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lecture 8, 9, 10-11
respiratory center is also referred as the ____________? what is it responsible for? what does it contain?
medullary central pattern generator
is responsible for generating and regulating the basic rhythm of respiration.
It consists primarily of neuronal groups within the medulla oblongata, with the pons providing additional fine-tuning
where is the dorsal respiratory group located? what is it important for?
within the primary nucleus of the tractus soliatarius
is particularly important for inspiration and receives sensory information from peripheral chemoreceptors, baroreceptors, gastrointestinal and visceral receptors, and pulmonary receptors.
the Dorsal respiratory group (DRG) generates what? how? what does this do for the lungs?
the basic inspiratory rhythm through an inspiratory ramp signal, in which neuronal activity gradually increases for approximately two seconds before abruptly stopping
allowing elastic recoil of the lungs and thoracic cage to produce expiration.
can you modify the rate at which the ramp increases?
yes, the rate at which the ramp increases and the point at which it terminates can be modified to alter the depth and frequency of breathing.
ventral respiratory group: location, what does it do?
located bilaterally within the medulla
contributes to both inspiration and expiration by either VRG neurons stimulating inspiration or activate expiratory muscles, particularly the abdominal m. during forceful expiration
what is the VRG neurons that stimulate inspiration similar to?
like the Pre-Bötzinger complex in assisting with generation of the fundamental rhythm
when is neurons of VRG active and inactive? why
during quiet, normal breathing, some of the neurons within the VRG are relatively inactive
because inspiration is primarily driven by the DRG and expiration occurs passively through elastic recoil.
As respiratory demand increases, such as during heavy exercise, activity spreads into the VRG, providing additional respiratory drive.
pontine respiratory center is also called the
pneumotaxic center in the upper pons
what does the pontine respiratory center do?
modifies the basic medullary rhythm by controlling the point at which the inspiratory ramp is switched off
Strong pneumotaxic activity does what? weaker activity?
Strong pneumotaxic activity: shortens inspiration
which also shortens the overall respiratory cycle and therefore increases respiratory rate
weaker activity: allows inspiration to continue for a longer period, producing larger breaths and a slower respiratory rate.
what does the apneustic center do?
provides an opposing stimulatory influence on inspiration
precise anatomical organization and interaction with the pneumotaxic center remain incompletely defined.
Hering-Breuer inflation reflex? how does it work?
regulates respiration by sensory feedback
works when pulmonary stretch receptors located in the bronchi and bronchioles detect excessive lung inflation and send signals through the vagus nerves to the DRG
what does the signal sent to the DRG in the hering breuer inflation reflex do? when is it important? factors that influence it?
inhibits the inspiratory ramp, terminates inspiration, and promotes expiration, helping prevent over-inflation of the lungs.
Because the reflex depends on vagal input, bilateral vagotomy abolishes it and produces a slower, deeper breathing pattern.
The reflex is particularly important as lung volume increases and is influenced by factors such as age and anesthesia.
what does the chemical regulation of respiration do?
ensures that the ventilation matches the body’s metabolic requirements and maintains appropriate levels of O2, CO2, and H+
what does increased blood CO2, H+, and O2 do
CO2 and H+ strongly stimulate respiratory centers
O2 little direct effect on brainstem respiratory centers
what are decreased O2 levels detected by?
peripheral chemoreceptors located in the carotid and aortic bodies.
The carotid bodies contain?
type I glomus cells, which detect changes in PO₂, PCO₂, and pH and release neurotransmitters that increase respiratory drive
central chemoreceptors: location? do what? how does it work?
located near the ventral surface of the medulla are particularly sensitive to changes in CO₂ through its effect on CNS H⁺ concentration
CO₂ readily crosses the blood-brain barrier, where it reacts with water to generate H⁺; because H⁺ itself crosses the blood-brain barrier poorly, changes in arterial CO₂ are a particularly powerful stimulus for increasing respiratory activity
A dog is anesthetized and undergoes bilateral vagotomy. Which change in respiratory pattern would be expected?
Faster and shallower breathing
Slower and deeper breathing
Complete cessation of spontaneous respiration
Prolonged inspiration with no expiration
• Slower and deeper breathing
A cat experiences strong activation of its pneumotaxic center. Which change in breathing would be expected?
Prolonged inspiration and decreased respiratory rate
Shortened inspiration and increased respiratory rate
Increased duration of expiration with no change in inspiration
Complete inhibition of the respiratory rhythm generator
Shortened inspiration and increased respiratory rate
During heavy exercise, which change in respiratory control would be expected?
