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Title: Physiology notes by Parth Ghotekar
Description: Complete human physiology notes by a 2nd year medical student at the University of Szeged, Hungary.
Description: Complete human physiology notes by a 2nd year medical student at the University of Szeged, Hungary.
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Table of Content
Chapter Name (#1)
Page no
...
Introduction
3
Glucose Metabolism
235
Control Theory
5
Osmovolume Regulation
248
Cell Membrane & Transport
9
Potassium & Calcium
262
Cell Signalling
18
Acid-Base Balance
270
Cell & Membrane
Electrophysiology
21
Thermophysiology
278
Synapsis
29
Sport Physiology
284
Neurotransmitters
35
Reproductive physiology
291
Autonomic Nervous System
38
Cerebral Circulation
317
Skeletal & Smooth Muscles
44
Somatosensory System
324
Blood Plasma
56
Smell & Taste
338
RBC
64
Vision
342
WBCs & Immune System
70
Hearing
359
Hemostasis
79
Motor physiology
370
Respiration
82
CNS
390
Heart
93
Sleep
397
ECG notes
104
Limbic System
400
Cardiovascular system
108
Hypothalamus
402
Circulation
130
Renal physiology
141
GI physiology
161
Nutrition
186
Hormones
213
Thyroid hormones
229
1
Note
These notes are full of text only and no images are present
...
Good luck and may the force be with you
...
Metabolism happens via the cell membrane which is very important
...
In multicellular organisms, individual cells are not in contact with the environment
...
Nervous and Humoral (hormones) systems helps maintain the normal conditions in the cells
...
Diffusion is usually used but only work over short distances
...
Homeostasis - The processes which maintains nearly constant internal conditions
...
38-7
...
60% of total body weight is is water
...
From this 20%,
15% is interstitial fluid
4-5%is blood plasma
1% is transcellular fluid
Prolactin: Milk production
Oxytocin: Milk ejection
4
Control Theory
Feed forward control systems:
Anticipates the disturbances coming so the body prepares for the changes
Feedback control systems:
The disturbance occurs and acts on the body causing a change
...
Open loop control system:
Uses effectors to get the desired response
...
Guidance vs Control
Guidance:
Feed forward
No feedback
Not sure exactly what happens
Stable
No acting back
Control:
Feedback
Knows exactly what happens
A bit unstable
Acting back
In a control circuit:
- Controlled parameter
5
- Sensor
- Controlling center
- Effector system
- back to controlled parameter
Set Point - The optimal value of something
...
Control circuits can be Neuronal or Humoral
Neuronal: Fast, Well Localized, Shorter acting time
Humoral: Slower, More diffused, Greater acting time
...
Excess thyroid hormone prevents its own production
...
Humoral Controlling Circuit:
Hypothalamus
Ant
...
pituitary gland
...
Neuronal + Humoral = Mixed control circuit
Example of Mixed Control Circuit is the oxytocin reflex
...
Neuronal afferentation & Humoral efferentation
...
(Eg: saliva secretion)
Negative feedback is very common
...
Positiove feedback is rare
...
To make the control range wider: effector mechanisms + Behavioural mechanisms
...
There is usually some residual error
...
In a normal case:
disturbing signal pushes the system out of balance and then control system gets activated
In servo mechanisms:
Reference range changes and then control system gets activated
...
7
afferent
efferent
branch
branch
Receptor ------------> CNS -----------------> Effector
Effector branches can be motor neurons and autonomic nerves
Effectors are skeletal muscles and glands
The receptor checks the actual value against controlled parameters
...
Humoral regulation:
Hypothalamus ----------> Hypophysis ----------> Target gland
eg:
TRH ---------------------------> TSH ---------------------> (At thyroid) T3,T4
T3,T4 hormones give feedback to the hypothalamus
...
Insulin is released when blood glucose levels rise because insulin reduces blood glucose
concentration by encouraging the uptake of glucose and its conversion to glycogen
...
Baby sucking on mothers nipples has both humoral and neural systems involved
...
8
Cell membrane & Transport
Biomembrane functions:
- Transport (regulates intracellular & intercellular transport processes)
- Compartmentalization (closed room for chemical reactions)
- Signal sending & transduction (senses and transducts signals extracellular signal to
intracellular area)
- Interceullular interactions
- Biomechanical activity (with membrane bound enzymes)
- Energy production (mitochondrial ATP synthesis)
- Cell - Cell recognition (distinguishing between foreign & own cells/particles
...
Has a polar, hydrophilic head (phosphate group)
and a hydrophobic, apolar tail/chain (fatty acid chain)
Since both hydrophilic and hydrophobic parts both exist, it is amphipathic
...
Van der Waals forces stabilizes the membrane structures
...
Glycolipids are carbohydrate units bound ontop of the head group of lipids
...
They can have different 3D structures
...
Lipid interdigitation: Phosphlipid molecules with different fatty acid length arepositioned
accordingly
...
Phospholipid molecules can move throughout the
membrane
...
- rotation: Rotates around its own longitudinal axis
- flexion: Fatty acid chains flex, bend sideways
...
Few micrometer per second
...
Uses the
enzyme flippase
...
At high temperatures:
Cholesterol decreases membrane fluidity
...
Lipid rafts:
10
Part of phospholipid bilayer where the components of of the bilayer is different compared
to the rest of the bilayer
...
Thus the membrane is thicker and more stable
...
Has caveolin protein
...
Transmembrane proteins have intramembrane, cytoplasmic and extracellular domains
...
There are also membrane proteins that are:
In the inner layer only
In the outer layer only
...
Glycolipids connect with each other
to form it
...
It is better to have the proteins condensated at one site where they are required
...
11
Osmosis: Movement of water molecules from a region of high water/slovent potential to a
region of low water/solvent potential through a semi permeable membrane
Osmolarity = Amt of solute (mol) / Volume of solvent (l)
Use osmolarity for highly diluted solutions
Osmolality - Amt of solute (mol) / Mass of solvent (kg)
Use osmolality for highly concentrated solutions
...
Water cannot diffuse fast enough through a membrane due to its high concentration
...
Faciliated diffusion relies on intramembrane proteins that can undergo conformational
changes
...
There is a maximal transporter speed
...
Ping pong mechanism: Irrevesrsible conformational change
...
Inhiibtion of tranposrter can be competitive, non competitive or uncompetitve
...
Energy is required
...
Usually sodium gradient is used
...
ATP molecule binds and loses a phosphate group
...
Release of ADP causes the pump to return to its original shape and potassium is
transported inwards
...
1/3 of total cellular energy is spent on the sodium potassium pump
...
With the use of ATP phosphorylation, Ca2+ ions are pumped out of the cell
...
Due to the change in intracellular Ca2+ concentrations:
Protein activation
Muscular contraction
Neuronal transmission
Apoptosis
...
Usually 10^-7 M
ABC transporters
13
ATP
Binding
Casette sequence
Has a double nucleotide binding domains
Funtions:
Bile secretaions of hepatocytes
Drug elimination
Drug and toxin transport
Transmembrane ion channels are proteins that transport ions along the electrochemical
graidient towards the space with lower concentration
...
Such ion channels can be:
Ligand gated
Phosjyrylation gated
Voltage gated
Strech or pressure gated
Ion channels are selective
...
Electrochemical gradient influences the direction of ion transport
...
Very important in neural communication:
1) Neurotransmitters go into vesicles in the cell
14
2) Vesicles dock at and join plasma membrane and releases neurotransmitters via
exocytosis (triggered by influx of Ca2+) into extracellular matrix
...
Phospholipids have hydrophilic phosphate head and 2 hydrophobic fatty acid chains
...
Integral proteins are present in the membrane
...
Must use
integral proteins
...
Primary active transport uses energy from ATP hydrolyzation
...
Diffusion, Osmosis and facilitated diffusion don't use energy
...
Neurotransmitters produced in neurons are transported to the synaptic cleft by
exocytosis
...
Proteins are next to phospholipids within it
...
Water soluble molecules only pass through via transporters or channel proteins
...
Substances do not bind to the channel proteins
...
Water channels and ion channels can be opened and closed by:
membrane potential changes
Chemical substances
15
Mechanical effect
Carrier proteins have a maximum capacity
...
If 2 substances are transported by a carrier protein in the same direction - symport
If 2 substances are transported by a carrier protein in opposite directions - antiport
...
All active transport and facilitated diffusion uses carrier proteins
...
Primary active transport = Energy is provided by ATP
...
Secondary active transport: No ATP is split
...
Voltage gated - due to change in membrane potential
Ligand gated - Due to ligand binding
Strech and movement gating - Due to stretch
Phosphorylation gated - Due to addition or removal of phosphate group
...
In osmosis, water flows to the more concentrated area (place of higher osmolarity)
Na/K pump moves both the ions against their concentration gradient
...
Indirectly, ionic gradients do use ATP
...
G proteins Activate 2nd messenger systems (cAMP, Ca2+)
G proteins activate phospholipase C which gives rise to IP3 and DAG
...
- Tyrosine Kinase Receptors do phosphorylation
...
Opening a sodium ion channel opens the neighbouring Na+ channels
...
Resting Na+ permeability is low
...
Absoluete Refractory period - Cant evoke an action potential at all
Relative Refractory period - A second action potential can be activated but initiation will
require a greater stimulus than before
...
Depolarization also deactivates the Na+ channels with a delay
...
Impules jump from one
Node of Ranvier to the next Node of Ranvier
...
Seperate from membrane transport
...
Ligand binding is super specific
...
Receptors: Specifically recognize and bind to ligands with high affinity
...
Ions and small molecules can be
transported freely via passive transport
...
Local communication
method, communicating cells are very close to one another
...
Similar to endocrine but distance is very low
...
Endocrine: Hormones
...
in bloodstream
...
Physical contact between cells
...
Receptors in the cell membrane undergo conformational change upon ligand binding thus
signal is relayed across the membrane to the receptor cytoplasmic domain
...
There is always a terminating downstream mechanism
...
Competitive antagonist: Competes for ligand binding site
Non competitive antagonist: Allosteric binding site
...
Specificity of kinases and phosphatases is super high
...
Phosphatases remove phosphate molecules
...
G proteins have guanine nucleotides - GDP and GTP
...
There is also effector activation
...
Arrestin binding (competitive inhibition)
First messenger is a ligand that causes intracellular changes
...
Second messengers (cAMP) moves intracellularly
...
Activates many ceullar activities
Phospholipase C causes diacylglycerol (DAG) and IP3 to be released
...
IP3 is a soluble second messenger
...
Glucose is stored as glycogen
...
19
Receptor Protein Tyrosin Kinases (RTKs)
...
Due to ligand binding, 2 RTKs bind together and thus signalling complexes bind are started
Insulin receptors are present as stable dimers
...
(Transautophosphyrlation)
In type 2 diabetes, due to overstimulation of insulin, insulin receptors become desensitized
and stop responding
...
Ca2+ signalling can be global or local
...
Activates cGMP which relaxes smooth
muscle cells
...
Receptors can be present on the nuclear membrane itself
...
20
Cell & Membrane Electrophysiology
Transmembrane potential can be changed by:
the types of pumps present
...
Transmembrane potential is present in almost every cell
...
Howerve, in the pacemaker of the heart, this transmembrane potential oscillates
...
5
150
Ca2+
1
...
0001
Steady state: Point at which diffusion force and electrical force is the same at a given
potential level
...
This potential level is the Nerst potential
...
Nerst equation: Determines equilibrium potential of a given ion having different
extracellular and intracellular concentrations
...
Nerst Potentials:
Na = +60mV
Ca = +130mV
K = -90mV
21
Cl = -80mV
The entire membrane potential is influenced by many ions, ion pumps, Donnan Effect
(immobile charged macromolecules ka effect in intracellular effect)
Goldman-Hodgkin-Katz (GHK equation) determines the whole resting membrane potential
...
04
:
0
...
Whenever membrane potential becomes more negative, it is hyperpolarization
...
3 Na+ go into extracellular fluid
...
Plasma membrane can act as a capacitor
...
Natural changes of membrane potential:
- Post synaptic potentials (Na+ ion channels open, Na+ ion flood into cell)
- Receptor potentials
- Pacemaker potentials
In graded membrane potentials:
There are graded changes
...
Doesnt cross threshold
...
Not a proportional response
...
22
Myelin sheaths decrease axonal capacitance and increases axonal membrane resistance
...
Thus impulses get sped up due to myelin
sheaths
...
At depolarization (-40 mV), ion channels are opened
...
As depolarisation occurs, Na+ channels show inward current (Na+ ions go into the cell)
...
-40mV is when depolarisation begins and takes place
...
(This is the reversal potential for Na+
...
-90mVmV is the reversal potential for K+
...
At resting potential, Na+ concentration is greater outside the cell and K+ concentration is
greater inside the cell
...
Different cell types show different action potential widths
...
All
or none principle
...
Action potentials are generated in the axon initial segment
...
Na+ channels can be inactivated which stops ions from going through
...
There is absolute and relative refractory period
...
Relative: Is the interval
immediately following the Absolute Refractory Period during which initiation of a second
action potential is INHIBITED, but not impossible
...
IV lowest for both
...
Depolarisation occurs at the end of the presynaptic neuron
...
Ca2+ causes vesicles containing neurotransmitters to dock at the plasma membrane
...
Endocytosis is receptor mediated
...
5
15
150
Electrochemical gradient drives the movement of ions
...
This is due to the
presence of carrier proteins
...
GLUT 1 present on RBC membranes
GLUT 2 in the islets of Langerhans
...
Nephron is the functional and morphological unit of kidney
Na+ - Glucose transporter is present in nephrons
...
If there is a hyphen between 2 things: Co transporter (Na+ - Glucose)
If there is a slash between 2 things: Anti transporter (Cl-/HCO3)
25
Osmotic pressure: the pressure value at which osmosis stops
...
Doesnt always have to be water
...
Makes intracellular more -ve and makes extracellular more +ve
...
Resting membrane potential is the potential difference between the 2 sides of the
membrane when there is no depolarization or hyperpolarization
...
Na+ has very low membrane permeability
...
31)
F = Faraday Constant (96485)
T = temperature in Kelvin
P Na [Na+ o] means:
permeability of Na+ x Concentration of Na+ intracellularly
...
Local potential changes wont spread on the plasma membrane
...
Eg: Sensory neurons)
Pacemaker potential (at pacemaker cells in heart)
Electrotonic potential
Post synaptic potential
...
If depolarization crosses the threshold then this causes action potential
...
Chemical synapse has neurotransmitters and receptors
...
If a post synaptic potential caused depolarisation - Excitory post synaptic potential
If a post synaptic potential causes hyperpolarization - Inhibitory post synaptic potential
...
Nerst equation is for 1 ion only
...
Na+ equilibrium potential is +60mV
K+ equilibrium potential is -110mV
K+ is the most permeable ion to the lipid due to the many K+ leaky channels
...
After crossing the threshold, very sharp increases in slope due to voltage gated channel
...
Increases permeability of Na+
...
These voltage gated channels can be open or inactive
...
Tetraethyl ammonium (TEA) blocks voltage gated K+ channel
...
Electrotonic Potential is the potential before an action potential
...
Electrotonic potential is due to ligand gated leaky channels
...
Places where neurons communicate with each other are called synapses
...
Electrical synapses have gap junctions between 2 neurons
...
Transmitter types:
1) Excitaory transmitters
...
Such transmitters are stored in round vesicles in the presynaptic neuron
...
2) Inhibitory transmitters (Gray II)
Eg: GABA
...
Inhibitory synapses are symmetrical
3) Modulatory transmitters
Uses monoamines as neurotransmitters
...
(Have a black spot in
the center)
4) Peptide transmitters
Stored in large, dense vesicles
...
Post synaptic
density contains proteins
...
There are tunnels/channels (Connexon pores) which connect the membranes
...
Connexon pores allow ions, ATP, cAMP, amino acids to move from one membrane to another,
in either direction
...
Direction of transport depends on concentration
...
No synaptic delay
...
Chemical Synapses
There are no pore/tunnels between 2 membranes
Needs neurotransmitters and receptors
Relatively slow
Synaptic Delay (Time you need to transfer info from one neuron to another via a chemical
synapse)
One way transport
...
A synapse is made up of a tetrapartite
Tetrapartite:
Presynaptic terminal + Post synaptic membrane + Astrogilal cells + Microglial cells
1) Transmitters are stored in vesicles in the presynaptic terminal
2) Action potential arrives at the presynaptic terminal
3) Opening of voltage gated calcium channels
30
4) Calcium ion inflow into presynaptic terminal
...
Synaptic Vesicle Fusion:
1) Vesicle docking
This happens in the active zone of the presynaptic membrane
...
In the vesicle membrane: Synaptobrevin & Synaptotagmin
In pre synaptic membrane: SNAP-25, Syntaxin
...
At this stage, there are no pores between vesicles and
membranes
...
Neurotransmitter content of 1 vesicle = 1 quantum
...
EPSP - Excitatory Post Synaptic Potential
31
Excitatory transmitter - Glutamate
...
This causes local and graded depolarisation of the post synaptic membrane
IPSP - Inhibitory Post Synaptic Potential
Inhibitory transmitter - GABA/Glycine
After binding to a post synaptic receptors, inhibitory neurotransmitters cause an inflow of
Cl- ions via chloride channels into the post synaptic neuron
...
This causes hyperpolarization in the post synaptic neuron
...
Temporal Summation:
EPSPs and IPSPs do not appear at the same time
...
Summation allows the threshold to be crossed
...
5 millisecond
...
Connexons are made from 6 connexions with a hole in between
...
Chemical synapses
Presynaptic terminus is always a neuron
...
Neurotransmitters:
- Acetylcholine
- Amines (Dopamine, Serotonin, Noradrenaline, Adrenaline)
- Gases (NO, CO)
- Peptides (VIP)
- Amino Acids: Glycine, Glutamate, GABA
...
Ca2+ channels open
...
Calmoduline + Ca2+ activates the calmoduline-calcium dependent kinase
...
After vesilce docks at presyanptic membrane, neurotransmitters are released into
synaptic cleft
...
Metabotropic receptors have 5 transmembrane domains
...
After a ligand binds to a metabotropic receptor, secondary messenger system is activated
...
(Has 3 different subunits)
Alpha subunits binds the GDP - Resting phase
...
33
Gq ka alpha subunit will activate phospholipase C
...
IP3 goes to sarcoplasmic reticulum of cell
...
Ca2+ also acts as a second messenger
...
Gs ka alpha subunit activates adenyl cyclase which makes cAMP from ATP
...
Gi inhibits adenyl cyclase and prevents cAMP production
...
Action potential shape is characteristic for each cell type
...
Nerve cell resting potential = -70mV
...
(Na+ flows into cell because voltage
gated Na+ channel open)
After opening, Na+ channels become inactive
...
Membrane
potential becomes more and more negative
...
Na+/K+ pump restores resting membrane potential
...
They often use co transmitters
...
They prolong the
EPSPs and IPSPs
Neurotransmitter - Co Transmitter
Acetylcholine - Vasoactive Intestinal Polypeptide (VIP)
Norepinephrine - Neuropeptide (WPY)
Glutamate - Substance P (SP) / Calcitonin Gene Related Peptide (GRP)
Classification of neurotransmitters:
1) Acetylcholine
2) Amino Acids (GABA, Glycine, Glutamate)
3) Biogenic Amines (Dopamine, Serotonin, Adrenaline)
4) Peptides (Endorphins)
5) Gases (NO, CO)
6) Purines (ADP, ATP, Adenosine)
7) Lipids (prostaglandins)
7 is synthesized from plasma membranes
...
Neurotransmitter receptors can be:
Ionotropic (ligand gated) ion channels
Metabotropic (G protein coupled receptors)
Acetylcholine is the key of the autonomic nervous system
...
Also in
motor endplates
Used for attention, memory, autonomic neurons
...
Ionotropic receptors: NMDA, AMPA
Metabotropic receptors: mGlu R1-R8
Is a general excitatory transmitter
...
GABA (gamma amino butryic acid)
Present in Purkinje cells, neocortex interneurons
...
Used in anxiety
...
Present in the spinal cord and in the brainstem
...
Is an inhibitory transmitter
...
Myeline sheaths are made by oligodendrite cells
Synapsis between neurons and astrocytes (and other glial cells) do exist
...
1) Endocannabinoid
2) NGF (nerve Growth Factor): Travels in the presynaptic neuron in vesicles
...
Act on extrasynaptic
receptors
...
These classical neurotransmitters:
- stored in vesicles
- Have specific post synaptic receptors
- Eliminated from synaptic cleft
...
NO doesn't need post synaptic
receptors because it'll just diffuse to its target
...
Sympathetic - Uses energy
Parasympathetic - Saves energy
...
(uses acetylcholine)
Thoracolumbar division is sympathetic
...
At
target organs, sympathetic system uses norepinephrine and epinephrine as
neurotransmitters instead
...
Released in post ganglionic terminus
Eliminated via: Presynaptic reuptake, Diffusion into metabolism, Break down by MAO
...
Peripheral vasoconstriction
...
Inhibits overactivity
...
All 3 Beta receptors increase cAMP which activates protein kinase A
Beta 1: Receptor for heart
Beta 2: Receptor for blood vessels
...
Beta 3: Present in adipose tissues
...
38
Chromaffin cells in the adrenal medulla synthesize and release epinephrine
...
Receptor for acetylcholine is Nicotonic acetylcholine receptors in ganglion
...
In target organs, acetylcholine bind to a muscarinic receptor
...
Acetyl CoA + Choline -----------------> Acetylcholine
Enzyme used is choline-acetyl transferase
In the synaptic cleft, acetylcholinesterase degrades Acetylcholine to acetate and choline
There is choline reuptake
...
They contain vesicles
...
39
Sympathetic Cholinergic Innervation:
In some places, sympathetic fibres use acetylcholine (Those that innercate sweat glands
and their vessels)
Non Adregenic non Cholinergic Transmission
There is synaptic activity in autonomic nervous system independent of acetylcholine and
catecholamines
...
Propogation from periphery to CNS
(relays sensory neruon)
In autonomic and somatic motor neuron, propagation is from CNs to periphery
...
Voluntary movement
Autonomic: Involuntary
...
In an autonomic ganglia, 1st and 2nd motor neurons meet
...
In parasympathetic system, Acetylcholine is used in preganglionic and postganglionic
neurons and in motor end plates (skeletal muscle)
Elimination of acetylcholine is by acetylcholinesterase
...
Botulinum toxin blocks the release of Acetylcholine
Ca2+ channels are voltage gated
...
Tyrosine -----> Dopamine ----> Norepinephrine -----> Epinephrine
Norepinephrine receptors are G protein coupled receptors
...
MAO is responsible for neuronal degradation of norepinephrine
...
Cotransmitters are released at the same time as neurotransmitters
...
On their own, they can mediate some effects
...
Present at skeletal muscle and autonomic ganglia
...
Ca2+ Intracellular - 10^-4 millimole
Ca2+ Extracellular 1 millimole
Ionotropic receptors can be AMPA, NMDA, Kainate
Chloride ion inflow causes hyperoplarization in the cell
Higher the action potential, more the neurotransmitters released
...
41
CNS --------(Preganglionic fiber)----------(Ganglia)-----------(postganglionic
fiber)------------- Target Organ
...
Preganglionic fibers form the spinal and cranial nerves
...
Contain synaptic vesicles
...
Postganglionic fiber is long
...
Post ganglionic fiber is short
...
In postganglionic fibers: Sympathetic - Noradrenaline
Parasympathetic - Acetylcholine
Sweat glands are an exception
...
Have acetylcholine instead of
noradrenaline
...
Sympathetic and parasympathetic usually have antagonistic pathways
...
Sympathetic nerves produce mucous rich saliva
...
Adrenal gland, Arterioles, Pilloerector muscles have only sympathetic innervation
...
Sympathetic innervation increases heart rate and contraction force
...
Heart ventricles don't have
parasympathetic innervation
...
Limbic system is for memory and learning
...
Medulla for cardiovascular and respiratory function
...
PNMT is present in the adrenal medulla
...
MAO oxidizes noradrenaline
...
Acetylcholien is stored in light, small vesicles
...
Cotransmitters of acetylcholine: NO and VIP
...
NO is made from arginie via the enzyme NOS (NO synthase)
NO synthase activated by calmodulin-calcium complex
43
Skeletal & Smooth Muscles
Skeletal muscles have cross striations and voluntary control
...
10-100 micrometer in diameter
...
Z lines
...
Sarcomere is the contracting unit of muscle fibers
...
These membrane invaginations carries action potential to deep part of muscle fiber and
the middle myofibrils
...
Endoplasmic reticulum in muscles is called sarcoplasmic reticulum
...
Sarcoplasmic Reticulum stores Ca2+
Sarcoplasmic Reticulum, Transversal Tubule, Sarcoplasmic Reticulum: Triad
Thick filament (middle of sarcomere) has myosin
...
Tropomyosin and Troponin are regulatory proteins for sarcomere contraction
...
Thick filament is made up of 200-300 myosin molecules
...
Myosin has 2 heavy and 4 light chains
...
Myosin head could form cross bridges with actin filaments
...
Troponin complex is at the end of the tropoyosin band
...
In relaxed muscles:
Troponin Complex makes sure myosin binding sites on actin are blocked
...
Sets the myosin binding sites on actin
free from tropomyosin and able to bond
...
This is cuz thin filament is pulled inwards
...
Axons of motor neurons are thick with myelin sheaths
...
Surface of muscle membrane communicates with motor neurone terminal junction
...
Nicotinic Receptors of Ach are ionotropic
...
End plate potential is an electronic potential
...
Excitation-Contraction Coupling:
45
- Action potential depolarizes muscle fibers
...
Deeper fibres depolarized due to T tubules
- T tubules contain Dihydropyridine Receptors (DHPR)
- Once depolarisation reaches DHPR, it changes conformation
...
- RyR is a Ca2+ channel
...
Release of energy changes the conformation of myosin neck
...
Now myosin head can bind to actin
...
1st power stroke: Pi leaves and actin is pulled by 6-8nanometer
2nd power stroke: ADP leaves myosin head and actin is further pulled 2-4 nanometer
...
If Ca2+ concentration reduces, Ca2+ leave troponin complex
...
5 cross bridges formed per cycle
...
Free fatty acid, glucose, glycogen breakdown are all sources of energy for skeletal muscle
contraction
...
Tupe I: Slow Oxidative
Type IIa: Fast Oxidative
46
Type IIb: Fast glycolytic
Type I (slow oxidative) muscle fibres permanently produce ATP
...
Slow but long lasting contraction
Type I muscle fibres are red
...
Doesnt need oxygen
...
Activity of muscle enzymes are negatively affected by lower pH which comes from the
buildup of LActic Acid (due to anaerobic respiration)
Depletion of Acetylcholine also leads to muscle fatigue
Rigor Mortis - Stiffness after death due to lack of ATP
ATP binds to myosin head during cross bridge formation
...
Lactic Acid buildup and filament breakdown leads to muscle fatigue
Androgens and growth hormones do influence muscle mass
...
There is a significant gap between muscle fiber action potential and muscle fiber
contraction because the intracelluar steps take time
...
Multiple unfuse tetanus make up a fused, complete tetanus
...
The force of muscle contraction increases if:
Frequency of action potentials increase
Number of motor units increase
...
In isotonic contraction:
Muscle tensions stays the same but the muscle got shorter
...
Most contractions in humans are auxotonic
...
2 micrometer
...
Anything shorter or longer will give a lower percentage of maximum force due to imperfect
fitting
...
Myosin and Actin filaments positions are not strictly regulated
...
When a smooth muscle contracts, all muscle dimensions get shorter in all directions due to
fastening
...
48
Smooth muscle cells have no troponin and contracts to 30% of its initial length
...
In smooth muscle, myosin head has a regulatory function on one of its light chains
...
Ca2+ - Calmodulin complex forms and this complex activates MLCK
...
Further process is the same
...
In smooth muscles, ligand and voltage gated Ca2+ channels open and and provide Ca2+ from
extracellular sources along with sarcoplasmic reticulum
...
In smooth muscle cells, there is Ca2+ induced Ca2+ release
...
MLCP - Myosin Light Chain Phosphatase
MLCK - Myosin Light Chain Kinase
To increase the contractility of smooth muscle cells:
MLCK increase and MLCP decrease
...
This is because MLCK activates myosin head and cross bridge formation
...
49
Smooth muscles can be multi units or single units
...
Force generated however is not very high
...
Epimysium surrounds the whole muscle
...
Endomysium surrounds surrounds the muscle fibres
...
Myofibrils are surrounded by sarcoplasmic reticulum
...
Myosin head has ATP activity
...
Action potential activates DHPR
...
Rianodine Receptors are activated by DHPR
...
Troponin has 3 parts
...
A motor unit is made up of a single motor neuron + muscle fibres that it innervates
...
Acetylcholine can have ionotropic (Nicotinic) or Metabotropic (Muscarnic) receptors
...
Curare binds to acetylcholine receptors and prevents acetylcholine from binding
Choline acetyl transferase generates acetylcholine by joining Acetyl Coenzyme A group and
Choline group
...
Glucose forms ATP in mitochondria
ATP is used to shorten muscles
...
White muscles have a short twitch duration
...
More the cross bridges formed, stronger is the force generated
...
2 micrometers is the length at which maximum number of cross bridges form in a
sarcomere
...
Isometric contraction - Same length, change in muscle tension
...
Smooth muscles have random arrangement of filaments and no troponin
...
Smooth muscles contain caldesmin which slows down ATPase activity
...
In smooth muscles, Ca2+ comes from extracellular and intracellular sources
Intracelluklary from sarcoplasmic reticulum (IP3) and extracellularyly via ligand and
voltage gated ion channels
...
In smooth muscles, myosin head is not active until MLCK phosphorylates myosin head
...
Higher the cAMP, more relaxed is the smooth muscle
...
Single unit is activated by mechanical, electrical, neuronal way
...
Receptor can be alpha or beta
...
This means its a GPCR
G protein is a trimer
...
Phospholipas C makes IP3 and DAG (both are secondary
messengers) from the phospholipid membrane
...
IP3: Activates IP3 gated Ca2+ channels on sarcoplasmic reticulum membrane
Ca2+ is also a secondary messenger
...
Gs activates Adenylate Cyclase which makes cAMP from ATP
...
cAMP activates protein kinase A
...
Gi decreases the activity of cAMP
...
Nicotinic receptors can be Muscle type or Ganglion type
...
Muscarinic is a metabotropic type of receptor
...
