contains 17 amino acid (little gastrin)
Little gastrin is the form secreted in response to a meal.
Action of gastrin:
1- increased H+ secretion by the gastric parietal cells.
2- stimulates growth of gastric mucosa by stimulating the synthesis of RNA and new
protein. Patients with gastrin-secreting tumors have hypertrophy and hyperplasia
of the gastric mucosa.
Stimuli for secretion of gastrin
Gastrin is secreted from the G cells of the gastric antrum in response to a meal.
Gastrin is secreted in response to the following:
1- small peptides and amino acids in the lumen of the stomach
the most potent stimuli for gastrin secretion are phenylalanin and tryptophan.
2- Distention of the stomach
3- vagal stimulation, mediated by gastrin-releasing peptide (GRP)
Inhibition of gastrin secretion
H+ in the lumen of the stomach inhibits gastrin release.
This negative feedback control ensures that gastrin secretion is inhibited if the
stomach contents are sufficiently acidified.
Zollinger- Ellison syndrome (gastrinoma)
Occurs when gastrin is secreted by non-β- cell tumors of the pancreas.
Regulatory substances in the Gastrointestinal (GI) tract:
GI hormones
CCK
Contains 33 amino acids.
Is homologous to gastrin.
Actions of CCK:
1- stimulates contraction of gallbladder and simultaneously causes relaxation
of the sphincter of Oddi for secretion of bile.
2- stimulates pancreatic enzyme secretion.
3- potentiates secretin-induced stimulation of pancreatic HCO3- secretion.
4- stimulates growth of the exocrine pancreas.
5- Inhibits gastric emptying. Thus, meals containing fat stimulate the secretion
of CCK, which slows gastric emptying to allow more time for intestinal
digestion and absorption.
Stimuli for the release of CCK:
CCK is released from the I cells of the duodenal and jejunal mucosa by:
a- small peptides and amino acids
b- fatty acids and monoglycerides.
Triglycerides do not stimulate the release of CCK because they cannot cross
intestinal cell membranes.
Regulatory substances in the Gastrointestinal (GI) tract:
GI hormones
Secretin
-Contains 27 amino acid
-Is homologous to glucagon, fourteen of the twenty-seven amino acids in secretin
are the same as those in glucagon.
All of the amino acids are required for biologic activity.
Actions of secretin:
Are coordinated to reduce the amount of H+ in the lumen of the small intestine.
1- stimulates pancreatic HCO3- secretion and increases growth of exocrine
pancreas. Pancreatic HCO3- neutralizes H+ in the lumen of the small intestine.
2- stimulates HCO3- and H2O secretion by the liver, and increases bile production.
3- inhibits H+ secretion by gastric parietal cells.
Stimuli for the release of secretin:
Secretin is released by the S cells of the duodenum in response to:
a- H+ in the lumen of the duodenum
b- Fatty acids in the lumen of the duodenum
Regulatory substances in the Gastrointestinal (GI) tract:
GI hormones
Gastric Inhibitory Peptide (GIP):
Contains 42 amino acids
Is homologous to secretin and glucagon
Actions of GIP:
1- stimulates insulin release. In the presence of an oral glucose load, GIP causes
the release of insulin from the pancreas.
Thus, oral glucose is more effective than intravenous glucose in causing insulin
release and, therefore, glucose utilization.
2- inhibits H+ secretion by gastric parietal cells
Stimuli for the release of GIP
GIP is released by duodenum and jejunum.
GIP is the only GI hormone that is released in response to fat, protein, and
carbohydrate.
GIP secretion is stimulated by fatty acids, amino acids, and orally administered glucose
Paracrines
Are released from endocrine cells in the GI mucosa.
Diffuse over short distances to act on target cells located in the GI tract.
The GI paracrines are somatostatin and histamine.
Somatostatin:
Is secreted by cells throughout the GI tract in response to H+ in the lumen.
Its secretion is inhibited by vagal stimulation.
Inhibits the release of all GI hormones.
Inhibits gastric H+ secretion.
Histamine:
Is secreted by mast cells of the gastric mucosa.
Increases gastric H+ secretion directly and by potentiating
vagal stimulation and effect of gastrin
Salivary glands: Parotid gland, Submandibular gland, and Sublingual gland
Produce saliva, and release it to the oral cavity through their ducts, e.g. the parotid
(Stensen’s) duct.
They receive parasympathetic innervation from superior and inferior salivatory nuclei,
through CN VII and CN IX.
Mumps: Inflammation of the parotid gland caused by Mumps virus (myxovirus).
Parotid gland
big gland under skin
covering facial nerve
Parotid gland
big gland under skin
covering facial nerve
Facial nerve temporal branch zygomatic buccal branch mandibular superior cervical
Facial nerve temporal branch zygomatic buccal branch mandibular superior cervical
If something happens to parotid gland then the facial nerve will be impacted
mumps is viral infection of parotid gland
50-60% of children impacted are infertile because it impacts sex hormones FSH
If something happens to parotid gland then the facial nerve will be impacted
mumps is viral infection of parotid gland
50-60% of children impacted are infertile because it impacts sex hormones FSH
Submandibular and sublingual are exocrine glands
secrete contents into oral cavity
Submandibular and sublingual are exocrine glands
secrete contents into oral cavity
Salivary glands
Innervation is by Vagus(CN 10) and glossalpharangeal(CN 9)
Innervation is by Vagus(CN 10) and glossalpharangeal(CN 9)
Composition of saliva
important enzymes
lingual lipase – for lipids
amylase – for starch
Composition of saliva
important enzymes
lingual lipase – for lipids
amylase – for starch
Gastrointestinal secretion
Salivary secretion
1- functions of saliva
a- initial starch digestion by α-amylase (ptyalin) and initial triglyceride digestion
by lingual lipase.
b- lubrication of digested food by mucus
c- protection of the mouth and esophagus by dilution and buffering of ingested foods
Gastrointestinal secretion
Composition of saliva
A- saliva is characterized by:
1- high volume (relative to the small size of the salivary glands)
2- high K+ and HCO3- concentration
3- low Na+ and Cl- concentration
4- hypotonicity
5- presence of a-amylase, lingual lipase, and kallikrein
B- composition of saliva
It varies with the salivary flow rate:
1- at the lowest flow rate, saliva has the lowest osmolarity and lowest Na+, Cl-,
and HCO3- concentrations, but has highest K+ concentration.
2- at the highest flow rates (up to 4 ml/min), the composition of saliva is closest
to that of plasma.
Gastrointestinal secretion
formation of saliva
Saliva is formed by three major glands- the parotid, submaxillary, and sublingual glands.
The structure of each gland is similar to a bunch of grapes.
The acinus (the blind end of each duct) is lined with acinar cells and secretes an initial saliva.
A branching duct system lined with columnar epithelial cells modifies the initial saliva.
Contraction of myoepithelial cells lining of acinus and the ducts, ejects the saliva into the mouth.
The acinus
Produces an initial saliva with a composition similar to plasma
This initial saliva is isotonic; has the same Na+, K+, Cl-, HCO3- plasma concentrations
Gastrointestinal secretion
Regulation of saliva production
Saliva production is controlled by the parasympathetic and sympathetic nervous
systems (not by GI hormones).
Saliva production is unique in that it is increased by both parasympathetic and
sympathetic activity.
A- parasympathetic stimulation (cranial nerves VII and IX):
Increases saliva production by increasing the transport processes in the acinar
and ductal cells by causing vasodilation.
Cholinergic receptors on acinar and ductal cells are muscarinic.
The second messenger is inositol 1,4,5-triphosphate (IP3) and increased
intracellular [Ca++].
*Anticholinergic drugs (e.g. atropin) inhibit the production of saliva and cause dry mouth.
B- Sympathetic stimulation
*increases the production of saliva and the growth of salivary glands, although the
effects are smaller than those of parasympathetic stimulation.
*Receptors on acinar and ductal cells are B2-adrenergic
*The second messenger is cyclic adenosine monophosphate (cAMP)
C- Saliva production Is increased (parasympathetic) by food in mouth, smell, conditioned reflexes/nausea. Is decreased (inhibition of parasympathetic) by sleep, dehydration, fear, anticholinergics.
Saliva secretion
both sympathetic and parasympathetic increase saliva secretion by different mechanisms
Parasympathetic
increases transporting of saliva under control of Cholinergic receptors(muscarinic)
when a person takes anti cholinergic drugs(antropin) the parasympathetic system is impacted and saliva is reduced
Sympathetic
Saliva secretion
both sympathetic and parasympathetic increase saliva secretion by different mechanisms
Parasympathetic
increases transporting of saliva under control of Cholinergic receptors(muscarinic)
when a person takes anti cholinergic drugs(antropin) the parasympathetic system is impacted and saliva is reduced
Sympathetic
Gastric secretion
gastric cell types and their secretions
gastric cell types and their secretions
Parietal cells: located in the body and fundus, secrete HCl (hydrochloric acid) and intrinsic factor.
