MT 2
Muscle Learning Objectives
Distinguish different muscle types and functions.
Skeletal muscle (striated/voluntary)
multinucleated fibers arranged in parallel
responsible for voluntary movements of skeleton. allows actions: walking, running, lifting
attached to bones via tendons, makes up bulk of muscle mass (30-40%)
Cardiac muscle (striated/involuntary)
branched fibers with intercalated discs that connect individual cells, allowing for coordinated contractions
pump blood throughout the heart and into the circulatory system. the rhythmic contractions are essential for maintaining blood circulation
found only in heart
Smooth muscle (unstriated/involuntary)
spindle shaped cells with a single nucleus. the fibers are arranged in sheets or layers
regulates the diameter of blood vessels, propels food through the digestive tract, and controls other internal processes like urination and childbirth
found in the walls of hollow organs (intestines, blood vessels, bladder) and in respiratory tract
Identify the anatomy of skeletal muscles.
muscle fibers
myofibers: the basic building blocks of skeletal muscle. long cylindrical cells contain multiple nuclei
striations: alternating light and dark bands that indicate presence of myofibrils which is responsible for contractions
myofibrils
myofilaments: each myofibril contains two types of protein filaments:
actin (thin filament): primary component of light bands. helical each with a myosin binding site to allow for cross-bridge formation
myosin (thick filament): primary component of dark bands. 2 golf club-shaped subunits with tails aligned towards middle. globular heads (cross-bridge) protrude out at regular intervals
sarcomeres: basic unit of myofibril, defined by the region between two Z-lines. contract to produce muscle movement. shortening occurs when two filament types slide along another
connective tissue components
endomysium: thin layer surround each individual muscle fiber
perimysium: thick layer sheath that groups muscle fibers into bundles called fascicles
epimysium: dense layer that encases the entire muscle and provides structural support and protection
tendons: attach muscle to bones
satellite cells
stem cells between muscle fibers and basement membrane. responsible for muscle repair and regeneration
blood vessels and nerves
blood supply: deliver oxygen and nutrients and remove waste product
nerve supply: skeletal muscle is innervated by moto neurons that transmit signals from the nervous system to initiate contraction
sarcoplasmic reticulum
stores calcium ions which is crucial for muscle contraction
Identify the contractile and regulatory proteins and understand
their arrangement within muscle.contractile proteins
actin: composed of globular actin monomers that polymerize to form long filaments. each actin filament is associated with proteins: tropomyosin and troponin. actin provides the track along which the myosin moves to produce contraction
myosin: composed of long tails and globular heads. The heads bin to actin and have ATPase activity which provides energy for contraction. the heads for cross-bridges with actin filaments, pulling them closer together during contraction
Regulatory proteins
troponin: three proteins (TnC, Tnl, TnT) that are bound to actin and tropomyosin. troponin regulates muscle contraction by binding calcium ions to TnC, which causes a conformational change that moves the tropomyosin away from the myosin-binding site on actin, allowing for contraction to occur
tropomyosin: long rod-shaped protein that wraps around the actin filament covering the myosin-binding sites. tropomyosin blocks myosin from binding to actin when the muscle is relaxed. when calcium ions are present due to muscle activation, tropomyosin shifts position, exposing the binding sites for myosin
Arrangement within muscle
sarcomeres: arrange end-to-end along myofibrils. each sarcomere contains:
Z-lines: boundaries of each sarcomere, anchoring the thin filaments
A band: the dark region where thick filament (myosin) overlap with thin filaments (actin)
I band: the light region containing only thin filaments; it spans two adjacent sarcomeres
H zone: lighter region in the middle of the A band where there are only thick filaments (relaxed)
Understand neural control of muscles including excitation-
contraction coupling.Neural Control:
motor unit consists of a moto neuron and all the muscle fibers it innervates
vary in size <10 to >1000 muscle fibers per unit
each muscle fiber in innervated by just one axon, but each axon branches to innervate all of the fibers in its unit
motor units are intercalated within bulk muscle
Excitation-Contraction Coupling
Motor Neuron Activation
action potential generation: motor neuron receives signals from the central nervous system (CNS). when the neuron is sufficiently stimulated, an action potential is generated
neurotransmitter release: action potential travels down the axon to the neuromuscular junction(NMJ) where it triggers the release of acetylcholine (ACh) from synaptic vesicles into the synaptic cleft
Neuromuscular Junction
ACh binding: ACh binds to nicotinic receptors on the muscle fiber’s sarcolemma (membrane)
depolarization: binding causes ion channels to open, allowing sodium ions to enter the muscle cell, leading to depolarization (less negative charge inside the cell) of the sarcolemma and generation of an action potential in the muscle fiber
Propagation of Action Potential
T-Tubules: the action potential travels along the sarcolemma and into the muscle fiber through structures called transverse tubules (T-tubules). these invaginations allow the action potential to spread rapidly throughout the muscle fiber
Calcium Release
sarcoplasmic reticulum: action potential reaches sarcoplasmic reticulum (SR) a specialized endoplasmic reticulum that stores calcium ions (Ca2+)
calcium release: action potential causes voltage sensitive proteins in the T-tubules to trigger the release of Ca2+ from the SR into the cytoplasm of the muscle fiber
Contraction Mechanism
calcium binding: released Ca2+ binds to troponin a regulatory protein on the thin filament (actin)
tropomyosin shift: binding causes conformational change in troponin which moves tropomyosin away from the myosin binding sites on actin
cross-bridge formation: myosin heads bind to the exposed binding sites on actin forming a cross-bridge
power stroke: myosin head pivots pulling actin filaments towards the center of the sarcomere which leads to muscle contraction. ATP is required for this process, specifically for detaching myosin heads from actin and re-cocking them for the next contraction cycle
Relaxation
calcium reuptake: action potential stops, Ca2+ is actively pumped back into the sarcoplasmic reticulum
return to resting state: Ca2+ levels drop and troponin and tropomyosin return to their original positions blocking the myosin-binding sites on actin which leads to muscle relaxation
Understand the sliding filament theory of contraction.
Nerve Stimulation
muscle contraction begins with arrival of cation potential from a motor neuron, leading to the release of calcium ions from sarcoplasmic reticulum into muscle fiber
Calcium Binding
Ca2+ binds to troponin causing conformational change that moves tropomyosin away from myosin-binding sites on actin filament
Cross-Bridge Formation
myosin heads in an energized state (ADP and inorganic phosphate bound) attach to the exposed binding sites on actin, forming cross-bridges
Power Stroke
myosin heads pivots, pulling actin filament towards the center of the contraction. ADP and inorganic phosphate are released from the myosin head
Cross-Bridge Detachment
a new ATP molecule binds to myosin head causing it to detach from actin. this allows the myosin head to release and re-cock for another cycle
Resetting Myosin
the hydrolysis of ATP (break down into ADP and inorganic phosphate) re-energizes the myosin head, positioning it for another attachment to actin if Ca2+ remains present
Overall Effect: many sarcomeres contract simultaneously along the length of a muscle fiber, the entire muscle shortens. this is why muscle contraction appears to be coordinated, smooth process
Describe sensory aspects of muscle.
Proprioceptors (specialized sensory receptors)
Muscle Spindles( muscle contraction)
found within belly of skeletal muscles
detects changes in the muscle length (stretch) and the rate of that stretch (speed). crucial for reflex actions and maintaining muscle tone
when at endpoint of the stretch, the spindle sends a reflex arc signal to spinal column telling you not to stretch anymore
prevents and protects from overstretching/stretching too fast
composed of intrafusal muscle fibers surrounded by a connective tissue capsule. sensory neurons (1a afferent fiber) wrap around these fibers
Golgi Tendon Organs (GTOs): muscle relaxation
found at the junction between muscles and tendons
monitor muscle tension and prevent excessive force that could lead to injury. provide feedback to inhibit muscle contraction when tension is too high (autogenic inhibition)
tells you how much tension the muscle is exerting
if there is too much tension, the GTO will inhibit the muscle from creating any force via reflex arc to protect you from injury
composed of sensory nerve endings interwoven among collagen fibers within the tendon (1b afferent fiber)
Sensory Nerve Endings
various types of sensory nerve endings found in and around the muscle that respond to different stimuli such as stretch, pressure, and pain
contribute to the sensation of muscle fatigue, discomfort, and pain during intense exercise
Central Processing
integration in CNS: sensory info from proprioceptors are transmitted via afferent nerve fibers to the CNS where it is integrated and processed
role in movement control: sensory feedback is critical for adjusting muscle contractions, maintaining posture, and coordinating complex movements
Reflex Arc
spinal reflexes: proprioceptors feedback plays a vital role in reflex actions such as stretch reflex. ex: when a muscle is stretched, muscle spindles send signals to the spinal cord, leading to an immediate contraction of the muscle and often inhibit the antagonist muscle
Describe the basic mechanics of bulk muscle contraction.
Muscle Fiber Activation
motor unit recruitment: bulk muscle contraction begins with activation of motor units which consist of a motor neuron and the muscle fibers it innervates. the more motor units recruited, the greater the force produced
frequency of stimulation: the frequency of action potentials from the motor neuron can increase the force of contraction through temporal summation, where the muscle fibers do not have time to relax between stimuli
Muscle Fiber Contraction
excitation-contraction coupling: action potential triggers the release of calcium ions from the sarcoplasmic reticulum leading to the binding of calcium to troponin allowing the myosin heads to bind to actin filaments and initiate contraction through the sliding filament mechanism
Sarcomere Shortening
sliding filament mechanism: during contraction, myosin heads pull actin filaments toward the center of the sarcomere, causing them to shorten. This occurs simultaneously across many sarcomeres within a muscle fiber
force generation: amount of force generated by a muscle depends on the number of cross-bridges formed between actin and myosin. more cross-bridges result in greater force
Muscle Tension and Force Production
isometric vs isotonic contraction
isometric contraction: muscle fibers generate force without changing length (steady weight)
isotonic contraction: muscle fibers change length while generating force which can further be divided into:
concentric contraction: muscle shortens while generating force (lift weight)
eccentric contraction: muscle lengthens while still generating force (lower weight)
Bulk Movement
coordination of muscle groups: bulk muscle contraction often involves coordination action between multiple muscles and muscle groups, working together to produce smooth and controlled movements. antagonistic muscles (muscles that oppose each other) work in tandem to control the direction and strength of movements
Force Transmission
tendons and joints: the force generated by the muscle fibers is transmitted through tendons to bones, resulting in movement at the joints. the mechanical leverage provided by the skeletal system amplifies the force produced by muscles.