M1, M3, M5 all activate Gq proteins
...
1 motor unit = 1 motor neuron + all the skeletal muscle fibres that it innervates
...
Axon of motor neuron is usually myelinated
...
This also happens in smooth muscle cells
...
53
Acetylcholine will usually bind to ionotropic, nicotinic (muscle type) receptor which can hold
2 Acetylcholines each
...
When Na+ flows in, electronic potential increases and due to summation, depolarisation
occurs
...
Motor End Plate - Part of the muscle fiber below the synaptic cleft
...
In skeletal muscles: Troponin C binds to Ca2+
...
Higher the Ca2+ concentration, more myosin binding sites will be available and more myosin
heads can bind to actin
...
Titin stabilizes the sarcomere
...
DHPR and RYR receptors are present
...
RYR on sarcoplasmic
reticulum
...
Action potential spreads into T tubules
...
DHPR now activates RyR receptor on sarcoplasmic reticulum
...
Myosin head has ATPase activity and binds to Actin as well
...
Sliding filament mechanism causes shortneing of sarcomere and thus muscle contracts
...
54
SERCA pumps Ca2+ out of the cell and pumps Na+ into the cell
...
Without Ca2+, smooth muscle relaxes as Ca2+ calmodulin complex breaks down and cant
activate MLCK
...
Multi unit (Autonomic neuron is in between individual muscle cells)
Single unit (Autonomic neuron borders all individual muscle cell
...
)
Both skeltal and smooth muscle contraction uses Ca2+
In smooth muscles, there is calcium induced calcium release
...
When there is increased Ca2+ concentration in smooth muscle cell, Ca2+ binds to
calmodulin
...
Thus MLCK is dependent on Ca2+ and calmodulin
...
In smooth muscles contraction, Ca2+ can come from intracellular and extracellular space
...
DHPR means dihydropyridine receptor
...
RyR get activated by change in conformation of DHPR
...
Isotonicity:
concentration/osmolarity should be the same in all 3 compartments
...
Too much water in a cell leads to swollen cell and ruptured cell membrane
...
Edema is due to changes in isotonicity
...
VIQ:
Total water in human body = 0
...
4 x body weight
Extracellular fluid = 0
...
The interstital fluid - 0
...
25 of extracellular fluid
Transcellular is part of extracellular compartment
...
VIQ:
To measure volume of fluid compartments:
Amount of indicator/concentration of equilibrium
Indicator gets distributed in the body after administration
...
56
Intravasal measurement uses albumin because it stays in the intravasal space
...
For measuring extracellular space: Inulin is used
...
To measure total fluid in every compartment: radioactive water is used
...
There is no or reduced flow in the blood vessel
...
Behind the thrombosis there is congestion, increase in pressure and edema (due to
disruption of isotonicity and isovalemia of blood)
Centrifugation is required to separated blood cells and fluid
...
45% of total blood volume is RBC
Less than 1% is WBC and platelets
55% is blood plasma
...
Blood plasma made up of electrolytes, proteins,
blood glucose
...
Males: 0
...
46
Females: 0
...
43
Difference is due to testosterone production
Components of plasma:
1) Inorganic electrolytes (Na, K, Ca, Cl, Mg ions)
2) Organic substances (proteins, glucose, urea, amino acids, lipids)
Proteins of blood plasma are mostly synthesized in liver and gut
...
57
Albumin
...
Attracts/Binds to water
Tranpsorts/binds to drugs
Can donate protons cuz protons are present on their surface
...
Importaant cuz free copper is toxic
...
60% of blood plasma proteins are albumin
...
There is less albumin and increased gamma globulin (antibodies) in the blood plasma
...
Multiple myeloma: Albumin and gamma globulin are present at the same level
...
Hydrophobic core is triglycerides and cholesterol
...
58
Lipoproteins can be chylomicron, VLDL, IDL, LDL, HDL
This is in increasing density and protein content
...
HDL is the good cholesterol
...
It picks up cholesterol from the blood vessel walls and protects against atherosclerosis
...
Blood:
Erythrocytes: Approx 5 million per microlitre
Leukocytes: 4000 - 10,000 per microlitre
Thrombocytes: 150,000 - 300,000 per microlitre
...
Hematocrit is the:
volume of corpuscular elements/total blood volume
...
Usual hematocrit level: 0
...
46
Leukocytes can be granulocytes, monocytes, lymphocytes
...
59
Neutrophils (50-70%) have segmented nucleus
...
Cytokine production
Eosinophils (1-6%) have bilobed nucleus
...
Invoved in inflammation
Lymphocyes make up 20-40% of leukocytes
B lymphocytes do antibody production
...
Monocytes (2-10%) of leukocytes
...
Largest leukocyte
...
Blood sedimentation rate is up to 20mm/hour
If greater than 20mm/hour then patient has a problem
...
More the albumin, higher is the blood sedimentation rate
...
Especially transport function
...
Albumin
...
Hemoglobin concentration of blood is 150g per litre
...
Eg of transcellular is Cerebrospinal fluid
...
Crystalloid (saline) is in extracellular compartments
...
To increase blood pressure use crystalloid (saline) or plasma expanders
...
Adema (swelling of cells due to fluids going into cells)
Intravasal compartment can be measured using I131 (radioactive isotope) albumin
...
Extravasal measurement = Extraceullular volume - Intravasal volume
For whole body fluid measurement, tricium (radioactive water) is used
...
Hematocrit = volume of RBC / volume of blood
Female hematocrit level: 0
...
42
Male hematocrit levels: 0
...
52
Roughly 45% of blood is erythrocytes
1% of blood volume is buffer coat (WBC + platelets)
55% of blood is plasma
...
Plasma has fibrinogen
...
4-5
...
Cl- : 101-111 mmol/L
Ca++free : 1
...
5 mmol/L
1 mmol/L of Ca2+ is bound to proteins
...
5 mmol/L
H+ : 10^-4 mmol/L
61
Organic elements of plasma:
Urea
Glucose : 4
...
9 mmol/L
Triglycerides
Cholesterol
LDL - creates plaques
...
Good cholesterol
...
Albumin has 35-45g/L
Albumin does non specific transport (eg: drugs, bilirubin)
...
The other groups of plasma proteins are:
Alpha 1 globulins
Alpha 2 globulins
Beta globulins
Gamma globulins
Alpha 1, Alpha 2, Beta globulins are all transporter proteins
...
Gamma globulins are immunoglobulins
(antibodies)
Plasma cell aka activated B lymphocyte
Antibodies have 2 heavy and 2 light chains
...
This binds to pathogens
IgG (monomer) Anti D antibody
IgE (monomer) for allergic reactions, parasitic infections
IgD (monomer)
62
IgA (dimer)
IgM (pentamer) for blood group antibodies
Erythrocytes: 4
...
2 million per microlitre
Erythrocytes cant perform aerobic respiration
...
Band 3 transporter also present on RBC membrane
RBC diameter: 7-8 micrometer
MCV (mean corpuscular volume) - Volume in a RBC
94 x 10^-15 litre
MCH (mean corpuscular hemoglobin) - Amount of hemoglobin in a RBC
29 x 10^-12 g
MCHC (mean corpuscular hemoglobin concentration) - MCH/MCV
usually 333 g/L
RBc is made in the bone marrow from hematopoietic stem cells
...
Erythroblast loses nucleus to become reticulocyte (has endoplasmic reticulum, golgi
apparatus)
Reticulocytes loses its organelles to become erythrocytes
...
Vitamin B12 and folate are used for DNA production
Stomach makes intrinsic factors
...
Lack of B12 or intrinsic factor causes macrocytic hyperchromic anaemia
...
RBC contains lots of hemoglobin
...
Glycolysis is the only metabolism in mature RBCs
...
There are 4-5 million RBC per microlitre
...
Reticulocyte is another name for young, non matured RBCs
...
Parameters of RBCs:
MCH (mean corpuscular hemoglobin):
Amount of hemoglobin in a single cell
MCV (mean corpuscular volume):
volume of a single RBC
Price Jones Curve shows the distribution of MCV in RBCs
...
Blood sedminetation rate is less than 20 mm/hr
In sedimentation, RBCs aggregate with plasma globulins
...
RBC membranes are fluid and flexible
...
Ankyrin is a very important stabilizing protein in the RBC membrane
Glycolysis is the only metabolism inside RBC
Under the membrane is a cytoskeleton (mesh) which provides flexibility
...
The required iron uptake is 1-2 mg/day
...
Free iron is toxic
...
In circulation (plasma), iron binds to transferrin
...
This iron storage complex is
called hemosiderin
Ferroportin causes the release of iron from storage cells
...
Iron deficiency causes Microcyter Hypochrom anaemia
...
MCH and MCV will be low
...
Vitamin B12/Folic Acid is used in the synthesis of DNA
...
Intrinsic factors are protecting proteins for B12
...
65
Deficinecy of B12 or intrinsic factors causes Macrocyter Hyperchrom Anemia
Hemoglobin is made up of Beta globulin + heme (in the middle)
Fe2+ is in the middle of the porphyrin ring
...
(Methemoglobin)
Hemoglobin has 4 subunits
...
Hemoglobin affinity to oxygen is variable
...
Factors that decrease the affinity:
- Increased temperature
- Bohr Effect (CO2 and protons increase, pH reduces) [ muscle contraction]
- Presence of 2,3 bisphosphoglycerate (by product of glycolysis)
An increase in haemoglobin affinity for oxygen means that oxyegn is not released by
hemoglobin
...
Carbonic acid dissociates to give a free proton ion in RBC
...
63% of oxygen transport is done by this mechanism
...
(Band 3)
In old erythrocytes: hemoglobin is released
...
66
Fe2+ is dissociated and stored
...
For its degradation biliverdin (green) and then bilirubin (yellow)
...
(indirect bilirubin)
Liver can take up bilirubin and join it with glucuronide (direct bilirubin)
From the liver to gut, bilirubin becomes urobilin and stercobilin
...
Developed erythrocytes have no nucleus, mitochondria or endoplasmic reticulum
...
Heme has a porphyrin ring with Fe in the middle
In osmosis, solvent flows from low osmolarity to high osmolarity
...
If erythrocyte is in a hypertonic solution, solvent flows out of the RBC and crenation
occurs
...
Due to the erythrocyte shape, volume can increase with the same surface area
...
Water volume of erythrocyte can increase without immediate lysis
...
0
...
For hemoglobin you need iron
...
Leaves enterocytes via ferroporta
...
This Fe3+ is bound to transferrin in the blood
...
Erythropoeitin is made in the kidney
...
Anaemia - low number of erythrocytes
...
Thus
number of erythrocytes is low and there is a certain type of anemia
...
Intrinsic factors are essential for the absorption of vitamin B12
...
RBC lifespan is 120 days
...
1) Hemoglobin is taken up by the macrophage
...
2) Biliverdin formed
...
Jaundice - too much bilirubin
...
Bilirubin normal levels - 17micromol/litre
4) In blood plasma: Bilirubin + Albumin ----> Unconjucgated (indirect) bilirubin
5) In liver: albumin leaves and Bilirubin + Glucoronic Acid ----------> Conjugated (direct
bilirubin)
Conjgated bilirubin sent to bile and excreted as
urobilinogen (urine) and stercobilinogen (faecese)
Transition of unconjugated bilirubin to conjugated bilirubin is the rate limiting factor
...
Lack of iron causes microcytic hypochromic anaemia
...
There is 8-27 micromol of iron in blood plasma
...
68
From the diet, humans absorb Fe2+, Fe3+ and Heme-iron
Heme-iron enters the enterocytes via HTP 1
Fe3+ cant go into enterocyte so it is reduced by ferrireductase enzyme
(Fe3+ ---->
Fe2+)
Fe2+ is absorbed into enetrocyte using DNT 1 transporter on enterocyte membrane
...
Iron ferritin complex leaves the cell via ferroportin and foes to blood
...
Iron is stored in the liver
...
Liver produces hepcidin which inhibits ferroportin transporters
...
RBC lifespan is 120 days
...
In macrophages, hemoglobin breaks down to globin (used in amino acid synthesis) and heme
...
(hemosiderin)
Porphyrin of heme becomes bilirubin in macrophage
...
Indirect bilirubin goes to the liver
...
In liver, due to glucoronin attachment direct bilirubin is formed
...
Direct bilirubin goes to gall bladder and then blood
...
Could be reabsorbed by liver
...
Normal bilirubin range: 15-17 micromolar
...
(yellow skin)
69
WBCs & Immune system
Normal WBC count: 4000 - 10000 cells per microlitre of blood
...
Staining of bloodmear (Pappenheim model):
Concentrated May Grunwald solution (3 minutes)
Dilute with equal amount of distilled water (1 minute)
Add freshly diluted Giemsa solution (1:20 ratio with distilled water)
Wash off Giemsa solution after 15 minutes
All blood cells originate in the bone marrow (multipotential hematopoietic stem cells)
Gives rise to either common myeloid progenitor or common lymphoid progenitor
...
3) Basophils
(0
...
Inflammatory response, inhibition of blood clotting, Allergic reactions, produces pro
inflammatory cytokine
...
Bean shaped nucleus
Have lysosomes and phagosomes in its cytoplasm
Carry out phagocytosis and are antigen presenting cells
...
Lymphocyte (20%-30% of WBC)
Smallest white blood cell
Have large nucleus
T lymphocyte - 80%
B lymphocyte - 20%
Primary lymphoid organs: Thymus, Red Bone Marrow
Secondary lympoid organ: Tonsils, spleen, lymph nodes, Peyer Patches
...
Plasma cell production
Natural Killer Cells kill tumor cells and infected cells using perforin
...
B lymphocytes differentiates into plasma cells which produces antibodies
...
Antibodies also activate complement system
...
Chemokines attract WBC to the site of penetration
...
Recognition of pathogen associated molecular pattern (PAMP) or antigens labelled with
antibodies
...
Phagosome merges with lysosome
...
Neutrohils carry out cytokine production and release
...
Releases proteolytic enzymes and defenzins, ROS (reactive oxygen species) and Netosis
(traps pathogens)
Complement system - Humoral system of innate immune system
Made up of proteolytic enzymes till C4
...
MAC create a hole in the membrane of the bacteria
...
Tkiller cells have CD8 maker and are on MHC I
...
Activation of B and T cells happens in the secondary lymphoid organ
...
Memory cells helps the efficient and rapid development of a repeated immune response
...
Antibodies aka Immunoglobulins
...
IgM (pentamer) - antibody of primary response
IgG (monomer) - antibody of secondary response
IgE (monomer) - antibody of allergic reactions
IgD (monomer) - B cell receptor
IgA (dimer) - Secretory immunoglobulin
...
Eg: Antigen B on RBC so Antibody A in plasma
ABO antigens are carbohydrates
Presence or absence of antigens A & B determines the 4 blood groups
...
D antigen is the most important antigen of the Rh blood groups system
...
Due to hemolysis, hematocrit levels reduce and bilirubin levels increase
...
Immune response can be specific (acts on only one substance) or non specific (acting on
wide range of substances)
...
These memory cells cause a quicker
response during the 2nd infection
...
Monocytes
have an unspecific immune response
...
Neutrophils also have non specific immune response
...
Only B and T lymphocytes can produce a specific immune response
...
After contact with the antigen both T and B lymphocytes will form memory cells
...
T lymphocytes can become:
T helper cells (CD4 receptor) - produce cytokines which enhance the immune system
...
T and B lymphocytes will only become active after antigen presentation
...
74
Antibodies have heavy and light chains
...
Can pass through placenta barrier
IgE (monomer) Releases histamine
IgD (monomer)
Secondary immune response is much faster than the primary immune response due to the
presence of memory cells
...
The complement system opsonizes, activates mast cells and basophils
...
C5, C6, C7, C8, C9 do the lysis of cells together via MAC (membrane attack complex)
...
Thymus - site of production of T lymphocyte
Red Bone Marrow - site of production of B lymphocyte
Neutrophils are phagocytes - produce reactive oxygen metabolites, cytokines
Eosinophils - Fight against parasites
Basophile granules have heparin (antithrombin effect - anticoagulant) and histamine
(inflammation, allergic reaction)
At the site of infection there is vasodilation
...
Phagocytes do antigen presentation
...
Effector T cells: T killer and T helper cells
T regulator and T mediator cells also exist
...
MHC I and MHC II does antigen presentation
...
MHC I binds to CD 8 marker
...
MHC II binds to CD 4 marker
...
T killer cells kill pathogens by secreating granzymes and perforins
...
Granzymes go through this hole
...
Capazes induce apoptosis
...
T helper cells then produce cytokines which activates B lymphocytes to produce antibodies
Cytokines are signal molecules for the immune system (Interleukins)
B lymphocytes produce immunoglobulins (antibodies)
...
IgD - Rh antibodies
Antibodies have Y shape with 2 heavy and 2 light chains
...
FAB part on antibody is for antigens
FC part is for NK cells
...
Immune system:
Innate
Cellular
Humoral
Phagocytes
Complenet System
Adaptive
T, B lymphocytes
Antibodies
Complenet system acts as a cascade
Have C1-C9
C1 to C5a are proteolytic enzymes
...
1st Landsteiner rule is valid for ABO and Rh
2nd Landsteiner rule only valid for ABO
Immunization occurs when Rh+ blood of fetus goes into Rh- blood of mother
...
Every time Rh- mother is expecting Rh+ baby, Rh profilaxis has to be done
Rh antigens are proteins encoded by genes
...
A antigen produced when someone genotype is AA, AO
B antigen produced when genotype: BB, BO
AB antigen produced when genotype: AB
Neither A or B antigen made when genotype: OO
Rh antibodies are IgG type
...
77
ABO antibodies are IgM
...
Blood group A:
Have A antigen, anti B antibodies
Blood group B:
B antigen, anti A antibodies
Blood group AB:
AB antigen, neither anti A or anti B antibody
Blood group O:
Neither A or B antigen, both anti A and anti B antibody
...
There are no anti D antibodies in the blood plasma of a Rh - person
...
Agglutination reaction 0 between antigens and antibodies
...
Primary: Local vasoconstriction, activation of platelets, plug formation, adhesion, activation
Secondary: Blood coagulation
Platelets change shape upon activation due to actin-myosin interaction
...
Phosphodiesteras breaks down cAMP and cGMP
...
Vitamin K converts inactive proteins with Glu residue to active proteins with Gla residue
...
Vitamin K1: Phylloquinone is known well for clotting
...
Heparin is an anticoagulant in the human body
...
Thrombin creates fibrin monomers from fibrinogen
...
79
Factor IV is calcium
Intrinsic and Extrinisc pathways both use Factor IV, V, X
...
- This amount of thrombin activates the intrinsic pathway which makes a large amount of
thrombin - enough for fibrin formation
...
Activates factor V and XIII
Detached plasmingen is quickly inactivated thus it is always attached
...
Hemostasis: Process which leads to cessation of bleeding
Includes blood clotting
...
Ends with the formation of white clot
...
4) Fibrinolysis (breakdown of fibrin mesh)
Prothrombin becomes Thrombin
...
Thrombin causes shape change in platelets
...
They are released by activated
thrombocytes
...
Factor III - tissue factor
Released by injured endothelial cells
...
Calcium (Factor IV) is essential for blood clotting
...
Clotting factors V, VII are produced by thrombocytes
Vitamin K is important for blood clotting as there are Vitamin K dependent factors for
blood clotting
- Blood clotting is initiated by tissue factor (Factor III) as it activates extrinsic pathway
...
- Thrombin then splits inactive fibrinogen to active fibrin
- Thrombin also activates production of Factor 13 which makes fibrin polymers
...
After healing from injury, red clot has to be removed
...
Tissue Plasminogen activator activates plasminogen to plasmin
...
Partial pressure is the pressure the gas would exert alone in a given space
...
In inspired air:
total partial pressure = 760 mm Hg
Oxygen partial pressure = 160 mm Hg
In deoxygenated blood:
Oxygen partial pressure is 40 mm Hg
The difference in partial pressures drives the diffusion of O2 into the blood stream
...
At this equilibrium, partial pressure of fluid
and gas is the same
...
It
is inversely proportional to membrane thickness
...
This is
because air is warmed and becomes saturated with water vapor
...
Decreases partial pressure of CO2
Metabolism: Increases partial pressure of CO2
...
At rest, the partial pressure for oxygen in alveolus is 100 mm Hg
...
Gas transport could be limited due to too little perfusion or too slow diffusion
Gas equilibration takes 0
...
Reserve time is 0
...
Total time = 0
...
Lung gas transport is always limited by cardiovascular system
...
Basal part has better perfusion gradient and is more flexible (expands more) than the
apical part
...
There are different rates of perfusion
...
83
Better the perfusion, better the ventilation
...
V/Q mismatch leads to a slight fall in partial pressure of oxygen
...
Euler Liljestrand mechanism - Local vasoconstriction in the hypoxic lung regions
...
34 ml oxygen
...
Low temperature, partial pressure of CO2, 2-3 DPG and high pH increases the affinity of
oxygen to hemoglobin
...
High temperature, partial pressure of CO2, 2-3 DPG and low pH decreases the affinity of
oxygen to hemoglobin and makes it easier for oxygen to be released from hemoglobin
...
If the concentration of deoxygenated hemoglobin is less than 50g/L then the skin will get
a bluish discoloration
...
Normoventilation: Ventilation is normal
Hypoventilation: Ventilation is too low
Hyperventilation: Ventilation is too high
Eupnea: Normal breathing rate
Bradypnea: Lower than normal breathing rate
Tachypnea: Higher than normal breathing rate
Dyspnea: Subjective feeling of not being able to breathe
Orthopnea: Can only breathe while sitting and standing straight
inputs of respiration:
- Lung receptors
- Arterial blood (chemoreceptors) - O2 and CO2 conc
The information goes to the medulla
output:
- Ventilation
- Bronchiol muscles
- Secretory glands
Driving force if normal respiration is the increase in CO2 in the blood
...
Controlled system - lung/blood gas exchange
Respiratory centres are in the medulla and 2 in the pons
...
Dorsal respiratory group projects to diaphragm and external intercostal muscles (muscles
for inspiration)
...
85
The pneumotaxic centre has an inhibitory effect on dorsal respiratory group
...
(Exercise)
Due to inspiration, lung volume increases, pressure decreases and thus air flows in
...
Internal
intercostal muscle is used
...
This happens during inspiration
...
Connected to diaphragm and external
intercostal muscles
...
H+ stimulates the medulla
...
Peripheral chemoreceptors primary sense O2 partial pressure levels
...
Then blood pH
...
If there is a change in O2, CO2 partial pressures and pH then there will be accumulation
of positive charge in receptor cells cuz Na+/K+ pump will still be working but K+ channels
sensitive to O2, CO2 and pH might close
...
partial pressure of O2 and partial pressure of CO2 have synergic effect, they amplify
each others effects
...
CO2 content of air - 0
...
Increase in CO2 causes alveolar ventilation to increase
Neurons don't work at pH below 6
...
Decreased partial pressure of oxygen increases alveolar ventilation but not linearly
...
High CO2 levels is a more potent stimulus for respiration, ventilation than low O2 levels
...
This reflex can change the respiratory rhythm
To protect airways: coughing and mucus secretion is done
...
Kussmal respiration - when one has acidosis
Tries to remove CO2 by deep and high frequency ventilation
Cheyne Stokes respiration - amplitude gradually increases and decreases in sleep and at
high altitudes
...
(has feedback)
Chemoreceptors present in blood (has feedback)
Mechanoreceptors in joints (no feedback
...
Biology fo airway:
- protection of the airway (sneezing and coughing in upper airway, surfactant production by
clara cells and making air wet
...
Tissue mast cells
create histamine
- Mucociliar clearance - mechanism by which airway clears itself
...
Lung has physical filtering (trapping things),
chemical filtering (heparin, plasminogen activator),
neutralizing vasoactive substances (serpotonin, adenozin),
Converting Angiotensin I (inactive) to Angiotensin II (active)
...
Airways have a conducting and respiratory zone
...
Voluem is 150 ml
Epithelial cells in this zone are ciliated and produce mucus
...
This is wth rhythmic movement of cilia which moves foreign particles stuck in
mucus
...
The respiratory zone has alveoli
...
Type I pneumocytes do gas exchange
Type II pneumocytes produce surfactant
...
Lung volume is measured using spirometry
...
Ventilation rate: Volume of air moved into and out of the lung per unit time
Breathing rate = 14 per minute
Minute ventilation = Tidal volume x breathing rate = 7000 ml/minute
Alveolar ventilation = 4000 ml/minute
Alveolar ventilation is directly proportional to CO2 partial pressure & directly proportional
to volume of CO2
Forced Vital Capacity: Total volume of air that can be forcibly expired after maximal
inspiration = 80%
Inspiration
89
Inspiration is an active process and requires active muscle contraction
...
The diaphragm contracts, flattens and goes downwards
...
Lung volume increases, lung pressure decreases and air
flows in
...
The inspiratory muscles relax
...
Ribs move downward and inward so lung
volume decreases, lung pressure increases and air flows out
...
Prevents the collapse of
alveoli
...
Smaller alveoli will have higher collapsing pressure than larger alveoli
...
Lungs have a tendency to collapse and surfactant prevents the collapse
...
Transmural pressure - pressure across alveoli wall
...
Hysteresis: Difference between inspiration and expiration compliance curves
Hysteresis arises due to surfactant production
Surfactant increases the distensibility during inspiration
...
Lung tissue and alveoli stiffens and lung volume decreases
This is because fibrotic connective tissue replaces the alveoli
...
Q = ΔP/R
Q = airflow
ΔP = pressure gradient
R = resistance of airways
...
Medium sized bronchi have the greatest resistance
Sympathetic innervation decreases resistance in airways (bronchodilator)
Parasympathetic innervation increases resistance in airways (bronchoconstriction)
Histamine (from mast cells) cause bronchoconstriction
...
Fick Diffusion Law:
V = (D x A x ΔP) / X
V = volume of gas transferred
D = gas diffusion coefficient
A = surface area
P = partial pressure difference
X = Membrane thickness
...
CO2 + H2O -------------> H2CO3 (carbonic acid)
91
H2CO3 -------------> HCO3 - + H+
There is bicarbonate-chloride exchange
...
oxygen diffuses from alveoli to capillaries due to partial pressure difference
...
CO2 goes from plasma to alveoli due to partial pressure difference
...
Neuronal control center is in medulla and pons
...
Used during exercise
Pontine respiratory group - Regulates breathing rate
Chemoreceptors are present in the medulla, carotid and aortic bodies
...
CO2 diffuses into cerebrospinal fluid and binds with water
...
Chemoreceptor cells recognize higher H+ concentration and activates inspiratory center to
remove CO2 and bring in O2
...
Such
substances cause vasoconstriction and vasodilatoin
Lungs can eliminate vasoactive hormones (vasopresisn)
92
Heart
Blood flows down the pressure gradient which is made by the heart
...
Cardiac muscles have gap junctions between them
...
Cardiac muscles have sarcomeres, many mitochondria, sarcoplasmic reticulum and many
capillaries
...
Cardiac ventricle cells have a much larger refractory period than other cells (approx 200
ms)
There is no tetanic contraction in cardiac muscle cells
...
During repolarization, Ca2+ permeability reduces and K+ permeability increases
...
Myocardiac cells also have T tubules along with gap junctions
...
This
triggers the release of Ca2+ in sarcoplasmic reticulum via Ryanodine receptors
3) Intracellular Ca2+ levels increases
4) Contraction between actin and myosin fibres
5) Removal of Ca2+ ions via 3 mechanisms
...
Cardiac muscle is the only muscle type wherein Ca2+ required for muscle contraction comes
from extracellular and intracellular sources
...
This is an intrinsic regulation and is + inotropic (increases contraction force)
Na+ Ca2+ antiport exchanger and be influenced indirectly
...
By slowing down the Na+/K+ pump, we can slow down the Na+ Ca2+ exchanger
...
Human heart has very low parasympathetic innervation
...
Rhytmic contraction causes cardiac cycle
...
Pressure gradient causes blood flow
...
Blood flow causes a change in volume of both compartments
...
In this volume doesn't change but pressure does
...
Ventricle gets filled with blood from the atria
Period of filling
B) Mitral valve closes
Pressure increases, volume stays the same
Isovolumetric contraction
C) Aortic Valve opens
Pressure increases, volume decreases
Blood flows out of ventricles
Period of ejection
D) Aotric Valve closes
Pressure decreases, Volume stays the same
Isovoluetric relaxation
A) Mitral Valve opens
A---->B: Filling period
B------->C: Isovolumetric contraction
C---------->D Ejection period
D-----------> A: Isovolumetric relaxation
Cardiac Cycle takes 0
...
Systole - 0
...
53 seconds
95
Systole: Isovolumetric contraction, maximal & decreased ejection
Diastole: Isovolumetric relaxataion, Rapid & Slow filling
...
Should be 50-70%
If ejection fraction is lower then heart is not healthy
Atrial contraction (atrial systole) contributes to 20-25% of pumping blood into ventricles
towards the end of filling period
...
Jugular venous pulse is directly connected with the atrial pressure
...
Cardiac Output (volume of blood leaving the ventricle in one minute):
5
...
7, 1
...
Louder)
2) Diastolic sound - Relaxation, closing of semilunar valves
...
Less loud)
96
There are also 3rd and 4th sounds which are very very soft
...
Druring diastole: Volume increases and pressure is mostly the same
During systole: Volume decreases
I: Filling period (V inc, P same)
II: Isovolumetric contraction (V same, P inc)
III: Ejection period (V dec, P increases a bit)
IV: Isovolumetric relaxation (V same, P decreases)
The resting length of cardiac muscle determines how powerful contraction would be
...
(Volume of blood that flows into heart)
Afterload - Pressure Value (Pressur that the ventricle must overcome to circulate blood
...
Increased heart rate alone will not increase cardiac output
...
Rhythmic excitation of heart is due to natural pacemakers (SA node, AV node)
SA node --------> AV node -----------> AV bundle -----------> AV bundle branches
---------------> Purkinje Fibres
Fast action potentials are Na+ channel dependent
...
3-0
...
Less negative, less steep, lower amplitude (0
...
2 m/s)
Slow action potential don't have a resting potential value
...
Heart rate decreases during during vagal nerve stimulation
...
Vagal
stimulation delays repolarisation and prevents Ca2+ ions from flowing in
...
Sympathetic innervation of heart is diffuse and more spread out
...
Neuronal regulation:
Vagal innervation decreases heart rate and contraction force
...