Chief cells: located in the body and fundus, secrete pepsinogen.
G cells: located in the antrum, secrete gastrin.
Mucus cells: produce mucus and
some pepsinogen.
Oxyntic glands
Parietal cells secrete acid containing 160 millimoles HCl per liter (isotonic) with a pH of 0.8
This pH represents 3 x 106 fold
H+ ions compared to arterial blood and takes about 1500 calories per liter of secretion to produce!
Gastric secretion
Mechanism of gastric H+ secretion
Parietal cells secrete HCl into the lumen of the stomach and concurrently, absorb
HCO3- into the bloodstream as follows:
a. in the parietal cells, CO2 and H2O are converted to H+ and HCO3-, catalyzed
by carbonic anhydrase.
b. H+ is secreted into the lumen of the stomach by the H+/K+ pump (H+/K+-ATPase).
Cl- is secreted along with H+; thus, the secretion product of the parietal cells is HCl.
The drug omeprazole inhibits the H+/K+-ATPase and blocks H+ secretion.
c. the HCO3- produced in the cells is absorbed into the bloodstream in exchange for
Cl- (Cl / HCO3- exchange). As HCO3- is added to the venous blood, the pH of the
blood increases (alkaline tide). Eventually, this HCO3- will be secreted in pancreatic
secretions to neutralize H+ in the small intestine.
If vomiting occurs, gastric H+ never arrives in the small intestine, there is no stimulus
for pancreatic HCO3- secretion, and the arterial blood becomes alkaline
(metabolic alkalosis).
Steps for HCl formation
in slide above for gastric secretion
Parietal cell in fundus of stomach after cell respiration CO2 combines with H2O together form carbonic acid. The carbonic acid releases bicarbonate and hydrogen ions. Hydrogen ions then are secreted into lumen of stomach by potassium antiport(potassium back into parietal cell). Cl-(chloride) secretion into lumen then the secreted hydrogen ion combines with secreted chloride to form HCl in the lumen of stomach.
Clinical point
when acid level is high then gastritis
medication Omeprazole is proton pump inhibitor which blocks H+/K+ interchange
sometimes Omeprazole does not work
second option: H2 receptor blocker
medication: cimetidine to decrease histamine secretion/effect
third option: anticholernergic drugs
receptor for Ach needs to be blocked by medication Atropine
Steps for HCl formation
in slide above for gastric secretion
Parietal cell in fundus of stomach after cell respiration CO2 combines with H2O together form carbonic acid. The carbonic acid releases bicarbonate and hydrogen ions. Hydrogen ions then are secreted into lumen of stomach by potassium antiport(potassium back into parietal cell). Cl-(chloride) secretion into lumen then the secreted hydrogen ion combines with secreted chloride to form HCl in the lumen of stomach.
Clinical point
when acid level is high then gastritis
medication Omeprazole is proton pump inhibitor which blocks H+/K+ interchange
sometimes Omeprazole does not work
second option: H2 receptor blocker
medication: cimetidine to decrease histamine secretion/effect
third option: anticholernergic drugs
receptor for Ach needs to be blocked by medication Atropine
Intrinsic Factor (IF)
- Produced by Parietal cells
- Binds to vitamin B12 in the stomach
- Absorption of vitamin B12- IF in the ileum
- Vit B12 used in bone marrow for RBC maturation
*IF is a co-secretion product with HCl, so destruction of parietal cells (e.g., gastritis) leads to achlorhydria (the production of gastric acid in the stomach is absent or low) and pernicious anemia
Vitamin D is carried by IF into ileum
Vitamin D is carried by IF into ileum
Stimulation of gastric H+ secretion
A- Vagal stimulation:
Increases H+ secretion by direct pathway and an indirect pathway.
Direct pathway: the vagus N. innervates parietal cells and stimulates H+ secretion.
The neurotransmitter is Ach, the receptor on parietal cells is muscarinic.
2nd messenger is IP3, and increased intracellular Ca++.
Indirect pathway: Vagus nerve innervates the G cells and stimulates gastrin secretion.
Neurotransmitter at these synapses is GRP (not Ach).
Gastrin stimulates H+ secretion by an endocrine action.
Atropine: a cholinergic muscarinic antagonist, inhibits H+ secretion by blocking the
direct pathway which uses Ach as a neurotransmitter, however, it can not
block the indirect pathway since it uses GRP and not Ach. Therefore, atropine
can not block H+ secretion completely.
Vagotomy: eliminates both direct and indirect pathways.
Stimulation of gastric H+ secretion
B- Histamine:
- Is released from mast cells in the gastric mucosa and diffuses to nearby parietal cells.
- Stimulates H+ secretion by activating H2 receptors on the parietal cell membrane.
- The 2nd messenger for histamine is cAMP.
- H2 receptor-blocking drugs, such as Cimetidine, inhibits H+ secretion.
Stimulation of gastric H+ secretion
C- Gastrin:
*Is increased in response to eating a meal (small peptides, distention of the stomach,
vagal stimulation).
*Stimulate H+ secretion by interacting with an unidentified receptor on parietal cells.
*The 2nd messenger for gastrin on the parietal cells has not been identified, but it should
be different from those for Ach and histamine, because their actions are additive.
Atropine: a cholinergic muscarinic antagonist, inhibits H+ secretion by blocking the
direct pathway which uses Ach as a neurotransmitter, however, it can not
block the indirect pathway since it uses GRP and not Ach. Therefore, atropine
can not block H+ secretion completely.
Atropine: a cholinergic muscarinic antagonist, inhibits H+ secretion by blocking the
direct pathway which uses Ach as a neurotransmitter, however, it can not
block the indirect pathway since it uses GRP and not Ach. Therefore, atropine
can not block H+ secretion completely.
Vagotomy: eliminates both direct and indirect pathways.
Vagotomy: eliminates both direct and indirect pathways.
Vagus nerve is main nerve for parasympathetic
increases everything
peristalsis, gastric hormones gastric enzymes
Vagus nerve is main nerve for parasympathetic
increases everything
peristalsis, gastric hormones gastric enzymes
Vagus nerve directly and indirectly increases acid secretion(increases HCl secretion)
Directly by innervating the parietal cells which secrete HCl
indirectly by innervating g cells which increase acid secretion
g cells secrete gastrin which then increases HCl secretion
Vagus nerve directly and indirectly increases acid secretion(increases HCl secretion)
Directly by innervating the parietal cells which secrete HCl
indirectly by innervating g cells which increase acid secretion
g cells secrete gastrin which then increases HCl secretion
Zollinger Ellison syndrome:
Increased H+ secretion due to gastrin-secreting non β-cell tumor of the pancreas
H+ secretion continues unabated because the gastrin secreted by pancreatic
tumor cells is not subject to negative feedback inhibition.
Drugs that block H+ secretion
A- atropine: blocks H+ secretion by inhibiting cholinergic muscarinic receptors
on parietal cells, thereby inhibiting Ach stimulation of H+ secretion.
B- Cimetidine: blocks H2 receptors and thereby inhibits histamine stimulation
of H+ secretion. Particularly effective, since it not only blocks the histamine
stimulation of H+ secretion, but also blocks histamine’s potentiation of Ach effects.
C- Omeprazole: directly inhibits H+/K+ -ATPase and H+ secretion.
phases of gastric secretion
Cephalic phase – starts in the head (sight, smell, thought, taste, appetite). Neurogenic signals from cerebrum, appetite centers (amygdala, hypothalamus) travel via parasympathetic (dorsal motor nuclei) vagi to ENS. This causes about 20% of the acid secretion associated with a meal
Gastric Phase – presence (chemical)/distention in stomach, causes vagovagal and enteric reflexes and activate the gastrin mechanism. This causes about 65% of the acid secretion associated with a meal
Intestinal Phase – presence (chemical)/distension in duodenum causes stomach to enhance gastric fluid secretion (another type of enterogastric reflex) as well as the duodenum secreting some gastrin.
phases of gastric secretion
Cephalic phase
starts in the head (sight, smell, thought, taste, appetite). Neurogenic signals from cerebrum, appetite centers (amygdala, hypothalamus) travel via parasympathetic (dorsal motor nuclei) vagi to ENS. This causes about 20% of the acid secretion associated with a meal
phases of gastric secretion
Gastric Phase
presence (chemical)/distention in stomach, causes vagovagal and enteric reflexes and activate the gastrin mechanism. This causes about 65% of the acid secretion associated with a meal
phases of gastric secretion
Intestinal Phase
presence (chemical)/distension in duodenum causes stomach to enhance gastric fluid secretion (another type of enterogastric reflex) as well as the duodenum secreting some gastrin.
Inhibition of Gastric H+ secretion
Negative feedback mechanisms inhibit the secretion of H+ by the parietal cells.
A- Low pH (<3.0) in the stomach
Inhibits gastrin secretion and thereby inhibits H+ secretion.