Increased activity limited to the dorsal respiratory group
Increased activity of the ventral respiratory group, including neurons driving active expiration
Inhibition of the pre-Bötzinger complex
Complete reliance on passive elastic recoil for expiration
Increased activity of the ventral respiratory group, including neurons driving active expiration
A dog develops an increase in arterial PCO₂. Why does this strongly stimulate the respiratory centers?
CO₂ directly crosses the blood-brain barrier and binds to respiratory neurons
CO₂ cannot cross the blood-brain barrier, so it remains in the blood
CO₂ crosses the blood-brain barrier, forms H⁺ in the CNS, and the resulting increase in H⁺ stimulates chemosensitive neurons
CO₂ directly stimulates pulmonary stretch receptors
CO₂ crosses the blood-brain barrier, forms H⁺ in the CNS, and the resulting increase H+ stimulates chemosensitive neurons
Oxygen primarily regulates what? how?
respiration through peripheral chemoreceptors located in the carotid and aortic bodies
when do peripheral chemoreceptors have influence over PO2? what stimulates peripheral chemo receptors?
little influence when arterial PO2 is relatively high, but activity increases substantially as PO2, esp. when PO2 is between 60-20mm Hg
Increased CO₂ and H⁺ can also stimulate these peripheral receptors, although their direct effects on the respiratory centers are considerably stronger.
Type I glomus cells contain? what do the continments do?
oxygen-sensitive potassium channels
they when PO₂ decreases markedly, these channels are inhibited, causing cellular depolarization, opening of voltage-gated calcium channels, and neurotransmitter release onto afferent neurons that stimulate respiration.
relationship between arterial PO2 and ventilation
significant during hypoxemia
When arterial PO₂ remains above approximately 100 mm Hg, changes in oxygen have little effect on ventilation. As PO₂ falls below 100 mm Hg, ventilation begins to increase, but becomes especially sensitive by the time PO₂ reaches 60 mm Hg and potentially increasing several-fold at very low PO₂
at normal conditions (sea level?) what are the primary chemical regulators of ventilation? when does hypoxia become important?
PCO₂ and H⁺ are the primary chemical regulators of ventilation,
while hypoxia becomes a more important respiratory stimulus when arterial oxygen falls substantially
what happens to ventilation during exercise? what is that response thought to involve?
ventilation increases almost precisely in proportion to the increased metabolic demand even though arterial PO₂, PCO₂, and pH remain close to normal.
the response is thought to involve anticipatory neural signals from the brain to the respiratory centers that occur simultaneously with motor signals to the exercising muscles.
so how fast does ventilation increase?
almost immediately at the onset of exercise, before arterial PCO₂ has had time to rise
it may even exceed the amount required, causing a transient decrease in arterial PCO₂.
After approximately 30–40 seconds, CO₂ production from the active muscles catches up with the increased ventilation, allowing arterial PCO₂ to return toward normal while exercise continues.
Which change in arterial blood produces the greatest increase in alveolar ventilation within the normal physiological range?
A decrease in PCO₂
An increase in PCO₂
A decrease in H⁺ concentration
An increase in PO
• An increase in PCO₂
Which statement best describes the direct effect of changes in arterial O₂ on the respiratory center?
A. Changes in O₂ have a strong direct effect on the respiratory center B. Changes in O₂ have virtually no direct effect on the respiratory center
C. Increased O₂ directly stimulates the medullary respiratory centers • D. O₂ is detected primarily by central chemoreceptors
B. Changes in O₂ have virtually no direct effect on the respiratory center
A dog develops a substantial decrease in arterial PO₂. Which receptors are primarily responsible for detecting this change?
A. Central chemoreceptors in the medulla
B. Pulmonary stretch receptors
C. Chemoreceptors in the carotid and aortic bodies
D. Baroreceptors in the carotid sinus
C. Chemoreceptors in the carotid and aortic bodies
At approximately what arterial PO₂ does hypoxia begin to produce a substantially stronger ventilatory response?