Ca2+ and K+ concentrations also regulates heart activity
...
Higher the K+ conc in extracellular fluid, lower is the heart rate and contraction force
...
Heart Action potential:
Steep depolarisation (influx of Na+)
Long plateau phase - delays repolarisation
...
Long plateau phase delays repolarisation
...
Extracellular is +ve
...
Extracellular is -ve
Heart has pacemaker cells and contractile cells
...
Pcaemaker cells depolarisation is due to influx of ca2+
...
SA node is the source of electrical activity in the heart
...
Slight delay at AV node
...
Bundle branches
...
PQ interval from start of atrial activation to start of ventricular activation
...
RR interval - One complete cycle
...
12-0
...
1s
QT interval - 0
...
45s
Cardiommyocytes have gap junctions and are smaller than skeletal muscles
...
Gap junctions have fast conduction of impulses
...
Not in smooth muscles
...
SA node creates impulse
...
Skeletal muscles can undergo tetanic contraction
...
Cardiac Muscle Contraction:
Action potentials (from SA node) spread into T tubules
...
Due to action potential , DHPR opens and extracellular Ca2+ enters cytosol
...
In skeletal muscles, only intracellular Ca2+ needed for contraction
...
In the plateau phase, action potential is constant due to inflow of Ca2+ (through DHPR)
Cardiac muscles (like skeletal muscles) use Ca2+ for actin, myosin cross bridge formation
...
Na+ Ca2+ antiport transporter present on cell membrane
...
This reduces intracellular Ca2+ levels
There are also Ca2+ ATPase on cell membrane and ER membrane which reduce intracellular
Ca2+ levels
...
Higher power = + inotropic effect
Due to sympathetic stimulation and adrenaline
...
Inhibition of the Na+/K+ pump pumps leads to extended contraction because Na+ levels
stay high in the cell
...
When there is more venous blood returning, heart contracts stronger
...
Luzitropic effect: Relaxation of ventricular muscle
Inotropic effect: Contraction force
Chronotropic effect: Impulse rate
Dromotropic effect: Condcution velocity
Bathmotropic effect: Excitability of Purkinje fibres
A positive effect causes faster or increased of the above
...
Protein Kinase A can phosphorylate ion channels of the SA node
...
(+ chronotropic effect
...
Action potential times:
Contractile cells: 200-300 ms
101
Pacemaker cells: 150 ms
Contractle cells have the plateau phase in their action potential
Dromotropy (conduction velocity) due to cells of AV node
Chromotropy (Impulse rate) due to cells of SA node
...
Thus parasympathetic stimulation only causes -ve chronotropy, dromotropy effects
...
Duration of cardiac cycle = 0
...
3 s
Diastole = 0
...
Durinf diastole stuff rlaxes and volume increases
...
Volume stays the same, pressure increases
...
Volume decreases
...
3) Isovolumetric relaxation
Mitral valves closed
Volume stays the same, Pressure decreases
...
Blood flows into venticles
Isovolumetric relaxation and period of filling makes up ventriccular diastole
P wave - Atrial depolarisation
QRS complex - Ventricular depolarisation
T wave - Ventricular repolarisation
QRS complex covers the curve of atrial repolarisation
1st heart sound is due to closure of mitral valve
2nd heart sound due to closure of semilunar valve
...
103
ECG notes
Fluctuations in the right atrial pressure causes changes in jugular pulse
...
Its the volume of blood that leaves the heart after systole
When describing pulse waves:
1) By frequency
Frequents x Rarus
2) By amplitude
Altus x Parvus
3) By speed
Celer x Tardus
5) By compressibility
Durus x Mollis
7) By rhytm
Regularis x Irregularis
9) By similarity
Aequalis x Inaqualis
ECG - For measuring electrical activity of the heart
Inside cell
Resting
-
Depolarization
+
Repolarization
-
Outside Cell
+
+
Every cardiac fibre produces vectors
Propogation of electric vector must be in the plane of the eCG lead
...
Q wave - Starting of depolarisation of ventricles
104
R wave - Activation of cardiac muscle
...
S wave - When almost all the ventricles have been active
...
Normal ECG, Cardiac Cycle = 0
...
PQ segment shows how much time it takes for atrial depolarisation to spread to ventricles
...
2 seconds
1 small box = 0
...
Einthoven - Bipolar between 2 limbs
...
08 seconds
PQ interval = 0
...
08 seconds
...
Leads can be unipolar or bipolar
...
For the limb leads, we put the electrodes on 3 limbs: both the arms and the left leg
...
P wave: <0
...
1 s
In ECG we have waves, segments and intervals
...
This complex also hides the atrial
repolarisation
...
PQ segment - conduction of AV node
...
In a complete cardiac cycle, there are 2 intervals
...
2 s), Atrial depolarisation
2) QT interval: From start of Q wave to end of T wave
320 - 390 ms (0
...
39s)
...
QT interval contains QRS complex, T wave, ST segment
...
04s long and 0
...
Heart axis:
aVR: -30
aVF: +90
Pressure graident is the driving force of flow
...
Blood flow = Pressure gradient/Resistance
Transmural pressure = Pressure in capillaries - Pressure in interstitum
...
Blood flow = Blood flow velocity x cross sectional area
Q=VxA
Inverse proportionality between blood flow velocity and cross sectional area
...
About 5
...
Eg:
Aorta velocity = 22 cm/s
...
Compliance of vessel depends on distensibility of vessel
Veins have higher compliance than arteries, thus veins are called capacitance vessels
...
Aorta has windkessel effect
...
Blood vessels are elastic and branching
...
Transmural pressure: Differenece between blood pressure and pressure outside the vessel
wall (interstitial pressure)
Transmural pressure keeps the vessel circular
...
Venous compliance is 20 times higher than arterial compliance
...
Critical closing pressure (20 mm Hg): If transmural pressure falls below this value, blood
vessels collapse
...
Veins are at low risk of wall rupture (large radius and low blood pressure)
Capillaries at low risk of wall rupture (small radius, low blood pressure)
Aorta, large elastic arteries have high risk of wall rupture (large radius with thin walls +
high pressure)
Vessels of the same class are connected in parallel
...
Organs of systemic circulation are connected in parallel
...
In series: R(total) = R1 + R2 + R3
...
The blood pressure drop is greatest in the arterioles because the arterioles have the
largest vascular resistance
...
108
Velcoity of blood flow:
Aorta: 22
...
03 cm/s
Vena Cava: 11 cm/s
Velocity and cross sectional area are inversely proportional
...
Aorta has the lowest cross sectional area thus it has the highest velocity of blood flow
...
Blood volume distribution depends on pressure and compliance
...
In non invasive blood pressure determination, the first sound is systolic blood pressure
...
Critical Reynold number: 2200
Greater than this then flow becomes turbulent
...
Cardiac cycle: 0
...
27s
Diastole: 0
...
Longer the cardiac cycle, longer the diastole and systole, higher the mean arterial blood
pressure
...
Aging decreases aortic elasticity
...
Compliance especially reduces in high blood
pressure range
...
Pulse wave velocity is increased by decreased wall elasticity, decreased vascular
resistance, increased wall thickness
...
Pressure changes in aorta are transmitted along the arteries as a pressure pulse
...
Capillary Bed - where microcirculation happens
...
Smooth muscle is also present at the beginning of capillaries
...
)
Metarterioles are a bypass to precapillary sphinctres
110
Arteriole Venule anastomosis is another bypass to precapillary sphinctres
...
When precapillaty sphincter is relaxed, blood flows from arteriole to venules
...
Resistance vessels of microcirculation: Arterioles, metarterioles, precapillary sphincters
...
Vascular smooth muscles in these vessels have a resting tone that can be modified
...
Even RBCs can fit through these
(in liver, spleen, bone marrow)
All capillaries service the tissues to meet their metabolic demands
...
Thus plasma proteins are transported in part by vesicular transport
...
Inside the capillary:
- Capillary pressure (acting on capillary wall)
111
- Plasma colloid osmotic pressure (acting against from capillary wall)
Outside the capillary:
- Interstitial fluid pressure (acts on capillary wall)
- Interstital fluid colloid osmotic pressure (acts against capillary wall)
Capillary blood pressure
Start: 25 - 40 mm Hg
End: 10 - 15 mm Hg
Mean: 17
...
These 2 cant cross capillary wall
...
8 mm Hg), Globulin (6 mm
Hg), Fibrinogen (0
...
3 mm Hg in general in continuous capillaries
...
Lymphatic vessel is also present in microcirculation
...
Lymphatic capillary endothelial cells form valves allowing interstital fluid to enter
...
Lymph vessels flow through lymph nodes
Main function of lymphatic system:
Drainage of interstital proteins
Return of excess filtrate
Absorption of lipids
112
Moving lymphocytes
Interstital tissue space has many connective tissue fibres and non fibrous adherent
matrixproteins
Interstitial fluid levels vary in different tissues
...
Increased filtration ------------> Increased interstital pressure ---------> increased lymph
flow -----------> Excess fluid accumulates in interstitium (interstital compliance increaseS)
Due to this edema develops
...
Thus edema is due to filtration or reabsorption imbalance
...
From venous end of capillary to right atrium, only 10 mm Hg pressure gradient is needed to
maintain flow
...
Because of the high venous compliance, 64% of total blood volume resides in the venous
system
...
Compliace: How volume of vessel changes when the pressure changes
...
113
Stress relaxation is a feature of venous smooth muscle
Venous smooth muscle adapt to increased volumes by active relaxation (in response to
stretching of vessel)
Blood pressure is reduced above the heart and elevated below the heart
Arteries don't dilate much but veins do
...
What provides venous return?
Heart activity (pumping, sucking)
Muscle pumps + Valves
Sympathetic venoconstriction
Walking and movement decreases venous pressure
...
Vericose veins:
Incompetent veins,
Vein valves fail and edema is frequent
...
During inspiration, venous return increases
...
During inspiration, venous return decreases
...
This maneuver evokes complex cardiovascular reflexes
...
115
Purpose of cardiovascular system:
Facilitates exchange of gases, fluids, electrolytes between cells and outside environment
...
Output of right and left heart are independent of each other
...
Except portal circulation
...
Pressure gradient is the energy that drives movement of the fluid
...
Hydraulic resistance is determined by fluid viscosity, tube length and tube radius
...
In parallel circuit, total resistance is less than sum of resistance
Organ blood flow is not driven by the output of the heart but instead by the pressure
generated within the arterial system
...
Transmurla pressure within the vessel exerts a force on the vessel wall causing it to be
stretched
116
This wall tension could tear the vessel wall
...
Aorta and large, elastic arteries are at high risk of a tear in the vessel wall due to high
blood pressure and a large radius with relatively thin walls
...
Veins are the most distensible vessel
...
Thus even a slight increases in venous pressure causes the veins to store lots of blood
...
Compliance - Ability of vessel to respond to an increase/decrease in pressure by distending
or not distending and thus increasing/decreasing the volume of blood that it can hold
...
They hold the more blood at lower pressure than arteries
...
Both arteries and veins have:
Tunica Intima (endothelieum, internal elastic membrane only in arteries)
Tunica Media (smooth muscle cells in circular arrangement)
Tunica external (Collagen fibres)
In veins, tunica externa is relatively musch thicker
...
Diameters
Aorta - up to 25 mm
Arteries - up to 100 micrometer
Arterioles: 10-100 micrometer
Capillary: 8 micrometer
Arterial walls are thick, capillary walls are not thick
...
117
Distribution vessels: Aorta, large arteries
Resistance vessels: small arteries, arterioles
Exchange vessels: capillaries
Capacitance vessels: veins, venules
...
Elastic arteries are near the heart
...
They act as control conducts
...
Venules collect blood from capillaries
...
Veins serve as a major
reservoir of extra blood
...
Mean pressure in aorta = 95 mm Hg
Pressure remains high in large arteries (due to high elastic recoil of arterial wall)
...
At the end of arterioles, mean pressure in arterioles = 30 mm Hg
In capillaries, venules and veins pressure decreases further
pressure in vena cava = 4 mm Hg
pressure in right atrium = 0-2 mm Hg
There are pulsations of arterial pressure
...
7% of blood is in the heart
118
9% of blood is in pulmonary vessels
...
They can acts as reservoirs for blood
...
Mean arterial pressure = diastolic pressure + 1/3 pulse pressure
...
Aorta has smallest cross sectional area and highest flow velocity
...
Local control of circulation: Maintains adequate blood flow to tissues to meet their their
metabolic and functional tissue needs
...
Done by volume regulation, pressure diuresis
...
119
Delta P = Q x R
Q = cardiac output
R = Total peripheral Resistamce
A small increase in blood pressure causes a massive increase in urine output
...
Increased urine output decreases blood pressure cuz an increased urine output means
decreased extracellular fluid volume
...
Opposite is true
...
Blood pressure regulation by volume regulation is done by hormones
...
These 2 hormones retain salts and water respectively and thus the activity of these 2
hormones decreases the urine output
...
ANH (atrial natriuretic peptide hormone) is secreated by the heart
...
ANH also causes vasodilation, thus reducing mean arterial blood pressure
...
Efferebts of systemic neural regulation of circulation:
Sympathetic fibres innervates the heart (atria + ventricles) and the vessels (arterioles +
veins)
Parasympathetic fibres innervate the heart (atria only)
Only sympathetic system has a role in the rehilation of total peripheral resistance when it
comes to blood pressure control
...
Normal peripheral resistance is made up of the sum of resistances
...
In the sympathetic vasoconstriction innervation of smooth muscles, there is role of
norepinephrine and ATP cotransmission
...
(These
can tolerate a temporary reduction in blood pressure)
121
Cerebral and Coronary vessels don't have significant sympathetic vasoconstrictor tones
...
Origin of sympathetic tone is in the medulla
...
Caudal ventrolateral Medulla (CVLM) inhibits RVLM and stimulates the cardiac
parasympathetic tone
...
Present in the carotid sinus and aortic arch
...
Baroreceptors are primary sensory neurons, pseudounipolar and are interaceptive
mechanoreceptors
...
Baroreceptors have an initial input to nucleus tractus solitarius
...
Due to the baroreceptor control system:
if there's increased blood pressure, increased parasympathetic activity, decreased cardiac
output so blood pressure decreases
...
Baroreceptor activity falls if blood pressure decreases
...
122
The set point can be shifted however
...
This happens in response to exercise, sense of danger or if PO2
decreases and PCO2 increases
Carotid sinus reflex is a defense against oscillation in blood pressure
...
Carotid sinus receptors are more sensitive than receptors in the aortic arch
...
It only prevents
sudden changes in blood pressure due to sudden changes in posture
...
Long term control of blood pressure is by volume regulation
...
Local vascular resistance is the key determinant of local blood flow
...
Vasodilatory innervation can increase blood flow locally
...
Bayliss effect: Some arteriolar smooth muscles are sensitive to stretching
...
Thus blood pressure reduces
...
Endothelial factors regulating arteriolar smooth muscle tone can be dialators or
constrictors
...
All this is produced by the endothelial cells
...
K+ ions, NO, PGI2, PGE2, ATP, ADP are all signals for vasodilation
...
Can be active hyperemia (to meet metabolic/functional demands)
Or
Reactive hyperemia (following an interruption to flow)
124
Blood flow autoregulation is present in every organ and is most prominent in cerebral and
coronary circulation
...
Blood flow regulation is based on the parallel increase or decrease of local vascular
resistance with changes in arterial blood pressure
...
Due to the
release of vasodilatory tissue metabolites -------------> Arteriolar dilation ----------> Local
vascular resistance decreases ------------> blood flow increases ---------> O2 and nutrient
supply increases
...
During active hyperemia, endothelial cells of the arterioles proximal to the tissues will
sense the increased flow due to increased shear stress
...
Due to this, even arterioles that are not exposed to the tissue metabolites
are involved in active hyperemia
...
Arterioles constrict and blood flow returns to normal
...
Capillary density is determined by maximum flow need
...
Inflammation induced vasodilation is done by:
histamine, PGE2, Bradykinin, Substance P
Histamine is the most important inflammatory mediator
...
Causes vasodilation
...
Kinins (Bradykinin & Lysil bradykinin) also cause endothelium dependent vasodilation
...
Factors determining cardiac output:
Heart
Blood volume
Venous Compliance
126
Total Peripheral Resistance
Cardiac Output does not have homeostatic regulation
...
Vascular function curve: As venous pressure increases, cardiac output decreases
...
It is the organ with the highest blood flow
...
Pulmonary systolic pressure = 24 mm Hg
Pulmonary diastolic pressure = 9 mm Hg
Pulmonary mean pressure = 14 mm Hg
In pulmonary circulation, arterial compliance is similar to venous
...
Bronchiol arteries provide nutritive blood flow to the larger airways
...
Pulmonary vascular resistance decreases if blood pressure or cardiac output increases
...
Blood flow in pulmonary capillaries surrounds the alveoli like a sheet of blood flow
...
Pulmonary microcirculation have very thin capillaries that are permeable to fluid
...
Factors that affect the cardiac output also effect the pulmonary circulation
...
Usually if there is hypoxia (lack of oxygen) there will be vasodilation but not in the lungs
...
It optimizes gas exchange
...
Vasoconstriction is an inherent, intrinsic feature of pulmonary circulation
...
Many vasoactive substances that are wahsed out of organs are degraded by the pulmonary
endothelial cells
Pulmonary endothelium does the metabolic clearance of serotonin, PGE2 and bradykinin
...
Right coronary artery has 15% of blood flow
...
(Blood actually goes backwards a little bit in
the left coronary arteries during systole)
In right ventricle, blood flow happens during diastole and systoole both
...
There
is no sympathetic vasoconstrictor tone here
...
This metabolite is
adenosine
...
Coronary blood flow increases proportionally with the cardiac output
...
Skeletal muscle:
Takes up 15% of cardiac output during rest (1/ / minute)
Takes up 80% of cardiac output during exercise (20l / minute)
20% oxygen consumption during rest
...
Regulation of skeletal muscle circulation:
Resting muscles have sympathetic vasoconstrictor tone, sympathetic cholinergic,
anticipating vasodilation and active hyperemia by metabolites
...
129
Circulation
Systemic control of circulation: Maintains constant perfusion pressure by regulating mean
arterial blood pressure
...
Systemic control of circulation is done by renal and hormonal regulation of mean arterial
blood pressure
...
Is long term
...
This is
diuresis
...
A decrease in blood pressure also causes a decrease in urine output
...
Renal and Hotmonal blood pressure control: slow, powerful
Central Nervous System blood pressure control: fast, adaptable
...
Renin-Angiotensin-Aldosterone axis and Vasopressin
...
Thus vasopressin and RAA decreases diuresis and increases mean arterial blood pressure
...
It inihibts salt
retainance by kidney and thus increases urine output
Thus ANH increases diuresis and decreases mean arterial blood pressure
...
(NPR 1 receptor,
cGMP coupling)
131
Angiotensin 2 causes vasoconstriction, thus increasing mean arterial blood pressure (AT 1
receptor - IP3, DAG coupling)
Vasopressin also causes vasoconstriction, thus increasing mean arterial blood pressure (V1
receptor - IP3, DAG coupling)
Neural regulation of mean arterial blood pressure via reflexes of the autonomic nervous
system is short term
...
Systemic effect of catecholamines on circulation:
We are using noradrenaline/adrenaline
- Stimulation of the heart (causing increased cardiac output)
- Contraction of veins ---> Increased venous return (causing increased cardiac output)
- Contraction of arterioles (increases total peripheral resistance)
All above 3 increase the blood pressure
...
Resting tone (in arteriolar smooth muscles) = Basal tone + Neurogenic Tone
Neurogenic Tone - Sympathetic vasoconstrictor tone
Basal Tone - Systemic hormones, Myogenic tone, local vascular factors, local tissue
humoral factors)
Increase in sympathetic tone -------------> Vasoconstriction
Increase in parasympathetic tone -------------> Vasodilation
...
Sympathetic vasoconstrictor effect is most powerful in kidney, gut, spleen, skin
...
(These cannot tolerate a temporary reduction in blood pressure)
Sympathetic system maintains a normal sympathetic vasoconstrictor tone
...
The rostral ventrolateral medullar (RVLM) is the generator of the sympathetic tone
...
Baroreceptors are pressure sensors
...
Baroreceptors keep the blood pressure within a narrow range
...
Baroreceptors respond to pressure induced changes in wall tension and thus indirectly
respond to mean pressure, pulse pressure and rate of change in pressure
...
Then an excitatory connection to CVLM and an inhibitory connection to RVLM>
Thus increased baroreceptor input leads to lower sympathetic activity and higher
parasympathetic activity
...
133
Baroreceptor activity increases if blood pressure increases
...
Baroreceptor input inhibits RVLM, sympathetic output
...
Increased set point for baroreceptors will allow for
higher blood pressure
...
Reflex is active in normal range of blood pressure
...
Carotid sinus reflex cannot correct chronic alterations in blood pressure
...
Chemoreceptor reflex function is the stimulation of breathing
...
(renal & Hormonal)
134
Local control of circulation: Maintains adequate blood flow to meet local metabolic and
functional needs of tissues
...
Basal tone of arteriolar smooth muscle is controlled by local vascular and tissue hormonal
factors and myogenic tone
...
Myogenic tone - spontaneous contraction maintained by arteriolar smooth muscle
...
They respond
to stretching with contraction
...
Increased transmural pressure induces arteriolar contraction
...
Dialators: Nitric Oxide, prostacyclin, EDHF
Constrictor: Endothelin
...
Local vasodilator tissue metabolites are released from active cells that are not getting
enough blood flow/ not getting enough oxygen (hypoxia) / getting too much CO2 or lactic
acid (acidosis)
...
135
Hyperemia - Increased blood flow above the base line
...
This is where systemic circulation doesn't happen
...
Change in perfusion pressure -----------> Sudden increase/decrease in local blood flow
---------------> appropriate constriction/dilation of arterioles
(The appropriate constriction/dilation of arterioles is an autoregulatory response)
Autoregulation is unable to prevent sudden changes in blood flow is blood pressure changes
drastically (more than 1 mm Hg/s)
Autoregulation:
1) Myogenic (Bayliss effect)
2) Metabolic (accumulation or washout of vasodilatory metabolites)
Long term accumulation (takes weeks to months): new vessel growth, vessel degenration
Active hyperemia:
Increase in tissue metabolism will proportionally increase tissue blood flow
...
This only happens as long as tissue metabolic rate is increased
...
They will release NO inducing
136
vasodilation
...
Reactive hyperemia:
Ischemia occurs ---------> Vasodilatory tissue metabolism accumulate -----------> Arteriolar
dilation ----------> Occlusion is removed ------------> Blood flow increases ------------>
Vasodilators are washed away
...
Chronic elevation of metabolic activity or hypoxia triggers angiogenesis (making new
vessels)
Hypoxia also triggers vascular endothelial growth factor, fibroblast growth factor,
angiopoeitins
...
Hemostasis induced vasoconstriction:
Loss of functional endothelieum -----------> Reduced releases of NO, prostacyclin and
EDHF -------------> Vasodilator mediators will be ineffective
...
Released by mast cells, basophils
...
Is endothelieum dependent
...
Locally important vasodilatory autonomic innervation:
- parasympathetic innervation of salivary glands, external genitalia
- Enteral nervous system innervation of arterioles in GI tract glands
...
Cardiac Function Curve: As right atrial pressure increases, cardiac output increases
...
Increased blood volume ------> Venoconstriction (compliance reduces)
Decreased blood volume ------> Venodilation (compliance increaseS)
Lung gas pulmonary circulation
...
Pulmonary circulation ha smuch lower pressure values than systemic circulation
...
Thus blood volume is evenly distributed between pulmonary arteries and veins
...
Pulmonary vascular resistance is affected greatly by passive mechanisms due to the low
pressures and large compliance values present in the pulmonary circulation
...
Blood flow per alveolus is much higher in the base of the lung compared to the top
...
138
If lung is inflated (too much air), alveoli inflate and blood vessels get compressed
...
Rich lymphatic vascularization protects against edema
Pulmonary circulation has no autoregulation
...
There is unique hypoxic pulmonary vasoconstriction
...
Hypoxic pulmonary vasoconstriction regulates the distribution of blood flow within the
lung
...
It is used if a bronchi is blocked
...
Long lasting hypoxia leads to pulmonary hypertension
...
Distribution of resting cardiac output:
Cerebral + Coronoary blood flow: 20%
Renal blood flow: 20%
Skeletal muscle blood flow: 20%
Skin blood flow: 20%
Splachnic & rest blood flow: 20%
Left coronary artery has 85% of heart blood flow
...
139
In left ventricle, blood vessels are compressed during systole so most blood flow in the
left ventricle happens only during diastole
...
Resting tone of arterioles in coronary circulation is determined by basal tone only
...
Blood flow is regulated by metabolites released from cardiomyocytes
...
When oxygen extraction is maximal (80%), increased metabolism must be supported by
increased flow
...
Cardiac work:
The heart increases momentum of blood by 15% and also increases the pressure of the
blood by 85%
In general: higher the metabolism of the organ, higher the oxygen uptake
...
80% oxygen consumption during exercise
...
(K+, acidosis, adenosine,
PGE2)
Skeletal muscles have significant capillary recruitment during exercise
...
37-7
...
Endogenous (metabolic end products) &
Exogenous (organic and inorganic substances)
- Endocrine function (renin, erythropoietin, calcitrol)
- Gluconeogenesis
Functional unit of kidney is nephron
...
2 million nephrons
...
Superficial nephrons are called cortical nephron
...
Loop of Henle is always in the medulla
Cortical nephron (aka short looped nephron): Has a short loop of Henle
...
Juxtamedullary nephron (aka long looped nephron): Has long loop of Henle
...
Malphigian Corpuscle: Ultrafiltration - 180 litre/day
...
Transport
processes are not regulated here
...
Phosphate is an exception
...
Building of medullary gradient
which is needed for water reabsorption
...
1-2 litres of urine is produced everyday
...
Perfusion of the renal cortex is very high compared to the renal medulla
...
Cortical nephrons use peritubular capillaries and juxtamedullary nephrons use vasa recta
...
Renal blood flow is fairly constant between the mean arterial pressure values (80-180 mm
Hg)
Kidney autoregulation has:
- Bayliss effect (biogenic vasoconstriction) (regulates perfusion of kidneys)
- Production of local vasoactive metabolites (regulates resistance of arterioles in kidney)
- Tubuloglomerular feedback
If mean arterial pressure is less than 60 mm Hg, there is no urine production in the kidney
...
Gets blood from afferent arteriole and blood taken away by efferent arteriole
...
143
Juxtaglmerular apparatus - Renin and Adenosine production
...
(Diameter, radius, shape of substances)
Glomerular membrane (blood plasma transported through it) has:
- Capillary endothelieum
- Basal membrane
- Podocytes
...
Glomerular capillaries have relatively high pressure for normal ultrafiltration
Vasoconstriction: Vasopressin, Angiotensin II, Adenosin
Vasodilation: PGE, PGI2
Proteins cannot be filtered through the glomerulus
...
Pressure in bowmans capsule is pretty much constant
...
Lower the molecular weight, molecular radius and molecular diameter, greater the chances
it'll be filtered
...
Urine production: 650-3500 ml/day or 0
...
Transport from peritubular capillary to tubular fluid is secretion
...
For Na reabsorption
70% in proximal convulated tubule
20% in Loop of Henle
9% in distal convulated tubule
For water reabsoroption
70% in proximal convulated tubule
10% in loop of Henle
19% in distal convulated tubule
...
Epithelial transport processes transport stuff through the epithelial monolayer of tubules
...
Epithelial cells have luminal cell membrane projecting into lumen of tubule
...
145
Proximal Convulated tubule
...
Basal membrane has interdigitations, many mitochondrial, tight junctions are relatively
open
...
In the proximal convulated tubule, there is high transport capacity
...
Paracellular and Transcellular transport happens here
...
Small membrane surface thus transport capacity is relatively low
...
In the ascending thick segment: no brush border, plenty of mitochondria
...
Active transport can
happen here
...
Distal Convoluted Tubule
Has juxtaglomerular apparatus - renin production
...
Less transport capacity than PCT
...
Only
transcellular transport in DCT as the tight junctions are closed here
...
Thus only transcellular transport here
All regulated transport is in DCT except for phosphate ions whos regulation happens in
PCT
...
Water impereable epithelium is in the ascending limb of loop of Henle
...
Salt removed from luminal compartment into interstital fluid without changing
fluid volume in each compartment)
146
If tight junctions open, paracellular transport can happen
...
Transcellular transport isn't dependent on tight junctions because movement is through
the cell
...
Epithelial cell -------> Capillary : Efflux
Capillary ------------> Epithelial cell: Influx
Tubule Lumen ----------> Capillary: Reabsorption
Capillary ---------> Tubule Lumen: Secretion
Tubule lumen -------> Epithelial cells :Influx
Epithelial cells ---------> Tubule lumen: Efflux
...
50% of Na reabsorbed is due to solvent drag mechanism
...
This can be saturated
...
Primary active transport can build up gradients
Secondary active transport uses the gradient made by primary active transport and can
build up gradient of its own
...
Ca2+ ATPase (Ca2+ pumps) can be found in DCT
147
Clearance principal: Amount of plasma that is cleared of a substance during one minute
(ml/min)
Clearance gives information about the kidney function
...
Things are reabsorbed by tubular transport processes
...
This is the theoretical maximal value of clearance
...
Glomerular filtrate
Volume
180 l/day
Glucose
16 g/day
Protein
20 g/day
Sodium
Cells
Urine
1
...
Transcellular and paracellular pathways both happen here
...
In the proximal tubule, there are 2 secondary active transport and 1 passive transport for
Na+ reabsorption
...
All this reabsorbs 70% of water of glomerular filtrate
...
Reabsorbed into epithelial cell by Na+ solute symport (cotransport)
...
In the basal membrane of epithelium, GLUT transporter is used to transport glucose out
of the cells to the capillaries
...
Glucose transporter is only in PCT
...
Arteries:
Renal ------> Interlobar -----------> Arcuate ----------> Interlobular ----------> Afferent
arteriole --------> glomerulus ------------> Efferent arteriole ------> Peritubular capillary
Glmoerulus - Ball of capillaries
Nephron is the functional unit of kidneys
...
Macula Densa is
involved in hormonal regulation and feedback mechanism
...
No vasa recta
...
Juxtamedullary nephron:
Near the border between cortex and medulla
...
Has Vasa Recta
...