After ingestion of a meal, H+ secretion is stimulated. After digestion and stomach
being emptied, further H+ secretion decreases the pH of the stomach.
This low pH is a negative feedback mechanism inhibiting gastrin secretion.
B- Chyme in the duodenum
inhibits H+ secretion both directly and via hormonal mediators.
The hormonal mediators are GIP (released by fatty acids in the duodenum) and
secretin (released by H+ in the duodenum)
Pathophysiology of gastric H+ secretion
Gastric Ulcers
If the normal protective barrier of the stomach is damaged, the presence of H+ and
pepsin may injure the gastric mucosa.
A major causative factor in the development of gastric ulcers is Helicobacter pylori
infection. This bacteria has high urease activity and converts urea to NH4+,
which damages the gastric mucosa.
H+ secretion is decreased
Gastrin levels are increased (by negative feedback) in patients with gastric ulcer
diseases because of lower than normal H+ secretion.
Pathophysiology of gastric H+ secretion
Duodenal ulcers
More common than gastric ulcers
H+ secretion is higher than normal (plus pepsin are responsible for mucosal damage.
Gastrin levels in response to a meal are higher than normal
Parietal cell mass is increased because of the trophic effect of gastrin.
Gastritis Causes
Gastritis is an inflammation, irritation, or erosion of the lining of the stomach. It can occur suddenly (acute) or gradually (chronic).
Causes
Gastritis can be caused by
irritation due to excessive alcohol use,
chronic vomiting,
stress,
medications such as aspirin or other anti-inflammatory drugs.
It may also be caused by any of the following:
Helicobacter pylori (H. pylori): A bacteria that lives in the mucous lining of the stomach. Without treatment the infection can lead to ulcers, and in some people, stomach cancer.
Pernicious anemia: A form of anemia that occurs when the stomach lacks a naturally occurring substance needed to properly absorb and digest vitamin B12.
Bile reflux
Infections caused by bacteria and viruses
If gastritis is left untreated, it can lead to a severe loss in blood, or in some cases increase the risk of developing stomach cancer.
Symptoms of Gastritis
Nausea or recurrent upset stomach Abdominal bloating Abdominal pain Vomiting Indigestion Burning feeling in the stomach between meals or at night Hiccups Loss of appetite Vomiting blood or coffee ground-like material Black, tarry stools
Gastritis Treatment
Antacids, Antacids neutralize stomach acid and can provide fast pain relief. Maalox.
Acid blockers. When antacids don’t provide enough relief, recommend a medication, such as Cimetidine, reduce the amount of acid.
Medications to shut down acid ‘pumps.’ Medications called proton pump inhibitors reduce acid by blocking the action of tiny pumps within the acid-secreting cells of your stomach. This class of medications includes Omeprazole.
Medications to treat H. pylori combination of two antibiotics and a proton pump inhibitor.
Hypertrophic gastritis (Menetrier’s disease):
giant rugal folds simulating cancer.
Mucosa is atrophic actually, associated protein loss.
Gastric ulcers
acid, No ulcer. Gastric ulcers are due to defective mucosal barrier
(decreased prostaglandin E, bile reflux…), including the same causes of gastritis.
Most common on the lesser curvature, has a pain which is increased by eating;
*Vagotomy is used for treating the gastric ulcers not responding to drug. Perforation of
the gastric ulcers is uncommon but, if a posterior gastric ulcer for example perforates
the stomach wall, it can involve the pancreas resulting in referred pain to the back.
Erosion of the splenic artery results in hemorrhage into the peritoneal cavity.
Ulcer treatment
A peptic ulcer with an H. pylori infection, the standard treatment uses different combinations of the following medications for 5 - 14 days:
Two different antibiotics to kill H. pylori, such as amoxicillin, tetracycline,
Proton pump inhibitors such as omeprazole (Prilosec).
An ulcer without an H. pylori infection, or one that is caused by taking aspirin or NSAIDs,
-a proton pump inhibitor, such as omeprazole for 8 weeks.
**Surgical treatment of gastric ulcers:
Hemigastrectomy: Billroth I (A) and II (B), vagotomy and antrectomy
**Surgical treatment of gastric ulcers:
Hemigastrectomy: Billroth I (A) and II (B), vagotomy and antrectomy
Surgical treatment of the duodenal ulcers:
Vagotomy and pyloroplasty (C)
Vagotomy and gastrojejunostomy (D)
Parietal cell vagotomy (E)
Surgical treatment of the duodenal ulcers:
Vagotomy and pyloroplasty (C)
Vagotomy and gastrojejunostomy (D)
Parietal cell vagotomy (E)
Crohn’s disease
Cause
Crohn’s disease is a form of inflammatory bowel disease (IBD). It usually affects the intestines, but may occur anywhere from the mouth to the end of the rectum (anus).
Cause:
The result is an overactive immune response that leads to chronic inflammation. This is called an autoimmune disorder.
Crohn’s disease may occur in any area of the digestive tract. The ongoing inflammation causes the intestinal wall to become thick.
Crohn’s disease
Symptoms
The main symptoms of Crohn’s disease are:
Crampy abdominal pain
Fever
Fatigue
Loss of appetite
Pain with passing stool (tenesmus)
Persistent, watery diarrhea
weight loss
Crohn’s disease
Treatment
DIET AND NUTRITION
- Eat small amounts of food throughout the day.
- Drink lots of water
- Avoid high-fiber foods
- Avoid fatty greasy or fried foods.
- Avoid or limit alcohol and caffeine consumption
Iron supplements
Calcium and vitamin D supplements
Vitamin B-12 to prevent anemia
Crohn’s disease
Medications
- Antidiarrheal drugs Loperamide (Imodium)
- Corticosteroids, prednisone and methylprednisolone are used to treat moderate to severe Crohn’s disease. They may be taken by mouth or inserted into the rectum.
- Immunomodulators such as azathioprine quiet the immune system’s reaction.
- Antibiotics may be prescribed for abscesses or fistulas.
Cirrhosis
Causes
Cirrhosis is scarring of the liver and poor liver function as a result of chronic liver disease.
Causes
Cirrhosis is caused by chronic liver disease.
- Hepatitis C, Hepatitis B infection
- Long-term alcohol abuse
Other causes of cirrhosis include:
-Autoimmune inflammation of the liver
Disorders of the drainage system of the liver (the biliary system),
-such as primary biliary cirrhosis,
-Metabolic disorders of iron and copper (hemochromatosis and Wilson’s disease)
Cirrhosis
Symptoms
Abdominal indigestion or pain
Nausea and vomiting
Pale or clay-colored stools
Small, red spider-like blood vessels on the skin
The legs (edema)
Ascites (an accumulation of fluid in the abdomen)
Vomiting blood or blood in stools
Weakness
Weight loss
Yellow color in the skin, mucus membranes, or eyes (jaundice)
Gallstones
Gallstones are hard, pebble-like deposits that form inside the gallbladder. Gallstones may be as small as a grain of sand or as large as a golf ball.
Gallstones causes
There are two main types of gallstones:
Stones made out of cholesterol. Gallstones made out of cholesterol are by far the most common type.
Stones made from too much bilirubin in the bile. Bile is a liquid made in the liver that helps the body digest fats. Bile is made up of water, cholesterol, bile salts, and other chemicals, such as bilirubin. Such stones are called pigment stones.
Medical conditions that cause the liver to make too much bilirubin, such as chronic hemolytic anemia, including sickle cell anemia
Liver cirrhosis and biliary tract infections (pigmented stones)
Gallstones
Symptoms
Pain:
In the right upper or middle upper abdomen:
May go away and come back
May be sharp, cramping, or dull
May spread to the back or below the right shoulder blade
Occurs within minutes of a meal
Fever
jaundice: Yellowing of skin and whites of the eyes
Additional symptoms that may occur with this disease include:
Abdominal fullness
Clay-colored stools
Nausea and vomiting
Spleen Function
The spleen removes old red blood cells,
The large number of sinuses and sinusoids filled with blood, which act as a storage, provide the supply of blood in case of any emergency which may cause severe blood loss.
Stores and produces white blood cell lymphocytes. These stored lymphocytes produce antibodies and assist in removing microbes.
Duodenum:
Is related to L1-L3 vertebrae and partly to T12.
Has 4 parts:
1st or superior part (B),
and Common Bile Duct.
*Duodenal cap: site of ulcer
**2nd or descending part (C), This part has a common opening for the common bile duct (CBD) and the main pancreatic duct in its postero-medial wall, called: major duodenal papilla. Within the wall, the common opening is dilated and forms the hepatopancreatic ampulla of Vater which is surrounded by the ampullary sphincter of Oddi. The 2nd part has the minor duodenal papilla as well, which is upper to the major opening.