Energy Supply
ATP production: bulk muscle contraction requires energy, primarily provided by adenosine triphosphate (ATP). ATP is generated through aerobic respiration, anaerobic glycolysis, and creatine phosphate breakdown, depending on the intensity and duration of the activity
Understand frequency-tension and length-tension relationships
and the development of graded force.Frequency-Tension Relationship: describes how the rate at which a muscle fiber is stimulated affects the amount of tension it produces
twitch contraction: single action potential leads to a brief contraction known as twitch. quick rise and fall in tension
summation: muscle fiber is stimulated repeatedly at a higher frequency before it has completely relaxed from a previous twitch, the tension produced increases—temporal summation. the increased tension occurs because the calcium ions released from the sarcoplasmic reticulum have not returned to baseline levels before the next action potential arrives, allowing for more cross-bridge cycling
tetanus: the length -tension relationship describes how the length of a muscle fiber affects its ability to generate tension
Length-Tension Relationship: describes how the length of a muscle fiber affects its ability to generate tension
optimal length: corresponds to the ideal overlap of actin and myosin filaments allowing for the maximum number of cross-bridges to form
length variations
shortened: if muscle fiber is too short, there is excess overlap between actin and myosin filaments which hinders the ability to form new cross-bridges, reducing tension
stretched: if muscle fiber is too stretched, there is insufficient overlap between actin and myosin filaments, leading to fewer cross-bridges and a reduction in tension
Graded Force Development: ability of a muscle to generate varying levels of force based on the recruitment of motor units and frequency of stimulation
recruitment of motor units: muscles are composed of multiple motor units, each consisting of motor neuron and muscle fibers. smaller motor units (fewer fibers) are recruited for fine movements while larger motor units (more fibers) are recruited for stronger contractions
size principle: smaller motor units are activated first, followed by larger ones as more force is needed. allows for smooth controlled increases in force
combined effects: combine recruitment of motor units and frequency of stimulation (temporal summation), muscles can generate a wide range of forces, allowing for precise control over movements
Identify energy sources within muscle factors affecting fatigue.
Energy Sources
ATP: immediate source, provides energy for muscle contractions but is limited and can sustain maximal activity for only a few seconds
Creatine Phosphate (CP): rapidly regenerate ATP from ADP during short bursts of intense activity y donating its phosphate group
Anerobic Respiration: short term energy production through glycolysis by breaking down glucose into pyruvate and produce ATP without oxygen. relatively fast but leads to accumulation of lactate and hydrogen ions which contribute to fatigue
Aerobic Respiration: sustained energy production by breaking down carbohydrates, fats, and proteins to produce ATP. slower than anaerobic processes but it produces significantly more ATP per glucose molecule and is sustainable for longer durations of exercise
Glycogen Stores: (carbohydrate reserve) muscles store glycogen which can be mobilized for energy during aerobic and anaerobic conditions. depletion of glycogen stores during extended exercise can lead to fatigue
Factors Affecting Fatigue
Energy Depletion:
ATP and CP depletion- prolonged or intense activity can deplete ATP and creatine phosphate stores, limiting muscles ability to contract effectively.
Glycogen Depletion- low glycogen levels can impair energy production, especially in endurance activities, leading to a decrease in performance
Lactic Acid Accumulation: during anaerobic glycolysis, lactate and hydrogen ions accumulate causing a decrease in pH (acidosis) within the muscle. this can interfere with the contraction mechanism and lead to sensations of fatigue and muscle soreness
Ion Imbalances: prolonged activity can cause imbalances in key ions (K+ and Ca2+). elevated potassium levels outside the muscle cell can reduce the excitability of the muscle membrane, impairing contraction
Neuromuscular Factors:
Decreased Neural Drive- fatigue can affect the CNS ability to send signals to muscles, leading to reduced motor unit recruitment and lower force production
Altered Motor Unit Recruitment- as fatigue sets in, efficiency of motor unit recruitment may decline, resulting in less effective contractions
Recruitment:
Metabolic Byproducts: accumulation of metabolites such as Pi from ATP breakdown can affect the muscles ability to contract by interfering with cross-bridge cycling and Ca2+ release
Hydration and Electrolyte Levels: dehydration and electrolyte imbalances can impair muscle function and contribute to fatigue. adequate hydration and maintaining electrolyte balance are critical for optimal performance
3 Muscle Fiber Types
fast and slow fibers contain forms of myosin that differ in maximal rates at which they use ATP and corresponding differences in proteins that affect the speed of membrane excitation, excitation-contraction coupling, and ATP-production mechanisms
Slow Oxidative Fibers (type 1): combine high myosin-ATPase activity with high oxidative capacity and intermediate glycolytic capacity
Fast Oxidative Glycolytic Fibers (type 2A): combine high myosin-ATPase activity with high glycolytic capacity
Fast Glycolytic Fibers (type 2X): combine high myosin-ATPase activity with high glycolytic capacity
Study Guide Muscles
1. Skeletal and cardiac muscle are striated, similar in structure due to their arrangement of
contractile elements. Smooth muscle is not striated and has a different arrangement.
Skeletal muscle is responsible for voluntary movement (and execution of spinal reflexes)
while cardiac and smooth muscle are involuntary and under ANS control.
2. Organization of muscle: bulk muscle, muscle fiber (single cell), myofibrils, sarcomeres, thick
and thin filaments (the ‘sliding filament’ mechanism).
3. Know all steps of excitation-contraction coupling as summarized on Table 9-1, slide 8, lecture 16. This includes synaptic transmission at the NMJ, action potential generation in
the muscle membrane, t-tubules, DHP receptors, ryanodine receptors and the release of Ca
from internal stores, the structure of sarcomeres, actin-myosin interactions, the role of Ca,
troponin, tropomyosin, ATP (and its sources within muscle cells) and the power stroke.
You will not be tested on the terms A band, I band, Z line, M line or H zone.
4. Muscle contraction is defined as engagement of the sliding filament mechanism. Isotonic
contraction = muscle changes length; Concentric isotonic contraction = shortening;
Eccentric isotonic contraction = lengthening; Isometric contraction = no length change. The
force a contracting muscle exerts on an object = tension. The force exerted by an object on
muscle = load. If tension > load, the muscle shortens. If load > tension, the muscle
lengthens.
5. Twitch is defined as the tension developed in response to a single action potential. You
should know the approximate time-course of tension developed during an isometric twitch
and length change during an concentric twitch.
6. Frequency-tension and length-tension relationships. The latter is important for the Frank-Starling law.
7. Weight training can result in strength gains without muscle mass gains due to enhanced
neuromuscular efficiency, strength gains with muscle mass gains due to myofibril addition
to pre-existing muscle fibers (rarely in adult life with addition of new muscle fibers), and
muscle mass gains without strength gains due to increased sarcoplasm.
8. Motor unit is defined as a single motor axon and all of the muscle fibers it innervates. Each
fiber is innervated by exactly one axon. Motor units vary in size from 5-10 fibers/unit to
~1,000 fibers per unit. Smaller units tend to be recruited first. If they do not generate
sufficient force for the task, larger units are recruited.
9. There are three main types of muscle fibers intercalated throughout bulk muscle:
Slow-oxidative fibers (type 1) combine low myosin-ATPase activity with high oxidative
capacity. These are slow-twitch muscles ideal for endurance running as they fatigue slowly.
Fast-oxidative-glycolytic fibers (type 2A) combine high myosin-ATPase activity with high
oxidative capacity and intermediate glycolytic capacity.
Fast-glycolytic fibers (type 2X) combine high myosin-ATPase activity with high glycolytic
capacity. These are fast-twitch muscles good for sprinting; they fatigue quickly.
10. While it is possible to selectively train fast vs slow twitch muscle fibers, there is a significant
genetic component to their relative abundance within an individual.
Kidney Physiology Learning Objectives
Functions Anatomy, and basic processes
Describe the urinary system and its components.
Urinary System=Renal System
responsible for production, storage, and excretion of urine
Kidneys: responsible for filtering blood, remove waste, produce urine, and regulate electrolyte balance, blood pressure, and acid-base balance
Structure
cortex: outer region containing renal corpuscles and proximal and distal convoluted tubules
medulla: inner region organized into renal pyramids where urine concentrates. it contains loop of henle and collecting ducts
nephrons: each nephron consists of renal corpuscle (glomerulus and bowman’s capsule), and a renal tubule (proximal tubule, loop of henle, and distal tubule)
Ureters: tubes that transport urine from kidney to bladder. each is 25-30 cm long and lined with smooth muscle that contract in waves to push urine to bladder
Bladder: temporary storage for urine. bladder is composed of smooth muscle and lined with transitional epithelium that allows for expansion as it fills with urine. can hold 400-600 mL of urine
Urethra: tube that carries urine from bladder to outside. male urethra is 20 cm and serves as both urinary and reproductive functions. female urethra is 4 cm and serves as only urinary system
Renal Pelvis: funnel shaped structure at the beginning of ureter where urine collects before entering ureter
Perirenal Fat: surrounds kidney for protection
Renal Blood Vessels: kidneys receive blood through the renal arteries and return it via renal veins
Describe and understand the main kidney functions.