In glomerulus, there are fenestrated epithelium + basement membrane + podocytes
...
After filtration, soluts can undergo: partial reabsorption, complete reabsorption or
secretion
...
DCT does fine adjustment
...
Clearance = urea conc x urine flow rate / plasma conc
Concentration is of a particular substance
...
In this scenario, clearance = GFR
- If a substance is filtrated and less amount is excreted then GFR > Clearance
This is due to tubular partial reabsorption
...
This is due to tubular secretion
- If total filtrated amount of substance is reabsorbed, Clearance = 0
There is complete reabsorption
...
Afferent and efferent arterioles make up nearly 70% of total renal vascular resistance
...
(favors filtration)
Glomerular colloid osmotic pressure and Bowmans capusle pressure act in the opposite
direction
...
Sensed by macula
densa, alters GFR and afferent arteriole resistance
...
This means usually, glucose and amino acid clearance = 0
...
Urine made up of urea, creatinine and small amounts of ions
...
(these 2 are primarily in the 1st half of the proximal tubule)
In the 2nd half of proixmal tubule is:
Na+/proton exchanger and paracellular transport
151
Water can be reabsorbed paracellularly and transcellularly in the proximal tubule
...
Organic cation transporteres are present
...
Nephron: Morphological and functional unit of kidney
Malphigian corpuscle: Glomerulus + Bowmans capsule
...
Macula densa of DCT is near the afferent and efferent arterioles where they are close
together at the Bowmans Capsule
...
part of the juxtaglomerular apparatus
...
Tubuloglomerular feedback:
Macula densa sends information to renin producing cells and afferent and efferent
arterioles
...
If blood pressure is high, macula densa senses the increased Na+, Cl- concentration in
blood
...
Adenosine constricts afferent and dilates efferent arterioles
...
152
Renin hormones also breaks down angiotensinogen to angiotensin I and then angiotensin II
...
In the proximal tubules, epithelial cells have luminal and basolateral membrane
...
Na+ reabsorption happens in the PCT using 3 mechanisms including Na+/proton antiporter
on luminal membrane
...
Glucose is completely reabsorbed in proximal tubule
...
If blood glucose level is above 10 mmol/l, not all glucose will be taken up by the cell as
glucose transporters will be saturated
...
15% of filtrated water is reabsorbed in the descending limb of the loop of Henle
...
It makes the
filtarte hypoosmotic
...
Distal convulated tubule does reabsorption of 15% of filtrated water
...
There are 2 types of collecting ducts: Inner medullary and cortical
...
Cortical collecting duct: Na+ reabsorption and K+ interstitium secretion are coupled
...
Urea: end product of protein metabolism
...
Urea transporters - UT1
Upto 40% Urea can be reabsorbed from the collecting duct if ADH present
...
ADH - anti diuretic hormone
...
Stimiuls for ADH release is increased plasma Na+ concentration
...
GFR = glomerular filtration rate = 180l/day (120 ml/min)
Inulin and creatinine is used to determine GFR
...
If low blood pressure, there is decreased Na+, Cl- concentration in distal convulated
tubules
...
In proximal tubule:
peptides with small molecular weight are reabsorbed by carrier mediated mechanisms
...
Only very small peptides and proteins pass through into the glomerular filtrate
...
Basolateral membrane of epithelial cell has amino acid transporters
...
This and pinocytosis removes all filtered proteins/peptides from tubules
...
in the 3rd segment of proximal tubules, uric acid will be secreated
...
Uric acid, K+, H+, organic acids, organic bases are secreated into the proximal tubules
...
Osmolarity is unchanged in the entire proximal tubule
...
Both thin segments have exclusively passive transport cuz of very few mitochondrial
present
...
Loop of Henle reabsorbs 20% filtered Na, 10% filtered water
Lets hypotonic fluid go into the distal tubule
Does concentration (descending segment) and dilution (ascending segment) of tubullary
fluid
...
Thin descending limb:
- No active transport
- Freely permeable to water
- Osmolarity increases from 300 to 1200 due to water leaving tubular fluid (water
reabsorption)
- Na+, Cl- in tubular lumen
...
Thin ascending limb:
- impermeable to water
- Freely permeable to Na+, Cl- (passive reabsorption of them)
- Osmolarity decreases but volume of fluid doesn't change
...
Thick ascending limb:
- 0 water permeability
- Actively and passively reabsorbs Na+, Cl- Osmolarity decreases in tubular fluid
- Concentration of urea unchanged because of low water permeability
...
Na+/K+ pump on its basolateral membrane
which causes Na+ - K+ - Cl2- symport (secondary active transport) on luminal membrane
...
50% of filtered urea will be reabsorbed in proximal tubule
...
Distal tubule - Concentration of urea in the tube increases due to water reabsorption
Urea permeability transporters are observed in the medullary part of collecting duct
...
They can take urea from tubular fluid to intersitium
...
Has many mitochondria and tight junctions are closed
...
At basolateral membrane, there is Na+/K+ pump and K+ - Cl- pump
...
Both go through respective ion channels present on lumina membrane by diffusion
...
At the basal membrane, there are Ca2+ and Mg2+ pumps (primary transport) and Na+/Ca2+
and Mg2+/Ca2+ antiport exchange (secondary transport)
Vitamin D3 regulates Ca2+ reabsorption
...
1% of filtrated Ca is excreted
...
This by
separate Na+ and K+ channel;s
...
Basal membrane once again has Na+/K+ pump
Na+ intake from drinks and food
...
Also due to sweat, stool
...
Angiotensinogen produced in liver
...
Angtiotensin Converting Enzyme (ACE) converts angiotensin I (10 amino acids) to
angiotensin II (8 amino acids) in the lung
...
It also stimulates thirst, salt appetite centers in hypothalamus
Also regulates aldosterone production in adrenal cortex
...
Increases ADH, atrial stretch and adrenalin
...
99% of filtered Na is reabsorbed by kidney
...
Water in urine output is 1000 - 2000 ml per day
Thirst sensation by angiotensin II, hypothalamic centers (barorevptord affect these decrease in blood pressure sensed by baroreceptors causes thirst)
159
Vasopressin (ADH) mainly regulates control of water loss from the body
...
ADH does water reabsorption from collecting ducts through aquaporine channels using V2
receptors
...
Collecting duct is impermeable to water and urea in the absence of ADH
...
No paracellular transport
...
This is diabetes
onspidus
...
Urine concentrations are affected by length of loop of Henle and the % of long loop and
short looped nephrons
Hyperosmolarity in renal medulla (needed for water reabsorption) comes from ions and
urea
...
Na+ and Claccumulation
...
Urea accumulation
...
Renal cortex is isosmotic
...
Cl-, Na+ recirculates from ascending to descending limb in loop of Henle
...
Urea concentration increases in distal tubule due to water getting reabsorbed
Urea reabsorption in medullary collecting duct is ADH dependent
...
Vasa Recta also has counter current mechanism
...
Concentration of urine decreases (more water present in urine) due to:
- increased blood pressure
- Diabetes insipidus
- Thiazide (inhibits Na+ - Cl- cotransport)
- Loop Diuretics (inhibits Na+ - K+ - 2Cl- symprt)
(ions not reabsorbed so medullary gradient not built and thus water is not reabsorbed
...
Only stomach stores food, for up to several hours, and then sends it in small portions to
the duodenum
...
161
There are 500 species of bacteria in the GI tract
...
9l/day is secreated and absorbed from the GI tract
...
If there's too little reabsorption - Diarrhea
If there's too much reabsorption - Constipation
...
Key site of nutrient and fluid absorption is the small intestine
...
Fluid secretion is done by crypts
FLuid reabsorption is done by villus
...
As you move from the proximal part of the small intestine to the large intestine:
Permeability reduces
Gap between cells reduces
Resistance increases
Gut cells can be controlled by mechanical, chemical and osmotic stimuli of foodstuff
...
All this controls the motility, blood perfusion and secretory amounts of the GI tract
...
Enteric Nervous System is influenced by sympathetic and parasympathetic systems but it
can work properly on its own as well
...
Hirschsprung disease is due to local absences of ENS in the colon
...
Effector systems related to ENS are muscles, secretory epithelium
...
Parasympathetic nerves innervate GI tract with preganglionic fibres,
Sympathetic nerves innervate GI tract with postganglionic fibres
...
Sympathetic effects takes place mainly via the ENS and there are also direct effects
...
Sympathetic nerves inhibit GI function
...
Long reflex1: reflex integrated in CNS through the brainstem and spinal cord
...
These cells are found only in the mucosal epithelium
...
Secretins act as physiological antasctids
...
- CCK is a hormone that does gall bladder contraction
...
- Motilin does coordination of the cleansing movements of the empty stomach/small
intestine
...
Due to insulin, glucose is taken up by the cells
...
This causes a change in the osmolarity leading to thirst
...
If BER crosses the threshold, there is influx of Ca2+ ions eventually leading to contraction
of smooth muscle cells,
Number of Ca2+ spikes determine how long and how strong smooth muscle contraction is
...
Segmental contractions are responsible for mixing only
...
MMC (migrating myoelectric complex)
It is the periodic electrical and peristaltic activity in the EMPTY stomach, small intestine
...
Then 1
...
This moves undigested food to the colon
...
Damaged part of GI tract gets sympathetic signals which could lead to paralytic ileus
...
Biting and the 1st part of chewing is voluntary
...
Thus chewing is partly automated, partly myotatic (stretch) reflex
...
Oral cavity: Not much digestion happens here (only amylase breaks down starch here)
165
Initial part of swallowing is controlled by striated muscles
...
Contact with esophageal mucosa causes peristalsis
...
Efferents are CN 9 and 10
Issues with swallowing can be due to inflammation, narrowing, diverticulim of esophagus
...
Acidic reflux happens when acid from the stomach enters the esophagus
...
Primary peristalsis: Peristaltic wave initiated from pharynx (voluntary action)
Secondary perisatic waves: Removes residual bolus
...
At both esophageal sphincters there are changes in the pressure leading to opening and
closings
...
Achalasia: Lower Esophageal Sphincter doesn't open
...
However food must be made moist
...
This lubrication is
done by the saliva
...
Saliva secretion is about 1
...
Acinus: Primary secretion (isotonic, similar amounts of Na, K, Cl)
Ductus: Secondary secretion (Hypotonic)
Between acinus and ductus are intercalated ducts
Primary saliva has:
Na+ : 140 mmol/l
K+ : 10 mmol/l
Cl- : 110 mmol/l
HCO3- : 40 mmol/l
As saliva flows through the channel, Na and Cl is absorbed and K+ and HCO3- is added to
the saliva
...
Na+ is actively reabsorbed using aldosterone
...
Higher the saliva flow rate, higher the Na+, Cl- content in saliva as it cant be reabsorbed
as quickly
...
Both systems promote saliva secretion
...
167
Conditioning (cephalic), food and smell all increase parasympathetic activity causing more
saliva secretion
...
Dehydration, fear, sleep reduces parasympathetic activity causing less saliva secretion
...
In terms of motility, the stomach can be divided into 2 parts:
proximal part
distal part
...
- HCl acts as defense line against invasive bacteria
- Partial digestion of proteins happens in stomach
...
HCl does this denaturation
...
There is no peristalsis at the fundus of the stomach
...
In the distal portion of the stomach, motility:
Empty stomach motility is controlled by MMC
Filled stomach motility is controlled by peristalsis
...
Distal part of stomach has BER/pacemaker cells
Duodeneum has an even greater number of BER/pacemaker cells
...
Eventually these waves open up the pyloric sphincter
...
Control of gastric peristalsis:
Neural control, Strech and Content of stomach stimulate ENS neurons promoting gastric
motility
Gastrin (hormone) is also produced in response to neuronal and chemical stimuli
Intestinal phase inhibition - prevents too much food from coming into the intestines from
the stomach
...
CCK is produced in the duodenal wall in response to fat content of the stomach
Gastric mechanisms promote emptying
...
Stimuli for vomitus: GI tract irritation, Visceral pain, drugs, visual/olfactory stimulus,
pregnancy, irradiation
169
Area postream is a thermosensitive trigger zone with no blood brain barrier
...
Nausea: Symptoms preceding vomitus
Retrograde intestinal contractions causes reverse filling of the stomach
...
Small intestine functions:
digestion, mixing, absorption of water and digested food
...
When the small intestine is not empty, motility is done by peristalsis and segmentation
...
In peristalsis, food actually moves forward
...
Gastrin hormone does stimulation of motility
...
Stores and controls defecation
...
Gastrin causes the ileocecal sphincter to open allowing motility
...
Colon contains gas bubbles
...
External anal sphincter is under voluntary control
...
170
Cephalic phase of GI tract secretion - Secretion of GI juices when there has been no
contact with food
...
In the stomach you have:
Mucous neck cells: Secreates mucus (protects the gastric lining) & bicarbonate
Parietal cells: Secreates gastric acid (HCl) & Intrinsic factors
Chief cells: Secretes pepsionogen and gastric lipase
D cells: Secreates somatostatin (inhibits gastric acid)
G cells: Secreates gastrin (main hormone, stimulates gastric acid)
Stomach pH: 1 - 1
...
5L / day
Gastric juice contains HCl, pepsinogens, gastric lipase, mucus, intrinsic factors, alkaline
fluid and HCO3 HCl does protein denaturation, activation of pepsinogens and has bactericid effect
Parietal cells:
In the resting phase - Canals for gastric acid secretion are less in number and are
narrower
...
The pump responsible for gastric secretion is H+/K+ ATPase
...
H+ and Cl- are separately secreated into the lumen and then they join together in the
lumen
...
Regulation for gastric HCl secretion is very complex
...
- Parasympathetic activity (using acetylcholine) stimulates gastric acid secretion
...
- Prostaglandins can enhance gastric acid secretion
- Bacterium H
...
Higher the secretory rate, higher the gastric acid secretion, higher the H+ & Cl- in the
lumen
...
Cephalic phase: Food not yet in stomach
...
Gastric phase: Food already in stomach
...
Elevated pH registered by chemoreceptors
...
172
Somatostatin is an inhibitor for gastrin and gastric juice secretion
...
2) Increased HCl from parietal cells increases the secretion of somatostatin from D cells
...
PErfect negative feedback loop
...
Prevents really fast emptying of foodstuff from
stomach into duodenum
...
CCK and GIP also have similar effects
...
The stomach has mucosal defense mechanisms:
- Secreating mucin (becomes a thick mucous film ontop of the gastric surface
...
Bicarbonate neutralizes acids
...
The mucosal barrier can be destroyed by: alcohol, stress, glucocorticoids and heliobacter
pylori
...
173
- Osmotic activity could increase leading to diahrrea
- Lipids, fat soluble vitamins are not digested
Chief cells secreate pepsinogen (proteolytic proenzymes) via exocytosis
...
Chief cell secretion is regulated by the vagus nerve (PSY) - Acetylcholie - M3 receptor,
Gastrin, CCK, Secretin
Parietal cells secreate HCl
...
HCl also converts pepsinogen (inactive form) to pepsin (active form) which can then digest
proteins
...
Acinar cells secreate digestive enzymes
...
Pancreatic juice secretion: 200-700 ml/day
Contain proteolytic enzymes, lipases and pancreatic amylase
...
As they move through the ducts, the environment becomes more and more alkaline
...
Pancreatic duct cells have HCO3- and Cl- transports facing the duct lumen
...
Cephalic phase - sight, smell, thought of food has a parasympathetic effect via the vagus
nerve
...
174
CCK, Secretin and vagus nerve thus control pancreatic juice secretion
...
This protects against self digestion
...
There is also a pressure gradient forcing proenzymes to move away from the pancreas
reducing the chances of self digestion
...
Trypsin then activates the other proenzymes
...
This eventually causes Na_ and water to follow via passive osmosis
...
Bile is produced by hepatocytes (60%)
Cholangiocytes (epithelial cells of bile duct) produce HCO3- & water (40%)
Bile promotes lipid digestion & absorption by using emulsification and micelle formation
...
Bile from liver:
Rich in bilirubin, golden yellow in color
...
Parasympathetic input stimulates bile production by the liver
...
Cholelithasis - Gall stones (bile contains too much cholesterol & not enough bile salts)
GI system does:
uptake of food, fluid
Transport, temporal storage of food, fluid
Digestion, Absorption of food, fluid
Waste management
Only the upper 1/3 of esophagus and external anal sphincter have skeletal muscle fibres
with somatic motor innervation (controlled only by CNS)
Thus chewing, swallowing, defecation are all voluntary
...
176
Regulation of GI function:
Neuronal (Nervous system vua reflexes)
Endocrine (hormones)
Paracrine (local regulators)
Sympathetic system:
inhibition of bowel movement and GI function
Contraction of sphincter muscles (phospholipase C enzyme activates IP3, DAG)
Increases saliva production
Can act directly or indirectly on GI tract
...
Alpha 2 receptors, cAMP levels reduce
Direct action: Beta 2 receptors on smooth muscles, cAMP levels increase
Both sympathetic and parasympathetic activity increases saliva production
...
Vagus nerve is used
...
Mostly postganglionic neurons
Parasympathetic: From vagus & pelvic splanchnic nerves
...
Enteric Nervous system can act independent of central nervous system
...
Neurotransmitters of ENS are:
Excitatory: AcH, CGRP
Inhibitory: VIP, NO, ATP (These inactivate the smooth muscle and thus dilate the wall)
177
Enteric nervous system has submucosal and myenteric plexus
...
Vagovagal reflexs:
Vagus nerve has 75% efferent (parasympathetic preganglionic) & 25% afferent (Sensory)
fibres
...
Afferent is GI wall
...
Long reflex: Parasympathetic reflexes (stimulate GI activity)
Info goes to CNS and comes back via the vagus nerve
Blood flow increases in the working sections of the GI tract
...
Cholinergic effector neurons innervate endothelieum of blood vessel,
Endothelieum cells release NO which causes vasodilation
...
Such reflexes are done only by sympathetic psotganglionic fibres
...
178
Secreated when amino acids, peptides detected in stomach, vagal stimulation, distension of
stomach
...
Secreated when small peptides and amino acids have been detected
...
Stimulates contraction of gall
bladder, relaxation of sphincter of Oddi
...
Effects: Increases pancreatic and biliary HCO3- secretion
...
Inhibits the trophic effect of gastrin on gastric mucosa
...
- Ghrelin - hunger hormone
...
Secreated when empty stomach
...
- Leptin - Satiety hormone
Produced by fat cells in proportion to amount of fat stored in adipose tissue
...
All GI hormones are peptides having plasma membrane receptors
...
Stimulated by pH decrease in duodenal lumen
Effect: It inhibits the secretion of G and ECL cells
...
179
Somatostatin can also be released by hypothalamus and pancreas to inhibit insulin and
glucagon
Histamine (amine)
Produced by ECL (enterochromaffin like cells) of gastric mucosa
...
Parietal cells (body of the stomach) produce HCl & Intrinsic factor (for absorption of
vitamin B12)
Chief cells (body of the stomach) produce pepsinogen
G cells produce gastrin (hormone)
D cells (antrum of stomach) produce somatostatin
...
Pepsin is a protein digesting enzyme
...
Basolateral side has Na+/K+ ATPase and Cl-/HCO3- exchanger
...
This pumps H+ into the lumen
Cl- leaves the parietal cell and goes into the lumen via Cl- leaky channel on the luminal side
...
Phases of HCl production:
Cephalic, Gastric, Intestinal
...
Food only been seen, smelt or
thought of
...
Gastric phase has local reflexes due to mechanoreceptors & chemoreceptors
...
Zollinger Ellison syndrome
Gastrinoma: Too much gastrin produced, too much HCl produced
...
This mucus layer contains bicarbonates in it which make it a very effective barrier
...
Pylori all damage the gastric mucous layer
...
Sympathetic preganglionic come from thoracolumbar spinal cord
...
Both preganglionic neurons use acetylcholine
...
Short reflex: Protective reflexes inhibiting GI activity
...
Gastrin, Secretin, CCK, VIP are all endocrine
...
Gastrin
Made by: G cells of stomach
Secreated when: small amino acids, peptides present in stomach
...
Action: Enhances production of gastric acid, stimulates growth of gastric mucosa,
emptying of stomach
...
Effect: Induces gall bladder contraction & emptying
...
Inhibits gastric emptying
...
Secretin
Made by: S cells of duodenum
Secreated when: Duodenal pH reduces
...
GIP (glucose dependent insulinotropic peptide)
Made by: Duodenum and jejunum
182
Secreated when: Fatty acid, amino acid, oral glucose presence
Contraction on oral side, relaxation on caudal side moves the food forward (peristalsis)
Segmentation - Mixing food
...
MMC (migrating motor complex)
Sucking is an innate brainstem reflex
Saliva functions:
Digestion (amylase), lubricants, moisturizes, promotes taste and has alkaline pH
...
Both sympathetic and parasympathetic fibres increase saliva production
...
Rich in digestive enzymes
Sympathetic effecr: Lesser amounts of saliva produced
...
Swallowing phases:
Oral phase (voluntary)
Pharyngeal phase (involuntary)
Esophageal phase (involuntary)
Primary peristalsis: Peristaltic waves are initiated only in the pharynx by contact with
food
...
Secondary peristalsis: Residual bolus left in the esophagus initates a new peristaltic wave
...
During filling of stomach, there is receptive relaxation (local reflex, vago vagal reflex)
After filling, there is tonic contraction (proximal portions of the stomach does not
participate in peristalsis)
183
Movement in the distal portion of the stomach:
During fasting state: MMC
During filled started: peristalsis
...
Gastric acid converts pepsinogen (inactive) to pepsin (active)
...
These reactions happen inside the parietal cell
...
Chief cells produce pepsinogen
...
Somatostatin produced in stomach, pancreas and hypothalamus
...
How to measure gastric acid secretion?
BAO (basal acid output)
MAO (mean acid output) - the output of gastric acid 1 hour after stimulation
184
Pancreas has endocrine and exocrine parts
...
Also produces bicarbonate to neutralize gastric acid and the acidic environment and
provide a proper, suitable environment for pancreatic function
...
They are then split and converted to their active form in the small intestine by
enteropeptidase only
...
Sends out bilirubin and cholesterol
...
Simultaneously, cAMP inhibits Cl absorption
...
Lactose broken down by Lactase
...
Saacrose broken down by Sacchrase
...
Both are broken down by Maltase to give glucose
...
Bile emulsifes fats
...
Cholesterol, fatty acids, monoglycerides are absorbed by the small intestine epithelial
cells
...
Induced by stretch of rectum wall leading to relaxation of internal anal sphincter
...
- Transoprt of absorbed products into blood or lymph
...
186
Amylase found in saliva along with very little lipase
...
Esophagus: swallowing
Stomach: Storage & Grinding
...
Drugs, alcohols are absorbed here
...
Here the intestinal juice, pancreatic juice (which has enzymes to digest everything) and
bile combine to do digestion of all nutrients
...
Vitamin B12 and bile acids are absored only in the ileum
...
Mouth contains amylase, lingual lipase (insignificant)
Stomach has pepsinogen (with gastric acid its converted to) pepsin
...
Proenzymes (inactive form) are secreated from the pancreas
...
These enteropeptidases convert
proenzymes to proper enzymes
...
Absorption done by intestinal villi
...
187
Humans can digest starch but not cellulose
...
Carbohydrate requirement (400-500 g/day)
Carbohydrate digestion starts in mouth by salivary amylase
...
Brush border enzymes: lactase, maltase, sucrase break it all down to monosaccharides:
glucose, galactose, fructose
...
Only monosaccharides can be absorbed by intestinal wall
...
If they
have milk or dairy products they will suffer from diarrhoea cuz lactose remains in the
intestinal lumen and draws water towards it into the lumen
...
Sucrase is one of the intestinal wall enzymes
Protein requirement (100 g/day)
Dietary proteins -------------(In stomach, they are exposed to HCl & Pepsin)--------------->
Denatured & partially hydrolyzed protein ----------- (In small intestine, they are exposed
to trypsin, chymotrypsin, aminopeptidase)-------------------------------------> Small
peptides, amino acids
Due to brush border enzymes (aminopeptidase, dipeptidase), they are converted to amino
acids and transported to the blood stream by active transport
...
H+ leaves the cell using H+/N+ antiport
...
Due to cotransport, along with H+ di & tripeptides enter the cell
...
Small peptides can also be taken into the intestinal cell by endocytosis and sent out to
blood via exocytosis
...
Lipids requirement is 50-100 g/day
...
These are taken up into the intestinal cell
...
Fats are not only an energy source
...
Ca2+ enters cell via Ca2+ channel
...
189
Ca2+ is removed from cell into interstitium via primary and secondary active transport
...
Removal of Ca2+:
- Na+/K+ ATPase present which removes Na+ from the cell
...
Entry of Na+ sends Ca2+ out (secondary active transport)
- Ca2+ is also removed by Ca2+ ATPase to the interstitium (primary active transport)
Patacellular diffusion of calcium is also possible
...
This doesn't increase Ca2+
concentration in cell
...
Vitamin D3 is made from cholesterol
...
Iron daily required intake is 10-20 mg/day
Iron is necessary for hemoglobin
Only Fe2+ can be absorbed
...
In the cell Fe2+ cam become Fe3+ (storage)
Fe2+ leaves the cell using ferroportin
...
Heme can be taken up by enterocytes and broken down within
...
Lack of vitamin B12 causes abnormally large RBCs
...
Intrinsic factor is vital for Vitamin B12 absorption
Intrinsic factor produced in the stomach
...
Forms B12-R protein complex in stomach
...
B12 intrinsic factor complex present in the intestine
...
On the basolateral surface, there is always Na+/K+ pump which pumps Na+ out of cell to
interstitium
...
(in colon, ileum)
In this, H2O is split into H+ and OH-
...
The OH- combines with CO2 to form HCO3- which is exchanged with Cl- coming into the
cell
Water absorption can be stimulated by organic solute/sodium absorption
...
In colon, water and salts only are reabsorbed
...
Antiperistalsis - forward and backward movement only
...
slow anal propulsion
...
no mixing
...
When rectum is full then defecation happens
...
This principle applies to entire GI tract
...
In the colon, Na+ enters cell by multiple pathways:
- Na+ channels (enterogenic)
- Na+ and Cl- symport
- 4) Na+/H+ exchange with net NaCl absorption
...
The H+ is exchanged with Na+ coming into the cell
...
Gut flora can:
Synthesize vitamin B and Vitamin K
...
Defecation - release of feaces
...
Afferent: ENS sensory cell fibres
Center: Medulla, hypothalamus, sacral spinal cord
Efferent: Pudendal nerve, pelvic nerve
Effects: Relaxation of internal anal sphincter, abdominal pressure increase
...
Parasympathetic fibres trigger contraction of rectum wall
...
Metabolism converts nutrients to heat, mechanical energy and is used for synthesis
(building up reactons)
Metabolism = Catabolism + Anabolism
Catabolism is breakdown
...
Anabolism is synthesis
...
(transferred energy/elapsed time)
1 kJ = 0
...
2 kJ
Efficiency is given in %
...
Normal body efficiency = 20%
Heart efficiency is up to 40%
Basal Metabolic Rate is between 6500 kJ/day (75 W) - 7100 kJ/day (100 W)
193
Basal Metabolic Rate includes homeostasis, metabolism, respiration, circulation, CNS
function, exocrine & endocrine function
...
Food uptake increases BMR
...
Proteins have a much larger and longer thermic effect than other nutrients
...
Physical activity increases energy expenditure and thus BMR
...
Average energy expenditures:
Sleeping - 280 kJ/hour
Standing - 420 kJ/hour
Swimming - 2000 kJ/hour
Walking up the stairs - 4400 kJ/hour
Mental activity also increases the work/activity of the skeletal muscles and thus
influences the metabolic rate too
...
194
Every 10 degrees rise in the temperature results in 2-4x increase in the speed of chemical
reactions
This increased activity of chemical reactions increases heat production
...
Age and Gender also affects the BMR
...
Males have higher Basal MEtabolic Rate than females cuz males have less adipose tissue
than females
...
Increased thyroid hormone value leads to increased basal metabolic rate by 80% of normal
value
...
Oxidative metabolism:
Nutrients combine with O2 to give CO2, heat, water
...
Proteins, peptides, amino acids + O2 ---------> CO2 + H2O + urea + heat
This oxidation is incomplete oxidation
...
2 kJ/g
Protein
Fats
17
...
9 kJ/g
Required intake per day
370 g/day
70 g/day
65 g/day
195
Direct calorimetry: Determination of the used energy based on the body heat release
...
Total energy expenditure during work can be measured
...
Caloric equivalent values for O2 at 37 degrees
...
1 kJ/l O2
Lipid: 19
...
8 kJ/l O2
RQ means respiratory quotient
...
7
Oxidation of mixed food - RQ = 0
...
If oxygen consumption increases, RQ decreases
...
Basal Metabolic Rate is measured most importantly to check for diseases of the thyroid
gland (T3, T4 hormones)
...
Essential macronutrients: Carbohydrates, Fats, Proteins
Also needed from diet:
Ions (Na+, K+, Ca2+, Mg2+, Cl-) These are vital ions which our body contain in very small
quantities
...
Vitamins are important because of their biological effects as coeznymes
...
Intake of water should be 40-50 ml/kg per day
...
Daily energy requirement is approximately 10,000 kJ/day
...
Neurons and RBCs are glucose dependent cells
...
Glycemic index: Indicates how fast the carbohydrates in a given food is absorbed
...
0 is the lowest
...
Low GI means there isn't a high increase in blood glucose levels
...
Mainly triglycerides are taken up
Fats are important in thermoregulation
...
Many unsaturated fatty acids are essential
...
Eg of polyunsaturated fatty acid:
Omega 6 (linoleic acid) from meats, plant oils, seeds
Omega 3 (anti inflammatory) from walnuts and linseeds
Omega 6 : Omega 3 ratio should be
1:3
Higher the serum cholesterol level, higher is the incidence of Coronary Heart Disease
...
Animal origin proteins: Complete proteins (contain all the essential amino acids in close to
optimal proportions)
N content of amino acids of food equals the N content excreated in urine and feaces
...
Otherwise, they are metabolized (gluconeogenesis or ketone bpdy production)
Positive N balance: During growth, pregnancy, breastfeeding
...
Negative N balance: During starvation
...
Daily protein intake should be 1 - 1
...
Essential nutrients: Cannot be made by the human body in sufficient quantities
...
Eg: Some amino acids, vitamins, some fatty acids
...
Can
replace each other
...