3rd or horizontal part, 4th or ascending part,
Transverse, descending, horizontal, and ascending duodenum
Hepatopancreatic duct AKA ampulla of Vater
Sphincter of Oddi is under control of CCK
received contents of common bile duct and pancreatic duct
Transverse, descending, horizontal, and ascending duodenum
Hepatopancreatic duct AKA ampulla of Vater
Sphincter of Oddi is under control of CCK
received contents of common bile duct and pancreatic duct
**Function of Duodenum:
It regulates stomach and gallbladder emptying
in response to acid chyme.
It secretes Secretin due to high acid and fatty acids in its lumen; Secretin inhibits the gastric acid secretion.
- It secretes Cholecystokinin, in response to fatty chyme which induces
gallbladder contraction. - It secretes the hormone enterogastrone, that inhibits stomach peristalsis.
Function of small intestine :
Digestion and absorption of food.
Digestion is the enzymatic breakdown of nutrients into absorbable components i.e.: of carbohydrates into monosaccharides, of proteins into amino
acids and of fat into fatty acids and glycerol.
The most important source of the enzymes responsible for digestion, is pancreas.
Endocrine cells of the intestinal mucosa stimulate pancreatic and gall bladder secretion and peristalsis of intestine.
Small intestinal motility:
The small intestine mixes nutrients with digestive enzymes, exposes the digested nutrients to the absorptive mucosa, and then propels any non-absorbed material to the large intestine.
Basic electrical rhythm (BER):
As in the stomach, slow waves set the basic electrical rhythm (12/ min). Action potentials occur on the top of the slow waves and lead to contraction.
Don’t forget slow wave
weak contraction converted to segmental contraction for mixing of chyme before peristalsis
Every 90 minutes is a strong contraction of GI
to clear out the digestive tract from residual food
small + strong = BER
Segmental contractions:
Mix the intestinal contents, a section of the intestine contracts, sending the intestinal contents (chyme) in both orad and caudad directions. That section of the small intestine then relaxes and the contents move back into the segment.
*this back-and-forth movement produced by segmentation contractions causes mixing
without any net forward movement of the chyme.
The length of GI involved in each contraction is about 1 cm. This causes a
phenomenon called segmentation. These contractions happen sequentially
at a rate of 8-12/min to create a chopping action.
Propulsive contractions:
Peristalsis occurs after digestion and absorption have taken place.
The overall effect is a forward flow. A peristaltic signal will run for about
3-5cm over the circular and longitudinal muscle and fade.
These are highly coordinated and propel the chyme through
the small intestine toward the large intestine.
The transit time from pylorus to ileocecal valve is about 3-5h.
*contraction behind the bolus and, simultaneously, relaxation in front of the bolus
cause the chyme to be propelled caudally. Enteric nervous system controls reflexes
Gastroileal reflex:
is mediated by the ANS and by Gastrin.
Presence of food in the stomach triggers increased peristalsis in the
ileum and relaxation of the ileocecal sphincter.
Ileocecal junction
chyme becomes fecal matter as it enters the large intestine
Digestion and absorption of nutrients occur in small intestinal epithelial cells
90% of absorption of fluid that exist in fecal material by large intestine
it means the fluid in fecal matter should be reabsorbed by large intestine(uptake of nutrients)
Ileocecal junction
chyme becomes fecal matter as it enters the large intestine
Digestion and absorption of nutrients occur in small intestinal epithelial cells
90% of absorption of fluid that exist in fecal material by large intestine
it means the fluid in fecal matter should be reabsorbed by large intestine(uptake of nutrients)
Functions of the Ileocecal Valve
Prevent backflow of fecal contents
Normally the ileocecal valve is closed (under tonus except after a meal: gastroileal reflex allows relaxation (gastrin) and increases terminal ileal peristalsis.
Gastrin relaxes the ileocecal valve
Functions of the Ileocecal Valve
Normally 1500ml of chyme passes to cecum each day.
Significant input to ileocecal valve control from cecum distention signals (colonoileal reflex). This increases ileal sphincter tone and reduces ileal peristalsis.
Irritation of cecum delays emptying and triggers the same reflex.
Vomiting
Irritation or inflammation leads to diarrhea and leads to increased pressure in GI tract which
Clinical note:
The appendix is a cecal vestige and during appendicitis give a massive signal to ileocecal sphincter causing spasm and paralysis which completely blocks flow. Consider the signals forwards and backwards: get diminished cecal/colonic activity and also get upper distress due to distension which may culminate in additional abdominal pain over the RUQ inflammation and reflux and vomiting.
Clinical note:
The appendix is a cecal vestige and during appendicitis give a massive signal to ileocecal sphincter causing spasm and paralysis which completely blocks flow. Consider the signals forwards and backwards: get diminished cecal/colonic activity and also get upper distress due to distension which may culminate in additional abdominal pain over the RUQ inflammation and reflux and vomiting.
Peristaltic rush
A phenomenon triggered by irritation such as infectious diarrhea whereby the normally weak peristalsis action become more powerful and rapid. This is driven by nervous activity as you’d expect from the GI afferents signaling the brainstem to remove the irritant (or bloating distension) and the local plexus augmenting the movement activity.
Peristalsis during fasting
migrating motor complex (MMC):
In general the distension signal to the GI causes motor functions to handle the food load but in the case of a long duration following eating or fasting another pattern of GI activity occurs. Once initiated in a relatively empty GI tract approximately every 1.5 to 2 hours moderate peristalsis occurs. This is the migrating motor complex, it is distinct from the hunger pangs and serves to clear the build up of excessive (potentially harmful) levels of digestive secretions in the upper GI tract.
From considerations of peristalsis you appreciate that only small portions of the GI tract are active at a time but in the MMC this is a 40cm section that undergoes 6-10 minutes of activity then the signal migrates to the next region in a purposefully sequential manner.
Actions of folds and villi
The muscularis can cause folding on the wall and cause the folds to move along the wall. The purpose of this is to increase the contact with the chyme, by churning and increasing surface area.
The villi have muscles capable of causing them to squeeze and contract. This serves to empty the lacteal (milking action) creating a flow of nutrients and physically turning over the chyme in contact with the villi
Vomiting
A wave of reverse peristalsis begins in the small intestine, moving the GI
content in the orad direction.
The gastric contents are eventually pushed into esophagus. If the upper
esophageal sphincter remains closed, retching occurs.
If the pressure in the esophagus becomes high enough to open the upper
esophageal sphincter, vomiting occurs.
The vomiting center in the medulla is stimulated by tickling the back of the
throat, gastric distention, and vestibular stimulation (motion sickness).
- The chemoreceptor trigger zone in the 4th ventricle is activated by emetics,
radiation, and vestibular stimulation.
4th ventricle in brain
can cause stimulation of vomiting center in medulla oblongata
Large intestine (Colon):
It is about one meter in length.
Cecum Ascending colon Transverse colon Descending colon Sigmoid Rectum
90% of fluid absorption occurs in large intestine
Large intestinal motility:
- Fecal material moves from the cecum to the colon (through the ascending,
transverse, descending, and sigmoid colons), to the rectum, and then to
the anal canal.
Cecum and proximal colon:
- when the proximal colon is distended with fecal material, the ileocecal sphincter
contracts to prevent reflux into the ileum - Segmentation contractions in the proximal colon mix the contents and are
responsible for the appearance of haustra. - Mass movements occur 1-3 times/day and cause the colonic contents to move
distally for long distances (i.e., from transverse colon to the sigmoid colon).
Distal colon:
Fecal material in the distal colon becomes semisolid and moves slowly, since
most colonic water absorption occurs in the proximal colon.
Mass movements propel it into the rectum.
Rectum, anal canal, and defecation:
The sequence of events for defecation is as follows:
A- As the rectum fills with fecal material, it contracts and the internal anal sphincter
relaxes (rectosphincteric reflex).
B- once the rectum is filled to about 25% of its capacity, there is an urge to defecate.
however, defecation is prevented because of external anal sphincter (under voluntary
control, tonic contraction).
C- When it is convenient to defecate, the external anal sphincter is relaxed
voluntarily. The smooth muscle of the rectum contracts, forcing the feces out
of the body. Intra-abdominal pressure increases by expiring against a closed
glottis (Valsalva maneuver).
Valsalva maneuver
defecation
intraabdominal pressure increases leading to opening of anal sphincter
Small wave -> segmental -> peristalsis
Pressure on anal canal leads to relaxation of anal muscles
the relaxation of internal is involuntary
external is voluntary
Valsalva maneuver
defecation
intraabdominal pressure increases leading to opening of anal sphincter
Small wave -> segmental -> peristalsis
Pressure on anal canal leads to relaxation of anal muscles
the relaxation of internal is involuntary
external is voluntary
Pancreas:
Is an elongated (14-18cm and 65-75g)
pinkish and glandular accessory digestive
gland, which is retroperitoneal and lies
transversely between the duodenum
and the spleen, posterior to the stomach.
Pancreas is divided into 4 parts:
Head, neck, body and tail.