Kidneys in concert with hormonal and neural inputs that control their function and are primarily responsible for maintaining stable volume, electrolyte composition, and osmolarity of the ECF
maintain H2O balance in body
maintain proper osmolarity of body fluids, primarily through regulating H2O balance
regulate the quantity and concentration of most ECF ions
maintain proper plasma volume
help maintain proper acid-base balance
eliminate wastes of bodily metabolism
excrete foreign compounds
produce renin
produce erythropoietin
convert vitamin D into its active form
Describe the kidney anatomy.
bean shaped organ located retroperitoneally (behind abdominal cavity) on either side of the spine
surrounding structures
renal capsule: tough fibrous outer layer that protects kidney and maintain shape
perirenal fat: adipose tissue surrounding kidney for cushion and protection
renal fascia: connective tissue layer anchoring kidneys to surrounding structure
internal anatomy
renal cortex: outer region containing renal corpuscles (glomeruli and bowman’s capsules) and proximal and distal convoluted tubules. responsible for initial filtration of blood and reabsorption of nutrients
renal medulla: inner region organized into renal pyramids. each pyramid contains nephron structures including the loop of henle and collecting ducts. responsible for concentrating urine
renal pyramid: cone shaped structure within medulla that contain nephron’s loop of henle and collecting ducts. the apex of each pyramid (renal papilla) drains urine into renal pelvis
renal column: extensions of the renal cortex that lie between the renal pyramids. contain blood vessels and nephrons
renal pelvis: funnel shaped cavity that collects urine from renal pyramid and channel into the ureter. it is continuous with the ureter at the hilum of the kidney
Vascular Supply
renal artery: kidney receives blood through renal artery which branches from the abdominal aorta. it divides into smaller arteries that supply the kidney
renal vein: blood is returned from the kidney through the renal vein which drains into the inferior vena cava
Understand that the nephron is the basic functional unit of the kidney.
smallest unit capable of preforming all the tasks of an organ
1 million nephrons per kidney
vascular component of the nephron
afferent arteriole: carries blood to glomerulus
glomerulus: tuft if capillaries that filters a protein free plasma into the tubular component
efferent arteriole: carries blood from the glomerulus
peritubular capillaries: supply the renal tissue involved in exchanges with the fluid in the tubular lumen
tubular component of the nephron
bowman’s capsule: collects the glomerular filtrate
proximal convoluted tubule (PCT): uncontrolled reabsorption and secretion of selected substances (water, ions, nutrients
loop of henle (juxtamedullary nephrons only): establishes an osmotic gradient in renal medulla that is important in the kidney’s ability to produce urine of varying concentration
distal convoluted tubule (DCT) and collecting duct: variable controlled reabsorption of Na+, H2O and secretion of K+ and H+. fluid leaving the collecting duct is urine and enter the renal pelvis
combined vascular/tubular component
juxtaglomerular apparatus: produces substances involved in the control of he kidney function. region where the ascending look of henle passes through the fork formed by the afferent and efferent arteriole close to the glomerulus
cortical and juxtamedullary nephrons
glomeruli of cortical nephrons (80%) lie in the outer cortex layer and glomeruli of juxtamedullary nephrons (20%) lie in the inner cortex layer
Explain in detail how liquid flow in the vascular and the tubular components of the nephron support kidney function.
Vascular component
blood flow
renal artery: blood enters the kidney through renal artery which branches into smaller arteries and arterioles leading to the afferent arterioles that supply blood to glomeruli
glomerulus
filtration: blood filtrates in glomerulus. high pressure in glomerular capillaries facilitates movement of water, electrolytes, and smaller molecules from the blood into bowman’s capsule (the initial filtrate). larger molecules like proteins and blood cells are retained in the bloodstream due to size
glomerular filtration rate (GFR): rate of filtrate produced and is influenced by blood pressure, afferent and efferent arteriole diameter, and overall kidney health
efferent arterioles
after passing through glomerulus, blood exits via afferent arterioles which maintain glomerular pressure and regulate blood flow to nephron’s tubules
peritubular capillaries and vasa recta
peritubular capillaries: surround proximal and distal convoluted tubules. it receives reabsorbed substances from renal tubules and transport them back into bloodstream. crucial role in reabsorption and secretion
vasa recta: network of capillaries that run alongside loop of henle, provides oxygen and nutrients to medulla and aids in concentration of urine by maintaining osmotic gradient in renal medulla
Tubular component
bowman’s capsule
collects filtrate produced from glomerulus consisting of water, electrolytes, and waste
proximal convoluted tubule
reabsorption: 65-70% of filtrate is reabsorbed. essential nutrients (glucose, amino acids), ions (sodium, bicarbonate), and water are reabsorbed back into blood through active and passive transport mechanisms
secretion: waste products and excess ions (potassium, hydrogen ions) are secreted into tubular fluid
loop of henle
descending limb: permeable to water but not ions. allows water to be reabsorbed into surrounding interstitium concentrating filtrate
ascending limb: impermeable to water but actively transports sodium, potassium, and chloride ions out of the filtrate into the interstitium. creates a hyperosmotic medullary environment. crucial for kidney’s ability to concentrate urine
distal convoluted tubule
fine tuning: further reabsorption of sodium (regulated by hormones like aldosterone) and calcium (regulated by parathyroid hormone). the DCT is also involved in secreting additional waste
collecting duct
final adjustment: receives filtrate from multiple nephrons. influenced by hormones such as antidiuretic hormone (ADH) which increases water reabsorption, and aldosterone, which promotes sodium reabsorption
concentration of urine: as the filtrate moves through the collecting duct, water is reabsorbed, concentrating the urine before it enters the renal pelvis
Basic renal processes: glomerular filtration
Describe the anatomy of the glomerulus
located in renal cortex at beginning of nephron
composed of glomerular capillaries
capillary endothelium: has small pores that allow water, ions, and small molecules in. prevents larger molecules such as protein and blood cells from entering filtrate
basement membrane: surrounds capillaries. its a thin layer of extracellular matric that acts as a filtration barrier. composed of collagen and glycoproteins and provides structural support while selectively allowing substances to pass based on size and charge
podocytes: surrounds glomerulus. has foot-like extensions (pedicels) that wrap around the capillaries. creates a filtration slit between extensions which further restrict passage of large molecules
filtration barrier (3 layers)
fenestrated endothelium: allows small molecules and water to pass through while retaining blood cells
basement membrane: restricts large proteins based on size and charge
filtration slit: formed by podocytes further controlling wat enters the filtrate
afferent and efferent arterioles: blood enters through afferent arteriole. blood exits through efferent arteriole. diameter of arteriole is regulated to control blood flow and pressure within glomerulus which maintains glomerular filtration rate (GFR)
Explain what substances are excluded from the filtrate, and how.
large molecules: proteins (plasma proteins: albumin and globulin) is prevented from entering bowman’s capsule by glomerular basement membrane and filtration slits
blood cells
RBC: erythrocytes are larger than filtration pore and are retained in bloodstream
WBC: like WBC, leukocytes are too large to pass through glomerular filtration barrier
platelets: also excluded due to size
macromolecules
lipoprotein: large complexes that transport lipids in the blood are too large to be filtered
complex carbohydrates: large polysaccharides are excluded due to size and structure
charged particles: glomerular basement membrane has negative charge which repels negatively charged molecules such as albumin
certain hormones and large particles: larger hormones and hormones bound to proteins are excluded such as peptide hormones
Describe and understand the three forces that control glomerular filtration rate (GFR)
glomerular capillary blood pressure (glomerular hydrostatic pressure/GHP): pressure exerted by blood within glomerular capillaries. it derives water and solutes out of the blood and into bowman’s capsule. the higher the GHP, the greater the filtration rate. GHP is influenced by diameter of afferent and efferent arterioles. dilation of afferent increases GHP and thus GFR. constriction decreases GHP and GFR
plasma-colloid osmotic pressure (blood colloid osmotic pressure/BCOP): pressure from the presence of proteins (albumin) in the blood. it pulls water back into capillaries, opposing filtration. higher levels of protein in blood increase BCOP which reduces GFR by drawing water back into bloodstream. conditions such as dehydration (increasing protein concentration) or nephrotic syndrome (protein loss in urine) can affect BCOP and GFR
bowman’s capsule hydrostatic pressure (capsular hydrostatic pressure/CHP): pressure exerted by fluid already present in bowman’s capsule. opposes movement of fluid from capillaries into capsule. when CHP is high, it recues net filtration pressure, lowering GFR. conditions such as urinary obstruction or conditions that cause swelling of kidney can elevate CHP
Net Filtration Pressure (NFP)
NFP=GHP - (CHP + BCOP)
positive NFP = filtration is occurring
GFR Regulation
autoregulation: kidneys regulate through mechanisms
myogenic response (arteriolar smooth muscle contraction in response to increased pressure)
tubuloglomerular feedback (macula densa sensing changes in sodium chloride concentration and release paracrine factors that constrict adjacent afferent arteriole): increased BP, increased GFR, increase sodium to distal tubules. GHP and GFR decrease
increase BP during exercise would increase GFR and lead to unnecessary loss of water and salts to urine. tubuloglomerular feedback prevents this
hormonal regulation: hormones like renin (renin angiotensin aldosterone system) influences arteriolar tone, affecting GHP and GFR
net filtration pressure (major)
glomerular surface areas available for penetration (minor)
permeability of glomerular membrane (minor)
glomerular capillary blood pressure (GHP) controls GFR
Explain how glomerular capillary blood pressure is controlled by the diameter of the afferent arteriole.
blood vessel that carries blood into glomerulus. smooth muscle contracts/relax to change diameter
dilation: resistance to blood flow decreases (more blood flows into glomerulus). influx of more blood raises the hydrostatic pressure within the glomerular capillaries leading to an increase in GHP. increase in GHP enhances the net filtration pressure (NFP), resulting in higher GFR, meaning more filtrate is produced
constriction: resistance to flow increases (less blood entering glomerulus). reduction in blood flow leads to decrease in GHP within glomerular capillaries. decrease in GHP lowers NFP resulting in reduced GFR which helps conserve water and maintain blood pressure during low blood volume/dehydration
Describe how autoregulation can adjust GFR via 2 intrinsic mechanisms.