Groups of nutrients:
Macro:
Water
Energy (Carbohydrates, fats, proteins)
Proteins
Fiber
Micro:
Minerals
Vitamins
Trace elements
Nutritional balance: Uptake quals utilization
...
Overweight and obesity are risk factors for atherosclerosis and type 2 diabetes mellitus
...
Total energy demand = Basal Metabolic Rate + Work Metabolic Rate
BMR - no physical activity, normal ambient temperature
...
Metabolic rate of adipose tissue is much lower than that of muscle mass
...
This all causes acidotic metabolic state
...
Lipohilic vitamins can be taken up by the body only if we take up fats
...
Arachidonic acid is an essential lipid
...
Humans can get arachidonic acid directly from the diet or indirectly from linoleic or
linolenic acid
...
Recommended ratio of fats in diet
Polyunsaturated : Monounsaturated : Saturated
200
1:1:1
Proteins
Essential amino acids (we cant produce them, must be taken up in the diet)
Histidine, Isoleucine, Leucine, Lysine, Methioninie, Phenylalanine, Threonine, Tryptophan,
Valine
...
Carboxyglutamate is needed for blood clotting
...
NH3 and urea amount are indicators of N balance and protein consumption
...
Proteins from animal sources have perfect composition
...
Proteins from vegetable sources have less favorable composition
...
Thus required total protein intake must be higher for vegetable proteins
...
8 g/kg
Min: 0
...
Essential amino acid requirement:
20% in adult
40% in children
Vitamins can either be fat soluble or water soluble
...
Slightly increased vitamin uptake can have a positive effect
...
Too much fat soluble vitamin uptake is toxic
...
Not the case for fat soluble vitamins however
...
Vitamin E: Inhibition of immune system
...
Vitamin K: GI react disorder
...
Basically, antivitamins inhibit the physiological effect of vitamins
...
Cycloserin: binds to vit b6, prevents its effects
...
Need more minerals than trace elements daily
...
Eg: Cellulose, Lignin, polysaccharides
...
Energy in chemical form/storage is usable energy
...
Human body is an open system
...
1 mol Glucose -------------> 1 mol Glycogen
2780 kJ
1488 kJ
There is 46% heat disspation
203
BMR = resting metabolic rate under standard measurement conditions
...
Heat dissipation is proportional to body surface area
...
c) due to nutrition
Food intake leads to digestion, absorption, storage of food
...
Fasting leads to reduced BMR (by up to 40%)
Pregnancy, emotions, sympathetic nervous system activation, isotonic & isometric muscle
contraction all lead to a higher basal metabolic rate
1kCal = 4
...
Physiological caloric value: if the end products are CO2 and O2, it is equal to physical
caloric value
...
9 kJ/g
Carbohydrate 17
...
2 kJ/g
Glycogen - storage form of glucose
...
Makes up maximum 1% of body weight
...
Around 1L produced per day
...
Secondary saliva is hypotonic
...
Basolateral side has leaky Cl- channels and Na+/K+ ATPase
...
K+ enters the cell
...
H+, Cl-, Na+ come into the ductal cell from the lumen
...
Salivary ductal cells are impermeable to water
...
Sliva has alpha amylase enyme (for digestion of carbohydrates), lingual lipase, water,
electrolytes, mucin, immunoglobulin, kallikrein (an enzyme that breaks down HMWK to
bradykinin (vasodilator))
When there is vasodilation, saliva production is increased
When myoepithelial cells are contracted, saliva flows more smoothly
...
Food smell, taste, nausea activates parasympathetic nervous system
For parasympathetic system, both pre and post ganglionic neurons use acetylcholine as the
neurotransmitter
...
205
Approximatley 1L pancreatic juice is produced per day
Endocrine pancreas:
Alpha cells produce glucagon
Beta cells produce insulin
Delta cells produce somatostatin - inhibitor of glucagon & insulin
Exocrine pancreas produces digestive enzymes
...
Pancreatic secretion is isotonic
...
Cl- into cell, HCO3- into lumen
Basolateral side has Na+/K+ ATPase, Na+/H+ antiport exchanger
...
Na+ and H+ sent out to the blood
Carbonic acid (H2CO3) is present within the cell
...
H2CO3 breaks down to HCO3- & H+ which are sent out of the cell
...
These are present only in the lumen of the duodenum
...
Sympathetic activity inhibits pancreatic secretion
...
I cells produce CCK
...
Low pH acts on S cells
...
Secretin acts on ductal cells and thus aqueous secretion increases (more Na+ and HCO3secreated)
HCO3- neutralizes acidic pH from stomach
...
In duodenum, pancreatic amylase does this too
...
Protein digestion ends in intestinal mucosa (done by dipeptidases)
Trypsinogen (inactive) becomes trypsin (active) due to the action of enteropeptidases
which are anchored to the intestinal brush border
...
Lipids are digested by pancreatic juices which have lipases
...
Bile is composed of cholesterol (4%), bile salts (50%), phospholipids (40%), bile pigments
(bilirubin, urobilin)
600 ml of bile produced per day
...
Gall bladder also concentrates the bile
...
Bile piments & bile salts go to enterohepatic circulation (portal circulation)
...
Due to this, liver must only replace small amounts of the bile
...
Big drops to small droplets
Bile also does solubilization
...
Bilirubiin comes from the breakdown of hemoglobin
...
At liver, albumin dissociates
...
Bilirubin becomes urobilinogen due to the action of bacterial enzymes
...
The precursor for bile acids is cholesterol
...
From primary bile acids, you get secondary bile acids (deoxycholic and lithocholic acids)
...
MDR 2 transports conjugated bilirubin from hepatocyte to the bile caniculi
...
Puts the toxic stuff
into caniculi
...
This activates CCK which relaxes Oddi sphincter and contracts the bladder wall
...
CCK is a hormone
...
Motility of GI tract - grinding, mixing, propels food
...
Cajal cells are the
pacemaker cells similar to SA node
...
This causes burst of action
potentials
...
With action potentials, there are much stronger contractions
...
Oral phase: Food in the mouth starts the reflex
...
209
Irregular/rapid heart beat, paleness, sweating, increased secretion of saliva are all
vegetative symptoms before vomiting
...
During vomiting, constriction ring appears in the small intestine, glottis closes, Muller
mechanism happens, intrathoracic pressure decreases, constriction ring appears in the
stomach
...
There is mixing & propelling movements
...
Parasympathetic activity increases contractions
...
Only mixing, no
forward movement
...
Nutrition is needed for energy and anabolism (body composition)
Macronutrients (carbohydrates, proteins, lipids, nucleic acids) - building blocks is needed
in grams/day
Micronutrients (vitamins, trace elements) - special role
...
In terms of sheer quantity
...
Muscle and nerve cells have a very low turnover rate
...
2 J
1 cal is the amount of energy energy that can heat up 1g of H2O by 1 degrees Celsius
...
Energy efficiency of humans is approximately 20%
...
40% of available nutrients is converted to ATP
...
Energy in food is measured by:
Energy density (kJ/g)
Caloric equivalent (kJ/L O2)
Fats have the highest energy density
...
2 kJ/g
21
...
9 kJ/g
19
...
2 kJ/g
18
...
Calorimetry measures energy expenditure by measuring heat production (direct
calorimetry) or O2 consumption (indirect calorimetry)
Basal Metabolic Rate is the bare minimum, for basic life functions
...
Measured by calorimetry under standard conditions (not eating for at least 12 hours, after
a night of restful sleep, no physical activity before measurement, no causes of excitement,
20-26 degrees (thermoneutral))
DIT: diet induced thermogenesis
...
Balanced Diet: no wasting, no gaining, no lacking of macronutrients from diet
...
Minimum intake should be around 0
...
Daily oxygen consumption: 500 L per person
Maintaining a moderate blood glucose level at all times is beneficial (low GI is beneficial)
Too high GI means there will be a large spike in blood sugar levels leading to a large spike
in blood insulin levels which could cause insulin resistance
...
Essential nutrients: Our body doesn't have the enzymes required to synthesize them thus
we cant make them
...
They cannot be synthesized in human cells
...
Highly active cell types are more prone to vitamin deficiency
212
Hormones
Hormone - a chemical substance that is transported in the blood from site of production
to target organs
...
It is not a hormone
...
However, endocrine glands also have paracrine effect (act on neighbouring cells)
via diffusion
...
Endocrine and nervous system communicate with each other
...
Adenohypophysis
Thyroid gland
Parathyroid gland
Adrenal cortex
Pancreas (Langerhans islets)
Ovaries
Testes
...
Only present during pregnancy
...
214
Solubility determines the biological properties
...
ACTH preprohormone is called pre-pro-opiomelancortin (POMC)
...
Steroid hormones are produced from cholesterol
...
Enzymes used are cytochrome P450 and hydroxysteroid dehydrogenase
...
Thyroid hormones are stored in colloid
...
They are released into the bloodstream
because of passive diffusion through the lipid membrane
...
215
Increase in blood glucose levels cause increase in blood insulin levels
...
1 cycle takes about 15 minutes
...
Rise in GnRH is followed by a rise in LH
...
Daily cycles There is a very high cortisol concentration in early morning
...
Somatotropin peaks during early sleep every day and then reduces
...
1/2 life of hormone in blood - period of time needed for its concentration in blood to be
reduced by half
...
Insulin 1/2 life is 3-5 minutes
...
Usually, biologically active hormones are released
...
Eg: Thyroxine ---------> Triiodothyroxine
Testosterone ---------> dihydrotestosterone
Water soluble hormones are usually transported in free form
...
Protein bound hormones can be treated as a hormone pool
...
Liver also does reduction or conjugation of steroid hormones with glucoronic acid
...
Could be G protein coupled receptors (parathyroid hormone, Arginine vasopressin)
Could be guanylate cyclase coupled receptor (atrial natriuretic peptide)
Could be tyrosin kinase receptor (insulin)
2) Intracellular receptors - for lipid soluble hormones as they can get through the plasma
membrane
...
Peptide & protein hormones have much more rapid effects than steroid hormones
...
Positive feedback also present
...
This happens during the middle of the menstrual cycle
...
Vasoconstriction and vasodilation also affect hormone release
...
Pathophysiology could be because hormone levels are too high or too less or because
receptors levels are too less
...
Adenohypohysis produces and secreates growth hormone, adrenocorticotrophic hormone,
thyroid stimulating hormone, lutenizing hormone, follicle stimulating hormone, prolactin
...
Hypothalamus creates releasing and inhibiting hormones and sends them to
adenohypohysis
...
The adrenal gland sits omtop of both kidneys
...
(dehydroepiandrosterone)
218
Minearlocortioids are made from cholesterol
Enzymes used to modify cholesterol to aldosterone include desmolase, 21 OHase, 11
OHase, 18 OHase, 18 HSDH, 3 HSDH
...
40% of aldosterone is circulating as free aldosterone in the blood
...
Albumin - 40%, CBG - 20%
...
Lifespan of a hormone is elongated once it is bound to transport proteins as the binding
prevents the hormone breakdown
...
Once a mineralocorticoid hormone binds, new proteins are transcribed and made
...
Minerelocorticoids are steroid hormones
...
We have much more cortisol concentration in the blood than aldosterone
...
Aldosterone mostly acts on distal tubule of kidney
...
Aldosterone causes new proteins to form which act on transporters involved with Na+
...
Coupled with this is the increased secretion of K+, H+
...
219
High plasma K+ concentration, low plasma Na+ concentration and ACTH all directly cause
more aldoserone to be secreated from zona glomerulosa
...
Angiotensin II and III are made from angiotensin I which is made from angiotensinogen
...
Too much aldosterone (minerlocorticcoid) causes too much Na+ and water reabsorption hypertension
...
Cortisol production includes enzymes like 17 OH ase
...
15% is bound to albumin
...
Cortisol metabolic effects:
affects protein, glucose & lipid metabolism
...
Muscle tissue releases amino acids, fat tissue releases free fatty acids
...
Overall effect of cortisol: increased blood glucose concentration
...
There is a paracrine effect of glucocorticoids on catecholamine secretion
...
CRH from the hypothalamus and ADH acts on the pituitary gland to release ACTH
...
During fight or flight situations, glucocorticoid concentration increases
...
Cortisol concentration is usually highest in the morning, reduces during the day and
increases from midnight onwards
...
Cortisol production is under negative feedback control
...
ACTH acts on the adrenal cortex to release cortisol
...
ADH (vasopressin) acts like CRH, it stimulates ACTH production at the adenohypophysis
...
Can help maintain high levels of
cortisol
...
Protein kinase is made which converts cholesterin
ester to cholesterin
...
Thus ACTH main function: mobilize cholesterin and prepare it for cortisol production
...
Androgens also made from cholesterol
...
Only 7% DHEA is free in the blood
90% transported by albumin
...
Adrenal cortex may be destroyed by infection, cancer or autoimmune disease
...
Hormones are grouped by their chemical composition:
Protein/Peptide hormones
Amino Acid hormones
Steroid hormones (derived from cholesterol)
Steroid and thyroid hormones are fat soluble
...
Protein/peptide hormones are water soluble and have plasma membrane receptors
...
Free hormones in the blood are biologically active
...
Glucocorticoids are important for catecholamine release and catecholamine receptors
...
From the hypothalamus you get releasing hormones:
CRH, GnRH, TRH, GHRH
and inhibiting hormones: dopamine and somatostatin
Dopamine inhibits prolactin
...
Supraoptic and Paraventricular nuclei (in the hypothalamus) produce vasopressin and
oxytocin which go to the neurohypophysis and it is stored in vesicles here
...
Anterior pituitary has pulsatile secretion
...
Hypothalamus is influenced by the limbic system (sensory system, pain, sexual function,
metabolism) and by the suprachiasmatic nucleus of hypothalamus
...
Testosterone and cortisol release peaks in the early morning
...
Cortisol and ACTH plasma concentrations are lowest at midnight and peak round 7am
...
223
eg of negative feedback: testosterone negatively influences/inhibits GnRH from
hypothalamus
...
LH goes to testes and makes testosterone
...
Mid ovarian cycle, estradiol (hormone) increases the activity of anterior pituitary cells
which increases the release of FSH and LH and the cycle continues
...
Is a mixed reflex
...
- Cycle repeats until the baby is born
...
GnRH (Gonadotrophin releasing hormone) of hypothalamus causes FSH, LH to be released
from anterior pituitary
...
TRH (thyrotropin releasing hormone) of hypothalamus acts on TSH (thyroid stimulating
hormone) releasing cells of the anterior pituitary
...
GHRH (growth hormone releasing hormone) of hypothalamus acts on GH (growth hormone)
producing cells of the anterior pituitary
...
Angiotensin and renin needed for mineralocorticoid release
...
Oxytocin - ejection of milk
Calcitonin from C cells of thyroid gland and parathyroid hormone are antagonistic
...
224
Sympathetic stimulus and angiotensin II increase the ADH (vasopressin) release from
posterior pituitary
...
Vasopressin effect:
(on V1 receptors) Does vasoconstriction throughout the body
...
Due to this, blood volume and blood pressure increases
...
Use 2nd messengers
...
Steriod hormone action:
activates transcription factors, changes transcription and translation and thus alters
protein making
...
Cortex has zona glomerulosa (mineralocorticoids like aldosterone), zone fasiculata
(glucocorticoids like cortisol) and zona reticularis (androgens)
ACTH from anterior pituitary mainly affects zona fasiculata and zona reticularis
...
Higher the K+ level, more the aldosterone production
...
Cortisol is produced in response to stress
...
Cortisol causes:
increased gluconeogenesis
increased protein metabolism
increased free fatty acid in blood
Also acts as an immunosuppressant
...
Activates insulin
...
Growth hormone causes:
protein deposition into tissue,
fat utilization,
increased RNA translation,
increased DNA transcription,
decreased protein catabolism,
decreased glucose uptake,
increased gluconeogenesis
...
Things that inhibit growth hormone release:
increased blood glucose level
increased blood free fatty acid level
obesity
somatostatin
Effects of growth factors:
1) Increase cell mass by stimulating the production and inhibiting the degradation of
macromolecules
...
226
Eg of growth factors:
Epidermal growth factor
Fibroblast growth factor
Platelet derived growth factor
Insulin like growth factor
Nerve growth factor
Growth hormone is produced by acidophilic cells of the adenohypophysis
...
Growth hormone acts directly on peripheral tissues and organs to stimulate growth and
differentiation
...
Growth hormone receptors are transmembrane proteins
...
Binding causes growth hormone receptors to bind to JAK2 intracellularly
...
Growth hormone:
has anabolic effect on proteins (does synthesis of proteins)
Does lipolysis (mobilization of stored fat)
Has anti insulin effect on carbohydrate metabolism (decreases glucose sensitivity of cells,
decreases glucos uptake and increases glucose output)
At the liver, growth hormone promotes the secretion of somatomedins (Insulin like growth
factors)
...
IGF 2 is more important before birth of the baby
...
227
Hypothalamus releases GHRH (growth hormone releasing hormone, stimulates growth
hormone secretion) or somatostatin (inhibits growth hormone secretion)
Both act on cAMP of growth hormone producing cells
...
The following can increase Growth Hormone release:
Ghrelin
Androgens, estrogen
Genetics
Stress
Exercise
Sleep
T3/T4
IGF 1
increased glucose concentration
decreased amino acid concentration,
increased free fatty acid concentration
all feedback to hypothalamus and eventually reduce growth hormone secretion
...
228
Thyroid hormones
Hormones - chemical substances released by the endocrine glands, move via circulation and
reach receptor organs
...
Thus they have intracellular receptors
...
229
For excretion, steroid hormones first become water soluble in the liver by conjugation
...
Most hormones in the blood are bound to transport proteins (albumin which is non specific
or specific ones too)
Permissive effect present:
Glucocorticoids for catecholamines
Thyroid hormones for GnRH
...
Hypothalamus and pituitary gland is the center of the endocrine system
...
Somatostatin inhibits almost every hormone of the anterior
pituitary
...
Released upon
signals
...
This means secretion is not constant
...
When we consider the daily rhythm:
Vasopressin, TSH, prolactin, Growth hormone, ghrelin, melatonin, leptin release all peak at
night
...
Insulin release peaks in the evening
...
230
Centers for feedback are hypothalamus and anterior pituitary
...
It can also inhibit LH coming from the anterior pituitary
...
eg of positive feedback
...
Ferguson reflex (example of positive feedback)
...
- Baby head stretches cervix, feedback sent to pituitary
- Pituitary secreates oxytocin into blood which travels to uterine muscle
- Oxytocin stimulates uterine contraction, pushes the baby down and stretches the cervix
...
Estrogen is important in the action of oxytocin
...
Dopamine (catecholamine) inhibits GnRH and prolactin
...
TSH causes T3, T4 to be made from thyroid gland
...
ACTH is important for glucocorticoid and weak androgen release
...
Prolactin - production of milk
...
Calcitonin decreases Ca2+ concentration of blood
Parathyroid hormone increases Ca2+ concentration of blood by removing calcium from
bones
...
Signals for increased ADH release include:
decreased blood volume, decreased blood pressure, increased osmotic pressure
...
(on V2 receptors) increases reabsorption of water from tubular fluid
...
V2 and V1 receptors are both metabotropic
...
Steriod hormone receptors are intracellular receptors, could be in the nucleus
...
TSH regulates iodine uptake, thyroid hormone synthesis and secretion
...
Thyroglobulin is a large protein that
has tyrosine residues
...
- Leaves the cell by exocytosis and goes to colloid (lumen)
- The tyrosine resides only are iodinated in the colloid to give a precursor to T4
Iodine is crucial for T3, T4 production
...
Moves
sodium and iodine from the circulation into the thyrocyte
...
Iodine moves down its concentration gradient and goes into the colloid from the cell
...
Iodinattion of tyrosine residues in thyroglobulin creates MIT and DIT using thyroid
peroxidase enzyme
...
It produces H2O2 from H2O
...
Thyroglobulin goes back into the thyrocyte from the colloid via pinocytosis
...
There is
cleavage now
...
MIT and DIT are recycled
...
T3 and T4 are transported either in their free forms (less than 1%) or bound to
albumin/TBG (thyroid binding globulin
...
Thyroid hormones increase BMR by increasing the activity of Na+/K+ pump
...
Thyroid hormones also increase metabolism, blood glucose level, lipolysis, heart rate and
contractility
...
Iodine uptake should be at least 150 microgram/day
233
Iodine is mostly stored in the thyroid gland but can also be stored in the form of T4
...
Amino acids, glucose, triglycerides (in chylomicrons) are all absorbed from the GI tract
...
Liver turns glucose to glycogen or fatty acids
...
This is a one way process
...
In muscle cells, glucose is taken up and converted to glycogen
...
In liver, glycogen can be converted into glucose
...
Free Fatty Acid oxidation occurs in the liver
...
Glucagon (most effective), growth hormone, cortisol, adrenaline, T3 all increase blood
glucose level
...
After a large addition of growth hormone, there will be a slight drop and then long,
continuous rise in the blood glucose level
...
If blood glucose level is too high - insulin level increases
If blood glucose level is too low - glucagon level increases
Both insulin and glucagon are synthesized in the Islets of Langerhans in the pancreas
...
2% of pancreas is islets (endocrine cells of pancreas)
Of this 2%:
alpha cells - 10%
Beta cells - 80%
Delta cells - 5-10%
There is paracrine communication in the islets
...
Insulin has an alpha and a beta chain
...
It is initially synthesized as proinsulin and is broken down to insulin & C peptide
...
Glucose undergoes oxidation, converts ADP to ATP
...
This causes depolarisation which opens Ca2+ channels
...
Ca2+ evokes secretion of insulin by exocytosis
Higher the plasma glucose concentration, higher the insulin secretion
...
During intestinal phase, insulin secretion under control of GIP hormone
Then comes pancreatic phase
...
Insulin receptors have an alpha subunit (outside the membrane) and Beta subunit (inside
the membrane)
237
Beta receptors phosphorylates/activates enzymes which cause protein, fat, glycogen
synthesis, growth and gene expression
...
In muscle cells, due to insulin:
Increased uptake of glucose
Increased glycogen synthesis
Increased uptake of amino acids
Increased protein synthesis
Decreased proteolysis
In liver due to insulin:
Increased glycogen synthesis
Increased lipid synthesis
Decreased glycogenolysis
Decreased glucose output
Decreased ketogenesis
...
Glucagon activates cAMP system
...
Glucagon receptors are G protein coupled receptors
...
Glucagon is suppressed by:
- increased plasma glucose levels
- insulin
- somatostatin
...
Carbohydrate rich nutrition leads to high insulin and low glucagon secretion to prevent
hyperglycemia
...
Only insulin reduces the blood glucose level
...
Diabetes Mellitus (high blood glucose level) can be caused by extremely high secretions of
glucagon, cortisol, growth hormone
After feeding blood glucose level increases and then 3 hours after feeding, blood glucose
level drops due to high insulin level
...
If its above 10 mmol/L then there will be sugar in the urine
...
Is hereditary
...
Usually this type of diabetes is due to lifestyle
...
Normal level of glucose in blood is 4-6mmol/L
After a meal, blood glucose level should not go above 8 mmol/L
High blood glucose level: can glycate proteins, change their shape and activity thus causing
dysfunction of proteins and cells
...
Very high blood glucose level causes glucosuria (glucose in urine)
...
Very low blood clusoe level causes CNS malfunction and thus death
...
To control blood sugar levels:
In digestive phase (to prevent hyperglycemia):
240
a) Stop eating (satiety)
b) Slow absorption from GI system using hormones
c) enhance glucose utilisation
d) decrease hepatic glucose production
...
Absorptive phase - filling of stores
Lipids are resynthesized in enterocytes
...
Adipocytes metabolizes chylomicrons and takes
up its contents (free fatty acids, etc
...
Glucose and amino acids that are absorbed go first to the liver via portal circulation
...
Ingested fats are mostly stored in adipocytes
...
Insulin wants to make sure glucose isnt released
...
In interdigestive phase and fasting phase, there is release of macronutirents from storage
pools
...
Gluconeogenesis (dependent on protein stores of
skeletal muscles and lactate amount) cause release of glucose
...
Other organs are convinced to use
other nutrients (free fatty acids) for ATP production
...
After fasting phase is the protein conservation phase in which:
- CNS and most tissues use glucose from glycogen breakdown
- Protein catabolism are used to feed glucose to CNS
- Other tissues feed on ketones and fats
...
Normoglycemia is maintained mainly by insulin, glucagon and catecholamines
...
- Decreases HSL (hormone sensitive lipase)
Glucagon increases blood glucose levels by:
- Increases hepatic glucose production (gluconeogenesis & glycogenolysis)
- Decreases hepatic conversion of glucose to glycogen or lipids
- Decreases uptake of glucose by adipose tissue and muscle cells
- Increases HSL
...
Low blood glucose levels stimulates glucagon secretion
...
Insulin binding causes enzymes dephosphorylation
...
242
Insulin and Glucagon also control gene expression
...
Glycogenesis (promoted by insulin) is activated by enzyme dephosphorylation
...
Glycolysis (breakdown of glucose) activated by dephosphorylation and gene expression
...
Glucagon prevents hypoglycemia
...
Cortisol is required for the continuous expression of genes required for gluconeogenesis &
lipolysis (cortisol has a permissive effect)
...
Thus fasting is impossible without cortisol
...
Hypoglycemia and ghrelin stimulates growth hormone secretion
...
Growth hormone secretion promotes lipolysis
...
Will use anything for energy
...
Catecholamine receptors are present on skeletal muscles
...
This is done by AMP kinase which is activated by AMP (low energy indicator)
Obesity - imbalance of energy intake and expenditure
243
Controlled by
T4/T3 (balance of BMR)
Physical activity (balance of lifestyle)
Food intake (controlled by hormones)
Assesment of lean body mass vs body fat is more accurate than BMI
...
This leads to insulin resistance, high triglyceride, high LDL, low HDL
...
Adipokkines - hormones of adipose tissue
...
Adiponectin
Stimulated by: Decreased fat storage
Targets: muscle cells
Stimulates: Free fatty acid use
...
Targets the liver and adipocytes
Is proinflammatory and insulin resistance
...
MSH/CART neurons inhibits food intake
...
They control
feeling of hunger
...
Ghrelin promotes hunger
...
Endocrine pancreas:
alpha cells (25%) make glucagon
beta cells (60%) make insulin
delta cells (10%) make somatostatin
...
Insulin causes protein, fat and glycogen synthesis
GIP - gastric inhibiting peptide
...
This is facilitated by Ca2+
Hyperglycemia, Arg & Leu, incretin all stimulate insulin release
Somatostatin and catecholamines inhibit insulin release
...
Glucagon increases gluconeogenesis thus glucose increase in blood is countered by insulin
...
Is hereditary
In type II: sensitivity to insulin is decreased
...
Too much glucose in blood would cause a loss of lot of water as glucose would go into the
urine and take water with it
...
low insulin increases glucagon effect and causes decreased glycogenesis, lipogenesis
...
5 litres of blood leaves the right and left ventricles per minute
...
Glucocorticoid Receptors have higher affinity for glucocorticoids than mineralocorticoids
...
Cortisol acts on liver, fat tissue and muscle tissue
...
In muscle and fat tissue, Cortisol decreases glucose uptake
...
In fat tissue, Cortisol inhibits lipogenesis and stimulates lipolysis
...
Stress activates the sympathetic nervous system
...
Insulin release is is inhibited during stress response
...
Also could cause muscle
atrophy and obesity
Cushing syndrome - ACTH overproduction
246
Hormone producing cells of pancreas - Langerhans Islets
...
Alpha cells - glucagon
Beta cells - insulin
Delta cells - somatostatin
Insulin promotes synthesis, glucagon promotes breakdown
...
Glucose causes ATP production
ATP closes ATP sensitive K+ channels
...
Ca2+ induces exocytosis of insulin containing vesicles
Adrenal cortex hormones - steroids
Pancreas hormones - peptides
Type I diabetes mellitus is caused by a destruction of beta cells (autoimmune diseass)
Type II diabetes is caused by down regulation of insulin receptors in target tissues and
insulin resistance
...
Very high amount of urine is produced (upto 20 L per day)
Glucose blood level is 4
...
5 mmol/L
If renal blood glucose above 10 mmol/L, glucose is not reabsorbed and is present in the
urine causing osmotic diuresis
...
Insulin inhibits glycogenolysis and gluconeogenesis, lipolysis and hormone sensitive lipase
In muscle tissue, uptake of glucose increases due to insulin
In the liver, glucose uptake is not insulin dependent
...
Osmovolume Regulation
Urine osmotic concentration: 70-1200 milliosmol/L
Urine production
...
There is no physiological control of Na+ intake
...
Na+ regulation is done by kidney through urine
...
248
20% of filtered Na+ is reabsorbed in Loop of Henle
9% of filtered Na+ is reabsorbed in the distal convoluted tubule and collecting duct
...
In the proximal convoluted tubule, there is passive and secondary active Na+ reabsorption
...
Solute usually glucose
...
These 2 mechanisms reabsorb half the Na+ in the proximal convulated tubule
...
On the basolateral side there is Na+/K+ ATPase
...
Goes from 300-1200
miliosmol
...
Na+ is transported from intersitium to the tubular fluid
...
Ascending limb is not permeable to water and freely permeable to Na+ and Cl-
...
Na+ and Cl- reabsorption into the interstitum, without water reabsorption builds up
medullary gadient which is required later for H2O reabsorption from collecting duct
...
Na+ - Cl- - K+ symport is driven by Na+/K+ ATPase on the basal membrane
...
It has only
Na+ - Cl- cotransport driven by Na+/K+ ATPase
...
PCT - Na+/proton antiporter, Na+ - solute symporter and paracellular transport
Loop of Henle - Na+ - K+ - Cl- symport and paracellular transport
DCT - Na+ - Cl- symport and aldosterone dependent Na channels
...
ANP has an anti aldosterone effect, inhibits Na+ reabsorption
...
Cuts angiotensinogen (biologically inactive) to angiotensin I (10 amino acids)
...
Angiotensin II is biologically active
Juxtaglomerular apparatus control renin production
...
Local mechanisms for renin production:
decreased renal perfusion
decreased arterial pressure
decreased Na,Cl in macula densa
increased intrarenal tissue pressure
All of the above increase renin production
...
250
Sympathetic nervous system increases renin production if:
- Decreased arterial pressure (checked by baroreceptors)
- decreased blood volume (checked by left atrial stretch receptors)
Angiotensin II:
- regulates vascular smooth muscle (these cells have a angiotensine II receptor) and is a
strong vasoconstrictor
...