Uncinate process is an extension of
the lower part of the head
Relation to the surrounding: Head is in close relation to the C-shaped curve of the duodenum. Tail is anterior to kidney (in the left) and reaches the spleen.
Between duodenum and spleen
Pancreas is the largest gland in the body
exocrine and endocrine
exocrine secrete 3 enzymes
Between duodenum and spleen
Pancreas is the largest gland in the body
exocrine and endocrine
exocrine secrete 3 enzymes
Pancreatic secretion:
Pancreas contains a high concentration of HCO3-, whose purpose is to neutralize
the acidic chyme that reaches the duodenum.
Contains enzymes essential for digestion of protein, carbohydrate, and fat.
A- Composition and characteristics of pancreatic secretion:
1- high volume
2- same Na+ and K+ concentrations as plasma
3- much higher HCO3- concentrations than plasma
4- much lower Cl- concentrations than plasma
5- Isotonicity
6- pancreatic lipase, amylase and proteases.
A- Composition and characteristics of pancreatic secretion:
1- high volume
2- same Na+ and K+ concentrations as plasma
3- much higher HCO3- concentrations than plasma
4- much lower Cl- concentrations than plasma
5- Isotonicity
6- pancreatic lipase, amylase and proteases.
Lipase = digestion of fats
Amylase = digestion of starch
Protease = digestion of protein
Bicarbonate is released to neutralize the acidic chyme from the stomach in the duodenum
Lipase = digestion of fats
Amylase = digestion of starch
Protease = digestion of protein
Bicarbonate is released to neutralize the acidic chyme from the stomach in the duodenum
B- the composition of the aqueous component
of pancreatic secretion
At low flow rates: the pancreas secrets an isotonic fluid that is composed mainly of
Na+ and Cl-.
- At high flow rates: the pancreas secrets an isotonic fluid that is composed mainly of
Na+ and HCO3-.
Regardless of the flow rate, the pancreatic secretions are isotonic.
B- the composition of the aqueous component
of pancreatic secretion
At low flow rates: the pancreas secrets an isotonic fluid that is composed mainly of
Na+ and Cl-.
- At high flow rates: the pancreas secrets an isotonic fluid that is composed mainly of
Na+ and HCO3-.
Regardless of the flow rate, the pancreatic secretions are isotonic.
Formation of pancreatic secretion
The exocrine part of the pancreas also resembles a bunch of grapes.
Pancreas is composed of both exocrine and endocrine parts.
The acinar cells of the exocrine pancreas make up most of its weight.
a- Acinar cells:
Produce a small volume of initial pancreatic secretion, which is mainly Na+ and Cl-
b- Ductal cells:
modify the initial pancreatic secretion by secreting HCO3- and absorbing Cl- via
a Cl-_HCO3- exchange mechanism in the luminal membrane.
Because the pancreatic ducts are
permeable to water, H2O moves
into the lumen to make the pancreatic
secretion isosmotic.
Exocrine part is made of
acinar cells to secrete the enzymes
connected to the duct
Stimulation of pancreatic secretion
A- Secretin:
- Is secreted by S cells in the duodenum in response to H+ in the duodenal lumen.
- Acts on pancreatic ductal cells to increase HCO3- secretion.
- This is in response to the H+ content of the chyme entering the duodenum.
- As a result, HCO3- is secreted from pancreas into duodenum to neutralize the H+
Stimulation of pancreatic secretion
b- CCK (Cholecystokinin ):
- Is secreted by I cells in the duodenum in response to small peptides, amino acids,
and fatty acids in the duodenal lumen.- Acts on pancreatic acinar cells to increase enzyme secretion (amylase,
lipases, and proteases).
- Acts on pancreatic acinar cells to increase enzyme secretion (amylase,
Stimulation of pancreatic secretion
C- Ach (by vagovagal reflexes):
- Ach is released in response to H+, small peptides, amino acids, and fatty acids
in the duodenal lumen.- Stimulates enzyme secretion by the acinar cells and, like CCK, potentiates the effect of secretin on HCO3- secretion.
Ach is neurotransmitter for parasympathetic system which is main system for peristalsis
Bile secretion and gallbladder function
composition and function of bile
Bile contains bile salts, phospholipids, cholesterol, and bile pigments (bilirubin).
Bile is secreted by hepatocytes(liver cells) 50% of bile contains bile salt 2% is bilirubin product of damaged RBCs 4% contains cholesterol 40% are phospholipid
Bile is secreted by hepatocytes(liver cells) 50% of bile contains bile salt 2% is bilirubin product of damaged RBCs 4% contains cholesterol 40% are phospholipid
Formation of Bile
Bile is produced continuously by hepatocytes.
Bile drains into the hepatic ducts and is stored in the gallbladder for
subsequent release.
(on test)Bile is formed by the following process:
A- Primary bile acids (cholic acid and chenodeoxycholic acid) are synthesized
from cholesterol by hepatocytes.
In the intestine, bacteria convert a portion of each of the primary bile acids to
secondary bile acids (deoxycholic acid and lithocholic acid).
Synthesis of new bile acids occurs, as needed, to replace bile acids that are
excreted in the feces.
B- the bile acids are conjugated with glycine or taurine to form their respective
bile salts, which are named for the parent bile acid (e.g., taurocholic acid is
cholic acid conjugated with taurine).
C- electrolytes and H2O are added to the bile.
D- during the interdigestive period, the gallbladder is relaxed, the sphincter of Oddi is closed, and the gallbladder fills with bile.
E- bile is concentrated in the gallbladder as a result of isosmotic absorption of
solutes and H2O.
F- Bile and bile salts are essential to digestive and absorbtive activity but are also the vehicle for excretion of bilirubin and other waste products or toxins
Bilirubin – heme metabolite (breakdown product), Greenish
on test
Primary bile acid is on test
Hepatocyte in liver uptakes cholesterol and converts it into primary bile acid(cholic acid and chenodeoxycholic acid)
Blood stream carries primary bile acid to intestine
contains bacteria which is helpful for conversion of primary bile acid into secondary bile acids
Secondary bile acid is called deoxycholic acid and lithocholic acid
Bile salt is released by common bile duct in 2nd part of duodenum
Primary bile acid is on test
Hepatocyte in liver uptakes cholesterol and converts it into primary bile acid(cholic acid and chenodeoxycholic acid)
Blood stream carries primary bile acid to intestine
contains bacteria which is helpful for conversion of primary bile acid into secondary bile acids
Secondary bile acid is called deoxycholic acid and lithocholic acid
Bile salt is released by common bile duct in 2nd part of duodenum
on test
Bile salt has 2 surfaces
inside toward lipid droplets is lipophilic
outside towards lumen is hydrophilic
Amphipathic
see picture
soluble in watery environment of duodenum
bile acid is not soluble because it does not have the amphipathic nature
bile salt pH is close to duodenal pH
Bile salt has 2 surfaces
inside toward lipid droplets is lipophilic
outside towards lumen is hydrophilic
Amphipathic
see picture
soluble in watery environment of duodenum
bile acid is not soluble because it does not have the amphipathic nature
bile salt pH is close to duodenal pH
on test
Function of bile salts on their amphipathic properties
Bile salt is for emulsification of lipids
without bile salts the lipids are not soluble in watery environment of the lumen of the small intestine
After emulsification of lipid then it is converted into lipid droplets
Bile salts surrounding lipids called micelle
The lipid droplets are
monoglycerides
lysolecithin
fatty acids
Function of bile salts on their amphipathic properties
Bile salt is for emulsification of lipids
without bile salts the lipids are not soluble in watery environment of the lumen of the small intestine
After emulsification of lipid then it is converted into lipid droplets
Bile salts surrounding lipids called micelle
The lipid droplets are
monoglycerides
lysolecithin
fatty acids
on test
Clinical point
deficiency of bile salts leads to failure of lipid absorption by small intestine
excreted by fecal material
whiteish/yellowish tissue in feces
lack of cholesterol/lipids leads to
deficiency of sex hormones = infertility
deficiency of aldosterone = hypotension
lack of sodium leads to impact on cellular activity like depolarization and action potential and blood pressure
Clinical point
deficiency of bile salts leads to failure of lipid absorption by small intestine
excreted by fecal material
whiteish/yellowish tissue in feces
lack of cholesterol/lipids leads to
deficiency of sex hormones = infertility
deficiency of aldosterone = hypotension
lack of sodium leads to impact on cellular activity like depolarization and action potential and blood pressure
on test
The secondary bile acids are conjugated with glycine and taurine
form bile salts
**the pH of bile salts fits with duodenum pH
compatible
Bile salts
like a bubble
one side is hydrophilic and the other side it lipophilic
Important for emulsification of fat in duodenum
contains H2O and ions(sodium and potassium) and bilirubin(product of damaged RBCs)
Bilirubin
The secondary bile acids are conjugated with glycine and taurine
form bile salts
**the pH of bile salts fits with duodenum pH
compatible
Bile salts
like a bubble
one side is hydrophilic and the other side it lipophilic
Important for emulsification of fat in duodenum
contains H2O and ions(sodium and potassium) and bilirubin(product of damaged RBCs)
Bilirubin
on test
Digestion of lipids(all by pancreatic enzymes
triglyceride converts into 2 molecules of fatty acid and monoglyceride.