myogenic response
when systemic blood pressure increases, smooth muscle in afferent arteriole responds by constricting to reduce blood flow into glomerulus preventing an excessive rise in GHP and protecting glomeruli from damage
if systemic blood pressure decreases, smooth muscle relaxes, allowing more blood to flow into glomerulus and increasing GHP to maintain filtration
tubuloglomerular feedback
macula densa cells located in distal convoluted tubule monitors sodium chloride concentration of filtrate.
if GFR is too high (high sodium concentration in filtrate) the macula densa signals the afferent arteriole to constrict, reducing GHP and GFR
if GFR is too low (low sodium concentration) the macula densa signals for dilation of afferent arteriole to increase GHP and GFR
Explain how extrinsic sympathetic control can also control GFR using the baroreceptor reflex as example.
baroreceptor reflex
baroceptor: stretch-sensitive nerve endings located in major arteries, particularly in carotid sinus and aortic arch. they continuously monitor blood pressure
detection of blood pressure changes: when blood pressure decreases (hemorrhage, dehydration, stress), baroreceptors detect the reduced stretch and send fewer signals to the CNS
sympathetic nervous system activation: the reduced baroreceptor firing triggers an increase in sympathetic nervous system activity leading to several physiological response aimed at restoring blood pressure and maintaining vital organ perfusion
activation of baroreceptor reflex during low blood pressure situations serves to prioritize blood flow to vital organs (heart/brain) by reducing renal blood flow. this helps maintain systemic blood pressure and preserve overall homeostasis
**sudden drop in blood pressure —> body responds with general vasoconstriction to help bring blood pressure back up —> constriction of afferent arteriole —> reduce GFR —> reduce volume of filtrate —> reduce urine produced
Effect on GFR
afferent arteriole constriction
sympathetic stimulation: increased sympathetic tone cause afferent arterioles to constrict. mediated by norepinephrine released from sympathetic nerve endings
impact on GHP: constriction of afferent arterioles reduces blood flow into glomerulus which decreases GHP
reduced GFR: as GHP decreases, NFP decreases, resulting in a lower GFR. this helps conserve water and electrolytes during states of low blood volume
efferent arteriole effects
while afferent arteriole constricts, sympathetic nervous system also affects the efferent arteriole (less pronounced)
efferent arteriole constriction can occur which would increase GHP, but this response is more context-dependent and occurs during more severe drops in blood pressure
Basic renal processes: tubular reabsorption
Define tubular reabsorption
selective movement of filtered substances from the tubular lumen into the peritubular capillaries (H2O, Na+, Cl-)
Describe the differences between tubular epithelium and capillary endothelium
tubular epithelium: tubule is one cell layer thick. it has a luminal membrane and a basolateral membrane. adjacent tubular cells form tight junctions (barrier)
capillary endothelium: capillary is one thin cell layer thick. no tight junctions between endothelial cells and little barrier for water and solutes. fenestrated capillaries are even more permeable
Explain how these properties constitute barriers that afford selective control over reabsorption
transepithelial transport requires 5 barriers
luminal membrane of tubular cell
cytosol of tubular cell
basolateral membrane of tubular cell
interstitial fluid
capillary wall
barriers afford selective control over reabsorption even for H2O
permeability of tubular cell membrane varies along length of the tubule and subject to hormonal control
Understand the difference between passive and active reabsorption.
passive reabsorption: movement down an osmotic or electrochemical gradient (H2O)
active reabsorption: requires energy, includes Na+, glucose, amino acids, other electrolytes
Understand that Na+ reabsorption is a key driver of tubular reabsorption
99.5% of filtered sodium is reabsorbed
67% in proximal tubule (occurs regardless of amount of Na+)
25% in loop of henle (occurs regardless of Na+)
8% in distal and collecting tubules (under hormonal control)
Explain where reabsorption of Na+ takes place and what proportion is subject to hormonal control.
proximal tubule: sodium reabsorption plays a pivotal role in reabsorption of glucose, amino acids, H2O, Cl-, and urea
loop of henle: sodium reabsorption plays a critical role in kidneys ability to produce urine of varying concentrations and volumes
distal tubule: sodium reabsorption is subject to hormonal control, important int he regulation of ECF volume
Understand how active Na+ reabsorption drives passive reabsorption of H2O, Cl-, and urea.
active transport of ion against concentration gradient
involves the energy-dependent Na+, K+, ATPase located in the tubular cell’s basolateral membrane
intracellular concentration of Na+ is low, Na+ diffuses into the tubular cell down its concentration gradient
interstitial concentration of Na+ is high, Na+ diffuses into the peritubular capillary down its concentration gradient
H2O down osmotic gradient: facilitated by aquaporins (AQP). proximal tubules express AQP1 (always open). distal and collecting tubules express AQP2 (regulated by vasopressin)
Cl- down electrochemical gradient
urea diffusion is not very effective, half of urea in filtrate is still excreted via urine
Explain how aldosterone and ANP have opposing actions on Na+ reabsorption.
Aldosterone stimulates reabsorption
produced by adrenal cortex (zona glomerulosa) and acts on distal convoluted tubule and collecting ducts of nephron
secreted due to increase plasma potassium (K+) levels, decreased blood pressure or blood volume (detected by renin angiotensin aldosterone system / RAAS), or increased angiotensin II levels
inserting additional leak channels in the luminal membrane
inserting additional sodium potassium ATPase in the basolateral membrane
Na+ reabsorption
aldosterone promotes the reabsorption of sodium by increasing the expression and activity of sodium channels (ENaC) on the apical membrane of tubular cells
increases activity of sodium potassium ATPase pumps on the basolateral membrane, facilitating the movement of sodium into bloodstream while promoting K+ secretion into tubular fluid
effect on blood volume/pressure: increasing sodium reabsorption, aldosterone leads to water retention which increases blood volume and pressure
Atrial Natriuretic Peptide (ANP) inhibits Na+ reabsorption
produced by atrial myocytes of the heart in response to increase blood volume and atrial stretch
acts in glomerulus and distal nephron (distal convoluted and collecting ducts)
Na+ excretion
ANP inhibits sodium reabsorption by decreasing the expression and activity of ENaC and sodium potassium ATPase in distal nephron
promotes natriuresis which is the excretion of sodium in the urine
effect on blood volume/pressure: by increasing sodium excretion, ANP leads to increased urine output, reducing blood volume and pressure
in the distal and collecting tubules, reabsorption of a small percentage of Na+ is subject to hormonal control. the extent of this reabsorption is inversely related to the magnitude of the Na+ load in the body
Draw a schematic of the RAAS system, its components and how they affect urine production via aldosterone.
Angiotensinogen: synthesized in liver, always present in plasma
Renin: released from kidney (granular cells) into plasma. activates/converts angiotensinogen into angiotensin I
Angiotensin-converting enzyme (ACE): enzyme present in the lungs converts angiotensin I to angiotensin II
Angiotensin II: has many effects (stimulates vasopressin, thirst, arteriolar vasoconstriction). also stimulates the adrenal cortex to release aldosterone
Aldosterone: increases Na+ reabsorption in the distal and collecting tubules by promoting the insertion of Na+ channels (luminal membrane) and Na+K+ ATPase carriers (basolateral membranes)
Explain how inhibition of Na+ reabsorption by natriuretic peptides reduces blood pressure.
Atrial Natriuretic peptide (ANP; from atria) and Brain Natriuretic Peptide (BNP; from ventricles) are released in response to high blood pressure/volume/NaCl load
ANP/BNP inhibit:
Na+ reabsorption
RAAS activity
smooth muscle of afferent arterioles —> increased GFR
inhibits sympathetic nervous system to reduce cardiac output and peripheral resistance —> reduced blood pressure
Understand how nutrients (glucose and amino acids) are reabsorbed and explain why some patients present with glucose in their urine.
Glucose and amino acids are actively reabsorbed in the proximal tubule by Na+ dependent by specific symport carriers )ex-sodium glucose linked transporter; SGLT) across the tubular membrane into the cell (secondary active transport)
glucose then diffuses across the basolateral tubular membrane via glucose transports (glut) (facilitated diffusion)
glucose reabsorption is efficient and complete but the number of sodium glucose symporters if finite —> tubular maximum. excess glucose is lost in urine
Basic renal processes: tubular secretion
Understand that organic anions and cations are cleared via tubular secretion.
facilitates rapid clearance of certain hormones (prostaglandins, epinephrin)
facilitate removal of organic ions that circulate in complex to carrier proteins (not filtered)
elimination of foreign compounds (drugs, food additives, pollutants and their metabolites)
Explain the important role for the secretion of hydrogen
hydrogen ion secretion is important in acid-base balance
renal H+ is secreted in proximal tubules
renal H+ can either be secreted or reabsorbed by special intercalated cells in the distal and collection tubules depending on the acid balance in the plasma
Describe the path of a K+ cation during tubular secretion
K+ is selectively moves in opposite directions along the tubules
most of the K+ in the filtrate is reabsorbed in the proximal tubules via leak channels in the basolateral membrane, tubular reabsorption
tubular cells in the distal and collecting tubes have leak channels in the tubular membrane, tubular secretion
high plasma K+ directly stimulates aldosterone from the adrenal cortex. aldosterone stimulates insertion of K+ leak channels in the luminal membrane of the distal and collecting tubules. almost all K+ in urine is the result of secretion
Be able to calculate the plasma clearance rate based on the whether a substance is filtered, absorbed and secreted in the nephron.