- Acts on the hypothalamus, inducing thirst and thus increases H2O in the body
...
ACTH secretion from anterior pituitary also increases aldosterone production
...
More the aldosterone, higher the Na+ reabsorption
...
ANP inhibits aldosterone production
...
Steriod hormones are hydrophobic
...
ADH acts only in the kidney
...
Atrial Natriuretic Peptide/Hormone/Factor (ANP/ANH/ANF) is produced in the right
atrium
...
Increased atrial stretch means increased blood volume and pressure
ANF effects:
251
- Vasodilation
- Increased glomerular filtration rate (vasodilation of afferent arteriole)
- inhibits renin secretion
- decreases aldosterone secretion
- inhibits ADH
- causes Na+ and water excretion
- decreases cardiac output
Overall ANF decreases blood pressure and blood volume
...
Converts angiotensin I to angiotensin II
...
ADH/vasopressin main effect - increased water reabsorption in collecting duct, decreases
urine secretion
...
Urinary solute excretion stays mostly the same
...
Made in the hypothalamus by supraoptic neurons
...
ADH decreases urine flow and makes urine more concentrated
...
ADH also does vasoconstriction
...
Urea is osmotically active
...
If no ADH produced, more urine is secreated and the urine is more dilute
...
Descending part of loop of Henle is water permeable
...
Osmolarity increases
...
Na,Cl leave the tubular system
...
In counter current exchange, water moves from the descending limb to the ascending limb
...
When ADH increases:
Blood volume increases
Blood pressure increases
plasma osmolarity decreases
When ADH decreases:
Blood volume decreases
blood pressure decreases
plasma osmolarity increases
Except ADH, all hormones follow the Na+ transport
...
Sympathetic effect of heart:
Positive chronotropic, dromotropic, ionotropic, bathmotropic, lusitropic effect
An increase in venous return ----> increases in stroke volume -----> increase in mean
arterial pressure
...
This is a fast neural response for volume regulation
...
Na, Cl in the distal nephron promotes renin release
...
This is converted to angiotensin II by ACE
...
Aldosterone increases Na and Cl reabsorption in collecting duct
...
Thus aldosterone causes higher water reabsorption
...
More Na is sent out by aldosterone so the Na permeability in apical membrane (facing
lumen) increases
...
ANP is produced in response to too high blood pressure and blood volume
...
Decreases Na, H2O reabsorption in the collecting duct
...
Adrenal cortex has zona glomerulosa, zona fasiculata and zona reticularis
...
Blood flows from the cortex to the medulla
...
PNMT present only in the adrenal medulla
...
CRH from hypothalamus facilitates ACTH release from the anterior pituitary
...
Cortisol has negative feedback on ACTH and CRH producing cells
...
Adrenaline increases ACTH production and due to this, more cortisol (stress hormone) is
produced
POMC is the precursor of ACTH and alpha MSH
...
High pressure baroreceptors (carotid sinus and aortic body) monitor blood pressure
...
These receptors are activated
by high blood pressure
...
Activated when blood volume decreases
...
JGA produces renin
...
Increase in K+ conc in extracellular fluid also increases renin production from
juxtaglomerular apparatus
...
Renin: facilitates the conversion of angiotensinogen (made in liver) to angiotensin I
Converting enzyme changes angiotensin I to angiotensin II
Angiotensin II stimulates aldosterone production by stimulating the aldosterone synthase
enzyme
...
Angiotensin II also increases Na+ reabsorption at the proximal tubule and release of ADH,
thus water absorption
...
Addison disease - hormones of the adrenal cortex are decreased due to autoimmune
destruction of the adrenal cortex
...
Water intake: 2100-3400 ml/day
Water output: 2100-3400 ml/day
Water intake from fluid intake, oxidative water production and water content of
foodstuff
Water output from perspiration, stool, urine, sweating
...
Minimal urine output: 500-600 ml
...
Water intake and output can both be regulated
...
Water intake control: angiotensin II, osmoreceptors of hypothalamus
Hypothalamus gets information from osmoreceptors, mechanosreceptors and angiotensin
II
...
257
Dry oral mucosa (oral mucosa sensory receptors), angiotensin II, decreased blood volume
and decreased arterial pressure (checked by mechanoreceptors) all act on the
hypothalamus and induce thirst
...
Regulating water output is done at the kidney by vasopressin (produced by supraoptic
neurons)
...
Decreased blood pressure and decreased blood volume stimulates ADH production
...
ADH made in supraoptic nuclei of hypothalamus, released from posterior pituitary into
blood
...
Aquaporine 1 is independent of ADH
...
Aquaporine 2 water channel is dependent on ADH
...
Target cells of ADH are principal cells
Basal membrane of principal cells have V2 receptors
...
cAMP dependent protein kinase does aquaporine-2-water channel phosphorylation
...
ADH, ADH receptors (V2 receptors), aquaporine-2-water channels are all necessary for
water reabsorption
...
Reabsorbes 70% of filtrated Na+, Cl- and water
...
Water reabsorption from descending limb and Na+,Cl- recirculation in the descedning limb
does concentration of tubular fluid
...
Most concentrated part of the nephron
...
Tubular fluid becomes diluted
...
Late distal tubule onwards there is regulated water absorption (via aquaporine-2-water
channel)
The kidney can produce:
highly concentrated urine (1200 mOsm/l)
strongly diluted urine (70 mOsm/l)
Factors affecting urine concentration:
- Length of loop of Henle: short loops concentrate the tubular fluid
- ratio of long looped nephrons to short looped ones
- urea presence
- fluid flow through the loop of Henle & collecting duct (makes 2 countercurrent systems
...
Deeper the position of the nephron, higher is the concentration
...
Thus Na+ and Claccumulation in the renal medulla
...
Countercurrent mechanism - Na+ and Cl- recirculation from ascedning to
descending limb
Descending limb is freely permeable to water, water leaves it and that's why tubular fluid
becomes concentrated
...
Ascedning limb and collecting duct have countercurrent mechanism for urea
...
Then some urea is reabsorbed from medullary and papillary part of the collecting duct
...
Loop shape of vasa recta prevents dilution of renal medulla
...
Vasa Recta transports reabsorbed water from renal medulla
...
Clearance means: amount of plasma that is cleared of a substance during one minute
Osmotic diuresis is usually above water diuresis
...
- Thiazide (inhibits Na+,Cl- cotransport in distal tubule)
Basically in all of these, Na+ reabsorption is inhibited and thus H2O secretion is elicited
...
261
Potassium & Calcium
98% of K+ in the body is intracellular
...
5 mmol/L
Hypokalemia when its less than 3
...
Symptoms of hypokalemia and hyperkalemia are fatigue, muscle weakness, cramps,
numbness, tingling
...
Excretion should be 50-100 mmol/day (mostly in urine)
Absorption of Na+, K+ from GI tract is not controlled
...
262
K+ absorption in small intestine is by passive paracellular transport (not regulated)
...
Insulin and thyroid hormones stimulates K+ uptake by target cells
Proximal tubule and Loop of Henle do more than 90% of K+ reabsorption
...
K+ is secreated into the collecting duct via K+ channels if it needs to be excreted in the
urine
...
K+ secretion in the collecting duct is done also in principal cells
...
Then passive diffusion through the luminal ROMK K+ channels (K+
goes from within cell to the lumen)
Controlled by aldosterone
...
Aldosterone stimulates renal K+ secretion
...
This increases the gene expression of Na/K ATPase and ROMK and thus more K+ is
secreated
...
Loop diuretics causes increased flow rate of tubular fluid in the collecting duct which also
increases K+ secretion
...
99% is in the bones
...
1% is in extracellular fluid
...
1 to 2
...
Ca2+ is needed for muscle contraction
...
Could be fatal if the muscles
affected are laryngeal or respiratory muscles
...
If Ca2+ concentration decreases, voltage gates don't function properly and open on their
own
...
In humans, there is positive calcium balance until bone formation ends
...
Net Ca2+ absorption is 5 mmol/day
...
There is increased Ca2+ demand during pregnancy, growth, lactation
...
Ca2+ balance maintained by parathyroid hormone, Calcitrol (from vitamin D), calcitonin
(From thyroid gland)
Ca2+ levels control these hormone production
...
Parathyroid hormone acts on bone and kidney
Calcitriol acts on bone and GI tract
Both parathyroid hormone and calcitriol increase the plasma Ca2+ concentration
...
Ca2+ inhibits parathyroid hormone through the stimulation of cell membrane Ca2+ sensor
receptors
...
264
Parathyroid hormone secretion is thus very tightly coupled to normal extracellular Ca2+
levels
...
Synthesis of calcitriol is stimulated by parathyroid hormone action in kidney and by
hypocalcemia
...
Kidney determines how much calcitriol is made from vitamin D sources (sun, pills)
Calcitriol can stimulate Ca2+ and phosphate absorption
...
Too little vitamin D, decreased Ca2+ and minealization of bones causes rickets
...
Calcitonin is produced by C cells of the thyroid gland
...
Intracellular trafikking of Ca2+ by calbindin and active secretion of Ca2+ from basal side
...
10% of filtered Ca2+ recahes the distal convoluted tubule
...
This is controlled by parathyroid hormone
...
Ca2+ can directly inhibit Ca2+ reabsorption
...
Has a glucose type reabsorption (secondary active transport with Na+)
Parathyroid hormone inhibits inorganic phosphate reabsorption
...
Osteoblast: produce osteoid proteins like collagen, promotes mineralization and increases
inorganic phosphate levels
...
This signalling causes bone degradation releasing Ca2+
...
Osteomalacia - bone softening
...
Could be due to vitamin D deficiency, parathyroid hormone overproduction
...
Loss of bone mass
Due to loss of both mineral & organic materials,
98% of K+ is intracellular
2% if K+ is extracellular
Normal K+ levels in serum: 3
...
2 mmol/L
Hyperkalemia: > 5
...
5 mmol/L
Both lead to severe organ damage
...
Both hyperkalemia & hypokalemia cause depolarisation
...
266
K+ level is not regulated by its absorption
...
T3, T4, insulin all increase cellular K+ uptake
...
K+ freely filtrated through the glomerulus
...
Loop of Henle thick ascending limb absorbs 27% K+
...
In PCT: K+ moves paracellulary
...
Water moves with K+ to the blood
Loop of Henle thick ascending limb also has paracellular K+ transport
...
Here, basolateral membrane has K-Cl cotransport
...
Presence of mineralocorticoid receptors
Binding of aldosterone promotes gene expression
Cortical collecting duct has principal cells & alpha intercalated cells
...
Here Na-K pumps are active causing high K+ concentration intracellularly
...
Alpha intercalated cells: K+ reabsorption & H+ secretion
Acidosis: Hyperkalemia
Alkalosis: Hypokalemia
This is cuz K+ reabsorption is proportionally connected to H+ secretion
Aldosterone production is regulated by renin-angiotensin system
...
267
JGA is stimulated by macula densa (low Na+ in distal tubule), Beta 1 receptors
(sympathetic activation & catecholamines), baroreceptors (low blood pressure)
Aldosterone is made at the zona glomerulosa of adrenal cortex
...
Plasma Ca2+ level: 2
...
6 mmol/L
50% is ionized, 40% is bound to protein, 10% is in salt complexes
...
16 - 1
...
Ca2+ level regulated only by hormones
...
Produced in C cells of thyroid gland
...
Leads to Ca2+ buildup in the bone (osteoclast inactivity)
Inhibits vitamin D3 synthesis
...
Calcitrol (Vitamin D)
Intake from plant & cod liver
...
Liver & kidney involved in the synthesis
...
Effect: Increases Ca2+ & phosphate absorption from intestine & kidney
...
Calcitrol can inhibit PTH & calcitriol synthesis (negative feedback)
PTH
Secreated by parathyroid gland
...
There is Ca2+ negative feedback mechanism on PTH via Ca2+ sensor receptor stimulation
...
Effects: Increases osteolysis, increases osteoclast activity, increases Vit D3 synthesis
Insulin & Growth Hormone increase bone formation
...
Ca2+ is absorbed in the intestines through Ca2+ channels
...
On the basolateral membrane there is Na+ - Ca2+ exchanger & plasma membrane Ca2+
pump
90% of filtrated Ca2+ is reabsorbed in PCT & loop of Henle paracellualry
Na-K-2Cl transporter & K+ channels generates the gradient for Ca2+ paracellular
transport
...
Maintian mechanical stability
Neuromuscular system is very sensitive to hypocalcemia
...
269
Acid-Base balance
Acid production is continuous in the human body due to normal metabolism
...
Acid is anything that donates H+ ions in aqueous solution
...
Acids in the body include carbonic acid, lactic acid, ketone bodies, sulphuric acid
H+ concentration of body fluids is at a very low level
...
35-7
...
35
...
45
...
35) due to accumulation of CO2 in it
...
15-1
...
Volatile acids: CO2 - H2CO3
Removed by the action of the lung
Non volatile acid: lactic acid, ketone bodies
Removed by the kidney
...
Kidney, lungs, respiratory center, chemical acid-base buffer all regulate H+ concentration
in the body
...
The chemical acid-base buffer doesn't eliminate acid or bases, just negates its effects
...
Kidney is relatively slow to respond but is the most powerful acid-base regulatory system
...
Due to this, changes in H+ is minimized
...
Bicarbonate buffer system is made up of weak acid (carbonic acid) and bicarbonate salt
Carbonic acid is made in the body due to the action of carbonic anhydrase enzyme
...
Na+ can bind to HCO3-
...
Bicarbonate buffer system is used to eliminate acids & bases
...
For OH- elimination:
CO2 + H2O decreases so respiration decreases
...
Buffer power is determined by the amount and relative concentration of the buffer
components
...
Buffers are usually most effective between pH of 5 and 7
...
If a strong acid is added, H+ is accepted by the base
...
Proteins are important intracellular buffers
...
Respiratory regulation has a peripheral and central pathway
...
Acts on medullary respiratory center and thus ventilation is increased and CO2 is removed
...
If H+ concentration is above normal, respiratory system is stimulated, alveolar ventilation
increases and more CO2 is removed
...
273
Kidney removes non volatile acids
...
For every HCO3- reabsorbed, kidney must secreate a proton
...
In the proximal tubule, HCO3- is reabsorbed with Na+
In tubule lumen, HCO3- + H+ -----------> H2CO3 --------> H2O + CO2
...
Simulataneously H+ secretion is done by apical Na+/H+ antiporter
...
Simultaneously, H+ secretion is done by apical Na+/H+ antiporter
...
(during alkalosis - stimulated by high pH)
Intercalated type B cells have:
H+ reabsorption by basolateral H+ ATPase & HCO3- secretion by apical Cl-/HCO3exchanger
...
Kidney must reabsorb HCO3- if there is excess acid
Most of the H+ in urine combines with urinary buffers (phosphate, creatinine) or combines
with free base NH3 to be excreted as NH4+
274
Titratable acid is formed when secreated H+ is bound to buffer base in the tubular urine
...
Lower the pH, more the H+ concentration, more the titratable acid is made
...
NH4+ can be reabsorbed later
...
They combine with each other to form CO2
and H2O
...
Fall in pH means increases in H+ secretion
Rise in pH means decreases in H+ secretion
Decreased pH increases the activity of Na+/H+ exchanger & H+ ATPases
Increased pCO2 leads to more H+ secretion
...
Na+ and H+ are directly linked in the proximal tubule (Na+/H+ exchanger)
Decreased ECF volume causes increased H+ secretion
...
Aldosterone stimulates the collecting ducts to secreate H+ by:
directly stimulating H+ ATPase,
enhancing collecting duct Na+ reabsorption
promoting K+ secretion
...
275
Hypokalemia is a stimulus for H+ secretion in exchange for K+ absorption in the collecting
duct
...
There is inward H+ movement into cells
...
Intracellularly, H+ gets buffered and there is no buffering for extracellular K+
...
Acid-base disorders occur when the lung or kidney do not work properly
...
Respiratory acidosis means there is increased CO2 in the arterial blood
...
Is compensated by H+ secretion and HCO3- absorption
...
An increase in non volatile acids leads to metabolic acidosis with high anion gap
Compensation of metabolic acidosis:
renal secretion of more H+
more reabsorption of HCO3deeper & more breathing
...
4
plasma pCO2 is more than 40 mm Hg
elevation in HCO3- concentration above normal is present to compensate for the
respiratory acidosis
276
Blood pH should be 7
...
42
...
Uses kidney & respiration to regulate
Carbonic acid level is regulated by respiration
...
In Alkalosis we do hypoventilation - CO2 increases leading to respiratory acidosis
...
Hamburger shift happens heren
Renal regulation is possible for acidosis & Alkalosis
...
This decreases H+ in the body & increases pH
...
This increases H+ in the body & decreases the pH
...
The core body temperature is only relatively constant
...
Body temperature is highest in late afternoon and reduces and is at its lowest during REM
sleep (1 degree fluctuation)
...
Body temperature avegare: 36
...
278
Radiation, convection, conduction are involved in heat production and heat loss both
...
Heat production by the body is metabolic
...
Heat flows from warmer object to colder
object
Convection is caused by air currents
Evaporation of every ml of water removes 2
...
Only heat loss mechanism that works when environment is hotter than the skin
Insensible perspiration: through skin and lungs
...
Is high when the air is dry
...
To gain heat you need food
To lose heat your need water
Thermoneutral zone (TNZ)
No heat production or heat loss mechanisms are active
...
Includes the vasomotor zone - control of body temperature by skin blood flow only
...
Decreased skin blood flow saves heat
Metabolic zone is when temperature is below the thermoneutral zone
...
Sudomotor zone is when temperature is above the thermoneutral zone
...
If body temperature starts to fall almost 3x more heat production happens
...
At rest, the heart, brain and liver produce the most heat
...
White adipose tissue does storage of fat and provides insulation
...
In brown adipose tissue, terminal oxidation and ATP synthesis are dissociated
...
In brown adipose tissue, uncoupling proteins allow protons to go back into the
mitochondrial matrix bypassing ATP synthase
...
Clothing is involved in behavioral thermoregulation
...
Skin is usually recieeving 5% of cardiac output
280
Can go up to 60% depending on thermoregulatory needs, not depending on metabolic needs
...
Acral areas - Large surface/weight ratio (nose, ear, lips, fingers)
Non acral areas - Small surface/weight ratio (neck, trunk)
Acral areas have arteriovenous anastomosis (shortcut connection between arteries and
veins)
...
Non acral areas have no arteriovenous anastomosis
...
Here, sweating happens along with sympathetic withdrawal at the same time
...
Doesnt have to be sweat
Heat dissipation:
By panting: Evaporation from tongue and upper airways
...
Evaporation: Sweat only cools you down when it evaporates from the skin
...
Duct does reabsorption of Na+ and Clions
...
Neurotransmitter: acetylcholine
...
Due to duct activity it becomes hypotonic
...
Pumps Na+ out of the cell which causes Na+ to be
reabsorbed from the duct lumen (Secondary active transport)
...
Thermoregulatory response:
Against cold:
- Behavioral response
- Shivering (motor response)
- Vasoconstriction at the skin (sympathetic vasoconstriction tone increases)
- Brown adipose tissues activation
Against heat:
- Behwvioral response
- Sweating
- Vasodilation at skin (sympathetic vasoconstriction tone decreases)
- Brown adipose tissue inactivated
Thermoreceptors can be central or peripheral
...
Hypothalamus activates/inhibits the different thermoregulatory effector mechanisms
...
These neurons have an inhibitoryeffect on the thermogenesis command neurons (shiver,
brown adipose tissue command)
Warm sensitive neurons have positive vasomotor and sweating command
Peripheral thermoreceptors: some are cold receptors (A delta fibres), some are warm
receptors (C fibres)
282
Signals from peripheral and central thermoreceptors mediate an integrated metabolic
response
...
Sports also lowers the risk of bone fracture as it increases bone density
...
Static work: Body not moving
Conracted muscles constrict blood vessels
...
Muscle work aka performance
Efficiency is the ratio of energy consumption
...
Muscle contraction means shortening of the sarcomere
...
Is a slow oxidative fiber
...
Uses O2 for metabolism
...
White fibres (type IIa, IIb)
Fast glycolytic, use anerobic mechanism for energy production
...
Fatigue resistance could be moderate (IIa) or low (IIb)
For low intensity muscle activity type I fibers are used
...
Proportion of muscle fiber type is determined by genetics
Only a few percent change can be achieved by training
...
Marathon runners have 93
...
Auxotonic muscle contraction:
Mix of isometric and isotonic
...
Eccentric muscle contraction has more force per active motor unit and thus risk of muscle
damage is higher
...
Isotonic muscle contraction: length is changed but muscle tension changes
...
5 kJ/mol of energy
...
Creatine phosphate is stored in type II fibres (is an energy pool)
285
Creatine phosphate can give its phosphate to ADP to make ATP + creatinine
...
Oxidation of carbohydrates
...
Once glucose gets over, oxidation of fats happens
...
After fat store is depleted, oxidation of proteins happens
...
Some amino acids can be used in gluconeogenesis
...
Carbohydrates come from glucose in body fluids, liver and muscle glycogen
...
Provides energy for 1/2 minute
...
No lactate made
...
Lactate is used up to make ATP in the presence of oxygen
Anaerobic glycolysis is a rapid processes
...
Provides energy for fast, high intensity exercise
...
Aerobic metabolism:
Slow and long term energy source
...
286
VO2 - oxygen consumption of working muscles
VO2 max - the volume of oxygen that can be consumed while exercising at a maximum
capacity
...
However a 70 year old active person has a higher VO2 max than a sedentary 20 year old
...
Sports improves lung diffusing capacity and lung volume capacity
...
(oxygen
is needed to break down lactate produced during anaerobic exercise)
EPOC (excess post exercise O2 consumption) is used for oxidation of glucose
...
At the heart, removal of excess lactate happens
...
Lactate undergoes oxidation to pyruvate and gives off CO2 + H2O + ATP
Lactate can also undergo gluconeogenesis at the liver and skeletal muscle
...
For elite athletes it could be 70-80% of VO2 max
...
Arm work also increases mean arterial blood pressure and diastolic blood pressure
...
Blood pressure increases the most if work is static
...
Blood flow to splanchnic regions decrease (vasoconstriction) except kidney which has
autoregulation
...
Long term effects of training will be that:
performance will be better
cardiac muscle becomes stronger and thicker (stronger contractions, increased stroke
volume, more sustained work)
Size of heart ventricles increases to receive more blood
Muscle strength increases cuz there's an increase in cross sectional area and a slight
increase in the ratio of type II fibers
...
Eventually stroke volume decreases (due to reduced plasma volume)
Heart rate increases slowly
Blood pressure declines
...
Muscle pain is due to lactic acid production
...
Due to microtraumas in muscle causing
inflammation, edema which affect pain receptors
Exercise stimulates bone density
...
Exercise increases muscle strength and functional capacity
...
Estrogen is important in bone homeostasis in young women
...
High carbohydrate diet causes increased tome to exhaustion compared to a low
carbohydrate diet
...
NO fiber and fat because they slow
down the absorption of glucose
...
Reversible by rest
...
289
290
Reproductive physiology
Testosterone comes from Leydig cells
...
Adrenal cortex produces weak androgens (DHEA)
XX or XY chromosomes cause testes or ovaries to be made from undifferentiated gonadal
tissue
...
At prostate gland, seminal fluid is added
...
Here sperms are made and mature
...
Leydig cells are outside the wall of seminiferous tubules (in the interstitium)
...
Lots of vascularization around it
...
291
Testosterone can be further metabolized
...
Dihydrotestosterone has 3 times stronger biological activity than testosterone
...
In the body, the amount of testosterone is 100x more than dihydrotestosterone
...
Testosterone and its derivatives act on transcription and translation of new proteins
...
SRY gene causes embryonic testis to be made from indifferent embryonic gonadal tissue
...
In the fetus, Leydig cells produce testosterone which promotes Wolffiaan duct
development
...
hCG (human chorionic gonadotropin) of placenta stimulates Leydig cells
...
Testosterone gives rise to dihydrotestosterone which promotes penis and scrotum
(external genitalia) development
...
Testosterone: Differentation of male internal genital ducts
Dihydrotestosterone: Differentiation of male external genitalia
...
During childhood, very low testosterone in the blood
...
Both now stay
high throughout adult life
292
Effects of testosterone
Prepubertal:
Differentiation & growth of external genitalia, differentiation of Wolffian duct
Pubertal:
Further growth & differentiation of prostate gland, seminal vesicle, growth of external
genitalia, voice change, hair growth, bone growth (Ca2+, PO4 3- retention), hormonal
support for spermatogenesis, anabolism of skeletal muscle (muscle growth), erythropoesis
(production of erythropoietin), more aggressive behavior
Hypothalamus does pulastile secretion of GnRH
...
In fetus: hCG stimulates the release of LH
LH stimulates testosterone secretion from Leydig cells
...
FSH stimulates sperm production in seminiferous tubules
...
Sertoli cells have negative feedback on FSH by producing inhibin hormone
...
They prevent blood from entering the
tubule lumen
...
Sertoli cells secreate androgen binding protein and estradiol
...
Most importantly, Sertoli cells provide nourishment to developing sperm and provides the
Mullerin duct regression factor
Vasectomy: Vas deferens are severed and tied
...
Castration: Removal of the whole testes
...
293
Functional unit of ovary is the follicles
...
Female fetal development is spontaneous
...
Follicles are responsible for germ cell production and hormone production
Women have approximately 4 million primordial follicles (these develop during fetal life)
...
During puberty only 300,000 are present in the ovary
300-400 follicles reach maturity only
...
At menopause, no follicles are left (all follicles have been used up or have died)
Puberty usually takes 3-5 years
...
Adrenarche happens
which means weak androgens are released
...
Once the hypothalamus and anterior pituitary are activated, there is secretion of GnRH,
LH, FSH and sex hormones
...
First few menstrual cycles have no oocyte release
...
This is due to improved health and nutrition worldwide
...
This is a critical value
...
Inhibitory GABA and NPY neurins prevent GnRH release
Presence of kisspeptin peptide activates GnRH release
Ovarian cycle: 28 days
Follicular phase: 14 days
Ovulation
Luteal phase: 14 days
At the start of the cycle, 6-8 primordial follicles are activated
...
Rest die off
...
After ovulation, cholesterol is deposited on the remaining follicle and this forms the
corpus luteum
...
Ovarian hormones
Steroids: Estradiol, progesterone, androgens
Antrum has peptide hormone like inhibin, relaxin
...
After ovulation, progesterone concentration increases
295
During follicular phase, cholesterol goes to theca cells from circulation
...
These diffuse to granulosa cells
where they are further modified to estradiol
During luteal phase, LH stimulates progesterone to be made from cholesterol only
...
Transport of estradiol & progesterone
Free estradiol: 2%
Free progesterone: 2%
Albumin with estradiol: 60%
Albumin with progesterone: 50%
Gonadal steroid binding globulin: 38% for estradiol
Corticosteriod binding globulin: 48% for progesterone
Receptors for estradiol and progesterone are both intracellular
...
Estradiol also:
Does mineral deposition at the bone
Increases HDL:LDL ratio (anti atherosclerotic) effect
Increases hepatic protein synthesis (transport & clotting proteins)
296
Progesterone effects:
Increases mucus viscosity of the cervix
Hyperpolarisation of the myometrium
Brings secretory phase to the endometriuem
Lobular Alveolar development of the mammary gland
...
Hypothalamus produces GnRH which stimulates anterior pituitary to make FSH and LH
...
Towards the end of the 1st cycle, LH & FSH levels increase stimulating follicular
development for the next cycle
...
The largest developing follicle secreates estrogen which inhibits FSH and LH production
...
The estrogen secretion eventually causes LH surge around day 14 leading to ovulation
...
Progesterone maintains and supports the thickened endometrieum
...
Once corpus luteum dies, progesterone secretion stops
...
297
Oral contraception contains modified estrogen and progesterone molecules
...
These molecules inhibit estrogen and progesterone binding and this causes:
Inhibition of ovulation
Thins the endometrial level
Increases mucus consistency/viscosity of the cervix
...
Leading up to menopause, menstrual cycles become irregular and take longer
...
Estradiol and progesterone are not present so there is no negative feedback on GnRH,
FSH, LH
Thus after menopause, LH, GnRH, FSH secretion increases leading to heat flushes
(sweating, feeling hot)
Even after menopause, androgen hormones are still produced in normal quantities
...
Further maturation & incapacitation (receiving covering protein) & protection of sperm
happens in the epididymis
...
Contains 150
million sperm
Fertilisation: sperm and ovulated oocyte fuse
298
Male Sexual Act
1) Erection
Penis smooth muscle relax, corpus cavernosa fill with blood and dilates
...
Constriction of internal sphincter of bladder
...
Endothelial cells can also release NO
...
Viagra elongates the effect of NO
In males, increased blood flow to the penis is stimulated by parasympathetic effect
...
This center stimulates smooth muscle contraction (in
prostate gland, seminal vesicle) and thus expulsion of ejaculate
...
Thus both sympathetic and parasympathetic system are active
...
Oxytocin participates in this too
...
Only one single sperm is needed for fertiisation
...
299
Uterus contains 100,000 sperm
In oviduct there is 200 sperm
...
This allows sperm to escape and
increases the probability of fertilisation
...
Ovulated oocytes live for 24 hours max
...
Capacitation of sperm - inhibitory proteins around sperm are lost
...
Hydrolytic enzymes and proteases are released from
acrosome
- Sperm crosses the zona pellucida
- Sperm head binds to membrane and penetrates ovum, completes meiosis II
...
- Cortical degranulation - blocks polyspermy
...
Fertilised oocyte moves from fallopian tube to the uterus
...
There is cellular division during these 8-9 days (2 cell stage, 4 cell stage, 8 cell
uncompacted morula, 8 cell compacted morula, blastocyte)
A week is taken for the implantation of blastocyte as the endometrial sheath is simply not
ready right after fertilisation
...
There is no direct mixing of fetal and mothers blood
...
Pregnancy duration is 38 weeks post conception or 40 weeks post last mestruation
hCG (human chorionic gonadotropin) is the first hormone secreated
...
Peaks in week 10
Produced by placenta
Is a glycoprotein hormone (like FSH, TSH, LH)
...
Beta chain of LH and hCG are basically the same
...
Due to this progesterone and estradiol don't decrease till week
10
...
Cant support corpus luteum anymore
...
Presence of hCG fragment is used to test if woman pregnant
or not
...