pancreatic lipase is critical to this breakdown
cholesterol ester coverts into cholesterol and fatty acid
cholesterol ester hydrolase enzyme is used
phospholipid converts into lysolecithin and fatty acid
enzyme phospholipase A2
Digestion of lipids(all by pancreatic enzymes
triglyceride converts into 2 molecules of fatty acid and monoglyceride.
pancreatic lipase is critical to this breakdown
cholesterol ester coverts into cholesterol and fatty acid
cholesterol ester hydrolase enzyme is used
phospholipid converts into lysolecithin and fatty acid
enzyme phospholipase A2
on test
Five steps for reabsorption of lipids(know it)
step one: the product of lipid digestion are soluble at the lumen of small intestine which is mixed with micelle except glycerol which is itself water soluble
step two: after formation of micelle then it is diffused into apical membrane of intestinal epithelial cell. Micelles enter into epithelial cell of small intestine but bile salt is left behind. The bile salt is absorbed in the ileum which is last part of small intestine. From ileum the BS is reabsorbed by enterohepatic circulation(portal vein) to the liver.
the bile salt comes back to liver for next emulsification process
step three: inside the intestinal epithelial cell the lipid products are connected/fused with fatty acid. This process is called “reesterified”
reesterified = lipid products fuse with fatty acids
step four: reesterified lipids again are fused with a protein and that protein comes from small intestine. The protein is called apoprotein(beta apoprotein). The reesterifiedlipid combine with the protein to form chylomicrons.
step five: chylomicron is released into lymphatic system by exocytosis then lymphatic systems opens to venous system and it is released into it. The release is how it is absorbed.
left thoracic duct and right lymphatic ducts
**the bile salt is absorbed by ileum and from ileum is absorbed by portal system which carries the bile salt to liver
Five steps for reabsorption of lipids(know it)
step one: the product of lipid digestion are soluble at the lumen of small intestine which is mixed with micelle except glycerol which is itself water soluble
step two: after formation of micelle then it is diffused into apical membrane of intestinal epithelial cell. Micelles enter into epithelial cell of small intestine but bile salt is left behind. The bile salt is absorbed in the ileum which is last part of small intestine. From ileum the BS is reabsorbed by enterohepatic circulation(portal vein) to the liver.
the bile salt comes back to liver for next emulsification process
step three: inside the intestinal epithelial cell the lipid products are connected/fused with fatty acid. This process is called “reesterified”
reesterified = lipid products fuse with fatty acids
step four: reesterified lipids again are fused with a protein and that protein comes from small intestine. The protein is called apoprotein(beta apoprotein). The reesterifiedlipid combine with the protein to form chylomicrons.
step five: chylomicron is released into lymphatic system by exocytosis then lymphatic systems opens to venous system and it is released into it. The release is how it is absorbed.
left thoracic duct and right lymphatic ducts
**the bile salt is absorbed by ileum and from ileum is absorbed by portal system which carries the bile salt to liver
on test
clinical point deficiency of apoprotein = failure of absorption of lipid products into systemic circulation leading to hypolipidemia A beta lipoprotenima deficiency of lipid having fat tissue in fecal matter is called “steatorrhea” steatorrhea causes mental retardation muscle weakness pigmental retinitis inflammation of pigment in retina hypolipidemia and hypocholesterolemia
clinical point deficiency of apoprotein = failure of absorption of lipid products into systemic circulation leading to hypolipidemia A beta lipoprotenima deficiency of lipid having fat tissue in fecal matter is called “steatorrhea” steatorrhea causes mental retardation muscle weakness pigmental retinitis inflammation of pigment in retina hypolipidemia and hypocholesterolemia
The many faces and places of Bilirubin
Bile and bile salts are essential to digestive and absorbtive activity but are also the vehicle for excretion of bilirubin and other waste products or toxins
Bilirubin – heme metabolite (breakdown product), Greenish – yellow in first step, then red-orange in final step, colors bile. Excess circulating colors skin yellow
Not just garbage: it serves as a clinical readout for hemolytic blood and liver diseases!
Bilirubin –
Generated when rbc dies, lyses hemoglobin which is phagocytosed and processed by tissue macrophages collectively known as the reticuloendothelial system.
Hemoglobin is split into heme and globin
Heme ring is “opened” to release iron binds transferrin
The remaining straight chain (four pyrrole nuclei) biliverdin becomes bilirubin in a couple of steps
Biliverdin is reduced by the macrophages to free bilirubin and released to the plasma where it binds albumin
The “free bilirubin” is absorbed at the hepatic membrane where it cleaves from albumin and is 80% conjugated to glucuronic acid to form bilirubin glucuronide, 10% conjugates to sulfate to form bilirubin sulfate and the remaining 10% bind other compounds
Bilirubin –
Generated when rbc dies, lyses hemoglobin which is phagocytosed and processed by tissue macrophages collectively known as the reticuloendothelial system.
Hemoglobin is split into heme and globin
Heme ring is “opened” to release iron binds transferrin
The remaining straight chain (four pyrrole nuclei) biliverdin becomes bilirubin in a couple of steps
Biliverdin is reduced by the macrophages to free bilirubin and released to the plasma where it binds albumin
The “free bilirubin” is absorbed at the hepatic membrane where it cleaves from albumin and is 80% conjugated to glucuronic acid to form bilirubin glucuronide, 10% conjugates to sulfate to form bilirubin sulfate and the remaining 10% bind other compounds
Urobilinogen –
A GI bacterial metabolite on the pathway to excreting bilirubin as stercobilin or urobilin
About half of the urobilinogen ends up being transported out of the gut and then gets harvested by the liver which sends 95% of it back to the gut and the small amount (5%) which makes it past the liver is filtered by the kidneys.
Urobilinogen is converted to stercobilinogen and oxidized to stercobilin (brownish), any unconverted urobilinogen is oxidized to urobilin
Urobilinogen excreted by the kidneys gets oxidizes in the air after it is micturated as urine and is reduced to urobilin which is yellowish
Urobilinogen –
A GI bacterial metabolite on the pathway to excreting bilirubin as stercobilin or urobilin
About half of the urobilinogen ends up being transported out of the gut and then gets harvested by the liver which sends 95% of it back to the gut and the small amount (5%) which makes it past the liver is filtered by the kidneys.
Urobilinogen is converted to stercobilinogen and oxidized to stercobilin (brownish), any unconverted urobilinogen is oxidized to urobilin
Urobilinogen excreted by the kidneys gets oxidizes in the air after it is micturated as urine and is reduced to urobilin which is yellowish
Bilirubin excretion
Sterocobilin released in fecal matter
brownish
Urobilin is released in urine
yellowish
Sterocobilin released in fecal matter
brownish
Urobilin is released in urine
yellowish
Jaundice –
Named for the color yellow and refers to the taint of the skin seen in bilirubin build up in the tissue fluid and plasma
Normal plasma level: 0.5 mg/dl
Skin turns color at 1.5 mg/dl
Can survive 40 mg/dl
Common causes of jaundice
Hemolytic jaundice – increased rbc lysis
Obstructive jaundice – blockage of the bile duct or liver damage prevents bilirubin excretion to GI
Jaundice –
Named for the color yellow and refers to the taint of the skin seen in bilirubin build up in the tissue fluid and plasma
Normal plasma level: 0.5 mg/dl
Skin turns color at 1.5 mg/dl
Can survive 40 mg/dl
Common causes of jaundice
Hemolytic jaundice – increased rbc lysis
Obstructive jaundice – blockage of the bile duct or liver damage prevents bilirubin excretion to GI
Neonatal jaundice
could be due to deficiency of an enzyme called glucuronyl transferase
converts conjugated bilirubin
deficiency of the enzyme leads to neonatal jaundice
may take a few days for the body to adjust and begin to produce the conjugated bilirubin
Neonatal jaundice
could be due to deficiency of an enzyme called glucuronyl transferase
converts conjugated bilirubin
deficiency of the enzyme leads to neonatal jaundice
may take a few days for the body to adjust and begin to produce the conjugated bilirubin
Hemolytic jaundice – increased rbc lysis
Excretion overwhelmed not impaired, get increased plasma levels of free bilirubin
Get increased levels of urobilinogen, again overwhelm the liver system and the excess is attempted to be cleared by the kidney see darker/yellower foamy urine.
Hemolytic jaundice – increased rbc lysis
Excretion overwhelmed not impaired, get increased plasma levels of free bilirubin
Get increased levels of urobilinogen, again overwhelm the liver system and the excess is attempted to be cleared by the kidney see darker/yellower foamy urine.