plasma clearance is the volume of plasma cleared of a particular substance per minute
typical blood flow to the kidneys: 1140 ml/min
plasma flow: 625ml/min
20% is filtered
GFR = (625ml/min) (0.2) = 125 ml/min
filtered, not absorbed, not secreted —> clearance rate=GFR (insulin, creatine)
filtered, reabsorbed, not secreted —> clearance rate<GFR (normally 0)(glucose)
filtered, partially reabsorbed, not secreted —> clearance rate<GFR (but not 0) (urea)
filtered, not reabsorbed, secreted —> clearance rate>GFR (H+)
Countercurrent multiplication
Understand the special importance of the loops of Henle of juxtamedullary nephrons
filtrate status before loop of henle
after filtrate is formed, uncontrolled osmotic reabsorption of filtered H2O occurs in the proximal tubule (secondary to active Na+ reabsorption)
about 65% of filtrate is reabsorbed (35%) remaining by time filtrate reaches the loop of henle
filtrate is isotonic as it enters the loop of henle
loop of henle establishes the vertical osmotic gradient in the medulla of the kidney by countercurrent multiplication
properties of the descending and ascending limbs of a long henle loop
mechanism of countercurrent multiplication
benefits of counter current multiplication
at normal fluid balance and solute concentration, body fluids are isotonic: ECF osmolarity is 300 mOsm/liter
if excess H2O relative to solute, a solution is hypotonic: ECF osmolarity<300 mOsm/liter —> kidneys will produce dilute urine
if too little H2O relative to solute, a solution is hypertonic: ECF osmolarity>300mOsm/liter —> kidneys will produce more concentrated urine
Describe how the different permeabilities of the ascending and descending loop for H2O and Na+ enable countercurrent multiplication.
descending limb (H2O leaves tubule): does not extrude Na+ and is highly permeable to H2O (AQP1)
ascending limbNa+ leaves tubule): actively transports Na+ out of the tubule into the interstitial fluid and is always impermeable to H2O
Explain how countercurrent multiplication provides the ability to produce both highly concentrated or dilute.
as urine travels down the descending limb it concentrates
as urine goes up ascending limb it dilutes
two purposes
produce hypotonic urine that cna be excreted if ECF within body has too much H2O
establish vertical osmotic gradient that can be sed by the collecting ducts to concentrate urine if the ECF within body doesn’t have enough H2O
vasopressin controls H2O reabsorption in the collecting tubules
water excess: no vasopressin, hypotonic urine (impermeable to H2O) —> large volume of dilute urine is excreted. no H2O reabsorbed in distal portion of nephron. excess water eliminated in urine
water deficit: vasopressin leads to insertion of AQP2 in luminal membrane (permeable to H2O) —> small volume of concentrated urine is excreted. reabsorbed H2O picked up by peritubular capillaries and conserved for body
Explain the role of the vasa recta.
hairpin loop of vasa recta by passive countercurrent exchange preserves the vertical osmotic gradient while supplying the blood to the medulla
Describe how the actions of AVP at the distal and collecting tubules determine whether filtrate is concentrated or stays dilute.
collecting tubules use the gradient to produce urine of varying concentrations under the influence of AVP (arginine vasopressin) — also called antidiuretic hormone (ADH)
DCT
AVP increase the permeability of he tubule cells to water by promoting the insertion of AQP2 channels into the apical membrane of epithelial cells
if AVP is present, more water is reabsorbed back into the bloodstream, reducing the volume of dilute filtrate and concentrating the urine
Collecting Duct
primary site of AVP
when AVP binds to receptor, it trigger a signaling cascade that promotes the insertion of AQP2 channels
allows more water to be reabsorbed as the filtrate passes through the collecting ducts, which is surrounded by hyperosmotic medullary interstitium leading to further concentration of urine
in the absence of AVP, collecting duct remains impermeable to water and filtrate stays dilute as it exits into the renal pelvis
Micturition
Describe the anatomy of the urogenital system.
ureters: two tubes that transport urine from kidney to bladder
peristaltic contractions: smooth muscle within uretal wall propel urine to the bladder
as bladder fills, pressure against the ureters prevents black flow of urine however, urine can still enter
urinary bladder: hollow muscular organ located in pelvic cavity
stores urine until it is excreted. has a muscular wall that contracts during urination
urethra: tube that carries the urine from bladder to outside
Explain the role of the sphincters controlling micturition.
sphincters: prevent bladder from emptying continuously
internal urethral sphincter: smooth muscle and not under voluntary control. when the bladder is relaxed, the sphincter closes the outlet of the bladder. when the bladder contracts, the internal sphincter opens
external urethral sphincter: skeletal muscle and under voluntary control. the motor neurons supplying the external sphincter are continuously firing (keeping sphincter closed) unless they are inhibited
Explain how micturition is controlled reflexively and voluntarily.
reflex (spinal cord reflex): initiated when stretch receptors in the bladder wall stimulate the parasympathetic supply to the bladder and inhibit the bladder motor neurons.
voluntary: can be prevented by deliberately tightening the external sphincter
Cardiovascular Physiology Objectives
• Describe the ionic basis of APs in pacemaker cells and contractile cells.
Pacemaker Cells: grouped together into specialized regions called nodes that control the rate and coordination of cardiac contractions. initiate their own action potentials at a regular frequency
resting membrane potential: unstable resting membrane potential (pacemaker potential). due to slow influx of sodium ions through funny channels and the gradual decrease in potassium permeability
a transient increase in Na+
permeability (Na funny channels)
which causes the membrane
potential to depolarize
depolarization phase: as threshold is reached, voltage gated calcium channels ( L-type Ca2+ channels/long lasting DHP channel) open causing rapid depolarization. influx of Ca2+ ions drives the AP
depolarization causes an increase
in permeability to Ca++ (T-channel)
that leads to further depolarization
of the membrane potential and
causes the cell to reach thresholdThe cell generates an action
potential when a second increase in
permeability to Ca ++ occurs (L-
channelThe depolarization resulting from
the action potential causes an
increase in K+ permeability
(K channels) and the membrane
potential repolarizes
repolarization phase: after the peak of depolarization, calcium channels close and voltage gated potassium channels open resulting in efflux of K+ leading to repolarization of the cell
When the cell repolarizes, the K +
permeability again decreases and the
process starts over again.
Note: spike itself does not involve
voltage-gated Na+ channels.
return to pacemaker potential: K+ channels eventually close and the pacemaker potential starts to rise again, leading to next AP
Contractile Cells
resting membrane potential: stable (-90mV) maintained by high permeability to K+ through voltage gated K+ channels
depolarization phase: stimulated by AP of pacemaker cell, fast gated Na+ channels open rapidly, rapid depolarization of cell
plateau phase: follows rapid depolarization, membrane potential remained relatively stable due to opening of L-type Ca2+ channels, allowing Ca2+ influx. simultaneously, K+ channels begin to close, preventing repolarization during this phase. the plateau is crucial for ensuring that the contraction of cardiac muscle is sustained and prevents tetany
repolarization phase: L-type Ca2+ channels close and voltage gated K+ channels reopen, allowing K+ to exit the cell. efflux of K+ leads to repolarization back to resting membrane potential
summary
pacemaker cells generate action potentials through a combination of Na⁺ and Ca²⁺ influx and K⁺ efflux, leading to rhythmic depolarization. In contrast, contractile cells rely on a rapid influx of Na⁺ for initial depolarization, followed by a prolonged plateau phase due to Ca²⁺ influx, and finally, repolarization through K⁺ efflux. These differences are essential for the coordinated contraction of the heart muscle and the rhythmic pacing of heartbeats
Interpret the ECG and heart sounds (other than murmurs which were not
discussed).Electrocardiogram - the electrical currents generated by the
coordinated action potentials of the heart muscle can reach the
surface of the body and be detected as voltage differences between
two points on the body surface. The reading is a composite of the
electrical activity, not a single action potential.The record resulting from measuring these voltage changes is
referred to as the electrocardiogram or ECG. Disturbances in
heart function can be detected as changes in the ECG.Interpretation:
P-wave: depolarization of atria (electrical activation) small round wave
PR segment: AV nodal delay (atria contract and fill ventricles
QRS complex: depolarization of ventricles: (electrical activation of ventricles) sharp and narrow wave
SR segment: ventricles are contracting and emptying
T-wave: repolarization of ventricles (recovery of ventricles after contraction)
TP interval: ventricles are relaxing and filling
QT interval: total time for ventricular depolarization/repolarization
Heart Sounds
first heart sound: low pitched, soft and relatively long sound associated with the closure of AV valves. “lub”
second heart sound: high pitched, sharp and relatively short sound associated with the closing of the semilunar valves. “dup”
stenotic valve (narrow valve): stiff, narrow valve that does not open completely. turbulent flow is induced because blood must be forced through the valve at high velocity. produce abnormal whistling sound
insufficient valve (leaky valve): structurally damaged valve that does not close properly. turbulence occurs when the blood flows backward through the valve and collides with blood moving in the opposite direction. produces abnormal swishing sound
Describe the cardiac cycle during a heartbeat.