A. 150 mm Hg
B. 100 mm Hg
C. 60 mm Hg
D. 30 mm Hg
C. 60 mm Hg
why is the regulation of H+ concentration important?
hydrogen ion (H⁺) concentration is essential for maintaining normal physiological function because even small changes in H⁺ can significantly affect enzyme activity and cellular processes.
range of H+ in arterial blood?
extremely low, must be maintained within a narrow range
acid production varies with?
diet, exercise, organ function and, in birds, the egg-laying cycle
3 mechanisms to regulate acid-base balance:
chemical buffer systems (within seconds to min)
respiratory regulation (within min)
renal excretion (long term, powerful regulation, hours-days)
relationship between H⁺ concentration and pH is proprtional/inverse?
inverse, meaning that increased H⁺ decreases pH
normal arterial blood pH? venous and interstitial? intraceulluler?
arterial: approx. 7.4
venous/interstitial fluid: 7.35 bc of additional CO2 produced by tissues
intracellular : lower bc cellular metabolism generates acids
acidosis occurs when? alkalosis?
Acidosis occurs when H⁺ accumulates and pH decreases
alkalosis occurs when H⁺ is removed and pH increases.
chemical buffers: what are they and what are the 3 a major types
they are to minimize changes in pH by reversibly binding or releasing H+
provide immediate protection against acid base disturbances but do not permanently eliminate excess acid or base
the 3 major types:
bicarbonate,
phosphate
proteins
bicarbonate buffer system? what accelerates this rxn
primary extracellular buffering mechanism
involves reversible rxn between CO2, water, carbonic acid, H and bicarbonate
Carbonic anhydrase (abundant in RBC, pulmonary tissues, and renal tubes) accelerates this reaction
phosphate buffer system
less important in extracellular fluid bc is concentration is relatively lower
particularly important in intracellular fluid and renal tubular fluid, where phosphate concentrations are higher.
why are proteins important buffers?
they are abundant and contain amino acid groups capable of binding H⁺
Approximately 60–70% of the body's chemical buffering occurs intracellularly, with proteins accounting for much of this activity.
Hemoglobin is a major protein buffer in red blood cells that does what
can rapidly bind to H+
Although CO₂ readily diffuses across cell membranes, the slower movement of H⁺ and bicarbonate can do what to intracellular protein buffers?
delay the full contribution of intracellular protein buffers to extracellular acid–base regulation
respiratory system
provides the second line of defense against acid–base disturbances by regulating extracellular CO₂ concentration.
changes in ventilation influences what? why?
ventilation directly influence H⁺ concentration and blood pH.
Increased ventilation removes CO₂, shifts the bicarbonate reaction toward reduced H⁺ concentration and increases pH.
Conversely, decreased ventilation retains CO₂, increases carbonic acid formation and lowers pH. Please remember to note the use of H+ concentration versus pH.
ventilation influences H+ and pH of blood Because CO₂ combines with water to form carbonic acid, changes
Please remember to note the use of H+ concentration versus pH.
how do pulmonary CO2 and metabolic CO2 production work together?
Under normal conditions, pulmonary CO₂ excretion balances metabolic CO₂ production
increased metabolic activity generates additional CO₂ and H⁺, stimulating ventilation.
respiratory compensation?
Respiratory compensation is approximately 50–75% effective and can produce substantial improvements in pH within minutes.
For example, a decrease in extracellular pH from 7.4 to 7.0 may be partially corrected to approximately 7.2–7.3 within 3–12 minutes.
Nevertheless, respiratory compensation cannot permanently eliminate nonvolatile acids, making renal regulation essential for complete correction.
diving mammals contain what?
high concentrations of histidine-containing dipeptides, such as carnosine and anserine, in skeletal muscle
The compounds provide additional buffering capacity during prolonged anaerobic metabolism
water breathing animals rely heavily on?
n ion transporters in their gills, including H⁺-ATPases and Na⁺/H⁺ and Cl⁻/HCO₃⁻ exchangers, to regulate acid–base balance
reptiles acidify bladder fluid through?
H⁺-ATPase activity, while insects regulate acid–base balance through their respiratory and excretory systems.
insects containing ____ _____ _____can maintain what?
highly alkaline lakes can maintain relatively stable internal pH despite extreme environmental conditions
bohr effect
the relationship between acid–base balance and oxygen delivery.
Increased tissue CO₂ and H⁺ decrease hemoglobin's affinity for oxygen, shifting the oxygen–hemoglobin dissociation curve to the right.
promotes oxygen unloading into metabolically active tissues, particularly during exercise. In the lungs, where CO₂ concentrations are lower, the opposite effect promotes oxygen loading.
The magnitude of the Bohr effect varies among species, reflecting differences in metabolic requirements, hemoglobin properties and environmental adaptati
how are acid based disorders classified?
according to what their primary disturbance involves (respiratory or metabolic)
Respiratory acidosis: occurs? potential causes?
occurs: when inadequate ventilation causes CO₂ retention, increasing carbonic acid formation and extracellular H⁺ concentration.
potential causes: include airway obstruction, severe pulmonary disease, respiratory center depression and neuromuscular disorders that impair ventilation.