Obstructive jaundice – blockage of the bile duct or liver damage prevents bilirubin excretion to GI
Conjugated bilirubin ends up in the blood due to rupture of congested bile canniliculi, get increased plasma levels of conjugated bilirubin
Obstructive jaundice – blockage of the bile duct or liver damage prevents bilirubin excretion to GI
Conjugated bilirubin ends up in the blood due to rupture of congested bile canniliculi, get increased plasma levels of conjugated bilirubin
Gallbladder: pathology
Gall stones (cholelithiasis):
are formed due to an imbalance in the concentration
of the cholesterol and the bile salts in the bile, as a result, bile salts are no more in
suspension. Precipitation of the salts or cholesterol leads to gall stone formation.
Acute Cholecystitis: acute inflammation of the gallbladder wall, usually due to cystic duct obstruction by a gallstone. Bile accumulation in the gallbladder, enlargement and pain in epigastric and right hypochondriac regions in transpyloric line.
Pain, nausea and vomiting and involuntary muscle guarding, Painful splinting of respiration during deep inspiration in the palpation of right upper quadrant (Murphy’s sign).
Cholecystectomy: removal of the gallbladder due to severe biliary colic eg: cystic duct obstruction or cholecystitis etc.
Acute Cholecystitis: acute inflammation of the gallbladder wall, usually due to cystic duct obstruction by a gallstone. Bile accumulation in the gallbladder, enlargement and pain in epigastric and right hypochondriac regions in transpyloric line.
Pain, nausea and vomiting and involuntary muscle guarding, Painful splinting of respiration during deep inspiration in the palpation of right upper quadrant (Murphy’s sign).
Acute Cholecystitis: acute inflammation of the gallbladder wall, usually due to cystic duct obstruction by a gallstone. Bile accumulation in the gallbladder, enlargement and pain in epigastric and right hypochondriac regions in transpyloric line.
Pain, nausea and vomiting and involuntary muscle guarding, Painful splinting of respiration during deep inspiration in the palpation of right upper quadrant (Murphy’s sign).
Cholecystectomy: removal of the gallbladder due to severe biliary colic eg: cystic duct obstruction or cholecystitis etc.
Cholecystectomy: removal of the gallbladder due to severe biliary colic eg: cystic duct obstruction or cholecystitis etc.
Physiological Anatomy of the Liver
Functional unit – liver lobule
Liver has 50-100 thousand lobules
Organization of liver cells in plates and sinuses radiating out around a central vein which drains the lobule
Between the plates is the bile canaliculi
The lobule is fed blood from the portal and arteriole circulation which travels within the fibrous septa that delineates the lobule
The bile canaliculi flow outwards to bile ductules which are also in the septa
The plates have two cell types: endothelial cells and Kupffer cells
Physiological Anatomy of the Liver
Functional unit – liver lobule
Liver has 50-100 thousand lobules
Organization of liver cells in plates and sinuses radiating out around a central vein which drains the lobule
Between the plates is the bile canaliculi
The lobule is fed blood from the portal and arteriole circulation which travels within the fibrous septa that delineates the lobule
The bile canaliculi flow outwards to bile ductules which are also in the septa
The plates have two cell types: endothelial cells and Kupffer cells
Blood Flow into the Liver
Total at 1450 ml/min
Portal vein - 1100 ml/min
Hepatic artery - 350 ml/min
Blood Flow into the Liver
Total at 1450 ml/min
Portal vein - 1100 ml/min
Hepatic artery - 350 ml/min
Blood Flow into the Liver
Filtration – not just harvesting/sequestering nutrients but acting as a filter/screen for bacteria – remember the leakiness that allowed the larger nutrient particles to be transported also allowed bacteria to enter the portal circulation.
Portal blood if cultured always shows colonic bacteria but systemic blood doesn’t. The Kupffer cells are specialized macrophage type cells that ingest bacteria in 1/100th of a second so the liver can effectively screen >99% of the bacterial load in the blood transit time through the liver.
Blood Flow into the Liver
Filtration – not just harvesting/sequestering nutrients but acting as a filter/screen for bacteria – remember the leakiness that allowed the larger nutrient particles to be transported also allowed bacteria to enter the portal circulation.
Portal blood if cultured always shows colonic bacteria but systemic blood doesn’t. The Kupffer cells are specialized macrophage type cells that ingest bacteria in 1/100th of a second so the liver can effectively screen >99% of the bacterial load in the blood transit time through the liver.
Metabolic Functions of the Liver
Carbohydrates
Anabolic/Catabolic functions of the liver are:
- Storage of glycogen
- Gluconeogenesis (the formation of glucose from certain amino acids, lactate or glycerol)
- Glycogenolysis
- Glycogenesis (the formation of glycogen from glucose)
- The breakdown of insulin and other hormones
Metabolic Functions of the Liver
Carbohydrates
Anabolic/Catabolic functions of the liver are:
- Storage of glycogen
- Gluconeogenesis (the formation of glucose from certain amino acids, lactate or glycerol)
- Glycogenolysis
- Glycogenesis (the formation of glycogen from glucose)
- The breakdown of insulin and other hormones
Metabolic Functions of the Liver
Other metabolic activities
Storage of Vitamins
A (10 mo), D (3-4 mo), B12 (1 yr)
Coagulation components
-As stated the liver makes most plasma proteins including the coagulation proteins. Vitamin K is required for 7 clotting proteins synthesis: prothrombin, Factors, VII, IX and X, protein S and Z (accelerator globulin) generation
Metabolic Functions of the Liver
Other metabolic activities
Storage of Vitamins
A (10 mo), D (3-4 mo), B12 (1 yr)
Coagulation components
-As stated the liver makes most plasma proteins including the coagulation proteins. Vitamin K is required for 7 clotting proteins synthesis: prothrombin, Factors, VII, IX and X, protein S and Z (accelerator globulin) generation
Metabolic Functions of the Liver
Other metabolic activities
- Storage of Iron
- Removal or excretion of drugs, hormones
- Liver can detoxify and/or excrete (bile) many drugs (sulfonamides, penicillin, ampicillin, erythromycin)
- Hormones or metabolites are reduced and excreted, ie thyroxine, steroids (estrogen, cortisol, aldosterone)
- Excess plasma Ca++ is excreted via bile
Clinical note: liver damage can cause a build up of these agents (vs overdose/overproduction) and lead to toxicity or hyperactivity
Metabolic Functions of the Liver
Other metabolic activities
- Storage of Iron
- Removal or excretion of drugs, hormones
- Liver can detoxify and/or excrete (bile) many drugs (sulfonamides, penicillin, ampicillin, erythromycin)
- Hormones or metabolites are reduced and excreted, ie thyroxine, steroids (estrogen, cortisol, aldosterone)
- Excess plasma Ca++ is excreted via bile
Clinical note: liver damage can cause a build up of these agents (vs overdose/overproduction) and lead to toxicity or hyperactivity
A common sign of a damaged liver is jaundice, a yellowness of the eyes and skin. This happens when bilirubin, a yellow breakdown product of red blood cells, builds up in the blood.
A common sign of a damaged liver is jaundice, a yellowness of the eyes and skin. This happens when bilirubin, a yellow breakdown product of red blood cells, builds up in the blood.
Hepatitis (inflammation of the liver), caused mainly by various viruses but also by some poisons, autoimmunity, or hereditary conditions.
Hepatitis (inflammation of the liver), caused mainly by various viruses but also by some poisons, autoimmunity, or hereditary conditions.
Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by viral hepatitis, alcoholism or contact with other liver-toxic chemicals.
Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by viral hepatitis, alcoholism or contact with other liver-toxic chemicals.
Hemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage.
Hemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage.
Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract).
Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract).
Wilson’s disease, a hereditary disease which causes the body to retain copper.
Wilson’s disease, a hereditary disease which causes the body to retain copper.