all the events involves with blood flow through the heart during one beat
systole: ventricular contraction phase
diastole: ventricular relaxation phase
cardiac cycle
late diastole: ventricular relax/fill (volume increases)
early systole: isovolumetric ventricular contraction (volume remains constant)
during systole: ejection phase (volume decreases)
early diastole: isovolumetric ventricular relaxation (volume remains constant)
steps
pressure rises causing the AV valves to shut and the SL valves are still closed (isovolumetric ventricular contraction)
ejection (pressure in left V>aorta), ventricular volume decreases
pressure in left ventricle lowers below aorta —> SL valve shuts (isovolumetric ventricular relaxation)
pressure in the ventricles falls below that of the atria —>AV opens (filling)
atrial contraction delivers the final blood to the ventricles
end-diastolic volume (EDV): amount of blood in ventricle at end of diastole
end-systolic volume (ESV): amount of blood left in ventricle at end of systole
stroke volume (SV): amount of blood ejected during systole (EDV-ESV)
ejection fraction (EF): SV/EDV (typically 50-75% at rest
atrioventricular (AV) valves: heart valves separating the atria from the ventricles and control the direction of he blood flow. open during diastole and close during systole
Describe the electrical conduction system of the heart and how it
controls the cardiac cycle.Sinoatrial (SA) node
located in right atrium near the entrance of the superior vena cava
serves as the hearts natural pacemaker, generating electrical impulses at a rate of about 60-100 beats per min. these impulses initiate the cardiac cycle by triggering atrial contraction
Atrioventricular (AV) Node
at the junction of the atria and ventricles near the interatrial septum
receives impulses from the SA node and briefly delays them. this delay allows the atria to contract and fully empty their blood into the ventricles before ventricular contraction begins
Bundle of His (atrioventricular bundle)
in the interventricular septum and divides into right and left bundle branches
carries the electrical impulses from the AV node into the ventricles. the bundle branches run along the septum towards the apex of the heart
Purkinje Fibers
throughout the ventricular myocardium
conduct the electrical impulses rapidly through the ventricles, causing them to contract from the bottom upward. this coordinated contraction helps effectively pump blood out of the heart
Control of Cardiac Cycle
impulse generation: SA node generates an impulse, initiating atrial systole, filling ventricles
conduction through AV node: impulse travels to the AV node where it is delayed to allow the atria to finish contracting
ventricular contraction: after the delay, impulse moves through the bundle of His, down the bundle branches, and into the purkinje fibers causing the ventricles to contract (ventricular systole)
repolarization: after contraction, heart muscle cells repolarize, returning to a resting state, allowing the heart to fill with blood again
Understand and apply the Frank-Starling Law.
critical factor controlling stroke volume is preload
preload is the degree to which the cardiac muscle cells are stretched before they contract. an optimal length/tension relationship is needed for maximal force generation
the amount of blood in the ventricles causes stretch and the amount of blood in he ventricles is controlled by venous return
relaxed sarcomere length in the ventricle’s normal resting is lower than the optimal length/tension relationship needed for maximal force generation
greater venous return increases contraction strength and the stroke volume (intrinsic mechanism_
Understand the regulation of cardiac output via ANS action on heart rate
and stroke volume.Heart Rate (HR): beats per min and primarily regulated by SA node. ANS influences HR through its sympathetic and parasympathetic branches
sympathetic nervous system (SNS)
activation: stress/physical activity, SNS release norepinephrine that binds to beta-1 adrenergic receptors
increases the rate of depolarization in the SA node resulting in higher heart rate. enhances conduction through the AV node and increases the force of contraction
parasympathetic nervous system (PNS)
through vagus nerve releasing acetylcholine
decreases the rate of depolarization in the SA node leading to lower heart rate. slows conduction to AV node
Stroke Volume (SV)
preload: stretch of cardiac muscle fibers at end of diastole, influenced by volume of blood returning to heart (venous return). increased venous return stretched ventricles enhancing stroke volume dur to frank-starling mech
afterload: ventricles must overcome resistance to eject blood during systole. increased afterload can reduce stroke volume. decreased afterload enhances stroke volume
contractility: intrinsic ability of the cardiac muscle to contract. SNS increases contractibility through norepinephrine, improving stroke volume.
Regulation of Cardiac Output: balance of heart rate and stroke volume determines cardiac output
increased physical activity: SNS increases HR and contractility while venous return also increases, leading to higher stroke volume. this raises cardiac output
resting state: PNS may dominate, results in lower HR and stable stroke volume, maintains lower but adequate cardiac output for resting metabolic needs
stress/emergency: SNS dominates, increases both HR and SV, maximized cardiac output
Overall
ANS provides dynamic and rapid response mech to regulate cardiac output based on needs ensuring good blood flow
Understand how blood vessel diameter affects pressure and flow, and the
intrinsic and extrinsic factors that regulate diameter.blood vessels: arteries, arterioles, capillaries, venules, veins
arteries: carry oxygenated blood away from heart
veins: carry deoxygenated blood to the heart
exception: pulmonary arteries carry deoxygenated blood to the lungs to get oxygenated and the pulmonary veins carry oxygenated blood to the heart to get sent to the rest of the body
Microcirculation
arteries: composed of large vessels that carry blood from heart
arterioles: small diameter vessels that arise from the branching of arteries when they reach the organs they are supplying
capillaries: smallest diameter vessels that are formed when arterioles branch
venules: the vessels that form when capillaries join together
veins: large diameter vessels formed by merging venules
blood vessel diameter on pressure and flow
blood flow F through a vessel is directly proportional to the pressure difference (ΔP) between the two ends of the vessel and inversely proportional to the resistance 9R) of the vessel
Poiseuille’s Law
F=ΔP/R
increase resistance (vasoconstriction), decrease flow to tissue if pressure is the same
increase flow to tissue, either increase pressure or vasodilate to decrease resistance
blood flow is determined by pressure gradient and resistance to flow caused by friction, viscosity of the blood, and vessel radius
vessel radius
Resistance (R) ∝ 1/r 4
Flow (F) ∝ r 4
blood viscosity: friction developed in blood, determined by the concentration of plasma proteins, and the number of circulating red blood cells
vessel length: friction between blood and the inner surface of a vessel is proportional to the vessel length
vessel radius: friction between blood and the inner surface of a vessel is inversely proportional to the 4th power of the vessel radius
Understand how the muscle pump and respiratory pump affect venous
return.venous return: volume of blood entering each atrium per min.
muscle pump: skeletal muscles aid in venous return.
muscle contracts, compresses veins, increasing pressure and forcing blood to flow upwards towards the heart
venous valves prevent backflow of blood
muscle pump is most effective when legs or other body parts are in motion.
increase in exercise, increase in venous return
respiratory pump: changes in pressure within thoracic cavity during breathing. driven by cyclical nature of inhalation and exhalation
inhalation: diaphragm contracts/moves down, reduces pressure in thoracic cavity while increasing abdominal pressure. pressure gradient encourages blood flow from the abdomen to thorax.
increased pressure in abdomen compresses veins and help push blood towards heart. reduced pressure in the thoracic cavity allows blood to flow into the chest towards heart more easily
exhalation: pressure difference is reversed, but continuous alternation between low thoracic pressure and high abdominal pressure during respiratory cycle supports ongoing venous return
respiratory pump aids venous return by creating a pressure gradient that helps blood flow from the abdominal vein to thoracic veins and ultimately into the heart
important during deep breathing and increases venous return during normal breathing as well as during activities like exercise
Overall
muscle pump: propel blood upward from lower extremities
respiratory pump: facilitate blood movement into thoracic cavity with each breath
together they ensure that blood is efficiently returned to the heart, helping to maintain cardiac output and the overall circulation during exercise and at rest. maintains blood pressure and facilitate cardiovascular system during physical activity
Define blood pressure and describe its regulation via baroreceptors.
baroreceptor reflex: autonomically regulates cardiac output and total peripheral resistance. respond to changes in arterial blood pressure by elevating or reducing their rate of firing. signals alter the ratio of activity in the parasympathetic and sympathetic neurons of the cardiovascular control centers
increase in arterial pressure, increase in firing arterial baroreceptors, increase in parasympathetic outflow to heart, decrease in sympathetic outflow to heart, arterioles, veins
parasympathetic stimulation —> decrease in blood pressure
sympathetic stimulation —> increase in blood pressure
Cardio 1-2
1. The cardiovascular/circulatory system consists of the heart, blood vessels and blood. Blood contains plasma, red blood cells and component of the immune system. Plasma carries electrolytes, nutrients, wastes, gases and hormones for delivery to and from virtually all cells in the body.
2. The basic anatomy of the heart (chambers and valves) and circulatory loops (systemic and
pulmonary) i.e. basically everything on slides 5-8.
pulmonary loop carries oxygen poor blood to the lungs and back to the heart
systemic
3. That the heart is a functional syncytium supported by desmosomes and gap junctions
between cardiac cells. 99% are contractile cells and 1% are pacemaker cells. Each cell is
electrically coupled with multiple neighbors.
4. The ionic basis of the action potential in pacemaker cells, in detail.
5. The conduction system: SA node, interatrial pathway, AV node, bundle of His and Purkinje
fibers.
Sinoatrial (SA) Node:
- Bundle of specialized cardiac pacemaker cells located in the wall of
the right atrium near the opening of the superior vena cava
- This node exhibits an autorhythmicity of 70 action potentials per
minute and leads the activity of the other pacemaker structures in
the heart
Atrioventricular (AV) Node:
- Bundle of specialized, cardiac pacemaker cells located at the
base of the right atrium.
- This node exhibits an autorhythmicity of 50 action potentials per
minute.
- Under normal conditions, this node follows the faster SA node at
70 A.P./min.
Bundle of His: A tract of specialized, cardiac pacemaker cells that originates at the
AV node and divides and projects into the left and right ventricles.
Purkinje Fibers:
- Small terminal fibers of specialized, cardiac pacemaker cells that
extend from the Bundle of His and spread throughout the ventricular
myocardium. Very fast conduction velocity.
- These fibers exhibits an autorhythmicity of 30 action potentials per
minute.
- Under normal conditions, they follow the faster AV node which is
following the faster AV node at 70 A.P./min.
Interatrial Pathway: a pathway of specialized, cardiac cells that
conducts pacemaker activity from the right atrium to the left atrium.
Fast conduction velocity
6. The SA node normally sets the pace and everything else follows. Resting heart rate as set by SA node = 70bpm. The AV node and Purkinje fibers also have autorhythmic activity at 50
and 30 bpm, respectively. Under normal operation, those intrinsic rates are not expressed
as all elements of the syncytium follow the leader (SA node).
7. Conduction is generally very fast except through the AV node, where a 100ms delay ensures that the ventricles contract only after the atria do.
8. The ionic basis of the action potential in contractile cells, in detail.
9. Excitation-contraction coupling in cardiac contractile cells. While there will not be any
questions on excitation-contraction coupling in skeletal muscle for this set of lectures, it
might be helpful to study that too (slides 26-28) as the similarities and differences between
the two could reinforce understanding of either.