Control is always positive - always shows a one
If in the test region there is also a line that means pregnant
...
Makes membrane potential excited
...
Once the corpus luteum dies, progesterone and estradiol concentrations don't drop
because now the fetoplacental unit produces the 2 hormones
...
Mothers blood provides cholesterol for steroid hormone synthesis
...
Progesterone activity overrides stimulating activity estradiol from week 10 towards the
end
...
Helps in preparation for delivery
...
Increased estrogen:
Increase in oxytocin receptors
Causes depolarisation
(These 2 increase excitability causing stimulus)
Increase gap junctions (cause conduction)
Increase contractile proteins (causing contraction)
Oxytocin also causes stimulation
...
Positive feedback of oxytocin
...
After delivery, there is a very sudden drop in all steriod hormone concentrations
...
Durinf the 40 weeks of pregnancy, there is further growth & differentiation of mammary
gland
...
Insulin & glucocorticoids also have effects on mammary glands
...
Acts like prolactin - stimulates milk secretion and supports the growth of the baby
...
Prolactin
During pregnancy, there is full lobuloalveeolar development of the mammary gland and
secretion of milk
...
WBCs have receptors for prolactin
...
Secretion regulated from hypothalamus by inhibitory dopamine mostly
...
TRH, VIP, estrogen, glucocorticoids can all stimulate prolactin production
...
Oxytocin - ejection of milk by smooth muscle relaxation
...
Its effects are: galactorrhea (secretion from breast gland), sexual dysfunction
...
Only effect is that after delivery, secretion
of milk is not possible
...
Maternal steroid hormones and thyroid hormones cross the placenta
...
Insulin & glucagon from pancreas produced week 8 onwards
...
In males, testosterone and mullerin duct regression factor are produced from the testis
...
APGAR score - quickly asses the health and vital signs of a newborn after delivery
...
0-3 is a problem
...
From the right atrium, some of the blood goes through the foramen ovale to the left
atrium and left ventricle
...
These hypoxic conditions induce pulmonary vasoconstriction
...
From the left ventricle, blood flows out of the aorta to the systemic circulation
...
Oxygen saturation of blood is very low in the fetus
...
Fetal hemoglobin structure is also different
...
This
increases hemoglobin affinity to oxygen
...
Mother cant transport blood and oxygen
so baby must begin breathing
...
Stress conditions (mild hypoxia) activates sympathetic nervous system which activates
transport mechanisms and amniotic fluid is reabsorbed from respiratory system
...
Surfactant must be present to reduce surface tension
...
There is local release of endothelial prostacyclin and NO
...
There is increased resistance in systemic circulation
...
Foramen ovale closes after birth - separation of lung & systemic perfusion
...
Arterial pO2 increases from 25-30 to 80-100 mm Hg
...
Neonatal jaundice - jaundice due to elevation of unconjugated bilirubin during the first
week
...
From the fertilised egg it is possible:
Hyperplasia: increase in number of cells
Hypertrophy: Enlargment of cells
...
Wollfian and Mullerin ducts both present
...
Mullerin duct - gives rise to female internal sex organs)
PResnce of SRY gene (testis determining factor gene) on Y chromosome induces testis
formation after the 5th week
...
This degenrates the Mullerin duct and allows Wolffian duct to develop
...
This induces the development of Wolffian duct (gives rise to epididymis, seminal vesicle,
vas deferens) from 7th week onwards
...
This induces the formation of the scrotum and penis
...
FSH induces Sertoli cell secretion and spermatogensis
...
Leydig cells produce testosterone
...
For males and females both:
GnRH release is pulsatile at the start of puberty
...
This cycle release is stimulated by kisspeptin (from hypothalamus) and leptin (from adipose
tissue)
Decreased fat mass in girls could delay the onset of puberty
...
FSH, LH pulses follow GnRH pulses
...
For males and females both:
GnRH levels are high during gestation, low during infancy and childhood and increases
during puberty
...
During senesce, GnRH release increases due to the reduced negative feedback
...
LH induces testosterone production in Leydig cells by the activity of desmolase enzyme
...
307
Here, there are 2 enzyme: 5 alpha reducatse and aromatase
...
Maternal estrogen cant penetrate the the blood brain barrier as it is bound to fetoprotein
...
Becomes estrogen due
to aromatase enzyme and defeminizes the brain
...
These cells produce testosterone
...
The lining of seminiferous tubules is made up of Sertoli cells
...
Between the Sertoli cells are the developing gametes in their different stages
...
LH binding on Leydig cells will promote testosterone production
...
On Sertoli cells, FSH binding induces androgen binding protein production
...
Testsoterone is a steroid hormone
...
Activates or inactivates transcription factors
...
98% is bound to SHBG or albumin
...
Testosterone production has peaks in fetal and neonatal life
...
Testosterone production increases during puberty and stays high till the endo of life
...
Here primordial germ cells are made
...
At puberty, these primordial germ cells are converted to spermatogonia
...
1 spermatogonium can give 500 mature sperm cells
...
Androgen binding protein + testosterone ca go through the blood testis barrier but toxins
cannot
...
Penis has both sympathetic and parasympathetic innervation
...
Ejaculation is a sympathetic mechanism
...
There is increased inflow and decreased outflow of blood in the penis causing erection
...
Contains 40 - 200 million sperm
309
Female gonads: ovaries
This is the site of hormone production and development of oocytes
...
Oviduct: site of fertilisation
Uterus: site of implantation
GnRH secretion becomes pulsatile at the start of puberty
...
FSH & LH act on the ovary
...
This makes up the follicle
...
Granulosa cells are similar to Sertoli cells
...
During the follicular phase of the ovarian cycle, estrogen level is high
...
Progesterone increases just before ovulation due to LH peak
...
If estradiol level is low, there is negative feedback
...
If frequency of GnRH pulses is low (like in follicular phase), then FSH is mostly produced
...
310
During puberty, estrogen levels increase and from now on there's 28 day cycles of
estrogen production
...
Progesterone slightly higher (it inhibits contractions)
37th week onwards, progesterone levels decrease below the estrogen levels
...
After menopause, follicles become empty, estrogen secretion decreases
...
Progesterone effect:
Maintainance of pregnancy
...
Day 1-4: Menstruation
Day 5-13 is the follicular phase
Day 14 ovulation
Day 15-28 is the luteal phase
FSH increases during the follicular phase so estrogen is produced by granulosa cell
...
An increased LH causes the progesterone level to increase
...
These help dissolve layers
of theca and granulosa cells in Graffian follicle
...
Survives for 12 days if there is no fertilisation
...
hCG (similar structure to LH) helps the corpus luteum survive for 6-8 weeks into
pregnancy
...
Menstruation - 50 ml blood leaves
Day 5,6 onwards is the proliferative phase of endometrieum
...
After ovulation is the secretory phase
...
Body temperature increases after ovulation
...
Testosterone made from progesterone on the theca cells due to the action of LH
...
The follicle with the highest estrogen content is the most sensitive to FSH
...
Inhibin inhibits FSH secretion
...
Other follicles undergo apoptosis
...
More matrix metalloproteinases made os ovulation occurs
...
Theca cells take up cholesterol, make testosterone and send it to granulosa cells
...
During luteal phase, granulosa cells also produce progesterone
FSH peaks turns primary oocyte to secondary oocyte via meiosis I
...
At puberty, there is loss of inhibition of GnRH - kisspeptin effect
GnRH secretion is pulsatile to prevent desensitization of gonadotropes
...
Steroidogenesis (production of testosterone)
Spermatogenesis (production of mature sperm)
In males, FSH acts mainly on Sertoli cells
...
Sertoli cells can release inhibin in response to FSH stimulation
...
Inhibin levels correlates with total sperm count
...
Sertoli cells:
- secreate androgen binding protein (can capture testosterone)
- produce antimullerin hormone
- Makes up the blood testis barrier
- Produces inhibin
- Produces aromatase enzyme (testosterone -----> estrogen)
Estrogen is essential for spermatogenesis
...
LH stimulates more cholesterol uptake by Leydig cells in increasing LDL, HDL receptor
activity
...
Testosterone can be converted to estrogen (17 beta estradiol) by aromatase enzyme or to
DHT (dihydrotestosterone) by reductase enzyme
...
Capability of movement by sperm happens in epididymis
...
Erection, Emission and Ejaculation
...
Erection: Due to increased efferent parasympathetic activity leading to vasodilation
...
100,000 remain at puberty
...
One follicle is more dominant than the other (is more sensitive to FSH)
...
Hormone production also occurs in follicles
...
The direct precursor of estrogen is androgens via aromatase enzyme activity
...
Menopause is due to not enough follicles present anymore
...
Theca cells and Granulosa cells
...
These andorgen diffuse to granulosa cells and are nir converted to estrogen
...
To make estrogen, granulosa cells need androgens from theca cells
...
The follicles produce estrogen which inhibits FSH
...
Estrogen levels keep rising till ovulation
...
At around day 14, estrogen positive feedback on LH is responsible for LH surge
...
After ovulation is luteal phase
...
LH surge: 10-12 hours
Menstruation: 4-6 days
Menstrual cycle: 28 days
FSH stimulates follicular recruitment & growth and estrogen synthesis
...
315
In epididymis, sperm get the capability to move
...
In the female reproductive system, these inhibitory factors disappear allowing sperm to
move
...
Is rich in enzymes involved in sperm penetration of ovum
...
They move 3
ml/min
In scrotum, sperm are kept in cooler conditions - 32 degrees celsius
Thermotaxis - chemical signals from oocyte & higher temperature around oocyte attract
sperm towards it
Fertilization occurs in the ampulla of the fallopian tubes
...
Produces hormones (progesterone, hCG, Progestin, estriol)
Progestin: helps in the uptake of progesterone
Estriol: enlargment of mother uterus and breasts
...
Estriol precursor comes from fetus liver
hCG: maintains progesterone production in early pregnancy
...
PEaks in
the first trimester then falls
...
Progesterone decreases contractility of pregnant uterus
...
316
Cerebral circulation
Cerebral blood flow: 750 ml/min
Takes up 20% of resting oxygen metabolism and 15% of cardiac output
...
Cerebral Blood flow supplies cerebral metabolism (neuronal function, for production and
absorption of cerebrospinal fluid) and transports hormones made in the pituitary gland,
hypothalamus
...
No significant communication between them under physiological conditions
...
There are no valves in the cerebral veins
...
Pial arteriole diameter can be affected by innervation (sympathetic, parasympathetic and
trigeminal)
There is no sympathetic tone despite sympathetic innervation being present
...
Intraparenchymal arterioles + glial cells + intrinsic neuron endings = neurovascular unit
...
317
Cerebral blood flow control is mostly due to autoregulation
...
If glucose or oxygen concentration decreases and if CO2 concentration increases then
blood flow to the brain will increase by arteriolar vasodilation
...
Global cerebral blood flow is stable
...
This variability is
due to changes in function
...
Flow metabolism coupling:
Local increase in neuronal activity -----------> Local increase in metabolism causing
vasodilation and increase in blood flow
...
This is rapid, happens within a few seconds
...
Hypoxia, hypoglycemia, hypercapnia do not occur during the coupling metabolism
...
Initiation is independent of how long the stimulation is
...
There is hyperpolarisation and relaxation of the smooth muscle of arterioles
...
Pial arterioles can also undergo vasodilation
...
318
Neurogenic regulation is of less importance under physiological function
Brain capillaries have endothelieum, basal membrane (with pericytes), astrocyte endfeet
Blood Brain Barrier has tight junctions
...
2 endothelial cells of blood brain barrier overla each other to make the tight junctions
...
Has a
zipper like structure, closes the paracellular space
...
Everything must move transcellulary across the blood brain barrier
...
Cerebral blood flow delivers 72 litres of oxygen, 100g of glucose and carries away 72 litres
of carbon dioxide daily
...
Brain needs amino acids for protein synthesis
...
Essential polyunsaturated fatty acids are also taken up by the brain for membrane
synthesis
...
Endogenous and exogenous substances in the blood that could harm the brain must be kept
out
...
It has different transporters on the blood and brain side
...
There is GLUT 1 on blood side and brain side of endothelial cell
...
Present on the blood and brain side of endothelial
cell both
...
319
Transcellular transport across blood brain barrier
...
Some substances cant pass blood brain barrier because:
- they are degraded by enzymes in the luminal membrane
- Pumped back to the blood by ABC transporters
Thus the blood brain barrier impedes the delivery of ssime substance into the CNS
...
Cerebral Spinal Fluid (CSF)
Largest transcellular fluid compartment
...
Its composition is isotinic, similar to protein free plasma
...
Choroid plexus is very permeable
...
Na+/K+ pump sends Na+ into the CSF
...
Glucose, some vitamins but no proteins present in the CSF,
CSF is virtually cell free too
...
CSF absorption is dependent on CSF pressure
...
320
In the brain parenchyma, CSF picks up waste molecules - serves as lymphatic drainage
...
If something is outside the blood brain barrier - circumventricular organs
...
At these organs, blood communicates with brain directly
...
Oxygen is used in brain for oxidation of glucose
...
There is no resting sympathetic vasoconstrictor tone in the brain
...
Is 100-160 mm Hg
...
However if pressure is below 60 mm Hg,
then vasodilation has no effect
Vasoconstriction of brain arterioles causes increased resistance
...
Chemical regulation of brain circulation is based on arterial partial pressure values of CO2
and O2
...
Narrows autoregulatory range
...
Hypoxia causes vasodilation
Functional hyperemia: Increased blood flow in active tissues
...
Glucose and O2 consumption is higher in active parts than resting parts
...
Metabolites released by neurons
...
Meninges also covers initial part of cranial nerves
...
Subarachnoidal space is filled with cerebrospinal fluid
...
4 fluid compartments of the brain: CSF, cell plasma, blood plasma, interstitial fluid
...
MABP: 93 mm Hg
CSF and Interstitial fluid have similar composition & can communicate with each other
...
Blood brain barrier is needed for filtration
...
Many amino acid transporters are also present
...
CSF Is produced by choroid plexuses of lateral ventricles
...
322
Reabsorption of CSF Is very important
...
Driving force of Reabsorption is the pressure difference
...
323
Somatosensory system
Somatosensory system senses, transmits information from external and internal stimulus
...
Causes action potential to be generated
...
Objective sensory physiology - we can measure, quantify what we feel
...
Different stimuli induce different perceptoins
...
Different stimuli induce set perceptions/modalities
Modalities: hearing, vision, smell, taste, touch, pain, temperature, hunger, thirst
The specific sensory pathways are discrete from sense organs to the cortex
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Receptors can also be activated by other forms of energy
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Primary sensory neurons are pseudounipolar
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Receptor is a part of the primary sensory neuron or is a molecule in the cell membrane
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In dorsal root ganglia, there are cell bodies + A alpha, A beta, A delta, C fibers
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Dermatome is an area of skin whose sensory nerves all come from a single spinal nerve
root
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Are adjacent to each other
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In primary sensory neurons, energy provided by stimulus changes the membrane potential
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This is called a generator/receptor potential
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Action potential only induced if threshold is crossed
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Larger the receptor potential, more or stronger the action potential generated
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Duration of a stimulus is measured
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If slow adaptation to a stimulus present: receptor potential is present as long as the
stimulus is present - much more action potential is induced
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2 point threshold - the ability to distinguish 2 closely spaced stimuli
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A stimuli wont just stimulate one neuron but neighbouring ones too
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One single primary sensory neuron may provide information to multiple secondary order
neuorns
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Inhibitory synapses exist which suppress activity in neighbouring neurons (lateral
inhibition)
Mechanoreception senses touch, pressure, vibration, stretch
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Fast pain sensed by A delta fibers
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Mechanoreceptors of the skin are encapsulated
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Hairy skin doesn't have Meisnner corpuscle
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Synapses with A beta afferent nerve
endings
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Ruffinin corpuscle - one single nerve fiber is present
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Senses stretch
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Is
sensitive to vibration
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Has very fast
adaptation
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The surrounding structure makes
the corpuscle a fast adapting structure
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Everyday activity stimulates multiple mechanoreceptors at the same time
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Cold receptors: 8-38 degrees celsius
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There are more cold spots than warm spots
Faster the change in temperature, stronger the effect on nerve fibers
At physiological body temperature, both warm receptors and cold receptors are active but
not highly so
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At high temperatures, warm receptors are activated at a higher rate than at rest
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At these points,
physiological thermoreceptors are not activated at all
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Transient receptor potential receptors are transmembrane proteins
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Afferent fiber for fast pain: A delta fiber
Afferent fiber for slow pain and itching: C fiber
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C fiber axons are unmyelinated thus A delta transports information quicker
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Nociception: reception of signals evoked by the activation of nociceptors that provide
information about tissue damage
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Nociceptors are free nerve endings of A delta or C fibers
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C fibers: dull, diffuse, pain sensation
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TrkA receptors for nerve growth factor leads to growth and regeneration of A delta and C
fibers
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This
is a fast pain component, gives protective reflex
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Transmits 'slow pain' via free nerve endings of C fibers (peptidergic)
3) Itch receptors (pruriceptors)
Free nerve endings of C fibers
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4) silent nociceptors
Not active under physiological conditions
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TRPV1 (transient receptor potential receptor) are activated by painfully warm sensation,
low pH (H+)
TRPA1 receptor is activated by painfully cold sensations
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Nociceptors may contain & release neuropeptided
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Once TRPV1 is activated, Na+ and Ca2+ enters
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Ca2+ induces release of neuropeptides by exocytosis
Neuropeptides (CGRP, substance P) released by nociceptors may induce neurogenic
inflammation
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Action potential generated by pain stimulus
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However action potential can also activate additional things by going to other terminals
(mast cells, blood vessels) not just CNS
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CGRP: Increase diameter of blood vessels thus increasing blood flow
Substance P: Increase permeability of blood vessels
CGRP and Substance P also cause histamine release from mast cells
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Acid sensing ion channels (activated by H+), purinergic ion channels (activated by ATP),
P2Y (G protein coupled purinergic receptor), stretch activated channels can also be
present on 1 single nerve terminal
Nociceptors may express multiple ion channels/receptors
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Sensitization of nociceptors by inflammatory mediators (bradykinin, prostaglandins)
Both cause protein kinase A or C which phosphorylates the ion channel (TRPV1) and makes
it more sensitive
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Itching (pruritus) Uses C fibers
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Rexed Lamina I has neurons that receives information from nociceptors (C and A delta
fibres)
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Via fasiculus gracilis and fasiculus cuneatus to nucleus gracilis and nucleus cuneatus
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Then information goes to somatic sensory cortex
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Transmitter substances ae glutamate, CGRP, substance P
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Goes up the CNS via tractus spinothalamus lateralis & tractus spinothalamus ventralis
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Goes to somatic sensory cortex
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For proprioception
Descending pathways modulating pain sensation (lateral and medial inhibitory pathway)
Uses noradrenaline and serotonin
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Myelination also reduces from top to bottom
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They convert stimulus into electrical signals
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If depolarisation occurs (actual potential increases), Na+ flows into the cell
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When intensity of stimulation reaches the threshold, action potential is formed and is
propagated
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Modality (type), location, intensity, duration of stimulus are sensed and encoded
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Rapidly adapting receptors are activated only at the start of the stimulus
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Meissner corpuscle is an encapsulated superficial receptor
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Is
a rapidly adapting receptor
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They have a small receptive field
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Are rapidly adapting receptors
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Merkel cells are superficially located
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They sense fine discriminative touch
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Smaller receptive field than Merkel cells
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Anterolater system transports information of pain and temperature
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Nociceptors are high threshold receptors
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Nociceptors cant adapt to stimulation but can be sensitized
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A delta fibers are lightly myelinated
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Activation of A delta fibers causes sharp, high intensity, we'll localized pain
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Referred pain - we feel visceral pain somewhere else in the skin
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Neuropeptides are released from nociceptors
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Histamine released leading to vasodilation
Pain is alleviated by endogenous opioids
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Receptors of the somatosensory system are primary sensory receptors (first order
neurons)
Receptors can be mechanoreceptors (Meisnner corpuscle, Merkel cell, Ruffini ending,
Pacinian corpuscle, hair follicles)
For proprioception we have muscle spindle afferents ( Ia & II fibers) and Golgi tendon
organs (Ib fibers)
Thermoreceptors are for temperature sensing
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Nociceptors are for pain, noxious stimuli (high intensity mechanical or chemical stimuli, too
hot or too cold stimuli)
Receptors can encoded the modality, location, duration, intensity of the stimulus
Modality means receptors transduce specific types of energies into an electrical signal
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Location of stimulus is encoded by receptive field of sensory neurons
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Receptive fields can either be excitatory or inhibitory
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With lateral inhibiton: Inhibitory interneurons inhibit the response of neurons
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Helps in the precise localization of the stimuli by defining it's
boundaries and providing a contrasting border
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During prolonged stimulus, receptors adapt to the stimulus and change their firing rate
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Frequency coded: Larger the stimulus, higher the firing rate
Population stimulus: Larger the stimulus, more the receptors are activated
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Receptor potential can be depolarizing or hyperpolarizing
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Receptor potential is a graded potential
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If Receptor potential Depolarisation crosses the threshold, action potential is formed
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The sensory neuron cell bodies located in the dorsal and trigeminal root Ganglion are
pseudounipolar neurons
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A Delta fibers are lightly myelinated
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Only nociceptors are high threshold receptors
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Hair follicles are activated by movement above the skin
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Meisnner corpuscle senses the motion of the skin
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A beta fibers are associated with it
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A beta fibers associated
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A alpha fibers are motor neurons
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A gamma fibers are motor neurons to muscle spindles (intrafusal fibers)
A delta fibers are sensory fibers for touch, pressure, fast pain, temperature
C fibers are for slow pain and temperature sensation
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Proprioception- sensing the position of the extremities
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Epicritic sensation:
fine aspects of touch, vibration and 2 point discrimination (detects gentle contact of the
skin ans localizes the position that is touched (topogenesis)
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Done by encapsulated receptors (Meisnner, Merkel)
Protopathic sensation:
Pain and temperature are sensed
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Dermatome: area of the skin innervated by one spinal segment
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Nociceptors and thermoreceptors are both free nerve endings
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Thermoreceptors have adaption present
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At normal body temperature, TRPV4 is activated
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17 degrees or lower
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TRPV4 senses above 27 degrees
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Pain is a conscious experience
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Pain ≠ nociception
Superficial Pain can be:
fast, sharp, we'll localized pain ( A delta fibers)
Slow, dull, diffuse pain (c fibers)
Encephalins cause the presynaptic and postsynaptic inhibition of type C and A delta fibers
from synapsing and thus block pain sensation
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Itch is a sensation that causes the desire or reflex to scratch
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Itch receptors are histamine sensitive C fibers
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Are mechanically insensitive and have slow conduction velocity
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Protopathic - spinothalamic tract (anterolateral column)
Epicritic - Dorsal Column medial leminscus pathway
Deep and chronic pain from deep somatic structures - spinoreticular pathway
Trigeminal system transports information of the head to the CNS
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Olfactory epithelium has primary sensory cells - neurons
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There is direct connections with the olfactory bulb via the 1st Cranial nerve (olfactory
nerve)
Olfactory cilia exist
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Axons are from primary nerve cells (information input) and dendrites are of mitral cells
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The number for axons is much higher than the number of dendrites
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Mitral cells are connected horizontally to each other
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This is where convergence happens
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There is lateral inhibiton in visual system along with olfactory system
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PPM number- how many molecules are needed for the stimuli to be sensed
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001 ppm
Detection limit is just to detect that a smell is existing
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The identification limit is thus higher than the Detection limit
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We can differentiate between 100,000 different smells
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Identifying smells can be subjective
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In odorant receptors, signalling cascade in the receptor is always G protein coupled
receptors
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If this is high enough, then an action potential is generated and transmitted
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Adenylate Cyclase - cAMP
Na+ ion channels open, receptor potential generated
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This assists in depolarisation
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Odorants are detected by activation of a combination of odorant receptors
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Thus there is concentration, specificity & combination dependence on odorant sensing
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There are specific connections between odorant receptor cells and mitral cells
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Receptors are in taste buds
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Fungiform papillae:
Anterior 2/3 of the tounge
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Circumvallate papillae:
At the rear of the tounge
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All taste buds can taste all groups
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Their function aint taste sensation but evoking movement that remove food
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They are secondary sensory epithelial cells
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Innervation of tounge taste buds:
CN VII, IX, X, V
Taste pathways can be specific or unspecific
Specific: Medial leminscus, VPM of thalamus, Anterior insula
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Detection limit of different tastes are very different
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Activation of receptors also partly depends on amount of chemical substances available
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Tatse can cause: insulin release, salivation, swallowing, coughing, tounge protrusions
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Transmitter between sensory cell and nerve fiber is ATP
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Even ATP can be degraded at the synapse
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There is conduction between the nasal and oral cavities
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There are also eyelids and tear secretion for this protective purpose
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Blinking reflex is evoked due to strong light, dryenss of cornea, touching the eyelashes,
approaching objects
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Vision affected
Lagopthalmos - eyelid doesn't close at all
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Tears lubricate and protects the eyes, rinses out foreign objects, contains lysosymes
(antimicrobial enzyme)
Lacrimal glands produce Tears
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Visible spectrum of lighy: 400-700 NM
Features of an image: Luminiscence, contrast, color contrast, pattern contrast
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Light has to pass through the pupil (small hole)
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Image created is only sharp if the focus point is on the retina
The retina is a curved surface
1 diopter means focal length is 1 meter from lens
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10 diopter means focal length is 10 cm from lens
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Ciliary muscles control the thickness of lens with the help of the suspoensory ligaments
Cornea (40-43) and lens (17-20) have the highest refractory power
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Closer the object we are viewing, stronger the refractory power needed
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Blue light has the highest refractory index of visible light
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Pupils are small
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When looking close, stronger refractory power is needed, that's why the lens are fatter
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When looking far, pupils are bigger to take in more information
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Looking close:
Contracted ciliary muscles, relaxed zonula fibers, lead to spherical, fatter lens
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Looking far:
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Relaxed ciliary muscles, contracted zonula fibers lead to thinner lens
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This is for looking far away
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With age, lens lose their flexibility and become more and more rigid - loss of
accommodating ability
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Visual acuity: Measure of the ability of the eye to distinguish between shapes and details
of objects at a given distance
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Light doesn't pass through
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Myopia (near sightedness)
Refractory power is stronger than it should be
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Can see near objects but not far away objects
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Focal points is after the retina
Can see far objects bit not near objects
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Curve of the cornea can also be checked
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Astigmatism - when vertical curvature of the cornea is less than the horizontal curvature
Intraocular pressure is controlled by the production and draiage of aqueous humor
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Aqueous humor is made of plasma ultrafiltrate
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Production is ana active process
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Parasympathetic effect:
Contraction of the pupil
Increased aqueous outflow
Lens are more spherical (contraction of ciliary body, relaxation of zonula fibers)
Sympathetic effect:
Dilation of the pupil
Lens are more flat (relaxation of ciliary body, contraction of zonula fibers)
When we look close, parasympathetic tone is active
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Balance between drainage and production of aqueous humor keeps intraocular pressure
normal (60 mm Hg)
If intraocular pressure is not normal, there's blurred vision and glaucoma
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Normal disc has a cup-disc ratio of 0
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In glaucoma: cup-disk ratio is 0
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This effects eye functioning
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Vergence movements:
Convergence: when object is close
Divergence: when object is far away
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Saccades: Short & fast with or without head movement
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Torsion eye movement - head shifts but pupil position doesn't change
Nuclei for eye movement:
Oculomotor, trochlear, abducens nucleus
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Details, good resolution images at the fovea of the retina
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Potential changes in the receptors are electrotonic potentials
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Inner segment of rod cells has nucleus, endoplasmic reticulum, mitochondria
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In rod cells, membrane discs are independent of cell membrane
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In the dark, cGMP level is high
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Na+, Ca2+ flows into rod cells & depolarizes the cell
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Opsin is sensitive to light
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All opsins have cis-retinal
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All trans-retinal once again becomes cis-retinal due to isomerase enzyme
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Na+, Ca2+ flows in, causes depolarisation which leads to glutamine release
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This enzyme degrades cGMP
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Membrane gets hyperpolarized and glutamine release is reduced
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Very dense at the fovea
Rods: 120 million
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Only at the periphery
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No color
Phototopic conditions (more light): Cones used
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Retina has:
outer nuclear layer (rods & cones)
outer plexiform layer (horizontal cells - do lateral inhibition)
Inner nuclear layer (bipolar cells, amacrine cells)
Inner plexiform layer
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Ganglion cell layer (ganglion cells)
Receptive fields of ganglion cells depends on how many rods, cones give information to that
1 ganglion cell
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Receptive field is higher & resolution is lower in the periphery
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On bipolar cells show depolarisation in response to light
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Cone sensitivity is super high
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Dark and light adaptation is done by the pupil
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Periphery has high rod density
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Receptive field of ganglion cells have a centrum and periphery
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Light acts on cone cell
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The neurotransmitter at the cone cell is glutamine
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Hyperpolarised cone cell will not inhibit ON bipolar cell
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OFF bipolar cells have ionotropic AMPA receptors
If there is no light, lots of neurotransmitter is released
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Show activity
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Made up of ON and OFF center cells
Light passes from bottom to top of retina (ganglion cell to receptor cell)
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Right visual field is represented on the left side of both retinas
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- Lesion at the chiasma causes nasal side of vision to be lost in both eyes
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- Lesion at optic tract (right tract for example), loss of vision of left side of both eyes
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Thalamic P cells - spatial resolution & color contrast
P and M cells communicate with each other
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There is parallel pathway of information from retina ganglion cells to lateral geniculate
body to boradman area 17
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Incoming signals from lateral geniculate body synapses on the 4th layer of the cortex
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Some areas have one eye input, other areas have input from the other eye
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Orientation columns are vertical
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If you move horizontally through the various orientation columns, then orientation change
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Some cortical cells can discriminate between movement of stimulus (right, left, up, down)
Layer IV of the cortex has simple receptive fields
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The orientation columns, ocular dominance columns, color sensitive CO blobs all make up
the hypercolumns of the primary visual cortex
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Dorsal pathway: recognizing movement
Ventral pathway: recognizing shapes, details and colors
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From primaty visual cortex:
Dorsal pathway goes to the parietak cortex ----> motor
Ventral pwathway goes to infratempotal cortex ----> memory
Spatial vision:
- Helps in judging distance
- Helps in making precise movements
- Helps in judging size & shape of objects
How do we judge object distance & posiiton in 3D?