Cholelithiasis in post hepatic jaundice leads to back flow
Cholelithiasis in post hepatic jaundice leads to back flow
Acute cholecystitis
inflammation of gallbladder
Acute cholecystitis
inflammation of gallbladder
Murphy sign positive
when you touch RUQ and it huts patient then it is patient
signals something wrong with liver or gallbladder
Murphy sign positive
when you touch RUQ and it huts patient then it is patient
signals something wrong with liver or gallbladder
Cholecystectomy
removal of gallbladder in severe condition
Cholecystectomy
removal of gallbladder in severe condition
Mixed stone is high level of cholesterol and bilirubin
Mixed stone is high level of cholesterol and bilirubin
Portal vein is different than hepatic system
combination of veins which carry vitamins, AA, glucose, drugs, bacteria etc after absorption from small and large intestines and stomach
left gastric vein, superior mesenteric vein, inferior mesenteric vein, splenic vein = portal vein
portal vein carries all the absorbed items from GI to liver
everything comes to liver
hepatic vein
different than portal vein
left and right hepatic veins carry deoxygenated from liver tissue and release the content into inferior vena cava
hepatic artery(common hepatic artery)
indirect branch of abdominal aorta for blood supply to bring oxygenated blood to liver tissue
bile duct
released into common hepatic duct
Portal vein is different than hepatic system
combination of veins which carry vitamins, AA, glucose, drugs, bacteria etc after absorption from small and large intestines and stomach
left gastric vein, superior mesenteric vein, inferior mesenteric vein, splenic vein = portal vein
portal vein carries all the absorbed items from GI to liver
everything comes to liver
hepatic vein
different than portal vein
left and right hepatic veins carry deoxygenated from liver tissue and release the content into inferior vena cava
hepatic artery(common hepatic artery)
indirect branch of abdominal aorta for blood supply to bring oxygenated blood to liver tissue
bile duct
released into common hepatic duct
Digestion of carbohydrates
oral cavity -> stomach -> small intestine
Oral cavity
breaking down starch into alpha-Dextrins(by alpha-dextrinase), maltose(by maltase), and maltotriose(by sucrase)
these are converted into monosaccharide glucose
Breaking down maltotriose is by alpha-amylase(saliva)
In small intestine
pancreatic enzymes convert disaccharides into mono saccharides
Disaccharides to monosaccharides trehalose(by trehalase) converts to glucose Lactose(by lactase) converts to glucose and galactose sucrose(by sucrase) converts to glucose and fructose
Mechanism of absorption of carbs in small intestine Lumen to Epithelial cells SGLT1 symports Na+ and glucose SGLT1 symports Na+ and galactose GLUT5 ports fructose epithelial cells to blood(capillaries) GLUT2 – moves glucose GLUT2 – moves galactose GLUT2 – moves fructose review picture
before small intestine 5 pancreatic enzymes(all converted by trypsin from inactive to active NOT digestion step)
trypsingen -> trypsin
chymotrypsingen -> chymotrypsin
proelastase -> elastase
procarboxy peptidase A -> carboxy peptidase A
procarboxy peptidase B -> carboxy peptidase B
Activation of GI proteases(for protein digestion)
stomach
pepsinogen -> pepsin
by HCl-
pepsin converts protein to A.A. and oligopeptides
small intestine
protein converted to A.A.(amino acids), dipeptides, and tripeptides
converted by 5 pancreatic proteases after activation step above
Digestion of carbohydrates
oral cavity -> stomach -> small intestine
Oral cavity
breaking down starch into alpha-Dextrins(by alpha-dextrinase), maltose(by maltase), and maltotriose(by sucrase)
these are converted into monosaccharide glucose
Breaking down maltotriose is by alpha-amylase(saliva)
In small intestine
pancreatic enzymes convert disaccharides into mono saccharides
Disaccharides to monosaccharides trehalose(by trehalase) converts to glucose Lactose(by lactase) converts to glucose and galactose sucrose(by sucrase) converts to glucose and fructose
Mechanism of absorption of carbs in small intestine Lumen to Epithelial cells SGLT1 symports Na+ and glucose SGLT1 symports Na+ and galactose GLUT5 ports fructose epithelial cells to blood(capillaries) GLUT2 – moves glucose GLUT2 – moves galactose GLUT2 – moves fructose review picture
before small intestine 5 pancreatic enzymes(all converted by trypsin from inactive to active NOT digestion step)
trypsingen -> trypsin
chymotrypsingen -> chymotrypsin
proelastase -> elastase
procarboxy peptidase A -> carboxy peptidase A
procarboxy peptidase B -> carboxy peptidase B
Activation of GI proteases(for protein digestion)
stomach
pepsinogen -> pepsin
by HCl-
pepsin converts protein to A.A. and oligopeptides
small intestine
protein converted to A.A.(amino acids), dipeptides, and tripeptides
converted by 5 pancreatic proteases after activation step above
Protein absorption
from lumen into epithelial cell the amino acid(AA), dipeptides, and tripeptides absorption is by sodium symport and hydrogen ion symport
sodium has important role from epithelial cells into capillary
Protein absorption
from lumen into epithelial cell the amino acid(AA), dipeptides, and tripeptides absorption is by sodium symport and hydrogen ion symport
sodium has important role from epithelial cells into capillary
Absorption of calcium
by epithelial cells of small intestine but it is under control of PTH(parathyroid hormone)
PTH increases calcium absorption and increases blood calcium concentration(normal is 10mg/dL)
Absorption of calcium
by epithelial cells of small intestine but it is under control of PTH(parathyroid hormone)
PTH increases calcium absorption and increases blood calcium concentration(normal is 10mg/dL)
Absorption of sodium chloride
sodium symports many ions
sodium also symports glucose
sodium antiports hydrogen ion
absorption of Na+ is under control of aldosterone hormone
hyponatremia(low blood sodium) then aldosterone secretion increases which increases the blood sodium and blood pressure
Absorption of sodium chloride
sodium symports many ions
sodium also symports glucose
sodium antiports hydrogen ion
absorption of Na+ is under control of aldosterone hormone
hyponatremia(low blood sodium) then aldosterone secretion increases which increases the blood sodium and blood pressure
Absorption of potassium by small intestine epithelial cells decreased potassium could be in some pathologic conditions(diarrhea or vomiting) excess is excreted by urine under control of aldosterone
Absorption of potassium by small intestine epithelial cells decreased potassium could be in some pathologic conditions(diarrhea or vomiting) excess is excreted by urine under control of aldosterone
H2O absorption
more sodium ion leads to more H2O absorption and then drink more water
H2O absorption
more sodium ion leads to more H2O absorption and then drink more water
Vitamin absorption
occur by epithelial cells of small intestine
fat soluble vitamins such as Vitamin A,D,E,K there is collaboration with micelles(lipid droplets after emulsification)
water soluble vitamins are absorbed by sodium cotransport mechanism
Vitamin B12 is absorbed by ileum
ileum is extremely important for B12 and bile salt absorption
Vitamin absorption
occur by epithelial cells of small intestine
fat soluble vitamins such as Vitamin A,D,E,K there is collaboration with micelles(lipid droplets after emulsification)
water soluble vitamins are absorbed by sodium cotransport mechanism
Vitamin B12 is absorbed by ileum
ileum is extremely important for B12 and bile salt absorption
Iron absorption
absorbed as heme iron
iron bound to either hemoglobin or myoglobin(detects oxygenated cells)
in intestinal cells the heme iron has degradation and releases free iron
free iron is released into blood stream which is bound to transferrin. The transferrin transfers the free iron from small intestine to the liver for storage or iron. The liver releases free iron into blood stream and it is carried to bone marrow for formation of hemoglobin.
iron deficiency leads to anemia
Iron absorption
absorbed as heme iron
iron bound to either hemoglobin or myoglobin(detects oxygenated cells)
in intestinal cells the heme iron has degradation and releases free iron
free iron is released into blood stream which is bound to transferrin. The transferrin transfers the free iron from small intestine to the liver for storage or iron. The liver releases free iron into blood stream and it is carried to bone marrow for formation of hemoglobin.
iron deficiency leads to anemia
Liver is important for protein production
Kupffer cells are for filtration
cleans blood
Liver is important for protein production
Kupffer cells are for filtration
cleans blood
Glucagon is pancreatic hormone with receptor in liver
increases gluconeogenesis for new glucose
Glucagon is pancreatic hormone with receptor in liver
increases gluconeogenesis for new glucose
Hemochromatosis
patient may have excess accumulation of iron in liver causing liver tissue damage by fibrosis
Hemochromatosis
patient may have excess accumulation of iron in liver causing liver tissue damage by fibrosis
Cancer of liver
colon cancer can easily spread to liver
Cancer of liver
colon cancer can easily spread to liver
Wilson’s disease
excess generation of Kuffer
Wilson’s disease
excess generation of Kuffer
Conns is tumor of aldosterone cells
Crohn’s is autoimmune disorder
severe diarrhea
malabsorption and maldigestion
No exact treatment for Crohn’s
can control signs/symptoms
Conns is tumor of aldosterone cells
Crohn’s is autoimmune disorder
severe diarrhea
malabsorption and maldigestion
No exact treatment for Crohn’s
can control signs/symptoms
Antidiarrheal drugs Loperamide (Imodium)
Antidiarrheal drugs Loperamide (Imodium)
Corticosteroids, prednisone and methylprednisolone are used to treat moderate to severe Crohn’s disease. They may be taken by mouth or inserted into the rectum.
Corticosteroids, prednisone and methylprednisolone are used to treat moderate to severe Crohn’s disease. They may be taken by mouth or inserted into the rectum.
Immunomodulators such as azathioprine quiet the immune system’s reaction.
Immunomodulators such as azathioprine quiet the immune system’s reaction.
Antibiotics may be prescribed for abscesses or fistulas.
Antibiotics may be prescribed for abscesses or fistulas.