Chemical buffers initially bind excess H⁺, but because ventilation is already impaired, respiratory compensation is generally limited. The kidneys provide the principal long-term compensatory mechanism by increasing H⁺ excretion, conserving filtered bicarbonate and generating addition
metabolic acidosis: characterized by? common causes? compensation for this?
caused by: a reduction in plasma bicarbonate concentration or increase in plasma H+.
Common causes: include severe diarrhea, diabetic ketoacidosis, lactic acid accumulation during strenuous exercise and renal failure.
Compensation for metabolic acidosis involves: chemical buffers, increased ventilation and renal regulation when kidney function is intact.
Increased ventilation removes additional CO₂, reducing H⁺ concentration and partially restoring pH.
The kidneys increase H⁺ excretion and bicarbonate conservation, allowing more complete correction of the disturbance
Respiratory alkalosis: occurs? causes?
primarily occurs: when excessive ventilation reduces arterial CO₂ concentration, decreasing carbonic acid formation and H⁺ concentration.
Potential causes include fever, anxiety, toxins and exposure to high altitude.
At high altitude, reduced arterial oxygen stimulates ventilation, producing increased CO₂ elimination and respiratory alkalosis.
Chemical buffers initially release H⁺ to minimize the increase in pH.
Over several days, the kidneys compensate by conserving H⁺ and increasing bicarbonate excretion, helping restore the normal bicarbonate-to-CO₂ ratio
Metabolic alkalosis: characterized by? results from?
characterized by: an increase in extracellular bicarbonate concentration or decrease in acid.
It may result from: prolonged vomiting, excessive aldosterone activity, ingestion of alkaline medications or administration of certain diuretics.
Chemical buffers initially release H⁺ to counteract metabolic alkalosis.
Respiratory compensation occurs through reduced ventilation, allowing CO₂ retention and increased carbonic acid formation. If the disturbance persists, the kidneys conserve H⁺ and increase bicarbonate excretion to restore acid–base balance.
how are acid base disorders diagnosed?
by Clinical assessment
requires evaluating arterial pH, PCO₂ and plasma bicarbonate concentration together.
Compensation often produces corresponding changes in both CO₂ and bicarbonate.
cannot be diagnosed by using blood pH alone bc of compensatory mechanisms that may restore pH toward normal despite persistent abnormalities in Co2 and bicarbonate
Identifying the primary disturbance requires examining the direction of the pH change alongside the relative changes in CO₂ and bicarbonate.
what does compensated respiratory acidosis and metabolic alkalosis look like? compensated respiratory alkalosis and metabolic acidosis?
In compensated respiratory acidosis and metabolic alkalosis, both values may be elevated.
compensated respiratory alkalosis and metabolic acidosis may exhibit reductions in both values.
ectothermic animals
experience substantial changes in internal temperature that influence their acid–base physiology.
As temperature decreases, the neutral pH of water and the dissociation characteristics of protein buffers change, producing a corresponding increase in physiological pH.
ex. an ectotherm maintains a blood pH near 7.4 in warm environment but approx. 8.0 in cold environment.
This relationship highlights how acid–base regulation differs among animal species and how environmental temperature influences physiological homeostasis.
gills
extend outward from the body
Gills may be external, projecting directly into the surrounding water, or internal, enclosed within a superficial body cavity.
can animals be bimodal breathers? what is a bimodal breather?
yes, its when possessing two distinct respiratory structures that allow gas exchange in both aquatic and terrestrial environments.
water breathers arterial CO2 levels?
maintain very low arterial CO₂ partial pressures because CO₂ readily diffuses into the surrounding water.
Consequently, the partial pressure of CO₂ in blood leaving the gills closely resembles that of the environment
what happens to water animals if O2 bcomes limitd?
aquatic animals respond through increased gill ventilation and cellular adaptations mediated by hypoxia-inducible factors (HIF-1 and HIF-2).
These factors stimulate erythropoietin production, increase enzymes associated with anaerobic glycolysis, promote more efficient mitochondrial oxygen utilization and stimulate angiogenesis.
Collectively, these adaptations improve oxygen delivery and support cellular metabolism during periods of hypoxia.
The surface area and thickness of respiratory membranes between animals?
vary considerably among vertebrates and reflect differences in body size, metabolic demand and evolutionary adaptation.