10. The long twitch and prolonged refractory period of contractile cells allow time for ventricles to fill with blood prior to pumping.
11. How to read an ECG. Note: these are bulk current source recordings, not intracellular
recordings, and therefore you cannot interpret upward and downward deflections as
depolarization and hyperpolarization.
12. The cardiac cycle, in detail (slides 36-42).
13. Heart sounds/murmurs, in detail (slides 43-45, with emphasis on 45).
Cardio 3-5
1. Cardiac output = heart rate x stroke volume.
2. Heart rate is regulated by both branches of the autonomic nervous system, while stroke
volume is regulated extrinsically by the sympathetic nervous system and intrinsically by the
volume of venous return (Frank-Starling mechanism).
3. The mechanisms (neurotransmitter, receptors, downstream effects on ion channels and
slop of AP) by which sympathetic and parasympathetic input speed and slow heart rate,
respectively.
4. The influence of the sympathetic branch on ventricle contractility and stroke volume.
5. The Frank-Starling mechanism, in detail (see NEW slide).
6. Basic anatomy of the systemic circulation: aorta, arteries, arterioles, capillaries, venules,
veins and superior/inferior vena cava. A sense of the relative number, internal radii and
total cross-sectional areas of these structures is useful, but the specific numbers will not be
on the exam.
7. Flow = pressure gradient / resistance. While resistance is determined by several factors, the
main regulation is vessel radius. R is proportional to 1/r4 and therefore flow is proportional
to r4 . Thus, small changes in vessel radius can lead to large changes in local flow rate.
8. (smooth) muscular arteries constrict or dilate to change relative blood flow to different
organs in a task-specific manner.
9. Elastic arteries serve as pressure reservoirs to ensure continuous blood flow.
10. How a sphygmomanometer works.
11. Intrinsic and extrinsic control of arteriole constriction/dilation.
12. Basic capillary structure and mechanisms of exchange for small water-soluble substances,
lipid soluble substances and proteins.
13. The simple definitions of exchange via diffusion, bulk flow, ultrafiltration and reabsorption.
14. The structure and function of venous valves.
15. The skeletal muscle pump and respiratory pump increase venous return.
16. Blood pressure is monitored by baroreceptors (located in CNS) which signal changes in
pressure with increased or decreased firing rate. Through connections to the ANS, this leads
to changes in heart rate, contractility and vessel constriction which collectively alter blood
pressure. This is all nicely summarized in slide 46, which illustrates a homeostatic reflex and
negative feedback control e.g. when baroreceptors sense that blood pressure is too high,
parasympathetic tone will be turned up and sympathetic tone turned down in order to
lower BP
Respiratory Physiology Learning Objectives
Anatomy of the respiratory system
Understand the difference between external and internal (cellular) respiration
external respiration steps
ventilation or gas exchange between atmosphere and air sacs (alveoli) in the lungs
exchange (diffusion) of O2 and CO2 between air in the alveoli and the blood in the pulmonary capillaries (take in O2 by inhalation, expel CO2 by exhalation)
transport O2 and CO2 by the blood between lungs and tissues
exchange O2 and CO2 between the blood in the systemic capillaries and the tissue cells
goes to internal (cellular) respiration in tissue cells
cellular respiration
occurs in cells (mitochondria)
O2 delivered by blood (via external respiration) and is used by mitochondria to break down nutrients (glucose) through metabolic pathways (glycolysis, CAC, ETC)
this produces ATP, CO2 (waste), and water (waste)
oxygen acts as the final electron acceptor in the ETC (aerobic)
purpose: produce ATP (cellular functions) and CO2 (waste to be transported back to lungs via blood and expelled during external respiration/exhalation)
function
gas exchange: O2 brough into body and CO2 is removed
blood pH regulation: control level of CO2 in blood
protect: filter from inhaled pathogens, pollutants, and irritants
sound protect: air passing larynx allows for vocalization
BP regulation: influence BP through fluid dynamics and ACE system
temp regulation: release heat through breath, regulate body temp
metabolism/hormonal regulation: involved in certain metabolic and hormonal processes (ACE conversion)
Describe the general structure and function of the respiratory system.
respiratory airways leading into the lungs
lungs
structure of thorax involved in producing movement of air through the airways into and out of the lungs
trachea and large bronchi: rigid, non muscular tubes and rings of cartilage prevent collapse
bronchioles: no cartilage to hold it open, walls contain smooth muscle innervated by autonomic nervous system (ANS)
parasympathetic stimulation constricts
sympathetic stimulation weakly relaxes
epinephrine relaxes (2 receptors)
alveoli: thin walled inflatable sacs, function in gas exchange, walls consist of flattened type I alveolar cells. type II alveolar cells secrete pulmonary surfactant. alveolar macrophages guard lumen. pulmonary capillaries encircle each alveolus
surfactant produced by type II alveolar cells disrupts hydrogen bonding of water lining the alveolar wall
decreases surface tension so groups of little bubbles don’t collapse into a smaller number of bigger ones
surfactant induced by cortisol just prior to birth; premature infants may need synthetic glucocorticoid treatment to ensure proper lung function
Describe the specific function of the bronchioles (compare to arterioles), including their regulation by the autonomic nervous system.
Bronchioles
Arterioles
Function
Conduct and regulate airflow to alveoli
Regulate blood flow to tissues and organs, control blood pressure
Structure
Smooth muscle, no cartilage, leading to alveoli
Smooth muscle, smaller branches of arteries leading to capillaries
Regulation by ANS
- Sympathetic: bronchodilation (widening airways)
- Sympathetic: vasoconstriction (narrowing arterioles)
- Parasympathetic: bronchoconstriction (narrowing airways)
- Sympathetic: vasodilation (increased blood flow in certain organs)
Effect of Sympathetic Activation
Increases airflow (during exercise, stress, etc.)
Increases resistance and blood pressure (fight or flight response)
Effect of Parasympathetic Activation
Decreases airflow (during rest)
Less influence, but can cause vasodilation in digestive organs
Local Regulation
Affected by CO₂, O₂, and pH levels in the lungs
Affected by CO₂, O₂, pH, and metabolic activity in tissues
Describe the structure and function of the alveoli, including the cell types within the alveoli and the role of pulmonary surfactant.
details
Structure
- Tiny, sac-like structures with thin walls.
-alveolar wall (epithelial) thin for easy diffusion of O2 and CO2
- Surrounded by a dense network of capillaries for gas exchange.
Primary Function
- Gas exchange (oxygen in, carbon dioxide out).
- Large surface area and thin walls enhance diffusion.
Cell Types
- Type I Alveolar Cells: Thin, flat cells for gas exchange.
- Type II Alveolar Cells: Secrete pulmonary surfactant and maintain alveolar structure.
- Alveolar Macrophages: Immune cells that remove foreign particles and pathogens.
Pulmonary Surfactant
- Reduces surface tension to prevent alveolar collapse and facilitate breathing.
- Helps stabilize alveolar size and makes breathing easier.
- Prevents atelectasis (collapse of alveoli).
Mechanism of ventilation
Describe the mechanics of the respiratory cycle and how air pressure differences are created to move air in and out of the alveoli.
changes in intra-alveolar pressure produce flow of air into and out of the lungs
if this pressure is less than atmospheric pressure, air enters the lungs. if opposite occurs, air exits from the lungs
boyle’s law states that at any constant temp, pressure exerted by gas varies inversely with the volume of gas
Inhalation | Diaphragm and intercostal muscles contract, expanding the chest. | Intrapulmonary pressure decreases below atmospheric pressure. | Air flows into the lungs due to lower pressure inside the lungs. |
Exhalation | Diaphragm and intercostal muscles relax, causing the chest to contract. | Intrapulmonary pressure increases above atmospheric pressure. | Air flows out of the lungs due to higher pressure inside the lungs. |
Understand the role of the pleural sac and intra-pleural pressure in respiration.
Pleural Sac: double layer structure surrounding lungs (two layers)
visceral pleura: inner layer (attached to lung), covers lung tissue and direct contact with lung parenchyma
parietal pleura: outer layer (lines chest wall, diaphragm, mediastinum)
between these two layers is interpleural fluid: lubricant secreted by surfaces of pleura
Pressure in Ventilation
atmospheric (barometric) pressure: weight of gas in atmosphere on objects on earth
intra-alveolar pressure (intrapulmonary pressure): pressure within alveoli
intrapleural pressure (intrathoracic pressure): pressure within pleural sac—exerted from outside the lungs within the thoracic cavity
during the respiratory cycle
during inspiration, intra-alveolar pressure is less than atmospheric pressure
during expiration, intra-alveolar pressure is greater than atmospheric pressure
at the end of both inspiration and expiration, intra-alveolar pressure is equal to atmospheric pressure because the alveoli are in direct communication with the atmosphere and the air continues to flow down its pressure gradient until the two pressure equilibrate
throughout the respiratory cycle, intrapleural pressure is less than intra-alveolar pressure
thus a transmural pressure gradient always exists, and the lung is always stretched to so degree, even during expiration
Respiratory rate versus alveolar ventilation rate
Understand the difference in pulmonary versus alveolar ventilation rate and the contribution of anatomical dead space to their difference.
not all tidal volume actually fills the alveoli. therefore two equations
pulmonary ventilation = tidal volume (ml/breath) X respiratory rate (breath/min)
alveolar ventilation = (tidal volume - dead space) X respiratory rate
pulmonary: total air entering and exiting the lungs, includes dead space
alveolar: volume of air participating in gas exchange, excludes dead space
Describe the 4 factors that contribute to the composition of alveolar air to be different from atmospheric air.