Lens accommodation, size differences, overlapping & shadows, color fading
Light from the left visual field goes to the right half of both retinas
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An object goes to corresponding retina locations when both eyes fixate on one object
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Any object closer to the eye than the horopter circle has disparate retina locations due to
differences in light rays
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Objects within the horopter circle shift retina location to the lateral side
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200-400 nm
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Different cone types are sensitive to different wavelengths
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Usually, 3 different cone types present
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Trichromats: Have 3 types of cones
Dichromats: have 2 types of cones
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Bad resolution and no colors
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These 2 are antagonistic to each other
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Ganglion cell, bipolar cell, photoreceptor
-----> : direction of light
<---- : direction of neuronal communication
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Fovea - area where cone density is highest
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At the macula, photoreceptor density is still high
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This layer prevents reflections
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Inner segment has large number of mitochondria , nucleus
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It has connections to biploar & horizontal cells
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Cones
Contains color pigments
Senses lower light sensitivity
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11-cis-retinal makes up rhodopsin in rod cells
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11-trans-retinal activates rhodposin
11-cis-retinol (rhodposin) ------> 11-trans-retinol (metarhodopsin)
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cGMP level decreases
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Now hydrolysis of metarhodopsin
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cGMP gated Na+ & Ca2+ channels open
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In light, photoreceptors are hyperpolarized
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Glutamate release is reduced
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There are 3 types of cones: blue, gree, red
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Horizontal pathways create lateral inhibition
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Horizontal cells in the horizontal pathway are excited by glutamate released from
photoreceptors
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This is what
increases contrast
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Glutamate is released to OFF ganglion cells
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ON bipolar cel ls
In light
Glutamate is released from photoreceptors
Cation channels open, cell gets depolarized
Glutamate is released to ON ganglion cells
Basically ON bipolar cels activate ON ganglion cells in the light only
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They have excitatory synapses through gap junctions
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Ganglion cells can generate action potential and form the optic nerve
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Types of ganglion cells: Magnocellular & Parvocellular
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ON ganglion cells have:
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ON centre - firing for light
OFF periphery - silence for light
OFF ganglion cells have:
OFF centre - firing for dark
ON periphery - Silence for dark
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Both ON & OFF bipolar cells are connected to ON ganglion
The concentric receptive fields of ganglion cells are sensitive to color sensitivity
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Light from the nasal visual visual field reaches the fovea
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Fibers from nasal part of retina cross over at the optic chiasm
Optic tract connects the optic chiasm to the lateral geniculate body
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Retinotropic structure has 6 layers
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Layers 1,4,6 have contralateral ganglion cells
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Layers 3,4,5,6 carry information from P cells
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Lateral geniculate body then sends information to the primatu visual cortex
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Damage:
- To an optic nerve - total visual loss of that eye
- To the middle of the optic chiasm - Bitemporal hemianopia (Both eyes temporal side
vision is lost)
- To One side of the optic chiasm - Nasal or temporal side of one 1 eye loses vision
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Eg: right homonymous hemianopia
- To optic radiation: Loss of vision in nasal side of one eye and temporal side of the other
eye + macular sparing
Primary visual cortex has orientational columns
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The orientaational columns are sensitive to both the location and orientation of rectangles
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M pathway (dorsal):
Responsible for 3D vision, motion detection, insensitive to color
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Extrageniculate pathway:
Retina ----> Superior colliculus ------> pulvinar --------> higher visual cortex
This pathway processes movement, mediates attention, contributes to shape & form
discrimination
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At the same time, pupil constriction happens on the contralateral side
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Hearing
Sounds -----> vibration of solid (bones) -----> waves in cochlear fluid to be made ----->
displacement of cochlear membrane -----> bending of hair cells ----> generation of action
potential
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Bones of middle ear: Incus, Malleus, Stapes
Stapes footplate is connected to the oval window
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Tympanic membrane is the boundary between middle and outer ear
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Sound travles through gas, liquid, solid
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Determines loudness (dB)
To measure sound pressure level (dB): 20 x log P1/P0
P1 is the sound of interest
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Humans can hear between 0-120 dB
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Phon scale describes subjective loudness
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4 phone is the hearing threshold
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Conduction of vibration:
Sound can move through air or bone
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Air conduction is through the ear
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Air conduction:
Vibrations are collected by the outer ear, sent through the external canal, goes through
the tympanic membrane and vibrates eardrum
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Outer ear: collects & funnels sound to the eardrum
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Middle ear has Eustachian tube (equilisation function), oval and round windows, ossicles
(malleus, incus, stapes) and muscles
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Without amplification, most vibrations would be reflected from the oval window
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Middle ear is filled with air like the outer ear
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If these muscles are contracted then ossicle movement is inhibited
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This tympanic reflex prevents the amplification of loud sounds and reduces the
transmission of these loud sounds to the inner ear
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Malleus, Incus, Stapes
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This surface relation amplifies the signals
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Without amplification, 99% vibration would be reflected from the oval window
Bone conduction bypasses the outer and middle ear
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Main function of bone conduction is recognition of own voice
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Conductive hearing loss: Problem related to air conduction and middle ear
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If the problem is related to hair cells - Sensory hearing loss
If the problem is related to the cochlear merve - Neural hearing loss
Mixed hearing loss is a combination of all of these
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Its a temporary loss of hearing
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Failing eardrum or ossicles cause reduced air conduction
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If there is cochlear nerve damage or hair cell damage, both air and bone conduction is
reduced
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Hearing reduces
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When footplate of stapes vibrates:
Vibrations transports signals to fluid of inner ear
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We cannot hear without the middle ear at all
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Basilar membrane contains hair cells (receptor structures)
Scala vestibule and scala tympani are filled with perilymph
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Scala media is in between scala vestibule and scala tympani
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Basilar membrane is in between the cochlear duct and scala tympani
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Hair cells process vibrations and activate afferent fibers of cochlear nerves
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Apical part of hair cells connected to endolymph
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Perilymph is a typical extracellular fluid
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Is a product of filtration
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5-2 mmol Ca2+
Endolymph is a product of secretion
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Endolymph has high K+, low Na+ concentration and practically 0 Ca2+
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Apical part of hair cell connected to endolymph
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Potential difference is approximately 80-90 mV
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Potential difference between endolymph and intracellular fluid is 120-160 mV
This potential difference is required for signal transduction by K+ at hair cells
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3/4 are outer hair cells, 1/4 are inner hair cells
4,000 organs of corti in one cochlea
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Tiny movement of cilia system can activate hair cells
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Hair cells are a secondary sensory cells
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Outer and inner hair cells get different innervation
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They help inner hair cells to generate action potential by helping hair cell movement
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As you move from the beginning of the cochlea to the helicotrema of the cochlea, the
frequency of the stimulus decreases
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Apical part of hair cell in endolymph
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Movement of cochlear fluid deforms the ciliary structure of hair cells
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This causes movement of endolymph
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K+ inward current through activated mechanoreceptor cation channels
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Ca2+ inward current observed into hair cell
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Tip links contain mechanosensitive cation channels
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When smaller cilia are moved towards bigger cilia, there is stimulation of hair cells
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PAsses from scala tympani to the round window
Exits cochlea via the round window
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This causes a migrating wave on the basilar membrane
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Transmitter release from the inner hair cells
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The basilar membrane varies in thickness and stiffness along its length causing different
frequency tunings
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Low frequency is sensed at the end of the
basilar membrane
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Basiliar membrane is very stiff and narrow near the oval window
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1 basilar membrane is approximately 33 mm long
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Shortening of outer hair cells moves the basilar and tectorial membrane
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Voltage dependent proteins (prestin) are contractile proteins
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Prestins shorten after activation (Depolarisation)
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Thus prestins cause voltage dependent change of the length of the hair cells
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This activates afferent fiber of cochlear nerve near every hair cell
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Also more hair cells and afferent fibers will be activated
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Primary auditory cortex: Br 41, 42 in the temporal lobe
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Sound waves are made up of compressions and rarefractions
Frequency equalizer of inner ear is cochlea
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Outer ear has auricle, external acoustic meatus, external acoustic canal
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Middle ear separated from the outer ear by the tympanic membrane
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Malleus articulates with the tymapnic membrane
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Ossicles act as a lever
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Middle ear is filled with air
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Since fluid has greater resistance than air, sound must be amplified or else it'll be
reflected
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Both have protective reflex
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Organ of Corti is in the inner ear
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Perilymph - high Na+, low K+
concentration
Scala media - filled with endolymph (high K+, low Na+ conc)
Stria vascularis produces endolymph
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Hair cells sit on supporting cells on the basilar membrane
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2 types of hair cells present: Inner & Outer hair cells
Inner hair cells get receptor potentials, get depolarized and release neurotransmitters
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Mechanically gated K+ channels on stereocilia open
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K+ flows in, depolarisation occurs
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This open voltage dependent Ca2+ channels
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For outer hair cells, depolarisation causes shrinking
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Electromotility is due to a protein called prestin
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Causes shrinking of the cell
Shrinking of the cell body brings the tectorial membrane closer to the inner hair cells and
makes it more sensitive to sounds
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Basilar membrane:
Narrow and stiff at base
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Wide and flexible at the apex
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Spinal ganglion in modiolous of cochlea has bipolar neurons
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From cochlear nuclei, 2nd order neuron goes to pons & superior olivary complex
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4th order neuron goes from lateral leniscus tract & inferior colliculi to medial geniculate
nucleus
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This means tones close to each other in frequency
are represented in topologically neighbouring regions in the auditory cortex
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Vestibular system is responsible for body posture
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Vestibular system helps in eye movement control
Oculomotor reflex - maintains clear vision in case of moving head
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Receptors of semicircular canals are in crista ampularis (at the beginning of the canals)
Hair cells are the receptors
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When head rotates from left to right:
Left ear semicircular canal is inhibited, right ear semicircular canal is activated
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)
Linear acceleration causes movement of of the crystals
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Always:
Deflection of stereocilia to longer kinocilia causes depolarisation
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From vestibular ganglion, information goes to the cerebellum via inferior peduncle and to
cerebral cortex via the thalamus
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Information can also go to the vestibulospinal tract
...
There is no oxygen, nutrients in that certain area of the brain
...
Motor symptoms are the most important way to diagnose stroke
...
Spinal cord controls reflexes
...
Brainstem helps control muscle tone & posture
...
Cerebellum does coordination of movement
Motor cortex controls voluntary movements
...
Is connected to the cortex, basal ganglia, cerebellum, brainstem
...
Reflex occurs only if stimulus reaches a threshold
...
Reflex arc:
370
Receptor ---> Afferent nerve ----> Central processer (brain/spinal cord) ----> Efferent
nerve ---> Effector
Proprioceptive reflex: Receptor & effector are in the same organ (eg muscle spindle, golgi
tendon organ)
Exteroceptive reflex: Receptor and effector are in different organs (eg flexor reflex
elicited by skin injury)
Reflex modulation is by different tasks and aims
...
Muscle spindle - tiny, long fusiform receptor organs
...
These are intrafusal fibers
...
Muscle spindles detect muscle length change
...
Polar regions (edges) of fibers can contract
...
Central region has no actin or myosin and cannot contract
...
Sensory innervation is in the middle of the fiber
Ia afferents: detection of dynamic changes (fast, short duration activity)
...
IIa afferents - detection of long lasting & slow changes
Present only on nuclear static bag fiber & on nuclear chain fibers
...
Gamma loop
Alpha motor neurons are nerves to the extrafusal fibers (working muscle)
Contraction of extrafusal muscle causes decreased passive tension in intrafusal fibers
...
Contraction of the intrafusal muscle fiber increases tension in the intrafusal muscle fiber
...
Interaction of alpha & gamma motor neurons is called the gamma loop
...
Golgi tendon organ is innervated by I b afferents
I b afferents are activated during muscle contraction
...
Golgi tendon organs are located at the tendon-muscle boundary among collagen fibers
The golgi tendon organ detects active muscle contraction and tension
Reflexes of the muscle spindle:
Strech (myotatic) reflex
...
372
In the hoffmann reflex, myotatic reflex is elicited by electrical stimulation of I a
afferents
Bell Magendie rule:
Nerve impulse goes in at dorsal horn, motor info leaves at the ventral horn
...
Has a single synapse in the whole reflex
...
Enhancement of the knee jerk reflex is by Jendrasskin manoeuvre (cross fingers & pull
arms) or by arousal/anxiety
...
Muscle contraction detected by I b afferent neurons
...
In the dorsal horn, I b afferent synapses with inhibitory interneurons
...
Motorneurons are inhibited
...
A beta fibers sense stretch, skin pressure and touch
...
Type C fibers are unmyelinated
...
Sudden, sharp pain information is provided by A delta fibers
...
Pain reflexes are multisynaptic
...
373
Pain reflexes involve many neurons, many synapses
...
Intensity of pain decreases slowly
...
In the crossed flexor extensor reflex:
Ipsilateral extensors inhibited, ipsilateral flexors activated
Contralateral extensors activated, contralateral extensors inhibited
...
Eg of crossed flexor extensor reflex are plantar, sole reflex
...
The multisegmental and integrative functions of the spinal cord is done by interneurons
...
Most important function of interneurons is the intrinsic cyclic activity in ventral horn that
forms the locomotor drive potential
...
Central Pattern Generation (CPG) is involved
...
They use GABA & glycine as
neurotransmitters
...
Extensor motorneurons are found more towards the ventral horn of the spinal cord
...
Alpha motor neuons (lower motor neurons) innervate muscles
...
Somatic motor neurons innervate limb muscles
...
These start in the cortex and synapse with lower motor neurons
...
Muscle becomes flaccid
...
Due to peripheral paresis, there is rapid atrophy of muscles
...
Lower motor neurons do chemical stimulation along with electrical stimulation of of muscle
cells
...
This is because upper motor neruons send many inhibitory messages to lower motor
neurons
...
There is slow muscle atrophy (slower because lower motor neurons are still alive) and
Babinski sign
...
In spinal shock: motor, sensory, autonomic function is lost for a period of time
...
2) After 3-4 days, polysynaptic reflexes regenerate (eg: pain reflexes)
3) After 1 week - 1 year, tendon reflexes are restored and become
upregulated/hyperactivated
...
Not restored after spinal shock:
Voluntary movements below the level of the transsection
Standing & walking
Muscle tone proper regulation
...
Both white and gray matter of that side is destroyed
...
In the segment of the lesion there is reflex loss and flaccid paresis
Below the segment of the lesion
On the same side:
Spastic paresis (disconnection of the corticospinal tract)
Epicrtici sensory loss (fine touch, vibration, position)
Disconnection of the posterior ascending system)
On the opposite side of the lesion:
Protpathic sensory loss (heat, crude touch)
Disconnection of the spinothalamic tract
...
There could be
vegetative hyperactivity after 3-6 weeks
...
There is return of urination/defecation reflex
...
Responsible for voluntary control
...
All the above 4 have tracts connecting them to the spinal cord
...
Tasks are bilateral movements, pain control, posture
Vestibulospinal tract, reticulospinal tract, colliculospinal tract
...
Muscle tone always has resting contraction, gamma efferents, alpha motor neurons (small
activity without synchrony)
Marked tone: Axial muscles (neck & back), antigravity muscles (extensors)
Hypotonia - Peripheral paresis
Hypertonia - Central paresis
Catatonia - Random, bizarre movement without any aim
...
Effect limited to arms
...
These 4 systems all work together
...
Major extensor tone inhibition is done by the motor cortex
...
All 4 limbs are in extension and red nucleus has no effect
anymore
...
Leads to flexed arms, extended legs
...
Receptors in the vestibular system are the hair cells stimulated by the movement of
endolymph and cilia
...
K+ ions show high concentration in the endolymph (even higher than Na+ concentration)
Receptor potentials are generated in hair cells
...
Cupula is a gelatinous structure
...
Not sensitive to linear acceleration
...
Saccule is vertical
...
Hair cells are embedded in a gelatinous mass that contains small crystals - otoliths
...
Muscles have extrafusal fibers (do the movement) and intrafusal fibers, golgi tendon
organs which sense stuff and send information to the spinal cord
...
Brainstem also gets information from visual system, vestibular system, cerebellum along
with the spinal cord
...
In the spinal cord:
sensory information (proprioceptive or pain) goes via dorsal root into the spinal cord
...
380
Muscle spindle has D sensors and P sensors
...
Thus muscle spindles regulate muscle length and contain intrafusal fibers (nuclear chain
fibers - P sensors (I a), nuclear bag fibers (D sensors (I a, II))
...
Golgi tendon organs are found in tendons - at the end of the muscle
...
Golgi tendon organs are innervated by I b fibers
...
Gamma loop moudlates muscle tone
In the gamma loop there is coactivation of the alpha and gamma motorneurons
...
Nuclear chain fibers send stretch information to the spine and excites alpha motor
neurons
...
Proprioceptive reflex aka myotatic reflex aka muscle stretch reflex is by muscle spindle (I
a)
Inverse myotatic reflex is a tendon reflex - Golgi tendon organ
Flexor - crossed extensor reflex is an exteroceptive reflex
...
Strech reflex
In the agonist muscle there is streching
Muscle spindle senses stretching, sends information via I a fiber to spinal cord
...
381
Is a monosynaptic reflex
...
This uses inhibitory interneurons
...
It senses relaxation of agonist muscle, sends information to spinal cord via I b fiber
...
In the strech reflex extrafusal fibers of agonist muscle is stimulated and antagobist
muscle is relaxed
...
Pain infromation is sensed and carried by A delta/C fibers till the spinal cord
...
Thus with flexor reflex, theres always crossed extensor reflex
...
Flexor, crossed extensor reflex happens at the same time
Rhythmic movements are a complex spinal cord control
...
In rhythmic movements:
sensory informtion activates primary and third neurons
Primary neurons activates secondary neurons which carry out motor command
...
Required while walking
...
Semicircular canals sense rotation of head & body
...
This increases glutamate release & action potential frequency
...
On top of the membrane, we can the otoliths
...
These 2 detect linear acceleration & head position
...
They send infromation to the:
- spinal cord (via vestibulospinal tract)
- Flocculonodular lobe of cerebellum
- Occular motor nuclei via medial longitudinal fasiculus
- Thalamus and then vestibular cortex
Eventually goes to parietal cortex, somatomotor areas, hypothalamus, amygdala
Brainstem control of muscle tension
- Red nucleus (via rubrospinal tract)
Increases flexor tone, decreases extensor tone (only present on the upper limb)
- Medullary reticular system (via lateral reticulospinal tract)
Increases flexor tone, decreases extensor tone
- Pontone reticular system (via medial reticulospoinal tract)
Increases extensor tone, decreases flexor tone
- Deiters nucleus (via vestibulospinal tract)
Increases extensor tone, decreases flexor tone
...
Input to cerebellum comes via mossy fibers and climbing fibers
...
Input via mossy fibers excites unipolar brush cells (amplify the signal) & granule cells
...
Basket & stellate cells inhibit purkinje cells
...
Archiocerebellum coordinates equilibrium movement
...
Vestibulocerebellum gets information from vestibular system & visual information
...
Involves the fastigial nucleus, Deriters nucleus, flocculonodual lobe
...
Compares the 2
...
Cerebrocerebellum gets movement plan as senseory information
...
384
All ventral parts of the thalamus make up the motor thalamus
...
Maintains posture and generates general movement
...
Associative domain - Cognitive function (attention, time estimation, implicit learning)
Limbic domain is for emotions
Motor domain is for controlling movements
...
Supplementary and premotor area work together parallely and send their info to the
primary motor cortex
...
In cingulate gyrus, there is a cingulate motor area
...
All cortical motor areas send fibers to the pyramidal tract
...
50% of pyramidal tract comes from broadman area 4
...
The pyramidal tract goes through it
...
80-90% fibers cross over
...
10-20% fibers don't cross over
...
Motor fibers of pyramidal tract terminate in the ventral horn of spinal cord on motor
neurons or interneurons
...
Rest of the fibers terminate on the interneurons
...
No sensory layer
...
Granule cells in layer 4 is for receiving sensory information
...
Thus motor cortex has plasticity
...
Organizing principle of the motor cortex:
Body map (map of body parts)
Action map (map of complex, meaningful movements)
The primary motor cortex cells code for:
- speed of movement
- Direction of movement
- Strength of movement
- Coordination of muscle groups regulating multiple joints
- Reads movement trajectory of muscles & joints
...
386
Before, during & after movement - action potential frequency increases of excitatory
neurons
...
1 for proximal limb muscles
1 for distal limb muscles
...
Motor cortex has plasticity
...
In the spinal reflex pathway, part of the afferent nerve runs up to the motor cortex
...
This is called the long-loop pathway
...
This is especially important in grasping objects & stabilizing posture before goal
orientated movements
...
Mirror neurons are multisensory
...
387
Supplementary motor area can be activated without any movement
...
Is especially activated during bilateral coordination of 2 hands and fingers
...
There is no strict hierachal organisation in the motor cortexes
...
From here, complex plans go to the sensory cortical areas & supplementary & premotor
cortex
...
Sensory cortex receives an efferent copy from the prefrontal cortex
...
From here, majority of the pyramidal tract originates
...
Stimulus driven action goes from posterior parietal cortex ----------> premotor cortex
---------> primary motor cortex
...
Without it (preSMA lesion), there is action without intention
...
388
389
CNS
Cortical input goes to cerebellum from primary, suplementary & premotor cortex
Primary somatosensory cortex also projects to the cerebellum
...
All sensory modalities provide input to the cerebellum indirectly
...
From the cerebellum, information goes back to the cortex via the thalamus
...
Cerebellum has as many neurons as the entire cerebral cortex
...
Deep to that is the white matter
...
White matter of cerebellum has Dentate nucleus, fastigial nucleus, interpositus nucleus
(globusus + emboliformis)
Output nucleus of the medial side is the Deiters nucleus (aka deep nucleus of cerebellum)
...
Deiters nucleus receives all sensory modalities and information from the cerebellum
...
Corticospinal tract (via pontine nuclei) sends input to the cerebellum
...
Efferent copy is the command that the motor cortex is giving
...
These sensory inputs that the cerebellum gets is called afferent copy
...
If required, cerebellum can make an error signal which is sent to the cortex & brainstem
...
Molecular layer has dendritic tree of Purkinje cells, parallel fibers, stellate cells and
basket cells
...
Granular layer has granule cells in high numbers
...
Input to the cerebellum by climbing & mossy fibers
...
Purkinje cells also project to the deep nuclei and inhibits the deep nuclei
...
Interneurons such as stellate, basket cells
...
Inhibitory elements of cerebellum:
- Purkinje cell (inhibits deep nuclei - leads to no output information from cerebellum)
- Basket & stellate cells - inhibitory interneurons
...
They inhibit granule cells
...
All inhibitory elements of the cerebellum are GABAergic
...
Mossy fibers terminate on granule cells (also excitatory)
...
These cells use glutamate
...
Parallel fibers also form synapses with inhibitory basket cells
...
Inhibiting the inhibitory cells
...
Golgi cell: inhibition of granule cell
...
Lugaro cell: feedback modulation of Golgi cells
...
Thus there are direct and indirect inputs to the Purkinje cells
...
Indirect innervation when mossy fibers terminate on inhibitory interneurons and then
these go onto the purkinje fiber
...
Archiocerebellum: Fastigial nucleus
Plaeocerebellum: Interpositus nucleus
Neocerebellum: Dentate nucleus
Dentate nucleus is the output nucleus of the lateral part of the hemispheres
...
Most of the information from the vestibulocerebellum (vermis) goes to the brainstem
...
The other half goes
to the red nucleus
...
All information from the cerebellum to the motor cortex goes via the motor thalamus
...
Spinocerebellum does correction of movement patterns based on feedback
...
Cerebellar damage leads to balance disorders and coordination problems
Signs of cerebellar damage are ipsilateral (not contralateral like in the pyramidal tract)
Primary motor cortex is the primary input to the basal ganglia
...
They can send this information to the substantial
nigra or to the externa/internal globus pallidus
...
Input from the cortex (corticostriatal) is excitatory input
...
Cortex projects to the caudate & putamen by glutamate neurons
...
Uses GABA
...
Information is sent to the thalamus
...
- Indirect pathway: Input neurons project to external globus pallidus (GABAnergic) which
projects to subthalamic nucleus (GABAnergic) which projects to output nuclei (glutamate)
...
Subthalamic nucleus can be inhibited by globus pallidus external leading to no output nuelci
being inactivated
(Indirect pathway is aka no go pathway)
Cortex can also directly project to the subthalamic nucleus
...
These are projection neruons
...
These modulate medium spiny neurons
Interneurons can be GABAergic or cholinergic
...
Medium spiny neurons that project to globus pallidus external express D2 dopaminergic
receptors - inhibitory response
Dopamines stimulates direct and inhibits indirect pathway
...
Strong plasticity in brain that can adapt to extreme conditions so that homeostasis
maintenance can be carried out
...
Consciousness- state of awareness in relation to the environment
...
Self consciousness - aware of ourself
...
From complex structures, there are emergent properties
...
With all this, the brain decides on the best course of action
...
Prevent random movement
...
Identification of cell types including neurons is done by immunohistochemistry
...
Human brain is redundant
...
If 1 thing is harmed, the entire structure isn't harmed
...
This is the quickest and most economical way to share information
Communication in the brain is by electrical & chemical synapses and dendritic spines
...
Spines with lower neck has less resistance and thus higher EPSP (excitatory post synaptic
potential)
...
Glial tissue is also important in information transfer in the brain
...
Astrocytes communicate with each other by calcium wave
...
Transmembrane potential changes are due to this
...
Leads to potential changes in extracellular space
...
Due to sleep depriviation: body weight drastically decreases, even if food intake is high
...
Reaction time increase
...
Pretectum: Reflex control of pupil & lens
...
Due to prolonged light exposure, there is extended action potential of these cells
...
There is protein dimerization in the suprachiasmatic nucleus
...
During day, melatonin levels are low and during nighttime melatonin levels are high
...
When looking at EEG, look at the amplitude & frequency of the EEG waves
...
8 - 12 Hz
Beta activity: During active wakefulness, mental activity
...
397
Theta activity: During drowsiness and REM sleep
...
10 - 15 Hz
Stage 1 sleep: 3 -7 Hz
Stage 2 sleep: Slow waves
Stage 3 sleep: 0
...
Slow waves
Stage 4 sleep: 0
...
Slow waves
...
Is paradoxical
...
During REM sleep: Heart rate increases & respiratory function increases
REM sleep is when our dreams (that we remember) occur
...
During REM sleep, dorsolateral prefrontal cortex & posterior cingulate gyrus show
hypoactivity
...
Sleep can be REM or SWS (everything but REM sleep)
Neuromodulators of sleep regulation:
- Acetylcholine made at the basal forebrain regulates sleep
...
- Dopamine made at substantial nigra is involved in regulation of sleep
- Noradreanaline made at locus coeruleus
- Histamine made at tubermammilary nucleus
...
By activating noradrenaline, acetylcholine, dopamine, serotonin - they can stop sleep and
activate wakefulness
...
398
Ventrolateral preoptic area uses GABAergic neurons
...
During sleep (slow waves), there are rhythmic hyperpolarisations to prevent cell from
being active
...
Thalamocortical neurons
...
Release of neuromodulators changes the membrane potential
...
Relaxed wakefulness has alpha oscillations
...
Sleep spindles - plasticity
...
Alpha oscillations are present in perceptions
...
Papez circuit includes cingulate & parahippocampal gyrus
...
Emotion: temporary & volatile
Mood: Long lasting
Emotions govern the behaviour passively & subconsciously
Motivation: Ability to activley direct behavior towards specific goals
...
Drives can be homeostatic, hormonal, physiological
Drives & incentives causes motivation
Instinct - innate behaviour
...
Is automatic,
unmodifiable, irresistible, occurs in every member if the species
...
Hypothalamus - governs Autonomic response
...
No conscious control of hypothalamus is possible
...
Mamillary bodies relay information froombthr amygdala & hippocampus to the anterior
thalamus
...
400
Amygdala is connected to everywhere in the brain
...
Stimulation of amygdala leads to fear and can also have sexual effects (erection,
ovulation)
...
Blocks slow thinking & does quick threat assessment after sensory data is sent to the
amygdala via the thalamus
...
It is important in spatial navigation (path integration (self referenced) or map based
navigation (uses unrelated objects you've seen))
401
Hypothalamus
Hypothalamus- key to homeostasis & survival
...
All major ascending & descending tracts go through it
...
Hypothalamus can effect somatic nervous system, Autonomic Nervous system & pituitary
gland
...
Programs include: temperature regulation, salt & water homeostasis, energy homeostasis
(by feeding & Satiety control), growth & development, fight or flight reaction in response
to stress, sleep wake cycle, cardiorespiratory response to exercise
...
Lateral hypothalamus has many structures
...
Hypothalamus have many nuclear groups
...
Paravebtricular & Supraoptic nuclei (both are magnocellular) make ADH & oxytocin & send
it to the posterior pituitary
...
Endocrine clock is in response to dark & light
...
402
These form the retinohypothalamic tract & project to the suprachiasmatic nucleus
...
Melatonin concentration increases during sleep
...
Dual innervation is usually antagonistic
...
These control behaviour, create emotions & memories
...
Through the medial forebrain bundle there is ascending neural afferents going into the
hypothalamus
...
Emotions reach the hypothalamus via amygdala & hippocampal formation
...
Descending cortical control of Autonomic output: fear, panic, emotional stress, chronic
stress
...
For heat conservation: Can give shiver command, Brown Adiopose Tissue activation
command via the dorsomediak hypothalamus
...
Osmolality is checked by hypothalamus osmoreceptors
...
Free water increases the osmolality
...
Integrates hypothalamic & hormonal signals (ghrelin, leptin, insulin)
Paraventicular nucleus is involved in AVP release (arginine vasopressin), melatonin pathway
& energy homeostasis
...
Preoptic hypothalamus - control of sexual behaviour
Release of GnRH by MOPA (medial preoptic area of hypothalamus)
From preoptic nucleus, there is a projection to the ventral tegmental area which is
dopinergic
...
Molecular clock is in the suprahciasmatic nucleus
...
Melatonin secretion is always during the night
Title: Physiology notes by Parth Ghotekar
Description: Complete human physiology notes by a 2nd year medical student at the University of Szeged, Hungary.
Description: Complete human physiology notes by a 2nd year medical student at the University of Szeged, Hungary.