Mammals and birds: possess substantially greater gas-exchange surface areas than similarly sized amphibians, reptiles and most fish, supporting the higher metabolic demands associated with endothermy.
highly active fish, particularly tuna, possess specialized gills with exceptionally large surface areas and thin respiratory membranes comparable to those of mammals.
greater respiratory surface area does correspond to larger lungs? t/f why?
FALSE
greater respiratory surface area does not necessarily correspond to larger lungs, as mammals and birds achieve extensive surface areas through highly subdivided respiratory structures
The thickness of the gas-exchange barrier also varies.
ex of fish vs humans?
fish typically possessing membranes approximately 5–10 μm thick, mammals having considerably thinner membranes and birds exhibiting exceptionally thin barriers of approximately 0.2 μm.
what can animals also use for gas exchange in addition to respiratory organs?
some vertebrates utilize their skin for gas exchange, with lungless salamanders relying entirely on cutaneous respiration
Respiratory frequency
also exhibits an inverse relationship with body size,
smaller mammals have greater mass-specific metabolic demands and therefore breathe more frequently than larger mammals.
what does Active ventilation require? how is it controlled?
requires rhythmic contractions of respiratory muscles, generating pressure gradients necessary to move air or water across respiratory surfaces
contractions are controlled by central pattern generators located primarily within the brainstem, particularly the medulla.
Through rhythmogenesis, these neural networks produce the coordinated motor signals responsible for maintaining breathing patterns.
2 major respiratory patterns of vertebrae:
continuous and intermittent breathing
Continuous breathing: characteristic of humans and most mammals, involves regular, uninterrupted respiratory cycles.
intermittent breathing: commonly observed in amphibians, reptiles and air-breathing fish, consists of individual breaths or groups of breaths separated by prolonged periods of apnea
how do gills work?
Water enters through the mouth into the buccal cavity and passes across the gills before exiting through the opercular cavity.
Each gill is supported by skeletal gill arches bearing two rows of filaments arranged in a V-shaped configuration.
The filaments contain numerous secondary lamellae, typically 10–40 per millimeter of filament length on each side.
Water flows across the secondary lamellae from the buccal side toward the opercular side, while blood flows in the opposite direction.
what are filaments
thin-walled, richly vascularized structures provide the principal surfaces for gas exchange.
what does the countercurrent arrangement of gills create/maintain?
maintains a favorable oxygen partial-pressure gradient along the respiratory membrane, allowing efficient oxygen extraction from the surrounding water.
Depending on the species and environmental conditions, resting fish may extract approximately 30–85% of the oxygen available in ventilated water.
two pumping mechanisms that allow for unidirectional flow of water?
the buccal pressure pump and the opercular suction pump.
buccal pumping: the fish opens its mouth and lowers the floor of the buccal cavity, increasing its volume and decreasing internal pressure.
This draws water into the mouth. The mouth closes, and elevation of the buccal floor increases pressure, forcing water across the gills toward the opercular cavity.
opercular cavity: generates negative pressure, drawing water through the gills. Subsequent contraction of the opercular cavity increases pressure and expels water into the environment.
happens at the same time
ram ventilation
a specialized mechanism in which forward swimming generates the pressure necessary to move water across the gills.
speeds of approximately 50–80 cm/s or greater, water entering the open mouth produces sufficient buccal pressure to maintain gill ventilation without relying entirely on muscular pumping.
reduce the metabolic cost of ventilation and is particularly advantageous for species with high oxygen demands.
Tunas, mackerel, dolphinfish, billfish and certain sharks are obligate ram ventilators, meaning they must swim continuously to maintain adequate water flow across their gills.
ram ventilation means what for the gills?
reinforced gill structures, including specialized tissue bridges connecting the outer ends of secondary lamellae.
stabilize the respiratory surfaces against the mechanical forces associated with continuous, high-volume water flow.
The primary stimuli for increased ventilation in fish? how do they get stimulated?
reduced oxygen availability and increased metabolic demand during exercise.
Chemoreceptors located within the gills detect decreases in environmental or arterial oxygen partial pressure and stimulate increased ventilation.
can increase their rates of buccal–opercular pumping up to 30x
fish vs mammal ventilation sensitivity? what is another thing fish can do to increase ventilation?
Unlike mammals, in which elevated CO₂ is a powerful respiratory stimulus, fish generally exhibit relatively weak ventilatory sensitivity to CO₂.
In addition to increasing ventilation, some fish regulate oxygen exchange through lamellar recruitment, adjusting the proportion of secondary lamellae actively perfused with blood.