Oxygen: lower in alveolar air compared to atmospheric air
Carbon Dioxide: higher in alveolar air compared to atmospheric air
Water Vapor: present in alveolar air due to humidification, contributing to higher partial pressure of water vapor in alveolar air
Nitrogen: relatively similar, but lower in alveolar air because it is somewhat displaced by water vapor
Explain the mechanisms by which hemoglobin contributes to the transport of O2 from the lungs to tissues and CO2 from tissues to the lungs via circulation.
Oxygen Transport (lungs to tissue)
in lungs, oxygen binds to hemoglobin due to high pO2 (partial pressure), bohr effect- when O2 binds to hemoglobin, causes conformational change increasing affinity for more O2 resulting in hemoglobin becoming nearly saturated with oxygen
in tissues, low pO2, high CO2, and low pH promote release of O2 from hemoglobin, bohr effect- CO2 enters RBC and converted into carbonic acid (H2CO3) by carbonic anhydrase, then dissociates into bicarb (HCO3-) and hydrogen ions (H+)
Carbon Dioxide Transport (tissues to lung)
in tissues, CO2 is transported as bicarbonate (chloride shift), dissolved CO2, and carbaminohemoglobim. bohr effect- releases O2 and facilitates transportation of CO2
in the lungs, the lower pCO2 causes CO2 to be released from the hemoglobin and bicarbonate to convert back to CO2 for exhalation. bohr effect- when O2 binds to hemoglobin, it enhances the release of CO2 by reducing hemoglobins affinity for CO2, thus facilitating exhalation
Understand the differences in partial pressures of gases in the atmosphere and in alveoli.
O2: pO2 is higher in atmospheric air than in the alveoli due to constant diffusion of oxygen into the blood in the alveolar capillary interface
CO2: pCO2 is higher in alveolar air compared to atmospheric air because CO2 is continually diffusing from the blood into the alveoli to be exhaled
H2O vapor: pH2O is virtually absent in atmosphere but is significant in alveolar air due to humidification in the respiratory passages
N2: pN2 is relatively similar in both atmospheric and alveolar air as nitrogen is inert and does not participate in gas exchange
Describe the partial pressure gradients that lead to gas exchange at the lungs and peripheral tissues.
gas exchange occurs through diffusion of gases along partial pressure gradients that rely on Fick’s law of diffusion which states that gases move from high partial pressure to low partial pressure areas. the partial pressure gradients of O2 and CO2 are crucial for movement of gases into and out of the blood ensuring oxygen reaches tissues and carbon dioxide is removed
Lungs
O2 diffuses from the alveoli into the pulmonary capillary blood
CO2 diffuses from the pulmonary capillary blood into the alveolar air
Tissues
O2 diffuses from the arterial blood into the tissues
CO2 diffuses from the tissues into the venous blood where it is transported back to the lungs
Gas transport: O2 versus CO2
Describe the ways that oxygen and carbon dioxide are transported in blood.
partial pressure of oxygen determines the percentage of hemoglobin saturation
percent saturation is high where partial pressure of oxygen is high (lungs)
percent saturation is low where the partial pressure of oxygen is low (tissues). at the tissue cells, oxygen tends to dissociate from hemoglobin, the opposite of saturation
oxygen is mainly transported bound to hemoglobin with a small amount of dissolved plasma
carbon dioxides is primarily carried as bicarbonate ions in plasma with significant amounts also bound to hemoglobin and a smaller portion dissolved directly in plasma
exchange of gas occur by diffusion down the concentration gradient (driven by partial pressure gradient)
Describe the role of hemoglobin in O2 and CO2 transport, and the role of the heme group.
O2: hemoglobin binds oxygen in the lungs via the iron in the heme group. the heme groups undergo cooperative binding, making hemoglobin highly efficient at picking up oxygen and releasing it when needed in tissues
CO2: hemoglobin aids in CO2 transport. when bound to heme group, it is carbaminohemoglobin which promotes a conformational change that reduces hemoglobin’s affinity for oxygen (bohr effect), which makes it release the oxygen in tissues where CO2 concentrations are high. bohr effect- presence of CO2 and H+ decreases pH of blood, promotes release of O2 from hemoglobin.
Understand each key part of the oxygen hemoglobin dissociation curve in terms of its functional significance at the lungs and peripheral tissues.
lungs (high pO2): hemoglobin binds oxygen efficiently (plateau region of curve), ensuring oxygen uptake into the blood
peripheral tissue (low pO2): hemoglobin releases oxygen efficiently (steep region of curve), ensuing oxygen delivery to metabolically active tissues
rightward shift (increase CO2, decrease pH, increase temp): facilitates oxygen unloading in active tissues where oxygen demand is high
leftward shift (decrease CO2, increase pH, decrease temp): facilitates oxygen loading in the lungs where oxygen concentration is high
shape of oxygen-hemoglobin dissociation curve allows hemoglobin to optimize both uptake of oxygen in lungs and its release in tissues based on environmental and metabolic conditions
Understand the importance of the Bohr effect, what causes it, and what benefit it has for gas exchange at tissues.
its describes how changes in pH and CO2 concentration influences the affinity of hemoglobin for O2
important for efficient oxygen delivery
bohr effect: increase CO2 and low pH reduces hemoglobin’s affinity for oxygen, promoting oxygen release in tissues where CO2 levels are high
effect is essential for efficient oxygen delivery to tissues that need it most, especially during exercise or in tissues with high metabolic rates
Understand the Haldane effect and what it means for gas exchange in the tissues and the lung.
Haldane effect: describes how the binding of oxygen to hemoglobin (Hb) influences he ability of hemoglobin to bind and transport CO2. hemoglobin’s affinity for CO2 is inversely related to its affinity for O2.
O2 binding to hemoglobin reduces its capacity to carry CO2 while CO2 binding to hemoglobin reduces affinity for O2
haldane effect enhances transport of CO2 from tissues to lungs
tissues: O2 is being used up and CO2 is produced, hemoglobin is deoxygenated and has high capacity to find to CO2 facilitating transport to lungs
lungs: oxygen is abundant so it binds to hemoglobin, reducing affinity to CO2 allowing CO2 to be released from blood and exhaled
What makes us breathe? Chemical factors influencing ventilation rate
Define hyper and hypoventilation, and understand what it means for arterial blood O2, CO2, and pH.
hypoventilation: underventilation in relation to metabolic requirements, resulting in increased pCO2 and respiratory acidosis
hyperventilation: increased pulmonary ventilation in excess of metabolic requirements, resulting in decreased pCO2 and respiratory alkalosis
hyperventilation | hypoventilation | |
Ventilation Rate | Increased (rapid or deep breathing) | Decreased (slow or shallow breathing) |
CO₂ Levels (pCO₂) | Decreased (hypocapnia) | Increased (hypercapnia) |
Oxygen Levels (pO₂) | Normal or slightly increased | Decreased (hypoxia) |
pH | Increased (alkalosis) | Decreased (acidosis) |
Effect on Breathing | May be compensatory for metabolic acidosis | May occur due to respiratory or neurological conditions |
Describe the role of the brainstem respiratory centers in the regulation of respiration.
Medullary respiratory centers
dorsal respiratory group (DGR): inspiratory neurons; active in normal quiet breathing
ventral respiratory group (VRG): inspiratory and expiratory neurons; activated upon demand
Pons respiratory centers (PRG)
modulate activity of medullary centers to promote smooth breathing rhythms
Pre-Botzinger complex
a region rostral from the VRG where respiratory rhythm is generated
Hering Breuer reflex
stretch receptors in the smooth muscle of the bronchioles inhibit the medullary center to prevent over-inflation of the lungs
Understand the chemical factors that influence respiration, and where in the body their chemoreceptors are located.
carotid bodies are located in the carotid sinus
aortic bodies are located in the aortic arch
Stimulation on peripheral chemoreceptors
decrease in pO2 in arterial blood: stimulates only when the arterial pO2 has fallen to the point of being life-threatening
increase in pCO2 in the arterial blood: weakly stimulates
increase in H+ in the arterial blood: stimulates; important in acid-base balance
Stimulation on central chemoreceptors
decrease in pO2 in arterial blood: directly depresses central chemoreceptor and respiratory center
increase in arterial blood/increase in H+ in brain ECF: strongly stimulates; dominant control of ventilation
increase in H+ in arterial blood: no effect; cannot penetrate blood-brain barrier
Describe the location and role of the peripheral chemoreceptors in sensing partial pressures of O2 and CO2, and arterial pH changes - and their role in homeostasis.
peripheral chemoreceptors: carotid bodies (bifurcation of common carotid artery) and aortic bodies (aortic arch), sensitive to O2 levels and to a lesser extent, CO2 and pH
primarily monitor O2 levels and increase ventilation when O2 falls below a critical level (hypoxia).
detect high CO2 (hypercapnia) and low pH (acidosis) by responding to changes in CO2 concentration, which affects blood pH. send signal to brain to increase ventilation and expel CO2
regulate blood gases (O2 and CO2) and pH to maintain stable conditions, ensuring efficient gas exchange and prevent harmful shifts in acid-base balance
Describe the role of the central chemoreceptors in sensing changes in arterial CO2 via proportional changes in brain pH - and their role in homeostasis.
central chemoreceptors: medulla oblongata (brainstem), primarily detects changes in pCO2 and pH in the cerebrospinal fluid (CSF) which is influenced by CO2 levels in blood
when CO2 increases in blood, it diffuses into the CSF leading to formation of carbonic acid and production of H+ which lower pH of the CSF. chemoreceptors sense acidification and stimulate medullary respiratory center to increase ventilation
regulate CO2 blood levels and maintain acid-base balance. detect high CO2 (hypercapnia) or low (acidosis), they initiate increase breathing to expel CO2, restoring normal blood pH and CO2 levels
reduce breathing when low CO2 (hypocapnia) to retain CO2 and correct high pH (alkalosis)
central chemoreceptors regulate CO2 and pH and work together with peripheral chemoreceptors that sense O2 and Co2 levels to coordinate body’s response to changes in blood gases, ensuring proper oxygenation and CO2 elimination